Miracle-dz/UniFAR-FTUs huggingface dataset:
Do Markers of Inflammation and/or Muscle Regeneration in Lumbar Multifidus Muscle and Fat Differ Between Individuals with Good or Poor Outcome Following Microdiscectomy for Lumbar Disc Herniation?

Study Design. Observational study. Objective. The aim of this study was to evaluate whether inflammatory and/or muscle regeneration markers in paraspinal tissues (multifidus muscle/fat) during microdiscectomy surgery in patients with lumbar disc herniation (LDH) with radiculopathy, differ between individuals with good or poor outcome. Summary of Background Data. Structural back muscle changes, including fat infiltration, muscle atrophy, and fiber changes, are ubiquitous with LBP and are thought to be regulated by inflammatory and regeneration processes. Muscle changes might be relevant for recovery after microdiscectomy, but a link between expression of inflammatory and muscle regeneration genes in paraspinal tissues and clinical outcome has not been tested. Method. Paraspinal tissues from deep multifidus muscles and fat (intramuscular, sub-cutaneous, epidural) were harvested from twenty-one patients with LDH undergoing microdiscectomy surgery. Quantitative polymerase chain reaction (qPCR) measured expression of 10 genes. Outcome was defined as good (visual analogue scale (VAS) low back pain (LBP)+) or poor (VAS LBP−) by an improvement of >33% or ≤33% on the pain VAS, respectively. Good functional improvement was defined as 25% improvement on the physical functioning scale (PFS). Results. Brain-derived neurotrophic factor expression in deep multifidus was 91% lower (P = 0.014) in the VAS LBP- than VAS LBP+ group. Expression of interleukin-1β in subcutaneous fat was 48% higher (P = 0.026) in the VAS LBP– than VAS LBP+ group. No markers differed based on PFS. Conclusion. Results show a relationship between impaired muscle regeneration profile in multifidus muscle and poor outcome following microdiscectomy for LDH. Inflammatory dysregulation in subcutaneous fat overlying the back region might predict poor surgical outcome. Level of Evidence: 4
The Roles of Sodium-Independent Inorganic Phosphate Transporters in Inorganic Phosphate Homeostasis and in Cancer and Other Diseases

Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na+/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-independent Pi transporter has been identified. This transporter assists in the absorption of Pi by intestinal cells and renal proximal tubule cells and in the reabsorption of Pi by osteoclasts and capillaries of the blood–brain barrier (BBB). Hyperphosphatemia is a risk factor for mineral deposition, the development of diseases such as osteoarthritis, and vascular calcifications (VCs). Na+-independent Pi transporters have been identified and biochemically characterized in vascular smooth muscle cells (VSMCs), chondrocytes, and matrix vesicles, and their involvement in mineral deposition in the extracellular microenvironment has been suggested. According to the growth rate hypothesis, cancer cells require more phosphate than healthy cells due to their rapid growth rates. Recently, it was demonstrated that breast cancer cells (MDA-MB-231) respond to high Pi concentration (2 mM) by decreasing Na+-dependent Pi transport activity concomitant with an increase in Na+-independent (H+-dependent) Pi transport. This Pi H+-dependent transport has a fundamental role in the proliferation and migratory capacity of MDA-MB-231 cells. The purpose of this review is to discuss experimental findings regarding Na+-independent inorganic phosphate transporters and summarize their roles in Pi homeostasis, cancers and other diseases, such as osteoarthritis, and in processes such as VC.
Fabrication and Characterization of Single-Crystal Diamond Membranes for Quantum Photonics with Tunable Microcavities

