bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics
Authors: Kobow Katja , Khan Nadia
Published: July 2024

Epigenetics refers to those mechanisms that allow a transient stimulus to induce long-lived programs of gene expression changes without altering the underlying DNA sequence itself. Epigenetic regulators function by catalyzing the modification of DNA or histone protein tails, which, in turn, up- or down-regulate the transcription of target genes. Originally thought to be static in terminally differentiated cells, it is now known that epigenetic processes are active and dynamic in mature neurons. Their function or perturbation may be sufficient to develop common neurological disorders such as epilepsy. This chapter provides a critical overview of key epigenetic changes detected in human patients and experimental epilepsy models. The chapter reflects on how these data impact epileptogenesis, what role epigenetic mechanisms may play in facilitating disease pathogenesis, and how it influences the chronic epileptic state. In the end, the chapter briefly discusses the potential for targeting epigenetic modulators as a new source of therapeutic intervention in epilepsy.
Machine-Learning Approach to Discover Novel Biomarkers for Posttraumatic Epilepsy
Authors: Ciszek Robert , Manninen Eppu , Gröhn Olli , Tohka Jussi , Pitkänen Asla
Published: July 2024

In this chapter, machine learning was applied to detect traumatic brain injury (TBI), posttraumatic epilepsy (PTE), and severity of PTE in a rat TBI model using data from animal weight, parameters related to TBI induction, multiple behavioral tests, and cortical lesion volumes calculated from magnetic resonance imaging (MRI). The combined data from all assays allowed perfect separation of naïve and sham-operated control animals from TBI animals. However, PTE was only detectable when the threshold for PTE was set at three or more observed seizures. These results imply that less severe forms of PTE were poorly reflected on the assays used.
Human Epilepsy Gene Discovery
Authors: Bonkowski Emily S. , Mefford Heather C.
Published: July 2024

The application of genome-wide technologies has accelerated the discovery of genetic and genomic etiologies for the epilepsies. Gene discovery has been most successful in the developmental and epileptic encephalopathies, and genetic testing is now routinely implemented in the clinical setting. Yet a significant percentage of affected individuals remain undiagnosed, and identifying the genetic underpinnings of generalized and focal epilepsies has lagged. Emerging technologies and analysis approaches offer promise for continued discovery of disease-associated variation. Examples include long-read sequencing, genome-wide methylation studies, and development and application of polygenic risk estimates.
Functional Exploration of Epilepsy Genes in Patient-Derived Cells
Authors: Varela Maria C. , Samarasinghe Ranmal , Parent Jack M.
Published: July 2024

Advances in human induced pluripotent stem cell (iPSC) approaches have greatly expanded the use of patient-derived cellular models, including cortical-like neurons and brain organoids, to study genetic epilepsies. New protocols to differentiate iPSCs into various neural cell types, and to generate brain region-specific organoids, have accelerated progress. In addition, the application of gene editing techniques adds rigor to these studies and offers the opportunity to model rare genetic epilepsies by enabling correction or insertion of mutations to generate isogenic controls or virtual patients, respectively. Studies using patient-derived cells have provided insight into the mechanisms underlying seizures and associated comorbidities for an increasing number of epilepsy gene variants. In this chapter, methods for generating iPSCs, the culture and gene editing of human pluripotent stem cells (hPSCs; both iPSCs and human embryonic stem cells), and differentiation strategies to derive cortical-like neurons are described. Next, physiological assays that can be applied to study hPSC-derived neuronal and network activity are discussed. Finally, the chapter reviews studies interrogating the functional effects of specific epilepsy gene variants using hPSC-derived 2D neural and 3D brain organoid cultures, as well as the use of iPSC-derived cardiac myocytes to study the most devastating epilepsy complication, sudden unexpected death in epilepsy (SUDEP).The chapter ends with a description of current challenges and future directions for hPSC modeling of genetic epilepsies.
The Neuronal Ceroid Lipofuscinoses
Authors: Mole Sara E.
Published: July 2024

The neuronal ceroid lipofuscinoses (NCL), also known as Batten disease, are a group of inherited lysosomal storage disorders that share similar pathological and clinical features. They are characterized by accumulation of autofluorescent storage material within the lysosome and the death of neurons. Clinical presentation includes medically refractory epilepsy, visual failure, and motor and cognitive decline, usually beginning in childhood and ending in premature death. Each NCL is caused by mutations in a single gene and is associated with a typical age of onset and disease progression. However, all NCL also have a broader age of onset and disease course. Considerable expertise has been developed in the care and management of patients. There is one treatment in the clinic and others are in development.
Artificial Intelligence–Guided Behavioral Phenotyping in Epilepsy
Authors: Gschwind Tilo , Soltesz Ivan
Published: July 2024

