bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis D virus infection, innate immune response and antiviral treatments in stem cell‐derived hepatocytes
Authors: Lange Frauke , Garn Jonathan , Anagho Holda A. , Vondran Florian W. R. , von Hahn Thomas , Pietschmann Thomas , Carpentier Arnaud
Published: June 2023

Background

Human pluripotent stem cell (hPSC)‐derived hepatocyte‐like cells (HLCs) are a valuable model to investigate host‐pathogen interactions of hepatitis viruses in a mature and authentic environment. Here, we investigate the susceptibility of HLCs to the hepatitis delta virus (HDV).

Methods

We differentiated hPSC into HLCs, and inoculated them with infectious HDV produced in Huh7NTCP. HDV infection and cellular response was monitored by RTqPCR and immunostaining.

Results

Cells undergoing hepatic differentiation become susceptible to HDV after acquiring expression of the viral receptor Na+‐taurocholate co‐transporting polypeptide (NTCP) during hepatic specification. Inoculation of HLCs with HDV leads to detection of intracellular HDV RNA and accumulation of the HDV antigen in the cells. Upon infection, the HLCs mounted an innate immune response based on induction of the interferons IFNB and L, and upregulation of interferon‐stimulated genes. The intensity of this immune response positively correlated with the level of viral replication and was dependant on both the JAK/STAT and NFκB pathway activation. Importantly, this innate immune response did not inhibit HDV replication. However, pre‐treatment of the HLCs with IFNα2b reduced viral infection, suggesting that ISGs may limit early stages of infection. Myrcludex efficiently abrogated infection and blocked innate immune activation. Lonafarnib treatment of HDV mono infected HLCs on the other hand led to exacerbated viral replication and innate immune response.

Conclusion

The HDV in vitro mono‐infection model represents a new tool to study HDV replication, its host‐pathogen interactions and evaluate new antiviral drugs in cells displaying mature hepatic functions.
Music Education and Neurophysiological Regulation in Early Childhood: Should Teachers Guide or Get Out of the Way?
Authors: Brown Eleanor D. , Holochwost Steven J. , Palmer Wolf Dennie , Allen Alyssa A. , Garnett Mallory L. , Velazquez‐Martin Blanca , Varnell Suzanne , Malatesta Jessa L.
Published: June 2023

Access to high‐quality early music education programs may mitigate the effects of poverty on the hypothalamic–pituitary–adrenal (HPA) axis, but fundamental questions remain about the role of early educators in conveying these benefits. In the current study, we measured the basal or resting cortisol levels of 76 children (Mage = 4.17 years; 42% female) over the course of the school day while they attended a Head Start preschool that included early music education classes. The results of a series of hierarchical linear models (HLMs) indicated that child‐directed music and movement activities during these classes were associated with lower levels of cortisol (relative to teacher‐directed activities; B = −0.019, p = .013), as were higher quality teacher–child interactions (B = −0.018, p = .013); both associations were moderated by child age. We discuss the implications of these results for future educational neuroscience research that seeks to inform early education programs for young children placed at risk by poverty.
A vacuolar transporter plays important roles in zinc and cadmium accumulation in rice grain
Authors: Ning Min , Liu Shi Jia , Deng Fenglin , Huang Liyu , Li Hu , Che Jing , Yamaji Naoki , Hu Fengyi , Lei Gui Jie
Published: June 2023

Rice grain is a poor dietary source of zinc (Zn) but the primary source of cadmium (Cd) for humans; however, the molecular mechanisms for their accumulation in rice grain remain incompletely understood.

This study functionally characterized a tonoplast‐localized transporter, OsMTP1. OsMTP1 was preferentially expressed in the roots, aleurone layer, and embryo of seeds. OsMTP1 knockout decreased Zn concentration in the root cell sap, roots, aleurone layer and embryo, and subsequently increased Zn concentration in shoots and polished rice (endosperm) without yield penalty. OsMTP1 haplotype analysis revealed elite alleles associated with increased Zn level in polished rice, mostly because of the decreased OsMTP1 transcripts.

OsMTP1 expression in yeast enhanced Zn tolerance but did not affect that of Cd. While OsMTP1 knockout resulted in decreased uptake, translocation and accumulation of Cd in plant and rice grain, which could be attributed to the indirect effects of altered Zn accumulation.

