bluuebunny/crossref_metadata_2025 huggingface dataset:
AGRISENSE: SMART IOT-BASED AGRICULTURAL SYSTEM
Authors: Gulhane Atharva , Mishra Varun , PralhadNehe Samarth , Saikarthik P.G.V ,   Vellore Institute of Technology
Published: October 2023

-Agriculture is most labor intensive as well as a very important field of occupation and because of environmental variations plant growth is affected a lot. Stabilizing the growth of plants and thereby increasing the output is a topic of major concern and by using the present technology automation can be provided in this field which will definitely help the farmers in the long run. Our idea is to build a system that will implement the use of microcontrollers and sensors to increase crop productivity. We aim to extract soil parameters like humidity, temperature, etc., and to display the same in a web interface (in this case a web page) for constant monitoring of the crop field. An irrigation system will also be installed which will operate according to the extracted parameters of the soil. The system will monitor the soil parameters constantly and in case of high humidity requirement the irrigation system will supply water to the field to meet the crop’s moisture requirement.
ROLE OF GREEN TECHNOLOGY IN DESIGNING SUSTAINABLE ENGINEERING FRAMEWORK-A REVIEW
Authors: Chougule Dr. M. B. , Chougule Vaishnavi , Chougule Prajakta ,   DKTE Society’s Textile and Engineering Institute
Published: October 2023

Since the stone age, humanity has discovered different phenomenon by observing nature and has utilized them for its welfare. Today, as we proceed towards erudite civilization, more resources are required to aid our advancement in technology. Hence, the energy crisis and ecocide have taken a significant toll on us and it has alarmed many scientific societies all around the world. In regards to sustainable growth aspects, UNESCO has announced 17 Sustainable Development Goals to help and guide nations to align their policies while keeping sustainability in mind. In this SDG list, 5 of the goals are related to the energy crisis highlighting its urgency. As future generation engineers, practicing sustainability engineering is essential to ensure safe energy production and resource sustainability. To battle this havoc of energy crisis, green energy emerged as a weapon for engineers but its proper utilization is still a mystery to those in the fieldwork. This paper, with help of case studies, is intended to help understand the role of green technology in the professional field while practicing sustainability engineering.
AETIOLOGY ON EMOTION RECOGNITION STRATEGIES USING VIDEO, ELECTROENCEPHALOGRAM AND PHYSIOLOGICAL SIGNALS
Authors: Vala Jay M. , Jaliya Prof. (Dr.) Udesang K. ,   Gujarat Technological University
Published: October 2023

Multimodal emotion recognition is a research area that involves using signals of various natures, such as facial expressions, speech, gestures, and physiological signals, to recognize emotions accurately. This field has gained importance due to its potential applications in decision-making, human recognition, and social interaction. One of the significant challenges in multimodal emotion recognition is feature extraction, which involves identifying the relevant features from the signals that carry emotional information. Various techniques have been developed for feature extraction, including machine learning-based methods, such as deep learning, feature fusion, and feature selection. These techniques aim to extract the most relevant and discriminative features from the signals to improve the accuracy of emotion recognition.
‘Adiutores Mahumet compilauerunt Alchoran’: The Role of ‘the Jews’ in Understanding and Refuting the Qur'an and Islam at Cluny
Authors: Di Cesare Michelina
Published: October 2023

This paper investigates the reasons for the selection of the three texts that, in the Corpus islamolatinum, were meant to represent the foundational texts of Islam along with the Qur'an. Indeed, these texts do not play this momentous role in Islamic tradition. By analysing specific passages of Muḥammad's biography found in the polemical writings framing the core of the Corpus, and Peter's later works against Muslims and Jews, it will be argued that the three texts were chosen for their authors and contents: two of the three Jews who, according to the translation of the Risālat al-Kindī included in the Corpus, instructed Muḥammad in their apocryphal writings and edited the Qur'an; the acknowledgment of Muḥammad's prophetical status as due to Jewish messianism. Thus, the fabule Sarracenorum, as the three texts and the Qur'an are labelled in the oldest manuscript of the Corpus, turn out to be fabule Iudeorum, and Islam is presented as the product of Judaism. By contextualising this conclusion within the previous Cluniac reflection on the religious identity of Muslims, a possible identification of the concepteur of the Corpus islamolatinum will also be proposed.
Variae lectiones de la traducción latina del Alcorán de Robert de Ketton en el Itinerarium Symonis Semeonis
Authors: Justicia Lara Agustín
Published: October 2023

