bluuebunny/crossref_metadata_2025_split huggingface dataset:
An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells
Authors: Abedi Fatemeh , Davaran Soodabeh , Hekmati Malak , Akbarzadeh Abolfazl , Baradaran Behzad , Moghaddam Sevil Vaghefi 
Published: January 2021

AbstractThe combination therapy which has been proposed as the strategy for the cancer treatment could achieve a synergistic effect for cancer therapies and reduce the dosage of the applied drugs. On account of the the unique properties as the high absorbed water content, biocompatibility, and flexibility, the targeting nanogels have been considred as a suitable platform. Herein, a non-toxic pH/thermo-responsive hydrogel P(NIPAAm-co-DMAEMA) was synthesized and characterized through the free-radical polymerization and expanded upon an easy process for the preparation of the smart responsive nanogels; that is, the nanogels were used for the efficient and controlled delivery of the anti-cancer drug doxorubicin (DOX) and chemosensitizer curcumin (CUR) simultaneously like a promising strategy for the cancer treatment. The size of the nanogels, which were made, was about 70 nm which is relatively optimal for the enhanced permeability and retention (EPR) effects. The DOX and CUR co-loaded nanocarriers were prepared by the high encapsulation efficiency (EE). It is important to mention that the controlled drug release behavior of the nanocarriers was also investigated. An enhanced ability of DOX and CUR-loaded nanoformulation to induce the cell apoptosis in the HT-29 colon cancer cells which represented the greater antitumor efficacy than the single-drug formulations or free drugs was resulted through the In vitro cytotoxicity. Overall, according to the data, the simultaneous delivery of the dual drugs through the fabricated nanogels could synergistically potentiate the antitumor effects on the colon cancer (CC).
Engagement of TREM2 by a novel monoclonal antibody induces activation of microglia and improves cognitive function in Alzheimer’s disease models
Authors: Fassler Michael , Rappaport Maya Saban , Cuño Clara Benaim , George Jacob 
Published: January 2021

Abstract
Background
Genetic variants and mutations in triggering receptor expressed in myeloid cells (TREM2) are associated with premature and late onset Alzheimer’s disease (AD).

Methods
We developed a panel of monoclonal antibodies, the selected lead of which was avidly shown to bind the extracellular domain of human and murine TREM2.

Results
By engaging membrane-bound TREM2, the selected antibody was shown to promote their cellular proliferation, uptake of oligomeric beta amyloid/apoptotic neurons, and activation in a Syk and Akt dependent manner. The antibody was shown to avidly bind soluble TREM2 in the CSF from AD patients and blunted the proinflammatory program driven by its intracerebral injection. Upon in vivo treatment, the antibody was shown to improve cognitive function in experimental amyloidopathy models and to facilitate plaque-associated microglial coverage and activation.

Conclusion
Thus, we describe a novel monoclonal antibody targeting membrane bound and soluble TREM2, that improves cognitive function by inducing microglial activation and attenuating chronic neuroinflammation.
The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson’s disease
Authors: Dwyer Zach , Chaiquin Melany , Landrigan Jeffrey , Ayoub Kiara , Shail Pragya , Rocha Julianna , Childers Christie L. , Storey Kenneth B. , Philpott Dana J. , Sun Hongyu , Hayley Shawn 
Published: January 2021

Abstract
Background
Recent work has established that Parkinson’s disease (PD) patients have an altered gut microbiome, along with signs of intestinal inflammation. This could help explain the high degree of gastric disturbances in PD patients, as well as potentially be linked to the migration of peripheral inflammatory factors into the brain. To our knowledge, this is the first study to examine microbiome alteration prior to the induction of a PD murine model.

Methods
We presently assessed whether pre-treatment with the probiotic, VSL #3, or the inflammatory inducer, dextran sodium sulphate (DSS), would influence the PD-like pathology provoked by a dual hit toxin model using lipopolysaccharide (LPS) and paraquat exposure.

