bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Studies of Renin-Null Zebrafish and Mice Provide New Functional Insights
Authors: Hoffmann Scott , Mullins Linda , Rider Sebastien , Brown Cara , Buckley Charlotte B. , Assmus Adrienne , Li Ziwen , Sierra Beltran Mariana , Henderson Neil , del Pozo Jorge , De Goes Martini Alexandre , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel , Mullins John
Published: January 2022

Background:

The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin.

Methods:

We generated zebrafish with CRISPR-Cas9-targeted knockout of renin (
ren
−/−
) to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of
ren
−/−
with
ren
+/+
zebrafish and with the metanephric kidneys of
Ren1

c
−/−

and
Ren1

c
+/+

mice.

Results:

The
ren
−/−
larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The
ren
−/−
mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in
Ren1

c
−/−

mouse kidney. Fluorescent reporters for renin and smooth muscle actin (
Tg(ren:LifeAct-RFP; acta2:EGFP
)), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult
ren
−/−
fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the
Ren1
YFP
Ren1

c
−/−

mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function.

Conclusions:

Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.
Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes
Authors: Kivipelto Miia , Palmer Katie , Hoang Tina D. , Yaffe Kristine
Published: January 2022

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the COVID-19 pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals’ vascular risk profiles and subsequent risk of cognitive decline.
Unconventional Monetary Policy through Open Market Operations: A Principal Component Analysis
Authors: Heckel Markus , Nishimura Kiyohiko G.
Published: January 2022

This paper examines the unconventional monetary policies of the Bank of Japan from 2002 to 2019 with a focus on open market operations.  We apply a principal component analysis to investigate the complexity of monetary policy.  Our results identify four principal components that explain the variance of measures taken by the Bank of Japan and its operations of various facilities: asset purchase measures including Japanese Government Bonds (JGBs), Exchange-Traded Funds (ETFs), Japanese Real Estate Investment Trusts (J-REITs), and three different liquidity supply measures. Complexity differs substantially among different governorships of Fukui, Shirakawa (most complex), and Kuroda. We derive some conclusions from the increased complexity with implications for the economy.
Cymbopleura huohuaensis sp. nov. (Cymbellaceae; Bacillariophyceae), a new species from Sichuan Province, China
Authors: GUO JI-SHU , MENG WEN-WEN , KOCIOLEK JOHN PATRICK , YANG SOPHIA , LI YAN-LING
Published: January 2022

Cymbopleura huohuaensis sp. nov. is identified as a new species and described from stone surfaces in Huohua Lake, Sichuan Province, China. A detailed morphological description of the new species is presented, based on light and scanning electron microscopy. Cymbopleura huohuaensis sp. nov. has the features that assign it to the genus Cymbopleura, including the raphe with dorsally deflected terminal fissures and ventrally curved central raphe ends, punctate-lineate striae, and the absence of apical pore fields and stigmata. There are five features that easily distinguish the new species from the other similar taxa within the genus: 1) linear-lanceolate central area, 2) mostly slit-like, partly T-shaped, V-shaped or irregularly-shaped areolae, 3) strongly reverse-lateral raphe, 4) slightly truncate to obtusely rounded ends and 5) the highest density of areolae (30–50 in 10 μm). Among the currently described species of Cymbopleura, the new species is in general most similar to C. subaequalis var. pertruncata in valve shape and possessing a reverse-lateral raphe, but is easily distinguished from that taxon by the size and shape of valve, shape of central area, and the degree of asymmetry about the apical axis and its notable lack of an intermissio. This species might be better placed in the C. austriaca group due to its lack of an intermissio. These findings increase our understanding the morphology and distribution of the genus Cymbopleura in China.
Aubrieta necmi-aksoyi (Brassicaceae), a new species from Turkey and a key to the species of Aubrieta
Authors: TUNÇKOL BILGE , ÖZKAN NEVAL GÜNEŞ , AL-SHEHBAZ IHSAN A.
Published: January 2022

Aubrieta necmi-aksoyi is described as a new Turkish species endemic to Bolu Province. Its relationships to the closely related A. alshehbazii and A. ekimii are discussed. A detailed genereic description and a key to all Turkish species of Aubrieta are presented.
Type studies on two Paxillus species (Paxillaceae, Boletales) described from China
Authors: LIU LI-RONG , WANG GENG-SHEN , JIA LIU-KUN , KANG JU-QING , YANG ZHU-LIANG , LI YAN-CHUN
Published: January 2022

