Miracle-dz/UniFAR-FTUs huggingface dataset:
Catalogue of bias: publication bias

Dickersin and Min define publication bias as the failure to publish the results of a study ‘on the basis of the direction or strength of the study findings’. 1 This non-publication introduces a bias which impacts the ability to accurately synthesise and describe the evidence in a given area.2 Publication bias is a type of reporting bias and closely related to dissemination bias, although dissemination bias generally applies to all forms of results dissemination, not simply journal publications. A variety of distinct biases are often grouped into the overall definition of publication bias.3 4 There are a number of risk factors and causes for publication bias identified in the literature.5 Research has shown causes of publication bias ranging from trialist motivation, past experience, and competing commitments; perceived or real lack of interest in results from editors, reviewers, or other colleagues; or conflicts of interest that would lead to the suppression of results not aligned with a specific agenda.3 6–9 The role of journal editors is particularly complex as the gatekeepers to publication. Significant results are more widely cited in medicine aligning the incentives of both investigators and editors towards these studies.10 A review by Song and colleagues reports studies showing that strength and …
Listeria monocytogenes virulence factors, including listeriolysin O, are secreted in biologically active extracellular vesicles

Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secrete extracellular vesicles (EVs) was not pursued until recently due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following their discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteria are implicated in virulence, toxin release, and transference to host cells, eliciting immune responses, and spread of antibiotic resistance. Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis. Here we report that L. monocytogenes produces EVs with diameters ranging from 20 to 200 nm, containing the pore-forming toxin listeriolysin O (LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Cell-free EV preparations were toxic to mammalian cells, the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion of plcA increased EV toxicity, suggesting PI-PLC reduced LLO activity. Using simultaneous metabolite, protein, and lipid extraction (MPLEx) multiomics we characterized protein, lipid, and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Using immunogold EM we detected LLO at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released from L. monocytogenes during infection. Our findings demonstrate that L. monocytogenes uses EVs for toxin release and implicate these structures in mammalian cytotoxicity.
Effect of amantadine on vegetative state after traumatic brain injury: a functional magnetic resonance imaging study

Objective We assessed the use of functional magnetic resonance imaging (fMRI) to observe residual brain function and responsiveness to amantadine in a patient in a vegetative state (VS) following traumatic brain injury. Method We observed cerebral cortex activation in a 52-year-old man in a VS, and in a healthy individual using fMRI during passive listening and motor-imagery tasks. The patient received oral amantadine for 3 months. fMRI was repeated after treatment. Results Activation around the left insular regions occurred during stimulation by a familiar voice, and activity in the left temporal and bi-occipital cortices occurred during stimulation by a familiar/unfamiliar voice. Activity in the bilateral frontal and parietal cortices occurred during the motor-imagination task. Brain cortex activation was reduced in the VS patient compared with the healthy volunteer. However, the patient responded to certain auditory stimuli and motor imagery, suggesting that he retained some intact auditory and motor cortical functions. fMRI scans after 3 months of treatment showed increased activation of brain areas corresponding to task instructions. Conclusion fMRI could be used to observe the effects of amantadine on brain function, and to aid the diagnosis and prognostic prediction in VS patients in terms of recovery and rehabilitation planning.
What does the ecological and epidemiological evidence indicate about the potential for cannabinoids to reduce opioid use and harms? A comprehensive review

Abstract Pre-clinical research supports that cannabinoids reduce opioid dose requirements, but few studies have tested this in humans. This review evaluates ecological and epidemiological studies that have been cited as evidence that medical cannabis use may reduce opioid use and opioid-related harms. Medline and Embase were searched for relevant articles. Data were extracted on study setting, analyses approach, covariates, and outcomes. Eleven ecological and 14 epidemiological studies were found. In ecological studies, states that allow medical cannabis laws have reported a slower rate of increase in opioid overdose deaths compared with states without such laws. These differences have increased over time and persisted after controlling for state sociodemographic characteristics and use of prescription monitoring programmes. Few studies have controlled for other potential confounders such as opioid dependence treatment and imprisonment rates. Some epidemiological studies provide evidence that cannabis availability may reduce opioid use, but are limited by selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects of cannabis. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and harms, although important methodological weaknesses were identified. Well-designed clinical studies may provide more conclusive evidence on whether cannabinoids can reduce opioid use and related harm.
The effect of thyroid functions on osteopenia of prematurity in preterm infants

