bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of ATLG serum levels on CD3/CD19-depleted hematopoietic grafts and on immune recovery in pediatric haplo-HSCT
Authors: Maier Claus-Philipp , Klose Chihab , Seitz Christian Martin , Heubach Florian , Döring Michaela , Meisel Roland , Schuster Friedhelm , Gruhn Bernd , Keller Frieder , Rabsteyn Armin , Arendt Anne-Marie , Amorelli Germano , Eichholz Thomas , Feuchtinger Tobias , Martinius Holger , Nierkens Stefan , Teltschik Rouwen , Schulte Johannes Hubertus , Lengerke Claudia , Handgretinger Rupert , Lang Peter
Published: January 2024

Anti–T lymphocyte globulin (ATLG) significantly reduces the risk of engraftment failure in allogeneic hematopoietic stem cell transplant (HSCT) but hampers posttransplant immune reconstitution. We hypothesized that in patients receiving haploidentical CD3/CD19-depleted grafts, these double-edged effects could be better balanced by attaining high ATLG serum concentrations before transplant but as low as possible on the day of transplant. Therefore, we moved the start of ATLG application to day −12 and determined serum concentrations of T-cell–specific ATLG in pediatric patients treated with 3 established dosing regimens (15, 30, or 60 mg/kg). Corresponding mean T-cell–specific ATLG serum concentrations at day 0 were 1.14, 2.99, or 12.10 μg/mL, respectively. Higher ATLG doses correlated with higher peak levels at days −8 and −7 and reduced graft rejection, whereas lower ATLG doses correlated with significantly faster posttransplant recovery of T and natural killer cells. The rate of graft-versus-host disease remained low, independent of ATLG doses. Moreover, in vitro assays showed that ATLG concentrations of 2.0 μg/mL and lower only slightly reduced the activity of natural killer cells, and therefore, the function of such effector cells might be preserved in the grafts. Pharmacokinetic analysis, compatible with linear first-order kinetics, revealed similar half-life values, independent of ATLG doses. Hence, the day on which a desired ATLG serum level is reached can be calculated before HSCT. Our retrospective study demonstrates the relevance of dosing and time of administration of ATLG on engraftment and immune recovery in ex vivo CD3/CD19-depleted haploidentical HSCT.
Impact of different genetic mutations on granulocyte development and G-CSF responsiveness in congenital neutropenia
Authors: Meng Xin , Zhang Hai , Dong Lulu , Min Qing , Yu Meiping , Li Yaxuan , Liu Lipin , Wang Wenjie , Ying Wenjing , Sun Jinqiao , Wang Ji-Yang , Hou Jia , Wang Xiaochuan
Published: January 2024

Congenital neutropenia (CN) is a genetic disorder characterized by persistent or intermittent low peripheral neutrophil counts, thus increasing susceptibility to bacterial and fungal infections. Various forms of CN, caused by distinct genetic mutations, exhibit differential responses to granulocyte colony–stimulating factor (G-CSF) therapy, with the underlying mechanisms not fully understood. This study presents an in-depth comparative analysis of clinical and immunological features in 5 CN patient groups (severe congenital neutropenia [SCN]1, SCN3, cyclic neutropenia [CyN], warts, hypogammaglobulinaemia, infections and myelokathexis [WHIM], and Shwachman-Bodian-Diamond Syndrome [SBDS]) associated with mutations in ELANE, HAX1, CXCR4, and SBDS genes. Our analysis led to the identification of 11 novel mutations in ELANE and 1 each in HAX1, CXCR4, and G6PC3 genes. Investigating bone marrow (BM) granulopoiesis and blood absolute neutrophil count after G-CSF treatment, we found that SCN1 and SCN3 presented with severe early-stage disruption between the promyelocyte and myelocyte, leading to a poor response to G-CSF. In contrast, CyN, affected at the late polymorphonuclear stage of neutrophil development, showed a strong G-CSF response. WHIM, displaying normal neutrophil development, responded robustly to G-CSF, whereas SBDS, with moderate disruption from the early myeloblast stage, exhibited a moderate response. Notably, SCN1 uniquely impeded neutrophil development, whereas SCN3, CyN, WHIM, and SBDS also affected eosinophils and basophils. In addition, SCN1, SCN3, and CyN presented with elevated serum immunoglobulins, increased BM plasma cells, and higher A Proliferation-Inducing Ligand levels. Our study reveals a strong correlation between the stage and severity of granulocyte development disruption and the efficacy of G-CSF therapy.
PredictEFC: a fast and efficient multi-label classifier for predicting enzyme family classes
Authors: Chen Lei , Zhang Chenyu , Xu Jing
Published: January 2024