El presente artículo se propone examinar las variantes textuales de la traducción del Alcorán de Robert de Ketton en el Itinerarium Symonis Semeonis, la narración de la peregrinación desde Irlanda hacia Tierra Santa llevada a cabo por los franciscanos irlandeses Symon Semeonis y Hugo Illuminator entre 1323 y 1324. El uso polémico que dio Symon Semeonis a la primera traducción latina del Alcorán para describir la población musulmana y el credo islámico en su paso por Egipto, ha permitido realizar un análisis filológico para lograr una aproximación a la familia de manuscritos del Corpus Islamolatinum utilizada por el franciscano irlandés. Para ello, se ha dividido el artículo en tres partes: en primer lugar, una introducción al único manuscrito conservado del Itinerarium Symonis Semeonis, así como un resumen de su peregrinación, poniendo atención en las principales características; en segundo lugar, tras una breve introducción a la historia textual del Corpus Islamolatinum, se han registrado las principales omisiones y variantes textuales encontradas en el Itinerarium Symonis Semeonis; el artículo concluye con una discusión de los resultados obtenidos y una hipótesis de identificación.
Presenza del Corano in due Itineraria quattrocenteschi
Authors: Burgio Eugenio , Simion Samuela
Published: October 2023

L’articolo si occupa della ricezione del Corano in due testi di pellegrinaggio in Terrasanta scritti alla fine del XV secolo, gli Itineraria dei patrizi di Bruges Anselmo e Giovanni Adorno (1470–71) e del giudice mantovano Antonio da Crema (1486–89). Le due esperienze si collocano nella zona ‘autunnale’ della peregrinatio medievale, dopo il fallimento dei progetti di Crociata seguiti alla caduta di Costantinopoli (1453). Entrambi i testi presentano un profilo duplice: da una parte essi conservano il carattere e la forma tradizionali, per cui il testo è veridica certificazione e memoria di un atto devoto, il ritorno ai luoghi di Cristo e delle Scritture. Dall’altra essi innestano sulla registrazione dell’esperienza diretta informazioni derivate da più fonti scritte. In questo intreccio di dato empirico e filtro letterario si colloca lo sforzo di mettere ordine razionale nei segni dell’Alterità religiosa, percepita nel Corano.
ECZANE İŞLETMELERİNDE TEMEL ETİK DEĞERLER: ANKARA İLİ ÖRNEĞİ
Authors: AKTAŞ Kadir
Published: October 2023

Etik kurallar; kanuni yükümlülüklerle yapılan işlere kıyasla daha hassas normları içeren ve toplumsal hayatta “neyin iyi, neyin doğru olduğunu” gösterici davranış kalıpları olarak ifade edilmektedir. Etik kurallar sabit ilkeler olmayıp, dünyadaki inanç ve kültürlerden etkilenen dinamik kurallar silsilesidir. Bu kurallar silsilesi, doğal olarak toplumsal hayatın bir parçası olan mesleki etiğin de oluşumuna zemin hazırlamış; sonuçta muhasebe etiği, basın etiği, eczacılık etiği ve tıp etiği gibi kavramlar ortaya çıkmıştır. Mesleklerin dünyadaki gelişmelerden etkilenerek gelişmesiyle birlikte, mesleki etik kodları da gelişmektedir. Bu sürece katkıda bulunmak maksadıyla, eczacılık mesleğindeki etik anlayışa yönelik bir araştırma yapılmıştır. Araştırmada Ankara’da görev yapmakta olan 13’ü yüz yüze ve 1’i telefon ile olmak üzere toplam 14 eczane çalışanıyla (12 eczacı ve 2 eczane çalışanı) önceden yapılandırılmamış mülakat yöntemiyle (eczacı, eczacı kalfası ve ecza depo bölge yöneticisi) “Eczacılık mesleğinde etik ve etik olmayan davranışlar nelerdir?” sorularını cevaplamak üzere icra edilmiştir. Bu kapsamda en çok dile getirilen etik davranışlar; önce insana değer verilmesi, önce sağlık çalışanı olduğunun bilinmesi, iş disiplinine uyum, hastanın tam bilgilendirilmesi, dürüstlük ve hasta mahremiyetinin korunması şeklinde sıralanmıştır. Etik olmayan davranışlar olarak ise; haksız rekabet, iş disiplinsizliği, hastayı tam bilgilendirmeme, ilaç dışı ürünlerden haksız kazanç, muvazaa (diplomanın ticarileştirilmesi), nöbetin usulüne uygun tutulmaması ve muadil ilacın dayatılması olarak sıralanmıştır.
The use of nanomaterials in advancing photodynamic therapy (PDT) for deep-seated tumors and synergy with radiotherapy
Authors: Dinakaran Deepak , Wilson Brian C.
Published: October 2023

