bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-assembled Janus base nanotubes: chemistry and applications
Authors: Zhang Wuxia , Chen Yupeng
Published: January 2024

Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and π-π stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while π-π interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water.
Freeboard life-cycle benefit-cost analysis of a rental single-family residence for landlord, tenant, and insurer
Authors: Gnan Ehab , Mostafiz Rubayet Bin , Rahim Md Adilur , Friedland Carol J. , Rohli Robert V. , Taghinezhad Arash , Al Assi Ayat
Published: January 2024

Flood risk to single-family rental housing remains poorly understood, leaving a large and increasing population underinformed to protect themselves, including regarding insurance. This research introduces a life-cycle benefit-cost analysis for the landlord, tenant, and insurer [i.e., (U.S.) National Flood Insurance Program (NFIP)] to optimize freeboard [i.e., additional first-floor height above the base flood elevation (BFE)] selection for a rental single-family home. Flood insurance premium; apportioned flood risk among the landlord, tenant, and NFIP by insurance coverage and deductible; rental loss; moving and displacement costs; freeboard construction cost; and rent increase upon freeboard implementation are considered in estimating net benefit (NB) by freeboard. For a 2,500 square-foot case study home in Metairie, Louisiana, a two-foot freeboard optimizes the combined savings for landlord and tenant, with joint life-cycle NB of $23,658 and $14,978, for a 3% and 7% real discount rate, respectively. Any freeboard up to 2.5 feet benefits the tenant and NFIP, while the landlord benefits for freeboards up to 4.0 feet. Collectively, results suggest that at the time of construction, even minimal freeboard provides substantial savings for the landlord, tenant, and NFIP. The research provides actionable information, supporting the decision-making process for landlords, tenants, and others, thereby enhancing investment and occupation decisions.
Deep learning-based classification of eye diseases using Convolutional Neural Network for OCT images
Authors: Elkholy Mohamed , Marzouk Marwa A.
Published: January 2024

Deep learning shows promising results in extracting useful information from medical images. The proposed work applies a Convolutional Neural Network (CNN) on retinal images to extract features that allow early detection of ophthalmic diseases. Early disease diagnosis is critical to retinal treatment. Any damage that occurs to retinal tissues that cannot be recovered can result in permanent degradation or even complete loss of sight. The proposed deep-learning algorithm detects three different diseases from features extracted from Optical Coherence Tomography (OCT) images. The deep-learning algorithm uses CNN to classify OCT images into four categories. The four categories are Normal retina, Diabetic Macular Edema (DME), Choroidal Neovascular Membranes (CNM), and Age-related Macular Degeneration (AMD). The proposed work uses publicly available OCT retinal images as a dataset. The experimental results show significant enhancement in classification accuracy while detecting the features of the three listed diseases.
Association between triglyceride glucose index and adverse clinical outcomes in patients with acute myocardial infarction and LDL-C≤1.8 mmol/L who underwent percutaneous coronary intervention: a prospective cohort study
Authors: Zhao Hong-wei , Wang Yong , Wang Cheng-fu , Meng Qing-kun
Published: January 2024

Background

Recently, the triglyceride glucose (TyG) index has emerged as a reliable predictive indicator for adverse outcomes of cardiovascular disease. However, the roles of the TyG index in patients with acute myocardial infarction (AMI) and low-density lipoprotein cholesterol (LDL-C)≤1.8 mmol/L after percutaneous coronary intervention (PCI) remain unclear.

Methods

A total of 599 patients diagnosed with AMI and LDL-C ≤ 1.8 mmol/L at the 1-month follow-up after PCI were consecutively enrolled between January 2017 and January 2020. The patients were subsequently divided into three groups based on tertiles of the TyG index. The parameters, including the TyG index, were compared to explore the risk factors associated with major adverse cardiovascular and cerebrovascular events (MACCEs) during the 1-year follow-up.

Results

Sixty-nine patients (11.5%) with 90 MACCEs were recorded during the 1-year follow up, including 13 patients (8.6%) in the Tertile 1 group, 36 (12.0%) in the Tertile 2 group, and 20 (13.4%) in the Tertile 3 group. Patients with a higher TyG index had a significantly increased incidence of MACCEs compared to those with a lower TyG index (22.1% vs. 14.0% vs. 9.9%, p=0.010). Kaplan–Meier analysis demonstrated that patients with a higher TyG index had a significantly lower probability of survival without MACCEs. Furthermore, a binary logistic regression model indicated that the TyG index was the only independent predictor for MACCEs in these patients.

