bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of connected conduit on pumping-induced seawater intrusion in a coastal karst aquifer
Authors: Wu Xiujie , Xu Zhongyuan , Xu Zexuan , Hu Bill X.
Published: September 2023

Introduction

Coastal karst aquifers face the risk of seawater intrusion due to groundwater development. Based on the conceptualization of Woodville Karst Plain (WKP), this study investigates the effect of karst conduit and pumping conditions on the aquifer vulnerability and pumping security.

Methods

According to the purposes of this study, two cases are considered: one with conduit and one without. Salinization levels are compared between two cases, considering pumping rates ranging from 50 to 200 m3/day and various pumping locations throughout the on-shore region.

Results

The results reveal that the aquifer with conduit is more susceptible to seawater intrusion at low pumping rates, whereas both scenarios experience significant salinization at high pumping rates. Specifically, in the non-conduit case, contamination is most prevalent when wells are located in the middle of the aquifer, while in the conduit case, pumping from inland areas poses high vulnerability. Moreover, conduit case and non-conduit case display different regions for pumping clean water. At low pumping rates, both cases show saline water being pumped from wells near the shore, and clean water is obtained from inland wells. At high pumping rates, the non-conduit case allows for clean water extraction from wells situated further inland, while in the conduit case, no wells within the entire aquifer are deemed safe.

Discussion

The analysis and findings of this study offer valuable insights for the management of groundwater in coastal karst aquifers, encompassing vulnerability assessment, selection of pumping locations, and determination of pumping rates.
A review on the mechanical metamaterials and their applications in the field of biomedical engineering
Authors: Wang Hao , Lyu Yongtao , Bosiakov Sergei , Zhu Hanxing , Ren Yuanfei
Published: September 2023

Metamaterials are a group of materials/structures which possess novel behaviors not existing in nature. The metamaterials include electromagnetic metamaterials, acoustic metamaterials, mechanical metamaterials, etc. among which the mechanical metamaterials are widely used in the field of biomedical engineering. The mechanical metamaterials are the ones that possess special mechanical behaviors, e.g., lightweight, negative Poisson’s ratio, etc. In this paper, the commonly used mechanical metamaterials are reviewed and their applications in the field of biomedical engineering, especially in bone tissue engineering and vascular stent, are discussed. Finally, the future perspectives of this field are given.
Experimental study of high temperature on the shear properties of early-age concrete
Authors: Li Meilin , Gan Fei
Published: September 2023

Fire accidents happen randomly which may occur in the construction of concrete buildings. In this study, the effects of high temperature and curing ages on shear properties of early-age concrete were experimentally studied. The pore structure of early-age concrete before heating, after heating, and re-curing after heating were examined through nuclear magnetic resonance and scanning electron microscope tests. Experimental results reveal that high temperature treatment of early-age concrete multiplies the number of pores but has little influence on the change of pore size distribution, while the re-curing treatment reduces pore size but has little influence on the change of pore numbers. Under the same exposed temperature, the shear strength of concretes before heating, after heating, and re-curing after heating increases gradually with curing ages. For concretes with certain curing ages, the shear strength increases first and then decreases with the exposed high temperature. While the cohesion and internal friction angle show a negative relationship with elevated temperature. The research can provide base data for buildings encountering fire accidents.
Implications of immersive technologies in healthcare sector and its built environment
Authors: Yang Eunsil
Published: September 2023

Objectives

This research focuses on how built environment experts can contribute to the MXR-enabled digital innovation as part of the multidisciplinary team effort to ensure post-pandemic resilience in healthcare built environment. The goal of this research is to help healthcare providers, built environment experts, and policy makers respectively: (1) Advocate the benefits of MXR for innovating health and social care; (2) Spark debate across networks of expertise to create health-promoting environment; and (3) Understand the overriding priorities in making effective pathways to the implementation of MXR.

Methods

To highlight the novelty of this research, the study relies on two qualitative methodologies: exploratory literature review and semi-structured interviews. Based on the evaluation of prior works and cross-national case studies, hypotheses are formulated from three arenas: (1) Cross-sectional Initiatives for Post-pandemic Resilience; (2) Interoperability and Usability of Next-gen Medicines; and (3) Metaverse and New Forms of Value in Future Healthcare Ecosystems. To verify those hypotheses, empirical findings are derived from in-depth interviews with nine key informants.

Results

The main findings are summarized under the following three themes: (1) Synergism between Architecture and Technology; (2) Patient Empowerment and Staff Support; and (3) Scalable Health and Wellbeing in Non-hospital and Therapeutic Settings. Firstly, both built environment and healthcare sectors can benefit from the various capabilities of MXR through cross-sectional initiatives, evidence-based practices, and participatory approaches. Secondly, a confluence of knowledge and methods of HCI and HBI can increase the interoperability and usability of MXR for the patient-centered and value-based healthcare models. Thirdly, the MXR-enabled technological regime will largely affect the new forms of value in healthcare premises by fostering more decentralized, preventive, and therapeutic characteristics in the future healthcare ecosystems.