Photodynamic therapy (PDT) has been under development for at least 40 years. Multiple studies have demonstrated significant anti-tumor efficacy with limited toxicity concerns. PDT was expected to become a major new therapeutic option in treating localized cancer. However, despite a shifting focus in oncology to aggressive local therapies, PDT has not to date gained widespread acceptance as a standard-of-care option. A major factor is the technical challenge of treating deep-seated and large tumors, due to the limited penetration and variability of the activating light in tissue. Poor tumor selectivity of PDT sensitizers has been problematic for many applications. Attempts to mitigate these limitations with the use of multiple interstitial fiberoptic catheters to deliver the light, new generations of photosensitizer with longer-wavelength activation, oxygen independence and better tumor specificity, as well as improved dosimetry and treatment planning are starting to show encouraging results. Nanomaterials used either as photosensitizers per se or to improve delivery of molecular photosensitizers is an emerging area of research. PDT can also benefit radiotherapy patients due to its complementary and potentially synergistic mechanisms-of-action, ability to treat radioresistant tumors and upregulation of anti-tumoral immune effects. Furthermore, recent advances may allow ionizing radiation energy, including high-energy X-rays, to replace external light sources, opening a novel therapeutic strategy (radioPDT), which is facilitated by novel nanomaterials. This may provide the best of both worlds by combining the precise targeting and treatment depth/volume capabilities of radiation therapy with the high therapeutic index and biological advantages of PDT, without increasing toxicities. Achieving this, however, will require novel agents, primarily developed with nanomaterials. This is under active investigation by many research groups using different approaches.
25 Years of PI5P
Authors: Rameh Lucia E. , Blind Raymond D.
Published: October 2023

The accidental discovery of PI5P (phosphatidylinositol-5-phosphate) was published 25 years ago, when PIP5K type II (phosphoinositide-4-phosphate 5-kinase) was shown to actually be a 4-kinase that uses PI5P as a substrate to generate PI(4,5)P2. Consequently, PIP5K type II was renamed to PI5P4K, or PIP4K for short, and PI5P became the last of the 7 signaling phosphoinositides to be discovered. Much of what we know about PI5P comes from genetic studies of PIP4K, as the pathways for PI5P synthesis, the downstream targets of PI5P and how PI5P affects cellular function all remain largely enigmatic. Nevertheless, PI5P and PI5P-dependent PI(4,5)P2 synthesis have been clearly implicated in metabolic homeostasis and in diseases such as cancer. Here, we review the past 25 years of PI5P research, with particular emphasis on the impact this small signaling lipid has on human health.
SARS-COV-2 protein NSP9 promotes cytokine production by targeting TBK1
Authors: Zhang Yihua , Xin Bowen , Liu Yinan , Jiang Wenyi , Han Wendong , Deng Jian , Wang Peihui , Hong Xiaowu , Yan Dapeng
Published: October 2023

SARS-COV-2 infection-induced excessive or uncontrolled cytokine storm may cause injury of host tissue or even death. However, the mechanism by which SARS-COV-2 causes the cytokine storm is unknown. Here, we demonstrated that SARS-COV-2 protein NSP9 promoted cytokine production by interacting with and activating TANK-binding kinase-1 (TBK1). With an rVSV-NSP9 virus infection model, we discovered that an NSP9-induced cytokine storm exacerbated tissue damage and death in mice. Mechanistically, NSP9 promoted the K63-linked ubiquitination and phosphorylation of TBK1, which induced the activation and translocation of IRF3, thereby increasing downstream cytokine production. Moreover, the E3 ubiquitin ligase Midline 1 (MID1) facilitated the K48-linked ubiquitination and degradation of NSP9, whereas virus infection inhibited the interaction between MID1 and NSP9, thereby inhibiting NSP9 degradation. Additionally, we identified Lys59 of NSP9 as a critical ubiquitin site involved in the degradation. These findings elucidate a previously unknown mechanism by which a SARS-COV-2 protein promotes cytokine storm and identifies a novel target for COVID-19 treatment.
Causality of occupational exposure on rheumatoid arthritis and ankylosing spondylitis: a two-sample mendelian randomization study
Authors: Du Kai , Zhang Chen-Yu , Li Ao , Hu Jia-Ze , Guo Ren , Li Shu-Ming
Published: October 2023

Objective

This study aimed to explore the potential causal link between three specific types of occupational exposure on rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

Method

A Two-sample Mendelian randomization (TSMR) analysis, comprising univariate MR (UVMR) and multivariate MR (MVMR) analyses, was performed to investigate the potential causal association between three types of occupational exposures, jobs involving mainly walking or standing (JWS), jobs involving heavy manual or physical work (JMP), and jobs involving shift work(JSW) on RA and AS. Genetic variants for genome-wide association studies (GWAS) of occupational exposure and AS were obtained from the UK Biobank. GWAS summary data for RA were obtained from FinnGen Biobank analysis. For UVMR, six methods of Inverse Variance Weighted (IVW), MR-Egger, Weighted Mode, Weighted Median, Simple Mode, MR pleiotropy residual sum, and outlier (MR-PRESSO) were used for the analysis. The MVMR was analyzed using the IVW model as well as the MR-Egger model.

