bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xylopic acid-amodiaquine and xylopic acid-artesunate combinations are effective in managing malaria in Plasmodium berghei-infected mice
Authors: Osei Silas Acheampong , Biney Robert Peter , Obese Ernest , Agbenyeku Mary Atta-Panyi , Attah Isaac Yaw , Ameyaw Elvis Ofori , Boampong Johnson Nyarko 
Published: February 2021

Abstract
Background
Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore, this study evaluated whether the co-administrations of xylopic acid-amodiaquine and xylopic acid-artesunate combinations will produce a synergistic anti-malarial effect.

Methods
Antiplasmodial effect of xylopic acid (XA: 3, 10, 30, 100, 150 mg kg−1), artesunate (ART: 1, 2, 4, 8, 16 mg kg−1), and amodiaquine (AQ: 1.25, 2.5, 5, 10, 20 mg kg−1) were evaluated in Plasmodium berghei (strain ANKA)-infected mice to determine respective ED50s. Artemether/lumefantrine was used as the positive control. XA/ART and XA/AQ were subsequently administered in a fixed-dose combination of their ED50s (1:1) and the combination fractions of their ED50s (1/2, 1/4, 1/8, 1/16, and 1/32) to determine the experimental ED50s (Zexp). An isobologram was constructed to determine the nature of the interaction between XA/ART, and XA/AQ combinations by comparing Zexp with the theoretical ED50 (Zadd). Bodyweight and 30-day survival post-treatment were additionally recorded.

Results
ED50s for XA, ART, and AQ were 9.0 ± 3.2, 1.61 ± 0.6, and 3.1 ± 0.8 mg kg−1, respectively. The Zadd, Zexp, and interaction index for XA/ART co-administration was 5.3 ± 2.61, 1.98 ± 0.25, and 0.37, respectively while that of XA/AQ were 6.05 ± 2.0, 1.69 ± 0.42, and 0.28, respectively. The Zexp for both combination therapies lay significantly (p < 0.001) below the additive isoboles showing XA acts synergistically with both ART and AQ in clearing the parasites. High doses of XA/ART combination significantly (p < 0.05) increased the survival days of infected mice with a mean hazard ratio of 0.40 while all the XA/AQ combination doses showed a significant (p < 0.05) increase in the survival days of infected mice with a mean hazard ratio of 0.27 similar to AL. Both XA/ART and XA/AQ combined treatments significantly (p < 0.05) reduced weight loss.

Conclusion
Xylopic acid co-administration with either artesunate or amodiaquine produces a synergistic anti-plasmodial effect in mice infected with P. berghei.
The effect of temperature on the stability of PCSK-9 monoclonal antibody: an experimental study
Authors: Kongmalai Tanawan , Chuanchaiyakul Nalinee , Sripatumtong Chattip , Tansit Tunsuda , Srinoulprasert Yuttana , Klinsukon Nareerak , Thongtang Nuntakorn 
Published: February 2021

Abstract
Background
PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries.

Methods
Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA.

Results
Average subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was − 5.8 ± 4.4% (P = 0.005) and − 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and − 9.7 ± 11.8% (P = 0.04) and − 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were − 5.2 ± 2.9% (P = 0.001) and − 2.6 ± 4.9% (P = 0.16) for alirocumab, and − 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab.

Conclusion
Proper drug storage according to manufacturer’s recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.
Regulating the immunosuppressive tumor microenvironment to enhance breast cancer immunotherapy using pH-responsive hybrid membrane-coated nanoparticles
Authors: Gong Chunai , Yu Xiaoyan , Zhang Wei , Han Lu , Wang Rong , Wang Yujie , Gao Shen , Yuan Yongfang 
Published: February 2021

