bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactive effects of nutrients and salinity on zooplankton in subtropical plateau lakes with contrasting water depth
Authors: Yang Li-Juan , Tao Ya , Jiang Xia , Wang Ying , Li Ye-Hao , Zhou Long , Wang Pu-Ze , Li Yuan-Yuan , Zhao Xu , Wang Hai-Jun , Jeppesen Erik , Xie Ping
Published: February 2023

Both eutrophication and salinization are growing global environmental problems in freshwater ecosystems, threatening the water quality and various aquatic organisms. However, little is known about their interactive effects on theses stressors and the role of lake depth on these interactions. We used field surveys to compared zooplankton assemblages over four seasons in eight Yunnan Plateau lakes with different trophic states, salinization levels, and water depths. The results showed that: 1) the species number (S), density (DZoop), and biomass (BZoop) of zooplankton exhibited strong seasonal dynamics, being overall higher in the warm seasons. 2) Data collected over four seasons and summer data both revealed highly significant positive relationships of S, DZoop, and BZoop with total nitrogen (TN), total phosphorus (TP), and phytoplankton chlorophyll a (Chl a). 3) S, DZoop, and BZoop displayed a unimodal relationship with salinity, peaking at 400–1000 μS/cm (conductivity, to reflect salinity). 4) The two large-sized taxa (cladocerans and copepods) generally increased at low-moderate levels of TN, TP, Chl a, and Cond and was constant or decreased at high levels. The average body mass (biomass/density) of crustaceans decreased with increasing TN, TP, Chl a, and conductivity. Our findings indicate that zooplankton may be more vulnerable in deep lakes than in shallow lakes when exposed to conductivity stress even under mesotrophic conditions, and the overall decrease in size in zooplankton assemblages under the combined stress of eutrophication and salinization may result in a lowered grazing effect on phytoplankton.
A new hypercarnivorous hyaenodont from the Eocene of South China
Authors: Averianov Alexander , Obraztsova Ekaterina , Danilov Igor , Jin Jian-Hua
Published: February 2023

A new hyaenodont Maocyon peregrinus, gen. et sp. nov., is described based on a partial skull and associated mandible from the upper Eocene Youganwo Formation at Maoming locality in Guangdong Province, China. It shows certain similarities with the Hyainailouroidea in the skull structure, including anteroposteriorly extended jugal/squamosal suture, presence of a preglenoid crest, a lateral expansion of the squamosal posterior to the zygomatic arch, a transversally expanded mastoid process, a nuchal crest that does not extend laterally to mastoid process, and large occipital condyles. The phylogenetic analysis clusters the new taxon with Orienspterodon dahkoensis from the late middle Eocene of China and Myanmar and places this clade within the Hyainailouridae in a polytomy with the Apternodontinae and the Hyainailourinae.
Identification and validation of metabolism-related hub genes in idiopathic pulmonary fibrosis
Authors: Zeng Youjie , Huang Jun , Guo Ren , Cao Si , Yang Heng , Ouyang Wen
Published: February 2023

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal and irreversible interstitial lung disease. The specific mechanisms involved in the pathogenesis of IPF are not fully understood, while metabolic dysregulation has recently been demonstrated to contribute to IPF. This study aims to identify key metabolism-related genes involved in the progression of IPF, providing new insights into the pathogenesis of IPF.

Methods: We downloaded four datasets (GSE32537, GSE110147, GSE150910, and GSE92592) from the Gene Expression Omnibus (GEO) database and identified differentially expressed metabolism-related genes (DEMRGs) in lung tissues of IPF by comprehensive analysis. Then, we performed GO, KEGG, and Reactome enrichment analyses of the DEMRGs. Subsequently, key DEMRGs were identified by machine-learning algorithms. Next, miRNAs regulating these key DEMRGs were predicted by integrating the GSE32538 (IPF miRNA dataset) and the miRWalk database. The Cytoscape software was used to visualize miRNA-mRNA regulatory networks. In addition, the relative levels of immune cells were assessed by the CIBERSORT algorithm, and the correlation of key DEMRGs with immune cells was calculated. Finally, the mRNA expression of the key DEMRGs was validated in two external independent datasets and an in vivo experiment.

Results: A total of 101 DEMRGs (51 upregulated and 50 downregulated) were identified. Six key DEMRGs (ENPP3, ENTPD1, GPX3, PDE7B, PNMT, and POLR3H) were further identified using two machine-learning algorithms (LASSO and SVM-RFE). In the lung tissue of IPF patients, the expression levels of ENPP3, ENTPD1, and PDE7B were upregulated, and the expression levels of GPX3, PNMT, and POLR3H were downregulated. In addition, the miRNA-mRNA regulatory network of key DEMRGs was constructed. Then, the expression levels of key DEMRGs were validated in two independent external datasets (GSE53845 and GSE213001). Finally, we verified the key DEMRGs in the lung tissue of bleomycin-induced pulmonary fibrosis mice by qRT-PCR.

