Miracle-dz/UniFAR-FTUs huggingface dataset:
Animal Models of (or for) Aggression Reward, Addiction, and Relapse: Behavior and Circuits

Inappropriate and pathological aggression plays a leading role in the suffering and death of millions of people, and further places an untenable strain on the caregivers and families of those afflicted. In some cases, such as addictive drugs, aggression can be highly rewarding (appetitive) and continually pursued despite short- and long-term negative consequences. Similarly, recidivism (relapse) rates for repeat violent offenders are as high as relapse rates for drug addicts. Appetitive aggression and relapse to aggression seeking can be modeled in mice studies using conditioned place preference and self-administration procedures followed by a period of abstinence and subsequent tests for relapse to aggression preference and aggression seeking. These procedures allow for the study of the mechanisms that control the appetitive versus the consummatory (attack) phases of aggressive behavior. In this review, we first discuss the behavioral procedures developed to probe appetitive aggression in mouse models, spanning from Pavlovian to operant tasks, and we also describe the recently proposed phenomenon of “aggression addiction. ” Next, we discuss the pharmacological and circuit mechanisms of aggression conditioned place preference and aggression self-administration, seeking, and relapse, highlighting mechanistic congruence and divergence between appetitive and consummatory phases of aggression. We conclude by discussing clinical implications of the studies reviewed.
In vivo imaging reveals reduced activity of neuronal circuits in a mouse tauopathy model

Pathological alterations of tau protein play a significant role in the emergence and progression of neurodegenerative disorders. Tauopathies are characterized by detachment of the tau protein from neuronal microtubules, and its subsequent aberrant hyperphosphorylation, aggregation and cellular distribution. The exact nature of tau protein species causing neuronal malfunction and degeneration is still unknown. In the present study, we used mice transgenic for human tau with the frontotemporal dementia with parkinsonism-associated P301S mutation. These mice are prone to develop fibrillar tau inclusions, especially in the spinal cord and brainstem. At the same time, cortical neurons are not as strongly affected by fibrillar tau forms, but rather by soluble tau forms. We took advantage of the possibility to induce formation of neurofibrillary tangles in a subset of these cortical neurons by local injection of preformed synthetic tau fibrils. By using chronic in vivo two-photon calcium imaging in awake mice, we were able for the first time to follow the activity of individual tangle-bearing neurons and compare it to the activity of tangle-free neurons over the disease course. Our results revealed strong reduction of calcium transient frequency in layer 2/3 cortical neurons of P301S mice, independent of neurofibrillary tangle presence. These results clearly point to the impairing role of soluble, mutated tau protein species present in the majority of the neurons investigated in this study.
Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT).

OBJECTIVE The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with open distal gastrectomy (ODG). SUMMARY BACKGROUND DATA Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. METHODS Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups. RESULTS A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients' reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days' mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682). CONCLUSIONS Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.
NBS1 promotes the endonuclease activity of the MRE11‐RAD50 complex by sensing CtIP phosphorylation

DNA end resection initiates DNA double‐strand break repair by homologous recombination. MRE11‐RAD50‐NBS1 and phosphorylated CtIP perform the first resection step via MRE11‐catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its homologue Xrs2 in Saccharomyces cerevisiae, is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in higher eukaryotes. Using a reconstituted system, we show here that NBS1, through its FHA and BRCT domains, functions as a sensor of CtIP phosphorylation. NBS1 then activates the MRE11‐RAD50 nuclease through direct physical interactions with MRE11. In the absence of NBS1, MRE11‐RAD50 exhibits a weaker nuclease activity, which requires CtIP but not strictly its phosphorylation. This identifies at least two mechanisms by which CtIP augments MRE11: a phosphorylation‐dependent mode through NBS1 and a phosphorylation‐independent mode without NBS1. In support, we show that limited DNA end resection occurs in vivo in the absence of the FHA and BRCT domains of NBS1. Collectively, our data suggest that NBS1 restricts the MRE11‐RAD50 nuclease to S‐G2 phase when CtIP is extensively phosphorylated. This defines mechanisms that regulate the MRE11 nuclease in DNA metabolism.
Multispectral analysis tools can increase utility of RGB color images in histology

