bluuebunny/crossref_metadata_2025 huggingface dataset:
A Crucial Role for Astrocytes in Epileptogenesis
Authors: Bedner Peter , Peterson Allison R. , Binder Devin K. , Steinhäuser Christian
Published: July 2024

A growing body of evidence suggests that astrocytes are crucial actors in the initiation and progression of epilepsy. Reactive astrocytes in human and experimental epilepsy display marked morphological, transcriptional, and functional changes, but it is still often unclear whether this represents a causative factor, a consequence, or an adaptive response in epileptogenesis. A distinctive feature of astrocytes is their extensive intercellular coupling via gap junction channels. This allows them to form large syncytium-like functional networks that play essential roles in ion and neurotransmitter homeostasis, gliotransmission, nutrient supply to neurons, and regulation of the extracellular space volume. The first part of this chapter summarizes current knowledge on the role of gap junction channels in epilepsy, their expression and activity in human and experimental epilepsy, and the consequences of their genetic and pharmacological modulation on neuronal excitability and epileptogenesis. Astrocytes also regulate and respond to extracellular glutamate levels in the central nervous system via the Na+-dependent glutamate transporters glutamate transporter-1 (GLT-1) and glutamate aspartate transporter (GLAST) and the metabotropic glutamate receptors (mGluR) 3 and mGluR5. Both impaired astrocytic glutamate clearance and changes in mGluR signaling could contribute to the development of epilepsy. The second part of this chapter summarizes the changes in astrocyte glutamate receptors and transporters in epilepsy. Overall, both astrocytic gap junction channels and glutamate transporters and receptors could serve as novel therapeutic targets for epilepsy.
Brain Mosaicism in Epileptogenic Cortical Malformations
Authors: Ribierre Théo , Baulac Stéphanie
Published: July 2024

This chapter focuses on focal cortical dysplasia type II (FCDII) and mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), a mild malformation of cortical development, for which genetic advances have been remarkable in recent years. There is now clear evidence that FCDII is caused by brain somatic mutations in genes belonging to the mTOR pathway, and that MOGHE, a mild malformation of cortical development, is due to somatic mutations in the SLC35A2 gene, encoding the major Golgi-localized UDP-galactose transporter. Numerous rodent models using the in utero electroporation procedure have been used to model FCDII and recapitulate most neuropathological and clinical features. This chapter discusses the recent advances in using cerebral organoids to model neurodevelopmental disorders.
GABAA Receptors, Seizures, and Epilepsy
Authors: Olsen Richard W. , Wallner Martin , Rogawski Michael A.
Published: July 2024

GABAA receptors (GABARs), the main inhibitory neurotransmitter receptors in the mammalian brain, exist in a multitude of subtypes, including forms that predominantly mediate fast inhibitory synaptic transmission and other highly GABA-sensitive extrasynaptic forms that mediate tonic inhibition. GABARs are heteropentameric proteins formed by three different, yet homologous, subunits. Synaptic and extrasynaptic GABARs are targets of some medications used clinically in the treatment of seizures and epilepsy, including the barbiturates phenobarbital, primidone, and pentobarbital; propofol, and the neuroactive steroid ganaxolone. Synaptic GABARs are the targets of benzodiazepines, including diazepam, lorazepam, midazolam, and clobazam. Other epilepsy medications may also interact with GABARs in addition to affecting other antiseizure targets. This chapter gives a brief history of the GABAR involvement in the epilepsies and then describes developments since the publication of the last volume in this series in 2012. Greater understanding of the roles of GABAR isoforms has suggested strategies to target subpopulations of GABAR to more effectively treat various types of epilepsy and its comorbidities. Subtype specific GABAR positive modulators that selectively act on α2, α3, and α5 GABAR isoforms, and may have enhanced efficacy and reduced tolerance liability, are under investigation.
Strategies on Gene Therapy in Progressive Myoclonus Epilepsies
Authors: Kayani Saima , Gumusgoz Emrah , Minassian Berge A. , Dolce Alison
Published: July 2024

Progressive myoclonus epilepsies (PMEs) are a group of genetically and clinically heterogeneous diseases characterized by an invariable neurodegenerative decline leading to devastating disabilities and often fatal outcomes. Although there is a broad range of clinical manifestations, the shared features are encompassed within the name. Typically beginning in childhood and adolescence, patients present with very frequent myoclonus in addition to other types of epileptic seizures that very soon become refractory to medication. This is accompanied by a progressive neurocognitive decline along with other devastating changes including, but not limited to, vision loss, neuropathy, myopathy, and ataxia in a child that was otherwise previously normal. This chapter will review the potential therapeutic strategies for various PMEs.
Attention-Deficit Disorders and Epilepsy
Authors: Maheshwari Atul
Published: July 2024

