bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid parameter estimation for selective inversion recovery myelin imaging using an open-source Julia toolkit
Authors: Sisco Nicholas J. , Wang Ping , Stokes Ashley , Dortch Richard
Published: September 2021

Background

Magnetic resonance imaging (MRI) is used extensively to quantify myelin content, however computational bottlenecks remain challenging for advanced imaging techniques in clinical settings. We present a fast, open-source toolkit for processing quantitative magnetization transfer derived from selective inversion recovery (SIR) acquisitions that allows parameter map estimation, including the myelin-sensitive macromolecular pool size ratio (PSR). Significant progress has been made in reducing SIR acquisition times to improve clinically feasibility. However, parameter map estimation from the resulting data remains computationally expensive. To overcome this computational limitation, we developed a computationally efficient, open-source toolkit implemented in the Julia language.

Methods

To test the accuracy of this toolkit, we simulated SIR images with varyingPSRand spin-lattice relaxation time of the free water pool (R1f) over a physiologically meaningful scale from 5 to 20% and 0.5 to 1.5 s-1, respectively. Rician noise was then added, and the parameter maps were estimated using our Julia toolkit. Probability density histogram plots and Lin’s concordance correlation coefficients (LCCC) were used to assess accuracy and precision of the fits to our known simulation data. To further mimic biological tissue, we generated five cross-linked bovine serum albumin (BSA) phantoms with concentrations that ranged from 1.25 to 20%. The phantoms were imaged at 3T using SIR, and data were fit to estimatePSRandR1f. Similarly, a healthy volunteer was imaged at 3T, and SIR parameter maps were estimated to demonstrate the reduced computational time for a real-world clinical example.

Results

Estimated SIR parameter maps from our Julia toolkit agreed with simulated values (LCCC> 0.98). This toolkit was further validated using BSA phantoms and a whole brain scan at 3T. In both cases, SIR parameter estimates were consistent with published values using MATLAB. However, compared to earlier work using MATLAB, our Julia toolkit provided an approximate 20-fold reduction in computational time.

Conclusions

Presented here, we developed a fast, open-source, toolkit for rapid and accurate SIR MRI using Julia. The reduction in computational cost should allow SIR parameters to be accessible in clinical settings.
Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis
Authors: Ortega-Gonzalez Paula , Taylor Gwen , Jangra Rohit K. , Tenorio Raquel , de Castro Isabel Fernández , Mainou Bernardo A. , Orchard Robert C. , Wilen Craig B. , Brigleb Pamela H. , Sojati Jorna , Chandran Kartik , Risco Cristina , Dermody Terence S.
Published: September 2021

Cholesterol homeostasis is required for the replication of many viruses, including Ebola virus, hepatitis C virus, and human immunodeficiency virus-1. Niemann-Pick C1 (NPC1) is an endosomal-lysosomal membrane protein involved in cholesterol trafficking from late endosomes and lysosomes to the endoplasmic reticulum. We identified NPC1 in CRISPR and RNA interference screens as a putative host factor for infection by mammalian orthoreovirus (reovirus). Following internalization via clathrin-mediated endocytosis, the reovirus outer capsid is proteolytically removed, the endosomal membrane is disrupted, and the viral core is released into the cytoplasm where viral transcription, genome replication, and assembly take place. We found that reovirus infection is significantly impaired in cells lacking NPC1, but infection is restored by treatment of cells with hydroxypropyl-β-cyclodextrin, which binds and solubilizes cholesterol. Absence of NPC1 did not dampen infection by infectious subvirion particles, which are reovirus disassembly intermediates that bypass the endocytic pathway for infection of target cells. NPC1 is not required for reovirus attachment to the plasma membrane, internalization into cells, or uncoating within endosomes. Instead, NPC1 is required for delivery of transcriptionally active reovirus core particles into the cytoplasm. These findings suggest that cholesterol homeostasis, ensured by NPC1 transport activity, is required for reovirus penetration into the cytoplasm, pointing to a new function for NPC1 and cholesterol homeostasis in viral infection.

Author summary

Genetic screens are useful strategies to identify host factors required for viral infection. NPC1 was identified in independent CRISPR and RNA interference screens as a putative host factor required for reovirus replication. We discovered that NPC1-mediated cholesterol transport is dispensable for reovirus attachment, internalization, and disassembly but required for penetration of the viral disassembly intermediate from late endosomes into the cytoplasm. These findings pinpoint an essential function for cholesterol in the entry of reovirus and raise the possibility that cholesterol homeostasis regulates the entry of other viruses that penetrate late endosomes to initiate replication.
The APC/CCCS52A2 E3-Ligase Complex targeted PKN1 Protein is a Plant Lineage-Specific Driver of Cell Division
Authors: Willems Alex , Liang Yuanke , Heyman Jefri , Eekhout Thomas , Van den Daele Hilde , Vercauteren Ilse , De Veylder Lieven
Published: September 2021