The development of quantum technologies is one of the big challenges in modern research. A crucial component for many applications is an efficient, coherent spin–photon interface, and coupling single-color centers in thin diamond membranes to a microcavity is a promising approach. To structure such micrometer thin single-crystal diamond (SCD) membranes with a good quality, it is important to minimize defects originating from polishing or etching procedures. Here, we report on the fabrication of SCD membranes, with various diameters, exhibiting a low surface roughness down to 0.4 nm on a small area scale, by etching through a diamond bulk mask with angled holes. A significant reduction in pits induced by micromasking and polishing damages was accomplished by the application of alternating Ar/Cl2 + O2 dry etching steps. By a variation of etching parameters regarding the Ar/Cl2 step, an enhanced planarization of the surface was obtained, in particular, for surfaces with a higher initial surface roughness of several nanometers. Furthermore, we present the successful bonding of an SCD membrane via van der Waals forces on a cavity mirror and perform finesse measurements which yielded values between 500 and 5000, depending on the position and hence on the membrane thickness. Our results are promising for, e.g., an efficient spin–photon interface.
Apoptotic Effects of Bilirubin on Skin Cancer Cell Lines SK-MEL-3 (Melanoma) and A431 (Non-Melanoma).

BACKGROUND Bilirubin has long been exclusively considered as a potentially dangerous sign of liver diseases, but it is currently regarded as a reliable signaling molecule as well. OBJECTIVE This study investigated the effects of unconjugated bilirubin on survival, proliferation, apoptotic and cell arrest capacities of melanoma SKMEL-3 and non-melanoma A431 skin cancer cells in comparison with normal human dermal fibroblast (HDF) cells. METHODS The MTT assay test was used to identify survival and the IC50 at various concentrations of bilirubin on SKMEL-3, A431, and HDF cells for 24h and 48h. The comet assay technique was used to investigate genotoxicity effects and flow cytometry was run to investigate apoptotic and cell arresting effects of bilirubin on the cells. The gene expression of cyclin D1, cyclin E1, survivin, Bcl-2, and p53 was investigated by qRT-PCR. The molecular docking of bilirubin on CDKs (Cyclin-dependent kinases 2, 4, and 6) and pro-apoptotic factors Bad, Bak, Bax, Bid, Bik, and Bim were done by Autodock software version 2. RESULTS The IC50 of bilirubin on HDF, A431, and SKMEL-3 cells were 125, 115, and 95 μM at 24h and 115, 100, and 75 μM at 48h, respectively. Although cell arrest in the G1 phase occurred in all cells, bilirubin induced the genotoxicity and apoptosis in SKMEL-3 and A431 cancer cells more pronouncedly than those in normal HDF cells. CONCLUSION Bilirubin led to cell arrest in the G1 phase in SKMEL-3, A431, and HDF cells. Additionally, bilirubin induced apoptotic pathways in SKMEL-3 and A431 cancer cells.
Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test

Idiopathic Normal Pressure Hydrocephalus (iNPH)—the leading cause of reversible dementia in aging—is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH‐specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting‐state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive‐control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD‐pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross‐network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.
Altered Circulating Cell-Free Mitochondrial DNA of Patients with Congenital Scoliosis.

STUDY DESIGN Case-control study. OBJECTIVE To estimate the relationship between circulating cell-free DNA (ccf DNA) and clinical parameters of patients with congenital scoliosis (CS). SUMMARY OF BACKGROUND DATA CS is a complex spinal deformity characteristic of congenital vertebral malformations. Although numerous studies have centered on the etiology of CS, the cause of CS remains unclear. Previously, we reported that circulating cell-free DNA (ccf DNA) is altered in adolescent idiopathic scoliosis (AIS). However, the relationship between ccf DNA and the clinical parameters of patients with CS remains unclear. METHODS The plasma of peripheral blood from 35 patients with CS and 32 age-matched controls was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between ccf n-DNA and ccf mt-DNA levels were conducted. Receiver operating characteristic (ROC) curves were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. RESULTS The plasma ccf mt-DNA levels of both ND1 and CYTC were significantly decreased in patients with CS compared with levels in controls both in total and by sex, while the plasma ccf n-DNA levels showed no significant difference. There is no difference in both ccf mt-DNA and ccf n-DNA between S-SDV and M-SDV according to ICVAS classification. The ROC curve analyses showed a reliable sensitivity and specificity of CS predicted by ccf mt-DNA levels in total but failed to distinguish different ICVAS types. CONCLUSION Significantly decreased plasma ccf mt-DNA levels were observed in patients with CS compared with those in controls. Although this finding has limited significance for clinical practice, it indicates that ccf mt-DNA may predict the onset or development of CS. Further studies should focus on the role of ccf mt-DNA in embryo development and whether ccf mt-DNAs could be considered as a marker for prenatal screening in development disorder like CS. LEVEL OF EVIDENCE 4.
Management for lumbar spinal stenosis: Protocol for a network meta-analysis and systematic review

Introduction: Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS. Methods and analysis: We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.
Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate to Severe Asthma.