Types and recently collected samples of two Paxillus species namely P. rhytidophyllus and P. yunnanensis, originally described from southwestern China, were critically restudied based on morphology and molecular phylogenetic data of DNA sequences from the large subunit of the nuclear ribosomal RNA (nrLSU), the nuclear ribosomal internal transcribed spacer (ITS), and the translation elongation factor 1-α (tef1-α). The results showed that these two species belong to Boletinellus and Tricholomopsis, respectively. Thus, two new combinations, Boletinellus rhytidophyllus and Tricholomopsis yunnanensis are proposed. Boletinellus rhytidophyllus is characterized by a deeply decurrent and shallow hymenophore which is poroid-lamellate to alveolate, slightly thick-walled (0.6–1 μm) basidiospores, occasionally 2- to 4-spored basidia, rare or infrequent hymenial cystidia, and a trichodermal pileipellis. Tricholomopsis yunnanensis is characterized by a convex pileus densely covered by red-violet to red-brown fibrillose squamules, a yellowish stipe sparsely covered with red to red-brown fibrillose squamules, subglobose to broadly ellipsoid basidiospores, prominent large cheilocystidia measuring 60–195 × 11–39 μm, and a palisadic pileipellis. New descriptions and line drawings of these two species and their comparisons with allied taxa are presented.
Expended range of Gomphonema firmum (Bacillariophyceae), once considered a Lake Baikal endemic, with notes on the identity of G. lanceolatum var. maximum
Authors: VISHNYAKOV VASILY S.
Published: January 2022

This note describes a new record of Gomphonema firmum Skvortzow, which expanded both morphological and distributional ranges of the species. This conspicuous diatom was previously unknown outside of Lake Baikal, where it inhabits deep-water areas. The newly discovered locality belongs to a small stream at a distance of 180 km west from Lake Baikal, where the species was found in a relatively high abundance that enabled to trace a size diminution series including specimens shorter than previously described. In addition, G. lanceolatum var. maximum Poretzky, a name for a diatom from Lake Teletskoe, was included in a synonymy of G. firmum that further expanded the species distribution. In the light of the presented data, the species appears to be a rare diatom with current distribution limited to a few scattered localities in southern Siberia.
A new species of oak gall wasp (Hymenoptera: Cynipidae, Cynipini) from Turkey
Authors: DEMİREL MUSTAFA , AZMAZ MUSA , KATILMIŞ YUSUF
Published: January 2022

A new species of the genus Andricus Hartig, 1840 (Cynipidae: Cynipini) is described from Burdur province in Turkey: Andricus arslani Azmaz & Katılmış sp. n. sexual generation. The new species induce galls on Quercus cerris L. belonging to section Cerris. SEM images, photos of the host galls, and data on the diagnosis, distribution, and biology of the new species are provided.
Who operates on the children?
Authors: Mlay K , Hampton T , Sharma R , Howard D , Chussi D , Shija P
Published: January 2022

An unexpectedly high burden of elective paediatric surgery is being performed by the Ear, Nose and Throat (ENT) surgeons in Moshi, Tanzania.

We believe this brief survey demonstrates the capacity for elective paediatric surgery in the sub-Saharan setting, comparable to the elective operative numbers of an equivalent tertiary centre in Liverpool, UK.
Dynamics of Information Acquisition: Does Investment in Information Technology Matter?
Authors: Arabyat Yaser Ahmed , Aziz Omar G.
Published: January 2022

The purpose of the study is to develop a theoretical model to ascertain if the IT investment in the banking sector is capable of generating a new equilibrium with increased efficiency. The empirical strategy is to seek an indirect test for Jordanian banking sector by looking at the time profile of banking profits as a temporal function of IT investment. The study enquires if the banking sector, as an iterative process of credit allocation and information acquisition through IT investment, lead to a stable equilibrium? Does IT investment ensure stable market shares for Jordanian banks in the long run? The study finds that investment in IT has led the banking system in Jordan away from an efficient equilibrium. We also find that the banks in Jordan directly interact with each other, although they may have collusive arrangements with some of their rivals, this means the banking market is not fragmented.
Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer
Authors: Chen Jia , Yao Dongting , Chen Weiqin , Li Zhen , Guo Yuanyuan , Zhu Fan , Hu Xiaobo
Published: January 2022

Objectives

The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer.

Methods

Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls.

Results

The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse.

Conclusions

Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.
Dating Apps: The Uncertainty of Marketised Love
Authors: Bandinelli Carolina , Gandini Alessandro
Published: January 2022

Dating apps promise a ‘digital fix’ to the ‘messy’ matter of love by means of datafication and algorithmic matching, realising a platformisation of romance commonly understood through notions of a market’s rationality and efficiency. Reflecting on the findings of a small-scale qualitative research on the use of dating apps among young adults in London, we problematise this view and argue that the specific form of marketisation articulated by dating apps is entrepreneurial in kind, whereby individuals act as brands facing the structural uncertainty of interacting with ‘quasi-strangers’. In so doing, we argue, dating app users enact a Luhmanian notion of interpersonal trust, built on the assessment of the risk of interacting with unfamiliar others that is typical of digitally mediated contexts dominated by reputational logics. From a sociocultural perspective, dating apps emerge as sociotechnical apparatuses that remediate the demand to rationally choose a partner while at the same time reproducing the (im)possibility of doing so. In this respect, far from offering a new form of efficiency, they (re)produce the ontological uncertainty (Illouz, 2019) that characterises lovers as entrepreneurs.
RNA sequencing of chronic GVHD skin lesions defines shared and unique inflammatory pathways characterizing lichen planus and morphea
Authors: Zouali Habib , Lemasson Juliette , Calugareanu Andreea , Battail Christophe , Michonneau David , le Buanec Hélène , Grolleau Chloé , Cassius Charles , Robin Marie , Merandet Marine , Dobos Gabor , Mahevas Thibault , Rybojad Michel , de Masson Adèle , Amode Reyhan , Boland Anne , Michel Laurence , Sicre de Fontbrune Flore , Peffault de Latour Régis , Bruneval Patrick , Ait-Oufella Hafid , Battistella Maxime , Jachiet Marie , Bagot Martine , Deleuze Jean-François , Socié Gérard , Bouaziz Jean-David
Published: January 2022