Conclusion

A higher TyG index was associated with a higher incidence of MACCEs in patients with AMI and well-controlled LDL-C levels after PCI. This suggests that the TyG index can serve as a predictive indicator for adverse cardiovascular outcomes in these patients.
Hypoparathyroidism following total thyroidectomy: high rates at a low-volume, non-parathyroid institution
Authors: Abood Ali , Ovesen Therese , Rolighed Lars , Triponez Frédéric , Vestergaard Peter
Published: January 2024

Background

Hypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be highly dependent on the surgical experience. In this study we aimed to evaluate the rate of hypoparathyroidism following primary total thyroidectomy at a low-volume institution that only performs thyroid surgery and does not have any experience with parathyroid surgery.

Methods

Retrospective cohort study. All patients undergoing primary total thyroidectomy at the ENT-Department, Goedstrup Hospital, Denmark, over a 5-year period (2016-2020) were identified through the procedure codes for total thyroidectomy. Medical records, pathology reports, biochemical and medical histories were fully assessed for each patient. The primary endpoint was the rate of hypoparathyroidism- both immediate and permanent. Secondary outcomes were parathyroid gland identification rates, rates of parathyroid gland autotransplantation, and rates of inadvertent parathyroid gland excision.

Results

A total of 89 patients were included in the final analysis. A total of 33 patients (37.1%) experienced immediate hypoparathyroidism following surgery, while 30 patients (33.7%) still were on active vitamin D two months postoperatively. One year following surgery, 28 patients (31.5%) were still on active vitamin D and were considered as having permanent hypoparathyroidism. Sixty-one percent of the parathyroid glands were identified intraoperatively, and 19% of the patients experienced parathyroid autotransplantation. Inadvertent parathyroid gland excision occurred for 21% of the patients and was associated with a significantly increased risk of permanent hypoparathyroidism (RR = 2.99; 95% CI: 1.36 – 6.62, p = 0.005).

Conclusion

Both transient and permanent hypoparathyroidism following total thyroidectomy at a low-volume, non-parathyroid institution occurred with much higher frequencies than previously reported. The elevated rates were most likely due to the low-volume, non-parathyroid nature of the surgeons which in part was mirrored in low parathyroid gland identifications rates, and high rates of autotransplantation and inadvertent parathyroid gland excision.
Optimal design of solar/wind/battery and EV fed UPQC for power quality and power flow management using enhanced most valuable player algorithm
Authors: Srilakshmi Koganti , Gaddameedhi Sravanthy , Borra Subba Reddy , Balachandran Praveen Kumar , Reddy Ganesh Prasad , Palanivelu Aravindhababu , Selvarajan Shitharth
Published: January 2024

The behavior and performance of distribution systems have been significantly impacted by the presence of solar and wind based renewable energy sources (RES) and battery energy storage systems (BESS) based electric vehicle (EV) charging stations. This work designs the Unified Power Quality Conditioner (UPQC) through optimal selection of the active filter and PID Controller (PIDC) parameters using the enhanced most valuable player algorithm (EMVPA). The prime objective is to effectively address the power quality (PQ) challenges such as voltage distortions and total harmonic distortions (THD) of a distribution system integrated with UPQC, solar, wind, BESS and EV (U-SWBEV). The study also aims to manage the power flow between the RES, grid, EV, BESS, and consumer loads by artificial neuro-fuzzy interface system (ANFIS). Besides, this integration helps to have a reliable supply of electricity, efficient utilization of generated power, and effective fulfillment of the demand. The proposed scheme results in a THD of 4.5%, 2.26%, 4.09% and 3.98% for selected four distinct case studies with power factor to almost unity with an appropriate power sharing. Therefore, the study and results indicate that the ANFIS based power flow management with optimal design of UPQC addresses the PQ challenges and achieves the appropriate and effective sharing of power.
A dynamic hierarchical partition method for optimal power balance of urban power system with high renewables
Authors: Ye Jun , Li Xianfeng , He Yibing , Lin Rouyu , Tian Wei
Published: January 2024

With the development of new urban power systems, the centralized-distributed hierarchical partition management architecture has gradually become a consensus. Existing hierarchical partition methods are mostly static. And if the partition results are determined, it will remain unchanged for a relatively long time. However, the new type power system experiences more frequent and larger fluctuations in power generation and load, requiring dynamic responses to the system’s real-time operation. In this case, traditional partition methods are no longer applicable, and new hierarchical partition methods for system operation need to be adopted. Therefore, this paper proposes a power balance mechanism of urban power system based on dynamic hierarchical partition method, including dynamic hierarchical partition method and corresponding decoupling power balance models. The former can continuously change the results of hierarchical partition according to the real-time state of the power system, so as to reduce the inter-regional liaison cost and improve the economy. The latter improves the independence of the region and the security of the power system through decoupling power balance. Eventually, the proposed method is validated with an modified Hawaii 37-node system.
Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria mitochondrial disorder: case report and literature review
Authors: Gurusamy Umamaheswaran , Ramadesikan Swetha , Marhabaie Mohammad , Colwell Caitlyn M. , Hunter Jesse M. , Leung Marco L. , Mardis Elaine R. , White Peter , Manickam Murugu , Wilson Richard K. , Koboldt Daniel C.
Published: January 2024