Conclusion

Whether it's virtual or physical, our healthcare systems have placed great emphasis on the rigor of evidence-based approach linking health outcome to a clinical environment. Henceforth, built environment experts should seek closer ties with the MXR ecosystems for the co-production of scalable health and wellbeing in non-hospital and therapeutic settings. Ultimately, this is to improve resource efficiency in the healthcare sector while considering the transition of health resources towards in silico status by increasing the implementation of MXR.
Advances in the application of CRISPR-Cas technology in rapid detection of pathogen nucleic acid
Authors: Li Xiaoping , Zhong Jiaye , Li Haoyu , Qiao Yinbiao , Mao Xiaolei , Fan Huayan , Zhong Yiwu , Imani Saber , Zheng Shusen , Li Jianhui
Published: September 2023

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) are widely used as gene editing tools in biology, microbiology, and other fields. CRISPR is composed of highly conserved repetitive sequences and spacer sequences in tandem. The spacer sequence has homology with foreign nucleic acids such as viruses and plasmids; Cas effector proteins have endonucleases, and become a hotspot in the field of molecular diagnosis because they recognize and cut specific DNA or RNA sequences. Researchers have developed many diagnostic platforms with high sensitivity, high specificity, and low cost by using Cas proteins (Cas9, Cas12, Cas13, Cas14, etc.) in combination with signal amplification and transformation technologies (fluorescence method, lateral flow technology, etc.), providing a new way for rapid detection of pathogen nucleic acid. This paper introduces the biological mechanism and classification of CRISPR-Cas technology, summarizes the existing rapid detection technology for pathogen nucleic acid based on the trans cleavage activity of Cas, describes its characteristics, functions, and application scenarios, and prospects the future application of this technology.
Feasibility, usability, and acceptance of “Brain-IT”—A newly developed exergame-based training concept for the secondary prevention of mild neurocognitive disorder: a pilot randomized controlled trial
Authors: Manser Patrick , Poikonen Hanna , de Bruin Eling D.
Published: September 2023

Background

Exergames provide a promising new approach to implement simultaneous motor–cognitive training, which may support preventing the decline in cognitive functioning in older adults who have a mild neurocognitive disorder (mNCD).

Objectives

To evaluate feasibility, system usability, and acceptance of “Brain-IT”, a newly developed training concept combining exergame-based motor-cognitive training and heart rate variability (HRV) guided resonance breathing for the secondary prevention of mNCD.

Methods

A pilot randomized controlled trial (RCT) with an allocation ratio of 2:1 (i.e., intervention:control) was conducted. The control group proceeded with usual care. The intervention group performed a 12-week training according to the “Brain-IT” training concept implemented with the “Senso Flex” (Dividat AG) exergaming system in addition to usual care. Feasibility and usability outcomes were analyzed using descriptive statistics. User acceptance was analyzed qualitatively and using Friedman analysis of variance (ANOVA), as well as Wilcoxon signed-rank tests.

Results

Eighteen participants (77.3 ± 9.8 years; 44.4% females) were included. On average, we recruited 2.2 participants per month, and 35.3% of the individuals contacted were included. The intervention group had an attrition rate of 20% and mean adherence and compliance rates of 85.0 and 84.1%, respectively. The mean system usability score, measured with the system usability scale, was 71.7. High levels of exergame enjoyment, an increase in exergame enjoyment, and internalization of training motivation with large effect sizes (p = 0.03, r = 0.75 and p = 0.03, r = 0.74, respectively), as well as acceptable perceived usefulness, were observed. Preliminary data on the effects of the “Brain-IT” training are promising.

Conclusion

The feasibility and usability of the “Brain-IT” training are acceptable. However, frequent occurrences of technical problems and difficulties in using the exergame training system were identified as barriers to performing the “Brain-IT” training. To optimize feasibility, either improvements or alternative solutions are required in the hardware and software of the exergame used to implement the “Brain-IT” training. The “Brain-IT” training itself was well-accepted by older adults who have mNCD. Therefore, the effectiveness of the “Brain-IT” training concept should be investigated in future studies.

Trial registration

clinicaltrials.gov/ct2/show/NCT04996654.
Directly reprogrammed fragile X syndrome dorsal forebrain precursor cells generate cortical neurons exhibiting impaired neuronal maturation
Authors: Edwards Nicole , Combrinck Catharina , McCaughey-Chapman Amy , Connor Bronwen
Published: September 2023

Introduction

The neurodevelopmental disorder fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability associated with autism spectrum disorder. Inaccessibility to developing human brain cells is a major barrier to studying FXS. Direct-to-neural precursor reprogramming provides a unique platform to investigate the developmental profile of FXS-associated phenotypes throughout neural precursor and neuron generation, at a temporal resolution not afforded by post-mortem tissue and in a patient-specific context not represented in rodent models. Direct reprogramming also circumvents the protracted culture times and low efficiency of current induced pluripotent stem cell strategies.

Methods

We have developed a chemically modified mRNA (cmRNA) -based direct reprogramming protocol to generate dorsal forebrain precursors (hiDFPs) from FXS patient-derived fibroblasts, with subsequent differentiation to glutamatergic cortical neurons and astrocytes.