Results
While VSL #3 has been reported to have anti-inflammatory effects, DSS is often used as a model of colitis because of the gut inflammation and the breach of the intestinal barrier that it induces. We found that VSL#3 did not have any significant effects (beyond a blunting of LPS paraquat-induced weight loss). However, the DSS treatment caused marked changes in the gut microbiome and was also associated with augmented behavioral and inflammatory outcomes. In fact, DSS markedly increased taxa belonging to the Bacteroidaceae and Porphyromonadaceae families but reduced those from Rikencellaceae and S24-7, as well as provoking colonic pro-inflammatory cytokine expression, consistent with an inflamed gut. The DSS also increased the impact of LPS plus paraquat upon microglial morphology, along with circulating lipocalin-2 (neutrophil marker) and IL-6. Yet, neither DSS nor VSL#3 influenced the loss of substantia nigra dopamine neurons or the astrocytic and cytoskeleton remodeling protein changes that were provoked by the LPS followed by paraquat treatment.

Conclusions
These data suggest that disruption of the intestinal integrity and the associated microbiome can interact with systemic inflammatory events to promote widespread brain-gut changes that could be relevant for PD and at the very least, suggestive of novel neuro-immune communication.
Required concentration index quantifies effective drug combinations against hepatitis C virus infection
Authors: Kakizoe Yusuke , Koizumi Yoshiki , Ikoma Yukino , Ohashi Hirofumi , Wakita Takaji , Iwami Shingo , Watashi Koichi 
Published: January 2021

AbstractSuccessful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-hepatitis C virus (HCV) drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-HCV treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1b and 2a. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.
Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment
Authors: Buck W. Chris , Nguyen Hanh , Siapka Mariana , Basu Lopa , Greenberg Cowan Jessica , De Deus Maria Inês , Gleason Megan , Ferreira Ferreira , Xavier Carla , Jose Benedita , Muthemba Criménia , Simione Beatriz , Kerndt Peter 
Published: January 2021

Abstract
Background
Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique.

Methods
A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0–14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data.

Results
Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001).

Conclusions
Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed.
False negative rate of COVID-19 PCR testing: a discordant testing analysis
Authors: Kanji Jamil N. , Zelyas Nathan , MacDonald Clayton , Pabbaraju Kanti , Khan Muhammad Naeem , Prasad Abhaya , Hu Jia , Diggle Mathew , Berenger Byron M. , Tipples Graham 
Published: January 2021

Abstract
Background
COVID-19 is diagnosed via detection of SARS-CoV-2 RNA using real time reverse-transcriptase polymerase chain reaction (rtRT-PCR). Performance of many SARS-CoV-2 rtRT-PCR assays is not entirely known due to the lack of a gold standard. We sought to evaluate the false negative rate (FNR) and sensitivity of our laboratory-developed SARS-CoV-2 rtRT-PCR targeting the envelope (E) and RNA-dependent RNA-polymerase (RdRp) genes.

Methods
SARS-CoV-2 rtRT-PCR results at the Public Health Laboratory (Alberta, Canada) from January 21 to April 18, 2020 were reviewed to identify patients with an initial negative rtRT-PCR followed by a positive result on repeat testing within 14 days (defined as discordant results). Negative samples from these discordant specimens were re-tested using three alternate rtRT-PCR assays (targeting the E gene and N1/N2 regions of the nucleocapsid genes) to assess for false negative (FN) results.

Results
During the time period specified, 95,919 patients (100,001 samples) were tested for SARS-CoV-2. Of these, 49 patients were found to have discordant results including 49 positive and 52 negative swabs. Repeat testing of 52 negative swabs found five FNs (from five separate patients). Assuming 100% specificity of the diagnostic assay, the FNR and sensitivity in this group of patients with discordant testing was 9.3% (95% CI 1.5–17.0%) and 90.7% (95% CI 82.6–98.9%) respectively.

