bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory Strategies for Disease Modification
Authors: Vezzani Annamaria , Balosso Silvia , Varvel Nicholas H. , Dingledine Ray 
Published: July 2024

Abstract
Clinical and preclinical studies have confirmed that neuroinflammation is a salient feature of the epileptic brain. The engagement of several neuroinflammatory pathways has been documented after epileptogenic injuries and in the aftermath of ongoing seizure activity. Preclinical research over the past decade has demonstrated that the ensuing neuroinflammation after epileptogenic triggers promotes seizures, neuronal injury, blood–brain barrier dysfunction, and behavioral comorbidities. Thus, successful modulation of the neuroinflammatory cascade is a potential therapeutic strategy. An overarching goal of anti-inflammatory approaches is to quench pathogenic neuroinflammation while maintaining, or promoting, the homeostatic effects. In this chapter we focus on treatments that are close to clinical translation, outlining the experimental evidence supporting the use of the anti-inflammatory therapy for both reducing drug-resistant seizures and for providing disease-modification effects. Approaches targeting IL-1β-IL-1R1 signaling, COX-2 pathways, immune-endothelial cell interations, statins, and dexamethasone are discussed. Recent combinatorial approaches with disease-modifying effects are highlighted. Successful development of anti-inflammatory therapies for epilepsy faces hurdles. The timing of therapeutic administration after epileptogenic triggers should, ideally, preserve the physiological roles of inflammation while opposing pathological ones. Biomarkers and consideration of epilepsy etiology can help identify patients who will best benefit from anti-inflammatory drugs. Clinical studies of anti-inflammatory treatments are underway in patients with drug-resistant seizures, and the results are described here. New clinical trial designs are likely needed to take into account the differences in mechanism of action between anti-inflammatory and conventional antiseizure medications.
Cell Therapy for Treatment of Epilepsy
Authors: Bröer Sonja , Vogt Daniel 
Published: July 2024

Abstract
Cell transplantation could offer a strategy to overcome pharmacoresistance in epilepsy if transplanted cells can survive long term within the host brain, migrate into appropriate brain regions, differentiate into interneurons (INs) that increase inhibitory tone within the epileptic network, and integrate into the circuitry by forming synapses with host neurons. Several studies have demonstrated all of the above-mentioned prerequisites of a successful IN transplantation using rodent INs derived from the medial ganglionic eminence (MGE). They showed that INs are effective in decreasing seizure frequency consistently and in the long term across a variety of animal models. Behavioral comorbidities of epilepsy could be alleviated, and even hippocampal neuropathology of the disease was reduced. While use of rodent INs is feasible for preclinical research, a human cell product is needed for clinical translation. Protocols for IN in vitro differentiation from human pluripotent stem cells (PSCs) have been developed. First, data from transplantation studies in models of epilepsy confirm the promising disease-modifying activity that was observed with rodent MGE-derived INs: human IN transplantation was effective in reducing seizure burden, while no obvious adverse effects were associated with it. Further research on characterization of cells prior to transplant, process improvements, and good manufacturing practice production will be needed to ensure safety of an IN cell product; however, the recent advances in our ability to generate MGE-like cells from PSCs, in-depth characterization of cells with modern techniques and the combinatorial use of electrophysiology, optogenetics, and translational immunodeficient animal models to evaluate disease-modifying activity have brought human IN transplantation significantly closer to clinical application.
Mechanisms of Ketogenic Diet Action
Authors: Williams Robin S. B. , Boison Detlev , Masino Susan A. , Rho Jong M. 
Published: July 2024

