Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotective Effects of Forced Exercise and Bupropion on Chronic Methamphetamine-induced Cognitive Impairment via Modulation of cAMP Response Element-binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway, Oxidative Stress, and Inflammatory Biomarkers in Rats

Background: Forced exercise can act as non-pharmacologic neuroprotective agent. In current study, we tried the involved molecular mechanisms of protective effects of forced exercise against methamphetamine induced neurodegeneration. Materials and Methods: Forty adult male rats were divided to Group 1 and 2 which received normal saline and methamphetamine (10 mg/kg) respectively for 30 days. Groups 3, 4 and 5 were treated with methamphetamine for first 15 days and then were treated by forced exercise, bupropion (20 mg/kg/day) or combination of them for the following 15 days. Between 26th and 30th days, Morris Water Maze (MWM) was used to evaluate the cognition. On day 31, hippocampus was isolated from each rat and oxidative, antioxidant and inflammatory factors also the level of total and phosphorylated forms of cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) proteins were also evaluated. Results: Chronic abuse of methamphetamine could decreases cognition and increase malondialdehyde (MDA), Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), while caused decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities all these changes was significant (P < 0.001) in compared to control group while treatment with bupropion, forced exercise and bupropion in combination with forced exercise could prevent all these malicious effects of methamphetamine (P < 0.001). Bupropion, forced exercise and bupropion in combination with forced exercise could activate CREB (both forms) and activates BDNF proteins' expression with P < 0.001 in methamphetamine treated rats. Conclusions: P-CREB/BDNF signaling pathways might have critical role in forced exercise protective effects against methamphetamine induced neurodegeneration.
Nonselective Cyclooxygenase Inhibition Retards Cyst Progression in a Murine Model of Autosomal Dominant Polycystic Kidney Disease

Aim: Autosomal dominant polycystic kidney disease is one of the most common genetic renal diseases. Cyclooxygenase plays an important role in epithelial cell proliferation and may contribute to the mechanisms underlying cyst formation. The aim of the present study was to evaluate the role of cyclooxygenase inhibition in the cyst progression in polycystic kidney disease. Method: Pkd2WS25/- mice, a murine model which harbors a compound cis-heterozygous mutation of the Pkd2 gene were used. Cyclooxygenase expression was assessed in both human and murine kidney specimens. Pkd2WS25/- mice were treated with Sulindac (a nonselective cyclooxygenase inhibitor) or vehicle for 8 months starting at three weeks age, and then renal cyst burden was assessed by kidney weight and volume. Results: Cyclooxygenase-2 expression was up-regulated compared to control kidneys as shown by RNase protection in human polycystic kidneys and immunoblot in mouse Pkd2WS25/- kidneys. Cyclooxygenase-2 expression was up-regulated in the renal interstitium as well as focal areas of the cystic epithelium (p<0.05). Basal Cyclooxygenase-1 levels were unchanged in both immunohistochemistry and real-time PCR. Administration of Sulindac to Pkd2WS25/- mice and to control mice for 8 months resulted in reduced kidney weights and volume in cystic mice. Renal function and electrolytes were not significantly different between groups. Conclusion: Thus treatment of a murine model of polycystic kidney disease with Sulindac results in decreased kidney cyst burden. These findings provide additional implications for the use of Cyclooxygenase inhibition as treatment to slow the progression of cyst burden in patients with polycystic kidney disease.
Relevance of Modified Debridement-Irrigation, Antibiotic Therapy and Implant Retention Protocol for the Management of Surgical Site Infections: A Series of 1694 Instrumented Spinal Surgery

Introduction: Management of surgical site infections (SSI) after instrumented spinal surgery remains controversial. The debridement-irrigation, antibiotic therapy and implant retention protocol (DAIR protocol) is safe and effective to treat deep SSI occurring within the 3 months after instrumented spinal surgery. Methods: This retrospective study describes the outcomes of patients treated over a period of 42 months for deep SSI after instrumented spinal surgery according to a modified DAIR protocol. Results: Among 1694 instrumented surgical procedures, deep SSI occurred in 46 patients (2.7%): 41 patients (89%) experienced early SSI (< 1 month), 3 (7%) delayed SSI (from 1 to 3 months), and 2 (4%) late SSI (> 3months). A total of 37 patients had a minimum 1 year of follow-up; among these the modified DAIR protocol was effective in 28 patients (76%) and failed (need for new surgery for persistent signs of SSI beyond 7 days) in 9 patients (24%). Early second-look surgery (≤ 7days) for iterative debridement was performed in 3 patients, who were included in the cured group. Among the 9 patients in whom the modified DAIR protocol failed, none had early second-look surgery; 3 (33%) recovered and were cured at 1 year follow-up, and 6 (66%) relapsed. Overall, among patients with SSI and a minimum 1 year follow-up, the modified DAIR protocol led to healing in 31/37 (84%) patients. Conclusions: The present study supports the effectiveness of a modified DAIR protocol in deep SSI occurring within the 3 months after instrumented spinal surgery. An early second-look surgery for iterative debridement could increase the success rate of this treatment.
Recognizing and appraising symptoms of breast cancer as a reason for delayed presentation in Ghanaian women: A qualitative study

