bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Effect of Topically Applied Resveratrol Gel as Adjunctive Treatment for Periodontitis
Authors: Hussein Mahmoud Hassan , Badr Bahaa Mohammed , Hassan Khalid Seddik , Ibrahim Ibrahim Hammad 
Published: November 2024

Abstract
Objective Our objective was to evaluate the impact of topically applied resveratrol (RES) gel as adjunctive to conventional periodontal therapy on both clinical periodontal parameters as well as to assess interleukin-1β (IL-1β) level in gingival crevicular fluid (GCF) in patients with stage I and II grade A periodontitis.
Materials and Method This study was performed on 40 cases aged from 26 to 47 years with means of (37.02 ± 6.88) of both sexes (16 females and 24 males) with stage І and П grade A periodontitis. They were divided into two groups: group Ι consisted of 20 cases with stage I and II grade A periodontitis who were treated only with conventional periodontal care (scaling and root planning [SRP]), and group Π consisted of 20 cases with stage I and II grade A periodontitis who were subjected to conventional periodontal therapy (SRP) in conjunction with intrapocket RES gel application. At baseline, 3 months, and 6 months following therapy, all patients had clinical evaluation using gingival index (GI), plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL). Also, an enzyme-linked immune-sorbent assay-based biochemical analysis of IL-1β was conducted at baseline, 3 months, and 6 months.
Results Clinical findings were different significantly as correlated within the same group; however, there was no significant difference between both groups. Biochemical evaluation of IL1β revealed no significant variation at baseline and 3 months between both groups, while there was a significant difference during treatment at 6 months.
Conclusion Our findings indicate that RES as supplementary in addition to conventional periodontal therapy may improve periodontitis through anti-inflammatory effects.
Modified Lateral Supraorbital Craniotomy with Posterior Orbitotomy and Anterior Clinoidectomy for Resection of a Midline Planum and Tuberculum Sellae Meningioma
Authors: Stevens Baylee H. , Prather Kiana Y. , Bialek Shannan , Graffeo Christopher S. 
Published: November 2024

AbstractThe patient is a 51-year-old woman who had been experiencing syncope and near-syncopal events for at least 10 years with an otherwise benign neurological exam. Magnetic resonance imaging revealed an extra-axial mass consistent with a midline planum and tuberculum sellae meningioma, for which the patient opted to have resected. We demonstrate how performing a posterior orbitotomy with anterior clinoidectomy can enhance a lateral supraorbital craniotomy. The patient did well following surgery, with marked improvement in syncopal symptoms. Pertinent surgical anatomy and techniques are highlighted in this video demonstration.
The Evolution of Hemophilia Pharmacological Treatments and Therapeutic Targets at the Turn of the Third Millennium
Authors: Coppola Antonio , Zani Matteo , Quintavalle Gabriele , Focosi Daniele , Franchini Massimo 
Published: November 2024

AbstractHistorically, the aim of treatment for hemophilia, the congenital X-linked hemorrhagic disorder due to deficiencies of coagulation Factor (F) VIII (hemophilia A) or FIX (hemophilia B), has been the replacement through factor concentrates, whose regular administration (i.e., prophylaxis) has been shown to be highly effective in preventing bleeding complications and it is currently considered the gold standard of hemophilia treatment. However, continuous technological progress (i.e., plasma-derived factor concentrates, recombinant standard and extended half-life [EHL] products) has allowed clinicians operating at hemophilia treatment centers to individualize the management of persons with hemophilia, improving outcomes, adherence to therapy, and their quality of life. The achievement of normal hemostasis, the final goal that now seems possible with new-generation EHL products, non-replacement and gene therapies, will translate into normalization of life for persons with hemophilia, also addressing health equity (i.e., rendering them indistinguishable from their healthy peers). The evolution of hemophilia treatment and, in parallel, of therapeutic targets in the management of hemophilia patients over the last decades will be critically discussed in this narrative review.
Abdominal Tuberculosis in Children
Authors: Emiroglu Melike , Alkan Gulsum , Kiymaz Meltem , Tuter Oz Sadiye Kubra , Turk Dagi Hatice , Öztürk Mehmet , Çelik Zeliha Esin 
Published: November 2024

