bluuebunny/crossref_metadata_2025 huggingface dataset:
Context-aware lightweight remote-sensing image super-resolution network
Authors: Peng Guangwen , Xie Minghong , Fang Liuyang
Published: June 2023

In recent years, remote-sensing image super-resolution (RSISR) methods based on convolutional neural networks (CNNs) have achieved significant progress. However, the limited receptive field of the convolutional kernel in CNNs hinders the network's ability to effectively capture long-range features in images, thus limiting further improvements in model performance. Additionally, the deployment of existing RSISR models to terminal devices is challenging due to their high computational complexity and large number of parameters. To address these issues, we propose a Context-Aware Lightweight Super-Resolution Network (CALSRN) for remote-sensing images. The proposed network primarily consists of Context-Aware Transformer Blocks (CATBs), which incorporate a Local Context Extraction Branch (LCEB) and a Global Context Extraction Branch (GCEB) to explore both local and global image features. Furthermore, a Dynamic Weight Generation Branch (DWGB) is designed to generate aggregation weights for global and local features, enabling dynamic adjustment of the aggregation process. Specifically, the GCEB employs a Swin Transformer-based structure to obtain global information, while the LCEB utilizes a CNN-based cross-attention mechanism to extract local information. Ultimately, global and local features are aggregated using the weights acquired from the DWGB, capturing the global and local dependencies of the image and enhancing the quality of super-resolution reconstruction. The experimental results demonstrate that the proposed method is capable of reconstructing high-quality images with fewer parameters and less computational complexity compared with existing methods.
The toxic metal hypothesis for neurological disorders
Authors: Pamphlett Roger , Bishop David P.
Published: June 2023

Multiple sclerosis and the major sporadic neurogenerative disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are considered to have both genetic and environmental components. Advances have been made in finding genetic predispositions to these disorders, but it has been difficult to pin down environmental agents that trigger them. Environmental toxic metals have been implicated in neurological disorders, since human exposure to toxic metals is common from anthropogenic and natural sources, and toxic metals have damaging properties that are suspected to underlie many of these disorders. Questions remain, however, as to how toxic metals enter the nervous system, if one or combinations of metals are sufficient to precipitate disease, and how toxic metal exposure results in different patterns of neuronal and white matter loss. The hypothesis presented here is that damage to selective locus ceruleus neurons from toxic metals causes dysfunction of the blood–brain barrier. This allows circulating toxicants to enter astrocytes, from where they are transferred to, and damage, oligodendrocytes, and neurons. The type of neurological disorder that arises depends on (i) which locus ceruleus neurons are damaged, (ii) genetic variants that give rise to susceptibility to toxic metal uptake, cytotoxicity, or clearance, (iii) the age, frequency, and duration of toxicant exposure, and (iv) the uptake of various mixtures of toxic metals. Evidence supporting this hypothesis is presented, concentrating on studies that have examined the distribution of toxic metals in the human nervous system. Clinicopathological features shared between neurological disorders are listed that can be linked to toxic metals. Details are provided on how the hypothesis applies to multiple sclerosis and the major neurodegenerative disorders. Further avenues to explore the toxic metal hypothesis for neurological disorders are suggested. In conclusion, environmental toxic metals may play a part in several common neurological disorders. While further evidence to support this hypothesis is needed, to protect the nervous system it would be prudent to take steps to reduce environmental toxic metal pollution from industrial, mining, and manufacturing sources, and from the burning of fossil fuels.
Functional outcomes of ischemic stroke patients aged over 80 years treated with acute revascularization therapy according to pre-morbid disability: a PARADISE study
Authors: Ruel Ségolène , Baptiste Laura , Duloquin Gauthier , Béjot Yannick
Published: June 2023

Introduction

Aging population leads to changes in the profile of patients with acute ischemic stroke (IS), and older adults were largely excluded from randomized clinical trials of acute revascularization therapy. This study aimed to assess functional outcomes of treated IS patients > 80 years old according to prior disability and identify associated factors.

Methods

Consecutively older patients with acute IS treated with either IV thrombolysis and/or mechanical thrombectomy were enrolled between 2016 and 2019. Pre-morbid disability was assessed using the modified Rankin Scale (mRS) score, and patients were classified as being independent (mRS score, 0–2) or having pre-existing disability (mRS score, 3–5). A multivariable logistic regression analysis was performed to assess factors associated with a poor functional outcome (mRS score > 3) at 3 and 12 months in each group of patients.

