bluuebunny/crossref_metadata_2025 huggingface dataset:
One-core neuron deep learning for time series prediction
Authors: Peng Hao , Chen Pei , Yang Na , Aihara Kazuyuki , Liu Rui , Chen Luonan
Published: December 2024

The enormous computational requirements and unsustainable resource consumption associated with massive parameters of large language models and large vision models have given rise to challenging issues. Here, we propose an interpretable ‘small model’ framework characterized by only a single core-neuron, i.e. the one-core-neuron system (OCNS), to significantly reduce the number of parameters while maintaining performance comparable to the existing ‘large models’ in time-series forecasting. With multiple delay feedback designed in this single neuron, our OCNS is able to convert one input feature vector/state into one-dimensional time-series/sequence, which is theoretically ensured to fully represent the states of the observed dynamical system. Leveraging the spatiotemporal information transformation, the OCNS shows excellent and robust performance in forecasting tasks, in particular for short-term high-dimensional systems. The results collectively demonstrate that the proposed OCNS with a single core neuron offers insights into constructing deep learning frameworks with a small model, presenting substantial potential as a new way for achieving efficient deep learning.
A deep learning framework for in silico screening of anticancer drugs at the single-cell level
Authors: Zhang Peijing , Wang Xueyi , Cen Xufeng , Zhang Qi , Fu Yuting , Mei Yuqing , Wang Xinru , Wang Renying , Wang Jingjing , Ouyang Hongwei , Liang Tingbo , Xia Hongguang , Han Xiaoping , Guo Guoji
Published: December 2024

Tumor heterogeneity plays a pivotal role in tumor progression and resistance to clinical treatment. Single-cell RNA sequencing (scRNA-seq) enables us to explore heterogeneity within a cell population and identify rare cell types, thereby improving our design of targeted therapeutic strategies. Here, we use a pan-cancer and pan-tissue single-cell transcriptional landscape to reveal heterogeneous expression patterns within malignant cells, precancerous cells, as well as cancer-associated stromal and endothelial cells. We introduce a deep learning framework named Shennong for in silico screening of anticancer drugs for targeting each of the landscape cell clusters. Utilizing Shennong, we could predict individual cell responses to pharmacologic compounds, evaluate drug candidates’ tissue damaging effects, and investigate their corresponding action mechanisms. Prioritized compounds in Shennong's prediction results include FDA-approved drugs currently undergoing clinical trials for new indications, as well as drug candidates reporting anti-tumor activity. Furthermore, the tissue damaging effect prediction aligns with documented injuries and terminated discovery events. This robust and explainable framework has the potential to accelerate the drug discovery process and enhance the accuracy and efficiency of drug screening.
Achieving High Protein Quality Is a Challenge in Vegan Diets: A Narrative Review
Authors: Soh Bi Xue Patricia , Smith Nick W , von Hurst Pamela R , McNabb Warren C
Published: December 2024

The transition toward plant-based (PB) diets has gained attention as a plausible step toward achieving sustainable and healthy dietary goals. However, the complete elimination of all animal-sourced foods from the diet (ie, a vegan diet) may have nutritional ramifications that warrant close examination. Two such concerns are the adequacy and bioavailability of amino acids (AAs) from plant-sourced foods and the consequences for older vegan populations who have elevated AA requirements. This narrative review describes the challenges of achieving high protein quality from vegan diets. Data were synthesized from peer-reviewed research articles and reviews. Plant-sourced proteins provide poorer distribution of indispensable AAs (IAAs) and have poorer digestibility, partly due to their inherent structural components within the food matrix. The review addresses complexities of combinations of varied plant protein sources and why the inclusion of novel PB alternatives adds uncertainty to the achievement of adequate protein adequacy. Meal distribution patterns of protein and the ensuing physiological impacts deserve further research and are outlined in this review. Particular attention is given to describing the challenges of achieving sufficient protein and IAA intakes by aging populations who choose to follow a vegan diet. This review contributes to the emerging discussions of nutritional risks associated with vegan diets and adds perspective to the current dietary shifts toward PB diets.
Self-reported symptoms or activity limitations and job loss during the COVID-19 pandemic in Japan
Authors: Okahara S , Fujino Y , Nagata T , Kuwamura M , Mafune K , Muramatsu K , Tateishi S , Ogami A , Mori K ,   for the CORoNaWork project
Published: December 2024

Background

Previous studies have reported the impact of a diagnosed disease or self-perceived poor overall health on job loss. However, evidence is lacking on which self-reported symptoms or activity limitations are related to job loss, especially during the coronavirus disease 2019 (COVID-19) pandemic.

Aims

We investigated whether self-reported symptoms or activity limitations were correlated with the occurrence of job loss within 1 year during the COVID-19 pandemic.

Methods

In this prospective cohort study, we used questionnaires administered to Japanese workers. A baseline survey conducted in December 2020 was used to determine workers’ symptoms or activity limitations. Experiencing job loss since the baseline survey was ascertained with a follow-up survey in December 2021. The odds ratios of experiencing job loss were estimated using a logistic model with adjusted covariates.

Results

Men (n = 8682) accounted for 58% of the total sample (n = 14 910), and the respondent mean age was 48.2 years. Multivariate analysis showed that workers with pain-related problems; limited physical movement and mobility; fatigue, loss of strength or appetite, fever, dizziness and moodiness; mental health problems; sleep-related problems or eye-related matters had a greater probability of experiencing job loss owing to health reasons.