Abstract
Objective To provide an insight into the presentation, diagnosis, and management of gastrointestinal tuberculosis in children.
Methods We reviewed the medical records of children who were diagnosed with gastrointestinal tuberculosis, between October 2013 and October 2023. The analysis was performed using descriptive statistics.
Results During the study period, 11 of 76 tuberculosis pediatric patients (14.5%) were diagnosed with gastrointestinal tuberculosis. Six of 11 patients (54.5%) were female. The median age of the patients was 60 months (51–205 months). Eight of 11 patients had intra-abdominal lymph node involvement, 3 of 11 patients had intestinal tuberculosis, and 2 of 11 patients had also active pulmonary tuberculosis. Multiple intra-abdominal areas were involved in six patients. Mean duration of symptoms before admission was 60 days (5–180 days). The most common symptoms were abdominal pain (63.7%), weight loss (63.7%), and weakness/fatigue (54.5%). Acid-fast bacilli and tuberculosis polymerase chain reaction were positive in only two patients. Tuberculosis culture positivity was detected in two patients, both of them showed Mycobacterium bovis growth. Necrotizing granulomatous inflammation was the most frequently observed histopathological finding. Anemia was detected in six patients. There was elevated erythrocyte sedimentation rate in eight patients and elevated C-reactive protein in six patients. In one patient, recurrent obstruction symptoms developed due to stenosis of terminal ileum. Clinical cure was achieved with supportive treatment.
Conclusion Diagnosis of gastrointestinal tuberculosis is very difficult due to nonspecific clinical and radiological features. Microbiological confirmation of the disease is often challenging. Making a definitive diagnosis requires reliance on strong clinical suspicion, imaging and histopathological findings, microbiological tests, and/or response to treatment.
Comparison of Delta Neutrophil Index and Inflammatory Markers in the Diagnosis of Late-Onset Neonatal Sepsis in Preterm Infants
Authors: Yazici Aybuke , Kanmaz Kutman Hayriye Gozde , Kadioglu Simsek Gulsum , Siyah Bilgin Betul , Canpolat Fuat Emre , Dinc Bedia , Oguz Serife Suna 
Published: November 2024

Abstract
Objective This study aimed to assess the performance of the relatively new hematological marker delta neutrophil index (DNI) and other inflammatory markers in proven sepsis of the very preterm infant.
Methods Infants with a gestational age of <32 weeks, who were examined retrospectively for suspected late-onset sepsis (LOS), were evaluated in the study.. Demographic characteristics, laboratory findings, and neonatal morbidity and mortality were compared between infants with blood culture-confirmed sepsis and clinical sepsis.
Results The study included 358 infants, 90 with proven sepsis and 268 with clinical sepsis. The mean gestational ages in these groups were 28.2 ± 2 and 28.2 ± 2.1 weeks, and the mean birth weights were 1139 ± 372 and 1148 ± 370 g, respectively (p > 0.05). The proven sepsis group had higher DNI (median 7.1% [range: 0.1–74] vs. 0.6% [range: 0.1–24.7%], p < 0.01], C-reactive protein (CRP; median 5 [range: 1–38] mg/L vs. 1 [range: 1–15] mg/L, p < 0.001), interleukin-6 (median 620 [range: 6.9–5,500] pg/mL vs. 42.2 [range: 2.2–5500] pg/mL, p < 0.01), and procalcitonin (median 6.2 [range: 0.26–86] µg/L vs. 0.6 [range: 0.06–25.7] µg/L, p = 0.002). According to receiver operating characteristic curve analysis, interleukin-6 had the highest area under the curve (AUC) at 0.74 (95% CI: 0.60–0.88, p < 0.01). The AUC values were 0.73 (95% CI: 0.59–0.88, p = 0.01) for procalcitonin, 0.62 (95% CI: 0.44–0.80, p = 0.18) for DNI, and 0.66 (95% CI: 0.50–0.82, p = 0.05) for CRP.
Conclusion The DNI showed a statistically significant elevation in infants with proven sepsis; however, its diagnostic performance was lower than that of interleukin-6, CRP, and procalcitonin. Although the results are encouraging in determining the utility of DNI in predicting LOS in preterm infants, further research is needed to validate its predictive value, specifically in this population.
A new approach to study stochastic epigenetic mutations in sperm methylome of Vietnam war veterans directly exposed to Agent Orange
Authors: Corsaro Luigi , Sacco Davide , Corbetta Carlo , Gentilini Davide , Faversani Alice , Ferrara Fulvio , Costantino Lucy 
Published: November 2024

