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Abstract Brain mapping is vital in understanding the brain’s functional organization. Electroencephalography (EEG) is one of the most widely used brain mapping approaches, primarily because it is non-invasive, inexpensive, straightforward, and effective. Increasing the electrode density in EEG systems provides more neural information and can thereby enable more detailed and nuanced mapping procedures. Here, we show that the central sulcus can be clearly delineated using a novel ultra-high-density EEG system (uHD EEG) and somatosensory evoked potentials (SSEPs). This uHD EEG records from 256 channels with an inter-electrode distance of 8.6 mm and an electrode diameter of 5.9 mm. Reconstructed head models were generated from T1-weighted MRI scans, and electrode positions were co-registered to these models to create topographical plots of brain activity. EEG data were first analyzed with peak detection methods and then classified using unsupervised spectral clustering. Our topography plots of the spatial distribution from the SSEPs clearly delineate a division between channels above the somatosensory and motor cortex, thereby localizing the central sulcus. Individual EEG channels could be correctly classified as anterior or posterior to the central sulcus with 95.2% accuracy, which is comparable to accuracies from invasive intracranial recordings. Our findings demonstrate that uHD EEG can resolve the electrophysiological signatures of functional representation in the brain at a level previously only seen from surgically implanted electrodes. This novel approach could benefit numerous applications, including research, neurosurgical mapping, clinical monitoring, detection of conscious function, brain–computer interfacing (BCI), rehabilitation, and mental health.

The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.

An apple's aroma is a major determinant of its desirability by consumers. To better understand the aroma of apples, 2-dimensional gas-chromatography mass-spectrometry (2D-GCMS) was used to quantify 106 volatile organic compounds (VOCs) from 515 apple varieties. We identified esters and aldehydes as the most abundant classes of VOCs, with butyl acetate and hexyl acetate being present in nearly every variety. Principal component analysis (PCA) revealed that the primary axis of variation in the apple volatilome is correlated with harvest date, with early-harvested apples expressing a greater number and higher concentration of VOCs compared to late-harvested apples. Genome-wide association studies (GWAS) using 250,579 single nucleotide polymorphisms (SNPs) identified a significant association between SNPs near the alcohol acyltransferase (AAT1) locus and the abundance of several esters. Additionally, strong associations were observed between SNPs at the NAC18.1 transcription factor locus and the abundances of 1-hexanol and 1-butanol, which serve as precursors for hexyl acetate and butyl acetate, respectively. These findings provide a foundation for understanding the genetic basis of apple aroma production and pave the way for the genomics-assisted enhancement of the aroma profiles of apple varieties to meet consumer preferences.

Abstract Background HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. Methods We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. Results Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and ‘overarching’. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The ‘adherence motivation’ subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The ‘healthcare burden’ subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The ‘ART overreliance’ subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. Conclusions Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.

Brain-Computer Interface (BCI) technology enables users to operate external devices without physical movement. Electroencephalography (EEG) based BCI systems are being actively studied due to their high temporal resolution, convenient usage, and portability. However, fewer studies have been conducted to investigate the impact of high spatial resolution of EEG on decoding precise body motions, such as finger movements, which are essential in activities of daily living. Low spatial sensor resolution, as found in common EEG systems, can be improved by omitting the conventional standard of EEG electrode distribution (the international 10–20 system) and ordinary mounting structures (e.g., flexible caps). In this study, we used newly proposed flexible electrode grids attached directly to the scalp, which provided ultra-high-density EEG (uHD EEG). We explored the performance of the novel system by decoding individual finger movements using a total of 256 channels distributed over the contralateral sensorimotor cortex. Dense distribution and small-sized electrodes result in an inter-electrode distance of 8.6 mm (uHD EEG), while that of conventional EEG is 60 to 65 mm on average. Five healthy subjects participated in the experiment, performed single finger extensions according to a visual cue, and received avatar feedback. This study exploits mu (8–12 Hz) and beta (13–25 Hz) band power features for classification and topography plots. 3D ERD/S activation plots for each frequency band were generated using the MNI-152 template head. A linear support vector machine (SVM) was used for pairwise finger classification. The topography plots showed regular and focal post-cue activation, especially in subjects with optimal signal quality. The average classification accuracy over subjects was 64.8 (6.3)%, with the middle versus ring finger resulting in the highest average accuracy of 70.6 (9.4)%. Further studies are required using the uHD EEG system with real-time feedback and motor imagery tasks to enhance classification performance and establish the basis for BCI finger movement control of external devices.