Background The burden of late presentation is well established in women presenting with advanced breast cancer in Africa. This paper aims to explore the reasons for delayed presentation in Ghanaian women with breast cancer. Method Eleven (11) women diagnosed with advanced breast cancer were purposively sampled within three years of diagnosis at the palliative care clinic of the Komfo Anokye Teaching Hospital, Ghana. Participation was voluntary. Data was collected through in-depth interviews using a self-devised semi-structured interview guide. The interviews were conducted in “Twi” (local language), audio-tape recorded and covered the women’s journey from symptom discovery to their intention to seek help. All audio-taped interviews were transcribed based on the meaning of the respondents’ comments. The data was managed using Nvivo version 11 qualitative software. Data was analyzed concurrently with data collection applying the principles of thematic analysis. Key findings All the women delayed presentation due to overlapping reasons. Symptom appraisal among the women occurred in two main stages: individual understanding of breast symptom and interactive understanding of the breast symptom. These stages were based on cognitive, psycho-cultural and social factors. The five main themes generated from the data were: symptom experience, knowledge of breast cancer, role of social life and network, coping with a breast symptom and lastly intent to seeking health care. A conceptual model was developed to illustrate the relationships among the key factors and concepts emanated from this study. Conclusion Recognition and appraisal of breast cancer symptom in the eleven (11) Ghanaian women interviewed in this study was poor. For instance, a painless breast lump was considered not serious until a sensory symptom appears. This led women to experience appraisal and time point intervals. To minimize the incidence of late presentation of breast cancer cases in Ghana, adequate educational intervention should be provided for Ghanaian women and their social network, and other stakeholders.
Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells

Baicalein, a flavonoid extracted from the roots of Scutellaria baicalensis Georgi. , has various pharmacological effects due to its high antioxidant activity. However, no study has yet been conducted on the protective efficacy of baicalein against oxidative stress in Schwann cells. In this study, we evaluated the protective effect of baicalein on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in HEI193 Schwann cells. For this purpose, HEI193 cells exposed to H2O2 in the presence or absence of baicalein were applied to cell viability assay, immunoblotting, Nrf2-specific small interfering RNA (siRNA) transfection, comet assay, and flow cytometry analyses. Our results showed that baicalein effectively inhibited H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Baicalein also weakened H2O2-induced mitochondrial dysfunction, increased the Bax/Bcl-2 ratio, activated caspase-9 and -3, and degraded poly(ADP-ribose) polymerase. In addition, baicalein increased not only the expression but also the phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, although the expression of kelch-like ECH-associated protein-1 was decreased. However, the inhibition of Nrf2 expression by transfection with Nrf2-siRNA transfection abolished the expression of HO-1 and antioxidant potential of baicalein. These results demonstrate that baicalein attenuated H2O2-induced apoptosis through the conservation of mitochondrial function while eliminating ROS in HEI193 Schwann cells, and the antioxidant efficacy of baicalein implies at least a Nrf2/HO-1 signaling pathway-dependent mechanism. Therefore, it is suggested that baicalein may have a beneficial effect on the prevention and treatment of peripheral neuropathy induced by oxidative stress.
Basic knowledge of social hierarchies and physiological profile of reared sea bass Dicentrarchus labrax (L.)

The effects of social hierarchies (dominant/subordinate individuals), such as aggressiveness, feeding order, and territoriality, are some of the characteristics used for describing fish behaviour. Social hierarchy patterns are still poorly understood in European-reared sea bass (Dicentrarchus labrax). In this work, we examine the social interactions among captive fish integrating behavioural and physiological profiles. Groups of three fish with EMG (electromyogram) radio transmitters were monitored for two weeks via video recording. Plasma levels of cortisol, glucose, lactate and lysozyme as well as haematological parameters such as haemoglobin, haematocrit and RBCC (red blood cell count) were measured at the beginning and end of the experiments. Behaviour and muscle activity were monitored daily. The results highlighted that the social hierarchic order was established after one to two days, and it was maintained throughout the experimental period. Dominant and subordinate fish (ß and γ) showed significant differences in muscle activity, hormonal profile (cortisol), aspecific immunity (lysozyme), carbohydrate metabolism (lactate) and behavioural patterns (food order and aggressiveness). This holistic approach helps to provide insights into the physiological status of the subordinate (ß and γ) and dominant individuals. These data have wide implications for aquaculture practice.
Cophylogenetic analysis suggests cospeciation between the Scorpion Mycoplasma Clade symbionts and their hosts

