bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of 3D vertebral and pelvic position by surface topography in asymptomatic females: presentation of normative reference data
Authors: Wolf Claudia , Betz Ulrich , Huthwelker Janine , Konradi Jürgen , Westphal Ruben Sebastian , Cerpa Meghan , Lenke Lawrence , Drees Philipp
Published: December 2021

Background

Deviations from a conventional physiologic posture are often a cause of complaint. According to current literature, the upright physiological spine posture exhibits inclinations in the sagittal plane but not in the coronal and transverse planes, but individual vertebral body positions of asymptomatic adults have rarely been described using surface topography. Therefore, this work aims to form a normative reference dataset for the thoracic and lumbar vertebral bodies and for the pelvis in all three planes in asymptomatic women.

Methods

In a prospective, cross-sectional, monocentric study, 100 pain-free asymptomatic women, aged 20–64 years were enrolled. Habitual standing positions of the trunk were measured using surface topography. Data were analyzed in all three planes. Age sub-analysis was: 1) ages ≤ 40 years and 2) ages ≥ 41 years. Two-sample t-tests were used for age comparisons of the vertebral bodies, vertebra prominence (VP)–L4, and global parameters. One-sample t-tests were used to test deviations from symmetrical zero positions of VP–L4.

Results

Coronal plane: on average, the vertebral bodies were tilted to the right between the VP and T4 (maximum: T2 − 1.8° ± 3.2), while between T6 and T11 they were tilted to the left (maximum: T7 1.1° ± 1.9). T5 and L2 were in a neutral position, overall depicting a mean right-sided lateral flexion from T2 to T7 (apex at T5). Sagittal plane: the kyphotic apex resided at T8 with − 0.5° ± 3.6 and the lumbar lordotic apex at L3 with − 2.1° ± 7.4. Transverse plane: participants had a mean vertebral body rotation to the right ranging from T6 to L4 (maximum: T11 − 2.2° ± 3.5). Age-specific differences were seen in the sagittal plane and had little effect on overall posture.

Conclusions

Asymptomatic female volunteers standing in a habitual posture displayed an average vertebral rotation and lateral flexion to the right in vertebral segments T2–T7. The physiological asymmetrical posture of women could be considered in spinal therapies. With regard to spinal surgery, it should be clarified whether an approximation to an absolutely symmetrical posture is desirable from a biomechanical point of view? This data set can also be used as a reference in clinical practice.

Trial registration: This study was registered with WHO (INT: DRKS00010834) and approved by the responsible ethics committee at the Rhineland–Palatinate Medical Association (837.194.16).
Bletilla striata polysaccharide cryogel scaffold for spatial control of foreign-body reaction
Authors: Chen Jiaxi , Zhou Huiqun , Xie Daping , Niu Yiming
Published: December 2021

Background

Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants.

Methods

First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials.

Results

Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure.

Conclusions

Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.
Analysis of cognitive ability and adaptive behavior assessment tools used in an observational study of patients with mucopolysaccharidosis II
Authors: Yee Karen S. , Wu Yanyu , Harrington Magdalena , Waisbren Susan E.
Published: December 2021

Background

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by cognitive impairment in most patients. This post hoc analysis evaluated changes in cognitive function, adaptive behavior and functional outcomes in patients with neuronopathic MPS II over time. Fifty-five children with MPS II were enrolled in a 24-month observational study (NCT01822184). The Differential Ability Scales, second edition (DAS-II; early years battery for ages 2 years 6 months to 6 years 11 months, school age battery for ages 7 years to 17 years 11 months), Vineland Adaptive Behavior Scales, second edition (VABS-II) and the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) were performed at baseline and 3-month intervals over 2 years. A subgroup of 38 children with a DAS-II General Conceptual Ability (GCA) score of 55–85 (below average–very low abilities) at any time during the study were included in this analysis.