Results

Among 300 included patients (mean age: 86.3 ± 4.6 years, 63% women, median NIHSS score: 14, IQR: 8–19), 100 had a pre-existing disability. In patients with a pre-morbid mRS score of 0–2, 51% had mRS >3 including 33% of deaths at 3 months. At 12 months, 50% had a poor outcome including 39% of deaths. In patients with a pre-morbid mRS score of 3–5, 71% had a poor outcome at 3 months including 43% of deaths, and at 12 months, 76% had mRS >3 including 52% of deaths. In multivariable models, the NIHSS score at 24 h was independently associated with poor outcomes at 3 and 12 months in both patients with (OR = 1.32; 95% CI: 1.16–1.51, p < 0.001 for 12 months outcome) or without (OR = 1.31; 95% CI: 1.19–1.44, p < 0.001 for 12 months outcome) pre-morbid disability.

Conclusion

Although a large proportion of older patients with a pre-existing disability had a poor functional outcome, they did not differ from their non-impaired counterparts regarding prognostic factors. This means that there were no factors in our study that would help clinicians identify patients at risk of poor functional outcomes after revascularization therapy among those with prior disability. Further studies are needed to better understand the post-stroke trajectory of older IS patients with a pre-morbid disability.
Electrophysiological network predicts clinical response to vigabatrin in epileptic spasms
Authors: Kim Junhyung , Kim Min-Jee , Kim Hyun-Jin , Yum Mi-Sun , Ko Tae-Sung
Published: June 2023

Purpose

This study aimed to discover electrophysiologic markers correlated with clinical responses to vigabatrin-based treatment in infants with epileptic spasms (ES).

Method

The study involved a descriptive analysis of ES patients from a single institution, as well as electroencephalogram (EEG) analyses of 40 samples and 20 age-matched healthy infants. EEG data were acquired during the interictal sleep state prior to the standard treatment. The weighted phase-lag index (wPLI) functional connectivity was explored across frequency and spatial domains, correlating these results with clinical features.

Results

Infants with ES exhibited diffuse increases in delta and theta power, differing from healthy controls. For the wPLI analysis, ES subjects exhibited higher global connectivity compared to control subjects. Subjects who responded favorably to treatment were characterized by higher beta connectivity in the parieto-occipital regions, while those with poorer outcomes exhibited lower alpha connectivity in the frontal regions. Individuals with structural neuroimaging abnormalities exhibited correspondingly low functional connectivity, implying that ES patients who maintain adequate structural and functional integrity are more likely to respond favorably to vigabatrin-based treatments.

Conclusion

This study highlights the potential utility of EEG functional connectivity analysis in predicting early response to treatments in infants with ES.
Feeling without localizing: exploring tactile misperception in a patient with uncommon parietal left brain damage
Authors: Have Laurence , Quesque François , Priot Anne-Emmanuelle , Chastres Véronique , Revol Patrice , Delporte Ludovic , Chabanat Eric , Obadia Nathalie , Cotton François , Reilly Karen T. , Rossetti Yves
Published: June 2023

Introduction

We report a very unique clinical presentation of a patient who complained, after a left parietal brain damage, about feeling tactile stimulations on his right upper limb without being able to localize them.

Methods

Using a single case study approach, we report three experiments relying on several custom-made tasks to explore the different levels of somatosensory information processing, ranging from somato-sensation to somato-representation.

Results

Our results showed a preserved ability to localize tactile stimuli applied on the right upper limb when using pointing responses while the ability to localize was less efficient when having to name the stimulated part (akin Numbsense). When the stimuli were applied on more distal locations (i.e., on the hand and on fingers), the number of correct responses decreased significantly independently of the modality of response. Finally, when visually presented with a stimulus delivered on the hand of an examiner in synchrony with the stimulation on the hidden hand of the patient, responses were largely influenced by the visual information available. Altogether, the convergence of these different customized tasks revealed an absence of autotopagnosia for motor responses for the right upper limb, associated with altered abilities to discriminate stimulus applied on distal and restricted/closer zones in the hand.

Discussion

The somato-representation of our patient seemed to significantly rely on visual information, leading to striking deficits to localize tactile stimuli when vision and somesthesic afferences are discordant. This case report offers a clinical illustration of pathological imbalance between vision and somesthesia. Implications of these troubles in somato-representation on higher cognitive level processes are discussed.
Motor synchronization and impulsivity in pediatric borderline personality disorder with and without attention-deficit hyperactivity disorder: an eye-tracking study of saccade, blink and pupil behavior
Authors: Calancie Olivia G. , Parr Ashley C. , Brien Don C. , Huang Jeff , Pitigoi Isabell C. , Coe Brian C. , Booij Linda , Khalid-Khan Sarosh , Munoz Douglas P.
Published: June 2023

