bluuebunny/crossref_metadata_2025 huggingface dataset:
Mothers’ and daughters’ employment in Europe. A comparative analysis
Authors: Berloffa Gabriella , Matteazzi Eleonora , Şandor Alina , Villa Paola
Published: August 2022

This article analyzes the intergenerational correlation of employment between young women (at about 30 years of age) and their mothers (when their daughters were about 14 years old), using 2011 European Union Survey on Income and Living Conditions data. It examines the extent to which this correlation varies across 19 European countries and is associated with the socioeconomic context at the national level. Having grown up with a working mother is associated with a sizeable increase in the daughters’ employment probability in almost all countries, with greater effect for women with children. For this group, the intergenerational correlation is smaller in countries where the policy context is less favorable to maternal employment. It is crucial to promote gender equality, challenging individuals’ gender stereotypes through education and in society at large, and create conditions that allow young women’s preferences for work to be realized, enhancing policies that favor a balanced sharing of unpaid work.
When Pandemic Interferes with Work: Psychological Capital and Mental Health of Social Workers during COVID-19
Authors: Ho Henry C Y , Chui On Sang , Chan Ying Chuen
Published: August 2022

The impact of the COVID-19 pandemic is not only limited to physical health but also extends to various aspects of everyday life. The present study proposes that the prolonged pandemic can lead to pandemic–work conflict (PWC). The article examines how the pandemic interferes with work, the association between PWC and mental health, and the underlying mechanism of this process. A total of 303 full-time social workers in Hong Kong responded to measures on PWC, psychological capital (PsyCap), and anxiety and depressive symptoms. Data were collected between February and April 2020, when the COVID-19 outbreak was beginning to worsen; 15.8 percent and 14.9 percent of the participants reported mild to severe anxiety and depression, respectively. Time-based PWC was positively associated and strain-based PWC was negatively associated with PsyCap, which was in turn negatively associated with anxiety and depressive symptoms. PsyCap was a significant mediator of these relationships. The findings suggest that the relationship between strain-based PWC and psychological distress can be explained by PsyCap, whereby the depletion of psychological resources may contribute to anxiety and depressive symptoms. Positive psychological resources may be an intervening point for promoting mental health among the social services workforce.
Principal forms of commercial trusts in the UK and the rethinking of traditional approaches
Authors: Zhang Ruiqiao
Published: August 2022

Trusts, which originated in common law and are used to protect family landholdings over generations, have developed into a vehicle that is more often used for commercial purposes. This shift has occurred without any systematic understanding of in what form and to what extent trusts can be adopted in a commercial context. Furthermore, few have considered whether existing trust law can adequately govern commercial trusts; that is, whether or not the commercial use of trusts requires a redeveloped trust law regime, distinguished from traditional approaches. This article offers a critical analysis of these issues, identifying and categorising the principal forms of commercial trusts that are currently employed in the UK. It argues that, given the different settings and contexts in which commercial trusts are found, trust law should be developed to serve the way in which trusts are now used in a commercial context.
Monensin supplementation during late gestation of beef cows alters maternal plasma concentrations of insulin-like growth factors 1 and 2 and enhances offspring preweaning growth
Authors: Vedovatto Marcelo , Izquierdo Vinicius , Palmer Elizabeth , Oliveira Rhaiza A , Silva Hiran M , Vendramini João M B , Moriel Philipe
Published: August 2022

This study evaluated the effects of maternal prepartum supplementation of dried distillers grains (DDG), with or without monensin addition, on maternal performance and physiology and offspring preweaning growth. On day 0 (approximately 197 ± 4 d prepartum), 150 multiparous, Brangus crossbred beef cows were ranked by their initial body weight (BW; 524 ± 51 kg) and body condition score (BCS; 5.0 ± 0.63), and then randomly assigned into one of 15 bahiagrass (Paspalum notatum) pastures (10 cows and 8.1 ha/pasture). Maternal treatments were randomly assigned to pastures (5 pastures/treatment) and consisted of no prepartum supplementation of DDG (NOSUP) or supplementation of DDG at 1 kg/cow/d (dry matter basis; DM) added with 0 mg (SUP) or 200 mg/d of monensin (SUPMO) from days 0 to 77. Effects of maternal treatment and maternal treatment × day of the study were not detected (P ≥ 0.63) for any forage data. Cow BCS on day 35 and near calving (day 77) did not differ (P ≥ 0.19) between SUP and SUPMO cows but both groups had greater (P ≤ 0.001) BCS compared with NOSUP cows. Cow BCS at the start of the breeding season (day 142) and on day 168 were the greatest (P < 0.0001) for SUPMO cows, least for NOSUP cows, and intermediate (P ≤ 0.02) for SUP cows. Maternal plasma concentrations of glucose did not differ (P ≥ 0.25) among treatments. Plasma concentrations of insulin-like growth factor 1 (IGF-1) on day 77 were the least for NOSUP cows (P ≤ 0.05) and did not differ (P = 0.66) between SUP and SUPMO cows, whereas plasma concentrations of IGF-2 on days 35 and 77 were greatest (P ≤ 0.05) for SUPMO cows and did not differ (P ≥ 0.60) between NOSUP and SUP cows. Birth BW of first offspring did not differ (P = 0.77) between SUP and SUPMO calves but NOSUP calves were lighter at birth (P ≤ 0.05) compared with SUP and SUPMO calves. Percentage of cows pregnant with a second offspring did not differ (P = 0.72) between SUP and SUPMO cows and were the least for NOSUP cows (P ≤ 0.05). First offspring BW at weaning (day 325) was greatest (P ≤ 0.05) for SUPMO calves, least for NOSUP calves, and intermediate for SUP calves. Therefore, adding monensin into prepartum DDG supplements for Bos indicus-influenced beef cows did not increase cow prepartum BCS but led to greatest offspring preweaning growth, likely by modulating maternal plasma concentrations of IGF-1 and IGF-2 during gestation.
Low Back Pain in People With Lower Limb Amputation
Authors: Sadowski Piotr K. , Battista Simone , Leuzzi Gaia , Sansone Lucia G. , Testa Marco
Published: August 2022

