bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern methods in vital signs monitoring
Authors:   , van Goor Harriëtte Margaretha Rosalie
Published: April 2023

Vital signs provide an indication of the patient's health and stability. Technological innovation, which has been boosted by the COVID-19 pandemic, creates the possibility to measure vital parameters continuously and remotely, without restricting the patient's mobility. Consequently, deterioration might be seen earlier than with current intermittent measurements. In this thesis we highlight several aspects of these modern methods of measurement. In the first part we show that a circadian rhythm can be seen in the continuously measured data, and explore how continuous data can best be summarized. Both aspects are important for the interpretation of the data and for use in prediction models. The second part shows that there is currently still a lot of variation in how doctors and nurses interpret continuous data. In addition to training, the aforementioned prediction models could help to achieve a more standardized assessment. Furthermore, we show that the use of continuous monitoring does not result in less patient visits by nurses, even though they can assess vital signs remotely. In the last part, we describe a randomized trial of a common intervention during the pandemic: hospital care at home assisted by remote monitoring. We could not demonstrate a clear gain in number of days at home in this study. Notably, only a small proportion of the patients were eligible and wanted to participate. In the last study we therefore focus on developing a similar intervention for internal medicine patients with an infection. We explore for which group of patients this could be a valuable intervention, and what care is needed to make it successful. In the discussion, reflections on the studies in this dissertation and suggestions for future research and interventions are discussed. Important points that emerge regarding continuous monitoring are: 1). Aspects of data that a predictive algorithm should take into account. 2). Ways to improve the interpretation by healthcare providers. 3). How continuous monitoring can be integrated into daily practice at the ward. Regarding hospital care at home using remote monitoring, the following topics are discussed: 1). The selection of the right patient population. 2). Providing the right intervention for the right patient population. 3). Considerations involving effectiveness and costs. Important research questions that will need to be answered in the future are discussed in the last part. Ultimately, modern vital signs measurement methods can help bring the patient even further to the center of care.
Mechanically induced alterations in chromatin architecture guide the balance between cell plasticity and mechanical memory
Authors: Scott Adrienne K. , Rafuse Michael , Neu Corey P.
Published: April 2023

Phenotypic plasticity, or adaptability, of a cell determines its ability to survive and function within changing cellular environments. Changes in the mechanical environment, ranging from stiffness of the extracellular matrix (ECM) to physical stress such as tension, compression, and shear, are critical environmental cues that influence phenotypic plasticity and stability. Furthermore, an exposure to a prior mechanical signal has been demonstrated to play a fundamental role in modulating phenotypic changes that persist even after the mechanical stimulus is removed, creating stable mechanical memories. In this mini review, our objective is to highlight how the mechanical environment alters both phenotypic plasticity and stable memories through changes in chromatin architecture, mainly focusing on examples in cardiac tissue. We first explore how cell phenotypic plasticity is modulated in response to changes in the mechanical environment, and then connect the changes in phenotypic plasticity to changes in chromatin architecture that reflect short-term and long-term memories. Finally, we discuss how elucidating the mechanisms behind mechanically induced chromatin architecture that lead to cell adaptations and retention of stable mechanical memories could uncover treatment methods to prevent mal-adaptive permanent disease states.
Vestibular physiology and function in zebrafish
Authors: Baeza-Loya Selina , Raible David W.
Published: April 2023

The vestibular system of the inner ear provides information about head motion and spatial orientation relative to gravity to ensure gaze stability, balance, and postural control. Zebrafish, like humans, have five sensory patches per ear that serve as peripheral vestibular organs, with the addition of the lagena and macula neglecta. The zebrafish inner ear can be easily studied due to its accessible location, the transparent tissue of larval fish, and the early development of vestibular behaviors. Thus, zebrafish are an excellent model for studying the development, physiology, and function of the vestibular system. Recent work has made great strides to elucidate vestibular neural circuitry in fish, tracing sensory transmission from receptors in the periphery to central computational circuits driving vestibular reflexes. Here we highlight recent work that illuminates the functional organization of vestibular sensory epithelia, innervating first-order afferent neurons, and second-order neuronal targets in the hindbrain. Using a combination of genetic, anatomical, electrophysiological, and optical techniques, these studies have probed the roles of vestibular sensory signals in fish gaze, postural, and swimming behaviors. We discuss remaining questions in vestibular development and organization that are tractable in the zebrafish model.
Prevalence and molecular characteristics of polymyxin-resistant Enterobacterales in a Chinese tertiary teaching hospital
Authors: Xiao Chenlu , Li Xuming , Huang Lianjiang , Cao Huiluo , Han Lizhong , Ni Yuxing , Xia Han , Yang Zhitao
Published: April 2023

Introduction

Polymyxin-resistant Enterobacterales poses a significant threat to public health globally, but its prevalence and genomic diversity within a sole hospital is less well known. In this study, the prevalence of polymyxin-resistant Enterobacterales in a Chinese teaching hospital was investigated with deciphering of their genetic determinants of drug resistance.

