bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective connectivity between deep brain stimulation targets in individuals with treatment-resistant depression
Authors: Amiri Saba , Arbabi Mohammad , Rahimi Milad , Parvaresh-Rizi Mansour , Mirbagheri Mehdi M 
Published: October 2023

Abstract
The therapeutic effect of deep brain stimulation on patients with treatment-resistant depression is strongly dependent on the connectivity of the stimulation region with other regions associated with depression. The aims of this study are to characterize the effective connectivity between the brain regions playing important roles in depression and further investigate the underlying pathophysiological mechanisms of treatment-resistant depression and the mechanisms involving deep brain stimulation. Thirty-three individuals with treatment-resistant depression and 29 healthy control subjects were examined. All subjects underwent resting-state functional MRI scanning. The coupling parameters reflecting the causal interactions among deep brain stimulation targets and medial prefrontal cortex were estimated using spectral dynamic causal modelling. Our results showed that compared to the healthy control subjects, in the left hemisphere of treatment-resistant depression patients, the nucleus accumbens was inhibited by the inferior thalamic peduncle and excited the ventral caudate and the subcallosal cingulate gyrus, which in turn excited the lateral habenula. In the right hemisphere, the lateral habenula inhibited the ventral caudate and the nucleus accumbens, both of which inhibited the inferior thalamic peduncle, which in turn inhibited the cingulate gyrus. The ventral caudate excited the lateral habenula and the cingulate gyrus, which excited the medial prefrontal cortex. Furthermore, these effective connectivity links varied between males and females, and the left and right hemispheres. Our findings suggest that intrinsic excitatory/inhibitory connections between deep brain stimulation targets are impaired in treatment-resistant depression patients, and that these connections are sex dependent and hemispherically lateralized. This knowledge can help to better understand the underlying mechanisms of treatment-resistant depression, and along with tractography, structural imaging, and other relevant clinical information, may assist to determine the appropriate region for deep brain stimulation therapy in each treatment-resistant depression patient.
A blunted TH17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults
Authors: Bachstetter Adam D , Lutshumba Jenny , Winford Edric , Abner Erin L , Martin Barbra J , Harp Jordan P , Van Eldik Linda J , Schmitt Frederick A , Wilcock Donna M , Stowe Ann M , Jicha Gregory A , Nikolajczyk Barbara S 
Published: October 2023

Abstract
People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells from cognitively healthy women, while myeloid-targeted stimuli elicited similar amounts of cytokines from cells of both groups. This TH17 signature correlated with the proportion of circulating CD4+ and CD8+ T cells and plasma glial fibrillary acidic protein and neurofilament light concentrations. These results suggest that decreases in TH17 cytokines could be an early systemic change in women at risk for developing dementia. Amelioration of TH17s cytokines in early cognitive impairment could, in part, explain the compromised ability of older adults to respond to vaccines or defend against infection.
How embodied is cognition? fMRI and behavioral evidence for common neural resources underlying motor planning and mental rotation of bodily stimuli
Authors: Doganci Naz , Iannotti Giannina Rita , Coll Sélim Yahia , Ptak Radek 
Published: October 2023

Abstract
Functional neuroimaging shows that dorsal frontoparietal regions exhibit conjoint activity during various motor and cognitive tasks. However, it is unclear whether these regions serve several, computationally independent functions, or underlie a motor “core process” that is reused to serve higher-order functions. We hypothesized that mental rotation capacity relies on a phylogenetically older motor process that is rooted within these areas. This hypothesis entails that neural and cognitive resources recruited during motor planning predict performance in seemingly unrelated mental rotation tasks. To test this hypothesis, we first identified brain regions associated with motor planning by measuring functional activations to internally-triggered vs externally-triggered finger presses in 30 healthy participants. Internally-triggered finger presses yielded significant activations in parietal, premotor, and occipitotemporal regions. We then asked participants to perform two mental rotation tasks outside the scanner, consisting of hands or letters as stimuli. Parietal and premotor activations were significant predictors of individual reaction times when mental rotation involved hands. We found no association between motor planning and performance in mental rotation of letters. Our results indicate that neural resources in parietal and premotor cortex recruited during motor planning also contribute to mental rotation of bodily stimuli, suggesting a common core component underlying both capacities.
Graded brain fMRI response to somatic and visual acupuncture stimulation
Authors: Yoon Da-Eun , Lee Seoyoung , Kim Jundong , Kim Kyuseok , Park Hi-Joon , Napadow Vitaly , Lee In-Seon , Chae Younbyoung 
Published: October 2023

