Decoding Micro-Electrocorticographic Signals by Using Explainable 3D Convolutional Neural Network to Predict Finger Movements.

BACKGROUND: Electroencephalography (EEG) and electrocorticography (ECoG) recordings have been used to decode finger movements by analyzing brain activity. Traditional methods focused on single bandpass power changes for movement decoding, utilizing machine learning models requiring manual feature extraction. NEW METHOD: This study introduces a 3D convolutional neural network (3D-CNN) model to decode finger movements using ECoG data. The model employs adaptive, explainable AI (xAI) techniques to interpret the physiological relevance of brain signals. ECoG signals from epilepsy patients during awake craniotomy were processed to extract power spectral density across multiple frequency bands. These data formed a 3D matrix used to train the 3D-CNN to predict finger trajectories. RESULTS: The 3D-CNN model showed significant accuracy in predicting finger movements, with root-mean-square error (RMSE) values of 0.26-0.38 for single finger movements and 0.20-0.24 for combined movements. Explainable AI techniques, Grad-CAM and SHAP, identified the high gamma (HG) band as crucial for movement prediction, showing specific cortical regions involved in different finger movements. These findings highlighted the physiological significance of the HG band in motor control. COMPARISON WITH EXISTING METHODS: The 3D-CNN model outperformed traditional machine learning approaches by effectively capturing spatial and temporal patterns in ECoG data. The use of xAI techniques provided clearer insights into the model's decision-making process, unlike the "black box" nature of standard deep learning models. CONCLUSIONS: The proposed 3D-CNN model, combined with xAI methods, enhances the decoding accuracy of finger movements from ECoG data. This approach offers a more efficient and interpretable solution for brain-computer interface (BCI) applications, emphasizing the HG band's role in motor control.

Occipital nerve stimulation for cluster headache: lessons to learn from the 'voltage tuners'.

BACKGROUND: Cluster headache (CH) is a significant health concern due to its major socioeconomic consequences and most patients being refractory to conventional strategies. For treatment resistant CH, occipital nerve stimulation (ONS) is considered an effective treatment option. Whereas most patients do not adjust the amplitude of the ONS system, a subset changes the amplitude on a regular basis using their remote control, and are therefore referred to as 'voltage tuners'. Anxiety and self-control are thought to be central themes to this behavior. Research on this voltage tuning behavior could provide new insights in the use of ONS as acute attack treatment. To date, voltage tuning has not been assessed for CH. Hence this is a unique study aiming to investigate the occurrence and efficacy of voltage tuning in patients with CH and ONS. METHODS: For this analysis, patients with CH who received ONS from 2020-2024, at our university medical center, were included. All patients underwent bilateral ONS implantation. Data on attack frequency, intensity and duration were collected retrospectively. Outcomes on the response, frequency, moment during the day, duration, rationale, sensation, average increase in amplitude, and efficacy of voltage tuning were collected with prospective interviews. RESULTS: Thirty-three patients (M = 20) (42 ± 12.7 years) were included in the current analysis. At 1y follow-up, an overall response rate of 70% (23/33) was found for ONS. In total, 48% (18/33) of patients were defined as voltage tuners. Voltage tuning was performed with an average increase in amplitude of 92 (20-360)%, a frequency of 1-20 times/month and duration of 20 minutes-48 hours. Sensations of voltage tuning were described as "tingling" and/or "pinching". The rationale for voltage tuning in patients varied from prevention and ceasing to lowering the intensity and enhance control of CH attack. CONCLUSIONS: Outcomes show that voltage tuning may cease and/or terminate CH attacks and therefore raise interests in the use of ONS as acute attack treatment for patients with resistant CH treated with ONS. Future research on the occurrence and potential of voltage tuning will provide valuable insights for achieving optimal efficacy of ONS and quality of life in patients with CH.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome ß5 active-site (Pfß5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto ß7. Inhibition of Pfß5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the ß5/ß6/ß3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Do All Postoperative Vancouver B2 Fractures Require Revision Arthroplasty With Cementless Stems?