Methods

Polymyxin-resistant Enterobacterales isolates identified by matrix-assisted laser desorption were collected in Ruijin Hospital from May to December in 2021. Both the VITEK 2 Compact and broth dilution methods were used to determine polymyxin B (PMB) susceptibility. Polymyxin-resistant isolates were further characterized by molecular typing using PCR, multi-locus sequence typing, and sequencing of the whole genome.

Results

Of the 1,216 isolates collected, 32 (2.6%) across 12 wards were polymyxin-resistant (minimum inhibitory concentration (MIC) range, PMB 4–256 mg/ml, and colistin 4 ≥ 16 mg/ ml). A total of 28 (87.5%) of the polymyxin-resistant isolates had reduced susceptibility to imipenem and meropenem (MIC ≥ 16 mg/ml). Of the 32 patients, 15 patients received PMB treatment and 20 survived before discharge. The phylogenetic tree of these isolates showed they belonged to different clones and had multiple origins. The polymyxin-resistant Klebsiella pneumoniae isolates belonged to ST-11 (85.72%), ST-15 (10.71%), and ST-65 (3.57%), and the polymyxin-resistant Escherichia coli belonged to four different sequence types, namely, ST-69 (25.00%), ST-38 (25.00%), ST-648 (25.00%), and ST-1193 (25.00%). In addition, six mgrB specific mutations (snp_ALT c.323T>C and amino acid change p.Val8Ala) were identified in 15.6% (5/32) of the isolates. mcr-1, a plasmid-mediated polymyxin-resistant gene, was found in three isolates, and non-synonymous mutations including T157P, A246T, G53V, and I44L were also observed.

Discussion

In our study, a low prevalence of polymyxin-resistant Enterobacterales was observed, but these isolates were also identified as multidrug resistant. Therefore, efficient infection control measures should be implemented to prevent the further spread of resistance to last-line polymyxin therapy.
TimeTeller for timing health: The potential of circadian medicine to improve performance, prevent disease and optimize treatment
Authors: Dose Benjamin , Yalçin Müge , Dries Sebastian P. M. , Relógio Angela
Published: April 2023

Circadian medicine, the study of the effects of time on health and disease has seen an uprising in recent years as a means to enhance health and performance, and optimize treatment timing. Our endogenous time generating system -the circadian clock- regulates behavioural, physiological and cellular processes. Disruptions of the clock, via external factors like shift work or jet lag, or internal perturbations such as genetic alterations, are linked to an increased risk of various diseases like obesity, diabetes, cardiovascular diseases and cancer. By aligning an individual's circadian clock with optimal times for performing daily routines, physical and mental performance, and also the effectiveness of certain therapies can be improved. Despite the benefits of circadian medicine, the lack of non-invasive tools for characterizing the clock limits the potential of the field. TimeTeller is a non-invasive molecular/digital tool for the characterization of circadian rhythms and prediction of daily routines, including treatment timing, to unlock the potential of circadian medicine and implementing it in various settings. Given the multiple known and potentially yet unknown dependent health factors of individual circadian rhythms, the utility of this emerging biomarker is best exploited in data driven, personalized medicine use cases, using health information across lifestyle, care, and research settings.
Internal structure and water routing of an ice-debris landform assemblage using multiple geophysical methods in the semiarid Andes
Authors: Navarro Gonzalo , Valois Rémi , MacDonell Shelley , de Pasquale Giulia , Díaz Juan Pablo
Published: April 2023