Conclusions
Studies to understand the FNR of routinely used assays are important to confirm adequate clinical performance. In this study, most FN results were due to low amounts of SARS-CoV-2 virus concentrations in patients with multiple specimens collected during different stages of infection. Post-test clinical evaluation of each patient is advised to ensure that rtRT-PCR results are not the only factor in excluding COVID-19.
Post-traumatic stress disorder and its associated factors among people who experienced traumatic events in east African countries, 2020: a protocol for systematic review and meta-analysis
Authors: Biresaw Mengesha Srahbzu , Gebeyehu Enguday Tirfeneh 
Published: January 2021

Abstract
Background
Post-traumatic stress disorder (PTSD) is the most commonly reported mental health consequence following disasters and traumatic events, either natural or man-made. Nothing is written regarding its pooled prevalence and pooled estimate of factors. Therefore, this study aimed to determine the pooled prevalence of PTSD and estimate the pooled effect of associated factors.

Methods
An English version of published articles will be retrieved using the following; PubMed/Medline, Africa-wides, Science Direct, Cochrane Library, Global Health, Google Scholar, EMBASE, and psycINFO. Research reports will be searched from October 10/2020 to November 10/2020. The research reports quality will be assessed using the Newcastle–Ottawa Scale. Relevant information from the searched research reports will be extracted in a Microsoft Excel format. After extraction, the data will be imported to STATA version 14.0 for analysis. An appropriate guideline for a systematic review and meta-analysis report will be used, i.e. the Preferred Reporting Items for Systematic reviews and Meta-Analyses. A random-effects meta-analysis model will be used to estimate the Der Simonian and Laird’s pooled prevalence of PTSD and its associated factors.

Discussion
This study aims to determine the pooled prevalence of PTSD and estimate the pooled effect of associated factors. Several kinds of research have reported the increasing magnitude of PTSD and its determinants in a different population. This might be due to reasons, such as little attention being given to the issue. Therefore, this study will try to fill this gap by giving new evidence-based results to attract policymakers’ attention.
Split-root systems: detailed methodology, alternative applications, and implications at leaf proteome level
Authors: Saiz-Fernández Iñigo , Černý Martin , Skalák Jan , Brzobohatý Břetislav 
Published: January 2021

AbstractBackgroundSplit-root systems (SRS) have many applications in plant sciences, but their implementation, depending on the experimental design, can be difficult and time-consuming. Additionally, the system is not exempt from limitations, since the time required for the establishment of the SRS imposes a limit to how early in plant development experiments can be performed. Here, we optimized and explained in detail a method for establishing a SRS in youngArabidopsis thalianaseedlings, both in vitro and in soil.ResultsWe found that the partial de-rooting minimized the recovery time compared to total de-rooting, thus allowing the establishment of the split-root system in younger plants. Analysis of changes in the Arabidopsis leaf proteome following the de-rooting procedure highlighted the distinct metabolic alterations that totally and partially de-rooted plants undergo during the healing process. This system was also validated for its use in drought experiments, as it offers a way to apply water-soluble compounds to plants subjected to drought stress. By growing plants in a split-root system with both halves being water-deprived, it is possible to apply the required compound to one half of the root system, which can be cut from the main plant once the compound has been absorbed, thus minimizing rehydration and maintaining drought conditions.ConclusionsPartial de-rooting is the suggested method for obtaining split-root systems in small plants likeArabidopsis thaliana, as growth parameters, survival rate, and proteomic analysis suggest that is a less stressful procedure than total de-rooting, leading to a final rosette area much closer to that of uncut plants. Additionally, we provide evidence that split root-systems can be used in drought experiments where water-soluble compounds are applied with minimal effects of rehydration.
Reliability of circulating fibrinogen in the diagnosis of prosthesis-related infections: a systematic review and meta-analysis
Authors: Zhu Xingyang , Zhang Haitao , Sun Xiaobo , Li Yijin , Li Jiahao , Zeng Yuqing , Deng Peng , Qi Xinyu , Chen Jinlun , Ye Pengcheng , Feng Wenjun , Li Jie , Zeng Jianchun , Zeng Yirong 
Published: January 2021

Abstract
Background
Fibrinogen (FIB) has recently been used as a biomarker to diagnose periprosthetic joint infection (PJI), but its reliability is still questionable. The aim of this study was to investigate the accuracy of FIB in the diagnosis of PJI after joint replacement.