Background

Enzymes play an irreplaceable and important role in maintaining the lives of living organisms. The Enzyme Commission (EC) number of an enzyme indicates its essential functions. Correct identification of the first digit (family class) of the EC number for a given enzyme is a hot topic in the past twenty years. Several previous methods adopted functional domain composition to represent enzymes. However, it would lead to dimension disaster, thereby reducing the efficiency of the methods. On the other hand, most previous methods can only deal with enzymes belonging to one family class. In fact, several enzymes belong to two or more family classes.

Results

In this study, a fast and efficient multi-label classifier, named PredictEFC, was designed. To construct this classifier, a novel feature extraction scheme was designed for processing functional domain information of enzymes, which counting the distribution of each functional domain entry across seven family classes in the training dataset. Based on this scheme, each training or test enzyme was encoded into a 7-dimenion vector by fusing its functional domain information and above statistical results. Random k-labelsets (RAKEL) was adopted to build the classifier, where random forest was selected as the base classification algorithm. The two tenfold cross-validation results on the training dataset shown that the accuracy of PredictEFC can reach 0.8493 and 0.8370. The independent test on two datasets indicated the accuracy values of 0.9118 and 0.8777.

Conclusion

The performance of PredictEFC was slightly lower than the classifier directly using functional domain composition. However, its efficiency was sharply improved. The running time was less than one-tenth of the time of the classifier directly using functional domain composition. In additional, the utility of PredictEFC was superior to the classifiers using traditional dimensionality reduction methods and some previous methods, and this classifier can be transplanted for predicting enzyme family classes of other species. Finally, a web-server available athttp://124.221.158.221/was set up for easy usage.
Parallels of quantum superposition in ecological models: from counterintuitive patterns to eco-evolutionary interpretations of cryptic species
Authors: Angeler David G. , Fried-Petersen Hannah B.
Published: January 2024

Background

Superposition, i.e. the ability of a particle (electron, photon) to occur in different states or positions simultaneously, is a hallmark in the subatomic world of quantum mechanics. Although counterintuitive at first sight, the quantum world has potential to inform macro-systems of people and nature. Using time series and spatial analysis of bird, phytoplankton and benthic invertebrate communities, this paper shows that superposition can occur analogously in redundancy analysis (RDA) frequently used by ecologists.

Results

We show that within individual ecosystems single species can be associated simultaneously with different orthogonal axes in RDA models, which suggests that they operate in more than one niche spaces. We discuss this counterintuitive result in relation to the statistical and mathematical features of RDA and the recognized limitations with current traditional species concepts based on vegetative morphology.

Conclusion

We suggest that such “quantum weirdness” in the models is reconcilable with classical ecosystems logic when the focus of research shifts from morphological species to cryptic species that consist of genetically and ecologically differentiated subpopulations. We support our argument with theoretical discussions of eco-evolutionary interpretations that should become testable once suitable data are available.
Genomic insights into the endangered white-eared night heron (Gorsachius magnificus)
Authors: Luo Haoran , Lin Qingxian , Fang Wenzhen , Chen Xiaolin , Zhou Xiaoping
Published: January 2024

Objectives

A genome sequence of a threatened species can provide valuable genetic information that is important for improving the conservation strategies. The white-eared night heron (Gorsachius magnificus) is an endangered and poorly known ardeid bird. In order to support future studies on conservation genetics and evolutionary adaptation of this species, we have reported a de novo assembled and annotated whole-genome sequence of the G. magnificus.