AbstractThe combination of an immuno-metabolic adjuvant and immune checkpoint inhibitors holds great promise for effective suppression of tumor growth and invasion. In this study, a pH-responsive co-delivery platform was developed for metformin (Met), a known immuno-metabolic modulator, and short interfering RNA (siRNA) targeting fibrinogen-like protein 1 mRNA (siFGL1), using a hybrid biomimetic membrane (from macrophages and cancer cells)-camouflaged poly (lactic-co-glycolic acid) nanoparticles. To improve the endo-lysosomal escape of siRNA for effective cytosolic siRNA delivery, a pH-triggered CO2gas-generating nanoplatform was developed using the guanidine group of Met. It can react reversibly with CO2to form Met-CO2for the pH-dependent capture/release of CO2. The introduction of Met, a conventional anti-diabetic drug, promotes programmed death-ligand 1 (PD-L1) degradation by activating adenosine monophosphate-activated protein kinase, subsequently blocking the inhibitory signals of PD-L1. As a result, siFGL1 delivery by the camouflaged nanoparticles of the hybrid biomimetic membrane can effectively silence the FGL1 gene, promoting T-cell-mediated immune responses and enhancing antitumor immunity. We found that a combination of PD-L1/programmed death 1 signaling blockade and FGL1 gene silencing exhibited high synergistic therapeutic efficacy against breast cancer in vitro and in vivo. Additionally, Met alleviated tumor hypoxia by reducing oxygen consumption and inducing M1-type differentiation of tumor-related macrophages, which improved the tumor immunosuppressive microenvironment. Our results indicate the potential of hybrid biomimetic membrane-camouflaged nanoparticles and combined Met-FGL1 blockade in breast cancer immunotherapy.
Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers
Authors: Nooraei Saghi , Bahrulolum Howra , Hoseini Zakieh Sadat , Katalani Camellia , Hajizade Abbas , Easton Andrew J. , Ahmadian Gholamreza 
Published: February 2021

AbstractVirus-like particles (VLPs) are virus-derived structures made up of one or more different molecules with the ability to self-assemble, mimicking the form and size of a virus particle but lacking the genetic material so they are not capable of infecting the host cell. Expression and self-assembly of the viral structural proteins can take place in various living or cell-free expression systems after which the viral structures can be assembled and reconstructed. VLPs are gaining in popularity in the field of preventive medicine and to date, a wide range of VLP-based candidate vaccines have been developed for immunization against various infectious agents, the latest of which is the vaccine against SARS-CoV-2, the efficacy of which is being evaluated. VLPs are highly immunogenic and are able to elicit both the antibody- and cell-mediated immune responses by pathways different from those elicited by conventional inactivated viral vaccines. However, there are still many challenges to this surface display system that need to be addressed in the future. VLPs that are classified as subunit vaccines are subdivided into enveloped and non- enveloped subtypes both of which are discussed in this review article. VLPs have also recently received attention for their successful applications in targeted drug delivery and for use in gene therapy. The development of more effective and targeted forms of VLP by modification of the surface of the particles in such a way that they can be introduced into specific cells or tissues or increase their half-life in the host is likely to expand their use in the future. Recent advances in the production and fabrication of VLPs including the exploration of different types of expression systems for their development, as well as their applications as vaccines in the prevention of infectious diseases and cancers resulting from their interaction with, and mechanism of activation of, the humoral and cellular immune systems are discussed in this review.
Health-related quality of life and self-reported cognitive function in patients with delayed neurocognitive recovery after radical prostatectomy: a prospective follow-up study
Authors: Kahl Ursula , Callsen Sarah , Beck Stefanie , Pinnschmidt Hans , von Breunig Franziska , Haese Alexander , Graefen Markus , Zöllner Christian , Fischer Marlene 
Published: February 2021

Abstract
Background
Delayed neurocognitive recovery (DNCR) is a common and serious complication after radical prostatectomy. We hypothesized that patients with DNCR in the early postoperative period would report reduced health-related quality of life (HRQoL) and more cognitive failures 12 months after surgery, compared with patients without DNCR.