Results

The UVMR suggested no causal relationship between the three occupational exposure and RA [IVW: P=0.59,0.21,0.63] or AS [IVW: P=0.43,0.57,0.04], as did the bidirectional MR [IVW: P=0.73,0.70,0.16], [IVW: P=0.65,0.68,0.74]. Although unadjusted MVMR suggested a causal relationship between JMP and AS [IVW: OR = 1.01, 95% CI = 1.00- 1.02, p = 0.02], the adjusted MVMR denied this relationship and concluded that there was no causal relationship between the other occupational exposure and either RA or AS.

Conclusion

Our MR analysis did not establish a direct causal relationship between certain occupational exposures and either RA or AS.
Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome
Authors: Röhl Louisa , Wellhausen Jana , Berszin Michael , Krücken Irene , Zebralla Veit , Pirlich Markus , Wiegand Susanne , Dietz Andreas , Wald Theresa , Wichmann Gunnar
Published: October 2023

Background

Immune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy.

Methods

Along five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan–Meier plots and multivariate Cox regression.

Results

We detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual’s risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1–36.2) months and median OS of 11.3 (8.8–13.8) and 2.9 (0.4-5.4) months were found.

Conclusion

Whereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.
Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology
Authors: Mazzarino Morgane , Cetin Esra , Bartosova Maria , Marinovic Iva , Ipseiz Natacha , Hughes Timothy R. , Schmitt Claus Peter , Ramji Dipak P. , Labéta Mario O. , Raby Anne-Catherine
Published: October 2023

Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory endogenous TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and progression of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression in the blood and aorta. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.
Distinct molecular subtypes of systemic sclerosis and gene signature with diagnostic capability
Authors: Wang Qi , Li Chen-Long , Wu Li , Hu Jing-Yi , Yu Qi , Zhang Sheng-Xiao , He Pei-Feng
Published: October 2023

Background

As Systemic Sclerosis (SSc) is a connective tissue ailment that impacts various bodily systems. The study aims to clarify the molecular subtypes of SSc, with the ultimate objective of establishing a diagnostic model that can inform clinical treatment decisions.

Methods

Five microarray datasets of SSc were retrieved from the GEO database. To eliminate batch effects, the combat algorithm was applied. Immune cell infiltration was evaluated using the xCell algorithm. The ConsensusClusterPlus algorithm was utilized to identify SSc subtypes. Limma was used to determine differential expression genes (DEGs). GSEA was used to determine pathway enrichment. A support vector machine (SVM), Random Forest(RF), Boruta and LASSO algorithm have been used to select the feature gene. Diagnostic models were developed using SVM, RF, and Logistic Regression (LR). A ROC curve was used to evaluate the performance of the model. The compound-gene relationship was obtained from the Comparative Toxicogenomics Database (CTD).

Results

The identification of three immune subtypes in SSc samples was based on the expression profiles of immune cells. The utilization of 19 key intersectional DEGs among subtypes facilitated the classification of SSc patients into three robust subtypes (gene_ClusterA-C). Gene_ClusterA exhibited significant enrichment of B cells, while gene_ClusterC showed significant enrichment of monocytes. Moderate activation of various immune cells was observed in gene_ClusterB. We identified 8 feature genes. The SVM model demonstrating superior diagnostic performance. Furthermore, correlation analysis revealed a robust association between the feature genes and immune cells. Eight pertinent compounds, namely methotrexate, resveratrol, paclitaxel, trichloroethylene, formaldehyde, silicon dioxide, benzene, and tetrachloroethylene, were identified from the CTD.