A major impediment to progress in basic epilepsy research is the fact that evidence-based, rigorous translational research is not only prohibitively time and labor-intensive, such as 24/7 video-electroencephalogram recordings, but rests on inherently subjective scoring by human observers, as exemplified by the Racine scale. Recent technical progress in machine learning and computer vision highlighted a variety of novel possibilities for quantifying behavior in animal models of epilepsies. This chapter briefly reviews the latest advances in artificial intelligence (AI)-guided animal motion tracking and segmentation of pose dynamics that bear great potential of revolutionizing behavioral phenotyping in basic epilepsy research. As an emerging field fueled by the recent successes of deep learning, AI-guided behavioral phenotyping will be discussed primarily in order to provide insights into the fundamentals of the field and at the same time raise awareness of potential pitfalls of the underlying technology. By concisely surveying the diverse and rapidly growing landscape of the relevant methods and toolboxes available in neuroscience research, this chapter aims to spark interest in AI-aided behavioral phenotyping in the epilepsy community.
Disease Biology Factors Accounting for Epilepsy Severity
Authors: Dedeurwaerdere Stefanie , Marra Vincenzo , Johnson Michael R.
Published: July 2024

Over the last decade substantial progress has been made in understanding the genetic contributions to epilepsy. While targeted treatments for monogenic epilepsies are starting to emerge, the substantial heterogeneity of epilepsy poses a challenge to the development of broadly useful therapeutics for the refractory complex genetic epilepsies as well as acquired forms of the disease. The next frontier will be to increase our understanding of convergent epilepsy pathways so as to discover novel and broadly applicable disease-modifying therapies. This chapter posits a unifying conceptual framework for epilepsy for identifying convergent mechanisms across diverse genetic and acquired epilepsies. It is framed in earlier work around the nature of drug-resistant epilepsy which points to an inherent epilepsy severity rather than in the traditional pharmacological considerations external to the development and maintenance of the disease itself. This chapter aims to develop the intrinsic severity hypothesis beyond the nature of the epileptic perturbation and consider its cellular and molecular context more broadly. Specifically, the chapter reconceptualizes drug refractory epilepsy as a failure of homeostatic mechanisms to maintain the set point of the brain within boundaries responsive to standard antiseizure medication within the context of heterogeneous epileptogenic substrates. This framework offers a potential new insight both into the classification of an individual’s epilepsy and innovative therapeutic strategies that go beyond merely targeting the ictal substrate.
Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6
Authors: Johnson J. P. , Cutts Alison J. , Empfield James R. , Cohen Charles J.
Published: July 2024

NBI-921352 is the first highly isoform selective inhibitor of NaV1.6 voltage-gated sodium channels (NaVs) to enter clinical development for epilepsy. Nonselective inhibitors of NaVs have long been a mainstay of epilepsy pharmacotherapy. Many such NaV inhibitors are available, but they are not mechanistically well differentiated. They all inhibit via the same highly conserved binding site, and they inhibit the distinct NaV isoforms equivalently. This broad NaV inhibition limits the utility of these drugs, as dose levels required to reduce seizures can cause tolerability issues in both the central nervous and cardiovascular systems. The rationale to develop NBI-921352 was to take a precision medicine approach to developing novel NaV inhibitors. This approach has been validated preclinically, both in scn8a gain-of-function mutant cell lines and in Scn8a gain-of-function mice. NBI-921352 should improve tolerability by stripping away effects mediated by inhibition of the NaVs of cardiac cells (NaV1.5), muscle cells (NaV1.4), and inhibitory interneurons (NaV1.1). Despite the selective nature of NBI-921352, the compound retains the ability to reduce neural excitability and increases seizure resistance in rodents. NBI-921352 is currently entering clinical trials to establish whether the improved properties observed in rodents translate to human epilepsy patients
A tight N/O–potential relation in star-forming galaxies
Authors: Boardman N , Wild V , Asari N Vale
Published: July 2024

We report a significantly tighter trend between gaseous N/O and $M_*/R_\mathrm{ e}$ (a proxy for gravitational potential) than has previously been reported between gaseous metallicity and $M_*/R_\mathrm{ e}$, for star-forming galaxies in the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. We argue this result to be a consequence of deeper potential wells conferring greater resistance to metal outflows while also being associated with earlier star-formation histories, combined with N/O being comparatively unaffected by metal-poor inflows. The potential–N/O relation thus appears to be both more resistant to short time-scale baryonic processes and also more reflective of a galaxy’s chemical evolution state, when compared to previously considered relations.
Ethical Dimensions of Population-Based Lung Cancer Screening in Canada: Key Informant Qualitative Description Study
Authors: Pahwa Manisha , Abelson Julia , Demers Paul A , Schwartz Lisa , Shen Katrina , Vanstone Meredith
Published: July 2024