Our results suggest that rice OsMTP1 primarily functions as a tonoplast‐localized transporter for sequestrating Zn into vacuole. OsMTP1 knockout elevated Zn concentration but prevented Cd deposition in polished rice without yield penalty. Thus, OsMTP1 is a candidate gene for enhancing Zn level and reducing Cd level in rice grains.
Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa
Authors: Scollan Margaret E. , Levin Laura E. , Lucky Anne W. , Hook Kristen P. , Peoples Kathleen , Bruckner Anna L. , Feinstein James A. , Pope Elena , McCuaig Catherine C. , Powell Julie , Eichenfield Lawrence F. , Levy Moise L. , Diaz Lucia , Glick Sharon A. , Paller Amy S. , Browning John C. , Morel Kimberly D.
Published: June 2023

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.
You'll never walk alone: Loneliness, religion, and politico‐economic transformation
Authors: Tubadji Annie
Published: June 2023

The rise of subversive religious beliefs has been recently documented as related to the politico‐economic radicalization of places that feel left behind. When is the traditional local religious institution so socio‐economically inefficient in providing hope for “not walking alone” to become substituted by subversive religious beliefs on the market for hope? This article suggests a detailed methodology, linking micro and macro levels, that starts from the quantification of the individual gain from religion as a source for well‐being by providing the feeling of “not walking alone.” This micro gain is next used: (i) to evaluate a religious institution in terms of the social welfare that it generates, and (ii) to monitor this religious institution for losing its market to subversive religious beliefs, related to radical politico‐economic transformations. To illustrate this methodology, I analyze the socio‐economic efficiency of the Church of England as a predictive tool for the Brexit vote.

Related Articles

Gainous, Jason, and Bill Radunovich. 2008. “Religion and Core Values: A Reformulation of the Funnel of Causality.” Politics & Policy 33(1): 154–80. https://doi.org/10.1111/j.1747‐1346.2005.tb00213.x.

Giugni, Marco, and Maria T. Grasso. 2016. “How Civil Society Actors Responded to the Economic Crisis: The Interaction of Material Deprivation and Perceptions of Political Opportunity Structures.” Politics & Policy 44(3): 447–72. http://onlinelibrary.wiley.com/doi/10.1111/polp.12157/abstract.

Temple, Luke, Maria T. Grasso, Barbara Buraczynska, Sotirios Karampampas, and Patrick English. 2016. “Neoliberal Narrative in Times of Economic Crisis: A Political Claims Analysis of the U.K. Press, 2007–14.” Politics & Policy 44(3): 553–76. https://doi.org/10.1111/polp.12161.
Misrecognition and Well‐being in Culturally White Northern New England☆
Authors: Walton Emily
Published: June 2023

Rural America is undergoing a demographic transition, as the white population decline is matched by a growing movement of racialized minorities into small towns. In the current study, I examine processes of belonging among middle‐class racialized minorities living in predominantly white and rural Northern New England. Through an analysis of in‐depth interviews with n = 58 individuals of color, I show how “misrecognition,” or the processes through which community members fail to affirm the humanity of others, can lead to diminished well‐being. I elaborate a novel conceptual model linking a stigmatizing cultural context (chilly social climate; ignorance and racism) with misrecognition (social distancing; having to prove oneself) and well‐being (unease; weariness). The study's main contribution is the generation of theory regarding symbolic boundary processes that undergird racialized minority residents' negotiation of the right to belong in a rapidly changing rural America.
Endoplasmic reticulum stress in T cell‐mediated diseases
Authors: Chen Shaodan , Wang Qiulei , Wang Hui , Xia Sheng
Published: June 2023

T cells synthesize a large number of proteins during their development, activation, and differentiation. The build‐up of misfolded and unfolded proteins in the endoplasmic reticulum, however, causes endoplasmic reticulum (ER) stress. Thus, T cells can maintain ER homeostasis via endoplasmic reticulum‐associated degradation, unfolded protein response, and autophagy. In T cell‐mediated diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, type 1 diabetes and vitiligo, ER stress caused by changes in the internal microenvironment can cause disease progression by affecting T cell homeostasis. This review discusses ER stress in T cell formation, activation, differentiation, and T cell‐mediated illnesses, and may offer new perspectives on the involvement of T cells in autoimmune disorders and cancer.
Eurowhiteness in Science: Privilege Escalation and Intentional Sludge
Authors: Ziegler Tamas Dezso , Unger Anna
Published: June 2023