Cutaneous involvement of chronic graft-versus-host disease (cGVHD) has a wide range of manifestations including a lichenoid form with a currently assumed mixed Th1/Th17 signature and a sclerotic form with Th1 signature. Despite substantial heterogeneity of innate and adaptive immune cells recruited to the skin and of the different clinical manifestations, treatment depends mainly on the severity of the skin involvement and relies on systemic, high-dose glucocorticoids alone or in combination with a calcineurin inhibitor. We performed the first study using RNA sequencing to profile and compare the transcriptome of lichen planus cGVHD (n = 8), morphea cGVHD (n = 5), and healthy controls (n = 6). Our findings revealed shared and unique inflammatory pathways to each cGVHD subtype that are both pathogenic and targetable. In particular, the deregulation of IFN signaling pathway was strongly associated with cutaneous cGVHD, whereas the triggering receptor expressed on myeloid cells 1 pathway was found to be specific of lichen planus and likely contributes to its pathogenesis. The results were confirmed at a protein level by performing immunohistochemistry staining and at a transcriptomic level using real-time quantitative polymerase chain reaction.
Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment
Authors: Teipel Raphael , Kroschinsky Frank , Kramer Michael , Kretschmann Theresa , Egger-Heidrich Katharina , Krüger Thomas , Ruhnke Leo , Herold Sylvia , Stasik Sebastian , Sockel Katja , Middeke Jan M. , Trautmann-Grill Karolin , Bornhäuser Martin , Thiede Christian , von Bonin Malte
Published: January 2022

Inflammation plays an important role in chimeric antigen receptor (CAR) T-cell therapy, especially in the pathophysiology of cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Clonal hematopoiesis of indetermined potential (CHIP) has also been associated with chronic inflammation. The relevance of CHIP in the context of CAR T-cell treatment is widely unknown. We evaluated the prevalence of CHIP, using a targeted deep sequencing approach, in a cohort of patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma before and after CAR T-cell treatment. The aim was to define the prevalence and variation of CHIP over time and to assess the influence on clinical inflammation syndromes (CRS/ICANS), cytopenia, and outcome. Overall, 32 patients were included. CHIP was found in 11 of 32 patients (34%) before CAR T-cell therapy. CHIP progression was commonly detected in the later course. Patients with CHIP showed a comparable response rate to CAR T-cell treatment but had an improved overall survival (not reached vs 265 days, P = .003). No significant difference was observed in terms of the occurrence and severity of CRS/ICANS, therapeutic use of tocilizumab and glucocorticosteroids, paraclinical markers of inflammation (with the exception of ferritin), or dynamics of hematopoietic recovery. CHIP is commonly observed in patients undergoing CD19-directed CAR T-cell therapy and is not associated with an inferior outcome.
Impact of environmental factors on human semen quality and male fertility: a narrative review
Authors: Kumar Naina , Singh Amit Kant
Published: January 2022

Background

Worldwide rising trend in infertility has been observed in the past few years with male infertility arising as a major problem. One main reason for the rise in male infertility cases is declining semen quality. It was found that any factor that affects semen quality can affect male fertility. There are several modifiable factors affecting semen quality including air pollution, use of pesticides and harmful chemicals, exposure to excessive heat, and can lead to decreased male fertility.

Main body

The present review focuses on some of these environmental factors that affect semen quality and hence, can cause male infertility. The literature from 2000 till June 2021 was searched from various English peer-reviewed journals and WHO fact sheets using the USA National Library of Medicine (PubMed) database, the regional portal of Virtual Health Library, and Scientific Electronic Library Online. The search terms used were: “Air pollution and male fertility”, “Chemicals and male infertility”, “Heat exposure and infertility”, “heavy metals and male fertility”.