RATIONALE It is unclear why select patients with moderate to severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of severe decline in lung function. OBJECTIVE To evaluate corticosteroid response phenotypes as longitudinal predictors of lung decline. METHODS Adults with in the NHLBI Severe Asthma Research Program (SARP3; (1, 2)) who had undergone a course of intramuscular triamcinolone at baseline and ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/year; mild decline, >0.5 to 2.0% loss/year; no change, 0.5% loss/year to <1% gain/year; improve, ≥1% gain/year. Regression models were used to develop predictors of severe decline. MEASUREMENTS AND MAIN RESULTS Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (tdFEV1; derived by baseline subtraction) was related to the 4-yr change in lung function or slope category in univariable models (p < 0.001). For each 5% decrement in the tdFEV1, there was a 50% increase in the odds of being in the severe decline group (OR 1.5, 95% CI 1.3 to 1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and BMI. CONCLUSIONS Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk of severe decline in lung function.
Air Pollution and Risk of Placental Abruption: A Study of Births in New York City, 2008-2014.

We evaluated the associations amongst fine particulate matter (PM2.5 <12, 12-14, and ≥15 μg/m3) and nitrogen dioxide (NO2 <26, 26-29, and ≥30 ppb) and abruption in prospective cohort of 685,908 pregnancies in New York City (2008-2014). In co-pollutant analyses these associations were examined using distributed lag non-linear models based on Cox models. The prevalence of abruption was 0.9% (n=6025). Compared to PM2.5 <12 μg/m3, women exposed to PM2.5 ≥15 μg/m3 in the third trimester experienced higher abruption rate (hazard ratio [HR] 1.68, 95% confidence interval [CI]: 1.41, 2.00). Compared to NO2 <26 ppb, women exposed to 26-29 ppb (HR 1.11, 95% CI: 1.02, 1.20) and ≥30 ppb (HR 1.06, 95% CI: 0.91, 1.24) in the first trimester were associated with higher abruption rate. Compared to both PM2.5 and NO2 <95th percentile in the third trimester, rates of abruption were increased with both PM2.5 and NO2 ≥95th percentile (HR 1.44, 95% CI: 1.15, 1.80) and PM2.5 ≥95th percentile and NO2 <95th percentile (HR 1.43 95% CI: 1.23, 1.66). Increased PM2.5 levels in the third trimester and NO2 in the first trimester are associated with elevated abruption rates, suggesting that these exposures may be important triggers of premature placental separation through different pathways.
Cutaneous Kikuchi disease-like inflammatory pattern without lymph node involvement is associated with systemic disease and severe features in lupus erythematous: A case-control study

Introduction Kikuchi-Fujimoto disease (KFD) is a self-limited histiocytic necrotizing lymphadenitis sometimes affecting the skin. “Kikuchi disease-like inflammatory pattern” (KLIP) has been described in cutaneous lesions as similar pathological features in patients without lymph node involvement and as a potential clue for the diagnosis of lupus. We aimed to describe KLIP-associated clinical and immunological features in lupus patients with a retrospective case-control study. Methods Thirteen cases of KLIP were included as well as thirty-nine age- and sex-matched control lupus patients without KLIP. At the time of KLIP diagnosis, 4/13 patients (31%) had isolated cutaneous lupus erythematosus (CLE) and 9/13 had (69%) systemic lupus erythematosus (SLE) including 6 (46%) with severe haematological, lung, cardiac or renal disease. KLIP features were observed in skin biopsies of different clinical presentations. Results Compared with our control group, KLIP patients more frequently had SLE 9/13 (69%) versus 8/39 (21%) (OR 12.9; IC95% [2.86–58.2]; p = 0.0004) and more frequently severe SLE. Two out of four CLE exhibiting KLIP lesions (50%) developed severe SLE with cardiac or renal involvement after 12 and 24 months, respectively. Treatment with thalidomide 100 mg/day allowed rapid and complete clearance of cutaneous lesions in 6/6 KLIP patients. The need to use thalidomide tended to be more frequent in KLIP patients than in controls. Conclusion Our study suggests that KLIP features in lupus skin lesions are associated with SLE and severe systemic features. Despite a limited number of isolated CLE patients with KLIP features in the skin, this observation may warrant closer follow-up on patients with a higher risk of developing SLE.
RNA Biogenesis Instructs Functional Inter-Chromosomal Genome Architecture