This article connects Böröcz's (2021) Eurowhiteness concept with a critical dissection of Western European academia's stance on ‘outsiders’, including Eastern Europeans and non‐Europeans. It explains how an exclusivist Western science is created, where, behind the seemingly open and diverse environment, we find monolithic privileges helping participants inside and blocking participation from the outside. The article claims that in the present Western European academic setting, there are two tendencies that seriously harm diversity and the free flow of ideas. First, Western scholarly communities boost their potential through structural advantage. In this environment, scientific excellence becomes a form of privilege. However, it does not necessarily mean proper excellence, but more an exclusionary system of greater financial assets, personal connections, and shared knowhow among the participants, as well as access to gatekeepers. Second, the article uses Cass R. Sunstein's theory on sludge in public management to explain how the European Union boosts this phenomenon with its inequitable ways of allocating research funding: this is how privilege escalation is created through a pseudo‐meritocratic system. Finally, the article explains how Eastern European scholars adhered to these requirements with a self‐colonizing attitude, which limits their long‐term capability to carry out original science.
Evaluation of adapted dermocosmetic regimens for perimenopausal and menopausal women using an artificial intelligence‐based algorithm and quality of life questionnaires: An open observational study
Authors: Flament Frederic , Jiang Ruowei , Delaunay Caroline , Kerob Delphine , Leclerc‐Mercier Stéphanie , Kosmadaki Marita , Roó Elia , Haag Thierry , Passeron Thierry , Zouboulis Christos C.
Published: June 2023

Background

The decline in estrogen levels from several years before (perimenopause) and during menopause has various negative effects, including skin specific issues, which often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life (QoL). The objective of this study was to evaluate the effectiveness of anti‐aging dermocosmetic products designed for women during the perimenopause and menopause.

Materials and methods

An open study of 101 perimenopausal women (no menstruation for 4–12 months or irregular menstruation for <5 years) and 101 menopausal women (no menstruation for >12 months), not taking hormone replacement therapy, was conducted. Adapted dermocosmetic regimens, specific to each group (day cream, night cream and serum), were applied for 56 days. Assessments included automatic artificial intelligence diagnostics of eight clinical facial signs, hydration and transepidermal water loss (TEWL), and a menopause skin QoL questionnaire.

Results

Mean age was 50 ± 3.9 years (range 41–57) and 59 ± 3.8 years (range 50–66) for the perimenopause and menopause groups, respectively. Significant improvements in wrinkles and vascular signs, increases in hydration, decreases in TEWL, and a positive impact on QoL were observed after 56 days of application of the respective dermocosmetic regimens for both the perimenopause and menopause groups.

Conclusion

The anti‐aging skin care products designed specifically for perimenopausal and menopausal women increased skin hydration and improved wrinkles with a positive impact on QoL.
Hepatitis E virus seropositivity in an ethnically diverse community blood donor population
Authors: Mah Jordan K. , Keck MeiLe , Chu Daniel Y. , Sooryanarain Harini , Sahoo Malaya K. , Lau Patrick , Huang ChunHong , Weber Jenna , Belanger Geoffrey A. , Keck Zhenyong , Shan Hua , Meng Xiang‐Jin , Foung Steven K. H. , Pinsky Benjamin A. , Pham Tho D.
Published: June 2023

Background and Objectives

Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion‐associated HEV infections.

Materials and Methods

We screened 10,002 randomly selected donations over an 8‐month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT‐qPCR). Donor demographic information, including gender, age, self‐identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity.

Results

A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT‐qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties.

Conclusion

Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.
Cluster and Factor Analyses as Contributions to the Groundwater Quality Monitoring of the Marizal/São Sebastião Aquifer System, Alagoinhas (Bahia, Brazil)
Authors: Da Costa Maíra Sampaio , Gomes Maria da Conceição Rabelo , De Morais Nascimento Sérgio Augusto
Published: June 2023

The Marizal/São Sebastião aquifer system is the main water supply of the municipality of Alagoinhas in the state of Bahia. However, anthropic interventions contribute to soil and groundwater pollution, increasing the need for related research. Multivariate statistical analysis is a widely used tool, helping in the investigation of groundwater quality while being capable of simultaneously evaluating diverse variables of a sample set. In this study, factor analysis and multivariate cluster analysis methodologies were applied. Ten of the most influential variables for groundwater quality were selected and then grouped into two factors. The first factor included electrical conductivity, salinity, calcium, chloride, sulfate, manganese, and iron, which are indicators of water salinity. The second factor encompassed pH,  bicarbonate, and phosphate, indicating anthropic interventions and alkalinity in the environment. The multivariate cluster analysis was applied to the parameters of both factors, resulting in dendrograms with four clusters. The present study showed that the multivariate statistical analysis is an efficient tool for monitoring and can contribute to the management of groundwater quality.
Flight Path and Scheduling Effects on Perceived Jet Lag, Fatigue, and Sleep in Footballers Traveling to and From National Teams
Authors: Clements Ewan , Ehrmann Fabian , Clark Andrew , Jones Mark , McCall Alan , Duffield Rob
Published: June 2023

