bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation and Adaptation for Medieval Castles: The Case of Messner Mountain Museums
Authors: Özmen Ayça
Published: October 2022

In international conservation documents, adaptation is considered an important conservation process for culturally important places. It is especially important when the cultural context changes, as is the case with medieval castles, many of which were altered or built for military and domestic use in the Middle Ages. Medieval castles which are no longer used for their initial functions, are mostly non-functional today, and non-functional buildings often disintegrate into nature and disappear in time. Therefore, maintaining their relevance and cultural significance depends on appropriate adaptation strategies. When adapting a historic building, it is essential to design for the current use and needs, referring to conservation principles. It is also important to blend cultural heritage consciousness with creativity, and this can be achieved by balancing conservation and design practices. Therefore, in addition to design parameters, characteristics of the existing building should be meticulously analysed, and design concepts should be predicated on sustaining the existing values and meanings while adding contemporary ones. It is the purpose of this research to discuss and contribute to the theory of adaptation regarding medieval castle conversions by analysing three related case studies from Northern Italy. The findings lead to the proposal of a diagram, the focus of which is on the conceptual parameters of the multi-dimensional theory of adaptive (re)use, to be used for the design process of historic buildings.
Deadbeat Predictive Control Method for 4-leg Inverters
Authors: Khan Tuhin Ibrahim , Luu Hai Tung , Szamel Laszlo
Published: October 2022

Until now, computational burden alleviation and stability issues for the three-phase four-leg converter has not yet been thoroughly investigated. However, compared to the conventional controllers, the implementation of predictive current control approach for 3-Ø, 4-L inverter suffers a large computational burden due to its additional fourth-leg. Motivated by this fact, this article provides an alternative predictive current control implementation for 3-Ø, 4-L inverter which offers reduced computational effort to achieve similar performance as the conventional FCS-MPC and ensures the global stability of the closed-loop system. To further understand the consequences of the developed control law, theoretical stability analysis has been carried out that links Lyapunov's direct method with the closed-loop system behavior. The outcome of the theoretical stability analysis demonstrates the global stability of the overall system which is later supported by the experimental results. With the proposed method, the number of possible voltage vectors required to obtain the optimal voltage vector in each sampling interval reduces from sixteen to five and thereby simplifies the prediction process. It is also derived that the Lyapunov function-based approach actually yields to the dead-beat control, which has not been previously highlighted in the previous papers. The current work also provides experimental results for different loading conditions (balanced and unbalanced) which further demonstrates the efficacy of the proposed method.
Incidentally Detected Rare Retroperitoneal Tumor: Ganglioneuroma
Authors: Khalequezzarnan Syed , Ahsan Sania , Khandker Dilruba , Khan Biva Shrestha , Huda Atia
Published: October 2022

A primary extra-adrenal retroperitoneal ganglioneuroma was found incidentally in a 22-year-old woman during screening for suspected pregnancy by transvaginal ultrasonography (TVS) and subsequently by magnetic resonance imaging (MRI). TVS and MRI revealed well defined solid mass in retroperitoneal at the level of L5 to S2 vertebrae and displace right common iliac and external iliac vessels. Limited cuts of the region of Computed tomography (CT) were taken and no calcification was identified. Histological examination showed that the lesion was an extra-adrenal retroperitoneal ganglioneuroma composed of mature ganglion cells and subsequently confirmed by immunohistochemistry.

Pulse volumel.11 January-December 2018-2019 p.13-18
Tuhatvuotinen korruptio ja Venäjä
Authors: Korpela Jukka
Published: October 2022

Lännessä totuus on matemaattisesti mitattava ja rationaalisesti selitettävä asia. Täällä moniarvoisen, demokraattisen sekä läpinäkyvyyttä ja ihmisoikeuksia kunnioittavan laillisuusyhteiskunnan ajatellaan olevan absoluuttinen, historiasta ja kulttuurista irti oleva asia ja kaikkien tavoite. Historiatiede kuitenkin selittää myös moraaliset ja tiedolliset rakenteet ajasta ja paikasta riippuviksi. Sattumien summana länsimainen, mutta maailman mitassa poikkeuksellinen arvomaailma syntyi vähitellen keskiajalta lähtien ja levisi läntisen talouden myötä ja alkoi dominoida viimeisen vuosisadan aikana. Valtaa ja oikeudenmukaisuutta voidaan kuitenkin toteuttaa myös yksilöitä syrjivissä, mystiikkaa ja salakähmäisyyttä suosivissa klaaniverkostoissa. Ne myös tarjoavat suuret näköalat rikkauksiin. Venäjän yhteiskunta näyttää länsimaista käsin korruptoituneelta, irrationaalilta, rosvoklaanien hallitsemalta ja ihmisoikeuksia loukkaavalta. Pyrkimys rakentaa Venäjästä länsimainen demokratia on epäonnistunut useasti. Artikkeli esittää syyksi sen, että kun lännestä poikkeavat perusrakenteet on valittu kaukana historiassa, uuden toimintatavan liimaaminen päälle ei onnistu, koska perinteinen järjestelmä on oman kulttuurin silmissä legitiimi ja toimiva. Artikkelissa käydään läpi näkemyksen tueksi aate- ja taloushistorian pitkiä rakenteita ja niiden kehitystä varhaiskeskiajalta nykyisyyteen.
Nicotinamide Mononucleotide Adenylyl Transferase 2 Inhibition Aggravates Neurological Damage after Traumatic Brain Injury in a Rat Model
Authors: Gu Xiaoyu , Ni Haibo , Kan XuGang , Chen Chen , Zhou Zhiping , Ding Zheng , Li Di , Liu Bofei
Published: October 2022

