bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of diabetes and hypertension and their interaction effects on cardio-cerebrovascular diseases: a cross-sectional study
Authors: Wang Zhehui , Yang Tubao , Fu Hanlin
Published: June 2021

Background

Hypertension and diabetes mellitus are two of the major risk factors for cardio-cerebrovascular diseases (CVDs). Although prior studies have confirmed that the coexistence of the two can markedly increase the risk of CVDs, few studies investigated whether potential interaction effects of hypertension and diabetes can result in greater cardio-cerebrovascular damage. We aimed to investigate the prevalence of hypertension and diabetes and whether they both affect synergistically the risk of CVDs.

Methods

A cross-sectional study was conducted by using a multistage stratified random sampling among communities in Changsha City, Hunan Province. Study participants aged > = 18 years were asked to complete questionnaires and physical examinations. Multivariate logistic regression models were performed to evaluate the association of diabetes, hypertension, and their multiplicative interaction with CVDs with adjustment for potential confounders. We also evaluated additive interaction with the relative excess risk ratio (RERI), attribution percentage (AP), synergy index (SI).

Results

A total of 14,422 participants aged 18–98 years were collected (men = 5827, 40.7%). The prevalence was 22.7% for hypertension, 7.0% for diabetes, and 3.8% for diabetes with hypertension complication, respectively. Older age, women, higher educational level, unmarried status, obesity (central obesity) were associated with increased risk of hypertension and diabetes. We did not find significant multiplicative interaction of diabetes and hypertension on CVDs, but observed a synergistic additive interaction on coronary heart disease (SI, 1.43; 95% CI, 1.03–1.97; RERI, 1.94; 95% CI, 0.05–3.83; AP, 0.26; 95% CI, 0.06–0.46).

Conclusions

Diabetes and hypertension were found to be associated with a significantly increased risk of CVDs and a significant synergistic additive interaction of diabetes and hypertension on coronary heart disease was observed. Participants who were old, women, highly educated, unmarried, obese (central obese) had increased risk of diabetes and hypertension.
A comparison between femoral neck and LS-BMD with LS-TBS in T2DM patients: a case control study
Authors: Delbari Negar , Rajaei Alireza , Oroei Mahbobeh , Ahmadzadeh Arman , Farsad Faraneh
Published: June 2021

Background

Despite having higher bone mineral density (BMD) values, type 2 diabetes mellitus (T2DM) patients are at increased risk of fracture. Trabecular bone score (TBS) obtained by evaluating bone microarchitecture might be a more accurate factor for determining bone strength in T2DM patients. In this study, we aimed at investigating the mean values of lumbar spine (LS) TBS, LS-BMD, and femoral neck BMD in T2DM patients and controls, as well as the ability of LS-TBS and BMD in distinguishing between T2DM patients and controls.

Methods

This case-control study was conducted on 150 patients with T2DM (129 women, 21 men) and 484 controls (424 women, 60 men) in Tehran, Iran. LS-TBS along with femoral neck BMD and LS-BMD was computed using dual-energy X-ray absorptiometry images. Diagnostic accuracy and discriminative capacity of LS-TBS, femoral neck BMD, and LS-BMD between the case and control groups were assessed.

Results

T2DM patients showed significantly lower LS-TBS values compared to the control group in the total population and in women. However, in T2DM patients, femoral neck BMD and LS-BMD were found to be significantly higher in the total population and in men, respectively, compared to the control group. Based on area under the curve (AUC) and after adjusting for age and BMI, TBS, LS-BMD, and femoral neck BMD were shown to have the acceptable ability in distinguishing T2DM patients and controls.

Conclusion

Besides higher BMD and lower TBS values in T2DM patients compared to controls, a similar acceptable discriminative ability of LS-TBS, LS-BMD, and femoral neck BMD in differentiating between T2DM patients and controls was observed in the total population and in women.
Effect of virtual reality distraction on pain and anxiety during infiltration anesthesia in pediatric patients: a randomized clinical trial
Authors: Felemban Osama M. , Alshamrani Rawan M. , Aljeddawi Doha H. , Bagher Sara M.
Published: June 2021

Background

Different distraction techniques have been used in dentistry and have shown great results in managing anxious pediatric patients specially during local anesthesia administration. One of the recently invented techniques is virtual reality. The purpose of the study was to evaluate the effect of virtual reality distraction on anxiety and pain during buccal infiltration anesthesia in pediatric patients.

Methods

Healthy, cooperative 6- to 12-year-old children requiring buccal infiltration anesthesia were randomly assigned to a test or control group. In the test group, local anesthesia was administered while the subjects were watching a cartoon video using virtual reality goggles. Subjects in the control group watched a cartoon video on a screen during the administration of local anesthesia. To assess anxiety in both groups, heart rate was recorded using a pulse oximeter at five time points: (1) once the subject sets on the dental chair as a baseline; (2) when video is on; (3) at topical anesthesia application; (4) during needle insertion; (5) after the administration of local anesthesia. The face, legs, activity, cry, consolability (FLACC) behavioral pain assessment scale and the Wong–Baker FACES pain rating scale were used to assess pain.