Conclusions

Several self-reported symptoms or activity limitations can lead to job loss after 1 year, indicating that prevention and resolution of symptoms or activity limitations are important to reduce workers’ risk of losing their jobs.
In-depth characterization of T cell responses with a combined Activation-Induced Marker (AIM) and Intracellular Cytokine Staining (ICS) assay
Authors: Lee Yeji , Tarke Alison , Grifoni Alba
Published: December 2024

Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific T cell immune responses is pivotal to understanding immune function. Commonly used methods for measuring T cell responses include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported. This study describes a combined AIM + ICS assay and the effect of collecting the supernatant. Peripheral blood mononuclear cells (PBMCs) from seven healthy donors were stimulated with DMSO (negative control), Epstein-Barr virus (EBV) peptide pools, and PHA (positive control). The AIM markers OX40 + CD137+ were used for CD4+ T cells and CD69 + CD137+ and CD107a + CD137+ for CD8+ T cells. Cytokine-secreting cells were identified as CD40L+ cytokine+ for CD4+ and CD69+ or CD107 + cytokine+ for CD8+ T cells. Half of the supernatant was collected before adding the BFA/Monensin/CD137 antibody solution to assess the impact on T cell responses. The CD107a + CD137+ AIM markers combination had a lower background than CD69 + CD137+, making CD107a+ a more sensitive marker for CD8+ AIM markers. Collecting half of the supernatant did not significantly affect the immune responses. Our AIM + ICS combined protocol enables the simultaneous assessment of activation and cytokine release reducing the sample volume for testing T cell responses. We also show that collecting half of the supernatant does not significantly interfere with immune responses detection.
Complements and competitors: Examining technological co-diffusion and relatedness on a collaborative coding platform
Authors: Sirianni Antonio D , Morgan Jonathan H , Zöller Nikolas , Rogers Kimberly B , Schröder Tobias
Published: December 2024

Diffusive and contagious processes spread in the context of one another in connected populations. Diffusions may be more likely to pass through portions of a network where compatible diffusions are already present. We examine this by incorporating the concept of “relatedness” from the economic complexity literature into a network co-diffusion model. Building on the “product space” concept used in this work, we consider technologies themselves as nodes in “product networks,” where edges define relationships between products. Specifically, coding languages on GitHub, an online platform for collaborative coding, are considered. From rates of language co-occurrence in coding projects, we calculate rates of functional cohesion and functional equivalence for each pair of languages. From rates of how individuals adopt and abandon coding languages over time, we calculate measures of complementary diffusion and substitutive diffusion for each pair of languages relative to one another. Consistent with the principle of relatedness, network regression techniques (MR-QAP) reveal strong evidence that functional cohesion positively predicts complementary diffusion. We also find limited evidence that functional equivalence predicts substitutive (competitive) diffusion. Results support the broader finding that functional dependencies between diffusive processes will dictate how said processes spread relative to one another across a population of potential adopters.
Topological zero modes and bounded modes at smooth domain walls: Exact solutions and dualities
Authors: Marra Pasquale , Nigro Angela
Published: December 2024

Topology describes global quantities invariant under continuous deformations, such as the number of elementary excitations at a phase boundary, without detailing specifics. Conversely, differential laws are needed to understand the physical properties of these excitations, such as their localization and spatial behavior. For instance, topology mandates the existence of solitonic zero-energy modes at the domain walls between topologically inequivalent phases in topological insulators and superconductors. However, the spatial dependence of these modes is only known in the idealized (and unrealistic) case of a sharp domain wall. Here, we find the analytical solutions of these zero-modes by assuming a smooth and exponentially-confined domain wall. This allows us to characterize the zero-modes using a few length scales: the domain wall width, the exponential decay length, and oscillation wavelength. These quantities define distinct regimes: featureless modes with “no hair” at sharp domain walls, and nonfeatureless modes at smooth domain walls, respectively, with “short hair”, i.e., featureless at long distances, and “long hair”, i.e., nonfeatureless at all length scales. We thus establish a universal relation between the bulk excitation gap, decay rate, and oscillation momentum of the zero modes, which quantifies the bulk-boundary correspondence in terms of experimentally measurable physical quantities. Additionally, we reveal an unexpected duality between topological zero modes and Shockley modes, unifying the understanding of topologically-protected and nontopological boundary modes. These findings shed some new light on the localization properties of edge modes in topological insulators and Majorana zero modes in topological superconductors and on the differences and similarities between topological and nontopological zero modes in these systems.
Acute endothelial stresses identify microRNA let-7b-5p and non-coding SLC11A2 (NRAMP2/DMT1) exon as biomarkers that overlap with those detected in malignant and non-malignant diseases
Authors: Bielowka Adrianna M , Patel Dilip , Li Dongyang , Bernabeu-Herrero Maria E , Game Laurence , Aldred Micheala A , Mollet Inês G , Shovlin Claire L
Published: December 2024

Background

Disease biomarkers are often identified long after initiating pathologies, hampering mechanistic understanding and the development of preventative strategies. We hypothesized that aberrant cellular responses to normally-encountered stresses may be relevant to later disease states.

