Search

Sepsis remains an important healthcare challenge. The lungs are often affected in sepsis, resulting in acute lung injury characterized by inflammation. Mechanisms involving lipopolysaccharide (LPS) stimulation of toll-like receptor (TLR) signaling with induction of proinflammatory pathways have been implicated in this process. To date, however, studies targeting these pathways have failed to improve outcomes. We have found that LPS may also promote lung injury through the activation of α4 nicotinic acetylcholine receptors (α4 nAChRs) in immune cells. We observed increased expression of α4 nAChRs in human THP-1 monocytic cells exposed to LPS (100 ng/mL, 24 h). We also observed that LPS stimulated the expression of other relevant genes, including tumor necrosis factor-α, interleukin-1β, plasminogen activator inhibitor-1, the solute carrier family 7 member 11, extracellular superoxide dismutase, and transforming growth factor-β1. Of interest, dihydro-β-erythroidine hydrobromide (DHβE), a specific chemical inhibitor of α4 nAChRs, inhibited the LPS-induced expression of these genes. We generated mice with a global knockout mutation of the α4 nAChR subunit in the C57BL/6 background using CRISPR/Cas9 technology. The lungs of these LPS-treated animals demonstrated a reduction in the expression of the above-mentioned genes when compared with the lungs of wild-type animals. In support of the role of oxidative stress, we observed that LPS induced expression of the cystine transporter Slc7a11 in both THP-1 cells and in wild-type mouse lungs. The effects of LPS on THP-1 cells were blocked by the thiol antioxidant N-acetylcysteine and mimicked by redox stress. Importantly, the induction of IL-1β by redox stress was inhibited by the α4 nAChR inhibitor DHβE. Finally, we showed that LPS stimulated calcium influx in THP-1 cells, which was blocked by the α4 nAChR inhibitor. Our observations suggest that LPS promotes lung injury by stimulating redox stress, which activates α4 nAChR signaling and drives proinflammatory cytokine expression. [ABSTRACT FROM AUTHOR]

This article provides ten simple rules for successfully carrying out funded research projects. The rules include focusing efforts on achieving project goals and deliverables, defining and assigning responsibilities to team members, scheduling regular meetings, complying with regulatory and ethical guidelines, following predefined data analysis plans, using validated methods for data collection and keeping backups of data, implementing the research budget and promoting administrative management, assigning enough time for reports, publishing findings and sharing results, and sharing results with the general public. The authors emphasize the importance of adhering to ethical practices and research integrity, as well as the need for effective communication and dissemination of research findings. [Extracted from the article]

Objectives To present a new method for displaying blood utilization data based on analysis of decision time intervals (DTIs). Methods Retrospective study of patients treated in a medical intensive care unit (ICU), surgical ICU, or postcardiac surgery ICU at an academic hospital between January 2018 and June 2023. Each patient's episode of care was divided into a series of DTIs. Transfusions during each time interval were recorded. Results In total, 16,562 patients received 6980 units of plasma and 21,034 units of red blood cells during 111,557 time intervals of care. Patients had international normalized ratio (INR) values ranging from less than 1.0 to more than 4.0. Data on plasma transfusion at different INR values were displayed as the number of transfusion episodes, number of units given, or the proportion of DTIs with transfusion. Clinicians transfused plasma on 1.5% of occasions when the INR was 1.5 or less and on 2.2% of occasions when the INR was less than 2.0. Plasma was transfused without red blood cells in only 0.75% of DTIs. Transfusion practice was statistically different among the 3 ICUs. Conclusions Compared with traditional methods of displaying the results of blood audits, DTI analysis displays information regarding the decision both to transfuse and to not transfuse. Utilization reviews that display data based on decision time analysis reveal clinical practice patterns very different from those suggested by traditional displays of plasma audit data. [ABSTRACT FROM AUTHOR]

Climate change has myriad impacts on ecosystems, but the mechanisms by which it affects individual species can be difficult to pinpoint. One strategy to discover such mechanisms is to identify a specific ecological factor related to survival or reproduction and determine how that factor is affected by climate. Here we used Landsat imagery to calculate water clarity for 127 lakes in northern Wisconsin from 1995 to 2021 and thus investigate the effect of clarity on the body condition of an aquatic visual predator, the common loon (Gavia immer). In addition, we examined rainfall and temperature as potential predictors of water clarity. Body mass tracked July water clarity strongly in loon chicks, which grow chiefly in that month, but weakly in adult males and females. Long‐term mean water clarity was negatively related to chick mass but positively related to adult male mass, suggesting that loons foraging in generally clear lakes enjoy good foraging conditions in the long run but might be sensitive to perturbations in clarity during chick‐rearing. Finally, chick mass was positively related to the density of docks, perhaps because angling removes large fishes and thus boosts the abundance of the small fishes on which chicks depend. Water clarity itself declined strongly from 1995 to 2021, was negatively related to July rainfall, and was positively related to July air temperature. Our findings identified both long‐term and short‐term water clarity as strong predictors of loon foraging efficiency, and suggest that climate change, through water clarity, impacts freshwater ecosystems profoundly. Moreover, our results identified the recent decrease in water clarity as a likely cause of population decline in common loons. [ABSTRACT FROM AUTHOR]

A non geometric sector of the duality group emerging in Kaluza-Klein reductions is realized as an effective symmetry in the low energy action of uncompactified type II theories. This is achieved by extending the so called β symmetry of the universal NS-NS sector to the R-R sector of type IIA, IIB and massive type IIA. [ABSTRACT FROM AUTHOR]

Pool-breeding amphibians are reliant upon small, isolated, and fishless wetlands as sites for oviposition and larval development. These pools are often susceptible to impacts from anthropogenic disturbances, with off-road vehicle (ORV) trail development becoming an increasingly common form of wetland disturbance in the southwest Virginia coalfields. I performed a before-after control-impact (BACI) comparison of egg mass loss at 15 pools impacted and unimpacted by ORV trail development at a recently-opened public ORV trail system in Russell County, Virginia during the spring of 2024. Pools impacted by ORV use showed a mean 83% egg mass loss rate over just one week of trail use relative to no egg loss in unimpacted pools, with distinct mechanisms associated with ORV use (physical crushing, wheel-thrown eggs, and egg mass relocation) acting in concert to drive egg mass loss. My results provide some of the first empirical data documenting mechanisms of egg mass loss and embryonic mortality in poolbreeding amphibians from ORV disturbance and support several best management practices that land managers in Virginia and elsewhere can use to minimize impacts to resident amphibian populations on public and private lands managed for recreation. [ABSTRACT FROM AUTHOR]