Conclusion

The present study has effectively devised an innovative molecular subtyping methodology for patients with SSc and a diagnostic model based on machine learning to aid in clinical treatment. The study has identified potential molecular targets for therapy, thereby offering novel perspectives for the treatment and investigation of SSc.
Effects of inflammation on myopia: evidence and potential mechanisms
Authors: Xu Ran , Zheng Jing , Liu Longqian , Zhang Wenqiu
Published: October 2023

As the most common type of refractive error, myopia has become one of the leading causes of visual impairment. With the increasing prevalence of myopia, there is a growing need to better understand the factors involved in its development. Inflammation, one of the most fundamental pathophysiological processes in humans, is a rapid response triggered by harmful stimuli and conditions. Although controlled inflammatory responses are necessary, over-activated inflammation is the common soil for many diseases. The impact of inflammation on myopia has received rising attention in recent years. Elevated inflammation may contribute to myopia progression either directly or indirectly by inducing scleral remodeling, and myopia development may also increase ocular inflammation. This article provides a comprehensive review of the interplay between inflammation and myopia and the potential biological mechanisms, which may present new targets for understanding the pathology of myopia and developing myopia therapies.
Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
Authors: Al-Awadhi Solaf , Raynaud Marc , Louis Kevin , Bouquegneau Antoine , Taupin Jean-Luc , Aubert Olivier , Loupy Alexandre , Lefaucheur Carmen
Published: October 2023

Introduction

Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.

Methods

We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.

Results

In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.

Discussion

We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Non-capsulated Neisseria meningitidis sepsis in a paroxysmal nocturnal hemoglobinuria patient treated with ravulizumab: case report and review of the literature
Authors: Galli Nicole , Pettine Loredana , Panigada Mauro , Daprai Laura , Suriano Grazia , Grancini Anna , Barcellini Wilma , Fattizzo Bruno
Published: October 2023

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease characterized by complement-mediated intravascular hemolysis, thrombosis, and bone marrow failure. Eculizumab and ravulizumab are anti-C5 monoclonal antibodies that reduce hemolysis, anaemia and thrombotic risk, but are associated with increased risk of infection with encapsulated bacteria, including Neisseria meningitidis. We report a case of life-threatening infection by non-groupable Neisseria meningitidis in a young PNH patient treated with ravulizumab. Despite prompt admission to the intensive care unit, microbe isolation was delayed due to the negativity of capsular antigens, and the patient required intubation, dialysis, and transfusion support for pancytopenia. Notably, PNH disease activity remained controlled and no additional anti-C5 doses were administered. Increasing awareness regarding septic risk in PNH patients on complement inhibitors despite vaccinations is pivotal. A warning about serotypes generally not pathogenetic and not covered by vaccination, such as non-capsulated forms, is emerging.
Longitudinal evaluation of innate immune responses to three doses of CoronaVac vaccine
Authors: Cao Cheng , Jiang Junfeng , Liu Min , Dai Yaping , Chang Tianzhi , Ji Tuo , Gong Fang
Published: October 2023

The adaptive immune responses induced by inactivated COVID-19 vaccine has been extensively studied. However, few studies have analyzed the impact of COVID-19 vaccination on innate immune cells. Here in this study, we recruited 62 healthcare workers who received three doses of CoronaVac vaccine and longitudinally profiled the alterations of peripheral monocytes and NK cells during vaccination. The results showed that both the monocyte and NK cell subsets distribution were altered, although the frequencies of the total monocyte and NK cells remained stable during the vaccination. Additionally, we found that both the 2nd and 3rd dose of CoronaVac vaccination elicited robust IFN-γ-producing NK cell response. Our data provided necessary insights on innate immune responses in the context of three homologous CoronaVac dose vaccination, and supplied immunological basis for the future design of inactivated vaccines against SARS-CoV-2 or other viruses.
Exploring alternative approaches to precision medicine through genomics and artificial intelligence – a systematic review
Authors: Mumtaz Hassan , Saqib Muhammad , Jabeen Sidra , Muneeb Muhammad , Mughal Wajiha , Sohail Hassan , Safdar Myra , Mehmood Qasim , Khan Muhammad Ahsan , Ismail Syed Muhammad
Published: October 2023