Shifting motor actions from reflexively reacting to an environmental stimulus to predicting it allows for smooth synchronization of behavior with the outside world. This shift relies on the identification of patterns within the stimulus – knowing when a stimulus is predictable and when it is not – and launching motor actions accordingly. Failure to identify predictable stimuli results in movement delays whereas failure to recognize unpredictable stimuli results in early movements with incomplete information that can result in errors. Here we used a metronome task, combined with video-based eye-tracking, to quantify temporal predictive learning and performance to regularly paced visual targets at 5 different interstimulus intervals (ISIs). We compared these results to the random task where the timing of the target was randomized at each target step. We completed these tasks in female pediatric psychiatry patients (age range: 11–18 years) with borderline personality disorder (BPD) symptoms, with (n = 22) and without (n = 23) a comorbid attention-deficit hyperactivity disorder (ADHD) diagnosis, against controls (n = 35). Compared to controls, BPD and ADHD/BPD cohorts showed no differences in their predictive saccade performance to metronome targets, however, when targets were random ADHD/BPD participants made significantly more anticipatory saccades (i.e., guesses of target arrival). The ADHD/BPD group also significantly increased their blink rate and pupil size when initiating movements to predictable versus unpredictable targets, likely a reflection of increased neural effort for motor synchronization. BPD and ADHD/BPD groups showed increased sympathetic tone evidenced by larger pupil sizes than controls. Together, these results support normal temporal motor prediction in BPD with and without ADHD, reduced response inhibition in BPD with comorbid ADHD, and increased pupil sizes in BPD patients. Further these results emphasize the importance of controlling for comorbid ADHD when querying BPD pathology.
Training augmentation using additive sensory noise in a lunar rover navigation task
Authors: Sherman Sage O. , Jonsen Anna , Lewis Quinlan , Schlittenhart Michael , Szafir Daniel , Clark Torin K. , Anderson Allison P.
Published: June 2023

Background

The uncertain environments of future space missions means that astronauts will need to acquire new skills rapidly; thus, a non-invasive method to enhance learning of complex tasks is desirable. Stochastic resonance (SR) is a phenomenon where adding noise improves the throughput of a weak signal. SR has been shown to improve perception and cognitive performance in certain individuals. However, the learning of operational tasks and behavioral health effects of repeated noise exposure aimed to elicit SR are unknown.

Objective

We evaluated the long-term impacts and acceptability of repeated auditory white noise (AWN) and/or noisy galvanic vestibular stimulation (nGVS) on operational learning and behavioral health.

Methods

Subjects (n = 24) participated in a time longitudinal experiment to access learning and behavioral health. Subjects were assigned to one of our four treatments: sham, AWN (55 dB SPL), nGVS (0.5 mA), and their combination to create a multi-modal SR (MMSR) condition. To assess the effects of additive noise on learning, these treatments were administered continuously during a lunar rover simulation in virtual reality. To assess behavioral health, subjects completed daily, subjective questionnaires related to their mood, sleep, stress, and their perceived acceptance of noise stimulation.

Results

We found that subjects learned the lunar rover task over time, as shown by significantly lower power required for the rover to complete traverses (p < 0.005) and increased object identification accuracy in the environment (p = 0.05), but this was not influenced by additive SR noise (p = 0.58). We found no influence of noise on mood or stress following stimulation (p > 0.09). We found marginally significant longitudinal effects of noise on behavioral health (p = 0.06) as measured by strain and sleep. We found slight differences in stimulation acceptability between treatment groups, and notably nGVS was found to be more distracting than sham (p = 0.006).

Conclusion

Our results suggest that repeatedly administering sensory noise does not improve long-term operational learning performance or affect behavioral health. We also find that repetitive noise administration is acceptable in this context. While additive noise does not improve performance in this paradigm, if it were used for other contexts, it appears acceptable without negative longitudinal effects.
Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study
Authors: Zhang Zhiyun , Wang Shengnan , Ren Fei , Yang Laiyu , Xie Haoqun , Pan Lin , Li Yifan , Yu Bingcheng , Yang Yifan , Su Haoyi , Chen Youqi , Zhang Chuyi , Chen Hongyu , Yang Wenzhuo , An Nan , Bai Yang
Published: June 2023

Background

Meningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear.

Method

Mendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It’s a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome.

Results

This research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-β, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood.

Conclusion

These findings suggest that TNF-β, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas.
SENECA: building a fully digital neuromorphic processor, design trade-offs and challenges
Authors: Tang Guangzhi , Vadivel Kanishkan , Xu Yingfu , Bilgic Refik , Shidqi Kevin , Detterer Paul , Traferro Stefano , Konijnenburg Mario , Sifalakis Manolis , van Schaik Gert-Jan , Yousefzadeh Amirreza
Published: June 2023