Normative issues associated with the design and implementation of population-based lung cancer screening policies are underexamined. This study was an exposition of the ethical justification for screening and potential ethical issues and their solutions in Canadian jurisdictions. A qualitative description study was conducted. Key informants, defined as policymakers, scientists and clinicians who develop and implement lung cancer screening policies in Canada, were purposively sampled and interviewed using a semi-structured guide informed by population-based disease screening principles and ethical issues in cancer screening. Interview data were analyzed using qualitative content analysis. Fifteen key informants from seven provinces were interviewed. Virtually all justified screening by beneficence, describing that population benefits outweigh individual harms if high-risk people are screened in organized programs according to disease screening principles. Equity of screening access, stigma and lung cancer primary prevention were other ethical issues identified. Key informants prioritized beneficence over concerns for group-level justice issues when making decisions about whether to implement screening policies. This prioritization, though slight, may impede the implementation of screening policies in a way that effectively addresses justice issues, a goal likely to require justice theory and critical interpretation of disease screening principles.
A sucrose-binding protein and β-conglycinins regulate soybean seed protein content and control multiple seed traits
Authors: Lakhssassi Naoufal , El Baze Abdelhalim , Knizia Dounya , Salhi Yasser , Embaby Mohamed G , Anil Erdem , Mallory Cullen , Lakhssassi Aicha , Meksem Jonas , Shi Haiying , Vuong Tri D , Meksem Kenza , Kassem My Abdelmajid , AbuGhazaleh Amer , Nguyen Henry T , Bellaloui Nacer , Boualem Adnane , Meksem Khalid
Published: July 2024

Expanded agriculture production is required to support the world's population but can impose substantial environmental and climate change costs, particularly with intensifying animal production and protein demand. Shifting from an animal- to a plant-based protein diet has numerous health benefits. Soybean (Glycine max [L.] Merr.) is a major source of protein for human food and animal feed; improved soybean protein content and amino acid composition could provide high-quality soymeal for animal feed, healthier human foods, and a reduced carbon footprint. Nonetheless, during the soybean genome evolution, a balance was established between the amount of seed protein, oil, and carbohydrate content, burdening the development of soybean cultivars with high proteins (HPs). We isolated 2 high-seed protein soybean mutants, HP1 and HP2, with improved seed amino acid composition and stachyose content, pointing to their involvement in controlling seed rebalancing phenomenon. HP1 encodes β-conglycinin (GmCG-1) and HP2 encodes sucrose-binding protein (GmSBP-1), which are both highly expressed in soybean seeds. Mutations in GmSBP-1, GmCG-1, and the paralog GmCG-2 resulted in increased protein levels, confirming their role as general regulators of seed protein content, amino acid seed composition, and seed vigor. Biodiversity analysis of GmCG and GmSBP across 108 soybean accessions revealed haplotypes correlated with protein and seed carbohydrate content. Furthermore, our data revealed an unprecedented role of GmCG and GmSBP proteins in improving seed vigor, crude protein, and amino acid digestibility. Since GmSBP and GmCG are present in most seed plants analyzed, these genes could be targeted to improve multiple seed traits.
The Inter-Phase Gap Offset Effect as a Measure of Neural Health in Cochlear Implant Users With Residual Acoustic Hearing
Authors: Sijgers Leanne , Röösli Christof , Bertschinger Rahel , Epprecht Lorenz , Veraguth Dorothe , Dalbert Adrian , Huber Alexander , Pfiffner Flurin
Published: July 2024

Objectives:

The inter-phase gap (IPG) offset effect is defined as the dB offset between the linear parts of electrically evoked compound action potential (ECAP) amplitude growth functions for two stimuli differing only in IPG. The method was recently suggested to represent neural health in cochlear implant (CI) users while being unaffected by CI electrode impedances. Hereby, a larger IPG offset effect should reflect better neural health. The aims of the present study were to (1) examine whether the IPG offset effect negatively correlates with the ECAP threshold and the preoperative pure-tone average (PTA) in CI recipients with residual acoustic hearing and (2) investigate the dependency of the IPG offset effect on hair cell survival and intracochlear electrode impedances.

Design:

Seventeen adult study participants with residual acoustic hearing at 500 Hz undergoing CI surgery at the University Hospital of Zurich were prospectively enrolled. ECAP thresholds, IPG offset effects, electrocochleography (ECochG) responses to 500 Hz tone bursts, and monopolar electrical impedances were obtained at an apical, middle, and basal electrode set during and between 4 and 12 weeks after CI surgery. Pure-tone audiometry was conducted within 3 weeks before surgery and approximately 6 weeks after surgery. Linear mixed regression analyses and t tests were performed to assess relationships between (changes in) ECAP threshold, IPG offset, impedance, PTA, and ECochG amplitude.

Results:

The IPG offset effect positively correlated with the ECAP threshold in intraoperative recordings (p < 0.001) and did not significantly correlate with the preoperative PTA (p = 0.999). The IPG offset showed a postoperative decrease for electrode sets that showed an ECochG amplitude drop. This IPG offset decrease was significantly larger than for electrode sets that showed no ECochG amplitude decrease, t(17) = 2.76, p = 0.014. Linear mixed regression analysis showed no systematic effect of electrode impedance changes on the IPG offset effect (p = 0.263) but suggested a participant-dependent effect of electrode impedance on IPG offset.

Conclusions:

The present study results did not reveal the expected relationships between the IPG offset effect and ECAP threshold values or between the IPG offset effect and preoperative acoustic hearing. Changes in electrode impedance did not exhibit a direct impact on the IPG offset effect, although this impact might be individualized among CI recipients. Overall, our findings suggest that the interpretation and application of the IPG offset effect in clinical settings should be approached with caution considering its complex relationships with other cochlear and neural health metrics.
The Dangers of Distracted Driving: A Substudy of Patient Perception Data From the DRIVSAFE Observational Study
Authors:   The DRIVSAFE Team
Published: July 2024

OBJECTIVE:

To determine how fracture clinic patients perceive the dangers of distracted driving.

