bluuebunny/crossref_metadata_2025 huggingface dataset:
Small molecule glucagon release inhibitors with activity in human islets
Authors: Kalwat Michael A. , Rodrigues-dos-Santos Karina , Binns Derk D. , Wei Shuguang , Zhou Anwu , Evans Matthew R. , Posner Bruce A. , Roth Michael G. , Cobb Melanie H.
Published: April 2023

Purpose

Type 1 diabetes (T1D) accounts for an estimated 5% of all diabetes in the United States, afflicting over 1.25 million individuals. Maintaining long-term blood glucose control is the major goal for individuals with T1D. In T1D, insulin-secreting pancreatic islet β-cells are destroyed by the immune system, but glucagon-secreting islet α-cells survive. These remaining α-cells no longer respond properly to fluctuating blood glucose concentrations. Dysregulated α-cell function contributes to hyper- and hypoglycemia which can lead to macrovascular and microvascular complications. To this end, we sought to discover small molecules that suppress α-cell function for their potential as preclinical candidate compounds. Prior high-throughput screening identified a set of glucagon-suppressing compounds using a rodent α-cell line model, but these compounds were not validated in human systems.

Results

Here, we dissociated and replated primary human islet cells and exposed them to 24 h treatment with this set of candidate glucagon-suppressing compounds. Glucagon accumulation in the medium was measured and we determined that compounds SW049164 and SW088799 exhibited significant activity. Candidate compounds were also counter-screened in our InsGLuc-MIN6 β-cell insulin secretion reporter assay. SW049164 and SW088799 had minimal impact on insulin release after a 24 h exposure. To further validate these hits, we treated intact human islets with a selection of the top candidates for 24 h. SW049164 and SW088799 significantly inhibited glucagon release into the medium without significantly altering whole islet glucagon or insulin content. In concentration-response curves SW088799 exhibited significant inhibition of glucagon release with an IC50 of 1.26 µM.

Conclusion

Given the set of tested candidates were all top hits from the primary screen in rodent α-cells, this suggests some conservation of mechanism of action between human and rodents, at least for SW088799. Future structure-activity relationship studies of SW088799 may aid in elucidating its protein target(s) or enable its use as a tool compound to suppress α-cell activity in vitro.
Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?
Authors: Fanciulli Giuseppe , Modica Roberta , La Salvia Anna , Grossrubatscher Erika Maria , Florio Tullio , Ferraù Francesco , Veresani Alessandro , Russo Flaminia , Colao Annamaria , Faggiano Antongiulio
Published: April 2023

Introduction

Medullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.

Aim of the study

This review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.

Materials and methods

We performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.

Results

Our search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.

Conclusion

We found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials’ implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients’ outcome and survival.
From mitochondria to sarcopenia: role of 17β-estradiol and testosterone
Authors: Tian Xu , Lou Shujie , Shi Rengfei
Published: April 2023

Sarcopenia, characterized by a loss of muscle mass and strength with aging, is prevalent in older adults. Although the exact mechanisms underlying sarcopenia are not fully understood, evidence suggests that the loss of mitochondrial integrity in skeletal myocytes has emerged as a pivotal contributor to the complex etiology of sarcopenia. Mitochondria are the primary source of ATP production and are also involved in generating reactive oxygen species (ROS), regulating ion signals, and initiating apoptosis signals in muscle cells. The accumulation of damaged mitochondria due to age-related impairments in any of the mitochondrial quality control (MQC) processes, such as proteostasis, biogenesis, dynamics, and mitophagy, can contribute to the decline in muscle mass and strength associated with aging. Interestingly, a decrease in sex hormones (e.g., 17β-estradiol and testosterone), which occurs with aging, has also been linked to sarcopenia. Indeed, 17β-estradiol and testosterone targeted mitochondria and exhibited activities in regulating mitochondrial functions. Here, we overview the current literature on the key mechanisms by which mitochondrial dysfunction contribute to the development and progression of sarcopenia and the potential modulatory effects of 17β-estradiol and testosterone on mitochondrial function in this context. The advance in its understanding will facilitate the development of potential therapeutic agents to mitigate and manage sarcopenia.
Association of NAD+ levels with metabolic disease in a community-based study
Authors: Liu Yuhe , Chen Xueyu , Deng Xuan , Yang Fan , Zheng Jinping , Zhou Tianyun , Xu Ling , Xie Xiaomei , Ju Zhenyu , Wang Baoguo , Zhang Caiping , Zhou Yong
Published: April 2023

Background

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and plays a crucial role in several metabolic processes. This study explored the association of nicotinamide adenine dinucleotide (NAD+) levels with metabolic disease (MD) in adults.

