bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional outcomes after transanal total mesorectal excision (TaTME): a random forest analysis to predict patients’ outcomes
Authors: Tirelli F. , Lorenzon L. , Biondi A. , Neri I. , Santoro G. , Persiani R.
Published: March 2023

Purpose

Anorectal, sexual, and urinary dysfunction are common issues after rectal cancer surgery, although seldom explored. The primary aim of this study was to investigate postoperative anorectal functional results.

Methods

Patients with mid/low-rectal cancer treated with transanal TME (TaTME) with primary anastomosis with/without diverting stoma between 2015 and 2020 were reviewed and selected if they had a minimum follow-up of 6 months (from the primary procedure or stoma reversal). Patients were interviewed using validated questionnaires and the primary outcome was bowel function based on Low Anterior Resection Syndrome (LARS) scores. Statistical analyses were performed to identify clinical/operative variables correlated with worse outcomes. A random forest (RF) algorithm was computed to classify patients at a greater risk of minor/major LARS.

Results

Ninety-seven patients were selected out of 154 TaTME performed. Overall, 88.7% of the patients had a protective stoma and 25.8% reported major LARS at mean follow-up of 19.0 months. Statistical analyses documented that age, operative time, and interval to stoma reversal correlated with LARS outcomes. The RF analysis disclosed worse LARS symptoms in patients with longer operative time (> 295 min) and stoma reversal interval (> 5.6 months). If the interval ranged between 3 and 5.6 months, older patients (> 65 years) reported worse outcomes. Finally, no statistical difference was documented when comparing the rate of minor/major LARS in the first 27 cases versus others.

Conclusion

One-quarter of the patients developed major LARS after TaTME. An algorithm based on clinical/operative variables, such as age, operative time, and time to stoma reversal, was developed to identify categories at risk for LARS symptoms.
A temporal assessment of risk of non-indigenous species introduction by ballast water to Canadian coastal waters based on environmental similarity
Authors: Song Ruixin , Tavakoli Yashar , Bailey Sarah A. , Soares Amilcar
Published: March 2023

The environmental similarity scores between source and recipient locations are essential in ballast water risk assessment (BWRA) models used to estimate the potential for non-indigenous species (NIS) introduction, survival, and establishment, and to guide management strategies aiming to minimize biodiversity loss and economic impacts. Previous BWRA models incorporate annual-scale environmental data, which may overlook seasonal variability. In this study, temporal variation in sea surface temperature and salinity data were examined at global ports, and the influence of this variation on environmental distance calculations (and corresponding risk of NIS) was examined for ballast water discharges in Canada by comparing outputs from monthly and annual scale assessments in a BWRA model. Except for some outliers in the Pacific region, the environmental distances based on monthly scale data generally become smaller in all regions, demonstrating that the model using annual decadal average environmental data to inform environmental matching can underestimate risk of NIS survival and establishment in comparison to monthly data. The results of this study suggest future evaluations incorporating the date of ballast water uptake and discharge can provide a more sensitive assessment of risk reflecting seasonal variability compared to an annual average risk model.
Revisiting the Digital Plumber: Modifying the Installation Process of an Established Commercial IoT Alarm System
Authors: Castle-Green Teresa , Reeves Stuart , Fischer Joel E. , Koleva Boriana
Published: March 2023

The ‘digital plumber’ is a conceptualisation in ubicomp research that describes the work of installing and maintaining IoT devices. But an important and often understated element of commercial IoT solutions is their long-term socio-technical infrastructural nature, and therefore long-term installation and maintenance needs. This adds complexity to both the practice of digital plumbing and to the work of design that supports it. In this paper we study a commercial company producing and installing IoT alarm systems. We examine video recordings that capture how a digital plumbing representative and software development team members make changes to both the installation process and supporting technology. Our data enables us to critically reflect on concepts of infrastructuring, and uncover the ways in which the team methodically foreground hidden elements of the infrastructure to address a point of failure experienced during field trials of a new version of their product. The contributions from this paper are twofold. Firstly, our findings build on previous examples of infrastructuring in practice by demonstrating the use of notions of elemental states to support design reasoning through the continual foregrounding and assessment of tensions identified as key factors at the point of failure. Secondly, we build on current notions of digital plumbing work. We argue that additional responsibilities of ‘reporting failure’ and ‘facilitation of change’ are part of the professional digital plumbing role and that commercial teams should support these additional responsibilities through collaborative troubleshooting and design sessions alongside solid communication channels with related stakeholders within the product team.
Parliamentary Debates Concerning the Living Conditions of Pigs in Sweden’s Factory Farms Between 1980–2018
Authors: Nilsson Daniel
Published: March 2023

