Miracle-dz/UniFAR-FTUs huggingface dataset:
Steering the Volume of Tissue Activated With a Directional Deep Brain Stimulation Lead in the Globus Pallidus Pars Interna: A Modeling Study With Heterogeneous Tissue Properties

Objective: To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi). Background: Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS. However, many computational models of VTA are limited by assuming tissue homogeneity. Methods: We generated a multimodal image-based detailed anatomical (MIDA) computational model with a directional DBS lead (1.5 mm or 0.5 mm vertical electrode spacing) placed with segmented contact 2 at the ventral posterolateral “sensorimotor” region of the GPi. The effect of tissue heterogeneity was examined by replacing the MIDA tissues with a homogeneous tissue of conductance 0.3 S/m. DBS pulses (amplitude: 1 mA, pulse width: 60 μs, frequency: 130 Hz) were used to produce VTAs. The following DBS contact configurations were tested: single-segment monopole (2B-/Case+), two-segment monopole (2A-/2B-/Case+ and 2B-/3B-/Case+), ring monopole (2A-/2B-/2C-/Case+), one-cathode three-anode bipole (2B-/3A+/3B+/3C+), three-cathode three-anode bipole (2A-/2B-/2C-/3A+/3B+/3C+). Additionally, certain vertical configurations were repeated with 2 mA current amplitude. Results: Using a heterogeneous tissue model affected both the size and shape of the VTA in GPi. Electrodes with both 0.5 mm and 1.5 mm vertical spacing (1 mA) modeling showed that the single segment monopolar VTA was entirely contained within the GPi when the active electrode is placed at the posterolateral “sensorimotor” GPi. Two segments in a same ring and ring settings, however, produced VTAs outside of the GPi border that spread into adjacent white matter pathways, e.g., optic tract and internal capsule. Both stacked monopolar settings and vertical bipolar settings allowed activation of structures dorsal to the GPi in addition to the GPi. Modeling of the stacked monopolar settings with the DBS lead with 0.5 mm vertical electrode spacing further restricted VTAs within the GPi, but the VTA volumes were smaller compared to the equivalent settings of 1.5 mm spacing.
Bidirectional association between leisure time physical activity and well-being: Longitudinal evidence

Abstract Leisure-time physical activity (LTPA) is an important means of enhancing well-being. Although previous research has typically documented the cross-sectional associations between LTPA and well-being, the longitudinal bidirectional association remains relatively unexplored. Using a latent growth curve model, this study examined the longitudinal association between the intensity of LTPA, psychological well-being, and social well-being. The results revealed that the longitudinal associations differed, depending on the intensity of the LTPA and the type of well-being. Specifically, the longitudinal associations of moderate LTPA with psychological and social well-being were bidirectional. However, psychological and social well-being at baseline directly influenced the growth of vigorous LTPA, but not conversely (i.e. vigorous LTPA at baseline → change in psychological and social well-being), indicating no bidirectional association. These findings could contribute to a better understanding of ways in which different intensities of LTPA are associated with distinct types of well-being over a long time.
“It’s like she’s talking about me” — Exploring the value and potential impact of a YouTube film presenting a qualitative evidence synthesis about chronic pain: An analysis of online comments

ABSTRACT Background There is very limited research exploring the value and impact of qualitative research in chronic pain despite the large volume of research. Aims The aim of this study was to find out whether viewers’ comments in response to a YouTube film, portraying findings from a qualitative evidence synthesis about living with pain, revealed any potential value or impact to viewers. Methods We collected online data posted in response to the film Struggling to Be Me. We used themes from a large review of qualitative research as an a priori analytic framework. We used inductive thematic analysis to distil the essence of data that did not fit this framework. A thematic analysis of online comments to evaluate the impact of an arts-based health research film on people living with chronic pain is presented. Results We developed two inductive themes that explored the value and potential impact of watching the film online: (1) It has given voice to our suffering and (2) it makes me feel that I am not alone. Two subthemes added insight to the a priori framework: First, I have had enough of me added insight to the theme my life is impoverished and confined; second, I am treated like a criminal because I take opioids added insight to the theme lost personal credibility. Conclusions Our findings indicate that watching the YouTube film has potential value and impact, giving voice to suffering and making people feel that they are not alone. There are specific ethical challenges relating to internet-mediated research.
Trust, Happiness, and Pro-Social Behavior

