bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of soil inorganic nitrogen on bacterial phylogeny in estuarine intertidal zones: a study of nitrogen metabolism
Authors: Li Siqi , Liu Tianyang , Liu Cheng , Sun Donglei , Yan Qin , Gao Dengzhou , Zhang Zongxiao
Published: January 2024

Here we investigated the potential impacts of soil inorganic nitrogen (SIN) content on the phylogenetic characteristics and ecological functions of soil bacterial communities in estuarine intertidal zones in China, aiming to comprehend the response mechanism of soil microorganisms to variations in SIN content within estuarine wetlands. Our results show that SIN in estuarine areas has a significant spatiotemporal variation on spatial and seasonal scales, in this study and is significantly associated with the phylogenetic diversity and phylogenetic turnover of soil bacterial communities. In addition, the results of the metagenomic analysis showed that the relative abundance of nitrogen-cycling functional genes in bacterial communities did not differ significantly in sampling sites and seasons, and weakly correlated with SIN content. Further, the results based on structural equation modeling (SEM) analysis showed that SIN directly and significantly regulated the phylogenetic characteristics of bacterial communities, thereby indirectly affecting the potential of bacterial nitrogen metabolism. This study emphasizes the key influence of SIN variations on the phylogenetic dissimilarity in soil bacterial communities. Moreover, although there was a weak direct relationship between the functional characteristics of the bacterial nitrogen metabolism and SIN content, the spatiotemporal variation of bacterial nitrogen metabolic potential may be indirectly regulated by SIN content by influencing the phylogenetic diversity in bacterial communities. Our study unravels the pivotal mechanisms through which SIN content influences bacterial communities, thereby offering novel insights into the microbial intricacies governing nitrogen metabolism within estuaries.
Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides
Authors: Parisi Giacomo , Piacentini Roberta , Incocciati Alessio , Bonamore Alessandra , Macone Alberto , Rupert Jakob , Zacco Elsa , Miotto Mattia , Milanetti Edoardo , Tartaglia Gian Gaetano , Ruocco Giancarlo , Boffi Alberto , Di Rienzo Lorenzo
Published: January 2024

The development of methods able to modulate the binding affinity between proteins and peptides is of paramount biotechnological interest in view of a vast range of applications that imply designed polypeptides capable to impair or favour Protein-Protein Interactions. Here, we applied a peptide design algorithm based on shape complementarity optimization and electrostatic compatibility and provided the first experimental in vitro proof of the efficacy of the design algorithm. Focusing on the interaction between the SARS-CoV-2 Spike Receptor-Binding Domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor, we extracted a 23-residues long peptide that structurally mimics the major interacting portion of the ACE2 receptor and designed in silico five mutants of such a peptide with a modulated affinity. Remarkably, experimental KD measurements, conducted using biolayer interferometry, matched the in silico predictions. Moreover, we investigated the molecular determinants that govern the variation in binding affinity through molecular dynamics simulation, by identifying the mechanisms driving the different values of binding affinity at a single residue level. Finally, the peptide sequence with the highest affinity, in comparison with the wild type peptide, was expressed as a fusion protein with human H ferritin (HFt) 24-mer. Solution measurements performed on the latter constructs confirmed that peptides still exhibited the expected trend, thereby enhancing their efficacy in RBD binding. Altogether, these results indicate the high potentiality of this general method in developing potent high-affinity vectors for hindering/enhancing protein-protein associations.
Text clustering based on pre-trained models and autoencoders
Authors: Xu Qiang , Gu Hao , Ji ShengWei
Published: January 2024

Text clustering is the task of grouping text data based on similarity, and it holds particular importance in the medical field. sIn healthcare, medical data clustering is a highly active and effective research area. It not only provides strong support for making correct medical decisions from medical datasets but also aids in patient record management and medical information retrieval. With the development of the healthcare industry, a large amount of medical data is being generated, and traditional medical data clustering faces significant challenges. Many existing text clustering algorithms are primarily based on the bag-of-words model, which has issues such as high dimensionality, sparsity, and the neglect of word positions and context. Pre-trained models are a deep learning-based approach that treats text as a sequence to accurately capture word positions and context information. Moreover, compared to traditional K-means and fuzzy C-means clustering models, deep learning-based clustering algorithms are better at handling high-dimensional, complex, and nonlinear data. In particular, clustering algorithms based on autoencoders can learn data representations and clustering information, effectively reducing noise interference and errors during the clustering process. This paper combines pre-trained language models with deep embedding clustering models. Experimental results demonstrate that our model performs exceptionally well on four public datasets, outperforming most existing text clustering algorithms, and can be applied to medical data clustering.
Network analysis of multimorbidity and health outcomes among persons with spinal cord injury in Canada
Authors: Fallah Nader , Hong Heather A. , Wang Di , Humphreys Suzanne , Parsons Jessica , Walden Kristen , Street John , Charest-Morin Raphaele , Cheng Christiana L. , Cheung Candice J. , Noonan Vanessa K.
Published: January 2024

