bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Polymerization Approach to Synthesize Acid‐Degradable Block Copolymers Bearing Imine Pendants for Tunable pH‐Sensitivity and Enhanced Release
Authors: Hu Xiaolei , Oh Jung Kwon 
Published: September 2020

AbstractThe development of effective approaches to synthesize smart amphiphilic block copolymers (ABPs) exhibiting acid‐responsive degradation through the cleavage of acid‐labile imine bonds is extensively explored for controlled release of encapsulated biomolecules, particularly in drug delivery. Here, a new approach based on direct polymerization utilizing a controlled radical polymerization technique to synthesize acid‐degradable ABPs bearing pendant imine linkages in hydrophobic block is reported. The approach centers on the synthesis of a novel methacrylate bearing benzoic imine group that can be polymerized to form the hydrophobic imine pendant block. The formed ABPs respond to mild acidic pHs equivalent to tumoral and endosomal/lysosomal acidic environments. This causes the dissociation of self‐assembled nanoassemblies through change in their hydrophilic/hydrophobic balance upon the cleavage of pendant imine linkages to the corresponding aldehyde and primary amine, thus leading to the enhanced release of encapsulated drugs. The proof‐of‐concept results suggest that this robust approach is versatile to further design advanced nanoassemblies responding to dual/multiple stimuli, thus being more effective to intracellular drug delivery.
Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?
Authors: Dommershuijsen Lisanne J. , Heshmatollah Alis , Mattace Raso Francesco U.S. , Koudstaal Peter J. , Ikram M. Arfan , Ikram M. Kamran 
Published: September 2020

AbstractBackgroundOrthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population.MethodsThis study was embedded in the Rotterdam Study, a large prospective population‐based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD‐free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex.ResultsAt baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09–3.24). During a median (interquartile range) follow‐up of 16.1 years (8.5–22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59–1.58).ConclusionsOur study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia
Authors: Zamanpoor Mansour , Ghaedi Hamid , Omrani Mir Davood 
Published: September 2020

AbstractIntroductionRheumatoid arthritis is a common autoimmune disease and schizophrenia is a relatively common and debilitating neurological disorder. There are several common features between rheumatoid arthritis and schizophrenia. The inverse relationship between rheumatoid arthritis and schizophrenia has been replicated in several studies. Despite evidence for an inverse epidemiological relationship and negative correlations for risk between rheumatoid arthritis and schizophrenia, there are no biological data that directly support this inverse relationship.Materials and Methods’We meta‐analyzed the genome‐wide association studies to investigate the shared association loci between rheumatoid arthritis and schizophrenia at the genome‐wide scale. Rheumatoid arthritis‐ and schizophrenia‐associated loci in most recent genome‐wide association studies of rheumatoid arthritis and schizophrenia were tested. Genetic risk score analysis was also conducted to investigate the collective contribution of schizophrenia risk loci to rheumatoid arthritis risk.ResultsRheumatoid arthritis and schizophrenia meta‐genome‐wide association study showed a significant peak at the major histocompatibility complex locus on chromosome 6 in both rheumatoid arthritis‐schizophrenia meta‐genome‐wide association study and inverted meta‐genome‐wide association study datasets. Testing rheumatoid arthritis‐ and schizophrenia‐associated loci outside the human leukocyte antigen region showed no association with both rheumatoid arthritis and schizophrenia at a genome‐wide level of significance. Weighted genetic risk scores showed no evidence for a statistically significant association between rheumatoid arthritis and schizophrenia.ConclusionThe finding of our study is consistent with the role of the major histocompatibility complex locus in the genetic correlation between rheumatoid arthritis and schizophrenia, and suggests that either schizophrenia has an autoimmune basis and/or rheumatoid arthritis has an active neurological component.
REDBot: Natural language process methods for clinical copy number variation reporting in prenatal and products of conception diagnosis
Authors: Liu Mengmeng , Zhong Yunshan , Liu Hongqian , Liang Desheng , Liu Erhong , Zhang Yu , Tian Feng , Liang Qiaowei , Cram David S. , Wang Hua , Wu Lingqian , Yu Fuli 
Published: September 2020