Background: Leigh syndrome is a rare, genetic, and severe mitochondrial disorder characterized by neuromuscular issues (ataxia, seizure, hypotonia, developmental delay, dystonia) and ocular abnormalities (nystagmus, atrophy, strabismus, ptosis). It is caused by pathogenic variants in either mitochondrial or nuclear DNA genes, with an estimated incidence rate of 1 per 40,000 live births.

Case presentation: Herein, we present an infant male with nystagmus, hypotonia, and developmental delay who carried a clinical diagnosis of Leigh-like syndrome. Cerebral magnetic resonance imaging changes further supported the clinical evidence of an underlying mitochondrial disorder, but extensive diagnostic testing was negative. Trio exome sequencing under a research protocol uncovered compound-heterozygous missense variants in the HTRA2 gene (MIM: #606441): NM_013247.5:c.1037A>T:(p.Glu346Val) (maternal) and NM_013247.5:c.1172T>A:(p.Val391Glu) (paternal). Both variants are absent from public databases, making them extremely rare in the population. The maternal variant is adjacent to an exon-intron boundary and predicted to disrupt splicing, while the paternal variant alters a highly conserved amino acid and is predicted to be damaging by nearly all in silico tools. Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria, type VIII (MGCA8), an extremely rare autosomal recessive disorder with fewer than ten families reported to date. Variant interpretation is challenging given the paucity of known disease-causing variants, and indeed we assess both paternal and maternal variants as Variants of Uncertain Significance under current American College of Medical Genetics guidelines. However, based on the inheritance pattern, suggestive evidence of pathogenicity, and significant clinical correlation with other reported MGCA8 patients, the clinical care team considers this a diagnostic result.

Conclusion: Our findings ended the diagnostic odyssey for this family and provide further insights into the genetic and clinical spectrum of this critically under-studied disorder.
Spatial gene expression profile of Wnt-signaling components in the murine enteric nervous system
Authors: Scharr Melanie , Hirt Bernhard , Neckel Peter H.
Published: January 2024

Introduction

Wnt-signaling is a key regulator of stem cell homeostasis, extensively studied in the intestinal crypt and other metazoan tissues. Yet, there is hardly any data available on the presence of Wnt-signaling components in the adult enteric nervous system (ENS) in vivo.

Methods

Therefore, we employed RNAscope HiPlex-assay, a novel and more sensitive in situ hybridization technology. By amplifying target specific signals, this technique enables the detection of low abundance, tightly regulated RNA content as is the case for Wnt-signaling components. Additionally, we compared our data to previously published physiological single cell RNA and RiboTag-based RNA sequencing analyses of enteric gliosis using data-mining approaches.

Results

Our descriptive analysis shows that several components of the multidi-mensional regulatory network of the Wnt-signaling pathway are present in the murine ENS. The transport and secretion protein for Wnt-ligands Wntless as well as canonical (Wnt3a and Wnt2b) and non-canonical Wnt-ligands (Wnt5a, Wnt7a, Wnt8b and Wnt11) are detectable within submucosal and myenteric plexus. Further, corresponding Frizzled receptors (Fzd1, Fzd3, Fzd6, and Fzd7) and regulatory signaling mediators like R-Spondin/DKK ligands are present in the ENS of the small and large intestine. Further, data mining approaches revealed, that several Wnt-related molecules are expressed by enteric glial cell clusters and are dynamically regulated during the inflammatory manifestation of enteric gliosis.

Discussion

Our results suggest, that canonical and non-canonical Wnt-signaling has a much broader impact on the mature ENS and its cellular homeostasis in health and inflammation, than previously anticipated.
The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment
Authors: Dusoswa Sophie A. , Verhoeff Jan , van Asten Saskia , Lübbers Joyce , van den Braber Marlous , Peters Sophie , Abeln Sanne , Crommentuijn Matheus H.W. , Wesseling Pieter , Vandertop William Peter , Twisk Jos W. R. , Würdinger Thomas , Noske David , van Kooyk Yvette , Garcia-Vallejo Juan J.
Published: January 2024

Background

Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.

Methods

High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses.

Results

Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells.