The anaphase-promoting complex/cyclosome (APC/C) marks key cell cycle proteins for proteasomal breakdown, thereby ensuring unidirectional progression through the cell cycle. Its target recognition is temporally regulated by activating subunits, one of which is called CELL CYCLE SWITCH 52 A2 (CCS52A2). We sought to expand the knowledge of identified APC/C targets by using the severe growth phenotypes of CCS52A2-deficient Arabidopsis thaliana plants as a readout in a suppressor mutagenesis screen, resulting in the identification of the previously undescribed gene called PIKMIN1 (PKN1). PKN1 deficiency rescues the disorganized root stem cell phenotype of the ccs52a2-1 mutant, whereas an excess of PKN1 inhibits growth of ccs52a2-1 plants, indicating the importance of PKN1 abundance for proper development. Accordingly, the lack of PKN1 in a wild-type background negatively impacts cell division, while its ectopic expression promotes proliferation. PKN1 shows a cell cycle phase-dependent accumulation pattern, localizing to microtubular structures, including the preprophase band, the mitotic spindle, and phragmoplast. PKN1 is conserved throughout the plant kingdom, with its function in cell division being evolutionary conserved in the liverwort Marchantia polymorpha. Our data thus demonstrate that PKN1 represents a novel, plant-specific gene with a rate-limiting role in cell division, which is proteolytically controlled by the CCS52A2-activated APC/C.

One-Sentence Summary

PKN1 is a conserved plant-specific protein that is rate-limiting for cell division, likely through its interaction with microtubuli, and is proteolytically controlled by APC/CCCS52A2.
Dynein acts to cluster glutamate receptors and traffic the PIP5 kinase, Skittles, to regulate postsynaptic membrane organization at the neuromuscular junction
Authors: Neisch Amanda L. , Pengo Thomas , Avery Adam W. , Li Min-Gang , Hays Thomas S.
Published: September 2021

Cytoplasmic dynein is essential in motoneurons for retrograde cargo transport that sustains neuronal connectivity. Little, however, is known about dynein’s function on the postsynaptic side of the circuit. Here we report distinct postsynaptic roles for dynein at neuromuscular junctions (NMJs). Intriguingly, we show that dynein punctae accumulate postsynaptically at glutamatergic synaptic terminals. Moreover, Skittles, a phosphatidylinositol 4-phosphate 5-kinase that produces PI(4,5)P2 to organize the spectrin cytoskeleton, also localizes specifically to glutamatergic synaptic terminals. Depletion of postsynaptic dynein disrupts the accumulation of Skittles, PI(4,5)P2 phospholipid, and organization of the spectrin cytoskeleton at the postsynaptic membrane. Coincidental with dynein depletion, we observe an increase in the clusters size of ionotropic glutamate receptor (iGluR), and an increase in the amplitude and frequency of mEJPs. However, PI(4,5)P2 levels do not affect iGluR clustering and dynein does not affect the protein levels of iGluR subunits at the NMJ, suggesting a separate, transport independent function for dynein in iGluR cluster organization. As dynein punctae closely associate with iGluR clusters, we propose that dynein physically tethers iGluR clusters at the postsynaptic membrane to ensure proper synaptic transmission.
Leukocyte adhesion is governed by endolysosomal two pore channel 2 (TPC2)
Authors: Goretzko Jonas , Heitzig Nicole , Thomas Katharina , Krogsaeter Einar Kleinhans , Naß Johannes , Linard Matos Anna Lívia , Wegner Tristan , Schloer Sebastian , Gerke Volker , Rossaint Jan , Glorius Frank , Bracher Franz , Grimm Christian , Rescher Ursula
Published: September 2021

In response to pro-inflammatory challenges including pathogenic attack and tissue damage, the endothelial cell surface is rearranged to present leukocyte-engaging cell surface receptors. The initial contact needed for leukocyte tethering and rolling is mediated via adhesion demand-driven exocytosis of Weibel-Palade bodies (WPB) that contain the leukocyte receptor P-selectin together with the stabilizing co-factor CD63. We found that diminished expression of the endolysosomal non-selective cation channel TPC2 or inhibition of TPC2-mediated Ca2+-release via trans-Ned 19 led to reduced endolysosomal Ca2+ efflux, and blocked transfer of CD63 from late endosomes/lysosomes (LEL) to WPB, and a concomitant loss of P-selectin on the endothelial cell surface. Accordingly, P-selectin-mediated leukocyte recruitment to trans-Ned 19-treated HUVEC under flow was significantly reduced without disturbing VWF exocytosis. Our findings establish the endolysosome-related TPC2 Ca2+ channel as a key element in the maintenance of proper endothelial functions and a potential pharmacological target in the control of inflammatory leukocyte recruitment.
The influence of refinement strategies on the wavefunctions derived from an experiment
Authors: Landeros-Rivera Bruno , Contreras-García Julia , Dominiak Paulina M.
Published: September 2021

