bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cost‐effective blood DNA methylation‐based age estimation method in domestic cats, Tsushima leopard cats (Prionailurus bengalensis euptilurus) and Panthera species, using targeted bisulphite sequencing and machine learning models
Authors: Qi Huiyuan , Lim Qi Luan , Kinoshita Kodzue , Nakajima Nobuyoshi , Inoue‐Murayama Miho 
Published: January 2024

AbstractIndividual age can be used to design more efficient and suitable management plans in both in situ and ex situ conservation programmes for targeted wildlife species. DNA methylation is a promising marker of epigenetic ageing that can accurately estimate age from small amounts of biological material, which can be collected in a minimally invasive manner. In this study, we sequenced five targeted genetic regions and used 8–23 selected CpG sites to build age estimation models using machine learning methods at only about $3–7 per sample. Blood samples of seven Felidae species were used, ranging from small to big, and domestic to endangered species: domestic cats (Felis catus, 139 samples), Tsushima leopard cats (Prionailurus bengalensis euptilurus, 84 samples) and five Panthera species (96 samples). The models achieved satisfactory accuracy, with the mean absolute error of the most accurate models recorded at 1.966, 1.348 and 1.552 years in domestic cats, Tsushima leopard cats and Panthera spp. respectively. We developed the models in domestic cats and Tsushima leopard cats, which were applicable to individuals regardless of health conditions; therefore, these models are applicable to samples collected from individuals with diverse characteristics, which is often the case in conservation. We also showed the possibility of developing universal age estimation models for the five Panthera spp. using only two of the five genetic regions. We do not recommend building a common age estimation model for all the target species using our markers, because of the degraded performance of models that included all species.
A systematic review of risk prediction model of venous thromboembolism for patients with lung cancer
Authors: Wang Yan , Li Qiuyue , Zhou Yanjun , Dong Yiting , Li Jinping , Liang Tao 
Published: January 2024

AbstractBackgroundVenous thromboembolism (VTE) increases the risk of death or adverse outcomes in patients with lung cancer. Therefore, early identification and treatment of high‐risk groups of VTE have been the research focus. In this systematic review, the risk assessment tools of VTE in patients with lung cancer were systematically analyzed and evaluated to provide a reference for VTE management.MethodsRelevant studies were retrieved from major English databases (The Cochrane Library, Embase, Web of Science, PubMed, Scopus, Medline) and Chinese databases (China National Knowledge Infrastructure [CNKI] and WanFang Data) until July 2023 and extracted by two researchers. This systematic review was registered at PROSPERO (no. CRD42023409748).ResultsFinally, two prospective cohort studies and four retrospective cohort studies were included from 2019. There was a high risk of bias in all included studies according to the Prediction Model Risk of Bias Assessment tool (PROBAST). In the included studies, Cox and logistic regression were used to construct models. The area under the receiver operating characteristic curve (AUC) of the model ranged from 0.670 to 0.904, and the number of predictors ranged from 4 to 11. The D‐dimer index was included in five studies, but significant differences existed in optimal cutoff values from 0.0005 mg/L to 2.06 mg/L. Then, three studies validated the model externally, two studies only validated the model internally, and only one study validated the model using a combination of internal and external validation.ConclusionVTE risk prediction models for patients with lung cancer have received attention for no more than 5 years. The included model shows a good predictive effect and may help identify the risk population of VTE at an early stage. In the future, it is necessary to improve data modeling and statistical analysis methods, develop predictive models with good performance and low risk of bias, and focus on external validation and recalibration of models.
Proteomic profiling of tear fluid from offspring of Keratoconus patients: New insights into pathways and molecular drivers of disease development
Authors: López‐López Maite , Regueiro Uxía , Alvite‐Piñeiro Tania , Díez‐Feijoo Elío , Lema Isabel 
Published: January 2024