Conclusion

Adverse environmental factors have a significant impact on semen quality, leading to decreased sperm concentration, total sperm count, motility, viability, and increased abnormal sperm morphology, sperm DNA fragmentation, ultimately causing male infertility. However, all these factors are modifiable and reversible, and hence, by mere changing of lifestyle, many of these risk factors can be avoided.
Polygenic risk prediction based on singular value decomposition with applications to alcohol use disorder
Authors: Yang James J. , Luo Xi , Trucco Elisa M. , Buu Anne
Published: January 2022

Background/aim

The polygenic risk score (PRS) shows promise as a potentially effective approach to summarize genetic risk for complex diseases such as alcohol use disorder that is influenced by a combination of multiple variants, each of which has a very small effect. Yet, conventional PRS methods tend to over-adjust confounding factors in the discovery sample and thus have low power to predict the phenotype in the target sample. This study aims to address this important methodological issue.

Methods

This study proposed a new method to construct PRS by (1) approximating the polygenic model using a few principal components selected based on eigen-correlation in the discovery data; and (2) conducting principal component projection on the target data. Secondary data analysis was conducted on two large scale databases: the Study of Addiction: Genetics and Environment (SAGE; discovery data) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; target data) to compare performance of the conventional and proposed methods.

Result and conclusion

The results show that the proposed method has higher prediction power and can handle participants from different ancestry backgrounds. We also provide practical recommendations for setting the linkage disequilibrium (LD) andpvalue thresholds.
Video-telehealth to support clinical assessment and management of acutely unwell older people in Residential Aged Care: a pre-post intervention study
Authors: Hullick Carolyn , Conway Jane , Hall Alix , Murdoch Wendy , Cole Janean , Hewitt Jacqueline , Oldmeadow Christopher , Attia John
Published: January 2022

Background

Older people living in Residential Aged Care (RAC) are at high risk of clinical deterioration. Telehealth has the potential to provide timely, patient-centred care where transfer to hospital can be a burden and avoided. The extent to which video telehealth is superior to other forms of telecommunication and its impact on management of acutely unwell residents in aged care facilities has not been explored previously.

Methods

In this study, video-telehealth consultation was added to an existing program, the Aged Care Emergency (ACE) program, aiming at further reducing Emergency Department (ED) visits and hospital admissions. This controlled pre-post study introduced video-telehealth consultation as an additional component to the ACE program for acutely unwell residents in RACs. Usual practice is for RACs and ACE to liaise via telephone. During the study, when the intervention RACs called the ED advanced practice nurse, video-telehealth supported clinical assessment and management. Five intervention RACs were compared with eight control RACs, all of whom refer to one community hospital in regional New South Wales, Australia. Fourteen months pre-video-telehealth was compared with 14 months post-video-telehealth using generalized linear mixed models for hospital admissions after an ED visit and ED visits. One thousand two hundred seventy-one ED visits occurred over the 28-month study period with 739 subsequent hospital admissions.

Results

There were no significant differences in hospital admission or ED visits after the introduction of video-telehealth; adjusted incident rate ratios (IRR) were 0.98 (confidence interval (CI) 0.55 to 1.77) and 0.89 (95% CI 0.53 to 1.47) respectively.

Conclusions

Video-telehealth did not show any incremental benefit when added to a structured hospital avoidance program with nursing telephone support.

Trial registration

The larger Aged Care Emergency evaluation is registered with ANZ Clinical Trials Registry, ACTRN12616000588493.
A comparative study of human glomerular basement membrane thickness using direct measurement and orthogonal intercept methods
Authors: Viana Débora Leal , Alladagbin Dona Jeanne , dos-Santos Washington L. C. , Figueira Claudio Pereira
Published: January 2022

Introduction

Here we report estimates of glomerular basement membrane (GBM) thickness in the Brazilian population performed using direct (DM) and orthogonal interception methods (OIM), and comment on potential sources of variation among estimates made by different laboratories.

Methodology

A total of 38 patients, ranging from 3 to 78 years of age, 26 (68%) males and 12 (32%) females, were submitted to kidney biopsy procedures for renal disease diagnosis. Glomeruli were diagnosed with minor histological changes by conventional, immunofluorescence and electron microscopy. GBM thickness was estimated using both DM and OIM methods.

Results

Estimates of GBM thickness obtained using DM were higher than those obtained by OIM. However, the application of a correction for non-perpendicular membrane sectioning to DM estimates yielded similar results to those obtained under OIM. The estimated GMB thickness using DM after correction was 289 + 44 nm, versus 287 + 48 nm by OIM. No statistically significant differences were detected in GMB thickness, nor with respect to patient age or sex.

Conclusions

GBM thickness in the studied Brazilian population measured approximately 290 nm. The application of criteria for estimating the shortest distance between the endothelial and podocyte cell membranes with correction for non-perpendicular membrane sectioning can increase the accuracy of GBM thickness estimates using DM and OIM.
Chronic kidney disease and its health-related factors: a case-control study
Authors: Ghelichi-Ghojogh Mousa , Fararouei Mohammad , Seif Mozhgan , Pakfetrat Maryam
Published: January 2022

Background

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders that are associated with abnormal renal function and progressive decline in glomerular filtration rate (GFR). This study aimed to investigate the associations of several behavioral and health-related factors with CKD in Iranian patients.