The synergy between theory and experiment found in X-ray wavefunction refinement (XWR) makes it one of the most compelling techniques available for chemical physics. The foremost benefit of XWR – obtaining wavefunctions constrained to experimental data – is at the same time its Achilles heel, because of the dependence of the results on the quality of both empirical and theoretical data. The purpose of this work is to answer the following: What is the effect of the refinement strategy and manipulation of input data on the physical properties obtained from XWR? With that in mind, cutoffs based on data resolution and F/σ(F) ratios were applied for both steps of XWR, the Hirshfeld atom refinement (HAR) and the X-ray constrained wavefunction fitting (XCW), for four selected systems: sulfur dioxide, urea, carbamazepine and oxalic acid. The effects of changing the weighting scheme or the method to transform σ(F
2) to σ(F) were also analysed. The results show that while HAR always reaches the same result, XCW is extremely sensitive to crystallographic data manipulation. This is a result of the variability of the experimental uncertainties for different resolution shells, and of not having proper standard uncertainties. Therefore, the use of distinct constraints for each resolution interval in XCW is proposed to fix this instability.
Crystal structure and Hirshfeld surface analysis of 2,2,2-trichloro-N,N-bis{[(1RS,4SR)-1,4-dihydro-1,4-epoxynaphthalen-1-yl]methyl}acetamide
Authors: Atioğlu Zeliha , Akkurt Mehmet , Mammadova Gunay Z. , Bhattarai Ajaya
Published: September 2021

In the title compound, C24H18Cl3NO3, the tetrahydrofuran rings adopt envelope conformations. In the crystal, C—H...O hydrogen bonds connect molecules, generating layers parallel to the (001) plane. These layers are connected along the c-axis direction by C—H...π interactions. The packing is further stabilized by interlayer van der Waals and interhalogen interactions. The most important contributions to the surface contacts are from H...H (36.8%), Cl...H/H...Cl (26.6%), C...H/H...C (18.8%) and O...H/H...O (11.3%) interactions, as concluded from a Hirshfeld surface analysis.
The role of social media in food waste prevention behaviour
Authors: Teoh Chai Wen , Koay Kian Yeik , Chai Pei Sun
Published: September 2021

Purpose

This research aims to investigate consumers' food waste prevention behaviour through the lens of an extended theory of planned behaviour. The extension includes the examination of the role of social media usage in affecting consumers' decision-making process of food waste prevention behaviour.

Design/methodology/approach

A survey questionnaire is developed based on measurement items of previously validated studies. 210 samples are collected and analysed using partial least squares structural equation modelling (PLS-SEM).

Findings

The results show that social media usage has a significant influence on attitude and injunctive norms. In addition, intention can be predicted by injunctive norms, moral norms and perceived behavioural control but not attitude. Lastly, the intention to reduce food waste is a significant predictor of food waste prevention behaviour.

Originality/value

Overall, the extended theory of planned behaviour is useful in explaining consumers' food waste prevention behaviour. Interestingly, this study reveals that a negative attitude towards food waste behaviour does not translate into the intention to engage in food waste prevention behaviour. Furthermore, it is found that social media usage plays a significant in shaping consumers' attitudes towards food waste and injunctive norms.
Numerical simulation of the electroosmotic flow of the Carreau-Yasuda model in the rectangular microchannel
Authors: Ghorbani Saeed , Jabari Moghadam Ali , Emamian Amin , Ellahi R. , Sait Sadiq M.
Published: September 2021

Purpose

In this paper aims to investigate the numerical simulation of the electroosmotic flow of the Carreau-Yasuda model in the rectangular microchannel. Electromagnetic current is generated by applying an effective electric field in the direction of the current.

Design/methodology/approach

The non-Newtonian model used is the five-constant Carreau-Yasuda model which the non-Newtonian properties of the fluid can be well modeled. Using the finite difference method, the potential values at all points in the domain are obtained. Then, the governing equations (momentum conservation) and the energy equation are segregated and solved using a finite difference method.

Findings

In this paper, the effect of various parameters such as Weisenberg number, electrokinetic diameter, exponential power number on the velocity field and Brinkman and Pecklet dimensionless numbers on temperature distribution are investigated. The results show that increasing the Weissenberg dimensionless number and exponential power and diameter parameters reduces the maximum velocity field in the microchannel.

Originality/value

To the best of the authors’ knowledge, this study is reported for the first time.
Bansho as part of lesson and lesson study: from the origins to the present
Authors: Tan Shirley
Published: September 2021

Purpose

This paper aims to provide an overview of the origins of bansho, how it has developed to be an indispensable practice in Japan and its influence on countries outside Japan. The integration of bansho into lesson study (LS) will also be presented.

Design/methodology/approach

This paper draws on the vast literature on bansho from both in and outside Japan to illustrate the points mentioned above.

Findings

Recapitulation on the history of chalkboard and bansho in different eras in Japan illustrated its endurance towards the test of time, geographical space and functions. While bansho remains a constant presence in LS research, there has not been any work that outlines how bansho is integrated into the LS cycle. Thus, a guideline on how bansho can be incorporated in the LS cycle is provided.

Originality/value

A comprehensive overview of bansho allows educators and researchers outside Japan to move beyond the know-how and know-what of bansho; it would serve as an invaluable source to understand the core concepts underlying this classroom practice, thus avoiding the mere adaptation of bansho superficial aspects. This study also provides precise instruction on how bansho can be integrated into each step of the LS cycle, which will guide teachers and researchers in the future implementation of LS.
Software platform owners' entry and application developers' innovations: a conceptual model
Authors: Zuo Yan , Song Di
Published: September 2021

Purpose

The primary aim of this article is to develop an understanding that resolves and integrates the conflicting findings with regard to the effects of platform-owner entry on the innovation of individual complementors.

