Miracle-dz/UniFAR-FTUs huggingface dataset:
A concurrently available negative reinforcer robustly decreases cocaine self-administration in male and female rats

Continued drug-taking despite adverse consequences is hypothesized to be an insidious behavioral hallmark of drug addiction. Although most preclinical research has focused on drug self-administration in the presence of positive punishment, another source of potential adverse consequences is behavioral allocation away from negative reinforcers (i.e., escape/avoid electric shock) and towards drug reinforcers. The goals of the present study were to establish a discrete-trial cocaine-vs-negative reinforcer choice procedure in male and female rats and determine sensitivity of choice behavior to environmental and pharmacological manipulations. Rats could make up to nine discrete choices between an intravenous cocaine infusion (0.32 – 1.8 mg/kg/inf) under a fixed-ratio (FR) 3 schedule and a negative reinforcer (escape or avoidance of electric shock, 0.1 – 0.7 mA) under an FR1 schedule. The negative reinforcer was consistently chosen over all cocaine doses. Lowering shock magnitude decreased negative reinforcer trials, increased omitted trials, and failed to promote behavioral reallocation towards cocaine. Increasing the negative reinforcement response requirement between sessions only increased omitted trials. Introduction of 12-hr extended access cocaine self-administration sessions across two weeks resulted in high daily cocaine intakes but failed to significantly increase cocaine choice. Acute diazepam pretreatment also did not impact choice behavior up to doses that produced behavioral depression. Overall, the lack of behavioral allocation between cocaine infusions and a negative reinforcer suggests these two reinforcers may be economic independents. Additionally, the failure of extended cocaine access to increase cocaine choice highlights the importance of alternative reinforcers and environmental context in preclinical models of drug addiction.
Implementation of biotic interactions in niche analyses unravels the patterns underneath community composition in clownfishes

Aim Biotic interactions are key to understanding the ecology of species and communities. As such, integrating biotic interactions into ecological niche modelling methods has been a central topic of research for the last decade. Yet, the role of biotic interactions remains overlooked. Mutualistic systems constitute perfect study cases for analysing the effect of biotic interactions on species niches and communities’ composition. Location Indo-Pacific Ocean Time period Current Major taxa studied Clownfish-sea anemone mutualistic system Methods We integrate mutualistic interactions into a niche quantification framework to analyse the effect of biotic interactions in the estimation of species niches, and competition patterns among clownfish communities. Results Implementing biotic interactions in ecological niche modelling can improve the reliability of niche estimations, especially in specialist species. Additionally, resource partitioning decreases niche overlap among clownfishes allowing coexistence in species-rich habitats. Main conclusions We provide a framework to estimate the effects of species interactions and demonstrate the importance of including biotic interaction to improve the estimation of species’ ecological niches. Finally, we show how resource partitioning regulates competition and provides the ecological basis to explain why clownfishes have different sets of associations with sea anemones. The variety of mutualistic strategies serves to ecosystem sustainability, reducing the effect of saturation by species richness and competitive exclusion. Competition avoidance through resource partitioning may be the primary mechanism that shapes clownfish communities across the Indo-Pacific. These findings strongly support the importance of biotic interactions in shaping communities. Future studies could use the proposed analytical framework to serve multiple conservation purposes.
Impact of pathogen genetics on clinical phenotypes in a population of Talaromyces marneffei from Vietnam

Talaromycosis, a severe and invasive fungal infection caused by Talaromyces marneffei, is difficult to treat and impacts those living in endemic regions of southeast Asia, India, and China. While 30% of infections result in mortality, our understanding of the genetic basis of pathogenesis for this fungus is limited. To address this, we apply population genomics and genome wide association study approaches to a cohort of 336 T. marneffei isolates collected from patients who enrolled in the Itraconazole versus Amphotericin B for Talaromycosis (IVAP) trial in Vietnam. We find that isolates from northern and southern Vietnam form two distinct geographical clades, with isolates from southern Vietnam associated with increased disease severity. Leveraging longitudinal isolates, we identify multiple instances of disease relapse linked to unrelated strains, highlighting the potential for multi-strain infections. In more frequent cases of persistent talaromycosis caused by the same strain, we identify variants arising over the course of patient infections that impact genes predicted to function in the regulation of gene expression and secondary metabolite production. By combining genetic variant data with patient metadata for all 336 isolates, we identify pathogen variants significantly associated with multiple clinical phenotypes. In addition, we identify genes and genomic regions under selection across both clades, highlighting loci undergoing rapid evolution, potentially in response to external pressures. With this combination of approaches, we identify links between pathogen genetics and patient outcomes and identify genomic regions that are altered during T. marneffei infection, providing an initial view of how pathogen genetics affects disease outcomes.
The lexical processing of Japanese collocations by Chinese Japanese-as-a-Foreign-Language learners: An experimental study by manipulating the presentation modality, semantic transparency, and translational congruency