Methods

A hospital-based case-control study was conducted on 700 participants (350 cases and 350 controls). Logistic regression was applied to measure the association between the selected factors and CKD.

Results

The mean age of cases and controls were 59.6 ± 12.4 and 58.9 ± 12.2 respectively (p = 0.827). The results of multiple logistic regression suggested that many factors including low birth weight (OR yes/no = 4.07, 95%CI: 1.76–9.37, P = 0.001), history of diabetes (OR yes/no = 3.57, 95%CI: 2.36–5.40, P = 0.001), history of kidney diseases (OR yes/no = 3.35, 95%CI: 2.21–5.00, P = 0.001) and history of chemotherapy (OR yes/no = 2.18, 95%CI: 1.12–4.23, P = 0.02) are associated with the risk of CKD.

Conclusions

The present study covered a large number of potential risk/ preventive factors altogether. The results highlighted the importance of collaborative monitoring of kidney function among patients with the above conditions.
Chest radiography in children aged 2–59 months enrolled in the Innovative Treatments in Pneumonia (ITIP) project in Lilongwe Malawi: a secondary analysis
Authors: Mvalo Tisungane , McCollum Eric D. , Fitzgerald Elizabeth , Kamthunzi Portia , Schmicker Robert H. , May Susanne , Phiri Melda , Chirombo Claightone , Phiri Ajib , Ginsburg Amy Sarah
Published: January 2022

Background

Pneumonia is the leading infectious cause of death in children aged under 5 years in low- and middle-income countries (LMICs). World Health Organization (WHO) pneumonia diagnosis guidelines rely on non-specific clinical features. We explore chest radiography (CXR) findings among select children in the Innovative Treatments in Pneumonia (ITIP) project in Malawi in relation to clinical outcomes.

Methods

When clinically indicated, CXRs were obtained from ITIP-enrolled children aged 2 to 59 months with community-acquired pneumonia hospitalized with treatment failure or relapse. ITIP1 (fast-breathing pneumonia) and ITIP2 (chest-indrawing pneumonia) trials enrolled children with non-severe pneumonia while ITIP3 enrolled children excluded from ITIP1 and ITIP2 with severe pneumonia and/or selected comorbidities. A panel of trained pediatricians classified the CXRs using the standardized WHO CXR research methodology. We analyzed the relationship between CXR classifications, enrollee characteristics, and outcomes.

Results

Between March 2016 and June 2018, of 114 CXRs obtained, 83 met analysis criteria with 62.7% (52/83) classified as having significant pathology per WHO standardized interpretation. ITIP3 (92.3%; 12/13) children had a higher proportion of CXRs with significant pathology compared to ITIP1 (57.1%, 12/21) and ITIP2 (57.1%, 28/49) (p-value = 0.008). The predominant pathological CXR reading was “other infiltrates only” in ITIP1 (83.3%, 10/12) and ITIP2 (71.4%, 20/28), while in ITIP3 it was “primary endpoint pneumonia”(66.7%, 8/12,; p-value = 0.008). The percent of CXRs with significant pathology among children clinically cured (60.6%, 40/66) vs those not clinically cured (70.6%, 12/17) at Day 14 was not significantly different (p-value = 0.58).

Conclusions

In this secondary analysis we observed that ITIP3 children with severe pneumonia and/or selected comorbidities had a higher frequency of CXRs with significant pathology, although these radiographic findings had limited relationship to Day 14 outcomes. The proportion of CXRs with “primary endpoint pneumonia” was low. These findings add to existing data that additional diagnostics and prognostics are important for improving the care of children with pneumonia in LMICs.

Trial registration

ITIP1, ITIP2, and ITIP3 were registered with ClinicalTrials.gov (NCT02760420, NCT02678195, and NCT02960919, respectively).
The effect of sexual abuse and dissociation on suicide attempt
Authors: Brokke Silje Støle , Bertelsen Thomas Bjerregaard , Landrø Nils Inge , Haaland Vegard Øksendal
Published: January 2022

Background

Suicide attempt is the most predictive risk factor of suicide. Trauma – especially sexual abuse – is a risk factor for suicide attempt and suicide. A common reaction to sexual abuse is dissociation. Higher levels of dissociation are linked to self-harm, suicide ideation, and suicide attempt, but the role of dissociation in suicidal behavior is unclear.

Methods

In this naturalistic study, ninety-seven acute psychiatric patients with suicidal ideation, of whom 32 had experienced sexual abuse, were included. Suicidal behaviour was assessed with The Columbia suicide history form (CSHF). The Brief trauma questionnaire (BTQ) was used to identify sexual abuse. Dissociative symptoms were assessed with Dissociative experiences scale (DES).