Conclusion

High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.
Atmospheric CO2 emissions and ocean acidification from bottom-trawling
Authors: Atwood Trisha B. , Romanou Anastasia , DeVries Tim , Lerner Paul E. , Mayorga Juan S. , Bradley Darcy , Cabral Reniel B. , Schmidt Gavin A. , Sala Enric
Published: January 2024

Trawling the seafloor can disturb carbon that took millennia to accumulate, but the fate of that carbon and its impact on climate and ecosystems remains unknown. Using satellite-inferred fishing events and carbon cycle models, we find that 55-60% of trawling-induced aqueous CO2 is released to the atmosphere over 7-9 years. Using recent estimates of bottom trawling’s impact on sedimentary carbon, we found that between 1996-2020 trawling could have released, at the global scale, up to 0.34-0.37 Pg CO2 yr-1 to the atmosphere, and locally altered water pH in some semi-enclosed and heavy trawled seas. Our results suggest that the management of bottom-trawling efforts could be an important climate solution.
CNT-doped transition metal carbide enables sensitive organic electrochemical transistor based carcinoembryonic antigen aptasensor towards precise lung cancer diagnosis
Authors: Zhang Yunzeng , Shen Changming , Tang Yan , Li Xiaofeng , Liu Dawei , Wei Ailin , Wang Cheng , Zhao Xiaogang
Published: January 2024

Effective detection of carcinoembryonic antigen (CEA) plays an important role in the diagnosis of lung cancer. Given the challenges posed by the low abundance and complexity of biosamples, it is urgent to develop sensitive, cost-effective and fast detection strategies. In this paper, a novel platform is developed using doped transition metal carbides as semiconductor materials for organic electrochemical transistor (OECT) aptamer-based sensors to satisfy sensitivity, specificity, rapidity, and low cost. A new material, CNT-doped MXene, was synthesized and utilized in the fabrication of CM-OECATs. The morphology and doping of CNT-doped MXene were validated effectively. 2.0 wt% CNT achieved maximum doping efficiency at transconductance (Gm) of 0.801 ms. Through systematic optimization of temperature, pH, aptamer concentration and incubation time, a wide detection range ranging from 0.1 pg/mL to 100 ng/mL was achieved, and the lower limit was 0.051 pg/mL. Favorable stability (0.819% decline), specificity and repeatability (RSD = 2.05%) were demonstrated. CM-OECATs effectively distinguished between 11 biosamples of lung cancer from 12 healthy controls (AUC = 0.9748, specificity = 0.9565, sensitivity = 0.9978) for the clinics. The test carried out in two batches gave p-values <0.05, indicating the effectiveness of the CM-OECATs in discriminating effectively. In addition, CM-OECATs demonstrated a favourable correlation in 25 clinical samples (y = 0.9782x + 0.7532, R2 = 0.9723). To sum up, an organic electrochemical transistor aptamer-based sensor based on CNT-doped MXene (CM-OECATs) is promising for future real-time monitoring in clinical settings, paving the way for an efficient, cost-effective and highly sensitive detection strategy.
Cooling enhancement for engine parts using jet impingement
Authors: Nasif G. , Shinneeb A.-M. , Balachandar R.
Published: January 2024

A computational study has been performed to evaluate the use of jet impingement for cooling applications in the automotive industry. The current study uses an entire internal combustion engine cylinder with its components as a computational domain. An unsteady numerical solution for the Navier-Stokes equations was carried out using Improved Delayed Detached Eddy Simulation (IDDES). The volume of fluid approach is proposed to track and locate the liquid jet surface that is in contact with the air. The conjugate heat transfer approach is used to link the heat transfer solution between the fluid and the solid. The boundary conditions that are employed in the study are provided from lab experiments and one-dimensional simulations. The cooling jet in this study targets the hottest region in the piston, i.e., the region underneath the exhaust valve. Three nozzle sizes with flows at different Reynolds numbers are chosen to examine the thermal characteristics of the cooling jet. The computational study reveals that for a specific Reynolds number, the smaller diameter nozzle provides the highest heat transfer coefficient around the impingement point. The maximum relative velocity location at the impingement point slightly leads the location of the maximum Nusselt number. The maximum temperature in the piston decreases by 7% to 11% as the nozzle diameter changes from 1.0 to 3.0 mm for a jet Reynolds number of 4,500. If a correct selection is made for the nozzle size, the cooling jet can be efficiently used to reduce the temperature and alleviate the thermal stresses in the piston in the region underneath the exhaust valve where the maximum temperature occurs.
Microcurrent therapy as the nonpharmacological new protocol against Alzheimer’s disease
Authors: Kim Eun Ho , Lee Won Seok , Lee Jae Hee , Kwon Dong Rak
Published: January 2024

Introduction

Alzheimer’s disease (AD) poses an increasing global health challenge and is marked by gradual cognitive deterioration, memory impairment, and neuroinflammation. Innovative therapeutic approaches as non-pharmacological protocol are urgently needed with side effect risk of drugs. Microcurrent therapy, a non-invasive modality involving low-level electrical currents, has emerged as a potential solution to address AD’s complex pathogenesis. This study investigates the optimal application of microcurrent therapy as a clinical protocol for AD, utilizing a comprehensive approach that integrates behavioral assessments and neuroinflammation evaluation in a mouse model of dementia.