Introduction

Multimorbidity, defined as the coexistence of two or more health conditions, is common in persons with spinal cord injury (SCI). Network analysis is a powerful tool to visualize and examine the relationship within complex systems. We utilized network analysis to explore the relationship between 30 secondary health conditions (SHCs) and health outcomes in persons with traumatic (TSCI) and non-traumatic SCI (NTSCI). The study objectives were to (1) apply network models to the 2011–2012 Canadian SCI Community Survey dataset to identify key variables linking the SHCs measured by the Multimorbidity Index-30 (MMI-30) to healthcare utilization (HCU), health status, and quality of life (QoL), (2) create a short form of the MMI-30 based on network analysis, and (3) compare the network-derived MMI to the MMI-30 in persons with TSCI and NTSCI.

Methods

Three network models (Gaussian Graphical, Ising, and Mixed Graphical) were created and analyzed using standard network measures (e.g., network centrality). Data analyzed included demographic and injury variables (e.g., age, sex, region of residence, date, injury severity), multimorbidity (using MMI-30), HCU (using the 7-item HCU questionnaire and classified as “felt needed care was not received” [HCU-FNCNR]), health status (using the 12-item Short Form survey [SF-12] Physical and Mental Component Summary [PCS-12 and MCS-12] score), and QoL (using the 11-item Life Satisfaction questionnaire [LiSAT-11] first question and a single item QoL measure).

Results

Network analysis of 1,549 participants (TSCI: 1137 and NTSCI: 412) revealed strong connections between the independent nodes (30 SHCs) and the dependent nodes (HCU-FNCNR, PCS-12, MCS-12, LiSAT-11, and the QoL score). Additionally, network models identified that cancer, deep vein thrombosis/pulmonary embolism, diabetes, high blood pressure, and liver disease were isolated. Logistic regression analysis indicated the network-derived MMI-25 correlated with all health outcome measures (p <0.001) and was comparable to the MMI-30.

Discussion

The network-derived MMI-25 was comparable to the MMI-30 and was associated with inadequate HCU, lower health status, and poor QoL. The MMI-25 shows promise as a follow-up screening tool to identify persons living with SCI at risk of having poor health outcomes.
The usefulness of global longitudinal peak strain and left atrial volume index in predicting atrial fibrillation in patients with ischemic stroke
Authors: Park Soo-Hyun , Kim Yerim , Lee Minwoo , Lee Sang-Hwa , Bae Jong Seok , Lee Ju-Hun , Kim Tae Jung , Ko Sang-Bae , Jeong Sang-Wuk , Kim Dong-Eog , Ryu Wi-Sun
Published: January 2024

Introduction

Detection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke.

Methods

We prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI).

Results

The mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P < 0.001) and a higher GLPS than those without AF (−14.0 vs. −17.3, P < 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, −14.6 vs. −18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03).

Discussion

The LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.
A deep learning wearable-based solution for continuous at-home monitoring of upper limb goal-directed movements
Authors: Nunes Adonay S. , Yildiz Potter İlkay , Mishra Ram Kinker , Bonato Paolo , Vaziri Ashkan
Published: January 2024

Introduction

Monitoring upper limb function is crucial for tracking progress, assessing treatment effectiveness, and identifying potential problems or complications. Hand goal-directed movements (GDMs) are a crucial aspect of daily life, reflecting planned motor commands with hand trajectories towards specific target locations. Previous studies have shown that GDM tasks can detect early changes in upper limb function in neurodegenerative diseases and can be used to track disease progression over time.

Methods

In this study, we used accelerometer data from stroke survivor participants and controls doing activities of daily living to develop an automated deep learning approach to detect GDMs. The model performance for detecting GDM or non-GDM from windowed data achieved an AUC of 0.9, accuracy 0.83, sensitivity 0.81, specificity 0.84 and F1 0.82.