AbstractBackgroundCurrent copy number variation (CNV) identification methods have rapidly become mature. However, the postdetection processes such as variant interpretation or reporting are inefficient. To overcome this situation, we developed REDBot as an automated software package for accurate and direct generation of clinical diagnostic reports for prenatal and products of conception (POC) samples.MethodsWe applied natural language process (NLP) methods for analyzing 30,235 in‐house historical clinical reports through active learning, and then, developed clinical knowledge bases, evidence‐based interpretation methods and reporting criteria to support the whole postdetection pipeline.ResultsOf the 30,235 reports, we obtained 37,175 CNV‐paragraph pairs. For these pairs, the active learning approaches achieved a 0.9466 average F1‐score in sentence classification. The overall accuracy for variant classification was 95.7%, 95.2%, and 100.0% in retrospective, prospective, and clinical utility experiments, respectively.ConclusionBy integrating NLP methods in CNVs postdetection pipeline, REDBot is a robust and rapid tool with clinical utility for prenatal and POC diagnosis.
Targeted muscle reinnervation at the time of amputation in the management of complex regional pain syndrome of the lower extremity
Authors: Stoehr Jenna R. , Sood Rachita , Jordan Sumanas W. , Dumanian Gregory A. 
Published: September 2020

AbstractBackgroundComplex regional pain syndrome (CRPS) is a chronic, posttraumatic condition defined by severe pain and sensorimotor dysfunction. In cases of severe CRPS, patients request amputation, which may cause phantom limb pain (PLP) and residual limb pain (RLP). Targeted muscle reinnervation (TMR) reduces the risk of PLP and RLP. This report describes the use of TMR at the time of amputation in a series of patients with CRPS.Patients and methodsFour patients (ages 38–71 years) underwent TMR at the time of amputation for CRPS between April 2018 and January 2019. Three patients had a history of trauma and surgery to the affected limb. All patients attempted pharmacologic and interventional treatments for 1–7 years before requesting amputation. Three patients underwent below‐knee amputations (BKA) and one had an above‐knee amputation (AKA). Target muscles included the soleus, gastrocnemius, and flexor hallucis longus (BKA), and semitendinosus, biceps femoris, and vastus medialis (AKA). Postoperative phantom and residual limb pain symptoms were collected via a telephone survey adapted from the Patient‐Reported Outcomes Measurement Information System (PROMIS).ResultsThere were no complications related to the TMR procedure. Average follow‐up time was 12.75 months. Patients reported varied outcomes: two had RLP and PLP, one had RLP only, and one had PLP only. All patients reported successful prosthetic use.ConclusionTMR may be performed at the time of amputation for CRPS. Further study is necessary to determine the effect of TMR on pain, pain medication use, prosthesis use, and other domains of function.
Food Structure Modulates the Bioavailability of Triglycerides and Vitamin D, and Partly That of Lutein: A Randomized Trial with a Crossover Design in Adults
Authors: Gleize Béatrice , Hiolle Manon , Meunier Nathalie , Pereira Bruno , Richard Ruddy , Savary‐Auzeloux Isabelle , Buffière Caroline , Peyron Marie‐Agnès , Halimi Charlotte , Caris‐Veyrat Catherine , Nau Françoise , Reboul Emmanuelle 
Published: September 2020

