bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigations into disease associations with feline immunodeficiency virus (FIV) infection in lions (Panthera leo) in Australia: a case–control study
Authors: Dabydeen A , Herrin KV , Woolfenden L , Hall E , Westman ME , Norris JM 
Published: November 2024

BackgroundFeline immunodeficiency virus (FIV) is a highly mutable retrovirus with numerous species‐specific strains, such as those infecting domestic cats (Felis catus, FIVFca) and wild populations of nondomestic cats including lions (Panthera leo, FIVPle). When FIVFca infection manifests as disease in domestic cats, common presentations include lymphadenopathy, lymphoid malignancies, oral cavity disease, immunological dysfunctions and neurological abnormalities. In contrast to domestic cats, there has been little published evidence of direct FIVPle disease associations in lions. The objective of the study, therefore, was to conduct a longitudinal case–control comparison of clinical findings and survival analysis of FIVPle‐infected and FIVPle‐uninfected captive lions to investigate possible FIVPle disease associations in nondomestic felids in Australia.MethodsBetween 2005 and 2023, 38 lions were recruited from zoos across Australia. Lions had been FIV tested as part of a routine diagnostic service. The 38 lions included in the study comprised 15 FIV‐infected (9 males, 6 females) and 23 FIV‐uninfected (9 males, 14 females) animals. Lifetime longitudinal clinical histories and clinicopathological data collected by zoos for these lions were interrogated, including survival data.ResultsFIV‐infected lions were more likely to be reported with lower mean corpuscular volume (MCV) (fL) (P = 0.015), monocytes (%) (P = 0.023), chloride (mmol/L) (P = 0.016) and phosphate (mmol/L) (P = 0.029), but with a higher mean corpuscular hemoglobin concentration (MCHC) (g/L) (P = 0.001) and bicarbonate (mmol/L) (P = 0.035), than FIV‐uninfected lions. The disease associations usually seen in domestic cats with FIV infection were not observed in lions, and there was no difference in survival between FIV‐infected and FIV‐uninfected lions. The main limitation of the study was a small sample size dictated by the number of lions able to be recruited from zoos in Australia over an 18‐year period.ConclusionFew differences were found between case and control groups, suggesting that FIV‐infected lions did not experience clinicopathological changes that predisposed them to future disease compared with FIV‐uninfected lions. Further research will help to determine whether these results are indicative of a general absence of FIV‐associated disease in captive lions, or the result of nonpathogenic FIVPle subtype(s) present in Australia.
Chronic eosinophilic leukaemia—Not otherwise specified: Clinical features, genomic insight and therapeutic strategies
Authors: Costa Alessandro , Scalzulli Emilia , Breccia Massimo 
Published: November 2024

SummaryChronic eosinophilia leukaemia—not otherwise specified (CEL‐NOS) is a rare myeloproliferative neoplasm characterized by persistent clonal hypereosinophilia. Recent advances in genetics have refined diagnostic criteria, leading to the identification of CEL subtypes with specific cytogenetic and molecular abnormalities now classified as myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, which may benefit from targeted therapies. In contrast, CEL‐NOS lacks specific genetic drivers and intervention points to halt leukemogenesis. Molecular techniques have also enabled the definition of clonality in a considerable percentage of cases otherwise classified as idiopathic hypereosinophilic syndrome. CEL‐NOS poses a significant therapeutic challenge due to limited treatment options, poor prognosis and the risk of progression to acute leukaemia. Patients, often elderly and with comorbidities, face restricted access to transplantation, the only potentially curative treatment. Unfortunately, the prognosis remains poor even post‐transplant, with a 5‐year survival rate of only one‐third of patients. Other therapies, including steroids, cytoreductive and immunomodulatory treatments, offer limited and temporary responses with significant side effects. This review aims to consolidate current knowledge on CEL‐NOS, covering diagnostic approaches, genetic advancements and therapeutic challenges. It seeks to provide a comprehensive overview and highlight critical areas for future research.
Exploring the Cognitive and Behavioral Aspects of Shprintzen‐Goldberg Syndrome; a Novel Cohort and Literature Review
Authors: Sjøstrøm Emilie , Bruel Ange‐Line , Philippe Christophe , Delanne Julian , Faivre Laurence , Menke Leonie A. , Au P. Y. Billie , Cormick Jessica Jane , Moosa Shahida , Bayat Allan 
Published: November 2024