Age often indicates phenotypic quality, ecological experience or social status in animals. Consequently, behavioural signals in territorial animals that accurately convey age to potential mates or rivals might provide useful information for both signaller and receiver about the likelihood of aggression. We tested whether male territorial yodels convey information about age in the common loon, Gavia immer. Using a sample of male loons of known age, we found that the dominant frequency of Fintro3, a dominant syllable in the beginning sequence of a male yodel, increases strongly with age, but we were unable to replicate an earlier finding linking Fintro3 to body mass. We hypothesize that older male loons, which yodel more often than young males, might do so as a means to advertise their age and higher likelihood of aggression to potential rivals. • We tested whether male yodels convey information about age in common loons. • Dominant frequency of a dominant syllable (Fintro3) in male yodels increased with age. • Fintro3 was found previously to decrease with body mass, but not in our study. • Age may have a more significant effect on yodel acoustics than body mass. • Older males may yodel more often to advertise their age and likelihood of aggression. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has exposed significant gaps in healthcare access, quality, and the urgent need for enhancing the capacity of digital health human resources, particularly in Latin America. During the pandemic, online courses and telehealth initiatives supported by governmental agencies, the Pan American Health Organization, and other public and private resources, have played a crucial role in meeting training demands. This article discusses the role of capacity building programs in digital health within the context of Latin America, with a specific focus on the Peruvian case. We highlight the development of digital health competencies and related policies, while also describing selected experiences related to capacity building in this field. Additionally, we discuss the pivotal role of collaborative partnerships among institutions and countries, emphasizing the importance of culturally relevant training programs in digital health. These initiatives have the potential to accelerate training and research opportunities in Latin America, drawing on the involvement of government agencies, non-governmental organizations, industry, universities, professional societies, and communities. [ABSTRACT FROM AUTHOR]

Background: The use of encapsulated cells for the in vivo delivery of biotherapeutics is a promising new technology to potentiate the effectiveness of cell-based therapies for veterinary and human application. One use of the technology is to locally activate chemotherapeutics to their short-lived highly active forms. We have previously shown that a stable clone of HEK293 cells overexpressing a cytochrome P450 enzyme that has been encapsulated in immunoprotective cellulose sulphate beads can be implanted near solid tumours in order to activate oxazaphosphorines such as ifosfamide and cyclophosphamide to the tumour-killing metabolite phosphoramide mustard. The efficacy of this approach has been shown in animal models as well as in human and canine clinical trials. In these previous studies, the oxazaphosphorine was only given twice. An analysis of the Kaplan–Meier plots of the results of the clinical trials suggest that repeated dosing might result in a significant clinical benefit. Aims: In this study, we aimed to (i) demonstrate the stable long-term expression of cytochrome P450 from a characterized, transfected cell clone, as well as (ii) demonstrate that one implanted dose of these encapsulated cytochrome P450-expressing cells is capable of activating multiple doses of ifosfamide in animal models. Methodology: We initially used cell and molecular methods to show cell line stability over multiple passages, as well as chemical and biological function in vitro. This was followed by a demonstration that encapsulated HEK293 cells are capable of activating multiple doses of ifosfamide in a mouse model of pancreatic cancer without being killed by the chemotherapeutic. Conclusion: A single injection of encapsulated HEK293 cells followed by multiple rounds of ifosfamide administration results in repeated anti-tumour activity and halts tumour growth but, in the absence of a functioning immune system, does not cause tumour regression. [ABSTRACT FROM AUTHOR]

Kaluza-Klein reductions of low energy string effective actions possess a continuous O(d, d) symmetry. The non-geometric elements of this group, parameterized by a bi-vector β, are not inherited from the symmetries of the higher-dimensional theory, but constitute instead a symmetry enhancement produced by the isometries of the background. The realization of this enhancement in the parent theory was recently defined as β symmetry, a powerful tool that allows to avoid the field reparameterizations of the Kaluza-Klein procedure. In this paper we further explore this symmetry and its impact on the first order α′-corrections. We derive the β transformation rules from the frame formulation of Double Field Theory (DFT), and connect them to the corresponding rules in the Metsaev-Tseytlin and Bergshoeff-de Roo supergravity schemes. It follows from our results that β symmetry is a necessary condition for the uplift of string α′-expansions to DFT. [ABSTRACT FROM AUTHOR]

Many roles of human platelets in health and disease are linked to their ability to transport and secrete a variety of small molecules and proteins carried in dense (d-) and a-granules. Determination of granule number and content is important for diagnosis of platelet disorders and for studies of platelet structure, function, and development. We have optimized methods for detection and localization of platelet proteins via antibody and lectin staining, imaging via structured illumination laser fluorescence microscopy (SIM), and three-dimension (3D) image analysis. The methods were validated via comparison with published studies based on electron microscopy and high-resolution fluorescence microscopy. The a-granule cargo proteins thrombospondin-1 (TSP1), osteonectin (SPARC), fibrinogen (FGN), and Von Willebrand factor (VWF) were localized within the granule lumen, as was the proteoglycan serglycin (SRGN). Colocalization analysis indicates that staining with fluorescently labeled wheat germ agglutinin (WGA) allows detection of a-granules as effectively as immunostaining for cargo proteins, with the advantage of not requiring antibodies. RAB27B was observed to be concentrated at dense granules, allowing them to be counted via visual scoring and object analysis. We present a workflow for counting dense and a-granules via object analysis of 3D SIM images of platelets stained for RAB27B and with WGA. [ABSTRACT FROM AUTHOR]