Purpose: This study examined posttravel perceptual responses of national-team footballers (soccer) following different flight paths, arrival/departure times, and trip contexts. Methods: Details of 396 flights from national-team players (N = 68) were obtained and verified via an online flight database. Each player provided ratings of perceptual fatigue, sleep, soreness, stress, and jet lag for 2 days before and after each trip. The flight path (continents of departure and arrival), travel context (into vs out of national team), and arrival and departure times were obtained for each trip. Linear mixed models compared the pretravel with posttravel change in perceptual responses based on flight path, context, and schedule. Results: Perceived jet-lag ratings were more responsive to travel variables (R2 = .48) than other perceptual ratings (R2 < .26). Travel from Asia to Europe (P < .05) and Europe to Australia (P < .001) had significantly higher jet-lag ratings than all other paths. Fatigue scores were worst following Asia to Europe (P < .05) and Europe to Australia (P < .05) travel, while sleep scores were worst following Europe to Australia travel (P < .01). Perceptual responses were poorer following travel from national team to club compared with all other travel contexts (P < .05). Arrival during the daytime (11 AM to 5 PM) resulted in better perceptual responses than early-morning or late-night arrivals (P < .05). Conclusions: Perceived jet-lag ratings are more responsive to travel demands than perceptual wellness scales in national-team football athletes. Poorer perceptual responses may be expected when travel is longer in nature, ends later in the day, or involves travel out of the national team back to club.
The transcription factor XBP1 in dendritic cells promotes the T
H
2 cell response in airway allergy
Authors: Yang Gui , Zeng Xian-Hai , Geng Xiao-Rui , Liu Jiang-Qi , Mo Li-Hua , Luo Xiang-Qian , Liu Hua-Zhen , Zhang Yuan-Yi , Yang Li-Teng , Huang Qin-Miao , Xiao Xiao-Jun , Liu Jie , Xu Ling-Zhi , Liu Da-Bo , Liu Xiao-Yu , Liu Zhi-Qiang , Yang Ping-Chang
Published: June 2023

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (T
H
2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box–binding protein-1 (XBP1) in the induction of the T
H
2 cell response through its role in generating TIM4
+
DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2–XBP1–TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant T
H
2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for T
H
2 cell responses by inducing the development of TIM4
+
DCs, which depends on the IL-2–XBP1–SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of T
H
2 cell–dependent inflammation or allergic diseases.
Fitness-Dependent, Mild Mutagenic Activity of Sofosbuvir for Hepatitis C Virus
Authors: Martínez-González Brenda , Gallego Isabel , Gregori Josep , Soria María Eugenia , Somovilla Pilar , de Ávila Ana Isabel , García-Crespo Carlos , Durán-Pastor Antoni , Briones Carlos , Gómez Jordi , Quer Josep , Domingo Esteban , Perales Celia
Published: June 2023

The concept of a mild mutagen was coined to describe a minor mutagenic activity exhibited by some nucleoside analogues that potentiated their efficacy as antiretroviral agents. In the present study, we report the mild mutagen activity of sofosbuvir (SOF) for hepatitis C virus (HCV).
Supplementation with Amino Acid Sources Facilitates Fermentative Growth of Shewanella oneidensis MR-1 in Defined Media
Authors: Ikeda Sota , Tomita Keisuke , Nakagawa Gen , Kouzuma Atsushi , Watanabe Kazuya
Published: June 2023

It is an enigma why
S. oneidensis
MR-1 is incapable of fermentative growth despite having complete sets of genes for reconstructing fermentative pathways. Understanding the molecular mechanisms behind this defect will facilitate the development of novel fermentation technologies for the production of value-added chemicals from biomass feedstocks, such as electro-fermentation.
SHIP1 modulates antimalarial immunity by bridging the crosstalk between type I IFN signaling and autophagy
Authors: Li Hongyu , Yang Shuai , Zeng Ke , Guo Jiayin , Wu Jian , Jiang Huaji , Xie Yingchao , Hu Zhiqiang , Lu Jiansen , Yang Jianwu , Su Xin-zhuan , Cui Jun , Yu Xiao
Published: June 2023

Stringent control of the type I interferon (IFN-I) signaling is critical for host immune defense against infectious diseases, yet the molecular mechanisms that regulate this pathway remain elusive. Here, we show that Src homology 2 containing inositol phosphatase 1 (SHIP1) suppresses IFN-I signaling by promoting IRF3 degradation during malaria infection. Genetic ablation of
Ship1
in mice leads to high levels of IFN-I and confers resistance to
Plasmodium yoelii nigeriensis
(
P.y.
) N67 infection. Mechanistically, SHIP1 promotes the selective autophagic degradation of IRF3 by enhancing K63-linked ubiquitination of IRF3 at lysine 313, which serves as a recognition signal for NDP52-mediated selective autophagic degradation. In addition, SHIP1 is downregulated by IFN-I-induced miR-155-5p upon
P.y
. N67 infection and severs as a feedback loop of the signaling crosstalk. This study reveals a regulatory mechanism between IFN-I signaling and autophagy, and verifies SHIP1 can be a potential target for therapeutic intervention against malaria and other infectious diseases.