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats.Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out.Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax).Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.
The Effect of Burnout on Professional Commitment: A Field Research on Teachers
Authors: BAKAN İsmail , AMIRLI Hamran
Published: October 2022

The aim of this study is to investigate whether teachers' burnout levels have an effect on their professional commitment. While teachers working in public and private education institutions in Ağrı Doğubayazıt constitute the universe of the research, the sample consists of 100 teachers selected by simple randomization among these existing teachers. The data of the research were obtained by applying the questionnaire technique. The “Maslach Burnout Scale” developed by Maslach and Jackson (1981) and Meyer et al. The “Professional Commitment Scale” developed by (1993) was used. In this direction, SPSS package program was used in the analysis of the collected data. Correlation analysis was conducted to reveal the relationship between the burnout levels of teachers in the study and their professional commitment levels, and regression analysis was conducted to reveal the effect of burnout sub-dimensions on professional commitment sub-dimensions. According to the results of the analysis, there was no significant effect of the emotional exhaustion sub-dimension of burnout on the sub-dimensions of professional commitment. Depersonalization, which is another sub-dimension of burnout, was found to have a negative effect on the emotional professional commitment and professional continuance commitment dimensions of professional commitment, while it did not have a significant effect on normative professional commitment.
Connecting the Dots Between Skin and Allergy
Authors: Humphry Nicola
Published: October 2022

This symposium took place during the 28th congress of the European Academy of Dermatology and Venereology (EADV). Dr Seité began the meeting by emphasising the rising incidence of allergy, and the societal and economic impact this has in Europe. This was followed by the presentation of a worldwide epidemiology study conducted this year, which found that 20–42% of the population in the countries surveyed reported being affected by allergies, most commonly skin allergies followed by respiratory and food allergies. Of these individuals, 48–89% in each country experienced skin reactions, and these were treated primarily with oral or topical medication. Dr Lazic Strugar introduced the skin barrier as the first interface between the environment and the immune system, and she explained that its disruption can lead to immune dysfunction, resulting in dermatitis, skin infections, and allergies. Skincare products such as emollients can provide moisture and lipids, supporting bacterial diversity in the microbiome and restoration of the skin barrier. Dr Seité followed up with a report of a recent observational study investigating the benefits of a facial moisturiser designed specifically for sensitive skin and individuals with allergies. In this study, patients with allergies experiencing skin reactions used the product for up to 1 month, in addition to taking antihistamines alone or in combination with steroids. After 4.9 days, all subjects felt their symptoms had improved, and after the full month of treatment, both cutaneous clinical signs and subjective signs had significantly improved in most participants (>95% and 90%, respectively). Dr Seité concluded the meeting by stressing that dermatologists have an important role to play to help patients with allergies to manage their skin reactions.
Pathways to Silencing Psoriasis: Remission or Cure?
Authors: Breuer Megan
Published: October 2022

The symposium “Pathways to silencing psoriasis: Remission or Cure?” took place during the 2019 European Society for Dermatological Research (ESDR) annual congress in Bordeaux, France. The presentations reviewed the role of the IL-23 pathway in psoriasis pathogenesis and other immune-mediated inflammatory diseases (IMID), underlined the importance of assessing and treating comorbidities in patients with psoriasis, and concluded with a glimpse into the future of psoriasis management, examining whether drug-free remission from disease is a viable goal for future treatment plans.

After defining and giving some examples of familial and poly-autoimmunity, Prof Jörg Prinz described the common pathways shared by several IMID. The involvement of the IL-23/Th(c)17 pathway in the pathogenesis of various IMID may represent opportunities for future therapeutic targets and treatment strategies.

The importance of holistic treatment in psoriasis management was illustrated by Prof Jo Lambert, who showed the audience how psoriasis can be linked to several different comorbidities, all of which should be addressed when making treatment decisions. Proper assessments and informed treatment choices could help patients with psoriasis achieve better clinical outcomes and help improve their long-term health expectations.