Grazing is the de facto method of habitat management used in much of the Nebraska Sandhills. Ranchers use a variety of grazing systems, and our goal was to evaluate the effects of systems on grassland birds. We estimated the species richness and density of grassland birds for three grazing systems used on private ranches: long, medium, and short duration grazing systems. We observed sixty species, and the grazing system with pastures utilizing long duration grazing periods had the highest estimates of species richness as well as the most heterogeneous habitat structure. Differences in species richness among systems were most pronounced in years of limited precipitation. Together, grasshopper sparrows (Ammodramus savannarum), western meadowlarks (Sturnella neglecta), and brown-headed cowbirds (Molothrus ater) accounted for 72% of our observations. We used a model comparison approach to determine the effects of habitat on the densities of six species. Densities of grasshopper sparrows and mourning doves showed effects of the grazing system. More species had higher densities in short duration, rotational systems than other grazing systems. However, species of grassland birds showed responses to a variety of cover types and habitat structures depending on life history needs. Regardless of the grazing system used, managers can use grazing and other tools such as prescribed burning to maintain habitat heterogeneity to support diverse bird communities. [ABSTRACT FROM AUTHOR]

Most studies of vertebrate breeding success have been unable to pinpoint the cause for a simple and almost universal pattern: its steady increase during an animal's lifetime. Yet potential causes of increased breeding success have profound implications for the evolution of reproductive behaviour. An age-related increase might come about through (1) higher breeding investment by older animals, (2) breeding improvement through learning, (3) better reproductive coordination between familiar mates or (4) accumulated benefits of site familiarity. We used mixed models to investigate age-related predictors of hatching and fledging success in a population of common loons, Gavia immer , that contained many known-age breeders and has been under continuous study for 30 years. Hatching success of breeding pairs increased between the female's first and second years on territory but did not increase with further female experience. In contrast, pair hatching success increased in proportion to the cube root of the males' residency on a territory, a pattern that persisted beyond 15 years. Hatching date was earlier for pairs that had spent at least 1 year together and in which the female was young but had spent at least one prior year on the territory. Fledging rate of hatched young was greater among pairs that nested early but decreased with female age, an apparent indication of female reproductive senescence. Overall, breeding pairs fledged more young when the breeding male had many years of experience on the territory and the breeding female had been on territory for at least 1 year and was of moderate age. Our findings highlight the persistent influence of both site familiarity and chronological age on reproductive fitness. • We examined attributes of male and female loons that affect reproductive success (RS). • Territory familiarity improved female RS only between the first and second years. • Age negatively affected RS in young and old females but made no difference in males. • Males showed increases in RS for over 15 years when they remained on familiar territory. • Mate familiarity had little impact on RS, but pairs with ≥1 year together nested earlier. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (cSVD) involves several pathologies affecting the small vessels, including blood-brain barrier (BBB) impairment. Dynamic susceptibility contrast (DSC) MRI is sensitive to both blood perfusion and BBB leakage, and correction methods may be crucial for obtaining reliable perfusion measures. These methods might also be applicable to detect BBB leakage itself. This study investigated to what extent DSC-MRI can measure subtle BBB leakage in a clinical feasibility setting. In vivo DCE and DSC data were collected from fifteen cSVD patients (71 (±10) years, 6F/9M) and twelve elderly controls (71 (±10) years, 4F/8M). DSC-derived leakage fractions were obtained using the Boxerman-Schmainda-Weisskoff method (K2). K2 was compared with the DCE-derived leakage rate K i , obtained from Patlak analysis. Subsequently, differences were assessed between white matter hyperintensities (WMH), cortical gray matter (CGM), and normal-appearing white matter (NAWM). Additionally, computer simulations were performed to assess the sensitivity of DSC-MRI to BBB leakage. K2 showed significant differences between tissue regions (P < 0.001 for CGM-NAWM and CGM-WMH, and P = 0.001 for NAWM-WMH). Conversely, according to the computer simulations the DSC sensitivity was insufficient to measure subtle BBB leakage, as the K2 values were below the derived limit of quantification (4∙10−3 min−1). As expected, K i was elevated in the WMH compared to CGM and NAWM (P < 0.001). Although clinical DSC-MRI seems capable to detect subtle BBB leakage differences between WMH and normal-appearing brain tissue it is not recommended. K2 as a direct measure for subtle BBB leakage remains ambiguous as its signal effects are due to mixed T 1 - and T 2 ∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects. [ABSTRACT FROM AUTHOR]

[Display omitted] Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation. [ABSTRACT FROM AUTHOR]

In his seminal paper [On the XY-model on two-sided infinite chain, Publ. RIMS Kyoto Univ. 20 (1984) 277–296], Araki introduced an elegant extension of the Jordan–Wigner transformation which establishes a precise connection between quantum spin systems and Fermi lattice gases in one dimension in the so-called infinite system idealization of quantum statistical mechanics. His extension allows in particular for the rigorous study of numerous aspects of the prominent XY chain over the two-sided infinite discrete line without having to resort to a thermodynamic limit procedure at an intermediate or at the final stage. We rigorously review and elaborate this extension from scratch which makes the paper rather self-contained. In the course of the construction, we also present a simple and concrete realization of Araki's crossed product extension. [ABSTRACT FROM AUTHOR]

Background: Low‐titer group O whole blood (LTOWB) is increasingly used for emergency transfusion. We studied whether initial release of LTOWB compared with packed red blood cells (pRBCs) reduced overall blood requirements for patients needing emergency transfusion. Secondary outcomes examined included survival and non‐lethal adverse clinical outcomes. Study Design and Methods: A retrospective, single‐center, before‐versus‐after study compared patients transfused with emergency‐release, uncrossmatched pRBC followed by component therapy (2016–2019) versus patients transfused with emergency‐release, uncrossmatched LTOWB followed by component therapy (2019–2022). Results: Outcomes were available for 602 patients in the pRBC group versus 749 in the whole blood group. The two groups were similar for age, sex, race, estimated blood volume, ABO blood groups, and underlying diagnosis. Use of LTOWB was associated with increased blood product use at 24 h (4.0 (2.0–12.0) in pRBC group versus 6.5 (4.2–12.7) in LTOWB group, p <.0001) and at 7 days (5.5 (3.0–13.0) in pRBC group versus 7.3 (4.3–14.3) in LTOWB group, p <.0001). Initial use of LTOWB was not associated with improved 24 h or 30 day survival nor lower incidence of non‐lethal adverse clinical outcomes compared with pRBC. Discussion: Our study showed a statistically significant increase in total blood use and blood acquisition costs for patients receiving initial emergency transfusion with LTOWB compared with pRBC. The initial use of LTOWB offered no advantage over component therapy for 30 day survival or selected non‐lethal adverse outcomes. [ABSTRACT FROM AUTHOR]