Study Design.

A cross-sectional study based on an online questionnaire.

Objective.

The aim was to investigate the prevalence and intensity of low back pain (LBP) in people with lower limb amputation (LLA) and to analyze the association factors that can influence the genesis of LBP.

Summary of Background Data.

It is still unclear whether LBP is more prevalent in the amputated population than in its nonamputated counterpart. Given the multifactorial nature of LBP, it is necessary to explore possible factors that can influence its presence and intensity, to build a solid background to define a better rehabilitation pathway for the management of these people.

Methods.

The online questionnaire included six sections: informed consent of the study, demographic information, comorbid conditions, history of LLA, history of LBP, and acceptance of the amputation.

Results.

Between March and June 2021, 239 participants [mean age (SD): 49.2 (11.5); female 11%] completed the survey (response rate: 32%). From the results of this study, LBP in LLA showed a prevalence of 82% postamputation and 70% in the last year. A logistic regression with a backward method showed that participants who had problems in the not affected leg presented 1.58 (95% confidence interval: 0.70; 2.45) times higher odds to have LBP after the amputation.

Conclusion.

This study shows that the prevalence of LBP in lower limb amputees appears to be higher than in the general population, with similar levels of pain intensity and frequency. The highest percentage of people with a sedentary lifestyle not practicing any kind of sports emphasizes the importance of educating this population on the importance of physical activity. New strategies to invest in the education of this population in terms of physical activity are needed.

Level of Evidence:

Level 4.
Approach to Fine Needle Aspiration of Giant Cell-rich Tumors of Soft Tissue
Authors: Rottmann Douglas , Pantanowitz Liron
Published: August 2022

Giant cells may be found in a wide variety of reactive and neoplastic soft tissue lesions. Because of their distinct histomorphology, they often stand out in procured samples such as fine needle aspirates. The giant cells themselves may be benign or neoplastic. However, the presence, type, and quantity of giant cells are usually not specific and in some cases can even be misleading when making a diagnosis. The aim of this review is to guide the practicing cytopathologist in narrowing their differential diagnosis when encountering one of these challenging giant cell-rich lesions of the soft tissue.
James Floyd Scott. 4 May 1942—6 April 2020
Authors: Catalan Gustau , Marty Gregg J. , Zubko Pavlo
Published: August 2022

Jim Scott was a larger-than-life figure who performed pioneering academic and commercial research, mainly on Raman spectroscopy, ferroelectrics, and multiferroics. His career developed at the same time as methodological advances were being made in thin-film deposition and in growth and patterning of complex nanoscale materials. Such advances gave him the opportunity to lead the charge in the integration of ferroelectric oxide films with semiconductors for microwave antennae (predominantly for mobile phones), and in the creation and integration of thin-film capacitor structures for ferroelectric random access memory (FeRAM) chips. He made particularly noteworthy contributions in overcoming the fatigue problem, critical to FeRAM technology. He also played a central role in pushing nanoscale ferroelectrics beyond thin films and into three-dimensional geometries and was an important figure in the birth, and in the renaissance, of magnetoelectric multiferroics. Like many great scientists, Jim was adept at spotting connections between seemingly unconnected topics, establishing new conceptual frameworks and discovering new phenomena that were often received sceptically at first and then embraced by the community.
Plasmodium berghei
leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development
Authors: Fréville Aline , Gnangnon Bénédicte , Tremp Annie Z. , De Witte Caroline , Cailliau Katia , Martoriati Alain , Aliouat El Moukthar , Fernandes Priyanka , Chhuon Cerina , Silvie Olivier , Marion Sabrina , Guerrera Ida Chiara , Dessens Johannes T. , Pierrot Christine , Khalife Jamal
Published: August 2022

Protein phosphatase 1 (PP1) is a key enzyme for
Plasmodium
development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the
Plasmodium berghei
leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of
Plasmodium
PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of
Plasmodium
oocyst development through its interaction with PbLRR1.
Macrophage polarization as a potential therapeutic target for atherosclerosis: a dynamic stochastic modelling study
Authors: Liu Mengchen , Cai Yan , Pan Jichao , Peter Karlheinz , Li Zhiyong
Published: August 2022

