bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delta Tocotrienol as a Supplement to FOLFOXIRI in First Line Treatment of Metastatic Colorectal Cancer. A Randomized, Double-blind, Placebo-controlled Phase II Study
Authors: Raunkilde Louise , Hansen Torben Frøstrup , Havelund Birgitte Mayland , Thomsen Caroline Brenner , Rafaelsen Søren Rafael , Lindebjerg Jan , Jensen Lars Henrik 
Published: January 2022

Abstract
Purpose Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with its possible neuroprotective and anti-inflammatory effects reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo controlled trial in mCRC patients receiving first line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI).Methods We randomly assigned 70 mCRC patients to FOLFOXIRI plus δ-tocotrienol or FOLFOXIRI plus placebo. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo x 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy.Results Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio (HR) of 0.70 (95% CI 0.36-1.36, p=0.29)). In the placebo group 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p=0.047).Conclusion The addition of δ-tocotrienol to FOLFOXIRI did not significantly prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different between the two groups. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.Clinicaltrials.gov identifier NCT02705300. Date of registration March 10, 2016.
Gait Rehabilitation for Foot and Ankle Impairments in Early Rheumatoid Arthritis: a Feasibility Study of a New Gait Rehabilitation Programme (GREAT Strides)
Authors: Hendry Gordon , Bearne Lindsay , Foster Nadine E , Godfrey Emma L , Hider Samantha , Jolly Lisa , Mason Helen , McConnachie Alex , McInnes Iain B , Patience Aimie , Sackley Catherine , Sekhon Mandeep , Stanley Bethany , Leeden Marike Van Der , Williams Anita , Woodburn Jim , Steultjens Martijn 
Published: January 2022

Abstract
BackgroundFoot impairments in early rheumatoid arthritis are common and lead to progressive deterioration of lower limb function. A gait rehabilitation programme underpinned by psychological techniques to improve adherence, may preserve gait and lower limb function. This study evaluated the feasibility of a novel gait rehabilitation intervention (GREAT Strides) and a future trial. MethodsThis was a mixed methods feasibility study with embedded qualitative components. People with early (<2 years) rheumatoid arthritis (RA) and foot pain were eligible. Intervention acceptability was evaluated using a questionnaire. Adherence was evaluated using the Exercise Adherence Rating Scale (EARS). Safety was monitored using case report forms. Participants and therapists were interviewed to explore intervention acceptability. Deductive thematic analysis was applied using the Theoretical Framework of Acceptability. For fidelity, audio recordings of interventions sessions were assessed using the Motivational Interviewing Treatment Integrity (MITI) scale. Measurement properties of four candidate primary outcomes, rates of recruitment, attrition and data completeness were evaluated.Results35 participants (68.6% female) with median age (inter-quartile range [IQR]) 60.1 [49.4-68.4] years and disease duration 9.1 [4.0-16.2] months), were recruited and 23 (65.7%) completed 12-week follow-up. Intervention acceptability was excellent; 21/23 were confident that it could help and would recommend it; 22/23 indicated it made sense to them. Adherence was good, with a median [IQR] EARS score of 17/24 [12.5-22.5]. One serious adverse event that was unrelated to the study was reported. Twelve participants’ and 9 therapists’ interviews confirmed intervention acceptability, identified perceptions of benefit, but also highlighted some barriers to completion. Mean MITI scores for relational (4.38) and technical (4.19) aspects of motivational interviewing demonstrate good fidelity. The Foot Function Index disability subscale performed best in terms of theoretical consistency and was deemed most practical. ConclusionGREAT Strides was viewed as acceptable by patients and therapists, and we observed high intervention fidelity, good patient adherence and no safety concerns. A future trial to test the additional benefit of GREAT Strides to usual care will benefit from amended eligibility criteria, refinement of the intervention and strategies to ensure higher follow-up rates. The Foot Function Index disability subscale was identified as the primary outcome.Trial registrationISRCTN14277030
A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects
Authors: Ding Fangfang , Huang Jie , Feng Zeying , Kuang Yun , Yang Shuang , Xiang Yuxia , Zou Chan , YANG Guoping 
Published: January 2022

