Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis

Introduction: We sought to identify patients with amyotrophic lateral sclerosis (ALS) who displayed suspected peripheral nervous system (PNS) inflammation to compare them to those with suspected PNS degeneration. Methods: We measured sonographic median and ulnar nerve cross‐sectional area (CSA) and cerebrospinal fluid albumin/serum albumin ratio (Qalb) in patients with ALS to classify them as having suspected PNS degeneration (small CSA/low Qalb) or inflammation (larger CSA/high Qalb). Results: Fifty‐seven percent of patients had suspected PNS degeneration, 21% had suspected PNS inflammation, and 21% displayed suspected “normal PNS state. ” Suspected PNS degeneration was related to classic ALS, shorter disease duration, and a smaller hypoechoic nerve area. Suspected PNS inflammation was associated with men, longer disease duration, and a larger hypoechoic nerve area and was the dominant finding in superoxide dismutase 1 mutation carriers. Discussion: Our simple approach might aid in the in vivo differentiation of supposed ALS subtypes, those with suspected PNS degeneration vs. inflammation, for stratification in clinical trials. Muscle Nerve 59:567–567, 2019
The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.
Complexity of Medicine Regimens and Patient Perception of Medicine Burden

From the patient perspective, medicine burden is more than the number of medicines, or the complexity of medicine regimens they need to manage. Relationships between the number of medicines, regimen complexity and patient perception of medicine burden are under-researched. This cross-sectional study measured regimen complexity and determined how this and patient perceived burden are affected by the therapeutic group. Regimen complexity was measured in patients presenting prescriptions to six community pharmacies in South-East England. A sub-sample (166) also completed the Living with Medicines Questionnaire which measures patient perceived burden. The 492 patients were prescribed 2700 medicines (range 1 to 23). Almost half used at least one non-oral formulation. Complexity was correlated strongly with the number of medicines (r = 0.94), number of therapeutic groups (r = 0.84) and number of formulations (r = 0.73). Patients using medicines for skin, eye and respiratory conditions had the highest complexity scores. Increasing the number of medicines, frequency of dosing, number of non-oral formulations and number of different therapeutic groups all increased medicine burden. Although cardiovascular medicines were the most common medicines used by the majority of patients (60%), those for neurological, psychiatric and gastro-intestinal conditions were most strongly associated with high burden. Studies are required to determine medicine burden in different conditions, especially neurological conditions, including chronic pain.
Examining item content validity using property fitting analysis via multidimensional scaling

Multiple‐item measuring instruments are frequently used in a wide range of disciplines for the purpose of research in substantive areas. The quality of items in these instruments determine to a large extent whether the results are trustworthy. In this paper, we suggested to use property fitting analysis to evaluate the appropriateness of items content validity based on explicit item property criteria.
IL-4R Drives Dedifferentiation, Mitogenesis, and Metastasis in Rhabdomyosarcoma

Purpose: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. The alveolar subtype of rhabdomyosarcoma (ARMS) is a paradigm for refractory and incurable solid tumors because more than half of the children at diagnosis have either regional lymph node or distant metastases. These studies follow our previous observation that Interleukin-4 receptor α (IL-4Rα) is upregulated in both human and murine ARMS, and that the IL-4R signaling pathway may be a target for abrogating tumor progression. Experimental Design: By in vitro biochemical and cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of IL-4 and IL-13 in IL-4R–mediated mitogenesis, myodifferentiation, and tumor progression. Results: IL-4 and IL-13 ligands accelerated tumor cell growth and activated STAT6, Akt, or MAPK signaling pathways in the human RMS cell lines, RD and Rh30, as well as in mouse primary ARMS cell cultures. IL-4 and IL-13 treatment also decreased protein expression of myogenic differentiation factors MyoD and Myogenin, indicating a loss of muscle differentiation. Using a genetically engineered mouse model of ARMS, we have shown that inhibition of IL-4R signaling pathway with a neutralizing antibody has a profound effect on the frequency of lymph node and pulmonary metastases, resulting in significant survival extension in vivo. Conclusions: Our results indicate that an IL-4R-dependent signaling pathway regulates tumor cell progression in RMS, and inhibition of this pathway could be a promising adjuvant therapeutic approach. Clin Cancer Res; 17(9); 2757–66. ©2011 AACR.
ANXA10 induction by interaction with tumor‐associated macrophages promotes the growth of esophageal squamous cell carcinoma