Reducing treatment burden for patients, and the possibility of achieving and maintaining drug-free remission, was discussed by Prof Carle Paul, who underlined the importance of examining several important predictive biomarkers of treatment response. Early, intensive treatment and disease modification could result in long-term remission of severe psoriasis and further decrease the treatment burden for patients.
Epithelial Barrier Dysfunction in Type 2 Inflammatory Diseases
Authors: Humphry Nicola
Published: October 2022

This satellite symposium took place during the 49th annual meeting of the European Society for Dermatological Research (ESDR). Prof Dávila began the symposium by describing the immunology behind Type 2 inflammation as a complex interaction between environmental factors, immune response, and barrier dysfunction. He explained that the principal cells participating in innate Type 2 immunity are Type 2 innate lymphoid cells (ILC2), eosinophils, basophils, and mast cells, and that Th2 lymphocytes, dendritic cells (DC), and their main cytokines (IL-4, IL-5, and IL-13) comprise the adaptive arm of the Type 2 immune response and are essential in IgE-mediated reactions. Prof Seneschal followed by explaining that Type 2 inflammation in atopic dermatitis (AD) is a combination of immune and epidermal barrier components influenced by genetic and environmental factors. Epidermal barrier proteins are expressed in lower levels in AD, and other proteins are also dysregulated, disrupting tight junctions. Both lesional and nonlesional skin in patients with AD show epithelial barrier dysfunction, and inflammation can lead to a vicious cycle of itching and damage. Prof Dahlén concluded the meeting by explaining that airway inflammation is one of the major factors involved in Type 2 asthma, and this can be driven by an allergic route, involving mast cells, or a nonallergic route, involving ILC2. Inflammatory cytokines also increase mucus production, one of the main causes of asthma-related death. Recent studies of asthma immunology have suggested that ILC2 are subject to feedback modulation by prostaglandin D2 (PGD2), and that both IL-4 and IL-13 are involved in hyper-responsiveness in asthmatic lung tissue.
Los estudios de la(s) violencia(s) en la frontera noreste de México
Authors: López Hernández Olga Nacori
Published: October 2022

This article aims to carry out a semi-systematic review of the academic literature that studies violence in Tamaulipas from 2008 to 2019. It is argued that violence in that state is studied primarily from a broad perspective. However, regardless of the study perspective, there is a close relationship between violence, organized crime, and drug trafficking. Two lines of research little explored in the literature are proposed: the first studies risks associated with the analysis of violence(s) in each context; the second analyzes violence(s) from a gender perspective. The main limitation of this semi-systematic review is that the results presented are descriptive and only classify the literature to find gaps in it.
STRATEGI KOMUNIKASI PEMASARAN DIGITAL UPN VETERAN JAKARTA
Authors: Waluyo Lukman Saleh , Wahyuningratna Ratu Nadya , Falih Noor
Published: October 2022

Dalam perkembangan teknologi yang sangat pesat saat ini, para pebisnis memanfaatkan media sosial untuk menguasai pangsa pasar. Instagram saat ini menjadi media sosial paling populer bagi kebanyakan orang. Oleh sebab itu Universitas Pembangunan Nasional Veteran Jakarta memanfaatkan media sosial Instagram sebagai alat untuk promosi. Strategi komunikasi pemasaran dibuat oleh Universitas Pembangunan Nasional Veteran Jakarta dengan tujuan meningkatkan jumlah mahasiswa baru Universitas Pembangunan Nasional Veteran Jakarta. Jenis penelitian ini adalah kualitatif deskriptif. bertujuan untuk menemukan dan memahami fenomena sedalam-dalamnya. Analisis data dilakukan secara induktif. Peneliti memilih jenis penelitian kualitatif deskriptif karena dengan metode ini dapat menggali informasi secara mendalam melalui wawancara mendalam dan pengamatan langsung di lapangan untuk mendapatkan data yang jelas dan akurat. Penelitian ini menggunakan teknik wawancara mendalam dan observasi nonpartisipatif. Dalam observasi nonpartisipatif, peneliti tidak terlibat dan hanya sebagai pengamat independen. Setelah dilakukan analisis, maka hasil dan kesimpulan dari penelitian ini adalah Universitas Pembangunan Nasional Veteran Jakarta menggunakan bauran promosi periklanan, personal selling dan promosi penjualan. dan humas menggunakan jejaring sosial Instagram sebagai tempat berbagi informasi tentang produk mereka dan melakukan kegiatan promosi.
ANALISIS STIKER WHATSAPP SEBAGAI SIMBOL DALAM KOMUNIKASI DIKALANGAN MANULA (WHATSAPP GRUP KELUARGA BESAR ASRAMA POLISI NELAYAN (ARNEL)
Authors: Roosyidah Thifaal Kautsar , Febriana Poppy
Published: October 2022