Attention-deficit/hyperactivity disorder (ADHD) is a common comorbidity in patients with epilepsy. A polygenic predisposition likely interacts with environmental factors to determine the ultimate likelihood and severity of comorbid attention deficits. Epilepsy syndromes such as Dravet syndrome, juvenile myoclonic epilepsy, childhood absence epilepsy, and fragile X syndrome all have a high prevalence of ADHD. Many of these epilepsy syndromes are associated with monogenic mutations that have been implicated in inhibitory neurotransmission (Scn1a, GABRA1, Cacna1a, SNAP25, and FMR1, respectively). Monogenic rodent models carrying these genetic mutations have recapitulated varying degrees of epilepsy, hyperactivity, and attention deficits. Specifically testing various aspects of attention in rodents has been performed with validated procedures such as the Attention Set-Shifting task (ASST) or the 5-Choice Serial Reaction Time task (5-CSRTT). Recent studies have found cell-type-specific dysfunction in subsets of inhibitory neurons, most prominently in parvalbumin-expressing neurons. This underlying dysfunction likely leads to the symptomatic expression of both seizures and attention deficits. Both can be treated independently with antiseizure drugs and stimulant therapy, respectively. However, there remain no specific therapies for the underlying epileptogenic insult. Further studies should aim to combine the pathophysiological insight gained from monogenic models with targeted therapies on the genetic, molecular, cellular, and/or network levels. These therapies can then be screened on mutant rodent models using the ASST or 5-CSRTT to identify therapies with the greatest chance of improving quality of life in patients with comorbid epilepsy and ADHD.
Gene Therapy for Epilepsy
Authors: Goodspeed Kimberly , Armstrong Dallas , Boitnott Andrea , Dolce Alison , Ling Qinglan , Gray Steven J.
Published: July 2024

Epilepsy is a disease with diverse etiology; however, greater than 70%–80% of epileptic syndromes are thought to be associated with some genetic abnormality. Because of our fast-expanding genetic knowledge in epilepsy, we are approaching a new era of clinical management. We have an increased understanding of the underlying pathogenesis of genetic epilepsy as well as novel targets for precision therapies. Gene therapy, including gene transfer therapy, gene silencing, and gene editing, are promising new approaches to genetic epilepsy which have the potential to treat more than just the seizure manifestation of these devastating disorders. This chapter briefly reviews the role of genetic testing in epilepsy and introduces the application of gene therapy to genetic epilepsy syndromes as well as epileptogenesis more broadly.
Gene Therapy for Refractory Epilepsy
Authors: Kullmann Dimitri M.
Published: July 2024

Pharmacoresistance in epilepsy is common and represents a substantial unmet need. Of the advanced therapies for focal epilepsy in preclinical development, gene delivery using viral vectors to alter neuronal or circuit excitability in epileptogenic zones is arguably the closest to clinical translation. Monogenic disorders underlying severe childhood-onset epilepsies are also candidates for such treatments, because the genetic defect may be amenable to correction, although the brain areas that need to be targeted are less clearly defined. Several gene therapies have been validated in experimental rodent models, mainly based on the delivery of DNA or RNA encoding ion channels, neurotransmitters, or receptors. Some ion channel genes, however, are too big to package into adeno-associated or lentiviral vectors, and alternative approaches to manipulate gene expression have been proposed. Current obstacles to clinical translation center on optimizing delivery to defined brain areas, determining the correct dosage, and evaluating the long-term safety and efficacy of irreversible modification of the genetic makeup of neurons.
Environmental effects on low surface brightness galaxies in the IllustrisTNG simulation
Authors: Pérez-Montaño Luis Enrique , Cervantes Sodi Bernardo , Rodriguez-Gomez Vicente , Zhu Qirong , Ogiya Go
Published: July 2024

Employing the TNG100 run of the IllustrisTNG project, we characterize the environment of low surface brightness galaxies (LSBGs) across varying scales, from their associated dark matter haloes to their distribution within the broader cosmic structure. We find no significant differences in the halo concentration index $c_{200}$ between LSBGs and their high surface brightness galaxy (HSBG) counterparts, with LSBGs residing in haloes with higher spin parameter $\lambda$ and slightly more spherical shapes than HSBGs. LSBGs show a stronger alignment between the dark and stellar angular momentum vectors than their high surface brightness counterparts. The relative abundance of LSBGs within groups and clusters displays a central deficit, hinting at potential destruction upon reaching these core regions. Studying the density field, we find a preference for rotation-dominated LSBGs to reside in low-density environments, while dispersion-dominated LSBGs thrive in high-density regions where galaxy interactions govern their evolution, an observation corroborated by our analysis of the two-point correlation function $\xi (r)$. Our examination of the cosmic web reveals no significant differences in the distance to the closest large-scale structure, barring a few exceptions. This suggests a limited impact of large-scale spatial distribution on mechanisms driving LSBG evolution. All together, we conclude that the halo vicinity and local environment at the scale of galaxy clusters, where mechanisms such as galaxy mergers and tidal stripping, as well as stellar and gas accretion take place, is the most likely environment that favour the emergence of LSBGs with different morphologies, mostly driven by the presence or absence of important local interaction phenomena.
Parallel Evolution at the Regulatory Base-Pair Level Contributes to Mammalian Interspecific Differences in Polygenic Traits
Authors: Okamoto Alexander S , Capellini Terence D
Published: July 2024