Design/methodology/approach

Drawing on the platform ecosystem literature and the profiting from innovation (PFI) framework, this study presents a conceptual model that articulates how developers' marketing capabilities and the size of platform's installed base are two key moderators that explain the conflicting results between platform-owner entry and complementor innovations.

Findings

This article theorizes that platform owners' entry stimulates developers' innovations when the size of platform's installed base is large or when developers' marketing capabilities are strong while the entry can discourage innovations otherwise.

Originality/value

By proposing the conceptual model, this article makes important theoretical contributions to the rising literature on platform governance and complementor innovations. It lays a foundation for future research exploring the implications of platform-owner entry.
The factors influencing technological entrepreneurship in nanotechnology businesses
Authors: Nikraftar Tayebeh , Hosseini Elahe , Mohammadi Elham
Published: September 2021

Purpose

Technological entrepreneurship has been a very significant topic in recent decades. It has a crucial role in economic modernization and growth. The need for technological entrepreneurship is because technology-based industries are expanding rapidly and are replacing traditional industries. Therefore, this study aimed at identifying the factors affecting the success of technological entrepreneurship in Iranian nanotechnology businesses.

Design/methodology/approach

The research was conducted through mixed method. The participants in the qualitative section included 17 university experts and executive managers in the field of nanotechnology in Iran, and 75 nanotechnology business managers participated in the quantitative section. The interview and questionnaire were used to collect information. In order to measure and fit the models, the confirmatory factor analysis method and PLS3 software were used.

Findings

The results indicated that the key factors affecting the success of the technological entrepreneurship process in nanotechnology were classified into five general categories: organizational, environmental, institutional, individual and technology factors. Moreover, it was shown that all these dimensions had a positive and significant effect on technological entrepreneurship. In addition, the organizational dimension has an essential role.

Originality/value

Companies' ability to engage technological entrepreneurship is a vital factor in human resource management and strategic management. However, technological entrepreneurship in Iranian nanotechnology businesses has not been involved integrally in the context of companies.
Functional diversity of macroinvertebrates as a tool to evaluate wetland restoration
Authors: Coccia Cristina , Almeida Bia A. , Green Andy J. , Gutiérrez Ana Belén , Carbonell José Antonio
Published: September 2021

Ecological restoration of aquatic ecosystems has become widespread in recent decades. Although the recovery of biodiversity in restored wetlands has been studied from a taxonomic perspective, our knowledge of how functional biodiversity recovers remains poorly understood.

We studied the functional diversity of macroinvertebrate communities in 32 Mediterranean temporary ponds 6–7 years after their creation during a restoration in South‐West Spain, and compared them with 10 natural reference sites during two consecutive hydroperiods. We compared alpha functional diversity indices, and the individual contributions of new ponds and reference sites to the regional functional beta diversity, as well as to its turnover and nestedness components. We also investigated the influence of environmental and spatial variables on the dissimilarities of functional beta diversity and its components between new ponds and reference sites.

Alpha functional diversity in new ponds was lower than in reference sites. Although the contribution of new ponds to the regional functional beta diversity was similar to that of reference sites, the latter contributed more to functional turnover while new ponds contributed more to functional nestedness.

Dispersal limitation coupled with environmental filtering structured the functional variation in communities between new ponds and reference sites, but their relative importance differed between beta components. New ponds can hold species with unique functional compositions, but their contribution to the regional functional beta diversity was mostly due to trait losses with respect to reference sites.

Synthesis and applications. Considering different aspects of functional diversity of invertebrate communities can help elucidate the processes and mechanisms through which ecosystems recover following restoration. We encourage the use of trait‐based approaches to identify trends in processes and patterns that can guide future wetland restoration projects.
Variation in biomass allocation and root functional parameters in response to fire history in Brazilian savannas
Authors: Le Stradic Soizig , Roumet Catherine , Durigan Giselda , Cancian Leonardo , Fidelis Alessandra
Published: September 2021

Fire is a fundamental ecological factor in savannas because it affects vegetation dynamics and ecosystem functioning. However, the effects of fire on below‐ground compartments, including biomass and root traits, and their regeneration remain poorly understood. In this study, we assess the variation of above‐ and below‐ground plant components along fire‐history gradients in Brazilian open savannas and investigate whether changes in vegetation and soil properties are associated with the responses of below‐ground biomass and root traits.

The study was conducted in eight sampling areas of open savanna (campo sujo, i.e. vegetation having low woody cover) within the Cerrado (Brazilian savannas), located along a gradient of time since the last fire (1–34 years); the number of fires that occurred within the past 34 years (0–9 fires) varied by sampling area. In each sampling area, we measured above‐ and below‐ground biomass, root depth distribution, root functional parameters and nutrient levels in the upper soil layers (0–10 cm).

Rapid recovery of above‐ground live biomass after a fire was primarily due to resprouting of graminoids. This recovery was associated with an increase in absorptive root biomass in the upper soil layer in the most recently burnt sites, whereas root biomass was unaffected in deeper layers. Root parameters remained constant regardless of fire history but responded to variations in vegetation structure and soil properties. Specific root length (SRL) decreased with K, Mg2+, Al3+, N and C and increased with P concentration. In contrast, root tissue density (RTD) and absorptive root proportion were negatively correlated with soil P. RTD was strongly associated with the above‐ground biomass of graminoids. Soil texture impacted the root system: the proportion of absorptive roots increased with fine sand content in the soil, inversely to transport root biomass. The relationship between fire and soil properties was insignificant.