Abstract
Among the various environmental pollutants, dioxin, a highly toxic and widely used compound, is associated with numerous adverse health effects, including a potentially toxic multigenerational effect. Understanding the mechanisms by which dioxin exposure can affect sperm epigenetics is critical to comprehending the potential consequences for offspring health and development. This study investigates the possible association between weighted epimutations, hypothesized as markers of epigenetic drift, and dioxin exposure in sperm tissues. We used a public online methylation dataset consisting of 37 participants: 26 Vietnam veterans exposed to Agent Orange, an herbicide contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 11 individuals not directly exposed to TCDD but whose serum dioxin levels are equivalent to the background. In our study, conducted at the gene level, 437 epimutated genes were identified as significantly associated with each single-digit increase in serum dioxin levels. We found no significant association between the rise in total epimutation load and serum dioxin levels. The pathway analysis performed on the genes reveals biological processes mainly related to changes in embryonic morphology, development, and reproduction. Results from our current study suggest the importance of further investigations on the consequences of dioxin exposure in humans with specific reference to germinal tissue and related heredity.
A review of antimicrobial stability testing guidance for outpatient parenteral antimicrobial therapy programmes: is it time for global harmonization of testing frameworks?
Authors: Naicker Saiyuri , Roberts Jason A , Cheng Vesa , Parker Suzanne L , Seaton R Andrew , Gilchrist Mark , Sime Fekade B 
Published: November 2024

Abstract
Antimicrobial stability is an important consideration for treatment planning and service delivery in outpatient parenteral antimicrobial therapy (OPAT) programmes. Regulation of stability assessment varies by region, and conflicting guidance and standards exist. This leads to disparity of equity in access and limits availability of certain antimicrobials for managing infections in the outpatient setting. This review discusses the degree to which the international regulatory bodies have reached consensus on the regulation of antimicrobial stability testing, specifically for OPAT, and describes the variation in antimicrobial recommendations across regulatory bodies. The three major findings in this review are (i) variation in antimicrobial stability testing guidance, particularly in relation to temperature; (ii) lack of regulatory guidance, specifically in that some regions did not have OPAT guidelines; and (iii) only the UK’s NHS has provided non-regulatory OPAT-specific advice on antimicrobial stability testing. In conclusion, harmonization of antimicrobial stability testing to form a global OPAT-specific regulatory framework, particularly considering ‘areas of variation’ amongst current guidance, is required. We call for the development of a global OPAT antimicrobial stability testing framework with consensus from accepted antimicrobial stability criteria, expert opinion and pharmacopoeial best practice.
Bone marrow mesenchymal stem cell‐derived exosomal miR‐181a‐5p promotes M2 macrophage polarization to alleviate acute pancreatitis through ZEB2‐mediated RACK1 ubiquitination
Authors: Li Hanyu , Du Ruifeng , Xiang Andong , Liu Yankui , Guan Ming , He Hongchun 
Published: November 2024