Methods

In this cross-sectional study, all data were collected from the Jidong community. MD was defined as the presence of one or more of the following disease components: hypertension, dyslipidemia, diabetes, hyperuricemia, obesity, and non-alcoholic fatty liver disease (NAFLD). The MD components were categorized into three groups: those with one component, those with two components, and those with three to six components. The whole blood NAD+ level was measured using a cycling assay and LC-MS/MS analysis. The participants were divided into four groups based on their NAD+ level quartiles. Multivariable logistic regression was used to evaluate the association of the whole blood NAD+ levels with MD.

Results

Of the 1,394 eligible participants, the average age was 43.2 years, and 74.3% had MD. In the top quartile of NAD+, the prevalence of MD and each of its components (hypertension, hyperlipidemia, diabetes, hyperuricemia, obesity, and NAFLD) were 87.9% 35.2%, 62.3%, 8.7%, 36.9%, 21.0%, and 60.5%, respectively. As compared with the lowest NAD+ quartile (≤29.4 μmol/L), the adjusted odds ratios and 95% confidence interval of the highest quartile were 3.01 (1.87-4.87) for MD, 2.48 (1.44-4.29) for 1 MD component, 2.74 (1.45-5.17) for 2 MD components, and 4.30 (2.32-7.98) for 3-6 MD components. The risk of MD began to increase at NAD+ levels of 31.0 μmol/L, as revealed by the gradient associations of NAD+ levels with MD. There was no significant interaction between age, sex, drinking, smoking, and NAD+ for MD (p for interaction ≥0.10).

Conclusions

Increased NAD+ was significantly associated with MD, as well as its individual components. Our findings provide new evidence for the relationship between blood NAD+ levels and MD.
Current prospects of building-integrated solar PV systems and the application of bifacial PVs
Authors: Abojela Zuher R. Khalifa , Desa Mohd Khairunaz Mat , Sabry Ahmad H.
Published: April 2023

Building-integrated solar photovoltaic (BIPV) systems have gained attention in current years as a way to recover the building’s thermal comfort and generate sustainable energy in building structures. BIPV systems can provide shade against sunshine while generating ancillary electrical power. Over the last decades, engineers have been trying to improve the efficiency of BIPV systems. BIPV systems with various installation types, including rooftop, balcony, curtain, sunshade, and wall façade types, are being constantly researched and intensively presented for improving power efficiency and reducing air-conditioning use. This work provides an overview of solar BIPV systems and focuses particularly on existing applications of the bifacial type of BIPV systems. The motivation and an overview of BIPV systems are first introduced, followed by the study methodology considered and the contributions. This work discusses PV technologies of bifacial PVs (monocrystalline and polycrystalline bifacial modules), BIPV installation [curtains, rooftop, flat rooftop, transparent faced, balcony windows (transparent), wall opaque facade, flat roof-faced, and skylight sunshade types], simulation and optimization software (simulation software and future trends), zero-energy BIPV technology, and optimization techniques of BIPV systems. Last, suggestion amendments to the current BIPV design that possibly contribute to growing the system’s effectiveness, reliability, and cost as future design theories for the whole system are presented.
Scalability and replicability analysis of smart grid projects: Insights from the H2020 CROSSBOW project
Authors: Makrygiorgou Despoina I. , Andriopoulos Nikos , Georgantas Ioannis , Rong Jun , Moraitis Ioannis , Calatayud Esteban Pastor , Matoses Manuel Serrano
Published: April 2023

The scalability and replicability analysis (SRA) is usually performed for Smart Grid Architecture Model (SGAM) projects to assess the applicability of proposed solutions in various regions, conditions, densities, and sizes. In this framework, the replication and scaling-up roadmap of the Horizon 2020 (H2020) CROSSBOW project encompasses a variety of interesting aspects. This study evaluates CROSSBOW results and their impact under various technical, regulatory, market, and social factors. The relevant methodology follows the literature and is properly adjusted to investigate the level at which the CROSSBOW concepts can be escalated and transferred to different scenarios and regions in an efficient and cost-effective manner. Limitations and challenges regarding scalability and replicability are also illustrated. The results depict the total impact of specific factors on scalability and replicability while useful conclusions are drawn. Lessons learnt from the CROSSBOW are very insightful for the scalability and replicability of other upcoming projects.
Territorial planning and sustainable development—case study: Protected areas in the territory of the Aspiring West Geopark, Portugal
Authors: Dias Alline , Robina-Ramírez Rafael , Sánchez-Oro Sánchez Marcelo
Published: April 2023

Introduction:The holistic concept of the sustainable development of United Nations Educational, Scientific and Cultural Organization (UNESCO) Global Geoparks encompasses the promotion of connected protected areas and activities that link geological heritage with other aspects of natural and cultural heritage. This case study aims to identify points of articulation and/or to identify conflicts in the overlap between protected areas and UNESCO World Geoparks in Portugal, and to provide information to improve the interrelation of these designations.