Penelitian dengan judul “Analisis Stiker WhatsApp Sebagai Simbol Dalam Komunikasi Dikalangan Manula”, memiliki rumusan masalah seberapa pengaruhnya Stiker pada WhatsApp untuk berkomunikasi dikalangan manula.iiPenelitian ini bertujuan untuk mengetahui pengaruh stiker WhatsApps sebagai simbol dalam komunikasi dikalangan manula.   Analisis penelitian ini menggunakan teori semiotika Charles Sanders Pierce yaitu didasarkan pada logika melalui pemaknaan tanda,  objek dan interpretan,  penelitian ini menggunakan metode kualitatif.   WhatsApp merupakan salah satu aplikasi messenger yang memiliki kemiripan dg aplikasi SMS namun WhatsApp tidak lagi menggunakan pulsa melainkan data internet.  Dengan aplikasi ini kita dapat mengirim pesan teks, gambar/foto, mengirim video, berbagi berkas" tugas atau yg lainnya, menelpon, berbagi lokasi dengan GPS belum lama ini WhatsApp kembali menawarkan fitur baru yakni Stiker Emoticon, fitur baru WhatsApp ini menawarkan stiker dalam mode diam maupun bergerak.   Stiker WhatsApp menjadi media penghidup komunikasi favorit dikalangan manula karena banyak ditawarkannya beragam expresi.   Serta aplikasi WhatsApp sndiri yg terus menawarkan fitur" baru lain yg semakin mempermudah komunikasi.  Aktivitas bersosial melalui WhatsApp kini sudah menjadi gaya hidup bagi para anak muda hingga orang tua.  Tak jarang karena penggunaan WhatsApp yg cukup sering menjadikan WhatsApp seperti kawan keseharian.  Karena kebutuhan komunikasi yg cepat, praktis dan mudah dijangkau/digunakan menjadikan WhatsApp sebagai salah satu aplikasi yg banyak mereka pilih.  Ditambah WhatsApp yg kini telah menambahkan fitur stiker yg menarik membuat WhatsApp semakin banyak diminati dikalangan berbagai usia.
microRNAs associated with the pathogenesis and their role in regulating various signaling pathways during Mycobacterium tuberculosis infection
Authors: Davuluri Kusuma Sai , Chauhan Devendra S.
Published: October 2022

Despite more than a decade of active study, tuberculosis (TB) remains a serious health concern across the world, and it is still the biggest cause of mortality in the human population. Pathogenic bacteria recognize host-induced responses and adapt to those hostile circumstances. This high level of adaptability necessitates a strong regulation of bacterial metabolic characteristics. Furthermore, the immune reponse of the host virulence factors such as host invasion, colonization, and survival must be properly coordinated by the pathogen. This can only be accomplished by close synchronization of gene expression. Understanding the molecular characteristics of mycobacterial pathogenesis in order to discover therapies that prevent or resolve illness relies on the bacterial capacity to adjust its metabolism and replication in response to various environmental cues as necessary. An extensive literature details the transcriptional alterations of host in response to in vitro environmental stressors, macrophage infection, and human illness. Various studies have recently revealed the finding of several microRNAs (miRNAs) that are believed to play an important role in the regulatory networks responsible for adaptability and virulence in Mycobacterium tuberculosis. We highlighted the growing data on the existence and quantity of several forms of miRNAs in the pathogenesis of M. tuberculosis, considered their possible relevance to disease etiology, and discussed how the miRNA-based signaling pathways regulate bacterial virulence factors.
An early novel prognostic model for predicting 80-day survival of patients with COVID-19
Authors: Chen Yaqiong , Gong Jiao , He Guowei , Jie Yusheng , Chen Jiahao , Wu Yuankai , Hu Shixiong , Xu Jixun , Hu Bo
Published: October 2022

The outbreak of the novel coronavirus disease 2019 (COVID-19) has had an unprecedented impact worldwide, and it is of great significance to predict the prognosis of patients for guiding clinical management. This study aimed to construct a nomogram to predict the prognosis of COVID-19 patients. Clinical records and laboratory results were retrospectively reviewed for 331 patients with laboratory-confirmed COVID-19 from Huangshi Hospital of Traditional Chinese Medicine (TCM) (Infectious Disease Hospital) and Third Affiliated Hospital of Sun Yat-sen University. All COVID-19 patients were followed up for 80 days, and the primary outcome was defined as patient death. Cases were randomly divided into training (n=199) and validation (n=132) groups. Based on baseline data, we used statistically significant prognostic factors to construct a nomogram and assessed its performance. The patients were divided into Death (n=23) and Survival (n=308) groups. Analysis of clinical characteristics showed that these patients presented with fever (n=271, 81.9%), diarrhea (n=20, 6.0%) and had comorbidities (n=89, 26.9.0%). Multivariate Cox regression analysis showed that age, UREA and LDH were independent risk factors for predicting 80-day survival of COVID-19 patients. We constructed a qualitative nomogram with high C-indexes (0.933 and 0.894 in the training and validation groups, respectively). The calibration curve for 80-day survival showed optimal agreement between the predicted and actual outcomes. Decision curve analysis revealed the high clinical net benefit of the nomogram. Overall, our nomogram could effectively predict the 80-day survival of COVID-19 patients and hence assist in providing optimal treatment and decreasing mortality rates.
Gut microbiota display alternative profiles in patients with early-onset colorectal cancer
Authors: Xiong Huan , Wang Jiaqi , Chang Zewen , Hu Hanqing , Yuan Ziming , Zhu Yihao , Hu Zhiqiao , Wang Chunlin , Liu Yunxiao , Wang Yang , Wang Guiyu , Tang Qingchao
Published: October 2022

Background

The incidence of early-onset colorectal cancer (EOCRC) is increasing worldwide. This study aimed to explore whether there is an alternative gut microbiota profile in patients with early-onset colorectal cancer.

Methods

A total of 24 patients with EOCRC, 43 patients with late-onset colorectal cancer and 31 young volunteers were included in this study. The diversity of their fecal bacteria was explored using 16S ribosomal RNA gene sequencing. Cluster of ortholog genes (COG) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) were used to detect enrichment pathways among the three groups.

