Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of patients with neuropathic pain syndromes screened by the painDETECT questionnaire and diagnosed by physician exam

Background The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians. Methods Adults with scores exceeding the threshold for probable NeP (painDETECT ≥19) and diagnosed with NeP by a qualified physician completed a questionnaire that included comorbid conditions, pain symptoms and experiences, medication use, health status (3-level EuroQol 5 Dimensions (EQ-5D-3L]: health utilities index and visual analog scale), pain severity and interference with functioning (Brief Pain Inventory), and work and activity impairment (Work Productivity and Activity Impairment questionnaire). Descriptive analyses were performed for each NeP subtype. Results Participants (n=295) were predominantly female (64.4%), middle-aged (53.9%), and white (51.5%). Chronic low back pain was the most frequently diagnosed major NeP syndrome (n=166), followed by diabetic peripheral neuropathy (n=58), post-trauma neuropathy (n=47), post-surgical neuropathy (n=28), and central NeP (n=23). An additional 45 participants were diagnosed, but did not meet the criteria for the aforementioned subtypes. Participants could be diagnosed with multiple subtypes. Across each NeP subtype, patients reported high rates of comorbid disease, including arthritis (range: 39.1%–64.3%) and high blood pressure (range: 26.1%–69.0%), as well as symptomology that included numbness (range: 68.1%–91.4%) and changes in muscular strength (range: 24.1%–65.2%). The majority of patients reported back pain (range: 77.8%–95.7%) and arthritis/joint pain (range: 68.1%–78.6%). The most commonly reported types of NeP pain medication were non-steroidal anti-inflammatory drugs (range: 43.1%–70.2%), weak opioids (range: 22.2%–39.3%), and strong opioids (range: 8.7%–28.6%). All six NeP groups generally reported similar levels of dysfunction on all self-report measures. The most notable finding was that the EuroQol-5D-3L health utilities index scores for each of the six groups were lower than the US norms by a clinically important amount. Conclusion These exploratory findings indicate that patients with NeP across different etiologies are medically complex and experience impaired function across multiple domains.
Interventions for obesity among schoolchildren: A systematic review and meta-analyses

Background Childhood overweight and obesity has emerged as a major public health threat worldwide with challenges in its management. This review assessed the effectiveness of interventions for childhood overweight and obesity. Methods A systematic literature search was conducted using CINAHL, EMBASE, Ovid MEDLINE, PsycINFO and SPORTDiscus databases to retrieve articles published from 1st January 2000 to 31st December 2017. Randomised controlled trials (RCTs) and quasi-experimental studies comparing different strategies in managing overweight and obesity among schoolchildren (6 to 12 years of age) were included. The main outcomes of interest were reductions in weight related variables included anthropometry and body composition measurements. All variables were analysed using random effects meta-analyses. Results Fourteen studies were reviewed, 13 were RCTs and one was a quasi-experimental study. The risk of bias for randomisation was low risk for all of RCTs except for one, which was unclear. The risk of bias for randomisation was high for the quasi-experimental study. Most interventions incorporated lifestyle changes and behavioural strategies such as coping and problem solving skills with family involvement. The meta-analyses did not show significant effects of the intervention in reducing weight related outcomes when compared with controls. Conclusion Meta-analyses of the selected studies did not show significant effects of the interventions on weight related outcomes among overweight and obese schoolchildren when compared with controls. The role of interdisciplinary team approaches with family involvement using behaviour and lifestyle strategies to curb obesity among schoolchildren is important.
Detection of ethyl carbamate in liquors using surface-enhanced Raman spectroscopy

Ethyl carbamate (EC), a potential carcinogen, can be formed during the fermentation and storage of alcoholic beverages. In this work, quantitative detection of EC in alcoholic beverages by using surface-enhanced Raman spectroscopy (SERS) is reported. Flower-shaped silver nanostructure substrates and silver nanocube substrates were prepared and employed as SERS platform. Flower-like silver substrates had better Raman enhancement effect on EC and were selected for further EC detection. In EC SERS spectra based on flower-shaped silver substrates, the strongest and reproducible characteristic band at 857 cm−1 was chosen for establishing a linear regression model in the concentrations ranging from 10−5 to 10−9 M, which effectively extended the application scope of the quantitative model for determination EC. Furthermore, a real alcoholic beverage was tested to verify the feasibility and reliability of the method.
Health-related outcomes, health care resource utilization, and costs of multiple sclerosis in Japan compared with US and five EU countries