ScopeThe specific effect of the food matrix structure on fat‐soluble micronutrient bioavailability is only partly understood. Evaluating fat‐soluble micronutrient bioavailability after consumption of foods displaying similar composition but different structure is aimed at.Methods and resultsTwelve healthy subjects are enrolled in a randomized, open label, crossover postprandial trial. Four different model foods are tested: custard, pudding, sponge cake, and biscuit. Vitamin D3, lutein, and triglyceride chylomicron responses, evaluated as postprandial areas under the curve, are then assayed. Custard triglyceride response is higher than pudding and biscuit responses (up to +122.7%, p < 0.0001). Sponge cake vitamin D3 response is higher than biscuit response (+26.6%, p = 0.047). No difference between the model foods are observed regarding lutein responses. Triglyceride responses peak at 3 h for all conditions, while vitamin D3 and lutein peaks are delayed by 1 h with the biscuit matrix compared to other model foods.ConclusionFood structure can significantly impact on triglyceride and vitamin D3 bioavailability in terms of absorbed amounts and/or maximum absorption time. The data highlight positive correlations between triglyceride, vitamin D, and lutein nutrient responses. These results are of particular interest to develop functional foods for population subgroups such as the elderly.
Fabrication and characterization of a stemless plastic scintillation detector
Authors: Hupman Michael A. , Monajemi Thalat , Valitova Irina , Hill Ian G. , Syme Alasdair 
Published: September 2020

PurposeTo fabricate a stemless plastic scintillation detector (SPSD) and characterize its linearity and reproducibility, and its dependence on energy and dose per pulse; and to apply it to clinical PDD and output factor measurements.MethodsAn organic bulk heterojunction photodiode was fabricated by spin coating a blend of P3HT and PCBM onto an ITO‐coated glass substrate and depositing aluminum top contacts. Eljen scintillators (~5 × 5 × 5 mm3; EJ‐204, EJ‐208, and EJ‐260) or Saint‐Gobain scintillators (~3 × 3 × 2 mm3; BC‐400 and BC‐412) were placed on the opposite side of the glass using a silicone grease (optical coupling agent) creating the SPSD. Energy dependence was measured by using 100, 180, and 300 kVp photon beams from an orthovoltage treatment unit (Xstrahl 300) and 6 and 10 MV photons from a Varian TrueBeam linear accelerator. Linearity, dose per pulse dependence, output factors, and PDDs were measured using a 6 MV photon beam. PDDs and output factors were compared to ion chamber measurements. A control device was fabricated by substituting polystyrene (PS) for the P3HT/PCBM layer. No photocurrent should be generated in the control device and so any current measured is due to Compton current in the electrodes, wires, and surroundings from the irradiation. Output factors were corrected by subtracting the signal measured using the control device from the photodiode measured signal to yield the photocurrent.ResultsEach SPSD had excellent linearity with dose having an r2 of 1 and sensitivities of 1.07 nC/cGy, 1.04 nC/cGy, 1.00 nC/cGy and 0.10 nC/cGy, and 0.10 nC/cGy for EJ‐204, EJ‐208, EJ‐260 (5 × 5 × 5 mm3 volumes), BC‐400, and BC‐412 (3 × 3 × 2 mm3 volumes), respectively. No significant dose per pulse dependence was measured. Output factors matched within 1% for the large scintillators for field sizes of 5 × 5 cm2 to 25 × 25 cm2, but there was a large under‐response at field sizes below 3 × 3 cm2. After correcting the signal of the small scintillators by subtracting the current measured using the PS control, the output factors agreed with the ion chamber measurements within 1% from field sizes 1 × 1 cm2 to 20 × 20 cm2. The impact of Cerenkov emissions in the scintillator was effectively corrected with a simple reflective coating on the scintillator. In comparison to a 6 MV photon beam, the large scintillator SPSDs exhibited 37%, 52%, and 73% of the response at energies 100 kVp, 180 kVp and 300 kVp, respectively.ConclusionThe principle of the SPSD was demonstrated. Devices had excellent linearity, reproducibility, and no significant dose per pulse dependence, and a simple reflective coating was sufficient to correct for Cerenkov emissions from within the scintillator. The devices demonstrated similar energy dependence to other scintillator detectors used in a radiotherapy setting.
Muscle phenotype of a rat model of Duchenne muscular dystrophy
Authors: Iyer Shama R. , Xu Su , Shah Sameer B. , Lovering Richard M. 
Published: September 2020