Results

A total of 50 subjects were included with a mean age of 8.4 ± 1.46 years. Twenty-nine (58.0%) of the subjects were females. The mean heart rate at all time points except baseline was significantly higher among the test group compared to the control group. Multiple regression analysis showed that younger subjects and females had higher mean FLACC behavioral pain assessment scale scores (P = 0.034 and P = 0.004, respectively) regardless of the distraction technique used. Younger subjects and subjects with higher baseline heart rate reported higher mean Wong–Baker FACES pain rating scale score (P = 0.031 and P = 0.010, respectively), controlling for all other variables.

Conclusion

Female subjects and the younger age group were more likely to report higher pain scores during local anesthesia administration regardless of the type of distraction used.

Trial registration

The study was retrospectively registered in ClinicalTrials.gov with the identifier: NCT04483336 on 23/07/2020.
OLIG2 regulates lncRNAs and its own expression during oligodendrocyte lineage formation
Authors: Wei Haichao , Dong Xiaomin , You Yanan , Hai Bo , Duran Raquel Cuevas-Diaz , Wu Xizi , Kharas Natasha , Wu Jia Qian
Published: June 2021

Background

Oligodendrocytes, responsible for axon ensheathment, are critical for central nervous system (CNS) development, function, and diseases. OLIG2 is an important transcription factor (TF) that acts during oligodendrocyte development and performs distinct functions at different stages. Previous studies have shown that lncRNAs (long non-coding RNAs; > 200 bp) have important functions during oligodendrocyte development, but their roles have not been systematically characterized and their regulation is not yet clear.

Results

We performed an integrated study of genome-wide OLIG2 binding and the epigenetic modification status of both coding and non-coding genes during three stages of oligodendrocyte differentiation in vivo: neural stem cells (NSCs), oligodendrocyte progenitor cells (OPCs), and newly formed oligodendrocytes (NFOs). We found that 613 lncRNAs have OLIG2 binding sites and are expressed in at least one cell type, which can potentially be activated or repressed by OLIG2. Forty-eight of them have increased expression in oligodendrocyte lineage cells. Predicting lncRNA functions by using a “guilt-by-association” approach revealed that the functions of these 48 lncRNAs were enriched in “oligodendrocyte development and differentiation.” Additionally, bivalent genes are known to play essential roles during embryonic stem cell differentiation. We identified bivalent genes in NSCs, OPCs, and NFOs and found that some bivalent genes bound by OLIG2 are dynamically regulated during oligodendrocyte development. Importantly, we unveiled a previously unknown mechanism that, in addition to transcriptional regulation via DNA binding, OLIG2 could self-regulate through the 3′ UTR of its own mRNA.

Conclusions

Our studies have revealed the missing links in the mechanisms regulating oligodendrocyte development at the transcriptional level and after transcription. The results of our research have improved the understanding of fundamental cell fate decisions during oligodendrocyte lineage formation, which can enable insights into demyelination diseases and regenerative medicine.
Understanding the role of the paramedic in primary care: a realist review
Authors: Eaton Georgette , Wong Geoff , Tierney Stephanie , Roberts Nia , Williams Veronika , Mahtani Kamal R.
Published: June 2021

Background

Since 2002, paramedics have been working in primary care within the United Kingdom (UK), a transition also mirrored within Australia, Canada and the USA. Recent recommendations to improve UK NHS workforce capacities have led to a major push to increase the numbers of paramedics recruited into primary care. However, gaps exist in the evidence base regarding how and why these changes would work, for whom, in what context and to what extent. To understand the ways in which paramedics impact (or not) the primary care workforce, we conducted a realist review.

Methods

A realist approach aims to provide causal explanations through the generation and articulation of contexts, mechanisms and outcomes. Our search of electronic databases was supplemented with Google and citation checking to locate grey literature including news items and workforce reports. Included documents were from the UK, Australia, Canada and the Americas—countries within which the paramedic role within primary care is well established.

Results

Our searches resulted in 205 included documents, from which data were extracted to produce context-mechanism-outcome configurations (CMOCs) within a final programme theory. Our results outline that paramedics are more likely to be effective in contributing to primary care workforces when they are supported to expand their existing role through formal education and clinical supervision. We also found that unless paramedics were fully integrated into primary care services, they did not experience the socialisation needed to build trusting relationships with patients or physicians. Indeed, for patients to accept paramedics in primary care, their role and its implications for their care should be outlined by a trusted source.

Conclusions

Our realist review highlights the complexity surrounding the introduction of paramedics into primary care roles. As well as offering an insight into understanding the paramedic professional identity, we also discuss the range of expectations this professional group will face in the transition to primary care. These expectations come from patients, general practitioners (family physicians) and paramedics themselves. This review is the first to offer insight into understanding the impact paramedics may have on the international primary care workforce and shaping how they might be optimally deployed.
Cyclic tensile tests of Shetland pony superficial digital flexor tendons (SDFTs) with an optimized cryo-clamp combined with biplanar high-speed fluoroscopy
Authors: Wagner Franziska C. , Reese Sven , Gerlach Kerstin , Böttcher Peter , Mülling Christoph K. W.
Published: June 2021

Background

Long-term cyclic tensile testing with equine palmar/plantar tendons have not yet been performed due to problems in fixing equine tendons securely and loading them cyclically. It is well established that the biomechanical response of tendons varies during cyclic loading over time. The aim of this study was to develop a clamping device that enables repetitive cyclic tensile testing of equine superficial digital flexor tendon for at least 60 loading cycles and for 5 min.

