bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxa de mortalidade durante episódios de exacerbação da Doença Pulmonar Obstrutiva Crônica (DPOC) em indivíduos idosos hospitalizados em uma instituição universitária no Estado do Paraná, Brasil
Authors: Ferreira Bruna Paludo , Genske Juliana Hering , Abramovecht Janaina , Genske Bruno Hering , Schaefer Alessandro , Almeida Caio Fernandes de , Pastorio Daiane Maria , Abramovecht Gustavo , Magnante Jéssica , Burgarelli Juliana Almeida
Published: January 2024

As exacerbações agudas (EADPOC) da DPOC impactam negativamente o estado de saúde, as taxas de hospitalização, a progressão da doença e os custos do sistema de saúde, e outros eventos agudos podem mimetizar ou agravar uma EADPOC, podendo levar à dificuldade diagnóstica, sobretudo em pacientes idosos com múltiplas comorbidades associadas. A idade avançada é um fator de risco isolado e corresponde à mediana de idade dos pacientes com estágios mais graves da doença, sendo assim, é crucial a identificação precoce de pacientes com risco de mortalidade hospitalar. Estudo observacional, retrospectivo, quantitativo, aprovado no CEP/CAAE 63850022.8.0000.0107. Foram coletados dados de prontuários eletrônicos entre março/2019 e fevereiro/2023, de pacientes com idade ≥60 anos com CID-10 J44 e busca ativa de prontuários de pacientes com hipótese diagnóstica de EADPOC com outras classificações de CID. Internaram 169 pacientes com hipótese diagnóstica de EADPOC em evoluções médicas, muitos com outras CID-10 (entre elas J96, J15, J18, B342, R060) que podem estar relacionadas à EADPOC. A mortalidade (n=169) foi de 46,15%. No total, 59 pacientes com CID-10 J44 caracterizaram a amostra, com mortalidade de 37,5%. A mortalidade de pacientes com EADPOC ˃60 anos é elevada, sendo ureia, LA e PCR elevados na admissão fatores predisponentes. O presente estudo, teve como objetivo analisar fatores clínicos relacionados à mortalidade em pacientes idosos com 60 anos ou mais, hospitalizados em uma instituição de ensino vinculada ao Sistema Único de Saúde (SUS) devido à Exacerbação Aguda da Doença Pulmonar Obstrutiva Crônica (EADPOC), e avaliou a existência de possíveis casos de subdiagnóstico entre os pacientes.
Inovasi pembelajaran digital berbasis satu sekolah satu chanel TV dalam pendidikan anak usia dini
Authors: Watini Sri , Wijayanthi Tika , Hendrica Mega , Maulidina Farah Ayu , Erlina  , Putri Mulyana Sukarni
Published: January 2024

Pola konsumsi media yang sudah beralih ke media digital saat ini, tidak membuat masyarakat di Indonesia mengesampingkan televisi sebagai media sumber informasi dan hiburan di ruang keluarga mereka. Akses rumah tangga terhadap perangkat TIK (Teknologi Informasi dan Komunikasi) tertinggi ada pada Televisi yakni sebesar 86,7%. Angka akses yang masih tinggi ini sayangnya tidak sejalan dengan indeks kualitas program televisi. Hasil indeks kualitas program siaran televisi untuk program acara yang diperuntukan untuk anak-anak hasilnya menunjukkan kualitas program acara anak-anak masih kurang baik. Media dan dampaknya merupakan isu yang selalu menjadi kajian bagi para peneliti dan akademisi, terutama jika audiensnya adalah anak-anak. Riset sebelumnya mengenai dampak tayangan televisi menunjukan beberapa dampak yang bersifat positif dan juga negatif. Tim Pengabdian Pada Masyarakat Universitas Pancasakti Bekasi berupaya untuk mengurangi dampak negatif tayang televisi pada anak-anak Usia Dini, maka kami memberikan penyuluhan terkait literasi media tayang televisi pada kepala sekolah, operator sekolah, dan guru yang tergabung dalam Organisasi IGTKI Kota Serang. Kegiatan PKM dilakukan kepada 50 kepala sekolah, Operator sekolah, dan guru yang tergabung dalam Organisasi IGTKI Kota Serang dengan mengadakan Kegiatan Workshop Inovasi Pembelajaran Digital Berbasis Satu Sekolah Satu Chanel TV Pada Lembaga PAUD Kota Serang dengan harapan agar guru bisa berinovasi di dalam media pembelajaran melalui TV Sekolah sebagai menanggulangi indeks negative dari kualitas program televisi.
PENDAMPINGAN BIMBINGAN BELAJAR UNTUK MENUMBUHKAN MOTIVASI PADA SISWA DI TPQ NURUL WATHAN DESA TRIWUNGAN KABUPATEN PROBOLINGGO
Authors: Juhairiyah Juhairiyah , Putri Purwaning , Wasilah Mariatul Kiftiah , Yahmun Yahmun , Susandi Susandi , Sari Ike Dian Puspita
Published: January 2024