Abstract
At the turn of the first century of ketogenic diet (KD) use for medically intractable epilepsy, investigators have uncovered a multiplicity of potential mechanisms that may underlie the clinical effects of this metabolism-based treatment. In the process, there have emerged important insights into the biochemical and metabolic bases of epilepsy, and novel approaches and targets that can be exploited for experimental and clinical therapeutics. Historically, metabolic changes thought to mediate the KD’s antiseizure effects have included—but are not limited to—ketosis, glycolytic restriction, increased purinergic and GABAergic neurotransmission, fatty acid modulation of ion channels, improved cellular and mitochondrial bioenergetics, and a reduction in oxidative stress. More recently, it has been shown that the KD and its variants, such as the medium-chain triglyceride diet, may induce anti-inflammatory, neuroprotective, epigenetic, and even antiepileptogenic effects. Finally, the gut microbiome has been linked to enhanced central inhibitory-excitatory balance through changes in the blood metabolome. As dietary treatments have been increasingly shown to evoke a wide array of metabolic, physiologic, and hormonal effects, future research will undoubtedly reveal an even more complex mechanistic framework for KD action, but one which should enable the development of improved dietary formulations, or simplified treatments based on the biology of specific biochemical substrates and enzymes, not only for epilepsy but also potentially for a broader range of neurological disorders.
The hydrodynamic response of small-scale structure to reionization drives large IGM temperature fluctuations that persist to z = 4
Authors: Cain Christopher , Scannapieco Evan , McQuinn Matthew , D’Aloisio Anson , Trac Hy 
Published: July 2024

ABSTRACT
The thermal history and structure of the intergalactic medium (IGM) at $z \ge 4$ is an important boundary condition for reionization, and a key input for studies using the Ly $\alpha$ forest to constrain the masses of alternative dark matter candidates. Most such inferences rely on simulations that lack the spatial resolution to fully resolve the hydrodynamic response of IGM filaments and minihaloes to H i reionization heating. In this letter, we use high-resolution hydrodynamic + radiative transfer simulations to study how these affect the IGM thermal structure. We find that the adiabatic heating and cooling driven by the expansion of initially cold gas filaments and minihaloes sources significant small-scale temperature fluctuations. These likely persist in much of the IGM until $z \le 4$. Capturing this effect requires resolving the clumping scale of cold, pre-ionized gas, demanding spatial resolutions of ${\le} 2$ $h^{-1}$kpc. Pre-heating of the IGM by X-rays can slightly reduce the effect. Our preliminary estimate of the effect on the Ly $\alpha$ forest finds that, at $\log (k /[{\rm km^{-1} s}]) = -1.0$, the Ly $\alpha$ forest flux power (at fixed mean flux) can increase ${\approx} 10~{{\ \rm per\ cent}}$ going from 8 and 2 $h^{-1}$kpc resolution at $z = 4{\!-\!}5$ for gas ionized at $z \ \lt\ 7$. These findings motivate more careful analyses of how the effects studied here affect the Ly $\alpha$ forest.
Upper limit on the coronal cosmic ray energy budget in Seyfert galaxies
Authors: Inoue Yoshiyuki , Takasao Shinsuke , Khangulyan Dmitry 
Published: July 2024

Abstract
The IceCube Collaboration has reported possible detections of high-energy neutrinos from nearby Seyfert galaxies. While central hot coronae are proposed as the primary neutrino production site, the exact coronal cosmic ray energy budget has been loosely constrained. In this study, we propose a new stringent upper bound on the coronal cosmic ray energy budget of Seyfert galaxies, considering both accretion dynamics and observed properties of radio-quiet Seyfert galaxies. Notably, even under the calorimetric condition where cosmic rays lose all their energy, our limit indicates that the coronal neutrino flux of NGC 1068 is about an order of magnitude fainter than the observed levels. This discrepancy suggests the need for further theoretical and observational investigations on the IceCube signals from Seyfert galaxies.
The intron binding protein EMB-4 is an opposite regulator of cold and high temperature tolerance in Caenorhabditis elegans
Authors: Ohta Akane , Sato Yuki , Isono Kazuho , Kajino Takuma , Tanaka Keisuke , Taji Teruaki , Kuhara Atsushi 
Published: July 2024