Aims: To analyse the tear proteome of the offspring of Keratoconus (KC) patients in comparison with control subjects, trying to elucidate the molecular drivers underlying the risk of KC development in this population and providing a better understanding of the molecular mechanisms involved in the preclinical stages of the disease.Methods: This study included 72 offspring of KC patients and 25 control subjects with no family history of corneal ectasia (age‐ and sex‐matched). In the study group, only cases without tomographic alterations of clinical KC were included in the proteomic analysis. Pentacam was used for tomographic study. Tear sample was collected using Schirmer strips and analysed by liquid chromatography with tandem mass spectrometry. SWATH‐MS was used as a quantification tool for the tear proteomic profile. Protein expression was compared between groups, and the molecular functions of the dysregulated ones and their functional relationships were studied by in silico analysis.Results: 14 eyes (10%) of the study group showed clinical KC, therefore, they were excluded from the proteomic analysis. Among the total proteins quantified in the tear fluid of offspring and controls, 21 were statistically differentially expressed (p < 0.05) between groups. Increased expression of 6 proteins and decreased expression of 15 proteins were observed in the tear samples of the study group. ZAG, LF, S100A9 and Annexin5 were some of the most dysregulated proteins. Protein–protein interactions and gene ontology analysis revealed the involvement of these dysregulated proteins in structural, apoptosis, iron homeostasis, oxidative stress and inflammation processes.Conclusions: In the tear fluid of KC patients' offspring without tomographic alterations differences in the expression of proteins previously associated with KC disease were observed, suggesting potential molecular drivers leading to KC development and strengthening the susceptibility of this population to disease onset.
Comparing and combining bovine cornea decellularization methods for ocular surface biomaterials and tissue engineering applications
Authors: Caliskan Mert Egemen , Arslan Ilayda , Yalcin Musacan , Ozer Taylan Can , Soykan Merve Nur , Tasa Burcugül Altuğ , Atalay Eray 
Published: January 2024

Aims/Purpose: The purpose of this research was to evaluate the decellularization efficiency of various individual protocols and their combinations for bovine cornea intended for ocular surface biomaterial applications.Methods: Two fundamental decellularization protocols, namely sodium chloride (NaCl) and Ammonium & Triton X‐100 were taken as benchmark and their combinations with freeze–thaw and lyophilization, were assessed whether, the decellularization efficiency improved (n = 3). Overall, protocols that were investigated were as follows: (1) Lyophilization followed by NaCl, (2) Freeze–Thaw followed by NaCl, (3) Lyophilization, Ammonium and Triton X‐100 (1%), (4) Ammonium and Triton X‐100 (5%), (5) Freeze–thaw, Ammonium and Triton X‐100 (1%), (6) Lyophilization, Ammonium and Triton X‐100 (5%), (7) Freeze–thaw and (8) NaCl. These methods were assessed using gel electrophoresis for qualitative DNA analysis and NanoDrop for quantitative DNA content. Efficient decellularization was achieved in the presence of DNA content below 50 ng/mg ECM dry weight and <200 bp DNA fragment length.Results: Gel electrophoresis revealed DNA content over 200 bp in groups 1, 2,7 and 8 while other groups fulfilled the criterion for efficient decellularization. DNA content as measured by NanoDrop indicated efficient decellularization in all groups, except group 7.Conclusions: Our study provides valuable insights into the effectiveness of combined and individual decellularization protocols for bovine cornea. Our findings suggest, that NaCl and its combinations with lyophilization and freeze–thaw yield in ineffective decellularization. On the other hand, Ammonium and Triton X‐100, individually or in combinations, result in favourable decellularization.
Sex‐related differences in the visual function of an animal model of type 1 diabetes
Authors: Oliveira Sara , Campos Elisa Julião , Fernandes Rosa , Bernardes Rui , Matafome Paulo , Ambrósio António Francisco 
Published: January 2024

Aims/Purpose: Recent basic and clinical research evidence suggests that male–female differences may influence retinal function and structure. It is also well‐established that diabetes affects retinal function. This work aimed to assess whether type 1 diabetes differentially affects neuroretinal function in male and female Wistar rats.Methods: To induce type 1 diabetes, male and female Wistar rats were injected (i.p.) with streptozotocin (65 mg/kg). Electroretinograms (ERGs) were recorded before and 1, 2, and 4 weeks after diabetes induction (n = 12–13 animals/group). To assess the effect of chronic hyperglycemia on the content of molecular components of the blood‐retinal barrier (BRB), specific tight junction proteins were assessed by Western Blotting. Neuroinflammation was evaluated by measuring the retinal levels of pro‐inflammatory cytokines.Results: Some sex‐related changes in retinal function were detected in the diabetic animals. Overall, in male diabetic rats, compared to control male rats, the differences found under scotopic conditions were mainly in the positive scotopic threshold response (pSTR), with decreased amplitudes (at weeks 2 and 4), and higher latencies (at weeks 1 and 4). In contrast, diabetic female rats, compared to control females, presented a higher increase in the latency value of the negative STR (nSTR; at weeks 1 and 4), a‐wave (at weeks 1, 2, and 4), and oscillatory potentials 2, 3, and 4 (at weeks 1, 2, and 4). Under photopic conditions, male diabetic rats showed higher implicit time values of the fundamental flicker wave (at week 4) and a decrease in the amplitude of the flicker 2nd harmonic (at week 4) compared to control males. Conversely, in diabetic female rats, there were no differences in these parameters compared to control female rats. Concerning the BRB and neuroinflammation, no changes were found in diabetic males and females compared to their respective controls.Conclusions: Our findings suggest that type 1 diabetes differentially affects the retinal function in male and female Wistar rats.Support: FCT‐Portugal: PEst UIDB/04539/2020 and UIDP/04539/2020; 2020.07432.BD.
Ocular pharmacokinetics of a new preservative‐free bimatoprost 0.01% ophthalmic gel
Authors: Rokicki Dariusz , Ghione Silvia , Allan Richard , Viaud Karen , Allan Fanny 
Published: January 2024