METHODS:

Design:

Analysis of patient perception subset data from the original DRIVSAFE study; a large, multicenter cross-sectional study, surveying fracture clinic patients about distracted driving.

Setting:

Four Level 1 Canadian trauma center fracture clinics.

Patient Selection Criteria:

English-speaking patients with a valid Canadian driver's license and a traumatic musculoskeletal injury sustained in the past 6 months.

Outcome Measures and Comparisons:

Primary outcome was patients' safety ratings of driving distractions. As per the original DRIVSAFE study, patients were categorized as distraction-prone or distraction-averse using their questionnaire responses and published crash-risk odds ratios (ORs). A regression analysis was performed to identify associations with unsafe driving perceptions.

RESULTS:

The study included 1378 patients, 749 (54.3%) male and 614 (44.6%) female. The average age was 45.8 ± 17.0 years (range 16–87). Sending electronic messages was perceived as unsafe by 92.9% (1242/1337) of patients, while reading them was seen as unsafe by 81.2% (1086/1337). Approximately three-quarters of patients viewed making (78.9%, 1061/1344) and accepting (74.8%, 998/1335) calls on handheld mobile phones as unsafe. However, 31.0% (421/1356) of patients believed that they had no differences in their driving ability when talking on the phone while 13.1% (175/1340) reported no driving differences when texting. Younger age (OR, 0.93 [95% confidence interval (CI) 0.90–0.96], P < 0.001), driving experience (OR, 1.06 [95% CI 1.02–1.09], P < 0.001), and distraction-prone drivers (OR, 3.79 [95% CI 2.91–4.94], P < 0.001) were associated with unsafe driving perceptions.

CONCLUSIONS:

There is a clear association between being prone to distractions and unsafe driving perceptions, with distraction-prone drivers being 3.8 times more likely to perceive driving distractions as safe. This information could potentially influence the appropriate delivery and content of future educational efforts to change the perception of driving distractions and thereby reduce distracted driving.

LEVEL OF EVIDENCE:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Exposure to Ambient Heat and Risk of Spontaneous Abortion: A Case–Crossover Study
Authors: Wesselink Amelia K. , Gause Emma L. , Spangler Keith D. , Hystad Perry , Kirwa Kipruto , Willis Mary D. , Wellenius Gregory A. , Wise Lauren A.
Published: July 2024

Background:

Few epidemiologic studies have examined the association of ambient heat with spontaneous abortion, a common and devastating pregnancy outcome.

Methods:

We conducted a case–crossover study nested within Pregnancy Study Online, a preconception cohort study (2013–2022). We included all participants reporting spontaneous abortion (N = 1,524). We defined the case window as the 7 days preceding the event and used time-stratified referent selection to select control windows matched on calendar month and day of week. Within each 7-day case and control window, we measured the mean, maximum, and minimum of daily maximum outdoor air temperatures. We fit splines to examine nonlinear relationships across the entire year and conditional logistic regression to estimate odds ratios (ORs) and 95% confidence interval (CI) of spontaneous abortion with increases in temperature during the warm season (May–September) and decreases during the cool season (November–March).

Results:

We found evidence of a U-shaped association between outdoor air temperature and spontaneous abortion risk based on year-round data. When restricting to warm season events (n = 657), the OR for a 10-percentile increase in the mean of lag 0–6 daily maximum temperatures was 1.1 (95% CI: 0.96, 1.2) and, for the maximum, 1.1 (95% CI: 0.99, 1.2). The OR associated with any extreme heat days (>95th county-specific percentile) in the preceding week was 1.2 (95% CI: 0.95, 1.5). Among cool season events (n = 615), there was no appreciable association between lower temperatures and spontaneous abortion risk.

Conclusion:

Our study provides evidence of an association between high outdoor temperatures and the incidence of spontaneous abortion.
A Counterfactual Analysis of Impact of Cesarean Birth in a First Birth on Severe Maternal Morbidity in the Subsequent Birth
Authors: Bane Shalmali , Snowden Jonathan M. , Simard Julia F. , Odden Michelle , Kan Peiyi , Main Elliott K. , Carmichael Suzan L.
Published: July 2024

Background:

It is known that cesarean birth affects maternal outcomes in subsequent pregnancies, but specific effect estimates are lacking. We sought to quantify the effect of cesarean birth reduction among nulliparous, term, singleton, vertex (NTSV) births (i.e., preventable cesarean births) on severe maternal morbidity (SMM) in the second birth.

Methods:

We examined birth certificates linked with maternal hospitalization data (2007–2019) from California for NTSV births with a second birth (N = 779,382). The exposure was cesarean delivery in the first birth and the outcome was SMM in the second birth. We used adjusted Poisson regression models to calculate risk ratios and population attributable fraction for SMM in the second birth and conducted a counterfactual impact analysis to estimate how lowering NTSV cesarean births could reduce SMM in the second birth.