Neuromorphic processors aim to emulate the biological principles of the brain to achieve high efficiency with low power consumption. However, the lack of flexibility in most neuromorphic architecture designs results in significant performance loss and inefficient memory usage when mapping various neural network algorithms. This paper proposes SENECA, a digital neuromorphic architecture that balances the trade-offs between flexibility and efficiency using a hierarchical-controlling system. A SENECA core contains two controllers, a flexible controller (RISC-V) and an optimized controller (Loop Buffer). This flexible computational pipeline allows for deploying efficient mapping for various neural networks, on-device learning, and pre-post processing algorithms. The hierarchical-controlling system introduced in SENECA makes it one of the most efficient neuromorphic processors, along with a higher level of programmability. This paper discusses the trade-offs in digital neuromorphic processor design, explains the SENECA architecture, and provides detailed experimental results when deploying various algorithms on the SENECA platform. The experimental results show that the proposed architecture improves energy and area efficiency and illustrates the effect of various trade-offs in algorithm design. A SENECA core consumes 0.47 mm2 when synthesized in the GF-22 nm technology node and consumes around 2.8 pJ per synaptic operation. SENECA architecture scales up by connecting many cores with a network-on-chip. The SENECA platform and the tools used in this project are freely available for academic research upon request.
Neuroprotective effects of coenzyme Q10 on neurological diseases: a review article
Authors: Bagheri Shokufeh , Haddadi Rasool , Saki Sahar , Kourosh-Arami Masoumeh , Rashno Masome , Mojaver Ali , Komaki Alireza
Published: June 2023

Neurological disorders affect the nervous system. Biochemical, structural, or electrical abnormalities in the spinal cord, brain, or other nerves lead to different symptoms, including muscle weakness, paralysis, poor coordination, seizures, loss of sensation, and pain. There are many recognized neurological diseases, like epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, autosomal recessive cerebellar ataxia 2 (ARCA2), Leber's hereditary optic neuropathy (LHON), and spinocerebellar ataxia autosomal recessive 9 (SCAR9). Different agents, such as coenzyme Q10 (CoQ10), exert neuroprotective effects against neuronal damage. Online databases, such as Scopus, Google Scholar, Web of Science, and PubMed/MEDLINE were systematically searched until December 2020 using keywords, including review, neurological disorders, and CoQ10. CoQ10 is endogenously produced in the body and also can be found in supplements or foods. CoQ10 has antioxidant and anti-inflammatory effects and plays a role in energy production and mitochondria stabilization, which are mechanisms, by which CoQ10 exerts its neuroprotective effects. Thus, in this review, we discussed the association between CoQ10 and neurological diseases, including AD, depression, MS, epilepsy, PD, LHON, ARCA2, SCAR9, and stroke. In addition, new therapeutic targets were introduced for the next drug discoveries.
New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation
Authors: Infantes-López María Inmaculada , Nieto-Quero Andrea , Chaves-Peña Patricia , Zambrana-Infantes Emma , Cifuentes Manuel , Márquez Javier , Pedraza Carmen , Pérez-Martín Margarita
Published: June 2023

In recent years, the hypothalamus has emerged as a new neurogenic area, capable of generating new neurons after development. Neurogenesis-dependent neuroplasticity seems to be critical to continuously adapt to internal and environmental changes. Stress is a potent environmental factor that can produce potent and enduring effects on brain structure and function. Acute and chronic stress is known to cause alterations in neurogenesis and microglia in classical adult neurogenic regions such as the hippocampus. The hypothalamus is one of the major brain regions implicated in homeostatic stress and emotional stress systems, but little is known about the effect of stress on the hypothalamus. Here, we studied the impact of acute and intense stress (water immersion and restrain stress, WIRS), which may be considered as an inducer of an animal model of posttraumatic stress disorder, on neurogenesis and neuroinflammation in the hypothalamus of adult male mice, focusing on three nuclei: PVN, VMN and ARC, and also in the periventricular area. Our data revealed that a unique stressor was sufficient to provoke a significant impact on hypothalamic neurogenesis by inducing a reduction in the proliferation and number of immature neurons identified as DCX+ cells. These differences were accompanied by marked microglial activation in the VMN and ARC, together with a concomitant increase in IL-6 levels, indicating that WIRS induced an inflammatory response. To investigate the possible molecular mechanisms responsible for neuroplastic and inflammatory changes, we tried to identify proteomic changes. The data revealed that WIRS induced changes in the hypothalamic proteome, modifying the abundance of three and four proteins after 1 h or 24 h of stress application, respectively. These changes were also accompanied by slight changes in the weight and food intake of the animals. These results are the first to show that even a short-term environmental stimulus such as acute and intense stress can have neuroplastic, inflammatory, functional and metabolic consequences on the adult hypothalamus.
Facilitating or disturbing? An investigation about the effects of auditory frequencies on prefrontal cortex activation and postural sway
Authors: Belluscio Valeria , Cartocci Giulia , Terbojevich Tommaso , Di Feo Paolo , Inguscio Bianca Maria Serena , Ferrari Marco , Quaresima Valentina , Vannozzi Giuseppe
Published: June 2023