Sweden’s Animal Welfare Act of 1988 stated that regulations and directives within the law should be in favor of animals’ wellbeing, protect them against unnecessary harm, allow them to express their natural behavior, and prevent behavioral disorders. However, ethological studies present several welfare problems found in animals held legally in factory farming settings. By using one of Sweden’s most commonly slaughtered animals—the pig—this paper scrutinizes how politicians consider different interests while debating animal living conditions in factory farms. The results demonstrate an overall absence of discussions addressing welfare problems in Swedish pig farming. When such welfare issues are addressed, they are often overlooked in favor of interests that cannot directly be associated with animal welfare. Political claims of having the best animal welfare legislation in the world are used when arguing for decreasing as well as enhancing the living conditions.
An Analytical Dashboard of Collaborative Activities for the Knowledge Building
Authors: Gutiérrez-Braojos C. , Rodríguez-Domínguez C. , Daniela L. , Carranza-García F.
Published: March 2023

Knowledge building (KB) is an educatioanl theory framework that shows interest in the benefits that the technology offers to teaching and evaluation. In this study, a dashboard that facilitates the reflective assessment of KB communities supported by the knowlege forum platform was evaluated. The design-based research study was conducted with 126 undergraduate students enrolled in an educational research course at the University of (Name, country). Using a survey methodology, data was collected on the students’ perception regarding epistemic collective agency, research skills, and dashboard assessment. The conclusions about the value of the dashboard are broken down into two axes. On the one hand, the students state that they are satisfied with the dashboard, although they indicate that there is room for improvement. On the other hand, according to the KB reflective assessment, the dahsboard provided students with educational experiences that have empowered them in the collaborative construction of knowledge and promoted the development of their specific educational research skills. Future technological improvements and implementations of the Knowledge Building are discussed.
Normal periocular anthropometric measurements in an Australian population
Authors: Rana Khizar , Beecher Mark B. , Caltabiano Carmelo , Zhao Yang , Verjans Johan , Selva Dinesh
Published: March 2023

Purpose

To report the normative ocular and periocular anthropometric measurements in an Australian cohort and investigate how these may be affected age, gender, and ethnicity.

Methods

Prospective study of patients presenting to the Royal Adelaide Hospital. Patient with orbital or eyelid disease, previous surgery, craniofacial abnormalities, pupil abnormalities, strabismus, and poor image quality was excluded. Standardised photographs were taken in a well-illuminated room. A green dot with a diameter of 24 mm was placed on the participant’s foreheads for calibration between pixels and millimetres. Ocular and periocular landmarks were segmented to calculate the periorbital measurements. Independent sample t test was used to compare male and female subjects, Pearson’s correlation was used to correlate periocular dimensions with age, and ANOVA with Bonferroni was used to compare periocular dimension between ethnic groups.

Results

Seven hundred and sixty eyes from 380 participants (215 female, mean age 58 ± 18 years) were included. The mean marginal reflex distance (MRD) 1 was 3.5 mm and decreased with increasing age (r =  − 0.09, p = 0.01) and MRD 2 was 5.2 mm. Compared to Caucasians, African subjects had a significantly larger interpupillary distance and outer intercanthal distance, whereas East Asians had a significantly larger inner intercanthal distance (p < 0.05). The values of marginal reflex distance 2, palpebral fissure height, horizontal palpebral aperture, inner intercanthal distance, interpupillary distance and outer intercanthal distance were significantly higher in male subjects than female subjects (p < 0.05).

Conclusions

Normative periocular dimensions may vary according to age, gender, and ethnicity. An understanding of normal periocular dimensions is important in the evaluation of orbital disease across different ethnic groups and may serve as reference points for oculoplastic surgery and industry.
Dinoflagellate cell density limits explored using Scrippsiella lachrymosa cultured in flow-through cages
Authors: Smith Barry C. , Persson Agneta , Alix Jennifer H.
Published: March 2023

Dinoflagellates constitute one of the most important groups of primary producers and micro-zooplankton on earth, common in both marine and freshwater environments. Despite their prominent position among phytoplankton, they are difficult to grow into dense cultures in the laboratory. This discrepancy between field and laboratory indicates serious limitations caused by the laboratory culturing conditions. A difficult to study but important factor is the constraints of enclosure in a limited volume of water. We conducted an experiment wherein the dinoflagellate Scrippsiella lachrymosa was grown in “flow cells” – 100 cm3 cylindrical cages constructed from plankton net, inserted in larger volumes of growth medium, allowing an exchange of medium without dilution of the culture. Cell numbers far exceeding the normal for culturing of this species and dinoflagellates in general were attained, even though the experiment was terminated before cultures reached stationary phase. A cell number ten times higher than under regular batch culturing was achieved (up to 340,000 cells mL−1). Pattern formation was distinct in cultures when cells were plentiful and water movements caused cell accumulation, not dispersion. High cell density concurrent with access to new growth medium promoted induction of the sexual cell cycle. The results indicate serious limitations to growth set by enclosure in a limited water volume in laboratory experiments; thus, maximum growth rates of dinoflagellates in favourable field conditions may be vastly underestimated. Cell accumulation behavior of dinoflagellates during the sexual life cycle may together with physical transport by larger forces in nature explain sudden bloom occurrences.
Spirituality in the Context of Well-being. Evaluation of the Psychometric Properties and Added Value of the Spiritual Attitude and Involvement List Short Form (SAIL-SF)
Authors: Bohlmeijer E. T. , Frielingsdorf L. , Kraiss J. T. , de Jager-Meezenbroek E. , Visser A. , ten Klooster P. M.
Published: March 2023