Data description

The final draft genome assembly of the G. magnificus was 1.19 Gb in size, with a contig N50 of 187.69 kb and a scaffold N50 of 7,338.28 kb. According to BUSCO analysis, the genome assembly contained 97.49% of the 8,338 genes in the Aves (odb10) dataset. Approximately 10.52% of the genome assembly was composed of repetitive sequences. A total of 14,613 protein-coding genes were predicted in the genome assembly, with functional annotations available for 14,611 genes. The genome assembly exhibited a heterozygosity rate of 0.49 heterozygosity per kilobase pair. This draft genome of G. magnificus provides valuable genomic resources for future studies on conservation and evolution.
Novel compound heterozygous mutations of the NPC1 gene associated with Niemann-pick disease type C: a case report and review of the literature
Authors: Tao Chaoxin , Zhao Min , Zhang Xiaohui , Hao Jihong , Huo Qiuyue , Sun Jie , Xing Jiangtao , Zhang Yuna , Zhao Jianhong , Huang Huaipeng
Published: January 2024

Background

Niemann-Pick Disease type C is a fatal autosomal recessive lipid storage disorder caused byNPC1orNPC2gene mutations and characterized by progressive, disabling neurological deterioration and hepatosplenomegaly. Herein, we identified a novel compound heterozygous mutations of theNPC1gene in a Chinese pedigree.

Case presentation

This paper describes an 11-year-old boy with aggravated walking instability and slurring of speech who presented as Niemann-Pick Disease type C. He had the maternally inherited c.3452 C > T (p. Ala1151Val) mutation and the paternally inherited c.3557G > A (p. Arg1186His) mutation using next-generation sequencing. The c.3452 C > T (p. Ala1151Val) mutation has not previously been reported.

Conclusions

This study predicted that the c.3452 C > T (p. Ala1151Val) mutation is pathogenic. This data enriches theNPC1gene variation spectrum and provides a basis for familial genetic counseling and prenatal diagnosis.
Clinical features and outcomes of influenza and RSV coinfections: a report from Canadian immunization research network serious outcomes surveillance network
Authors: Pott Henrique , J. LeBlanc Jason , S. ElSherif May , Hatchette Todd F. , McNeil Shelly A. , Andrew Melissa K. ,   on behalf of the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)
Published: January 2024

Background

Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults.

Methods

A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization.

Results

Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes.

Conclusions

Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.
Obstetric blood transfusion in placenta previa patients with prenatal anemia: a retrospective study
Authors: Zhang Baolian , Liu Hong , Li Haiyan , Wang Jia , Zhu He , Yu Peijia , Huang Xianghua , Wang Wenli
Published: January 2024

Background

The appropriate use of obstetric blood transfusion is crucial for patients with placenta previa and prenatal anemia. This retrospective study aims to explore the correlation between prenatal anemia and blood transfusion-related parameters in this population.

Methods

We retrieved the medical records of consecutive participants who were diagnosed with placenta previa and underwent cesarean section in our hospital. We compared the baseline demographics and clinical characteristics of patients with and without anemia. The correlation between prenatal anemia and obstetric blood transfusion-related parameters was evaluated using multivariate regression analysis.

Results

A total of 749 patients were enrolled, with a mean prenatal hemoglobin level of 10.87 ± 1.37 g/dL. Among them, 54.87% (391/749) were diagnosed with anemia. The rate of obstetric blood transfusion was significantly higher in the anemia group (79.54%) compared to the normal group (44.41%). The median allogeneic red blood cell transfusion volume in the anemia group was 4.00 U (IQR 2.00–6.00), while in the normal group, it was 0.00 U (IQR 0.00–4.00). The prenatal hemoglobin levels had a non-linear relationship with intraoperative allogeneic blood transfusion rate, massive blood transfusion rate, red blood cell transfusion units, and fresh plasma transfusion volume in patients with placenta previa, with a threshold of 12 g/dL.