ABSTRACTShprintzen‐Goldberg‐syndrome (SGS) is caused by pathogenic exon 1 variants of SKI. Symptoms include dysmorphic features, skeletal and cardiovascular comorbidities, and cognitive and developmental impairments. We delineated the neurodevelopmental and behavioral features of SGS, as they are not well‐documented. We collected physician‐reported data of people with molecularly confirmed SGS through an international collaboration. We identified and deep‐phenotyped the neurodevelopmental and behavioral features in four patients. Within our cohort, all exhibited developmental delays in motor skills and/or speech, with the average age of first words at 2 years and 6 months and independent walking at 3 years and 5 months. All four had learning disabilities and difficulties regulating emotions and behavior. Intellectual disability, ranging from borderline to moderate, was present in all four participants. Moreover, we reviewed the literature and identified 52 additional people with SGS, and summarized the features across both datasets. Mean age was 23 years (9–48 years). When combining our cohort and reported cases, we found that 80% (45/56) had developmental and/or cognitive impairment, with the remainder having normal intelligence. Our study elucidates the developmental, cognitive, and behavioral features in participants with SGS and contributes to a better understanding of this rare condition.
Allergic contact dermatitis caused by glucose sensors and insulin pumps: A full review
Authors: de Groot Anton , van Oers Emma M. , Ipenburg Norbertus A. , Rustemeyer Thomas 
Published: November 2024

AbstractDuring the past 8 years, a large number of reports have appeared on allergic contact dermatitis to glucose sensors and insulin pumps in paediatric and adult patients with type 1 diabetes mellitus. Isobornyl acrylate in one particular sensor sensitised many hundreds of (published) individuals, and many other allergens were discovered in a large number of sensors and pumps. Diagnostic procedures with patch tests proved very complicated, as manufacturers showed a serious lack of cooperation with dermatologists in providing information on the ingredients of their products and samples for patch testing. This two‐part article provides a full and detailed review of all aspects of the subject of allergic contact dermatitis to glucose sensors and insulin pumps. Part 1 begins with a general introduction to sensors and pumps, followed by the cutaneous adverse reactions that they have caused and a full account of the allergens in the diabetes devices. In addition, an overview of the glucose sensors and insulin pumps that have caused allergic contact dermatitis is presented. Part 2 presents all published case reports and case series, clinical features of allergic contact dermatitis to sensors and pumps, patch test procedures, differentiation from irritant dermatitis, management of allergic patients and (proposed) legislation.
Trends of in vitro pharmacological potency and in vivo pharmacokinetics parameters of modern drugs: Can the therapeutic/subtherapeutic dose be estimated from in vitro Ki and pharmacokinetic parameters?
Authors: Tsuchitani Toshiaki , Kato Motohiro , Tomaru Atsuko , Aoki Yasunori , Sugiyama Yuichi 
Published: November 2024

AbstractIn drug discovery and development, estimating therapeutic and subtherapeutic doses is crucial for designing early‐phase clinical trials, particularly first‐in‐human (FIH) studies. While increasing the in vitro pharmacological potency (lowering Ki) of a compound to its target is expected to decrease the therapeutic dose, its benefit is not necessarily clarified. We analyzed in vitro Ki, human in vivo pharmacokinetics (PK) parameters, and therapeutics doses of 144 oral small‐molecule drugs approved in Japan (2010–2021). The data on classic drugs were obtained from Goodman and Gilman's textbook, 9th ed. (published in 1996). Modern drugs had lower Ki (2.5 nM) and daily doses (88 μmol/day) than classic drugs (33 nM and 313 μmol/day), but 3.6‐fold higher intrinsic clearance (CLint; 171 vs. 47 L/h), suggest that increasing potency over the years has not resulted in a reduction in dosage as expected. Estimating therapeutic doses using target receptor occupancy (tRO)‐optimized approach improved estimation accuracy (63% within 10‐fold of observed values) compared with tRO‐fixed approaches. Subtherapeutic dose estimations revealed a risk of overdosing in FIH trials, indicating that these estimates are not necessarily as conservative as is generally understood. Notably, the unbound average concentration‐to‐Ki ratio (Cave,u/Ki) varied among drugs and correlated negatively with Ki, suggesting the possible necessity of incorporating it into dose estimation methods. This study provides insights into the relationship between in vitro Ki, in vivo PK parameters, and therapeutic dose of modern drugs, proposing strategies and revealing the risk for dose estimation and drug development in the era of highly potent small molecules.
Differential effects of imeglimin and metformin on insulin and incretin secretion—An exploratory randomized controlled trial
Authors: Usui Ryota , Hamamoto Yoshiyuki , Imura Masahiro , Omori Yasuhiro , Yamazaki Yuji , Kuwata Hitoshi , Tatsuoka Hisato , Shimomura Kazuhiro , Murotani Kenta , Yamada Yuichiro , Seino Yutaka 
Published: November 2024