Abstract
Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021
Seasonal Variation and Source Apportionment of Inorganic and Organic Components in PM2.5: Influence of Organic Markers Application on PMF Source Apportionment
Authors: Xue Qianqian , Tian Ying-Ze , Wei Yang , Song Danlin , Huang Fengxia , Tian Shanshan , Feng Yinchang 
Published: January 2022

Abstract
PM2.5 samples collected over a 1-year period in a Chinese megacity were analyzed for organic carbon (OC), elemental carbon (EC), water soluble ions, elements and organic markers such as polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes, and n-alkanes. In order to study the applicability of organic markers in source apportionment, this study analyzes the relationship between organic and inorganic components, and four scenarios were implemented by incorporating different combinations of organic and inorganic tracers. A positive correlation of SO42− with 4 rings PAHs can prove that coal burning directly emits a portion of sulfate. A positive correlation of NO3− with 5-7 rings PAHs are found, implying collective impacts from the vehicle source. The concentrations of OC and EC positively correlate with the 5-7 rings PAHs and Cu and Zn, which proves that part of Cu and Zn comes from vehicle emissions. Five factors were identified by incorporating only conventional components, including secondary source (SS, 30%), urban fugitive dust (UFD, 14%), cement dust (CD, 4%), traffic source (TS, 19%) and coal combustion (CC, 14%). Six factors were identified by incorporating conventional components and PAHs, including SS (28%), UFD (15%), CD (4%), CC (13%), gasoline vehicles (GV, 12%) and diesel vehicles (DV, 10%). Eight factors were identified by incorporating conventional components, PAHs, hopanes, and n-alkanes, including SS (26%), UFD (17%), CD (3%), GV (14%), DV (8%), immature coal combustion (ICC, 5%), mature coal combustion (MCC, 10%) and biogenic source (BS, 1%).
Analysis of Exotic Parasitic Infection in a Large Group of Imported Dogs Following an Animal Welfare Investigation
Authors: Wright Ian , Whitfield Vanessa , Hanaghan Runa , Upjohn Melissa , Boyden Paula 
Published: January 2022

Abstract
Background: Increased dog relocation can cause dissemination of parasite and vector populations and this is being recognised in countries across Northern Europe, including the UK. Data regarding the prevalence of exotic infections entering the UK would be beneficial to vets to help assess pets entering the UK from abroad, and to help calculate risk of establishment of novel pathogens. One such group of dogs were seized as part of an RSPCA-led animal welfare investigation and blood tested for exotic pathogens. Methods: As part of the RSPCA investigation, 151 dogs were removed from the site. Blood tests were performed for Babesia. canis, Ehrlichia canis, Hepatozoon canis and Leishmania infantum by PCR, Br.canis by antibody serology and D.immitis by blood antigen. In addition to pathogen screening, a serology titre for Rabies was measured for each dog. A clinical examination was performed by a veterinary surgeon and clinical signs recorded. Clinical signs data were analysed by the Fisher-Freeman-Halton Exact TestResults: Overall, 24% of the dogs tested positive for an infection. Two dogs were positive for Br.canis antibodies and had no clinical signs indicative of infection. Leishmania infantum was identified in 10.5% of dogs with all but two cases being diagnosed in dogs whose microchip originated in Romania. Hepatozoon canis was identified in 9.6% of dogs, all of which had a Romanian microchip. Dirofilaria immitis was identified in 4.1% of dogs, B.canis in 2.3% of dogs and E.canis was only present in 1.5% of dogs tested. Only four dogs were found to have co-infections. No significant association was found between the pathogens detected and presenting clinical signs. Conclusions: This study demonstrates a range of exotic pathogens entering the UK including Br.canis and demonstrates the importance of screening imported dogs. The emphasis for early recognition of exotic pathogens in imported dogs has relied on screening based on relevant clinical signs and the country of origin. While these factors are useful, this study demonstrated no significant association between presenting clinical signs and the pathogens carried.
Local Recurrence After Endoscopic Submucosal Dissection of Early Gastric Cancer
Authors: Choi Cheol Woong , Kim Su Jin , Ryu Dae Gon , Kang Dae Hwan , Kim Hyung Wook , Park Su Bum , Nam Hyeong Seok , Lee Si Hak , Hwang Sun Hwi 
Published: January 2022