A Cold Atmospheric Plasma (CAP) apparatus was designed and developed for SARS-CoV-2 killing as evaluated by pseudotyped viral infectivity assays. The reactive species generated by the plasma system was fully characterized by using Optical Emission Spectroscopy (OES) measurement under given conditions such as plasma power, flow rate, and treatment time. A variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) were identified from plasma plume with energies of 15–72 eV in the frequency range between 500–1000 nm. Systematic virus killing experiments were carried out, and the efficacy of CAP treatment in reducing SARS-CoV-2 viral infectivity was significant following treatment for 8 s, with further enhancement of killing upon longer exposures of 15–120 s. We correlated killing efficacy with the reactive species in terms of type, intensity, energy, and frequency. These experimental results demonstrate effective cold plasma virus killing via ROS and RNS under ambient conditions.

Face recognition is impaired in patients with prosopagnosia, which may occur as a side effect of neurosurgical procedures. Face selective regions on the ventral temporal cortex have been localized with electrical cortical stimulation (ECS), electrocorticography (ECoG), and functional magnetic resonance imagining (fMRI). This is the first group study using within-patient comparisons to validate face selective regions mapping, utilizing the aforementioned modalities. Five patients underwent surgical treatment of intractable epilepsy and joined the study. Subdural grid electrodes were implanted on their ventral temporal cortices to localize seizure foci and face selective regions as part of the functional mapping protocol. Face selective regions were identified in all patients with fMRI, four patients with ECoG, and two patients with ECS. From 177 tested electrode locations in the region of interest (ROI), which is defined by the fusiform gyrus and the inferior temporal gyrus, 54 face locations were identified by at least one modality in all patients. fMRI mapping showed the highest detection rate, revealing 70.4% for face selective locations, whereas ECoG and ECS identified 64.8 and 31.5%, respectively. Thus, 28 face locations were co-localized by at least two modalities, with detection rates of 89.3% for fMRI, 85.7% for ECoG and 53.6 % for ECS. All five patients had no face recognition deficits after surgery, even though five of the face selective locations, one obtained by ECoG and the other four by fMRI, were within 10 mm to the resected volumes. Moreover, fMRI included a quite large volume artifact on the ventral temporal cortex in the ROI from the anatomical structures of the temporal base. In conclusion, ECS was not sensitive in several patients, whereas ECoG and fMRI even showed activation within 10 mm to the resected volumes. Considering the potential signal drop-out in fMRI makes ECoG the most reliable tool to identify face selective locations in this study. A multimodal approach can improve the specificity of ECoG and fMRI, while simultaneously minimizing the number of required ECS sessions. Hence, all modalities should be considered in a clinical mapping protocol entailing combined results of co-localized face selective locations.