Conclusion: Our study identified key metabolism-related genes that are differentially expressed in the lung tissue of IPF patients. Our study emphasizes the critical role of metabolic dysregulation in IPF, offers potential therapeutic targets, and provides new insights for future studies.
Molecular dynamics and minigene assay of new splicing variant c.4298-20T>A of COL4A5 gene that cause Alport syndrome
Authors: Liang Lei , Wu Haotian , Cai Zeyu , Zhao Jianrong
Published: February 2023

Introduction: Alport syndrome (AS; OMIM#308940) is a progressive hereditary kidney disease characterized by hearing loss and ocular abnormalities. According to the mode of inheritance, AS has three subtypes: X-linked (XL; OMIM#301050), autosomal recessive (AR; OMIM#203780), and autosomal dominant (AD; OMIM#104200). XLAS is caused by a pathogenic variant in COL4A5 (OMIM*303630) gene encoding type IV collagen (Col-IV) α5 chain, while ADAS and ARAS are consequences of a variant in COL4A3 (OMIM*120070) and COL4A4 (OMIM*120131) genes that encode Col-IV α3 and α4 chains, respectively. Usually, diagnosis of AS requires hereditary or pathological examinations. Splicing variants are hard to be determined as pathogenic or non-pathogenic based on the results of gene sequencing.

Methods: This study focused on a splicing variant in COL4A5 gene, termed NM_000495.5: c.4298–20T>A, and to analyzed its authenticity and damaged α5 chain. In vitro minigene splicing assay was applied to investigate the effect of splicing variant, c.4298–20T>A, on COL4A5 mRNA synthesis. Molecular dynamics method was used to predict the capability of the responsible α5(IV) to form a triple helix.

Results: The intron 46 of COL4A5 mRNA retained 18 bp, resulting in insertion of six amino acids behind the amino acid at position 1,433 of α5(IV). The predicted protein effect of this variant: p. (Pro1432_Gly1433insAspTyrPheValGluIle). As a consequence, the stability of α5(IV) secondary structure was impaired, probably leading to the unusual configuration of α345(IV).

Discussion: Normally, splicing variant in COL4A5 gene can lead to phenotypes of XLAS, and the effect is associated with the extent of splicing. The patient reported here carried a c.4298–20T>A splicing variant in COL4A5 gene, and AS was highly suspected based on the pathology results. However, the patient did not manifest any ocular or ear abnormalities. We therefore present the c.4298–20T>A splicing variant in COL4A5 gene as likely-pathogenic splicing variant that leads to XLAS with mild phenotypes.
Genes and models for estimating genetic parameters for heat tolerance in dairy cattle
Authors: Habimana Vincent , Ekine-Dzivenu Chinyere Charlotte , Nguluma Athumani Shabani , Nziku Zabron Cuthibert , Morota Gota , Chenyambuga Sebastian Wilson , Mrode Raphael
Published: February 2023

Dairy cattle are highly susceptible to heat stress. Heat stress causes a decline in milk yield, reduced dry matter intake, reduced fertility rates, and alteration of physiological traits (e.g., respiration rate, rectal temperature, heart rates, pulse rates, panting score, sweating rates, and drooling score) and other biomarkers (oxidative heat stress biomarkers and stress response genes). Considering the significant effect of global warming on dairy cattle farming, coupled with the aim to reduce income losses of dairy cattle farmers and improve production under hot environment, there is a need to develop heat tolerant dairy cattle that can grow, reproduce and produce milk reasonably under the changing global climate and increasing temperature. The identification of heat tolerant dairy cattle is an alternative strategy for breeding thermotolerant dairy cattle for changing climatic conditions. This review synthesizes information pertaining to quantitative genetic models that have been applied to estimate genetic parameters for heat tolerance and relationship between measures of heat tolerance and production and reproductive performance traits in dairy cattle. Moreover, the review identified the genes that have been shown to influence heat tolerance in dairy cattle and evaluated the possibility of using them in genomic selection programmes. Combining genomics information with environmental, physiological, and production parameters information is a crucial strategy to understand the mechanisms of heat tolerance while breeding heat tolerant dairy cattle adapted to future climatic conditions. Thus, selection for thermotolerant dairy cattle is feasible.
Comparison of the salt resistance of Solanum lycopersicum x Solanum chilense hybrids and their parents
Authors: Bigot Servane , Leclef Claire , Rosales Camila , Martínez Juan-Pablo , Lutts Stanley , Quinet Muriel
Published: February 2023

Introduction

Soil salinization is a major global problem. Tomato (Solanum lycopersicum) is one of the main crops produced in the world and is cultivated in areas affected by salinity. However, it is considered as a glycophyte species and is sensitive to salt stress. Solanum chilense is a wild tomato native to the Atacama Desert and is therefore adapted to harsh environmental conditions, including salinity. It is considered as a promising source of genes for tomato improvement. However, the physiology of abiotic stress resistance remains largely unknown in S. chilense and no studies have investigated the resistance of S. lycopersicum x S. chilense interspecific hybrids and the potential value of their use in harsh environments.