Results

A novel cryo-clamp was developed and built. Healthy and collagenase-treated pony SDFTs were mounted in the custom-made cryo-clamp for the proximal tendon end and a special clamping device for the short pastern bone (os coronale). Simultaneously with tensile testing, we used a biplanar high-speed fluoroscopy system (FluoKin) to track tendon movement. The FluoKin system was additionally validated in precision measurements. During the cyclic tensile tests of the SDFTs, the average maximal force measured was 325 N and 953 N for a length variation of 2 and 4 % respectively. The resulting stress averaged 16 MPa and 48 MPa respectively, while the modulus of elasticity was 828 MPa and 1212 MPa respectively. Length variation of the metacarpal region was, on average, 4.87 % higher after incubation with collagenase. The precision of the FluoKin tracking was 0.0377 mm, defined as the standard deviation of pairwise intermarker distances embedded in rigid bodies. The systems accuracy was 0.0287 mm, which is the difference between the machined and mean measured distance.

Conclusion

In this study, a good performing clamping technique for equine tendons under repetitive cyclic loading conditions is described. The presented cryo-clamps were tested up to 50 min duration and up to the machine maximal capacity of 10 kN. With the possibility of repetitive loading a stabilization of the time-force-curve and changes of hysteresis and creep became obvious after a dozen cycles, which underlines the necessity of repetitive cyclical testing. Furthermore, biplanar high-speed fluoroscopy seems an appropriate and highly precise measurement tool for analysis of tendon behaviour under repetitive load in equine SDFTs.
Inter and intraspecies comparison of the level of selected bacterial phyla in in cattle and sheep based on feces
Authors: Szeligowska Natalia , Cholewińska Paulina , Czyż Katarzyna , Wojnarowski Konrad , Janczak Marzena
Published: June 2021

Background

The microbiome of the digestive tract of ruminants contains microbial ecosystem that is affected by both environmental and genetic factors. The subject of this study concerns the influence of selected genetic factors, such as species of animals and “host” individual differences on the digestive tract microbiome composition. The results show the core microbiological composition (Firmicutes and Bacteroidetes) of ruminants digestive tract (based on feces) depending on breed and “host”. The Bacteroidetes and Firmicutes phyla are the most abundant in ruminants digestive tract. The aim of the study was to determine the differences prevalence level of Bacteroidetes and Firmicutes phyla in feces of Charolaise cattle and Polish Olkuska Sheep with respect to intra- and inter-species variability.

Results

The research group in the experiment consisted of animals at the age of 3 months kept in the same environmental conditions – rams of Polish Olkuska Sheep (n = 10) and Charolaise bulls (n = 10). Feces were collected individually from each animal (animals without disease symptoms were selected), living on the same environmental conditions. The analysis of the results in terms of species showed differences in the Firmicutes phylum level andLactobacillaceaefamily between rams and bulls. Subsequently, the analysis performed for the “host effect” showed differentiation in the levels of the Bacteroidetes and Firmicutes phyla between individuals in a group and also between the groups.

Conclusion

The obtained results suggest that, apart from the diet and the environment, the species and the individual host are equally important factors influencing the microbiological composition of the digestive system of ruminants.
Systems glycobiology for discovering drug targets, biomarkers, and rational designs for glyco-immunotherapy
Authors: Chiang Austin W. T. , Baghdassarian Hratch M. , Kellman Benjamin P. , Bao Bokan , Sorrentino James T. , Liang Chenguang , Kuo Chih-Chung , Masson Helen O. , Lewis Nathan E.
Published: June 2021

Cancer immunotherapy has revolutionized treatment and led to an unprecedented wave of immuno-oncology research during the past two decades. In 2018, two pioneer immunotherapy innovators, Tasuku Honjo and James P. Allison, were awarded the Nobel Prize for their landmark cancer immunotherapy work regarding “cancer therapy by inhibition of negative immune regulation” –CTLA4 and PD-1 immune checkpoints. However, the challenge in the coming decade is to develop cancer immunotherapies that can more consistently treat various patients and cancer types. Overcoming this challenge requires a systemic understanding of the underlying interactions between immune cells, tumor cells, and immunotherapeutics. The role of aberrant glycosylation in this process, and how it influences tumor immunity and immunotherapy is beginning to emerge. Herein, we review current knowledge of miRNA-mediated regulatory mechanisms of glycosylation machinery, and how these carbohydrate moieties impact immune cell and tumor cell interactions. We discuss these insights in the context of clinical findings and provide an outlook on modulating the regulation of glycosylation to offer new therapeutic opportunities. Finally, in the coming age of systems glycobiology, we highlight how emerging technologies in systems glycobiology are enabling deeper insights into cancer immuno-oncology, helping identify novel drug targets and key biomarkers of cancer, and facilitating the rational design of glyco-immunotherapies. These hold great promise clinically in the immuno-oncology field.
Pyriproxyfen-treated bed nets reduce reproductive fitness and longevity of pyrethroid-resistant Anopheles gambiae under laboratory and field conditions
Authors: Grisales Nelson , Lees Rosemary S. , Maas James , Morgan John C. , Wangrawa Dimitri W. , Guelbeogo Wamdaogo M. , N’Fale Sagnon , Lindsay Steven W. , McCall Philip J. , Ranson Hilary
Published: June 2021