Rock glaciers are the most abundant (peri) glacial landform in the semiarid Andes (SA, 29–34°S), covering about three times the area of mountain glaciers. Recent studies suggest they may play an important hydrological role, including generating, storing and routing water. However, processes governing these roles are still poorly known especially for glacier complex units, i.e., where there is a juxtaposition or continuity of different (peri) glacial landforms, which are common in semiarid Andean and Himalayan areas. This study aims to understand how the internal structure of an ice-debris landform assemblage controls hydrological routing. To address this aim, we used a combination of three geophysical techniques to qualitatively determine the internal structure and favourable water routing and storage zones at the Tapado glacier complex (30°S), Chile. The Tapado glacier complex consists of an assemblage of a debris-free glacier, a debris-covered glacier and two rock glaciers. For the purpose of this study, we focused on the debris-covered and active rock glacier connection. At this site, the debris-covered glacier has a relatively thin debris-cover that increases thickness downglacier. This debris cover connects to the active rock glacier and forms the active layer. The rock glacier contains a heterogenous internal structure consisting of debris with water or segregated ice filling the voids, which likely derives from the massive ice of the debris-covered glacier. The superficial debris layer of the ice-debris landforms may act as a transmissive medium by routing water downstream above the massive ice of the debris-covered glacier, but also into deeper areas, as intra-permafrost flow, in the rock glacier. The rock glacier likely has a higher capacity to transmit vertical and horizontal flows, thereby enhancing infiltration processes. This study reinforces the value of geophysical methods to determine the internal structure of ice-debris landforms, particularly in the transition between landforms, and highlights how a warming climate and consequent paraglacial processes will impact the hydrological system not only in terms of water storage, but also water transfer.
Distinct modes of meltwater drainage and landform development beneath the last Barents Sea ice sheet
Authors: Shackleton Calvin , Patton Henry , Winsborrow Monica , Esteves Mariana , Bjarnadóttir Lilja , Andreassen Karin
Published: April 2023

The flow of glacial ice is impacted by basal meltwater drainage systems that fluctuate on a continuum from distributed, high-pressure environments to channelized, lower pressure networks. Understanding the long-term development of dominant drainage modes and impacts on ice flow and landform development is a crucial step in predicting palaeo and contemporary ice-mass response to changes in climate. The spatial and temporal scales at which different drainage modes operate are largely unknown, and the geomorphological legacy of subglacial meltwater networks that evolve over a glaciation provide composite records of drainage system development. Here, we use high-resolution bathymetric data from shallow banks in the central Barents Sea to map the geomorphological imprint of meltwater drainage beneath the collapsing marine-based Barents Sea Ice Sheet (BSIS). We observe a succession of distinct meltwater landforms that provide relative timing constraints for subglacial drainage modes, indicating that extensive networks of channelized drainage were in operation during deglaciation. Interlinked basins and channels suggest that meltwater availability and drainage system development was influenced by filling and draining cycles in subglacial lakes. Networks of eskers also indicate near-margin meltwater conduits incised into basal ice during late-stage deglaciation, and we suggest that these systems were supplemented by increased inputs from supraglacial melting. The abundance of meltwater during the late stages of BSIS deglaciation likely contributed to elevated erosion of the sedimentary substrate and the mobilisation of subglacial sediments, providing a sediment source for the relatively abundant eskers found deposited across bank areas. A newly discovered beaded esker system over 67 km long in Hopendjupet constrains a fluctuating, but generally decelerating, pace of ice retreat from ∼1,600 m a−1 to ∼620 m a−1 over central Barents Sea bank areas during a 91-year timespan.
Multiproxy analyses of paleoenvironmental and paleoceanographic changes during the Danian-Selandian in East Central Sinai: An integrated stable isotope and planktic foraminiferal data
Authors: Farouk Sherif , Jain Sreepat , Ahmad Fayez , Abu-Alam Tamer , Al-Kahtany Khaled , El Agroudy Ibrahim S. , Bazeen Youssef S. , Shaker Fatma
Published: April 2023

Forty-three planktic foraminifera samples from the Themed section (East Central Sinai; Egypt) spanning the Zone Parvularugoglobigerina eugubina (Pα) to the Subzone Acarinina subsphaerica (P4b) have been studied. Data from δ13C, δ18O, and planktic foraminifera-based species diversity, depth habitat, preference for warm and cool surface waters, and nutrients (oligotrophic, mesotrophic, and eutrophic conditions) are used to infer paleoenvironmental changes throughout the Danian‒Selandian duration. Based on quantitative multivariate analyses (hierarchical cluster and principal component), three distinct intervals were recognized, Interval 1 (Pα‒P1b), Interval 2 (P1c‒P3a), and Interval 3 (P3a‒P4b). Interval 2 is further subdivided into three subintervals, 2a (part P1c), 2b (part P1c), and 2c (P2‒P3a). Two δ13C events are identified, Dan-C2 and Latest Danian Event (LDE) and elaborated concerning paleoenvironmental changes. During the earliest Danian planktic foraminiferal Pα Zone, moderately shallow and eutrophic conditions prevailed with cool surface waters and a shallow thermocline. Comparable conditions were still prevailing during P1a‒P1b, but with slightly deeper and mesotrophic conditions and a somewhat deeper thermocline and reduced stratification. P1b‒P1c exhibits a major shift from Eoglobigerina to Subbotina‒Parasubbotina with cooler surface waters and moderate mesotrophic conditions. For Subzone P1c (upper part), slightly mesotrophic conditions were inferred, whereas for P2‒P3a (lower part), surface water warming and thermocline shallowing events have inferred with increased oligotrophic conditions. The Latest Danian Event (mid-P3a) is marked by a dramatic negative δ13C excursion, warm waters, increased mesotrophic conditions, and enhanced stratification. The dominance of Morozovella, Acarinina, and Igorina specify warm and oligotrophic conditions for subzones P3b‒P4b.
Virtual professional development on conflict management for school leaders
Authors: Irby Beverly J. , Pashmforoosh Roya , Druery Donna M. , Lara-Alecio Rafael , Tong Fuhui , Etchells Matthew J. , Algert Nancy T.
Published: April 2023