Background: Management of periprosthetic fractures has been guided by the Vancouver classification, which recommends revision for fractures around a loose femoral implant (B2). New studies have challenged this approach, demonstrating acceptable outcomes with internal fixation. This study evaluates our experience with Vancouver B2 fractures, comparing internal fixation to femoral revision. We hypothesized that in select cases with cementless stems, internal fixation would provide acceptable results with reduced morbidity. Methods: A retrospective review was performed of periprosthetic hip fractures treated at our institution between 1 January 2012 and 4 November 2022. We excluded patients who did not have prior radiographs and evidence of stem subsidence, suggestive of a Vancouver B2 fracture. Thirteen patients were included in the analysis. Results: Four patients (31%) underwent revision of the femoral component, 4 patients (31%) underwent plating, and 5 patients (38%) underwent internal fixation with cerclage cabling. The average operative duration was 158 minutes, 203 minutes, and 62 minutes for the revision, plating, and cabling cohorts, respectively (P = .009). Blood loss was 463 cc, 510 cc, and 90 cc for the revision, plating, and cabling cohorts, respectively (P = .036). Three patients in both the revision and plating cohorts each received a transfusion (75%), whereas no patients in the cabling cohort required a transfusion (P = .033). All patients demonstrated fracture healing on the postoperative radiographs. No patients required additional surgery during the follow-up period. Conclusions: We have demonstrated that Vancouver B2 periprosthetic fractures with intact lateral cortices may be treated with internal fixation with cerclage cabling with excellent results.

Complex hydrology and variability of nitrogen sources in a karst watershed.

Streams draining karst areas with rapid groundwater transit times may respond relatively quickly to nitrogen reduction strategies, but the complex hydrologic network of interconnected sinkholes and springs is challenging for determining the placement and effectiveness of management practices. This study aims to inform nitrogen reduction strategies in a representative agricultural karst setting of the Chesapeake Bay watershed (Fishing Creek watershed, Pennsylvania) with known elevated nitrate contamination and a previous documented groundwater residence time of less than a decade. During baseflow conditions, streamflow did not increase with drainage area. Headwaters and the main stem lost substantial flow to sinkholes until eventually discharging along large springs downstream. Seasonal hydrologic conditions shift the flow and nitrogen load spatially among losing and gaining stream sections. A compilation of nitrogen source inputs with the geochemistry and the pattern of enrichment of δ15N and δ18O suggest that the nitrogen in streams and springs during baseflow represents a mixture of manure, fertilizer, and wastewater sources with low potential for denitrification. The pH and calcite saturation index increased along generalized flow paths from headwaters to springs and indicate shorter groundwater residence times in baseflow during the spring versus summer. Given the substantial investment in management practices, fixed monitoring sites could incorporate synoptic water sampling to properly monitor long-term progress and help inform management actions in karst watersheds. Although karst watersheds have the potential to respond to nitrogen reduction strategies due to shorter groundwater residence times, high nitrogen inputs, effectiveness of conservation practices, and release of legacy nutrients within the karst cavities could confound progress of water quality goals.

Application of a Machine Learning-Based Classification Approach for Developing Host Protein Diagnostic Models for Infectious Disease.

In recent years, infectious disease diagnosis has increasingly turned to host-centered approaches as a complement to pathogen-directed ones. The former, however, typically requires the interpretation of complex multiple biomarker datasets to arrive at an informative diagnostic outcome. This report describes a machine learning (ML)-based classification workflow that is intended as a template for researchers seeking to apply ML approaches for developing host-based infectious disease biomarker classifiers. As an example, we built a classification model that could accurately distinguish between three disease etiology classes: bacterial, viral, and normal in human sera using host protein biomarkers of known diagnostic utility. After collecting protein data from known disease samples, we trained a series of increasingly complex Auto-ML models until arriving at an optimized classifier that could differentiate viral, bacterial, and non-disease samples. Even when limited to a relatively small training set size, the model had robust diagnostic characteristics and performed well when faced with a blinded sample set. We present here a flexible approach for applying an Auto-ML-based workflow for the identification of host biomarker classifiers with diagnostic utility for infectious disease, and which can readily be adapted for multiple biomarker classes and disease states.

Interspecific dispersal constraints suppress pattern formation in metacommunities.

Decisions to disperse from a habitat stand out among organismal behaviours as pivotal drivers of ecosystem dynamics across scales. Encounters with other species are an important component of adaptive decision-making in dispersal, resulting in widespread behaviours like tracking resources or avoiding consumers in space. Despite this, metacommunity models often treat dispersal as a function of intraspecific density alone. We show, focusing initially on three-species network motifs, that interspecific dispersal rules generally drive a transition in metacommunities from homogeneous steady states to self-organized heterogeneous spatial patterns. However, when ecologically realistic constraints reflecting adaptive behaviours are imposed-prey tracking and predator avoidance-a pronounced homogenizing effect emerges where spatial pattern formation is suppressed. We demonstrate this effect for each motif by computing master stability functions that separate the contributions of local and spatial interactions to pattern formation. We extend this result to species-rich food webs using a random matrix approach, where we find that eventually, webs become large enough to override the homogenizing effect of adaptive dispersal behaviours, leading once again to predominately pattern-forming dynamics. Our results emphasize the critical role of interspecific dispersal rules in shaping spatial patterns across landscapes, highlighting the need to incorporate adaptive behavioural constraints in efforts to link local species interactions and metacommunity structure. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.