Background

The efficacy of insecticide-treated nets (ITNs) containing the insect growth regulator pyriproxyfen (PPF) and pyrethroid insecticides (PPF-ITNs) is being assessed in clinical trials to determine whether they provide greater protection from malaria than standard pyrethroid-treated ITNs in areas where mosquitoes are resistant to pyrethroids. Understanding the entomological mode of action of this new ITN class will aide interpretation of the results from these trials.

Methods

Anopheles gambiae sensu lato (s.l.) mosquitoes from a susceptible laboratory strain were exposed to PPF-treated netting 24 h, 6 h, and immediately prior to, or 24 h post blood feeding, and the impact on fecundity, fertility and longevity recorded. Pyrethroid-resistant populations were exposed to nets containing permethrin and PPF (PPF-ITNs) in cone bioassays and daily mortality recorded. Mosquitoes were also collected from inside houses pre- and post-distribution of PPF-ITNs in a clinical trial conduced in Burkina Faso; female An. gambiae s.l. were then assessed for fecundity and fertility.

Results

PPF exposure reduced the median adult lifespan of insecticide-susceptible mosquitoes by 4 to 5 days in all exposure times (p < 0.05) other than 6 h pre-blood meal and resulted in almost complete lifelong sterilization. The longevity of pyrethroid-resistant mosquitoes was also reduced by at least 5 days after exposure to PPF-ITNs compared to untreated nets, but was unaffected by exposure to standard pyrethroid only ITNs. A total of 386 blood-fed or gravid An. gambiae s.l. females were collected from five villages between 1 and 12 months before distribution of PPF-ITNs. Of these mosquitoes, 75% laid eggs and the remaining 25% appeared to have normal ovaries upon dissection. In contrast, only 8.6% of the 631 blood-fed or gravid An. gambiae s.l. collected post PPF-ITN distribution successfully oviposited; 276 (43.7%) did not oviposit but had apparently normal ovaries upon dissection, and 301 (47.7%) did not oviposit and had abnormal eggs upon dissection. Egg numbers were also significantly lower (average of 138/female prior distribution vs 85 post distribution, p < 0.05).

Conclusion

Exposure to a mixture of PPF and pyrethroids on netting shortens the lifespan of mosquitoes and reduces reproductive output. Sterilization of vectors lasted at least one year under operational conditions. These findings suggest a longer effective lifespan of PPF-pyrethroid nets than reported previously.
A handheld device for measuring the diameter at breast height of individual trees using laser ranging and deep-learning based image recognition
Authors: Song Chuangye , Yang Bin , Zhang Lin , Wu Dongxiu
Published: June 2021

Background

Accurate and efficient measurement of the diameter at breast height (DBH) of individual trees is essential for forest inventories, ecological management, and carbon budget estimation. However, traditional diameter tapes are still the most widely used dendrometers in forest surveys, which makes DBH measurement time-consuming and labor-intensive. Automatic and easy-to-use devices for measuring DBH are highly anticipated in forest surveys. In this study, we present a handheld device for measuring the DBH of individual trees that uses digital cameras and laser ranging, allowing for an instant, automated, and contactless measurement of DBH.

Results

The base hardware of this device is a digital camera and a laser rangefinder, which are used to take a picture of the targeted tree trunk and record the horizontal distance between the digital camera and the targeted tree, respectively. The core software is composed of lightweight convolutional neural networks (CNNs), which includes an attention-focused mechanism for detecting the tree trunk to log the number of pixels between the edges. We also calibrated the digital camera to correct the distortion introduced by the lens system, and obtained the normalized focal length. Parameters including the horizontal distance between the digital camera and the targeted tree, number of pixels between the edges of the tree trunk, and normalized focal length were used to calculate the DBH based on the principles of geometrical optics. The measured diameter values, and the longitudes and latitudes of the measurement sites, were recorded in a text file, which is convenient to export to external flash disks. The field measurement accuracy test showed that the BIAS of the newly developed device was − 1.78 mm, and no significant differences were found between the measured diameter values and the true values (measured by the conventional tape). Furthermore, compared with most other image-based instruments, our device showed higher measurement accuracy.