Community Service which is one of the ways or efforts to implement the tri dharma of higher education. This is done with the aim of fostering student motivation and interest in the learning provided by the teacher. The learning assistance methods that are applied to students at TPQ Wathan, include; students and students carry out learning and teaching procedures directly. This tutoring assistance is carried out at TPQ Wathan, Triwungan Village, Probolinggo Regency, the material provided and taught by the teacher in tutoring assistance is desired by students The target object in the tutoring assistance research is students at the elementary level grades 1-6.
Everything Decomposes: Survivance Beyond the Human-Animal
Authors: Culpepper Abigail
Published: January 2024

The notion of survivance is central to Derrida’s later thinking. Much of that thinking, for example in addressing the non–human in The Animal That Therefore I Am and The Beast and the Sovereign, is more precisely a thinking of the human in relation to the animal. Taking inspiration from the recent turn towards biodeconstruction, this essay works through the implications of survivance beyond the human-animal by considering the synergy between biological and textual survivance. And in so doing, this essay outlines a new way of conceptualizing the living self as a composite form made up of many non-human and even textual others.
Experience, Excription, Existence: Nancy with Derrida, between Kant and Bataille
Authors: Hodge Joanna
Published: January 2024

This essay locates Jean-Luc Nancy's analyses, developed in relation to three invented terms, expeausition, excription, sexistence, in a threefold context: between Immanuel Kant on experience and Heidegger on existence; with Derrida on rethinking life and death ( lavielamort); and as a response to the alteration in phenomenology consequent on a transposition of key themes out of the German speaking context of the analyses of Husserl and Heidegger into the French language context of the French reception. An intensification ( survie) of life forces may arrive in a ‘living on’ ( survivre) where thought processes only partially brought to expression in the lifetimes of their originators acquire precision and definition in moments of extremity, danger and horror, adding a fourth dimension to the initial three.
Macrophages in Bone and Synovial Inflammation in Rheumatoid Arthritis
Authors: Jalalvand Mobina , Khanmohammadi Shaghayegh , Akhtari Maryam , Farhadi Elham , Jamshidi Ahmadreza , Mahmoudi Mahdi
Published: January 2024

Macrophages are members of the innate immune system; that originate from monocyte cells from the myeloid stem cells. In response to the tissue environment, monocytes differentiate into two subtypes of macrophages, M1, or M2. The M1 or classically activated macrophages (CAM) aggravate immune responses by releasing reactive oxygen species (ROS), and pro-inflammatory cytokines. The alternatively activated or M2 macrophages (AAM), are involved in the process of tissue repair by suppressing immune responses. The other type of macrophages are called tissue-resident macrophages and they originate from the primitive myeloid precursor cells of the yolk sac. Different types of macrophages affect the immune system through various pathways. Rheumatic diseases are inflammatory; disorders with an auto-immune basis that usually involve the musculoskeletal system, lungs, kidneys, and eyes. In rheumatoid arthritis (RA), the main affected organs are joints, bones, and cartilage; which cause joint swelling, tenderness, redness, decreased range of motion, and morning stiffness. The roles of macrophages in RA include the production of cytokines, activation of autoreactive B- and T-cells, and impairment of tissue repair in joints. The main purpose of this review article is to further discuss the underlying role of macrophages in inflammatory articular changes in RA patients.
A Narrative Development Process to Enhance Mental Health Considering Recent Hippocampus Research
Authors: Nash Carol
Published: January 2024

Narrative development is fundamental to human mental health. Interventions providing individuals with the means to construct and recall robust and effective narratives are necessary in promoting positive mental health outcomes. The primary embodied location of personal narrative development is the hippocampus. Recent advances regarding the relationship among the hippocampus, narrative, and mental health are thus relevant concerning the hippocampal mechanisms that simultaneously function to map environmental position and to generate episodic memories. Consequently, this study considers the role of the hippocampus with a limited, six-database review of “hippocampus, narrative, mental health” that located 127 records, and included 14 reports for study. The results support creating and maintaining stable and coherent narratives as fundamental to human mental health. Without this, people distort facts in their personal accounts, their body functions are disrupted, and their DNA becomes altered (critical to cancer formation and development) in the effort to sustain these personal narratives. As such, narrative construction is found to lead to negative mental health in a variety of ways unless positively developed in a manner compatible with identified hippocampal functions. One intervention proven successful in enhancing robust and effective narratives that are stable and coherent is the Health Narratives Research Process developed for those researchers self-identifying as experiencing burnout. This process is outlined, and its most recent results presented, demonstrating not only improved mental health but doing so in support of identified hippocampal function—offering the opportunity for future research regarding the relationship among narrative development, mental health, and the hippocampus.
BATI AFRİKA’DA NİJER-TÜRKİYE DOSTLUK HASTANESİ’NDE “HASTA MEMNUNİYETİ” ÜZERİNE YAPILMIŞ ARAŞTIRMA
Authors: YILDIRIM Gülsüm , AKYURT Nuran , GÜLER İlkay , SİNA İde
Published: January 2024

