bluuebunny/crossref_metadata_2025 huggingface dataset:
Signal amplification and optimization of riboswitch-based hybrid inputs by modular and titratable toehold switches
Authors: Hwang Yunhee , Kim Seong Gyeong , Jang Sungho , Kim Jongmin , Jung Gyoo Yeol
Published: March 2021

Background

Synthetic biological circuits are widely utilized to control microbial cell functions. Natural and synthetic riboswitches are attractive sensor modules for use in synthetic biology applications. However, tuning the fold-change of riboswitch circuits is challenging because a deep understanding of the riboswitch mechanism and screening of mutant libraries is generally required. Therefore, novel molecular parts and strategies for straightforward tuning of the fold-change of riboswitch circuits are needed.

Results

In this study, we devised a toehold switch-based modulator approach that combines a hybrid input construct consisting of a riboswitch and transcriptional repressor and de-novo-designed riboregulators named toehold switches. First, the introduction of a pair of toehold switches and triggers as a downstream signal-processing module to the hybrid input for coenzyme B12 resulted in a functional riboswitch circuit. Next, several optimization strategies that focused on balancing the expression levels of the RNA components greatly improved the fold-change from 260- to 887-fold depending on the promoter and host strain. Further characterizations confirmed low leakiness and high orthogonality of five toehold switch pairs, indicating the broad applicability of this strategy to riboswitch tuning.

Conclusions

The toehold switch-based modulator substantially improved the fold-change compared to the previous sensors with only the hybrid input construct. The programmable RNA-RNA interactions amenable to in silico design and optimization can facilitate further development of RNA-based genetic modulators for flexible tuning of riboswitch circuitry and synthetic biosensors.
Neurodegenerative phosphoprotein signaling landscape in models of SCA3
Authors: Sowa Anna S. , Popova Taissia G. , Harmuth Tina , Weber Jonasz J. , Pereira Sena Priscila , Schmidt Jana , Hübener-Schmid Jeannette , Schmidt Thorsten
Published: March 2021

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disorder resulting from an aberrant expansion of a polyglutamine stretch in the ataxin-3 protein and subsequent neuronal death. The underlying intracellular signaling pathways are currently unknown. We applied the Reverse-phase Protein MicroArray (RPMA) technology to assess the levels of 50 signaling proteins (in phosphorylated and total forms) using three in vitro and in vivo models expressing expanded ataxin-3: (i) human embryonic kidney (HEK293T) cells stably transfected with human ataxin-3 constructs, (ii) mouse embryonic fibroblasts (MEF) from SCA3 transgenic mice, and (iii) whole brains from SCA3 transgenic mice. All three models demonstrated a high degree of similarity sharing a subset of phosphorylated proteins involved in the PI3K/AKT/GSK3/mTOR pathway. Expanded ataxin-3 strongly interfered (by stimulation or suppression) with normal ataxin-3 signaling consistent with the pathogenic role of the polyglutamine expansion. In comparison with normal ataxin-3, expanded ataxin-3 caused a pro-survival stimulation of the ERK pathway along with reduced pro-apoptotic and transcriptional responses.
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study
Authors: Rovas Alexandros , Sackarnd Jan , Rossaint Jan , Kampmeier Stefanie , Pavenstädt Hermann , Vink Hans , Kümpers Philipp
Published: March 2021

Background

The availability of handheld, noninvasive sublingual video-microscopes allows for visualization of the microcirculation in critically ill patients. Recent studies demonstrate that reduced numbers of blood-perfused microvessels and increased penetration of erythrocytes into the endothelial glycocalyx are essential components of microvascular dysfunction. The aim of this study was to identify novel microvascular variables to determine the level of microvascular dysfunction in sepsis and its relationship with clinical variables.

Methods

This observational, prospective, cross-sectional study included 51 participants, of which 34 critically ill sepsis patients were recruited from intensive care units of a university hospital. Seventeen healthy volunteers served as controls. All participants underwent sublingual videomicroscopy by sidestream darkfield imaging. A new developed version of the Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell (RBC) velocity, RBC content, and blood flow in sublingual microvessels with diameters between 4 and 25 µm.

Results

A detailed analysis of adjacent diameter classes (1 µm each) of vessels between 4 and 25 µm revealed a severe reduction of vascular density in very small capillaries (5–7 µm), which correlated with markers of sepsis severity. Analysis of RBC velocity (VRBC) revealed a strong dependency between capillary and feed vessel VRBC in sepsis patients (R2 = 0.63, p < 0.0001) but not in healthy controls (R2 = 0.04, p = 0.43), indicating impaired capillary (de-)recruitment in sepsis. This finding enabled the calculation of capillary recruitment and dynamic capillary blood volume (CBVdynamic). Moreover, adjustment of PBR to feed vessel VRBC further improved discrimination between sepsis patients and controls by about 50%. By combining these dynamic microvascular and glycocalyx variables, we developed the microvascular health score (MVHSdynamic™), which decreased from 7.4 [4.6–8.7] in controls to 1.8 [1.4–2.7] in sepsis patients (p < 0.0001) and correlated with sepsis severity.