Purpose Multiple sclerosis (MS) imposes a huge burden on patients. This study examined the relationship between MS and health-related and economic burden in Japan; secondarily, health status was compared across patients with MS in Japan, US, and five European Union (5EU) countries (France, Germany, Italy, Spain, and UK). Methods A retrospective cross-sectional study was conducted using self-reported data from 2009 to 2014 Japan National Health and Wellness Survey (n=145,759). Health status, work productivity loss, activity impairment, health care resource utilization, and annual costs associated with MS (n=85) were compared with controls without MS (n=145,674). Propensity score matching and multivariable linear regressions determined the effect of MS after controlling for confounders. Health status in Japan was also compared with that of 5EU (n=62) and US (n=67) patients with MS. Results Patients with MS in Japan reported significantly worse health status via mental component summary score (MCS; 40.1 vs 45.8) and physical component summary score (PCS; 41.4 vs 51.2) and health state utility scores (0.63 vs 0.74; all P<0.001). They also reported more absenteeism (12.0% vs 3.7%), presenteeism (33.8% vs 19.8%), overall work impairment (40.9% vs 21.6%), and activity impairment (43.6% vs 24.0%), with higher indirect costs (¥2,040,672/US $20,102 vs ¥1,076,306/US$10,603) than controls (all P<0.001). Patients with MS reported higher resource use, including provider visits (8.0 vs 4.7), emergency room visits (0.03 vs 0.1), and hospitalizations (2.7 vs 0.69) in the past 6 months, with higher direct costs (¥3,670,906/US$36,162 vs ¥986,099/US$9,714) than controls (all P<0.001). Finally, Japanese patients with MS reported lower MCSs and higher PCSs than their US and 5EU counterparts. Conclusion MS in Japan is associated with poor health status and high work productivity loss, resource use, and costs, underscoring the need for improved treatment, especially vis-à-vis mental health, when comparing Japanese patients with their 5EU and US counterparts.
Remarkable problem-solving ability of unicellular amoeboid organism and its mechanism

Choosing a better move correctly and quickly is a fundamental skill of living organisms that corresponds to solving a computationally demanding problem. A unicellular plasmodium of Physarum polycephalum searches for a solution to the travelling salesman problem (TSP) by changing its shape to minimize the risk of being exposed to aversive light stimuli. In our previous studies, we reported the results on the eight-city TSP solution. In this study, we show that the time taken by plasmodium to find a reasonably high-quality TSP solution grows linearly as the problem size increases from four to eight. Interestingly, the quality of the solution does not degrade despite the explosive expansion of the search space. Formulating a computational model, we show that the linear-time solution can be achieved if the intrinsic dynamics could allocate intracellular resources to grow the plasmodium terminals with a constant rate, even while responding to the stimuli. These results may lead to the development of novel analogue computers enabling approximate solutions of complex optimization problems in linear time.
Response from the Authors (Kumar P et al)[]

1. We quote findings from a study[2] which was conducted in a busy village health and nutrition day of Purnea District, Bihar at a health sub‐centre (catering to a population of 7,000 people) where armband MUAC (a bangle, with circumference 23 cm) and MUAC non‐stretchable tape measurements were included in addition to weight and height measurements taken by a trained Auxillary Nurse Midwife (ANM), under supervision of a trained post‐graduate nutrition researcher. Measurement times for each were recorded. The measurement time for MUAC using non‐ stretchable tape was 54 seconds and height 59 seconds. This excludes the time taken for other steps like self‐introduction, obtaining informed consent, taking out tools for measurements and adjustment of clothes/footwear as the study was a part of a service delivery site where these aspects were already being done.
The Utilization of the Surviving Sepsis Campaign Care Bundles in the Treatment of Pediatric Patients with Severe Sepsis or Septic Shock in a Resource-Limited Environment: A Prospective Multicenter Trial

Background: Sepsis is a common condition affecting the lives of infants and children worldwide. Although implementation of the surviving sepsis campaign (SSC) care bundles was once believed to be effective in reducing sepsis mortality rates, the approach has recently been questioned. Methods: The study was a prospective, interventional, multicenter trial. Infants and children aged 1 month to 15 years in seven different large academic centers in Thailand who had been diagnosed with severe sepsis or septic shock. They were given treatment based on the SSC care bundles. Results: A total of 519 children with severe sepsis or septic shock were enrolled in the study. Among these, 188 were assigned to the intervention group and 331 were recruited to the historical case–control group. There were no significant differences in the baseline clinical characteristics. The intervention group was administered a significantly higher fluid bolus than was the control group (28.3 ± 17.2 cc/kg vs. 17.7 ± 10.6 cc/kg; P = 0.02) with early vasopressor used (1.5 ± 0.7 h) compared to control group (7.4 ± 2.4 h, P < 0.05). More importantly, our sepsis mortality reduced significantly from 37% ± 20.7% during the preintervention period to 19.4% ± 14.3% during the postintervention period (P < 0.001). Conclusion: Our study demonstrated a significant reduction in sepsis mortality after the implementation of the SSC care bundles. Early diagnosis of the disease, optimum hemodynamic resuscitation, and timely antibiotic administration are the key elements of sepsis management.
Psoralen Protects Chondrocytes, Exhibits Anti-Inflammatory Effects on Synoviocytes, and Attenuates Monosodium Iodoacetate-Induced Osteoarthritis