Methods
We searched for literatures published in PubMed, EMBASE, and the Cochrane Library from the time of database inception to September 2020 and screened the studies according to the inclusion criteria. Then, we calculated the diagnostic parameters of FIB, including the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the curve (AUC), and diagnostic odds ratio (DOR). In addition, we implemented subgroup analyses to identify the sources of heterogeneity.

Results
Seven studies including 1341 patients were selected in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of FIB for PJI diagnosis were 0.78 (95% confidence interval [CI], 0.73–0.82), 0.83 (95% CI, 0.81–0.86), 4.60 (95% CI, 3.30–6.42), 0.24 (95% CI, 0.18–0.34), and 20.13 (95% CI, 14.80–27.36), respectively, while the AUC was 0.896.

Conclusion
The present study indicated that FIB was a reliable detection method and might be introduced into the diagnostic criteria for PJI. However, more robust studies are still needed to confirm the current findings, because most of the included studies were retrospective and had small sample sizes.
Determining the stability of minimally displaced lateral humeral condyle fractures in children: ultrasound is better than arthrography
Authors: Wu Xing , Li Xiongtao , Yang Shaowei , Wang Si , Xia Jingdong , Chen Xiaoliang , Shen Xiantao 
Published: January 2021

Abstract
Background
Evaluating of the articular cartilage status of the distal humeral epiphysis is difficult. Ultrasound imaging of the elbow is increasingly being used to confirm the integrity of the articular cartilage of minimally displaced lateral humeral condyle fractures in children with minimally displaced fractures. The aims of this study were to assess the correlations between ultrasound and arthrography findings for predicting the integrity of the cartilage hinge and to describe the utility of ultrasound in determining the need for pre-treatment.

Methods
Thirty-nine patients with minimally displaced lateral humeral condyle fractures who underwent ultrasound and arthrography examinations before surgery from May 2018 to December 2019 were included in this study. Ultrasound and arthrography predictors of the cartilage hinge status were independently measured. The ultrasound and arthrography results were compared.

Results
The mean displacement of the fractures was 3.1 mm (range, 2.0~5.0 mm). Arthrography showed incomplete fractures in 24 patients (61.5%) and complete fractures in 15 patients (38.5%). Ultrasound showed incomplete fractures in 25 patients (64.1%) and complete fractures in 14 patients (35.9%). The ultrasound and arthrography results of the integrity of the articular surface were consistent in 92.3% of the cases, including 23 that were predicted to have an intact articular surface and 13 that were predicted to have an incongruity articular surface. There was no correlation between the displacement and the fracture appearing complete on the ultrasound scan. The Pearson coefficient between ultrasound and arthrography for assessing the integrity of the articular surface was 0.837.

Conclusions
Ultrasound and arthrography assessments of the integrity of the cartilage hinge status appear to be highly consistent. Ultrasound can be used as a complementary tool with arthrography to predict the integrity of the cartilage hinge status in children with minimally displaced lateral humeral condyle fractures.

Level of evidence
Prospective study; level II.
Mid-term outcomes of the R3™ delta ceramic acetabular system in total hip arthroplasty
Authors: Davis Edward T. , Remes Ville , Virolainen Petri , Gebuhr Peter , Van Backlé Bart , Revell Matthew P. , Kopjar Branko 
Published: January 2021

Abstract
Background
Whilst bony fixation of hip replacement has stable solutions, there remains controversy over which bearing best optimizes longevity and function. Ceramic-on-ceramic (CoC) bearing combinations are associated with lower risk of revision due to aseptic loosening and dislocation. Evidence for long-term functional outcomes of modern, 4th generation CoC bearings is limited. The aim of this study was to analyze outcomes and complications of the R3™ Acetabular System (Smith & Nephew, Inc., Cordova, TN, USA) in combination with BIOLOX® Delta ceramic femoral head in patients undergoing primary total hip arthroplasty (THA).