IMPORTANCE

Malaria remains a serious disease affecting millions of people worldwide. Malaria parasite infection triggers tightly controlled type I interferon (IFN-I) signaling that plays a critical role in host innate immunity; however, the molecular mechanisms underlying the immune responses are still elusive. Here, we discover a host gene [Src homology 2-containing inositol phosphatase 1 (SHIP1)] that can regulate IFN-I signaling by modulating NDP52-mediated selective autophagic degradation of IRF3 and significantly affect parasitemia and resistance of
Plasmodium
-infected mice. This study identifies SHIP1 as a potential target for immunotherapies in malaria and highlights the crosstalk between IFN-I signaling and autophagy in preventing related infectious diseases. SHIP1 functions as a negative regulator during malaria infection by targeting IRF3 for autophagic degradation.
Biophysical and proteomic analyses of
Pseudomonas syringae
pv.
tomato
DC3000 extracellular vesicles suggest adaptive functions during plant infection
Authors: Janda Martin , Rybak Katarzyna , Krassini Laura , Meng Chen , Feitosa-Junior Oséias , Stigliano Egidio , Szulc Beata , Sklenar Jan , Menke Frank L.H. , Malone Jacob G. , Brachmann Andreas , Klingl Andreas , Ludwig Christina , Robatzek Silke
Published: June 2023

Vesiculation is a process employed by Gram-negative bacteria to release extracellular vesicles (EVs) into the environment. EVs from pathogenic bacteria play functions in host immune modulation, elimination of host defenses, and acquisition of nutrients from the host. Here, we observed EV production of the bacterial speck disease causal agent,
Pseudomonas syringae
pv.
tomato
(
Pto
) DC3000, as outer membrane vesicle release. Mass spectrometry identified 369 proteins enriched in
Pto
DC3000 EVs. The EV samples contained known immunomodulatory proteins and could induce plant immune responses mediated by bacterial flagellin. Having identified two biomarkers for EV detection, we provide evidence for
Pto
DC3000 releasing EVs during plant infection. Bioinformatic analysis of the EV-enriched proteins suggests a role for EVs in antibiotic defense and iron acquisition. Thus, our data provide insights into the strategies this pathogen may use to develop in a plant environment.

IMPORTANCE

The release of extracellular vesicles (EVs) into the environment is ubiquitous among bacteria. Vesiculation has been recognized as an important mechanism of bacterial pathogenesis and human disease but is poorly understood in phytopathogenic bacteria. Our research addresses the role of bacterial EVs in plant infection. In this work, we show that the causal agent of bacterial speck disease,
Pseudomonas syringae
pv.
tomato
, produces EVs during plant infection. Our data suggest that EVs may help the bacteria to adapt to environments, e.g., when iron could be limiting such as the plant apoplast, laying the foundation for studying the factors that phytopathogenic bacteria use to thrive in the plant environment.
Akkermansia muciniphila
and
Lactobacillus plantarum
ameliorate systemic lupus erythematosus by possibly regulating immune response and remodeling gut microbiota
Authors: Guo Mengchen , Lu Mei , Chen Kun , Xu Rui , Xia Yumin , Liu Xingyin , Liu Zhi , Liu Qisha
Published: June 2023

Systemic lupus erythematosus (SLE), characterized by persistent inflammation, is a complex autoimmune disorder that affects all organs, challenging clinical treatment. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Modulating the gut microbiome is proposed as a promising approach for fine-running parts of the immune system, relieving systematic inflammation in multiple diseases. This study demonstrated that the administration of
Akkermansia muciniphila
and
Lactobacillus plantarum
contributed to an anti-inflammatory environment by decreasing IL-6 and IL-17 and increasing IL-10 levels in the circulation. The treatment of
A. muciniphila
and
L. plantarum
restored the intestinal barrier integrity to a different extent. In addition, both strains reduced the deposit of IgG in the kidney and improved renal function significantly. Further studies revealed distinct remodeling roles of
A. muciniphila
and
L. plantarum
administration on the gut microbiome. This work demonstrated essential mechanisms of how
A. muciniphila
and
L. plantarum
remodel gut microbiota and regulate the immune responses in the SLE mice model.