Abstract
Adaptation and tolerance to changes in heat and cold temperature are essential for survival and proliferation in plants and animals. However, there is no clear information regarding the common molecules between animals and plants. In this study, we found that heat, and cold tolerance of the nematode Caenorhabditis elegans is oppositely regulated by the RNA-binding protein EMB-4, whose plant homolog contains polymorphism causing heat tolerance diversity. Caenorhabditis elegans alters its cold and heat tolerance depending on the previous cultivation temperature, wherein EMB-4 respectively acts as a positive and negative controller of heat and cold tolerance by altering gene expression. Among the genes whose expression is regulated by EMB-4, a phospholipid scramblase, and an acid sphingomyelinase, which are involved in membrane lipid metabolism, were found to play essential roles in the negative regulation of heat tolerance.
Deformity Considerations in Cervical Laminoplasty
Authors: Drain Joseph P. , Alvarez Paul , Spiker William Ryan , Yu Elizabeth 
Published: July 2024

Objectives:
We discuss the incidence of postoperative kyphosis following laminoplasty and its impact on outcomes, as well as critical radiographic parameters, intraoperative technical factors, and postoperative protocols that can be used to improve results.

Summary of Background Data:
When appropriately selected, cervical laminoplasty is a motion-sparing treatment option for cervical myelopathy and is a valid alternative to laminectomy and fusion procedures. However, like other posterior-based cervical decompression techniques, laminoplasty can cause postoperative kyphosis.

Methods:
A PubMed search was performed to gather articles that focus on cervical deformity in the context of cervical laminoplasty.

Results:
The reported conversion rates of lordotic to kyphotic cervical alignment after laminoplasty range from 5.2% to 11.3%. Kyphosis likely reduces the benefit from the operation as measured by postoperative mJOA scores. A surgeon can minimize the risk of causing a clinically significant reduction in lordosis by screening out patients with certain radiographic characteristics. Intraoperative decisions such as dissection techniques, levels chosen, and hybrid constructs can preserve the cervical tension band. Certain postoperative protocols can improve cervical posture.

Conclusions:
Cervical laminoplasty is an effective tool for treating degenerative cervical myelopathy. Careful radiographic screening, intraoperative decision-making, and postoperative protocols can minimize the development of postoperative cervical deformity and improve outcomes.

Level of Evidence:
Level V.
The Role of Negative Pressure Wound Therapy in Temporizing Traumatic Wounds before Lower Limb Soft Tissue Reconstruction: A Systematic Review
Authors: Barone Natasha , Ziolkowski Natalia , Haykal Siba 
Published: July 2024

Background:In practice, there is often a delay from initial debridement and temporary fixation to definitive soft tissue coverage of traumatic leg wounds. Without clear evidence, conservative negative pressure wound therapy (NPWT) is increasingly used to temporize these wounds. This systematic review summarizes and synthesizes the literature on using NPWT to temporize traumatic leg wounds before surgery in adult surgical patients.Methods:A comprehensive search of Medline, Embase, and Cochrane Library was performed from inception until July 2022, inclusively. Two independent reviewers performed screening, data extraction, and risk of bias assessment. Primary English studies, including adult patients (≥16 years old) with a fracture below the knee up to and including the ankle that received NPWT to temporize wounds before definitive soft tissue reconstruction with a flap and/or graft, were included.Results:Thirty-four studies, including 804 patients who received NPWT, were included. The partial/total flap loss rate was 6.95% (n = 9 studies), the infection rate was 19.5% (n = 25 studies), the nonunion rate was 18% (n = 15 studies), the delayed union rate was 9.31% (n = 3 studies), and the amputation rate was 15.4% (n = 6 studies). The mean late stay was 43.1 days (n = 9 studies), and the follow-up length was 23.7 months (n = 9 studies). The mean time to wound healing was 5.63 months (n = 2 studies), and the time to soft tissue coverage was 40.8 days (n = 12 studies). The mean time to achieve bone union was 7.26 months (n = 6 studies).Conclusion:NPWT can be used to temporize traumatic wounds while awaiting soft tissue reconstruction.
Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitis
Authors: Yuan Qiaoping , Hodgkinson Colin , Liu Xiaochen , Barton Bruce , Diazgranados Nancy , Schwandt Melanie ,   with DASH, InTEAM, SCAHC, TREAT and Alcohol Hepatitis Genomics consortia, Morgan Timothy , Bataller Ramon , Liangpunsakul Suthat , Nagy Laura E. , Goldman David 
Published: July 2024