Results:

The adjusted risk ratio for SMM in the second birth given a prior cesarean birth was 1.7 (95% confidence interval: 1.5, 1.9); 15.5% (95% confidence interval: 15.3%, 15.7%) of this SMM may be attributable to prior cesarean birth. In a counterfactual analysis where 12% of the California population was least likely to get a cesarean birth instead delivered vaginally, we observed 174 fewer SMM events in a population of individuals with a low-risk first birth and subsequent birth.

Conclusion:

In our counterfactual analysis, lowering primary cesarean birth among an NTSV population was associated with fewer downstream SMM events in subsequent births and overall. Additionally, our findings reflect the importance of considering the cumulative accrual of risks across the reproductive life course.
Synthetic Simulators for Microsurgery Training: A Systematic Review
Authors: Sapino Gianluca , Gonvers Stephanie , Cherubino Mario , Ballestín Alberto , di Summa Pietro Giovanni
Published: July 2024

Background:

Microsurgery has a steep learning curve. Synthetic simulators have proven to be useful training tools for the initial learning stages, as well as being ethically sound, viable, safe, and cost-effective. The objective of this review was to determine the quality, effectiveness, and validity of these simulators as well as to assess their ability to evaluate microsurgical skills.

Methods:

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. We searched databases (Web of Science, Scopus, and PubMed) to identify original articles describing synthetic training models for microsurgery. Three reviewers evaluated articles for inclusion following predefined selection criteria. Data were extracted from full-texts of included articles.

Results:

Thirty-nine studies met the inclusion criteria. A total of 38 different devices have been recorded. Microsurgical training devices offer a low-cost, fast, and consistent method to concretely quantify and assess the initial microsurgical skills of trainees using standardized exercises that can be scored by the examiner. According to the authors, the outcomes were satisfactory, with a tangible improvement in microsurgical abilities, despite the lack of a common comparison scale.

Conclusions:

Thanks to their availability, cost, and effectiveness, synthetic models are the recommended option to train basic, intermediate and advanced procedures before executing them on in vivo models.
COMPLEX MACULAR HOLE CLOSURE BY TEMPORAL INTERNAL LIMITING MEMBRANE FLAP WITHOUT ENDOTAMPONADE
Authors: Szeto Simon K. H. , Yu Amy H. Y. , Tsang Chi Wai , Mohamed Shaheeda , Chen Li Jia , Lai Timothy Y. Y.
Published: July 2024

Purpose:

To evaluate the safety, efficacy, and imaging features of a novel surgical technique without endotamponade in repairing complex macular hole (MH).

Methods:

Retrospective review of consecutive cases with complex MH underwent pars plana vitrectomy with temporal internal limiting membrane flap, which was stabilized using perfluorocarbon liquid and viscoelastics. At the conclusion of surgery, perfluorocarbon liquid was removed, and no endotamponade agent would be used. Complex MH was defined as a basal linear diameter of ≥400 µm and/or associated with high myopia. Visual acuity, pattern of MH closure on optical coherence tomography, formation of epiretinal membrane, and operative complications were reported.

Results:

Twenty-four eyes were included, and the mean basal linear diameter was 988.3 µm. MH closure was achieved in 24 (100%), of which, 8 (33%) achieved type 1A closure. The mean postoperative logarithm of the minimum angle of resolution visual acuity improved from 0.93 at baseline to 0.74, 0.51, 0.55, and 0.52 at 1-month, 3-month, 6-month, and last follow-up, respectively. Foveal gliosis was observed in 3 eyes (12.5%), and 10 (41.7%) developed nasal epiretinal membrane. One eye developed vitreous hemorrhage, which resolved spontaneously.

Conclusion:

This novel surgical technique that requires no endotamponade is effective in achieving complex MH closure. A substantial proportion of patients developed epiretinal membrane, and its clinical significance requires further investigation.
Clinical Characteristics of Four Cases of Presumed Chloroquine Retinopathy
Authors: Hall Brian P. , Thomas Joanne , Yan Jiong , Jain Nieraj
Published: July 2024

Background:

Chloroquine (CQ), primarily used in the management of malaria and autoimmune diseases, has long been known to cause retinal toxicity. However, modern literature with multimodal fundus imaging findings remains limited. This retrospective study explores presumed CQ retinopathy cases at a tertiary United States referral center with an emphasis on multimodal fundus imaging characteristics.

Methods:

Retrospective series of cases of presumed CQ toxicity seen at the Emory Eye Center between 2015-2022.

Results:

Four males were identified with presumed CQ retinopathy, with median age of 57 years (range 50-59 years). CQ use occurred in malaria-endemic regions in each case, and the medication was self-administered in three cases. Optical coherence tomography consistently revealed outer band loss and varying degrees of foveal sparing. Fundus autofluorescence imaging demonstrated symmetric bull’s eye pattern of AF abnormality with hyperautofluorescence along the rim of diseased tissue. One case exhibited para-vascular hyperautofluorescence in the setting of repeated intravenous CQ exposure.