Aim

To model two under-explored acute cellular stresses for blood-exposed cells, and cross-reference to known biomarkers of disease.

Methods

Normal primary human endothelial cells (ECs) were treated for 1–6 h with cycloheximide (CHX) 100 μg/ml to inhibit protein translation and nonsense-mediated decay (modelling the integrated stress response), or 10 μmol/l ferric citrate (modelling diurnal variation in serum iron that can be augmented by treatments prescribed 8 million times/year in England). Directional whole transcriptome RNA-seq identified differentially expressed genes and micro(mi)RNAs. Customized novel scripts examined the expression of 517 225 exons to predict 1 h CHX-stabilized exons. Validations were by cel-miR-39-spiked qRT-PCR and RNA-seq in other EC types, peripheral blood mononuclear cells (PBMCs) and plasma.

Results

miRNAs fell transiently at 1 h after 10 μmol/l ferric citrate (P < 0.01), specifically in let-7 family member pre-miRNAs (‘let-7’, P < 0.05), where there was an accompanying differential 6 h increased expression of 570 let-7-target mRNAs identified through TargetScan (P < 0.0001). qRT-PCR and RNA-seq validations in other normal ECs, plasma and PBMCs confirmed up to 80% falls in pre-let-7b/let-7b-5p after 1 h iron, and exon 3B of the SLC11A2 (NRAMP2/DMT1)-encoded iron/copper transporter as a novel exon most consistently stabilized following 1 h treatment with CHX. Overlaps with disease biomarkers for cancer, growth retardation and multiple organ-specific diseases were identified.

Conclusions

Biomarkers for normal, acute cellular responses overlap with disease-state biomarkers, warranting further study.
A performance appraisal of the global survey and the fully automated methods of Forbush event identification and timing using small-amplitude Forbush decreases
Authors: Okike O , Menteso F M
Published: December 2024

Forbush decrease (FD), commonly defined as an abrupt reduction in the time-intensity flux of cosmic rays (CRs), is one of the long-investigated astrophysical phenomena. Though the subject has received considerable attention, the peculiarities of each event and different varieties of FDs still present them as the most spectacular and intractable CR intensity variations. Their unpredictable forms and diversities make accurate identification and precise timing of the events difficult. Event selection has remained predominantly manual up to the present era of high-speed and sophisticated computer software. Several catalogues appear in the literature. But no two event lists are comparable. The significant disparities among FD catalogues have led to many conflicting and controversial submissions. A comprehensive validation study of FD lists and their methods of selection are some of the important steps to settle or minimize the age-long disputes in the strongly disputed CR influence on space weather. Such a study will guarantee result reproducibility. Two comprehensive FD catalogues, prepared by the global survey method (GSM) and the recently developed fully automated method (FAM), are well suited for such a test. Our results show that the FAM is more efficient and accurate than the GSM. The presence of many other CR phenomena that constitute noise when timing/calculating the magnitude of small FDs requires both numerical filtering and harmonic analysis to handle. FAM is equipped with various subroutines that perform such analytical transformations and other rigorous analyses.
Varieties of capitalism and patient capital in developing and emerging economies: evidence from Kenya
Authors: Dafe Florence , Upadhyaya Radha
Published: December 2024

Patient capital (PC) has gained traction in discussions about how finance can better serve society. While PC is a central concept in comparative political economy (CPE), this literature has focused on advanced economies in conceptualizing PC and we know little about the conditions under which PC leads to positive outcomes. We extend the conceptualization of PC to enhance its relevance for developing and emerging economies (DEEs) and examine who provides it, when and how it leads to improvements in employment studying the case of Kenya. We find that the PC landscape in DEEs differs from the one in advanced economies and that institutions shape the extent to which capital is patient and has a positive impact on employment. Our analysis contributes to filling a gap in CPE on the role of PC in DEEs and speaks to broader debates about how to enhance the contribution of finance to society.
Does fragmented sleep mediate the relationship between deficits in sleep spindles and memory consolidation in schizophrenia?
Authors: Mylonas Dimitrios , Patel Rudra , Larson Olivia , Zhu Lin , Vangel Mark , Baxter Bryan , Manoach Dara S
Published: December 2024

Study Objectives

Sleep spindles, defining electroencephalographic oscillations of nonrapid eye movement (NREM) stage 2 sleep (N2), mediate sleep-dependent memory consolidation (SDMC). Spindles are also thought to protect sleep continuity by suppressing thalamocortical sensory relay. Schizophrenia is characterized by spindle deficits and a correlated reduction of SDMC. We investigated whether this relationship is mediated by sleep fragmentation.

Methods

We detected spindles (12–15 Hz) during N2 at central electrodes in overnight polysomnography records from 56 participants with chronic schizophrenia and 59 healthy controls. Our primary measures of sleep continuity were the sleep fragmentation index and, in a subset of the data, visually scored arousals. SDMC was measured as overnight improvement on the finger-tapping motor sequence task.

Results

Participants with schizophrenia showed reductions of both spindle density (#/min) and SDMC in the context of normal sleep continuity and architecture. Spindle density predicted SDMC in both groups. In contrast, neither increased sleep fragmentation nor arousals predicted lower spindle density or worse SDMC in either group.