Parallel evolution occurs when distinct lineages with similar ancestral states converge on a new phenotype. Parallel evolution has been well documented at the organ, gene pathway, and amino acid sequence level but in theory, it can also occur at individual nucleotides within noncoding regions. To examine the role of parallel evolution in shaping the biology of mammalian complex traits, we used data on single-nucleotide polymorphisms (SNPs) influencing human intraspecific variation to predict trait values in other species for 11 complex traits. We found that the alleles at SNP positions associated with human intraspecific height and red blood cell (RBC) count variation are associated with interspecific variation in the corresponding traits across mammals. These associations hold for deeper branches of mammalian evolution as well as between strains of collaborative cross mice. While variation in RBC count between primates uses both ancient and more recently evolved genomic regions, we found that only primate-specific elements were correlated with primate body size. We show that the SNP positions driving these signals are flanked by conserved sequences, maintain synteny with target genes, and overlap transcription factor binding sites. This work highlights the potential of conserved but tunable regulatory elements to be reused in parallel to facilitate evolutionary adaptation in mammals.
Electronic perturbation of Cu nanowire surfaces with functionalized graphdiyne for enhanced CO2 reduction reaction
Authors: Zou Haiyuan , Cheng Dongfang , Tang Chao , Luo Wen , Xiong Huatian , Dong Hongliang , Li Fan , Song Tao , Shu Siyan , Dai Hao , Cui Ziang , Lu Zhouguang , Duan Lele
Published: July 2024

Electronic perturbation of the surfaces of Cu catalysts is crucial for optimizing electrochemical CO2 reduction activity, yet still poses great challenges. Herein, nanostructured Cu nanowires (NW) with fine-tuned surface electronic structure are achieved via surface encapsulation with electron-withdrawing (–F) and -donating (–Me) group-functionalized graphdiynes (R-GDY, R = –F and –Me) and the resulting catalysts, denoted as R-GDY/Cu NW, display distinct CO2 reduction performances. In situ electrochemical spectroscopy revealed that the *CO (a key intermediate of the CO2 reduction reaction) binding affinity and consequent *CO coverage positively correlate with the Cu surface oxidation state, leading to favorable C–C coupling on F-GDY/Cu NW over Me-GDY/Cu NW. Electrochemical measurements corroborate the favorable C2H4 production with an optimum C2+ selectivity of 73.15% ± 2.5% observed for F-GDY/Cu NW, while the predominant CH4 production is favored by Me-GDY/Cu NW. Furthermore, by leveraging the *Cu–hydroxyl (OH)/*CO ratio as a descriptor, mechanistic investigation reveals that the protonation of distinct adsorbed *CO facilitated by *Cu–OH is crucial for the selective generation of C2H4 and CH4 on F-GDY/Cu NW and Me-GDY/Cu NW, respectively.
Coformulated Bictegravir/Emtricitabine/Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Assault: A Retrospective Real-World Study
Authors: Teresita de Jesús Cabrera-López , Edgar Pérez-Barragán , Carlos Ruben Nava-Campos , Marla Toiber-Rodríguez , Juan Carlos Rodríguez-Aldama , Raúl Adrián Cruz-Flores , Andrea González-Rodríguez
Published: July 2024

We report the experience of bictegravir/emtricitabine/tenofovir alafenamide for nonoccupational postexposure prophylaxis in sexual assault cases. Between June 2021 and October 2023, 39 individuals completed the 28-day follow-up; 41% experienced some side effects, and 1 person discontinued the drug because of a rash. No individuals seroconverted to HIV during the follow-up period.
Getting attached to membranes—How plant signaling networks employ PtdIns(4,5)P2
Authors: Heilmann Mareike , Heilmann Ingo
Published: July 2024

In eukaryotes, a small subset of membrane lipids, the phosphoinositides (PIs), exert regulatory effects on membrane-associated processes with profound impact on the organism, and PIs are relevant also for the physiology and development of plants. The PI, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) has emerged as an important regulatory player in plants, and in recent years this lipid has received substantial attention. This Update Review focuses on our current understanding of how PtdIns(4,5)P2 exerts its regulatory functions, how biosynthesis and degradation of this important regulatory lipid are controlled, and how PtdIns(4,5)P2 is linked to upstream and downstream elements within plant signalling networks.
Simultaneous knockout of cytosolic and plastidial disproportionating enzymes disrupts grain setting and filling in rice
Authors: Dong Xiangbai , Yang Huifang , Chai Yaru , Han Bin , Liu Jinxin , Tian Lihong , Cui Shuai , Xiong Shuo , Zhong Manfang , Fu Bo , Qu Le Qing
Published: July 2024