Methods

In this study, we compared the salt (0 vs. 100 mM NaCl) resistance of S. lycopersicum, S. chilense and their hybrids at vegetative and reproductive stages.

Results

Overall, hybrids showed an intermediate behavior between their parents and a higher salt resistance than S. lycopersicum. Their physiological behavior toward salt stress was sometimes closed to S. lycopersicum and sometimes closed to S. chilense. Their sodium accumulation was intermediate between parents, with a sodium concentration closer to S. lycopersicum than S. chilense in roots, but with an aerial concentration closer to S. chilense than to S. lycopersicum. In inflorescences and fruits, the sodium concentration of hybrids was closer to S. lycopersicum than to S. chilense. Despite a decrease in instantaneous transpiration, the photosynthetic nitrogen use efficiency of hybrids was not decreased by salt stress: our results suggest a greater tolerance to the osmotic phase of salt stress in hybrids compared to the parents. Regarding the reproductive stage, inflorescence production and fruit quality were not affected by salt in hybrids.

Discussion

This study highlights the potential use of hybrids in improving tomato for salt stress resistance.
Allergic adverse events following immunization: Data from post-marketing surveillance in Apulia region (South of Italy)
Authors: Stefanizzi Pasquale , Ferorelli Davide , Scazzi Francesco Livio , Di Lorenzo Antonio , Martinelli Andrea , Trinchera Chiara , Moscara Lorenza , Miniello Enrico , Di Bona Danilo , Tafuri Silvio
Published: February 2023

Introduction

Among adverse events following immunization (AEFIs), allergic reactions elicit the most concern, as they are often unpredictable and can be life-threatening. Their estimates range from one in 1,000,000 to one in 50,000 vaccine doses. This report describes allergic events following immunization reported from 2020 to 2021 in Puglia, a region in the South-East of Italy with around 4 million inhabitants. Its main objective is to describe the allergic safety profile of currently employed vaccines.

Materials and methods

This is a retrospective observational study. The study period spanned from January 2020 to December 2021, and the whole Apulian population was included in the study. Information regarding AEFIs reported in Puglia during the study period was gathered from the Italian Drug Authority’s pharmacovigilance database (National Pharmacovigilance Network, RNF). The overall number of vaccine doses administered was extrapolated by the Apulian online immunization database (GIAVA). Reporting rates were calculated as AEFIs reported during a certain time span/number of vaccine doses administered during the same period.

Results

10,834,913 vaccine doses were administered during the study period and 95 reports of allergic AEFIs were submitted to the RNF (reporting rate 0.88/100,000 doses). 27.4% of the reported events (26/95) were classified as serious (reporting rate 0.24/100,000 doses). 68 out of 95 (71.6%) adverse events were at least partially resolved by the time of reporting and none of them resulted in the subject’s death.

Conclusions

Allergic reactions following vaccination were rare events, thus confirming the favourable risks/benefits ratio for currently marketed vaccines.
Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation
Authors: Pinto Noy , Klein Yehuda , David Eilon , Polak David , Steinberg Daniel , Mizrahi Gilad , Khoury Yasmin , Barenholz Yechezkel , Chaushu Stella
Published: February 2023

Introduction

Allografts are the most common bone grafts for repairing osseous defects. However, their use is associated with an increased risk for infections, donor disease transmission and osteointegration deficiency. Resolvin D1 (RvD1) is an endogenous lipid with a scientifically proven pivotal role in inflammation resolution and osteoclastogenesis inhibition. Yet, its biological relevance as a potential bone regenerative drug has been scarcely studied. Here, we aim to investigate the RvD1 effect on allograft osteointegration in the alveolar bone regeneration (ABR) murine model.

Methods

ABR model consisted of osseous defects that were generated by the extraction of the maxillary first molar in C57BL/6 mice. The sockets were filled with allograft and analyzed via RNA sequencing. Then they were locally injected with either RvD1 or saline via single or repeated administrations. The mice were sacrificed 2W after the procedure, and regenerated sites were analyzed using µCT and histology. First, MC3T3-E1 preosteoblasts were plated with IL-17 pro-inflammatory medium, and RANKL/OPG ratio was measured. Secondly, the MC3T3-E1 were cultured w/o RvD1, for 3W. Osteoblasts’ markers were evaluated in different days, using qRT-PCR and Alizarin Red staining for calcified matrix.

Results

In vivo, neither allograft alone nor single RvD1 administration promote bone regeneration in comparison to the control of spontaneous healing and even triggered an elevation in NR1D1 and IL1RL1 expression, markers associated with inflammation and inhibition of bone cell differentiation. However, repeated RvD1 treatment increased bone content by 135.92% ± 45.98% compared to its specific control, repeated sham, and by 39.12% ± 26.3% when compared to the spontaneous healing control group (n=7/group). Histologically, repeated RvD1 reduced the number of TRAP-positive cells, and enhanced allograft osteointegration with new bone formation. In vitro, RvD1 rescued OPG expression and decreased RANKL/OPG ratio in IL-17 pro-inflammatory conditions. Furthermore, RvD1 increased the expression of RUNX2, OSX, BSP and OC/BGLAP2 and the mineralized extracellular matrix during MC3T3-E1 osteoblasts differentiation.