The core idea behind precision medicine is to pinpoint the subpopulations that differ from one another in terms of disease risk, drug responsiveness, and treatment outcomes due to differences in biology and other traits. Biomarkers are found through genomic sequencing. Multi-dimensional clinical and biological data are created using these biomarkers. Better analytic methods are needed for these multidimensional data, which can be accomplished by using artificial intelligence (AI). An updated review of 80 latest original publications is presented on four main fronts—preventive medicine, medication development, treatment outcomes, and diagnostic medicine—All these studies effectively illustrated the significance of AI in precision medicine. Artificial intelligence (AI) has revolutionized precision medicine by swiftly analyzing vast amounts of data to provide tailored treatments and predictive diagnostics. Through machine learning algorithms and high-resolution imaging, AI assists in precise diagnoses and early disease detection. AI’s ability to decode complex biological factors aids in identifying novel therapeutic targets, allowing personalized interventions and optimizing treatment outcomes. Furthermore, AI accelerates drug discovery by navigating chemical structures and predicting drug-target interactions, expediting the development of life-saving medications. With its unrivaled capacity to comprehend and interpret data, AI stands as an invaluable tool in the pursuit of enhanced patient care and improved health outcomes. It’s evident that AI can open a new horizon for precision medicine by translating complex data into actionable information. To get better results in this regard and to fully exploit the great potential of AI, further research is required on this pressing subject.
Complete genome sequence of “Candidatus Phytoplasma sacchari” obtained using a filter-based DNA enrichment method and Nanopore sequencing
Authors: Zhang Rong-Yue , Wang Xiao-Yan , Li Jie , Shan Hong-Li , Li Yin-Hu , Huang Ying-Kun , He Xia-Hong
Published: October 2023

Phytoplasmas are phloem-limited plant pathogens, such as sugarcane white leaf (SCWL) phytoplasma, which are responsible for heavy economic losses to the sugarcane industry. Characterization of phytoplasmas has been limited because they cannot be cultured in vitro. However, with the advent of genome sequencing, different aspects of phytoplasmas are being investigated. In this study, we developed a DNA enrichment method for sugarcane white leaf (SCWL) phytoplasma, evaluated the effect of DNA enrichment via Illumina sequencing technologies, and utilized Illumina and Nanopore sequencing technologies to obtain the complete genome sequence of the “Candidatus Phytoplasma sacchari” isolate SCWL1 that is associated with sugarcane white leaf in China. Illumina sequencing analysis elucidated that only 1.21% of the sequencing reads from total leaf DNA were mapped to the SCWL1 genome, whereas 40.97% of the sequencing reads from the enriched DNA were mapped to the SCWL1 genome. The genome of isolate SCWL1 consists of a 538,951 bp and 2976 bp long circular chromosome and plasmid, respectively. We identified 459 protein-encoding genes, 2 complete 5S-23S-16S rRNA gene operons, 27 tRNA genes, and an incomplete potential mobile unit (PMU) in the circular chromosome. Phylogenetic analyses and average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values based on the sequenced genome revealed that SCWL phytoplasma and sugarcane grassy shoot (SCGS) phytoplasma belonged to the same phytoplasma species. This study provides a genomic DNA enrichment method for phytoplasma sequencing. Moreover, we report the first complete genome of a “Ca. Phytoplasma sacchari” isolate, thus contributing to future studies on the evolutionary relationships and pathogenic mechanisms of “Ca. Phytoplasma sacchari” isolates.
Shifts in the swine nasal microbiota following Bordetella bronchiseptica challenge in a longitudinal study
Authors: Nielsen Daniel W. , Hau Samantha J. , Mou Kathy T. , Alt David P. , Brockmeier Susan L.
Published: October 2023

Bordetella bronchiseptica is a widespread, highly infectious bacterial pathogen that causes respiratory disease in swine and increases the severity of respiratory infections caused by other viral or bacterial pathogens. However, the impact of B. bronchiseptica infection on the swine respiratory microbiota has not been thoroughly investigated. Here, we aim to assess the influence of B. bronchiseptica infection on the community structure and abundance of members of the swine nasal microbiota. To do so, the nasal microbiota of a non-infected control group and a group infected with B. bronchiseptica (BB group) were characterized prior to B. bronchiseptica strain KM22 challenge (day 0) and on selected days in the weeks following B. bronchiseptica challenge (days 1, 3, 7, 10, 14, 21, 36, and 42). Bordetella bronchiseptica was cultured from nasal samples of the BB group to assess nasal colonization. The results showed that B. bronchiseptica colonization did not persistently affect the nasal bacterial diversity of either of the treatment groups (alpha diversity). However, the bacterial community structures (beta diversity) of the two treatment groups significantly diverged on day 7 when peak colonization levels of B. bronchiseptica were detected. This divergence continued through the last sampling time point. In addition, Pasteurella, Pasteurellaceae (unclassified), Mycoplasma, Actinobacillus, Streptococcus, Escherichia-Shigella, and Prevotellaceae (unclassified) showed increased abundances in the BB group relative to the control group at various time points. This study revealed that B. bronchiseptica colonization can disturb the upper respiratory tract microbiota, and further research is warranted to assess how these disturbances can impact susceptibility to secondary infections by other respiratory pathogens.
Recent advances on cyclodepsipeptides: biologically active compounds for drug research
Authors: Liu Si-Xuan , Ou-Yang Si-Yi , Lu Yong-Fu , Guo Chun-Lin , Dai Si-Yang , Li Chang , Yu Tian-Yi , Pei Yue-Hu
Published: October 2023