This paper combines several large-scale surveys and empirical strategies to shed new light on the determinants of cooperative behavior. We provide evidence indicating that the level of trust maximizing subjective well-being tends to be above the income maximizing level. Higher trust is also linked to more cooperative and pro-social behaviors, including the private provision of global public goods such as climate change mitigation. Consistent with “warm glow” theories of pro-social behavior, our results indicate that individuals may enjoy being more cooperative than what would lead them to maximize income, which can be reflected in higher levels of subjective well-being.
The Everyday Life of Patients With Tuberculosis in the Concentration Camp of Mittelbau-Dora (1943–1945)

The everyday life of patients with tuberculosis in the main prisoner infirmary of the Mittelbau-Dora concentration camp is analyzed historically-critically by medical records, documents of the Schutzstaffel (SS) physicians, contemporary medical textbooks and memoirs of former inmates from partly international archives. To compare the medical treatment in the three phases of the concentration camp, the representative months of February 1944, July 1944 and January 1945 were examined. The analysis shows that SS hygienists inspected the place for fear of a collapse of the V-2 rocket production. The primitive medical infrastructure was slowly expanded after its founding in 1943. SS physicians and medics led and supervised the treatment provided by inmates. These were in an ethical dilemma between cooperation with the SS and commitment to the sick prisoners. The Tuberculosis Department was used for isolation. Sputum diagnostics and X-ray equipment were utilized as selection tools. Infectious patients laid usually for weeks in the same bed with two other patients. Significantly more resources were available, however, for non-infectious tuberculosis patients. The therapy was based on the medical expert opinion of the time and was mainly symptomatic such as fever reduction. Rest and vitamins should make prisoners fit for the armament industry. Patients with tuberculosis had a high death rate. The prisoners who survived were discharged, but often did not recover. Several thousand prisoners were selected for transports, which led to special concentration camps for seriously ill prisoners (Lublin-Majdanek, Bergen-Belsen) and the subcamp Boelcke-Kaserne. There, they often died of catastrophic conditions or were killed.
Implications of Sea Level Rise for Bee Communities in Rural Eastern Virginia Coastal Habitats

ABSTRACT: In the coastal mid-Atlantic region of the USA, landscapes are a mosaic of upland habitats (woodland, grassland, old fields and farmland) and low-lying coastal salt marsh. Flooding and salinization of coastal areas due to sea-level rise result in the conversion of upland habitats to salt marsh, and change the relative proportion of habitat types surrounding coastal farmland. This has the potential to influence population sizes of organisms living in this area and could alter the ecosystem services, such as pollination, that these habitats provide. To examine the potential outcome of these habitat conversions, we used blue vane traps at 14 sites along the Eastern Shore of Virginia (USA) to compare the bee communities of salt marsh, old fields and agricultural fields. Although there was no difference among habitat types for total bee abundance per site, we found that the coastal marsh is depauperate in bee species relative to old fields and agricultural fields, and that the bee species using the marsh habitat tend to be specialists of plant families that are common in the marsh (Asteraceae and Malvaceae) but are relatively uncommon in local agriculture. Thus, the transition of upland areas to marsh not only has the potential to impact agricultural productivity directly through salt water intrusion, ultimately it may also reduce the species richness of native bees available to provide pollination services to coastal agriculture.
The Influence of Form- and Meaning-Based Predictions on Cortical Speech Processing Under Challenging Listening Conditions: A MEG Study

Under adverse listening conditions, prior linguistic knowledge about the form (i.e., phonology) and meaning (i.e., semantics) help us to predict what an interlocutor is about to say. Previous research has shown that accurate predictions of incoming speech increase speech intelligibility, and that semantic predictions enhance the perceptual clarity of degraded speech even when exact phonological predictions are possible. In addition, working memory (WM) is thought to have specific influence over anticipatory mechanisms by actively maintaining and updating the relevance of predicted vs. unpredicted speech inputs. However, the relative impact on speech processing of deviations from expectations related to form and meaning is incompletely understood. Here, we use MEG to investigate the cortical temporal processing of deviations from the expected form and meaning of final words during sentence processing. Our overall aim was to observe how deviations from the expected form and meaning modulate cortical speech processing under adverse listening conditions and investigate the degree to which this is associated with WM capacity. Results indicated that different types of deviations are processed differently in the auditory N400 and Mismatch Negativity (MMN) components. In particular, MMN was sensitive to the type of deviation (form or meaning) whereas the N400 was sensitive to the magnitude of the deviation rather than its type. WM capacity was associated with the ability to process phonological incoming information and semantic integration.
White Fulani cattle of West and Central Africa

