bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis Candidates Herbicide Through Optimization Quinclorac Containing 3-Methyl-1H-pyrazol-5-yl
Authors: Luo Dingfeng , Bai Haodong , Zhou Xiaomao , Wu Lamei , Zhang Chengjia , Wu Zhongchi , Li Zuren , Bai Lianyang 
Published: April 2021

To enhance quinclorac potency, twenty-five derivatives were synthesized containing 3-methyl-1H-pyrazol-5-yl by intermediate derivatization methods (IDMs). These compounds were confirmed by melting point (mp), 1HNMR, 13CNMR, and HRMS. The compound 1,3-dimethyl-1H-pyrazol-5-yl 3,7-dichloroquinoline-8-carboxylate (10a) was determined by X-ray diffraction. The activity of these compounds substituent on the phenyl was: electron-drawing group &gt; neutral group &gt; donor-drawing group, the results was like that of substituted benzyl group on pyrazole. The herbicidal activity assays showed that compounds 1-(2-fluorophenyl)-3-methyl-1H-pyrazol-5-yl 3,7-dichloroquinoline-8-carboxylate (8l, EC50 = 10.53 g/ha) and 10a (EC50 = 10.37 g/ha) had an excellent inhibition effect on barnyard grass in greenhouse experiment. Greenhouse safety experiment of rice exhibited almost no difference in plant height and fresh weight treated 10a at stage 1∼2-leaf of rice after 14 days but 8l had a detrimental effect. Two season field assays showed 10a herbicidal activity on barnyard grass at 150 g/ha as equal as 300 g/ha quinclorac in fields in 2019 and 2020. The study demonstrated that 10a could be further researched as a potential herbicide to control barnyard grass in fields.
Protective Effect of Intestinal Helminthiasis Against Tuberculosis Progression Is Abrogated by Intermittent Food Deprivation
Authors: Garrido-Amaro Cristina , Cardona Paula , Gassó Diana , Arias Lilibeth , Velarde Roser , Tvarijonativiciute Asta , Serrano Emmanuel , Cardona Pere-Joan 
Published: April 2021

BackgroundTuberculosis (TB) is still a major challenge for humankind. Because regions with the highest incidence also have a high prevalence of helminthiasis and nutritional scarcity, we wanted to understand the impact of these on TB progression.MethodsWe have developed an experimental murine model for active TB in C3HeB/FeJ, coinfected with Trichuris muris and Heligmosomoides polygyrus nematodes, and exposed to an environmental mycobacterium (M. manresensis) and intermittent fasting. Cause-effect relationships among these factors were explored with Partial Least Squares Path modelling (PLSPM).ResultsPrevious parasitization had a major anti-inflammatory effect and reduced systemic levels of ADA, haptoglobin, local pulmonary levels of IL-1β, IL-6, TNF-α, CXCL-1, CXCL-5 and IL-10. Oral administration of heat-killed M. manresensis resulted in a similar outcome. Both interventions diminished pulmonary pathology and bacillary load, but intermittent food deprivation reduced this protective effect increasing stress and inflammation. The PLSPM revealed nematodes might have protective effects against TB progression.ConclusionsSignificantly higher cortisol levels in food-deprivation groups showed it is a stressful condition, which might explain its deleterious effect. This highlights the impact of food security on TB eradication policies and the need to prioritize food supply over deworming activities.
The Seeds of Doubt: Finding Seeds in Intriguing Places
Authors: Grillo Federica , Campora Michela , Cornara Laura , Cascini Alberta , Pigozzi Simona , Migliora Paola , Sarocchi Francesca , Mastracci Luca 
Published: April 2021

Introduction: Seeds may be found in gastrointestinal tissue samples, and their multifaceted appearance may be challenging. The aim is to report a rough incidence of pathology samples which show seeds, specify the most frequent sample types and show an iconography of the most commonly identified seeds.Materials and Methods: Between 2017 and 2020, all gastrointestinal pathology cases in which seeds/seed parts were found, were collected and seed type described by referencing a seed image library.Results: Fifty cases with complete seeds/seed parts were collected: 16 colonic resections for colorectal cancer and diverticulosis, 13 appendiceal resections for appendicitis, 1 gastric resection. Fifteen cases were found in polypectomy specimens and 5 cases in colorectal endoscopic biopsies. Most frequent seed types were tomato, kiwi, blueberry, and blackberry seeds.Conclusion: Seeds may be found in up to 4% of specimens; their recognition may be useful to exclude parasitic infections as well as in forensic sciences.
Validating Automated Segmentation Tools in the Assessment of Caudate Atrophy in Huntington’s Disease
Authors: Mansoor Nina M. , Vanniyasingam Tishok , Malone Ian , Hobbs Nicola Z. , Rees Elin , Durr Alexandra , Roos Raymund A. C. , Landwehrmeyer Bernhard , Tabrizi Sarah J. , Johnson Eileanoir B. , Scahill Rachael I. 
Published: April 2021