There is growing evidence that spiritual well-being is positively associated with adaptive coping and health. The Spiritual Attitude and Involvement List (SAIL) was developed to measure a sense of connectedness to oneself, the environment and the transcendent as a universal experience. The aim of the current study was to develop a short form of the SAIL (SAIL-SF). A factor analytic approach was adopted to select the items for the SAIL-SF based on earlier studies among nurses (n = 458) and cancer patients (n = 445). The dimensionality, factor-loadings, internal consistency, construct validity and incremental validity of the final SAIL-SF were then evaluated in a new sample of adults (n = 225) participating in a trial assessing a positive psychology intervention. The first study yielded seven items, each representing one of the dimensions of the original SAIL: meaningfulness, trust, acceptance, caring for others, connectedness with nature, transcendent experiences, and spiritual activities. The seven items represented a single meaningful factor in both samples and the factor loadings of the items were adequately high. In the second study, a good fit across the various model indices was found and all items had adequately high factor loadings in a strict unidimensional confirmatory factor model and demonstrated good internal consistency. The SAIL-SF explained 7% of variance in ability to adapt above and beyond emotional, psychological, and social well-being. The current study shows that the SAIL-SF has good psychometric properties, and that spiritual well-being has a unique contribution to the ability to adapt in comparison with other types of well-being.
Ensifer meliloti denitrification is involved in infection effectiveness and N2O emissions from alfalfa root nodules
Authors: Pacheco Pedro J. , Bedmar Eulogio J. , Mesa Socorro , Tortosa Germán , Delgado María J.
Published: March 2023

Purpose

Alfalfa is one of the most valuable forage crops in temperate climate zones. Ensifer meliloti, the endosymbiont of alfalfa, contains all the denitrification genes but the capacity of alfalfa root nodules to produce nitrous oxide (N2O) is not known. In this work, N2O emissions as well as the influence of bacteroidal denitrification on nodulation competitiveness and N2O release from alfalfa nodules has been investigated.

Methods

Medicago sativa cv. Victoria plants were inoculated with E. meliloti 1021, a periplasmic nitrate reductase (Nap) defective mutant, a Nap overexpressing strain and a nitrous oxide reductase defective mutant. Plants were grown in the presence of different nitrate and copper treatments and subjected to flooding during one week before harvesting. N2O production by the nodules was analysed by using gas chromatography. Methyl viologen-dependent nitrate reductase (MV+-NR), nitrite reductase (MV+-NIR) and nitrous oxide reductase (N2OR) enzymatic activities were measured in isolated bacteroids.

Results

Alfalfa root nodules produce N2O in response to nitrate and flooding. Overexpression of Nap improved nodulation competitiveness and induced N2O emissions from nodules. Copper is required for an effective symbiosis as well as triggered a reduction of N2O production due to the induction of the N2OR and a reduction of NIR activities in the bacteroids.

Conclusion

Alfalfa root nodules emit N2O. Nap is involved in nodulation competitiveness and in N2O emissions by the nodules. Bacteroidal N2OR and NIR activities are modulated by Cu and may be considered as effective targets for the mitigation strategies of N2O emissions derived from alfalfa crops.
Analysis of the cytotoxic and genotoxic effects in a population chronically exposed to coal mining residues
Authors: León-Mejía Grethel , Rueda Robinson Alvarez , Pérez Pérez Jose , Miranda-Guevara Alvaro , Moreno Ornella Fiorillo , Quintana-Sosa Milton , Trindade Cristiano , De Moya Yurina Sh , Ruiz-Benitez Martha , Lemus Yesit Bello , Rodríguez Ibeth Luna , Oliveros-Ortiz Ludis , Acosta-Hoyos Antonio , Pacheco-Londoño Leonardo C. , Muñoz Amner , Hernández-Rivera Samuel P. , Olívero-Verbel Jesús , da Silva Juliana , Henriques João Antonio Pêgas
Published: March 2023