Results

We observed differential expression of mature neuronal markers suggesting impaired neuronal development and maturation in FXS- hiDFP-derived neurons compared to controls. FXS- hiDFP-derived cortical neurons exhibited dendritic growth and arborization deficits characterized by reduced neurite length and branching consistent with impaired neuronal maturation. Furthermore, FXS- hiDFP-derived neurons exhibited a significant decrease in the density of pre- and post- synaptic proteins and reduced glutamate-induced calcium activity, suggesting impaired excitatory synapse development and functional maturation. We also observed a reduced yield of FXS- hiDFP-derived neurons with a significant increase in FXS-affected astrocytes.

Discussion

This study represents the first reported derivation of FXS-affected cortical neurons following direct reprogramming of patient fibroblasts to dorsal forebrain precursors and subsequently neurons that recapitulate the key molecular hallmarks of FXS as it occurs in human tissue. We propose that direct to hiDFP reprogramming provides a unique platform for further study into the pathogenesis of FXS as well as the identification and screening of new drug targets for the treatment of FXS.
Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study
Authors: Lee Chan-Hyuk , Chung Jong-Won , Guk Hyung Seok , Hong Ji Man , Rosenson Robert S. , Jeong Seul-Ki
Published: September 2023

Purpose

Lenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism.

Methods

In this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge.

Results

A total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11–1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15–1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs.

Conclusion

Cerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction.
Association between serum sodium levels within 24 h of admission and all-cause mortality in critically ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database
Authors: Liu Junjie , Li Jianmin , Zhang Qiuhua , Wang Liang , Wang Yichao , Zhang Jingxi , Zhang Junwei
Published: September 2023

Objective

The study aimed to evaluate the relationship between serum sodium and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage.

Methods

This is a retrospective investigation of critically ill non-traumatic patients with subarachnoid hemorrhage (SAH) utilizing the MIMIC-IV database. We collected the serum sodium levels at admission and determined the all-cause death rates for the ICU and hospital. We employed a multivariate Cox proportional hazard regression model and Kaplan–Meier survival curve analysis to ascertain the relationship between serum sodium and all-cause mortality. In order to evaluate the consistency of correlations, interaction and subgroup analyses were also conducted.

Results

A total of 864 patients with non-traumatic SAH were included in this study. All-cause mortality in the ICU and hospital was 32.6% (282/864) and 19.2% (166/864), respectively. Sodium levels at ICU admission showed a statistically significant J-shaped non-linear relationship with ICU and hospital mortality (non-linear P-value < 0.05, total P-value < 0.001) with an inflection point of ~141 mmol/L, suggesting that mortality was higher than normal serum sodium levels in hypernatremic patients. Multivariate analysis after adjusting for potential confounders showed that high serum sodium levels (≥145 mmol/L) were associated with an increased risk of all-cause mortality in the ICU and hospital compared with normal serum sodium levels (135–145 mmol/L), [hazard ratio (HR) = 1.47, 95% CI: 1.07–2.01, P = 0.017] and (HR = 2.26, 95% CI:1.54–3.32, P < 0.001). Similarly, Kaplan–Meier (K-M) survival curves showed lower survival in patients with high serum sodium levels. Stratified analysis further showed that the association between higher serum sodium levels and hospital all-cause mortality was stronger in patients aged < 60 years with a hospital stay of <7 days.

Conclusion

High serum sodium levels upon ICU admission are related to higher ICU and hospital all-cause mortality in patients with non-traumatic SAH. A new reference is offered for control strategies to correct serum sodium levels.
Headache among combat-exposed veterans and service members and its relation to mild traumatic brain injury history and other factors: a LIMBIC-CENC study
Authors: Walker William C. , Clark Sarah W. , Eppich Kaleb , Wilde Elisabeth A. , Martin Aaron M. , Allen Chelsea M. , Cortez Melissa M. , Pugh Mary Jo , Walton Samuel R. , Kenney Kimbra
Published: September 2023

Background

Headache (HA) is a common persistent complaint following mild traumatic brain injury (mTBI), but the association with remote mTBI is not well established, and risk factors are understudied.

Objective

Determine the relationship of mTBI history and other factors with HA prevalence and impact among combat-exposed current and former service members (SMs).

Design

Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium—Chronic Effects of Neurotrauma Consortium prospective longitudinal study.

Methods

We examined the association of lifetime mTBI history, demographic, military, medical and psychosocial factors with (1) HA prevalence (“lately, have you experienced headaches?”) using logistic regression and (2) HA burden via the Headache Impact Test-6 (HIT-6) using linear regression. Each lifetime mTBI was categorized by mechanism (blast-related or not) and setting (combat deployed or not). Participants with non-credible symptom reporting were excluded, leaving N = 1,685 of whom 81% had positive mTBI histories.

Results

At a median 10 years since last mTBI, mTBI positive participants had higher HA prevalence (69% overall, 78% if 3 or more mTBIs) and greater HA burden (67% substantial/severe impact) than non-TBI controls (46% prevalence, 54% substantial/severe impact). In covariate-adjusted analysis, HA prevalence was higher with greater number of blast-related mTBIs (OR 1.81; 95% CI 1.48, 2.23), non-blast mTBIs while deployed (OR 1.42; 95% CI 1.14, 1.79), or non-blast mTBIs when not deployed (OR 1.23; 95% CI 1.02, 1.49). HA impact was only higher with blast-related mTBIs. Female identity, younger age, PTSD symptoms, and subjective sleep quality showed effects in both prevalence and impact models, with the largest mean HIT-6 elevation for PTSD symptoms. Additionally, combat deployment duration and depression symptoms were factors for HA prevalence, and Black race and Hispanic/Latino ethnicity were factors for HA impact. In sensitivity analyses, time since last mTBI and early HA onset were both non-significant.