Abstract
Background: Endoscopic submucosal dissection (ESD) is considered the treatment of choice for early gastric cancer (EGC) with a negligible risk of lymph node metastasis. However, locally recurrent lesions on artificial ulcer scars are difficult to manage. Therefore, predicting the risk of local recurrence after ESD is important to manage and prevent the event. This study aimed to elucidate risk factors associated with local recurrence after ESD of EGC.Methods: Between November 2008 and February 2016, consecutive patients (n=641; mean age, 69.3±9.5 years; men, 77.2%) with EGC who underwent ESD at a single tertiary referral hospital were retrospectively analyzed to evaluate the incidence and factors associated with local recurrence. Local recurrence was defined as the development of neoplastic lesions at or adjacent to the site of the post-ESD scar.Results: En bloc and complete resection rates were 97.8% and 93.6%, respectively. The local recurrence rate after ESD was 3.1%. The mean follow-up period after ESD was 50.7±32.5 months. One case of gastric cancer-related death (0.15%) was noted, wherein the patient had refused additive surgical resection after ESD for EGC with lymphatic and deep submucosal invasion. Lesion size ≥15 mm, incomplete histologic resection, undifferentiated adenocarcinoma, scar, and absence of erythema of the surface were associated with a higher risk of local recurrence. Conclusions: Predicting local recurrence during regular endoscopic surveillance after ESD is important, especially in patients with a larger lesion size (≥15 mm), incomplete histologic resection, surface changes of scars, and no erythema of the surface.
Mutational Analysis of Compound Heterozygous Mutation P.q6x/p.h232r in Srd5a2 Causing 46,xy Disorder of Sex Development
Authors: Yang Hui , Li Liwei , Zhang Junhong , Li Qing , Qiao Li , Li Pengcheng , Cui Yi , Li Shujun , Hao Shirui , Wu Tongqian , Liu Lili , Yin Jianmin , Hu Pingsheng , Dou Xiaowei , Li Shuping 
Published: January 2022

Abstract
Background: Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration. Results: To clarify the cause of 46,XY DSD in the affected family focused on here, SRD5A2 sequencing was performed. Heterozygous p.H232R mutation was identified in the proband’s father, so we concluded that this mutation originated from the paternal side of the family and did not cause 46,XY DSD. Meanwhile, heterozygous p.Q6X mutation was identified in the proband’s mother, maternal uncle, and maternal grandfather, indicating that this mutation originated from maternal side of the family and did not cause 46,XY DSD. To clarify the effect of the p.H232R mutation in SRD5A2 on dihydrotestosterone (DHT) production, p.H232R mutant SRD5A2 plasmids were transfected into HEK293 cells. LC-MS indicated that DHT production decreased compared with that in cells transfected with wild-type SRD5A2.Conclusions: Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.
Detection of Road Traffic Anomalies Based on Computational Data Science
Authors: Raiyn Jamal 
Published: January 2022

Abstract
The development of 5G has enabled the autonomous vehicles (AVs) to have full control over all functions. The AV acts autonomously and collects travel data based on various smart devices and sensors, with the goal of enabling it to operate under its own power. However, the collected data is affected by several sources that degrade the forecasting accuracy. To manage large amounts of traffic data in different formats, a computational data science approach (CDS) is proposed. The computational data science scheme introduced to detect anomalies in traffic data that negatively affect traffic efficiency. The combination of data science and advanced artificial intelligence techniques, such as deep leaning provides higher degree of data anomalies detection which leads to reduce traffic congestion and vehicular queuing. The main contribution of the CDS approach is summarized in detection of the factors that caused data anomalies early to avoid long- term traffic congestions. Moreover, CDS indicated a promoting results in various road traffic scenarios.
Main Controlling Factors and Empirical Models for Total Mercury and Methylmercury Accumulation in Rice (Oryza Sativa L.)
Authors: Du Shuyang , Wang Xingxiang , Zhou Zhigao , Zhang Taolin , Kamran Muhammad , Ding Changfeng 
Published: January 2022