Results

We further validated the utility of detecting GDM by extracting features from GDM periods and using these features to classify whether the measurements are collected from a stroke survivor or a control participant, and to predict the Fugl-Meyer assessment score from stroke survivors.

Discussion

This study presents a promising and reliable tool for monitoring upper limb function in a real-world setting, and assessing biomarkers related to upper limb health in neurological, neuromuscular and muscles disorders.
Electromyography varies by stage in inclusion body myositis
Authors: Mano Tomoo , Iguchi Naohiko , Eura Nobuyuki , Iwasa Naoki , Yamada Nanami , Horikawa Hirosei , Sugie Kazuma
Published: January 2024

Introduction

Inclusion body myositis (IBM) is a chronic inflammatory muscle disease that is characterized by mixed myogenic and neurogenic electromyography (EMG) findings. We investigated the association between EMG findings and the IBM stage.

Methods

We included consecutive patients diagnosed with IBM based on muscle biopsy and had needle EMG performed within 1 month of biopsy. Motor unit potential waveform (MUP) in EMG and pathological findings were compared between patients in early and late phases.

Results

In total, 30 patients with biopsy-confirmed IBM and 254 muscles were included. The rate of abnormal discharge did not differ according to disease stage. There was a difference in the frequency of occurrence between myogenic suggestive MUP and neurogenic of biceps and flexor digitorum profundus in the late phase. Abnormal MUP was observed even in muscles without muscle weakness, and myogenic changes were predominant in biceps and gastrocnemius with muscle weakness. The biopsy findings on the contralateral side of the muscle where electromyography was performed revealed a tendency for muscles that exhibited myogenic origin to have more inflammatory cells and RV; however, the difference was not significant.

Conclusion

The target muscles for EMG must be selected considering the disease stage as well. In the early stages of IBM, EMG results should be interpreted cautiously, as neurogenic suggestive pattern of MUP might also be exhibited. Contralateral electromyography findings may be helpful in selecting muscles for muscle biopsies, such as biceps and quadriceps.
Is catheter ablation associated with preservation of cognitive function? An analysis from the SAGE-AF observational cohort study
Authors: Srichawla Bahadar S. , Hamel Alexander P. , Cook Philip , Aleyadeh Rozaleen , Lessard Darleen , Otabil Edith M. , Mehawej Jordy , Saczynski Jane S. , McManus David D. , Moonis Majaz
Published: January 2024

Objectives

To examine the associations between catheter ablation treatment (CA) vs. medical management and cognitive impairment among older adults with atrial fibrillation (AF).

Methods

Ambulatory patients who had AF, were ≥65-years-old, and were eligible to receive oral anticoagulation could be enrolled into the SAGE (Systematic Assessment of Geriatric Elements)-AF study from internal medicine and cardiology clinics in Massachusetts and Georgia between 2016 and 2018. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline, 1-, and 2 years. Cognitive impairment was defined as a MoCA score ≤ 23. Multivariate-adjusted logistic regression of longitudinal repeated measures was used to examine associations between treatment with CA vs. medical management and cognitive impairment.

Results

887 participants were included in this analysis. On average, participants were 75.2 ± 6.7 years old, 48.6% women, and 87.4% white non-Hispanic. 193 (21.8%) participants received a CA before enrollment. Participants who had previously undergone CA were significantly less likely to be cognitively impaired during the 2-year study period (aOR 0.70, 95% CI 0.50–0.97) than those medically managed (i.e., rate and/or rhythm control), even after adjusting with propensity score for CA. At the 2-year follow-up a significantly greater number of individuals in the non-CA group were cognitively impaired (MoCA ≤ 23) compared to the CA-group (311 [44.8%] vs. 58 [30.1%], p = 0.0002).

Conclusion

In this 2-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.
Dyskinesia-hyperpyrexia syndrome in Parkinson's disease triggered by overdose of levodopa — a case report and literature review
Authors: Du Xiangnan , Wang Xuemei , Geng Xiaokun
Published: January 2024

Dyskinesia-hyperpyrexia syndrome, a rare medical emergency in Parkinson's disease, is first described in 2010. It is characterized by severe continuous dyskinesia associated with rhabdomyolysis, hyperthermia and subsequent alteration of the mental state. Gradual reduction of dopaminergic dose or DBS is recommended treatment. The prognosis is usually good, but sometimes fatal. But so far, this potentially fatal complication is not widely recognized by clinicians. In emergency, if clinicians fail to make prompt diagnosis and treatment, patients' conditions may get worse, and their lives may be threatened in serious cases.
Nomogram to predict 6-month mortality in acute ischemic stroke patients treated with endovascular treatment
Authors: Wen Rui , Wang Miaoran , Bian Wei , Zhu Haoyue , Xiao Ying , He Qian , Wang Yu , Liu Xiaoqing , Shi Yangdi , Hong Zhe , Xu Bing
Published: January 2024