Conclusion

The prevalence of HA symptoms among formerly combat-deployed veterans and SMs is higher with more lifetime mTBIs regardless of how remote. Blast-related mTBI raises the risk the most and is uniquely associated with elevated HA burden. Other demographic and potentially modifiable risk factors were identified that may inform clinical care.
Case report: Retrograde endovascular recanalization of vertebral artery occlusion with non-tapered stump via the deep cervical collateral
Authors: Qiu Han , Kang Zhiming , Sun Dong , Mei Bin , Zhang Junjian
Published: September 2023

Introduction

Vertebral artery (VA) occlusive disease is the major cause of posterior circulation ischemic stroke. Endovascular recanalization has been reported as a feasible treatment for patients with symptomatic VA occlusion refractory to optimal medical therapy. However, VA occlusion with non-tapered stump exhibits a low technique success rate when treated by antegrade endovascular therapy because of increased difficulty in passing the guidewire into the occluded segment. Herein, we presented a novel endovascular approach to recanalize chronically occluded VA with a non-tapered stump using a retrograde method via the deep cervical collateral, which has not been reported before.

Case presentation

The present case was a patient with VA ostial occlusion with non-tapered stump and distal severe stenosis of the left VA who had recurrent posterior circulation transit ischemic attacks under optimal medical therapy. CT angiography demonstrated proximal non-tapered occlusion and distal severe stenosis of the left VA, and that the right VA did not converge with the left VA into basilar artery. Endovascular treatment was recommended and performed on this patient. However, antegrade endovascular recanalization of the left VA origin occlusion failed because the micro guidewire was unable to traverse the occluded segment. Fortunately, robust collateral from the deep cervical artery to the V3 segment of the left VA developed, in which we advanced the micro guidewire to the V3 segment of the left VA and reversely passed the micro guidewire through the occluded segment. Then, the occlusion and stenosis of the left VA were successfully resolved with angioplasty and stenting. After the procedure, the patient reported no neurological symptoms under medical therapy during 3-month follow-up.

Conclusion

Antegrade endovascular recanalization of VA occlusion with a non-tapered stump is a challenge. The retrograde endovascular method via the cervical collateral may be an alternative for this type of VA occlusion, which requires further exploration.
Exploring the relationship between home environmental characteristics and restorative effect through neural activities
Authors: Shen Tao , Wang JunYao , Fu Yingfan
Published: September 2023

As society and the economy have advanced, the focus of architectural and interior environment design has shifted from practicality to eliciting emotional responses, such as stimulating environments and innovative inclusive designs. Of particular interest is the home environment, as it is best suited for achieving restorative effects, leading to a debate between interior qualities and restorative impact. This study explored the relationships between home characteristics, restorative potential, and neural activities using the Neu-VR. The results of the regression analysis revealed statistically significant relationships between interior properties and restorative potential. We examined each potential characteristic of the home environment that could have a restorative impact and elucidated the environmental characteristics that should be emphasized in residential interior design. These findings contribute evidence-based knowledge for designing therapeutic indoor environments. And combining different restorative potential environments with neural activity, discussed new neuro activities which may predict restorativeness, decoded the new indicators of neuro activity for environmental design.
MR imaging and outcome in neonatal HIBD models are correlated with sex: the value of diffusion tensor MR imaging and diffusion kurtosis MR imaging
Authors: Bao Jieaoxue , Zhang Xiaoan , Zhao Xin
Published: September 2023

Objective

Hypoxic-ischemic encephalopathy can lead to lifelong morbidity and premature death in full-term newborns. Here, we aimed to determine the efficacy of diffusion kurtosis (DK) [mean kurtosis (MK)] and diffusion tensor (DT) [fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD)] parameters for the early diagnosis of early brain histopathological changes and the prediction of neurodegenerative events in a full-term neonatal hypoxic-ischemic brain injury (HIBD) rat model.

Methods

The HIBD model was generated in postnatal day 7 Sprague-Dawley rats to assess the changes in DK and DT parameters in 10 specific brain structural regions involving the gray matter, white matter, and limbic system during acute (12 h) and subacute (3 d and 5 d) phases after hypoxic ischemia (HI), which were validated against histology. Sensory and cognitive parameters were assessed by the open field, novel object recognition, elevated plus maze, and CatWalk tests.

Results

Repeated-measures ANOVA revealed that specific brain structures showed similar trends to the lesion, and the temporal pattern of MK was substantially more varied than DT parameters, particularly in the deep gray matter. The change rate of MK in the acute phase (12 h) was significantly higher than that of DT parameters. We noted a delayed pseudo-normalization for MK. Additionally, MD, AD, and RD showed more pronounced differences between males and females after HI compared to MK, which was confirmed in behavioral tests. HI females exhibited anxiolytic hyperactivity-like baseline behavior, while the memory ability of HI males was affected in the novel object recognition test. CatWalk assessments revealed chronic deficits in limb gait parameters, particularly the left front paw and right hind paw, as well as poorer performance in HI males than HI females.