Introduction Research on collocations has become an essential issue in L2 acquisition and cognitive psychology. Previous studies have mainly focused on phonographic languages such as English, Swedish, and German, and primarily discussed the effect of semantic transparency and translational congruency. However, these studies have lacked (1) an analysis of the interactions between presentation modalities (visual vs. auditory) and the semantic transparency and translational congruency, and (2) a discussion of an ideographic language, such as Chinese and Japanese. Methods We conducted an experiment with 36 Chinese Japanese-as-a-Foreign-Language learners to examine the processing of Japanese collocations. In the experiment, we manipulated the presentation modality, semantic transparency, and translational congruency during a lexical judgment task. Results Data analysis using linear mixed-effects models revealed the following. (1) In both conditions of semantic transparency and translational congruency, the auditory presentation was associated with longer reaction times than the visual presentation. (2) In the visual presentation condition, neither semantic transparency nor translational congruency showed significant effects. (3) In the auditory presentation condition, the reaction time for collocations with high semantic transparency tended to be longer than that for collocations with medium semantic transparency and significantly longer than that for collocations with low semantic transparency. The reaction time for collocations with congruent translation was longer than that for collocations with incongruent translation. Discussion These results support the dual-route model of Japanese collocational processing by Chinese Japanese-as-a-Foreign-Language learners. Our findings suggest that whether the analytic or holistic processing dominates is closely related to the learners’ knowledge of Chinese and Japanese Kanji words and strongly influenced by the presentation modality, semantic transparency, and translational congruency.
Microbial gradual shifts during the process of species replacement in Taihang Mountain

Introduction Understanding microbial gradual shifts along species replacement can help elucidate the mechanisms driving secondary succession, and predict microbial responses to changing environments. However, how climate-induced species replacement alters microbial processes, and whether microbial shifts follow predictable assembly trajectories remain unclear. Methods Using space-for-time substitution approach, we studied shifts in bacterial and fungal communities in the succession from Leptodermis oblonga to Vitex negundo var. heterophylla shrubland in Taihang Mountain. Results and Discussion Species replacement, induced by climate related environmental change, significantly increased the above-ground biomass of shrublands, and TP and TK contents in topsoil. The succession from L. oblonga to V. negundo var. heterophylla communities resulted in the gradually replacement of cold-tolerant microbes with warm-affinity ones, and alterations of microbial communities involved in soil biogeochemical processes. Soil and plant variables, such as above-ground biomass, soil pH, total phosphorus, and total potassium, well explained the variations in microbial communities, indicating that the coordinated changes in plant communities and soil properties during secondary succession caused accompanied shifts in microbial diversity and composition.
Milk metabolomics analyses of lactating dairy cows with divergent residual feed intake reveals physiological underpinnings and novel biomarkers