Background

Acute Ischemic Stroke (AIS) presents significant challenges in evaluating the effectiveness of Endovascular Treatment (EVT). This study develops a novel prognostic model to predict 6-month mortality post-EVT, aiding in identifying patients likely to benefit less from this intervention, thus enhancing therapeutic decision-making.

Methods

We employed a cohort of AIS patients from Shenyang First People’s Hospital, serving as the Validation set, to develop our model. LASSO regression was used for feature selection, followed by logistic regression to create a prognostic nomogram for predicting 6-month mortality post-EVT. The model’s performance was validated using a dataset from PLA Northern Theater Command General Hospital, assessing discriminative ability (C-index), calibration (calibration plot), and clinical utility (decision curve analysis). Statistical significance was set at p < 0.05.

Results

The development cohort consisted of 219 patients. Six key predictors of 6-month mortality were identified: “Lack of Exercise” (OR, 4.792; 95% CI, 1.731–13.269), “Initial TICI Score 1” (OR, 1.334; 95% CI, 0.628–2.836), “MRS Score 5” (OR, 1.688; 95% CI, 0.754–3.78), “Neutrophil Percentage” (OR, 1.08; 95% CI, 1.042–1.121), “Onset Blood Sugar” (OR, 1.119; 95% CI, 1.007–1.245), and “Onset NIHSS Score” (OR, 1.074; 95% CI, 1.029–1.121). The nomogram demonstrated a high predictive capability with a C-index of 0.872 (95% CI, 0.830–0.911) in the development set and 0.830 (95% CI, 0.726–0.920) in the validation set.

Conclusion

Our nomogram, incorporating factors such as Lack of Exercise, Initial TICI Score 1, MRS Score 5, Neutrophil Percentage, Onset Blood Sugar, and Onset NIHSS Score, provides a valuable tool for predicting 6-month mortality in AIS patients post-EVT. It offers potential to refine early clinical decision-making and optimize patient outcomes, reflecting a shift toward more individualized patient care.
Comparative safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression in CT-guided and local anesthesia for recurrent trigeminal neuralgia
Authors: Xi Lulu , Liu Xiaohui , Shi Hongchen , Han Wenbiao , Gao Liqin , Wang Li , Liu Junpeng , Ren Yue , Du Yuanyuan , Liu Guangzhao
Published: January 2024

Background

There are several ways to treat trigeminal neuralgia (TN); however, TN may recur after treatment. Although microvascular decompression (MVD) is considered an effective treatment for trigeminal neuralgia, patients with recurrence may not be willing to undergo craniotomy.

Objective

This study compared the safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression for treating recurrent trigeminal neuralgia.

Methods

This was a prospective non-randomized controlled study. A total of 52 with recurrent TN were scheduled to undergo surgery in our Hospital from January–June 2021. The patients were classified into percutaneous radiofrequency thermocoagulation (PRT) and percutaneous balloon compression (PBC) groups based on the treatment. All surgeries were performed under computed tomography guidance and local anesthesia. Post-operative complications were also observed. Pain was assessed using the visual analog scale (VAS) and Barrow Neurological Institute (BNI) scale. Efficacy indices were evaluated at 3, 6, 12, and 18 months after surgery.

Results

During follow-up, the efficacy rates of the two methods within 18 months were 76.0 and 88.9%, respectively. All patients had hypoesthesia on the affected side, and no severe complications. Notably, 5 patients (20%) in the PRT group with multiple-branch pain, including the first branch of the trigeminal nerve (V1) pain in the PRT group, received radiofrequency therapy for the supraorbital notch (foramen) after puncture of the foramen ovale. However, multiple pain episodes resolved with only one operation in the PBC group.