Conclusions

Our results suggested that DK and DT parameters were complementary in the immature brain and provided great value in assessing early tissue microstructural changes and predicting long-term neurobehavioral deficits, highlighting their ability to detect both acute and long-term changes. Thus, the various diffusion coefficient parameters estimated by the DKI model are powerful tools for early HIBD diagnosis and prognosis assessment, thus providing an experimental and theoretical basis for clinical treatment.
The association between epilepsy and COVID-19: analysis based on Mendelian randomization and FUMA
Authors: You Mingyao , Yuan Ping , Li Liangqian , Li Baoduo , Peng Zijun , Xu Hongbei
Published: September 2023

Objective

A multitude of observational studies have underscored a substantial comorbidity between COVID-19 and epilepsy. This study was aimed at establishing a conclusive causal link between these two conditions.

Methods

We employed Mendelian randomization (MR) to evaluate the causal link between COVID-19 and epilepsy, as well as its focal and generalized subtypes. The GWAS for epilepsy and its subtypes database were abstracted from both FinnGen consortium and ILAE. Additionally, we leveraged functional mapping and annotation (FUMA) to integrate information from genome-wide association studies (GWAS) results.

Results

The MR analyses revealed that genetic liability to COVID-19 infection conferred a causal effect on epilepsy [FinnGen: OR: 1.5306; 95% confidence interval (CI): 1.1676–2.0062, PFDR (false discovery rate) = 0.0076; ILAE: OR: 1.3440; 95% CI: 1.0235–1.7649, PFDR = 0.0429], and generalized epilepsy (FinnGen: OR: 2.1155; 95% CI: 1.1734–3.8139, PFDR = 0.0327; ILAE: OR: 1.1245; 95% CI: 1.0444–1.2108, PFDR = 0.0114). Genetic liability to COVID-19 hospitalization conferred a causal effect on epilepsy (FinnGen: OR: 1.0934; 95% CI: 1.0097–1.1841, PFDR = 0.0422; ILAE: OR: 1.7381; 95% CI: 1.0467–2.8862, PFDR = 0.0451), focal epilepsy (ILAE: OR: 1.7549; 95% CI: 1.1063–2.7838, PFDR = 0.0338), and generalized epilepsy (ILAE: OR: 1.1827; 95% CI: 1.0215–1.3693, PFDR = 0.0406). Genetic liability to COVID-19 severity conferred a causal effect on epilepsy (FinnGen consortium: OR: 1.2454; 95% CI: 1.0850–1.4295, PFDR = 0.0162; ILAE: OR: 1.2724; 95% CI: 1.0347–1.5647, PFDR = 0.0403), focal epilepsy (FinnGen: OR: 1.6818; 95% CI: 1.1478–2.4642, PFDR = 0.0231; ILAE: OR: 1.6598; 95% CI: 1.2572–2.1914, PFDR = 0.0054), and generalized epilepsy (FinnGen: OR: 1.1486; 95% CI: 1.0274–1.2842, PFDR = 0.0335; ILAE: OR: 1.0439; 95% CI: 1.0159–1.0728, PFDR = 0.0086). In contrast, no causal linkage of epilepsy on COVID-19 was observed. Further, FUMA analysis identified six overlapping genes, including SMEK2, PNPT1, EFEMP1, CCDC85A, VRK2, and BCL11A, shared between COVID-19 and epilepsy. Tissue-specific expression analyses revealed that the disease-gene associations of COVID-19 were significantly enriched in lung, ovary, and spleen tissue compartments, while being significantly enriched in brain tissue for epilepsy.

Conclusion

Our study demonstrates that COVID-19 can be a contributing factor to epilepsy, but we found no evidence that epilepsy contributes to COVID-19.
Application of Entity-BERT model based on neuroscience and brain-like cognition in electronic medical record entity recognition
Authors: Lu Weijia , Jiang Jiehui , Shi Yaxiang , Zhong Xiaowei , Gu Jun , Huangfu Lixia , Gong Ming
Published: September 2023

Introduction

In the medical field, electronic medical records contain a large amount of textual information, and the unstructured nature of this information makes data extraction and analysis challenging. Therefore, automatic extraction of entity information from electronic medical records has become a significant issue in the healthcare domain.

Methods

To address this problem, this paper proposes a deep learning-based entity information extraction model called Entity-BERT. The model aims to leverage the powerful feature extraction capabilities of deep learning and the pre-training language representation learning of BERT(Bidirectional Encoder Representations from Transformers), enabling it to automatically learn and recognize various entity types in medical electronic records, including medical terminologies, disease names, drug information, and more, providing more effective support for medical research and clinical practices. The Entity-BERT model utilizes a multi-layer neural network and cross-attention mechanism to process and fuse information at different levels and types, resembling the hierarchical and distributed processing of the human brain. Additionally, the model employs pre-trained language and sequence models to process and learn textual data, sharing similarities with the language processing and semantic understanding of the human brain. Furthermore, the Entity-BERT model can capture contextual information and long-term dependencies, combining the cross-attention mechanism to handle the complex and diverse language expressions in electronic medical records, resembling the information processing method of the human brain in many aspects. Additionally, exploring how to utilize competitive learning, adaptive regulation, and synaptic plasticity to optimize the model's prediction results, automatically adjust its parameters, and achieve adaptive learning and dynamic adjustments from the perspective of neuroscience and brain-like cognition is of interest.