Auditory stimulation activates brain areas associated with higher cognitive processes, like the prefrontal cortex (PFC), and plays a role in postural control regulation. However, the effects of specific frequency stimuli on upright posture maintenance and PFC activation patterns remain unknown. Therefore, the study aims at filling this gap. Twenty healthy adults performed static double- and single-leg stance tasks of 60s each under four auditory conditions: 500, 1000, 1500, and 2000 Hz, binaurally delivered through headphones, and in quiet condition. Functional near-infrared spectroscopy was used to measure PFC activation through changes in oxygenated hemoglobin concentration, while an inertial sensor (sealed at the L5 vertebra level) quantified postural sway parameters. Perceived discomfort and pleasantness were rated through a 0–100 visual analogue scale (VAS). Results showed that in both motor tasks, different PFC activation patterns were displayed at the different auditory frequencies and the postural performance worsened with auditory stimuli, compared to quiet conditions. VAS results showed that higher frequencies were considered more discomfortable than lower ones. Present data prove that specific sound frequencies play a significant role in cognitive resources recruitment and in the regulation of postural control. Furthermore, it supports the importance of exploring the relationship among tones, cortical activity, and posture, also considering possible applications with neurological populations and people with hearing dysfunctions.
BNLoop-GAN: a multi-loop generative adversarial model on brain network learning to classify Alzheimer’s disease
Authors: Cao Yu , Kuai Hongzhi , Liang Peipeng , Pan Jeng-Shyang , Yan Jianzhuo , Zhong Ning
Published: June 2023

Recent advancements in AI, big data analytics, and magnetic resonance imaging (MRI) have revolutionized the study of brain diseases such as Alzheimer’s Disease (AD). However, most AI models used for neuroimaging classification tasks have limitations in their learning strategies, that is batch training without the incremental learning capability. To address such limitations, the systematic Brain Informatics methodology is reconsidered to realize evidence combination and fusion computing with multi-modal neuroimaging data through continuous learning. Specifically, we introduce the BNLoop-GAN (Loop-based Generative Adversarial Network for Brain Network) model, utilizing multiple techniques such as conditional generation, patch-based discrimination, and Wasserstein gradient penalty to learn the implicit distribution of brain networks. Moreover, a multiple-loop-learning algorithm is developed to combine evidence with better sample contribution ranking during training processes. The effectiveness of our approach is demonstrated through a case study on the classification of individuals with AD and healthy control groups using various experimental design strategies and multi-modal brain networks. The BNLoop-GAN model with multi-modal brain networks and multiple-loop-learning can improve classification performance.
Brain perivascular spaces and autism: clinical and pathogenic implications from an innovative volumetric MRI study
Authors: Sotgiu Maria Alessandra , Lo Jacono Alessandro , Barisano Giuseppe , Saderi Laura , Cavassa Vanna , Montella Andrea , Crivelli Paola , Carta Alessandra , Sotgiu Stefano
Published: June 2023

Introduction

Our single-center case–control study aimed to evaluate the unclear glymphatic system alteration in autism spectrum disorder (ASD) through an innovative neuroimaging tool which allows to segment and quantify perivascular spaces in the white matter (WM-PVS) with filtering of non-structured noise and increase of the contrast-ratio between perivascular spaces and the surrounding parenchyma.

Methods

Briefly, files of 65 ASD and 71 control patients were studied. We considered: ASD type, diagnosis and severity level and comorbidities (i.e., intellectual disability, attention-deficit hyperactivity disorder, epilepsy, sleep disturbances). We also examined diagnoses other than ASD and their associated comorbidities in the control group.

Results

When males and females with ASD are included together, WM-PVS grade and WM-PVS volume do not significantly differ between the ASD group and the control group overall. We found, instead, that WM-PVS volume is significantly associated with male sex: males had higher WM-PVS volume compared to females (p = 0.01). WM-PVS dilation is also non-significantly associated with ASD severity and younger age (< 4 years). In ASD patients, higher WM-PVS volume was related with insomnia whereas no relation was found with epilepsy or IQ.