Conclusions

Repeated administrations of RvD1 promote bone regeneration via a dual mechanism: directly, via enhancement of osteoblasts’ differentiation and indirectly, through reduction of osteoclastogenesis and RANKL/OPG ratio. This suggests that RvD1 may be a potential therapeutic bioagent for osseous regeneration following allograft implantation.
CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression
Authors: Yang Dianyin , Zhao Dongyang , Ji Jinlu , Wang Chunxue , Liu Na , Bao Xiaowei , Liu Xiandong , Jiang Sen , Zhang Qianqian , Tang Lunxian
Published: February 2023

Introduction

Circular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown.

Methods

In this study, we screened the differentially expressed circRNAs among the healthy individuals, pneumonia patients without sepsis and pneumonia-induced sepsis patients in the plasma by RNA sequencing (RNA-seq). Then we evaluated macrophage pyroptosis in sepsis patients and in vitro LPS/nigericin activated THP-1 cells. The lentiviral recombinant vector for circ_0075723 overexpression (OE-circ_0075723) and circ_0075723 silence (sh-circ_0075723) were constructed and transfected into THP-1 cells to explore the potential mechanism of circ_0075723 involved in LPS/nigericin induced macrophage pyroptosis.

Results

We found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and protects endothelial cell integrity.

Discussion

Our findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis.
Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells
Authors: Barbieri Laura , Veliça Pedro , Gameiro Paulo A. , Cunha Pedro P. , Foskolou Iosifina P. , Rullman Eric , Bargiela David , Johnson Randall S. , Rundqvist Helene
Published: February 2023

Introduction

CD8+ T cells infiltrate virtually every tissue to find and destroy infected or mutated cells. They often traverse varying oxygen levels and nutrient-deprived microenvironments. High glycolytic activity in local tissues can result in significant exposure of cytotoxic T cells to the lactate metabolite. Lactate has been known to act as an immunosuppressor, at least in part due to its association with tissue acidosis.

Methods

To dissect the role of the lactate anion, independently of pH, we performed phenotypical and metabolic assays, high-throughput RNA sequencing, and mass spectrometry, on primary cultures of murine or human CD8+ T cells exposed to high doses of pH-neutral sodium lactate.

Results

The lactate anion is well tolerated by CD8+ T cells in pH neutral conditions. We describe how lactate is taken up by activated CD8+ T cells and can displace glucose as a carbon source. Activation in the presence of sodium lactate significantly alters the CD8+ T cell transcriptome, including the expression key effector differentiation markers such as granzyme B and interferon-gamma.

Discussion

Our studies reveal novel metabolic features of lactate utilization by activated CD8+ T cells, and highlight the importance of lactate in shaping the differentiation and activity of cytotoxic T cells.
Unisexual infection with Schistosoma mansoni in mice has the potential to boost the immune response against eggs after challenge infection
Authors: Reinholdt Cindy , Winkelmann Franziska , Koslowski Nicole , Reisinger Emil C. , Sombetzki Martina
Published: February 2023

Introduction

The complexity of the Schistosoma spp. life cycle and their effective immune evasion strategies, makes vaccine development challenging. Unisexual infection models, that excludes any immunomodulatory effects of the parasite eggs, may contribute to a better understanding of complex immunological processes and identification of new targets for vaccine research. We have recently shown that long-term unisexual infection with schistosomes in mice results in an unpolarized Th1/Th2 response associated with an abnormally enlarged spleen and diffuse liver inflammation. Herein, we investigated whether (i) unisexual worms can mate after three months of single sex infection and (ii) thus the Th2 response induced by oviposition can reverse or heal the described systemic inflammation.

Methods

Therefore, we infected 6–8 weeks old female C57BL/6j mice with 100 male or female cercariae and reinfected with the opposite sex for the same period after 12 weeks. At 24 weeks after initial infection, we histologically examined worm mating, as evidenced by the presence of parasite eggs, infection-related pathology associated with eggs, and characterization of fibrosis in the livers.

Results

Single worms are able to mate months after unisexual infection and start oviposition. Egg deposition has been associated with a typical Th2 immune response in the liver after unisexual reinfection, accompanied by increased recruitment of CD4+ T cells. Hepatic collagen levels were significantly increased in the reinfected groups compared to the naive and unisexually infected group.