Rice (Oryza sativa) plants contain plastidial and cytosolic disproportionating enzymes (DPE1 and DPE2). Our previous studies showed that DPE2 acts on maltose, the major product of starch degradation in pollens, releasing one glucose to fuel pollen tube growth and fertilization, whereas DPE1 participates in endosperm starch synthesis by transferring maltooligosyl groups from amylose to amylopectin, and removing excess short maltooligosaccharides. However, little is known about their integrated function. Here, we report that the coordinated actions of DPE1 and DPE2 contribute to grain setting and filling in rice. The dpe1dpe2 mutants could not be isolated from the progeny of heterozygous parental plants but were obtained via anther culture. Unlike that reported in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum), the dpe1dpe2 rice plants grew normally but only yielded a small number of empty, unfilled seeds. In the dpe1dpe2 seeds, nutrient accumulation was substantially reduced, and dorsal vascular bundles were also severely malnourished. Zymogram analyses showed that changes in the activities of the major starch-synthesizing enzymes matched well with various endosperm phenotypes of mutant seeds. Mechanistically, DPE1 deficiency allowed normal starch mobilization in leaves and pollens but affected starch synthesis in endosperm, while DPE2 deficiency blocked starch degradation, resulting in substantially decreased levels of the sugars available for pollen tube growth and grain filling. Overall, our results demonstrate the great potential of DPE1-DPE2 as an important regulatory module to realize higher crop yields and present a promising target for regulating nutrient accumulation in cereal crop endosperm.
Predictability of human mobility during the COVID-19 pandemic in the United States
Authors: Hajlasz Michal , Pei Sen
Published: July 2024

Human mobility is fundamental to a range of applications including epidemic control, urban planning, and traffic engineering. While laws governing individual movement trajectories and population flows across locations have been extensively studied, the predictability of population-level mobility during the COVID-19 pandemic driven by specific activities such as work, shopping, and recreation remains elusive. Here we analyze mobility data for six place categories at the US county level from 2020 February 15 to 2021 November 23 and measure how the predictability of these mobility metrics changed during the COVID-19 pandemic. We quantify the time-varying predictability in each place category using an information-theoretic metric, permutation entropy. We find disparate predictability patterns across place categories over the course of the pandemic, suggesting differential behavioral changes in human activities perturbed by disease outbreaks. Notably, predictability change in foot traffic to residential locations is mostly in the opposite direction to other mobility categories. Specifically, visits to residences had the highest predictability during stay-at-home orders in March 2020, while visits to other location types had low predictability during this period. This pattern flipped after the lifting of restrictions during summer 2020. We identify four key factors, including weather conditions, population size, COVID-19 case growth, and government policies, and estimate their nonlinear effects on mobility predictability. Our findings provide insights on how people change their behaviors during public health emergencies and may inform improved interventions in future epidemics.
A structure-redesigned intrinsically disordered peptide that selectively inhibits a plant transcription factor in jasmonate signaling
Authors: Takaoka Yousuke , Liu Ruiqi , Ueda Minoru
Published: July 2024

Plant hormone-related transcription factors (TFs) are key regulators of plant development, responses to environmental stress such as climate changes, pathogens, and pests. These TFs often function as families that exhibit genetic redundancy in higher plants, and are affected by complex crosstalk mechanisms between different plant hormones. These properties make it difficult to analyze and control them in many cases. In this study, we introduced a chemical inhibitor to manipulate plant hormone-related TFs, focusing on the jasmonate (JA) and ethylene (ET) signaling pathways, with the key TFs MYC2/3/4 and EIN3/EIL1. This study revealed that JAZ10CMID, the binding domain of the repressor involved in the desensitization of both TFs, is an intrinsically disordered region in the absence of binding partners. Chemical inhibitors have been designed based on this interaction to selectively inhibit MYC TFs while leaving EIN3/EIL1 unaffected. This peptide inhibitor effectively disrupts MYC-mediated responses while activating EIN3-mediated responses and successfully uncouples the crosstalk between JA and ET signaling in Arabidopsis thaliana. Furthermore, the designed peptide inhibitor was also shown to selectively inhibit the activity of MpMYC, an ortholog of AtMYC in Marchantia polymorpha, demonstrating its applicability across different plant species. This underscores the potential of using peptide inhibitors for specific TFs to elucidate hormone crosstalk mechanisms in non-model plants without genetic manipulation. Such a design concept for chemical fixation of the disordered structure is expected to limit the original multiple binding partners and provide useful chemical tools in chemical biology research.
Platelet-derived Growth Factor Receptor-α Induces Contraction Knots and Inflammatory Pain–like Behavior in a Rat Model of Myofascial Trigger Points
Authors: Liu Yu , Jin Feihong , Zhou Lingwei , Li Xuan , Li Xiaoyue , Chen Qinghe , Yang Shaozhong , Sun Jintang , Qi Feng
Published: July 2024

Background:

Myofascial trigger points (MTrPs) are the primary etiological characteristics of chronic myofascial pain syndrome. Receptor tyrosine kinases (RTKs) are associated with signal transduction in the central mechanisms of chronic pain, but the role of RTKs in the peripheral mechanisms of MTrPs remains unclear. The current study aimed to identify RTKs expression in MTrPs and elucidate the molecular mechanisms through which platelet-derived growth factor receptor-α (PDGFR-α) induces contraction knots and inflammatory pain-like behavior in a rat model of myofascial trigger points.

Methods:

MTrPs tissue samples were obtained from the trapezius muscles of patients with myofascial pain syndrome through needle biopsy, and PDGFR-α activation was analyzed by microarray, enzyme-linked immunosorbent assay, and histological staining. Sprague–Dawley rats (male and female) were used to investigate PDGFR-α signaling, assessing pain-like behaviors with Randall–Selitto and nest-building tests. Muscle fiber and sarcomere morphologies were observed using histology and electron microscopy. The PDGFR-α binding protein was identified by coimmunoprecipitation, liquid chromatograph mass spectrometer, and molecular docking. PDGFR-α–related protein or gene levels, muscle contraction, and inflammatory markers were determined by Western blot and reverse-transcription quantitative polymerase chain reaction.