Abstract
It has been reported that rice consumption is the main mercury (Hg) exposure pathway for humans, and soil properties could significantly affect the methylation and accumulation process of Hg in soil-rice system. In this study, 19 paddy soil with various properties were spiked with exogenous Hg(II) at three concentration levels to conduct a pot experiment after a 60-days aging period. Stepwise multiple linear regression was applied to determine the controlling soil factors and develop prediction models for the methylmercury (MeHg) concentration in soil and total Hg (THg) and MeHg in brown rice. The results showed that THg in brown rice was positively correlated with THg in soil, while it had a negative correlation with soil pH and clay content. Soil organic matter (OM) promoted Hg methylation and inhibited the accumulation of MeHg in brown rice. Soil pH and clay content were negative factors when soil MeHg was used to predict MeHg in brown rice. THg and MeHg in brown rice could be well predicted by soil THg, pH and clay content. These results may provide a theoretical basis for safe production of rice in Hg contaminated paddy field.
Marked Changes in Biochar’s Ability to Directly Immobilize Cd in Soil: Implication for Biochar Remediation of Cd Contaminated Soil
Authors: Ren Xinhao , He Jiayi , Chen Qiao , He Fei , Wei Ting , Jia Honglei , Guo Junkang 
Published: January 2022

Abstract
To investigate the change in biochar’s ability to directly immobilize Cd in soil ，a successive wheat cultivation with experiment was conducted. Three biochar with different Cd adsorption mechanisms were added into soils and a mesh bag was used to separate the soil particles (> 1 μm) from biochar. The results showed that the ash contents and anionic contents (CO 3 2- and PO 4 3- ) of the biochar decreased with the cultivation time, while the oxygen-containing functional groups content and CEC of the biochar increased. Resultly, the Cd concentration on biochar decreased, highly decreased by 68.9% for WBC300, while unstable Cd species (acid soluble and reducible fraction of Cd) on biochar increased with successive cultivation, increasing from 3% to 17% for WBC300 in FS. Correspondingly, the ability of biochar to inhibit Cd accumulation in wheat decreased. The results of this study illustrated that the ability of biochar to directly immobilize Cd in soil is not permanent, it gradually decreases with aging in soil. The adsorption mechanism of Cd on biochar changed from precipitation to complexation and ion exchange processes could be the main reason.
Reconstructed Brain Like Neural Network R-KFDNN
Authors: rongrong zhu 
Published: January 2022

Abstract
Through the neural system damage and repair process of human brain, we can construct the complex deep learning and training of the repair process such as the damage of brain like high-dimensional flexible neural network system or the local loss of data, so as to prevent the dimensional disaster caused by the local loss of high-dimensional data. How to recover and extract feature information when the damaged neural system (flexible neural network) has amnesia or local loss of stored information. Information extraction generally exists in the distribution table of the generation sequence of the key group of the higher dimension or the lower dimension to find the core data stored in the brain. The generation sequence of key group exists in a hidden time tangent cluster. Brain like slice data processing runs on different levels, different dimensions, different tangent clusters and cotangent clusters. The key group in the brain can be regarded as the distribution table of memory fragments. Memory parsing has mirror reflection and is accompanied by the loss of local random data. In the compact compressed time tangent cluster, it freely switches to the high-dimensional information field, and the parsed key is buried in the information.
Flexible Material Formulations for 3D Printing of Porous Beds with Applications in Bioprocess Engineering
Authors: Dimartino Simone , Galindo-Rodriguez Giuseppe Rafael , Simon Ursula , Conti Mariachiara , Sarwar Sulaiman , Narayanan Selva Athi , Jiang Qihao , Christofi Nick 
Published: January 2022

Abstract
Background: 3D printing is revolutionizing many industrial sectors and has the potential to enhance also the biotechnology and bioprocessing fields. Here, we propose a new flexible material formulation to 3D print support matrices with complex, perfectly ordered morphology and with tuneable properties to suit a range of applications in bioprocess engineering. Findings: Supports for packed-bed operations were fabricated using functional monomers as the key ingredients, enabling matrices with bespoke chemistry such as charged groups, chemical moieties for further functionalization, and hydrophobic/hydrophilic groups. Other ingredients, e.g. crosslinkers and porogens, provide the opportunity to further tune the mechanical properties of the supports and the morphology of their porous network. Through this approach, we fabricated and demonstrated the operation of Schoen gyroid columns with I) positive and negative charges for ion-exchange chromatography, II) enzyme bioreactors with immobilized trypsin to catalyse hydrolysis, and III) bacterial biofilms bioreactors for fuel desulfurization. Conclusions: This study demonstrates a simple, cost-effective and flexible fabrication of customized 3D printed supports for different biotechnology and bioengineering applications.