Discussion

Our results indicate that the eggs are able to restore the Th1/Th2 immune balance of a previous unisexual infection. However, the organ damage caused by the unisexual worms does not subside, but rather provides the baseline for the emerging egg-triggered inflammation and fibrosis. Since single schistosomes can mate even several weeks after unisexual infection and then accumulate worm- and egg-related organ damage, infection status without positive egg detection is very important, especially in areas with low prevalence.
MODIS-derived green Noctiluca blooms in the upper Gulf of Thailand: Algorithm development and seasonal variation mapping
Authors: Luang-on Jutarak , Ishizaka Joji , Buranapratheprat Anukul , Phaksopa Jitraporn , Goes Joaquim I. , Maúre Elígio de Raús , Siswanto Eko , Zhu Yuanli , Xu Qian , Nakornsantiphap Phattaranakorn , Kobayashi Hiroshi , Matsumura Satsuki
Published: February 2023

In recent decades, red tides of non-toxic harmful algal blooms have frequently occurred in monsoon-influenced tropical areas, particularly the green form of Noctiluca scintillans (hereafter green Noctiluca). However, our understanding of the mechanism of red tide formation is hindered by spatial and temporal constraints of field data. In this study, we used moderate resolution imaging spectroradiometer (MODIS) ocean color data along with a locally developed algal-bloom classification algorithm to investigate the seasonal variability of dominant red tides across the upper Gulf of Thailand (uGoT). During our July 2018 observation, a super green Noctiluca bloom with extraordinarily high chl-a (>1,469 mg m-3) displayed a distinct spectral reflectance characteristic among red tides in blue-to-green and red-to-near infrared wavelengths. According to the distinctive in situ hyperspectral characteristics of uGoT algal blooms, we developed a classification algorithm for MODIS normalized at 488, 531, and 667 nm, which successfully discriminated green Noctiluca in three levels of blooms, namely, super (100%), strong (>80%), and weak (>40%), from other algal blooms (i.e., dinoflagellates, diatoms, cyanobacteria, and mixed red tide species) as well as non-bloom oceanic and coastal waters using MODIS data, as confirmed by uGoT red tide reports. Monthly MODIS-based discrimination composites from 2003 to 2021 revealed seasonal variability in the surface distribution and bloom frequency of green Noctiluca and other red tides according to the Asian monsoon seasons: the southwest monsoon (May–September) and the northeast monsoon (October–January of the following year). Green Noctiluca blooms occurred farther from the shore and estuaries than other red tides (dinoflagellates and cyanobacteria), and were much more frequent than other red tides between the Tha Chin and Chao Phraya River mouths during the non-monsoon period (February to April). The frequency and distribution of green Noctiluca blooms, as well as other algal blooms, varied with the monsoon season. By comparing MODIS-derived algal blooms to monsoon-induced factors (i.e., sea surface winds, precipitation, and river discharge), we present an unprecedented overview of the spatial and temporal dynamics of red tides throughout the uGoT under Asian monsoon conditions. This research contributes to our understanding of the impact of climate change on phytoplankton dynamics.
The oxygen dissociation curve of blood in COVID-19–An update
Authors: Böning Dieter , Kuebler Wolfgang M. , Vogel Dominik , Bloch Wilhelm
Published: February 2023

An impressive effect of the infection with SARS-Co-19 is the impairment of oxygen uptake due to lung injury. The reduced oxygen diffusion may potentially be counteracted by an increase in oxygen affinity of hemoglobin. However, hypoxia and anemia associated with COVID-19 usually decrease oxygen affinity due to a rise in [2,3-bisphosphoglycerate]. As such, COVID-19 related changes in the oxygen dissociation curve may be critical for oxygen uptake and supply, but are hard to predict. A Pubmed search lists 14 publications on oxygen affinity in COVID-19. While some investigations show no changes, three large studies found an increased affinity that was related to a good prognosis. Exact causes remain unknown. The cause of the associated anemia in COVID-19 is under discussion. Erythrocytes with structural alterations of membrane and cytoskeleton have been observed, and virus binding to Band 3 and also to ACE2 receptors in erythroblasts has been proposed. COVID-19 presentation is moderate in many subjects suffering from sickle cell disease. A possible explanation is that COVID-19 counteracts the unfavorable large right shift of the oxygen dissociation curve in these patients. Under discussion for therapy are mainly affinity-increasing drugs.
Multidrug resistance in Helicobacter pylori infection
Authors: Dascălu Raluca Ioana , Bolocan Alexandra , Păduaru Dan Nicolae , Constantinescu Alexandru , Mitache Magda Mihaela , Stoica Anca Daniela , Andronic Octavian
Published: February 2023

Helicobacter pylori (Hp), a well-known human pathogen, causes one of the most common chronic bacterial infections and plays an important role in the emergence of chronic progressive gastric inflammation and a variety of gastrointestinal diseases. The prevalence of Hp infection varies worldwide and is indirectly proportional to socio-economic status, especially during childhood. The response to the eradication therapy significantly depends on the antibiotic resistance specific to each geographical region; thus, currently, given the increasing prevalence of antimicrobial resistance (especially to clarithromycin, metronidazole, and levofloxacin), successful treatment for Hp eradication has become a real challenge and a critical issue. The most incriminated factors associated with multidrug resistance (MDR) in Hp proved to be the overuse or the improper use of antibiotics, poor medication adherence, and bacterial-related factors including efflux pumps, mutations, and biofilms. Up to 30% of first-line therapy fails due to poor patient compliance, high gastric acidity, or high bacteremia levels. Hence, it is of great importance to consider new eradication regimens such as vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, requiring further studies and thorough assessment. Strain susceptibility testing is also necessary for an optimal approach.
A genome–wide CRISPR activation screen identifies SCREEM a novel SNAI1 super-enhancer demarcated by eRNAs
Authors: Uthaya Kumar Dinesh Babu , Yurieva Marina , Grassmann Jessica , Kozhaya Lina , McBride Caleb Dante , Unutmaz Derya , Williams Adam
Published: February 2023