Nijer’in başkenti Niamey’de bulunan Nijer-Türkiye Dostluk Hastanesi’nde Haziran-Ağustos 2020 aylarında, hasta memnuniyet anketi yapılmıştır. Türkiye Sağlık Bakanlığı’nın hastanelerde kalite yönetim süreçlerinde uygulanan ayaktan ve yatan hasta hizmetleri memnuniyet anketleri kullanılmıştır. Anketlerin geçerlilik ve güvenilirlik testi için Cron-bach Alfa değeri kullanılarak ayaktan hasta memnuniyet anketi için %76.3, yatan hasta için %73.8 (>70) olarak tespit edilmiştir. Anlamlılık düzeyi p
Immune dysregulation and macrophage polarization in peri-implantitis
Authors: Li Yue , Li Xue , Guo Danni , Meng Lingwei , Feng Xianghui , Zhang Yi , Pan Shaoxia
Published: January 2024

The term “peri-implantitis” (peri-implantitis) refers to an inflammatory lesion of the mucosa surrounding an endosseous implant and a progressive loss of the peri-implant bone that supports the implant. Recently, it has been suggested that the increased sensitivity of implants to infection and the quick elimination of supporting tissue after infection may be caused by a dysregulated peri-implant mucosal immune response. Macrophages are polarized in response to environmental signals and play multiple roles in peri-implantitis. In peri-implantitis lesion samples, recent investigations have discovered a considerable increase in M1 type macrophages, with M1 type macrophages contributing to the pro-inflammatory response brought on by bacteria, whereas M2 type macrophages contribute to inflammation remission and tissue repair. In an effort to better understand the pathogenesis of peri-implantitis and suggest potential immunomodulatory treatments for peri-implantitis in the direction of macrophage polarization patterns, this review summarizes the research findings related to macrophage polarization in peri-implantitis and compares them with periodontitis.
Antimicrobial mechanisms of nanopatterned surfaces—a developing story
Authors: Pirouz Arash , Papakonstantinou Ioannis , Michalska Martyna
Published: January 2024

Whilst it is now well recognized that some natural surfaces such as seemingly fragile insect wings possess extraordinary antimicrobial properties, a quest to engineer similar nanopatterned surfaces (NPSs) is ongoing. The stake is high as biofouling impacts critical infrastructure leading to massive social and economic burden with an antimicrobial resistance (AMR) issue at the forefront. AMR is one of the most imminent health challenges the world is facing today. Here, in the effort to find more sustainable solutions, the NPSs are proposed as highly promising technology as their antimicrobial activity arises from the topographical features, which could be realized on multiple material surfaces. To fully exploit these potentials however, it is crucial to mechanistically understand the underlying killing pathways. Thus far, several mechanisms have been proposed, yet they all have one thing in common. The antimicrobial process is initiated with bacteria contacting nanopatterns, which then imposes mechanical stress onto bacterial cell wall. Hence, the activity is called “mechano-bactericidal”. From this point on, however, the suggested mechanisms start to diverge partly due to our limited understanding of force interactions at the interface. The aim of this mini review is to analyze the state-of-the-art in proposed killing mechanisms by categorizing them based on the characteristics of their driving force. We also highlight the current gaps and possible future directions in investigating the mechanisms, particularly by shifting towards quantification of forces at play and more elaborated biochemical assays, which can aid validating the current hypotheses.
Effect of sacubitril/valsartan on sinus rhythm maintenance after catheter ablation in patients with persistent atrial fibrillation without reduced ejection fraction heart failure: a study protocol for a multi-center, open-label, randomized, controlled, superiority clinical trial
Authors: Qiu Ruowu , Ni Qingqing , Wu Muli , Xiao Zhongbo , Xiao Jiaxin , Lin Weizhao , Huang Weipeng , Chen Yequn , Chen Chang , Hong Liekai
Published: January 2024

Introduction

A high recurrence rate of atrial fibrillation was monitored after catheter ablation for persistent atrial fibrillation. Sacubitril/valsartan can improve outcomes for patients with heart failure and ventricular tachycardia, but few studies examined whether it can reduce recurrence or improve cardiovascular outcomes in patients with persistent atrial fibrillation after catheter ablation. In this study, we will assess the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation through a randomized controlled trial (RCT).

Methods

This is a multi-center, randomized, controlled, open-label, superiority clinical trial involving 462 patients without reduced ejection fraction heart failure after catheter ablation of persistent atrial fibrillation. Patients will be randomized to (1) receive the standard treatment strategy plus sacubitril/valsartan titration, or (2) receive the standard treatment strategy without taking sacubitril/valsartan. The primary outcome will be sinus rhythm maintenance rate over 12 months, monitored by random electrocardiogram and 24-h Holter electrocardiogram.

Discussion

This study is designed to evaluate the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation. The results will evaluate sacubitril/valsartan as a novel treatment for improving prognosis and a complement to conventional drug therapy.