Conclusion

We introduce new important diameter-specific quantification and differentiated analysis of RBC kinetics, a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect microvascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.
Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies
Authors: Kudo Daisuke , Goto Tadahiro , Uchimido Ryo , Hayakawa Mineji , Yamakawa Kazuma , Abe Toshikazu , Shiraishi Atsushi , Kushimoto Shigeki
Published: March 2021

Background

A recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype.

Methods

This was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation.

Results

Four sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: − 17.8% [95% CI − 28.7 to − 6.9%]) and in-hospital (adjusted RD: − 17.7% [95% CI − 27.6 to − 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: − 24.9% [95% CI − 49.1 to − 0.7%]) and in-hospital mortality (RD: − 30.9% [95% CI − 55.3 to − 6.6%]).

Conclusions

We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.
Molecular and computational approaches to map regulatory elements in 3D chromatin structure
Authors: Lee Beoung Hun , Rhie Suhn K.
Published: March 2021

Epigenetic marks do not change the sequence of DNA but affect gene expression in a cell-type specific manner by altering the activities of regulatory elements. Development of new molecular biology assays, sequencing technologies, and computational approaches enables us to profile the human epigenome in three-dimensional structure genome-wide. Here we describe various molecular biology techniques and bioinformatic tools that have been developed to measure the activities of regulatory elements and their chromatin interactions. Moreover, we list currently available three-dimensional epigenomic data sets that are generated in various human cell types and tissues to assist in the design and analysis of research projects.
Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: A systematic review and meta-analysis
Authors: Alhumaid Saad , Al Mutair Abbas , Al Alawi Zainab , Zaidi Abdul Rehman Zia , Rabaan Ali A. , Elhazmi Alyaa , Al-Omari Awad
Published: March 2021

Background

Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs).

Aims

To re-assess the association between PPIs use and SBP incidence with larger and better-quality data.

Method

The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity.

Results

A total of twenty-three studies: seven case–control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chi2p = 57.68; I2 = 74%). For case–control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger’s test confirmed asymmetry suggesting publication bias (intercept = − 0.05, SE = 0.27, P = 0.850 two-tailed).

Conclusion

This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
Resistance-induced brain activity changes during cycle ergometer exercises
Authors: Lin Ming-An , Meng Ling-Fu , Ouyang Yuan , Chan Hsiao-Lung , Chang Ya-Ju , Chen Szi-Wen , Liaw Jiunn-Woei
Published: March 2021

Background

EEGs are frequently employed to measure cerebral activations during physical exercise or in response to specific physical tasks. However, few studies have attempted to understand how exercise-state brain activity is modulated by exercise intensity.

Methods

Ten healthy subjects were recruited for sustained cycle ergometer exercises at low and high resistance, performed on two separate days a week apart. Exercise-state EEG spectral power and phase-locking values (PLV) are analyzed to assess brain activity modulated by exercise intensity.

Results

The high-resistance exercise produced significant changes in beta-band PLV from early to late pedal stages for electrode pairs F3-Cz, P3-Pz, and P3-P4, and in alpha-band PLV for P3-P4, as well as the significant change rate in alpha-band power for electrodes C3 and P3. On the contrary, the evidence for changes in brain activity during the low-resistance exercise was not found.

Conclusion

These results show that the cortical activation and cortico-cortical coupling are enhanced to take on more workload, maintaining high-resistance pedaling at the required speed, during the late stage of the exercise period.
Heterogeneous field network for power distribution grid based on HPLC and RF adaptive communications technology
Authors: Huang Rui , Xiao Yu , Liu Mouhai , Liu Zhaoyang , Liu Xiaoping , Xu Huiting , Gao Yunpeng , Yang Maotao , Ye Liuqing
Published: March 2021

In order to improve the connection rate and transmission efficiency of field network for power distribution grid, a dual-mode heterogeneous field network with high-speed power line broadband carrier and micro-power radio frequency wireless communication capabilities was designed. First, the topological structure of the field network, the networking process of the central node and the free nodes and the dynamic maintenance mechanism of the network were discussed in detail. Secondly, the routing measurement mechanism for creating a hybrid routing table and the improved layer limit shortest path routing algorithm were presented. On this basis, each node in the network could choose the optimal communication media at any given moment to create communication links with the adaptive data transfer speed according to the real-time hybrid routing table. Finally, the dual-mode heterogeneous field network was applied to the electricity consumption information collection system and tested in the laboratory and jobsite. The test results show that the dual-mode field network was more effective than the single-mode field network in shortening the reading meter time and increasing networking success rate.
Computation of solutions to linear difference and differential equations with a prescribed asymptotic behavior
Authors: Baumann Hendrik , Hanschke Thomas
Published: March 2021