Conclusions

Our findings fail to support the hypothesis that sleep fragmentation accounts for spindle deficits, impaired SDMC, or their relationship in individuals with chronic schizophrenia. Instead, our findings are consistent with the hypothesis that spindle deficits directly impair memory consolidation in schizophrenia. Since sleep continuity and architecture are intact in this population, research aimed at developing interventions should instead focus on understanding dysfunction within the thalamocortical-hippocampal circuitry that both generates spindles and synchronizes them with other NREM oscillations to mediate SDMC.
A Student Teaching Assistant Program for Diversity, Equity, Inclusion, and Antiracism Curricular Enhancement
Authors: Tran Meagan T. , Dillard Desireé Brionne , Abdelwahab Rewan M. , Abdulwadood Isra , Wu Sarah Y. , Adeleye Olufunmilola , Shoukry Mira M. , Alamy Nadine H. , Elegbede Audrey M. , Keddis Mira T. , Valencia Elizabeth M. , Atunah-Jay Sarah J.
Published: December 2024

Problem

In the United States, physician bias is exhibited early in medical training and contributes to systemic inequities within the field of medicine. A lack of diversity, equity, inclusion, and antiracism (DEI-AR) content within medical curricula drives critical gaps in knowledge and deficiencies when preparing medical students to serve patients of diverse backgrounds. At the Mayo Clinic Alix School of Medicine (MCASOM), student-led curricular reviews between 2017 to 2018 and 2020 to 2021 revealed opportunities to improve DEI-AR content within preclinical courses. Course directors expressed concern of limited expertise and time to enact effective changes.

Approach

The MCASOM DEI-AR teaching assistant (TA) program aims to curate a collaborative partnership between course directors and compensated student TAs to facilitate course enhancements responsive to the prior preclinical course review while centering standardized DEI-AR best practices.

Outcomes

As of January 2024, the program has engaged 14 TAs and partnered with 24 preclinical courses. Postcourse student evaluation responses were collected from 8 courses for 2021 to 2022 (before enhancements) and 2022 to 2023 (after enhancements). Student satisfaction with DEI-AR content is tracked through postcourse evaluations, with preliminary data demonstrating improvement after DEI-AR curricular integration (improvement of mean preenhancement and postenhancement scores of 3.81 to 4.05; t
12 = 1.79, P = .21). Qualitative student comments were sorted into general categories of positive, negative, or neutral, showing a 6.25% median increase in positive perception of DEI.

Next Steps

Plans for the MCASOM DEI-AR TA program include application of quality improvement strategies to improve program processes and outcomes. Development of a centralized dashboard that integrates course enhancement progress and ongoing feedback from evaluations is anticipated to facilitate this effort. The program additionally aims to develop partnerships with clinical clerkships, which would allow for a more comprehensive enhancement of the overall medical education experience related to DEI-AR.
Anesthetic Considerations and Blood Utilization for Placenta Accreta Spectrum
Authors: Hess Philip E. , Li Yunping
Published: December 2024

The anesthetic management of the patient with placenta accreta spectrum begins before surgery by assessing the patient and their comorbidities and providing psychological preparation for the perioperative period. Choosing neuraxial or general anesthesia for surgery balances the procedure’s clinical needs with the patient’s desires. Intraoperatively, management of homeostasis during acute blood loss requires assessments of central volume to avoid over-transfusion. Viscoelastic testing may be useful to assess coagulation to target the replacement of coagulation factors. Postoperative care is an essential continuum of the procedure, and the availability of bedside ultrasound can aid rapid decision-making.
Treatment of Meibomian Gland Dysfunction by Classical Eyelid Hygiene Measures With and Without Additional Lipid Substitution for Tear Film Stabilization
Authors: Weinstein Isabel , Kelava Augustin , Dausch Dieter , Seitz Berthold
Published: December 2024

Objective:

This study aimed to document the treatment success of eyelid hygiene with liposomal suspension using new diagnostic tools and to determine whether additional lipid substitution provided measurable benefits in meibomian gland dysfunction.

Methods:

A single-center controlled, partially single masked study was conducted. Group A used eyelid hygiene only, whereas group B additionally applied a liposomal eye spray. Subjective perception using the Ocular Surface Disease Index (OSDI) questionnaire, measurement of tear film osmolarity, noninvasive tear film break-up time, assessment of the lipid layer, meibography, inspection of lid margins, assessment of the meibomian glands, and measurement of matrix-metallopeptidase-9 were collected at baseline and after 12 weeks.

Results:

Eighty-two patients were included and randomized into two groups. Both groups showed a decrease in OSDI score (P<0.001), an increase in lipid layer thickness (P<0.001), significant improvement in the degree of loss of meibomian glands (P<0.001), in the damage pattern of the eyelid margins (P<0.001), in the quality of meibomian gland secretion, and in matrix-metallopeptidase-9 after 12 weeks.

Conclusions:

Our study confirms the success of treatment with eyelid hygiene measures using a liposomal suspension. The additional benefit of lipid substitution was not significant after 12 weeks of treatment.
Quality of Life Survey Using NEI VFQ-25 in Japanese Patients With Fuchs Endothelial Corneal Dystrophy
Authors: Yamada Keiko , Oie Yoshinori , Nishida Nozomi , Maeno Sayo , Kai Chifune , Kitao Masahiro , Kobayashi Reiko , Soma Takeshi , Koh Shizuka , Kawasaki Ryo , Nishida Kohji
Published: December 2024

Objectives:

To assess the quality of life in Japanese patients with Fuchs endothelial corneal dystrophy (FECD) using The National Eye Institute Visual Function Questionnaire.