AbstractAimsImeglimin is a new oral anti‐diabetic drug with a similar structure to that of metformin; however, unlike metformin, clinical trials indicate that imeglimin elicits its glucose‐lowering effect mainly by enhancement of insulin secretion. The comparative effects of the two drugs on incretin secretion remains to be elucidated.Materials and MethodsA single‐center, open‐label, randomized controlled trial was conducted in patients with type 2 diabetes who were drug‐naïve or were on a single oral hypoglycaemic agent (OHA). For patients taking a single OHA, an 8‐week washout period was employed before randomization. Participants were randomized to the imeglimin group (IME, 2000 mg/day) or the metformin group (MET, 1000 mg/day), and OGTT was performed before treatment and after 12 and 24 weeks of treatment.ResultsThe reduction in HbA1c at 24 weeks was similar in IME and MET. OGTT revealed a comparable decrease in post‐challenge blood glucose excursion in both groups, but insulin levels were increased only in IME. Total and active glucagon‐like peptide‐1 (GLP‐1) levels were increased in both IME and MET; however, total and active glucose‐dependent insulinotropic peptide (GIP) levels were increased only in IME. Interestingly, while an increase in insulin levels in IME was positively correlated with an increase in GLP‐1 at 12 weeks, it was correlated only with an increase in GIP at 24 weeks.ConclusionsUnlike metformin, imeglimin enhances GIP secretion as well as GLP‐1 secretion, in addition to its direct insulinotropic mechanism of glucose control, emphasizing its potential as a therapeutic option in the treatment of patients with diabetes.
Network Mendelian randomisation analysis deciphers protein pathways linking type 2 diabetes and gastrointestinal disease
Authors: Geng Jiawei , Ruan Xixian , Wu Xing , Chen Xuejie , Fu Tian , Gill Dipender , Burgess Stephen , Chen Jie , Ludvigsson Jonas F. , Larsson Susanna C. , Li Xue , Du Zhongyan , Yuan Shuai 
Published: November 2024

AbstractAimsThe molecular mechanisms underlying the association between type 2 diabetes (T2D) and gastrointestinal (GI) disease are unclear. To identify protein pathways, we conducted a two‐stage network Mendelian randomisation (MR) study.Materials and MethodsGenetic instruments for T2D were obtained from a large‐scale summary‐level genome‐wide meta‐analysis. Genetic associations with blood protein levels were obtained from three genome‐wide association studies on plasma proteins (i.e. the deCODE study as the discovery and the UKB‐PPP and Fenland studies as the replication). Summary‐level data on 10 GI diseases were derived from genome‐wide meta‐analysis of the UK Biobank and FinnGen. MR and colocalisation analyses were performed. Pathways were constructed according to the directionality of total and indirect effects, and corresponding proportional mediation was estimated. Druggability assessments were conducted across four databases to prioritise protein mediators.ResultsGenetic liability to T2D was associated with 69 proteins in the discovery protein dataset after multiple testing corrections. All associations were replicated at the nominal significance level. Among T2D‐associated proteins, genetically predicted levels of nine proteins were associated with at least one of the GI diseases. Genetically predicted levels of SULT2A1 (odds ratio = 1.98, 95% CI 1.80–2.18), and ADH1B (odds ratio = 2.05, 95% CI 1.43–2.94) were associated with cholelithiasis and cirrhosis respectively. SULT2A1 and cholelithiasis (PH4 = 0.996) and ADH1B and cirrhosis (PH4 = 0.931) have strong colocalisation support, accounting for the mediation proportion of 72.8% (95% CI 45.7–99.9) and 42.9% (95% CI 15.5–70.4) respectively.ConclusionsThe study identified some proteins mediating T2D‐GI disease associations, which provided biological insights into the underlying pathways.
Effect of exercise on plasma insulin levels in individuals with type 1 diabetes: A systematic review and meta‐analysis
Authors: Kastrati Lum , Alvarez‐Martinez Mario , Thomas Andreas , Thevis Mario , Muka Taulant , Stettler Christoph , Herzig David , Glisic Marija , Bally Lia 
Published: November 2024