Results:

PDGFR-α phosphorylation levels were elevated in the MTrPs tissues of individuals with trapezius muscle pain and were positively correlated with pain intensity. In rats, PDGFR-α activation caused pain-like behaviors and muscle contraction via the Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathway. JAK2/STAT3 inhibitors reversed the pain-like behaviors and muscle contraction induced by PDGFR-α activation. Collagen type I α 1 (COL1A1) binds to PDGFR-α and promotes its phosphorylation, which contributed to pain-like behaviors and muscle contraction.

Conclusions:

COL1A1-induced phosphorylation of PDGFR-α and the subsequent activation of the JAK2/STAT3 pathway may induce dysfunctional muscle contraction and increased nociception at MTrPs.
Validation of Spanish-Language Surveys Utilized for the Navigator-Assisted Hypofractionation (NAVAH) Program to Aid Hispanic-American Breast Cancer Patients
Authors: Sanchez-Feliciano Abizairie , Onyewadume Louisa , Stephens Maya J. , Flores Laura E. , Cheatham Chesley , McClelland Shearwood
Published: July 2024

Objectives:

Cancer accounts for 22% of all mortality and is the leading cause of death among Hispanic and/or Latinx patients in the United States. The disparities in access to radiation therapy (RT), mortality rates, and treatment outcomes among Hispanic-American breast cancer patients compared with other populations highlight the urgent need for targeted interventions. The Navigator-Assisted Hypofractionation (NAVAH) program, with its innovative patient navigation approach and culturally sensitive survey, aims to better identify the specific barriers faced by this population. This study is a report of the NAVAH program experience piloting a Spanish-language culturally sensitive survey in Hispanic-American volunteers.

Methods:

Hispanic-American volunteers with fluency in Spanish were recruited to participate in survey conduction, identified from local networks. Survey information was assessed by topic category, and survey responses were amalgamated into a representative score for each category. Survey categories include acceptability (comfort and prejudice among interactions with the system), accessibility (transportation, distance to care, and health care literacy), accommodation (access to the internet, navigating transportation), affordability (financial considerations, employment, and level of education), and availability (access to a medical center, coordinating care, and overall quality of care).

Results:

A total of 6 volunteers meeting inclusion criteria completed the survey; 4 in person and 2 by telephone. The median survey completion time was 12 minutes 38 seconds. Respondents noted satisfaction and trust in their interactions with medical providers; however, responses in the acceptability category highlighted a high perception of disparities in the medical system, including a high prevalence of racial and ethnic prejudice and a high prevalence of treatment differences between high-income and low-income patients in clinical settings.

Conclusions:

In the first Spanish-language survey of its kind, our findings indicate that this survey design is feasible in the Hispanic-American population. Implementation of this survey in breast cancer patients will provide more definitive and comprehensive answers regarding other categories in the survey, including financial challenges during treatment, access to accommodations, and perception of treatment during cancer care. The investigation involving patients actively receiving breast cancer RT is currently underway.
Uveal effusion in Waldenstrom’s macroglobulinemia
Authors: Darmon Johanna , Anjou Mickael , Georgelin Denis , Brezin Antoine P. , Bremond-Gignac Dominique
Published: July 2024

Purpose:

To reastport a case of Waldenstrom macroglobulinemia-related choroidal detachments.

Method:

Case report.

Results:

A 80-year-old woman was referred for bilateral visual loss for few months. She was hospitalized for a Waldenstrom’s disease. Both anterior chambers were deep and quiet. Fundus revealed bilateral choroidal detachment without serous retinal detachments. No vitritis, retinal tear or pigmented lesion were observed. After eliminating all other causes of uveal effusion, the patient was treated for her hemopathy with chemotherapy associated with corticosteroids and plasmapheresis. One month later, fundus showed a complete disappearance of choroidal detachments and vision improved.

Conclusion:

Uveal effusion is an extremely rare ocular damage of Waldenström disease. As choroidal vessels are porous, they may allow immunoglobulins, over produced, to leak toward supra-choroidal space triggering choroidal detachments.
Perioperative Recommendations for Corneal Refractive Surgery Patients With Inherited Bleeding Disorders
Authors: Moshirfar Majid , Reynolds Jonathon C. , Moin Kayvon A. , Lim Ming Y. , Stoakes Isabella M. , Hoopes Phillip C.
Published: July 2024

Purpose:

To synthesize the current literature regarding patients with inherited bleeding disorders and suggest comprehensive evaluation and preoperative recommendations for these patients before undergoing corneal refractive surgery.

Methods:

The literature search was conducted through PubMed, Embase, and Google Scholar databases for publications through January 4, 2024 for reports of ocular bleeding manifestations in patients with inherited bleeding disorders and reports of patients without a history of bleeding disorders who had intraoperative or postoperative hemorrhagic complications with corneal refractive surgery. Additional cases from the literature and a retrospective chart review at a corneal practice were obtained describing patients with inherited bleeding disorders who underwent corneal refractive surgery.