Scorpions are predator arachnids of ancient origin and worldwide distribution. Two scorpion species, Vaejovis smithi and Centruroides limpidus, were found to harbor two different Mollicutes phylotypes: a Scorpion Mycoplasma Clade (SMC) and Scorpion Group 1 (SG1). Here we investigated, using a targeted gene sequencing strategy, whether these Mollicutes were present in 23 scorpion morphospecies belonging to the Vaejovidae, Carboctonidae, Euscorpiidae, Diplocentridae, and Buthidae families. Our results revealed that SMC is found in a species-specific association with Vaejovidae and Buthidae, whereas SG1 is uniquely found in Vaejovidae. SMC and SG1 co-occur only in Vaejovis smithi where 43% of the individuals host both phylotypes. A phylogenetic analysis of Mollicutes 16S rRNA showed that SMC and SG1 constitute well-delineated phylotypes. Additionally, we found that SMC and scorpion phylogenies are significantly congruent, supporting the observation that a cospeciation process may have occurred. This study highlights the phylogenetic diversity of the scorpion associated Mollicutes through different species revealing a possible cospeciation pattern.
Loss of ABAT-Mediated GABAergic System Promotes Basal-Like Breast Cancer Progression by Activating Ca2+-NFAT1 Axis

Basal-like breast cancer (BLBC) is the most aggressive subtype with a poor clinical outcome; however, the molecular mechanisms underlying aggressiveness in BLBC remain poorly understood. Methods: The effects of gamma-aminobutyrate aminotransferase (ABAT) on GABA receptors, Ca2+-NFAT1 axis, and cancer cell behavior were assessed by Ca2+ imaging, Western blotting, immunostaining, colony formation, and migration and invasion assays. We elucidated the relationship between ABAT and Snail by luciferase reporter and ChIP assays. The effect of ABAT expression on BLBC cells was determined by in vitro and in vivo tumorigenesis and a lung metastasis mouse model. Results: We showed that, compared to other subtypes, ABAT was considerably decreased in BLBC. Mechanistically, ABAT expression was downregulated due to Snail-mediated repression leading to increased GABA production. GABA then elevated intracellular Ca2+ concentration by activating GABA-A receptor (GABAA), which contributed to the efficient activation of NFAT1 in BLBC cells. ABAT expression resulted in inhibition of tumorigenicity, both in vitro and in vivo, and metastasis of BLBC cells. Thus, loss of ABAT contributed to BLBC aggressiveness by activating the Ca2+-NFAT1 axis. In breast cancer patients, loss of ABAT expression was strongly correlated with large tumor size, high grade and metastatic tendency, poor survival, and chemotherapy resistance. Conclusions: Our findings have provided underlying molecular details for the aggressive behavior of BLBC. The Snail-mediated downregulation of ABAT expression in BLBC provides tumorigenic and metastatic advantages by activating GABA-mediated Ca2+-NFAT1 axis. Thus, our results have identified potential prognostic indicators and therapeutic targets for this challenging disease.
The origins and evolution of macropinocytosis

In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Controlled clinical trial of canine therapy versus usual care to reduce patient anxiety in the emergency department

Objective Test if therapy dogs reduce anxiety in emergency department (ED) patients. Methods In this controlled clinical trial (NCT03471429), medically stable, adult patients were approached if the physician believed that the patient had “moderate or greater anxiety. ” Patients were allocated on a 1:1 ratio to either 15 min exposure to a certified therapy dog and handler (dog), or usual care (control). Patient reported anxiety, pain and depression were assessed using a 0–10 scale (10 = worst). Primary outcome was change in anxiety from baseline (T0) to 30 min and 90 min after exposure to dog or control (T1 and T2 respectively); secondary outcomes were pain, depression and frequency of pain medication. Results Among 93 patients willing to participate in research, 7 had aversions to dogs, leaving 86 (92%) were willing to see a dog six others met exclusion criteria, leaving 40 patients allocated to each group (dog or control). Median and mean baseline anxiety, pain and depression scores were similar between groups. With dog exposure, median anxiety decreased significantly from T0 to T1: 6 (IQR 4–9.75) to T1: 2 (0–6) compared with 6 (4–8) to 6 (2.5–8) in controls (P<0.001, for T1, Mann-Whitney U and unpaired t-test). Dog exposure was associated with significantly lower anxiety at T2 and a significant overall treatment effect on two-way repeated measures ANOVA for anxiety, pain and depression. After exposure, 1/40 in the dog group needed pain medication, versus 7/40 in controls (P = 0.056, Fisher’s exact test). Conclusions Exposure to therapy dogs plus handlers significantly reduced anxiety in ED patients.
Cohesion, order and information flow in the collective motion of mixed-species shoals