The genome is pervasively transcribed to produce a vast array of non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides and are best known for their ability to regulate gene expression. Enhancer RNAs (eRNAs) are subclass of lncRNAs that are synthesized from enhancer regions and have also been shown to coordinate gene expression. The biological function and significance of most lncRNAs and eRNAs remain to be determined. Epithelial to mesenchymal transition (EMT) is a ubiquitous cellular process that occurs during cellular migration, homeostasis, fibrosis, and cancer-cell metastasis. EMT-transcription factors, such as SNAI1 induce a complex transcriptional program that coordinates the morphological and molecular changes associated with EMT. Such complex transcriptional programs are often subject to coordination by networks of ncRNAs and thus can be leveraged to identify novel functional ncRNA loci. Here, using a genome-wide CRISPR activation (CRISPRa) screen targeting ∼10,000 lncRNA loci we identified ncRNA loci that could either promote or attenuate EMT. We discovered a novel locus that we named SCREEM (SNAI1 cis-regulatory eRNAs expressed in monocytes). The SCREEM locus contained a cluster of eRNAs that when activated using CRISPRa induced expression of the neighboring gene SNAI1, driving concomitant EMT. However, the SCREEM eRNA transcripts themselves appeared dispensable for the induction of SNAI1 expression. Interestingly, the SCREEM eRNAs and SNAI1 were co-expressed in activated monocytes, where the SCREEM locus demarcated a monocyte-specific super-enhancer. These findings suggest a potential role for SNAI1 in monocytes. Exploration of the SCREEM-SNAI axis could reveal novel aspects of monocyte biology.
The ventrolateral prefrontal cortex is part of the modular working memory system: A functional neuroanatomical perspective
Authors: Segal Orin , Elkana Odelia
Published: February 2023

For many years, the functional role of the ventrolateral Pre-Frontal Cortex (PFC) was associated with executive functions, specifically in the context of non-affective cognitive processes. However, recent research has suggested that the ventrolateral PFC is also involved in the attention system. The Ben Shalom model of the functional organization of the prefrontal cortex (2019) posits that the ventrolateral PFC selects perceptual stimuli after integration by the adjacent ventromedial PFC. This article reviews the state-of-the-art findings to better understand the role of the ventrolateral PFC in the selection of perceptual information as grounded in the Ben Shalom model. Numerous studies have reported converging evidence for the selective role of this area. However, most argue that this perceptual selection takes place through the active updating of information values linked to goal-oriented actions. These studies thus view the ventrolateral PFC as part of a system that actively manipulates and changes processed information such as the working memory function, rather than being part of the attention system. In agreement with this view, this review suggests that this area is part of a complex and modular working memory system and illustrates with reference to Diamond’s work on ADD. This working memory system is functionally and anatomically dispersed and includes the dorsolateral PFC, the ACC, the parietal cortex, the basal ganglia, and the cerebellum. Hence, future research should continue to explore the specific neurofunctional roles of these areas in working memory systems, and the connections between the different subareas in this complex array.
Comparison of the efficacy of the Epley maneuver and repeated Dix–Hallpike tests for eliminating positional nystagmus: A multicenter randomized study
Authors: Imai Takao , Uno Atsuhiko , Yamato Akiyuki , Takimoto Yasumitsu , Sato Go , Matsuda Kazunori , Takeda Noriaki , Nishiike Suetaka , Kawashima Kayoko , Iga Tomoko , Ueno Yuya , Ohta Yumi , Sato Takashi , Kamakura Takefumi , Shingai-Higashi Kayoko , Mikami Shinji , Kimura Naomiki , Nakajima Takashi , Tanaka Akihisa , Inohara Hidenori
Published: February 2023

Background and objectives

Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix–Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week.

Methods

This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%.

Results

Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin.

Discussion

This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living.

Classification of evidence

This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week.

Registration number

UMIN000016421.
FMRI study of implicit emotional face processing in patients with MDD with melancholic subtype
Authors: Kustubayeva Almira , Eliassen James , Matthews Gerald , Nelson Erik
Published: February 2023

Introduction

The accurate perception of facial expressions plays a vital role in daily life, allowing us to select appropriate responses in social situations. Understanding the neuronal basis of altered emotional face processing in patients with major depressive disorder (MDD) may lead to the appropriate choice of individual interventions to help patients maintain social functioning during depressive episodes. Inconsistencies in neuroimaging studies of emotional face processing are caused by heterogeneity in neurovegetative symptoms of depressive subtypes. The aim of this study was to investigate brain activation differences during implicit perception of faces with negative and positive emotions between healthy participants and patients with melancholic subtype of MDD. The neurobiological correlates of sex differences of MDD patients were also examined.