Results

Mean (standard deviation [SD]) early years DAS-II GCA score decreased from 73.4 (15.7, n = 22) at baseline to 62.7 (34.9, n = 6) at month 24. For the six patients with early years GCA assessments at baseline and month 24, mean (SD) GCA scores decreased from 72.3 (21.3) at baseline to 62.7 (34.9) at month 24. School age GCA scores were stable over 2 years: mean (SD) 72.4 (11.8, n = 10) at baseline; 74.3 (12.3, n = 8) at month 24. Mean (SD) VABS-II Adaptive Behavior Composite (ABC) scores were stable throughout the study (baseline, 81.8 [11.8, n = 36]; month 24, 81.0 [10.2, n = 13]). Some associations between items and domains of HS-FOCUS (p < 0.05) and DAS-II GCA and VABS-II ABC scores were shown, but there was no clear pattern of changes in HS-FOCUS over 2 years.

Conclusions

The DAS-II measured changes in cognitive function over 2 years in younger patients with MPS II, whereas cognitive function in older patients remained stable. Further research is required to confirm the content validity of the DAS-II in different patient populations with MPS II. The VABS-II and HS-FOCUS were not sensitive tools for measuring behavioral and functional changes over 2 years. These findings may inform selection of appropriate cognitive and behavioral assessment tools for future studies.
De novo balanced reciprocal translocation mosaic t(1;3)(q42;q25) detected by prenatal genetic diagnosis: a fetus conceived using preimplantation genetic testing due to a t(12;14)(q22;q13) balanced paternal reciprocal translocation
Authors: Zhang Shaoqin , Zhu Jianjiang , Qi Hong , Xu Limei , Cai Lirong , Meng Ran
Published: December 2021

Introduction

De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been rarely reported.

Methods

Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome.

Results

A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)[40]/46,XY[39] was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range.

Conclusion

We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.
Retrosplenial cortex in spatial memory: focus on immediate early genes mapping
Authors: Balcerek Edyta , Włodkowska Urszula , Czajkowski Rafał
Published: December 2021

The ability to form, retrieve and update autobiographical memories is one of the most fascinating features of human behavior. Spatial memory, the ability to remember the layout of the external environment and to navigate within its boundaries, is closely related to the autobiographical memory domain. It is served by an overlapping brain circuit, centered around the hippocampus (HPC) where the cognitive map index is stored. Apart from the hippocampus, several cortical structures participate in this process. Their relative contribution is a subject of intense research in both humans and animal models. One of the most widely studied regions is the retrosplenial cortex (RSC), an area in the parietal lobe densely interconnected with the hippocampal formation. Several methodological approaches have been established over decades in order to investigate the cortical aspects of memory. One of the most successful techniques is based on the analysis of brain expression patterns of the immediate early genes (IEGs). The common feature of this diverse group of genes is fast upregulation of their mRNA translation upon physiologically relevant stimulus. In the central nervous system they are rapidly triggered by neuronal activity and plasticity during learning. There is a widely accepted consensus that their expression level corresponds to the engagement of individual neurons in the formation of memory trace. Imaging of the IEGs might therefore provide a picture of an emerging memory engram. In this review we present the overview of IEG mapping studies of retrosplenial cortex in rodent models. We begin with classical techniques, immunohistochemical detection of protein and fluorescent in situ hybridization of mRNA. We then proceed to advanced methods where fluorescent genetically encoded IEG reporters are chronically followed in vivo during memory formation. We end with a combination of genetic IEG labelling and optogenetic approach, where the activity of the entire engram is manipulated. We finally present a hypothesis that attempts to unify our current state of knowledge about the function of RSC.
Incorporating a real-time automatic alerting system based on electronic medical records could improve rapid response systems: a retrospective cohort study
Authors: You Seung-Hun , Jung Sun-Young , Lee Hyun Joo , Kim Sulhee , Yang Eunjin ,   SAVER team
Published: December 2021

Background

Rapid response systems (RRSs) are essential components of patient safety systems; however, limited evidence exists regarding their effectiveness and optimal structures. We aimed to assess the activation patterns and outcomes of RRS implementation with/without a real-time automatic alerting system (AAS) based on electronic medical records (EMRs).

Methods

We retrospectively analyzed clinical data of patients for whom the RRS was activated in the surgical wards of a tertiary university hospital. We compared the code rate, in-hospital mortality, unplanned intensive care unit (ICU) admission, and other clinical outcomes before and after applying RRS and AAS as follows: pre-RRS (January 2013–July 2015), RRS without AAS (August 2015–November 2016), and RRS with AAS (December 2016–December 2017).