Cyclodepsipeptides are a large family of peptide-related natural products consisting of hydroxy and amino acids linked by amide and ester bonds. A number of cyclodepsipeptides have been isolated and characterized from fungi and bacteria. Most of them showed antitumor, antifungal, antiviral, antimalarial, and antitrypanosomal properties. Herein, this review summarizes the recent literatures (2010–2022) on the progress of cyclodepsipeptides from fungi and bacteria except for those of marine origin, in order to enrich our knowledge about their structural features and biological sources.
Ambient assisted living for frail people through human activity recognition: state-of-the-art, challenges and future directions
Authors: Guerra Bruna Maria Vittoria , Torti Emanuele , Marenzi Elisa , Schmid Micaela , Ramat Stefano , Leporati Francesco , Danese Giovanni
Published: October 2023

Ambient Assisted Living is a concept that focuses on using technology to support and enhance the quality of life and well-being of frail or elderly individuals in both indoor and outdoor environments. It aims at empowering individuals to maintain their independence and autonomy while ensuring their safety and providing assistance when needed. Human Activity Recognition is widely regarded as the most popular methodology within the field of Ambient Assisted Living. Human Activity Recognition involves automatically detecting and classifying the activities performed by individuals using sensor-based systems. Researchers have employed various methodologies, utilizing wearable and/or non-wearable sensors, and employing algorithms ranging from simple threshold-based techniques to more advanced deep learning approaches. In this review, literature from the past decade is critically examined, specifically exploring the technological aspects of Human Activity Recognition in Ambient Assisted Living. An exhaustive analysis of the methodologies adopted, highlighting their strengths and weaknesses is provided. Finally, challenges encountered in the field of Human Activity Recognition for Ambient Assisted Living are thoroughly discussed. These challenges encompass issues related to data collection, model training, real-time performance, generalizability, and user acceptance. Miniaturization, unobtrusiveness, energy harvesting and communication efficiency will be the crucial factors for new wearable solutions.
Resting-state EEG microstates as electrophysiological biomarkers in post-stroke disorder of consciousness
Authors: Yu Fang , Gao Yanzhe , Li Fenglian , Zhang Xueying , Hu Fengyun , Jia Wenhui , Li Xiaohui
Published: October 2023

Introduction

Ischemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology.

Methods

In our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC.

Results

Both groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates’ temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%).

Discussion

Our results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.
Multivariate piecewise linear regression model to predict radiosensitivity using the association with the genome-wide copy number variation
Authors: Tobiasz Joanna , Al-Harbi Najla , Bin Judia Sara , Majid Wakil Salma , Polanska Joanna , Alsbeih Ghazi
Published: October 2023

Introduction

The search for biomarkers to predict radiosensitivity is important not only to individualize radiotherapy of cancer patients but also to forecast radiation exposure risks. The aim of this study was to devise a machine-learning method to stratify radiosensitivity and to investigate its association with genome-wide copy number variations (CNVs) as markers of sensitivity to ionizing radiation.

Methods

We used the Affymetrix CytoScan HD microarrays to survey common CNVs in 129 fibroblast cell strains. Radiosensitivity was measured by the surviving fraction at 2 Gy (SF2). We applied a dynamic programming (DP) algorithm to create a piecewise (segmented) multivariate linear regression model predicting SF2 and to identify SF2 segment-related distinctive CNVs.

Results

SF2 ranged between 0.1384 and 0.4860 (mean=0.3273 The DP algorithm provided optimal segmentation by defining batches of radio-sensitive (RS), normally-sensitive (NS), and radio-resistant (RR) responders. The weighted mean relative errors (MRE) decreased with increasing the segments' number. The borders of the utmost segments have stabilized after partitioning SF2 into 5 subranges.

Discussion

The 5-segment model associated C-3SFBP marker with the most-RS and C-7IUVU marker with the most-RR cell strains. Both markers were mapped to gene regions (MCC and SLC1A6, respectively). In addition, C-3SFBP marker is also located in enhancer and multiple binding motifs. Moreover, for most CNVs significantly correlated with SF2, the radiosensitivity increased with the copy-number decrease.