Methods

Thirty patients diagnosed with MDD and 21 healthy volunteers were studied using fMRI while performing an emotional face perception task.

Results

Comparing general face activation irrespective of emotional content, the intensity of BOLD signal was significantly decreased in the left thalamus, right supramarginal gyrus, right and left superior frontal gyrus, right middle frontal gyrus, and left fusiform gyrus in patients with melancholic depression compared to healthy participants. We observed only limited mood-congruence in response to faces of differing emotional valence. Brain activation in the middle temporal gyrus was significantly increased in response to fearful faces in comparison to happy faces in MDD patients. Elevated activation was observed in the right cingulate for happy and fearful faces, in precuneus for happy faces, and left posterior cingulate cortex for all faces in depressed women compared to men. The Inventory for Depressive Symptomatology (IDS) score was inversely correlated with activation in the left subgenual gyrus/left rectal gyrus for sad, neutral, and fearful faces in women in the MDD group. Patients with melancholic features performed similarly to controls during implicit emotional processing but showed reduced activation.

Discussion and conclusion

This finding suggests that melancholic patients compensate for reduced brain activation when interpreting emotional content in order to perform similarly to controls. Overall, frontal hypoactivation in response to implicit emotional stimuli appeared to be the most robust feature of melancholic depression.
Advances in neurexin studies and the emerging role of neurexin-2 in autism spectrum disorder
Authors: Khoja Sheraz , Haile Mulatwa T. , Chen Lulu Y.
Published: February 2023

Over the past 3 decades, the prevalence of autism spectrum disorder (ASD) has increased globally from 20 to 28 million cases making ASD the fastest-growing developmental disability in the world. Neurexins are a family of presynaptic cell adhesion molecules that have been increasingly implicated in ASD, as evidenced by genetic mutations in the clinical population. Neurexins function as context-dependent specifiers of synapse properties and critical modulators in maintaining the balance between excitatory and inhibitory transmission (E/I balance). Disrupted E/I balance has long been established as a hallmark of ASD making neurexins excellent starting points for understanding the etiology of ASD. Herein we review neurexin mutations that have been discovered in ASD patients. Further, we discuss distinct synaptic mechanisms underlying the aberrant neurotransmission and behavioral deficits observed in different neurexin mouse models, with focus on recent discoveries from the previously overlooked neurexin-2 gene (Nrxn2 in mice and NRXN2 in humans). Hence, the aim of this review is to provide a summary of new synaptic insights into the molecular underpinnings of ASD.
Transparency – a patient-centric view on radiopharmaceutical extravasations
Authors: Kohl Pam
Published: February 2023

Most radiopharmaceuticals are intravenously administered during nuclear medicine imaging or therapy procedures. When a nuclear medicine clinician delivers some or all of a radioactive drug into a patient's healthy tissue rather than the vein as intended, a patient experiences an extravasation. Radiopharmaceutical extravasations provide zero patient benefit and considerable potential downsides, depending on the severity of the extravasations. What nuclear medicine patients want and need regarding the administration of radiopharmaceuticals is transparency. And yet in the year 2023, little transparency exists regarding these extravasations. From the patient perspective, transparency regarding extravasations is essential to improving care, ensuring radiation protection, reducing health inequities, and untangling the deeply disturbing and irregular relationship between the nuclear medicine community and their regulating body, The U.S. Nuclear Regulatory Commission. Transparency is also critical to help address many other questions regarding radiopharmaceutical extravasations.
TRIM37 interacts with PTEN to promote the growth of human T-cell acute lymphocytic leukemia cells through regulating PI3K/AKT pathway
Authors: Qu Honglan , Gao-wa HASEN , Hou Yanyan , Ren Mengwei , Li Jun , Jing Baoshong , Du YanDan
Published: February 2023

Background

TRIM37 has been reported to be associated with the tumorigenesis of cancers. However, the role of TRIM37 in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. This study aimed to characterize the effect of TRIM37 on T-ALL.

Methods

TRIM37 expression in T-ALL patients and T-ALL cell lines was determined by qRT-PCR and Western blot. Knockdown or overexpression of TRIM37 was conducted by transferring small-interfering TRIM37 or lentivirus-mediated transducing into T-ALL cells. CCK-8 assay and flow cytometry assay were conducted to analyze the proliferation and apoptosis of T-ALL cells. Co-immunoprecipitation experiments were conducted to investigate the relationship between TRIM37 and PTEN and the ubiquitination of PTEN.

Results

Our results suggested that TRIM37 expression was upregulated in the blood of T-ALL patients and T-ALL cell lines. Knockdown of TRIM37 noticeably inhibited the proliferation and promoted apoptosis of T-ALL cells. Ectopic expression of TRIM37 promoted the proliferation and suppressed the apoptosis rate of MOLT-4 cells and enhanced the phosphorylation of AKT. Moreover, TRIM37 interacted with PTEN and accelerated the degradation of PTEN via TRIM37-mediated ubiquitination in T-ALL cells. Moreover, TRIM37 reduced the sensitivity of T-ALL cells to bortezomib treatment. Additionally, PI3K/AKT signaling pathway was involved in the function of TRIM37 in T-ALL. TRIM37 contributed to the proliferation of T-ALL cells and reduced the susceptibility of T-ALL cells to bortezomib treatment through ubiquitination of PTEN and activating PI3K/AKT signaling pathway.