Synthesis. In savannas, fire stimulates absorptive root biomass in response to the higher demand for below‐ground resources. This response is correlated with shoot regrowth after a fire. Variations in morphological root parameters are not directly associated with fire history; instead, they reflect differences in soil chemistry, especially soil P and graminoid biomass changes.
Escalated grades of complications correlate with incremental costs of video‐assisted thoracoscopic surgery major lung resection for lung cancer in China
Authors: Lan Ke , Zhou Jian , Sui Xizhao , Wang Jun , Yang Fan
Published: September 2021

Objective

Few studies have focused on factors associated with the incremental cost of video‐assisted thoracoscopic surgery (VATS) in China. We aim to systematically classify the complications after VATS major lung resection and explore their correlation with hospital costs.

Methods

Patients with pathologically stage I–III lung cancer who underwent VATS major lung resections from January 2007 to December 2018 were included. The Thoracic Mortality and Morbidity (TM&M) Classification system was used to evaluate postoperative complications. Grade I and II complications, defined as minor complications, require no therapy or pharmacologic intervention only. Grade III and IV complications, defined as major complications, require surgical intervention or life support. Grade V results in death. A generalized linear model was used to explore the correlation of incremental hospital costs and complications, as well as other clinicopathologic parameters between 2013 and 2016.

Results

A total of 2881 patients were enrolled in the first part, and the minor and major complications rates were 24.3% (703 patients) and 8.3% (228 patients), respectively. Six hundred and eighty‐two patients were enrolled in the second part. The complications grade II (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.05–1.2, p = 0.0005), grade III (OR 1.55, 95% CI 1.26–1.9, p < 0.0001), grades IV and V (OR 1.09, 95% CI 1.04–1.13, p = 0.0002), diffusion capacity of carbon dioxide (OR 0.998, 95% CI 0.997–1.000, p = 0.004), and duration of chest drainage (OR 1.03, 95% CI 1.02–1.04, p < 0.001) and were independent risk factors for the increase in in‐hospital costs of VATS major lung resections.

Conclusions

The severity of complications graded by the TM&M system was an independent risk factor for increased in‐hospital costs.
Positive tone and initial coin offering
Authors: Zhang Shuyu , Aerts Walter , Zhang Dunli , Chen Zishan
Published: September 2021

An initial coin offering (ICO) has become a popular venue for crowdfunding at an early stage in a blockchain project. In the ICO process, a whitepaper may serve as an effective marketing tool to influence investor perception and investor trading behaviour. In this paper, we investigate whether management sentiment, as captured by the disclosure tone of the ICO whitepaper, is seen as a credible signal and capable of affecting price behaviour of the ICO on its first trading day. We document a positive association between management’s net positive tone in the whitepaper and ICO first‐day return, indicating that management sentiment has a significant impact on investor behaviour. Our findings show, however, that such association is contingent on the presence of causal argument, suggesting that disclosure tone needs a significant extent of causal reasoning support to back up its credibility and make it persuasive. These findings provide incremental evidence on the relationship between management tone and relative asset returns during an ICO process in the cryptocurrency markets. While management may benefit from soft information disclosure in the whitepaper, investors and regulators should be aware of self‐serving incentives in whitepaper disclosures.
Using drone imagery to upscale estimates of water capacity in tank bromeliads on steep neotropical inselbergs
Authors: Lehmann Jan R. K. , Prior Milan D. , de Paula Luiza F. A. , Azevedo Luísa , Porembski Stefan , Buttschardt Tillmann K. , Solar Ricardo
Published: September 2021

A substantial fraction of stored freshwater available on neotropical inselbergs is impounded within the rosettes of bromeliads. Their high water retention capacity can potentially have an outcome on the inselberg community as well as on the surrounding environment. However, there are no studies measuring and extrapolating the water retention capacity of bromeliads from single observations to larger spatial scales. Using simple drone‐based imagery, we were able to calculate and upscale the water tank capacity of Alcantarea distractila, a bromeliad genus which is widespread on inselbergs in Southeastern Brazil. Our results provide a firstarge scale quantification of the estimated availability of water tank reservoir of inselbergs, which highlights the potential provisional ecosystem service delivered by bromeliad species.
The role of hydrodissection in native tissue repair of anterior vaginal wall defects
Authors: Schwarzman Polina , Samueli Benzion , Shaco‐Levy Ruth , Baumfeld Yael , Leron Elad , Weintraub Adi Y.
Published: September 2021

Aims

A variety of surgical techniques are available for vaginal prolapse repair, indicating a lack of consensus. A debate regarding the utility of hydrodissection for splitting the surgical plane of the vaginal wall exists. The aim of this study is to evaluate the impact of hydrodissection in anterior colporrhaphy (AC).

Materials

Patients undergoing primary AC were randomly assigned to an approach with (study group) versus without (control group) hydrodissection. Five surgeons performed both techniques, and the trimmed vaginal tissue was retrieved for histological analysis. Two pathologists, blinded to the surgical approach, evaluated the presence of a loose connective tissue at the surgical dissection plane (controversially deemed ‘fascia’, as explained in this article). In addition, we compared the operative time, pain score and haemoglobin levels. After statistical analysis, data were presented using percentile, and statistical significance was tested using the χ2 and Fisher’s exact tests.