Methods
Between June 2009 and May 2011, 175 patients (178 hips) were enrolled into a prospective, study at 6 sites in Europe and prospectively followed-up at 3 months and 1, 3, 5, and 7 years postoperative.

Results
Total WOMAC score improved from 63 (range, 22–91) preoperative to 8 (range, 0–8) at 1-year follow-up and remained unchanged at 7-year follow-up. Modified Harris hip score improved from 45 (range, 10–87) preoperative to 83 (range, 25–100) at 3 months, 91 (range, 42–100) at 1 year, and 92 (range, 46, 100) at 7 years. UCLA Activity Rating Scale score improved from 3.3 (range, 1–8) preoperative to 6.2 (range, 2–8) at 1 year; it marginally declined to 5.8 (range, 3–8) at 7-year follow-up. There were 4 trochanteric fractures and 5 patients died of unrelated reasons. Three hips were revised (2 periprosthetic fractures and 1 subluxation). The 7-year cumulative survival rate was 98.3%.

Conclusion
Clinical and functional improvements of THA with CoC bearing are maintained at 7 years postoperative.

Trial registration
ClinicalTrials.Gov, NCT03566082, Registered 10 January 2018—retrospectively registered,
Wrist tuberculosis-experience from eighteen cases: a retrospective study
Authors: Zou Longfei , Guo Xing , Xue Hao , Huang Denghua , Lv Hui , Tan Meiyun 
Published: January 2021

Abstract
Background
Wrist tuberculosis is a rare disease, which is easy to be misdiagnosed, leading to delayed treatment and poor prognosis. In this study, the clinical manifestations, diagnosis, treatment, and prognosis of 18 cases of wrist tuberculosis were analyzed retrospectively.

Methods
A retrospective study was conducted, investigating tuberculosis of the wrist, diagnosed in 18 patients from August 2013 to November 2018. Puncture biopsy confirmed the diagnosis. The study includes 11 males and 7 females, and 8 left and 10 right wrists. The average age was 53.5 ± 18.3 years and ranged from 15 to 81 years. The disease course was 1 to 42 months, with an average of 15.1 ± 11.3 months. Eighteen patients were underwent surgery and chemotherapy, 3 patients with severe bone defects were treated with wrist fusion, and 15 patients were underwent focus removal. The Gartland and Werley score, DASH score, the range of motion (ROM), grip strength, and imaging examinations were used to evaluate the postoperative recovery of the patients.

Results
Eighteen patients were followed up for 15 to 77 months, with an average follow up of 39.7 ± 15.3 months. The ESR and CRP levels were normal for all patients after chemotherapy. No recurrence of tuberculosis was observed in any of the patients. Among the 15 focus removals, the Gartland and Werley scores at admission, two weeks of chemotherapy, 1 month after surgery, and the last follow-up were 21.73 ± 4.33, 18.60 ± 3.16,11.27 ± 2.79, and 5.07 ± 2.28, respectively; and the DASH scores were 45.87 ± 5.58, 39.47 ± 4.72, 22.67 ± 6.54, and 6.73 ± 2.94, respectively. The range of motion (ROM) of the wrist and grip strength improved significantly when compared to those at admission. Among the three cases of wrist fusion, 2 were fixed with a steel plate and the fixation position of wrist joint was good. One case was fixed with Kirschner wire and resulted in a slightly deformed wrist joint.

Conclusion
For patients with wrist tuberculosis, early diagnosis, preoperative and postoperative chemotherapy, thorough focus removal, and appropriate fixation of the affected limb can help restore the function of the affected wrist, reduce the recurrence rate, and improve the quality of life.