Three-dimensional (3D) genome organization has emerged as an important layer of gene regulation in development and disease. The functional properties of chromatin folding within individual chromosomes (i.e., intra-chromosomal or in cis) have been studied extensively. On the other hand, interactions across different chromosomes (i.e., inter-chromosomal or in trans) have received less attention, being often regarded as background noise or technical artifacts. This viewpoint has been challenged by emerging evidence of functional relationships between specific trans chromatin interactions and epigenetic control, transcription, and splicing. Therefore, it is an intriguing possibility that the key processes involved in the biogenesis of RNAs may both shape and be in turn influenced by inter-chromosomal genome architecture. Here I present the rationale behind this hypothesis, and discuss a potential experimental framework aimed at its formal testing. I present a specific example in the cardiac myocyte, a well-studied post-mitotic cell whose development and response to stress are associated with marked rearrangements of chromatin topology both in cis and in trans. I argue that RNA polymerase II clusters (i.e., transcription factories) and foci of the cardiac-specific splicing regulator RBM20 (i.e., splicing factories) exemplify the existence of trans-interacting chromatin domains (TIDs) with important roles in cellular homeostasis. Overall, I propose that inter-molecular 3D proximity between co-regulated nucleic acids may be a pervasive functional mechanism in biology.
Temperature adaptation of soil microbial respiration in alpine, boreal and tropical soils: An application of the square root (Ratkowsky) model

Warming is expected to stimulate soil microbial respiration triggering a positive soil carbon‐climate feedback loop while a consensus remains elusive regarding the magnitude of this feedback. This is partly due to our limited understanding of the temperature‐adaptive response of soil microbial respiration, especially over broad climatic scales. We used the square root (Ratkowsky) model to calculate the minimum temperature for soil microbial respiration (Tmin, which describes the temperature adaptation of soil microbial respiration) of 298 soil samples from alpine grasslands on the Tibetan Plateau and forest ecosystems across China with a mean annual temperature (MAT) range from −6°C to +25°C. The instantaneous soil microbial respiration was determined between 4°C and 28°C. The square root model could well fit the temperature effect on soil microbial respiration for each individual soil, with R2 higher than 0.98 for all soils. Tmin ranged from −8.1°C to −0.1°C and increased linearly with increasing MAT (R2 = 0.68). MAT dominantly regulated Tmin variation when accounting simultaneously for multiple other drivers (mean annual precipitation, soil pH and carbon quality); an independent experiment showed that carbon availability had no significant effect on Tmin. Using the relationship between Tmin and MAT, soil microbial respiration after an increased MAT could be estimated, resulting in a relative increase in respiration with decreasing MAT. Thus, soil microbial respiration responses are adapted to long‐term temperature differences in MAT. We suggest that Tmin = −5 + 0.2 × MAT, that is, every 1°C rise in MAT is estimated to increase Tmin of respiration by approximately 0.2°C, could be used as a first approximation to incorporate temperature adaptation of soil microbial respiration in model predictions. Our results can be used to predict future changes in the response of soil microbial respiration to temperature over different levels of warming and across broad geographic scales with different MAT.
Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Background: The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. Objective: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. Methods: We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with <5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. Results: Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. Conclusions: Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.