Conclusion

CT-guided percutaneous radiofrequency thermocoagulation and percutaneous balloon compression under local anesthesia may be good options for treating recurrent trigeminal neuralgia. Percutaneous balloon compression may be recommended when multiple branches are involved, particularly in cases of V1 neuralgia.
Global and local neuronal coding of tactile information in the barrel cortex
Authors: Sharma Hariom , Azouz Rony
Published: January 2024

During tactile sensation in rodents, the whisker movements across surfaces give rise to intricate whisker motions that encompass discrete and transient stick–slip events, effectively conveying valuable information regarding surface properties. These surface characteristics are transformed into cortical neuronal responses. This study examined the coding strategies underlying these transformations in rat whiskers. We found that changes in surface coarseness modified the number and magnitude of stick–slip events, which in turn both modulated properties of neuronal responses. Global changes in the number of stick–slip events primarily affected neuronal discharge rates and the degree of neuronal synchronization. In contrast, local changes in the magnitude of stick–slip events affected the transformation of these kinematic and kinetic characteristics into neuronal discharges. Most cortical neurons exhibited surface coarseness selectivity through global and local stick–slip event properties. However, this selectivity varied across coding strategies in the same neurons, given that each coding strategy reflected different aspects of changes in whisker-surface interactions. The degree of spatial similarity in surface coarseness preference in adjacently recorded neurons differed among these coding strategies. Adjacently recorded neurons exhibited the same surface coarseness preference in their firing rates but not through other coding strategies. Through these results, we were able to show that local stick–slip event properties contribute to texture discrimination, complementing and surpassing global coding in this context. These findings suggest that the representation of surface coarseness in the cortex may rely on concurrent coding strategies that integrate tactile information across different spatiotemporal scales.
Immediate neural effects of acupuncture manipulation time for stroke with motor dysfunction: a fMRI pilot study
Authors: Zhou Yihao , Dai Anhong , Feng Sifeng , Zhu Tao , Liu Meifang , Shi Jing , Wang Dongyan
Published: January 2024

Introduction

Acupuncture is widely utilized as a beneficial intervention for the treatment of motor dysfunction after stroke, and its effectiveness depends on the stimulation dose. Manipulation time is an important factor affecting the dose. This trial aimed use fMRI to explore the immediate neural effects in stroke patients with motor dysfunction by different acupuncture manipulation times, to reveal the neural mechanism of acupuncture manipulation.

Methods

Thirty participants were divided into three groups according to different acupuncture times. Each group received the same acupoint prescription, although the continuous manipulation time of each acupoint in three groups was 1-min, 2-min, and 3-min, respectively. The NIHSS, FMA and fMRI-BOLD in each participant we obtained before and after acupuncture manipulation. Then, we used the regional homogeneity (ReHo) algorithm to analyze the changes of brain function and to compare the neural effects at different acupuncture manipulation times.

Results

There were no significant differences in NIHSS and FMA scores between and within groups. Longitudinal analysis of ReHo values indicated that the right inferior frontal gyrus was activated in the 1-min group, the right insula in the 2-min group, and the right inferior temporal gyrus in the 3-min group. Compared with the 1-min group, the 2-min group showed the ReHo values of the right precentral gyrus was decreased, and the 3-min group showed the left cerebellum posterior lobe was increased, the right posterior cingulate gyrus and the right anterior cingulate gyrus were decreased. Compared with the 2-min group, the 3-min group showed the ReHo values of the right cerebellum anterior lobe was increased.

Conclusion

Our findings suggest that acupuncture at different manipulation times caused different changes of the neural effects in stroke patients, and the volume of activated voxel clusters is positively correlated with the manipulation time. Longer acupuncture manipulation could drive SMN and DMN in stroke patients, which may be the potential neurological mechanism of acupuncture manipulation affecting the recovery of motor dysfunction.
A pathogenic variant in the FLCN gene presenting with pure dementia: is autophagy at the intersection between neurodegeneration and cancer?
Authors: Bottillo Irene , Laino Luigi , Azzarà Alessia , Lintas Carla , Cassano Ilaria , Di Lazzaro Vincenzo , Ursini Francesca , Motolese Francesco , Bargiacchi Simone , Formicola Daniela , Grammatico Paola , Gurrieri Fiorella
Published: January 2024

Introduction

Folliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt–Hogg–Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax.

Patient and results

We report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1.