Results

In-hospital mortality per 1000 admissions decreased from 15.1 to 12.9 after RRS implementation (p < 0.001). RRS activation per 1000 admissions increased from 14.4 to 26.3 after AAS implementation. The severity of patients’ condition calculated using the modified early warning score increased from 2.5 (± 2.1) in the RRS without AAS to 3.6 (± 2.1) (p < 0.001) in the RRS with AAS. The total and preventable code rates and in-hospital mortality rates were comparable between the RRS implementation periods without/with AAS. ICU duration and mortality results improved in patients with RRS activation and unplanned ICU admission. The data of RRS non-activated group remained unaltered during the study.

Conclusions

Real-time AAS based on EMRs might help identify unstable patients. Early detection and intervention with RRS may improve patient outcomes.
Novel protocol combining physical and nutrition therapies, Intensive Goal-directed REhabilitation with Electrical muscle stimulation and Nutrition (IGREEN) care bundle
Authors: Nakano Hidehiko , Naraba Hiromu , Hashimoto Hideki , Mochizuki Masaki , Takahashi Yuji , Sonoo Tomohiro , Ogawa Yasuhiro , Matsuishi Yujiro , Shimojo Nobutake , Inoue Yoshiaki , Nakamura Kensuke
Published: December 2021

Background

Although the combination of rehabilitation and nutrition may be important for the prevention of intensive care unit (ICU)-acquired weakness, a protocolized intervention of this combination has not yet been reported. We herein developed an original combined protocol and evaluated its efficacy.

Methods

In this single-center historical control study, we enrolled adult patients admitted to the ICU. Patients in the control group received standard care, while those in the intervention group received the protocol-based intervention. The ICU mobility scale was used to set goals for early mobilization and a neuromuscular electrical stimulation was employed when patients were unable to stand. The nutritional status was assessed for nutritional therapy, and target calorie delivery was set at 20 or 30 kcal/kg/day and target protein delivery at 1.8 g/kg/day in the intervention group. The primary endpoint was a decrease in femoral muscle volume in 10 days assessed by computed tomography.

Results

Forty-five patients in the control group and 56 in the intervention group were included in the analysis. Femoral muscle volume loss was significantly lower in the intervention group (11.6 vs 14.5%, p = 0.03). The absolute risk difference was 2.9% (95% CI 0.1–5.6%). Early mobilization to a sitting position by day 10 was achieved earlier (p = 0.03), and mean calorie delivery (20.1 vs. 16.8 kcal/kg/day, p = 0.01) and mean protein delivery (1.4 vs. 0.8 g/kg/day, p < 0.01) were higher in the intervention group.

Conclusion

The protocolized intervention, combining early mobilization and high-protein nutrition, contributed to the achievement of treatment goals and prevention of femoral muscle volume loss.

Trial registration number

The present study is registered at the University Hospital Medical Information Network-clinical trials registry (UMIN000040290, Registration date: May 7, 2020).
A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial
Authors: Abayomi A. , Osibogun A. , Ezechi O. , Wright K. , Ola B. , Ojo O. , Kuyinu Y. , Zamba E. , Abdur-Razzaq H. , Erinoso O. A. , Anya S. E.
Published: December 2021

Background

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria.

Methods

This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software.

Discussion

The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria.

Trial registration

Pan African Clinical Trials Register PACTR202004801273802. Registered prospectively on April 2, 2020
SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) in African American veterans with gout: a trial study protocol
Authors: Singh Jasvinder A.
Published: December 2021

Objective

Medication adherence in gout is suboptimal, and the lack of effective interventions to address it presents a huge challenge. Medication adherence and gout outcomes are worse in racial/ethnic minorities. The objective of this paper was to provide the details of the study protocol for randomized, controlled trial (RCT) in African Americans (AAs) with gout that will test the effectiveness of a culturally appropriate gout storytelling intervention.

