Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic Treatment in Patients with Chronic Low Back Pain and Vertebral Bone Edema (Modic Type I Changes): A Randomized Clinical Controlled Trial of Efficacy

* Medical City-Baghdad, Hospital of Specialized Surgeries. **Consultant Orthopedic Surgeon, Baghdad Medical School, Medical City-Baghdad, Hospital of Specialized Surgeries. ***Medical City-Baghdad, Hospital of Specialized Surgeries. specific LBP’’ (80%), is not satisfactory for the LBP patient or the clinician. Therefore, the identification and diagnosis of relevant subgroups of patients with persistent LBP, preferably with a sound patho-anatomical basis, is strongly needed (3) . In the majority of cases the backache is associated with degeneration of the intervertebral discs in the lower lumbar spine. Disc herniation is considered a complication of disc degeneration in the dysfunction and instability stages. Bone marrow changes as a result of vertebral end plate changes have been associated with degenerative intervertebral disk disease. These changes have been classified into three types on the basis of chronicity of the degeneration (Modic changes) (4) (fig.1). ABSTRACT: BACKGROUND: Modic type I changes/bone edema in the vertebrae are present in 6 % of the general population and 35–40 % of the low back pain population. It is strongly associated with low back pain. Chronic Low back pain (CLBP) is a leading cause of disability. It occurs in similar proportions in all cultures, interferes with quality of life and work performance, and is the most common reason for medical consultations.A new method of treatment included the use of antibiotic in management of CLBP with Modic type I changes has proved to be effective in some cases. OBJECTIVE: The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type I changes (bone edema). PATIENTS AND METHODS: The study was a randomized clinical trial(RCT) with 71 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type I changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment or placebo and were evaluated at baseline, and end of treatment. Outcome measures: are the disease-specific disability Questionnaire, which is Roland Morris Disability Questionnaire (RMDQ) and lumbar pain. RESULTS: 43 of the 71 original patients were evaluated at baseline and at end of treatment follow-up. The two groups were similar at baseline. The antibiotic group had better improvement on the outcome measures and improvement continued after end of treatment. At baseline, 100 days follow-up the means of the disease specific disability-RMDQ changed: antibiotic 15.5, 12; placebo: 15, 14.8. For Lumbar pain: antibiotics 6.4, 4.8; placebo 6.1, 6.0. CONCLUSION: The antibiotic protocol in this study was more effective for this group of patients (CLBP associated with Modic changes type I) than placebo in the outcomes.
Efficacy of Er:YAG laser-assisted direct pulp capping in permanent teeth with cariously exposed pulp: A pilot study.

Direct pulp capping is a minimally invasive method to preserve pulp integrity. We evaluated the treatment efficacy of Er:YAG laser irradiation combined with direct pulp capping for pulp exposure due to caries. A total of 21 patients with 22 teeth were enrolled in the conventional group (calcium hydroxide), and 24 patients with 25 teeth were enrolled in the laser-assisted group (Er:YAG laser irradiation at settings of 10 Hz, 50 mJ; combined with calcium hydroxide). The cumulative success rate of the conventional group and the laser-assisted group was 68.2% and 91.7% at 12 months, respectively. Results showed that the laser-assisted procedure increased the survival time (β = 0.04, OR = 0.07), while proximal-occlusal cavities in molars decreased the survival time (β = 0.03, OR = 12.5). Er:YAG lasers improve the effectiveness of conventional direct pulp capping (using Dycal) with limited side-effects and can be applied clinically.
Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease

Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer’s disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein–protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.
Tick-borne encephalitis virus NS4A ubiquitination antagonizes type I interferon-stimulated STAT1/2 signalling pathway

ABSTRACT Tick-borne encephalitis virus (TBEV) accounts for approximately 10,000 annual cases of severe encephalitis in Europe and Asia and causes encephalitis in humans. In this study, we demonstrate TBEV appears to activate the interferon (IFN)-β dependent on RIG-I/MDA5. Both the IFN-β accumulation and the IFN stimulated genes (ISGs) transcription greatly delay. Further studies reveal that TBEV NS4A could block the phosphorylation and dimerization of STAT1/STAT2 to affect type I and II IFN-mediated STAT signalling. Additional data indicate that the residue at K132 of TBEV NS4A could be modified by ubiquitination and this modification is necessary for the interaction of NS4A with STAT1. Dynamic ubiquitination of the NS4 protein during TBEV infection might account for delayed activation of the ISGs. These results define the TBEV NS4A as an antagonist of the IFN response, by demonstrating a correlation between the association and STAT interference. Our findings provide a foundation for further understanding how TBEV evade innate immunity and a potential viral target for intervention.
Epidemiology of multiple sclerosis in Central Europe, update from Hungary

Not so long ago, a novel phenotypic classification of multiple sclerosis (MS) and revisions to the McDonald diagnostic criteria were published. Good quality, standardized, and therefore comparable epidemiological data from the Central European region altogether are scarce, and data based on the aforementioned criteria are nonexistent; thus, an update is needed.
Pharmacological target-focused transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia.