Abstract
Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as “dosage” has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.
EEG-based assessment of temporal fine structure and envelope effect in mandarin syllable and tone perception
Authors: Ni Guangjian , Xu Zihao , Bai Yanru , Zheng Qi , Zhao Ran , Wu Yubo , Ming Dong 
Published: October 2023

Abstract

In recent years, speech perception research has benefited from low-frequency rhythm entrainment tracking of the speech envelope. However, speech perception is still controversial regarding the role of speech envelope and temporal fine structure, especially in Mandarin. This study aimed to discuss the dependence of Mandarin syllables and tones perception on the speech envelope and the temporal fine structure. We recorded the electroencephalogram (EEG) of the subjects under three acoustic conditions using the sound chimerism analysis, including (i) the original speech, (ii) the speech envelope and the sinusoidal modulation, and (iii) the fine structure of time and the modulation of the non-speech (white noise) sound envelope. We found that syllable perception mainly depended on the speech envelope, while tone perception depended on the temporal fine structure. The delta bands were prominent, and the parietal and prefrontal lobes were the main activated brain areas, regardless of whether syllable or tone perception was involved. Finally, we decoded the spatiotemporal features of Mandarin perception from the microstate sequence. The spatiotemporal feature sequence of the EEG caused by speech material was found to be specific, suggesting a new perspective for the subsequent auditory brain-computer interface. These results provided a new scheme for the coding strategy of new hearing aids for native Mandarin speakers.

Highlights
Molecular mechanisms underlying human spatial cognitive ability revealed with neurotransmitter and transcriptomic mapping
Authors: Yang Jia , Chen Kexuan , Zhang Junyu , Ma Yingzi , Chen Meiling , Shao Heng , Zhang Xing , Fan Defang , Wang Zhengbo , Sun Zhenglong , Wang Jiaojian 
Published: October 2023

Abstract
Mental rotation, one of the cores of spatial cognitive abilities, is closely associated with spatial processing and general intelligence. Although the brain underpinnings of mental rotation have been reported, the cellular and molecular mechanisms remain unexplored. Here, we used magnetic resonance imaging, a whole-brain spatial distribution atlas of 19 neurotransmitter receptors, transcriptomic data from Allen Human Brain Atlas, and mental rotation performances of 356 healthy individuals to identify the genetic/molecular foundation of mental rotation. We found significant associations of mental rotation performance with gray matter volume and fractional amplitude of low-frequency fluctuations in primary visual cortex, fusiform gyrus, primary sensory-motor cortex, and default mode network. Gray matter volume and fractional amplitude of low-frequency fluctuations in these brain areas also exhibited significant sex differences. Importantly, spatial correlation analyses were conducted between the spatial patterns of gray matter volume or fractional amplitude of low-frequency fluctuations with mental rotation and the spatial distribution patterns of neurotransmitter receptors and transcriptomic data, and identified the related genes and neurotransmitter receptors associated with mental rotation. These identified genes are localized on the X chromosome and are mainly involved in trans-synaptic signaling, transmembrane transport, and hormone response. Our findings provide initial evidence for the neural and molecular mechanisms underlying spatial cognitive ability.
Connecting the dots: harnessing dual-site transcranial magnetic stimulation to quantify the causal influence of medial frontal areas on the motor cortex
Authors: Neige Cécilia , Vassiliadis Pierre , Ali Zazou Abdelkrim , Dricot Laurence , Lebon Florent , Brees Thomas , Derosiere Gerard 
Published: October 2023