Methods:The methodological procedures in analysing the organisational structures of different classified areas from the respective management documents. The technical procedure consisted of document consultation and on-site activities carried out between September 2020 and November 2021.

Results:The study resulted in the identification of points of natural objects that can be held together by protected natural spaces and aspiring Oeste Geopark. A proposal for synergistic action was presented, with the main pillars of integration in the territory. The different designations for sustainable territorial management in complementary to the conservation of natural heritage. The results of the analyses indicate that the overlap of the different designations of areas and territories studied here can act both in a joint and complementary way to conserve natural heritage.

Discussion:This reinforcement study, which has different designations of areas and/or territories for sustainable territorial planning at the local, regional, national, and international levels, is fundamental for nature conservation, lacking more in terms of efficient management and integration of the social component.
Heterogeneous impact of artificial intelligence on carbon emission intensity: Empirical test based on provincial panel data in China
Authors: Du Meng , Zhang Yifan , Dong Hai , Zhou Xiangjun
Published: April 2023

Introduction

Energy conservation and emission reduction, as a major policy of China for a long time, has been put on the key strategic position. Based on the panel data of 30 provinces, cities and districts in China from 2006 to 2019.

Methods

This paper uses fixed effect model and spatial Durbin model to explore the effect and mechanism of artificial intelligence (AI) on regional carbon emission intensity (CEI).

Results

The results show that: (1) there is a significant inverted U-shaped between AI and CEI, that is, with the deepening of the development of AI, CEI first increases and then decreases. (2) There is a significant spatial correlation between the development of AI and CEI in China. (3) AI has a significant spatial spillover effect on CEI of adjacent regions, and it shows an inverted U-shaped track-from promoting to restraining.

Discussion

The conclusion provides policy implications for the formulation of AI development strategy and so on during the specific period.
Effect of initial water content on soil failure mechanism of loess mudflow disasters
Authors: Yang Zhiquan , Chen Mao , Zhang Jie , Ding Pan , He Na , Yang Yi
Published: April 2023

The frequency of mudflow disasters induced by rainfall in the Loess Plateau is increasing with the occurrence of global warming. The initial water content is one of the basic properties of soil, which affects the initiation of loess mudflow. In this work, the field study of the debris flow gullies in Yan’an City, Shaanxi Province, China, was conducted, and the main factors that induce gully loess mudflow were summarized. Based on the investigation results, a flume model was designed to carry out flume tests with different initial soil water contents. The experimental results demonstrate the following. (1) Different initial soil water contents lead to different soil failure models. The damage of soil by water flow when the soil water content is in the range of 0−5% is mainly gully erosion; that within the range of 10−15% is mainly rill surface erosion; that within the range of 20−25% is mainly dam breach failure. (2) When the water content of loess is equal to or less than 5% or equal to or greater than 20%, soil can promote the formation of loess mudflow, and the destruction of soil is more likely to cause mudflow disasters. In contrast, when the water content is within 10−15%, loess mudflow is not easily produced. The research results of the initial water content provide not only theoretical support for the study of loess mudflow disasters, but also a reference for the prevention and control of loess mudflow disasters in the Loess Plateau.
Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity
Authors: von Werdt Diego , Gungor Bilgi , Barreto de Albuquerque Juliana , Gruber Thomas , Zysset Daniel , Kwong Chung Cheong K. C. , Corrêa-Ferreira Antonia , Berchtold Regina , Page Nicolas , Schenk Mirjam , Kehrl John H. , Merkler Doron , Imhof Beat A. , Stein Jens V. , Abe Jun , Turchinovich Gleb , Finke Daniela , Hayday Adrian C. , Corazza Nadia , Mueller Christoph
Published: April 2023

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1-/- and Rgs1+/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1+/+ T cells outnumbered the co-transferred OT-I Rgs1-/- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1-/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1+/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1-/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.
Insect chaperones Hsp70 and Hsp90 cooperatively enhance toxicity of Bacillus thuringiensis Cry1A toxins and counteract insect resistance
Authors: García-Gomez Blanca Ines , Sánchez Tamara Alejandrina , Cano Sayra Natalia , do Nascimento Nathaly Alexandre , Bravo Alejandra , Soberón Mario
Published: April 2023