Dorsal root ganglion (DRG) neurons detect sensory inputs and are crucial for pain processing. They are often studied in vitro as dissociated cell cultures with the assumption that this reasonably represents in vivo conditions. However, to our knowledge, no study has directly compared genome-wide transcriptomes of DRG tissue in vivo versus in vitro, or between laboratories and culturing protocols. Comparing RNA sequencing-based transcriptomes of native to cultured (4 days in vitro) human or mouse DRG, we found that the overall expression levels of many ion channels and GPCRs specifically expressed in neurons are markedly lower although still expressed in culture. This suggests that most pharmacological targets expressed in vivo are present under the condition of dissociated cell culture, but with changes in expression levels. The reduced relative expression for neuronal genes in human DRG cultures is likely accounted for by increased expression of genes in fibroblast-like and other proliferating cells, consistent with their mitotic status in these cultures. We found that the expression of a subset of genes typically expressed in neurons increased in human and mouse DRG cultures relative to the intact ganglion, including genes associated with nerve injury or inflammation in preclinical models such as BDNF, MMP9, GAL, and ATF3. We also found a striking upregulation of a number of inflammation-associated genes in DRG cultures, although many were different between mouse and human. Our findings suggest an injury-like phenotype in DRG cultures that has important implications for the use of this model system for pain drug discovery.
Regulation of the RNA and DNA nuclease activities required for Pyrococcus furiosus Type III-B CRISPR–Cas immunity

Abstract Type III CRISPR–Cas prokaryotic immune systems provide anti-viral and anti-plasmid immunity via a dual mechanism of RNA and DNA destruction. Upon target RNA interaction, Type III crRNP effector complexes become activated to cleave both target RNA (via Cas7) and target DNA (via Cas10). Moreover, trans-acting endoribonucleases, Csx1 or Csm6, can promote the Type III immune response by destroying both invader and host RNAs. Here, we characterize how the RNase and DNase activities associated with Type III-B immunity in Pyrococcus furiosus (Pfu) are regulated by target RNA features and second messenger signaling events. In vivo mutational analyses reveal that either the DNase activity of Cas10 or the RNase activity of Csx1 can effectively direct successful anti-plasmid immunity. Biochemical analyses confirmed that the Cas10 Palm domains convert ATP into cyclic oligoadenylate (cOA) compounds that activate the ribonuclease activity of Pfu Csx1. Furthermore, we show that the HEPN domain of the adenosine-specific endoribonuclease, Pfu Csx1, degrades cOA signaling molecules to provide an auto-inhibitory off-switch of Csx1 activation. Activation of both the DNase and cOA generation activities require target RNA binding and recognition of distinct target RNA 3′ protospacer flanking sequences. Our results highlight the complex regulatory mechanisms controlling Type III CRISPR immunity.
The conserved microRNA miR‐8‐3p coordinates the expression of V‐ATPase subunits to regulate ecdysone biosynthesis for Drosophila metamorphosis

The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the underlying mechanisms of ecdysone‐mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis‐associated microRNAs (miRNAs) and their potential targets by cross‐linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR‐8‐3p targeted five Vha genes encoding distinct subunits of vacuolar H+‐ATPase (V‐ATPase), which has a vital role in the organellar acidification. The expression of ecdysone‐responsive miR‐8‐3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR‐8‐3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR‐8‐3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR‐8‐3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone‐deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR‐8‐3p/miR‐200 family and V‐ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V‐ATPase subunits by miR‐8‐3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis.
Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age

Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox’s proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93–20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients.
sPLA2 behaves like a prophylactic agent and mediates cellular and humoral immune responses in Plutella xylostella.

Most immune effectors are inducible to microbial pathogen infection while some are already present to act as prophylactic immunity against as yet unseen infection. This study identified secretory phospholipase A2 (sPLA2 ) as a prophylactic factor in diamondback moth, Plutella xylostella. Western blotting using a polyclonal antibody raised against other lepidopteran sPLA2 reacted specifically with ∼25 kDa protein, which was present at approximately 0.4 mM in the plasma of naïve larvae. Interrogation of P. xylostella transcriptomes revealed an open-reading frame for sPLA2 (Px-sPLA2 ), exhibiting high homology with other Group III sPLA2 s. Px-sPLA2 was expressed in all developmental stages. In the larval stage, bacterial challenge induced its expression in hemocytes and fat body but not in gut or epidermis. RNA interference (RNAi) suppressed Px-sPLA2 messenger RNA level and sPLA2 activity in plasma. An inhibition zone assay showed that Px-sPLA2 exhibited antibacterial activities against different species, because specific RNAi knockdown impaired the activity. The RNAi treatment also suppressed the cellular immune response assessed by hemocyte nodule formation and humoral immune response assessed by antimicrobial peptide gene expression. Finally, benzylideneacetone (BZA, a specific sPLA2 inhibitor) treatment inhibited plasma sPLA2 activity of naive larvae in a dose-dependent manner. An addition of BZA significantly increased the bacterial virulence of an entomopathogen, Bacillus thuringiensis. These results suggest that Px-sPLA2 is an immune-associated factor of P. xylostella and its relatively high level of concentration in the plasma of naive larvae strongly suggests its role as a prophylactic factor in defending against pathogens at early infection stages.
A Novel Method to Estimate the Full Knee Joint Kinematics Using Low Cost IMU Sensors for Easy to Implement Low Cost Diagnostics