The opportunity to select for feed efficient cows has been limited by inability to cost-effectively record individual feed efficiency on an appropriate scale. This study investigated the differences in milk metabolite profiles between high- and low residual feed intake (RFI) categories and identified biomarkers of residual feed intake and models that can be used to predict residual feed intake in lactating Holsteins. Milk metabolomics analyses were undertaken at early, mid and late lactation stages and residual feed intake was calculated in 72 lactating dairy cows. Cows were ranked and grouped into high residual feed intake (RFI >0.5 SD above the mean, n = 20) and low residual feed intake (RFI <0.5 SD below the mean, n = 20). Milk metabolite profiles were compared between high residual feed intake (least efficient) and low residual feed intake (most efficient) groups. Results indicated that early lactation was predominantly characterized by significantly elevated levels of medium chain acyl carnitines and glycerophospholipids in high residual feed intake cows. Citrate cycle and glycerophospholipid metabolism were the associated pathways enriched with the significantly different metabolites in early lactation. At mid lactation short and medium chain acyl carnitines, glycerophospholipids and amino acids were the main metabolite groups differing according to residual feed intake category. Late lactation was mainly characterized by increased levels of amino acids in high residual feed intake cows. Amino acid metabolism and biosynthesis pathways were enriched for metabolites that differed between residual feed intake groups at the mid and late lactation stages. Receiver operating characteristic curve analysis identified candidate biomarkers: decanoylcarnitine (area under the curve: AUC = 0.81), dodecenoylcarnitine (AUC = 0.81) and phenylalanine (AUC = 0.85) at early, mid and late stages of lactation, respectively. Furthermore, panels of metabolites predicted residual feed intake with validation coefficient of determination (R 2) of 0.65, 0.37 and 0.60 at early, mid and late lactation stages, respectively. The study sheds light on lactation stage specific metabolic differences between high-residual feed intake and low-residual feed intake lactating dairy cows. Candidate biomarkers that distinguished divergent residual feed intake groups and panels of metabolites that predict individual residual feed intake phenotypes were identified. This result supports the potential of milk metabolites to select for more efficient cows given that traditional residual feed intake phenotyping is costly and difficult to conduct in commercial farms.
Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms. Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction. Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes. Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.
The safety, benefits and future development of overnight and outpatient thyroidectomy

With the development of medical care, the safety of thyroidectomy is improving year by year. Due to economic benefits and other advantages of the overnight and outpatient thyroidectomy, more and more patients and medical institutions have favored overnight and outpatient thyroidectomy, and its proportion in thyroidectomy has increased year by year. However, overnight and outpatient thyroidectomy still faces many challenges and remains to be improved. In this review, we focused on the recent progress and the relevant clinical features of overnight and outpatient thyroidectomy, including its safety, economic benefits, etc., which may bring valuable clues and information for further improvements of patient benefits and promotions of overnight or outpatient thyroidectomy in the future.
Results of vacuum cleaning techniques on the performance of LiF field-threshold ion sources on extraction applied-B ion diodes at 1-10 TW

Uncontrolled plasma formation on electrode surfaces limits performance in a wide variety of pulsed power devices such as electron and ion diodes, transmission lines, radio frequency (RF) cavities, and microwave devices. Surface and bulk contaminants on the electrodes in vacuum dominate the composition of these plasmas, formed through processes such as stimulated and thermal desorption followed by ionization. We are applying RF discharge cleaning, anode heating, cathode cooling, and substrate surface coatings to the control of the effects of these plasmas in the particular case of applied-B ion diodes on the SABRE (1 TW) and PBFA-X (30 TW) accelerators. Evidence shows that our LiF ion source provides a 200-700 A/cm/sup 2/ lithium beam for 10-20 ns which is then replaced by a contaminant beam of protons and carbon. Other ion sources show similar behavior. Our electrode surface and substrate cleaning techniques reduce beam contamination, anode and cathode plasma formation, delay impedance collapse, and increase lithium energy, power, and production efficiency. Theoretical and simulation models of electron-stimulated and thermal-contaminant desorption leading to anode plasma formation show agreement with many features from experiment. Decrease of the diode electron loss by changing the shape and magnitude of the insulating magnetic field profiles increases the lithium output and changes the diode response to cleaning. We also show that the LiF films are permeable, allowing substrate contaminants to affect diode behavior. Substrate coatings of Ta and Au underneath the LiF film allow some measure of control of substrate contaminants, and provide direct evidence for thermal desorption. We have increased lithium current density by a factor of four and lithium energy by a factor of five through a combination of in situ surface and substrate cleaning, substrate coatings, and field profile modifications.
SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice

Since SARM1 mutations have been identified in human neurological disease, SARM1 inhibition has become an attractive therapeutic strategy to preserve axons in a variety of disorders of the peripheral (PNS) and central nervous system (CNS). While SARM1 has been extensively studied in neurons, it remains unknown whether SARM1 is present and functional in myelinating glia? This is an important question to address. Firstly, to identify whether SARM1 dysfunction in other cell types in the nervous system may contribute to neuropathology in SARM1 dependent diseases? Secondly, to ascertain whether therapies altering SARM1 function may have unintended deleterious impacts on PNS or CNS myelination? Surprisingly, we find that oligodendrocytes express sarm1 mRNA in the zebrafish spinal cord and that SARM1 protein is readily detectable in rodent oligodendrocytes in vitro and in vivo. Furthermore, activation of endogenous SARM1 in cultured oligodendrocytes induces rapid cell death. In contrast, in peripheral glia, SARM1 protein is not detectable in Schwann cells and satellite glia in vivo and sarm1/Sarm1 mRNA is detected at very low levels in Schwann cells, in vivo, in zebrafish and mouse. Application of specific SARM1 activators to cultured mouse Schwann cells does not induce cell death and nicotinamide adenine dinucleotide (NAD) levels remain unaltered suggesting Schwann cells likely contain no functionally relevant levels of SARM1. Finally, we address the question of whether SARM1 is required for myelination or myelin maintenance. In the zebrafish and mouse PNS and CNS, we show that SARM1 is not required for initiation of myelination and myelin sheath maintenance is unaffected in the adult mouse nervous system. Thus, strategies to inhibit SARM1 function to treat neurological disease are unlikely to perturb myelination in humans.
DNA methylation enzymes in the kidneys of male and female BTBR ob/ob mice

Diabetic kidney disease (DKD) is the leading cause of the end-stage renal disease. Recent studies have shown that epigenetic modifications contribute to alterations in gene expression and the development of DKD. This study aimed to show an expression profile of key DNA (de)methylation enzymes (DNMT, TET proteins) and their differences between sexes under obesity and diabetic condition. Male and female black and tan brachyury (BTBR) ob/ob mice and their corresponding wild-type littermates (BTBR WT) were studied until 16 weeks of age. Metabolic parameters, kidney morphophysiology and the expression of fibrotic markers and epigenetic enzymes were studied in whole kidney tissue or specifically in the glomerulus. The results showed sexual dimorphism in the development of metabolic disease and in kidney morphophysiology. Female mice have a different profile of DNMTs expression in both WT and obese/diabetic condition. Furthermore, metabolic condition negatively modulated the glomerular expression of TET1 and TET3 only in females. To our knowledge, this is the first study that shows a kidney profile of the expression of key (de)methylation enzymes, DNMTs and TETs, in the BTBR ob/ob experimental model of DKD and its association with sex. The knowledge of this epigenetic profile may help future research to understand the pathophysiology of DKD in males and females.
Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy

Cholangiocarcinoma is a rare group of tumors that involve the hepatic biliary tree. Prognosis for patients with cholangiocarcinoma remains dismal. Herein, we present survival trends over a long time period spanning almost 20 years in patients with advanced cholangiocarcinoma receiving systemic chemotherapy. We retrospectively analyzed a large multicenter dataset of cholangiocarcinoma outpatients evaluated in 14 centers within the Cholangiocarcinoma Italian Group Onlus (Gruppo Italiano Colangiocarcinoma Onlus, G.I.C.O.) between 2000 and 2017 (first-line), and 2002 and 2017 (second-line). Three time periods were considered: 2000-2009, 2010-2013, and 2014-2017. A total of 922 patients (51.19% male) with cholangiocarcinoma undergoing first-line therapy were evaluated. The median durations of follow-up for progression-free survival (PFS) and overall survival (OS) were 37 and 57 months, respectively. PFS at 12 months in the three periods of starting first-line therapy was similar, ranging from 11.71% to 15.25%. OS at 12 months progressively improved (38.30%, 44.61% and 49.52%, respectively), although the differences were not statistically significant after adjusting for age, disease status, and primary tumor site. A total of 410 patients (48.5% male) underwent second-line chemotherapy. The median durations of follow-up for PFS and OS were 47.6 and 41.90 months, respectively. An OS of 24.3%, 32.3%, and 33.1% was observed in 2002-2009, 2010-2013, and 2014-2017, respectively. Despite incremental benefits across years, our clinical experience confirms that modest overall advances have been achieved with first- and second-line chemotherapy in advanced cholangiocarcinoma. Efforts should focus on the identification of patients who derive the greatest benefit from treatment.