Multispectral imaging (MSI) is increasingly finding application in the study and characterization of biological specimens. However, the methods typically used come with challenges on both the acquisition and the analysis front. MSI can be slow and photon-inefficient, leading to long imaging times and possible phototoxicity and photobleaching. The resulting datasets can be large and complex, prompting the development of a number of mathematical approaches for segmentation and signal unmixing. We show that under certain circumstances, just three spectral channels provided by standard color cameras, coupled with multispectral analysis tools, including a more recent spectral phasor approach, can efficiently provide useful insights. These findings are supported with a mathematical model relating spectral bandwidth and spectral channel number to achievable spectral accuracy. The utility of 3-band RGB and MSI analysis tools are demonstrated on images acquired using brightfield and fluorescence techniques, as well as a novel microscopy approach employing UV-surface excitation. Supervised linear unmixing, automated non-negative matrix factorization and phasor analysis tools all provide useful results, with phasors generating particularly helpful spectral display plots for sample exploration.
Histological and Cytological Characterization of Anther and Appendage Development in Asian Lotus (Nelumbo nucifera Gaertn.)

The lotus (Nelumbo Adans.) is a perennial aquatic plant with important value in horticulture, medicine, food, religion, and culture. It is rich in germplasm and more than 2000 cultivars have been cultivated through hybridization and natural selection. Microsporogenesis and male gametogenesis in the anther are important for hybridization in flowering plants. However, little is known about the cytological events, especially related to the stamen, during the reproduction of the lotus. To better understand the mechanism controlling the male reproductive development of the lotus, we investigated the flower structure of the Asian lotus (N. nucifera). The cytological analysis of anther morphogenesis showed both the common and specialized cytological events as well as the formation of mature pollen grains via meiosis and mitosis during lotus anther development. Intriguingly, an anatomical difference in anther appendage structures was observed between the Asian lotus and the American lotus (N. lutea). To facilitate future study on lotus male reproduction, we categorized pollen development into 11 stages according to the characterized cytological events. This discovery expands our knowledge on the pollen and appendage development of the lotus as well as improving the understanding of the species differentiation of N. nucifera and N. lutea.
Older Immigrants’ Access to Primary Health Care in Canada: A Scoping Review

RÉSUMÉ Le vieillissement et l’immigration ont significativement transformé la composition démographique au Canada, et les immigrants y représentent une proportion croissante de la population adulte plus âgée. L’accès adéquat aux services de santé est essentiel au bien-être et à l’inclusion sociale de cette population. Cet examen de la portée porte sur les connaissances actuelles concernant l’accès des immigrants d’âge avancé aux médecins omnipraticiens et à leur consultation, considérant que ces médecins jouent un rôle central dans la prestation de soins de première ligne, dans les soins préventifs et les soins de santé mentale. Le modèle en 5 étapes d’Arksey et O’Malley a été utilisé pour effectuer des recherches dans une grande variété de bases de données pour des articles publiés en anglais dans des revues avec comité de pairs concernant ce sujet dans le contexte canadien. Un total de 31 articles répondant aux critères d’inclusion ont été examinés en détail. Ces articles ont été classés en fonction de l’information disponible sur leurs auteurs, la population à l’étude, la méthodologie, le domaine de la santé et les obstacles mentionnés. Trois thèmes principaux ont émergé de cet examen de portée : l’accès et l’utilisation des soins de première ligne, la promotion de la santé et le dépistage du cancer, ainsi que l’utilisation des services de santé mentale. Les immigrants d’âge avancé font face à des obstacles en termes d’accès aux soins et ceux-ci seraient liés à la littératie en santé, à la langue, à la culture, aux croyances en matière de santé, aux inégalités spatiales et à des circonstances structurelles. L’examen de la portée présente de manière détaillée l’accès aux soins des personnes âgées immigrantes au Canada, et permet de dériver des implications sur les politiques qui permettraient de répondre à leurs besoins qui sont non comblés dans le domaine de la santé. ABSTRACT Aging and immigration have significantly shaped the population composition in Canada, where immigrants make up increasingly large proportions of the older adult population. This scoping review examines the existing knowledge surrounding older immigrants’ access to, and utilization of, primary care physicians, who play a pivotal role in the delivery of primary care, preventive care, and mental health care. We applied Arksey and O’Malley’s five-stage framework to search databases for Canadian-based, peer-reviewed English-language articles on the topic and examined 31 articles in detail. Three focus areas emerged: access and utilization of primary care, health promotion and cancer screening, and utilization of mental health services. Older immigrants face intertwining access barriers related to health literacy, language, culture, health beliefs, spatial inequality, and structural circumstances. The review provides a thorough understanding of the status of access to care among older immigrants in Canada, and yields policy implications to address their unmet health needs.
Antimicrobial Efficacy of the Silver Wound Dressing Biatain Ag in a Disc Carrier Test Simulating Wound Secretion