Bacillus thuringiensis (Bt) produces different insecticidal proteins effective for pest control. Among them, Cry insecticidal proteins have been used in transgenic plants for the control of insect pests. However, evolution of resistance by insects endangers this technology. Previous work showed that the lepidopteran insect Plutella xylostella PxHsp90 chaperone enhanced the toxicity of Bt Cry1A protoxins by protecting them from degradation by the larval gut proteases and by enhancing binding of the protoxin to its receptors present in larval midgut cells. In this work, we show that PxHsp70 chaperone also protects Cry1Ab protoxin from gut proteases degradation, enhancing Cry1Ab toxicity. We also show that both PxHsp70 and PxHsp90 chaperones act cooperatively, increasing toxicity and the binding of Cry1Ab439D mutant, affected in binding to midgut receptors, to cadherin receptor. Also, insect chaperones recovered toxicity of Cry1Ac protein to a Cry1Ac-highly resistant P. xylostella population, NO-QAGE, that has a disruptive mutation in an ABCC2 transporter linked to Cry1Ac resistance. These data show that Bt hijacked an important cellular function for enhancing its infection capability, making use of insect cellular chaperones for enhancing Cry toxicity and for lowering the evolution of insect resistance to these toxins.
Biomaterials promote in vivo generation and immunotherapy of CAR-T cells
Authors: Qin Ya-Ting , Li Ya-Ping , He Xi-Wen , Wang Xi , Li Wen-You , Zhang Yu-Kui
Published: April 2023

Chimeric antigen receptor-T (CAR-T) cell therapy based on functional immune cell transfer is showing a booming situation. However, complex manufacturing processes, high costs, and disappointing results in the treatment of solid tumors have limited its use. Encouragingly, it has facilitated the development of new strategies that fuse immunology, cell biology, and biomaterials to overcome these obstacles. In recent years, CAR-T engineering assisted by properly designed biomaterials has improved therapeutic efficacy and reduced side effects, providing a sustainable strategy for improving cancer immunotherapy. At the same time, the low cost and diversity of biomaterials also offer the possibility of industrial production and commercialization. Here, we summarize the role of biomaterials as gene delivery vehicles in the generation of CAR-T cells and highlight the advantages of in-situ construction in vivo. Then, we focused on how biomaterials can be combined with CAR-T cells to better enable synergistic immunotherapy in the treatment of solid tumors. Finally, we describe biomaterials’ potential challenges and prospects in CAR-T therapy. This review aims to provide a detailed overview of biomaterial-based CAR-T tumor immunotherapy to help investigators reference and customize biomaterials for CAR-T therapy to improve the efficacy of immunotherapy.
Rapid glycolytic activation accompanying innate immune responses: mechanisms and function
Authors: Namgaladze Dmitry , Brüne Bernhard
Published: April 2023

Innate immune responses to pathogens, mediated by activation of pattern recognition receptors and downstream signal transduction cascades, trigger rapid transcriptional and epigenetic changes to support increased expression of pro-inflammatory cytokines and other effector molecules. Innate immune cells also rapidly rewire their metabolism. The most prominent metabolic alteration following innate immune activation is rapid up-regulation of glycolysis. In this mini-review, we summarize recent advances regarding the mechanisms of rapid glycolytic activation in innate immune cells, highlighting the relevant signaling components. We also discuss the impact of glycolytic activation on inflammatory responses, including the recently elucidated links of metabolism and epigenetics. Finally, we highlight unresolved mechanistic details of glycolytic activation and possible avenues of future research in this area.
Salmonella Enteritidis clades in South Africa: why we should be paying more attention
Authors: Gallichan Sarah , Ramalwa Ntsieni , Thomas Juno , Feasey Nicholas , Smith Anthony M.
Published: April 2023

Salmonella Enteritidis is the most reported non-typhoidal Salmonella serovar and is implicated in both gastroenteritis and invasive non-typhoidal disease. Whole-genome sequence comparison of Salmonella Enteritidis isolates from across the world identified four definitive clades: Outlier, Global Epidemic, East African and West African. Three of these clades were implicated in epidemics: the Global Epidemic clade was linked to poultry-associated gastroenteritis, while the two African clades were related to invasive disease. Despite the recognition of different Salmonella Enteritidis clades, the distribution and epidemiology of these clades across Africa is poorly understood. In our proof-of-concept study, we classified 618 Salmonella Enteritidis isolates originating from four South African provinces over a period of two years (2012 – 2013) into clades using a clade-typing real-time PCR assay. Associations between clades and province of collection, antimicrobial resistance and HIV status were explored using statistical analysis. Majority of the South African isolates were classified within the Outlier clade (61.00%), with fewer classified within the Global Epidemic clade (38.83%) and only one isolate classified within the West African Clade (0.16%). Of note, were the isolates within the Global clade, which were strongly associated with ciprofloxacin resistance (15.42%, OR: 7.45, CI: 3.526 – 15.751) and invasive disease (58.33%, OR: 1.57, CI: 1.13 – 2.17) in humans. The increase in poultry consumption and importation in South Africa has placed the country at risk of a Salmonella Enteritidis epidemic. Thus, there is a necessity for routine monitoring of S. Enteritidis along the farm-to-fork continuum to implement preventative measures.
False perspectives on human language: Why statistics needs linguistics
Authors: Greco Matteo , Cometa Andrea , Artoni Fiorenzo , Frank Robert , Moro Andrea
Published: April 2023

A sharp tension exists about the nature of human language between two opposite parties: those who believe that statistical surface distributions, in particular using measures like surprisal, provide a better understanding of language processing, vs. those who believe that discrete hierarchical structures implementing linguistic information such as syntactic ones are a better tool. In this paper, we show that this dichotomy is a false one. Relying on the fact that statistical measures can be defined on the basis of either structural or non-structural models, we provide empirical evidence that only models of surprisal that reflect syntactic structure are able to account for language regularities.