Discussion

The MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.
Treatments and regulatory mechanisms of acoustic stimuli on mood disorders and neurological diseases
Authors: Chen Yikai , Sun Julianne , Tao Junxian , Sun Tao
Published: January 2024

Acoustic stimuli such as music or ambient noise can significantly affect physiological and psychological health in humans. We here summarize positive effects of music therapy in premature infant distress regulation, performance enhancement, sleep quality control, and treatment of mental disorders. Specifically, music therapy exhibits promising effects on treatment of neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). We also highlight regulatory mechanisms by which auditory intervention affects an organism, encompassing modulation of immune responses, gene expression, neurotransmitter regulation and neural circuitry. As a safe, cost-effective and non-invasive intervention, music therapy offers substantial potential in treating a variety of neurological conditions.
Targeting ion channels with ultra-large library screening for hit discovery
Authors: Melancon Kortney , Pliushcheuskaya Palina , Meiler Jens , Künze Georg
Published: January 2024

Ion channels play a crucial role in a variety of physiological and pathological processes, making them attractive targets for drug development in diseases such as diabetes, epilepsy, hypertension, cancer, and chronic pain. Despite the importance of ion channels in drug discovery, the vastness of chemical space and the complexity of ion channels pose significant challenges for identifying drug candidates. The use of in silico methods in drug discovery has dramatically reduced the time and cost of drug development and has the potential to revolutionize the field of medicine. Recent advances in computer hardware and software have enabled the screening of ultra-large compound libraries. Integration of different methods at various scales and dimensions is becoming an inevitable trend in drug development. In this review, we provide an overview of current state-of-the-art computational chemistry methodologies for ultra-large compound library screening and their application to ion channel drug discovery research. We discuss the advantages and limitations of various in silico techniques, including virtual screening, molecular mechanics/dynamics simulations, and machine learning-based approaches. We also highlight several successful applications of computational chemistry methodologies in ion channel drug discovery and provide insights into future directions and challenges in this field.
First activity and interactions in thalamus and cortex using raw single-trial EEG and MEG elicited by somatosensory stimulation
Authors: Karittevlis Christodoulos , Papadopoulos Michail , Lima Vinicius , Orphanides Gregoris A. , Tiwari Shubham , Antonakakis Marios , Papadopoulou Lesta Vicky , Ioannides Andreas A.
Published: January 2024

Introduction

One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation.

Methods

We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory.

Results

Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters.

Discussion

It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces.
Knowledge, attitude, and practice toward non-nutritive sweeteners among the population with reduced sugar intake requirement
Authors: Chen Qiao , Zhang Yan , Li Hui
Published: January 2024

Introduction

This study aimed to explore the knowledge, attitude, and practice (KAP) toward non-nutritive sweeteners among a population with reduced sugar intake requirements.

Methods

This cross-sectional study used self-developed questionnaires to collect demographic characteristics and KAP towards non-nutritive sweeteners among respondents with reduced sugar intake requirements, i.e., overweight or obese individuals and patients with pre-diabetes or diabetes.

Results

A total of 639 valid questionnaires were collected, and 51.64% of participants were male. The KAP scores were 7.63 ± 3.58 (range: 0–11), 34.28 ± 7.47 (range: 12–60), and 15.48 ± 3.97 (range: 7–35), respectively. Pearson’s correlation analysis showed that knowledge score was positively correlated with attitude (r = 0.229, p < 0.001) and practice score (r = 0.467, p < 0.001), while attitude was positively correlated with practice (r = 0.312, p < 0.001). The structural equation model showed that knowledge was directly and positively associated with attitude (path coefficient = 0.48, p < 0.001) and practice (path coefficient = 0.46, p < 0.001). In addition, the attitude was directly and positively associated with practice (path coefficient = 0.12, p < 0.001). Besides, diabetes was associated with lower knowledge (path coefficient = −0.81, p = 0.038) and practice (path coefficient = −0.42, p < 0.041).

Discussion

Population with the reduced sugar intake requirement showed poor knowledge, negative attitudes, and suboptimal practices toward non-nutritive sweeteners. To optimize the utilization of non-nutritive sweeteners in accordance with medical prescriptions, especially for individuals with diabetes, tailored educational interventions may be designed for participants with lower KAP.
Exploring health and toxicity in food choices: 10 examples navigating the gray area
Authors: Bast Aalt , Semen Khrystyna O.
Published: January 2024

People’s perception on what is healthy and what is toxic food, determines food preferences and eating behavior. The difference between heathy and toxic food and food ingredients is however not always clear. This is illustrated with 10 examples. Unjustly, all-natural food is regarded as safe. Regulation on health claims on food and food risks is not balanced. Biphasic responses of the physiological effect of food ingredients show that mild toxicity of these substances results in health promotion. Nutritional substances with drugs may have either a negative or a positive effect on health. New toxicological methodologies can be brought into play, to better understand the dynamics of health and disease. Unfortunately, we still cannot taste toxicity.
Case report: Life threatening hyponatremia in infants with urinary tract infections: two cases of type III pseudohypoaldosteronism and review of the literature
Authors: Carl Cécile , Dinkelbach Lars , Mohr Julia , Perez Ruy , Vera Lopez Tobias , Fricke-Otto Susanne , Niehues Tim
Published: January 2024