Results

Forty‐six patients underwent primary elective AC, with 23 patients in each, the study and control groups. The groups were comparable regarding age (study group 60.33 ± 11.95 years and control group 59.86 ± 12.04, P = 0.90), menopausal status (study group 17 (73.9%) and control group 15 (68.2%), P = 0.67) and other characteristics. We found no difference in sample characteristics between the two groups. Connective tissue was found in only 13.6% (n = 3) of patients after hydrodissection and in 27.3% (n = 6) of patients without hydrodissection (P = 0.46). The hydrodissection group had significantly less bleeding than the control group (ΔHB 0.66 ± 0.66 vs 1.21 ± 0.84, P = 0.05).

Conclusions

After hydrodissection, less bleeding was noted without compromise the surgical planes.
Etiology, risk factors, and prognosis of patients with syncope: A single‐center analysis
Authors: Ling Lin , Feng Tingting , Xue Xiaofeng , Ling Zicheng
Published: September 2021

Objective

To investigate the main causes, risk factors, and prognosis of patients hospitalized with syncope.

Methods

The patients admitted due to syncope were included. We analyzed the etiology, risk factors, and prognosis of patients with an average follow‐up of 15.3 months.

Results

High‐risk factors for cardiogenic syncope included age ≥60, male, hypertension, palpitation, troponin T‐positive, abnormal ECG, CHD history, and syncope‐related trauma. Mortality rate was 4.6%, recurrence rate of syncope was 10.5%, and the rehospitalization rate was 8.5%. Univariate analysis showed that prognosis of syncope was related to age ≥60 years old, hypertension, positive troponin T, abnormal electrocardiogram, and coronary heart disease (p < .05). Multivariate Cox proportional hazard analysis showed that age ≥60 years old (p = .021) and high‐sensitivity troponin‐positive (p = .024) were strongly related to the prognosis of syncope. Kaplan–Meier curve showed statistical difference in the survival rate between the groups divided by age ≥60 years (p = .028), hs‐TnT‐positive (p < .001), abnormal ECG (p = .027), and history of CHD (p = .020).

Conclusion

High‐risk factors for cardiogenic syncope included age ≥60, male, hypertension, palpitation, troponin T‐positive, abnormal ECG, CHD family history, and syncope‐related trauma. Age, hypertension, troponin T‐positive, abnormal ECG, and CHD history were associated with the prognosis of syncope.
Low muscularity increases the risk for post‐operative pneumonia and delays recovery from complications after oesophago‐gastric cancer resection
Authors: Murnane Lisa C. , Forsyth Adrienne K. , Koukounaras Jim , Pilgrim Charles H. C. , Shaw Kalai , Brown Wendy A. , Mourtzakis Marina , Tierney Audrey C. , Burton Paul R.
Published: September 2021

Background

Low muscularity is associated with adverse surgical outcomes. We aimed to determine whether low muscularity is associated with an increased risk of post‐operative complications and reduced long‐term survival after oesophago‐gastric cancer surgery.

Methods

Patients who underwent radical oesophago‐gastric cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Low skeletal muscle index (SMI), measured by CT, was determined using pre‐defined cut‐points. Oncological, surgical, complications and outcome data were obtained from a prospective database.

Results

Of 108 patients, 61% (n = 66) had low SMI preoperatively. Patients with low SMI had a higher rate of post‐operative pneumonia (30 vs. 7% normal muscularity, P = 0.004). Median length of stay (LOS) was higher in patients with low SMI if they had any complication (19.5 vs. 14 days, P = 0.026) or pneumonia (21 vs. 13 days, P = 0.018). On multivariate analysis, low SMI (OR 3.85, CI 1.10–13.4, P = 0.025), preoperative weight loss (OR 1.13, CI 1.01–1.25, P = 0.027), and smoking (OR 5.08, CI 1.24–20.9, P = 0.024) were independent predictors of having a severe complication. There was no difference in 5‐year overall (62% vs. 69%, P = 0.241) and disease‐free (11% vs. 21.4%, P = 0.110) survival between low SMI and normal muscle mass groups.

Conclusion

Low SMI is associated with a significantly increased risk of pneumonia and increased LOS for patients with complications. Assessment of muscle mass may require additional muscle quality, strength, and physical performance measures to enhance preoperative risk assessment.
Rehabilitation protocols following rotator cuff repair: a meta‐analysis of current evidence
Authors: Bandara Udara , An Vincent V. G. , Imani Sahand , Nandapalan Haren , Sivakumar Brahman S.
Published: September 2021

Background

Rotator cuff tears are a common shoulder pathology with an increasing incidence. The optimum post‐operative rehab protocol remains unclear and can consist of either conservative rehabilitation or more aggressive early range‐of‐motion. Multiple studies have assessed these treatment protocols. This meta‐analysis aims to compare post‐operative clinical outcomes following either conservative or aggressive rehabilitation post rotator cuff repair.