During coal mining activities, many compounds are released into the environment that can negatively impact human health. Particulate matter, polycyclic aromatic hydrocarbons (PAHs), metals, and oxides are part of the complex mixture that can affect nearby populations. Therefore, we designed this study to evaluate the potential cytotoxic and genotoxic effects in individuals chronically exposed to coal residues from peripheral blood lymphocytes and buccal cells. We recruited 150 individuals who lived more than 20 years in La Loma-Colombia and 120 control individuals from the city of Barranquilla without a history of exposure to coal mining. In the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, significant differences in the frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD), and apoptotic cells (APOP) were observed between the two groups. In the buccal micronucleus cytome (BM-Cyt) assay, a significant formation of NBUD, karyorrhexis (KRX), karyolysis (KRL), condensed chromatin (CC), and binucleated (BN) cells was observed in the exposed group. Considering the characteristics of the study group, a significant correlation for CBMN-Cyt was found between NBUD and vitamin consumption, between MN or APOP and meat consumption, and between MN and age. Moreover, a significant correlation for BM-Cyt was found between KRL and vitamin consumption or age, and BN versus alcohol consumption. Using Raman spectroscopy, a significant increase in the concentration of DNA/RNA bases, creatinine, polysaccharides, and fatty acids was detected in the urine of individuals exposed to coal mining compared to the control group. These results contribute to the discussion on the effects of coal mining on nearby populations and the development of diseases due to chronic exposure to these residues.
Contribution of alcohol use to the global burden of cirrhosis and liver cancer from 1990 to 2019 and projections to 2044
Authors: Liu Yang , Sun Zhouyi , Wang Qianwen , Wu Kangze , Tang Zhe , Zhang Bo
Published: March 2023

Background

Identifying the temporal trends of cirrhosis and liver cancer attributable to alcohol use in both the past and the future can formulate the control strategies.

Methods

Data on cirrhosis and liver cancer attributable to alcohol use from 1990 to 2019, including mortality and disability-adjusted life year (DALY) rates were collected from the 2019 Global Burden of Disease (GBD) study. To analyze the temporal trends, the average annual percentage change (AAPC) was calculated, and the Bayesian age-period-cohort model was applied.

Result

Deaths and DALY of cirrhosis and liver cancer attributable to alcohol use increased year by years, but the age-standardized death rate (ASDR) and age-standardized DALY rate declined or remained stable from 1990 to 2019 in most regions of the world. The burden of cirrhosis attributable to alcohol increased in low-middle social-development index (SDI) regions, while the burden of liver cancer increased in high-SDI regions. Eastern Europe and Central Asia have the highest burden of cirrhosis and liver cancer caused by alcohol use. Deaths and DALYs are mainly distributed in people aged 40+ years, but there is an increasing trend in people aged under 40 years. New deaths from cirrhosis and liver cancer attributable to alcohol use are predicted to increase in the next 25 years, but the ASDR of cirrhosis in males will increase slightly.

Conclusions

Although the age-standardized rate of cirrhosis and liver cancer due to alcohol use have decreased, the absolute burden increased and will continue to increase. Therefore, alcohol control measures should be further strengthened and improved through effective national policies.
Waste volatile fatty acids as a good electron donor in microbial fuel cell with the iron-modified anode
Authors: Nosek D. , Samsel O. , Pokój T. , Cydzik-Kwiatkowska A.
Published: March 2023

The commercialization of microbial fuel cell technology is limited by high operating costs and low electricity production due to poor electron transfer to the anode. Operational costs can be lowered by utilizing waste materials, and cell performance can be improved by anode modification. This study investigated how anode modification with iron compounds changed the efficiency of energy generation and the microbiome of microbial fuel cells fueled with waste volatile fatty acids from a full-scale anaerobic digestion. Anode modification with 2.5 g Fe2O3/m2 increased the power density, current density, and voltage by 3.6-fold, 1.8-fold, and 1.4-fold, respectively. In the microbial fuel cell influent, propionic, enanthic, and iso-caproic acids predominated (60, 15, and 13% of all volatile fatty acids, respectively); in the outflow, propionic (71%) and valeric acids (17%) predominated. In anodic biofilms, Acidovorax sp. were most abundant; they have a great capacity for volatile fatty acids decomposition, and their abundance doubled in the microbial fuel cell with an iron-modified anode. The presence of iron significantly increased the abundance of the genera Pseudomonas and Geothrix, which were mainly responsible for electricity production. These results indicate that anode modification with iron changes the anode microbiome, favoring efficient volatile fatty acids metabolism and a greater abundance of electrogens in the biofilm, which ensures better electricity generation.
A supervised method to enhance distance-based neural network clustering performance by discovering perfect representative neurons
Authors: Fu Qiang , Li Yuefeng , Albathan Mubarak
Published: March 2023

Distance-based neural network clustering requires the intrinsic assumption that a particular neuron in the network represents a cluster centroid. However, not all these neurons can perfectly represent the training data; these neurons can only represent part of the training samples. This paper proposes an effective training data splitting method (TDSM) to find perfect representative neurons and improve the clustering results in a distance-based neutral network without changing the original network’s internal algorithm or the training data quality. The method allows a network with N neurons to be enlarged to a new network with $$m\times N$$

m
×
N

neurons. These neurons represent m subnetworks, and each subnetwork perfectly represents a part of the training set, where the clustering qualification indicators (the purity, normalized mutual information, and adjusted rand index measures) all equal 1. The results are statistically validated with a t test, and we demonstrate that the TDSM performs better than the original clustering paradigm on some real datasets.
Promotion of Healthy Lifestyles Alone Might Not Substantially Reduce Socioeconomic Inequity-Related Mortality Risk in Older People in China: A Prospective Cohort Study
Authors: Wang Ziqiong , Zheng Yi , Ruan Haiyan , Li Liying , He Sen
Published: March 2023

Background

Whether healthy lifestyles mediate the association of socioeconomic status (SES) with mortality in older people is largely unknown.