One-sentence summary

Language processing does not only rely on some statistical surface distributions, but it needs to be integrated with syntactic information.
Impact of race and ethnicity on family participation in systemic lupus erythematosus genetic studies
Authors: Scofield R Hal , Sharma Rohan , Aberle Teresa , Cooney Carisa M , Kelly Jennifer A , Harley John B , Rasmussen Astrid
Published: April 2023

Objective

Systemic lupus erythematosus (SLE) has a higher prevalence and is more severe in African Americans and Hispanics than in non-Hispanic Whites. To understand the shared and unique genetic risk factors of these populations, an adequate representation of African Americans and Hispanics in clinical and genetic research is indispensable while challenging. The goal of this study was to identify differences in research participation of families of different racial and ethnic backgrounds and the potential causes for the disparities.

Methods

Families were screened for eligibility to the Lupus Family Registry and Repository (LFRR) after self-referral or physician referral. We recorded the sociodemographic characteristics, self-identified race and ethnicity, ACR-SLE criteria, and the reasons given for not completing study participation for all families.

Results

A total of 1,472 families (950 non-Hispanic White, 405 African American, and 117 Hispanic) were screened but only 366 completed study participation (25%). Participation rates and reasons for non-participation varied between racial and ethnic groups. The main reason for African American families to not participate was that subjects critical to the family structure declined participation (OR = 1.6, p = 0.0001), while for White families, the main cause was that purported SLE patients did not meet ACR SLE criteria (OR = 1.81, p < 0.00002). Hispanics were the most likely to complete participation (OR = 4.25, p < 0.0001).

Conclusions

Successful recruitment of patients, families, and specific demographic groups is critical for the study of genetically complex diseases, such as SLE. There are significant disparities in SLE family recruitment across groups of people, likely due to their richly different cultures and environments.
Moreton Bay; A previously unrecognized resting stopover for east-coast of Australia migrating humpback whales
Authors: Castrillon Juliana , Mayaud Raphael , Wilson Craig , Dalle Luche Greta , Allen Jenny , Bengtson Nash Susan
Published: April 2023

Humpback whales enter Moreton Bay, in southeast Queensland, Australia, each year during their annual migration. Little is known about the ecological significance of the bay for the humpback whale population. In a region characterised by rapid coastal and maritime development, as well as a growing humpback whale population, there is an urgent need to fill knowledge gaps surrounding the populations’ seasonal distribution and habitat use in these coastal waters. This study procured the first detailed information regarding humpback whale distribution, behaviour, and habitat use within Moreton Bay, relative to the main east coast migratory corridor. It was found that on average 42.41% of the individuals observed on the southern leg of the migration entered the bay. 76.78% of pods entering the bay had accompanying calves and 47.82% of these pods were found to be resting or logging, a behaviour often associated with nursing, at the time of observation. These findings provide strong evidence for a previously undocumented role of Moreton Bay as a resting stopover for migrating humpback whales.
Experimental transmission of piscine orthoreovirus-1 (PRV-1) in different life stages of Atlantic salmon (Salmo salar) and brown trout (Salmo trutta)
Authors: Kannimuthu Dhamotharan , Roh HyeongJin , Morton H Craig , Peñaranda Ma Michelle D. , Vossgård Anne , Hansen Tom , Fjelldal Per Gunnar , Karlsbakk Egil , Fiksdal Ingrid , Dahle Maria K. , Berg-Rolness Håkon , Mæhle Stig , Berhe Ghebretnsae Dawit , Nordbø Joachim , Patel Sonal , Madhun Abdullah , Grove Søren , Kvamme Bjørn Olav
Published: April 2023