Preparation and characterization of hybrid polypyrrole nanoparticles as a conducting polymer with controllable size.

Hybrid polypyrrole (PPy) nanoparticles were prepared using a low-temperature oxidative polymerization process in an acidic solution with polyethyleneimine (PEI) as a template and amine source. The results showed that the nanoparticles have an amorphous structure in the X-ray diffractogram and exhibited good dispersibility in water, uniform size, and a specific conductivity ranging from 0.1 to 6.9 S/cm. The particle size could be tuned from 85 to 300 nm by varying the reactant concentration. Undoping the samples with sodium hydroxide (NaOH) solution altered the optical absorption properties and surface roughness of the particles. However, it did not affect the particle size. The nanoparticles also exhibited optical sensing properties based on their UV-vis absorption changes with the pH. Moreover, nanoparticles could have potential applications in gene delivery and bio-adsorption for contaminant removal. This work demonstrates a simple and effective method for preparing hybrid polypyrrole nanoparticles with controllable size, dispersibility, and conductivity for various nanotechnology, biotechnology, and environmental engineering purposes.

Ladder Use Ability, Behavior and Exposure by Age and Gender.

This study aimed to quantify and compare ladder use ability and behavior in younger and older men and women from three ladder use behavior experiments. The experimental tasks comprised (1) changing a lightbulb on a household stepladder under two cognitive demands (single and dual task), (2) clearing a simulated roof gutter on a straight ladder and (3) querying ladder choice in different exigency scenarios. Ladder use ability and behavior data were captured from recorded time, performance, motion capture and user choice data. In addition, this study surveyed ladder use frequency and habitual behaviors. The experimental findings indicate that older adults require more time to complete ladder tasks; younger adults display riskier ladder use behaviors; men and women display similar ladder use ability; and men are more willing to climb riskier ladders. The survey found older adults to report more frequent ladder use than younger adults, and men use straight ladders more frequently than women. These results suggest that the reported higher ladder fall rates experienced by older adults and men are linked to increased ladder use exposure and riskier ladder choice. This knowledge can help guide population-specific interventions to reduce ladder falls in both young and older people.

Putative climate adaptation in American pikas (Ochotona princeps) is associated with copy number variation across environmental gradients.

Improved understanding of the genetic basis of adaptation to climate change is necessary for maintaining global biodiversity moving forward. Studies to date have largely focused on sequence variation, yet there is growing evidence that suggests that changes in genome structure may be an even more significant source of adaptive potential. The American pika (Ochotona princeps) is an alpine specialist that shows some evidence of adaptation to climate along elevational gradients, but previous work has been limited to single nucleotide polymorphism based analyses within a fraction of the species range. Here, we investigated the role of copy number variation underlying patterns of local adaptation in the American pika using genome-wide data previously collected across the entire species range. We identified 37-193 putative copy number variants (CNVs) associated with environmental variation (temperature, precipitation, solar radiation) within each of the six major American pika lineages, with patterns of divergence largely following elevational and latitudinal gradients. Genes associated (n = 158) with independent annotations across lineages, variables, and/or CNVs had functions related to mitochondrial structure/function, immune response, hypoxia, olfaction, and DNA repair. Some of these genes have been previously linked to putative high elevation and/or climate adaptation in other species, suggesting they may serve as important targets in future studies.

Global patterns of allochthony in stream-riparian meta-ecosystems.

Ecosystems that are coupled by reciprocal flows of energy and nutrient subsidies can be viewed as a single "meta-ecosystem." Despite these connections, the reciprocal flow of subsidies is greatly asymmetrical and seasonally pulsed. Here, we synthesize existing literature on stream-riparian meta-ecosystems to quantify global patterns of the amount of subsidy consumption by organisms, known as "allochthony." These resource flows are important since they can comprise a large portion of consumer diets, but can be disrupted by human modification of streams and riparian zones. Despite asymmetrical subsidy flows, we found stream and riparian consumer allochthony to be equivalent. Although both fish and stream invertebrates rely on seasonally pulsed allochthonous resources, we find allochthony varies seasonally only for fish, being nearly three times greater during the summer and fall than during the winter and spring. We also find that consumer allochthony varies with feeding traits for aquatic invertebrates, fish, and terrestrial arthropods, but not for terrestrial vertebrates. Finally, we find that allochthony varies by climate for aquatic invertebrates, being nearly twice as great in arid climates than in tropical climates, but not for fish. These findings are critical to understanding the consequences of global change, as ecosystem connections are being increasingly disrupted.