We proposed a dynamic stochastic mathematical model to evaluate the role of macrophage polarization in plaque development. The dynamic process of macrophages from proliferation to death was simulated under different lipid microenvironments. The probability of macrophage phenotypic switching was described using a Bernoulli distribution where the stochastic variable was determined by the local lipid level. Moreover, the interactions between macrophages and microenvironmental factors vary with macrophage phenotype. We investigated the distribution of key microenvironmental factors, the dynamics of macrophage polarization and its influence on foam cell formation. M1 macrophages were found to predominate in advanced plaque corresponding to the exacerbated inflammation observed in mice experiments. The imbalance between the deposition of oxidized low-density lipoprotein and phagocytic effects of macrophages governed the formation of foam cells. Furthermore, we simulated targeted therapies by either directly inhibiting the polarization probability to M1 macrophages or indirectly regulating macrophage polarization due to high-density lipoprotein levels. Comparison of simulation results with experimental findings in both therapies indicated that the intervention and regulation of macrophage polarization could influence plaque microenvironment and subsequently induce plaque regression, especially in the early stage. The proposed modelling system can facilitate the evaluation of novel therapies targeting macrophage polarization.
The persistent-predation strategy of the red lionfish (
Pterois
volitans
)
Authors: Peterson Ashley N. , McHenry Matthew J.
Published: August 2022

The pursuit of prey is vital to the biology of a predator and many aspects of predatory behaviour are well-studied. However, it is unclear how a pursuit can be effective when the prey is faster than a non-cryptic predator. Using kinematic measurements, we considered the strategy of red lionfish (
Pterois volitans
) as they pursued a faster prey fish (
Chromis viridis
) under laboratory conditions. Despite swimming about half as fast as
C. viridis
, lionfish succeeded in capturing prey in 61% of our experiments. This successful pursuit behaviour was defined by three critical characteristics. First, lionfish targeted
C. viridis
with pure pursuit by adjusting their heading towards the prey’s position and not the anticipated point of interception. Second, lionfish pursued prey with uninterrupted motion. By contrast,
C. viridis
moved intermittently with variation in speed that included slow swimming. Such periods allowed lionfish to close the distance to a prey and initiate a suction-feeding strike at a relatively close distance (less than 9 cm). Finally, lionfish exhibited a high rate of strike success, capturing prey in 74% of all strikes. These characteristics comprise a behaviour that we call the ‘persistent-predation strategy’, which may be exhibited by a diversity of predators with relatively slow locomotion.
Timescale reverses the relationship between host density and infection risk
Authors: Stewart Merrill Tara E. , Cáceres Carla E. , Gray Samantha , Laird Veronika R. , Schnitzler Zoe T. , Buck Julia C.
Published: August 2022

Host density shapes infection risk through two opposing phenomena. First, when infective stages are subdivided among multiple hosts, greater host densities decrease infection risk through ‘safety in numbers’. Hosts, however, represent resources for parasites, and greater host availability also fuels parasite reproduction. Hence, host density increases infection risk through ‘density-dependent transmission’. Theory proposes that these phenomena are not disparate outcomes but occur over different timescales. That is, higher host densities may reduce short-term infection risk, but because they support parasite reproduction, may increase long-term risk. We tested this theory in a zooplankton-disease system with laboratory experiments and field observations. Supporting theory, we found that negative density–risk relationships (safety in numbers) sometimes emerged over short timescales, but these relationships reversed to ‘density-dependent transmission’ within two generations. By allowing parasite numerical responses to play out, time can shift the consequences of host density, from reduced immediate risk to amplified future risk.
SARS-CoV-2 seroprevalence in hospital healthcare workers in Western Switzerland at the end of the second pandemic wave
Authors: Jacot Damien , von Rotz Urs , Blondet Fanny , Aebischer Oriane , Matthieu Perreau , De Rham Mikael , Pantaleo Giuseppe , Marchetti Oscar , Greub Gilbert
Published: August 2022

Introduction. In early January 2020, the pandemic of COVID-19 (coronavirus disease 2019) rapidly spread from China and caused a worldwide pandemic.

Hypothesis. Healthcare workers represent a high-risk group for acquiring COVID-19 and for nosocomial transmission of severe acute respiratory coronavirus 2 (SARS-CoV-2).

Aim. We aimed to investigate over a 1 year period, across two pandemic waves, the SARS-CoV-2 seroprevalence in employees at a Western Switzerland public hospital.

Methodology. A prospective observational SARS-CoV-2 seroprevalence study was proposed to all hospital employees who enrolled on a voluntary basis.