Conclusions

Our findings suggest that prenatal anemia is associated with a higher rate of blood transfusion-related parameters in women with placenta previa when the hemoglobin level is < 12 g/dL. These results highlight the importance of promoting prenatal care in placenta previa patients with a high requirement for blood transfusion.
When the second comes first– rhabdomyosarcoma preceding heritable retinoblastoma– a case report
Authors: Tripathy Devjyoti , Moulin Alexandre , Bijon Jacques , Gengler Carole , Beck-Popovic Maja , Munier Francis L. , Stathopoulos Christina
Published: January 2024

Background

Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb.

Case presentation

We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease.

Conclusions

Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.
Risk factors on surgical compliance and its impact on survival outcomes in meningioma patients: a SEER-based retrospective propensity-score matched analysis
Authors: Yang Shengkai , Teng Hongwei , Wang Yingdan , Ji Kangkang , Chen Weihua , Zhou Hai
Published: January 2024

Background

This study aimed to analyze the effect of surgical compliance on the survival outcome of patients with meningioma and explore the factors affecting surgical compliance.

Methods

We selected data from the Surveillance, Epidemiology, and End Results database for 122,632 meningioma patients diagnosed between 2004 and 2018. The effect of surgical compliance on patients’ overall survival (OS) was analyzed through Cox regression and Kaplan–Meier curves. Independent risk factors for surgical compliance were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves. Furthermore, we used univariate and multivariate logistic regression analyses to evaluate relevant variables linked to adherence with meningioma surgery. Moreover, 1:1 propensity score matching was applied to assess the validity of the results in patients with favorable and poor surgical compliance.

Results

A total of 48,735 were eligible from the initial cohort of 122,632 patients with meningioma. Among them, 45,038 (92.40%) exhibited good surgical compliance, while 3697 (7.60%) had poor surgical compliance. The rate of patients with good surgical compliance was significantly higher than that of patients with inadequate surgical compliance (p < 0.001). Moreover, surgical compliance is an independent prognostic factor for OS in meningioma patients. Univariate Cox regression analysis indicated that individuals with poor surgical compliance demonstrated lower OS rates than those with good surgical compliance (hazard ratio [HR 2.404; 95% confidence interval [CI] 2.276–2.54, p < 0.001], consistent with the observation in the multivariate analysis (HR 1.564; 95% CI 1.471–1.663, p < 0.001). We developed a prediction model using seven variables: age, sex, race, tumor behavior recode, tumor size, family income, and residential setting (p < 0.05). Surgical compliance was associated with patient age, sex, race, tumor behavior recode, tumor size, family income, and residential setting by logistic regression analysis.

Conclusions

Surgical compliance emerged as an independent prognostic factor for survival in patients with meningioma. Poor surgical compliance was associated with older age, black and other races, females, advanced-stage tumors, larger tumor size, lower household income, and rural residence. When patients experienced these conditions, OS was shorter, requiring more aggressive treatment.
Knowledge, attitude, and utilization of traditional medicine within the plural medical system in West Java, Indonesia
Authors: Febriyanti Raden Maya , Saefullah Kurniawan , Susanti Raini Diah , Lestari Keri
Published: January 2024

Background

The concept of ‘medical pluralism’ has become more popular among scholars in applied health science and prevalent in societies where one medical system alone cannot adequately meet the health care needs of the entire population.

Methods

The data collection is focused on the knowledge-belief-practice and the utilization of three medical systems in Kabupaten Bandung, West Java, Indonesia. Participants were purposively selected from households with at least one member experienced one of the listed diseases in the questionnaire. The extensive survey using a structured questionnaire has been undertaken to collect data on people’s health care utilization behaviour. The dataset is further analyzed using multivariate analysis through non-canonical correlation, with the analytical data provided by Statistical Package for Social Sciences (SPSS).

Results

With regards to the total utilization by patients, the traditional medical system presents as the dominant medical system in the research area, accounting for 59.3% (n = 419) of total utilization, followed by the modern medical system (33.0%,n = 233), and transitional medical system (7.7%,n = 54). This study identified that village category, illness, illness duration, occupation, belief in traditional medicine, knowledge of modern medicine, accessibility, cost, proximity to the medical service, and insurance have significant (χ2 = 0.000) relationship with the utilization of medical systems. The results of the multivariate analysis show that the block of the predisposing socio-demographic factors and the block of the predisposing psycho-social factors correlate strongly with the utilization of medical systems.