IMPORTANCE

Several pieces of research have demonstrated that certain probiotic strains contribute to regulating excessive inflammation and restoring tolerances in the SLE animal model. More animal trials combined with clinical studies are urgently needed to further elucidate the mechanisms for the effect of specific probiotic bacteria in preventing SLE symptoms and developing novel therapeutic targets. In this study, we explored the role of
A. muciniphila
and
L
.
plantarum
in ameliorating the SLE disease activity. Both
A. muciniphila
and
L. plantarum
treatment relieved the systemic inflammation and improved renal function in the SLE mouse model. We demonstrated that
A. muciniphila
and
L. plantarum
contributed to an anti-inflammatory environment by regulating cytokine levels in the circulation, restoring the intestinal barrier integrity, and remodeling the gut microbiome, however, to a different extent.
Quorum Sensing-Dependent Invasion of Ralstonia solanacearum into Fusarium oxysporum Chlamydospores
Authors: Tsumori Chiaki , Matsuo Shoma , Murai Yuta , Kai Kenji
Published: June 2023

Ralstonia solanacearum
species complex (RSSC) strains infect both plants and fungi. The
phc
quorum-sensing (QS) system of RSSC is important for parasitism on plants, because it allows them to invade and proliferate within the hosts by causing appropriate activation of the system at each infection step.
High Rate of Inappropriate Antibiotics in Patients with Hematologic Malignancies and Pseudomonas aeruginosa Bacteremia following International Guideline Recommendations
Authors: Chumbita Mariana , Puerta-Alcalde Pedro , Yáñez Lucrecia , Angeles Cuesta Maria , Chinea Anabelle , Español-Morales Ignacio , Fernandez-Abellán Pascual , Gudiol Carlota , González-Sierra Pedro , Rojas Rafael , Sánchez-Pina José María , Vadillo Irene Sánchez , Sánchez Miguel , Varela Rosario , Vázquez Lourdes , Guerreiro Manuel , Monzo Patricia , Lopera Carlos , Aiello Tommaso Francesco , Peyrony Oliver , Soriano Alex , Garcia-Vidal Carolina
Published: June 2023

Bloodstream infection (BSI) caused by
P. aeruginosa
is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia.
Rapid Establishment of a Biospecimen Resource To Study the Global Impact of COVID-19 Vaccines
Authors: Berliner K. E. , Ezzelle T. , Klenk T. , Dunn G. , Sischo J. , Campbell D. , McKee K. T.
Published: June 2023

The ability to rapidly create a biobank of high-quality specimens in response to emergent infectious diseases is critical to allow for the development of prevention and treatment, as well as to effectively monitor the spread of the disease. In this paper, we report on a novel approach to getting global clinical sites up and running within a short time frame and to monitor the quality of specimens collected to ensure their value in future research efforts.
Insights into the Differential Composition of Stem-Loop Structures of Nanoviruses and Their Impacts
Authors: Lal Aamir , Shamim Amen , Kil Eui-Joon , Vo Thuy T. B. , Qureshi Muhammad Amir , Bupi Nattanong , Tabassum Marjia , Lee Sukchan
Published: June 2023

Nanoviruses comprise multiple segments, each with a single open reading frame to perform a specific function and an intergenic region with a conserved stem-loop region. The genome expression of a nanovirus has been an intriguing area but is still poorly understood.
Can mediation avoid litigation in conflicts about medical treatment for children? An analysis of previous litigation in England and Wales
Authors: Neefjes Veronica
Published: June 2023

Objective

To investigate the reasons why parents disagree with their clinicians in cases reaching the court and to estimate the number of cases in which mediation might have avoided litigation.

Design

Analysis of 83 published cases regarding medical treatment decisions for children initiated either by an NHS Trust or Local Authority between 1990 and 1 July 2022.

Results

The analysis found that the main areas of contention are different value judgements, different interpretations of observable events such as the health of the child, their quality of life or burden of treatment and relational issues (ie, loss of trust). More than half of the cases are estimated not to have been preventable by mediation because either no conflict existed (n=13) or the parental decision was based on strongly held, mostly faith-based, views unlikely to be open for discussion (n=31).

Conclusion

The potential of mediation to avoid future litigation may be more limited than hoped for.
Mask ventilation using volume-targeted neonatal ventilator for neonatal resuscitation: a randomised cross-over simulation study
Authors: Law Brenda Hiu Yan , Madani Kia Tina , Trinh Faith , Schmölzer Georg M
Published: June 2023

Objective

To use simulations to compare a novel mask ventilation method using a neonatal ventilator, with mask ventilation using a T-piece resuscitator, to study human factors prior to clinical testing.

Design

Prospective randomised cross-over simulation study. Participants were briefly trained to use a neonatal ventilator for mask ventilation. Each participant was fitted with eye-tracking glasses to record visual attention (VA) and performed two simulated preterm neonatal resuscitations in a randomised sequence.

Setting

In situ in a neonatal resuscitation room within a Level 3 neonatal intensive care unit.

Participants

Healthcare professionals (HCPs) trained in neonatal resuscitation with experience as team leaders.

Interventions

Semiautomated, ventilator-based, volume-targeted positive pressure mask ventilation (VTV-PPV) versus manual mask ventilation via T-piece device (T-piece PPV).