Results. Out of 594 participants recruited on a voluntary basis, 269 volunteers (45.3 %) had anti-SARS-CoV-2 antibodies: this seroprevalence was twice higher than that reported in the local community. Healthcare workers with prolonged exposure to patients with COVID-19 showed a significantly higher odds ratio (OR) of having a positive SARS-CoV-2 serology [OR 3.19, 95 % confidence interval (CI) 2.16–4.74]. Symptoms showing the highest association with a positive serology were anosmia (OR 11.9, 95 % CI 5.58–30.9) and ageusia (OR 10.3, 95 % CI 4.8–26.3). A total of 17.1 % (95 % CI 12.2–21.1 %) of SARS-CoV-2 seropositive volunteers did not report a suspicion of COVID-19 in their personal history.

Conclusion. Overall, we observed that the impact of the second SARS-CoV-2 pandemic wave was considerable and significantly affected healthcare workers with prolonged exposure to patients with COVID-19.
Insertion sequences and other mobile elements associated with antibiotic resistance genes in Enterococcus isolates from an inpatient with prolonged bacteraemia
Authors: Udaondo Zulema , Abram Kaleb Z. , Kothari Atul , Jun Se-Ran
Published: August 2022

Insertion sequences (ISs) and other transposable elements are associated with the mobilization of antibiotic resistance determinants and the modulation of pathogenic characteristics. In this work, we aimed to investigate the association between ISs and antibiotic resistance genes, and their role in the dissemination and modification of the antibiotic-resistant phenotype. To that end, we leveraged fully resolved

Enterococcus faecium

and

Enterococcus faecalis

genomes of isolates collected over 5 days from an inpatient with prolonged bacteraemia. Isolates from both species harboured similar IS family content but showed significant species-dependent differences in copy number and arrangements of ISs throughout their replicons. Here, we describe two inter-specific IS-mediated recombination events and IS-mediated excision events in plasmids of

E. faecium

isolates. We also characterize a novel arrangement of the ISs in a Tn1546-like transposon in

E. faecalis

isolates likely implicated in a vancomycin genotype–phenotype discrepancy. Furthermore, an extended analysis revealed a novel association between daptomycin resistance mutations in liaSR genes and a putative composite transposon in

E. faecium

, offering a new paradigm for the study of daptomycin resistance and novel insights into its dissemination. In conclusion, our study highlights the role ISs and other transposable elements play in the rapid adaptation and response to clinically relevant stresses such as aggressive antibiotic treatment in enterococci.
The inhibitory effect of paeoniflorin on reactive oxygen species alleviates the activation of NF-κB and MAPK signalling pathways in macrophages
Authors: Li Yanyan , Yin Shaojie , Chen Xiaolan , Shi Feifei , Wang Jing , Yang Haifeng
Published: August 2022

Paeoniflorin (PF) has been proven to possess a protective effect in some inflammatory diseases, but the underlying mechanism remains unclear. Macrophages play central roles in inflammatory responses and LPS-stimulated RAW264.7 macrophage is an ideal model for studying the anti-inflammatory effects and mechanisms of drugs. Thus, it was used to explore the anti-inflammatory mechanism of PF in this study. The results showed that PF markedly attenuated the activation of NF-κB, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (p38) signalling pathways induced by LPS exposure. In addition, PF pretreatment dose-dependently suppressed the production of cytokines and the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Concomitantly, PF pretreatment dramatically inhibited the accumulation of intracellular reactive oxygen species (ROS) without affecting the phagocytosis of macrophages. Furthermore, it has proved the scavenging effect of PF on ROS was involved in the anti-inflammatory process. This study provides a novel aspect to the understanding of the anti-inflammatory mechanism of PF.
Modern human expansion from (southern?) Africa: Origin, non-African ancestry, and linearity
Authors: Cenac Zarus
Published: August 2022

Previous research favours the idea that modern humans spread worldwide from Africa. For instance, through autosomal diversity, a geographical area of origin for this worldwide expansion is indicated to entirely be within Africa. It remained to be seen if this indication happens for certain variables such as Y-chromosomal diversity. There is disagreement regarding where in Africa the origin is. Perhaps a region of Africa may seem to be the origin because of non-African ancestry rather than the expansion. The present research considered whether some genetic and cranial variables indicate the expansion, and, furthermore, where in Africa the expansion started. Variables included, for example, autosomal diversity (in sub-Saharan Africa) which was adjusted for non-African ancestry, Y-chromosomal diversity, and cranial sexual size dimorphism. For each variable, it was seen if the estimated area of origin was solely in Africa. Moreover, to generally estimate the origin, a centroid was calculated from potential origins which were obtained in the present, and past, research. The area of origin was completely within Africa for each variable except one – for Y-chromosomal diversity, the area was possibly in Asia only. The centroid of the potential origins was in southern Africa, consequently supporting a southern African origin. The autosomal diversity of sub-Saharan African populations, adjusted for non-African ancestry, indicated a southern African origin. The adjusted diversity appeared to start declining from about 2,000-3,000 km away from the origin – this non-linear pattern may be explained by travelling which happened after the expansion, or the expansion entering locations in Africa which were already populated, to differing extents, by modern humans.
High resolution dermal ultrasound (US) combined with superficial radiation therapy (SRT) versus non-image guided SRT or external beam radiotherapy (XRT) in early-stage epithelial cancer: a comparison of studies
Authors: Yu Lio , Moloney Mairead , Zheng Songzhu , Rogers James
Published: August 2022

Background

To compare the effectiveness of high-resolution dermal ultrasound (US) guided superficial radiotherapy (SRT) to non-image-guided radiotherapy in the treatment of early-stage epithelial cancer.