Surface coal extraction and subsequent reclamation activities alter habitat availability for Appalachian wildlife, although broad surveys of mine-associated taxa are still largely lacking from the Virginia coalfields. We utilized game cameras to survey the mammal diversity of three habitat types - mined and reclaimed scrub/shrub habitat, mined and reclaimed scrub/shrub habitat associated with constructed wetlands, and unmined reference forests - at a reclaimed surface mine in Wise County, Virginia. We encountered 14 mammal species at this site, with the highest mammal diversity at mined wetlands and in unmined reference forests. Mammal diversity was substantially lower on reclaimed upland scrub-shrub habitats, echoing past findings for other taxa regarding decreased wildlife diversity on former surface mines. Our data provide a preliminary comparison of mammal diversity across three habitats associated with a former surface mine in the Virginia coalfields and highlight several key recommendations for land managers charged with maintaining wildlife diversity on formerly mined sites. [ABSTRACT FROM AUTHOR]

Many roles of human platelets in health and disease are linked to their ability to transport and secrete a variety of small molecules and proteins carried in dense (δ-) and α-granules. Determination of granule number and content is important for diagnosis of platelet disorders and for studies of platelet structure, function, and development. We have optimized methods for detection and localization of platelet proteins via antibody and lectin staining, imaging via structured illumination laser fluorescence microscopy (SIM), and three-dimension (3D) image analysis. The methods were validated via comparison with published studies based on electron microscopy and high-resolution fluorescence microscopy. The α-granule cargo proteins thrombospondin-1 (TSP1), osteonectin (SPARC), fibrinogen (FGN), and Von Willebrand factor (VWF) were localized within the granule lumen, as was the proteoglycan serglycin (SRGN). Colocalization analysis indicates that staining with fluorescently labeled wheat germ agglutinin (WGA) allows detection of α-granules as effectively as immunostaining for cargo proteins, with the advantage of not requiring antibodies. RAB27B was observed to be concentrated at dense granules, allowing them to be counted via visual scoring and object analysis. We present a workflow for counting dense and α-granules via object analysis of 3D SIM images of platelets stained for RAB27B and with WGA. Abbreviation: SIM: structured illumination microscopy; WGA: wheat germ agglutinin; FGN: fibrinogen; TSP1: thrombospondin 1; ER: endoplasmic reticulum Platelets support blood clotting, wound healing, and other essential processes. These functions rely on the ability of platelets to transport and release small molecules like serotonin carried in dense granules and a wide range of proteins carried in alpha granules. Several conditions have been linked to abnormalities in one or more of platelet granule number, content, structure, and function. These conditions can be difficult to diagnose because platelet granules are so small they cannot be consistently resolved by conventional light microscopy, while higher power electron microscopy is not widely accessible. The goal of this study was to develop a method for counting and examining platelet dense and alpha granules without the need of electron microscopy. Key to this was the discovery that alpha granules can be reliably stained with the plant lectin wheat germ agglutinin, which has the advantages of being a smaller and less expensive molecule than the antibodies commonly used to detect alpha granule cargo proteins. We also establish that dense granules can be detected with high specificity via antibody staining of the membrane-associated protein RAB27B. We used structured illumination laser fluorescence microscopy to obtain high-resolution images of stained platelets. These were assembled into 3D renders using image analysis software, which was used to validate a protocol for rapidly counting granules within individual platelets. Our method supports the relatively rapid, accurate, and cost-effective assessment of platelet granules. We have already shown that it can confirm dense granule deficiency, and we anticipate that this approach will also prove useful in diagnosing and studying alpha granule abnormalities. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis, one of the main reasons for death globally, is a serious complication of chronic liver disorders. However, the available therapies for liver fibrosis are limited, ineffective, and often associated with adverse events. Hence, seeking for a novel, effective therapy is warranted. Our objective was to investigate the potential efficacy of ferulic acid (FA), a phenolic phytochemical, at different doses in hindering the progress of concanavalin A (Con A)-induced hepatic fibrosis and explore the involved mechanisms. Thirty-six mice were assorted into 6 groups (n = 6): Group I (control); group II received FA (20 mg/kg/day orally for 4 weeks); group III received Con A (6 mg/kg/week/i.v.) for 4 weeks; groups IV, V, and VI received Con A and were offered FA at 5, 10, and 20 mg/kg/day, respectively. The data showed the palliative effect of FA against Con A-induced fibrosis in a dose-dependent manner. This was obvious from the recovery of liver markers and hepatic architecture with the regression of fibrosis in FA-treated mice. FA abolished Con A-mediated oxidative insults and promoted the antioxidant enzyme activities, which run through the Nrf2/HO-1 signaling. Additionally, FA suppressed Con A-induced increase in NF-kB and IL-β levels, and TNF-α immune-expression. The anti-fibrotic effect of FA was evident from the drop in TGF-β, smad3 levels, α-SMA expression, and hydroxyproline content. FA attenuated Con A-induced liver fibrosis through stimulating Nrf2 signaling, suppressing NF-kB, and inhibiting the TGF-β/smad3 signaling pathway. Thus FA can be considered as a promising therapy for combating liver fibrosis. • Ferulic acid (FA) conferred protection against Con A-induced liver fibrosis in mice. • FA exhibited hepatoprotective effect against Con A intoxication in a dose-dependent manner. • FA exerted its protective effect via antioxidant, anti-inflammatory, and anti-fibrotic effects. • FA attenuated liver fibrosis via enhancing Nrf2 signaling, suppressing NF-kB, and modulating the TGF-β/smad3 signaling. • The recommended dose of FA to achieve the anti-fibrotic action in liver is 20 mg/kg/day orally. [ABSTRACT FROM AUTHOR]