Abstract Background It is known that thyroid hormones have effects on bone development. In particular, the effect of thyroid hormones on osteopenia of prematurity (OOP) has not been examined in preterm infants. Our study aimed to examine the relationship between OOP and congenital hypothyroidism (CH) in preterm infants. Methods Very low birth weight infants (VLBW, <1500 g) were included in the study. Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were measured on postnatal day 5. Serum calcium, phosphorus and alkaline phosphatase (ALP) levels were studied as standard screening parameters for OOP at postnatal week 4. Patients with serum ALP level >700 IU/L were included in the OOP group. We intended to figure out the relationship between OOP and CH in infants. Results In our study, OOP frequency was 14.9% among 543 VLBW infants. There was no statistically significant difference between groups with and without CH (21.7% and 14.8%, respectively) in terms of OOP (p=0.632). Gestational age (GA) was significantly lower in infants with diagnosed OOP (p<0.001, p<0.001, respectively). In addition, the prevalence rates of mothers with preeclampsia, small for gestational age (SGA), respiratory support requirement, late-onset neonatal sepsis (LOS), bronchopulmonary dysplasia (BPD) and full enteral feeding time were found to be higher in the OOP group (p<0.05). Conclusions We found that thyroid hormones had no effect on OOP in preterm infants. Therefore, future randomized controlled studies as well as long-term outcome studies are warranted on this topic.
Localized disorganization of the cochlear inner hair cell synaptic region after noise exposure

ABSTRACT The prevalence and importance of hearing damage caused by noise levels not previously thought to cause permanent hearing impairment has become apparent in recent years. The damage to, and loss of, afferent terminals of auditory nerve fibres at the cochlear inner hair cell has been well established, but the effects of noise exposure and terminal loss on the inner hair cell are less known. Using three-dimensional structural studies in mice we have examined the consequences of afferent terminal damage on inner hair cell morphology and intracellular structure. We identified a structural phenotype in the pre-synaptic regions of these damaged hair cells that persists for four weeks after noise exposure, and demonstrates a specific dysregulation of the synaptic vesicle recycling pathway. We show evidence of a failure in regeneration of vesicles from small membrane cisterns in damaged terminals, resulting from a failure of separation of small vesicle buds from the larger cisternal membranes. Summary: Hearing deficits after noise exposure are linked to afferent terminal loss. We show that afferent terminal loss is concomitant with changes to inner hair cell pre-synaptic ultrastructure indicating vesicle-recycling deficits.
Beyond interferon side effects: What residual barriers exist to DAA hepatitis C treatment for people who inject drugs?

Recent advances in the efficacy and tolerability of hepatitis C treatments and the introduction of a universal access scheme for the new Direct Acting Antiviral (DAA) therapies in March 2016, has resulted in a rapid increase in the uptake of hepatitis C treatment in Australia. Despite these positive developments, recent data suggest a plateauing of treatment numbers, indicating that more work may need to be done to identify and address ongoing barriers to hepatitis C treatment access and uptake. This paper aims to contribute to our understanding of the ongoing barriers to DAA therapies, with a focus on people who inject drugs. The paper draws on participant interview data from a qualitative research study based on a participatory research design that included a peer researcher with direct experience of both hepatitis C DAA treatment and injecting drug use at all stages of the research process. The study’s findings show that residual barriers to DAA treatment exist at personal, provider and system levels and include poor venous access, DAA treatments not considered ‘core-business’ by opioid substitution treatment (OST) providers, and patients having to manage multiple health and social priorities that interfere with keeping medical appointments such as childcare and poor access to transport services. Further, efforts to increase access to and uptake of DAA hepatitis C treatment over time will require a focus on reducing stigma and discrimination towards people who inject drugs as this remains as a major barrier to care for many people.
Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia

Significance Adult T-cell leukemia (ATL) is caused by the human T-cell lymphotropic virus-1 (HTLV-1). Presently there is no curative therapy for ATL. In the leukemic cells, the HTLV-1–encoded protein Tax (transactivator from the X-gene region) activates disordered interleukin expression, which triggers JAK/STAT signaling. The HTLV-1–encoded protein Tax also induces the expression of the antiapoptotic protein Bcl-xL (B-cell lymphoma-extra large). In the present study, the combination of the JAK inhibitor ruxolitinib and the Bcl-2/Bcl-xL inhibitor navitoclax provided additive/synergistic antitumor efficacy in IL-2–dependent ATL cell lines and in a mouse model of human ATL as well as with ex vivo peripheral blood mononuclear cells (PBMCs) from ATL patients compared with either drug alone, supporting a therapeutic trial of this combination in patients with ATL. Adult T-cell leukemia (ATL) develops in individuals infected with human T-cell lymphotropic virus-1 (HTLV-1). Presently there is no curative therapy for ATL. HTLV-1–encoded protein Tax (transactivator from the X-gene region) up-regulates Bcl-xL (B-cell lymphoma-extra large) expression and activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems, resulting in amplified JAK/STAT signaling. Inhibition of JAK signaling reduces cytokine-dependent ex vivo proliferation of peripheral blood mononuclear cells (PBMCs) from ATL patients in smoldering/chronic stages. Currently, two JAK inhibitors are approved for human use. In this study, we examined activity of multiple JAK inhibitors in ATL cell lines. The selective JAK inhibitor ruxolitinib was examined in a high-throughput matrix screen combined with >450 potential therapeutic agents, and Bcl-2/Bcl-xL inhibitor navitoclax was identified as a strong candidate for multicomponent therapy. The combination was noted to strongly activate BAX (Bcl-2-associated X protein), effect mitochondrial depolarization, and increase caspase 3/7 activities that lead to cleavage of PARP (poly ADP ribose polymerase) and Mcl-1 (myeloid cell leukemia 1). Ruxolitinib and navitoclax independently demonstrated modest antitumor efficacy, whereas the combination dramatically lowered tumor burden and prolonged survival in an ATL murine model. This combination strongly blocked ex vivo proliferation of five ATL patients’ PBMCs. These studies provide support for a therapeutic trial in patients with smoldering/chronic ATL using a drug combination that inhibits JAK signaling and antiapoptotic protein Bcl-xL.
The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.
Quantitative Behavioral Analysis of First Successful Captive Breeding of Endangered Ozark Hellbenders

Understanding behaviors associated with reproductive events is vital to management of captive breeding programs for threatened and endangered species. The Ozark hellbender (Cryptobranchus alleganiensis bishopi) is a federally endangered aquatic salamander with only one successful captive breeding program (the Saint Louis Zoo’s Ron Goellner Center for Hellbender Conservation). Although anecdotal observations have been reported for hellbender reproductive behavior from field observations, no quantitative assessments have been made. We quantified hellbender behavior from video-recordings of three successful breeding events at the Saint Louis Zoo that occurred in 2012, including aggressive, sexual, social, and locomotory behaviors. We used transition matrices to organize these data into kinematic diagrams that illustrated behavioral sequences for five time periods: pre-oviposition (2 nights), first oviposition night, inter-oviposition, second oviposition night, and post-oviposition. General activity and agonistic behaviors increased moderately through the first oviposition night, peaked during inter-oviposition, and declined abruptly following the second oviposition night. Agonistic behavior included bites, charges, chases, and flight. Female-female aggression was common. Surfacing (presumably for accessory air breathing) followed intense activity. Presumed courtship behaviors (tail swishing and circling) occurred at low rates. During oviposition, females remained in the nest box for 1—2+ hours. We encourage managers of captive breeding programs to use quantitative behavioral analyses to pin-point critical time periods and conditions for successful reproduction.
Driver’s Facial Expression Recognition in Real-Time for Safe Driving