AbstractIntroductionOur aim was to assess key muscle imaging and contractility parameters in the Duchenne muscular dystrophy (DMD) rat model (Dmd‐KO rat), which have not yet been characterized sufficiently.MethodsWe performed in‐vivo magnetic resonance imaging (MRI) for thigh and leg muscles, and performed hematoxylin and eosin (H&E) staining and in‐vivo muscle contractility testing in specific hindlimb muscles.ResultsMRI prior to testing muscle contractility revealed multiple, unevenly distributed focal hyperintensities in the Dmd‐KO rat quadriceps and tibialis anterior muscles. H&E staining showed corresponding areas of inflammation and ongoing regeneration. In‐vivo contractile testing showed maximal force generated by Dmd‐KO muscles was significantly lower, and susceptibility to injury was ~ two‐fold greater in the Dmd‐KO rats compared to wild‐type (WT) rats.DiscussionTogether, the MRI findings, histological findings, and the low strength and high susceptibility to injury in muscles support use of the Dmd‐KO rat as an animal model of DMD.
Low energy shock wave‐delivered intravesical botulinum neurotoxin‐A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder
Authors: Nageib Mohammed , Zahran Mohamed H. , El‐Hefnawy Ahmed S. , Barakat Nashwa , Awadalla Amira , Aamer Haytham G. , Khater S. , Shokeir Ahmed A. 
Published: September 2020

AbstractPurposeTo study the effect of intravesical instillation of botulinum neurotoxin‐A (BoNT‐A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process.Material and MethodsForty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT‐A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor‐α [TNF‐α] and interleukin‐6 [IL‐6]) were compared among groups.ResultsBoNT‐A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT‐A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT‐A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT‐A was associated with statistically significant lower expression of TNF‐α and IL‐6 expression by 37% and 66% in comparison to LESW group (p = .001).ConclusionIntravesical instillation of BoNT‐A plus LESW is an effective method for increasing the urothelial permeability to BoNT‐A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti‐inflammatory and antioxidative stress effect.
Which combination is most effective in women with idiopathic overactive bladder, including bladder training, biofeedback, and electrical stimulation? A prospective randomized controlled trial
Authors: Firinci Sule , Yildiz Necmettin , Alkan Hakan , Aybek Zafer 
Published: September 2020

AbstractObjectiveTo evaluate the efficacy of single and combined use of biofeedback (BF) and electrical stimulation (ES) added to bladder training (BT) on incontinence‐related quality of life (QoL) and clinical parameters in women with idiopathic overactive bladder (OAB).Material and MethodsSeventy women were randomized into four groups as follows: Group 1 received BT alone (n = 18), Group 2 received BT + BF (n = 17), Group 3 received BT + ES (n = 18), and Group 4 received BT + BF + ES (n = 17). BF and ES were performed 3 days a week, 20 min a day, a total of 24 sessions for 8 weeks. All women were evaluated in terms of incontinence severity (pad test), pelvic floor muscles strength (perineometer), 3‐day voiding diary (frequency of voiding, nocturia, incontinence episodes, and number of pads), QoL (incontinence impact questionnaire), treatment success (positive response rate), cure/improvement rate, treatment satisfaction (Likert scale), and discomfort level (visual analog scale).ResultsAt the end of the treatment, severity of incontinence, frequency of voiding, incontinence episodes, and treatment satisfaction significantly improved in Group 3 and Group 4 compared with the other two groups. In Group 3 and Group 4, high statistically significant values were found in cure/improvement and positive response rates as opposed to Group 1 and Group 2. In Group 2 and Group 3, statistically significant improvements were seen in nocturia and QoL compared with Group 1. Moreover, statistically significant improvements in nocturia and QoL were found in Group 4 compared with the other three groups. There was no difference in the discomfort level of application between the groups.ConclusionWe conclude that in the first‐line conservative treatment of women with idiopathic OAB: (i) adding BF and/or ES to BT increases treatment effectiveness, (ii) clinical efficiency is greater when the combination includes ES, (iii) BT + BF + ES (triple combination) is the most effective treatment option in reducing nocturia and improving QoL.
Assessing the incidence of osteosarcoma among teriparatide users based on Medicare Part D and US State Cancer Registry Data
Authors: Gilsenan Alicia , Midkiff Kirk , Harris David , McQuay Lisa , Hunter Shannon , Kellier‐Steele Nicole , Andrews Elizabeth 
Published: September 2020