Methods

A high-resolution dermal ultrasound (US) image guided form of superficial radiation therapy (designated here as US-SRT) was developed in 2013 where the tumor configuration and depth can be visualized prior to, during, and subsequent to treatments, using a 22 megahertz (MHz) dermal ultrasound (US) with a doppler component. We previously published the results using this technology to treat 2917 early-stage epithelial cancers showing a high local control (LC) rate of 99.3%. We compared these results with similar American studies from a comprehensive literature search used in an article/guideline published by American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions from 1988 to 2018. Only U.S. based studies with greater than 100 cases with similar patient/lesion characteristics and stages treated by external beam, electron, or superficial/orthovoltage radiation therapy were included in the criteria for selection. The resultant 4 studies had appropriate comparable cases identified and the data analyzed/calculated with regard to local control. Logistic regression analysis was performed comparing each study to US-SRT individually and collectively with stratification by histology (BCC, SCC, and SCCIS).

Results

US-SRT LC was found to be statistically superior to each of the 4 non-image-guided radiation therapy studies individually and collectively (as well as stratified by histology subtype) with p-values ranging from p< 0.0001 to p= 0.0438.

Conclusions

Results of US-SRT in local control were statistically significantly superior across the board versus non-image-guided radiation modalities in treatment of epithelial NMSC and should be considered a new gold standard for treatment of early-stage cutaneous BCC, SCC, and SCCIS.
“There’s a big tag on my head”: exploring barriers to treatment seeking with women who use methamphetamine in Sydney, Australia
Authors: Clifford Brendan , Van Gordon Kate , Magee Fiona , Malone Victoria , Siefried Krista , Graham Duncan , Ezard Nadine
Published: August 2022

Background

Australia has a high prevalence of regular use of methamphetamine (MA). While half of people who use MA regularly are women, they make up only one third of people seeking treatment for MA use disorder (MaUD). There is a lack of qualitative research into the facilitators and barriers to treatment for women who use MA regularly. The study seeks a better understanding of the experiences and treatment preferences of women who use MA, to inform person-centred changes in practice and policy that break down barriers to treatment.

Methods

We conducted semi-structured interviews with 11 women who frequently use MA (at least once a week), and who are not engaged in treatment. Women were recruited from health services surrounding a stimulant treatment centre at an inner-city hospital. Participants were asked about their MA use and health service needs and preferences. Thematic analysis was completed using Nvivo® software.

Results

Three themes were developed from participants’ responses around experiences of regular MA use and treatment needs: 1. Resistance of stigmatised identity including dependence; 2. Interpersonal violence; 3. Institutionalised stigma. Clear service delivery preferences were also elicited, including continuity of care, integrated health care, and provision of non-judgmental services.

Conclusion

Gender-inclusive health care services for people who use MA should actively work to address stigma, support a relational approach to assessment and treatment, and seek to provide structurally competent health care that is trauma and violence informed, and integrated with other services. Findings may also have application for substance use disorders other MA.
From signal to knowledge: The diagnostic value of rawdata in artificial intelligence prediction of human data for the first time
Authors: He Bingxi , Guo Yu , Zhu Yongbei , Tong Lixia , Kong Boyu , Wang Kun , Sun Caixia , Li Hailin , Huang Feng , Wu Liwei , Wang Meng , Meng Fanyang , Dou Le , Sun Kai , Tong Tong , Liu Zhenyu , Wei Ziqi , Mu Wei , Wang Shuo , Tang Zhenchao , Zhang Shuaitong , Wei Jingwei , Shao Lizhi , Fang Mengjie , Li Juntao , Zhu Shouping , Zhou Lili , Wang Shuo , Dong Di , Zhang Huimao , Tian Jie
Published: August 2022

Recently, image-based diagnostic technology has made encouraging and astonishing development. Modern medical care and imaging technology are increasingly inseparable. However, the current diagnosis pattern of Signal-to-Image-to-Knowledge inevitably leads to information distortion and noise introduction in the procedure of image reconstruction (Signal-to-Image). Artificial intelligence (AI) technologies that can mine knowledge from vast amounts of data offer opportunities to disrupt established workflows. In this prospective study, for the first time, we developed an AI-based Signal-to-Knowledge diagnostic scheme for lung nodule classification directly from the CT rawdata (the signal). We found that the rawdata achieved almost comparable performance with CT indicating that we can diagnose diseases without reconstructing images. Meanwhile, the introduction of rawdata could greatly promote the performance of CT, demonstrating that rawdata contains some diagnostic information that CT does not have. Our results break new ground and demonstrate the potential for direct Signal-to-Knowledge domain analysis.
CIARA: a cluster-independent algorithm for the identification of markers of rare cell types from single-cell RNA seq data
Authors: Lubatti Gabriele , Stock Marco , Iturbide Ane , Ruiz Tejada Segura Mayra L. , Tyser Richard , Theis Fabian J. , Srinivas Shankar , Torres-Padilla Maria-Elena , Scialdone Antonio
Published: August 2022