Despite the frequency with which mixed-species groups are observed in nature, studies of collective behaviour typically focus on single-species groups. Here, we quantify and compare the patterns of interactions between three fish species, threespine sticklebacks (Gasterosteus aculeatus), ninespine sticklebacks (Pungitius pungitius) and roach (Rutilus rutilus) in both single- and mixed-species shoals in the laboratory. Pilot data confirmed that the three species form both single- and mixed-species shoals in the wild. In our laboratory study, we found that single-species groups were more polarized than mixed-species groups, while single-species groups of threespine sticklebacks and roach were more cohesive than mixed shoals of these species. Furthermore, while there was no difference between the inter-individual distances between threespine and ninespine sticklebacks within mixed-species groups, there was some evidence of segregation by species in mixed groups of threespine sticklebacks and roach. There were differences between treatments in mean pairwise transfer entropy, and in particular we identify species-differences in information use within the mixed-species groups, and, similarly, differences in responses to conspecifics and heterospecifics in mixed-species groups. We speculate that differences in the patterns of interactions between species in mixed-species groups may determine patterns of fission and fusion in such groups.
Inversion of a large-scale circuit model reveals a cortical hierarchy in the dynamic resting human brain

Converging evidence from biophysical modeling, magnetic resonance imaging, and histology reveals a large-scale cortical gradient. We considered a large-scale dynamical circuit model of human cerebral cortex with region-specific microscale properties. The model was inverted using a stochastic optimization approach, yielding markedly better fit to new, out-of-sample resting functional magnetic resonance imaging (fMRI) data. Without assuming the existence of a hierarchy, the estimated model parameters revealed a large-scale cortical gradient. At one end, sensorimotor regions had strong recurrent connections and excitatory subcortical inputs, consistent with localized processing of external stimuli. At the opposing end, default network regions had weak recurrent connections and excitatory subcortical inputs, consistent with their role in internal thought. Furthermore, recurrent connection strength and subcortical inputs provided complementary information for differentiating the levels of the hierarchy, with only the former showing strong associations with other macroscale and microscale proxies of cortical hierarchies (meta-analysis of cognitive functions, principal resting fMRI gradient, myelin, and laminar-specific neuronal density). Overall, this study provides microscale insights into a macroscale cortical hierarchy in the dynamic resting brain.
Role of deformable image registration for delivered dose accumulation of adaptive external beam radiation therapy and brachytherapy in cervical cancer

Purpose Deformable image registration (DIR) can be used to accumulate the absorbed dose distribution of daily image-guided adaptive external beam radiation treatment (EBRT) and brachytherapy (BT). Since dose-volume parameter addition assumes a uniform delivered EBRT dose around the planned BT boost, the added value of DIR over direct addition was investigated for dose accumulation in bladder and rectum. Material and methods For 10 patients (EBRT 46/46.2 GyEQD2, EBRT + BT: D90 85-90 GyEQD2, in equivalent dose in 2 Gy fractions), the actually delivered dose from adaptive volumetric-modulated arc therapy (VMAT)/intensity-modulated radiotherapy (IMRT) EBRT was calculated using the daily anatomy from the cone-beam computed tomography (CBCT) scans acquired prior to irradiation. The CBCT of the first EBRT fraction and the BT planning MRI were registered using DIR. The cumulative dose to the 2 cm3 with the highest dose (D2cm3) from EBRT and BT to the bladder and rectum was calculated and compared to direct addition assuming a uniform EBRT dose (UD). Results Differences (DIR-UD) in the total EBRT + BT dose ranged between –0.2-3.9 GyEQD2 (bladder) and –1.0-3.7 GyEQD2 (rectum). The total EBRT + BT dose calculated with DIR was at most 104% of the dose calculated with the UD method. Conclusions Differences between UD and DIR were small (< 3.9 GyEQD2). The dose delivered with adaptive VMAT/IMRT EBRT to bladder and rectum near the planned BT boost can be considered uniform for the evaluation of bladder/rectum D2cm3.