Background: Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials.Methods: Using a cohort of early Huntington’s disease (HD) patients (n = 46) and controls (n = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. We then examined the effect of each of these baseline regions on the ability to detect change over 15 months using the established longitudinal Caudate Boundary Shift Integral (cBSI) method, an automated longitudinal pipeline requiring a baseline caudate region as an input.Results: All tools, except Freesurfer, generated significantly smaller caudate volumes than the manually derived regions. Jaccard indices showed poorer levels of overlap between each automated segmentation and manual delineation in the HD patients compared with controls. Nevertheless, each method was able to demonstrate significant group differences in volume (p &lt; 0.001). STEPS performed best qualitatively as well as quantitively in the baseline analysis. Caudate atrophy measures generated by the cBSI using automated baseline regions were largely consistent with those derived from a manually segmented baseline, with STEPS providing the most robust cBSI values across both control and HD groups.Conclusions: Atrophy measures from the cBSI were relatively robust to differences in baseline segmentation technique, suggesting that fully automated pipelines could be used to generate outcome measures for clinical trials.
Early Orthostatic Exercise by Head-Up Tilt With Stepping vs. Standard Care After Severe Traumatic Brain Injury Is Feasible
Authors: Riberholt Christian Gunge , Olsen Markus Harboe , Søndergaard Christian Baastrup , Gluud Christian , Ovesen Christian , Jakobsen Janus Christian , Mehlsen Jesper , Møller Kirsten 
Published: April 2021

Background:Intensive rehabilitation of patients after severe traumatic brain injury aims to improve functional outcome. The effect of initiating rehabilitation in the early phase, in the form of head-up mobilization, is unclear.Objective:To assess whether early mobilization is feasible and safe in patients with traumatic brain injury admitted to a neurointensive care unit.Methods:This was a randomized parallel-group clinical trial, including patients with severe traumatic brain injury (Glasgow coma scale &lt;11 and admission to the neurointensive care unit). The intervention consisted of daily mobilization on a tilt-table for 4 weeks. The control group received standard care. Outcomes were the number of included participants relative to all patients with traumatic brain injury who were approached for inclusion, the number of conducted mobilization sessions relative to all planned sessions, as well as adverse events and reactions. Information on clinical outcome was collected for exploratory purposes.Results:Thirty-eight participants were included (19 in each group), corresponding to 76% of all approached patients [95% confidence interval (CI) 63–86%]. In the intervention group, 74% [95% CI 52–89%] of planned sessions were carried out. There was no difference in the number of adverse events, serious adverse events, or adverse reactions between the groups.Conclusions:Early head-up mobilization is feasible in patients with severe traumatic brain injury. Larger randomized clinical trials are needed to explore potential benefits and harms of such an intervention.Clinical Trial Registration:[ClinicalTrials.gov], identifier [NCT02924649]. Registered on 3rd October 2016.
Natalizumab Pharmacokinetics and -Dynamics and Serum Neurofilament in Patients With Multiple Sclerosis
Authors: Proschmann Undine , Inojosa Hernan , Akgün Katja , Ziemssen Tjalf 
Published: April 2021

Background: Natalizumab (NAT) is a high-efficacy treatment for relapsing remitting multiple sclerosis (RRMS). However, it is associated with an increased risk of progressive multifocal leukoencephalopathy that sometimes requires treatment cessation with a risk of returning disease activity. The aim of this study was to characterize the pharmacokinetics and -dynamics as well as neurodestruction marker serum neurofilament light chain (sNfL) in patients with RRMS and secondary progressive MS (SPMS) stopping NAT in correlation to clinical data.Methods: In this study, 50 RRMS and 9 SPMS patients after NAT cessation were included. Five RRMS patients on NAT treatment holiday were evaluated. Clinical and radiological disease activity were systemically assessed by frequent exams after NAT stop. Free NAT concentration, cell bound NAT, α4-integrin expression and α4-integrin-receptor saturation as well as immune cell frequencies were measured for up to 4 months after NAT withdrawal. Additionally, sNfL levels were observed up to 12 months in RRMS and up to 4 months in SPMS patients.Results: NAT cessation was associated with a return of disease activity in 38% of the RRMS and 33% of the SPMS patients within 12 and 7 months, respectively. Concentration of free and cell bound NAT as well as α4-integrin-receptor saturation decreased in the RRMS and SPMS patients whereas α4-integrin expression increased over time. NAT induced increase of lymphocytes and its subsets normalized and a non-significant drop of NK and Th17 T-cells counts could be detected. All RRMS patients showed physiological sNfL levels &lt;8pg/ml 1 month after last NAT infusion. During follow-up period sNfL levels peaked up to 16-fold and were linked to return of disease activity in 19 of the 37 RRMS patients. Treatment holiday was also associated with a return of disease activity in 4 of 5 patients and with an increase of sNfL at an individual level.Conclusions: We demonstrate the reversibility of NAT pharmacodynamic and -kinetic markers. sNfL levels are associated with the recurrence of disease activity and can also serve as an early marker to predict present before onset of clinical or radiological disease activity on the individual level.
BPPV: Comparison of the SémontPLUS With the Sémont Maneuver: A Prospective Randomized Trial
Authors: Strupp Michael , Goldschagg Nicolina , Vinck Anne-Sophie , Bayer Otmar , Vandenbroeck Sebastian , Salerni Lorenzo , Hennig Anita , Obrist Dominik , Mandalà Marco 
Published: April 2021