Methods:

Here, 34 patients with FECD (FECD group) and 13 healthy individuals (control group) completed the National Eye Institute Visual Function Questionnaire Japanese version by interview format. The association between dominant eye corrected distance visual acuity and composite score (component 11) or subscales in the FECD group was evaluated using Spearman rank correlation coefficient.

Results:

The average age was 65.8±11.9 and 60.1±7.9 years in the FECD and control groups, respectively. Corrected distance visual acuity was significantly lower in the FECD group (0.021±0.21 logarithm of the minimum angle of resolution) than in the control group (−0.61±0.055 logarithm of the minimum angle of resolution) (P<0.0001). Composite scores were significantly lower in the FECD group (77.6±11.0) than in the control group (89.2±7.0) (P=0.0006). All subscale scores were lower in the FECD group, particularly for distance vision and mental health (81.4±13.1 and 84.0±15.6, respectively) than in the control group (90.7±12.0 and 95.7±5.7) (P=0.022 and P=0.0046, respectively). Corrected distance visual acuity in the dominant eye did not significantly correlate with composite scores or subscales in the FECD group.

Conclusions:

Quality of life is lower in patients with FECD than in healthy individuals, particularly regarding distance vision and mental health.
Social Risk Factors Associated With Microbial Keratitis
Authors: Lee Madeleine C. , Vogt Emily L. , Hicks Patrice M. , Pawar Mercy , Lu Ming-Chen , Niziol Leslie M. , Terek Danielle A. , Nallasamy Nambi , Hakim Farida E. , Woodward Maria A.
Published: December 2024

Purpose:

The objective of this study was to identify social risk factors (SRFs) that affect microbial keratitis (MK) care using the Penchansky–Thomas (P-T) health care access framework.

Methods:

This combined retrospective and prospective cohort study recruited participants with newly diagnosed MK at an academic medical center. Participant demographic information and SRFs were collected using in-person interviews and chart review. SRFs were categorized into P-T framework domains. Primary analysis included proportion of participants reporting SRFs, distribution of reported SRFs, and demographic differences associated with SRFs using descriptive statistics, chi-square, and two-sample t tests. A subgroup analysis for participants who were lost to follow-up (LTFU) was performed.

Results:

A total of 100 participants with MK were included in this study. Of the 100 participants, 60.0% reported at least 1 SRF affecting care, 42.0% reported ≥2 SRFs, and 12.0% reported ≥4 SRFs; 40.0% had no SRFs. More SRFs were reported for participants with lower income versus those with higher income ($25,000–$50,000 vs. $51,000–$100,000, P = 0.0363); there were no other demographic differences between groups. The most reported SRF was distance to appointment (45.0%). Accessibility was the most reported P-T domain (49.0%). Participants with LTFU, compared with those not LTFU, had more SRFs (100% vs. 52.4%, P = 0.0001) and reported a greater median number of SRFs (3.0 vs. 1.0, P < 0.0001).

Conclusions:

SRFs affected most patients with MK, most notably accessibility and affordability. Participants with lower income had more SRFs. SRFs are linked to patients being lost to follow-up care.
Assessing Corneal Tomographic Changes in Fuchs Endothelial Corneal Dystrophy Over 1 year: Scheimpflug Versus Anterior Segment Optical Coherence Tomography
Authors: Dorado Cortez Oliver , Fleischmann Caruso Delphine , Crouzet Emmanuel , Poinard Sylvain , Trone Marie-Caroline , Gain Philippe , Okumura Naoki , Koizumi Noriko , Thuret Gilles
Published: December 2024

Purpose:

The objective of this study was to compare the capacity of anterior segment optical coherence tomography (AS-OCT) and Scheimpflug camera in detecting tomographic changes over 1 year in a cohort of patients with Fuchs endothelial corneal dystrophy.

Methods:

We conducted a single-center prospective study which consisted of 2 identical visits spaced 1 year apart. At each visit, tomographic analyses were performed using Scheimpflug imaging (Pentacam HR, Oculus) and swept source AS-OCT (Casia SS-1000 Tomey). The resulting images were analyzed by 3 experienced independent observers. The main outcome was the agreement between the 2 devices for detecting subclinical corneal edema, as assessed using the interdevice reliability measured by the Cohen kappa coefficient. The criteria for subclinical edema were the presence of irregular isopachs, displacement of the thinnest point, and presence of posterior surface depression.

Results:

We analyzed 129 eyes of 81 patients with good quality images for both devices. The overall agreement between the 2 devices to detect subclinical edema was good, but the performance was significantly different for 2 parameters (thinnest point displacement and posterior depression). The interdevice reliability was 0.84 for the loss of parallel isopachs, 0.55 for the displacement of the thinnest point, and 0.40 for the focal posterior corneal surface depression.