Methods

The SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) study will be a 12-month, multicenter, open-label RCT that will assess the effect of a culturally appropriate gout storytelling in at least 300 AA veterans with gout. Participants will be randomized to gout-storytelling intervention vs. a stress reduction video in a 1:1 ratio. The primary outcome is urate-lowering therapy (ULT) adherence measured with MEMSCap™, an electronic monitoring system (efficacy, 6 months; sustenance of efficacy, 12 months). Secondary outcomes include gout flares, serum urate (SU), gout-specific health-related quality of life [HRQOL], self-reported ULT adherence, patient satisfaction with treatment, and patient understanding of the intervention. AA veterans with gout who met the 1977 Preliminary American College of Rheumatology (ACR) classification criteria for gout, currently prescribed an oral ULT medication (allopurinol or febuxostat) for at least 6 months, and not using a pillbox to redistribute their medications, will be invited to an in-person study visit. After the study coordinators obtain informed consent, and ensure that participants meet the inclusion criteria, the eligible participants will be provided with their current ULT in a MEMSCap™ bottle for the 1-month run-in period and asked to return to the clinic in 1 month. ULT adherence with MEMSCap™ will be recorded at a 1-month return visit. Interested participants will complete the baseline assessments, randomized using the computerized system to either gout-storytelling intervention or a stress reduction intervention video arm and watch the respective video in-clinic. Patients will be interviewed on the phone at 2 and 4 months regarding the viewing of the videos at home at each time. Participants will be assessed in-clinic at 3, 6, 9, and 12 months; MEMSCap™ data and patient surveys will be captured at each visit. For any missed visit, assessments will be completed on the phone and MEMSCap™ data captured at the next in-clinic visit.

Discussion

The study will assess the efficacy of a behavioral intervention to improve ULT adherence in minority populations with gout.

Trial registration

ClinicalTrials.gov NCT 02741700. Registered on 14 September 2018
Wood-feeding termite gut symbionts as an obscure yet promising source of novel manganese peroxidase-producing oleaginous yeasts intended for azo dye decolorization and biodiesel production
Authors: Al-Tohamy Rania , Sun Jianzhong , Khalil Maha A. , Kornaros Michael , Ali Sameh Samir
Published: December 2021

Background

The ability of oxidative enzyme-producing micro-organisms to efficiently valorize organic pollutants is critical in this context. Yeasts are promising enzyme producers with potential applications in waste management, while lipid accumulation offers significant bioenergy production opportunities. The aim of this study was to explore manganese peroxidase-producing oleaginous yeasts inhabiting the guts of wood-feeding termites for azo dye decolorization, tolerating lignocellulose degradation inhibitors, and biodiesel production.

Results

Out of 38 yeast isolates screened from wood-feeding termite gut symbionts, nine isolates exhibited high levels of extracellular manganese peroxidase (MnP) activity ranged between 23 and 27 U/mL after 5 days of incubation in an optimal substrate. Of these MnP-producing yeasts, four strains had lipid accumulation greater than 20% (oleaginous nature), with Meyerozyma caribbica SSA1654 having the highest lipid content (47.25%, w/w). In terms of tolerance to lignocellulose degradation inhibitors, the four MnP-producing oleaginous yeast strains could grow in the presence of furfural, 5-hydroxymethyl furfural, acetic acid, vanillin, and formic acid in the tested range. M. caribbica SSA1654 showed the highest tolerance to furfural (1.0 g/L), 5-hydroxymethyl furfural (2.5 g/L) and vanillin (2.0 g/L). Furthermore, M. caribbica SSA1654 could grow in the presence of 2.5 g/L acetic acid but grew moderately. Furfural and formic acid had a significant inhibitory effect on lipid accumulation by M. caribbica SSA1654, compared to the other lignocellulose degradation inhibitors tested. On the other hand, a new MnP-producing oleaginous yeast consortium designated as NYC-1 was constructed. This consortium demonstrated effective decolorization of all individual azo dyes tested within 24 h, up to a dye concentration of 250 mg/L. The NYC-1 consortium's decolorization performance against Acid Orange 7 (AO7) was investigated under the influence of several parameters, such as temperature, pH, salt concentration, and co-substrates (e.g., carbon, nitrogen, or agricultural wastes). The main physicochemical properties of biodiesel produced by AO7-degraded NYC-1 consortium were estimated and the results were compared to those obtained from international standards.