Methods
We performed a 12-month follow-up on 367 patients who had been enrolled in a prospective observational trial to study the incidence of DNCR after radical prostatectomy. Patients were screened for preoperative cognitive impairment and depression. We defined DNCR as a decline in cognitive function between days 3 and 5 after surgery, compared with baseline assessments. We evaluated HRQoL and cognitive failures 12 months after surgery with the 36-item Short Form Health Survey and the Cognitive Failures Questionnaire. General linear models were used to analyze associations of DNCR with HRQoL and cognitive failures.

Results
Delayed neurocognitive recovery in the early postoperative period was significantly associated with self-reported cognitive failures (B for no DNCR =  − 0.411 [95% CI: − 0.798;0.024], p = 0.038), but not with physical (B = 0.082 [95% CI: − 0.021;0.186], p = 0.118) or mental HRQoL (B =  − 0.044 [95% CI: − 0.149;0.062], p = 0.417) 12 months after surgery. Preoperative depression screening scores were significantly associated with self-reported cognitive failures and both physical and mental HRQoL 12 months after surgery.

Conclusions
Delayed neurocognitive recovery in the early period after radical prostatectomy has a long-term impact on patients’ daily lives by impairing memory, attention, action, and perception. Therefore, prevention of DNCR must be a priority for physicians and researchers. Consequent preoperative screening for depressive symptoms may facilitate early psycho-oncological intervention to improve postoperative HRQoL.

Trials registrationDRKS00010014, date of registration: 21.03.2016, retrospectively registered.
On the way home: a BCI-FES hand therapy self-managed by sub-acute SCI participants and their caregivers: a usability study
Authors: Zulauf-Czaja Anna , Al-Taleb Manaf K. H. , Purcell Mariel , Petric-Gray Nina , Cloughley Jennifer , Vuckovic Aleksandra 
Published: February 2021

Abstract
Background
Regaining hand function is the top priority for people with tetraplegia, however access to specialised therapy outwith clinics is limited. Here we present a system for hand therapy based on brain-computer interface (BCI) which uses a consumer grade electroencephalography (EEG) device combined with functional electrical stimulation (FES), and evaluate its usability among occupational therapists (OTs) and people with spinal cord injury (SCI) and their family members.

Methods
Users: Eight people with sub-acute SCI (6 M, 2F, age 55.4 ± 15.6) and their caregivers (3 M, 5F, age 45.3 ± 14.3); four OTs (4F, age 42.3 ± 9.8). User Activity: Researchers trained OTs; OTs subsequently taught caregivers to set up the system for the people with SCI to perform hand therapy. Hand therapy consisted of attempted movement (AM) of one hand to lower the power of EEG sensory-motor rhythm in the 8-12 Hz band and thereby activate FES which induced wrist flexion and extension. Technology: Consumer grade wearable EEG, multichannel FES, custom made BCI application. Location: Research space within hospital. Evaluation: donning times, BCI accuracy, BCI and FES parameter repeatability, questionnaires, focus groups and interviews.

Results
Effectiveness: The BCI accuracy was 70–90%. Efficiency: Median donning times decreased from 40.5 min for initial session to 27 min during last training session (N = 7), dropping to 14 min on the last self-managed session (N = 3). BCI and FES parameters were stable from session to session. Satisfaction: Mean satisfaction with the system among SCI users and caregivers was 3.68 ± 0.81 (max 5) as measured by QUEST questionnaire. Main facilitators for implementing BCI-FES technology were “seeing hand moving”, “doing something useful for the loved ones”, good level of computer literacy (people with SCI and caregivers), “active engagement in therapy” (OT), while main barriers were technical complexity of setup (all groups) and “lack of clinical evidence” (OT).

Conclusion
BCI-FES has potential to be used as at home hand therapy by people with SCI or stroke, provided it is easy to use and support is provided. Transfer of knowledge of operating BCI is possible from researchers to therapists to users and caregivers.
Trial registration Registered with NHS GG&C on December 6th 2017; clinicaltrials.gov reference number NCT03257982, url: https://clinicaltrials.gov/ct2/show/NCT03257982.
The occurrence rate and clinical application of Osteo-line on the femur neck
Authors: Zou Mingchen , Wu Haotian , Yao Shuangquan , Ren Dong , Liu Song , Liu Yueju , Song Zhaohui 
Published: February 2021

Abstract
Background
This study was done to observe the incidence of Osteo-line on the femur neck and to explore the clinical application of Osteo-line in osteotomy.