Results

Community separations were observed among the three groups. The Shannon index of the EOCRC group was significantly lower than the LOCRC group (P=0.007) and the NC group (P=0.008). Both PCoA analysis (Principal co-ordinates analysis, P=0.001) and NMDS (non-metric multidimensional scaling, stress=0.167, P=0.001) analysis indicated significant difference in beta diversity among the three groups. Fusobacteria, Bacteroidetes, and Clostridia were the most abundant bacteria in the EOCRC group, LOCRC group, and NC group, respectively. The results of COG showed that transcription (P=0.01398), defense mechanisms (P=0.04304), inorganic ion transport and metabolism (P=0.00225) and cell wall/membrane/envelope biogenesis (P=0.02534) were differentially expressed among the three groups. The KEGG modules involved in membrane transport (P=0.00856) and porphyrin and chlorophyll metabolism (P=0.04909) were differentially expressed among the three groups.

Conclusion

Early-onset colorectal cancer patients have a different gastrointestinal microbiota derangement compared to late-onset colorectal cancer patients. This dysbiosis can be reflected in the species diversity of the microbiota, the abundance of bacteria, and the abnormal functional predictions.
CircRNA and miRNA expression analysis in livers of mice with Toxoplasma gondii infection
Authors: Zou Yang , Meng Jin-Xin , Wei Xin-Yu , Gu Xiao-Yi , Chen Chao , Geng Hong-Li , Yang Li-Hua , Zhang Xiao-Xuan , Cao Hong-Wei
Published: October 2022

Toxoplasmosis is an important zoonotic parasitic disease caused byToxoplasma gondii(T. gondii). However, the functions of circRNAs and miRNAs in response toT. gondiiinfection in the livers of mice at acute and chronic stages remain unknown. Here, high-throughput RNA sequencing was performed for detecting the expression of circRNAs and miRNAs in livers of mice infected with 20T. gondiicysts at the acute and chronic stages, in order to understand the potential molecular mechanisms underlying hepatic toxoplasmosis. Overall, 265 and 97 differentially expressed (DE) circRNAs were found in livers at the acute and chronic infection stages in comparison with controls, respectively. In addition, 171 and 77 DEmiRNAs were found in livers at the acute and chronic infection stages, respectively. Functional annotation showed that some immunity-related Gene ontology terms, such as “positive regulation of cytokine production”, “regulation of T cell activation”, and “immune receptor activity”, were enriched at the two infection stages. Moreover, the pathways “Valine, leucine, and isoleucine degradation”, “Fatty acid metabolism”, and “Glycine, serine, and threonine metabolism” were involved in liver disease. Remarkably, DEcircRNA 6:124519352|124575359 was significantly correlated with DEmiRNAs mmu-miR-146a-5p and mmu-miR-150-5p in the network that was associated with liver immunity and pathogenesis of disease. This study revealed that the expression profiling of circRNAs in the livers was changed afterT. gondiiinfection, and improved our understanding of the transcriptomic landscape of hepatic toxoplasmosis in mice.
Preclinical evaluation of OMVs as potential vaccine candidates against Salmonella enterica serovar Enteritidis infection
Authors: Jiang Xi , Chu Chao , Wang Zhenyu , Gu Jiaojie , Hong Yaming , Li Qiuchun , Jiao Xinan
Published: October 2022

Salmonella enterica serovar Enteritidis is the most prevalent serotype that causes human infections worldwide. Consumption of S. Enteritidis-contaminated animal foods is a major source of human infections; however, eradicating bacteria from animals remains difficult. Therefore, it is necessary to develop new measures to prevent and control salmonellosis. Here, we used the outer-membrane vesicles (OMVs) of S. Enteritidis and assessed their protective efficacy and immune response in mice. Deletion of tolR in S. Enteritidis increased the production and size of OMVs compared to those in the wild type (WT) and ΔrfaQ strains. Intramuscular immunization with OMVs conferred greater protection than intraperitoneal and intranasal immunization. Moreover, OMVs extracted from both WT and ΔtolR strains provided an 83.3% protective rate in mice challenged with S. Enteritidis, which was higher than that provided by OMVs extracted from the ΔrfaQ strain. However, compared with OMVs from the ΔtolR strain, OMVs from WT and ΔrfaQ strains rapidly eradicated S. Enteritidis colonizing the liver, spleen, ileum, and cecum of BALB/c mice after immunization. Immunization with OMVs from each of the three strains induced humoral immune responses and showed no side effects on the growth of mice. Our study revealed that OMVs from various S. Enteritidis strains could be developed for use as subunit vaccine candidates against nontyphoidal Salmonella infections in mammals.
Evaluation of the metagenomic next-generation sequencing performance in pathogenic detection in patients with spinal infection
Authors: Zhang Yi , Chen Jinmei , Yi Xiaoli , Chen Zhiheng , Yao Ting , Tang Zhenghao , Zang Guoqing , Cao Xuejie , Lian Xiaofeng , Chen Xiaohua
Published: October 2022