Methods

A systematic electronic literature search was undertaken using a number of databases. Eligible studies included randomized control trials published between January 2013 and April 2019 in English with patients having had received rotator cuff repair. Post‐operative clinical outcomes considered included shoulder range‐of‐motion, overall function status (Costant–Murley score) and rates of rotator‐cuff re‐tear. Studies were evaluated for methodological quality in accordance with the Physiotherapy Evidence Database (PEDro) scale. Summarized pooled statistics were calculated using Review Manager (v5.3) software.

Results

A total of six randomized controlled trials were included. Standardized mean difference (SMD) in shoulder flexion, abduction and external rotation was not statistically significant at either 6 or 12 months post rotator cuff repair. Functional assessment suggests a slight benefit in Constant–Murley Score (SMD = 1.77; 95% CI −3.93, 7.47) in aggressive treatment groups with no significant risk increase for cuff re‐tear (RR = 1.22; 95% CI 0.60, 2.47).

Conclusion

This meta‐analysis suggests there is no clear benefit of either rehabilitation protocol when considering range‐of‐motion, with a possible benefit in functional outcome at the cost of increased re‐tear risk post aggressive rehabilitation. Both protocols have been shown to offer safe reproducible short‐ and long‐term outcomes.
First‐year weight loss following gastric band surgery predicts long‐term outcomes
Authors: Carvalho Silveira Flavia , Maranga Gabrielle , Mitchell Fernanda , Nowak Brittany A. , Ren‐Fielding Christine J. , Fielding George A.
Published: September 2021

Background

Laparoscopic adjustable gastric banding (LAGB) continues to be a valid surgical treatment option to address severe obesity. However, outcomes are varied and can be difficult to predict. Early prediction of suboptimal weight loss following LAGB may enable adjustments to postoperative care and consequently improve surgical outcomes. Therefore, our aim is to investigate the prognostic utility of using early weight loss following LAGB to predict long‐term weight outcomes.

Methods

Clinical data from patients undergoing LAGB between 2001 and 2007 at a single institution were retrospectively collected and analysed. The data was used to inform a model for predicting long‐term weight loss after LAGB surgery. Percent total weight loss (%TWL) greater than 20% 1 year after surgery was considered a measurement of success since it has been associated with the improvement of comorbidities and increased patient satisfaction.

Results

The average %TWL 1 year after LAGB surgery was 23.73% (n = 1524, SD = 8.68%). Weight loss of less than 10% in 1 year was a negative predictor of weight loss >20% in 8–12 years (OR = 0.449; p = 0.002; 95% CI = 0.272–0.742). Moreover, weight loss >20% in 1 year was a strong predictor of weight loss >20% in 8–12 years (OR = 5.33; p < 0.001; 95% CI = 3.17–8.97).

Conclusion

Total body weight reduction of less than 10% 1 year after LAGB surgery suggests a lesser weight loss at 8–12 years. For these patients, targeted interventions would be appropriate to increase the chances of long‐term success.
Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation
Authors: Riedell Peter A. , Hamadani Mehdi , Ahn Kwang W. , Litovich Carlos , Brunstein Claudio G. , Cashen Amanda F. , Cohen Jonathon B. , Epperla Narendranath , Hill Brian T. , Im Annie , Inwards David J. , Lister John , McCarty John M. , Ravi Kiran Pingali Sai , Shadman Mazyar , Shaughnessy Paul , Solh Melhem , Stiff Patrick J. , Vose Julie M. , Kharfan-Dabaja Mohamed A. , Herrera Alex F. , Sauter Craig S. , Smith Sonali M.
Published: September 2021

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front‐line setting. Recently, time‐to‐event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post‐autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six‐month [hazard ratio (HR) = 7·68], 12‐month (HR = 6·68), and 18‐month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non‐relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high‐risk group with inferior post‐relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up‐front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.
Bioengineering methods for organoid systems
Authors: Saleh Jad , Mercier Barbara , XI Wang
Published: September 2021

Organoids have been widely used in fundamental, biomimetic, and therapeutic studies. These multicellular systems form via cell‐autonomous self‐organization where a cohort of stem cells undergoes in vivo‐like proliferation, differentiation, and morphogenesis. They also recapitulate a series of physiological cell organization, complexity and functions that are untouchable by conventional bio‐model systems using immortal cell lines. However, the development of organoids is often not easily controlled and their shape and size are yet fully physiological. Recent research has demonstrated that multiple bioengineering tools could be harnessed to control important internal and external cues that dictate stem cell behavior and stem‐cell based organoid development. In this review, we introduce the current development of organoid systems and their potentials, as well as their limitations that impede their further utility in research and clinical fields. In comparison to conventional autonomous organoid system, we then review bioengineering approaches that offer improved control over organoid growth and development. We focus on the genetic editing tools that allow the program of build‐in responses and phenotypes for organoid systems with enhanced physiological relevance. We also highlight the advances in bioengineering methods to modify cellular external milieus to generate desirable cell composition, 3D micro‐architectures, and complex microfluidic systems. We conclude that the emerging biomimetic methods that employ multidisciplinary approaches could prevail in the future development of organoid systems.
All‐world aging: A gero of all things under the material press in time
Authors: Andrews Gavin J.
Published: September 2021