The paper reviews information on the White Fulani cattle under the headings: origin, classification, distribution, population statistics, ecological settings, utility, husbandry practices, physical characteristics, special genetic characteristics, adaptive attributes and performance characteristics. It was concluded that the breed is economically important for several local communities in many West and Central African countries. The population of the breed is substantial. However, introgression from exotic cattle breeds as well as interbreeding with local breeds represent the major threat to the breed. The review identified a lack of programmes to develop the breed as being inimical to its long-term existence.
Airway Natural Killer Cells and Bacteria in Health and Disease

Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field.
Validation of an Enzyme-Driven Model Explaining Photosynthetic Rate Responses to Limited Nitrogen in Crop Plants

The limited availability of nitrogen (N) is a fundamental challenge for many crop plants. We have hypothesized that the relative crop photosynthetic rate (P) is exponentially constrained by certain plant-specific enzyme activities, such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-G3PDH), 3-phosphoglyceric acid (PGA) kinase, and chloroplast fructose-1,6-bisphosphatase (cpFBPase), in Triticum aestivum and Oryza sativa. We conducted a literature search to compile information from previous studies on C3 and C4 crop plants, to examine the photosynthetic rate responses to limited leaf [N] levels. We found that in Zea mays, NADP-malic enzyme (NADP-ME), PEP carboxykinase (PCK), and Rubisco activities were positively correlated with P. A positive correlation was also observed between both phosphoenolpyruvate carboxylase (PEPC) and Rubisco activity with leaf [N] in Sorghum bicolor. Key enzyme activities responded differently to P in C3 and C4 plants, suggesting that other factors, such as leaf [N] and the stage of leaf growth, also limited specific enzyme activities. The relationships followed the best fitting exponential relationships between key enzymes and the P rate in both C3 and C4 plants. It was found that C4 species absorbed less leaf [N] but had higher [N] assimilation rates (A rate) and higher maximum photosynthesis rates (Pmax ), i.e., they were able to utilize and invest more [N] to sustain higher carbon gains. All C3 species studied herein had higher [N] storage (Nstore) and higher absorption of [N], when compared with the C4 species. Nstore was the main [N] source used for maintaining photosynthetic capacity and leaf expansion. Of the nine C3 species assessed, rice had the greatest Pmax , thereby absorbing more leaf [N]. Elevated CO2 (eCO2) was also found to reduce the leaf [N] and Pmax in rice but enhanced the leaf [N] and N use efficiency of photosynthesis in maize. We concluded that eCO2 affects [N] allocation, which directly or indirectly affects Pmax . These results highlight the need to further study these physiological and biochemical processes, to better predict how crops will respond to eCO2 concentrations and limited [N].
Influences of Environmental Variability, Genetics and Plant Size on Variation in Sexual and Clonal Reproduction and Allocation of Resources in Three Wetland Plant Species

Optimal Partitioning Theory (OPT) states organisms will give more resources to structures and functions that enhance fitness. OPT can be applied to reproduction in clonal plants, which allocate resources between two modes of reproduction—sexual through fruits and clonal through spacers and ramets. In nutrient rich environments, clonal growth allows offspring to stay in beneficial surroundings, while in nutrient poor conditions, sexual reproduction can allow escape and generation of new, potentially more fit offspring. I tested this hypothesis by comparing clonal and sexual reproductive allocation in Penthorum sedoides under differing nutrient levels over two generations. Genotypic and environmental influences on reproductive variation in Lythrum salicaria and Penthorum sedoides were separated by comparing clones within and between treatments. Allocation to fruits was higher in the control than the fertilized group, but only in the second year, providing partial support to an increase in sexual allocation in lower resource conditions. Allocation to spacer mass and ramet mass increased under high nutrients, while number of ramets did not, also providing limited support to the predictions of OPT. Genotype had little effect on sexual and clonal variation. Variation due to fertilizer was more influential, demonstrating plasticity in reproductive expression.
Diminished Frequencies of Cytotoxic Marker Expressing T- and NK Cells at the Site of Mycobacterium tuberculosis Infection

Tuberculous lymphadenitis (TBL) individuals exhibit reduced frequencies of CD8+ T cells expressing cytotoxic markers in peripheral blood. However, the frequencies of cytotoxic marker expressing CD4+, CD8+ T cells, and NK cells at the site of infection is not known. Therefore, we measured the baseline and mycobacterial antigen specific frequencies of cytotoxic markers expressing CD4+, CD8+ T cells, and NK cells in the LN (n = 18) and whole blood (n = 10) of TBL individuals. TBL LN is associated with lower frequencies of CD4+ T cells expressing cytotoxic markers (Granzyme B, CD107a) compared to peripheral blood at baseline and in response to PPD, ESAT-6, and CFP-10 antigen stimulation. Similarly, lower frequencies of CD8+ T cells expressing cytotoxic markers (Perforin, Granzyme B, and CD107a) were also present in the TBL LN at baseline and following (except perforin) antigen stimulation. Finally, at baseline and after antigen (PPD, ESAT-6, and CFP-10) stimulation, frequencies of NK cells expressing cytotoxic markers were also significantly lower in TBL LN compared to whole blood. Hence, TBL is characterized by diminished frequencies of cytotoxic marker expressing CD4+, CD8+ T cells, and NK cells at the site of infection, which might reflect the lack of protective immune responses at the site of Mycobacterium tuberculosis infection.
Leveraging Endogenous Dendritic Cells to Enhance the Therapeutic Efficacy of Adoptive T-Cell Therapy and Checkpoint Blockade