Discussion

We concluded that WM-PVS dilation can be a neuroimaging feature of male ASD patients, particularly the youngest and most severe ones, which may rely on male-specific risk factors acting early during neurodevelopment, such as a transient excess of extra-axial CSF volume. Our findings can corroborate the well-known strong male epidemiological preponderance of autism worldwide.
Confronting the loss of trophic support
Authors: Hu Hui-Lan , Khatri Latika , Santacruz Marilyn , Church Emily , Moore Christopher , Huang Tony T. , Chao Moses V.
Published: June 2023

Classic experiments with peripheral sympathetic neurons established an absolute dependence upon NGF for survival. A forgotten problem is how these neurons become resistant to deprivation of trophic factors. The question is whether and how neurons can survive in the absence of trophic support. However, the mechanism is not understood how neurons switch their phenotype to lose their dependence on trophic factors, such as NGF and BDNF. Here, we approach the problem by considering the requirements for trophic support of peripheral sympathetic neurons and hippocampal neurons from the central nervous system. We developed cellular assays to assess trophic factor dependency for sympathetic and hippocampal neurons and identified factors that rescue neurons in the absence of trophic support. They include enhanced expression of a subunit of the NGF receptor (Neurotrophin Receptor Homolog, NRH) in sympathetic neurons and an increase of the expression of the glucocorticoid receptor in hippocampal neurons. The results are significant since levels and activity of trophic factors are responsible for many neuropsychiatric conditions. Resistance of neurons to trophic factor deprivation may be relevant to the underlying basis of longevity, as well as an important element in preventing neurodegeneration.
Revisiting the expression of BDNF and its receptors in mammalian development
Authors: Esvald Eli-Eelika , Tuvikene Jürgen , Kiir Carl Sander , Avarlaid Annela , Tamberg Laura , Sirp Alex , Shubina Anastassia , Cabrera-Cabrera Florencia , Pihlak Arno , Koppel Indrek , Palm Kaia , Timmusk Tõnis
Published: June 2023

Brain-derived neurotrophic factor (BDNF) promotes the survival and functioning of neurons in the central nervous system and contributes to proper functioning of many non-neural tissues. Although the regulation and role of BDNF have been extensively studied, a rigorous analysis of the expression dynamics of BDNF and its receptors TrkB and p75NTR is lacking. Here, we have analyzed more than 3,600 samples from 18 published RNA sequencing datasets, and used over 17,000 samples from GTEx, and ~ 180 samples from BrainSpan database, to describe the expression of BDNF in the developing mammalian neural and non-neural tissues. We show evolutionarily conserved dynamics and expression patterns of BDNF mRNA and non-conserved alternative 5′ exon usage. Finally, we also show increasing BDNF protein levels during murine brain development and BDNF protein expression in several non-neural tissues. In parallel, we describe the spatiotemporal expression pattern of BDNF receptors TrkB and p75NTR in both murines and humans. Collectively, our in-depth analysis of the expression of BDNF and its receptors gives insight into the regulation and signaling of BDNF in the whole organism throughout life.
A generic theory of change-based framework with core indicators for monitoring the effectiveness of large-scale food fortification programs in low- and middle-income countries
Authors: Rodas-Moya Santiago , Giudici Francesca M. , Owolabi Adedotun , Samuel Folake , Kodish Stephen R. , Lachat Carl , Abreu Taymara C. , van het Hof Karin H. , Osendarp Saskia J. M. , Brouwer Inge D. , Feskens Edith J. M. , Melse-Boonstra Alida
Published: June 2023

Large-scale food fortification (LSFF) programs are widely implemented in low- and middle-income countries (LMIC) to alleviate micronutrient deficiencies. However, these programs may not achieve the desired impact due to poor design or bottlenecks in program implementation. Monitoring and evaluation (M&E) frameworks and a set of agreed indicators can help to benchmark progress and to strengthen the evidence-base of effectiveness in a standardized way. We aimed to formulate recommendations towards core indicators for evaluating the effectiveness of LSFF programs with their associated metrics, methods, and tools (IMMT). For this, we used a multi-method iterative approach, including a mapping review of the literature, semi-structured interviews with international experts, compilation of a generic Theory of Change (ToC) framework for LSFF program delivery, and selection of IMMT for M&E of LSFF programs at key stages along the ToC delivery framework. Lastly, we conducted exploratory, qualitative interviews with key informants in Nigeria to explore experiences and perceptions related to the implementation of LSFF programs in Nigeria’s context, and their opinion towards the proposed set of core IMMT. The literature search resulted in 14 published and 15 grey literature documents, from which we extracted a total of 41 indicators. Based on the available literature and interviews with international experts, we mapped a ToC delivery framework and selected nine core indicators at the output, outcome and impact level for M&E of the effectiveness of LSFF programs. Key informants in Nigeria revealed that the main bottlenecks for implementation of the proposed IMMT are related to the lack of technical capacity, equipment, laboratory infrastructure, and financial resources. In conclusion, we propose a set of nine core indicators for enabling comprehensive M&E of the effectiveness of LSFF programs in LMIC. This proposed set of core indicators can be used for further evaluation, harmonization and integration in national and international protocols for M&E of LSFF programs.
The prognostic index PRIMA-PI combined with Ki67 as a better predictor of progression of disease within 24 months in follicular lymphoma
Authors: Hu Jiaci , Gao Fenghua , Zhao Jin , Song Wenzhu , Wang Yanli , Zheng Yuping , Wang Lieyang , Han Weie , Ma Li , Wang Jingrong , Bai Min , Guan Tao , Xi Yanfeng , Zhang Huilai , Qiu Lixia , Su Liping
Published: June 2023

Background

Progression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction.