Trial Registration

Registered with Chinese Clinical Trials Registry on 27 August 2022, identifier: ChiCTR2200062995.
INSPIRE datahub: a pan-African integrated suite of services for harmonising longitudinal population health data using OHDSI tools
Authors: Bhattacharjee Tathagata , Kiwuwa-Muyingo Sylvia , Kanjala Chifundo , Maoyi Molulaqhooa L. , Amadi David , Ochola Michael , Kadengye Damazo , Gregory Arofan , Kiragga Agnes , Taylor Amelia , Greenfield Jay , Slaymaker Emma , Todd Jim ,   INSPIRE Network
Published: January 2024

Introduction

Population health data integration remains a critical challenge in low- and middle-income countries (LMIC), hindering the generation of actionable insights to inform policy and decision-making. This paper proposes a pan-African, Findable, Accessible, Interoperable, and Reusable (FAIR) research architecture and infrastructure named the INSPIRE datahub. This cloud-based Platform-as-a-Service (PaaS) and on-premises setup aims to enhance the discovery, integration, and analysis of clinical, population-based surveys, and other health data sources.

Methods

The INSPIRE datahub, part of the Implementation Network for Sharing Population Information from Research Entities (INSPIRE), employs the Observational Health Data Sciences and Informatics (OHDSI) open-source stack of tools and the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to harmonise data from African longitudinal population studies. Operating on Microsoft Azure and Amazon Web Services cloud platforms, and on on-premises servers, the architecture offers adaptability and scalability for other cloud providers and technology infrastructure. The OHDSI-based tools enable a comprehensive suite of services for data pipeline development, profiling, mapping, extraction, transformation, loading, documentation, anonymization, and analysis.

Results

The INSPIRE datahub's “On-ramp” services facilitate the integration of data and metadata from diverse sources into the OMOP CDM. The datahub supports the implementation of OMOP CDM across data producers, harmonizing source data semantically with standard vocabularies and structurally conforming to OMOP table structures. Leveraging OHDSI tools, the datahub performs quality assessment and analysis of the transformed data. It ensures FAIR data by establishing metadata flows, capturing provenance throughout the ETL processes, and providing accessible metadata for potential users. The ETL provenance is documented in a machine- and human-readable Implementation Guide (IG), enhancing transparency and usability.

Conclusion

The pan-African INSPIRE datahub presents a scalable and systematic solution for integrating health data in LMICs. By adhering to FAIR principles and leveraging established standards like OMOP CDM, this architecture addresses the current gap in generating evidence to support policy and decision-making for improving the well-being of LMIC populations. The federated research network provisions allow data producers to maintain control over their data, fostering collaboration while respecting data privacy and security concerns. A use-case demonstrated the pipeline using OHDSI and other open-source tools.
Combined obesity- and lipid-related indices are associated with hypogonadism in Chinese male patients with type 2 diabetes: a cross-sectional study
Authors: Yu Yongzhuo , Wang Yunyang , Xu Lili , Li Wenxuan , Wang Yangang
Published: January 2024

Background

There is insufficient attention to hypogonadism in Chinese males with type 2 diabetes mellitus (T2DM). We evaluated the relationship between Combined obesity- and lipid-related indices [Visceral Adiposity Index (VAI), Chinese Visceral Adiposity Index (CVAI), Triglyceride Glucose Index (TyG) and Lipid Accumulation Product (LAP)] with total testosterone (TT) and analyzed the predictive capability of the respective cut-off values.

Methods

We recruited 958 hospitalized male patients with T2DM at the Affiliated Hospital of Qingdao University, collected baseline data and four calculated indices, and obtained their dominance ratio (OR) and corresponding 95% confidence intervals (CI) with TT by multivariate logistic regression. Receiver operating characteristic (ROC) curves were then used to determine cutoff values in predicting hypogonadism (TT< 12 nmol/L), and we also analyzed the combinations between the different indices.

Results

VAI, CVAI, TyG, and LAP all have satisfactory predictive capabilities. The test capability (sensitivity and specificity) of all four indices was better or not worse than that of body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and waist circumference (WC). All four indices were effective predictors of hypogonadism at their respective cutoff values (VAI ≥ 2.284, CVAI ≥ 145.779, TyG ≥ 4.308, and LAP ≥ 59.850). Of these, LAP had the largest area under the curve (AUC, AUC = 0.852, Std. Error = 0.014, 95% CI = 0.818-0.873). However, the predictive capability of the combined indices was not significantly improved over the individual indices.