Conclusions

In general, people in Kabupaten Bandung, West Java, Indonesia seeks treatment from various sources, which in the context of the medical system, consists of the traditional, transitional, and modern medical system; therefore, it adopts the patterns of transcultural health care utilization. In terms of the knowledge, beliefs, and practices of traditional medicine in West Java, the inhabitants of the five research villages were commonly familiar with medicinal plants and speak profoundly about their knowledge of traditional medicine, which in the research area is perceived as accessible, efficacious, affordable and culturally appropriate with Sundanese community.
Awareness and practice of airway pressure release ventilation mode in acute respiratory distress syndrome patients among nurses in Saudi Arabia
Authors: Aldhahir Abdulelah M. , Alqarni Abdullah A. , Madkhali Mohammed A. , Madkhali Hussain H. , Bakri Abdullah A. , Shawany Mohammad A. , Alasimi Ahmed H. , Alsulayyim Abdullah S. , Alqahtani Jaber S. , Alyami Mohammed M. , Alghamdi Saeed M. , Alqarni Omar A. , Hakamy Ali
Published: January 2024

Background

This study aimed to assess the knowledge and current practice of using the airway pressure release ventilation (APRV) mode with acute respiratory distress syndrome (ARDS) patients and identify barriers to not using this mode of ventilation among nurses who work in critical areas in Saudi Arabia.

Methods

Between December 2022 and April 2023, a cross-sectional online survey was disseminated to nurses working in critical care areas in Saudi Arabia. The characteristics of the respondents were analyzed using descriptive statistics. Percentages and frequencies were used to report categorical variables.

Results

Overall, 1,002 nurses responded to the online survey, of whom 592 (59.1%) were female. Only 248 (24.7%) nurses had ever used APRV mode, whereas only 229 (22.8%) received training on APRV mode. Moreover, 602 (60.0%) nurses did not know whether APRV was utilized in their hospital. Additionally, 658 (65.6%) nurses did not know whether APRV mode was managed using a standard protocol. Prone positioning was the highest recommended intervention by 444 (43.8%) when a conventional MV failed to improve oxygenation in patients with ARDS. 323 (32.2%) respondents stated that the P-high should be set equal to the plateau pressure on a conventional ventilator, while 400 (39.9%) said that the P-low should match PEEP from a conventional ventilator. Almost half of the respondents (446, 44.5%) stated that the T-high should be set between 4 and 6 s, while 415 (41.4%) said that the T-low should be set at 0.4 to 0.8 s. Over half of the nurses (540, 53.9%) thought that the maximum allowed tidal volume during the release phase should be 4–6 ml/kg. Moreover, 475 (47.4%) believed that the maximum allowed P-high setting should be 35 cm H2O. One-third of the responders (329, 32.8%) stated that when weaning patients with ARDS while in APRV mode, the P-high should be reduced gradually to reach a target of 10 cm H2O. However, 444 (44.3%) thought that the T-high should be gradually increased to reach a target of 10 s. Half of the responders (556, 55.5%) felt that the criteria to switch the patient to continuous positive airway pressure (CPAP) were for the patient to have an FiO2 ≤ 0.4, P-high ≤ 10 cm H2O, and T-high ≥ 10 s. Lack of training was the most common barrier to not using APRV by 615 (61.4%).