Methods

A total of 22,093 older participants (age ≥ 65 years) from 5 waves (2002–2014) of Chinese Longitudinal Healthy Longevity Survey cohort were included for analysis. Mediation analysis of lifestyles on the association of SES with all-cause mortality was conducted.

Results

During a mean follow-up period of 4.92 ± 4.03 years, 15,721 (71.76%) deaths occurred. Compared with high SES, medium SES increased the risk of mortality by 13.5% (HR [total effect]: 1.135, 95% CI 1.067–1.205, p < 0.001), and the total effect was not mediated by healthy lifestyles (mediation proportion: − 0.1%, 95% CI − 3.8 to 3.3%, p = 0.936). The total effect when participants of low SES were compared with participants of high SES was HR = 1.161 (95% CI 1.088–1.229, p < 0.001) for mortality, and the total effect was modestly mediated through healthy lifestyles (mediation proportion: − 8.9%, 95% CI − 16.6 to − 5.1%, p < 0.001). Stratification analyses by sex, age and comorbidities, as well as a series of sensitivity analyses indicated similar results. In addition, mortality risk showed a downward trend with increased number of healthy lifestyles within each SES level (all p for trend < 0.050).

Conclusion

Promotion of healthy lifestyles alone can only reduce a small proportion of socioeconomic inequity-related mortality risk in older Chinese people. Even so, healthy lifestyles are important in reducing the overall mortality risk within each SES level.
On $$[p,q]_{,\varphi }$$-Order and Complex Differential Equations
Authors: Long Jianren , Qin Hongyan , Tao Lei
Published: March 2023

The fast growing solutions of the following linear differential equation $$(*)$$

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. The growth relationships between entire coefficients and solutions of the equation $$(*)$$

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-type, which extend and improve some previous results.
MoSe2/WS2 heterojunction photodiode integrated with a silicon nitride waveguide for near infrared light detection with high responsivity
Authors: Gherabli Rivka , Indukuri S. R. K. C. , Zektzer Roy , Frydendahl Christian , Levy Uriel
Published: March 2023

We demonstrate experimentally the realization and the characterization of a chip-scale integrated photodetector for the near-infrared spectral regime based on the integration of a MoSe2/WS2 heterojunction on top of a silicon nitride waveguide. This configuration achieves high responsivity of ~1 A W−1 at the wavelength of 780 nm (indicating an internal gain mechanism) while suppressing the dark current to the level of ~50 pA, much lower as compared to a reference sample of just MoSe2 without WS2. We have measured the power spectral density of the dark current to be as low as ~1 × 10−12 A Hz−0.5, from which we extract the noise equivalent power (NEP) to be ~1 × 10−12 W Hz−0.5. To demonstrate the usefulness of the device, we use it for the characterization of the transfer function of a microring resonator that is integrated on the same chip as the photodetector. The ability to integrate local photodetectors on a chip and to operate such devices with high performance at the near-infrared regime is expected to play a critical role in future integrated devices in the field of optical communications, quantum photonics, biochemical sensing, and more.
NUDT22 promotes cancer growth through pyrimidine salvage
Authors: Walter Melanie , Mayr Florian , Hanna Bishoy M. F. , Cookson Victoria , Mortusewicz Oliver , Helleday Thomas , Herr Patrick
Published: March 2023

The NUDIX hydrolase NUDT22 converts UDP-glucose into glucose-1-phosphate and the pyrimidine nucleotide uridine monophosphate but a biological significance for this biochemical reaction has not yet been established. Glucose-1-phosphate is an important metabolite for energy and biomass production through glycolysis and nucleotides required for DNA replication are produced through energetically expensive de novo or energy-efficient salvage pathways. Here, we describe p53-regulated pyrimidine salvage through NUDT22-dependent hydrolysis of UDP-glucose to maintain cancer cell growth and to prevent replication stress. NUDT22 expression is consistently elevated in cancer tissues and high NUDT22 expression correlates with worse survival outcomes in patients indicating an increased dependency of cancer cells to NUDT22. Furthermore, we show that NUDT22 transcription is induced after inhibition of glycolysis, MYC-mediated oncogenic stress, and DNA damage directly through p53. NUDT22-deficient cancer cells suffer from growth retardation, S-phase delay, and slower DNA replication fork speed. Uridine supplementation rescues replication fork progression and alleviates replication stress and DNA damage. Conversely, NUDT22 deficiency sensitizes cells to de novo pyrimidine synthesis inhibition in vitro and reduces cancer growth in vivo. In conclusion, NUDT22 maintains pyrimidine supply in cancer cells and depletion of NUDT22 leads to genome instability. Targeting NUDT22 therefore has high potential for therapeutic applications in cancer therapy.
Single molecule analyses reveal dynamics of Salmonella translocated effector proteins in host cell endomembranes
Authors: Göser Vera , Sander Nathalie , Schulte Marc , Scharte Felix , Franzkoch Rico , Liss Viktoria , Psathaki Olympia E. , Hensel Michael
Published: March 2023