Linear differential equations usually arise from mathematical modeling of physical experiments and real-world problems. In most applications these equations are linked to initial or boundary conditions. But sometimes the solution under consideration is characterized by its asymptotic behavior, which leads to the question how to infer from the asymptotic growth of a solution to its initial values. In this paper we show that under some mild conditions the initial values of the desired solution can be computed by means of a continuous-time analogue of a modified matrix continued fraction. For numerical applications we develop forward and backward algorithms which behave well in most situations. The topic is closely related to the theory of special functions and its extension to higher-dimensional problems. Our investigations result in a powerful tool for solving some classical mathematical problems. To demonstrate the efficiency of our method we apply it to Poincaré type and Kneser’s differential equation.
Generalized degenerate Bernoulli numbers and polynomials arising from Gauss hypergeometric function
Authors: Kim Taekyun , Kim Dae San , Jang Lee-Chae , Lee Hyunseok , Kim Hanyoung
Published: March 2021

A new family of p-Bernoulli numbers and polynomials was introduced by Rahmani (J. Number Theory 157:350–366, 2015) with the help of the Gauss hypergeometric function. Motivated by that paper and in the light of the recent interests in finding degenerate versions, we construct the generalized degenerate Bernoulli numbers and polynomials by means of the Gauss hypergeometric function. In addition, we construct the degenerate type Eulerian numbers as a degenerate version of Eulerian numbers. For the generalized degenerate Bernoulli numbers, we express them in terms of the degenerate Stirling numbers of the second kind, of the degenerate type Eulerian numbers, of the degenerate p-Stirling numbers of the second kind and of an integral on the unit interval. As to the generalized degenerate Bernoulli polynomials, we represent them in terms of the degenerate Stirling polynomials of the second kind.
Pre-Cambrian roots of novel Antarctic cryptoendolithic bacterial lineages
Authors: Albanese Davide , Coleine Claudia , Rota-Stabelli Omar , Onofri Silvano , Tringe Susannah G. , Stajich Jason E. , Selbmann Laura , Donati Claudio
Published: March 2021

Background

Cryptoendolithic communities are microbial ecosystems dwelling inside porous rocks that are able to persist at the edge of the biological potential for life in the ice-free areas of the Antarctic desert. These regions include the McMurdo Dry Valleys, often accounted as the closest terrestrial counterpart of the Martian environment and thought to be devoid of life until the discovery of these cryptic life-forms. Despite their interest as a model for the early colonization by living organisms of terrestrial ecosystems and for adaptation to extreme conditions of stress, little is known about the evolution, diversity, and genetic makeup of bacterial species that reside in these environments. Using the Illumina Novaseq platform, we generated the first metagenomes from rocks collected in Continental Antarctica over a distance of about 350 km along an altitudinal transect from 834 up to 3100 m above sea level (a.s.l.).

Results

A total of 497 draft bacterial genome sequences were assembled and clustered into 269 candidate species that lack a representative genome in public databases. Actinobacteria represent the most abundant phylum, followed by Chloroflexi and Proteobacteria. The “CandidatusJiangella antarctica” has been recorded across all samples, suggesting a high adaptation and specialization of this species to the harshest Antarctic desert environment.

The majority of these new species belong to monophyletic bacterial clades that diverged from related taxa in a range from 1.2 billion to 410 Ma and are functionally distinct from known related taxa.

Conclusions

Our findings significantly increase the repertoire of genomic data for several taxa and, to date, represent the first example of bacterial genomes recovered from endolithic communities. Their ancient origin seems to not be related to the geological history of the continent, rather they may represent evolutionary remnants of pristine clades that evolved across the Tonian glaciation. These unique genomic resources will underpin future studies on the structure, evolution, and function of these ecosystems at the edge of life.
Genetic-variant hotspots and hotspot clusters in the human genome facilitating adaptation while increasing instability
Authors: Long Xi , Xue Hong
Published: March 2021

Background

Genetic variants, underlining phenotypic diversity, are known to distribute unevenly in the human genome. A comprehensive understanding of the distributions of different genetic variants is important for insights into genetic functions and disorders.

Methods

Herein, a sliding-window scan of regional densities of eight kinds of germline genetic variants, including single-nucleotide-polymorphisms (SNPs) and four size-classes of copy-number-variations (CNVs) in the human genome has been performed.