Phylogenomics of American pika (Ochotona princeps) lineage diversification.

Quaternary climate oscillations have profoundly influenced current species distributions. For many montane species, these fluctuations were a prominent driver in species range shifts, often resulting in intraspecific diversification, as has been the case for American pikas (Ochotona princeps). Range shifts and population declines in this thermally-sensitive lagomorph have been linked to historical and contemporary environmental changes across its western North American range, with previous research reconstructing five mitochondrial DNA lineages. Here, we paired genome-wide data (25,244 SNPs) with range-wide sampling to re-examine the number and distribution of intra-specific lineages, and investigate patterns of within- and among-lineage divergence and diversity. Our results provide genomic evidence of O. princeps monophyly, reconstructing six distinct lineages that underwent multiple rounds of divergence (0.809-2.81 mya), including a new Central Rocky Mountain lineage. We further found evidence for population differentiation across multiple spatial scales, and reconstructed levels of standing variation comparable to those found in other small mammals. Overall, our findings demonstrate the influence of past glacial cycles on O. princeps lineage diversification, suggest that current subspecific taxonomy may need to be revisited, and provide an important framework for investigations of American pika adaptive potential in the face of anthropogenic climate change.

Adherence Monitoring Package (AMoPac) in patients suspected of non-response to antihypertensive treatment: perceived usefulness by general practitioners.

BACKGROUND: Non-adherence to antihypertensive agents is common, mainly because of the low perceived burden of high blood pressure. General practitioners (GPs) are unable to predict whether patients are adhering to a recommended treatment. Knowledge about adherence might be of clinical interest in patients non-responding to antihypertensive treatment. AIM: To assess the usefulness of an Adherence Monitoring Package (AMoPac) to identify non-adherence in patients non-responding to antihypertensive treatment. METHODS: AMoPac consists of (1) 4 weeks of electronic adherence monitoring, (2) pharmacist's feedback on patient's intake behaviour and (3) adherence metrics including clinical-pharmaceutical recommendations to the GP. AMoPac-HYP ('Adherence Monitoring Package to identify non-adherence in ambulatory HYPertensive patients') is an observational study among GPs and ambulatory patients with hypertension in a real-world setting. The primary outcome was GPs' perceived usefulness of AMoPac. Secondary outcomes were (1) frequency of medication problems and prescribing errors; (2) types of pharmacist's' recommendations; (3) acceptance of the recommendations by GPs; (4) medication adherence and (5) patients' satisfaction. Outcomes are reported descriptively. Data were collected with questionnaires and electronic monitoring of medicine intake. RESULTS: Fifteen GPs and 15 patients with hypertension participated in the AMoPac-HYP Study. Patients were on average 62 years old, and mean blood pressure was 137/83 mmHg. All GPs rated AMoPac as useful. The most frequently mentioned use was excluding non-adherence in patients with hypertension (93%). Medication problems and prescribing errors were observed in 80% of the patients. The study pharmacist recommended adherence support (N=9 patients) and treatment optimisation (N=8 patients). The recommendations were accepted and implemented in 10 of 17 cases by the GP. Patients' mean taking and timing adherence were 90% and 86%, respectively. Satisfaction with the study procedures among patients was high. CONCLUSION: AMoPac was rated as useful for identifying and excluding non-adherence in patients with hypertension and was highly accepted among patients. Including adherence data in clinical decision-making could contribute to optimising patient care.

A novel antibiotic class targeting the lipopolysaccharide transporter.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options1. No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years1. Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action of this molecule class involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB2FGC complex. A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. This chemical class represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate, and additionally identifies LptB2FGC as a tractable target for antimicrobial drug development.

Intake reminders are effective in enhancing adherence to direct oral anticoagulants in stroke patients: a randomised cross-over trial (MAAESTRO study).