Results:

Four articles were found detailing ocular bleeding manifestations in patients with inherited bleeding disorders who underwent ocular surgery other than corneal refractive surgery. Thirty articles were found detailing intraoperative and postoperative bleeding manifestations in patients without a history of inherited bleeding disorders who underwent corneal refractive surgery. Eight cases (3 patients from the literature search and 5 patients from a retrospective chart review) were found regarding patients with inherited bleeding disorders who underwent corneal refractive surgery.

Conclusions:

For corneal refractive surgery with topical anesthesia, the perioperative risk and need for any hemostasis intervention in individuals with an inherited bleeding disorder depends on the type of disorder, status of preoperative factor level concentrations, or a prior history of bleeding. If required, clotting factor optimization should be tailored to each candidate on a case-by-case basis.
Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain
Authors: Dogrul Bekir Nihat , Machado Kopruszinski Caroline , Dolatyari Eslami Mahdi , Watanabe Moe , Luo Shizhen , Moreira de Souza Luiz Henrique , Vizin Robson Lilo , Yue Xu , Palmiter Richard D. , Navratilova Edita , Porreca Frank
Published: July 2024

Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor–expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1

Cre
heterozygous (MORCre) or wild-type (MORWT) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. After partial sciatic nerve ligation (PSNL), we evaluated pain behaviors and descending control of nociception in response to acute or sustained chemogenetic inhibition of RVM-MOR cells expressing hM4D(Gi). A single systemic administration of hM4D(Gi) agonist clozapine-N-oxide (CNO) reversibly inhibited hind paw tactile allodynia and produced conditioned place preference only in MORCre mice with PSNL. Intrathecal CNO also reversibly inhibited PSNL-induced hind paw allodynia, suggesting that the spinal projections from these RVM-MOR cells are critical for manifestation of pain behaviors. Consistent with enhanced descending facilitation from RVM-MOR cells, MORCre-hM4D(Gi) mice with PSNL showed diminished descending control of nociception that was restored by systemic CNO. Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.
The challenges of Chile to achieve control the HIV/AIDS pandemic the year 2030: A review
Authors: Ferrer Campos Pablo
Published: July 2024

Chile is contending with the highest rates of new human immunodeficiency virus (HIV) cases in both Latin America and globally, despite substantial ongoing investments in treatment. This comprehensive study, derived from PUBMED and Google searches, ANID data, and various organizational reports, highlights key areas for improvement. Over the past decade, Chile’s annual infection rate has risen, signaling an urgent need for detailed analysis and effective solutions. The study includes 44 references, comprising 32 scientific articles and 12 reports from entities like the WHO and the Pan American Health Organization. Data was meticulously collected through diverse means, such as scientific congresses, meetings with authorities, and direct data requests. Fourteen critical points are identified for addressing the HIV epidemic in Chile, spanning from legislative reforms to enhanced prevention campaigns. Key recommendations include universal diagnosis, decentralized healthcare, the availability of self-tests, and a focus on mental health and the impact of migration. Despite Chile’s strong economic indicators, factors such as inadequate sexual education, outdated legislation, and centralized diagnostic processes contribute to the persistent increase in new cases. The study underscores the pressing need for enhanced investment in prevention policies. Chile faces significant challenges in meeting the 90/90/90 targets, yet there is optimism in aiming for the 95/95/95 strategy by 2030. Achieving success requires a global commitment, an emphasis on prevention, and collaborative efforts among authorities, healthcare providers, and patients. Overcoming these identified barriers is essential for Chile to reach its ambitious goal and ultimately end the HIV epidemic.
Risk factors and outcomes associated with systolic dysfunction following traumatic brain injury
Authors: Li Jungen , Miao Yuzhu , Zhang Guoxing , Xu Xiaowen , Guo Yanxia , Zhou Bingyuan , Jiang Tingbo , Lu Shiqi
Published: July 2024