Methods

This study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital.

Results

The multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient’s progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance.

Conclusion

As such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value.
Pan-cancer analysis of the prognostic and immunological role of GJB2: a potential target for survival and immunotherapy
Authors: Jia Yuting , Guo Bin , Zhang Wenbin , Wang Feng , Zhang Yong , Zhang Quanmao , Li Erfeng
Published: June 2023

Background

GJB2 plays an essential role in the growth and progression of several cancers. However, asystematic pan-cancer analysis of GJB2 is lacking. Therefore, in this study, we performed a comprehensive pan-cancer analysis to determine the potential role of GJB2 in prognostic prediction and cancer immunotherapy response.

Methods

The differential expression of GJB2 in the tumor and adjacent normal tissues of various cancer types was analyzed using the TIMER, GEPIA, and Sangerbox databases. GEPIA and Kaplan–Meier plotter databases were used to analyze the survival outcomes based on GJB2 expression levels in pan-cancer. Furthermore, the association of GJB2 expression with the immune checkpoint (ICP) genes, tumor mutational load (TMB), microsatellite instability (MSI), neoantigens, and tumor infiltration of immune cells was analyzed using via the Sangerbox database. The cBioPortal database was used to determine the characteristics of GJB2 gene alterations in the cancer tissues. The STRING database was used to identify the GJB2-binding proteins. GEPIA database was used to identify the GJB2 co-expressed genes. DAVID was used to perform the functional enrichment analysis of gene ontology (GO) terms and KEGG pathways associated with GJB2. Finally, the mechanistic role of GJB2 in pancreatic adenocarcinoma (PAAD) was analyzed using the LinkedOmics database.

Results

The GJB2 gene was highly expressed in a variety of tumors. Furthermore, GJB2 expression levels showed significant positive or negative association with the survival outcomes in various cancers. GJB2 expression levels cor related with tumor mutational burden, microsatellite instability, neoantigens, and tumor infiltration of immune cells in multiple cancers. This suggested that GJB2 played a critical role in the tumor microenvironment. Functional enrichment analysis showed that the biological role of GJB2 in tumors included modulation of gap junction-mediated intercellular transport, regulation of cell communication by electrical coupling, ion transmembrane transport, autocrine signaling, apoptotic signaling pathway, NOD-like receptor signaling pathway, p53 signaling pathway, and PI3K-Akt signaling pathway.

Conclusions

Our study demonstrated that GJB2 played a significant role in tumorigenesis and tumor immunity in multiple cancers. Furthermore, GJB2 is a potential prognostic biomarker and a promising therapeutic target in multiple types of cancers.
Identification and validation of m6A-GPI signatures as a novel prognostic model for colorectal cancer
Authors: Ma Bin , Bao Simeng , Li Yongmin
Published: June 2023

In order to develop an N6-methyladenosine-related gene prognostic index (m6A-GPI) that can predict the prognosis in colorectal cancer (CRC), we obtained m6A-related differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) and m6Avar database, seven genes were screened by weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis. Then, m6A-GPI was constructed based on the risk score. Survival analysis indicated that patients in the lower m6A-GPI group have more prolonged disease-free survival (DFS), and different clinical characteristic groups (tumor site and stage) also showed differential risk scores. In the analysis of the molecular characteristics, the risk score is positively associated with homologous recombination defects (HRD), copy number alterations (CNA), and the mRNA expression-based stemness index (mRNAsi). In addition, m6A-GPI also plays an essential role in tumor immune cell infiltration. The immune cell infiltration in the low m6A-GPI group is significantly higher in CRC. Moreover, we found that CIITA, one of the genes in m6A-GPI was up-regulated in CRC tissues based on real-time RT-PCR and Western blot. m6A-GPI is a promising prognostic biomarker that can be used to distinguish the prognosis of CRC patients in CRC.
Fluorescence microscopy imaging of mitochondrial metabolism in cancer cells
Authors: Gooz Monika , Maldonado Eduardo N.
Published: June 2023