Conclusions

The newly developed handheld device realized efficient, accurate, instant, and non-contact measurements of DBH, and the CNNs were proven to be successful in the detection of the tree trunk in our research. We believe that the newly developed device can fulfill the precision requirement in forest surveys, and that the application of this device can improve the efficiency of DBH measurements in forest surveys.
Protocol for a hybrid type 3 cluster randomized trial of a technical assistance system supporting coalitions and evidence-based drug prevention programs
Authors: Brown Louis D. , Chilenski Sarah M. , Wells Rebecca , Jones Eric C. , Welsh Janet A. , Gayles Jochebed G. , Fernandez Maria E. , Jones Damon E. , Mallett Kimberly A. , Feinberg Mark E.
Published: June 2021

Background

Over 5000 community anti-drug coalitions operating in the USA serve as a cornerstone of federal drug prevention. These coalitions, however, have demonstrated effectiveness in preventing substance use only when they use technical assistance (TA) and implement evidence-based programs (EBPs). The absence of TA and EBP implementation by coalitions is a key research-to-practice gap. The Coalition Check-Up TA system is designed to fill this gap by supporting community coalition implementation of EBPs. Existing TA models for evidence-based coalition approaches are resource intensive and coalition model specific. The Coalition Check-Up is a lower cost strategy that works with a variety of types of coalitions to support sustainable implementation of EBPs. This study protocol describes a hybrid type 3 effectiveness-implementation trial applying Wandersman’s Interactive Systems Framework to test the effects of the Coalition Check-Up on coalition EBP implementation capacity and outcomes. The Interactive Systems Framework outlines how the prevention support system—especially TA—bolsters EBP dissemination and implementation.

Methods

Using a cluster randomized controlled design, this trial will test the overall effectiveness of the Coalition Check-Up, including how it contributes to EBP implementation and prevention of youth substance use. The first aim is to estimate the impact of the Coalition Check-Up on coalitions’ capacity to do their work. We will recruit 68 anti-drug coalitions for random assignment to the Coalition Check-Up or “TA as usual” condition. We will evaluate whether the Coalition Check-Up improves coalition capacity using measures of coalition member responses about team processes, coalition network composition, and collaborative structure. Our second aim is to estimate the impact of the Coalition Check-Up on implementation of EBPs, and our third aim is to estimate the impact of the Coalition Check-Up on youth substance use.

Discussion

This project will clarify how the Coalition Check-Up, a scalable approach to TA due to its low cost, affects coalition capacity to support EBP implementation. Analyses also provide insight into causal pathways from the prevention support system to the prevention delivery system outlined by the Interactive Systems Framework. Results will build the evidence-base for how to support community coalitions’ sustainable implementation of evidence-based prevention programs and policies.

Trial registration

Clinicaltrials.gov registration number NCT04592120. Registered on October 19, 2020.
Retrospective analysis of recurrence patterns and clinical outcome of grade II meningiomas following postoperative radiotherapy
Authors: Hoffmann Elgin , Clasen Kerstin , Frey Bettina , Ehlers Jakob , Behling Felix , Skardelly Marco , Bender Benjamin , Schittenhelm Jens , Reimold Matthias , Tabatabai Ghazaleh , Zips Daniel , Eckert Franziska , Paulsen Frank
Published: June 2021

Background

Atypical meningiomas exhibit a high tendency for tumor recurrence even after multimodal therapy. Information regarding recurrence patterns after additive radiotherapy is scarce but could improve radiotherapy planning and therapy decision. We conducted an analysis of recurrence patterns with regard to target volumes and dose coverage assessing target volume definition and postulated areas of tumor re-growth origin. Prognostic factors contributing to relapse were evaluated.

Methods

The clinical outcome of patients who had completed additive, somatostatin receptor (SSTR)-PET/CT-based fractionated intensity-modulated radiotherapy for atypical meningioma between 2007 and 2017 was analyzed. In case of tumor recurrence/progression, treatment planning was evaluated for coverage of the initial target volumes and the recurrent tumor tissue. We proposed a model evaluating the dose distribution in postulated areas of tumor re-growth origin. The median of proliferation marker MIB-1 was assessed as a prognostic factor for local progression and new distant tumor lesions.

Results

Data from 31 patients who had received adjuvant (n = 11) or salvage radiotherapy (n = 20) were evaluated. Prescribed dose ranged from 54.0 to 60.0 Gy. Local control at five years was 67.9%. Analysis of treatment plans of the eight patients experiencing local failure proved sufficient extent of target volumes and coverage of the prescribed dose of at least 50.0 Gy as determined by mean dose, D98, D2, and equivalent uniform dose (EUD) of all initial target volumes, postulated growth-areas, and areas of recurrent tumor tissue. In all cases, local failure occurred in high-dose volumes. Tumors with a MIB-1 expression above the median (8%) showed a higher tendency for re-growth.

Conclusions

The model showed adequate target volume and relative dose distribution but absolute dose appears lower in recurrent tumors without reaching statistical significance. This might provide a rationale for dose escalation studies. Biological factors such as MIB-1 might aid patients’ stratification for dose escalation.
Development of the Fabry Disease Patient-Reported Outcome (FD-PRO): a new instrument to measure the symptoms and impacts of Fabry Disease
Authors: Hamed Alaa , DasMahapatra Pronabesh , Lyn Nicole , Gwaltney Chad , Hopkin Robert J.
Published: June 2021

Background

The systematic collection of disease-specific symptoms and impacts on the lives of patients with Fabry Disease (FD) can offer unique insights into the patient experience, yet no disease-specific tool to measure FD symptoms exists. This study describes the development of the Fabry Disease Patient-Reported Outcome (FD-PRO).