Conclusion

The findings of this study open up a new avenue for using peroxidase-producing oleaginous yeasts inhabiting wood-feeding termite gut symbionts, which hold great promise for the remediation of recalcitrant azo dye wastewater and lignocellulosic biomass for biofuel production.
Transcriptome analysis of Rhizopus oryzae seed pellet formation using triethanolamine
Authors: Wu Na , Zhang Jiahui , Ou Wen , Chen Yaru , Wang Ru , Li Ke , Sun Xiao-man , Li Yingfeng , Xu Qing , Huang He
Published: December 2021

Rhizopus oryzae (R. oryzae) can effectively produce organic acids, and its pellet formation in seed cultures has been shown to significantly enhance subsequent fermentation processes. Despite advances in strain development, simple and effective methods for inducing pellet morphology and a basic understanding of the mechanisms controlling this process could facilitate substantial increases in efficiency and product output. Here, we report that 1.5% triethanolamine (TEOA) in seed culture medium can activate the growth of R. oryzae spores in compact and uniform pellets which is optimal for fermentation conditions. Analysis of fermentation kinetics showed that the production of fumaric and L-malic acid increases 293% and 177%, respectively. Transcriptomic analysis revealed that exposure of R. oryzae to 1.5% TEOA during the seed culture activated the phosphatidylinositol and mitogen-activated protein kinase signaling pathways. Theses pathways subsequently stimulated the downstream carbohydrate-active synthases and hydrolases that required for cell wall component synthesis and reconstruction. Our results thus provide insight into the regulatory pathways controlling pellet morphology germane to the viability of seed cultures, and provide valuable reference data for subsequent optimization of organic acid fermentation by R. oryzae.
Introduction of ultrasound-based living anatomy into the medical curriculum: a survey on medical students’ perceptions
Authors: Kefala-Karli Pelagia , Sassis Leandros , Sassi Marina , Zervides Constantinos
Published: December 2021

Background

Traditional anatomy teaching methods are based on the models and cadaveric dissections, providing fixed views of the anatomical structures. However, in the last few years, the emerging concept of ultrasound-based teaching in anatomy has started to gain ground among medical curricula. This study aims to evaluate the integration of ultrasound as an adjunct tool to traditional anatomy teaching methods and explore students’ perceptions of whether ultrasound-based teaching enhances their interest and knowledge of anatomy. A cross-sectional study was carried out among the students of the 6-year undergraduate entry (MD) and 4-year graduate entry (MBBS) program of the University of Nicosia. A questionnaire was distributed to them after the delivery of several twenty minutes ultrasound sessions by an expert in the field during anatomy practicals. The data were analyzed utilizing SPSS software, and the statistical significance was determined as p value < 0.05.

Results

107 MD and 42 MBBS students completed the questionnaire. Both groups agreed that their ultrasound-based learning experience was good or excellent (79.4% MD students; 92.9% MBBS students), that it enhanced their knowledge of anatomy (68.2% MD students; 90.5% MBBS students) and boosted their confidence regarding their examination skills practice (69.2% MD students; 85.7% MBBS students). Although most students desired more time allocated to the ultrasound station (72% MD students; 85.7% MBBS students), they believed that ultrasound-based teaching is a necessary adjunct to the traditional teaching methods of anatomy (89.7% MD students; 92.9% MBBS students).

Conclusions

Overall, MBBS students were more confident about the benefits of ultrasound-based teaching. Most of the students agreed that cross-sectional sessions of traditional teaching and ultrasound-based teaching strengthened their knowledge of anatomy and enhanced their confidence concerning their clinical examination skills. Medical schools should embrace the advantages that ultrasound-based teaching offers in order future doctors to be qualified to utilize ultrasound for procedural and diagnostical purposes.
Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden
Authors: Holm Karin , Lundgren Maria N. , Kjeldsen-Kragh Jens , Ljungquist Oskar , Böttiger Blenda , Wikén Christian , Öberg Jonas , Fernström Nils , Rosendal Ebba , Överby Anna K. , Wigren Byström Julia , Forsell Mattias , Landin-Olsson Mona , Rasmussen Magnus
Published: December 2021

Objective

Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.

Results

Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.