Methods
Eighty-nine adult femur specimens were selected to observe the incidence of Osteo-line on the femur neck. From August 2015 to January 2019, a total of 278 patients who completed unilateral hip arthroplasty at the Third Hospital of Hebei Medical University were retrospectively included. Patients who accepted osteotomy via Osteo-line on the femur neck were defined as the experimental group (n = 139), and patients who accepted osteotomy via traditional method (The femoral distance 1.5 cm above the trochanter was retained for osteotomy by visual inspection.) were defined as the control group (n = 139). According to the postoperative pelvic X-ray, Photoshop was used to evaluate the leg length discrepancy (LLD) by the CFR-T-LT method.

Results
Among the 89 specimens, the incidence of anterior Osteo-line was 75.28%, and the incidence of posterior Osteo-line was 100%. According to the clinical application results, the incidence of anterior Osteo-line on the femur neck was 80%, and the incidence of posterior Osteo-line was 100%. The Osteo-line was clearer than those on the femoral specimens. Twenty-six cases had LLD greater than 1 cm (9.29%), including 2 cases in the experimental group and 24 cases in the control group. The average postoperative LLD in the experimental group (0.19 ± 0.38 mm) was significantly shorter than in the control group (0.54 ± 0.51 mm)(P = 0.005).

Conclusion
The incidence of Osteo-line on the femur neck was high, and patients who accepted osteotomy via Osteo-line on the femur neck can achieve shorter postoperative LLD than the control group.
Inter-rater variability of three-dimensional fracture reduction planning according to the educational background
Authors: Zindel Christoph , Fürnstahl Philipp , Hoch Armando , Götschi Tobias , Schweizer Andreas , Nagy Ladislav , Roner Simon 
Published: February 2021

AbstractBackgroundComputer-assisted three-dimensional (3D) planning is increasingly delegated to biomedical engineers. So far, the described fracture reduction approaches rely strongly on the performance of the users. The goal of our study was to analyze the influence of the two different professional backgrounds (technical and medical) and skill levels regarding the reliability of the proposed planning method. Finally, a new fragment displacement measurement method was introduced due to the lack of consistent methods in the literature.Methods3D bone models of 20 distal radius fractures were presented to nine raters with different educational backgrounds (medical and technical) and various levels of experience in 3D operation planning (0 to 10 years) and clinical experience (1.5 to 24 years). Each rater was asked to perform the fracture reduction on 3D planning software.ResultsNo difference was demonstrated in reduction accuracy regarding rotational (p= 1.000) and translational (p= 0.263) misalignment of the fragments between biomedical engineers and senior orthopedic residents. However, a significantly more accurate planning was performed in these two groups compared with junior orthopedic residents with less clinical experience and no 3D planning experience (p< 0.05).ConclusionExperience in 3D operation planning and clinical experience are relevant factors to plan an intra-articular fragment reduction of the distal radius. However, no difference was observed regarding the educational background (medical vs. technical) between biomedical engineers and senior orthopedic residents. Therefore, our results support the further development of computer-assisted surgery planning by biomedical engineers. Additionally, the introduced fragment displacement measure proves to be a feasible and reliable method.Level of EvidenceDiagnostic Level II
Small supernumerary marker chromosomes derived from chromosome 14 and/or 22
Authors: Liehr Thomas , Williams Heather E. , Ziegler Monika , Kankel Stefanie , Padutsch Niklas , Al-Rikabi Ahmed 
Published: February 2021