BACKGROUND: Direct oral anticoagulants (DOAC) effectively prevent recurrent ischaemic events in atrial fibrillation (AF) patients with recent stroke. However, excellent adherence to DOAC is mandatory to guarantee sufficient anticoagulation as the effect quickly subsides. AIM: To investigate the effect of intake reminders on adherence to DOAC. METHODS: MAAESTRO was a randomised, cross-over study in DOAC-treated AF patients hospitalised for ischaemic stroke. Adherence was measured by electronic monitoring for 12 months. After an observational phase, patients were randomised to obtain an intake reminder either in the first or the second half of the subsequent 6-month interventional phase. The primary outcome was 100%-timing adherence. Secondary outcomes were 100%-taking adherence, and overall timing and taking adherence. We analysed adherence outcomes using McNemar's test or mixed-effects logistic models. RESULTS: Between January 2018 and March 2022, 130 stroke patients were included, of whom 42 dropped out before randomisation. Analysis was performed with 84 patients (mean age: 76.5 years, 39.3% women). A 100%-timing adherence was observed in 10 patients who were using the reminder, and in zero patients without reminder (p = 0.002). The reminder significantly improved adherence to DOAC, with study participants having 2.7-fold increased odds to achieve an alternative threshold of 90%-timing adherence (OR 2.65; 95% CI 1.05-6.69; p = 0.039). A similar effect was observed for 90%-taking adherence (OR 3.06; 95% CI 1.20-7.80; p = 0.019). Overall timing and taking adherence increased significantly when using the reminder (OR 1.70; 95% CI 1.55-1.86, p < 0.01; and OR 1.67; 95% CI 1.52-1.84; p < 0.01). CONCLUSION: Intake reminders increased adherence to DOAC in patients with stroke attributable to atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03344146.

Sequence analysis of Discoknowium, an A5 mycobacteriophage.

Discoknowium is a temperate A5 bacteriophage that infects the bacterial host Mycobacterium smegmatis. Isolated from a rat fecal sample, Discoknowium's genome is 50,222 bp in length, contains 84 genes and 1 tRNA, and shares 82%-98% nucleotide identity with other A5 subcluster phages.

Seasonal trends in lysogeny in an Appalachian oak-hickory forest soil.

Since 1989, investigations into viral ecology have revealed how bacteriophages can influence microbial dynamics within ecosystems at global scales. Most of the information we know about temperate phages, which can integrate themselves into the host genome and remain dormant via a process called lysogeny, has come from research in aquatic ecosystems. Soil environments remain under-studied, and more research is necessary to fully understand the range of impacts phage infections have on the soil bacteria they infect. The aims of this study were to compare the efficacy of different prophage-inducing agents and to elucidate potential temporal trends in lysogeny within a soil bacterial community. In addition to mitomycin C and acyl-homoserine lactones, our results indicated that halosulfuron methyl herbicides may also be potent inducing agents. In optimizing chemical induction assays, we determined that taking steps to reduce background virus particles and starve cells was critical in obtaining consistent results. A clear seasonal trend in inducible lysogeny was observed in an Appalachian oak-hickory forest soil. The average monthly air temperature was negatively correlated with inducible fraction and burst size, supporting the idea that lysogeny provides a mechanism for phage persistence when temperatures are low and host metabolism is slower. Furthermore, the inducible fraction was negatively correlated with both soil bacterial and soil viral abundance, supporting the idea that lysogeny provides a mechanism for temperate phage persistence when host density is lower. The present study is the first of its kind to reveal clear seasonal trends in inducible lysogeny in any soil.IMPORTANCELysogeny is a relationship in which certain viruses that infect bacteria (phages) may exist within their bacterial host cell as a segment of nucleic acid. In this state, the phage genome is protected from environmental damage and retains the potential to generate progeny particles in the future. It is thought that lysogeny provides a mechanism for long-term persistence for phages when host density is low or hosts are starved-two conditions likely to be found in soils. In the present study, we provide the first known evidence for a seasonal trend in lysogeny in a forest soil. Based on clear relationships observed between lysogeny, temperature, and soil microbial abundance, we find support for previous hypotheses regarding the factors governing lysogeny.

Prospective validity assessment of a friction prediction model based on tread outsole features of slip-resistant shoes.

Shoe outsole design strongly influences slip and fall risk. Certain tread features that can be readily measured have been shown to predict friction performance. This research aimed to replicate those findings and quantify their ability to predict slipping. Participants (n = 34) were exposed to a low friction oil-coated floor surface, while wearing slip-resistant shoes. The coefficient of friction (COF) of each shoe were predicted based on tread surface area, the presence of a bevel, and hardness. The COF was measured, and the slip outcome was determined. Predicted and measured COF were correlated, and measured COF was a sensitive predictor of slip outcome. The relationship of predicted COF on slip outcome was weaker than anticipated and was not statistically significant. This study partially confirmed the ability of previous regression equations to predict COF. However, the effect size was weaker than previously reported and predicted COF was not sensitive for predicting slips.