Results

The study has identified 44,379 hotspots with high genetic-variant densities, and 1135 hotspot clusters comprising more than one type of hotspots, accounting for 3.1% and 0.2% of the genome respectively. The hotspots and clusters are found to co-localize with different functional genomic features, as exemplified by the associations of hotspots of middle-size CNVs with histone-modification sites, work with balancing and positive selections to meet the need for diversity in immune proteins, and facilitate the development of sensory-perception and neuroactive ligand-receptor interaction pathways in the function-sparse late-replicating genomic sequences. Genetic variants of different lengths co-localize with retrotransposons of different ages on a “long-with-young” and “short-with-all” basis. Hotspots and clusters are highly associated with tumor suppressor genes and oncogenes (p < 10−10), and enriched with somatic tumor CNVs and the trait- and disease-associated SNPs identified by genome-wise association studies, exceeding tenfold enrichment in clusters comprising SNPs and extra-long CNVs.

Conclusions

In conclusion, the genetic-variant hotspots and clusters represent two-edged swords that spearhead both positive and negative genomic changes. Their strong associations with complex traits and diseases also open up a potential “Common Disease-Hotspot Variant” approach to the missing heritability problem.
Video-feedback promotes sensitive limit-setting in parents of twin preschoolers: a randomized controlled trial
Authors: Euser Saskia , Vrijhof Claudia I. , Van den Bulk Bianca G. , Vermeulen Rachel , Bakermans-Kranenburg Marian J. , van IJzendoorn Marinus H.
Published: March 2021

Background

Primary aim of the current randomized controlled trial was to test the effectiveness of the parenting intervention ‘Video-feedback to promote Positive Parenting and Sensitive Discipline’ (VIPP-SD) in a sample of parents of preschool-aged twins, as well as differential susceptibility to intervention efforts, that is, whether more temperamentally reactive parents would profit more from the VIPP-SD than parents with lower reactivity.

Methods

The sample consisted of 202 families with same-sex twins [N = 404 children, mean age 45 months (SD = 6.81)]. Randomization was done at the family level in a 2:3 ratio, with 83 families (41%) randomized to the VIPP-SD group, and 119 families (59%) to the control group. After two pre-tests in year 1 and year 2 of the study, the VIPP-SD was implemented in the third year, with a post-test assessment 1 month after the five intervention sessions. Parental sensitivity was observed during structured play in which parent and child copied a drawing together in a computerized Etch-A-Sketch paradigm. Parental limit-setting was observed in a ‘don’t touch’ task in which the parent required from the child to abstain from playing with attractive toys. Parents interacted with each of their twins in separate sessions.

Results

The VIPP-SD intervention had a positive impact on the level of parents’ positive limit-setting in interaction with their preschool twins, and this positive effect was most pronounced when the parents completed at least five intervention sessions. However, the intervention did not enhance parental sensitivity during structured play. Parents with higher reactivity were not more open to the impact of the intervention, thus for this temperamental marker differential susceptibility in adults was not supported.

Conclusions

The current study is unique in targeting families with twin preschoolers, providing proof of principle that coaching parents with video-feedback promotes parental sensitive limit-setting to both children. It remains to be seen whether this finding can be replicated in families with non-twin siblings, or other parental susceptibility markers.

Trial registrationTrial NL5172 (NTR5312), 2015-07-20.
Evaluation of drug prescription pattern using World Health Organization prescribing indicators in public health facilities found in Ethiopia: systematic reviews and meta-analysis
Authors: Tefera Bereket Bahiru , Getachew Melese , Kebede Bekalu
Published: March 2021

Background

Drug use evaluation is a structured, methodological, and criteria-based drug assessment system that helps to evaluate the actual trend of drug use in a particular setting. If drug prescription practices are inappropriate, need to examine the patterns of drug use is necessary to change prescribing patterns accordingly. Therefore, this review aimed to determine the drug prescription pattern in public health facilities found in Ethiopia using prescribing indicators developed by the World Health Organization.

Methods

This review was conducted as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Extensive searching to identify articles was conducted in PubMed, Medline, Web of Science, Research Gate, Africa Journal of Online, and Google scholar. Finally, 10 eligible articles were selected for analysis based on inclusion and exclusion criteria. The median value, as well as the 25th and 75th percentiles for each WHO prescribing indicator, were computed.

Result

The pooled median value of WHO prescribing indicators was reported as follows: the average number of drugs prescribed per encounter = 2.14 (IQR 1.79–2.52), the percentage of encounters with antibiotics prescribed = 43.46% (IQR 30.01–58.67), the percentage of encounters with an injection prescribed = 13.20% (6.47–40.7), percentage of drugs prescribed by generic name = 93.49% (89.13–97.96), and the percentage of medicines prescribed from essential medicines list = 92.54% (85.10–97.7). The forest plots determined for each prescribing indicator indicated that there is a high degree of heterogeneity across articles.

