Takshan/R1 huggingface dataset:
Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol).

BACKGROUND: This is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms. METHODS: MEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis. DISCUSSION: This systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42017076957.
I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma.

BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine "cold" codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated. RESULTS: Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab. CONCLUSIONS: I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed.
Factors affecting the extent of utilization of physiotherapy services by physicians in Saudi Arabia.

[Purpose] To investigate physicians' attitudes, opinions and experiences towards physiotherapy services as well as to identify the potential factors that may affect the extent of utilization of physiotherapy services (based on physicians' beliefs) in Saudi Arabia (SA). [ Subjects and Methods] A cross-sectional study was conducted. [ Results] A total of 108 respondents met the inclusion criteria. The respondents' attitude towards physiotherapy was slightly low (53.5%), while their opinions and experiences of physiotherapy indicated some important issues. For example, 50% of them believed that physiotherapists did not create a good awareness about physiotherapy services and 55.5% admitted that they did not have enough information about physiotherapy services. The most potential factor reported by physicians that may affect the extent of utilization of physiotherapy services was the lack of physiotherapist's skills and knowledge to assess and treat patients (55.3%), followed by the limited knowledge of physicians regarding the types of physiotherapy services (44.5%) and the lack of cooperation between physicians and physiotherapists (40.7%). [ Conclusion] There were some factors that limited the extent of utilization of physiotherapy services in SA. Physiotherapy academics and clinicians should attempt to change physicians' negative attitudes, promoting awareness to provide them with a better understanding of physiotherapy services.
Effects of Varying Photoperiodic Regimens on Critical Biological Fitness Traits of

Culex quinquefasciatus (Diptera: Culicidae) Mosquito Vector. This study investigated the effects of varying photoperiodic conditions on critical life stages' parameters of Culex quinquefasciatus. To this end, first larval stage was reared under different constant photoperiodic regimens: 0, 6 (short), 12 (equal), 13 (prevailing condition), and 18 and 24 (long) hours of light (hL). Duration of development, survivorship, emergence successes, adult longevity, caloric indices (CIs), and utilisation of teneral reserves for metamorphosis at each regimen were monitored. Analyses revealed significant negative effects of increasing photoperiod on all entomological variables measured. Short photo-phases elicited faster development times, increased life stages' survivorship and number at emergence, adult longevity, and CI for all life stages while increasing teneral components for adult life traits. The information generated in this study is important in understanding the role played by photoperiod in disease transmission and for development of integrated vector control strategies based on environmental manipulation.
Extended IgE profile based on an allergen macroarray: a novel tool for precision medicine in allergy diagnosis.

Background: Precision medicine (PM) is changing the scope of allergy diagnosis and treatment. An in vitro IgE assay, a prototype PM method, was developed in the sixties and has garnered increasing interest because of the introduction of recombinant components in the test. More recently, microarrays of allergen components have significantly improved the ability to describe the IgE profile. Aim of this study was to evaluate the characteristics of the newly developed Allergy Explorer (ALEX), a macroarray containing both extracted "whole" allergens and molecular components. This method allows the acquisition of an IgE profile comprising 282 reagents (157 allergen extracts and 125 components), resulting in the widest screening of potential allergens available. Methods: Sera from 43 patients with allergies were assayed with ALEX and then with ImmunoCAP ISAC. The results of the two tests were compared, and the consistency of the molecular results with the presence of IgE in the relevant extract was also evaluated. Results: A good correlation between ISAC and ALEX was observed. The ALEX results for second-level tests (i.e., specific IgE to complete extracted allergens) were consistent with the results obtained for the relevant components. Discussion: Despite differences in the methodology, the IgE profiles detected for molecular allergens by ALEX and ISAC were very similar. The differences were mainly related to the lower dynamic range of ALEX and to the use of a CCD inhibitor in the first incubation phase, which reduced the binding of IgE to CCD, as represented in the extracted allergens and components. Conclusion: Based on our findings, ALEX is a novel tool for describing the IgE profile in a PM setting, where the IgE assay must be performed on many allergens and components. In particular, polysensitized patients and patients with pollen-food syndrome will have a real advantage due the combination of the second and third levels of allergy diagnostics in the same chip.
Phytochemical Composition and Antioxidant Activities of Dianthus Thunbergii Hooper and Hypoxis Argentea Harv Ex Baker: Plants Used for the Management of Diabetes Mellitus in Eastern Cape, South Africa.