AbstractAs a common digestive disease, acute pancreatitis (AP) often threatens the life of patients. Bone marrow mesenchymal stem cells (BMSCs) derived exosomes have exhibited some benefits for AP. However, the mechanism remains unclear and deserves to be further investigated. The characteristics of BMSCs‐exosomes (BMSCs‐Exos) were identified. The abundance of genes and proteins was evaluated using quantitative real‐time PCR (RT‐qPCR), western blot, enzyme‐linked immunosorbent assay (ELISA) and IF assay. Cell apoptosis and CD206‐positive cells were measured by flow cytometry. The interactions among miR‐181a‐5p, Zinc finger E‐box binding homeobox 2 (ZEB2) and Receptor for Activated C Kinase 1 (RACK1) were verified using dual luciferase reporter assay, RNA immunoprecipitation (RIP), coimmunoprecipitation (Co‐IP). BMSCs‐Exos effectively improved AP injury through restraining AR42J cell apoptosis and promoting M2 macrophage polarization, which was realized due to BMSCs‐Exos harboring an abundance of miR‐181a‐5p. Further experiments validated miR‐181a‐5p silenced ZEB2 and ZEB2 reduced RACK1 expression through mediating RACK1 ubiquitination. ZEB2 knockdown decreased AR42J cell apoptosis and induced M2 macrophage polarization to alleviate AP injury, whereas RACK1 downregulation abolished these phenomena. BMSCs‐Exos harboring miR‐181a‐5p suppressed AR42J cell apoptosis and promoted M2 macrophage polarization to delay AP progression through ZEB2‐mediated RACK1 ubiquitination.
The central role of creatine and polyamines in fetal growth restriction
Authors: Di Giorgio Eros , Xodo Serena , Orsaria Maria , Mariuzzi Laura , Picco Raffaella , Tolotto Vanessa , Cortolezzis Ylenia , D'Este Francesca , Grandi Nicole , Driul Lorenza , Londero Ambrogio , Xodo Luigi E. 
Published: November 2024

AbstractPlacental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short‐ and long‐term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR. These changes include adaptations to reduced oxygen levels and modifications in arginine metabolism, particularly within the polyamine and creatine phosphate synthesis pathways. Specifically, we found that placentas with FGR utilize arginine to produce phosphocreatine, a crucial energy reservoir for ATP production that is essential for maintaining trophoblast function. In addition, we found polyamine insufficiency in FGR placentas due to increased SAT1 expression. SAT1 facilitates the acetylation and subsequent elimination of spermine and spermidine from trophoblasts, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation alone, unless SAT1 expression is suppressed. Our study contributes significantly to the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights into potential therapeutic opportunities for the future.
Cutting a nerve of the hand alters the organisation of digit maps in primary somatosensory cortex
Authors: Weber Martin , Marshall Andrew , Timircan Ronan , McGlone Francis , Tucciarelli Raffaele , Onyekwelu Obi , Booth Louise , Jesudason Edwin , Lees Vivien , Valyear Kenneth F. 
Published: November 2024

AbstractHand nerve transection injuries precipitate a variety of reorganisational changes in both the peripheral and central nervous systems. Surgical repair restores the continuity of severed nerves, yet regenerating fibres establish new connections without topographical guidance, rearranging the branching architecture of peripheral nerves in the hand.In non-human primates, forelimb nerve transection and repair dramatically alters the otherwise orderly and highly conserved organisation of the digit maps in primary somatosensory areas 3b and 1. Digit-map organisation becomes patchwork and highly variable. Although without compelling evidence, these same reorganisational changes are presumed to occur in humans and to have significant functional implications for patient recovery. In the current study, we evaluate these assumptions.Functional MRI is used to characterise the fine-grained organisation of digit responses in the primary somatosensory cortex in twenty-one patients with nerve transection injuries and thirty healthy controls. Both univariate dice ‘overlap’ coefficients and state-of-the-art multivariate representational distances are used to quantify the extent and pattern of interdigit response separability in primary somatosensory cortex. Our results reveal significant differences between patients and controls. The fine-grained organisation of the primary somatosensory cortex is altered in nerve repair. Average dice coefficients reveal significantly increased interdigit response overlap. These effects are specific to the hemisphere contralateral to the nerve-repaired hand, reflecting inputs from reinnervated digits, and are more robust within the cortical zones of the repaired nerves. Nerve repair also alters the relative functional structure of the primary somatosensory cortex, changing the otherwise stereotypical pattern of interdigit response separability seen in healthy controls. Unexpectedly, these later alterations manifest bilaterally, as maps for the healthy hand of patients also show an atypical pattern of interdigit response separability.Our findings provide the first compelling evidence for altered digit maps following nerve repair in humans, bridging results from animal models. Nonetheless, the clinical significance of the changes we observe remains unclear. No reliable relationships between fMRI measures of cortical reorganisation and behavioural measures of functional impairments are observed. Altered digit maps are not found to correlate with impairments in touch localisation or with broader measures of functional impairment as captured by sensory Rosen scores.
Increased Prevalence of Oxytocin Receptor Gene Variant in Functional Neurological Disorder: A Preliminary Case-Control Study
Authors: Weber Samantha , Stoffel Natascha , Rey Álvarez Lucía Trinidad , Ansede-Bermejo Juan , Cruz Raquel , Del Real Bolt Álvaro , Bühler Janine , Carracedo Ángel , Aybek Selma 
Published: November 2024