Piscine orthoreovirus -1 (PRV-1) causes the disease heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon, and the virus has been detected in wild anadromous Atlantic salmon and brown trout. However, the infection prevalence, viral kinetics, and disease severity in different life stages of Atlantic salmon and brown trout are unknown. The current study aimed to evaluate and compare susceptibility to PRV-1 infection and development of HSMI in different life stages of anadromous Atlantic salmon (Salmo salar) and brown trout (Salmo trutta). We challenged Atlantic salmon and brown trout fry, parr, and post-smolts with PRV-1 by bath, cohabitation, or IP injection. The kinetics of viral infection and disease development were evaluated by RT-qPCR, in situ hybridization, and histology. Our results indicated that PRV-1 infection prevalence and viral kinetics depend on the developmental stage and challenge method in both Atlantic salmon and brown trout. All developmental stages of Atlantic salmon and brown trout can be infected with PRV-1. However, brown trout showed a lower infection prevalence, with positive cases exhibiting only mild infections without any pathological changes in the target organs, while all life stages of Atlantic salmon developed heart lesions characteristic of HSMI. These results strongly suggest that brown trout are less susceptible to PRV-1 infection than Atlantic salmon and further confirm the species-specific susceptibility and disease development for PRV-1 infection.
Distribution of stable isotopes of Mo and W from a river to the ocean: signatures of anthropogenic pollution
Authors: Matsuoka Kohei , Tatsuyama Tomomichi , Takano Shotaro , Sohrin Yoshiki
Published: April 2023

Molybdenum and tungsten are redox-sensitive elements, and their stable isotope ratios have attracted attention as paleoceanographic proxies. However, our knowledge of the distribution of stable Mo and W isotopes in the modern hydrosphere remains limited. In this study, we provided the concentrations and isotope ratios of dissolved Mo and W in the oceans (the North Pacific and Indian Oceans), marginal seas (the East China Sea and Sea of Japan), and a river-estuary system in Japan (from the Uji-Yodo rivers to Osaka Bay). In the North Pacific and Indian Oceans, the W concentration was 48.2 ± 6.2 pmol/kg (ave ± 2sd, n = 109), δ186/184W was 0.52 ± 0.06 ‰, the Mo concentration was 105.1 ± 8.0 nmol/kg, and δ98/95Mo was 2.40 ± 0.06 ‰. The results indicate that W has the constant concentration and isotopic composition in the modern ocean as well as Mo. In the East China Sea and the Sea of Japan, the W concentration and δ186/184W in the upper water (< 1000 m depth) were different from those in the ocean (W = 56 ± 18 pmol/kg, δ186/184W = 0.45 ± 0.06 ‰, n = 24). However, the concentrations in deeper water were congruent with those in the oceans (W = 49.9 ± 7.6 pmol/kg, δ186/184W = 0.50 ± 0.02 ‰, n = 7). The Mo concentration was 105.4 ± 3.1 nmol/kg and δ98/95Mo was 2.36 ± 0.03 ‰ (n = 31) throughout the water column, congruent with those in the ocean. In the Uji River-Yodo River-Osaka Bay system, the W concentration reached 1074 pmol/kg and δ186/184W reached 0.20 ‰. We propose that the enrichment of W with a low δ186/184W in the river-estuary system and marginal seas is caused by anthropogenic pollution. Anthropogenic Mo pollution was not detected in marginal seas. However, the Mo concentration and δ98/95Mo showed high anomalies above the mixing line of river water and seawater in the lower Yodo River and Osaka Bay, implying possible anthropogenic pollution of Mo in the metropolitan area.
Disrespect and abuse of women during childbirth at health facilities in Eastern Africa: systematic review and meta-analysis
Authors: Gebeyehu Natnael Atnafu , Adella Gtachew Asmare , Tegegne Kirubel Dagnaw
Published: April 2023

Background

Disrespectful and abusive maternity care is a sign of poor treatment that influences women’s choice to deliver their babies in institutions. Such malpractices continue to go unreported and are rarely exposed in developing countries, despite their serious burden. Therefore, this meta-analysis study aimed to estimate disrespect and abuse of women during childbirth in East Africa.

Methods

PubMed, Google Scholar, Scopus, and Science Direct databases were searched. Data were extracted using Microsoft Excel and analyzed using STATA statistical software (v. 14). Publication bias was checked by forest plot, Begg’s rank test, and Egger’s regression test. To look for heterogeneity, I2 was computed, and an overall estimated analysis was carried out. Subgroup analysis was done by study region, sample size, and publication. The pooled odds ratio for associated factors was also computed.

Results

Out of 654 articles assessed, 18 met the criteria and were included in this study. There were a total of 12,434 study participants. The pooled prevalence of disrespect and abuse of women during childbirth in East Africa was 46.85% (95% CI: 45.26.72–66.98), I2 = 81.9%. It was lower in studies with sample size greater than 5000 (33%). The disrespect and abuse rates between community-based studies (44.96%) and institutional-based studies (47.35%) did not differ significantly, though. Instrumental delivery (AOR = 2.70; 95%CI: 1.79–4.08), presence of complications (AOR = 6.41; 95% CI: 1.36–30.14), receiving care at government hospitals (AOR = 3.66; 95% CI: 1.09–12.23), and poor wealth index (AOR = 2.16; 95% CI: 1.26–3.70) were associated factors.