Conclusions

VAI, CVAI, TyG, and LAP are sensitive indices for predicting hypogonadism in Chinese male patients with T2DM. Considering the need for concise and accurate indices in clinical practice, we suggest LAP as a commonly used index.
Evaluation of 19 years of international external proficiency testing for high-resolution HLA typing
Authors: Voorter C. E. M. , Groeneveld L. , Heidt S. , Wieten L.
Published: January 2024

The international high-resolution external proficiency testing (EPT) started in 2004 with high-resolution typing of human leucocyte antigen (HLA) class I (HLA-A,B,C) and HLA class II (HLA-DRB1, DRB345, DQB1, and DPB1) alleles, since possibilities for such an EPT within Europe were limited and all existing EPTs at that time made use of the comparison of HLA typing results without a reference. This EPT was set up as a collaboration between the HLA laboratory of Leiden, providing DNA samples to the participants, and the laboratory of Maastricht, performing the high-resolution typing as the reference result and evaluating the results of all participants according to the prevailing European Federation for Immunogenetics (EFI) standards. Once a year, 12 samples were sent to the participating laboratories, and evaluation and certificates were provided at the end of that same year. During the years, the EPT was extended to low-resolution HLA class I and II typing, high-resolution typing including DQA1 and DPA1, and allelic resolution typing for HLA class I, the latter one being unique in this field. Evaluation of the high-resolution typing results of the last 19 years showed a clear increase in the number of loci tested by the participating laboratories and a clear change of method from Sanger sequencing with additional other techniques (SSO/SSP) to the nowadays widely used next-generation sequencing method. By strictly using the EFI rules for high-resolution HLA typing, the participants were made aware of the ambiguities within exons 2 and 3 for class I and exon 2 for class II and the presence of null alleles even in a two-field HLA typing. There was an impressive learning curve, resulting in >98% correctly typed samples since 2017 and a 100% fulfillment of EFI rules for all laboratories for all loci submitted in the last 2 years. Overall, this EPT meets the need of an EPT for high-resolution typing for EFI accreditation.
An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio
Authors: Wang Qiong , Qin Yu , Ma Jingyun , Zhou Kehao , Xia Guiping , Li Ya , Xie Li , Afful Richmond Godwin , Lan Qian , Huo Xingyu , Zou Jian , Yang Hailin
Published: January 2024

Background

Neutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge.

Objective

We employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19.

Methods

Peripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators.

Results

Morphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels.

Conclusion

Observing blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.
An in silico modeling approach to understanding the dynamics of the post-burn immune response
Authors: Korkmaz H. Ibrahim , Sheraton Vivek M. , Bumbuc Roland V. , Li Meifang , Pijpe Anouk , Mulder Patrick P. G. , Boekema Bouke K. H. L. , de Jong Evelien , Papendorp Stephan G. F. , Brands Ruud , Middelkoop Esther , Sloot Peter M. A. , van Zuijlen Paul P. M.
Published: January 2024

Introduction

Burns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data.

Methods

The simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system.

Results

We developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 – 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants.

Conclusion

Our findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 – 4 days post-burn.
Roles of tumor necrosis factor-like ligand 1A in γδT-cell activation and psoriasis pathogenesis
Authors: Wang Shangyi , Kozai Mina , Hiraishi Masaya , Rubel Md. Zahir Uddin , Ichii Osamu , Inaba Mutsumi , Matsuo Kazuhiro , Takada Kensuke
Published: January 2024

Background

Interleukin (IL)-17-producing γδT (γδT17) cells mediate inflammatory responses in barrier tissues. Dysregulated γδT17 cell activation can lead to the overproduction of IL-17 and IL-22 and the development of inflammatory diseases, including psoriasis. IL-23 and IL-1β are known to synergistically activate γδT17 cells, but the regulatory mechanisms of γδT17 cells have not been fully elucidated. This study aimed to reveal the contribution of the inflammatory cytokine tumor necrosis factor-like ligand 1A (TL1A) to γδT17 cell activation and psoriasis development.

Methods

Anti-TL1A antibody was injected into an imiquimod (IMQ)-induced murine psoriasis model. TL1A receptor expression was analyzed in splenic and dermal γδT cells. γδT cells were tested for cytokine production in vitro and in vivo under stimulation with IL-23, IL-1β, and TL1A. TL1A was applied to a psoriasis model induced by intradermal IL-23 injection. Mice deficient in γδT cells were intradermally injected with IL-23 plus TL1A to verify the contribution of TL1A-dependent γδT-cell activation to psoriasis development.

Results

Neutralization of TL1A attenuated γδT17 cell activation in IMQ-treated skin. TL1A induced cytokine production by splenic γδT17 cells in synergy with IL-23. Dermal γδT17 cells constitutively expressed a TL1A receptor at high levels and vigorously produced IL-22 upon intradermal IL-23 and TL1A injection but not IL-23 alone. TL1A exacerbated the dermal symptoms induced by IL-23 injection in wild-type but not in γδT cell–deficient mice.

Conclusion

These findings suggest a novel regulatory mechanism of γδT cells through TL1A and its involvement in psoriasis pathogenesis as a possible therapeutic target.
The expanding clinical spectrum of autoinflammatory diseases with NOD2 variants: a case series and literature review
Authors: Karamanakos Anastasios , Vougiouka Olga , Sapountzi Evdoxia , Venetsanopoulou Aliki I. , Tektonidou Maria G. , Germenis Anastasios E. , Sfikakis Petros P. , Laskari Katerina
Published: January 2024

Objective

To assess the impact conferred by NOD2 variants on the clinical spectrum of patients with systemic autoinflammatory diseases (SAIDs) in Greece.