Aim: The efficacy of antimicrobial compounds included in wound dressings has been determined using the quantitative suspension test according to EN 13727 before. However, as suspension tests are not an accurate reflection of the conditions under which wound antiseptics are used, it was investigated if a disc carrier test would yield results simulating practical conditions on wound surfaces. A silver-leaching foam wound dressing was used for evaluation of the disc carrier test method. Method: The disc carriers consisted of circular stainless-steel discs measuring 2 cm in diameter and 1.5 mm in thickness, complying with the requirements of EN 10088-2. Carriers were contaminated with Staphylococcus aureus, methicillin-resistant S. aureus or Pseudomonas aeruginosa, respectively, together with an artificial wound secretion and left to dry at room temperature for 30 min. The wound dressings being tested were placed on the discs for the length of the exposure time, and after neutralization by thioglycolate in phosphate-buffered saline the number of surviving test organisms was then counted. The logarithmic reduction factor was calculated from the difference between the initial inoculum and the number of recovered test organisms. Results: The disc carrier test allowed determination of an antimicrobial efficacy in a realistic setting. It also imposed more stringent requirements on efficacy over time than the quantitative suspension test. The silver foam wound dressing showed a time-dependent antimicrobial efficacy. After 24-hour application time, the reduction factors against S. aureus, P. aeruginosa and the methicillin-resistant S. aureus were 1.9 ± 0.15, 2.1 ± 0.14 and 3.1 ± 0.18, respectively. Conclusion: The disc carrier test was a useful method for testing the antimicrobial efficacy of a foam silver dressing. The antimicrobial dressing exhibited an antimicrobial effect after 3 h and achieved a reduction >2 log against the tested bacterial strains in the presence of a simulated wound secretion after 24 h.
Surgeon Energy Expenditure and Substrate Utilization During Simulated Spine Surgery.

INTRODUCTION Orthopaedic surgery can be a physically demanding occupation with high rates of fatigue and burnout. Fatigue has been shown to affect surgeon performance with higher rates of errors in fatigued surgeons. The metabolic cost of performing surgery has yet to be quantified. A better understanding of these costs may provide insights into surgeon fatigue and its effect on patient safety. METHODS Eight subjects performed a one-level lumbar laminectomy and fusion on cadavers. Oxygen consumption (VO2) was measured via indirect calorimetry and used to calculate energy expenditure (EE). Substrate utilization was estimated from measurements of inspired and expired gases (ie, O2 and CO2, respectively). EE was also measured with the use of triaxial accelerometers. RESULTS The peak VO2 was 11.3 ± 0.4 mL/kg/min. The EEtotal was 132 ± 6 kcal corresponding to the EEtotal/hr of 142 ± 7 kcal/hr. Upper arm accelerometers (154.8 ± 9.8 kcal; r = 0.54) accurately estimated total EE. Subjects used, on average, 53% ± 4% CHO versus 47% ± 7% fat, with peak utilization of 65% ± 5% CHO versus 35% ± 15% fat. DISCUSSION Simulated orthopaedic spine surgery elicited modest but significant increases in EE over resting. Surgeons used a higher percentage of carbohydrate than would be expected for the intensity of the activity.
The physiological response of marine diatoms to ocean acidification: differential roles of seawater pCO2 and pH