Systolic dysfunction has been observed following isolated moderate–severe traumatic brain injury (Ims-TBI). However, early risk factors for the development of systolic dysfunction after Ims-TBI and their impact on the prognosis of patients with Ims-TBI have not been thoroughly investigated. A prospective observational study among patients aged 16 to 65 years without cardiac comorbidities who sustained Ims-TBI (Glasgow Coma Scale [GCS] score ≤12) was conducted. Systolic dysfunction was defined as left ventricular ejection fraction <50% or apparent regional wall motion abnormality assessed by transthoracic echocardiography within 24 hours after admission. The primary endpoint was the incidence of systolic dysfunction after Ims-TBI. The secondary endpoint was survival on discharge. Clinical data and outcomes were assessed within 24 hours after admission or during hospitalization. About 23 of 123 patients (18.7%) developed systolic dysfunction after Ims-TBI. Higher admission heart rate (odds ratios [ORs]: 1.05, 95% confidence interval [CI]: 1.02–1.08; P = .002), lower admission GCS score (OR: 0.77, 95% CI: 0.61–0.96; P = .022), and higher admission serum high-sensitivity cardiac troponin T (Hs-cTnT) (OR: 1.14, 95% CI: 1.06–1.22; P < .001) were independently associated with systolic dysfunction among patients with Ims-TBI. A combination of heart rate, GCS score, and serum Hs-cTnT level on admission improved the predictive performance for systolic dysfunction (area under curve = 0.85). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality of patients with systolic dysfunction was higher than that of patients with normal systolic function (P < .05). Lower GCS (OR: 0.66, 95% CI: 0.45–0.82; P = .001), lower admission oxygen saturation (OR: 0.82, 95% CI: 0.69–0.98; P = .025), and the development of systolic dysfunction (OR: 4.85, 95% CI: 1.36–17.22; P = .015) were independent risk factors for in-hospital mortality in patients with Ims-TBI. Heart rate, GCS, and serum Hs-cTnT level on admission were independent early risk factors for systolic dysfunction in patients with Ims-TBI. The combination of these 3 parameters can better predict the occurrence of systolic dysfunction.
Necroptosis in recurrent implantation failure: A bioinformatics analysis of key genes and therapeutic targets
Authors: Xing Xiuye , Ni Xiaoxiao , Wang Jiaojiao , Shi Junmei
Published: July 2024

Recurrent implantation failure (RIF), a major issue in assisted reproductive technology (ART), may be influenced by necroptosis, a form of cell death linked to several diseases. This study was aimed at investigating the involvement of necroptosis in RIF. Using RNA-sequencing data from the Gene Expression Omnibus database, we identified differentially expressed necroptosis-related genes (DENRGs) in RIF patients compared with those in controls. Functional enrichment, protein–protein interaction (PPI) networks, and transcription factor (TF) regulatory networks were analyzed to identify key genes. Immune cell infiltration was analyzed using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, potential therapeutic drugs targeting key genes were explored using a Drug Gene Interaction Database. In total, 20 DENRGs associated with RIF were identified, with a focus on 6 key genes (MLKL, FASLG, XIAP, CASP1, BIRC3, and TLR3) implicated in necroptosis and immune processes. These genes were used to develop a predictive model for RIF, which was validated in 2 datasets. The model and TF network analysis underscored the importance of TLR3. Immune infiltration analysis showed reduced levels of 16 immune cells in RIF patients, highlighting immune system alterations. Several drugs targeting CASP1, such as nivocasan and emricasan, were identified as potential treatments. The study sheds light on the role of necroptosis in RIF, identifying key genes and immune alterations that could serve as biomarkers and therapeutic targets. These findings pave the way for future experimental research and clinical applications targeting necroptosis in RIF treatment.
Correlation in retinal thickness and macular retina plus choroidal microcirculation in pediatric myopia
Authors: Cheng Fang , Tian Dan
Published: July 2024

To analyze the relationship in retinal thickness, macula retina and choroidal microcirculation in pediatric patients with myopia. Pediatric patients with high myopia (high myopia group, n = 30, 60 eyes) and pediatric patients with low to moderate myopia (low myopia group, n = 30, 60 eyes) admitted to our hospital from January 2021 to January 2022 were randomly selected as the study subjects. Retinal thickness, the blood density of retina, and the blood density of the choroid were collected in each area of the macula by taking optical coherence tomography (OCT) and OCT angiography (OCTA). Pearson correlation analysis was conducted to compare the results from the 2 groups. Outer retinal thickness showed a weak positive correlation with Superficial vascular complex flow density (SVD) and deep vascular complex flow density (DVD) (P < .05), but no significant correlation with choroidal capillary density (P > .05); inner retinal thickness showed a weak positive correlation with SVD and DVD (P < .05), but no significant correlation with choroidal capillary density (P > .05). In pediatric patients with myopia, there is a positive correlation between the blood flow density of macular retina and retinal thickness, and the retinal thickness will become thinner with increasing myopia.
Research progress on humoral biomarkers of Alzheimer’s disease: A review
Authors: Zhang Hao , Fu Xiaofeng , Yang Mengyu , Song Xiaowen , Li Min , Wang Xuezhen
Published: July 2024

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss. The main pathological features are neuronal fibrillary tangles caused by amyloid beta deposition and hyperphosphorylation of tau protein, accompanied by neuronal death and loss of synaptic structure. Early diagnosis is the key to the treatment of AD. It is known that some small molecular components are related to the pathogenesis of AD. This article will summarize the common AD biomarkers in cerebrospinal fluid and blood and analyze the current status of AD biomarkers and future research directions. This review summarizes the promising biomarkers for the diagnosis of AD in the last decade and describes their changes in AD body fluids. The diagnostic biomarkers related to AD were mainly distributed in cerebrospinal fluid and blood. Significant changes in these molecules can be detected in cerebrospinal fluid and blood, and they are correlated with AD severity. These humoral molecules have necessary relationship with AD and can be used as AD biomarkers to assist early diagnosis of AD.
The impact of cognitive functions, psychological disorders, and coping strategies on quality of life and disease outcomes in patients with inflammatory bowel diseases: A cross-sectional study
Authors: Almarzouki Abeer F. , Alluhaibi Waad , Salman Basma , Almuhaiyawi Maha , Alreemi Maha , Alsahafi Majid
Published: July 2024