AbstractAimsCurrent evidence of the impact of acute exercise on insulin levels in individuals with type 1 diabetes remains controversial. Therefore, we conducted a systematic review and meta‐analysis to explore exercise‐induced changes in insulin levels.Materials and MethodsWe conducted a systematic review (until 05 November 2023) and meta‐analysis exploring the effect of exercise on insulin concentration in individuals with type 1 diabetes. We included randomised cross‐over studies for rapid‐acting insulin and pre‐ and post‐studies for long‐acting insulin in individuals with type 1 diabetes performing any type of acute exercise and had a control condition. The exercise‐induced change in insulin levels was the outcome of interest. When possible, the mean differences (MDs) in insulin levels were pooled using the DerSimonian and Laird random effect method. Risk of bias was assessed for each included study.ResultsSeventeen trials, encompassing 186 participants with type 1 diabetes, were included in the systematic review. Twelve out of 17 studies included participants on rapid‐acting insulin regimens and used a cross‐over design, whereas five out of 17 single‐arm studies included participants on (ultra)long‐acting insulin. Seven out of 12 studies on rapid‐acting insulins and all the single‐arm studies were at high risk of bias. Results suggest a statistically significant, small‐to‐moderate increase of rapid‐acting insulin after 30 min of exercise (MD of 18.44 [95% CI 0.02; 36.86; I2 0%] pmol/L); meanwhile, findings on (ultra)long‐acting insulin were inconclusive.ConclusionsA small‐to‐moderate increase of insulin levels in studies including rapid‐acting insulin was found after a bout of physical exercise in individuals with type 1 diabetes. However, current gaps in high‐quality evidence challenge our understanding of insulin kinetics around exercise.
Study of Degenerative Mitral Regurgitation Using Three‐Dimensional Echocardiography and EchoPAC GE Health Care Software 4D Auto MVQ: Comparison Between Transthoracic and Transesophageal Examination
Authors: Fioretti Ginevra , Tolomei Alice , Ciaramella Piera , Lio Antonio , Cristiano Ernesto , Cacioli Giulio , Tempestini Federica , Ranocchi Federico , Maestrini Viviana , Pergolini Amedeo 
Published: November 2024

ABSTRACTBackgroundPreoperative echocardiographic assessment is critical for patients with severe degenerative mitral regurgitation to ensure personalized surgical mitral valve repair. This study aimed to compare the diagnostic accuracy of three‐dimensional transthoracic echocardiography (3D TTE) and three‐dimensional transesophageal echocardiography (3D TEE) in identifying valvular lesions, using surgical findings as the reference. Additionally, we evaluated whether annular dimensional parameters derived from TTE and TEE, using dedicated 3D software, could confirm whether 3D TTE alone offers a comprehensive preoperative evaluation.MethodsWe enrolled 60 patients with severe organic mitral regurgitation scheduled for surgical valve repair. Each patient underwent preoperative 3D TTE, intraoperative 3D TEE prior to surgery, followed by annuloplasty. Mitral valve reconstructions from both TTE and TEE were compared, and dedicated 3D software (EchoPAC GE‐Health‐Care Software 3D‐auto‐MVQ) was employed to reconstruct annular geometries from both methods.ResultsBoth 3D TTE and 3D TEE demonstrated comparable accuracy in identifying diseased scallops (overall accuracy: 3D TTE 91.8%, 3D TEE 98.1%, p > 0.05). However, 3D TTE was inferior to 3D TEE in identifying multiple chordal ruptures (accuracy: 3D TTE 80%, 3D TEE 100%). Quantitative analysis of the mitral annulus revealed that 3D TTE and 3D TEE yielded overlapping results for static parameters (p > 0.05), whereas dynamic parameters differed significantly (p < 0.05).ConclusionsIn the selected population, 3D TTE demonstrated diagnostic accuracy comparable to transesophageal echocardiography in identifying mitral valve lesions. Furthermore, with the use of dedicated 3D software, TTE alone may provide a comprehensive and noninvasive preoperative evaluation, particularly for static annular parameters. Further studies are warranted to corroborate these findings.
Interdisciplinary Approach to Managing Complex Traumatic Dental Injuries in the Young Permanent Dentition
Authors: Gorp Gertrude Van , EzEldeen Mostafa 
Published: November 2024