Background: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).Objective: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.Methods: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.Results: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.Conclusion: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy. [ABSTRACT FROM AUTHOR]

A systematic review and meta-analysis published in the Journal of the National Cancer Institute examined the effectiveness of fertility-preserving treatments for a precancerous condition called endometrial intraepithelial neoplasia (EIN) in women under 50 years old. The study found that a levonorgestrel-containing intrauterine device (IUD) had a higher resolution rate (96%) compared to oral progestins (86%). However, it is important to note that surgery remains the definitive treatment for women with EIN. Progestin treatment can be considered as a temporary option for women who wish to preserve fertility, but it is not a definitive treatment. [Extracted from the article]

Background: Chronic heavy alcohol consumption is a major risk factor for the development of liver steatosis, fibrosis, and cirrhosis, but the mechanisms by which alcohol causes liver damage remain incompletely elucidated. This group has reported that α4 nicotinic acetylcholine receptors (α4 nAChRs) act as sensors for alcohol in lung cells. This study tested the hypothesis that α4 nAChRs mediate the effects of alcohol in the liver. Methods: Expression of acetylcholine receptor subunits in mouse liver was determined by RNA sequencing (RNA‐seq). α4 nAChR knockout (α4 KO) mice were generated in C57BL/6J mice by introducing a mutation encoding an early stop codon in exon 4 of Chrna4, the gene encoding the α4 subunit of the nAChR. The presence of the inactivating mutation was established by polymerase chain reaction and genomic sequencing, and the lack of α4 nAChR function was confirmed in primary fibroblasts isolated from the α4 KO mice. Wild‐type (WT) and α4 KO mice were fed the Lieber‐DeCarli diet (with 36% of calories from alcohol) or pair fed an isocaloric maltose‐dextrin control diet for a 6‐week period that included a ramping up phase of increasing dietary alcohol. Results: Chrna4 was the most abundantly expressed nAChR subunit gene in mouse livers. After 6 weeks of alcohol exposure, WT mice had elevated serum transaminases and their livers showed increased fat accumulation, decreased Sirt1 protein levels, and accumulation of markers of oxidative stress and inflammation including Cyp2E1, Nos2, Sod1, Slc7a11, TNFα, and PAI1. All these responses to alcohol were either absent or significantly attenuated in α4 KO animals. Conclusion: Together, these observations support the conclusion that activation of α4 nAChRs by alcohol or one of its metabolites is one of the initial events promoting the accumulation of excess fat and expression of inflammatory mediators. Thus, α4 nAChRs may represent viable targets for intervention in chronic alcohol‐related liver disease. [ABSTRACT FROM AUTHOR]

Site fi delity data are presented for four banding sites in southern California for seven species of passerines. The fi rst site is a year round constant eff ort bird banding station in Zuma Canyon in the Santa Monica Mountains. The second site is at the University of California Burns Piñon Ridge Reserve, located in the high desert north of Joshua Tree National Park. The third and fourth sites are in residential areas in greater Los Angeles. The seven species are Gambel’s Whitecrowned Sparrow (Zonotrichia leucophys gambelii), Fox Sparrow (Passerella iliaca), Golden-crowned Sparrow (Zonotrichia atricapilla), Lincoln’s Sparrow (Melospiza lincolnii), Audubon’s Warbler (Setophaga coronata auduboni), Hermit Thrush (Catharus guttatus), and Ruby-crowned Kinglet (Regulus calendra). Site fi delity was divided into annual winter site fi delity (birds returning in subsequent years) and overwintering site fi delity (birds remaining for the entire winter). Diff erences in site fi delity between Hatching Year/Second Year and After Hatching Year/ After Second Year birds were also examined with no clear trends. The distances birds traveled during their fall migration showed no clear trends. Comparisons between sites had as much as an order of magnitude diff erence, but inferences were diffi cult to make as there are diff erences in habitats, bird species, and banding eff ort in published works. Most of the fi ndings here were on the lower end of published works. This is attributed a greater eff ort to detect site fi delity in published works compared to the constant eff ort, passive mist-netting conducted at my banding sites. [ABSTRACT FROM AUTHOR]

I suggest a method for converting geodetic height and latitude from one oblate ellipsoid of revolution to another having the same center and symmetry axis. Unlike other approaches, the method here does not obtain height and latitude from Earth-centered, Earth-fixed (ECEF) Cartesian coordinates; this feature allows height conversion with high accuracy even in cases where the data format limits the precision of the latitude data. Height and latitude conversions can be expressed as a Fourier series in even multiples of latitude, with height changes having only cosines and latitude changes having only sines. The absolute difference of the flattenings of the two ellipsoids furnishes a simple upper bound on the maximum absolute latitude change. Conversions between the TOPEX and WGS84 ellipsoids, a practical necessity for the inter-mission comparison of satellite laser and radar altimeter data, illustrate the findings. Because the differences in the flattenings and semi-major axes of these ellipsoids are small, truncating the Fourier series after the term in twice the latitude gives an approximate conversion with an error less than 9 × 10–12 radians of latitude and about 6 × 10–6 m of height. [ABSTRACT FROM AUTHOR]

Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by a variety of factors, but none more than the highly selective blood-brain barrier. Intranasal administration can bypass this barrier completely and allow direct access to brain tissues, enabling a large number of potential new therapies ranging from bioactive peptides to stem cells. Current research indicates that merely administering simple solutions is inefficient and may limit therapeutic success. While many therapies can be delivered to some degree without carrier molecules or significant modification, a growing body of research has indicated several methods of improving the safety and efficacy of this administration route, such as nasal permeability enhancers, gelling agents, or nanocarrier formulations. This review shall discuss promising delivery systems and their role in expanding the clinical efficacy of this novel administration route. Optimization of intranasal administration will be crucial as novel therapies continue to be studied in clinical trials and approved to meet the growing demand for the treatment of patients with neurological diseases. [ABSTRACT FROM AUTHOR]