AbstractSmall supernumerary marker chromosomes (sSMCs) are additional derivative chromosomes present in an otherwise numerically and structurally normal karyotype. They may derive from each of the 24 human chromosomes, and most contain a normal centromeric region with an alphoid sequence from a single chromosome. The majority of human chromosomes have a unique centromeric DNA-sequence enabling their indubitable characterization. However, chromosomes 14 and 22 share a common centromeric sequence D14/22Z1, and sSMCs with this DNA-stretch can derive from either chromosome. Euchromatin-carrying sSMCs(14 or 22) may be further characterized by molecular cytogenetics. However, in most diagnostic laboratories, heterochromatic sSMCs cannot be differentiated between chromosomes 14 or 22 derivation and are often reported as der(14 or 22). Still, heterochromatic sSMC(14 or 22) can be distinguished from each other using the D22Z4 probe (non-commercial) localized to 22p11.2. Herein, 355 sSMC(14 or 22) analyzed in the authors’ laboratory during the last ~ 20 years are summarized to address the questions: (1) What are the true frequencies of chromosome 14- and chromosome 22- derived sSMCs within D14/22Z1-positive cases? (2) Does sub-characterization of sSMC(14) and sSMC(22) make a difference in routine diagnostics? These questions could be answered as follows: (ad 1) within the studied group of sSMCs ~ 40% are derived from chromosome 14 and ~ 60% from chromosome 22; (ad 2) the knowledge on exact sSMC origin can help to save costs in routine diagnostics; i.e. in a clinically abnormal person with sSMC(14) a test for uniparental disomy is indicated, which is not necessary if a chromosome 22 origin for the sSMC was determined.
Enhanced contextual fear memory in peroxiredoxin 6 knockout mice is associated with hyperactivation of MAPK signaling pathway
Authors: Phasuk Sarayut , Pairojana Tanita , Suresh Pavithra , Yang Chee-Hing , Roytrakul Sittiruk , Huang Shun-Ping , Chen Chien-Chang , Pakaprot Narawut , Chompoopong Supin , Nudmamud-Thanoi Sutisa , Liu Ingrid Y. 
Published: February 2021

AbstractFear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemicPrdx6knockout (Prdx6−/−) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mousePrdx6into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTRK2, AKT, and phospho-ERK1/2, cPLA2 were significantly upregulated in the hippocampus ofPrdx6−/−mice during the retrieval stage of contextual fear memory. The distribution of PRDX6 found in the astrocytes was also observed throughout the hippocampus. This study identifies PRDX6 as a participant in the regulation of fear response. It suggests that PRDX6 and related molecules may have important implications for understanding fear-dysregulation associated disorders like PTSD.
High-Fidelity simulation-based program improves flow state scale in the perinatal team
Authors: Strozzi Mariachiara Martina , Varrica Alessandro , Colivicchi Micaela , Pelazzo Claudia , Negri Rossana , Galante Anna , Ianniello Patrizia , Sterpone Rossella , Nannini Priscilla , Leo Daniela , Mannarino Francesca , Striani Manuel , Montani Stefania , Gazzolo Diego 
Published: February 2021

Abstract
Background
We aimed to evaluate the degree of realism and involvement, stress management and awareness of performance improvement in practitioners taking part in high fidelity simulation (HFS) training program for delivery room (DR) management, by means of a self-report test such as flow state scale (FSS).

Methods
This is an observational pretest-test study. Between March 2016 and May 2019, fourty-three practitioners (physicians, midwives, nurses) grouped in multidisciplinary teams were admitted to our training High Fidelity Simulation center. In a time-period of 1 month, practitioners attended two HFS courses (model 1, 2) focusing on DR management and resuscitation maneuvers. FSS test was administred at the end of M1 and M2 course, respectively.

Results
FSS scale items such as unambiguous feed-back, loss of self consciousness and loss of time reality, merging of action and awareness significantly improved (P < 0.05, for all) between M1 and M2.

Conclusions
The present results showing the high level of practitioner involvement during DR management-based HFS courses support the usefulness of HFS as a trustworthy tool for improving the awareness of practitioner performances and feed-back. The data open the way to the usefulness of FSS as a trustworthy tool for the evaluation of the efficacy of training programs in a multidisciplinary team.