Results

Patients who had experienced sexual abuse reported higher levels of dissociation and were younger at onset of suicidal thoughts, more likely to self-harm, and more likely to have attempted suicide; and they had made more suicide attempts. Mediation analysis found dissociative experiences to significantly mediate a substantive proportion of the relationship between sexual abuse and number of suicide attempts (indirect effects = 0.17, 95% CI = 0.05, 0.28, proportion mediated = 68%). Dissociative experiences significantly mediated the role of sexual abuse as a predictor of being in the patient group with more than four suicide attempts (indirect effects = 0.11, 95% CI = 0.02, 0.19, proportion mediated = 34%).

Conclusion

The results illustrate the importance of assessment and treatment of sexual abuse and trauma-related symptoms such as dissociation in suicide prevention. Dissociation can be a contributing factor to why some people act on their suicidal thoughts.
Implementation evaluation of a collective impact initiative to promote adolescent health in Oklahoma County, USA
Authors: Garney Whitney R. , Panjwani Sonya , Wilson Kelly , Garcia Kristen E. , Fore Sharayah , Lautner Shelby C. , Lang Laura , Criswell Brittney , Mathews Ronneal
Published: January 2022

Background

The teenage birth rate in the USA has considerably decreased in recent decades; however, more innovative, collaborative approaches are needed to promote adolescent health and prevent teenage pregnancy at the community level. Despite literature on the promising results of the collective impact (CI) model for health promotion, there is limited literature on the model’s ability to reduce teenage pregnancies in a community. The Central Oklahoma Teen Pregnancy Prevention Collaboration is applying the CI model to foster collaboration among multiple stakeholders with the goal of increasing community and organizational capacity to improve adolescent health outcomes. This paper reports the findings from the initiative’s implementation evaluation, which sought to understand whether the CI model improved collaboration among organizations and understand barriers and facilitators that affected program delivery.

Methods

Program implementers and evaluators jointly developed research questions to guide the intervention and evaluation design. The Consolidated Framework for Implementation Research (CFIR) was used to assess program components including the intervention characteristics, organization setting, community setting, facilitator characteristics, and the process of implementation. Primary sources of data included performance measures, meeting observations (n = 11), and semi-structured interviews (n = 10). The data was thematically analyzed using CFIR constructs, community capacity domains, and the five constructs of CI.

Results

Key findings include the need for shortened meeting times for meaningful engagement, opportunities for organizations to take on more active roles in the Collaboration, and enhanced community context expertise (i.e., those with lived experience) in all Collaboration initiatives. We identified additional elements to the core constructs of CI that are necessary for successful implementation: distinct role identification for partner organizations and incorporation of equity and inclusivity into collaboration processes and procedures.

Conclusions

Results from this implementation evaluation provide valuable insights into implementation fidelity, participant experience, and implementation reach of an innovative, systems-level program. Findings demonstrate the context and requirements needed to successfully implement this innovative program approach and CI overall. Additional core elements for CI are identified and contribute to the growing body of literature on successful CI initiatives.
Safety profile and risk factors for bleeding in transbronchial cryobiopsy using a two-scope technique for peripheral pulmonary lesions
Authors: Nakai Toshiyuki , Watanabe Tetsuya , Kaimi Yuto , Ogawa Koichi , Matsumoto Yoshiya , Sawa Kenji , Okamoto Atsuko , Sato Kanako , Asai Kazuhisa , Matsumoto Yuji , Ohsawa Masahiko , Kawaguchi Tomoya
Published: January 2022

Background

A balloon occlusion technique is suggested for use in cryobiopsy for interstitial lung diseases because of the bleeding risk. However, it may interfere with selection of the involved bronchus for peripheral pulmonary lesions (PPLs). A two-scope technique, in which two scopes are prepared and hemostasis is started using the second scope immediately after cryobiopsy, has also been reported. This study aimed to evaluate the safety and diagnostic utility of transbronchial cryobiopsy using the two-scope technique for PPLs.

Methods

Data of patients who underwent conventional biopsy followed by cryobiopsy using the two-scope technique for PPLs from November 2019 to March 2021 were collected. The incidence of complications and risk factors for clinically significant bleeding (moderate to life-threatening) were investigated. Diagnostic yields were also compared among conventional biopsy, cryobiopsy, and the combination of them.

Results

A total of 139 patients were analyzed. Moderate bleeding occurred in 25 (18.0%) patients without severe/life-threatening bleeding. Although five cases required transbronchial instillation of thrombin, all bleeding was completely controlled using the two-scope technique. Other complications included two pneumothoraces and one asthmatic attack. On multivariable analysis, only ground-glass features (P < 0.001, odds ratio: 9.30) were associated with clinically significant bleeding. The diagnostic yields of conventional biopsy and cryobiopsy were 76.3% and 81.3%, respectively (P = 0.28). The total diagnostic yield was 89.9%, significantly higher than conventional biopsy alone (P < 0.001).