Conclusion

In East Africa, disrespect and abuse of women during childbirth was high. Instrumental delivery, presence of complications during childbirth, receiving care at government hospitals and poor wealth index were predictors of maternal disrespect and abuse. Safe delivery practice should be promoted. Training in compassionate and respectful maternity care, particularly in public hospitals, has also been recommended.
Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies
Authors: Dong Qingfu , Bao Haolin , Wang Jiangang , Shi Wujiang , Zou Xinlei , Sheng Jialin , Gao Jianjun , Guan Canghai , Xia Haoming , Li Jinglin , Kang Pengcheng , Xu Yi , Cui Yunfu , Zhong Xiangyu
Published: April 2023

In recent years, the prevalence of metabolic-associated fatty liver disease (MAFLD) has reached pandemic proportions as a leading cause of liver fibrosis worldwide. However, the stage of liver fibrosis is associated with an increased risk of severe liver-related and cardiovascular events and is the strongest predictor of mortality in MAFLD patients. More and more people believe that MAFLD is a multifactorial disease with multiple pathways are involved in promoting the progression of liver fibrosis. Numerous drug targets and drugs have been explored for various anti-fibrosis pathways. The treatment of single medicines is brutal to obtain satisfactory results, so the strategies of multi-drug combination therapies have attracted increasing attention. In this review, we discuss the mechanism of MAFLD-related liver fibrosis and its regression, summarize the current intervention and treatment methods for this disease, and focus on the analysis of drug combination strategies for MAFLD and its subsequent liver fibrosis in recent years to explore safer and more effective multi-drug combination therapy strategies.
Update on cryptogenic organizing pneumonia
Authors: Radzikowska Elzbieta , Fijolek Justyna
Published: April 2023

Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that results from the pulmonary reaction to various unidentified injuries. Secondary organizing pneumonia is diagnosed when the triggering factor has been identified; it is mainly caused by infections, toxic substance exposure, drugs, connective tissue diseases, malignancies, autoimmune diseases, bone marrow, or organ transplantation, and radiotherapy. There has been an increase in the number of reports of drug-induced organizing pneumonia (OP). New biological therapies, interferon, monoclonal antibodies, anti-interleukin antibodies, and PD1/PDL-1 inhibitors may induce this specific pulmonary reaction. The classical form of COP is usually subacute and does not manifest as severe disease. Patients maintain sufficient respiratory function, and treatment with steroids is usually effective. Several specific forms of OP (e.g., the cicatricial variant or acute fibrinous type) have distinct clinical and histological features, require higher doses of immunosuppressive drugs, and have a worse prognosis. In the era of administering steroid-sparing therapies for the treatment of interstitial lung diseases, connective tissue dases, and other conditions, it is important to emphasize this type of therapy for patients with COP.
Combination therapy with 3% diquafosol tetrasodium ophthalmic solution and sodium hyaluronate: an effective therapy for patients with dry eye after femtosecond laser-assisted in situ keratomileusis
Authors: Wang Tianjiao , Di Yu , Li Ying
Published: April 2023

Purpose

To assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK).

Design

Prospective nonrandomized comparative trial.

Methods

The prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor’s advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively.

Results

OSDI score (p = 0.024) and vision-related score (p = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS (p = 0.018), bulbar redness score (p = 0.021), and limbal redness score (p = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week (p = 0.004) and 1 month (p < 0.001) after surgery, especially in patients with high meiboscore. Additional DQS significantly improved corneal sensitivity in patients without preoperative dry eye symptoms at 1 month after FS-LASIK (p = 0.041).

Conclusion

The combination therapy with DQS and HA significantly relieved subjective symptoms, improved ocular surface status, and had the potential to promote corneal nerve growth in patients after FS-LASIK.
Meta-Analysis of Caenorhabditis elegans Transcriptomics Implicates Hedgehog-Like Signaling in Host-Microbe Interactions
Authors: Zárate-Potes Alejandra , Ali Irtiqa , Ribeiro Camacho Margarida , Brownless Hayley , Benedetto Alexandre
Published: April 2023

Graphical Abstract

Graphical abstract of the approach employed in this study. Combined analyses of C. elegans-microbe transcriptomics (1) and gene tissue expression maps (2), with high-throughput stress and infection assays following host-gene inactivation (3), can guide predictions and accelerate identification of genetic interactions involved in nematode-microbe interactions.
DNA extraction protocol impacts ocular surface microbiome profile
Authors: Delbeke Heleen , Casteels Ingele , Joossens Marie
Published: April 2023

Purpose

The aim of this study is to provide a reference frame to allow the comparison and interpretation of currently published studies on 16S ribosomal ribonucleic acid amplicon sequencing of ocular microbiome samples using different DNA extraction protocols. Alongside, the quantitative and qualitative yield and the reproducibility of different protocols has been assessed.