Results and discussion

Experimental results demonstrate that the Entity-BERT model achieves outstanding performance in entity recognition tasks within electronic medical records, surpassing other existing entity recognition models. This research not only provides more efficient and accurate natural language processing technology for the medical and health field but also introduces new ideas and directions for the design and optimization of deep learning models.
A role for pathogenic autoantibodies in small fiber neuropathy?
Authors: Daifallah Omar , Farah Adham , Dawes John M.
Published: September 2023

The immune system has a role in neuropathic pain which includes autoimmune mechanisms (e.g., autoantibodies). Clinical studies have identified a number of conditions where neuropathic pain is common and that are associated with autoantibodies targeting antigens within the nervous system. Interestingly sensory symptoms can be relieved with immunotherapies or plasma exchange, suggesting that pain in these patients is antibody-mediated. Recent preclinical studies have directly addressed this. For example, passive transfer of CASPR2 autoantibodies from patients cause increased pain sensitivity and enhanced sensory neuron excitability in mice confirming pathogenicity and demonstrating that patient autoantibodies are a mechanism to cause neuropathic pain. Small fiber neuropathy (SFN) exclusively affects small sensory fibers (typically nociceptors) and is characterized by severe neuropathic pain. Known causes include diabetes, B12 deficiency and rare variants in sodium channel genes, although around 50% of cases are idiopathic. SFN is associated with autoimmune conditions such as Sjorgen’s syndrome, Sarcoidosis and Celiac disease and immunotherapy in the form of Intravenous immunoglobulin (IVIG) has proved an effective treatment. Autoantibodies have been identified and, in some cases, passive transfer of SFN patient IgG in mice can recapitulate neuropathic pain-like behavior. Here we will discuss clinical and preclinical data relating to the idea that pathogenic autoantibodies contribute to SNF. We discuss putative pathogenic antibodies, cellular targets and the molecular mechanisms by which they cause sensory neuron damage and the development of neuropathic pain. Finally, we will comment on future directions which may provide further insights into the mechanisms underlying SFN in patients.
Quality of dietary macronutrients is associated with glycemic outcomes in adults with cystic fibrosis
Authors: Daley Tanicia C. , Cousineau Benjamin A. , Nesbeth Paula-Dene C. , Ivie Elizabeth A. , Bellissimo Moriah P. , Easley Kirk A. , Vellanki Priyathama , Vos Miriam B. , Hunt William R. , Stecenko Arlene A. , Ziegler Thomas R. , Alvarez Jessica A.
Published: September 2023

Objective

Poor diet quality contributes to metabolic dysfunction. This study aimed to gain a greater understanding of the relationship between dietary macronutrient quality and glucose homeostasis in adults with cystic fibrosis (CF).

Design

This was a cross-sectional study of N = 27 adults with CF with glucose tolerance ranging from normal (n = 9) to prediabetes (n = 6) to being classified as having cystic fibrosis-related diabetes (CFRD, n = 12). Fasted blood was collected for analysis of glucose, insulin, and C-peptide. Insulin resistance was assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). Subjects without known CFRD also underwent a 2-h oral glucose tolerance test. Three-day food records were used to assess macronutrient sources. Dietary variables were adjusted for energy intake. Statistical analyses included ANOVA, Spearman correlations, and multiple linear regression.

Results

Individuals with CFRD consumed less total fat and monounsaturated fatty acids (MUFA) compared to those with normal glucose tolerance (p < 0.05). In Spearman correlation analyses, dietary glycemic load was inversely associated with C-peptide (rho = −0.28, p = 0.05). Total dietary fat, MUFA, and polyunsaturated fatty acids (PUFA) were positively associated with C-peptide (rho = 0.39–0.41, all p < 0.05). Plant protein intake was inversely related to HOMA2-IR (rho = −0.28, p = 0.048). Associations remained significant after adjustment for age and sex.

Discussion

Improvements in diet quality are needed in people with CF. This study suggests that higher unsaturated dietary fat, higher plant protein, and higher carbohydrate quality were associated with better glucose tolerance indicators in adults with CF. Larger, prospective studies in individuals with CF are needed to determine the impact of diet quality on the development of CFRD.
Prediction of adenocarcinoma and squamous carcinoma based on CT perfusion parameters of brain metastases from lung cancer: a pilot study
Authors: Jiang Chuncheng , Liu Xin , Qu Qianqian , Jiang Zhonghua , Wang Yunqiang
Published: September 2023

Objectives

Predicting pathological types in patients with adenocarcinoma and squamous carcinoma using CT perfusion imaging parameters based on brain metastasis lesions from lung cancer.