Aims/Purpose: The aim of this study was to compare the aqueous humour (AH) and iris‐ciliary body (ICB) concentrations of bimatoprost and its main metabolite bimatoprost free acid after topical instillation in rabbits of a new preservative‐free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) versus two commercially available preserved bimatoprost ophthalmic solutions ‐ PB 0.01% (200 ppm benzalkonium chloride [BAK], Lumigan® 0.01%) and PB 0.03% (50 ppm BAK, Lumigan® 0.03%).Methods: Female Dutch Belted rabbits (n = 45) were divided into three treatment groups (30 eyes per group): PFB 0.01% gel, PB 0.01% and PB 0.03% solutions. Animals received a single topical instillation (25 μL) into both eyes. AH and ICB samples were collected at 0.5 h, 1 h, 2 h, 4 h and 8 h post instillation. These samples were analysed by rapid resolution liquid chromatography tandem mass spectrometry for bimatoprost and bimatoprost free acid concentrations.Results: Following a single topical instillation, Tmax of bimatoprost and bimatoprost free acid in both ocular matrices was 1 h across the 3 treatments. Cmax of bimatoprost/bimatoprost free acid was 50.2 ng/mL, 26.3 ng/mL and 59.9 ng/mL of AH respectively following PFB 0.01%, PB 0.01% and PB 0.03% treatments. Maximal concentrations and area under the curve in AH and ICB of bimatoprost/bimatoprost free acid were greater (from 2‐ to 2.6‐fold) with PFB 0.01% gel compared to PB 0.01% and similar (from 0.9‐ to 0.95‐fold) to PB 0.03%.Conclusions: Topical instillation of PFB 0.01% gel produced significantly higher bimatoprost/bimatoprost free acid concentrations in the AH and ICB of rabbits than PB 0.01% (despite a high BAK concentration) and was similar to PB 0.03%. The preservative‐free gel formulation improves corneal penetration and bioavailability of bimatoprost compared to a preserved solution at the same concentration.
Glaucoma in Sturge–Weber‐Krabbe syndrome about 10 cases
Authors: Benchekroun Reda , Ghizlane Daghouj , Mtalai Naoual , Rami Ali , El Maaloum Loubna , Allali Bouchra , El Kettani Asmaa 
Published: January 2024