Methods and results

The results reveal that microcurrent therapy holds promise in ameliorating memory impairment and reducing neuroinflammation in AD. Behavioral assessments, including the Novel Object Recognition Test (NOR) and Radial Arm Maze Test (RAM), demonstrated improved cognitive function following microcurrent therapy. Furthermore, microcurrent therapy inhibited expression of neuroinflammatory proteins, including ionized calcium binding adaptor molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) in current-treated group. Mechanistic insights suggest that microcurrent therapy may modulate neuroinflammation through the regulation of MAPK signaling pathways.

Conclusion

This study emphasizes the prospect of microcurrent therapy as a safe and efficacious non-pharmacological strategy for Alzheimer’s disease (AD), providing optimism to the countless individuals impacted by this debilitating ailment. These results contribute to the developments of an innovative clinical protocol for AD and recovery from neurological injury, underscoring the significance of investigating unconventional therapeutic approaches for addressing this complex condition.
MicroRNA profile of extracellular vesicles released by Müller glial cells
Authors: Lamb William D. B. , Eastlake Karen , Luis Joshua , Sharif Najam A. , Khaw Peng T. , Limb G. Astrid
Published: January 2024

Introduction

As with any other radial glia in the central nervous system, Müller glia derive from the same neuroepithelial precursors, perform similar functions, and exhibit neurogenic properties as radial glia in the brain. Müller glial cells retain progenitor-like characteristics in the adult human eye and can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via the secretion of nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) and proteins that induce phenotypic changes when internalised by recipient cells.

Methods

We conducted high-throughput sequencing to profile the microRNA signature of EV populations secreted by Müller glia in culture and used bioinformatics tools to evaluate their potential role in the neuroprotective signalling attributed to these cells.

Results

Sequencing of miRNA within Müller EV suggested enrichment with species associated with stem cells such as miR-21 and miR-16, as well as with miRNA previously found to play a role in diverse Müller cell functions in the retina: miR-9, miR-125b, and the let-7 family. A total of 51 miRNAs were found to be differentially enriched in EV compared to the whole cells from which EV originated. Bioinformatics analyses also indicated that preferential enrichment of species was demonstrated to regulate genes involved in cell proliferation and survival, including PTEN, the master inhibitor of the PI3K/AKT pathway.

Discussion

The results suggest that the release by Müller cells of miRNA-enriched EV abundant in species that regulate anti-apoptotic signalling networks is likely to represent a significant proportion of the neuroprotective effect observed after the transplantation of these cells into animal models of retinal ganglion cell (RGC) depletion. Future studies will seek to evaluate the modulation of putative genes as well as the activation of these pathways in in vitro and in vivo models following the internalisation of Müller-EV by target retinal neurons.
Information representation in an oscillating neural field model modulated by working memory signals
Authors: Nesse William H. , Clark Kelsey L. , Noudoost Behrad
Published: January 2024

We study how stimulus information can be represented in the dynamical signatures of an oscillatory model of neural activity—a model whose activity can be modulated by input akin to signals involved in working memory (WM). We developed a neural field model, tuned near an oscillatory instability, in which the WM-like input can modulate the frequency and amplitude of the oscillation. Our neural field model has a spatial-like domain in which an input that preferentially targets a point—a stimulus feature—on the domain will induce feature-specific activity changes. These feature-specific activity changes affect both the mean rate of spikes and the relative timing of spiking activity to the global field oscillation—the phase of the spiking activity. From these two dynamical signatures, we define both a spike rate code and an oscillatory phase code. We assess the performance of these two codes to discriminate stimulus features using an information-theoretic analysis. We show that global WM input modulations can enhance phase code discrimination while simultaneously reducing rate code discrimination. Moreover, we find that the phase code performance is roughly two orders of magnitude larger than that of the rate code defined for the same model solutions. The results of our model have applications to sensory areas of the brain, to which prefrontal areas send inputs reflecting the content of WM. These WM inputs to sensory areas have been established to induce oscillatory changes similar to our model. Our model results suggest a mechanism by which WM signals may enhance sensory information represented in oscillatory activity beyond the comparatively weak representations based on the mean rate activity.
Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study
Authors: Phillips Matthew C. L. , Johnston Samuel E. , Simpson Pat , Chang David K. , Mather Danielle , Dick Rognvald J.
Published: January 2024