Objective: To compare the efficacy of the Sémont maneuver (SM) with the new “SémontPLUS maneuver” (SM+) in patients with posterior canal BPPV canalolithiasis (pcBPPVcan).Methods and Patients: In a prospective trinational (Germany, Italy, and Belgium) randomized trial, patients with pcBPPVcan were randomly assigned to SM or SM+; SM+ means overextension of the head by 60+° below earth horizontal line during the movement of the patient toward the affected side. The first maneuver was done by the physician, and the subsequent maneuvers by the patients 9 times/day on their own. Each morning the patient documented whether vertigo could be induced. The primary endpoints were: “How long (in days) does it take until no attacks can be induced?” and “What is the efficacy of a single SM/SM+?”Results: In the 194 patients analyzed (96 SM, 98 SM+), it took 2 days (median, range 1–21 days, mean 3.6 days) for recovery with SM and 1 day (median, range 1-8 days, mean 1.8 days) with SM+ (p = 0.001, Mann-Whitney U-test). There was no difference in the second primary endpoint (chi2-test, p = 0.39).Interpretation: This prospective trial shows that SM+ is more effective than SM when repeated therapeutic maneuvers are performed but not when a single maneuver is performed. It also supports the hypothesis of the biophysical model: overextension of the head during step 2 brings the clot of otoconia beyond the vertex of the canal, which increases the effectivity.Classification of Evidence: This study provides Class I evidence that SM+ is superior to SM for multiple treatment maneuvers of pcBPPVcan.
Case Report: Ninjin'yoeito May Improve Quality of Life After Hospitalization for Acute Illness in Patients With Frailty
Authors: Kashima Masayuki 
Published: April 2021

Introduction: Frail patients are susceptible to a large number of diseases, and frailty particularly is known to develop after acute illness. No conventional drugs are known to prevent such exacerbation after acute illness. However, traditional Japanese medicine, Kampo, is thought to confer efficacious energy and nutritional supplements and serve to improve malaise after acute illness. Ninjin'yoeito is a representative Kampo medicine for such situation.Cases: We describe three frail patients hospitalized for acute illness who started taking ninjin'yoeito at the time of discharge.Case 1: An 87-year-old man admitted with acute prostatitis complicated by hypertension and chronic obstructive pulmonary disease (COPD). His 36-Item Short Form Health Survey (SF-36) score, which is representative of total quality of life and comprises eight components, showed consistent improvements after 4 and 12 weeks of ninjin'yoeito administration, especially for body pain (BP; scores from 41 to 51 and 100, respectively), social function (SF; 50, 100, 100), and mental health (MH; 75, 75, 90).Case 2: A 65-year-old man admitted with urinary tract infection complicated by primary sclerosing cholangitis and COPD. All SF-36 component scores showed improvement 12 weeks later: physical function (PF; 70–95), role physical (RP; 75–100), BP (72–84), general health (GH; 45–52), vitality (VT; 37.5–75), SF 75–100, role emotional (RE; 75–100), and MH (70–90).Case 3: An 80-year-old man admitted for pneumonia complicated with hypertension. SF-36 score was improved 4 weeks later for RP (68.8–100), BP (52–61), GH (52–72), VT (43.8–62.5), SF (37.5–100), and RE (58.3–91.7).Conclusion: Patients with frailty often have a worsened SF-36 score after discharge following acute illness, but the score may be improved by taking ninjin'yoeito.
Radiomic Analysis to Predict Outcome in Recurrent Glioblastoma Based on Multi-Center MR Imaging From the Prospective DIRECTOR Trial
Authors: Vils Alex , Bogowicz Marta , Tanadini-Lang Stephanie , Vuong Diem , Saltybaeva Natalia , Kraft Johannes , Wirsching Hans-Georg , Gramatzki Dorothee , Wick Wolfgang , Rushing Elisabeth , Reifenberger Guido , Guckenberger Matthias , Weller Michael , Andratschke Nicolaus 
Published: April 2021