Conclusions

The two-scope technique provides useful hemostasis for safe cryobiopsy for PPLs, with a careful decision needed for ground-glass lesions.
RNA binding protein HuD promotes autophagy and tumor stress survival by suppressing mTORC1 activity and augmenting ARL6IP1 levels
Authors: Bishayee Kausik , Habib Khadija , Nazim Uddin Md. , Kang Jieun , Szabo Aniko , Huh Sung-Oh , Sadra Ali
Published: January 2022

Background

Neuronal-origin HuD (ELAVL4) is an RNA binding protein overexpressed in neuroblastoma (NB) and certain other cancers. The RNA targets of this RNA binding protein in neuroblastoma cells and their role in promoting cancer survival have been unexplored. In the study of modulators of mTORC1 activity under the conditions of optimal cell growth and starvation, the role of HuD and its two substrates were studied.

Methods

RNA immunoprecipitation/sequencing (RIP-SEQ) coupled with quantitative real-time PCR were used to identify substrates of HuD in NB cells. Validation of the two RNA targets of HuD was via reverse capture of HuD by synthetic RNA oligoes from cell lysates and binding of RNA to recombinant forms of HuD in the cell and outside of the cell. Further analysis was via RNA transcriptome analysis of HuD silencing in the test cells.

Results

In response to stress, HuD was found to dampen mTORC1 activity and allow the cell to upregulate its autophagy levels by suppressing mTORC1 activity. Among mRNA substrates regulated cell-wide by HuD, GRB-10 and ARL6IP1 were found to carry out critical functions for survival of the cells under stress. GRB-10 was involved in blocking mTORC1 activity by disrupting Raptor-mTOR kinase interaction. Reduced mTORC1 activity allowed lifting of autophagy levels in the cells required for increased survival. In addition, ARL6IP1, an apoptotic regulator in the ER membrane, was found to promote cell survival by negative regulation of apoptosis. As a therapeutic target, knockdown of HuD in two xenograft models of NB led to a block in tumor growth, confirming its importance for viability of the tumor cells. Cell-wide RNA messages of these two HuD substrates and HuD and mTORC1 marker of activity significantly correlated in NB patient populations and in mouse xenografts.

Conclusions

HuD is seen as a novel means of promoting stress survival in this cancer type by downregulating mTORC1 activity and negatively regulating apoptosis.
Global prevalence and epidemiology of Strongyloides stercoralis in dogs: a systematic review and meta-analysis
Authors: Eslahi Aida Vafae , Hashemipour Sima , Olfatifar Meysam , Houshmand Elham , Hajialilo Elham , Mahmoudi Razzagh , Badri Milad , Ketzis Jennifer K.
Published: January 2022

Background

Strongyloides stercoralis, a soil-transmitted helminth, occurs in humans, non-human primates, dogs, cats and wild canids. The zoonotic potential between these hosts is not well understood with data available on prevalence primarily focused on humans. To increase knowledge on prevalence, this review and meta-analysis was performed to estimate the global status ofS. stercoralisinfections in dogs.

Methods

Following the PRISMA guidelines, online literature published prior to November 2020 was obtained from multiple databases (Science Direct, Web of Science, PubMed, Scopus and Google Scholar). Prevalence was calculated on a global and country level, by country income and climate, and in stray/animal shelter dogs versus owned dogs. Statistical analyses were conducted using R-software (version 3.6.1).

Results

From 9428 articles, 61 met the inclusion criteria. The estimated pooled global prevalence ofS. stercoralisin dogs was 6% (95% CI 3–9%). Infection was found to be the most prevalent in low-income countries with pooled prevalence of 22% (95% CI 10–36%). The highest pooled prevalence ofS. stercoralisin dogs was related to regions with average temperature of 10–20 °C (6%; 95% CI 3–11%), an annual rainfall of 1001–1500 mm (9%; 95% CI 4–15%) and humidity of 40–75% (8%; 95% CI 4–13%). Prevalence was higher in stray and shelter dogs (11%; 95% CI 1–26%) than in owned dogs (3%; 95% CI 1–7%).

Conclusions

As withS. stercoralisin humans, higher prevalence in dogs is found in subtropical and tropical regions and lower-income countries, locations which also can have high dog populations. While this study presents the first estimated global prevalence ofS. stercoralisin dogs, it is potentially an underestimation with 15 of 61 studies relying on diagnostic methods of lower sensitivity and a paucity of data from most locations. Standardized protocols (e.g. quantity of feces and number of samples for a Baermann) in future studies could improve reliability of results. More prevalence studies and raising veterinary awareness ofS. stercoralisare needed for a One Health approach to protect humans and dogs from the impact of the infection.

Graphical Abstract
Ultrasonographic evaluation of deep vein thrombosis related to the central catheter in hemodialytic patients
Authors: Silveira Vieira Ana Luisa , Muniz Pazeli Júnior José , Silva Matos Andrea , Marques Pereira Andreza , Rezende Pinto Izadora , Esteves de Oliveira Silva Letícia , Siqueira Guilherme Letícia , Archângelo e Silva Sofia Laura
Published: January 2022

Background

Point of care ultrasound (PoCUS) is a useful tool for the early diagnosis of thrombosis related to the central venous catheter for dialysis (TR-CVCd). However, the application of PoCUS is still not common as a bedside imaging examination and TR-CVCd remains often underdiagnosed in the routine practice. The aim of this study was to investigate if a compression technique for the diagnosis of TR-CVCd blindly performed by PoCUS experts and medical students is accurate when compared to a Doppler study.