Methods

We retrospectively studied adenocarcinoma and squamous carcinoma patients with brain metastases who received treatment and had been pathologically tested in our hospital from 2019 to 2021. CT perfusion images of the brain were used to segment enhancing tumors and peritumoral edema and to extract CT perfusion parameters. The most relevant perfusion parameters were identified to classify the pathological types. Of the 45 patients in the study cohort (mean age 65.64 ± 10.08 years; M:F = 24:21), 16 were found to have squamous cell carcinoma. Twenty patients were with brain metastases only, and 25 patients were found to have multiple organ metastases in addition to brain metastases. After admission, all patients were subjected to the CT perfusion imaging examination. Differences in CT perfusion parameters between adenocarcinoma and squamous carcinoma were analyzed. The receiver operating characteristic (ROC) curves were used to predict the types of pathology of the patients.

Results

Among the perfusion parameters, cerebral blood flow (CBF) and mean transit time (MTT) were significantly different between the two lung cancers (adenocarcinoma vs. squamous cell carcinoma: p < 0.001, p = 0.012.). Gender and tumor location were identified as the clinical predictive factors. For the classification of adenocarcinoma and squamous carcinoma, the model combined with CBF and clinical predictive factors showed better performance [area under the curve (AUC): 0.918, 95% confidence interval (CI): 0.797–0.979). The multiple organ metastasis model showed better performance than the brain metastasis alone model in subgroup analyses (AUC: 0.958, 95% CI: 0.794–0.999).

Conclusion

CT perfusion parameter analysis of brain metastases in patients with primary lung cancer could be used to classify adenocarcinoma and squamous carcinoma.
Third-line treatment options in metastatic pancreatic cancer patients: a real-world study
Authors: Lu Hong-Rui , Zhu Peng-Fei , Deng Ya-Ya , Chen Zhe-Ling , Yang Liu
Published: September 2023

Background

There are currently no standard therapy regimens for the third-line treatment of metastatic pancreatic cancer (mPC) patients. The aim of the present study was to compare the efficacy and safety of different third-line therapy regimens for mPC in the real-world.

Methods

This study retrospectively analyzed mPC patients admitted to Zhejiang Provincial People’s Hospital between June 2013 and January 2023. All patients’ diagnoses were pathologically confirmed and their treatment was continued after the second-line therapy failed. The primary study endpoints included median overall survival (mOS), median progression-free survival (mPFS), and disease control rate (DCR).

Results

A total of 72 patients were enrolled in the study. Of these, 36 patients received chemotherapy alone, 16 received chemotherapy combined with targeted therapy or immunotherapy, 14 received chemotherapy-free antitumor therapy, and six received palliative care. The mPFS value for these groups was 4.40 months, 5.20 months, 2.33 months, and 0.80 months, respectively. The mOS value was 6.90 months, 5.90 months, 3.33 months, and 0.80 months, respectively. The DCR was 33.4%, 31.3%, 21.4%, and 0.0%, respectively. Overall, there were significant differences in prognosis between the palliative care group and the other treatment groups (mOS, P < 0.001; mPFS P < 0.001; DCR, P < 0.001). The differences among the mPFS, mOS, and DCR for different antitumor therapy regimens were not statistically significant. Compared to the chemotherapy alone group, the chemotherapy combined with targeted therapy or immunotherapy group experienced more adverse events (100% vs. 75.0%; P = 0.002). Chemotherapy combined with targeted therapy or immunotherapy was associated with a higher risk of grade 3/4 hyperaminotransferemia compared to chemotherapy alone (31.3% vs. 0.0%; P = 0.020) and chemotherapy-free antitumor therapy (31.3% vs. 0.0%; P = 0.020).

Conclusions

Third-line antitumor therapy can prolong the survival time of patients with mPC. Targeted therapy or immunotherapy failed to further improve survival benefits based on chemotherapy results. Patients who underwent the third-line treatment with good physical status and family history of cancer were independent prognostic factors for longer mOS. The sequencing of fluorouracil and gemcitabine in the front-line therapy did not affect third-line mOS.
Case Report: Stereotactic body radiation treatment for immunotherapy escaped oligometastatic progression in cutaneous melanoma and merkel cell carcinoma
Authors: Khaddour Karam , Zhou Alice , Butt Omar , Huang Jiayi , Ansstas George
Published: September 2023

Oligometastatic progression represents a unique manifestation of tumor immune-escape that can lead to disease progression during treatment with immune checkpoint inhibitor (ICI). The diagnosis and further optimal management of oligometastatic progression through ICI remains unclear. Diagnostic challenges include practical limitations due to the anatomical sites of oligometastatic progression, such as the para-aortic region, where traditional tissue biopsy carries high risk, and circulating-tumor DNA (ctDNA) could aid in diagnosis and disease monitoring as a supplement to surveillance imaging. In this report, we describe two cases of one patient with metastatic melanoma and the other with metastatic Merkel cell carcinoma (MCC) who were treated with ICI and later developed localized resistance due to oligometastatic progression. We further highlight our experience using stereotactic body radiation therapy (SBRT) as a salvage approach to treat the oligometastatic progression. In addition, we describe the temporal and dynamic relationship of circulating-tumor DNA (ctDNA) prior to, during and after SBRT, which highly suggested the diagnosis without obtaining a histological specimen. Our cases highlight a potential role for SBRT in the management of oligometastatic progression. However, large prospective trials are essential to confirm the utility of this approach.
Exploring factors influencing skin incision to the delivery time and their impact on neonatal outcomes among emergency cesarean deliveries indicated for non-reassured fetal heart rate status
Authors: Zewdu Dereje , Tantu Temesgen , Degemu Fikretsion , Hawlet Michael , Dejene Nitsuh , Asefa Emebet
Published: September 2023