The facultative intracellular pathogen Salmonella enterica remodels the host endosomal system for survival and proliferation inside host cells. Salmonella resides within the Salmonella-containing vacuole (SCV) and by Salmonella-induced fusions of host endomembranes, the SCV is connected with extensive tubular structures termed Salmonella-induced filaments (SIF). The intracellular lifestyle of Salmonella critically depends on effector proteins translocated into host cells. A subset of effectors is associated with, or integral in SCV and SIF membranes. How effectors reach their subcellular destination, and how they interact with endomembranes remodeled by Salmonella remains to be determined. We deployed self-labeling enzyme tags to label translocated effectors in living host cells, and analyzed their single molecule dynamics. Translocated effectors diffuse in membranes of SIF with mobility comparable to membrane-integral host proteins in endomembranes. Dynamics differ between various effectors investigated and is dependent on membrane architecture of SIF. In the early infection, host endosomal vesicles are associated with Salmonella effectors. Effector-positive vesicles continuously fuse with SCV and SIF membranes, providing a route of effector delivery by translocation, interaction with endosomal vesicles, and ultimately fusion with the continuum of SCV/SIF membranes. This mechanism controls membrane deformation and vesicular fusion to generate the specific intracellular niche for bacterial survival and proliferation.
Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact
Authors: Spitzberg Joshua D. , Ferguson Scott , Yang Katherine S. , Peterson Hannah M. , Carlson Jonathan C. T. , Weissleder Ralph
Published: March 2023

Exosomes and extracellular vesicles (EV) are increasingly being explored as circulating biomarkers, but their heterogenous composition will likely mandate the development of multiplexed EV technologies. Iteratively multiplexed analyses of near single EVs have been challenging to implement beyond a few colors during spectral sensing. Here we developed a multiplexed analysis of EV technique (MASEV) to interrogate thousands of individual EVs during 5 cycles of multi-channel fluorescence staining for 15 EV biomarkers. Contrary to the common belief, we show that: several markers proposed to be ubiquitous are less prevalent than believed; multiple biomarkers concur in single vesicles but only in small fractions; affinity purification can lead to loss of rare EV subtypes; and deep profiling allows detailed analysis of EV, potentially improving the diagnostic content. These findings establish the potential of MASEV for uncovering fundamental EV biology and heterogeneity and increasing diagnostic specificity.
Mechanical metamaterials made of freestanding quasi-BCC nanolattices of gold and copper with ultra-high energy absorption capacity
Authors: Cheng Hongwei , Zhu Xiaoxia , Cheng Xiaowei , Cai Pengzhan , Liu Jie , Yao Huijun , Zhang Ling , Duan Jinglai
Published: March 2023

Nanolattices exhibit attractive mechanical properties such as high strength, high specific strength, and high energy absorption. However, at present, such materials cannot achieve effective fusion of the above properties and scalable production, which hinders their applications in energy conversion and other fields. Herein, we report gold and copper quasi-body centered cubic (quasi-BCC) nanolattices with the diameter of the nanobeams as small as 34 nm. We show that the compressive yield strengths of quasi-BCC nanolattices even exceed those of their bulk counterparts, despite their relative densities below 0.5. Simultaneously, these quasi-BCC nanolattices exhibit ultrahigh energy absorption capacities, i.e., 100 ± 6 MJ m−3 for gold quasi-BCC nanolattice and 110 ± 10 MJ m−3 for copper quasi-BCC nanolattice. Finite element simulations and theoretical calculations reveal that the deformation of quasi-BCC nanolattice is dominated by nanobeam bending. And the anomalous energy absorption capacities substantially stem from the synergy of the naturally high mechanical strength and plasticity of metals, the size reduction-induced mechanical enhancement, and the quasi-BCC nanolattice architecture. Since the sample size can be scaled up to macroscale at high efficiency and affordable cost, the quasi-BCC nanolattices with ultrahigh energy absorption capacity reported in this work may find great potentials in heat transfer, electric conduction, catalysis applications.
Open-label placebos—a systematic review and meta-analysis of experimental studies with non-clinical samples
Authors: Spille Lukas , Fendel Johannes C. , Seuling Patrik D. , Göritz Anja S. , Schmidt Stefan
Published: March 2023