Quality of life (QoL) in patients with inflammatory bowel disease (IBD) is influenced by several factors, many of which may also impact cognitive function. However, the extent of the interaction among these factors, QoL, and disease outcomes in IBD patients remains unknown. We thus aim to characterize the relationships among psychological disorders, coping mechanisms, cognitive function, and the overall impact on QoL and disease outcomes in patients with IBD. This cross-sectional observational study was conducted at an academic care center. QoL was evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and disease severity was evaluated using the Harvey–Bradshaw Index (HBI) for Crohn’s disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). We also used the Hospital Anxiety and Depression scale (HADS). Regression models were used to test the associations among QoL, number of hospitalizations, disease severity, cognitive functioning (working memory [WM] and reaction time), and coping strategies while controlling for anxiety and depressive symptoms, age, and sex. This study included 41 patients (24 patients with CD and 17 with UC) whose mean age was 28.2 (±8.4) years (23 males) and mean SIBDQ score was 51.5 (±10.0). Patients with more WM errors had lower QoL scores (P = .041), whereas patients with higher anxiety levels had lower QoL and more active UC (P = .008 and P = .016, respectively). The use of avoidant coping mechanisms was associated with a significantly higher number of hospitalizations (P = .038), and patients who adopted more emotion-focused coping strategies had a longer illness duration (P = .021). Finally, patients with higher education levels were found to use more active coping mechanisms than others. These results confirm the impact of cognitive, psychological, and coping factors on QoL and disease outcomes in patients with IBD; however, the mechanisms by which these factors interrelate remain unclear. Therapies aimed at improving both cognitive functions and psychological conditions may thus be effective at improving QoL and disease outcomes in IBD patients, and education may play a positive role in promoting the adoption of more effective coping strategies among IBD patients.
Case report: A case of primary renal osteosarcoma
Authors: Su Wei , Fu Hao , Mao Xiangming
Published: July 2024

Rationale:

Primary renal osteosarcoma is an exceedingly rare malignant tumor. Fewer than 30 cases have been reported in the literature since 1936. Furthermore, it has a high risk of metastasis and a poor overall prognosis rate.

Patient’s concerns:

In this report, we present a case of osteosarcoma originating from the left kidney (21 cm × 18 cm × 11 cm) with adhesions of the descending colon mesentery and the abdominal wall. A 63-year-old male patient presented with flank pain and gross hematuria.

Diagnoses:

A computed tomography scan revealed that the lesion with irregular margins was observed at the lower pole of the left kidney. Enhanced CT scan showed significant inhomogeneous enhancement of the lesion, with non-enhancing necrotic areas. A radical nephrectomy was performed. The immunohistochemistry results support the diagnosis of osteosarcoma.

Interventions:

Postoperatively, the patient participated in clinical trials and received treatment with a PD-1 antibody (2 weeks/once).

Outcomes:

At the one-year follow-up, the patient reported late-stage systemic cancer-related pain, necessitating daily pain relief medication. Unfortunately, the patient passed away 18 months after the surgery.

Lessons:

The case reported here is an exceedingly rare malignant osteosarcoma that originated from the kidney with the invasion of the descending colon mesentery and the abdominal wall. The patient received treatment with a PD-1 antibody (2 weeks/once). However, the patient passed away 18 months after the surgery. With the application of genetic testing technology and advancements in molecular biology, it was expected that specific targeted therapies for this condition would emerge in the future.
Case report: A case of renal vessel rupture caused by severe vomiting in early pregnancy
Authors: Deng Jiang , Huang He , Ma Jinhua , Wei Hongbing , Qu Xi , Hu Zheng , Zeng Hui , Zhou Jun
Published: July 2024

Objective:

Spontaneous renal vessel rupture is a rare clinical emergency. However, pregnancy symptoms and signs are not obvious, and the limited examination methods obscure the observation. Thus, early renal rupture is challenging to detect, leading to misdiagnosis and poor prognosis. This paper aims to improve clinicians’ understanding of this disease and reduce the rate of clinical misdiagnosis.

Patient concerns:

The patient, aged 23 and 11 weeks pregnant, developed severe right lumbar and abdominal pain for 14 hours after severe nausea, vomiting, and paroxysmal intensification. Color ultrasound of the urinary system at another hospital revealed right kidney stones and right ureter dilation. Thus, the patient came to our hospital for treatment.

Diagnoses:

Spontaneous renal vessel rupture.

Interventions:

In this case, the diagnosis of spontaneous renal vascular rupture and hemorrhage was confirmed. Following conservative treatment such as fluid replenishment, blood transfusion, and hemostasis, the patient was given an emergency renal artery embolization due to unstable hemodynamics during treatment and poor conservative treatment effect.

Outcomes:

Nephrectomy was performed after 1-week follow-up for renal necrosis.

Lessons:

To avoid missed diagnosis and misdiagnosis, patients with abdominal pain caused by severe vomiting during pregnancy must be closely monitored. Additionally, treatment should be considered individually to ensure the safety of both mother and child. Therefore, spontaneous renal vessel rupture should be considered as the differential diagnosis.