Conclusions:

Corneal tomographic features of Fuchs endothelial corneal dystrophy can be easily quantified in clinical routine and clinical research by AS-OCT and Scheimpflug imaging, but both are not fully interchangeable. A longitudinal follow-up should always be done with the same device. Neither appears to be more sensitive than the other for detecting minimal changes over 12 months.
Prospective Study of Corneal Sensitivity in Patients Treated With Proton Therapy for Extraocular Tumors
Authors: Lebrun Florian , Thariat Juliette , Marty Pierre-Alban , Bailleul Helélène , Quintyn Jean-Claude
Published: December 2024

Introduction:

Several cases of radio-induced neurotrophic keratitis had been observed after proton therapy delivering a mean corneal dose of ≥50 GyRBE. We conducted a prospective exploratory study to assess corneal sensitivity in subsequent patients undergoing proton therapy for cephalic extraocular tumors.

Material and Methods:

Forty-three patients (85 eyes) treated with high-energy proton therapy were included in this prospective, single-center, observational cohort study. All patients had their corneal sensitivity measured using Cochet–Bonnet esthesiometer, before and average 6 months after irradiation. Ocular surface was clinically assessed for stromal opacity, corneal thinning, corneal perforation, superficial punctate keratitis graded according to Oxford classification, and tear break-up time. Cornea and extraocular sensitive innervation structures of cornea were contoured and their dose metrics assessed.

Results:

No severe corneal damage was detected. Corneal sensitivity, superficial punctate keratitis according to Oxford classification, and tear break-up time did not vary significantly after irradiation. The mean value of maximal dose to cornea and extraocular sensory innervation of cornea were 10.7 GyRBE and 42.0 GyRBE, respectively. Doses to cornea and its innervation structures were not associated with significant changes in corneal sensitivity (P = 0.423 and P = 0.614). A dose per fraction greater than 2 GyRBE was significantly associated (P = 0.033) with a decrease of corneal sensitivity after proton therapy.

Conclusions:

This pilot study showed no excess risk of damage to corneal sensitivity 6 months after proton therapy, as doses to the cornea could be minimized. However, based on prior neurotrophic keratitis cases for corneal doses above 50 GyRBE, further investigation is needed to establish the impact of high-dose proton therapy on corneal sensitivity.
The Effect of Trabeculectomy on Disc Tissue Blood Flow Across Quadrants in Open-Angle Glaucoma
Authors: Shimazaki Takeru , Nitta Eri , Nakano Yuki , Kobayashi Nobuko , Kojima Hirokazu , Hara Ayaka , Suzuma Kiyoshi
Published: December 2024

Précis:

Trabeculectomy increases tissue blood flow superior and temporal in the optic nerve head. Improvement of tissue blood flow superior and temporal in the optic nerve could be an indicator of the effectiveness of glaucoma treatment.

Purpose:

To investigate changes in tissue blood flow at the optic nerve head before and after trabeculectomy.

Methods:

This prospective study included 53 eyes who underwent trabeculectomy. The mean blur rate of the tissue area (MT) was determined using laser speckle flowgraphy (LSFG) preoperatively and 1 and 3 months postoperatively. MT, LSFG waveform parameters (blowout score [BOS] and resistivity index [RI]), intraocular pressure (IOP), and ocular perfusion pressure (OPP) were analyzed preoperatively and at 3 months postoperatively.

Results:

Postoperatively, IOP decreased (17.9±6.0 to 9.2±3.4 mmHg) and OPP increased (43.3±9.2 to 52.1±6.4 mmHg). As previously described, BOS increased (73.5±8.3 to 76.7±6.5; P<0.001) with an inverse correlation to IOP and in proportion with OPP; RI decreased (0.40±0.1 to 0.35±0.08; P<0.001) with an inverse correlation to OPP and in proportion to IOP. However, we found that MT increased significantly after surgery (7.9±2.2 to 8.8±2.2 AU; P=0.002) without significant association between MT and IOP or OPP. In the four quadrants of the optic nerve head (ONH), BOS significantly increased, while RI significantly decreased after surgery in all quadrants. On the other hand, MT significantly increased in the superior and temporal quadrants only.

Conclusions:

Blood flow increases in the superior and temporal of optic nerve head.
Isolated Hemifacial Spasm as the Presenting Sign of Cerebral Glioblastoma
Authors: Kakouri Agni , Chen Ying , McCulley Timothy J.
Published: December 2024

The authors report a rare case of a 58-year-old female with mild right-sided hemifacial spasms and eyelid myokymia and a concomitant high-grade glial mass. This report outlines the clinical presentation, diagnostic approach, and management of right hemifacial spasms and eyelid myokymia. The patient had a 5-month history of gradually worsening right hemifacial spams accompanied by mild right lower eyelid twitching. Given the persistence and exacerbation of these symptoms, alongside episodes of dysphagia, an MRI was performed. Imaging revealed a heterogeneous, peripherally enhancing mass with central necrosis at the lateral aspect of the left precentral gyrus and posterior aspect of the left middle and inferior frontal gyri consistent with high-grade glial mass. The patient subsequently underwent an awake craniotomy with resection of a temporal lobe tumor. These initial episodes of isolated facial spasms may be attributed to epilepsia partialis continua, often indicative of subcortical lesions that can compress the motor cortex. Eyelid myokymia and hemifacial spasms, though common, present significant diagnostic and management challenges. Due to high rate of underdiagnosis or misdiagnosis of these conditions, increased clinical awareness and knowledge are essential for effective patient management.
Transitioning to oral therapy compared to IV in Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis
Authors: Salma Omme , Samee Mohammed Abdul , Mustafa Muhammad Saqlain , Haseeb Abdul , Ho Wing Lam , Chan Hin Ming , Pons Andrea Gómez , Shafique Muhammad Ashir , Ali Syed Muhammad Sinaan , Raheem Abdul , Fadlalla Ahmad Tagwa Kalool
Published: December 2024

Background and Objective:

Staphylococcus aureus bloodstream infections pose a significant threat to public health and necessitate substantial healthcare resources. The optimal antimicrobial therapy for these infections remains a subject of debate. This systematic review and meta-analysis evaluated the efficacy and safety of early transition to oral antimicrobial therapy compared with continued intravenous (IV) therapy in patients with MRSA and MSSA bloodstream infections.