Strawberry is the most studied nonclimacteric fruit for understanding the role ethylene has in ripening regulation. However, previous studies on the effects of ethylene on strawberry ripening were conducted with detached fruit. Thus, the aim of this work was to determine the effect of ethylene and the ethylene-action inhibitor 1-methylcyclopropene (1-MCP) applied at different developmental stages on important physical-chemical attributes of ripe ‘Albion’ strawberry. Fruit at four developmental stages that remained attached to the plant were dipped in one of three treatment solutions (Ethephon, 1-methylcyclopropene, and water), plus one absolute control that received no dip. Following treatment, when immature fruit were fully red or 24 h after treatment for red-treated fruit, strawberry fruit were assessed for physicochemical properties (mass, length, diameter, firmness, color, titratable acidity, soluble solids, pH, total phenolics, sugar, organic acid, amino acid, and volatile composition). The days following treatment required for fruit to ripen were also recorded. Treatments did not affect the rate of ripening nor fruit color, titratable acidity, pH, soluble solids, total phenolics, sugars, or organic acids of ripe fruit. Ethephon affected fruit mass, diameter, length, firmness, anthocyanins, amino acids, and volatiles, but these effects were dependent on fruit developmental stage at which the treatment was applied. When green fruit were treated with ethephon, ripe fruit had larger diameter and mass. Ethephon treatment of white fruit resulted in ripe fruit having greater anthocyanin content. Treatment of pink fruit resulted in ripe fruit having smaller diameter, length, and mass and greater firmness. Treatment of red fruit with ethephon altered fruit volatile composition, increasing concentrations of ethyl- and acetate-esters, which were reduced by the 1-MCP treatment. Ethephon treatment increased concentrations of 11 of the 19 free amino acids measured in ripe fruit with treatment of green and white fruit having the greatest effect. A total of 41 volatile compounds had significant correlations with 14 amino acids. While ethylene did not stimulate typical ripening of strawberry fruit, it does appear to alter fruit development and metabolism. The physiological effects of ethylene on strawberry fruit appear to depend on the developmental stage of the fruit.

Increasing evidence points to a key role for NK cells in controlling adaptive immune responses. In studies examining the role of CD1d on CD4+ T cell responses, we found that a line of CD1d-deficient mice on the C57BL/6J background had a homozygous 129 locus on chromosome 6 containing the entire NK cell gene cluster. Mice possessing this locus (C57BL/6.NKC129) displayed a >10-fold reduction in antigen-specific CD4+ T cell responses after intracranial infection with lymphocytic choriomeningitis virus (LCMV). Neither parental strain displayed defects in viral-specific CD4+ T cell responses. Interestingly, following infection, increased numbers of NK cells accumulated in the lymph nodes of C57BL/6.NKC129 mice and displayed enhanced in vivo functionality. Moreover, depletion of NK cells with anti-asialo-GM-1 antibody in C57BL/6.NKC129 mice resulted in a >20-fold increase in viral-specific CD4+ T cell responses. Mechanistically, we found that dendritic cell antigen presentation and early type I IFN production were significantly decreased in C57BL/6.NKC129 mice, but were restored in perforin-deficient C57BL/6.NKC129 mice or following NK depletion. Together, these data reveal that the variable genomic regions containing the activating/inhibitory NK cell receptors are key determinants of antigen-specific CD4+ T cell responses, controlling type I IFN production and the antigen-presenting capacity of dendritic cells.

Abstract A presumed abnormal electrocardiogram (ECG) was obtained from an asymptomatic patient with a pacemaker. Systematic evaluation of the ECG revealed that the artifact was due to a physiological sensor in the pacemaker which was displayed when the enhanced pacemaker detection features on the ECG machine was activated. The article discusses the possible causes and an approach to similar artifacts.

Gerald Irvin Wiliamson lahir di Des Moines, Lowa 19 Mei 1925. Williamson mendapat gelar B.A. dari Universitas Drake di Des Moines (1949) dan mendapatkan gelar B.D. (Bachelor of Divinity) dari Seminari Teologi di Pittsburgh-Xenia (1952). Williamson melayani sebagai seorang pendeta selama lima puluh tahun dan pada akhirnya ia pensiun dari Gereja Presbiterian Ortodoks pada tahun 2011. Williamson adalah seorang teolog Reformed, pendeta dan seorang penulis buku.