Aims/Purpose: The objective of this study is to evaluate the results of glaucoma treatment in a series of 10 children with Sturge–Weber syndrome.Methods: The objective of this study is to evaluate the results of glaucoma treatment in a series of 10 children with Sturge–Weber syndrome collected between 2010 and 2023 at the paediatric ophthalmology department of the 20 August 1953 hospital of the University Hospital of Casablanca.Results: The mean age at diagnosis was 11 months, with a Sex‐ratio of 1.5. Seven patients had a unilateral facial angioma occupying the V1 territory and three had a bilateral angioma, the cutaneous angioma was extended to the neck and thorax in one patient of these 10 cases. Two patients had a meningeal angioma revealed by hemicorporeal seizures contralateral to the cutaneous angioma. Buphthalmia was found in five cases, dilatation of the episcleral vessels in four patients, predominantly in the temporal area. No cases of choroidal angioma were noted. The average preoperative ocular tone was 18 mm Hg. The average c/d was 0.5. All 10 eyes had trabeculectomy under 5 Fluorouracil. 4 eyes were reoperated. We noted 1 case of vitreous exit intraoperatively. The final ocular tone was <20 mm Hg in eight eyes, four of which had adjuvant hypotonizing treatment with Beta‐blocker and Dorzolamide, after a mean follow‐up of 24 months.Conclusions: The risk of Glaucoma being important, the Sturge–Weber‐Krabbe syndrome must be evoked in front of any facial hemangioma and its existence should not delay the therapy.
New insights into idebenone therapy in relation to NQO1
Authors: La Morgia Chiara , Aleo Serena Jasmine , Del Dotto Valentina , Romagnoli Martina , Fiorini Claudio , Capirossi Giada , Peron Camille , Maresca Alessandra , Caporali Leonardo , Capristo Mariantonietta , Tropeano Concetta Valentina , Zanna Claudia , Ross‐Cisneros Fred , Sadun Alfredo A. , Pignataro Maria Gemma , Giordano Carla , Fasano Chiara , Porcelli Anna Maria , Tioli Gaia , Musiani Francesco , Catania Alessia , Lamperti Costanza , Marzoli Stefania Bianchi , De Negri Annamaria , Cascavilla Maria Lucia , Battista Marco , Barboni Piero , Carbonelli Michele , Amore Giulia , Smirnov Dmitrii , Vasilescu Catalina , Farzeen Aiman , Blickhäuser Beryll , Prokisch Holger , Catarino Claudia , Klopstock Thomas , Tiranti Valeria , Carelli Valerio , Ghelli Anna Maria 
Published: January 2024

Idebenone is the only approved treatment for Leber's hereditary optic neuropathy (LHON).It promotes recovery of visual function in up to 50% of patients, but, based on the current knowledge, we can neither predict nor understand the non‐responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON.We explored the possibility that genetic variant in the NQO1 enzyme can impact on idebenone response. We found that two polymorphic variants drastically reduce NQO1 protein levels, when homozygous or in compound heterozygote combination affecting idebenone reduction. In its oxidized form idebenone inhibits complex I, decreasing respiratory function in cells. We also retrospectively analysed a large cohort of LHON treated patients, classified by their response to therapy, demonstrating that patients homozygous or compound heterozygote for the NQO1 variants are characterized by the worst therapy response, particularly if carrying the m.3460G>A/MT‐ND1 LHON mutation.In summary, these results support the concept that the response to idebenone therapy may be influenced by the NQO1 genotype and the different mitochondrial DNA mutations.
Archaeometric investigations of the Late Roman Period red slip ware from Caesarea Germanicia (Kahramanmaraş, Southeastern Anatolia)
Authors: Semiz Barış , Ok Mehmet , Dumankaya Oktay 
Published: January 2024

AbstractIn the present study, red slip wares excavated from the ancient city of Germanicia (modern Kahramanmaraş, Southeastern Anatolia) were subjected to an archaeometric analysis. A multi‐analytical approach was employed, including stereomicroscopy, optical microscopy, XRPD, SEM‐EDS, and XRF to explore the mineralogical and chemical compositions of the samples. Based on both archaeological and archaeometric criteria, the samples were classified into three main categories: African, Phocaean, and Sagalassos red slip wares. The African red slip wares were characterized by an abundance of coarse quartz inclusion, accompanied by lesser quantities of plagioclase and mica. The Phocaean red slip wares primarily consisted of quartz, feldspar, and mica. In contrast, the Sagalassos red slip wares featured a groundmass rich in quartz, mica/biotite, hematite, and opaque minerals. Thermoanalytical data indicated that all samples were fired at temperatures between 800 and 900°C. The results suggest that red slip wares found at Germanicia were not manufactured using local available clay sources but rather originated from different regions. This evidence further provides that Germanicia was actively involved in trade networks and interacted with various ancient urban centers, such as Africa, Phocaean, and Sagalassos, during the Late Roman Period, between the fourth and fifth centuries AD.
Ovarian dynamics in progesterone tablet‐induced superovulation in goats assessed by magnetic resonance imaging
Authors: Hano Kazuki , Takashima Satoshi , Inatani Yuka , Kainuma Risa , Oiji Yuki , Nakamura Kotono , Yayota Masato , Takasu Masaki 
Published: January 2024