Spinal infection is a rarely occurred pathology, whose diagnosis remains a major challenge due to the low sensitivity of culturing techniques. Metagenomic next-generation sequencing (mNGS) is a novel approach to identify the pathogenic organisms in infectious diseases. In this study, mNGS technology was adopted for pathogenic detection in spinal infection from the tissue and pus samples. Additionally, the diagnostic performance of mNGS for spinal infection was evaluated, by comparing it with that of the conventional microbial culture, with the histopathological results as the gold standard. Overall, 56 samples from 38 patients were enrolled for mNGS testing, and 69 samples were included for microbial culture. 30 patients (78.95%) were identified to be positive by the mNGS method, which was higher than that of microbial culture (17, 44.74%). The sensitivity and specificity of mNGS with pus samples were 84.2% and 100.0%, respectively, which outperformed those of microbial culture (42.1% and 100.0%). The pathogen identification results were applied to medication guidance, and all 38 patients experienced favorable outcomes at three months, followed-up post-treatment, without any adverse effects. These findings proved that mNGS was superior to microbial culture in pathogenic identification of the spinal infection, thereby showing great promise in guiding drug administration and improving clinical outcomes.
Association of serum secreted protein acidic and rich in cysteine-like protein 1 with metabolic measures and dyslipidemia among Chinese adults
Authors: Hu Chunyan , Wang Shuangyuan , Lin Lin , Qi Hongyan , Lin Hong , Jia Xiaojing , Zhu Yuanyue , Wu Xueyan , Li Mian , Wang Tiange , Zhao Zhiyun , Xu Min , Xu Yu , Wang Weiqing , Ning Guang , Bi Yufang , Li Donghui , Chen Yuhong , Dai Meng , Lu Jieli
Published: October 2022

Objectives

Recent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study.

Methods

We determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia.

Results

With the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (β= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend <0.01). After controlling the potential confounders, participants in the highest quartile of sparcl1 concentration had the lowest prevalence of dyslipidemia (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.91), compared with the lowest quartile. Per SD increment of Sparcl1 was associated with 20% (OR, 0.80; 95%CI, 0.69-0.94) lower prevalence of hypertriglyceridemia and 12% (OR, 0.88; 95%CI, 0.79-0.97) lower prevalence of dyslipidemia. The association between serum Sparcl1 and dyslipidemia were generally consistent across subgroups (all P for interaction > 0.05).

Conclusion

Serum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.
Identification of risk model based on glycolysis-related genes in the metastasis of osteosarcoma
Authors: Huang Wei , Xiao Yingqi , Wang Hongwei , Chen Guanghui , Li Kaixiang
Published: October 2022

Background

Glycolytic metabolic pathway has been confirmed to play a vital role in the proliferation, survival, and migration of malignant tumors, but the relationship between glycolytic pathway-related genes and osteosarcoma (OS) metastasis and prognosis remain unclear.

Methods

We performed Gene set enrichment analysis (GSEA) on the osteosarcoma dataset in the TARGET database to explore differences in glycolysis-related pathway gene sets between primary osteosarcoma (without other organ metastases) and metastatic osteosarcoma patient samples, as well as glycolytic pathway gene set gene difference analysis. Then, we extracted OS data from the TCGA database and used Cox proportional risk regression to identify prognosis-associated glycolytic genes to establish a risk model. Further, the validity of the risk model was confirmed using the GEO database dataset. Finally, we further screened OS metastasis-related genes based on machine learning. We selected the genes with the highest clinical metastasis-related importance as representative genes for in vitro experimental validation.

Results

Using the TARGET osteosarcoma dataset, we identified 5 glycolysis-related pathway gene sets that were significantly different in metastatic and non-metastatic osteosarcoma patient samples and identified 29 prognostically relevant genes. Next, we used multivariate Cox regression to determine the inclusion of 13 genes (ADH5, DCN, G6PD, etc.) to construct a prognostic risk score model to predict 1- (AUC=0.959), 3- (AUC=0.899), and 5-year (AUC=0.895) survival under the curve. Ultimately, the KM curves pooled into the datasets GSE21257 and GSE39055 also confirmed the validity of the prognostic risk model, with a statistically significant difference in overall survival between the low- and high-risk groups (P<0.05). In addition, machine learning identified INSR as the gene with the highest importance for OS metastasis, and the transwell assay verified that INSR significantly promoted OS cell metastasis.

Conclusions

A risk model based on seven glycolytic genes (INSR, FAM162A, GLCE, ADH5, G6PD, SDC3, HS2ST1) can effectively evaluate the prognosis of osteosarcoma, and in vitro experiments also confirmed the important role of INSR in promoting OS migration.
Correlation of Baba’s diabetic neuropathy classification with various diabetes-related complications
Authors: Iwamoto Yuichiro , Nakanishi Shuhei , Itoh Takashi , Nakao Erina , Sugisaki Toshitomo , Kusano Takashi , Ohnishi Mana , Takenouchi Haruka , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Hemmi Shoji , Kimura Tomohiko , Tatsumi Fuminori , Shimoda Masashi , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: October 2022