Methods

A targeted literature search, interviews with key opinion leaders (KOLs), and concept elicitation (CE) interviews with patients identified the most frequent signs and symptoms associated with FD and their impact on daily life. Cognitive interviews evaluated patients’ ability to understand the FD-PRO instructions and respond to the items on the draft FD-PRO instrument.

Results

The targeted literature search identified key signs and symptoms in domains that were confirmed in KOL interviews. In CE interviews with 37 treated and treatment-naïve patients, neuropathic pain symptoms (95% treated, 82% treatment-naïve), temperature intolerance (95% treated, 88% treatment-naïve), energy difficulties (95% treated, 94% treatment-naïve), hearing/vision impairment (95% treated, 71% treatment-naïve), and gastrointestinal symptoms (80% treated, 59% treatment-naïve) were most frequently mentioned. Results were similar for men and women in both treated and treatment-naïve groups. While treatment-naïve patients in general expressed fewer and milder symptoms compared to treated patients, the overall sets of symptoms expressed by the two groups were similar. The most severe symptoms were neuropathic pain, stomach pain, burning pain, and fatigue. The most bothersome symptoms were stomach pain, breathing difficulty, fatigue, neuropathic pain, and constipation. The most frequent impacts were in the work/school limitations domain for both treated and treatment-naïve patients. The impacts with the highest difficulty ratings were stress, limited outdoor activity, and guilt. Cognitive interviews with 14 treated and treatment-naïve patients resulted in the refinement of FD-PRO items and language.

Conclusions

The FD-PRO is a novel, disease-specific instrument that measures the patient experience in Fabry disease. Such tools are valuable in capturing the burden of disease in patients with FD and demonstrating the value of treatment in clinical trials.
A proteomic network approach resolves stage-specific molecular phenotypes in chronic traumatic encephalopathy
Authors: Gutierrez-Quiceno Laura , Dammer Eric B. , Johnson Ashlyn Grace , Webster James A. , Shah Rhythm , Duong Duc , Yin Luming , Seyfried Nicholas T. , Alvarez Victor E. , Stein Thor D. , McKee Ann C. , Hales Chadwick M.
Published: June 2021

Background

There is an association between repetitive head injury (RHI) and a pathologic diagnosis of chronic traumatic encephalopathy (CTE) characterized by the aggregation of proteins including tau. The underlying molecular events that cause these abnormal protein accumulations remain unclear. Here, we hypothesized that identifying the human brain proteome from serial CTE stages (CTE I-IV) would provide critical new insights into CTE pathogenesis. Brain samples from frontotemporal lobar degeneration due to microtubule associated protein tau (FTLD-MAPT) mutations were also included as a distinct tauopathy phenotype for comparison.

Methods

Isobaric tandem mass tagged labeling and mass spectrometry (TMT-MS) followed by integrated differential and co-expression analysis (i.e., weighted gene co-expression network analysis (WGCNA)) was used to define modules of highly correlated proteins associated with clinical and pathological phenotypes in control (n = 23), CTE (n = 43), and FTLD-MAPT (n = 12) post-mortem cortical tissues. We also compared these findings to network analysis of AD brain.

Results

We identified over 6000 unique proteins across all four CTE stages which sorted into 28 WGCNA modules. Consistent with Alzheimer’s disease, specific modules demonstrated reduced neuronal protein levels, suggesting a neurodegeneration phenotype, while other modules were increased, including proteins associated with inflammation and glial cell proliferation. Notably, unique CTE-specific modules demonstrated prominent enrichment of immunoglobulins, including IGHM and IGLL5, and extracellular matrix (ECM) proteins as well as progressive protein changes with increasing CTE pathologic stage. Finally, aggregate cell subtype (i.e., neurons, microglia, astrocytes) protein abundance levels in CTE cases were similar in expression to AD, but at intermediate levels between controls and the more exaggerated phenotype of FTLD-MAPT, especially in astrocytes.

Conclusions

Overall, we identified thousands of protein changes in CTE postmortem brain and demonstrated that CTE has a pattern of neurodegeneration in neuronal-synaptic and inflammation modules similar to AD. We also identified unique CTE progressive changes, including the enrichment of immunoglobulins and ECM proteins even in early CTE stages. Early and sustained changes in astrocyte modules were also observed. Overall, the prominent overlap with FTLD-MAPT cases confirmed that CTE is on the tauopathy continuum and identified CTE stage specific molecular phenotypes that provide novel insights into disease pathogenesis.
The development of lived experience-centered word clouds to support research uncertainty gathering in degenerative cervical myelopathy: results from an engagement process and protocol for their evaluation, via a nested randomized controlled trial
Authors: Davies Benjamin M. , Mowforth Oliver D. , Khan Danyal Z. , Yang Xiaoyu , Stacpoole Sybil R. L. , Hazenbiller Olesja , Gronlund Toto , Tetreault Lindsay , Kalsi-Ryan Sukhvinder , Starkey Michelle L. , Sadler Iwan , Sarewitz Ellen , Houlton Delphine , Carter Julia , Howard Evangeline , Rahimi-Movaghar Vafa , Guest James D. , Aarabi Bizhan , Kwon Brian K. , Kurpad Shekar N. , Harrop James , Wilson Jefferson R. , Grossman Robert , Smith Emma K. , McNair Angus G.K. , Fehlings Michael G. , Kotter Mark R. N.
Published: June 2021

Objectives

AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as a nested methodological study within our PSP.