Conclusion

All of the prescribing indicators were not consistent with the standard values recommended by the World Health Organization. Therefore, public health facilities should take appropriate measures for improving the prescription patterns as per the recommendation set by the World Health Organization.
Submarine terraces reveal Late Quaternary tectonic deformation in the intermediate zone between the island shelf and rift zone of the middle part of the Nanseishoto Islands, southwest Japan
Authors: Goto Hideaki
Published: March 2021

Late Quaternary tectonic deformation of coastal areas is usually examined based on the height distribution of paleo-shorelines observed on marine terraces. However, it is difficult to examine deformation along the subduction zone, in which small, isolated islands are distributed. In this paper, the author focuses on the widespread shallow submarine terraces surrounding the Iheya–Izena islands in the middle part of the Nanseishoto Islands, Southwest Japan, where crustal deformation is not known. The islands are located in the intermediate zone between island shelf uplifted during the Late Quaternary and the rift zone occurred to the northwest, along the Okinawa trough. Detailed topographic anaglyph images and maps of the islands were produced using a digital elevation model (DEM) of the seafloor, which is stored by the Japan Coast Guard (JCG) and the Advanced Institute of Science and Technology (AIST). Topographic anaglyph images enabled us to identify the widespread distribution and deformation of the shallow seafloor above − 200 m using red–cyan glasses. Four terrace-like features divided by small steps were found on the shallow seafloor, which are named T1, T2, T3, and T4, in descending order. Topographic expressions of paleo-shoreline depths are preserved on submarine terraces formed during the last glacial period. The paleo-shoreline depths of terraces T2 and T3 are − 60 m and − 70 m on the west side and − 70 m and − 80 m, respectively, on the east side of Iheyajima Island; this indicates southeastward tilting. The tilting ratio of T2 and T3 was calculated to approximately 1‰. The tilting rate is approximately 1 × 10–4/kyr, assuming that the T2 was formed in 10–11 kyr. This is much more rapid than that of the last inter-glacial marine terraces in the Muroto peninsula of Shikoku, Japan, with a tilting rate of 4 × 10–5/kyr, which formed by steep northward tilting against the Nankai subduction zone. The author suggests that this phenomenon is not related to mega-thrusting along the subduction zone, but rather to local deformation, probably caused by the reverse faulting of nearby active submarine faults along the west side of the islands.
Laparoscopic approach to recurrence following multiple surgeries for external rectal prolapse: a case report
Authors: Toda Kosuke , Aoyama Taro , Hirai Kenjiro , Uemura Taisuke , Fujita Haruku , Okabe Asami , Ohe Hidenori , Tachibana Tsuyoshi , Mitsuyoshi Akira
Published: March 2021

Introduction

The optimal procedure for recurrent external rectal prolapse remains unclear, particularly in laparoscopic approach. In addition, pelvic organ prolapse (POP) is sometimes concomitant with rectal prolapse. We present a case who underwent laparoscopic procedure for the recurrence of full-thickness external rectal prolapse coexisting POP.

Case presentation

An 81-year-old parous female had a 10-cm full-thickness external rectal prolapse following the two operations: the first was perineal recto-sigmoidectomy and the second was laparoscopic posterior mesh rectopexy. Imaging study revealed that the recurrent rectal prolapse was concomitant with both cystocele and exposed vagina, what we call POP. We planned and successfully performed laparoscopic ventral mesh rectopexy (LVMR) with laparoscopic sacrocolpopexy (LSC) using self-cut meshes without any perioperative complication.

Conclusion

This is the first report of LVMR and LSC for recurrent rectal prolapse with POP following the perineal recto-sigmoidectomy and laparoscopic posterior mesh rectopexy. Even for recurrent rectal prolapse with POP, our experience suggests that LVMR and LSC could be utilized.
Qigong mind-body program for caregivers of cancer patients: design of a pilot three-arm randomized clinical trial
Authors: Shani Pinky , Raeesi Kristin , Walter Eli , Lewis Kai , Wang Wanyi , Cohen Lorenzo , Yeh Gloria Y. , Lengacher Cecile A. , Wayne Peter M.
Published: March 2021

Background

Informal caregivers, often family and friends, experience significant psychological and physical distress leading to reductions in health and quality of life (QOL). Mind-body interventions focused on caregivers are often limited and do not address multiple barriers, including caregivers’ economic, geographic, and time constraints. Translation of in-person, community-based interventions to Internet-based delivery may offer greater accessibility for caregivers, leading to increased adherence.