A powerful feature of single-cell RNA-sequencing data analysis is the possibility to identify novel rare cell types. However, rare cell types are often missed by standard clustering approaches. We have developed CIARA (Cluster Independent Algorithm for the identification of markers of RAre cell types), a computational tool available in R and Python that outperforms existing methods for rare cell type detection. With CIARA, we found a small group of precursor cells among mouse embryonic stem cells and previously uncharacterized rare populations of cells in a human gastrula.
Specific targeting of inflammatory osteoclastogenesis by the probiotic yeast S. boulardii CNCM I-745 reduces bone loss in osteoporosis
Authors: Madel Maria-Bernadette , Halper Julia , Ibáñez Lidia , Lozano Claire , Rouleau Matthieu , Boutin Antoine , Pontier-Bres Rodolphe , Ciucci Thomas , Topi Majlinda , Hue Christophe , Amiaud Jérôme , Iborra Salvador , Sancho David , Heymann Dominique , Garchon Henri-Jean , Czerucka Dorota , Apparailly Florence , Duroux-Richard Isabelle , Wakkach Abdelilah , Blin-Wakkach Claudine
Published: August 2022

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) TLR2, Dectin-1 and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardi CNCM I-745 (Sb) in vivo reduced bone loss in OVX but not sham mice by reducing inflammatory osteoclasts. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of TLR2, Dectin-1 and Mincle specifically inhibited directly the differentiation of inflammatory but not steady state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.
Mechanisms by Which Small Molecule Inhibitors Arrest Sec14 Phosphatidylinositol Transfer Protein Activity
Authors: Chen Xiao-Ru , Poudel Lokendra , Hong Zebin , Johnen Philipp , Katti Sachin S. , Tripathi Ashutosh , Nile Aaron H. , Green Savana M. , Schaaf Gabriel , Bono Fulvia , Bankaitis Vytas A. , Igumenova Tatyana I.
Published: August 2022

Phosphatidylinositol transfer proteins (PITPs) promote phosphoinositide signaling by enhancing phosphatidylinositol (PtdIns) 4-OH kinase activities in producing signaling pools of PtdIns-4-phosphate. As such, PITPs are key regulators of lipid signaling in eukaryotic cells. While the PITP phospholipid exchange cycle is the engine that stimulates PtdIns 4-OH kinase activity, the protein and lipid dynamics associated with this critical process are not understood. Herein, we use an integrative structural approach that takes advantage of small molecule inhibitors (SMIs) directed against the major yeast PITP (Sec14) to gain new insights into the mechanics of the Sec14 phospholipid exchange cycle from the perspective of protein, phospholipid and SMI dynamics. Moreover, as Sec14 has emerged as an attractive target for next-generation antifungal drugs, the structures of Sec14 bound to SMIs of four different chemotypes reported in this study provide critical information required for structure-based design of next-generation lead compounds that target Sec14 PITPs of virulent fungi.
Significance Analysis for Clustering with Single-Cell RNA-Sequencing Data
Authors: Grabski Isabella N. , Street Kelly , Irizarry Rafael A.
Published: August 2022

Abstract

Unsupervised clustering of single-cell RNA-sequencing data enables the identification and discovery of distinct cell populations. However, the most widely used clustering algorithms are heuristic and do not formally account for statistical uncertainty. Many popular pipelines use clustering stability methods to assess the algorithms’ output and decide on the number of clusters. However, we find that by not addressing known sources of variability in a statistically rigorous manner, these analyses lead to overconfidence in the discovery of novel cell-types. We extend a previous method for Gaussian data, Significance of Hierarchical Clustering (SHC), to propose a model-based hypothesis testing approach that incorporates significance analysis into the clustering algorithm and permits statistical evaluation of clusters as distinct cell populations. We also adapt this approach to permit statistical assessment on the clusters reported by any algorithm. We benchmarked our approach on real-world datasets against popular clustering workflows, demonstrating improved performance. To show its practical utility, we applied it to the Human Lung Cell Atlas and an atlas of the mouse cerebellar cortex. We identified several cases of over-clustering, leading to false discoveries, as well as under-clustering, resulting in the failure to identify new subpopulations that our method was able to detect.
Pregnenolone reorganizes cytoskeleton to promote neuron development via CLIP1
Authors: Viktoryia Kolas , Wu Yi-Ting , Bandonil Jose Sandino A. , Chung Bon-Chu
Published: August 2022