Main outcome measures

Subjective workload (Surgical Task Load Index, SURG-TLX), VA, quantitative and qualitative postsimulation survey responses.

Results

Thirty HCPs participated. HCPs reported higher total SURG-TLX scores (43.5/120 vs 33.8/120) and higher scores in mental demand (8.2/20 vs 5.6/20), physical demand (6.6/20 vs 5.1/20), task complexity (8.2/20 vs 6/20) and situational stress (8.3/20 vs 5.9/20) for VTV-PPV. Temporal demand and distraction scores were similar. While participants took longer to complete VTV-PPV simulations, participants dedicated similar a %VA to the mannikin and T-piece gauges or ventilator screen. More participants increased the rate of ventilation during VTV-PPV; other corrective steps were similar. Overall, participants rated VTV-PPV positively. Participants identified potential challenges with physical ergonomics, cognition and teamwork.

Conclusion

Using a neonatal ventilator to perform volume-targeted PPV is feasible, but human factors need to be considered.
Epidemiology of Robin sequence in the UK and Ireland: an active surveillance study
Authors: Wright Marie FA , Knowles Rachel L , Cortina-Borja Mario , Javadpour Sheila , Mehendale Felicity V , Urquhart Donald S
Published: June 2023

Background

Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000–14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth.

Objectives

To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment.

Methods

Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points.

Results

173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone.

Conclusions

Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence.
Yoga-based interventions may reduce anxiety symptoms in anxiety disorders and depression symptoms in depressive disorders: a systematic review with meta-analysis and meta-regression
Authors: Martínez-Calderon Javier , Casuso-Holgado María Jesús , Muñoz-Fernandez Maria Jesus , Garcia-Muñoz Cristina , Heredia-Rizo Alberto Marcos
Published: June 2023

Objective

To summarise the effect of mind–body exercises on anxiety and depression symptoms in adults with anxiety or depressive disorders.

Design

Systematic review with meta-analysis and meta-regression.

Data sources

Five electronic databases were searched from inception to July 2022. Manual searches were conducted to explore clinical trial protocols, secondary analyses of clinical trials and related systematic reviews.

Eligibility criteria

Randomised clinical trials evaluating qigong, tai chi or yoga styles with anxiety or depression symptoms as the outcomes were included. No intervention, waitlist or active controls were considered as control groups. The risk of bias and the certainty of the evidence were assessed. Meta-analyses, meta-regressions and sensitivity analyses were performed.

Results

23 studies, comprising 22 different samples (n=1420), were included. Overall, meta-analyses showed yoga interventions were superior to controls in reducing anxiety symptoms in anxiety disorders. Furthermore, yoga-based interventions decreased depression symptoms in depressive disorders after conducting sensitivity analyses. No differences between groups were found in the rest of the comparisons. However, the certainty of the evidence was judged as very low for all outcomes due to concerns of high risk of bias, indirectness of the evidence, inconsistency and imprecision of the results. In addition, there was marked heterogeneity among yoga-based interventions and self-reported tools used to evaluate the outcomes of interest.

Conclusion

Although yoga-based interventions may help to improve mental health in adults diagnosed with anxiety or depressive disorders, methodological improvements are needed to advance the quality of clinical trials in this field.

PROSPERO registration number

CRD42022347673.
Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): effects on outcomes at day 365 in a randomised, sham-controlled, blinded, phase III, superiority ambulance-based trial
Authors: Woodhouse Lisa J , Appleton Jason P , Ankolekar Sandeep , England Timothy J , Mair Grant , Muir Keith , Price Christopher I , Pocock Stuart , Randall Marc , Robinson Thompson G , Roffe Christine , Sandset Else C , Saver Jeffrey L , Siriwardena Aloysius Niroshan , Sprigg Nikola , Wardlaw Joanna M , Bath Philip M
Published: June 2023

Background

The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2) reported no overall treatment difference between glyceryl trinitrate (GTN) and sham at day 90. Here we assess participants’ outcomes 1 year after randomisation.

Methods

RIGHT-2 was an ambulance-based prospective randomised controlled trial where patients with presumed stroke and systolic blood pressure (BP) of >120 mm Hg received either GTN (5 mg/day) or sham patch. Centralised blinded telephone follow-up was performed at days 90 (primary endpoint) and 365 (secondary endpoint). The lead outcome was dependency assessed with the modified Rankin Scale (mRS).