Traditional motion capture systems are the current standard in the assessment of knee joint kinematics. These systems are, however, very costly, complex to handle, and, in some conditions, fail to estimate the varus/valgus and internal/external rotation accurately due to the camera setup. This paper presents a novel and comprehensive method to infer the full relative motion of the knee joint, including the flexion/extension, varus/valgus, and internal/external rotation, using only low cost inertial measurement units (IMU) connected to the upper and lower leg. Furthermore, sensors can be placed arbitrarily and only require a short calibration, making it an easy-to-use and portable clinical analysis tool. The presented method yields both adequate results and displays the uncertainty band on those results to the user. The proposed method is based on an fixed interval smoother relying on a simple dynamic model of the legs and judicially chosen constraints to estimate the rigid body motion of the leg segments in a world reference frame. In this pilot study, benchmarking of the method on a calibrated robotic manipulator, serving as leg analogue, and comparison with camera-based techniques confirm the method’s accurateness as an easy-to-implement, low-cost clinical tool.
Development of a biomimetic scallop robot capable of jet propulsion

Inspired by a scallop’s strong underwater propulsion mechanism, we designed and prototyped a scallop robot capable of clapping and swimming. In this work, an artificial velum was used to work as a check valve to stimulate the robot’s swimming. A couple of supporting plates were fixed on the robot shells to achieve the modulation of clapping process of the shells. The scallop robot can move at a maximum average and instantaneous speed of 3.4 and 4.65 body lengths per second, respectively. The effect of the supporting plates, the artificial velum, as well as the clapping frequency and amplitude on the swimming performance of the scallop robot was also experimentally evaluated. By tuning the sizes of the jet apertures, the scallop robot is capable of achieving high mobility actions such as turning. We also obtained the aperture ratio with the corresponding turning radius. This scallop robot provides a new propulsion mechanism in underwater bionic robots; it is also of help to understand the swimming principle of scallops in terms of jet propulsion and clapping motion.
Neurobiological Trajectories Involving Social Isolation in PTSD: A Systematic Review

Social isolation (SI) stress has been recognized as a major risk factor of morbidity in humans and animals, exerting damaging effects at the physical and mental health levels. Posttraumatic stress disorder (PTSD), on the other hand, occurs as a result of experiencing serious, life-threatening, traumatic events and involves involuntary re-experiencing trauma (intrusion), avoidance symptoms, and distortions of cognition and emotional arousal. The literature shows that PTSD is affected by genetic predisposition and triggers a large neurocircuitry involving the amygdala, insula, hippocampus, anterior cingulate- and prefrontal-cortex, and affects the function of the neuroendocrine and immune systems. Social isolation seems to influence the predisposition, onset and outcome of PTSD in humans, whereas it constitutes a valid model of the disorder in animals. According to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) protocol, we systematically reviewed all original studies involving the neurobiological trajectories between SI and PTSD published till July 2019 (database: PubMed/Medline). Out of 274 studies, 10 met the inclusion criteria. We present the results of the retrieved studies in terms of hypothalamic-pituitary-adrenal (HPA)-axis and endocannabinoid system function, immune reactions, neuroplasticity, novel pharmacological targets, and shortening of telomere length, which confirm a synergistic effect on a neurobiological level between the two entities.
Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis

Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations. The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus. Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab. The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions. Expert consensus recommendations for a pulmonary sarcoidosis treatment algorithm from a modified Delphi process include corticosteroids as initial therapy, immunomodulators for steroid-sparing or severe disease, and biologics for very severe disease http://bit.ly/2SmP3uG
Intraoperative Autofluorescence and Indocyanine Green Angiography for the Detection and Preservation of Parathyroid Glands

Fluorescence imaging is a well-known method for both the in vivo and in vitro identification of specific cells or tissues. This imaging tool is gaining importance in the intraoperative detection and preservation of parathyroid glands during endocrine surgery owing to the intrinsic properties of parathyroid tissue. The aim of this paper is to provide an overview of the basics of the technology, its history, and the recent surgical intraoperative applications of near-infrared imaging methods. Moreover, a literature review of the utilization of fluorescence devices in thyroid surgery suggests that the use of near-infrared imaging seems to be beneficial in reducing postoperative hypoparathyroidism, which is one of the most frequent complications of thyroid surgery.
Abortion seeking behaviour: a study from tertiary care hospital

Pregnancy is one of the most important events in the life of a woman. Unfortunately, all pregnancies are not welcomed. Among the 208 million women estimated to become pregnant each year worldwide, 123 million experience a planned (or intended) pregnancy leading to a birth or miscarriage or a stillbirth. The remaining 85 million (41%) of pregnancies are unintended (World Health Organization (2012). 1 A large proportion of these unintended pregnancies ends up in induced abortions.