Miracle-dz/UniFAR-FTUs huggingface dataset:
Unconventional mechanisms control cyclic respiratory gas release in flying Drosophila

SUMMARY The high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight, instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency (0.37±0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping, but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.
Listeria monocytogenesl‐forms respond to cell wall deficiency by modifying gene expression and the mode of division

Cell wall‐deficient bacteria referred to as l‐forms have lost the ability to maintain or build a rigid peptidoglycan envelope. We have generated stable, non‐reverting l‐form variants of the Gram‐positive pathogen Listeria monocytogenes, and studied the cellular and molecular changes associated with this transition. Stable l‐form cells can occur as small protoplast‐like vesicles and as multinucleated, large bodies. They have lost the thick, multilayered murein sacculus and are surrounded by a cytoplasmic membrane only, although peptidoglycan precursors are still produced. While they lack murein‐associated molecules including Internalin A, membrane‐anchored proteins such as Internalin B are retained. Surprisingly, l‐forms were found to be able to divide and propagate indefinitely without a wall. Time‐lapse microscopy of fluorescently labelled l‐forms indicated a switch to a novel form of cell division, where genome‐containing membrane vesicles are first formed within enlarged l‐forms, and subsequently released by collapse of the mother cell. Array‐based transcriptomics of parent and l‐form cells revealed manifold differences in expression of genes associated with morphological and physiological functions. The l‐forms feature downregulated metabolic functions correlating with the dramatic shift in surface to volume ratio, whereas upregulation of stress genes reflects the difficulties in adapting to this unusual, cell wall‐deficient lifestyle.
Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

Background Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). Patients and methods The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes.
Ginsenoside Rb3 exerts antidepressant-like effects in several animal models

Total ginsenosides have been shown to have therapeutic actions as antidepressants. We report a major active ingredient of total ginsenosides, the ginsenoside Rb3 (Rb3), which may have antidepressant-like effects. Using the forced swim test, tail suspension test, and learned helplessness procedure, we found that Rb3 had significant anti-immobility effects in mice in the forced swim and tail suspension tests and reduced the number of escape failures in the learned helplessness procedure. In a reserpine-induced syndrome model, Rb3 attenuated hypothermia, palpebral ptosis, and akinesia. In the chronic mild stress model, chronic Rb3 administration reversed the decrease in locomotor activity, novelty-suppressed feeding, and sucrose preference. Furthermore, neurochemical tests were performed to support our hypothesis that biochemical variations (i.e. brain-derived neurotrophic factor and the monoamine neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine) are involved in Rb3’s antidepressant-like effects. Finally, we found, using whole-cell patch-clamp recordings, that the action potential transmission in neurons within the somatosensory cortex was excited by Rb3 perfusion and blocked with Panax notoginseng total saponins extracted from leaves. This study provides evidence for the mechanism of action of the antidepressant-like effects of Rb3.
Inhibitor of DNA Binding 4 Is Expressed Selectively by Single Spermatogonia in the Male Germline and Regulates the Self-Renewal of Spermatogonial Stem Cells in Mice1

Continual spermatogenesis at a quantitatively normal level is required to sustain male fertility. The foundation of this process relies on maintenance of an undifferentiated spermatogonial population consisting of spermatogonial stem cells (SSCs) that self-renew as well as transient amplifying progenitors produced by differentiation. In mammals, type Asingle spermatogonia form the SSC population, but molecular markers distinguishing these from differentiating progenitors are undefined and knowledge of mechanisms regulating their functions is limited. We show that in the mouse male germline the transcriptional repressor ID4 is expressed by a subpopulation of undifferentiated spermatogonia and selectively marks Asingle spermatogonia. In addition, we found that ID4 expression is up-regulated in isolated SSC-enriched fractions by stimulation from GDNF, a key growth factor driving self-renewal. In mice lacking ID4 expression, quantitatively normal spermatogenesis was found to be impaired due to progressive loss of the undifferentiated spermatogonial population during adulthood. Moreover, reduction of ID4 expression by small interfering RNA treatment abolished the ability of wild-type SSCs to expand in vitro during long-term culture without affecting their survival. Collectively, these results indicate that ID4 is a distinguishing marker of SSCs in the mammalian germline and plays an important role in the regulation of self-renewal.
Banking sleep: realization of benefits during subsequent sleep restriction and recovery.