Trial registration ClinicalTrials NCT04600440, retrospectively registered Oct 23, 2020.
Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231
Authors: Bayoumy Sherif , Verberk Inge M. W. , den Dulk Ben , Hussainali Zulaiga , Zwan Marissa , van der Flier Wiesje M. , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Vanbrabant Jeroen , Stoops Erik , Vanmechelen Eugeen , Dage Jeffrey L. , Teunissen Charlotte E.
Published: December 2021

Introduction

Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer’s disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg).

Methods

We studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays.

Results

All assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936–0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman’s rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65).

Discussion

P-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.
MiRNA-221-5p suppressed the Th17/Treg ratio in asthma via RORγt/Foxp3 by targeting SOCS1
Authors: Guan Yuanyuan , Ma Yuemei , Tang Yao , Liu Xiaolei , Zhao Yan , An Lixin
Published: December 2021

Background

This study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma.

Methods

BALB/c mice were intranasally challenged with 100 µg OVA on 14 and 21 day. Mice were rechallenged with 2.5% OVA-PBS on 22 and 28 day. Mice were sacrificed using on day 30 under 35 mg/kg pentobarbital sodium. PBMCs were induced vitro model of asthma using 500 ng of lipopolysaccharides (LPS) for 4 h.

Results

The expression of miRNA-221-5p was reduced in in vivo model, compared sham group. The vitro model of asthma treated with miRNA-221-5p mimic resulted in the reduction of IL-6, IL-17, IL-21 and IL-22 levels, and induction of IL-10, IL-35 and TGF-β levels. In addition, down-regulation of miRNA-221-5p induced the protein expression of suppressor of cytokine signaling 1 (SOCS1) and receptor-related orphan receptor-gamma-t (RORγt) and suppressed that of FOXP3 in in vitro model of asthma. Over-expression of miRNA-221-5p induced the protein expression of FOXP3, and suppressed that of SOCS1 and RORγt in in vitro model of asthma. The inhibition of SOCS1 or RORγt attenuated the effects of anti-miRNA-221-5p on Th17/Treg ratio in asthma.

Conclusion

miRNA-221-5p may play critical roles in driving the differentiation of Th17/Treg ratio via RORγt/Foxp3 by Targeting SOCS1, reduced the function of Th17 cells by directly inhibiting RORγt/SOCS1 and promoted the function of Treg cells via Foxp3/ SOCS1 in asthma.
The European Society of Head and Neck Radiology Mentoring Programme: development and feedback during the first phase of the initiative
Authors: Connor Steve , Robinson Soraya
Published: December 2021

There is increasing awareness of the benefits of formal mentorship programmes in radiology. In the context of the COVID 19 pandemic which impacted on education, professional engagement and networking within the wider radiological community, the European Society of Head and Neck Radiology (ESHNR) decided to develop a formal mentoring programme. The ESHNR mentoring initiative is novel in its scope, whereby European and international members of a subspecialty radiology society are matched into mentor–mentee pairings to disseminate good practice, knowledge and ideas. The purpose of this report is to describe the motivations, planning, challenges and early experience of the ESHNR mentoring programme together with initial feedback from the scheme.

The development of the programme and iterative modifications during the first phase of the scheme are described. The programme has enrolled 33 mentors and 27 mentees with international representation and 24 mentor–mentee pairs have participated in 2.6 (mean) meetings. The experience and benefits reported by the participating ESHNR members (mentees and mentors) were evaluated by a questionnaire at six months following the start of the programme. There were 80% of mentors and 88% of mentees who strongly agreed that the mentoring programme was rewarding rather than an obligation, and all participants reported that they would recommend the scheme to colleagues.

A formal mentoring programme has been established for an international subspecialty radiology society. The early experience is encouraging and suggests that it is both useful and sustainable. Our experiences may be of benefit to other subspecialty societies considering a mentoring programme.
Graphene oxide-modified silk fibroin/nanohydroxyapatite scaffold loaded with urine-derived stem cells for immunomodulation and bone regeneration
Authors: Sun Jiachen , Li Lang , Xing Fei , Yang Yun , Gong Min , Liu Guoming , Wu Shuang , Luo Rong , Duan Xin , Liu Ming , Zou Min , Xiang Zhou
Published: December 2021

Background

The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration.

Methods

The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects.

Results

GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery.