Methods

Caring for Caregivers with Mind-Body implements a three-arm, pilot, randomized controlled trial to evaluate the feasibility of delivering a Qigong intervention (Eight Brocades) to cancer caregivers. A total of 54 cancer caregivers will be randomized into one of three 12-week programs: (1) community-based Qigong, (2) Internet-based Qigong, or (3) a self-care control group. Study-specific aims include (1) modify intervention content for online delivery, (2) evaluate the feasibility of recruiting and retaining cancer caregivers into a 12-week clinical trial, and (3) evaluate the feasibility of collecting and managing data, and the suitability of questionnaires for this population. Several outcomes will be assessed, including caregiver QOL, caregiver burden, caregiver distress, perceived social support, physical function, and cognitive function. A 6-month follow-up will also assess longer-term changes in QOL and psychosocial well-being.

Discussion

Findings will be used to inform the design and conduct of a large-scale comparative effectiveness trial evaluating caregivers who received Qigong training delivered through community-based vs Internet-based programs. A finding that either or both programs are effective would inform care and options for caregivers.

Trial registration

NCT04019301; registered on July 15, 2019; clinicaltrials.gov
The Odon Device™ for assisted vaginal birth: a feasibility study to investigate safety and efficacy—The ASSIST II study
Authors:   The ASSIST II Study Group, Hotton Emily J. , Alvarez Mary , Lenguerrand Erik , Wade Julia , Blencowe Natalie S. , Draycott Tim J. , Crofts Joanna F.
Published: March 2021

Background

The Odon Device™ is a new device for assisted vaginal birth that employs an air cuff around the fetal head for traction. Assisted vaginal birth (AVB) is a vital health intervention that can result in better outcomes for mothers and their babies when complications arise in the second stage of labour. Unfortunately, instruments for AVB (forceps and ventouse) are often not used in settings where there is most clinical need often due to lack of training and resources, resulting in maternal and neonatal morbidity and mortality which could have been prevented.

This is often due to a lack of trained operators as well as difficulties in the sterilisation and maintenance of AVB devices. This novel, single use device has the potential to mitigate these difficulties as it is single use and is potentially simpler to use than forceps and ventouse.

All the studies of the Odon Device to date (pre-clinical, preliminary developmental and clinical) suggest that the Odon Device does not present a higher risk to mothers or babies compared to current standard care, and recruitment to intrapartum research exploring the device is feasible and acceptable to women. The first study in which the Odon Device was used in clinically indicated conditions (the ASSIST Study) reported a lower efficacy than those reported with established devices. The reasons need to be explored, specifically focussing on learning curve, the technique of the doctors using this new device and potential modifications to device design. A follow-on clinical study to further investigate the efficacy and safety of the Odon Device in its indicated use, the ASSIST II Study, is therefore being undertaken.

Methods

The primary feasibility outcome is study feasibility (recruitment and retention rates) whilst the primary clinical outcome successful vaginal birth completed with the Odon Device. Key secondary feasibility outcomes include participant withdrawal, compliance in data collection and acceptability of the device to women and operators. Secondary clinical outcomes include maternal, neonatal and device outcomes. Safety data will be reviewed following every birth exploring maternal, neonatal and device risks. Using A’Hern approach for sample size calculation, we aim to recruit 104 women requiring an assisted vaginal birth for a recognised clinical indication. Assuming an AVB success rate of 65% or more, a one-sided alpha risk of 5% and power of 90%.

Discussion

The data from the ASSIST II Study will provide the information required regarding acceptability, recruitment, outcome data collection, device design, technique of device use and operator learning curve in order to design a future randomised controlled trial of the Odon Device versus current modes of assisted vaginal birth.

Trial registration

ISRCTN registration: 38829082 (prospectively registered July 26, 2019)
Factors contributing to fidelity in a pilot trial of individualized resistant starches for pediatric inflammatory bowel disease: a fidelity study protocol
Authors: Castillo Gisell , Mack David R. , Lalu Manoj M. , Singleton Ruth , Fergusson Dean A. , Stintzi Alain , Harrison Megan , Presseau Justin
Published: March 2021

Background

The consumption of resistant starches is a promising adjuvant therapy for patients with inflammatory bowel disease. Rigorous evaluation of resistant starches in this setting depends on the intervention being delivered, received, and enacted as intended, that is, with fidelity. As part of a planned pilot trial, participants will be randomized to ingest resistant starches or a placebo. They will also be asked to collect stool samples and keep symptom and dose diaries to inform trial outcomes.

We aim to identify potential factors impacting fidelity to the receipt and enactment of trial intervention and data collection activities from the perspective of patients and caregivers in the trial. Identifying fidelity barriers and enablers at the pilot trial phase of a clinical intervention may help to determine optimization processes when expanding to multiple sites in future trials.