Discussion:

Multimodal retinal imaging revealed distinct yet diverse patterns of degeneration not readily visible on clinical examination. More generally, these findings raise public health concerns regarding self-administration of CQ in malaria-endemic regions.
How is age at menopause and reproductive lifespan associated with chronic pain outcomes in postmenopausal women?
Authors: Lund Charlotte Indre , Rosseland Leiv Arne , Steingrímsdóttir Ólöf Anna , Engdahl Bo Lars , Stubhaug Audun , Furberg Anne-Sofie , Nielsen Christopher Sivert
Published: July 2024

Female sex is a prominent risk factor for chronic pain, although the underlying mechanisms are not fully understood. This cross-sectional study aimed to investigate the relationship between age at menopause, reproductive lifespan, and chronic pain in a sample of postmenopausal women aged 40 to 93 years. Data were collected from the Tromsø study conducted in Norway between 2015 and 2016 (Tromsø7). Chronic pain was assessed using a single question, which formed a sample size of 5741 participants. Chronic widespread pain was evaluated using the more comprehensive Graphical Index of Pain, resulting in a sample size of 5920 women. Premenopausal women and those who experienced menstrual cessation due to chemotherapy/radiation or hormonal intrauterine devices were excluded from the analysis. Adjusted relative risk ratios with 95% confidence intervals were calculated to determine associations. The results showed that early menopause was associated with a 1% increase in the prevalence of chronic pain for each year of earlier onset at menopause (0.992, CI 95% 0.985-0.998). This association was also observed in women who experienced natural menopause only. However, the association between menopause and chronic widespread pain did not reach statistical significance in the fully adjusted analysis (0.996, CI 95% 0.975-1.017). There were no significant associations found between reproductive lifespan and either outcome. In conclusion, the findings suggest that early menopause in postmenopausal women is linked to a higher prevalence of chronic pain. However, reproductive lifespan does not appear to have a significant impact on chronic pain or chronic widespread pain.
Effects of perceived risk of COVID-19 on fear among visiting workers: Mediating role of perceived stress
Authors: Baek Eun-Mi , Jung Hye-Sun , Kwon Suyoung , Hwang Jee-Hyun , Park Ji-Young
Published: July 2024

With the creation of a social distancing policy due to coronavirus disease 2019 (COVID-19), home visit workers are under mental stress as they are treated as the source of infection for COVID-19. Since door-to-door rental equipment examiners and gas inspectors must perform their duties even in the COVID-19 situation, they are being discriminated against so severely. The purpose of study was to examine the mediating role of perceived stress on the relationship between risk perception and fear. Data was collected data through labor unions among 275 home visiting workers who examine rental home appliance equipment or inspecting gas. On-line survey was conducted to assess COVID-19 risk perception, fear, perceived stress, and demographic characteristics. The data was analyzed using PROCESS Macro (Model 4). The results of the study showed that stress plays an important role in increasing COVID-19 fears when COVID-19 risk perception increases. Meanwhile, it was found that COVID-19 fear decreased when the level of perceived stress decreased. To reduce the impact of COVID-19 risk perception on COVID-19 fears, appropriate educational programs to reduce stress should be developed for home visit workers. Policymakers need to develop online or mobile Infectious disease education programs for COVID-19 risk at work and establish policies to apply legal education.
Omalizumab in the treatment of bullous pemphigoid: A single-center series of 15 cases
Authors: Altan Ferhatoglu Zeynep , Yucesoy Sera Nur , Ak Tumay , Demir Yusuf
Published: July 2024

Bullous pemphigoid (BP) is a chronic autoimmune disease affecting the elderly population and characterized by the formation of subepidermal tense bullae. Treatment options include topical steroids, systemic steroids, immunosuppressants, and antimicrobials, and there is emerging evidence of the efficacy of omalizumab. In this study, we aimed to demonstrate omalizumab’s efficacy for treating BP, and we also reported treatment-related adverse events. The retrospective cohort study included patients with BP who were followed up in our clinic’s bullous diseases department between 2016 and 2023. Patients who received omalizumab were included in the study. Treatment responses of all patients were assessed by BP Disease Area Index activity and damage scores, treatment scale scoring, steroid dose reduction, and the presence/absence of pruritus. Also, total IgE levels of patients before the treatment onset and at the last visit were compared. There were 15 (male/female = 8/7) BP patients receiving omalizumab treatment. Omalizumab therapy allowed steroid dose reduction at a median of 1 month. Omalizumab (25.5 mg, 95% confidence interval 17.2–33.9, P < .001) provided a significant steroid dose reduction at the last visit compared to the beginning of treatment. Omalizumab resulted in a decrease in BP Disease Area Index activity score of 80.8 (95% confidence interval 71.8–89.8, P < .001). Also, omalizumab caused significant decline in IgE levels compared to baseline (1102.5 ± 834.5 vs 834.6 ± 613.6, P = .002). In this study, omalizumab treatment was an effective and safe option in BP patients with high baseline IgE levels who are refractory to or cannot tolerate other immunosuppressive therapies.
Development and Validation of an Interpretable Machine Learning Model for Early Prognosis Prediction in ICU Patients with Malignant Tumors and Hyperkalemia
Authors: Bu Zhi-Jun , Jiang Nan , Li Ke-Cheng , Lu Zhi-Lin , Zhang Nan , Yan Shao-Shuai , Chen Zhi-Lin , Hao Yu-Han , Zhang Yu-Huan , Xu Run-Bing , Chi Han-Wei , Chen Zu-Yi , Liu Jian-Ping , Wang Dan , Xu Feng , Liu Zhao-Lan
Published: July 2024