Methods

An online poll asked PwCM to submit and vote on words associated with aspects of DCM. After review, a refined word list was re-polled for voting and word submission. Word clouds were generated and an implementation plan for AO Spine RECODE-DCM PSP surveys was subsequently developed.

Results

Seventy-nine terms were submitted after the first poll. Eighty-seven refined words were then re-polled (which added a further 39 words). Four word clouds were generated under the categories of diagnosis, management, long-term effects, and other. A 1:1 block randomization protocol to assess word cloud impact on the number and relevance of PSP research questions was generated.

Conclusions

We have shown it is feasible to work with PwCM to generate a tool for the AO Spine RECODE-DCM nested methodological study. Once the survey stage is completed, we will be able to evaluate the impact of the word clouds. Further research will be needed to assess the value of any impact in terms of stimulating a more creative research agenda.
SCAPP: an algorithm for improved plasmid assembly in metagenomes
Authors: Pellow David , Zorea Alvah , Probst Maraike , Furman Ori , Segal Arik , Mizrahi Itzhak , Shamir Ron
Published: June 2021

Background

Metagenomic sequencing has led to the identification and assembly of many new bacterial genome sequences. These bacteria often contain plasmids: usually small, circular double-stranded DNA molecules that may transfer across bacterial species and confer antibiotic resistance. These plasmids are generally less studied and understood than their bacterial hosts. Part of the reason for this is insufficient computational tools enabling the analysis of plasmids in metagenomic samples.

Results

We developed SCAPP (Sequence Contents-Aware Plasmid Peeler)—an algorithm and tool to assemble plasmid sequences from metagenomic sequencing. SCAPP builds on some key ideas from the Recycler algorithm while improving plasmid assemblies by integrating biological knowledge about plasmids.

We compared the performance of SCAPP to Recycler and metaplasmidSPAdes on simulated metagenomes, real human gut microbiome samples, and a human gut plasmidome dataset that we generated. We also created plasmidome and metagenome data from the same cow rumen sample and used the parallel sequencing data to create a novel assessment procedure. Overall, SCAPP outperformed Recycler and metaplasmidSPAdes across this wide range of datasets.

Conclusions

SCAPP is an easy to use Python package that enables the assembly of full plasmid sequences from metagenomic samples. It outperformed existing metagenomic plasmid assemblers in most cases and assembled novel and clinically relevant plasmids in samples we generated such as a human gut plasmidome. SCAPP is open-source software available from:https://github.com/Shamir-Lab/SCAPP.
Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice
Authors: Zheng Hong , Xu Pengtao , Jiang Qiaoying , Xu Qingqing , Zheng Yafei , Yan Junjie , Ji Hui , Ning Jie , Zhang Xi , Li Chen , Zhang Limin , Li Yuping , Li Xiaokun , Song Weihong , Gao Hongchang
Published: June 2021

Background

Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.

Results

We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.

Conclusions

Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.
Prevalence of intestinal schistosomiasis in pre-school aged children: a pilot survey in Marolambo District, Madagascar
Authors: Sheehy Caitlin , Lawson Heather , Andriamasy Emmanuel H. , Russell Hannah J. , Reid Alice , Raderalazasoa Gina U. , Dodge Graham , Kornitschky Robbie , Penney James M. StJ. , Ranaivoson Tahiry N. , Andrianiaina Antsa , Emmanoela Jenny S. , Bustinduy Amaya L. , Stothard J. Russell , Andrianjaka Louis , Spencer Stephen A.
Published: June 2021

School-aged children (SAC) have a considerable burden of intestinal schistosomiasis in Madagascar yet its burden in pre-school aged children (PSAC) is currently overlooked. To assess the at-risk status of PSAC, we undertook a pilot epidemiological survey in June 2019 examining children (n = 89), aged 2–4-years of balanced gender, in six remote villages in Marolambo District, Madagascar. Diagnosis included use of urine-circulating cathodic antigen (CCA) dipsticks and coproscopy of stool with duplicate Kato-Katz (K-K) thick smears. Prevalence of intestinal schistosomiasis by urine-CCA was 67.4% (95% confidence interval [CI]: 56.5–77.2%) and 35.0% (95% CI: 24.7–46.5%) by K-K. The relationship between faecal eggs per gram (epg) and urine-CCA G-scores (G1 to G10) was assessed by linear regression modelling, finding for every increment in G-score, epg increased by 20.4 (6.50–34.4, P = 0.006). Observed proportions of faecal epg intensities were light (78.6%), moderate (17.9%) and heavy (3.6%). Soil-transmitted helminthiasis was noted, prevalence of ascariasis was 18.8% and trichuriasis was 33.8% (hookworm was not reported). Co-infection of intestinal schistosomiasis and soil-transmitted helminthiasis occurred in 36.3% of PSAC. These results provide solid evidence highlighting the overlooked burden of intestinal schistosomiasis in PSAC, and they also offer technical  guidance for better surveillance data for the Madagascan national control programme.
STEAM in education: a bibliometric analysis of performance and co-words in Web of Science
Authors: Marín-Marín José-Antonio , Moreno-Guerrero Antonio-José , Dúo-Terrón Pablo , López-Belmonte Jesús
Published: June 2021

Background

Emerging methodologies that apply and integrate science, technology, engineering, art, and math (STEAM) in education have appeared in recent years as a pedagogical alternative providing more holistic and attractive education.