OBJECTIVE Determine whether sleep extension (a) improves alertness and performance during subsequent sleep restriction and (b) impacts the rate at which alertness and performance are restored by post-restriction recovery sleep. DESIGN Participants were randomly assigned to an Extended (10 h time in bed [TIB]) or Habitual TIB [mean (SD) hours = 7.09 (0.7)] sleep group for one week, followed by 1 Baseline (10 hours or habitual TIB), 7 Sleep Restriction (3 h TIB), and 5 Recovery Sleep nights (8 h TIB). Performance and alertness tests were administered hourly between 08:00-18:00 during all in-laboratory phases of the study. SETTING Residential sleep/performance testing facility. PARTICIPANTS Twenty-four healthy adults (ages 18-39) participated in the study. INTERVENTIONS Extended vs. habitual sleep durations prior to sleep restriction. RESULTS Psychomotor vigilance task (PVT) lapses were more frequent and modified maintenance of wakefulness (MWT) sleep latency was shorter in the Habitual group than in the Extended group across the sleep restriction phase. During the Recovery phase, PVT speed rebounded faster (and PVT lapsing recovered significantly after the first night of recovery sleep) in the Extended group. No group differences in subjective sleepiness were evident during any phase of the study. CONCLUSION The extent to which sleep restriction impairs objectively measured alertness and performance, and the rate at which these impairments are subsequently reversed by recovery sleep, varies as a function of the amount of nightly sleep obtained prior to the sleep restriction period. This suggests that the physiological mechanism(s) underlying chronic sleep debt undergo long-term (days/weeks) accommodative/adaptive changes.
Identification by Primary Care Clinicians of Patients with Obstructive Sleep Apnea: A practice-based research network (PBRN) study

Background: Obstructive sleep apnea (OSA) is a reasonably common disorder that is associated with daytime tiredness and a host of medical conditions. Little is known about how primary care clinicians (PCCs) detect, diagnose, and manage patients who have OSA. Methods: We gathered information from 44 randomly selected practices in 5 regional practice-based research networks. This included interviews with PCCs and sleep consultants, medical records abstraction, and patient surveys. Descriptive analyses of the quantitative data were used to describe the prevalence of sleep symptoms, the proportion of primary care patients at high risk for OSA, and the methods used by PCCs to detect and diagnose patients with OSA. Results: More than 90% of adult patients visiting a PCC on any given day are experiencing sleep-related symptoms. Based on their Berlin Questionnaire scores, more than one third are at high risk of having sleep apnea. However, most patients have not discussed their sleep-related symptoms with their PCC, and fewer than one third have sleep-related symptoms documented in their medical records. Very few PCCs routinely screen for OSA, and, despite using billing records, problem lists, clinician and staff recall, and prospective logs enhanced by waiting room posters, PCCs were generally unable to identify 25 patients with OSA in their practices. Conclusions: A substantial proportion of patients who see PCCs regularly are at high risk for OSA. Very few of them are being diagnosed or treated. Clearer guidelines and a systematic approach are needed if this is indeed a problem that should be addressed.
Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

Abstract Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99mTc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.
Participation in a social and recreational day programme increases community integration and reduces family burden of persons with acquired brain injury

Abstract Primary objective: To describe and evaluate a new day programme for persons living with an acquired brain injury (ABI), including persons exhibiting challenging behaviours. Activities were designed to reduce participants’ social isolation, increase participation in community activities and increase social and leisure skills. It was expected that community integration would increase and challenging behaviours and family burden would decrease for day programme participants. Methods and procedures: Pre–post convenience sample design. Sixty-one participants and family members completed questionnaires before starting the day programme and after 6-month participation. Measures: Community Integration Questionnaire, Overt Behaviour Scale, Burden Assessment Scale, Goal Attainment Scaling. Results: Participants had increased community integration (p = 0.000) and decreased family burden (p = 0.006). There was a trend to decreased severity of challenging behaviour. Participants and family members were very satisfied. Results suggest that the programme was effective in reducing participants’ social isolation and increasing appropriate interpersonal behaviours. Conclusions: Participation increased community integration and reduced burden on family caregivers. ABI day programmes help fill the void left after other rehabilitation services end and provide survivors with opportunities to engage in a variety of activities. Persons living with ABI have need for ongoing social, recreational and life skill coaching services after formal rehabilitation has been completed.
Olfactory hallucinations in primary headache disorders: Case series and literature review