Pregnenolone (P5) is a neurosteroid produced in the brain. It improves cognitive function and protects against cannabis intoxication as well as spinal cord injury. P5 activates CLIP1, which helps microtubule polymerization at its growing end; however, the significance of P5 activation of CLIP1 in the brain is still unknown. Here we examined the roles of P5 in cultured neurons and in zebrafish cerebellum. We show that P5 promotes neurite outgrowth and facilitates axon development of cultured cerebellar granule neurons. P5 also changes the morphology of axon growth cone and promotes dynamic microtubule invasion into the distal part of filopodia at the growth cone. We have used CRISPR to disrupt clip1a in zebrafish, disrupting the ability of P5 to change microtubule dynamics and growth cone morphology, as well as to reorganize cytoskeleton. In vivo, P5 accelerated cerebellum development in WT but not clip1a mutant zebrafish, and expression of exogenous CLIP1 in clip1a mutant promoted cerebellum development in response to P5. Thus, we have delineated the pathway by which P5 promotes cerebellum development by activating CLIP1 to promote microtubule dynamics leading to increased microtubule penetration into the growth cone and accelerated neurite outgrowth. This study reveals the mechanism by which P5 and CLIP1 function to promote neural development.

Significance Statement

1.

We have elucidated the mechanism of pregnenolone (P5) action

P5 enhances brain functions, but its mode of action was unclear. Here we show that P5 activates CLIP1 to promote microtubule dynamics at the growth cone and to accelerate neural development.

2.

We have generated a zebrafish model of CLIP1 deficiency

CLIP1 deficiency causes intellectual disability and defective neural development. Our zebrafish model can be used to study mechanisms related to this disease and other microtubule defects.

3.

We point to therapeutic intervention of neurological diseases using P5

P5 is beneficial to the brain. We elucidate the mechanism of P5 action, thus accelerate the development of therapeutics using P5 and its derivatives.
Comparative genomic analyses of Lactococcus garvieae isolated from bovine mastitis in China
Authors: Lin Yushan , Han Jinge , Barkema Herman W. , Wang Yue , Gao Jian , Kastelic John P. , Han Bo , Qin Shunyi , Deng Zhaoju
Published: August 2022

Lactococcus garvieae is an emerging zoonotic pathogen, but there are few reports regarding bovine mastitis. The recent prevalence of L. garvieae poses an increasing disease threat and global public health risk. A total of 39 L. garvieae isolates were obtained from 2899 bovine clinical mastitis milk samples in 6 provinces of China from 2017 to 2021. Five clonal complexes were determined from 32 MLST types of L. garvieae; ST46 was the predominant sequence type and 13 novel MLST types were identified. All isolates were resistant to chloramphenicol and clindamycin, but susceptible to penicillin, ampicillin, amoxicillin-clavulanic acid, imipenem, ceftiofur, enrofloxacin, and marbofloxacin. Based on genomic analyses, L. garvieae had 6310 genes, including 1015, 3641 and 1654 core, accessory and unique genes. All isolates had virulence genes coding for collagenase, fibronectin-binding protein, Glyceraldehyde-3-phosphate dehydrogenase, superoxide dismutase and NADH oxidase. Most isolates had lsaD and mdtA AMR genes. Based on COG results, the functions of defense, transcription and replication, recombination and repair were enhanced in unique genes, whereas functions of translation, ribosomal structure and biogenesis were enhanced in core genes. The KEGG functional categories enriched in unique genes included human disease and membrane transport, whereas COG functional categories enriched in core genes included energy metabolism, nucleotide metabolism and translation. No gene was significantly associated with host specificity. In addition, core genome SNPs analysis suggested potential host adaptation of some isolates in several sequence types. Therefore, this study characterized L. garvieae isolated from mastitis and assessed host adaptation of L. garvieae to various hosts.

IMPORTANCE

This study provides important insights on bovine mastitis key topic pathogen Lactococcus garvieae, which constitutes mastitis concerns. However, comprehensive genomic analyses of L. garvieae from dairy farms have not been performed. This study gives a detailed and comprehensive novel feature in L. garvieae, an important but poorly characterized bacterium, recovered in the past 5 years in 6 Chinese provinces. We documented diverse contributory genetic processes, including predominant sequence type ST46 and 13 novel MLST types. L. garvieae had 6310 genes, including 1015, 3641 and 1654 core, accessory and unique genes. All isolates had virulence genes coding for collagenase, fibronectin-binding protein, Glyceraldehyde-3-phosphate dehydrogenase, superoxide dismutase and NADH oxidase, and resistant to chloramphenicol and clindamycin. Most isolates had lsaD and mdtA antimicrobial resistance genes. No gene was significantly associated with host specificity. This is the first absolute quantification of L. garvieae isolated from mastitis and identified host adaptation of L. garvieae to various hosts.
Negative pressure pneumomediastinum: a novel concept of spontaneous pneumomediastinum without mediastinal widening following weight loss
Authors: Hagiwara Hiroaki , Kinno Yoshinori , Ikegami Tadashi
Published: August 2022

Purpose

Spontaneous pneumomediastinum, supposedly attributed to air leakage from the respiratory tract, is a common complication of interstitial lung disease often resulting in mediastinal widening. However, several cases of pneumomediastinum without mediastinal widening have been observed. This study aimed to investigate the cause of pneumomediastinum in patients without mediastinal widening.