In recent years, researchers of deep neural networks (DNNs)-based facial expression recognition (FER) have reported results showing that these approaches overcome the limitations of conventional machine learning-based FER approaches. However, as DNN-based FER approaches require an excessive amount of memory and incur high processing costs, their application in various fields is very limited and depends on the hardware specifications. In this paper, we propose a fast FER algorithm for monitoring a driver’s emotions that is capable of operating in low specification devices installed in vehicles. For this purpose, a hierarchical weighted random forest (WRF) classifier that is trained based on the similarity of sample data, in order to improve its accuracy, is employed. In the first step, facial landmarks are detected from input images and geometric features are extracted, considering the spatial position between landmarks. These feature vectors are then implemented in the proposed hierarchical WRF classifier to classify facial expressions. Our method was evaluated experimentally using three databases, extended Cohn-Kanade database (CK+), MMI and the Keimyung University Facial Expression of Drivers (KMU-FED) database, and its performance was compared with that of state-of-the-art methods. The results show that our proposed method yields a performance similar to that of deep learning FER methods as 92.6% for CK+ and 76.7% for MMI, with a significantly reduced processing cost approximately 3731 times less than that of the DNN method. These results confirm that the proposed method is optimized for real-time embedded applications having limited computing resources.
Opening toward life: Experiences of basic body awareness therapy in persons with major depression

Although there is a vast amount of research on different strategies to alleviate depression, knowledge of movement-based treatments focusing on body awareness is sparse. This study explores the experiences of basic body awareness therapy (BBAT) in 15 persons diagnosed with major depression who participated in the treatment in a randomized clinical trial. Hermeneutic phenomenological methodology inspired the approach to interviews and data analysis. The participants’ experiences were essentially grasped as a process of enhanced existential openness, opening toward life, exceeding the tangible corporeal dimension to also involve emotional, temporal, and relational aspects of life. Five constituents of this meaning were described: vitality springing forth, grounding oneself, recognizing patterns in one's body, being acknowledged and allowed to be oneself, and grasping the vagueness. The process of enhanced perceptual openness challenges the numbness experienced in depression, which can provide hope for change, but it is connected to hard work and can be emotionally difficult to bear. Inspired by a phenomenological framework, the results of this study illuminate novel clinical and theoretical insight into the meaning of BBAT as an adjunctive approach in the treatment of depression.
Leucine-rich repeat extensin proteins regulate plant salt tolerance in Arabidopsis

Significance Plants have evolved cell-wall integrity signaling pathways to maintain cell-wall homeostasis in response to stress conditions, but the components involved in the perception and transduction of cell-wall signals are largely unknown. Here we found that the Arabidopsis cell-wall–localized leucine-rich repeat extensins (LRX) 3/4/5 interact with RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23. Mature RALF22/23 peptides interact with the plasma membrane-localized FERONIA (FER) and induce FER internalization. The lrx345 and fer mutants and RALF22/23 overexpressing transgenic plants display similar phenotypes such as retarded growth and increased sensitivity to salt stress. Our work thus reveals that the LRX3/4/5 proteins function with RALF22/23 and FER to define a signaling pathway that is critical for regulating plant growth and salt tolerance. The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis. The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22/23. Salt stress promotes S1P protease-dependent release of mature RALF22 peptides. Treatment of roots with mature RALF22/23 peptides or salt stress causes the internalization of FER. Our results suggest that the LRXs, RALFs, and FER function as a module to transduce cell-wall signals to regulate plant growth and salt stress tolerance.