High-elevation wetlands of the CumberlandMountains physiographic province hold high conservation priority due to their relative rarity, with little knowledge in the literature related to amphibians’ use of these high-elevation habitats. Therefore, forest and wildlife managers have few data to use when designing management guidelines for these habitats. We sampled five high-elevation wetlands across Pine and Cumberland mountains along the Virginia-Kentucky border, United States of America to address gaps in knowledge about these habitats and their use by amphibians.We inventoried amphibian diversity at five wetlands using visual encounter and auditory surveys. We used standardized, area-constrained visual encounter surveys that consisted of searches of all available cover objects within a 10 m buffer of the wetland margin to inventory amphibian taxa at each site. We also used automated digital recorders to record auditory call data from anuran (frogs and toads) taxa. We encountered 18 total amphibian species (eight anuran and ten salamander species), recording numerous occurrences of some species, such as Mud Salamanders (Pseudotriton montanus Baird), that have previously been assumed to be absent from high-elevation wetlands in the Appalachian region. Statistical analyses further indicated high disparity in amphibian biodiversity between sites. Our results indicate that these wetlands should be of high conservation concern and should be given priority in regional habitat management efforts. [ABSTRACT FROM AUTHOR]

Key points: The unmet needs of women with gynecologic cancers (GCs) can be readily addressed using high quality e‐platformsThis pilot study documents women with GC perceptions of BELONG (https://belong.life/)—a cancer navigation and support Application (or App) connecting patients diagnosed with various types of cancersWomen (N = 25), with GCs (stages I to IV), used the App for 8 weeks and completed the user Mobile Application Rating ScaleRatings of BELONG in domains of engagement, functionality, aesthetics, and information were high, with Ask an Oncologist, Ovarian Cancer Community, Clinical Trials, Treatment Information, and Support Resources representing the most frequently accessed topicsAs e‐platforms are developed at a rapid pace, users' input and evaluation of platform quality and utility should be prioritized [ABSTRACT FROM AUTHOR]

Eating disorders (EDs) are often accompanied by gastrointestinal (GI) distress. Anxiety sensitivity is the tendency to interpret sensations of anxiety as threatening or dangerous, and includes both broad physical symptoms (e.g., elevated heartrate) and GI‐specific symptoms. Physical and GI‐specific anxiety sensitivity may be important risk and maintaining factors in EDs. This study tested the hypothesis that greater reductions in both types of anxiety sensitivity during the first month of treatment would predict lower ED symptoms and trait anxiety at discharge and 6‐month follow‐up. Patients (n = 424) in ED treatment reported physical and GI‐specific anxiety sensitivity, ED symptoms, and trait anxiety at treatment admission, 1‐month into treatment, discharge, and 6‐month follow‐up. Analyses were conducted with hierarchical linear regression with imputation, controlling for relevant covariates. Results indicated that early reduction in GI‐specific but not general physical anxiety sensitivity predicted both lower ED symptoms and lower trait anxiety at discharge and 6‐month follow‐up. These findings demonstrate the importance of GI‐specific anxiety sensitivity as a potential maintaining factor in EDs. Developing and refining treatments to target GI‐specific anxiety sensitivity may have promise in improving the treatment not only of EDs, but also of commonly co‐morbid anxiety disorders. Highlights: Anxiety sensitivity, the fear of symptoms of anxiety, is common in eating disorders (EDs), and may predict treatment outcomes.In this study, greater reduction in anxiety sensitivity for gastrointestinal symptoms within the first month of ED treatment predicted lower ED symptoms and anxiety at discharge from treatment but not 6‐month follow‐up. By contrast, reduction in more general physical anxiety sensitivity did not predict ED symptoms or anxiety at discharge or follow‐up.Findings highlight the importance of targeting anxiety about body sensations in treatment for EDs. [ABSTRACT FROM AUTHOR]

Most of the evidence that a human betaretrovirus (HBRV/HMTV) highly related to mouse mammary tumour virus (MMTV) has an etiological role in breast cancer has been summarized in a recent comprehensive Special Issue of "Viruses" entitled "Human Betaretrovirus (HBRV) and Related Diseases". Shortly after publication of this special issue, a detailed analysis of aligned env sequences was published and concluded that (i) MMTV and HBRV/HMTV cannot be distinguished on the basis of aligned env sequences and (ii) more sequence data covering the full-length env or HBRV/HMTV genomes from multiple isolates is needed. Although productive infection of human cells by MMTV (and presumably HBRV/HMTV) has been shown, it is imperative that the receptor(s) enabling HBRV/HMTV to infect human cells are defined. Moreover, there is currently no compelling data for common integration sites, in contrast to MMTV induced mammary tumorigenesis in mice, suggesting that other mechanisms of tumorigenesis are associated with HBRV/HMTV infection. These issues need to be resolved before a clear link between MMTV/HBRV/HMTV and human breast cancer can be concluded. [ABSTRACT FROM AUTHOR]

There has been an important global interest in Open Science, which include open data and methods, in addition to open access publications. It has been proposed that public availability of raw data increases the value and the possibility of confirmation of scientific findings, in addition to the potential of reducing research waste. Availability of raw data in open repositories facilitates the adequate development of meta-analysis and the cumulative evaluation of evidence for specific topics. In this commentary, we discuss key elements about data sharing in open repositories and we invite researchers around the world to deposit their data in them. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic requires an urgent action to transform health-care delivery and to promote research and capacity-building nursing programs. Specifically, many countries at the global level have described nursing informatics as an essential competence for nurse professionals. In Peru, nursing personnel represents the largest health workforce group and nursing informatics is still emerging, but the field appear to hold much promise. In this sense, the Peruvian Ministry of Health (MoH) defined in 2020 the core nursing competences, which included a technology and innovation domain. The competence established to apply scientifically based technology and innovation to improve the processes or health service resources. The minimum competencies established by the MoH were as follows: to carry out innovations in processes or resources in their different professional performance areas, to creatively adapt technology in different areas of professional performance, to make rational and ethical use of health technologies with focus on new developments that will be evaluated and applied critically, and to manage information and communication technologies, and health information systems, with emphasis on telehealth (i.e. telemedicine, telecare management, tele-education, and tele-training). Besides the nursing competences defined by the MoH is a good starting point, this special contribution discusses the urgent need to strengthen nursing informatics competencies in Peru. [ABSTRACT FROM AUTHOR]