Conclusion

The majority of nurses who work in critical care units have not received sufficient training in APRV mode. A significant discrepancy was observed regarding the clinical application and management of APRV parameters. Inadequate training was the most frequently reported barrier to the use of APRV in patients with ARDS.
Mapping cancer biology in space: applications and perspectives on spatial omics for oncology
Authors: Lee Sumin , Kim Gyeongjun , Lee JinYoung , Lee Amos C. , Kwon Sunghoon
Published: January 2024

Technologies to decipher cellular biology, such as bulk sequencing technologies and single-cell sequencing technologies, have greatly assisted novel findings in tumor biology. Recent findings in tumor biology suggest that tumors construct architectures that influence the underlying cancerous mechanisms. Increasing research has reported novel techniques to map the tissue in a spatial context or targeted sampling-based characterization and has introduced such technologies to solve oncology regarding tumor heterogeneity, tumor microenvironment, and spatially located biomarkers. In this study, we address spatial technologies that can delineate the omics profile in a spatial context, novel findings discovered via spatial technologies in oncology, and suggest perspectives regarding therapeutic approaches and further technological developments.
Role of meningeal immunity in brain function and protection against pathogens
Authors: Rebejac Julie , Eme-Scolan Elisa , Rua Rejane
Published: January 2024

The brain and spinal cord collectively referred to as the Central Nervous System (CNS) are protected by the blood-brain barrier that limits molecular, microbial and immunological trafficking. However, in the last decade, many studies have emphasized the protective role of ‘border regions’ at the surface of the CNS which are highly immunologically active, in contrast with the CNS parenchyma. In the steady-state, lymphoid and myeloid cells residing in the cranial meninges can affect brain function and behavior. Upon infection, they provide a first layer of protection against microbial neuroinvasion. The maturation of border sites over time enables more effective brain protection in adults as compared to neonates. Here, we provide a comprehensive update on the meningeal immune system and its role in physiological brain function and protection against infectious agents.
Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications
Authors: Bianchi Massimiliano G. , Chiu Martina , Taurino Giuseppe , Bergamaschi Enrico , Turroni Francesca , Mancabelli Leonardo , Longhi Giulia , Ventura Marco , Bussolati Ovidio
Published: January 2024

Amorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such as toothpastes, food additives, drug excipients, and carriers. Consolidated use and experimental evidence have consistently pointed to the very low acute toxicity and limited absorption of ASNP. However, slow absorption implies prolonged exposure of the intestinal epithelium to ASNP, with documented effects on intestinal permeability and immune gut homeostasis. These effects could explain the hepatic toxicity observed after oral administration of ASNP in animals. More recently, the role of microbiota in these and other ASNP effects has attracted increasing interest in parallel with the recognition of the role of microbiota in a variety of conditions. Although evidence for nanomaterial effects on microbiota is particularly abundant for materials endowed with bactericidal activities, a growing body of recent experimental data indicates that ASNPs also modify microbiota. The implications of these effects are recounted in this contribution, along with a discussion of the more important open issues and recommendations for future research.

Graphical Abstract
A new innovative method to measure the cost of war: future with fewer conflicts via harm reduction approaches
Authors: Jozaghi Ehsan
Published: January 2024

Background

The destruction of World War I (WWI) and World War II (WWII) changed the world forever. In this analysis, the economic costs of WWI and WWII are considered via a harm reduction approach to highlight the cost of war via the mortality of military personnel. The harm reduction philosophy and homeostasis of a biological cell are utilized as a pragmatic approach and analogy to give a greater context to the findings, despite the omission of civilian casualties and military disabilities.

Methods

Tangible (e.g., loss of wages, productivity, and contributions) and intangible (e.g., quality of life) costs are estimated based on the value of each military personnel derived from secondary data and a mathematical model. This is the first study to estimate the cost of war based on soldier’s mortality during the first and second World War.

Results

Based on the tangible value, the WWI and WWII cost for the military personnel was US$43.204 billion ($13 billion ≤ α ≤ $97 billion) and US$540.112 billion ($44 billion ≤ α ≤ $1 trillion). When the intangible cost is considered, it is estimated that the WWI cost was beyond US$124 trillion ($43 trillion ≤ β ≤ $160 trillion), and the WWII cost was above US$328 trillion ($115 trillion ≤ β ≤ $424 trillion). The sensitivity analyses conducted for WWI and WWII demonstrate different ranges based on tangible and intangible values.