Background

The time interval between skin incision and delivery (S-D) is crucial in determining neonatal outcome; however, little is known about the influencing factors and their impact on neonatal outcomes, particularly among emergency cesarean deliveries (ECD) indicated for fetal distress. This study investigated the factors influencing S-D time and their effects on neonatal outcomes among mothers who underwent ECD for non-reassured fetal heart rate status.

Methods

This retrospective cohort study involved 426 mother-infant pairs over four years. We retrieved data from the medical records, including baseline characteristics, perioperative data, and neonatal outcomes. Using multivariable logistic regression analysis, adjusted odd ratios, and a 95% confidence interval, potential factors influencing S-D time and their impacts on neonatal outcomes were assessed. A p-value of less than 0.05 was considered statistically significant.

Results

Factors independently associated with longer S-D time (>8 min) were mothers who had previous CD (AOR 5.9: 95% CI 2.2–16.1), obese mothers (AOR 6.2: 95% CI 1.6–24.5), and the second stage of labor (AOR 5.3: 95% CI 2.4–11.7). Adverse neonatal outcomes, including a 5th minute Apgar score of less than 7, the need for NICU admission, and neonatal death, were significantly higher in the longer S-D time interval [47.7% vs. 8.9%; p-value 0.001], [21.9% vs. 9.1%; p-value 0.001], and [32% vs. 11.8%; p-value = 0.004], respectively. Obese mothers and the second stage of labor, but not previous CD, adversely impact neonatal outcomes.

Conclusion

Longer S-D times are significantly associated with adverse neonatal outcomes. Factors that prolong the time interval between skin incision and delivery may or may not necessarily be associated with adverse neonatal outcomes. Considering surgical techniques that shorten the incision-delivery time and preparation for advanced neonatal care for risky subjects would help reduce detrimental neonatal consequences.
A proposed model of xeno-keratoplasty using 3D printing and decellularization
Authors: Wang Xinyu , Elbahrawi Rawdah Taha , Abdukadir Azhar Mohamud , Ali Zehara Mohammed , Chan Vincent , Corridon Peter R.
Published: September 2023

Corneal opacity is a leading cause of vision impairment and suffering worldwide. Transplantation can effectively restore vision and reduce chronic discomfort. However, there is a considerable shortage of viable corneal graft tissues. Tissue engineering may address this issue by advancing xeno-keratoplasty as a viable alternative to conventional keratoplasty. In particular, livestock decellularization strategies offer the potential to generate bioartificial ocular prosthetics in sufficient supply to match existing and projected needs. To this end, we have examined the best practices and characterizations that have supported the current state-of-the-art driving preclinical and clinical applications. Identifying the challenges that delimit activities to supplement the donor corneal pool derived from acellular scaffolds allowed us to hypothesize a model for keratoprosthesis applications derived from livestock combining 3D printing and decellularization.
Evaluation of anti-cancer effects of carnosine and melittin-loaded niosomes in MCF-7 and MDA-MB-231 breast cancer cells
Authors: Hussein Mohamed M. A. , Abdelfattah-Hassan Ahmed , Eldoumani Haitham , Essawi Walaa M. , Alsahli Tariq G. , Alharbi Khalid Saad , Alzarea Sami I. , Al-Hejaili Hassan Y. , Gaafar Sara F.
Published: September 2023

Background: We investigated the anti-cancer effect of carnosine-loaded niosomes (Car-NIO) and melittin-loaded niosomes (Mel-NIO) with olaparib in breast cancer cell lines (MCF-7 and MDA-MB-231).

Methods: The thin film method was used for preparing the niosomes and characterized in terms of morphology, size, and polydispersity index (PDI). We further evaluated the impact of these peptides on breast cancer cells viability, RT-qPCR assays, malondialdehyde (MDA) activity, and cell cycle progression, to determine if these are linked to carnosine and melittin’s anti-proliferative properties.

Results: Car-NIO and Mel-NIO in vitro study inhibited cancer cell viability. They have also upregulated the expression of protein 53 (P53), BCL2-Associated X Protein (Bax), caspase-9, caspase-3, programmed cell death 4 (PDCD4), and Forkhead box O3 (FOXO3), while downregulated the expression of B-cell lymphoma 2 (Bcl2), poly (ADP-ribose) polymerase (PARP 1), and MicroRNA-183 (miRNA-183). The MCF-7 cells were arrested at the G2/M phase in Car-NIO, on the other hand, the MDA-MB-231 cells were arrested at the S phase. While the Mel-NIO and olaparib arrested the MCF-7 and MDA-MB-231 cells at the G0/1 phase.

Conclusion: Our study successfully declared that Mel-NIO had more anti-cancer effects than Car-NIO in both MCF-7 and MDA-MB-231 breast cancer cells.