From 2017 until 2020, we held face-to-face professional development focused on enhancing instructional leadership for underserved schools at the campus level. We quickly determined in March 2020, based on the predicted situation of COVID-19, that we needed to change that venue to virtual professional development (VPD). The study was grounded in the theoretical base of adult learning theory and transformational learning since we were working with school leaders. The researchers used a mixed methods research design with a survey to examine to what extent school leaders perceived their engagement in a synchronous VPD webinar with facilitators increased their knowledge on the topic of conflict management. The findings showed that the participants perceived targeted VPD to have significantly increased their knowledge on conflict management. Additionally, the participating school leaders indicated a shift in their attitudes from negative to positive perceptions regarding conflict. The findings suggest that structured VPD for school leaders has the potential to advance school leaders’ knowledge on conflict management.
How to develop four competencies for teacher educators
Authors: Nguyen Ngan Thi Lan
Published: April 2023

Understanding competencies and the process of acquiring them contributes to a shared set of essential abilities for teacher educators’ professional development. Practical experiences of practitioners expose which competencies the work context requires them to possess and situations in which their learning is conducted. The necessity for essential contextual competency is pressing, particularly for teacher educators working in developing countries where teacher education has undergone reforms to respond to national and international demands.

This study explores competencies for teacher educators in Vietnam through in-depth interviews with experienced practitioners and their visual metaphors. Eight participants with working experience ranging from 6 to 26 years were interviewed for 60–180 min during January–April 2021.

The results reveal four competency areas of (1) knowledge and skills consisting of (a) teaching skill, (b) subject content, (c) scientific and subject-related information, (d) the reality of education and multidisciplinary knowledge, (e) research procedural knowledge, (f) collaboration with others, and (g) English language; (2) ethical manner; (3) motivation; and (4) self-reflection about personal values. Professional development includes learning from and working with others, learning in organized courses, conducting independent and collaborative research, and other field-related academic activities. An interesting highlight is that even motivational competency is gradually formed by professionals’ effort put into work.

The findings suggest these four competency components should be attended to when providing professional development activities for teacher educators. Motivational competency should be prioritized since it fosters job productivity and commitment. The findings also serve as practical guidance for self-preparation and development for those working as teacher educators in demanding contexts.
Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer
Authors: Li Yuezheng , Wang Haoyu , Pan Yang , Wang Shangren , Zhang Zhexin , Zhou Hang , Xu Mingming , Liu Xiaoqiang
Published: April 2023

Background

Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance.

Methods

The data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups.

Results

Two drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein–protein interaction network identified 10 hub genes in the brown module LUC7L3, SNRNP70, PRPF3, LUC7L, CLASRP, CLK1, CLK2, U2AF1L4, NXF1, and THOC1) and 13 in the yellow module (PNN, PPWD1, SRRM2, DHX35, DMTF1, SALL4, MTA1, HDAC7, PHC1, ACIN1, HNRNPH1, DDX17, and HDAC6). The prognostic model composed of RNF207, REC8, DFNB59, HOXA2, EPOR, PILRB, LSMEM1, TCIRG1, ABTB1, ZNF276, ZNF540, and DPY19L2 could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy.

Conclusion

In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.
A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma
Authors: Cipolletti Manuela , Leone Stefano , Bartoloni Stefania , Acconcia Filippo
Published: April 2023

Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.
A novel anatomy-based five-settlement method for endoscopic thyroid lobectomy and ipsilateral central compartment neck dissection via gasless unilateral axillary approach: a preliminary report
Authors: Ge Jun-Na , Yu Shi-Tong , Sun Bai-Hui , Wei Zhi-Gang , Zhang Zhi-Cheng , Chen Wei-Sheng , Li Ting-Ting , Lei Shang-Tong
Published: April 2023

Background

Endoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC).