Results

1149 patients were recruited to RIGHT-2 between October 2015 and May 2018, and 1097 (95.5%) had outcome data recorded at day 365. At baseline, the patients were; female (48%), had a mean age of 73 (15) years, BP of 162 (25)/92 (18) mm Hg, onset to randomisation of 70 (45–115) min, diagnosis of ischaemic stroke (52%), intracerebral haemorrhage (ICH) (13%), transient ischaemic attack (TIA) (9%) and mimics (26%). There was no effect of GTN on mRS score at day 365 in participants with confirmed stroke/TIA (adjusted common odds ratio (acOR) 1.10, 95% CI 0.86 to 1.42) or in all patients. In patients randomised to GTN, mRS at day 365 tended to be worse in those with ICH (acOR 1.65, 95% CI 0.84 to 3.25) and better in those with a mimic diagnosis (acOR 0.53, 95% CI 0.33 to 0.84).

Conclusion

At 1 year post randomisation, dependency did not differ between GTN and sham treatment in either the target population or overall. In prespecified subgroup analyses, GTN was associated with reduced dependency in participants with a final diagnosis of mimic and a non-significant worse outcome in participants with ICH.

Trial registration number

ISRCTN26986053.
Association between chronic obstructive pulmonary disease and periodontal disease: a systematic review and meta-analysis
Authors: Yang Mei , Peng Ran , Li Xiaoou , Peng Junjie , Liu Lin , Chen Lei
Published: June 2023

Objectives

Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events.

Design

A systematic review and meta-analysis.

Data sources

PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023.

Eligibility criteria for studies

We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking.

Data extraction and synthesis

Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method.

Results

22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies.

Conclusions

This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.
Changes on clinical and participatory outcomes in people with severe-to-profound hearing loss after cochlear implantation: protocol of a multicentre prospective observational cohort study – Societal Merit of Intervention on Hearing Loss Evaluation (SMILE)
Authors: Nijmeijer Hugo G B , Huinck Wendy J , Kramer Sophia E , Donders A Rogier T , van der Wilt Gert Jan , Mylanus Emmanuel A M
Published: June 2023

Introduction

Cochlear implantation (CI) is a (cost-)effective intervention for people with severe or profound hearing loss. Since its introduction experience increased and the technology evolved, leading to better results and relaxation of CI eligibility criteria. Meanwhile, with national healthcare costs increasing there is a need for evidence of healthcare technology’s value. This protocol describes a study to investigate clinical and participatory outcomes after CI for the currently (expanded) eligible hearing impaired population. The study adds to the current evidence base through its multicentre design, long-term follow-up and use of participatory outcomes alongside standard clinical outcomes.

Methods

This multicentre prospective observational cohort study will include at least 156 adult patients with severe-to-profound hearing loss, approximately evenly divided into two groups (1, ages 18–65 years and 2, age >65 years). The measurements consist of audiometry, cognition tests, listening effort tests and multiple generic and disease specific questionnaires. Questionnaires will be administered twice before CI, soon after inclusion at CI referral and shortly before CI surgery, with an annual follow-up of 3 years after CI. The Impact on Participation and Autonomy questionnaire will be used to assess participation. Generalised models (linear, logistic, Poisson) will be used. Mixed effects models will be used to investigate changes over time while exploring differences in subgroups and the influence of covariates.

Ethics and dissemination

The study has received ethical approval from the Medical Ethical Committee of all participating centres. The results could provide valuable insights into changes in participatory outcomes of people with severe-to-profound hearing loss after CI. Results will be disseminated through peer-reviewed journals, scientific conferences and professional and patient organisation meetings.

Trial registration number

NCT05525221.
Stakeholder-led understanding of the implementation of digital technologies within heart disease diagnosis: a qualitative study protocol
Authors: Abdullayev Kamilla , Chico Timothy JA , Manktelow Matthew , Buckley Oliver , Condell Joan , Van Arkel Richard J , Diaz Vanessa , Matcham Faith
Published: June 2023

Introduction

Cardiovascular diseases are highly prevalent among the UK population, and the quality of care is being reduced due to accessibility and resource issues. Increased implementation of digital technologies into the cardiovascular care pathway has enormous potential to lighten the load on the National Health Service (NHS), however, it is not possible to adopt this shift without embedding the perspectives of service users and clinicians.

Methods and analysis

A series of qualitative studies will be carried out with the aim of developing a stakeholder-led perspective on the implementation of digital technologies to improve holistic diagnosis of heart disease. This will be a decentralised study with all data collection being carried out online with a nationwide cohort. Four focus groups, each with 5–6 participants, will be carried out with people with lived experience of heart disease, and 10 one-to-one interviews will be carried out with clinicians with experience of diagnosing heart diseases. The data will be analysed using an inductive thematic analysis approach.

Ethics and dissemination

This study received ethical approval from the Sciences and Technology Cross Research Council at the University of Sussex (reference ER/FM409/1). Participants will be required to provide informed consent via a Qualtrics survey before being accepted into the online interview or focus group. The findings will be disseminated through conference presentations, peer-reviewed publications and to the study participants.