AbstractPurposeDuring preclinical testing, teriparatide caused a dose‐dependent increase in the incidence of osteosarcoma in rats. This study compared the incidence rate of osteosarcoma among patients aged ≥65 years treated with teriparatide vs a matched‐comparator cohort.MethodsThis population‐based comparative‐cohort study matched exposure details for each teriparatide user, identified via Medicare Part D prescription claims, and up to four comparators based on age, sex, zip code, date of claim for filled prescription, and number of unique therapeutic classes dispensed. Outcomes were identified via linkage with participating cancer registries. All US state cancer registries were invited to participate.ResultsOverall, 153 316 patients in the teriparatide cohort and 613 247 in the comparator cohort were linked to 811 osteosarcoma cases from 26 participating state cancer registries (68% of US patients aged ≥65 years diagnosed 2007‐2014). Analysis on a subset of cohorts revealed they were balanced for known osteosarcoma risk factors and Charlson comorbidity index. Mean duration of teriparatide treatment was 10 months. No osteosarcoma cases were observed in the teriparatide cohort; the incidence rate in the comparator cohort was consistent with the background incidence rate among adults aged ≥65 years. The incidence rate ratio was 0.0 (95% confidence interval, 0.0‐3.2).ConclusionsFor US patients aged ≥65 years, incidence of osteosarcoma among those treated with teriparatide ranges from 0 to 3.2 times the incidence of osteosarcoma in those treated with other medications. Given low incidence of osteosarcoma, this range of effect is inconsistent with a large absolute increase in osteosarcoma risk.
Impact of a nationwide prospective drug utilization review program to improve prescribing safety of potentially inappropriate medications in older adults: An interrupted time series with segmented regression analysis
Authors: Jang Suhyun , Jeong Sohyun , Kang Eunjeong , Jang Sunmee 
Published: September 2020

AbstractPurposeA nationwide prospective drug utilization review (DUR) for potentially inappropriate medications (PIMs) in older adults was implemented in October 2015 in South Korea. We aimed to evaluate the effects of the DUR on reducing PIMs, in comparison with the PIMs defined using the Beers criteria that were not included in the DUR.MethodsWe divided the study period into a pre‐ and post‐DUR period. The monthly percentage of patients or prescriptions with at least one PIM in the DUR or defined by the Beers criteria was calculated using national health insurance data. We evaluated the effect of the DUR on the prevalence of PIM use in older adults using an interrupted time series with segmented regression analysis.ResultsThe prevalence of older adults prescribed PIMs in the DUR decreased by 0.49% (95% confidence interval (CI) [−0.60, −0.37]) based on patient‐based measures and, by 0.41% (95% CI [−0.58, −0.23]) based on prescription‐based measure, immediately after DUR implementation. However, there were no statistically significant changes in trend. Further, the prevalence of PIMs based on the Beers criteria had no statistically significant changes in terms of either level or trend. After 12 months of DUR, there was a reduction of 11.5% (95% CI [2.6 20.4]) relative to the PIMs in Beers.ConclusionsThe implementation of a nationwide prospective DUR lowered the prescription of PIMs for older adults. On the other hand, PIMs that were not included were unchanged. Thus, it is worth considering expanding the DUR list to improve prescribing safety.