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder. The most devastating variant is bulbar-onset ALS, which portends a median survival of 24 months from the onset of symptoms. Abundant evidence indicates that neuron metabolism and mitochondrial function are impaired in ALS. Metabolic strategies, particularly fasting and ketogenic diet protocols, alter neuron metabolism and mitochondria function in a manner that may mitigate the symptoms of this disorder. We report the case of a 64-year-old man with a 21-month history of progressive, deteriorating bulbar-onset ALS, with an associated pseudobulbar affect, who implemented a time-restricted ketogenic diet (TRKD) for 18 months. During this time, he improved in ALS-related function (7% improvement from baseline), forced expiratory volume (17% improvement), forced vital capacity (13% improvement), depression (normalized), stress levels (normalized), and quality of life (19% improvement), particularly fatigue (23% improvement). His swallowing impairment and neurocognitive status remained stable. Declines were measured in physical function, maximal inspiratory pressure, and maximal expiratory pressure. Weight loss was attenuated and no significant adverse effects occurred. This case study represents the first documented occurrence of a patient with ALS managed with either a fasting or ketogenic diet protocol, co-administered as a TRKD. We measured improved or stabilized ALS-related function, forced expiratory volume, forced vital capacity, swallowing, neurocognitive status, mood, and quality of life. Measurable declines were restricted to physical function, maximal inspiratory pressure, and maximal expiratory pressure. Now over 45 months since symptom onset, our patient remains functionally independent and dedicated to his TRKD.
Artificial intelligence-based decision support software to improve the efficacy of acute stroke pathway in the NHS: an observational study
Authors: Nagaratnam Kiruba , Neuhaus Ain , Briggs James H. , Ford Gary A. , Woodhead Zoe V. J. , Maharjan Dibyaa , Harston George
Published: January 2024

Introduction

In a drip-and-ship model for endovascular thrombectomy (EVT), early identification of large vessel occlusion (LVO) and timely referral to a comprehensive center (CSC) are crucial when patients are admitted to an acute stroke center (ASC). Several artificial intelligence (AI) decision-aid tools are increasingly being used to facilitate the rapid identification of LVO. This retrospective cohort study aimed to evaluate the impact of deploying e-Stroke AI decision support software in the hyperacute stroke pathway on process metrics and patient outcomes at an ASC in the United Kingdom.

Methods

Except for the deployment of e-Stroke on 01 March 2020, there were no significant changes made to the stroke pathway at the ASC. The data were obtained from a prospective stroke registry between 01 January 2019 and 31 March 2021. The outcomes were compared between the 14 months before and 12 months after the deployment of AI (pre-e-Stroke cohort vs. post-e-Stroke cohort) on 01 March 2020. Time window analyses were performed using Welch’s t-test. Cochran–Mantel–Haenszel test was used to compare changes in disability at 3 months assessed by modified Rankin Score (mRS) ordinal shift analysis, and Fisher’s exact test was used for dichotomised mRS analysis.

Results

In the pre-e-Stroke cohort, 19 of 22 patients referred received EVT. In the post-e-Stroke cohort, 21 of the 25 patients referred were treated. The mean door-in-door-out (DIDO) and door-to-referral times in pre-e-Stroke vs. post-e-Stroke cohorts were 141 vs. 79 min (difference 62 min, 95% CI 96.9–26.8 min, p < 0.001) and 71 vs. 44 min (difference 27 min, 95% CI 47.4–5.4 min, p = 0.01), respectively. The adjusted odds ratio (age and NIHSS) for mRS ordinal shift analysis at 3 months was 3.14 (95% CI 0.99–10.51, p = 0.06) and the dichotomized mRS 0–2 at 3 months was 16% vs. 48% (p = 0.04) in the pre- vs. post-e-Stroke cohorts, respectively.

Conclusion

In this single-center study in the United Kingdom, the DIDO time significantly decreased since the introduction of e-Stroke decision support software into an ASC hyperacute stroke pathway. The reduction in door-in to referral time indicates faster image interpretation and referral for EVT. There was an indication of an increased proportion of patients regaining independent function after EVT. However, this should be interpreted with caution given the small sample size. Larger, prospective studies and further systematic real-world evaluation are needed to demonstrate the widespread generalisability of these findings.
Prognostic and predictive role of liquid biopsy in lung cancer patients
Authors: Goksel Tuncay , Özgür Su , Vardarlı Aslı Tetik , Koç Altuğ , Karakuş Haydar Soydaner , Özdemir Taha Reşid , Erdoğan Kadri Murat , Aldağ Ceyda , Veral Ali , Komurcuoglu Berna , Gursoy Pınar , Arayici Mehmet Emin , Leblebici Asim , Yiğitbaşı Türkan , Ellidokuz Hülya , Basbinar Yasemin
Published: January 2024

Introduction

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC.