Tumor‐associated macrophages (TAMs) have important roles in the growth, angiogenesis and progression of various tumors. Although we have demonstrated the association of an increased number of infiltrating CD204+ TAMs with poor prognosis in esophageal squamous cell carcinomas (ESCCs), the roles of TAMs in ESCC remain unclear. Here, to study the effects of TAMs on the tumor microenvironment of ESCCs, we established a co‐culture assay using a human ESCC cell line and TAM‐like peripheral blood monocyte‐derived macrophages and performed a cDNA microarray analysis between monocultured and co‐cultured ESCC cell lines. Our qRT‐PCR confirmed that in the co‐cultured ESCC cell lines, CYP1A1, DHRS3, ANXA10, KLK6 and CYP1B1 mRNA were highly up‐regulated; AMTN and IGFL1 mRNA were down‐regulated. We observed that the high expression of a calcium‐dependent phospholipid‐binding protein ANXA10 was closely associated with the depth of invasion and high numbers of infiltrating CD68+ and CD204+ TAMs and poor disease‐free survival (P = 0.0216). We also found ANXA10 promoted the cell growth of ESCC cell lines via the phosphorylation of Akt and Erk1/2 pathways in vitro. These results suggest that ANXA10 induced by the interaction with TAMs in the tumor microenvironment is associated with cell growth and poor prognosis in human ESCC tissues.
The Swedish version of the pelvic girdle questionnaire, cross-cultural adaptation and validation

Abstract Purpose: The aims of this study were to translate and culturally adapt The Pelvic Girdle Questionnaire to Swedish, and to evaluate the construct and discriminative validity. Materials and methods: A translation and cultural adaptation process was performed according to international guidelines. Pilot tests were conducted among 16 women during pregnancy and post-partum. Analysis of the construct and discriminative validity of the Swedish version of the Pelvic Girdle Questionnaire was performed in a sample of 177 pregnant women suffering from pain in the lumbo-pelvic area. Participants completed the Pelvic Girdle Questionnaire along with Oswestry Disability Index, numeric rating scales for pain intensity and for pelvic girdle pain concerns. Results: The Swedish version of the Pelvic Girdle Questionnaire showed high internal consistency with Cronbach’s alphas between 0.82 and 0.96, good convergent validity with high correlations with the Oswestry Disability Index and the pain intensity numeric rating scale, whereas moderate correlation was shown between the concerns numeric rating scale and the other instruments as hypothesized. Receiver operating characteristic curves showed good discriminatory capacity for women in need of treatment. Conclusions: The Swedish version of the Pelvic Girdle Questionnaire has patient acceptability. It has good construct and discriminative validity for measurements of consequences of pregnancy-related pelvic girdle pain among Swedish speaking women. IMPLICATIONS FOR REHABILITATION Pregnancy-related pelvic girdle pain may be disabling and long-lasting, however treatable when identified. The Pelvic Girdle Questionnaire is the only condition-specific, reliability tested and validated questionnaire for pelvic girdle pain. The Swedish version of the Pelvic Girdle Questionnaire has patient acceptability, good construct validity for pelvic girdle pain among Swedish speaking women, and shows good discriminative capacity for women in need of treatment.
Chemoprotective effects of Ulva lactuca (green seaweed) aqueous‐ethanolic extract against subchronic exposure to benzo(a)pyrene by CYP1A1 inhibition in mice

The protective effect of the supplementation with an aqueous‐ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene‐induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL‐1β and TNF‐α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene‐exposed group. The benzo(a)pyrene‐induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract‐supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene‐induced‐toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.
Scaling up analogical innovation with crowds and AI

Analogy—the ability to find and apply deep structural patterns across domains—has been fundamental to human innovation in science and technology. Today there is a growing opportunity to accelerate innovation by moving analogy out of a single person’s mind and distributing it across many information processors, both human and machine. Doing so has the potential to overcome cognitive fixation, scale to large idea repositories, and support complex problems with multiple constraints. Here we lay out a perspective on the future of scalable analogical innovation and first steps using crowds and artificial intelligence (AI) to augment creativity that quantitatively demonstrate the promise of the approach, as well as core challenges critical to realizing this vision.
Pulsed Excitation in Magnetic Particle Imaging