Background and Aims:
Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder. Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study aims to identify genes and genetic variations that contribute to the development of AH.

Approach and Results:
Exome-sequencing of patients with AH (N=784) and heavy drinking controls (N=951) identified an exome-wide significant association for AH at patalin-like phospholipase domain containing 3, as previously observed for AC in genome-wide association study, although with a much lower effect size. Single nucleotide polymorphisms (SNPs) of large effect size at inducible T cell costimulatory ligand (ICOSLG) (Chr 21) and TOX4/RAB2B (Chr 14) were also exome-wide significant. ICOSLG encodes a co-stimulatory signal for T-cell proliferation and cytokine secretion and induces B-cell proliferation and differentiation. TOX high mobility group box family member 4 (TOX4) was previously implicated in diabetes and immune system function. Other genes previously implicated in AC did not strongly contribute to AH, and the only prominently implicated (but not exome-wide significant) gene overlapping with alcohol use disorder was alcohol dehydrogenase 1B (ADH1B). Polygenic signals for AH were observed in both common and rare variant analysis and identified genes with roles associated with inflammation.

Conclusions:
This study has identified 2 new genes of high effect size with a previously unknown contribution to alcohol-associated liver disease and highlights both the overlap in etiology between liver diseases and the unique origins of AH.
NATURAL COURSE OF AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT
Authors: Su Yongyue , Wen Feng , Gan Yuhong , Zeng Yunkao , Zhuang Xuenan , He Guiqin , Zhang Yining , Yang Ruijun , Zhang Xiongze 
Published: July 2024

Purpose:
Retentional pigment epithelial detachment (PED) associated with age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) is hypothesized to be caused by Bruch membrane's lipid barrier. This study aimed to report the natural course of retentional PED and evaluate the relationship between retentional PED evolution and ASHS-LIA.

Methods:
Patients with treatment-naïve retentional PED were enrolled and observed every 3 months for at least 12 months. Treatment was not performed except for secondary macular neovascularization.

Results:
In 55 studied eyes with a median follow-up of 18.0 (range: 12–36) months, 87.3% (48/55) of the retentional PEDs persisted, 7.3% (4/55) resolved, and 5.5% (3/55) progressed to polypoidal choroidal vasculopathy. The mean PED area significantly increased during the follow-up (P < 0.001) and with the ASHS-LIA grade at each follow-up point (all P <0.05), especially during the first 6 months before approaching the edge of confluent ASHS-LIA. Persistent PEDs were mostly stable (52.1%) or enlarged (45.8%) but reduced in only 1 case (2.1%) because of retinal pigment epithelium microrip at the edge of PED. The persistent PEDs were all within the ASHS-LIA region, especially the macular confluence region. The resolved PEDs all had grade 1 ASHS-LIA and resolved after gradual expansion of PED beyond the confluent ASHS-LIA region. Pigment epithelial detachments that progressed to macular neovascularization all had confluent grade 2 or 3 ASHS-LIA. Retinal pigment epithelium microrips or apertures within PED did not affect the progression of the PED.

Conclusion:
The natural course of retentional PED is closely related to the features of ASHS-LIA and supports its lipid-barrier hypothesis.
Severe Circulatory Disturbance in Optic Disc, Retina, and Choroid Following Sub-Tenon Triamcinolone Acetonide Injection for Posterior Scleritis
Authors: Akada Masahiro , Muraoka Yuki , Morooka Satoshi , Ishihara Kenji , Hata Masayuki , Tsujikawa Akitaka 
Published: July 2024

Purpose:
To report a rare case of optic disc and chorioretinal vascular occlusions in the right eye following sub-Tenon injection of triamcinolone acetonide (STTA) in an older male patient with scleritis and to discuss the associated risk factors and potential alternative therapies.