Abstract
Dual-site transcranial magnetic stimulation has been widely employed to investigate the influence of cortical structures on the primary motor cortex. Here, we leveraged this technique to probe the causal influence of two key areas of the medial frontal cortex, namely the supplementary motor area and the medial orbitofrontal cortex, on primary motor cortex. We show that supplementary motor area stimulation facilitates primary motor cortex activity across short (6 and 8 ms) and long (12 ms) inter-stimulation intervals, putatively recruiting cortico-cortical and cortico-subcortico-cortical circuits, respectively. Crucially, magnetic resonance imaging revealed that this facilitatory effect depended on a key morphometric feature of supplementary motor area: individuals with larger supplementary motor area volumes exhibited more facilitation from supplementary motor area to primary motor cortex for both short and long inter-stimulation intervals. Notably, we also provide evidence that the facilitatory effect of supplementary motor area stimulation at short intervals is unlikely to arise from spinal interactions of volleys descending simultaneously from supplementary motor area and primary motor cortex. On the other hand, medial orbitofrontal cortex stimulation moderately suppressed primary motor cortex activity at both short and long intervals, irrespective of medial orbitofrontal cortex volume. These results suggest that dual-site transcranial magnetic stimulation is a fruitful approach to investigate the differential influence of supplementary motor area and medial orbitofrontal cortex on primary motor cortex activity, paving the way for the multimodal assessment of these fronto-motor circuits in health and disease.
Food and Drug Administration Public Workshop Summary—Addressing Challenges in Inhaled Antifungal Drug Development
Authors: Jjingo Caroline J , Bala Shukal , Waack Ursula , Needles Mark , Bensman Timothy J , McMaster Owen , Smith Thomas , Blakely Brandon , Chan Irene Z , Puthawala Khalid , Dixon Cheryl , Kim Yongman , Lim Robert , Colangelo Philip , St. Clair Christopher , Nambiar Sumathi , Moss Richard B , Botgros Radu , Bazaz Rohit , Denning David W , Marr Kieren A , Husain Shahid , Berman Lance , Christensen Dale J , Keywood Charlotte , Clayton Russell G , Walsh Thomas J , Song Hyo Sook E , Shukla Sunita J , Farley John 
Published: October 2023

Abstract
Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On 25 September 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.
3D Shape Marks: A 360-Degree Analysis
Authors: Fhima Ilanah 
Published: October 2023

Abstract
Today’s consumers use a range of cues to identify product origin, including brand names, logos, colours and shapes. The range of registrable marks has therefore expanded, but this brings a risk that features which others have a legitimate competitive need to use will fall under the exclusive control of a single undertaking. Registration may also be used to extend the finite duration of other IP rights that the owner has already enjoyed. Consequently, trade mark law contains functionality limitations on registration designed to protect these competitive concerns. This piece considers how well those limitations are working. The CJEU has also seemed to apply stricter distinctiveness rules to shape marks based on the assumption that consumers are not used to seeing shapes as origin indicators. Some have assumed this means that it is almost impossible to register shape marks—this research examines whether this is really so. How functionality and distinctiveness work in practice is examined through an empirical analysis over a 5-year period of all shape mark applications to the European Union Intellectual Property Office. This piece considers which types of marks are being registered, which are being refused and why. It reveals that distinctiveness, rather than functionality, is having the biggest impact on shape mark registration, and in fact a larger number of shape marks than expected are registered: often because of the addition of non-3D matter. However, are a significant number of marks comprised just of product shapes. It concludes with a discussion of competitive and policy challenges identified by this research.
SPAW-SMOTE: Space Partitioning Adaptive Weighted Synthetic Minority Oversampling Technique For Imbalanced Data Set Learning
Authors: Zhang Qiang , He Junjiang , Li Tao , Lan Xiaolong , Fang Wenbo , Li Yihong 
Published: October 2023

Abstract
The problem of data imbalance is common in reality, which greatly affects the performance of classifiers. Most of the solutions are to balance the data set by generating new minority class samples, which are faced with the problems of selecting the appropriate area for generating samples, fuzzy classification boundary and uneven distribution of samples. To solve these problems, we propose a novel oversampling algorithm named space partitioning adaptive weighted synthetic minority oversampling technique (SPAW-SMOTE). We first divide the data space into boundary space and non-boundary space based on spatial partitioning techniques. The number of samples to be generated is assigned to different spaces by the designed adaptive weighting algorithm, which is used to solve the problems of uneven distribution of samples and easy to blur the classification boundary. Finally, we also endeavor to develop a new generation algorithm to reduce the probability of overlapping samples generated when synthesizing new samples and to ensure the diversity of new samples. Experimental results on 18 real-world data sets show that the average performance (G-mean, F1-measure and Area Under Curve) of SPAW-SMOTE is significantly better than other existing oversampling techniques.
A novel in vitro model of the small intestinal epithelium in co-culture with ‘gut-like’ dendritic cells
Authors: Johnston Luke J , Barningham Liam , Campbell Eric L , Cerovic Vuk , Duckworth Carrie A , Luu Lisa , Wastling Jonathan , Derricott Hayley , Coombes Janine L 
Published: October 2023