Background: The Hispanic/Latino population in the US is experiencing high rates of obesity and cardio-metabolic disease that may be attributable to a nutrition transition away from traditional diets emphasizing whole plant foods. In the US, plant-based diets have been shown to be effective in preventing and controlling obesity and cardio-metabolic disease in large samples of primarily non-Hispanic subjects. Studying this association in US Hispanic/Latinos could inform culturally tailored interventions.Objective: To examine whether the plant-based diet pattern that is frequently followed by Hispanic/Latino Seventh-day Adventists is associated with lower levels of adiposity and adiposity-related biomarkers.Methods: The Adventist Multiethnic Nutrition Study (AMEN) enrolled 74 Seventh-day Adventists from five Hispanic/Latino churches within a 20 mile radius of Loma Linda, CA into a cross-sectional study of diet (24 h recalls, surveys) and health (anthropometrics and biomarkers).Results: Vegetarian diet patterns (Vegan, Lacto-ovo vegetarian, Pesco-vegetarian) were associated with significantly lower BMI (24.5 kg/m2 vs. 27.9 kg/m2, p = 0.006), waist circumference (34.8 in vs. 37.5 in, p = 0.01), and fat mass (18.3 kg vs. 23.9 kg, p = 0.007), as compared to non-vegetarians. Adiposity was positively associated with pro-inflammatory cytokines (Interleukin-6) in this sample, but adjusting for this effect did not alter the associations with vegetarian diet.Conclusions: Plant-based eating as practiced by US-based Hispanic/Latino Seventh-day Adventists is associated with BMI in the recommended range. Further work is needed to characterize this type of diet for use in obesity-related interventions among Hispanic/Latinos in the US.

The effects of 1-methylcyclopropene (1-MCP), storage atmosphere (controlled (CA) or regular (RA)), and juice processing (clear or cloudy) on the volatile aroma compounds from McIntosh and Honeycrisp apples following 4-month storage were studied. All the major esters, aldehydes, and total volatile content from McIntosh juice were significantly affected by the two-way interaction between harvest maturity and 1-MCP treatment (p ≤ 0.01), as well as harvest maturity and storage atmosphere (p ≤ 0.001). In McIntosh juices, a remarkable reduction of all types of esters, aldehydes, most alcohols, and total volatile compounds was found when juices were prepared from 1-MCP-treated apples. In Honeycrisp, significant differences in the level of esters and the total volatile aroma was caused by storage atmosphere and juice processing techniques (p ≤ 0.001), but not by 1-MCP treatment. As compared to clear juices, cloudy juice samples from Honeycrisp had a considerably higher content of total volatiles, esters, and aldehydes.

The hyperinflammatory syndrome hemophagocytic lymphohistiocytosis can occur in the context of malignancies. Malignancy-triggered hemophagocytic lymphohistiocytosis should be regarded seperately from hemophagocytic lymphohistiocytosis during chemotherapeutic treatment, which is frequently associated with an infectious trigger. The substantial overlap between the features of hemophagocytic lymphohistiocytosis with features of neoplasms makes its identification difficult when it occurs in malignant conditions. To facilitate recognition and diagnostic workup, and provide guidance regarding the treatment of malignancy-associated hemophagocytic lymphohistiocytosis, consensus recommendations were developed by the Study Group on Hemophagocytic Lymphohistiocytosis Subtypes of the Histiocyte Society, an interdisciplinary group consisting of pediatric and adult hemato-oncologists and immunologists.

A Protein Data Bank (PDB) survey has revealed noncovalent contacts involving Mn centres and protein residues. Their geometrical features are in line with the interaction between low electron density sites located along the Mn–O/N coordination bonds (σ-holes) and the lone pairs belonging to TYR, SER or HIS residues, known as a matere bond (MaB). Calculations at the PBE0-D3/def2-TZVP level of theory were used to investigate the strength and shed light on the physical nature of the interaction. We expect the results presented herein will be useful for those scientists working in the fields of bioinorganic chemistry, particulary in protein–metal docking, by providing new insights into transition metal⋯Lewis base interactions as well as a retrospective point of view to further understand the structural and functional implications of this key transition metal ion. [ABSTRACT FROM AUTHOR]