Method:

A PRISMA-guided systematic review and meta-analysis compared the early transition from intravenous to oral antibiotics with continued intravenous therapy in patients with S. aureus infections, utilizing relevant studies from the PubMed, Embase, Scopus, and Web of Science databases from August 2003 to June 2024.

Results:

This meta-analysis of 11 studies (N = 54–220, primarily male, age: mid-30s to early 70s) revealed a 71.6% higher risk of all-cause mortality for patients transitioned to early oral therapy than for those who continued IV therapy (RR: 1.716; 95% CI: 1.039–2.836; P = 0.035; I2 = 44%). Treatment failure, rehospitalization rates, adverse events, and hospital stay lengths did not differ significantly between groups.

Conclusion:

Early oral antimicrobial therapy for S. aureus bloodstream infections significantly reduces mortality compared to prolonged intravenous treatment, without increasing the incidence of adverse events or the risk of rehospitalization, suggesting its safety and efficacy as an alternative therapeutic approach; however, further randomized controlled trials are necessary to corroborate these findings.
The niosomal nelarabine as a promising nano combination for retinoblastoma treatment: an in vitro study—experimental research
Authors: Tohidian Mobina , Esmaeil Nafiseh , Soleimani Mitra , Khanehzad Maryam , Naderi Majd Amir H. , Zarinfard Giti
Published: December 2024

Introduction:

Retinoblastoma (RB), the most commonly occurring intraocular malignancy among children globally, represents 3% of childhood cancers. In the current study, the authors aim to evaluate the effectiveness of a new formulation of nelarabine (niosomal nelarabine) on RB cancer cells.

Methods:

Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) characterized the physical properties of nelarabine nanoparticles. After cultivation of the Y79 cell line, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to determine IC50 of niosomal nelarabine (Nio-Nelarobine) and also the cytotoxicity of Nio-Nelarobine and doxorubicin against Y79 cell line was investigated. The level of apoptosis was assessed by flow cytometry in selected groups. Also, the PTEN/AKT/FOXO1 gene expression level was measured using qRT-PCR.

Results:

Y79 cell lines were treated with Nio-Nelarobine and doxorubicin. The treatment resulted in a dose-dependent inhibition of Y79 cell viability. However, Nio-Nelarobine showed a higher inhibitory activity with a diameter of about 167 nm. Both Nio-Nelarobine and doxorubicin induced apoptosis in cells, but Nio-Nelarobine treatment resulted in a higher number of apoptotic cells than doxorubicin treatment. The qRT-PCR results showed that the treatment with Nio-Nelarobine and doxorubicin led to an increase in the expression of PTEN and FOXO1 genes, while decreasing the expression of the AKT gene. Furthermore, the statistical significance of these results was higher in the Nio-Nelarobine group than in the doxorubicin group.

Conclusions:

Nio-Nelarobine may be a functional therapeutic combination for RB treatment. Further experimental and preclinical investigations are necessary to verify this impact in greater detail.
Multicenter Randomised Controlled Trial of Single versus Double Venous Outflow Reconstruction in Right lobe Living Donor Liver Transplantation- Venous Outflow in Liver Transplantation (VOLT) Trial
Authors: Reddy Mettu Srinivas , Koneti Akshadhar J. , Chaudhary Abhideep , Rammohan Ashwin , Yelakanti Raghavendra Babu , Mallick Shweta , Patcha Rajanikanth , Singh Vipin Pal , Krishnan Satish Kumar , Kumar Niteen , Gopal Prasanna V. , Rela Mohamed , Sudhindran Surendran
Published: December 2024

Objective:

To compare early patency and outcomes of single outflow (SOT) and double outflow (DOT) reconstruction in right lobe living donor liver transplantation (RtLDLT) in a multicenter open-labelled randomized controlled trial.

Summary Background Data:

Optimum graft venous outflow is a key factor in determining outcomes of RtLDLT. There is no data directly comparing SOT and DOT technique of graft outflow reconstruction.

Methods:

Adult patients undergoing RtLDLT needing anterior sector vein (ASV) reconstruction were enrolled. Prosthetic graft was used to create a neo-middle hepatic vein (neoMHV). Web-based permuted block randomization was used to allocate patients to SOT or DOT (1:1) prior to graft implantation. Primary endpoint was neoMHV patency upto 6 weeks. Secondary endpoints were post-operative morbidity and survival. Intention-to-treat and as-treated analyses are reported.