Mitochondrial metabolism is an important contributor to cancer cell survival and proliferation that coexists with enhanced glycolytic activity. Measuring mitochondrial activity is useful to characterize cancer metabolism patterns, to identify metabolic vulnerabilities and to identify new drug targets. Optical imaging, especially fluorescent microscopy, is one of the most valuable tools for studying mitochondrial bioenergetics because it provides semiquantitative and quantitative readouts as well as spatiotemporal resolution of mitochondrial metabolism. This review aims to acquaint the reader with microscopy imaging techniques currently used to determine mitochondrial membrane potential (ΔΨm), nicotinamide adenine dinucleotide (NADH), ATP and reactive oxygen species (ROS) that are major readouts of mitochondrial metabolism. We describe features, advantages, and limitations of the most used fluorescence imaging modalities: widefield, confocal and multiphoton microscopy, and fluorescent lifetime imaging (FLIM). We also discus relevant aspects of image processing. We briefly describe the role and production of NADH, NADHP, flavins and various ROS including superoxide and hydrogen peroxide and discuss how these parameters can be analyzed by fluorescent microscopy. We also explain the importance, value, and limitations of label-free autofluorescence imaging of NAD(P)H and FAD. Practical hints for the use of fluorescent probes and newly developed sensors for imaging ΔΨm, ATP and ROS are described. Overall, we provide updated information about the use of microscopy to study cancer metabolism that will be of interest to all investigators regardless of their level of expertise in the field.
Ablation treatment of hepatocellular carcinoma: a bibliometric analysis
Authors: Song Jianping , Zhang Tingxiao , Wang Jianlei , Liu Yanfeng
Published: June 2023

Objective

Ablation is a common treatment for hepatocellular carcinoma (HCC). This study aimed to assess research trends in the ablation treatment of HCC using bibliometric analysis.

Methods

Publications between January 1, 1993 and December 31, 2022 were retrieved from the Web of Science database. The bibliometrix package from R software, CiteSpace, VOSviewer and an online analytical platform were used for data analysis and plotting.

Results

A total of 4,029 publications were retrieved from the Web of Science database between 1993 and 2022. The annual growth rate of publication numbers was 10.14%. China had the largest number of publications in the field of HCC ablation. China and the United States of America have the most notable cooperation. Sun Yat-sen University had the largest number of publications in the field of HCC ablation. The most relevant journals were Hepatology, Journal of Hepatology, Gastroenterology, and Radiology. High-frequency keywords mainly focused on “therapy,” “resection,” “radiofrequency ablation” and “survival”.

Conclusions

With the increase in related publications, the research direction of ablation treatment of HCC is mainly focused on “therapy,” “resection,” “radiofrequency ablation” and “survival”, and the ablation treatment method has gradually changed from percutaneous ethanol injection to radiofrequency ablation and microwave ablation. Irreversible electroporation may become the main method of ablation therapy in the future.
Could axillary lymph node dissection be omitted in the mastectomy patient with tumor positive sentinel node?
Authors: You Ji Young , Lee Eun Sook , Lim Siew Kuan , Kwon Youngmee , Jung So-Youn
Published: June 2023

Background

Recent data from the ACOSOG Z0011 trial suggest that axillary lymph node dissection (ALND) may not be necessary for patients with positive sentinel lymph node biopsy (SLNB) receiving breast-conserving surgery (BCS) with irradiation. However, consensus statements and guidelines have recommended that patients undergoing mastectomy with tumor-positive sentinel node undergo completion ALND. In this study, we compared the locoregional recurrence rate of patients with tumor-positive sentinel nodes among three groups: mastectomy with SLNB, mastectomy with ALND and BCS with SLNB.

Method

We identified 6,163 women with invasive breast cancer who underwent surgical resection at our institution between January 2000 and December 2011. Clinicopathologic data obtained from the prospectively collected medical database were analyzed retrospectively. Among the patients with sentinel node positive, mastectomy with SLNB was performed in 39 cases, mastectomy with ALND in 181 cases, and BCS with SLNB in 165 cases. The primary end point was the loco-regional recurrence rate.

Results

Clinicopathologic characteristics were similar among the groups. There were no cases of loco-regional recurrence in the sentinel groups. At a median follow-up of 61.0 months (last follow-up May 2013), the loco-regional recurrence rate of each group was 0% for BCS with SLNB and mastectomy with SLNB only, and 1.7% for mastectomy with ALND (p=0.182).

Conclusion

In our study, there was no significant difference in loco-regional recurrence rates between groups. This result lends weight to the argument that SLNB without ALND may be a reasonable management for selected patients with appropriate surgery and adjuvant systemic therapy.
Genomic signature to guide adjuvant chemotherapy treatment decisions for early breast cancer patients in France: a cost-effectiveness analysis
Authors: Curtit Elsa , Bellanger Martine Marie , Nerich Virginie , Hequet Delphine , Frenel Jean-Sebastien , Cristeau Olivier , Rouzier Roman
Published: June 2023

Introduction

Chemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence.

Methods

Clinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX® test or SoC) and a Markov model to capture long-term outcomes.

Results

In the base case, the Oncotype DX® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX® testing was the dominant strategy.

Discussion

Widespread implementation of Oncotype DX® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system.