This study aims to develop and validate a machine learning (ML) predictive model for assessing mortality in patients with malignant tumors and hyperkalemia (MTH). We extracted data on patients with MTH from the Medical Information Mart for Intensive Care-IV, version 2.2 (MIMIC-IV v2.2) database. The dataset was split into a training set (75%) and a validation set (25%). We used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential predictors, which included clinical laboratory indicators and vital signs. Pearson correlation analysis tested the correlation between predictors. In-hospital death was the prediction target. The Area Under the Curve (AUC) and accuracy of the training and validation sets of 7 ML algorithms were compared, and the optimal 1 was selected to develop the model. The calibration curve was used to evaluate the prediction accuracy of the model further. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) enhanced model interpretability. 496 patients with MTH in the Intensive Care Unit (ICU) were included. After screening, 17 clinical features were included in the construction of the ML model, and the Pearson correlation coefficient was <0.8, indicating that the correlation between the clinical features was small. eXtreme Gradient Boosting (XGBoost) outperformed other algorithms, achieving perfect scores in the training set (accuracy: 1.000, AUC: 1.000) and high scores in the validation set (accuracy: 0.734, AUC: 0.733). The calibration curves indicated good predictive calibration of the model. SHAP analysis identified the top 8 predictive factors: urine output, mean heart rate, maximum urea nitrogen, minimum oxygen saturation, minimum mean blood pressure, maximum total bilirubin, mean respiratory rate, and minimum pH. In addition, SHAP and LIME performed in-depth individual case analyses. This study demonstrates the effectiveness of ML methods in predicting mortality risk in ICU patients with MTH. It highlights the importance of predictors like urine output and mean heart rate. SHAP and LIME significantly enhanced the model’s interpretability.
The impact of human epidermal growth factor receptor-2 (low) status on the efficacy of first line cyclin-dependent kinase 4/6 inhibitors in advanced breast cancer
Authors: Yildirim Hasan Cagri , Buyukkor Mustafa , Kavgaci Gözde , Celik Buket Şahin , Yucel Kadriye Bir , Dursun Bengü , Chalabiyev Elvin , Yilmaz Funda , Yildirim Saadet Sim , Kus Fatih , Tay Fatih , Gecgel Asli , Koksal Bariş , Guven Deniz Can , Yazici Ozan , Urun Yüksel , Ozet Ahmet , Gokmen Erhan , Oksuzoglu Berna , Aksoy Sercan
Published: July 2024

The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33 ± 0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67–2.20, P = .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status.
Prediction of internal jugular vein catheter length inserted through the posterior approach of the sternocleidomastoid muscle
Authors: Chen Qunxiang , Zhang Xiaoyu , Zhang Huanlin , Li Jie , Zhang Yan , Zhang Kaixiang , Chen Xi
Published: July 2024

This study aimed to determine an equation to estimate the optimal insertion length for catheter placement via the posterior approach of the sternocleidomastoid muscle in cancer patients. This retrospective study included patients with cancer who underwent infusion port implantation surgery in the Oncology Department of the 900th Hospital of Joint Logistic Support Force of the Chinese People Liberation Army from April 2017 to September 2023. Patient height (H), weight (W), chest length (C), and length of the internal jugular vein catheter (L) were collected from medical records. The patients were randomized 7:3 to the training and validation sets. Linear regression analyses were used in the training set to determine formulas to predict catheter length. The formula predictive value was analyzed using the Bland-Altman method in the validation set. This study included 336 patients, with a mean age of 58.27 ± 11.70 years, randomized in the training (n = 235) and validation (n = 101) sets. Linear regression analysis revealed that the equations for catheter length relative to H, body mass index (BMI), and C are L = 0.144 × H - 8.258 (R² = 0.608, P < .001), L = −0.103 × B + 17.384 (R² = 0.055, P < .001), and L = 0.477 × C + 1.769 (R² = 0.342, P < .001), respectively. The multivariable linear regression analysis showed that the equation between the length of the catheter and H and C was L = 0.131 × H + 0.086 × C-8.515 (R² = 0.614, P < .001). The Bland-Altman analysis in the validation set showed that the predicted values of internal jugular vein catheter length and the actual values showed good agreement. The optimal L might be determined by simple formulas based on patients H and C.
Clinical presentation and symptomatology of Guillain-Barré syndrome: A literature review
Authors: Elendu Chukwuka , Osamuyi Emmanuella I. , Afolayan Ikeoluwa A. , Opara Nnamdi C. , Chinedu-Anunaso Nkeiruka A. , Okoro Chinonso B. , Nwankwo Augustine U. , Ezidiegwu Dianne O. , Anunaso Chinweike A. , Ogbu Collins C. , Aghahowa Samuel O. , Atuchukwu Chibuzor S. , Akpa Everister U. , Peterson Jesse C.
Published: July 2024