Methods

Consecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing (NGS) targeting 26 SAID-associated genes, and carried at least one NOD2 gene variant, were retrospectively studied. The demographic, clinical and laboratory parameters were recorded.

Results

In total, 24 rare NOD2 variants in 23/167 patients (14%) were detected. Notably, 18 patients had at least one co-existing variant in 13 genes other than NOD2. Nine patients had juvenile- and 14 adult-onset disease. All patients presented with symptoms potentially induced by the NOD2 variants. In particular, the candidate clinical diagnosis was Yao syndrome (YAOS) in 12 patients (7% of the whole SAID cohort). The clinical spectrum of patients with YAOS (mean episode duration 8 days) was fever (n=12/12), articular symptoms (n=8), gastrointestinal symptoms (n=7; abdominal pain/bloating in 7; diarrhea in 4; oral ulcers in 3), serositis (n=7), and rash (n=5), while the inflammatory markers were elevated in all but one patient. Most of these patients showed a poor response to nonsteroidal anti-inflammatory drugs (n=7/9), colchicine (n=6/8) and/or anti-TNF treatment (n=3/4), while a complete response was observed in 6/10 patients receiving steroids and 3/5 on anti-IL1 treatment. Another 8 patients were diagnosed with either FMF (n=6) or PFAPA syndrome (n=2) presenting with prominent diarrhea (n=7), oral ulcers (n=2), periorbital swelling and sicca-like symptoms (n=1), or maculopapular rash (n=1). One patient had a clinically undefined SAID, albeit characterized by oral ulcers and diarrhea. Finally, one patient presented with chronic relapsing urticaria with periorbital edema and inflammatory markers, and another one had a Crohn-like syndrome with good response to anti-IL-1 but refractory to anti-TNF treatment.

Conclusion

NOD2 variants were detected in 1 out of 7 SAID patients and seem to have an impact on disease phenotype and treatment response. Further studies should validate combined molecular and clinical data to better understand these distinct nosological entities.
Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine
Authors: Ahmadivand Sohrab , Krpetic Zeljka , Martínez Merce Márquez , Garcia-Ordoñez Marlid , Roher Nerea , Palić Dušan
Published: January 2024

Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. Infectious Hematopoietic Necrosis virus (IHNV) is the causative agent of the WOAH-listed IHN diseases for which there are currently no therapeutic treatments and no globally available commercial vaccine. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold, we constructed a self-assembling IHNV nanovaccine (FerritVac). Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH, and temperature conditions, mimicking the harsh gastrointestinal condition of the virus main host (trout). MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture (ZFL cells) incubated with different doses of up to 100 µg/mL for 14 hours. FerritVac NPs also upregulated expression of innate antiviral immunity, IHNV, and other fish rhabdovirus infection gene markers (mx, vig1, ifit5, and isg-15) in the macrophage cells of the host. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable, and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine. This self-assembling protein nanocages as novel vaccine approach offers significant commercial potential for non-mammalian and enveloped viruses.
The influence of low-temperature resistant lactic acid bacteria on the enhancement of quality and the microbial community in winter Jerusalem Artichoke (Helianthus tuberosus L.) silage on the Qinghai-Tibet Plateau
Authors: Wei Xiaoqiang , Sun Xuemei , Zhang Haiwang , Zhong Qiwen , Lu Guangxin
Published: January 2024

Jerusalem Artichoke (Helianthus tuberosus L.), an emerging “food and fodder” economic crop on the Qinghai-Tibet Plateau. To tackle problems such as incomplete fermentation and nutrient loss occurring during the low-temperature ensilage of Jerusalem Artichokes in the plateau’s winter, this study inoculated two strains of low-temperature resistant lactic acid bacteria, Lactobacillus plantarum (GN02) and Lactobacillus brevis (XN25), along with their mixed components, into Jerusalem Artichoke silage material. We investigated how low-temperature resistant lactic acid bacteria enhance the quality of low-temperature silage fermentation for Jerusalem Artichokes and clarify its mutual feedback effect with microorganisms. Results indicated that inoculating low-temperature resistant lactic acid bacteria significantly reduces the potential of hydrogen and water-soluble carbohydrates content of silage, while increasing lactic acid and acetic acid levels, reducing propionic acid, and preserving additional dry matter. Inoculating the L. plantarum group during fermentation lowers pH and propionic acid levels, increases lactic acid content, and maintains a dry matter content similar to the original material. Bacterial community diversity exhibited more pronounced changes than fungal diversity, with inoculation having a minor effect on fungal community diversity. Within the bacteria, Lactobacillus remains consistently abundant (>85%) in the inoculated L. plantarum group. At the fungal phylum and genus levels, no significant changes were observed following fermentation, and dominant fungal genera in all groups did not differ significantly from those in the raw material. L. plantarum exhibited a positive correlation with lactic acid and negative correlations with pH and propionic acid. In summary, the inoculation of L. plantarum GN02 facilitated the fermentation process, preserved an acidic silage environment, and ensured high fermentation quality; it is a suitable inoculant for low-temperature silage in the Qinghai-Tibet Plateau.
Harzianic acid exerts antimicrobial activity against Gram-positive bacteria and targets the cell membrane
Authors: Ouyang Xudong , Hoeksma Jelmer , Beenker Wouter A.G. , van der Beek Samantha , den Hertog Jeroen
Published: January 2024