Current study examined whether psoralen (PSO) exhibits anti-inflammatory responses, protection and activation of chondrocytes, and relieve osteoarthritis (OA). Rats chondrocytes and human synoviocytes were cultured in tumor necrosis factor-α (TNF-α) conditioned culture medium with/without PSO to test the cell morphologies and cytotoxicities in vitro. Cartilaginous extracellular matrix (ECM) and proliferative gene/protein expression levels were evaluated in chondrocytes. Meanwhile, matrix metalloproteinases (MMPs) and interleukins (ILs) gene/protein expression were analyzed in synoviocytes. SD rats of monosodium iodoacetate (MIA) induced OA model were used in order to assess the effects of PSO on attenuating degeneration of the articular cartilage in vivo. Results showed TNF-α conditioned culturing with/without PSO (1-100 µM) had no any toxicity on both the cell lines. PSO (10 µM) activated cartilaginous specific ECM expression along with up-regulation of proliferative genes at transcriptional levels. Interestingly, PSO significantly reversed TNF-α induced up-regulation of MMP13 and ILs synoviocytes in a dose-dependent manner (1 to 20 µM), while down-regulated cartilaginous ECM production. Following six weeks of PSO treatments to articular cartilage osteoarthritis, compared to MIA-induced group, the appearance and physiological structure of articular cartilage was more integrated with greatly organized chondrocytes and abundant cartilage matrix. In conclusion, PSO protects and activates chondrocytes, antagonizing the expression of MMPs and ILs secreted by synovial cells, and effectively attenuates MIA-induced OA.
Comparison of boundary detection techniques to improve image analysis in medical thermography

Abstract In digital imaging, poor contrast between the target and its background can affect the extraction of the object of interest and increase the time used in its analysis. Medical thermal imaging requires the correct interpretation of the thermal values obtained from the region of interest. In this investigation, a subjective and objective comparison of currently available outlining techniques is performed to determine the optimal method. Results indicate that probability-based operators produce the best outcome especially after pre-processing with a noise removal filter. The findings of this study suggest that probability-based edge detection techniques in combination with homomorphic filtering and limited post-processing provide initial estimate delineations of areas. These delineations are of sufficient quality for subsequent automatic or semiautomatic post-processing so that a maximum of the original information inside the regions is preserved without loss or distortion of data.
Single-molecule imaging of transcription at damaged chromatin

DNA damage within active genes drives bidirectional break-induced transcription initiation. How DNA double-strand breaks (DSBs) affect ongoing transcription remains elusive due to the lack of single-molecule resolution tools directly measuring transcription dynamics upon DNA damage. Here, we established new reporter systems that allow the visualization of individual nascent RNAs with high temporal and spatial resolution upon the controlled induction of a single DSB at two distinct chromatin locations: a promoter-proximal (PROP) region downstream the transcription start site and a region within an internal exon (EX2). Induction of a DSB resulted in a rapid suppression of preexisting transcription initiation regardless of the genomic location. However, while transcription was irreversibly suppressed upon a PROP DSB, damage at the EX2 region drove the formation of promoter-like nucleosome-depleted regions and transcription recovery. Two-color labeling of transcripts at sequences flanking the EX2 lesion revealed bidirectional break-induced transcription initiation. Transcriptome analysis further showed pervasive bidirectional transcription at endogenous intragenic DSBs. Our data provide a novel framework for interpreting the reciprocal interactions between transcription and DNA damage at distinct chromatin regions.
In situ graphene liquid cell-transmission electron microscopy study of insulin secretion in pancreatic islet cells

Background Islet cell transplantation is one of the key treatments for type 1 diabetes. Understanding the mechanisms of insulin fusion and exocytosis are of utmost importance for the improvement of the current islet cell transplantation and treatment of diabetes. These phenomena have not been fully evaluated due either to the lack of proper dynamic imaging, or the lack of proper cell preservation during imaging at nanoscales. Methods By maintaining the native environment of pancreatic β-cells between two graphene monolayer sheets, we were able to monitor the subcellular events using in situ graphene liquid cell (GLC)-transmission electron microscopy (TEM) with both high temporal and high spatial resolution. Results For the first time, the nucleation and growth of insulin particles until the later stages of fusion were imaged at nanometer scales. The release of insulin from plasma membrane involves the degradation of plasma membrane and drastic reductions in the shorter axis of the insulin particles. Sequential exocytosis results indicated the nucleation, growth and attachment of the new insulin particles to the already anchored ones, which is thermodynamically favorable due to the reduction in total surface, further reducing the Gibbs free energy. The retraction of the already anchored insulin toward the cell is also monitored for the first time live at nanoscale resolution. Conclusion Investigation of insulin granule dynamics in β-cells can be investigated via GLC-TEM. Our findings with this technology open new realms for the development of novel drugs on pathological pancreatic β-cells, because this approach facilitates observing the effects of the stimuli on the live cells and insulin granules.
The Risk of Gynecologic and Urinary Tract Cancer with Pelvic Inflammatory Disease: A Population-Based Cohort Study