Abstract
Cross-talk between dendritic cells (DCs) and the intestinal epithelium is important in the decision to mount a protective immune response to a pathogen or to regulate potentially damaging responses to food antigens and the microbiota. Failures in this decision-making process contribute to the development of intestinal inflammation, making the molecular signals that pass between DCs and intestinal epithelial cells potential therapeutic targets. Until now, in vitro models with sufficient complexity to understand these interactions have been lacking. Here, we outline the development of a co-culture model of in vitro differentiated ‘gut-like’ DCs with small intestinal organoids (enteroids). Sequential exposure of murine bone marrow progenitors to Flt3L, granulocyte macrophage colony-stimulating factor (GM-CSF) and all-trans-retinoic acid (RA) resulted in the generation of a distinct population of conventional DCs expressing CD11b+SIRPα+CD103+/− (cDC2) exhibiting retinaldehyde dehydrogenase (RALDH) activity. These ‘gut-like’ DCs extended transepithelial dendrites across the intact epithelium of enteroids. ‘Gut-like’ DC in co-culture with enteroids can be utilized to define how epithelial cells and cDCs communicate in the intestine under a variety of different physiological conditions, including exposure to different nutrients, natural products, components of the microbiota, or pathogens. Surprisingly, we found that co-culture with enteroids resulted in a loss of RALDH activity in ‘gut-like’ DCs. Continued provision of GM-CSF and RA during co-culture was required to oppose putative negative signals from the enteroid epithelium. Our data contribute to a growing understanding of how intestinal cDCs assess environmental conditions to ensure appropriate activation of the immune response.
A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: results of two phase I studies
Authors: Osmanska Joanna , Brooksbank Katriona , Docherty Kieran F , Robertson Stacy , Wetherall Kirsty , McConnachie Alex , Hu Jerry , Gardner Roy S , Clark Andrew L , Squire Iain B , Kalra Paul R , Jhund Pardeep S , Muntendam Pieter , McMurray John J V , Petrie Mark C , Campbell Ross T 
Published: October 2023

Abstract

Aims
Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early discharge, preventing hospitalizations, and in palliative care. A high-concentration, pH-neutral furosemide formulation has been developed for SC administration via a small patch infusor pump. We aimed to compare the bioavailability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of a new SC furosemide formulation with conventional IV furosemide and describe the first use of a bespoke mini-pump to administer this formulation.

Methods and results
A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 mL (infused over 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with IV furosemide. The second study investigated the same SC furosemide preparation delivered by a patch infusor in patients hospitalized with HF. Primary outcome measures were treatment-emergent adverse events, infusion site pain, device performance, and PK measurements.
The absolute bioavailability of SC furosemide in comparison to IV furosemide was 112%, resulting in equivalent diuresis and natriuresis. When SC furosemide was administered via the patch pump, there were no treatment-emergent adverse events and 95% of participants reported no/minor discomfort at the infusion site.

Conclusion
The novel preparation of SC furosemide had similar bioavailability to IV furosemide. Administration via a patch pump was feasible and well tolerated.
Is Digital Credit Filling a Hole or Digging a Hole? Evidence from Malawi
Authors: Brailovskaya Valentina , Dupas Pascaline , Robinson Jonathan 
Published: October 2023

Abstract
Digital credit has expanded rapidly in Africa, with opaque loan terms amidst low consumer financial literacy. Rich data from Malawi shows substantial demand for a digital loan with a base interest rate of 10% over 15 days, yet most borrowers are not aware of loan terms, repay late and incur substantial late fees. Regression discontinuity analyses show no evidence that access to small digital loans harms consumers’ perceived well-being. A short, randomised, phone-based financial literacy intervention improved knowledge, but did not increase timely loan repayment and modestly increased loan demand, ultimately increasing the likelihood of ever defaulting.