The thermophilic fungus Oidiodendron flavum is a saprobe that is commonly isolated from soil. Here, we identified a Gram-positive bacteria-selective antimicrobial secondary metabolite from this fungal species, harzianic acid (HA). Using Bacillus subtilis strain 168 combined with dynamic bacterial morphology imaging, we found that HA targeted the cell membrane. To further study the antimicrobial activity of HA, we isolated an HA-resistant strain, Bacillus subtilis strain M9015, and discovered that the mutant had more translucent colonies than the wild type strain, showed cross resistance to rifampin, and harbored five mutations in the coding region of four distinct genes. Further analysis of these genes indicated that the mutation in atpE might be responsible for the translucency of the colonies, and mutation in mdtR for resistance to both HA and rifampin. We conclude that HA is an antimicrobial agent against Gram-positive bacteria that targets the cell membrane.
Tetrathionate hydrolase from the acidophilic microorganisms
Authors: Kanao Tadayoshi
Published: January 2024

Tetrathionate hydrolase (TTH) is a unique enzyme found in acidophilic sulfur-oxidizing microorganisms, such as bacteria and archaea. This enzyme catalyzes the hydrolysis of tetrathionate to thiosulfate, elemental sulfur, and sulfate. It is also involved in dissimilatory sulfur oxidation metabolism, the S4-intermediate pathway. TTHs have been purified and characterized from acidophilic autotrophic sulfur-oxidizing microorganisms. All purified TTHs show an optimum pH in the acidic range, suggesting that they are localized in the periplasmic space or outer membrane. In particular, the gene encoding TTH from Acidithiobacillus ferrooxidans (Af-tth) was identified and recombinantly expressed in Escherichia coli cells. TTH activity could be recovered from the recombinant inclusion bodies by acid refolding treatment for crystallization. The mechanism of tetrathionate hydrolysis was then elucidated by X-ray crystal structure analysis. Af-tth is highly expressed in tetrathionate-grown cells but not in iron-grown cells. These unique structural properties, reaction mechanisms, gene expression, and regulatory mechanisms are discussed in this review.
Correlation between mismatch repair statuses and the prognosis of stage I–IV colorectal cancer
Authors: Tong Guojun , Zhang Guiyang , Hu Yan , Xu Xuting , Wang Yanyan
Published: January 2024

Background

The role of microsatellite instability (MSI) and prognosis for stage II–III colorectal cancer (CRC) has been described, but the role of MSI in stage I and IV CRC is controversial.

Methods

A total of 2,540 CRC patients were collected from Huzhou Central Hospital, China, from January 2006 to 2016, and 783 cases were excluded. This retrospective study illustrates the correlation between MMR status and prognosis for 1,757 CRC patients as well as the correlation between MSI and prognosis for CRC patients. Two groups were classified as MSI-H and MSI-L&MSS. If the expression of one or more mismatch repair (MMR) proteins was negative, it was considered as microsatellite instability high expression (MSI-H), whereas positive expression was considered as microsatellite instability low expression and microsatellite stability (MSI-L&MSS), as assessed by correlation analyses. Overall and disease-free survival were analyzed using the Kaplan–Meier method. Univariable and multivariable analyses were conducted using Cox regression.

Results

Preoperative serum S-CEA, positive lymph, tumor size, pathologic tumor (Pt) status, node (N) stage, differentiation, chemotherapy, and the 8th Edition of the American Joint Committee on Cancer (AJCC-8) were significantly correlated with MSI (P=0.028, 0.037, 0.019, 0.007, 0.002, <0.001, <0.001, and <0.001, respectively), whereas tumor location was not associated with MSI. Univariable and multivariable analyses showed that MSI was an independent factor for CRC. The 5-year overall survival (OS) and 5-year disease-free survival (DFS, P<0.001) rates differed significantly between the two groups in stages II, III, and IV, whereas stage I did not show a significant difference (P>0.05).