Method

The research methodology used in this work is of a bibliometric nature. Specifically, an academic performance analysis and a co-word analysis has been carried out. The term STEAM was analyzed in the Web of Science (WoS) database. The WoS programs Analyze Results, Creation Citation Report, and SciMAT were used. A total of 1116 manuscripts were analyzed.

Results

The results show that studies in the field education of STEAM began in 2006 and have continued uninterruptedly up to the present day, although interest generated in the scientific community has been irregular.

Conclusions

It can be concluded that STEAM studies have not had an established and robust line of research over time, although it can be observed that the trends in this aspect are focused on the scientific branch of education. In addition, the topics of study on STEAM include points related to gender differences, the influence of STEAM on people of different races, the skills developed by students, and training teachers to implement teaching and learning processes with STEAM.
Amelioration of hemodialysis-induced oxidative stress and fatigue with a hemodialysis system employing electrolyzed water containing molecular hydrogen
Authors: Satta Hidehisa , Iwamoto Tamio , Kawai Yuki , Koguchi Naoaki , Shibata Kazuhiko , Kobayashi Nobuteru , Yoshida Mariko , Nakayama Masaaki
Published: June 2021

Background

A novel hemodialysis (HD) system employing electrolyzed water containing molecular hydrogen (E-HD) has been developed to improve the bio-compatibility of HD. This study examined the impact of E-HD on changes in redox state during HD and HD-related fatigue.

Method

This single-arm, prospective observational study examined 63 patients on chronic HD (41 males; mean age, 72 ± 9 years; median duration of HD, 7 years). Redox parameters (serum myeloperoxidase [MPO], malondialdehyde-protein adduct [MDA-a], thioredoxin 1 [TRX]) during HD were compared between control HD (C-HD) and E-HD after 8 weeks. Fatigue was evaluated using a numerical rating scale (NRS) during the 8-week course.

Results

In C-HD, an increase in serum MPO accompanied increases in both oxidative products (MDA-a) and anti-oxidant molecules (TRX). In E-HD, although increases in MPO were accentuated during HD, changes in MDA-a and TRX were ameliorated as compared with C-HD. In patients who showed HD-related fatigue (47%) during C-HD, change in MDA-a by HD was a risk factor for the presence of fatigue. During the 8 weeks of observation on E-HD, those patients displayed significant decreases in fatigue scores.

Conclusion

E-HD ameliorates oxidative stress and supports anti-oxidation during HD, suggesting improved bio-compatibility of the HD system. E-HD may benefit patients with HD-related fatigue, but the mechanisms underlying changes to oxidative stress have yet to be clarified.
Adaptation and validation of the Nigerian Igbo Multidimensional Scale of Perceived Social Support in patients with chronic low back pain
Authors: Igwesi-Chidobe Chinonso Nwamaka , Kitchen Sheila , Sorinola Isaac Olubunmi , Godfrey Emma Louise
Published: June 2021

Introduction

Social support may be important in the perpetuation of symptoms in chronic low back pain (CLBP). The multidimensional scale of perceived social support (MSPSS) is one of the best measures of social support with applicability in Africa.

Aims

The aims of this study were to translate, culturally adapt, test–retest, and assess cross-sectional psychometric properties of the Igbo-MSPSS.

Methods

Forward and backward translation of the MSPSS was done by clinicians and non-clinician translators and evaluated by a specialist review committee. The adapted measure was piloted amongst twelve adults with CLBP in rural Nigeria. Cronbach’s alpha and McDonald’s omega coefficient were used for investigating internal consistency. Intra-class correlation coefficient (ICC: two-way random effects model, average of raters’ measurements, absolute definition of agreement) reflecting both the degree of correlation and agreement between measurements was used for the statistical investigation of test–retest reliability. Criterion validity of the adapted measure was investigated with the eleven-point box scale, back performance scale, Roland Morris Disability Questionnaire, and World Health Organisation Disability Assessment Schedule amongst 200 people with CLBP in rural Nigeria using Spearman’s correlation analyses. Exploratory factor analyses conducted using Kaiser criterion and parallel analysis as methods for determining dimensionality were used to determine the structural validity of the adapted measure amongst the same sample of 200 rural dwellers.

Results

Igbo-MSPSS had excellent internal consistency (0.88) and ICC of 0.82. There were moderate correlations with measures associated with the social support construct. The same item–factor pattern in the three-dimensional structure (with Kaiser criterion) as in the original measure and a two-dimensional structure (with parallel analysis) were produced.

Conclusions

Igbo-MSPSS is a measure of social support with some evidence of validity and reliability and can be used clinically or for research. Future studies are required to confirm its validity and reliability.