Methods

We will conduct 15-30 semi-structured interviews with pilot trial participants (aged 8-17) and their caregivers. Trial participants will be approached for interviews approximately 6 months after the start of their trial participation. Personal projects analysis, a tool for understanding how individuals manage competing demands in their daily lives, will guide an in-depth exploration of how trial participants engage in activities related to intervention and data collection fidelity (ingesting resistant starches or placebo, collecting stool samples, keeping a symptom and dose diary) amidst the complexities of daily living.

Discussion

The present study will seek to explore and demonstrate how theory-informed fidelity assessments can be conducted alongside pilot trials to inform future multisite trials. Study results will clarify what factors may affect fidelity to trial intervention and data collection activities. Results may suggest what to modify to optimize the design and conduct, and ensure the integrity, of future multisite trials. Conducting process evaluations alongside clinical trials has the potential to improve our understanding of trial participant experiences. Results will provide a better understanding of how trial participants manage to engage in necessary trial activities along with other priorities.
An external pilot cluster randomised controlled trial of a theory-based intervention to improve appropriate polypharmacy in older people in primary care (PolyPrime): study protocol
Authors:   On behalf of the PolyPrime team, Rankin Audrey , Cadogan Cathal A. , Barry Heather E. , Gardner Evie , Agus Ashley , Molloy Gerard J. , Gorman Ashleigh , Ryan Cristín , Leathem Claire , Maxwell Marina , Gormley Gerard J. , Ferrett Alan , McCarthy Pat , Fahey Tom , Hughes Carmel M.
Published: March 2021

Background

The use of multiple medications (polypharmacy) is a concern in older people (≥65 years) and is associated with negative health outcomes. For older populations with multimorbidity, polypharmacy is the reality and the key challenge is ensuring appropriate polypharmacy (as opposed to inappropriate polypharmacy). This external pilot cluster randomised controlled trial (cRCT) aims to further test a theory-based intervention to improve appropriate polypharmacy in older people in primary care in two jurisdictions, Northern Ireland (NI) and the Republic of Ireland (ROI).

Methods

Twelve GP practices across NI (n=6) and the six counties in the ROI that border NI will be randomised to either the intervention or usual care group. Members of the research team have developed an intervention to improve appropriate polypharmacy in older people in primary care using the Theoretical Domains Framework of behaviour change. The intervention consists of two components: (1) an online video which demonstrates how a GP may prescribe appropriate polypharmacy during a consultation with an older patient and (2) a patient recall process, whereby patients are invited to scheduled medication review consultations with GPs. Ten older patients receiving polypharmacy (≥4 medications) will be recruited per GP practice (n=120). GP practices allocated to the intervention arm will be asked to watch the online video and schedule medication reviews with patients on two occasions; an initial and a 6-month follow-up appointment. GP practices allocated to the control arm will continue to provide usual care to patients. The study will assess the feasibility of recruitment, retention and study procedures including collecting data on medication appropriateness (from GP records), quality of life and health service use (i.e. hospitalisations). An embedded process evaluation will assess intervention fidelity (i.e. was the intervention delivered as intended), acceptability of the intervention and potential mechanisms of action.

Discussion

This pilot cRCT will provide evidence of the feasibility of a range of study parameters such as recruitment and retention, data collection procedures and the acceptability of the intervention. Pre-specified progression criteria will also be used to determine whether or not to proceed to a definitive cRCT.

Trial registration

ISRCTN, ISRCTN41009897. Registered 19 November 2019. ClinicalTrials.gov, NCT04181879. Registered 02 December 2019.
Vitreomacular interface after anti-VEGF injections in diabetic macular edema
Authors: Veloso Carlos E. , Brocchi Daniel N. , Singh Rishi P. , Nehemy Márcio B.
Published: March 2021

Background

The purpose of this study was to evaluate the incidence of vitreomacular adhesion (VMA) release after anti-VEGF therapy for the treatment of diabetic macular edema (DME) and to evaluate further changes in outcome.

Methods

This was a retrospective study that enrolled 66 eyes of 66 patients with DME who presented with VMA diagnosed by spectral-domain optical coherence tomography (OCT) at baseline. VMA was classified as focal (attachment: ≤ 1500 μm) or broad (attachment: > 1500 μm). All patients received at least three monthly intravitreal injections of an anti-VEGF agent. Follow-up visits were performed 1 month after each injection to evaluate the incidence of VMA release.

Results

The mean patient age was 61.4 years (range: 29 to 78 years), and 72.7 % were male. The mean best-corrected visual acuity was 0.62 logMAR, and the mean central retinal thickness (CRT) was 473 μm at baseline. The mean length of follow-up was 18.5 months, and the mean number of injections was 5.8. The intravitreal drugs used were aflibercept (40.9 %), ranibizumab (37.9 %) and bevacizumab (21.2 %). Forty-seven eyes had broad VMA, and 19 had focal VMA. Twenty-two eyes (33.3 %) developed VMA release following a mean of 5.7 injections (range: 3–13). Sixteen eyes (72.7 %) with focal VMA and 6 eyes (27.3 %) with broad VMA at baseline developed VMA release. Twenty-one eyes that developed VMA release showed an improvement in CRT following VMA release (mean: -106 μm; range: 22 to 289 μm).