We describe two female infants at the age of five and six months with urinary tract infections presenting with vomiting and reduced drinking behavior. On laboratory analysis, severe hyponatremia (106 mmol/L and 109 mmol/L) was seen with hyperkalemia and compensated metabolic acidosis. Endocrinological analyses revealed massively increased levels of aldosterone and renin, leading to the diagnosis of type III pseudohypoaldosteronism (PHA). A review of the current literature 2013–2023 revealed 26 type III PHA cases aged up to ten months with reduced drinking behavior, weight loss and/or failure to thrive being the most common clinical presentations. Given the severe presentation of PHA electrolyte measurements in infants with urinary tract infections and/or in infants with congenital anomalies of the kidney and urinary tract (CAKUT) are strongly recommended.
Case Report: The unique case of flexible intramedullary nailing of pediatric radius complicated with temporary radial nerve’s motor branch damage
Authors: Wiktor Łukasz , Tomaszewski Ryszard
Published: January 2024

This study reported a case of radius flexible intramedullary nailing complicated by temporary paralysis of the posterior interosseous nerve due to compression of the ESIN on the nerve in an 8-year-old boy. The nerve damage resulted from an essential misconception at the surgery. Despite bad decisions made during qualifications and the procedure undertaken, restoring the nerve function, and gaining satisfactory functional fracture recovery was possible. Although it is generally acknowledged to perform retrograde flexible intramedullary nailing from the level of the distal radial metaphysis, the presentation of our case aims to emphasize the real risk of damage to the motor branch of the radial nerve when approaching the proximal metaphysis.
Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial
Authors: Kalinin Mikhail N. , Khasanova Dina R.
Published: January 2024

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair.

Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk.

Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method.

Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%–56.7%; H2, 1.56–2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found.

Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.
Cell death in cancer chemotherapy using taxanes
Authors: Xu Ana P. , Xu Lucy B. , Smith Elizabeth R. , Fleishman Joshua S. , Chen Zhe-Sheng , Xu Xiang-Xi
Published: January 2024

Cancer cells evolve to be refractory to the intrinsic programmed cell death mechanisms, which ensure cellular tissue homeostasis in physiological conditions. Chemotherapy using cytotoxic drugs seeks to eliminate cancer cells but spare non-cancerous host cells by exploring a likely subtle difference between malignant and benign cells. Presumably, chemotherapy agents achieve efficacy by triggering programmed cell death machineries in cancer cells. Currently, many major solid tumors are treated with chemotherapy composed of a combination of platinum agents and taxanes. Platinum agents, largely cis-platin, carboplatin, and oxaliplatin, are DNA damaging agents that covalently form DNA addicts, triggering DNA repair response pathways. Taxanes, including paclitaxel, docetaxel, and cabazitaxel, are microtubule stabilizing drugs which are often very effective in purging cancer cells in clinical settings. Generally, it is thought that the stabilization of microtubules by taxanes leads to mitotic arrest, mitotic catastrophe, and the triggering of apoptotic programmed cell death. However, the precise mechanism(s) of how mitotic arrest and catastrophe activate the caspase pathway has not been established. Here, we briefly review literature on the involvement of potential cell death mechanisms in cancer therapy. These include the classical caspase-mediated apoptotic programmed cell death, necroptosis mediated by MLKL, and pore forming mechanisms in immune cells, etc. In particular, we discuss a newly recognized mechanism of cell death in taxane-treatment of cancer cells that involves micronucleation and the irreversible rupture of the nuclear membrane. Since cancer cells are commonly retarded in responding to programmed cell death signaling, stabilized microtubule bundle-induced micronucleation and nuclear membrane rupture, rather than triggering apoptosis, may be a key mechanism accounting for the success of taxanes as anti-cancer agents.
Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus
Authors: Tan Xinrui , Pan Xiongfeng , Wu Xiaochuan , Zheng Songjia , Chen Yuyao , Liu Donghai , Zhang Xingxing
Published: January 2024

Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes.

Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model.

Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by −0.21% (95% CI, −0.33 to −0.10), weight by −4.04 kg (−4.8 to −3.27), systolic pressure by −2.57 mmHg (−4.11 to −1.03), and diastolic blood pressure by −1.02 mmHg (−1.99 to −0.06). In addition, there was a decrease in prandial insulin dose (WMD, −4.23 IU; 95% CI, −5.26 to −3.20), basal insulin dose (−2.40 IU; −3.93 to −0.87), and total insulin dose (−5.73 IU; −10.61 to −0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33–3.77).

Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events.

Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.
Autophagy machinery plays an essential role in traumatic brain injury-induced apoptosis and its related behavioral abnormalities in mice: focus on Boswellia Sacra gum resin
Authors: Interdonato Livia , Marino Ylenia , Impellizzeri Daniela , D’Amico Ramona , Siracusa Rosalba , Fusco Roberta , Cammilleri Gaetano , Pantano Licia , Modafferi Sergio , Abdelhameed Ali S. , Fritsch Tilman , Rashan Luay J. , Cuzzocrea Salvatore , Calabrese Vittorio , Cordaro Marika , Di Paola Rosanna
Published: January 2024

Traumatic brain injury (TBI) is described as a structural damage or physiological disturbance of brain function that occurs after trauma and causes disability or death in people of all ages. New treatment targets for TBI are being explored because current medicines are frequently ineffectual and poorly tolerated. There is increasing evidence that following TBI, there are widespread changes in autophagy-related proteins in both experimental and clinical settings. The current study investigated if Boswellia Sacra Gum Resin (BSR) treatment (500 mg/kg) could modulate post-TBI neuronal autophagy and protein expression, as well as whether BSR could markedly improve functional recovery in a mouse model of TBI. Taken together our results shows for the first time that BSR limits histological alteration, lipid peroxidation, antioxidant, cytokines release and autophagic flux alteration induced by TBI.
Deep learning for medicinal plant species classification and recognition: a systematic review
Authors: Mulugeta Adibaru Kiflie , Sharma Durga Prasad , Mesfin Abebe Haile
Published: January 2024

Knowledge of medicinal plant species is necessary to preserve medicinal plants and safeguard biodiversity. The classification and identification of these plants by botanist experts are complex and time-consuming activities. This systematic review’s main objective is to systematically assess the prior research efforts on the applications and usage of deep learning approaches in classifying and recognizing medicinal plant species. Our objective was to pinpoint systematic reviews following the PRISMA guidelines related to the classification and recognition of medicinal plant species through the utilization of deep learning techniques. This review encompassed studies published between January 2018 and December 2022. Initially, we identified 1644 studies through title, keyword, and abstract screening. After applying our eligibility criteria, we selected 31 studies for a thorough and critical review. The main findings of this reviews are (1) the selected studies were carried out in 16 different countries, and India leads in paper contributions with 29%, followed by Indonesia and Sri Lanka. (2) A private dataset has been used in 67.7% of the studies subjected to image augmentation and preprocessing techniques. (3) In 96.7% of the studies, researchers have employed plant leaf organs, with 74% of them utilizing leaf shapes for the classification and recognition of medicinal plant species. (4) Transfer learning with the pre-trained model was used in 83.8% of the studies as a future extraction technique. (5) Convolutional Neural Network (CNN) is used by 64.5% of the paper as a deep learning classifier. (6) The lack of a globally available and public dataset need for medicinal plants indigenous to a specific country and the trustworthiness of the deep learning approach for the classification and recognition of medicinal plants is an observable research gap in this literature review. Therefore, further investigations and collaboration between different stakeholders are required to fulfilling the aforementioned research gaps.
Walking in nature may improve affect but not cognition
Authors: Trammell Janet P. , Harriger Jennifer A. , Krumrei-Mancuso Elizabeth J.
Published: January 2024

Beneficial effects of natural environments on affect have been consistently reported, but effects on cognition have been less consistent. We examined affect and cognitive performance in the domains of attention, working memory, executive function, and recall and recognition memory in a sample of 188 undergraduate participants who completed a walk in one of three environments: an outdoor nature environment, an outdoor urban environment, or an indoor (treadmill) environment. Supporting the hypotheses, the outdoor nature environment resulted in the greatest increase in positive affect and decrease in negative affect from pre-to post-walk. However, there were no effects of location on any cognitive measure. These results suggest that cognitive effects do not always occur in tandem with affective benefits. Possible explanations, including prior frequent exposure to nature in our participants and extremity of the natural environment, are discussed.