Adoptive cell therapy (ACT), based on treatment with autologous tumor infiltrating lymphocyte (TIL)-derived or genetically modified chimeric antigen receptor (CAR) T cells, has become a potentially curative therapy for subgroups of patients with melanoma and hematological malignancies. To further improve response rates, and to broaden the applicability of ACT to more types of solid malignancies, it is necessary to explore and define strategies that can be used as adjuvant treatments to ACT. Stimulation of endogenous dendritic cells (DCs) alongside ACT can be used to promote epitope spreading and thereby decrease the risk of tumor escape due to target antigen downregulation, which is a common cause of disease relapse in initially responsive ACT treated patients. Addition of checkpoint blockade to ACT and DC stimulation might further enhance response rates by counteracting an eventual inactivation of infused and endogenously primed tumor-reactive T cells. This review will outline and discuss therapeutic strategies that can be utilized to engage endogenous DCs alongside ACT and checkpoint blockade, to strengthen the anti-tumor immune response.
Glucose-Mediated Protein Arginine Phosphorylation/Dephosphorylation Regulates ylxR Encoding Nucleoid-Associated Protein and Cell Growth in Bacillus subtilis

Glucose is the most favorable carbon source for many bacteria, and these bacteria have several glucose-responsive networks. We proposed new glucose responsive system, which includes protein acetylation and probable translation control through TsaEBD, which is a tRNA modification enzyme required for the synthesis of threonylcarbamoyl adenosine (t6A)-tRNA. The system also includes nucleoid-associated protein YlxR, regulating more than 400 genes including many metabolic genes and the ylxR-containing operon driven by the PylxS promoter is induced by glucose. Thus, transposon mutagenesis was performed for searching regulatory factors for PylxS expression. As a result, ywlE was identified. The McsB kinase phosphorylates arginine (Arg) residues of proteins and the YwlE phosphatase counteracts against McsB through Arg-dephosphorylation. Phosphorylated Arg has been known to function as a tag for ClpCP-dependent protein degradation. The previous analysis identified TsaD as an Arg-phosphorylated protein. Our results showed that the McsB/YwlE system regulates PylxS expression through ClpCP-mediated protein degradation of TsaD. In addition, we observed that glucose induced ywlE expression and repressed mcsB expression. It was concluded that these phenomena would cause glucose induction (GI) of PylxS, based on the Western blot analyses of TsaD-FLAG. These observations and the previous those that many glycolytic enzymes are Arg-phosphorylated suggested that the McsB/YwlE system might be involved in cell growth in glucose-containing medium. We observed that the disruption of mcsB and ywlE resulted in an increase of cell mass and delayed growth, respectively, in semi-synthetic medium. These results provide us broader insights to the physiological roles of the McsB/YwlE system and protein Arg-phosphorylation.
Cholera vaccines: the current status and problems

Large-scale field trials of cholera vaccines using either live or killed Vibrio cholerae O1 whole cells (WC) administered orally and parenterally have been carried out during the last 30 years in some countries in which cholera is endemic. Whereas adults in endemic areas are primed due to their natural exposure to cholera antigens, young children lack immunity and are vulnerable to the disease. Single dose parenteral WC vaccines with aluminium adjuvants offered high protective efficacy (PE) for 1 year in young children in Indonesia and India. Multiple oral doses containing high amounts of killed WC with or without the B subunit (BS) of cholera toxin were reactogenic and offered modest PE. A single dose of one live attenuated recombinant oral vaccine offered little protection in any age group. Parenteral WC-adjuvant vaccines are highly protective, and minor adverse reactions to them have been exaggerated. Several living and non-living cholera vaccine candidates are in the process of development. All vaccines should contain both Inaba and Ogawa serotypes and a third strain, O139 Bengal, may also need to be included for some countries. A non-reactogenic cholera vaccine that can offer a high degree of long-term protection in the population in endemic areas is still needed.