Conclusions

VMA release occurs in approximately 1/3 of patients with DME following anti-VEGF therapy. Most of them show a short-term decrease in CRT.
Grasshopper optimization algorithm optimized multistage controller for automatic generation control of a power system with FACTS devices
Authors: Nayak Pratap Chandra , Prusty Ramesh Chandra , Panda Sidhartha
Published: March 2021

This paper uses a Grasshopper Optimization Algorithm (GOA) optimized PDF plus (1 + PI) controller for Automatic generation control (AGC) of a power system with Flexible AC Transmission system (FACTS) devices. Three differently rated reheat turbine operated thermal units with appropriate generation rate constraint (GRC) are considered along with different FACTS devices. A new multistage controller design structure of a PDF plus (1 + PI) is introduced in the FACTS empowered power system for AGC while the controller gains are tuned by the GOA. The superiority of the proposed algorithm over the Genetic Algorithm (GA) and Particle Swarm Optimization (PSO) algorithms is demonstrated. The dynamic responses of GOA optimized PDF plus (1 + PI) are compared with PIDF, PID and PI controllers on the same system. It is demonstrated that GOA optimized PDF plus (1 + PI) controller provides optimum responses in terms of settling time and peak deviations compared to other controllers. In addition, a GOA-tuned PDF plus (1 + PI) controller with Interline Power Flow Controller (IPFC) exhibits optimal results compared to other FACTS devices. The sturdiness of the projected controller is validated using sensitivity analysis with numerous load patterns and a wide variation of parameterization. To further validate the real-time feasibility of the proposed method, experiments using OPAL-RT OP5700 RCP/HIL and FPGA based real-time simulations are carried out.
Capillaroscopy as a diagnostic tool in the diagnosis of mixed connective tissue disease (MCTD): a case report
Authors: Radić Mislav , Overbury Rebecca S.
Published: March 2021

Background

The concept of mixed connective tissue disease (MCTD) as a unique connective tissue disease has endured for half a century. Disease onset can be in adulthood (MCTD) or of juvenile onset (jMCTD) and is characterized by overlapping features of systemic lupus erythematosus (SLE), polymyositis or dermatomyositis (PM/DM) and systemic sclerosis (SSc). No universally accepted classification criteria for MCTD exists, however agreed upon overlapping disease features include the presence of high titers of U1 small nuclear ribonucleoprotein particle antibodies (U1snRNP) in the peripheral blood, Raynaud’s phenomenon, synovitis, myositis and swollen hands or fingers. Characteristic capillaroscopy findings are commonly seen in MCTD and jMCTD, which may represent a crucial and key clue for classification as well as prognosis in these patients.

Case presentation

We present a young male patient, with symptom onset as early as age 13, who was diagnosed with MCTD at age 16 and found to have high titers of anti-U1snRNP antibodies, Raynaud’s phenomenon, synovitis, and swollen hands and fingers. Most interestingly, his video capillaroscopy at diagnosis was abnormal and revealed an active SSc-like pattern. His presentation and course are described.

Conclusions

We conclude that based on existing data, and as highlighted by this case presentation, nailfold video capillaroscopy should be included as an early screening tool for the detection of microangiopathy in patients with the diagnosis MCTD and jMCTD. Additionally, given its prevalence in this population at disease diagnosis, we recommend consideration be given to nailfold video capillaroscopy as a potentially important classification criteria and prognostic tool for jMCTD and MCTD.
Super selective percutaneous transhepatic coil embolization of intrahepatic pseudoaneurysm after pediatric liver transplantation: a case report
Authors: Huf V. I. , Grothues D. , Knoppke B. , Goessmann H. , Wohlgemuth W. A. , Melter M. , Brunner S. M. , Schlitt H. J. , Uller W.
Published: March 2021

Background

Intrahepatic arterial pseudoaneurysms are a rare, life-threatening complication after pediatric liver transplantation. Treatment of choice represents interventional radiological management with endovascular embolization of the segmental artery proximal and distal to the aneurysm. However, this technique results in loss of arterial perfusion distal to the aneurysm with subsegment arterial ischemia.

Case presentation

We report a case of a 1-year-old girl with a pseudoaneurysm in the split-liver graft. Direct percutaneous, transhepatic access to the pseudoaneurysm was performed followed by super selective coil application into the aneurysm.

Conclusion

Super selective percutaneous, transhepatic coil application is feasible even in pediatric patients after liver transplantation and results in preservation of the entire course of the liver artery.