It is known that Baba’s diabetic neuropathy classification (BDC) is useful in quantitative evaluation of Diabetic polyneuropathy (DPN). In this study, we aimed to investigate the possible association between BDC and various diabetic microvascular and macrovascular complications in patients whose neuropathy was evaluated with BDC. As the results, BDC was significantly correlated with the severity of diabetic retinopathy and nephropathy. BDC was also significantly correlated with history of myocardial infarction or cerebral infarction, carotid IMT, and ABI. These data suggest that BDC may be useful in predicting the presence of various diabetic microvascular and macrovascular complications. The data also support the idea that we should perform further investigation of other diabetes-related complications in patients with severe DPN.
Underestimated and ignored? The impacts of microplastic on soil invertebrates—Current scientific knowledge and research needs
Authors: Möhrke Anne Christel Franka , Haegerbaeumer Arne , Traunspurger Walter , Höss Sebastian
Published: October 2022

The accumulation of plastics in the environment is a major problem in the Anthropocene. As most plastic is produced, used and discarded on land, ∼4–23 times more plastics are deposited in soils than in the oceans. However, there is far too little knowledge on the ecological consequences of plastic pollution, especially for soil ecosystems. Microplastics (<5 mm), whether derived from larger plastic pieces through physical, chemical and biological degradation or produced as primary particles, is of considerable interest, as they can be ingested by organisms at the basis of the trophic net and transferred to higher trophic levels. Nonetheless, although the assessment of microplastic effects on soil invertebrates is of undeniable relevance, most studies have focussed on nano- and microplastics in aquatic environments. This review examines the current state of knowledge regarding the effects of microplastics on soil invertebrates. As part of the soil biota, these organisms are of utmost importance for carbon cycling, respiration and biodiversity. Based on strict quality criteria, the data of 45 papers reporting ecotoxicological effects on soil invertebrates were analyzed, considering various test organisms and types of microplastic (in terms of polymer, shape and size). However, although different impacts were demonstrated, a deduction of general effect tendencies of microplastics in soils was difficult due to the scarcity of data and the use of diverse methodological setups. Moreover, almost all experiments were based on short-term single-species testing involving only a small number of species and single microplastic types. The review concludes with a discussion of the remaining knowledge gap and the needs for a standardized approach allowing an ecologically relevant risk assessment of the impacts of microplastic on invertebrates in terrestrial ecosystems.
Integrating new technologies to broaden the scope of northern spotted owl monitoring and linkage with USDA forest inventory data
Authors: Lesmeister Damon B. , Jenkins Julianna M. A.
Published: October 2022

Wildlife monitoring programs designed to inform forest management and conservation decisions in the face of climate change benefit from long-term datasets with consistent methodology. Nevertheless, many monitoring programs may seek to transition to alternative methods because emerging technologies can improve trend tracking and expand the number of target populations, increase spatial scale, and reduce long-term costs. Integrated models strengthen the capacity to adapt long-term monitoring programs to next generation methods. Here we present a case study of northern spotted owl (Strix occidentalis caurina) population monitoring that is under transition. The first monitoring phase focused on territory occupancy and mark-resighting individual owls. Owing to rapidly declining populations and increasing costs, traditional methods are less viable for long-term monitoring. A non-invasive approach, passive acoustic monitoring, is effective for detecting spotted owl presence, estimating occupancy rates, distinguishing sex, detecting trends in populations, and monitoring many additional species. A key component to support transition to passive acoustic monitoring was the development of machine learning models to automate species detections that enable rapid and effective data processing and analysis workflows. Coupling passive acoustic monitoring networks with Forest Inventory and Analysis (FIA) and gradient nearest neighbor (GNN) datasets provide powerful tools for predicting forest change impacts on wildlife populations and identify winners and losers in dynamic landscapes. The second monitoring phase will leverage new technologies, expand the scope of inference, link forest inventory and remote sensing datasets, and transition the program to broad biodiversity monitoring that assists managers as they face myriad challenges in dynamic landscapes.
The role of gut microbiota in liver regeneration
Authors: Xu Zhe , Jiang Nan , Xiao Yuanyuan , Yuan Kefei , Wang Zhen
Published: October 2022

The liver has unique regeneration potential, which ensures the continuous dependence of the human body on hepatic functions. As the composition and function of gut microbiota has been gradually elucidated, the vital role of gut microbiota in liver regeneration through gut-liver axis has recently been accepted. In the process of liver regeneration, gut microbiota composition is changed. Moreover, gut microbiota can contribute to the regulation of the liver immune microenvironment, thereby modulating the release of inflammatory factors including IL-6, TNF-α, HGF, IFN-γ and TGF-β, which involve in different phases of liver regeneration. And previous research have demonstrated that through enterohepatic circulation, bile acids (BAs), lipopolysaccharide, short-chain fatty acids and other metabolites of gut microbiota associate with liver and may promote liver regeneration through various pathways. In this perspective, by summarizing gut microbiota-derived signaling pathways that promote liver regeneration, we unveil the role of gut microbiota in liver regeneration and provide feasible strategies to promote liver regeneration by altering gut microbiota composition.
CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy
Authors: Pape Luca Julius , Hambach Julia , Gebhardt Anna Josephine , Rissiek Björn , Stähler Tobias , Tode Natalie , Khan Cerusch , Weisel Katja , Adam Gerhard , Koch-Nolte Friedrich , Bannas Peter
Published: October 2022

Rationale

Recent studies have demonstrated the feasibility of CD38-specific antibody constructs for in vivo imaging of multiple myeloma. However, detecting multiple myeloma in daratumumab-pretreated patients remains difficult due to overlapping binding epitopes of the CD38-specific imaging antibody constructs and daratumumab. Therefore, the development of an alternative antibody construct targeting an epitope of CD38 distinct from that of daratumumab is needed. We report the generation of a fluorochrome-conjugated nanobody recognizing such an epitope of CD38 to detect myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.