Methods

Both eyes of 7 eligible volunteers were sampled. Five commercially available DNA extraction protocols were selected based on previous publications in the field of the ocular surface microbiome and 2 host DNA depletion protocols were added based on their reported effective host DNA depletion without significant reduction in bacterial DNA concentration. The V3-V4 region of the 16S rRNA gene was targeted using Illumina MiSeq sequencing. The DADA2 pipeline in R was used to perform the bio-informatic processing and taxonomical assignment was done using the SILVA v132 database. The Vegdist function was used to calculate Bray-Curtis distances and the Galaxy web application was used to identify potential metagenomic biomarkers via linear discriminant analysis Effect Size (LEfSe). The R package Decontam was applied to control for potential contaminants.

Results

Samples analysed with PowerSoil, RNeasy and NucleoSpin had the highest DNA yield. The host DNA depletion kits showed a very low microbial DNA yield; and these samples were pooled per kit before sequencing. Despite pooling, 1 of both failed to construct a library.

Looking at the beta-diversity, clear microbial compositional differences - dependent on the extraction protocol used – were observed and remained present after decontamination. Eighteen genera were consistently retrieved from the ocular surface of every volunteer by all non-pooled extraction kits and a comprehensive list of differentially abundant bacteria per extraction method was generated using LefSe analysis.

Conclusion

High-quality papers have been published in the field of the ocular surface microbiome but consensus on the importance of the extraction protocol used are lacking. Potential contaminants and discriminative genera per extraction protocol used, were introduced and a reference frame was built to facilitate both the interpretation of currently published papers and to ease future choice – making based on the research question at hand.
The challenges of the genome-based identification of antifungal resistance in the clinical routine
Authors: Alastruey-Izquierdo Ana , Martín-Galiano Antonio J.
Published: April 2023

The increasing number of chronic and life-threatening infections caused by antimicrobial resistant fungal isolates is of critical concern. Low DNA sequencing cost may facilitate the identification of the genomic profile leading to resistance, the resistome, to rationally optimize the design of antifungal therapies. However, compared to bacteria, initiatives for resistome detection in eukaryotic pathogens are underdeveloped. Firstly, reported mutations in antifungal targets leading to reduced susceptibility must be extensively collected from the literature to generate comprehensive databases. This information should be complemented with specific laboratory screenings to detect the highest number possible of relevant genetic changes in primary targets and associations between resistance and other genomic markers. Strikingly, some drug resistant strains experience high-level genetic changes such as ploidy variation as much as duplications and reorganizations of specific chromosomes. Such variations involve allelic dominance, gene dosage increments and target expression regime effects that should be explicitly parameterized in antifungal resistome prediction algorithms. Clinical data indicate that predictors need to consider the precise pathogen species and drug levels of detail, instead of just genus and drug class. The concomitant needs for mutation accuracy and assembly quality assurance suggest hybrid sequencing approaches involving third-generation methods will be utilized. Moreover, fatal fast infections, like fungemia and meningitis, will further require both sequencing and analysis facilities are available in-house. Altogether, the complex nature of antifungal resistance demands extensive sequencing, data acquisition and processing, bioinformatic analysis pipelines, and standard protocols to be accomplished prior to genome-based protocols are applied in the clinical setting.
Comparative genomic insights into habitat adaptation of coral-associated Prosthecochloris
Authors: Nie Zhaolong , Tang Kaihao , Wang Weiquan , Wang Pengxia , Guo Yunxue , Wang Yan , Kao Shuh-Ji , Yin Jianping , Wang Xiaoxue
Published: April 2023

Green sulfur bacteria (GSB) are a distinct group of anoxygenic phototrophic bacteria that are found in many ecological niches. Prosthecochloris, a marine representative genus of GSB, was found to be dominant in some coral skeletons. However, how coral-associated Prosthecochloris (CAP) adapts to diurnal changing microenvironments in coral skeletons is still poorly understood. In this study, three Prosthecochloris genomes were obtained through enrichment culture from the skeleton of the stony coral Galaxea fascicularis. These divergent three genomes belonged to Prosthecochloris marina and two genomes were circular. Comparative genomic analysis showed that between the CAP and non-CAP clades, CAP genomes possess specialized metabolic capacities (CO oxidation, CO2 hydration and sulfur oxidation), gas vesicles (vertical migration in coral skeletons), and cbb3-type cytochrome c oxidases (oxygen tolerance and gene regulation) to adapt to the microenvironments of coral skeletons. Within the CAP clade, variable polysaccharide synthesis gene clusters and phage defense systems may endow bacteria with differential cell surface structures and phage susceptibility, driving strain-level evolution. Furthermore, mobile genetic elements (MGEs) or evidence of horizontal gene transfer (HGT) were found in most of the genomic loci containing the above genes, suggesting that MGEs play an important role in the evolutionary diversification between CAP and non-CAP strains and within CAP clade strains. Our results provide insight into the adaptive strategy and population evolution of endolithic Prosthecochloris strains in coral skeletons.