Conclusions

This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones.
Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles
Authors: Aneesh Anagha , Liu Alice , Moss Heather E. , Feinstein Douglas , Ravindran Sriram , Mathew Biji , Roth Steven
Published: December 2021

Background

Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss.

Main Body

Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression.

Conclusion

We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis.

Graphical Abstract
The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration
Authors: Chen Jialin , Mo Qingyun , Sheng Renwang , Zhu Aijing , Ling Chen , Luo Yifan , Zhang Aini , Chen Zhixuan , Yao Qingqiang , Cai Zhuoying , Zhang Wei
Published: December 2021

Background

With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration.

Methods

Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects.

Results

Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype.

Conclusions

In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.
Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma: sex differences
Authors: Fan Tao , Li Chunxiang , He Jie
Published: December 2021

Background

Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of sex differences on immune cell infiltration in lung tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME.

Methods

Using ESTIMATE algorithm, we calculated immune and stromal scores of tumor samples downloaded from TCGA database according to immune or stromal components in TME. GO and KEGG enrichment analysis were conducted to reveal biological processes of these intersecting genes of high- and low-score groups. Cox regression analysis and protein–protein interaction (PPI) network analysis were performed to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan–Meier survival analysis was used to evaluate prognostic value of these identified genes. Mann–Whitney test was used to compare various indicators of male patients and female patients. The main results were subsequently validated in 420 cases from GSE72094.

Results

304 and 368 intersecting genes were identified in female and male patients, respectively. The immune score ranged from −943.17 to 3229.35 among female patients and from −541.75 to 3441.78 among male patients. The stromal score ranged from −1790.23 to 2097.27 among female patients and from −1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (p < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in female LUAD patients. BTK and CCR2 were identified as the most important immune-related prognostic genes in male LUAD patients. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (p < 0.05).

Conclusions

This study comprehensively compared the differences in tumor immune microenvironment between male and female LUAD patients, and identified prognosis-related genes for patients of different sexes.
Three bedside techniques to quantify dynamic pulmonary hyperinflation in mechanically ventilated patients with chronic obstructive pulmonary disease
Authors: Roesthuis L. H. , van der Hoeven J. G. , Guérin C. , Doorduin J. , Heunks L. M. A.
Published: December 2021

Background

Dynamic pulmonary hyperinflation may develop in patients with chronic obstructive pulmonary disease (COPD) due to dynamic airway collapse and/or increased airway resistance, increasing the risk of volutrauma and hemodynamic compromise. The reference standard to quantify dynamic pulmonary hyperinflation is the measurement of the volume at end-inspiration (Vei). As this is cumbersome, the aim of this study was to evaluate if methods that are easier to perform at the bedside can accurately reflect Vei.

Methods

Vei was assessed in COPD patients under controlled protective mechanical ventilation (7 ± mL/kg) on zero end-expiratory pressure, using three techniques in a fixed order: (1) reference standard (Veireference): passive exhalation to atmosphere from end-inspiration in a calibrated glass burette; (2) ventilator maneuver (Veimaneuver): measuring the expired volume during a passive exhalation of 45s using the ventilator flow sensor; (3) formula (Veiformula): (Vt × Pplateau)/(Pplateau − PEEPi), with Vt tidal volume, Pplateau is plateau pressure after an end-inspiratory occlusion, and PEEPi is intrinsic positive end-expiratory pressure after an end-expiratory occlusion. A convenience sample of 17 patients was recruited.

Results

Veireference was 1030 ± 380 mL and had no significant correlation with Pplateau (r2 = 0.06; P = 0.3710) or PEEPi (r2 = 0.11; P = 0.2156), and was inversely related with Pdrive (calculated as Pplateau −PEEPi) (r2 = 0.49; P = 0.0024). A low bias but rather wide limits of agreement and fairly good correlations were found when comparing Veimaneuver and Veiformula to Veireference. Vei remained stable during the study period (low bias 15 mL with high agreement (95% limits of agreement from − 100 to 130 mL) and high correlation (r2 = 0.98; P < 0.0001) between both measurements of Veireference).

Conclusions

In patients with COPD, airway pressures are not a valid representation of Vei. The three techniques to quantify Vei show low bias, but wide limits of agreement.