Methods

We conjugated the CD38-specific nanobody JK36 to the near-infrared fluorescent dye Alexa Fluor 680. The capacity of JK36AF680 to bind and detect CD38-expressing cells pretreated with daratumumab was evaluated on CD38-expressing tumor cell lines in vitro, on primary myeloma cells from human bone marrow biopsies ex vivo, and in a mouse tumor model in vivo.

Results

Fluorochrome-labeled nanobody JK36AF680 showed specific binding to CD38-expressing myeloma cells pretreated with daratumumab in vitro and ex vivo and allowed for specific imaging of CD38-expressing xenografts in daratumumab-pretreated mice in vivo.

Conclusions

Our study demonstrates that a nanobody recognizing a distinct, non-overlapping epitope of CD38 allows the specific detection of myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.
Anakinra Pilot – a clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants
Authors: Green Elys A. , Metz David , Galinsky Robert , Atkinson Rebecka , Skuza Elizbeth M. , Clark Megan , Gunn Alistair J , Kirkpatrick Carl M. , Hunt Rod W. , Berger Philip J. , Nold-Petry Claudia A. , Nold Marcel F.
Published: October 2022

Background

Bronchopulmonary dysplasia (BPD), its complication pulmonary hypertension (BPD-PH) and preterm brain and gut injury lead to significant morbidity and mortality in infants born extremely prematurely. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses. Two decades of clinical use in paediatric and adult medicine have established an excellent safety and efficacy record for IL-1 blockade with IL-1 receptor antagonist (IL-1Ra, medication name anakinra). Building on robust pre-clinical evidence, the Anakinra Pilot trial aims to demonstrate safety and feasibility of administering anakinra to preterm infants, and to establish pharmacokinetics in this population. Its ultimate goal is to facilitate large studies that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity.

Methods and analysis

Anakinra Pilot is an investigator-initiated, single arm, safety and feasibility dose-escalation trial in extremely preterm infants born between 24 weeks 0 days (240) and 276 weeks of gestational age (GA). Enrolled infants will receive anakinra intravenously over the first 21 days after birth, starting in the first 24 h after birth. In the first phase, dosing is 1 mg/kg every 48 h, and dosage will increase to 1.5 mg/kg every 24 h in the second phase. Initial anakinra dosing was determined through population pharmacokinetic model simulations. During the study, there will be a interim analysis to confirm predictions before undertaking dose assessment. Anakinra therapy will be considered safe if the frequency of adverse outcomes/events does not exceed that expected in infants born at 240-276 weeks GA.

Clinical Trial Registration

https://clinicaltrials.gov/, identifier NCT05280340.
Combined unsupervised and semi-automated supervised analysis of flow cytometry data reveals cellular fingerprint associated with newly diagnosed pediatric type 1 diabetes
Authors: Bechi Genzano Camillo , Bezzecchi Eugenia , Carnovale Debora , Mandelli Alessandra , Morotti Elisa , Castorani Valeria , Favalli Valeria , Stabilini Angela , Insalaco Vittoria , Ragogna Francesca , Codazzi Valentina , Scotti Giulia Maria , Del Rosso Stefania , Mazzi Benedetta Allegra , De Pellegrin Maurizio , Giustina Andrea , Piemonti Lorenzo , Bosi Emanuele , Battaglia Manuela , Morelli Marco J. , Bonfanti Riccardo , Petrelli Alessandra
Published: October 2022

An unbiased and replicable profiling of type 1 diabetes (T1D)-specific circulating immunome at disease onset has yet to be identified due to experimental and patient selection limitations. Multicolor flow cytometry was performed on whole blood from a pediatric cohort of 107 patients with new-onset T1D, 85 relatives of T1D patients with 0-1 islet autoantibodies (pre-T1D_LR), 58 patients with celiac disease or autoimmune thyroiditis (CD_THY) and 76 healthy controls (HC). Unsupervised clustering of flow cytometry data, validated by a semi-automated gating strategy, confirmed previous findings showing selective increase of naïve CD4 T cells and plasmacytoid DCs, and revealed a decrease in CD56brightNK cells in T1D. Furthermore, a non-selective decrease of CD3+CD56+ regulatory T cells was observed in T1D. The frequency of naïve CD4 T cells at disease onset was associated with partial remission, while it was found unaltered in the pre-symptomatic stages of the disease. Thanks to a broad cohort of pediatric individuals and the implementation of unbiased approaches for the analysis of flow cytometry data, here we determined the circulating immune fingerprint of newly diagnosed pediatric T1D and provide a reference dataset to be exploited for validation or discovery purposes to unravel the pathogenesis of T1D.