Magnetic particle imaging (MPI) is a promising new tracer-based imaging modality. The steady-state, nonlinear magnetization physics most fundamental to MPI typically predicts improving resolution with increasing tracer magnetic core size. For larger tracers, and given typical excitation slew rates, this steady-state prediction is compromised by dynamic processes that induce a significant secondary blur and prevent us from achieving high resolution using larger tracers. Here, we propose a new method of excitation and signal encoding in MPI we call pulsed MPI to overcome this phenomenon. Pulsed MPI allows us to directly encode the steady-state magnetic physics into the time-domain signal. This in turn gives rise to a simple reconstruction algorithm to obtain images free of secondary relaxation-induced blur. Here, we provide a detailed description of our approach in 1D, discuss how it compares with alternative approaches, and show experimental data demonstrating better than 500- $\mu \text{m}$ resolution (at 7 T/m) with large tracers. Finally, we show experimental images from a 2D implementation.
Dynamic Processing of Displacement Loops During Recombinational DNA Repair

Displacement-loops (D-loops) are pivotal intermediates of homologous recombination (HR), a universal DNA double strand break (DSB) repair pathway. We developed a versatile assay for the physical detection of D-loops in vivo, which enabled studying the kinetics of their formation and defining the network of D-loop formation and reversal pathways. Nascent D-loops are detected within 2 hrs of DSB formation and extended over the next 2 hrs in a system allowing break-induced replication. The majority of D-loops are disrupted in wild type cells by two pathways: one supported by the Srs2 helicase and the other by the Mph1 helicase and the Sgs1-Top3-Rmi1 helicase-topoisomerase complex. Both pathways operate without significant overlap and are delineated by the Rad54 paralog Rdh54 in an ATPase-independent fashion. This study uncovers a novel layer of HR control in cells relying on nascent D-loop dynamics, revealing unsuspected complexities, and identifying a surprising role for a conserved Rad54 paralog.
Intrauterine CRH‐treated PBMC in repeated implantation failure

The intrauterine administration of activated autologous peripheral blood monocytes (PBMC) prior to embryo transfer seems to improve reproductive outcomes in women with repeated implantation failure (RIF). We have previously shown that the intrauterine administration of PBMC treated with corticotropin‐releasing hormone (CRH) prior to blastocyst transfer (day 5) improves significantly the clinical pregnancy rate of women with RIF. In the present crossover pilot study, we have investigated whether CRH‐PBMC treatment could be of benefit in case of fresh early cleavage stage embryo transfer (day 3) in women with RIF.
Comparison of selective hydrolysis of α-lactalbumin by acid Protease A and Protease M as alternative to pepsin: potential for β-lactoglobulin purification in whey proteins

Abstract The experiments reported in this research paper examine the potential of digestion using acidic enzymes Protease A and Protease M to selectively hydrolyse α-lactalbumin (α-La) whilst leaving β-lactoglobulin (β-Lg) relatively intact. Both enzymes were compared with pepsin hydrolysis since its selectivity to different whey proteins is known. Analysis of the hydrolysis environment showed that the pH and temperature play a significant role in determining the best conditions for achievement of hydrolysis, irrespective of which enzyme was used. Whey protein isolate (WPI) was hydrolysed using pepsin, Acid Protease A and Protease M by randomized hydrolysis conditions. Reversed-phase high performance liquid chromatography was used to analyse residual proteins. Regarding enzyme selectivity under various milieu conditions, all three enzymes showed similarities in the reaction progress and their potential for β-Lg isolation.
Challenges and Opportunities in Pediatric Heart Failure and Transplantation

503 In recent years, outcomes for pediatric cardiac transplantation (PCTx) have steadily improved, with current 5-year overall survival rates estimated at 83%. This progress may be attributed to improvements in pretransplantation management, selection of donor hearts, surgical technique, prevention and treatment of rejection, and minimization of treatment-related adverse events. Despite these advances, children who receive cardiac transplants experience significant morbidity and mortality, and there is considerable variability in outcomes, much of which cannot be explained by known clinical risk factors. One source of interindividual variability is genetic variation in the host. There is growing evidence that genomic variation leads to differences in immune response, response to therapies, and susceptibility to adverse outcomes such as malignancy and infection. This review will focus on the effect of variation in genes that encode enzymes, transporters, and drug target molecules that influence drug response. After review of the foundational principles of pharmacogenomics, evidence for the pharmacogenomic effects on cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil (MMF), and the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus will be reviewed and clinical implications of these findings discussed. Given the limited nature of evidence from studies of PCTx patients, support will also be drawn from non-PCTx research and pediatric renal transplantation. Genetic studies of nonpharmacogenes such as those in immunomodulatory pathways and variation in the donor genotype may contribute to risk prediction but are beyond the scope of this review.
A Dyadic Mediation Study on Social Support, Coping, and Stress Among Couples Starting Fertility Treatment