Normative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer's disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community. [ABSTRACT FROM AUTHOR]

With the help of time-dependent scattering theory on the observable algebra of infinitely extended quasifree fermionic chains, we introduce a general class of so-called right mover/left mover states which are inspired by the nonequilibrium steady states for the prototypical nonequilibrium configuration of a finite sample coupled to two thermal reservoirs at different temperatures. Under the assumption of spatial translation invariance, we relate the 2-point operator of such a right mover/left mover state to the asymptotic velocity of the system and prove that the system is thermodynamically nontrivial in the sense that its entropy production rate is strictly positive. Our study of these not necessarily gauge-invariant systems covers and substantially generalizes well-known quasifree fermionic chains and opens the way for a more systematic analysis of the heat flux in such systems. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the influence of verapamil‐mediated inhibition of P‐glycoprotein (P‐gp) on the pharmacokinetics of ivermectin (IVM) given orally and subcutaneously (SC) to rabbits. Twenty New Zealand rabbits were allotted to 4 groups (n = 5) and received IVM either orally or SC (0.4 mg/kg) alone or co‐administered with verapamil (2 mg/kg SC, 3 times at a 12‐hr interval). Plasma, fecal, and urine samples were collected over 30 days after medication to assess IVM concentrations in these samples. No significant differences were observed in the pharmacokinetic parameters of IVM between oral and SC administrations. The area under the plasma concentration–time curve was higher (p <.05) after IVM (oral)/verapamil treatment, compared with oral IVM alone. Moreover, the time to the Cmax of IVM was shorter (p <.05), whereas the elimination half‐life and the mean residence time were longer (p <.05) in the presence of verapamil. The IVM/verapamil combination administered orally or SC reduced fecal IVM concentrations, compared with IVM alone. In conclusion, the significant changes by verapamil on the pharmacokinetics of IVM, likely due to the inhibition of a P‐gp‐mediated intestinal secretion, may change IVM's antinematodal activity. [ABSTRACT FROM AUTHOR]

Citizen science approaches provide adaptable methodologies for enhancing the natural history knowledge of understudied taxa and engaging underserved populations with biodiversity. However, transitions to remote, virtual training, and participant recruitment in response to public health crises like the SARS‐CoV‐2 pandemic have the potential to disrupt citizen science projects. We present a comparison of outputs from a citizen science initiative built around call surveys for the Mountain Chorus Frog (Pseudacris brachyphona), an understudied anuran, in Appalachian Virginia, USA, prior to and during the SARS‐CoV‐2 pandemic. A transition to virtual training in this initiative did not lead to a decrease in scientific output and led to unexpected natural history insight about our focal taxon; however, a reliance on virtual instruction did decrease overall participation by local residents, particularly for rural K‐12 students. We discuss the trade‐offs exhibited by the adaptation of our initiative to a virtual format and provide recommendations for other citizen science initiatives facing similar restrictions in the face of current and future public health crises. [ABSTRACT FROM AUTHOR]

Background and Purpose: In 30% of the patients with focal epilepsy, an epileptogenic lesion cannot be visually detected with structural MRI. Ultra-high field MRI may be able to identify subtle pathology related to the epileptic focus. We set out to assess 7T MRI-derived volumetric and functional activity lateralization of the hippocampus, hippocampal subfields, temporal and frontal lobe in healthy subjects and MRI-negative patients with focal epilepsy.Methods: Twenty controls and 10 patients with MRI-negative temporal or frontal lobe epilepsy (TLE and FLE, respectively) underwent a 7T MRI exam. T1 -weigthed imaging and resting-state fMRI was performed. T1 -weighted images were segmented to yield volumes, while from fMRI data, the fractional amplitude of low frequency fluctuations was calculated. Subsequently, volumetric and functional lateralization was calculated from left-right asymmetry.Results: In controls, volumetric lateralization was symmetric, with a slight asymmetry of the hippocampus and subiculum, while functional lateralization consistently showed symmetry. Contrarily, in epilepsy patients, regions were less symmetric. In TLE patients with known focus, volumetric lateralization in the hippocampus and hippocampal subfields was indicative of smaller ipsilateral volumes. These patients also showed clear functional lateralization, though not consistently ipsilateral or contralateral to the epileptic focus. TLE patients with unknown focus showed an obvious volumetric lateralization, facilitating the localization of the epileptic focus. Lateralization results in the FLE patients were less consistent with the epileptic focus.Conclusion: MRI-derived volume and fluctuation amplitude are highly symmetric in controls, whereas in TLE, volumetric and functional lateralization effects were observed. This highlights the potential of the technique. [ABSTRACT FROM AUTHOR]

The use of machine learning (ML) algorithms has significantly increased in neuroscience. However, from the vast extent of possible ML algorithms, which one is the optimal model to predict the target variable? What are the hyperparameters for such a model? Given the plethora of possible answers to these questions, in the last years, automated ML (autoML) has been gaining attention. Here, we apply an autoML library called Tree‐based Pipeline Optimisation Tool (TPOT) which uses a tree‐based representation of ML pipelines and conducts a genetic programming‐based approach to find the model and its hyperparameters that more closely predicts the subject's true age. To explore autoML and evaluate its efficacy within neuroimaging data sets, we chose a problem that has been the focus of previous extensive study: brain age prediction. Without any prior knowledge, TPOT was able to scan through the model space and create pipelines that outperformed the state‐of‐the‐art accuracy for Freesurfer‐based models using only thickness and volume information for anatomical structure. In particular, we compared the performance of TPOT (mean absolute error [MAE]: 4.612 ±.124 years) and a relevance vector regression (MAE 5.474 ±.140 years). TPOT also suggested interesting combinations of models that do not match the current most used models for brain prediction but generalise well to unseen data. AutoML showed promising results as a data‐driven approach to find optimal models for neuroimaging applications. [ABSTRACT FROM AUTHOR]