Methods

PTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented.

Results

In total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1–30) and 1.0 ± 1.8 (range, 0–12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner’s syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred.

Conclusion

The five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.
Impact of inter-basin water diversion project operation on water quality variations of Hanjiang River, China
Authors: Nong Xizhi , Yi Xianjie , Chen Lihua , Shao Dongguo , Zhang Chi
Published: April 2023

The impact of the operation of inter-basin water diversion projects on the integrity and stability of regional ecosystems cannot be ignored. In this study, water quality samplings were conducted monthly at 16 national monitoring sites in the mid-downstream of the Hanjiang River (HJR, the downstream of the water source of the South-to-North Water Diversion Project of China) over 3 years, covering seven physiochemical water quality indicators and six heavy metal elements. The water quality index (WQI) and multivariate statistical techniques were introduced to comprehensively evaluate water quality status and understand the corresponding driving factors of water quality variations. The heavy metal risks were evaluated using the Nemerow Pollution Index (Pn), the Heavy Metal Pollution Index (HPI), and the human health risk assessment model. The results showed that after the operation of the Middle Route of the South-to-North Water Diversion Project of China (MRSNWDPC), water quality in the mid-downstream of the HJR was generally at a “good” status, with the average WQI of 86.37, showing no water quality deterioration trends. The operation of the MRSNWDPC did significantly decrease the monthly flow in the HJR by about 4.05–74.27%, and the flow variation processes also became more stable than before. Most water quality indicators and WQIs have no correlations with the flow and water level changes. The human health risks of all heavy metal elements caused by dermal exposure and ingestion pathways increased over time. The average individual health risk caused by carcinogenic heavy metal Cr was the highest. Chromium is the major carcinogenic factor and should be a critical indicator to pay special attention to for water risk management in the HJR. This study provides a scientific reference for the water quality safety management of HJR under the influence of a water diversion project.
Tilapia lake virus: A structured phylogenetic approach
Authors: Abbadi Miriam , Basso Andrea , Biasini Lorena , Quartesan Rosita , Buratin Alessandra , Davidovich Nadav , Toffan Anna
Published: April 2023

Tilapia Lake Virus (TiLV), also known as Tilapia tilapinevirus, is an emerging pathogen affecting both wild and farmed tilapia (Oreochromis spp.), which is considered one of the most important fish species for human consumption. Since its first report in Israel in 2014, Tilapia Lake Virus has spread globally causing mortality rates up to 90%. Despite the huge socio-economic impact of this viral species, to date the scarce availability of Tilapia Lake Virus complete genomes is severely affecting the knowledge on the origin, evolution and epidemiology of this virus. Herein, along with the identification, isolation and complete genome sequencing of two Israeli Tilapia Lake Virus deriving from outbreaks occurred in tilapia farms in Israel in 2018, we performed a bioinformatics multifactorial approach aiming to characterize each genetic segment before carrying out phylogenetic analysis. Results highlighted the suitability of using the concatenated ORFs 1, 3, and 5 in order to obtain the most reliable, fixed and fully supported tree topology. Finally, we also attempted to investigate the presence of potential reassortment events in all the studied isolates. As a result, we report a reassortment event detected in segment 3 of isolate TiLV/Israel/939-9/2018 involved in the present study, and confirmed almost all the other events previously reported.
Epigenetic regulation of stem cells in lung cancer oncogenesis and therapy resistance
Authors: Wu Jiayang , Feng Jiaming , Zhang Qiran , He Yazhou , Xu Chuan , Wang Chengdi , Li Weimin
Published: April 2023

Epigenetics plays an important role in regulating stem cell signaling, as well as in the oncogenesis of lung cancer and therapeutic resistance. Determining how to employ these regulatory mechanisms to treat cancer is an intriguing medical challenge. Lung cancer is caused by signals that cause aberrant differentiation of stem cells or progenitor cells. The different pathological subtypes of lung cancer are determined by the cells of origin. Additionally, emerging studies have demonstrated that the occurrence of cancer treatment resistance is connected to the hijacking of normal stem cell capability by lung cancer stem cells, especially in the processes of drug transport, DNA damage repair, and niche protection. In this review, we summarize the principles of the epigenetic regulation of stem cell signaling in relation to the emergence of lung cancer and resistance to therapy. Furthermore, several investigations have shown that the tumor immune microenvironment in lung cancer affects these regulatory pathways. And ongoing experiments on epigenetics-related therapeutic strategies provide new insight for the treatment of lung cancer in the future.
Use of whole-exome sequencing to identify novel monogenic gene mutations and genotype–phenotype correlations in Chinese Han children with urolithiasis
Authors: Wang Zhi , He Tianqu , liu Li , Tong Fangyun , Li Chuangye , Zhao Yaowang , Li Yanfang
Published: April 2023