This study adopted a dyadic approach to explore the associations between social support and stress as mediated by coping among infertile couples. All these variables were infertility-specific. A total of 201 couples starting their first assisted reproductive technology (ART) treatment completed self-reports of infertility-specific support from spouse and from social network, infertility-related coping with four strategies (active-avoidance, active-confronting, passive-avoidance, and meaning-based), and infertility stress. The actor-partner interdependence model was applied. Results indicated that dyadic associations between support and stress were either direct or mediated by individual or partner coping, with differences based on gender, source of support, and coping strategy. For both genders, greater support from spouse was associated with lower individual and partner stress directly and indirectly, through lower partner’s use of active-avoidance coping. In men, the relationship between support from spouse and stress was also mediated by individual/partner avoidance coping strategies. As for support from social network, greater levels were directly associated with a lower partner stress in women and with higher individual stress in men. For both genders, the relationship between support from social network and stress was also mediated by active-confronting coping, which was associated with higher individual and partner stress. The findings suggest a potential protective role of support from spouse and an adverse effect of that from people outside the dyad. Interventions for couples starting ART treatment should focus on promoting infertility-related communication and support within the couple, which might help to reduce the use of infertility-specific maladaptive coping strategies.
Detecting DSM-5 somatic symptom disorder: criterion validity of the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Scale-8 (SSS-8) in combination with the Somatic Symptom Disorder – B Criteria Scale (SSD-12)

Background The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced somatic symptom and related disorders (SSD) to improve the diagnosis of somatoform disorders. It is unclear whether existing questionnaires are useful to identify patients with SSD. Our study investigates the diagnostic accuracy of the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Scale-8 (SSS-8) in combination with the Somatic Symptom Disorder – B Criteria Scale (SSD-12). Methods For this cross-sectional study, participants were recruited from a psychosomatic outpatient clinic. PHQ-15, SSS-8, and SSD-12 were administered and compared with SSD criteria from a diagnostic interview. Sensitivity and specificity were calculated for optimal individual and combined cutpoints. Receiver operator curves were created and area under the curve (AUC) analyses assessed. Results Data of n = 372 patients [31.2% male, mean age: 39.3 years (s.d. = 13.6)] were analyzed. A total of 56.2% fulfilled the SSD criteria. Diagnostic accuracy was moderate for each questionnaire (PHQ-15: AUC = 0.70; 95% CI = 0.65–0.76; SSS-8: AUC = 0.71; 95% CI = 0.66–0.77; SSD-12: AUC = 0.74; 95% CI = 0.69–0.80). Combining questionnaires improved diagnostic accuracy (PHQ-15 + SSD-12: AUC = 0.77; 95% CI = 0.72–0.82; SSS-8 + SSD-12: AUC = 0.79; 95% CI = 0.74–0.84). Optimal combined cutpoints were ⩾9 for the PHQ-15 or SSS-8, and ⩾23 for the SSD-12 (sensitivity and specificity = 69% and 70%). Conclusions The combination of the PHQ-15 or SSS-8 with the SSD-12 provides an easy-to-use and time- and cost-efficient opportunity to identify persons at risk for SSD. If systematically applied in routine care, effective screening and subsequent treatment might help to improve quality of life and reduce health care excess costs.
Increased mortality in bulimia nervosa and other eating disorders.

OBJECTIVE Anorexia nervosa has been consistently associated with increased mortality, but whether this is true for other types of eating disorders is unclear. The goal of this study was to determine whether anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified are associated with increased all-cause mortality or suicide mortality. METHOD Using computerized record linkage to the National Death Index, the authors conducted a longitudinal assessment of mortality over 8 to 25 years in 1,885 individuals with anorexia nervosa (N=177), bulimia nervosa (N=906), or eating disorder not otherwise specified (N=802) who presented for treatment at a specialized eating disorders clinic in an academic medical center. RESULTS Crude mortality rates were 4.0% for anorexia nervosa, 3.9% for bulimia nervosa, and 5.2% for eating disorder not otherwise specified. All-cause standardized mortality ratios were significantly elevated for bulimia nervosa and eating disorder not otherwise specified; suicide standardized mortality ratios were elevated for bulimia nervosa and eating disorder not otherwise specified. CONCLUSIONS Individuals with eating disorder not otherwise specified, which is sometimes viewed as a "less severe" eating disorder, had elevated mortality risks, similar to those found in anorexia nervosa. This study also demonstrated an increased risk of suicide across eating disorder diagnoses.