Methods

One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene.

Results

Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy.

Discussion

The results showed that “liquid biopsy” is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.
Childhood leukemias in Mexico: towards implementing CAR-T cell therapy programs
Authors: Bustamante-Ogando Juan Carlos , Hernández-López Alejandrina , Galván-Díaz César , Rivera-Luna Roberto , Fuentes-Bustos Hugo E. , Meneses-Acosta Angélica , Olaya-Vargas Alberto
Published: January 2024

Leukemias are the most common type of pediatric cancer around the world. Prognosis has improved during the last decades, and many patients are cured with conventional treatment as chemotherapy; however, many patients still present with a refractory disease requiring additional treatments, including hematopoietic stem cell transplantation. Immunotherapy with monoclonal antibodies or cellular therapy is a promising strategy for treating refractory or relapsed hematological malignancies. Particularly, CAR-T cells have shown clinical efficacy in clinical trials, and different products are now commercially approved by regulatory agencies in the USA and Europe. Many challenges still need to be solved to improve and optimize the potential of these therapies worldwide. Global access to cell therapy is a significant concern, and different strategies are being explored in the middle- and low-income countries. In Mexico, leukemias represent around 50% of total cancer diagnosed in pediatric patients, and the rate of relapsed or refractory disease is higher than reported in other countries, a multi-factorial problem. Although significant progress has been made during the last decades in leukemia diagnosis and treatment, making new therapies available to Mexican patients is a priority, and cell and gene therapies are on the horizon. Efforts are ongoing to make CAR-T cell therapy accessible for patients in Mexico. This article summarizes a general landscape of childhood leukemias in Mexico, and we give a perspective about the current strategies, advances, and challenges ahead to make gene and cell therapies for leukemia clinically available.
Tumor-associated microbiome features of metastatic colorectal cancer and clinical implications
Authors: An Ho Jung , Partha Mira A. , Lee HoJoon , Lau Billy T. , Pavlichin Dmitri S. , Almeda Alison , Hooker Anna C. , Shin Giwon , Ji Hanlee P.
Published: January 2024

Background

Colon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of patients with metastatic CRC and determined the clinical implications.

Materials and methods

We enrolled 133 patients with metastatic CRC at St. Vincent Hospital in Korea. The V3-V4 regions of the 16S rRNA gene from the tumor DNA were amplified, sequenced on an Illumina MiSeq, and analyzed using the DADA2 package.

Results

After excluding samples that retained <5% of the total reads after merging, 120 samples were analyzed. The median age of patients was 63 years (range, 34–82 years), and 76 patients (63.3%) were male. The primary cancer sites were the right colon (27.5%), left colon (30.8%), and rectum (41.7%). All subjects received 5-fluouracil-based systemic chemotherapy. After removing genera with <1% of the total reads in each patient, 523 genera were identified. Rectal origin, high CEA level (≥10 ng/mL), and presence of lung metastasis showed higher richness. Survival analysis revealed that the presence of Prevotella (p = 0.052), Fusobacterium (p = 0.002), Selenomonas (p<0.001), Fretibacterium (p = 0.001), Porphyromonas (p = 0.007), Peptostreptococcus (p = 0.002), and Leptotrichia (p = 0.003) were associated with short overall survival (OS, <24 months), while the presence of Sphingomonas was associated with long OS (p = 0.070). From the multivariate analysis, the presence of Selenomonas (hazard ratio [HR], 6.35; 95% confidence interval [CI], 2.38–16.97; p<0.001) was associated with poor prognosis along with high CEA level.

Conclusion

Tumor microbiome features may be useful prognostic biomarkers for metastatic CRC.
Beam control system and output fine-tuning for safe and precise delivery of FLASH radiotherapy at a clinical linear accelerator
Authors: Konradsson Elise , Wahlqvist Pontus , Thoft Andreas , Blad Börje , Bäck Sven , Ceberg Crister , Petersson Kristoffer
Published: January 2024

Introduction

We have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery.

Materials and Methods

The beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time. For UHDR delivery, an optocoupler facilitates external control of the accelerator’s thyratron trigger pulses. A beam tuning process was established to maximize the output. We assessed the stability of the delivery, and the independent interruption capabilities of the three systems (monitor detector, pulse counter, and timer). Additionally, we explored a novel approach to enhance dosimetric precision in the delivery by synchronizing the trigger pulse with the charging cycle of the pulse forming network (PFN).