The incidence of urolithiasis (UL) in children has been increasing. Although the pathogenesis of pediatric UL is controversial and remains unclear, multiple monogenic causes of UL have been identified. We aim to investigate the prevalence of inherited UL causes and explore the genotype–phenotype correlation in a Chinese pediatric group. In this study, we analyzed the DNA of 82 pediatric UL patients using exome sequencing (ES). The data of metabolic evaluation and genomic sequencing were subsequently analyzed together. We detected 54 genetic mutations in 12 of 30 UL-related genes. A total of 15 detected variants were described as pathogenic mutations, and 12 mutations were considered likely pathogenic. Molecular diagnoses were made in 21 patients with pathogenic or likely pathogenic variants. Six novel mutations that were not previously reported were identified in this cohort. Calcium oxalate stones were detected in 88.9% cases (8/9) with hyperoxaluria-related mutations, while 80% of individuals (4/5) with cystinuria-causing defects were diagnosed with cystine stones. Our study highlights the significant genetic abnormalities in pediatric UL and demonstrates the diagnostic power of ES for screening patients with UL.
Case report: Two individuals with AEBP1-related classical-like EDS: Further clinical characterisation and description of novel AEBP1 variants
Authors: Angwin Chloe , Ghali Neeti , van Dijk Fleur Stephanie
Published: April 2023

Introduction:AEBP1-related classical-like EDS (clEDS type 2) is a rare type of Ehlers–Danlos syndrome (EDS) that was first reported in 2016. There are overlapping clinical features with TNXB-related classical-like EDS (or clEDS type 1), including skin hyperextensibility, joint hypermobility, and easy bruising. There are currently nine reported individuals with AEBP1-related clEDS type 2. This report confirms previous findings and provides additional clinical and molecular data on this group of individuals.

Materials and methods: Two individuals (P1 and P2), with features of a rare type of EDS, were clinically assessed in the London national EDS service and underwent genetic testing.

Results: Genetic testing in P1 revealed likely pathogenic AEBP1 variants: c.821del:p. (Pro274Leufs*18) and c.2248T>C:p. (Trp750Arg). In P2 pathogenic AEBP1 variants, c.1012G>T:p. (Glu338*) and c.1930C>T:p. (Arg644*) were identified.

Discussion: These two individuals increased the reported number of individuals with AEBP1-related clEDS to 11 (six females and five males). There are shared features with previously reported individuals, including hypermobility (11/11), skin hyperextensibility (11/11), presence of atrophic scarring (9/11), and easy bruising (10/11). In P1, a chronic right vertebral artery dissection, mild dilatation of the splenic artery, aberrant subclavian artery, and tortuous iliac arteries were observed at the age of 63 years. Cardiovascular disease has been reported, including mitral valve prolapse (4/11), peripheral arterial disease (1/11), and aortic root aneurysm requiring surgical intervention (1/11). Hair loss has been reported in 6/11 individuals (five females and one male), only one of which was documented to have a formal diagnosis of androgenetic alopecia, while other individuals were described as having thinning of hair, male pattern hair loss, or unspecified alopecia.

Conclusion: The clinical features of individuals with AEBP1-related EDS have not been fully elucidated yet. Hair loss is present in 6/11 individuals with AEBP1-related clEDS and appears to be a feature of this condition. This is the first time hair loss has been formally reported as a characteristic feature in a rare type of EDS. Cardiovascular surveillance seems warranted in this condition because 2/11 individuals have evidence of arterial aneurysm and/or dissection. Further descriptions of affected individuals are necessary to update diagnostic criteria and management guidelines.
Comparative transcriptomics identifies the key in planta-expressed genes of Fusarium graminearum during infection of wheat varieties
Authors: Tu Qiang , Wang Lirong , An Qi , Shuai Jie , Xia Xiaobo , Dong Yifan , Zhang Xu , Li Gang , He Yi
Published: April 2023