AbstractControlled internal drug‐releasing (CIDR) devices are commonly used for superovulation in goats. However, such devices are unavailable in some countries, including Japan. In this technical note, we aimed to explore the efficacy of an alternative superovulation protocol using progesterone tablets in goats. We employed intravaginal progesterone tablets (LUTINAS® Vaginal Tablet 100 mg) following a standard superovulation protocol. Additionally, we assessed the ovarian dynamics using 3T‐magnetic resonance imaging (MRI) 1 day preceding the progesterone treatment (Day “−1”) and 3 days before the end of treatment (Days 11–13). The ovarian monitoring was successfully performed in the short tau inversion recovery T2‐weighted images of MRI, and ovulation was confirmed by the disappearance of follicles on Day 13 post‐administration of the tablets. Immediately after ovulation, oviduct flushing yielded a substantial number of oocytes (13.5 ± 1.8 oocytes per animal). These findings provide evidence that the administration of progesterone tablets can serve as a viable alternative for inducing. Additionally, our findings suggest that 3T‐MRI is a promising alternative to conventional ultrasonography for monitoring ovarian dynamics following superovulation in experimental goats.
Exploring methods of improving patient understanding and communication in a complex anal fistula clinic: results from a randomized controlled feasibility study
Authors: Iqbal Nusrat , Fletcher Jordan , Bassett Paul , Hart Ailsa , Lung Phillip , Tozer Phil 
Published: January 2024

AbstractAimPatient understanding of disease can guide decision‐making in the management of anal fistula. This prospective feasibility study aimed to assess the acceptability and methods of assessing the impact of viewing realistic models on patients with anal fistula.MethodsNew referrals to a tertiary clinic participated in this single‐centre, parallel‐group randomized controlled study. Baseline characteristics, Decisional Conflict Scale and understanding of disease were assessed pre‐consultation. Participants were randomized to a standard consultation, where disease and treatment options were explained using magnetic resonance images and drawn diagrams, or a similar consultation supplemented with an appropriate generic three‐dimensional (3D) printed model. Understanding of disease and proposed surgery, Decisional Conflict Scale and ratings of visual aids were assessed post‐consultation, along with 3D model feedback.ResultsAll 52 patients who were approached agreed to be randomized (25 standard, 27 3D consultation). Understanding of disease increased post‐consultation in both groups. Post‐consultation decisional conflict (0, no; 100, high decisional conflict) was low (median 27 post‐standard vs. 24 post‐3D consultation). Patients scored highly on measures assessing understanding of proposed surgery. 3D models were rated highly, with 96% of patients wanting to see them again in future consultations.ConclusionsThree‐dimensional printed fistula models are a welcome addition to outpatient consultations with results suggesting that understanding of surgery is improved. A future trial should be powered to detect whether 3D models result in a significant improvement in understanding beyond traditional methods of explanation and explore the conditions in which models have their maximal utility.ClinicalTrials.gov Registration IDThis study was registered on ClinicalTrials.gov (ID: NCT04069728). Registered on 23 August 2019.
Comparing robotic with laparoscopic beyond total mesorectal excision for advanced rectal cancer—a propensity‐matched analysis
Authors: Kazi Mufaddal , Rastogi Aman , Raj Prudvi , Sadasivudu Vasireddy , Desouza Ashwin , Saklani Avanish 
Published: January 2024

AbstractAimRobotic surgery is increasingly being used for rectal resection, with short‐term benefits such as reduced hospital stay, faster bowel recovery and fewer complications. However, its utility for advanced rectal cancers requiring beyond total mesorectal excision has not been adequately evaluated. The aim of this study was to compare robotic and laparoscopic approaches for extended rectal resection, with postoperative and short‐term oncological outcomes as endpoints.MethodA retrospective, single‐centre study of patients with advanced rectal cancer requiring extended rectal resection between January 2017 and December 2022 was carried out. Beyond total mesorectal excisions included pelvic exenteration, en bloc soft tissue or partial organ resection with the rectum, and lateral pelvic node dissection. Propensity score matching in a 4:1 ratio of laparoscopic to robotic was performed with age, sex, comorbidities, body mass index, organs involved, clinical T stage and colonoscopic obstruction.ResultsA total of 425 beyond total mesorectal excisions were performed by minimally invasive approaches during the study period, and after propensity matching 228 laparoscopic operations were compared with 57 robotic resections. All baseline characteristics were balanced. No difference in blood loss, postoperative complications, length of hospital stay, positive resection margin or nodal yield was found, but there was a somewhat longer operating duration in robotics. The 2‐year disease‐free and overall survival were also similar.ConclusionsNo differences in postoperative or short‐term oncological outcomes were found between robotic and laparoscopic beyond total mesorectal excisions for advanced tumours when performed by teams experienced in both robotics and laparoscopy.