Results:

Five centers randomized 219 patients to SOT (n=110) or DOT (n=109). Both groups were similar in baseline characteristics. SOT had better neoMHV patency at 2 weeks (92.5% vs. 82.9%, P=0.032), 4 weeks (84% vs. 69%, P=0.011) but not at 6 weeks (69.5% vs. 59.2%,P=0.124). Cox- proportional hazards analysis revealed DOT (HR- 1.56 (95%ci=1.02,2.4); P=0.041) and use of Dacron graft (HR-2.83(95% ci=1.16,6.94), P=0.023) as independent risk factors for neoMHV thrombosis. SOT was associated with better in-hospital survival (97.3% vs. 90.8%; P=0.044) but similar one-year survival (89% vs. 85%, P=0.340). SOT was associated with improved survival in patients who developed early allograft dysfunction or needed re-operation.

Conclusions:

SOT has better early neoMHV patency than DOT and may be associated with better early survival.
Crocus sativus (saffron) adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled trial
Authors: Mazhar Siamand , Shamabadi Ahmad , Kazemzadeh Kimia , Farahvash Mohammad Aidin , Heidari Dalfard Atiye , Fallahpour Bita , Khodaei Ardakani Mohammad-Reza , Akhondzadeh Shahin
Published: December 2024

Current treatments for schizophrenia encounter resistance, limited efficacy, and limiting complications, necessitating novel approaches. The effects of saffron on negative symptoms were investigated as it has shown neuroprotective and antipsychotic properties. Fifty-six clinically stable chronic schizophrenic outpatients were equally assigned to saffron 15 mg q12hr or placebo groups while continuing risperidone. The Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia-related symptoms in weeks 4 and 8. Also, the patients were assessed for the Hamilton depression rating scale (HDRS) and adverse effects. The baseline characteristics of the groups were comparable (Ps > 0.05). There were significant time-treatment interaction effects on negative (

= 0.137), general psychopathology (

= 0.193), and total (

= 0.113) PANSS scores. Affirmatively, their reductions were significantly greater in the saffron group until weeks 4 (Cohen’s ds = 0.922, 0.898, and 0.759, respectively) and 8 (Cohen’s ds = 0.850, 1.047, and 0.705, respectively). Regarding the negative symptoms, a better 25% response rate was obtained in the saffron group until the endpoint (P = 0.003). The HDRS scores, extrapyramidal symptom rating scale scores, and side effect frequencies were comparable between the groups (Ps > 0.05). Saffron was beneficial for primary negative symptoms of chronic schizophrenia in a safe and tolerable manner. It also outperformed placebo in improving general psychopathology and total symptoms.
Analysing public goods games using reinforcement learning: effect of increasing group size on cooperation
Authors: Tamura Kazuhiro , Morita Satoru
Published: December 2024

Electricity competition, restrictions on carbon dioxide (CO2) emissions and arm races between nations are examples of social dilemmas within human society. In the presence of social dilemmas, rational choice in game theory leads to the avoidance of cooperative behaviour owing to its cost. However, in experiments using public goods games that simulate social dilemmas, humans have often exhibited cooperative behaviour that deviates from individual rationality. Despite extensive research, the alignment between human cooperative behaviour and game theory predictions remains inconsistent. This study proposes an alternative approach to solve this problem. We used Q-learning, a form of artificial intelligence that mimics decision-making processes of humans who do not possess the rationality assumed in game theory. This study explores the potential for cooperation by varying the number of participants in public goods games using deep Q-learning. The simulations demonstrate that agents with Q-learning can acquire cooperative behaviour similar to that of humans. Moreover, we found that cooperation is more likely to occur as the group size increases. These results support and reinforce existing experiments involving humans. In addition, they have potential applications for creating cooperation without sanctions.
Inter-call intervals, but not call durations, adhere to Menzerath’s Law in the submissive vocal bouts of meerkats
Authors: Watson Stuart Kyle , Zali Mara , Falk Nikola , Widmer Paul , Manser Marta B
Published: December 2024

Diverse information encoding systems, including human language, the vocal and gestural systems of non-human animals and the structure of DNA and proteins, have been found to conform to ‘Menzerath’s Law’—a negative relationship between the number of units composing a sequence, and the size of those units. Here, we test for the presence of Menzerath’s Law in the vocal bouts produced in a submissive context by meerkats (
Suricata suricatta
). Using a suite of Bayesian mixed effects models, we examined 1676 vocal bouts produced by 89 wild meerkats, ranging from 1 to 590 calls in length, to determine whether the number of calls composing each bout had a negative relationship with the duration of those calls or their inter-call intervals. In contradiction to Menzerath’s Law, we found that the duration of vocalizations had a positive relationship with the number of calls in a bout. However, the duration of intervals between calls did have a negative relationship with bout size. Moreover, both calls and intervals had longer durations the closer they were positioned to the end of the bout. These findings highlight the multi-faceted ways in which efficiency trade-offs can occur in the vocal repertoires of non-human animals, shaping variability in the production of signal forms.
Topological features in continuum mechanics: from simple to complex bodies
Authors: Mariano Paolo Maria
Published: December 2024

Topological features have a ubiquitous influence on the behaviour of condensed matter, from the qualitative analysis of fluids flows to the classification of defects in simple and complex solids. We review results concerning the incidence of topological features on foundational aspects of the mechanics of simple and complex bodies, with particular emphasis on the mechanics of defects. Pertinent to this last issue, unusual concepts such as the relative power or the structure invariance of the Clausius–Duhem inequality under diffeomorphism-based observer changes are discussed.