Background: Inhabitants of the Eastern Cape Province of South Africa use the roots of Dianthus thunbergii and corms of Hypoxis argentea to treat diabetes mellitus and other ailments. Objective: The objective of this study was to analyze the phytochemical composition and antioxidant activities of the aqueous and ethanol extracts of the roots and corms of two plants. Materials and Methods: Total phenolics, flavonoids, flavonols, proanthocyanidins, tannins, and alkaloids were determined by standard methods. The scavenging activities of the extracts against 1,1 diphenyl-2-picrylhydrazyl (DPPH), 2'-azino-bis (3-ethylbenthiazoline-6-sulfonic acid (ABTS), nitric oxide (NO), hydrogen peroxide (H2O2), and their ferric-reducing antioxidant potentials (FRAPs) were measured. Results: The ethanol extract of H. argentea had the highest content of phenolics (66.71 ± 2.71 mg gallic acid equivalent/g) and tannins (1.18 ± 0.07 mg TAE/g), while the ethanol extract of D. thunbergii gave higher contents of flavonoids and proanthocyanidins (62.21 ± 1.75 mg Qe/g and 432.62 ± 2.43 mg Ca/g, respectively). Flavonols were the most predominant in the aqueous extract of H. argentea (25.51 ± 1.92 mg Qe/g). We observed a concentration-dependent response in the ABTS- and H2O2-scavenging activities and FRAP values of the extracts and standards (Vitamin C, butylated hydroxytoluene, and rutin). The ethanol extracts of both plants generally demonstrated better antioxidant activities against H2O2, NO, and ABTS while also possessing better reducing power than the aqueous extracts. The aqueous extract of D. thunbergii, however, showed the best DPPH scavenging activity. Conclusion: The higher content of phytochemicals and antioxidant capacity obtained for the ethanol extracts of D. thunbergii and H. argentea may prove to be valuable information in selecting suitable extraction solvents for the medicinal applications of both plants. SUMMARY: Ethanol extracts of Hypoxis argentea had the highest levels of phenolics and tanninsEthanol extracts of Dianthus thunbergii had the highest levels of flavonoids and proanthocyanidinsEthanol extracts of both plants possess better antioxidant activityagainst hydrogen peroxide, nitric oxide, and ABTS as well as higher reducingpower than the aqueous extractsAqueous extract of Dianthus thunbergii had the highest free radical scavenging activity as measured with DPPH. Abbreviations used: ABTS: 2'-azino-bis (3-ethylbenthiazoline-6-sulfonic acid); BHT: Butylated hydroxytoluene; DPPH: 1,1 diphenyl-2-picrylhydrazyl; DTA: Dianthus thunbergii aqueous extract (16.6%); DTE: Dianthus thunbergii ethanol extract (2.4%); Fe3+-TPTZ: Ferric tripyridyltriazine; FRAP: Ferric-reducing antioxidant potentials; GAE: Gallic acid equivalent; HAA: Hypoxis argentea aqueous extract (3.2%); HAE: Hypoxis argentea ethanol extract (1.8%); Qe: Quercetin equivalence; ROS: Reactive oxygen species; TBA: Thiobarbituric acid;TCA: Trichloroacetic acid.
Spinal PA movements behave 'as if' there are limitations of local segmental mobility and are large enough to be perceivable by manual palpation: A synthesis of the literature.

BACKGROUND: Posterio-anterior (PA) movements are one type of passive intervertebral movement used to assess and treat perceived deficits in localized segmental mobility. OBJECTIVES: To describe: 1) The specific effects that reductions in segmental mobility would be expected to have on PA movements; 2) How differences in PA movements in clinical situations compare to what would be expected with reduced segmental mobility; and 3) Whether such differences in PA movements are likely to be perceivable by manual palpation. METHODS: Multiple modelling studies and in vivo measurements of PA movements are described. RESULTS: The findings indicate the differences in PA movements present in clinical conditions corresponds with the differences that would be expected with decreased segmental mobility. The differences both predicted from the modelling and found in clinical conditions were greatest at low levels of force. Additionally, the differences are large enough that individuals with training are likely to be capable of 1) consistently producing controlled movements with sufficiently small magnitudes of force to assess the movements, and 2) detecting the differences in stiffness expected from modelling and found in clinical situations. CONCLUSIONS: Implications for clinical practice and teaching include the need to attend to the stiffness of PA movements at lower levels of force than those typically described. The authors recommend a three tiered approach to assessment of PA movements which may assist in both clinical practice and teaching manual therapy skills.
Adoption of the American Academy of Pediatrics' neonatal hyperbilirubinemia guidelines and its effect on blood exchange transfusion rate in a tertiary care center in Amman, Jordan.