Conclusions

In the current climate of increasing hostilities, inequalities, global warming, and an ever-changing world, economic prosperities are directly linked to peace, stability, and security. Therefore, any future decisions for military conflicts need to increasingly consider harm reduction approaches by considering the cost of life and potential disabilities for each nations’ soldiers, sailors, and pilots.
Extracellular succinate derived from ectopic milieu drives adhesion and implantation growth of ectopic endometrial stromal cells via the SUCNR1 signal in endometriosis
Authors: Tian Qi , Ruan Jingyao , Wang Yuning , Xiao Yinping , Cheng Qi , Chen Yun , Li Mingqing , Chang Kaikai , Yi Xiaofang
Published: January 2024

Background

As a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring.

Objective

We mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study.

Methods

In this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms.

Results

By mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis.

Conclusions

Succinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs.
The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage
Authors: Pu Min , Zhang Jing , Hong Fuyan , Wang Yan , Zhang Chengwei , Zeng Yongcheng , Fang Zhenzhen , Qi Weiwei , Yang Xia , Gao Guoquan , Zhou Ti
Published: January 2024

Background

Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis.

Methods

Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms.

Results

Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3β/β-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells.

Conclusions

The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3β/β-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.
Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis
Authors: Ottaiano Alessandro , Iacovino Maria Lucia , Santorsola Mariachiara , Facchini Sergio , Iervolino Domenico , Perri Francesco , Nasti Guglielmo , Quagliariello Vincenzo , Maurea Nicola , Ronchi Andrea , Facchini Bianca Arianna , Bignucolo Alessia , Berretta Massimiliano
Published: January 2024

Background

Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis.

Methods

Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot.

Results

Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21–1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13–1.70) for patients with lower VD levels, as indicated by fixed-effects models.

Conclusions

Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.
PITPNC1 Suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155
Authors: Liang Junxian , Liao Limin , Xie Lang , Tang WenWen , Yu Xiang , Lu Yinghao , Chen Hongzhen , Xu Juanli , Sun Lei , Wu Huanmei , Cui Chunhui , Tan Yujing
Published: January 2024

Background

Radioresistance is a primary factor contributing to the failure of rectal cancer treatment. Immune suppression plays a significant role in the development of radioresistance. We have investigated the potential role of phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) in regulating immune suppression associated with radioresistance.

Methods

To elucidate the mechanisms by which PITPNC1 influences radioresistance, we established HT29, SW480, and MC38 radioresistant cell lines. The relationship between radioresistance and changes in the proportion of immune cells was verified through subcutaneous tumor models and flow cytometry. Changes in the expression levels of PITPNC1, FASN, and CD155 were determined using immunohistochemistry and western blotting techniques. The interplay between these proteins was investigated using immunofluorescence co-localization and immunoprecipitation assays. Additionally, siRNA and lentivirus-mediated gene knockdown or overexpression, as well as co-culture of tumor cells with PBMCs or CD8+ T cells and establishment of stable transgenic cell lines in vivo, were employed to validate the impact of the PITPNC1/FASN/CD155 pathway on CD8+ T cell immune function.

Results

Under irradiation, the apoptosis rate and expression of apoptosis-related proteins in radioresistant colorectal cancer cell lines were significantly decreased, while the cell proliferation rate increased. In radioresistant tumor-bearing mice, the proportion of CD8+ T cells and IFN-γ production within immune cells decreased. Immunohistochemical analysis of human and animal tissue specimens resistant to radiotherapy showed a significant increase in the expression levels of PITPNC1, FASN, and CD155. Gene knockdown and rescue experiments demonstrated that PITPNC1 can regulate the expression of CD155 on the surface of tumor cells through FASN. In addition, co-culture experiments and in vivo tumor-bearing experiments have shown that silencing PITPNC1 can inhibit FASN/CD155, enhance CD8+ T cell immune function, promote colorectal cancer cell death, and ultimately reduce radioresistance in tumor-bearing models.