Methods

Two medical students without prior knowledge in PoCUS received a short theoretical–practical training to evaluate TR-CVCd of the internal jugular vein by means of the ultrasound compression technique. After the training phase, patients with central venous catheter for dialysis (CVCd) were evaluated by the students in a private hemodialysis clinic. The results were compared to those obtained on the same population by doctors with solid experience in PoCUS, using both the compression technique and the color Doppler.

Results

Eighty-one patients were eligible for the study and the prevalence of TR-CVCd diagnosed by Doppler was 28.4%. The compression technique performed by the students and by experts presented, respectively, a sensitivity of 59.2% (CI 51.6–66.8) vs 100% and a specificity of 89.6% (CI 84.9–94.3) vs 94.8% (CI 91.4–98.2).

Conclusion

The compression technique in the hands of PoCUS experts demonstrated high accuracy in the diagnosis of TR-CVCd and should represent a standard in the routine examination of dialytic patients. The training of PoCUS inexperienced students for the diagnosis of TR-CVCd is feasible but did not lead to a sufficient level of sensitivity.
When stem cells meet COVID-19: recent advances, challenges and future perspectives
Authors: Li Shasha , Zhu Hecheng , Zhao Ming , Liu Weidong , Wang Lei , Zhu Bin , Xie Wen , Zhao Cong , Zhou Yao , Ren Caiping , Liu Hui , Jiang Xingjun
Published: January 2022

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory coronavirus 2 is currently spreading throughout the world with a high rate of infection and mortality and poses a huge threat to global public health. COVID-19 primarily manifests as hypoxic respiratory failure and acute respiratory distress syndrome, which can lead to multiple organ failure. Despite advances in the supportive care approaches, there is still a lack of clinically effective therapies, and there is an urgent need to develop novel strategies to fight this disease. Currently, stem cell therapy and stem cell-derived organoid models have received extensive attention as a new treatment and research method for COVID-19. Here, we discuss how stem cells play a role in the battle against COVID-19 and present a systematic review and prospective of the study on stem cell treatment and organoid models of COVID-19, which provides a reference for the effective control of the COVID-19 pandemic worldwide.
Context-dependent transcriptional regulations of YAP/TAZ in stem cell and differentiation
Authors: Luo Juan , Li Peng
Published: January 2022

Hippo pathway is initially identified as a master regulator for cell proliferation and organ size control, and the subsequent researches show this pathway is also involved in development, tissue regeneration and homeostasis, inflammation, immunity and cancer. YAP/TAZ, the downstream effectors of Hippo pathway, usually act as coactivators and are dependent on other transcription factors to mediate their transcriptional outputs. In this review, we will first provide an overview on the core components and regulations of Hippo pathway in mammals, and then systematically summarize the identified transcriptional factors or partners that are responsible for the transcriptional output of YAP/TAZ in stem cell and differentiation. More than that, we will discuss the potential applications and future directions based on these findings.
Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells
Authors: Su Liping , Kong Xiaocen , Loo Szejie , Gao Yu , Liu Bingli , Su Xiaofei , Dalan Rinkoo , Ma Jianhua , Ye Lei
Published: January 2022

Background

Prior studies show that signature phenotypes of diabetic human induced pluripotent stem cells derived endothelial cells (dia-hiPSC-ECs) are disrupted glycine homeostasis, increased senescence, impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. In the current study, we aimed to assess the role of thymosin β-4 (Tb-4) on endothelial function using dia-hiPSC-ECs as disease model of endothelial dysfunction.

Methods and results

Using dia-hiPSC-ECs as models of endothelial dysfunction, we determined the effect of Tb-4 on cell proliferation, senescence, cyto-protection, protein expression of intercellular adhesion molecule-1 (ICAM-1), secretion of endothelin-1 and MMP-1, mitochondrial membrane potential, and cyto-protection in vitro and angiogenic potential for treatment of ischemic limb disease in a mouse model of type 2 diabetes mellitus (T2DM) in vivo. We found that 600 ng/mL Tb4 significantly up-regulated AKT activity and Bcl-XL protein expression, enhanced dia-hiPSC-EC viability and proliferation, limited senescence, reduced endothelin-1 and MMP-1 secretion, and improved reparative potency of dia-hiPSC-ECs for treatment of ischemic limb disease in mice with T2DM. However, Tb4 had no effect on improving mitochondrial membrane potential and glycine homeostasis and reducing intercellular adhesion molecule-1 protein expression in dia-hiPSC-ECs.

Conclusions

Tb-4 improves endothelial dysfunction through enhancing hiPSC-EC viability, reducing senescence and endothelin-1 production, and improves angiogenic potency in diabetes.