This viewpoint considers extending aging studies beyond their current exclusive interest in human beings, conveying recent calls for this in more accessible terms. Specifically noted is that all entities/systems age relationally via the same universal entropic process and hence, based on this understanding, an “all‐world aging” perspective might be developed. A particular consideration is what such a broadening of horizons might offer for advancing our understandings of time—specifically with regard to the material press in time—and the issues it raises in terms of subjectivities.
Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents
Authors: King Ashley , Blackledge Meghan S.
Published: September 2021

Antibiotic resistance is a global and pressing concern. Our current therapeutic arsenal is increasingly limited as bacteria are developing resistance at a rate that far outpaces our ability to create new treatments. Novel approaches to treating and curing bacterial infections are urgently needed. Bacterial kinases have been increasingly explored as novel drug targets and are poised for development into novel therapeutic agents to combat bacterial infections. This review describes several general classes of bacterial kinases that play important roles in bacterial growth, antibiotic resistance, and biofilm formation. General features of these kinase classes are discussed and areas of particular interest for the development of inhibitors will be highlighted. Small molecule kinase inhibitors are described and organized by phenotypic effect, spotlighting particularly interesting inhibitors with novel functions and potential therapeutic benefit. Finally, we provide our perspective on the future of bacterial kinase inhibition as a viable strategy to combat bacterial infections and overcome the pressures of increasing antibiotic resistance.
Reduced ELANE and SLPI expression compromises dental pulp cell activity
Authors: Sriwattanapong Kanokwan , Sa‐Ard‐Iam Noppadol , Boonprakong Lawan , Subbalekha Keskanya , Trachoo Vorapat , Suratannon Narissara , Porntaveetus Thantrira , Shotelersuk Vorasuk
Published: September 2021

Background

Patients with ELANE variants and severe congenital neutropenia (SCN) commonly develop oral complications. Whether they are caused only by low neutrophil count or the combination of neutropenia and aberrant dental cells is unknown.

Methods

Genetic variant was identified with exome sequencing. Dental pulp cells isolated from the SCN patient with an ELANE mutation were investigated for gene expression, enzyme activity, proliferation, colony formation, wound healing, apoptosis, ROS, attachment, spreading and response to lipopolysaccharide.

Results

ELANE cells had diminished expression of ELANE and SLPI and reduced neutrophil elastase activity. Moreover, ELANE cells exhibited impaired proliferation, colony forming, migration, attachment and spreading; and significantly increased ROS formation and apoptosis, corresponding with increased Cyclin D1 and MMP2 levels. The intrinsic levels of TGF‐β1 and TNF‐α were significantly increased; however, IL‐6, IL‐8 and NF‐kB1 were significantly decreased in ELANE cells compared with those in controls. After exposure to lipopolysaccharide, ELANE cells grew larger, progressed to more advanced cell spreading stages and showed significantly increased SLPI, TNF‐α and NF‐kB1 and tremendously increased IL‐6 and IL‐8 expression, compared with controls.

Conclusion

This study, for the first time, suggests that in addition to neutropenia, the aberrant levels and functions of ELANE, SLPI and their downstream molecules in pulp cells play an important role in oral complications in SCN patients. In addition, pulp cells with diminished neutrophil elastase and SLPI are highly responsive to inflammation.
Dose‐dependent inactivation of airway tryptase with a novel dissociating anti‐tryptase antibody (MTPS9579A) in healthy participants: A randomized trial
Authors: Rymut Sharon M. , Sukumaran Siddharth , Sperinde Gizette , Bremer Meire , Galanter Joshua , Yoshida Kenta , Smith Jordan , Banerjee Prajna , Sverkos Viyia , Cai Fang , Steffen Verena , Henderson Lindsay M. , Rhee Horace , Belloni Paula N. , Lin Joseph H. , Staton Tracy L.
Published: September 2021

Tryptase is the most abundant secretory granule protein in human lung mast cells and plays an important role in asthma pathogenesis. MTPS9579A is a novel monoclonal antibody that selectively inhibits tryptase activity by dissociating active tetramers into inactive monomers. The safety, tolerability, pharmacokinetics (PKs), and systemic and airway pharmacodynamics (PDs) of MTPS9579A were assessed in healthy participants. In this phase I single‐center, randomized, observer‐blinded, and placebo‐controlled study, single and multiple ascending doses of MTPS9579A were administered subcutaneously (s.c.) or intravenously (i.v.) in healthy participants. In addition to monitoring safety and tolerability, the concentrations of MTPS9579A, total tryptase, and active tryptase were quantified. This study included 106 healthy participants (82 on active treatment). Overall, MTPS9579A was well‐tolerated with no serious or severe adverse events. Serum MTPS9579A showed a dose‐proportional increase in maximum serum concentration (Cmax) values at high doses, and a nonlinear increase in area under the curve (AUC) values at low concentrations consistent with target‐mediated clearance were observed. Rapid and dose‐dependent reduction in nasosorption active tryptase was observed postdose, confirming activity and the PK/PD relationship of MTPS9579A in the airway. A novel biomarker assay was used to demonstrate for the first time that an investigative antibody therapeutic (MTPS9579A) can inhibit tryptase activity in the upper airway. A favorable safety and tolerability profile supports further assessment of MTPS9579A in asthma. Understanding the exposure‐response relationships using the novel PD biomarker will help inform clinical development, such as dose selection or defining patient subgroups.