Fusarium head blight (FHB), caused mainly by the fungus Fusarium graminearum, is one of the most devastating diseases in wheat, which reduces the yield and quality of grain. Fusarium graminearum infection of wheat cells triggers dynamic changes of gene expression in both F. graminearum and wheat, leading to molecular interactions between pathogen and host. The wheat plant in turn activates immune signaling or host defense pathways against FHB. However, the mechanisms by which F. graminearum infects wheat varieties with different levels of host resistance are largely limited. In this study, we conducted a comparative analysis of the F. graminearum transcriptome in planta during the infection of susceptible and resistant wheat varieties at three timepoints. A total of 6,106 F. graminearum genes including those functioning in cell wall degradation, synthesis of secondary metabolites, virulence, and pathogenicity were identified during the infection of different hosts, which were regulated by hosts with different genetic backgrounds. Genes enriched with metabolism of host cell wall components and defense response processes were specifically dynamic during the infection with different hosts. Our study also identified F. graminearum genes that were specifically suppressed by signals derived from the resistant plant host. These genes may represent direct targets of the plant defense against infection by this fungus. Briefly, we generated databases of in planta-expressed genes of F. graminearum during infection of two different FHB resistance level wheat varieties, highlighted their dynamic expression patterns and functions of virulence, invasion, defense response, metabolism, and effector signaling, providing valuable insight into the interactions between F. graminearum and susceptible/resistant wheat varieties.
12/15-lipoxygenase activity promotes efficient inflammation resolution in a murine model of Lyme arthritis
Authors: Jackson Christa D. , Hilliard Kinsey A. , Brown Charles R.
Published: April 2023

Infection of C3H/HeJ (C3H) mice with Borrelia burgdorferi results in the development of a robust inflammatory arthritis that peaks around 3-4 weeks post-infection and then spontaneously resolves over the next few weeks. Mice lacking cyclooxygenase (COX)-2 or 5-lipoxygenase (5-LO) activity develop arthritis similar to wild-type mice but display delayed or prolonged joint resolution. Since 12/15-lipoxygenase (12/15-LO) activity is generally down-stream of both COX-2 and 5-LO activity and results in the production of pro-resolution lipids such as lipoxins and resolvins among others, we investigated the impact of 12/15-LO deficiency on the resolution of Lyme arthritis in mice on a C3H background. We found the expression of Alox15 (12/15-LO gene) peaked around 4-weeks post-infection in C3H mice suggesting a role for 12/15-LO in mediating arthritis resolution. A deficiency in 12/15-LO resulted in exacerbated ankle swelling and arthritis severity during the resolution phase without compromising anti-Borrelia antibody production and spirochete clearance. However, clearance of inflammatory cells was impeded. Therapeutic treatment of B. burgdorferi-infected C3H mice with lipoxin A4 (LXA4) near the peak of disease resulted in significantly decreased ankle swelling and a switch of joint macrophages to a resolving phenotype but did not directly impact arthritis severity. These results demonstrate that 12/15-LO lipid metabolites are important components of inflammatory arthritis resolution in murine Lyme arthritis and may be a therapeutic target for treatment of joint edema and pain for Lyme arthritis patients without compromising spirochete clearance.
Progressive cognitive impairment after recovery from neuroinvasive and non-neuroinvasive Listeria monocytogenes infection
Authors: Cassidy Benjamin R. , Logan Sreemathi , Farley Julie A. , Owen Daniel B. , Sonntag William E. , Drevets Douglas A.
Published: April 2023

Background

Neuro-cognitive impairment is a deleterious complication of bacterial infections that is difficult to treat or prevent. Listeria monocytogenes (Lm) is a neuroinvasive bacterial pathogen and commonly used model organism for studying immune responses to infection. Antibiotic-treated mice that survive systemic Lm infection have increased numbers of CD8+ and CD4+ T-lymphocytes in the brain that include tissue resident memory (TRM) T cells, but post-infectious cognitive decline has not been demonstrated. We hypothesized that Lm infection would trigger cognitive decline in accord with increased numbers of recruited leukocytes.

Methods

Male C57BL/6J mice (age 8 wks) were injected with neuroinvasive Lm 10403s, non-neuroinvasive Δhly mutants, or sterile saline. All mice received antibiotics 2-16d post-injection (p.i.) and underwent cognitive testing 1 month (mo) or 4 mo p.i. using the Noldus PhenoTyper with Cognition Wall, a food reward-based discrimination procedure using automated home cage based observation and monitoring. After cognitive testing, brain leukocytes were quantified by flow cytometry.

Results

Changes suggesting cognitive decline were observed 1 mo p.i. in both groups of infected mice compared with uninfected controls, but were more widespread and significantly worse 4 mo p.i. and most notably after Lm 10403s. Impairments were observed in learning, extinction of prior learning and distance moved. Infection with Lm 10403s, but not Δhly Lm, significantly increased numbers of CD8+ and CD4+ T-lymphocytes, including populations expressing CD69 and TRM cells, 1 mo p.i. Numbers of CD8+, CD69+CD8+ T-lymphocytes and CD8+ TRM remained elevated at 4 mo p.i. but numbers of CD4+ cells returned to homeostatic levels. Higher numbers of brain CD8+ T-lymphocytes showed the strongest correlations with reduced cognitive performance.