Although increasing the pCO2 for diatoms will presumably down‐regulate the CO2‐concentrating mechanism (CCM) to save energy for growth, different species have been reported to respond differently to ocean acidification (OA). To better understand their growth responses to OA, we acclimated the diatoms Thalassiosira pseudonana, Phaeodactylum tricornutum, and Chaetoceros muelleri to ambient (pCO2 400 μatm, pH 8.1), carbonated (pCO2 800 μatm, pH 8.1), acidified (pCO2 400 μatm, pH 7.8), and OA (pCO2 800 μatm, pH 7.8) conditions and investigated how seawater pCO2 and pH affect their CCMs, photosynthesis, and respiration both individually and jointly. In all three diatoms, carbonation down‐regulated the CCMs, while acidification increased both the photosynthetic carbon fixation rate and the fraction of CO2 as the inorganic carbon source. The positive OA effect on photosynthetic carbon fixation was more pronounced in C. muelleri, which had a relatively lower photosynthetic affinity for CO2, than in either T. pseudonana or P. tricornutum. In response to OA, T. pseudonana increased respiration for active disposal of H+ to maintain its intracellular pH, whereas P. tricornutum and C. muelleri retained their respiration rate but lowered the intracellular pH to maintain the cross‐membrane electrochemical gradient for H+ efflux. As the net result of changes in photosynthesis and respiration, growth enhancement to OA of the three diatoms followed the order of C. muelleri > P. tricornutum > T. pseudonana. This study demonstrates that elucidating the separate and joint impacts of increased pCO2 and decreased pH aids the mechanistic understanding of OA effects on diatoms in the future, acidified oceans.
Functional characterization of ultraspiracle in Leptinotarsa decemlineata using RNA interference assay

A heterodimer of ultraspiracle (USP) and ecdysone receptor (EcR) mediates 20‐hydroxyecdysone (20E) signalling cascade to regulate insect moulting and metamorphosis. However, at least two questions remain to be addressed in terms of the molecular importance of USP in insect species. First, is USP involved in both regulation of ecdysteroidogenesis and mediation of 20E signalling in non‐drosophilid insects, as in Drosophila melanogaster? Second, does USP play any role in larval metamorphosis except as the partner of heterodimeric receptor to activate the downstream 20E signalling genes? In this paper, we found that RNA interference (RNAi) of LdUSP in the final (fourth) instar larvae reduced the messenger RNA levels of four ecdysteroidogenesis genes (Ldspo, Ldphm, Lddib and Ldsad) and 20E titre, and repressed the expression of five 20E signal genes (EcRA, HR3, HR4, E74 and E75) in Leptinotarsa decemlineata. The LdUSP RNAi larvae remained as prepupae, with developing antennae, legs and discs of forewings and hindwings. Dietary supplement with 20E restored the expression of the five 20E signal genes, but only partially alleviated the decreased pupation rate in LdUSP RNAi beetles. Knockdown of LdUSP at the penultimate (third) instar larvae did not affect third–fourth instar moulting. However, silencing LdUSP caused similar but less severe impairments on pupation. Accordingly, we propose that USP is undoubtedly necessary for ecdysteroidogenesis, for mediation of 20E signalling and for initiation of metamorphosis in L. decemlineata.
Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.
A Simplified Approach to Reducing Cardiovascular Risk.

CLINICAL ISSUE Cardiovascular disease remains the number one cause of morbidity and mortality in the United States despite major advances in our understanding of its pathogenesis and prevention. One reason for this continued epidemic is the poor adherence to treatment guidelines by caregivers and the lack of understanding by patients relative to its reversibility with treatment. Current guidelines are complex and often contradictory as there are at least 21 organizations publishing guidelines. PURPOSE This article proposes a simplified approach that is based on the LDL hypothesis stating: the lower the LDL cholesterol, the less the cardiovascular disease. This goal focuses on obtaining a plasma LDL cholesterol of less than 50 mg/dl. METHODS A positive coronary artery calcium scan in conjunction with an intermediate online cardiovascular risk score will identify individuals with significant CVD risk. With lifestyle improvements (including a low cholesterol diet) and low dose hypolipemic generic oral medications, this LDLc concentration is readily achievable in the majority of asymptomatic patients at risk for atherosclerosis. CONCLUSION Controlling the cardiovascular epidemic will require participation of both the patient and the physician caregiver. By simplifying the therapeutic regimen, patient compliance will increase and a significant reduction in cardiovascular morbidity and mortality will follow.
Posttranslational regulation of PGC‐1α and its implication in cancer metabolism

Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator‐activated receptor γ coactivator 1a (PGC‐1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC‐1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC‐1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC‐1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC‐1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC‐1α modulators. A better understanding of the elegant function of PGC‐1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC‐1α signaling.