Introduction: Severe neonatal hyperbilirubinemia can cause mortality and serious morbidities. When phototherapy fails, neonates with severe hyperbilirubinemia should undergo double volume blood exchange transfusion (BET). As this procedure carries a significant risk of mortality and morbidity, adopting guidelines for the treatment of neonatal hyperbilirubinemia is critical to avoid hyperbilirubinemia toxicity and also the complication of an unindicated procedure. Methods: This study investigated the causes, complications, and trend of BET rate in our unit over a 13-year period. The medical charts and laboratory databases of all infants who underwent BET in Jordan University Hospital between 2003 and 2015 were retrospectively reviewed. Results: The rate of exchange cases decreased significantly after adopting the guidelines of American Academy of Pediatrics (P<0.0001). Most neonates were term newborns (69%). Average birth weight was 2,800 g. The most common causes of exchange transfusion were non-hemolytic conditions. Late prematurity alone accounted for 20% of the cases. Thrombocytopenia was the most commonly encountered complication (33%). Chronic neurological complications were seen in 12% of those who were followed for >12 months of age. Conclusions: This study showed a clear decline in the rate of BET after implementing the guidelines of American Academy of Pediatrics. In addition to improving the strategies for the identification and follow-up of at-risk newborns, we should intensify our efforts to prevent the progression of neonatal hyperbilirubinemia to the exchange level by enhancing parents' awareness of this potentially harmful neonatal condition.
Sepsis-induced long-term immune paralysis--results of a descriptive, explorative study.

BACKGROUND: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. METHODS: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4(+), CD8(+) T cells; CD25(+) CD127(-) regulatory T cells; CD14(+) monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. RESULTS: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8(+) cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4(+) T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. CONCLUSIONS: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.
A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury.

Introduction: C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP)]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI). Methods: Rat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN) was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine)-hexane (1,6-bisPC), which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS) induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68+ leukocytes. Results: The application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP). Structurally altered CRP induces leukocyte-endothelial interaction and induces ROS formation in leukocytes, the latter can be abrogated by blocking lipid raft-dependent signaling pathways with Nystatin. Stabilizing pCRP in its native pentameric state abrogates these pro-inflammatory effects. Importantly, these findings are confirmed in human IRI challenged muscle tissue. Conclusion: These results suggest that CRP is a potent modulator of IRI. Stabilizing the native pCRP conformation represents a promising anti-inflammatory therapeutic strategy by attenuation of leukocyte recruitment and ROS formation, the primary pathomechanisms of IRI.
No effect on the short-term of a decrease in blood viscosity on insulin resistance.

BACKGROUND: Blood viscosity (BV) might influence glucose delivery to peripheral tissues and play an important role in insulin resistance and diabetes mellitus. However, the exact relationship between BV and insulin resistance is not yet clear. OBJECTIVES: Aim of the present study is to evaluate the effects of the acute reduction in BV on insulin resistance, in healthy male subjects. METHODS: Fifteen healthy male blood donors have been studied before and 48 hours after blood donation. Blood and plasma viscosity have been measured at 37°C with a cone-plate viscometer. Insulin resistance has been evaluated by euglycemic/hyperinsulinemic clamp in eight subjects, and by iHOMA2 Index in further seven subjects. RESULTS: Blood viscosity was markedly reduced after blood donation (BV225 (cP) 4.53 ± 0.59 vs. 4.18 ± 0.31, p < 0.05). Insulin resistance was unchanged: MFFM clamp: 5.6 ± 4.5vs. 4.4 ± 2.2 and iHOMA2 Index 1.2 ± 0.6 vs. 1.2 ± 0.5, before vs. after respectively, p = NS. Blood pressure and lipids were unchanged after blood donation. CONCLUSIONS: The present results demonstrate that acute reduction of BV in healthy male subjects does not change the insulin resistance, measured using both euglycemic/hyperinsulinemic clamp and iHOMA2 Index. Further intervention studies are needed to assess the effect that the reduction in BV can have in subjects with insulin resistance.
Dental age estimation in southern Chinese population using panoramic radiographs: validation of three population specific reference datasets.

BACKGROUND: The accuracy of estimated age should depend on the reference data sets (RDS) from which the maturity scores or Ages of Attainment (AoA) were obtained. This study aimed to test the accuracy of age estimation from three different population specific dental reference datasets (RDS). METHODS: Two hundred and sixty six dental panoramic radiographs of subjects belonging to southern Chinese ethnicity were scored and dental age (DA) was estimated from three reference datasets: French-Canadian, United Kingdom (UK) Caucasian and southern Chinese. Statistical significance was set at p < 0.05 and for each method, the difference between the chronological age (CA) and dental age (CA-DA) was calculated using paired t-tests. In addition, Chi-square tests were performed to evaluate the accuracy of the age estimates within specific time interval from CA. RESULTS: The estimated age difference (CA-DA) using the French Canadian RDS was - 0.62 years for males and - 0.36 years for females. For the UK Caucasian RDS, the age difference was 0.25 years for males and 0.23 years for females. The difference observed using the southern Chinese RDS was - 0.02 years for both genders and the difference was not statistically significant (p > 0.05). The southern Chinese RDS estimated the age of 80% of subjects within ±12 months range, and 90% of subjects within ±18 months range (p < 0.05) showing it to be more accurate than other datasets. CONCLUSION: It is concluded that population specific Reference Data Sets improve the accuracy of dental age estimation.