ABSTRACTTraumatic dental injuries (TDIs) are a frequent challenge in pediatric dentistry, requiring a coordinated interdisciplinary approach for successful management. These injuries can affect various dental tissues and pose significant diagnostic and therapeutic challenges, particularly in young patients with developing dentition. This review aims to explore the complexities of managing TDIs in young permanent dentition, focusing on the role of orthodontics, endodontics, and other specialties in providing comprehensive care. We highlight the importance of interdisciplinary collaboration in achieving optimal functional and aesthetic outcomes, emphasizing the need for updated diagnostic tools and treatment protocols tailored to the growing child. Specific recommendations are provided for clinicians on integrating orthodontic and endodontic management in trauma cases, focusing on minimizing complications and ensuring long‐term prognosis.
Behaviour of the Apex Predator European Catfish (Silurus glanis) on a Recently Invaded Reservoir
Authors: Santos G. S. , Ribeiro F. , Pereira E. , Silva A. F. , Almeida P. R. , Ribeiro D. , Quintella B. R. 
Published: November 2024

ABSTRACTThe European catfish (Silurus glanis L.) is a large, non‐native, invasive freshwater species known for its high fecundity, long lifespan and significant predatory potential, possibly threatening native fish communities. While some studies exist on its spatial use, most focus on its native range and lack detailed circadian and annual activity patterns. This study uses acoustic biotelemetry to track 10 adult fish in the Tagus River's Belver reservoir, employing transmitters with 3D accelerometer and pressure sensors to record activity and depth over a year. Generalised additive models identify environmental variables influencing activity and depth patterns. The European catfish is active year‐round, with peak activity in summer and minimal in autumn. It occupies shallower depths in spring and summer (median depths of 2.6 and 4.8 m, respectively) and deeper waters in autumn and winter (median depths of 9.8 and 10.8 m, respectively). Circadian vertical movement patterns exhibit high seasonal and individual variability. Significant environmental predictors of the European catfish activity include river flow, water temperature and the photoperiod, while the predictors of depth use are river flow and the photoperiod. These insights can aid in developing effective control measures, such as optimising fishing efforts spatially and temporally to enhance the efficiency of removing this invasive fish.
Distribution and Diversity of Coastal Fish in Fresh and Oligohaline Waters: An Example of the Largest Baltic Sea Estuary of the Neva River
Authors: Uspenskiy Anton A. 
Published: November 2024

ABSTRACTUnderstanding how low salinity gradients (0‰–5‰) influence fish life cycles is critical for clarifying principles of fish assemblage formation in estuarine ecosystems. This study is intended to provide a foundation for predicting changes in fish populations amidst ongoing surface salinity decreases in the Baltic Sea. In the Neva River Estuary, differences in fish diversity and distribution between fish assemblages in freshwater and oligohaline areas were assessed using beach seine and multi‐mesh gillnet surveys. The use of multiple sampling gears greatly enhanced understanding of fish distribution across salinity gradients. Fish assemblages were analysed depending on the different areas of the estuary, seasons of sampling, salinity and confounding environmental variables such as water temperature and depth. Salinity was the major influencing factor for the surf zone fish assemblages and a season of sampling was the main factor for coastal assemblages of larger fish studied with the gillnets. Fish assemblages in the surf zone exhibited significant but gradual changes in freshwater and marine‐estuarine fish occurrence and abundance along the critical oligohaline barrier ‘δ‐horohalinicum’ (0.5‰–1.9‰). Although freshwater species showed high occurrence and abundance throughout the estuary, their juveniles were less abundant in the oligohaline surf zone with salinity ≥ 2‰, where small‐size marine‐estuarine and euryhaline species predominated. Coastal multi‐mesh gillnet catches showed remarkable similarity between assemblages of larger fish in freshwater and oligohaline areas. Differences in species richness and diversity indices were not pronounced throughout the salinity gradient; the decline in freshwater species was offset by an increase in marine‐estuarine and euryhaline species.