Guillain-Barré Syndrome (GBS) is a rare but potentially life-threatening neurological disorder characterized by acute onset ascending paralysis and sensory abnormalities. This article provides a comprehensive overview of GBS, covering its epidemiology, etiology, clinical presentation, diagnostic evaluation, management and treatment, prognosis, psychosocial impact, recent advances in research, public health implications, and ethical considerations. Epidemiological data reveal variations in GBS prevalence, incidence rates, and geographical distribution influenced by climate, infectious disease prevalence, and genetic susceptibility. Etiological factors include preceding infections, vaccinations, and autoimmune mechanisms, although the precise pathophysiology remains incomplete. Clinical presentation encompasses prodromal symptoms, motor deficits, sensory abnormalities, autonomic dysfunction, and variants such as Miller-Fisher Syndrome and Bickerstaff brainstem encephalitis. Neurological examination findings include weakness, paralysis, sensory deficits, and reflex changes, while autonomic dysfunction manifests as cardiovascular, respiratory, and gastrointestinal symptoms. Diagnostic evaluation relies on clinical criteria, laboratory tests (e.g., cerebrospinal fluid analysis, nerve conduction studies), and consideration of differential diagnoses. Management strategies encompass supportive care, immunomodulatory therapies (e.g., intravenous immunoglobulin, plasma exchange), and rehabilitation interventions to optimize functional outcomes and promote recovery. Prognosis varies depending on clinical features, treatment response, and complications such as respiratory failure and autonomic instability. Psychosocial impact encompasses psychological effects on patients and caregivers, highlighting the importance of coping strategies and support systems. Recent advances in research focus on emerging treatments, genetic predisposition, and biomarker discovery, offering promise for improving GBS outcomes. Public health implications include vaccination safety concerns and healthcare system considerations for GBS management. Ethical considerations encompass patient autonomy, resource allocation, and end-of-life decision-making.
Causal relationship between breakfast skipping and myocardial infarction: Two-sample Mendelian randomization
Authors: Guo Yuli , Lv Luo , Gao Hui , Feng Ruiting , Guo Min
Published: July 2024

While observational studies suggest a connection between skipping breakfast and myocardial infarction (MI), the causal nature of this relationship is unclear. This study aims to investigate the genetic causal relationships between breakfast skipping and MI through Mendelian randomization (MR). Employing genetic data from a public genome-wide association study, this research focuses on genetic variations linked to breakfast skipping and MI. The primary analytical method was the inverse variance-weighted approach, complemented by additional methods like MR-Egger, weighted median, and mode analyses. It also includes heterogeneity and horizontal pleiotropy tests such as the Cochrane Q test, MR-Egger intercept, and MR-PRESSO tests, with a leave-one-out analysis for enhanced sensitivity assessment reliability. The study discovered a notable association between breakfast skipping and an increased risk of MI (odds ratios: 1.34, 95% confidence intervals: 1.03–1.76, P = .027). The test revealed no heterogeneity or multiplicity, and the sensitivity analysis confirmed the robustness of the results. Our MR analysis suggests that habitual breakfast skipping might elevate the likelihood of MI, underlining the importance of regular breakfast consumption in potentially mitigating heart attack risks.
Effects of nonimmersive virtual reality using Wii-Fit exercises on balance and cognition in Parkinson disease: A meta-analysis
Authors: Hussain Fouzia , Farooqui Sumaira , Khan Amna Aamir , Khan Muhammad Usman , Khan Muhammad Abid , Hasan Ahad
Published: July 2024

Background:

Patients’ compliance and receptivity to nonimmersive virtual reality (NIVR) can enhance their long-term exercise therapy compliance for neurological illnesses. Patients with Parkinson disease (PD) have age-standardized rates of disability, death, and prevalence that are rising the fastest; several researches have revealed that there is no known cure for PD at this time. Thus, the current study investigates how NIVR affects patients with PD using Wii-Fit exercises. Therefore, the present study investigates the effects of NIVR using Wii-Fit exercises among patients with PD.

Materials and Methods:

The population, intervention, comparison, outcome approach was used to select the research studies. Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, PubMed, Physiotherapy Evidence Database, and ProQuest were checked for citations from 2012 to 2022. RevMan was used to analyze data. A fixed and random effects model was used to analyze the pooled effect size in terms of mean and standard deviation. The heterogeneity was calculated using the I2 statistic. Cochrane examined for bias in randomized controlled trials.

Results:

This review comprised 12 trials in total. Using the Berg Balance Scale, the pooled analysis showed statistically significant effects on the NIVR group (pooled standardized mean difference = 0.61 [95% confidence interval, 0.28–0.95]; I2 = 53%; P = .0003). The pooled effects of cognition showed nonsignificant effects of NIVR (pooled standardized mean difference = 0.15 [95% confidence interval, −0.21 to 0.51]; I2 = 0%; P = .41).

Conclusions:

The review suggests that NIVR is effective for balance rehabilitation but ineffective for cognitive improvement in patients with PD aged >18 to 85 years.