BackgroundBased on promising results from radiomic approaches to predict O6-methylguanine DNA methyltransferase promoter methylation status (MGMT status) and clinical outcome in patients with newly diagnosed glioblastoma, the current study aimed to evaluate radiomics in recurrent glioblastoma patients.MethodsPre-treatment MR-imaging data of 69 patients enrolled into the DIRECTOR trial in recurrent glioblastoma served as a training cohort, and 49 independent patients formed an external validation cohort. Contrast-enhancing tumor and peritumoral volumes were segmented on MR images. 180 radiomic features were extracted after application of two MR intensity normalization techniques: fixed number of bins and linear rescaling. Radiomic feature selection was performed via principal component analysis, and multivariable models were trained to predict MGMT status, progression-free survival from first salvage therapy, referred to herein as PFS2, and overall survival (OS). The prognostic power of models was quantified with concordance index (CI) for survival data and area under receiver operating characteristic curve (AUC) for the MGMT status.ResultsWe established and validated a radiomic model to predict MGMT status using linear intensity interpolation and considering features extracted from gadolinium-enhanced T1-weighted MRI (training AUC = 0.670, validation AUC = 0.673). Additionally, models predicting PFS2 and OS were found for the training cohort but were not confirmed in our validation cohort.ConclusionsA radiomic model for prediction of MGMT promoter methylation status from tumor texture features in patients with recurrent glioblastoma was successfully established, providing a non-invasive approach to anticipate patient’s response to chemotherapy if biopsy cannot be performed. The radiomic approach to predict PFS2 and OS failed.
Pharmacological Evaluation of Safoof-e-Pathar Phori- A Polyherbal Unani Formulation for Urolithiasis
Authors: Ahmad Wasim , Khan Mohammad Ahmed , Ashraf Kamran , Ahmad Ayaz , Daud Ali Mohammad , Ansari Mohd Nazam , Kamal YT , Wahab Shadma , Zaidi SM Arif , Mujeeb Mohd. , Ahmad Sayeed 
Published: April 2021

Safoof-e-Pathar phori (SPP) is an Unani poly-herbomineral formulation, which has for a long time been used as a medicine due to its antiurolithiatic activity, as per the Unani Pharmacopoeia. This powder formulation is prepared using six different plant/mineral constituents. In this study, we explored the antiurolithiatic and antioxidant potentials of SPP (at 700 and 1,000 mg/kg) in albino Wistar rats with urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC). Long-term oral toxicity studies were performed according to the Organization for Economic Co-operation and Development (OECD) guidelines for 90 days at an oral dose of 700 mg/kg of SPP. The EG urolithiatic toxicant group had significantly higher levels of urinary calcium, serum creatinine, blood urea, and tissue lipid peroxidation and significantly (p&lt; 0.001 vs control) lower levels of urinary sodium and potassium than the normal control group. Histopathological examination revealed the presence of refractile crystals in the tubular epithelial cell and damage to proximal tubular epithelium in the toxicant group but not in the SPP treatment groups. Treatment of SPP at 700 and 1,000 mg/kg significantly (p&lt; 0.001 vs toxicant) lowered urinary calcium, serum creatinine, blood urea, and lipid peroxidation in urolithiatic rats, 21 days after induction of urolithiasis compared to the toxicant group. A long-term oral toxicity study revealed the normal growth of animals without any significant change in hematological, hepatic, and renal parameters; there was no evidence of abnormal histology of the heart, kidney, liver, spleen, or stomach tissues. These results suggest the usefulness of SPP as an antiurolithiatic and an antioxidant agent, and long-term daily oral consumption of SPP was found to be safe in albino Wistar rats for up to 3 months. Thus, SPP may be safe for clinical use as an antiurolithiatic formulation.
Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation
Authors: Wang Yan , Chen Min , Chen Hui , Wang Fang 
Published: April 2021

Background and Objectives: Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of ABCB1 (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol.Patients and Methods: This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. ABCB1 single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication.Results: We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of ABCB1 genotypes conformed to the Hardy–Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.586; TT vs. CC, p = 0.802; and CT vs. CC, p = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, p = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.0651; TT vs. CT, p = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, p = 0.341; GG vs. AA, p = 0.612; AG vs. AA, p = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events.Conclusion: rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.