Conclusion

MSI-H was associated with a good prognosis for stages II to IV, whereas stage I did not show any significant correlation. Moreover, MSI expression was an independent prognostic factor.
Case report: Successful treatment of a patient with relapsed/refractory primary central nervous system lymphoma with thiotepa-based induction, autologous stem cell transplantation and maintenance
Authors: Wang Luyao , Fan Yili , Chen Boxiao , Zhang Jiawei , Yang Luyu , Qiu Xi , Jiang Huawei , Li Jinfan , Xiao Xibin , Huang Liansheng , Xu Yang
Published: January 2024

Despite significant improvements in prognosis, a subset of patients with primary central nervous system lymphoma (PCNSL) remains at high risk for relapse. The treatment of relapsed and refractory (R/R) PCNSL remains a major clinical challenge. Herein, we present a 24-year-old patient with PCNSL who relapsed 4 years after initial diagnosis and subsequently became refractory to high-dose methotrexate (HD-MTX), temozolomide, whole brain radiation therapy (WBRT), ibrutinib, and lenalidomide. She received thiotepa with anti-programmed cell death protein 1 (PD-1) antibody and achieved partial remission and then underwent autologous stem cell transplantation (ASCT) with thiotepa-based conditioning. Post-transplant maintenance with thiotepa and anti-PD-1 at 3-month intervals resulted in a durable complete response (CR) in this case of R/R PCNSL. Our report highlights the important role of thiotepa in the treatment of patients with R/R PCNSL.
Case report and literature analysis: solitary HCC- recurrence in the right maxillary sinus after curative resection
Authors: Madzikatire Tinotenda Blessing , Shan Yunfeng
Published: January 2024

Background

The primary treatment for eligible patients with hepatocellular carcinoma (HCC) is curative liver resection, offering a 5-year overall survival (OS) of 60%-80%. Despite this, the recurrence rate within five years post-resection remains notably high, ranging from 40% to 50%. Instances of recurrence in the maxillary sinus following liver resection are exceedingly uncommon. This report details a unique case of solitary maxillary sinus recurrence after the curative resection of HCC, which underwent maxillary tumor resection, along with a comprehensive review of pertinent literature. No similar cases have been documented previously.

Case presentation

In 2014, an 85-year-old male patient was diagnosed with HCC and subsequently underwent left hepatectomy. Following the resection, the patient underwent a 9-year follow-up period without any evidence of intra or extrahepatic recurrence. In 2023, a computed tomography (CT) scan revealed a 1.4 cm by 1.1 cm mass in the maxillary sinus, without discernible invasion of the alveolar sinus, nasal cavity, orbital cavity, or infratemporal space. We proceeded with the resection of the maxillary sinus mass. Patho-histochemical analysis indicated that the tumor cells in the maxillary sinus were metastatic HCC cells. As of now, the patient remains in good condition with no signs of tumor recurrence.

Conclusion

For patients presenting with solitary maxillary sinus metastasis, optimal liver function, and a favorable performance score, tumor resection may be the preferred treatment option. However, given the rarity of such cases, larger prospective trials are essential to determine an optimal treatment strategy that offers therapeutic benefits.
Primary vaginal cancer after hysterectomy for benign conditions: a systematic review of the literature
Authors: Qian Jing , Gracious Kaoma , Chen Li , Xu Song
Published: January 2024

Background

Primary vaginal cancer is a rare condition. Some studies have revealed an increased risk of vaginal cancer among patients who have undergone hysterectomy for premalignant and malignant cervical disease. However, there is limited literature available on primary vaginal cancer following hysterectomy for benign conditions.

Objectives

This review aimed to investigate available evidence on clinical characteristics, treatments, and outcomes of primary vaginal cancer following hysterectomy for benign diseases. Additionally, we provide a case of a patient who developed primary vaginal cancer 10 years after undergoing hysterectomy for abnormal uterine bleeding.

Search strategy

We conducted a comprehensive literature search on PubMed, Scopus, Web of Science using a combination of title and abstract represented by “hysterectomy”, and “vaginal cancer”; “vaginal neoplasm”; and “cancer of vagina”. No article type restrictions were applied.

Main results

Eight studies with a total of 56 cases were included in this review. The main symptom observed was vaginal bleeding. Squamous cancer was found to be the most common type, followed by adenocarcinoma. The majority of vaginal cancer cases occurred approximately 10 years after undergoing hysterectomy. The most common location of the tumor was in the vaginal apex. The management approaches varied and details were available in 25 cases. Among these, 7 cases were treated with radiotherapy alone, 1 case received concurrent chemoradiation therapy, and the of rest of the cases underwent surgery as the primary treatment, with or without additional adjuvant therapy. Data of follow-up was available for 15 cases, with 2 cases resulting in death and 2 cases experiencing recurrence. The other cases were alive and well at the time of considered follow up.

Conclusion

Primary vaginal cancer after hysterectomy for benign conditions is an extremely rare condition. It is essential to have high-level evidence to guide the screening and treatment strategy for this rare condition. A part of women who have undergone hysterectomy for benign disorders can benefit from vaginal cytology evaluation. It is reasonable to postpone the initial screening after surgery and to extend the interval between subsequent screenings. Further retrospective case-control trials are expected to determine which specific subgroups of patients mentioned above might most potentially benefit from screening. The treatment decision for vaginal cancer after hysterectomy is more favorable to radiotherapy-based management rather than surgery. Vaginal endometrioid adenocarcinoma may arise from the malignant transformation of endometriosis. More studies are expected to investigate the correlation between these two diseases.