Background: Olfactory hallucinations (phantosmias) have rarely been reported in migraine patients. Unlike visual, sensory, language, brainstem, and motor symptoms, they are not recognized as a form of aura by the International Classification of Headache Disorders. Methods: We examined the clinical features of 39 patients (14 new cases and 25 from the literature) with olfactory hallucinations in conjunction with their primary headache disorders. Results: In a 30-month period, the prevalence of phantosmias among all patients seen at our headache center was 0.66%. Phantosmias occurred most commonly in women with migraine, although they were also seen in several patients with other primary headache diagnoses. The typical hallucination lasted 5–60 minutes, occurred shortly before or simultaneous with the onset of head pain, and was of a highly specific and unpleasant odor, most commonly a burning smell. In the majority of patients, phantosmias diminished or disappeared with initiation of prophylactic therapy for headaches. Conclusions: We propose that olfactory hallucinations are probably an uncommon but distinctive form of migraine aura, based on their semiology, timing and response to headache prophylaxis.
Transcription Factor Egr-1 Regulates Glomerular Mesangial Cell Proliferation*

Increase of glomerular mesangial cells (MCs) is a prominent histopathological finding in many types of glomerulonephritis. We have shown previously that expression of the zinc-finger transcription factor, early growth response gene-1 (egr-1), is closely correlated with the proliferation of cultured MCs. To elucidate whether Egr-1 is required for MC proliferation, we inhibited serum-induced Egr-1 expression by phosphothioate-modified antisense oligonucleotides (ODNs). Uptake of antisense ODNs into MCs was demonstrated, and five different egr-1 antisense ODNs were tested for their impact on serum-induced egr-1 mRNA and protein levels and on MC growth. The most potent egr-1 antisense ODN inhibited serum-induced egr-1 mRNA by 68%, protein induction by 58%, and MC replication as measured by [3H]thymidine uptake and cell counts by 78 and 46%, respectively. The effects of antisense ODNs on MC growth correlated closely with their ability to inhibit Egr-1 protein. ODNs acted in a dose-dependent manner, the minimal effective concentration being 1 μM. Control ODNs had no significant effects. In addition, antisense ODNs against egr-1 potently inhibited endothelin-1-induced Egr-1 expression and MC growth. Heparin, a known inhibitor of MC growth, suppressed serum-induced [3H]thymidine uptake by 39% and egr-1 mRNA expression by 44%. We conclude that Egr-1 is an essential part of the mitogenic signal transduction cascade in cultured MCs.
Hyperactivated NF-κB and AP-1 Transcription Factors Promote Highly Accessible Chromatin and Constitutive Transcription across the Interleukin-6 Gene Promoter in Metastatic Breast Cancer Cells

ABSTRACT Interleukin-6 (IL-6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes the response to hormones and to chemotherapeutics. We explored transcription mechanisms involved in differential IL-6 gene expression in breast cancer cells with different metastatic properties. In weakly metastatic MCF7 cells, histone H3 K9 methylation, HP1 binding, and weak recruitment of AP-1 Fra-1/c-Jun, NF-κB p65 transcription factors, and coactivators is indicative of low chromatin accessibility and gene transcription at the IL-6 gene promoter. In highly metastatic MDA-MB231 cells, strong DNase, MNase, and restriction enzyme accessibility, as well potent constitutive transcription of the IL-6 gene promoter, coincide with increased H3 S10 K14 phosphoacetylation and promoter enrichment of AP-1 Fra-1/c-Jun and NF-κB p65 transcription factors and MSK1, CBP/p300, Brg1, and Ezh2 cofactors. Complementation, silencing, and kinase inhibitor experiments further demonstrate involvement of AP-1 Fra-1/c-Jun and NF-κB p65/RelB members, but not of the alpha estrogen receptor in promoting chromatin accessibility and transcription across the IL-6 gene promoter in metastatic breast cancer cells. Finally, the natural withanolide Withaferin A was found to repress IL-6 gene transcription in metastatic breast cancer cells upon dual inhibition of NF-κB and AP-1 Fra-1 transcription factors and silencing of IL-6 promoter chromatin accessibility.
Optimising care of acute coronary syndromes in three Australian hospitals.