Purpose: The aim of the study was to determine the association between pelvic inflammatory disease (PID) and breast, colorectal, gynecologic and urinary tract cancer. Methods: The source of data was a longitudinal dataset compiled by the Longitudinal Health Insurance Database 2000 (LHID2000) which was collected by the National Health Insurance program. Cases of PID, at least two outpatient visits and one admission, were diagnosed from 2000 to 2013. The data for controls, age matched women who were not diagnosed with PID from 2000 to 2013, were also obtained. Results: A total of 47,333 PID cases and 189,332 for control group were included in the study. The ectopic pregnancy incidence rate (per 10000 person months) was 1.912 and 0.595 in the PID and control group, respectively; the rate ratio was 3.211 (confidence interval, CI = 2.931-3.519). There were significantly different in gynecologic cancers and urinary tract cancers between the PID and control group; the rate ratios (95% C.I.) were 1.903 (1.672-2.166) and 1.566 (1.211-2.025), respectively. Conclusion: Our study found that PID was associated with increased risks of gynecologic and urinary tract cancer but not colorectal or breast cancer. The information may lead to a strategy for cancer prevention and a reasonable healthcare usage through understanding PID epidemiology and controlling the inflammatory responses.
An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency

Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.
Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence

Accumulating studies have shown that oxidative stress increases with aging, which is related to the pathophysiology of postmenopausal osteoporosis. Pyrroloquinoline quinone (PQQ) is a natural anti-oxidant with anti-oxidative and anti-aging effects. However, it is unclear whether PQQ has a protective role against estrogen deficiency-induced osteoporosis. Here, we evaluated the efficacy of PQQ on bone mineral density, bone microarchitecture, bone turnover and biomechanical strength in ovariectomy (OVX)-induced osteoporosis mouse model. Although dietary PQQ supplement did not affect serum E2 levels and uterine weight in OVX mice, it could prevent OVX-induced bone loss and improve bone strength by inhibiting oxidative stress, osteocyte senescence and senescence-associated secretory phenotype (SASP), subsequently promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption, which was comparable to treatment with exogenous estrogen. The results from our study provide experimental evidence for the clinical use of PQQ to prevent estrogen deficiency-induced osteoporosis.
B cells grow up: Studies of B cell activation, proliferation and differentiation in primary antibody deficiencies

Dit proefschrift richt zich op de primaire immuundeficienties (PIDs), waarvan sommige vormen zo mild zijn dat ze jaren onopgemerkt kunnen blijven, en andere zo ernstig zijn dat ze vrijwel direct na de geboorte worden ontdekt omdat er klachten ontstaan. Een ’primaire antistof deficientie (PAD)’ is de meest frequent voorkomende PID bij de mens. Het probleem berust op een verkeerde aanleg of het niet goed functioneren van de B-cellen, die weliswaar in normale aantallen aangemaakt zijn maar niet (of niet goed) differentieren naar hun eindstadium van plasmablast of plasmacell. Deze laatstgenoemde cellen van het afweersysteem zijn verantwoordelijk voor de productie van antistoffen (antilichamen). Bij de meeste patienten met een PAD is het pathofysiologische mechanisme onbekend en ook kennis over de onderliggende genetische afwijking ontbreekt vaak. Wij introduceren een test, waarin we met een kleine hoeveelheid bloed de functie van B-cellen kunnen bestuderen. We isoleren cellen van interesse uit het bloed en kweken deze dan in het laboratorium waarbij we de cellen op verschillende manieren activeren en na een week kunnen we ze analyseren. Deze test hebben we gevalideerd voor diagnostiek en research en hebben referentiewaarden gegenereerd voor alle leeftijden. We hebben hiermee een manier in handen om B-cel activatie, deling en differentiatie te bestuderen. Dit geeft ons de mogelijkheid om deze processen van de B-cel te bestuderen bij patienten waar de onderliggende genetisch oorzaak bekend is om het effect van het B-cel defect goed te karakteriseren en vervolgens ter vergelijking dezelfde testen te doen bij patienten met nog onbekende B-cel problemen.