In conclusion, the DP-based piecewise multivariate linear regression method helps narrow the set of CNV markers from the whole radiosensitivity range to the smaller intervals of interest. Notably, SF2 partitioning not only improves the SF2 estimation but also provides distinctive markers. Ultimately, segment-related markers can be used, potentially with tissues’ specific factors or other clinical data, to identify radiotherapy patients who are most RS and require reduced doses to avoid complications and the most RR eligible for dose escalation to improve outcomes.
Temporal changes in treatment patterns by age group and functional status before and after PD-1/L1 inhibitor approvals in advanced urothelial carcinoma
Authors: Doshi Gurjyot K. , Li Haojie , Burcu Mehmet , Annavarapu Srinivas , Wells Karen , Imai Kentaro , Moreno Blanca Homet , Singhal Puneet , Mamtani Ronac
Published: October 2023

Introduction

Metastatic urothelial carcinoma (mUC) has poor prognosis. A high unmet need exists for novel treatment for those who are unfit for platinum-based chemotherapy.

Methods

We aimed to describe real-world temporal changes in patient characteristics and 1L treatment selection for mUC patients in the United States following the approval of anti-PD-1/L1 treatments. This study was a retrospective, observational study using anonymized and structured oncology electronic medical record (EMR) data from IQVIA and the US Oncology Network iKnowMed (USON).

Results

After approval of 1L anti-PD-1/L1 treatment for mUC, there is a marked increase in the use of 1L anti-PD-1/L1 monotherapies, accompanied by a proportional decrease in 1L platinum-based treatments and non-guideline-based therapy; particularly among the elderly (> 75 years) and those with poor ECOG performance status (ECOG PS 2+).

Discussion

Anti-PD-1/L1 monotherapies fulfill the prior unmet need of frail mUC patients who are ineligible for platinum-based therapies.
Leader motivation identification: relationships with goal-directed values, self-esteem, self-concept clarity, and self-regulation
Authors: Van Doorn Judy R. , Raz Cody J.
Published: October 2023

Motivation tied to workplace performance is key to organizational effectiveness with visionary leadership. Identifying leaders on a spectrum of different motivation styles, culture values, self-concept clarity, self-esteem, and self-regulation factors may assist with company training goals and impact global organizational performance. The purpose of this study is to assess leader motivation through traits, cultural values, and behavior approaches including (1) motivation to lead (MTL)-style differences subsuming affective-identity, social-normative, and non-calculative styles; (2) the effect of MTL-style relationships to culture values, global self-esteem, and self-concept clarity; and (3) the effect of MTL styles to individual self-regulation subsuming goal-setting and impulse-control behaviors. Participants (N = 1,121) self-reported work and military experiences with managerial or supervisory experience. Research evidence included culture values of power and self-direction which predicted the affective-identity style. The values of power, achievement, conformity, and security positively predicted the social-normative style. Leader self-regulation factors of goal-setting and impulse control were positively predicted by achievement, self-direction, conformity, and benevolence values. Tradition and security values negatively predicted goal-setting, and values of tradition, security, stimulation, and universalism negatively predicted impulse control. Meaningful differences were found between MTL styles with values, global self-esteem, and self-regulation factors. This study may assist with identifying potential organizational leaders through MTL assessment and leader training needs that are focused on goal-setting and self-regulation diplomacy.
Impact of virtual reality on pain management in transrectal MRI-guided prostate biopsy
Authors: Perenic Emma , Grember Emilie , Bassard Sébastien , Koutlidis Nicolas
Published: October 2023

Background

The beneficial effect of virtual reality (VR) on pain management in the context of transrectal MRI-guided prostate biopsy is not well established. However, it remains unclear whether an adjunctive of VR also improves pain management. This study aimed to evaluate the impact of VR as adjunctive in pain management in transrectal MRI-guided prostate biopsy (PB).

Methods

We retrospectively evaluated the pain intensity incidence in the 153 patients with PB indication (of which 102 were naïve of PB) who were admitted to our hospital since the acquisition of the Healthy Mind virtual reality headset on 19 January 2021.

Results

Baseline characteristics of patients who received local anesthesia with 1% lidocaine periprostatic nerve block (PPNB) (Group SOC, N = 78) and patients who received VR associated with PPNB (Group VR, N = 75) were largely similar. One PB with general anesthesia was excluded. The mean pain score at day zero was respectively 3.4 (±2.5) and 2.9 (±2.3) for SOC and VR (p = 0.203). However, the mean pain score at day zero was significantly lower in naïve PB patients with VR [2.7 (±2.0)] than in naïve PB patients with SOC [3.8 (±2.5), p = 0.012] when patients were stratified in PB status. Similar results were found on day 3 for the analysis including naïve-PB patients with SOC vs. with VR [0.4 (±2.5) vs. 0.2 (±2.0); p = 0.023)].

Conclusions

The pain intensity was significantly lower in naïve PB patients with VR than in naïve PB patients with SOC. There were no side effects from VR and tolerability was excellent.