The use of open-label placebos (OLPs) has shown to be effective in clinical trials. We conducted a systematic review and meta-analysis to examine whether OLPs are effective in experimental studies with non-clinical populations. We searched five databases on April 15, 2021. We conducted separate analyses for self-reported and objective outcomes and examined whether the level of suggestiveness of the instructions influenced the efficacy of OLPs. Of the 3573 identified records, 20 studies comprising 1201 participants were included, of which 17 studies were eligible for meta-analysis. The studies investigated the effect of OLPs on well-being, pain, stress, arousal, wound healing, sadness, itchiness, test anxiety, and physiological recovery. We found a significant effect of OLPs for self-reported outcomes (k = 13; standardized mean difference (SMD) = 0.43; 95% CI = 0.28, 0.58; I2 = 7.2%), but not for objective outcomes (k = 8; SMD =  − 0.02; 95% CI =  − 0.25, 0.21; I2 = 43.6%). The level of suggestiveness of the instructions influenced the efficacy of OLPs for objective outcomes (p = 0.02), but not for self-reported outcomes. The risk of bias was moderate for most studies, and the overall quality of the evidence was rated low to very low. In conclusion, OLPs appear to be effective when examined in experimental studies. However, further research is needed to better understand the mechanisms underlying OLPs.
Allergic rhinitis children with obesity are more vulnerable to air pollution: a cross sectional study
Authors: Li Ruo-Ling , Wu Chia-Ta , Chen Shan-Ming , Lue Ko-Huang , Lee Shiuan-Shinn , Tsao Chang-Yao , Ku Min-Sho
Published: March 2023

The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7–17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM10, and PM2.5, the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM10, PM2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM10, PM2.5, NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM10, and PM2.5. Increased nasal inflammation induced by air pollutants might be the underlying mechanism.
Fate of arsenicals in mice carrying the human AS3MT gene exposed to environmentally relevant levels of arsenite in drinking water
Authors: Douillet Christelle , Miller Madison , Cable Peter H. , Shi Qing , El-Masri Hisham , Matoušek Tomáš , Koller Beverly H. , Thomas David J. , Stýblo Miroslav
Published: March 2023

Although mice are widely used to study adverse effects of inorganic arsenic (iAs), higher rates of iAs methylation in mice than in humans may limit their utility as a model organism. A recently created 129S6 mouse strain in which the Borcs7/As3mt locus replaces the human BORCS7/AS3MT locus exhibits a human-like pattern of iAs metabolism. Here, we evaluate dosage dependency of iAs metabolism in humanized (Hs) mice. We determined tissue and urinary concentrations and proportions of iAs, methylarsenic (MAs), and dimethylarsenic (DMAs) in male and female Hs and wild-type (WT) mice that received 25- or 400-ppb iAs in drinking water. At both exposure levels, Hs mice excrete less total arsenic (tAs) in urine and retain more tAs in tissues than WT mice. Tissue tAs levels are higher in Hs females than in Hs males, particularly after exposure to 400-ppb iAs. Tissue and urinary fractions of tAs present as iAs and MAs are significantly greater in Hs mice than in WT mice. Notably, tissue tAs dosimetry in Hs mice resembles human tissue dosimetry predicted by a physiologically based pharmacokinetic model. These data provide additional support for use of Hs mice in laboratory studies examining effects of iAs exposure in target tissues or cells.
Expression of SPAG7 and its regulatory microRNAs in seminal plasma and seminal plasma-derived extracellular vesicles of patients with subfertility
Authors: Abu-Halima Masood , Becker Lea Simone , Al Smadi Mohammad A. , Kunz Lea Sophie , Gröger Laura , Meese Eckart
Published: March 2023

Seminal plasma contains a variety of extracellular vesicles (EVs) that deliver RNAs including microRNAs (miRNAs) molecules. However, the roles of these EVs along with their delivered RNAs and their interactions with male infertility are not clear. Sperm-associated antigen 7 (SPAG 7) is expressed in male germ cells and plays a crucial role in several biological functions associated with sperm production and maturation. In this study, we aimed to identify the post-transcriptional regulation of SPAG7 in seminal plasma (SF-Native) and seminal plasma-derived extracellular vesicles (SF-EVs) collected from 87 men undergoing infertility treatment. Among the multiple binding sites for miRNAs within its 3’UTR of SPAG7, we identified the binding of four miRNAs (miR-15b-5p, miR-195-5p, miR-424-5p, and miR-497-5p) to the 3’UTR of SPAG7 by the dual luciferase assays. Analyzing sperm, we found reduced mRNA expression levels of SPAG7 in SF-EVs and SF-Native samples from oligoasthenozoospermic men. By contrast, two miRNAs (miR-424-5p and miR-497-5p) form the SF-Native samples, and four miRNAs (miR-195-5p, miR-424-5p, miR-497-5p, and miR-6838-5p) from the SF-EVs samples showed significantly higher expression levels in oligoasthenozoospermic men. The expression levels of miRNAs and SPAG7 were significantly correlated with basic semen parameters. These findings contribute significantly to our understanding of regulatory pathways in male fertility by showing a direct link between upregulated miRNA, notably miR-424, and downregulated SPAG7 both in seminal plasma and in plasma-derived EVs likely contributing to oligoasthenozoospermia.
Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload
Authors: Chan Kate C. , Au Chun T. , Leung Alex W. K. , Li Albert M. , Li Chi-kong , Wong Matthew M. T. , Li Carol S. T. , Cheung Hang L. , Fan Philip , Ling Siu C. , Li Rever C. H. , Ha S. Y.
Published: March 2023