Results

Improved beam tuning of gun current and magnetron frequency resulted in average dose rates at the dose maximum at isocenter distance of >160 Gy/s or >200 Gy/s, with or without an external monitor chamber in the beam path, respectively. The delivery showed a good repeatability (standard deviation (SD) in total film dose of 2.2%) and reproducibility (SD in film dose of 2.6%). The estimated variation in DPP resulted in an SD of 1.7%. The output in the initial pulse depended on the PFN delay time. Over the course of 50 measurements employing PFN synchronization, the absolute percentage error between the delivered number of MUs calculated by the monitor detector and the preset MUs was 0.8 ± 0.6% (mean ± SD).

Conclusion

We present an upgraded beam control system and beam tuning process for safe and stable UHDR electron delivery of hundreds of Gy/s at isocenter distance at a clinical linac. The system can interrupt the beam based on monitor units and utilize PFN synchronization for improved dosimetric precision in the dose delivery, representing an important advancement toward reliable clinical FLASH trials.
A tree species classification model based on improved YOLOv7 for shelterbelts
Authors: Liu Yihao , Zhao Qingzhan , Wang Xuewen , Sheng Yuhao , Tian Wenzhong , Ren Yuanyuan
Published: January 2024

Tree species classification within shelterbelts is crucial for shelterbelt management. The large-scale satellite-based and low-altitude drone-based approaches serve as powerful tools for forest monitoring, especially in tree species classification. However, these methods face challenges in distinguishing individual tree species within complex backgrounds. Additionally, the mixed growth of trees within protective forest suffers from similar crown size among different tree species. The complex background of the shelterbelts negatively impacts the accuracy of tree species classification. The You Only Look Once (YOLO) algorithm is widely used in the field of agriculture and forestry, ie., plant and fruit identification, pest and disease detection, and tree species classification in forestry. We proposed a YOLOv7-Kmeans++_CoordConv_CBAM (YOLOv7-KCC) model for tree species classification based on drone RGB remote sensing images. Firstly, we constructed a dataset for tree species in shelterbelts and adopted data augmentation methods to mitigate overfitting due to limited training data. Secondly, the K-means++ algorithm was employed to cluster anchor boxes in the dataset. Furthermore, to enhance the YOLOv7 backbone network’s Efficient Layer Aggregation Network (ELAN) module, we used Coordinate Convolution (CoordConv) replaced the ordinary 1×1 convolution. The Convolutional Block Attention Module (CBAM) was integrated into the Path Aggregation Network (PANet) structure to facilitate multiscale feature extraction and fusion, allowing the network to better capture and utilize crucial feature information. Experimental results showed that the YOLOv7-KCC model achieves a mean average precision@0.5 of 98.91%, outperforming the Faster RCNN-VGG16, Faster RCNN-Resnet50, SSD, YOLOv4, and YOLOv7 models by 5.71%, 11.75%, 5.97%, 7.86%, and 3.69%, respectively. The GFlops and Parameter values of the YOLOv7-KCC model stand at 105.07G and 143.7MB, representing an almost 5.6% increase in F1 metrics compared to YOLOv7. Therefore, the proposed YOLOv7-KCC model can effectively classify shelterbelt tree species, providing a scientific theoretical basis for shelterbelt management in Northwest China focusing on Xinjiang.
CRISPR/Cas StNRL1 gene knockout increases resistance to late blight and susceptibility to early blight in potato
Authors: Norouzi Moshen , Nazarain-Firouzabadi Farhad , Ismaili Ahmad , Ahmadvand Rahim , Poormazaheri Helen
Published: January 2024

With the development of genome editing technologies, editing susceptible genes is a promising method to modify plants for resistance to stress. NPH3/RPT2-LIKE1 protein (NRL1) interacts with effector Pi02860 of Phytophthora infestans and creates a protein complex, promoting the proteasome-mediated degradation of the guanine nucleotide exchange factor SWAP70. SWAP70, as a positive regulator, enhances cell death triggered by the perception of the P. infestans pathogen-associated molecular pattern (PAMP) INF1. Using a clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, a construct was made to introduce four guide RNAs into the potato cultivar Agria. A total of 60 putative transgenic lines were regenerated, in which 10 transgenic lines with deletions were selected and analyzed. A mutant line with a four-allelic knockdown of StNRL1 gene was obtained, showing an ~90% reduction in StNRL1 expression level, resulting in enhanced resistance to P. infestans. Surprisingly, mutant lines were susceptible to Alternaria alternata, suggesting that StNRL1 may play a role as a resistance gene; hence, silencing StNRL1 enhances resistance to P. infestans.