Patients and methods

This study included 41 patients diagnosed with pneumomediastinum using computed tomography (CT) between July 2011 and September 2021 at Yokohama Minamikyosai Hospital; they had undergone a previous CT showing no gas density. Based on a comparison with previous CT images, the patients were classified into two groups: without mediastinal widening and with mediastinal widening.

Results

Of the 41 patients, 13 and 28 had pneumomediastinum without and with mediastinal widening, respectively. There were no significant differences in the sex, age, body mass index, or pneumomediastinum distribution between the two groups. However, the rate of weight loss per month was significantly higher in the group without mediastinal widening than in that with mediastinal widening. No significant differences were observed in the respiratory function test results between the two groups; however, 11 of the 13 patients had restrictive disorders. Pulmonary disease in this group included idiopathic pulmonary fibrosis (n = 6) and interstitial lung disease with collagen disease (n = 4). Pneumomediastinum occurred during periods of weight loss in all the patients excluding two patients without data.

Conclusion

Pneumomediastinum without mediastinal widening occurs during rapid weight loss and is often associated with restrictive lung disorders. The negative pressure attributed to the decreased plasticity of the lungs, which complements the space where the mediastinal fat has disappeared, is presumably the cause of pneumomediastinum. This pathophysiology is different from that of conventional pneumomediastinum attributed to increased intrapleural space pressure; thus, we propose to name the abovementioned pathophysiology negative pressure pneumomediastinum.
A planetary health solution for disease, sustainability, food, water, and poverty challenges
Authors: Rohr Jason R , Bakhoum Sidy , Barrett Christopher B , Chamberlin Andrew J , Civitello David J , Doruska Molly J , De Leo Giulio A , Haggerty Christopher J E , Jones Isabel , Jouanard Nicolas , Ly Amadou T. , Ndione Raphael A , Remais Justin V , Riveau Gilles , Sack Alexandra , Schacht Anne-Marie , Senghor Simon , Sokolow Susanne H , Wolfe Caitlin
Published: August 2022

Global health and development communities lack sustainable, cost-effective, mutually beneficial solutions for infectious disease, food, water, and poverty challenges despite their regular interdependence worldwide1–7. Here, we show that agricultural development and fertilizer use in west Africa increase the devastating tropical disease schistosomiasis by fueling the growth of submerged aquatic vegetation that chokes out water access points and serves as habitat for snails that transmitSchistosomaparasites to >200 million people globally8–10. In a randomized control trial where we removed invasive submerged vegetation from water points, control sites had 124% higher fecalSchistosomareinfection rates in schoolchildren and lower open water access than removal sites without any detectable long-term adverse effects of the removal on local water quality or freshwater biodiversity. The removed vegetation was as effective as traditional livestock feed but 41-179 times cheaper and converting the vegetation to compost yielded private crop production and total (public health plus private benefits) benefit-to-cost ratios as high as 4.0 and 8.8, respectively. Thus, we provide an economic incentive – with important public health co-benefits – to maintain cleared waterways and return nutrients captured in aquatic plants back to agriculture with great promise of breaking poverty-disease traps. To facilitate targeting and scaling of this intervention, we lay the foundation for using remote sensing technology to detect snail habitat. By offering a rare, profitable, win-win innovation for food and water access, poverty, infectious disease emergence, and environmental sustainability, we hope to inspire the interdisciplinary search for other planetary health solutions11to the numerous and formidable, co-dependent global grand challenges of the 21st century.
Real-life evaluation of a rapid antigen test (DPP® SARS-CoV-2 Antigen) for COVID-19 diagnosis of primary healthcare patients, in the context of the Omicron-dominant wave in Brazil
Authors: Bezerra Matheus Filgueira , Amorim Silva Lilian Caroliny , Pessoa-e-Silva Rômulo , Soares Gisele Lino , Dezordi Filipe Zimmer , de Lima Gustavo Barbosa , de Lima Raul Emídio , Campos Tulio L. , Docena Cassia , de Oliveira Anderson Bruno , Rocha Pitta Maira Galdino da , da Silva Santos Francisco de Assis , Pereira Michelly , Wallau Gabriel Luz , Santos Paiva Marcelo Henrique
Published: August 2022

Rapid antigen tests play an important role in the monitoring and mitigation of the COVID-19 pandemic, as it provides an easy, fast and efficient diagnosis with minimum infrastructure requirements. However, as new variants of concern continue to emerge, mutations in the virus genome may impair the recognition of the mutated antigen by the tests. Therefore, it is essential to re-assess the test’s sensitivity as the virus mutation profile undergoes significant changes. Here, we prospectively accessed the performance of the DPP® SARS-CoV-2 Antigen test in the context of an omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing center in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct RT-qPCR methods was employed as reference and 13 samples with discordant PCR results were excluded. The assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5%, specificity of 99.2% and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct<31 = 93.7%; Ct>31 = 47.4%). Furthermore, we were able to confirm that the positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n=40) and multiplex RT-qPCR (n=17). Altogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for the Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in a setting with high disease prevalence and limited PCR testing capability.