AbstractBackgroundCurrent models on functional neurological disorders (FND) propose a multifactorial origin. Recent studies identified potential biological vulnerability factors – such as a reduced limbic volume or an altered stress response. These findings highlight the need to investigate a potential genetic contribution to the biological vulnerability to FND.MethodEighty-five mixed FND patients and seventy-six healthy controls (HC) were genotyped for ten single nucleotide polymorphisms within seven genes associated with the stress system. For the genetic variant that was found to be associated with FND, further associations to structural brain alterations were investigated using a region-of-interest approach. Regions were previously selected based on their biological involvement and as a vulnerability for FND.ResultsA significant association between the diagnosis of FND and the rs53576 of the oxytocin receptor (OXTR) gene was found. A significant association between decreased right insular volumes and rs53576 (OXTR) was identified in FND patients. In female patients, the rs53576 (OXTR) was associated with a reduced bilateral amygdalar volume.ConclusionThese preliminary results suggest a genetic contribution to the biological vulnerability for FND involving the oxytocinergic system, and (sex-specific) structural changes in insula and amygdala.
Trends and patterns of sedative prescribing in primary care in Ireland between 2014 and 2022 - a repeated cross-sectional study
Authors: Mattsson Molly , Ali Ahmed Hassan , Boland Fiona , Flood Michelle , Kirke Ciara , Wallace Emma , Corrigan Derek , Walsh Mary E , Fahey Tom , Moriarty Frank 
Published: November 2024

AbstractBackgroundThe trends in sedative use have varied in recent years. Benzodiazepines and z-drugs are indicated for anxiety and sleep disorders, but should be limited to short term use. The aim of this study is to examine trends and patterns in sedative prescribing in Ireland between 2014 and 2022, as well as comparing trends between Ireland and England within the same period.MethodsMonthly data on medicines prescribed and dispensed in primary care on the means-tested General Medical Services (GMS) scheme in Ireland was used. Volumes of prescribed benzodiazepine and z-drug use and patterns of prescribing, including initiations, discontinuations, chronic use, and high-risk prescribing were summarised per year. Other sedating agents (sedating antihistamines, antidepressants, and antipsychotics) were also analysed. Volume of use outcomes were compared with NHS data from England for the same period.ResultsThe rate of benzodiazepine and z-drug dispensings per 1,000 GMS population decreased by 4%, from 1,531 in 2014 to 1,474 in 2022. T By comparison in England, there was a steeper decrease of 27% in the dispensing rate and the level of use was substantially lower, falling from 288 dispensings per 1,000 population in 2014 to 210 in 2022. In Ireland, dispensing rates were highest amongst women and older age groups. High-risk dispensings of benzodiazepines and z-drugs decreased over the study periodDiscussionDespite decreases in benzodiazepine and z-drug dispensings, rates remain high in Ireland and may suggest a need for enhanced availability of non-pharmacological interventions, and improved education and deprescribing support for healthcare professionals.Statement of SignificanceThe use of benzodiazepines and z-drugs has decreased in many populations in recent years, while prescribing of other sedatives has increased. In Ireland, comparatively higher levels of prescribing have been previously identified. Describing and quantifying medication use is important to monitor medication safety at the population level, however this can be complex and therefore a range of indicators are needed to capture differences.The findings of this study suggest that benzodiazepine and z-drug dispensing is decreasing in Ireland, including high-risk dispensings and dispensings to older age groups. However, in comparison to England, dispensing rates remain high and suggest a need for enhanced availability of non-pharmacological services and interventions, as well as improved education and deprescribing support for healthcare professionals.