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B − 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89–0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.
Standard of care drugs do not modulate activity of senescent primary human lung fibroblasts
Authors: Badaro-Garcia Stephanie , Hohmann Miriam S. , Coelho Ana Lucia , Verri Waldiceu A. , Hogaboam Cory M.
Published: March 2023

Cellular senescence is crucial in the progression of idiopathic pulmonary fibrosis (IPF), but it is not evident whether the standard-of-care (SOC) drugs, nintedanib and pirfenidone, have senolytic properties. To address this question, we performed colorimetric and fluorimetric assays, qRT-PCR, and western blotting to evaluate the effect of SOC drugs and D + Q on senescent normal and IPF lung fibroblasts. In this study, we found that SOC drugs did not provoke apoptosis in the absence of death ligand in normal or IPF senescent lung fibroblasts. Nintedanib increased caspase-3 activity in the presence of Fas Ligand in normal but not in IPF senescent fibroblasts. Conversely, nintedanib enhanced B cell lymphoma 2 expression in senescent IPF lung fibroblasts. Moreover, in senescent IPF cells, pirfenidone induced mixed lineage kinase domain-like pseudokinase phosphorylation, provoking necroptosis. Furthermore, pirfenidone increased transcript levels of FN1 and COL1A1 in senescent IPF fibroblasts. Lastly, D + Q augmented growth differentiation factor 15 (GDF15) transcript and protein levels in both normal and IPF senescent fibroblasts. Taken together, these results establish that SOC drugs failed to trigger apoptosis in senescent primary human lung fibroblasts, possibly due to enhanced Bcl-2 levels by nintedanib and the activation of the necroptosis pathway by pirfenidone. Together, these data revealed the inefficacy of SOC drugs to target senescent cells in IPF.
Identification of m6A/m5C/m1A-associated LncRNAs for prognostic assessment and immunotherapy in pancreatic cancer
Authors: Huang Yuquan , Zhang Wu , Li Qingxia , Wang Zhe , Yang Xianghong
Published: March 2023

Methylation of RNA plays an important role in cancer. Classical forms of such modifications include N6-methyladenine (m6A), 5-methylcytosine (m5C), and N1-methyladenine (m1A). Methylation-regulated long non-coding (lnc) RNAs are involved in various biological processes, such as tumor proliferation, apoptosis, immune escape, invasion, and metastasis. Therefore, we performed an analysis of transcriptomic and clinical data of pancreatic cancer samples in The Cancer Genome Atlas (TCGA). Using the co-expression method, we summarized 44 m6A/m5C/m1A-related genes and obtained 218 methylation-associated lncRNAs. Next, with COX regression, we screened 39 lncRNAs that are strongly associated with prognosis and found that their expression differed significantly between normal tissues and pancreatic cancer samples (P < 0.001). We then used the least absolute shrinkage and selection operator (LASSO) to construct a risk model comprising seven lncRNAs. In validation set, the nomogram generated by combining clinical characteristics accurately predicted the survival probability of pancreatic cancer patients at 1, 2, and 3 years after diagnosis (AUC = 0.652, 0.686, and 0.740, respectively). Tumor microenvironment analysis showed that the high-risk group had significantly more resting memory CD4 T cells, M0 macrophages, and activated dendritic cells and fewer naïve B cells, plasma cells, and CD8 T cells than the low-risk group (both P < 0.05). Most immune-checkpoint genes were significantly different between the high- and low-risk groups (P < 0.05). The Tumor Immune Dysfunction and Exclusion score showed that high-risk patients benefited more from treatment with immune checkpoint inhibitors (P < 0.001). Overall survival was also lower in high-risk patients with more tumor mutations than in low-risk patients with fewer mutations (P < 0.001). Finally, we explored the sensitivity of the high- and low-risk groups to seven candidate drugs. Our findings indicated that m6A/m5C/m1A-associated lncRNAs are potentially useful biomarkers for the early diagnosis and estimating the prognosis of, and ascertaining the responses to immunotherapy in, patients with pancreatic cancer.