OBJECTIVE To improve quality of in-hospital care of patients with acute coronary syndromes using a multifaceted quality improvement program. DESIGN Prospective, before and after study of the effects of quality improvement interventions between October 2000 and August 2002. Quality of care of patients admitted between 1 October 2000 and 16 April 2001 (baseline) was compared with that of those admitted between 15 February 2002 and 31 August 2002 (post-intervention). SETTING Three teaching hospitals in Brisbane, Australia. STUDY PARTICIPANTS Consecutive patients (n = 1594) admitted to hospital with acute coronary syndrome [mean age 68 years (SD 14 years); 65% males]. INTERVENTIONS Clinical guidelines, reminder tools, and educational interventions; 6-monthly performance feedback; pharmacist-mediated patient education program; and facilitation of multidisciplinary review of work practices. MAIN OUTCOME MEASURES Changes in key quality indicators relating to timing of electrocardiogram (ECG) and thrombolysis in emergency departments, serum lipid measurement, prescription of adjunctive drugs, and secondary prevention. RESULTS Comparing post-intervention with baseline patients, increases occurred in the proportions of eligible patients: (i) undergoing timely ECG (70% versus 61%; P = 0.04); (ii) prescribed angiotensin-converting enzyme inhibitors (70% versus 60%; P = 0.002) and lipid-lowering agents (77% versus 68%; P = 0.005); (iii) receiving cardiac counselling in hospital (57% versus 48%; P = 0.009); and (iv) referred to cardiac rehabilitation (17% versus 8%; P < 0.001). CONCLUSIONS Multifaceted approaches can improve care processes for patients hospitalized with acute coronary syndromes. Care processes under direct clinician control changed more quickly than those reliant on complex system factors. Identifying and overcoming organizational impediments to quality improvement deserves greater attention.
Reversing the Translation Flow: Moving Organizational Practices from Japan to the U.S

Building on the neo‐institutional organizational translation approach and on interlingual translation studies, we undertake an historical case study of the movement of Japanese organizational practices to the USA from the 1970s through the mid‐1990s. Both American and Japanese translators struggled to bring Japanese management models into the USA, reversing the dominant translation flow and bridging wide differences between the sending and receiving contexts. We use the translation ecology approach to look at the interactions over time between translators, translations, and translation processes studied separately in much translation research. Our paper makes two contributions to research on organizational translation. First, it develops more precise and theoretically‐based categorizations of the elements of translation ecology – translators, translations, and translation processes. Second, it challenges the generalizability of the decontextualization/disembedding and recontextualization/re‐embedding processes that are widely accepted as a necessary process in moving management models and practices across contexts.
Virtual pattern classification of upper limbs motion using artificial neural networks

Virtual reality technology is common used to entertain people as movies or games. At present, this technology applies to medical field for training surgeon on operating simulation or patients with either neurological disease or psychiatric disorder. The study focused on the algorithm of pattern classification. The artificial neural network was considered to achieve this classification. The multilayer perceptron with four input nodes, thirty nodes in hidden layer and five output nodes were designed for this classification algorithm. The virtual reality showed the animator who acted as the trainer. The movement of trainer was used to be the supervised data of the neural network. The users moved their arms along with the animator and recorded the motion. These data were the testing data set of network. The results showed that the neural network could classify all motion patterns. It was difficult to classify the patterns in the same side Pattern 5 was correctly classified by this neural network model.