Background: Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient. Methods: Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology. Results: Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions. Conclusion: These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the 'dysconnectivity hypothesis' of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa.Methods: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity.Results: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group.Conclusions: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa. [ABSTRACT FROM AUTHOR]

Tuberculosis remains an urgent issue on the urban health agenda, especially in low- and middle-income countries. There is a need to develop and implement innovative and effective solutions in the tuberculosis diagnostic process. In this article, We describe the importance of artificial intelligence as a strategy to address tuberculosis control, particularly by providing timely diagnosis. Besides technological factors, the role of socio-technical, cultural and organizational factors is emphasized. The eRx tool involving deep learning algorithms and specifically the use of convolutional neural networks is presented as a case study. eRx is a promising artificial intelligence-based tool for the diagnosis of tuberculosis; which comprises a variety of innovative techniques involving remote X-ray analysis for suspected tuberculosis cases. Innovations based on artificial intelligence tools can optimize the diagnostic process for tuberculosis and other communicable diseases. [ABSTRACT FROM AUTHOR]

The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals and remains threatened as a result of intense environmental and anthropogenic pressure. The transformation and specialization of the giant panda's diet into a herbivorous diet have resulted in unique adaptabilities in many aspects of their biology, physiology and behavior. However, little is known about their adaptability at the molecular level. Through comparative analysis of the giant panda's genome with those of nine other mammalian species, we found some genetic characteristics of the giant panda that can be associated with adaptive changes for effective digestion of plant material. We also found that giant pandas have similar genetic characteristics to carnivores in terms of olfactory perception but have similar genetic characteristics to herbivores in terms of immunity and hydrolytic enzyme activity. Through the analysis of gene family expansion, 3752 gene families were found, which were enriched in functions such as digestion. A total of 93 genes under positive selection were screened out and gene enrichment identified these genes for the following processes: negative regulation of cellular metabolic process, negative regulation of nitrogen compound metabolic process, negative regulation of macromolecule metabolic process and negative regulation of metabolic process. Combined with the KEGG pathway, it was found that genes such as CREB3L1, CYP450 2S1, HSD11B2, LRPAP1 play a key role in digestion. These genes may have played a key role in the pandas' adaptation to its bamboo diet. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder associated with both structural and functional brain abnormalities. In the past few years, there has been growing interest in the application of machine learning techniques to neuroimaging data for the diagnostic and prognostic assessment of this disorder. However, the vast majority of studies published so far have used either structural or functional neuroimaging data, without accounting for the multimodal nature of the disorder. Structural MRI and resting‐state functional MRI data were acquired from a total of 295 patients with schizophrenia and 452 healthy controls at five research centers. We extracted features from the data including gray matter volume, white matter volume, amplitude of low‐frequency fluctuation, regional homogeneity and two connectome‐wide based metrics: structural covariance matrices and functional connectivity matrices. A support vector machine classifier was trained on each dataset separately to distinguish the subjects at individual level using each of the single feature as well as their combination, and 10‐fold cross‐validation was used to assess the performance of the model. Functional data allow higher accuracy of classification than structural data (mean 82.75% vs. 75.84%). Within each modality, the combination of images and matrices improves performance, resulting in mean accuracies of 81.63% for structural data and 87.59% for functional data. The use of all combined structural and functional measures allows the highest accuracy of classification (90.83%). We conclude that combining multimodal measures within a single model is a promising direction for developing biologically informed diagnostic tools in schizophrenia. [ABSTRACT FROM AUTHOR]

Considered as one aspect of the task of individuation, acknowledging the impermanence of life is recognized as a pivotal component of an individual's conscious relationship with a transcendent meaning. The death of a loved one brings the painful finality of physical life into sharp focus; the emotionally shattering ordeals of grief follow the mythological motif of the night sea journey, where the ego is confronted by the archetypal elements of the collective unconscious. The magnitude of the author's suffering in grieving multiple losses possessed a numinous quality, and it is his hope that the exploration of the vast territory of grief and mourning in this article may be of help to those who seek the soulful path in life. [ABSTRACT FROM AUTHOR]

The article focuses on the habitat of Plethodon welleri, a salamander species endemic to the southern Appalachian Mountains. Topics include its distribution within spruce-fir and northern hardwood forests, its limited tolerance for cleared bald habitat, and the first observation of the species within a wetland habitat and cleared balds, indicating its dispersal capabilities and the importance of reforestation for population connectivity.

Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined by spirometry, and plasma was collected for measurement of cysteine (Cys), cystine (CySS), glutathione (GSH) and GSH disulfide (GSSG) by HPLC followed by estimation of redox potentials (E h) using the Nernst equation. Results showed that patients with COPD had more oxidized plasma E h Cys/CySS than patients with normal lung function, but plasma E h GSH/GSSG was unaltered. In addition, there was a correlation between the extent of plasma E h Cys/CySS oxidation and loss of lung function, and this correlation remained even after correcting for age, sex, race and body mass index. HIV infection per se was not associated with increased oxidation of plasma E h Cys/CySS, but plasma E h Cys/CySS was more oxidized in patients with lower CD4-positve T cell counts. In patients with both HIV infection and COPD, there was a significant correlation between CD4 cell counts and lung function. Thus, systemic oxidation correlated with decreased lung function in subjects with COPD and decreased CD4 counts in subjects infected with HIV. Thus, factors contributing to plasma E h Cys/CySS may represent novel mechanisms underlying the increased prevalence of COPD in people living with HIV. Image 1 • COPD is a major cause of morbidity and mortality in patients infected with HIV. • Oxidative stress has been implicated in the pathogenesis of both COPD and HIV. • Decreased lung function and CD4 counts paralleled oxidation of plasma cysteine/cystine redox potential (E h Cys/CySS). • Plasma E h Cys/CySS is a marker of oxidative stress that may be used to identify subjects at risk for lung function decline. [ABSTRACT FROM AUTHOR]