Methods:
The medical history and clinical examination, including fundoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), were conducted to diagnose and evaluate the extent of vascular occlusion after STTA. An extensive literature review was undertaken to ascertain the associated risks and consider other treatment options for scleritis.

Results:
Severe circulatory disturbances in the optic disc and chorioretinal regions of the right eye developed after STTA for exacerbated scleritis, as confirmed by FA and ICGA, resulting in a significant decrease in visual acuity. A complex medical history encompassing ophthalmic and systemic health issues may have contributed to this negative outcome. A literature review pointed out the potential complications of STTA and highlighted alternative approaches to scleritis management.

Conclusions:
Cautious application of STTA in treating scleritis is crucial, especially in patients with pre-existing vascular or ocular conditions. Thus, a multidisciplinary approach and a careful assessment of various treatment options are vital to minimize the risk of severe complications and improve patient outcomes.
Evaluation of Host Gene Methylation as a Triage Test for HPV–Positive Women—A Cohort Study
Authors: Vieira-Baptista Pedro , Costa Mariana , Hippe Juliane , Sousa Carlos , Schmitz Martina , Silva Ana-Rita , Hansel Alfred , Preti Mario 
Published: July 2024

Abstract

Objectives
This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance.

Materials and Methods
Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice.

Results
The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1–71.6%) and 88.4% (83.2–92.5%), respectively. For CIN3+, it was of 78.0% (64.0–88.5%) and 86.0% (80.8–90.2%), respectively.
The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%.
The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel.

Conclusions
The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.
Development of Fournier’s gangrene after chemotherapy for the recurrence of testicular cancer despite the absence of anorectal lesions: A case report
Authors: Nonaka Kenichi , Kawase Kota , Takagi Kimiaki , Takatsu Yuta , Maniwa Koji , Takao Chika , Komura Minoru , Mushika Yoshinori , Takeuchi Noriyuki , Kato Toshio , Kusakabe Mitsuhiko , Kondo Mitsutaka 
Published: July 2024

Background:Fournier’s gangrene usually occurs when a specific bacterium intrudes into soft tissue, causing a wound or tumor. We encountered a patient with Fournier’s gangrene due to severe myelosuppression after chemotherapy, despite the absence of an initial lesion on the anus and rectum.Case presentation:A 54-year-old man with a left testicular cancer recurrence had undergone chemotherapy. He had asymptomatic hepatitis and high hepatitis B virus DNA levels, which were normalized by administering tenofovir alafenamide fumarate. Twelve days after the start of chemotherapy, he complained of severe pain around the anus. The following day, he went into septic shock. Visual inspection showed dark purple skin discoloration on the left side of the anus. Laboratory data revealed severe neutropenia. Computed tomography showed a high density of soft tissue on the left side of the anus and gas bubbles in the left femoral ring. We diagnosed the patient with Fournier’s gangrene due to a severe immunosuppressive state resulting from chemotherapy. We emergently removed necrotic tissue to the fullest extent possible. However, because the patient was in severe sepsis status, careful management in the intensive care unit was required for 32 days. After the first emergency operation, we performed several additional excisions. Finally, 391 days after the initial surgery, the patient was discharged from our hospital. The tumor has not recurred, and he is under outpatient observation in the urology department.Conclusion:Fournier’s gangrene should be considered in patients who are in a severe myelosuppressive state due to chemotherapy, have normal hepatitis B virus DNA levels but high hepatitis B surface antigen after tenofovir administration, complain of severe pain in the perianal area, and have a dark purple skin discoloration around the anus, despite having no initial anorectal lesions.