Conclusions

Our study suggested that TRIM37 could be considered as a therapeutic target for T-ALL.
Risk factor analysis and construction of prediction models of gallbladder carcinoma in patients with gallstones
Authors: Zhu Zhencheng , Luo Kunlun , Zhang Bo , Wang Gang , Guo Ke , Huang Pin , Liu Qiuhua
Published: February 2023

Background

Gallbladder carcinoma (GBC) is a biliary tract tumor with a high mortality rate. The objectives of this study were to explore the risk factors of GBC in patients with gallstones and to establish effective screening indicators.

Methods

A total of 588 patients from medical centers in two different regions of China were included in this study and defined as the internal test samples and the external validation samples, respectively. We retrospectively reviewed the differences in clinicopathologic data of the internal test samples to find the independent risk factors that affect the occurrence of GBC. Then, we constructed three different combined predictive factors (CPFs) through the weighting method, integral system, and nomogram, respectively, and named them CPF-A, CPF-B, and CPF-C sequentially. Furthermore, we evaluated these indicators through calibration and DCA curves. The ROC curve was used to analyze their diagnostic efficiency. Finally, their diagnostic capabilities were validated in the external validation samples.

Results

In the internal test samples, the results showed that five factors, namely, age (RR = 3.077, 95% CI: 1.731-5.496), size of gallstones (RR = 13.732, 95% CI: 5.937-31.762), course of gallstones (RR = 2.438, 95% CI: 1.350-4.403), CEA (RR = 9.464, 95% CI: 3.394-26.392), and CA199 (RR = 9.605, 95% CI: 4.512-20.446), were independent risk factors for GBC in patients with gallstones. Then, we established three predictive indicators: CPF-A, CPF-B, and CPF-C. These models were further validated using bootstrapping with 1,000 repetitions. Calibration and decision curve analysis showed that the three models fit well. Meanwhile, multivariate analysis showed that CPF-B and CPF-C were independent risk factors for GBC in patients with gallstones. In addition, the validation results of the external validation samples are essentially consistent with the internal test samples.

Conclusion

Age (≤58.5 vs. >58.5 years), size of gallstones (≤1.95 vs. >1.95cm), course of gallstones (≤10 vs. >10 years), CEA (≤5 vs. >5 ng/ml), and CA199 (≤37 vs. >37 U/ml) are independent risk factors for GBC in patients with gallstones. When positive indicators were ≥2 among the five independent risk factors or the score of the nomogram was >82.64, the risk of GBC was high in gallstone patients.
Zinc finger and SCAN domain containing 1, ZSCAN1, is a novel stemness-related tumor suppressor and transcriptional repressor in breast cancer targeting TAZ
Authors: Chu Jian , Li Yunzhe , He Misi , Zhang Hui , Yang Lingling , Yang Muyao , Liu Jingshu , Cui Chenxi , Hong Liquan , Hu Xingchi , Zhou Lei , Li Tangya , Li Changchun , Fan Huiwen , Jiang Guoqin , Lang Tingyuan
Published: February 2023

Introduction

Cancer stem cells (CSCs) targeted therapy holds the potential for improving cancer management; identification of stemness-related genes in CSCs is necessary for its development.

Methods

The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were used for survival analysis. ZSCAN1 correlated genes was identified by Spearman correlation analysis. Breast cancer stem-like cells (BCSLCs) were isolated by sorting CD44+CD24- cells from suspension cultured breast cancer (BC) spheroids. The sphere-forming capacity and sphere- and tumor-initiating capacities were determined by sphere formation and limiting dilution assays. The relative gene expression was determined by qRT-PCR, western blot. Lentivirus system was used for gene manipulation. Nuclear run-on assay was employed to examine the levels of nascent mRNAs. DNA pull-down and Chromatin immunoprecipitation (ChIP) assays were used for determining the interaction between protein and target DNA fragments. Luciferase reporter assay was used for evaluating the activity of the promoter.

Results and discussion

ZSCAN1 is aberrantly suppressed in BC, and this suppression indicates a bad prognosis. Ectopic expression of ZSCAN1 inhibited the proliferation, clonogenicity, and tumorigenicity of BC cells. ZSCAN1-overexpressing BCSLCs exhibited weakened stemness properties. Normal human mammary epithelial (HMLE) cells with ZSCAN1 depletion exhibited enhanced stemness properties. Mechanistic studies showed that ZSCAN1 directly binds to -951 ~ -925bp region of WWTR1 (encodes TAZ) promoter, inhibits WWTR1 transcription, thereby inhibiting the stemness of BCSCs. Our work thus revealed ZSCAN1 as a novel stemness-related tumor suppressor and transcriptional repressor in BC.