Conclusions

Systemic infection by neuroinvasive as well as non-neuroinvasive Lm triggers a progressive decline in cognitive impairment. Notably, the deficits are more profound after neuroinvasive infection that triggers long-term retention of CD8+ T-lymphocytes in the brain, than after non-neuroinvasive infection, which does not lead to retained cells in the brain. These results support the conclusion that systemic infections, particularly those that lead to brain leukocytosis trigger a progressive decline in cognitive function and implicate CD8+ T-lymphocytes, including CD8+TRM in the etiology of this impairment.
Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry
Authors: Le Rochais Marion , Hémon Patrice , Ben-guigui Danivanh , Garaud Soizic , Le Dantec Christelle , Pers Jacques-Olivier , Cornec Divi , Uguen Arnaud
Published: April 2023

Persistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling secondary lymphoid organs (SLO) such as lymph nodes (LN). The composition of TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO in cancers of the digestive tract and in inflammatory bowel diseases. Colorectal and gastric tissues with different inflammatory diseases and cancers from the department of pathology of CHU Brest were analyzed based on 39 markers using imaging mass cytometry (IMC). Unsupervised and supervised clustering analyses of IMC images were used to compare SLO and TLS. Unsupervised analyses tended to group TLS per patient but not per disease. Supervised analyses of IMC images revealed that LN had a more organized structure than TLS and non-encapsulated SLO Peyer’s patches. TLS followed a maturation spectrum with close correlations between germinal center (GC) markers’ evolution. The correlations between organizational and functional markers made relevant the previously proposed TLS division into three stages: lymphoid-aggregates (LA) (CD20+CD21-CD23-) had neither organization nor GC functionality, non-GC TLS (CD20+CD21+CD23-) were organized but lacked GC’s functionality and GC-like TLS (CD20+CD21+CD23+) had GC’s organization and functionality. This architectural and functional maturation grading of TLS pointed to differences across diseases. TLS architectural and functional maturation grading is accessible with few markers allowing future diagnostic, prognostic, and predictive studies on the value of TLS grading, quantification and location within pathological tissues in cancers and inflammatory diseases.
Presence of tophi and carotid plaque were risk factors of MACE in subclinical artherosclerosis patients with gout: a longitudinal cohort study
Authors: Wang Yu , Deng Xuerong , Zhang Xiaohui , Geng Yan , Ji Lanlan , Song Zhibo , Zhang Zhuoli
Published: April 2023

Background

Patients with gout carry an excess risk for cardiovascular disease (CVD), but the contribution of subclinical atherosclerosis to the CVD risk has never been reported. In this study, we aimed to explore the predictive factors for incident major adverse cardiovascular events (MACE) in gout patients without a previous history of CVD or cerebral vascular disease.

Methods

A single-center, long-term follow-up cohort analysis was performed to assess subclinical atherosclerosis at baseline since 2008. Patients with a previous history of CVD or cerebrovascular disease were excluded. The outcome of the study was the first MACE. The presence of subclinical atherosclerosis was assessed by carotid plaque (CP), and carotid intima-media thickness (CMIT) was determined by ultrasound. An ultrasound scan of bilateral feet and ankles was performed at baseline. The association between tophi, carotid atherosclerosis, and the risk of developing incident MACE was evaluated using Cox proportional hazards models with adjustment for the CVD risk scores.

Results

A total of 240 consecutive patients with primary gout were recruited. Their mean age was 44.0 years, with male predominance (238, 99.2%). During a median follow-up of 10.3 years, incident MACE was ascertained in 28 (11.7%) patients. In a Cox hazards model, controlling for the CV risk scores, the presence of at least two tophi (HR, 2.12–5.25, p < 0.05) and carotid plaque (HR, 3.72–4.01, p < 0.05) were identified as independent predictors of incident MACE in gout patients.

Conclusions

The presence of at least two tophi and carotid plaque on an ultrasound could independently predict MACE in addition to conventional cardiovascular risk factors in gout patients.
Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion
Authors: Shao Ming-Ming , Pei Xue-Bin , Chen Qing-Yu , Wang Feng , Wang Zhen , Zhai Kan
Published: April 2023

Introduction

Tumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined.

Methods

MPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival.

Results

Single-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process.

Conclusions

Taken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.