Conclusions

PITPNC1 regulates the expression of CD155 through FASN, inhibits CD8+ T cell immune function, and promotes radioresistance in rectal cancer.
Efficient transformation of the isolated microspores of Chinese cabbage (Brassica rapa L. ssp. pekinensis) by particle bombardment
Authors: Liu Yujia , Zhang Shujiang , Zhang Shifan , Zhang Hui , Li Guoliang , Sun Rifei , Li Fei
Published: January 2024

Background

The low efficiency of genetic transformation in Chinese cabbage (Brassica rapa L. ssp. pekinensis) is the key problem affecting functional verification. Particle bombardment is a widely used method along with the Agrobacterium-mediated method. As a physical means, it has almost no restrictions on the type of host and a wide range of receptor types, which largely avoids the restriction of explants. The bombardment parameters, which include the number of bombardments, the bombardment pressure, and the bombardment distance, may affect the microspores' genetic transformation efficiency.

Results

The transformation efficiency was improved using the particle bombardment method under the combination of bombardment shot times (3, 4, 5) × bombardment pressure (900, 1100, 1350 psi) × bombardment distance (3, 6, 9 cm). The average viability of microspores in the treatment group ranged from 74.76 to 88.55%, while the control group was 88.09%. When the number of shot times was 4, the number of embryos incubated in the treatment group ranged from 16 to 236 per dish, and the control group had 117 embryos per dish. When the bombardment parameters of the biolistic method were 4 shot times—1350 psi—3 cm, 4 times—1100 psi—3 cm, and 4 times—900 psi—3 cm, they had high transient expression efficiency, and the average number of transformed microspores was 21.67, 11.67, and 11.67 per dish (3.5 mL), respectively. When the bombardment parameters were 4 times, 900 psi, and 6 cm, the highest genetically transformed embryos were obtained, and the transformation efficiency reached 10.82%.

Conclusion

A new genetic transformation system with proper parameters for Chinese cabbage microspores was established using particle bombardment. This proper transformation system could provide a useful tool for the improvement of cultivar quality and the investigation of functional genes in Chinese cabbage.
Research on automatic recognition radiomics algorithm for early sacroiliac arthritis based on sacroiliac MRI imaging
Authors: Liu Wen-xi , Wu Hong , Cai Chi , Lai Qing-quan , Wang Yi , Li Yuan-zhe
Published: January 2024

Objective

To create an automated machine learning model using sacroiliac joint MRI imaging for early sacroiliac arthritis detection, aiming to enhance diagnostic accuracy.

Methods

We conducted a retrospective analysis involving 71 patients with early sacroiliac arthritis and 85 patients with normal sacroiliac joint MRI scans. Transverse T1WI and T2WI sequences were collected and subjected to radiomics analysis by two physicians. Patients were randomly divided into training and test groups at a 7:3 ratio. Initially, we extracted the region of interest on the sacroiliac joint surface using ITK-SNAP 3.6.0 software and extracted radiomic features. We retained features with an Intraclass Correlation Coefficient > 0.80, followed by filtering using max-relevance and min-redundancy (mRMR) and LASSO algorithms to establish an automatic identification model for sacroiliac joint surface injury. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. Model performance was assessed by accuracy, sensitivity, and specificity.

Results

We evaluated model performance, achieving an AUC of 0.943 for the SVM-T1WI training group, with accuracy, sensitivity, and specificity values of 0.878, 0.836, and 0.943, respectively. The SVM-T1WI test group exhibited an AUC of 0.875, with corresponding accuracy, sensitivity, and specificity values of 0.909, 0.929, and 0.875, respectively. For the SVM-T2WI training group, the AUC was 0.975, with accuracy, sensitivity, and specificity values of 0.933, 0.889, and 0.750. The SVM-T2WI test group produced an AUC of 0.902, with accuracy, sensitivity, and specificity values of 0.864, 0.889, and 0.800. In the SVM-bimodal training group, we achieved an AUC of 0.974, with accuracy, sensitivity, and specificity values of 0.921, 0.889, and 0.971, respectively. The SVM-bimodal test group exhibited an AUC of 0.964, with accuracy, sensitivity, and specificity values of 0.955, 1.000, and 0.875, respectively.

Conclusion

The radiomics-based detection model demonstrates excellent automatic identification performance for early sacroiliitis.
A shock to the (health) system: experiences of adults with rare disorders during the first COVID-19 wave
Authors: Bogart Kathleen R. , Hartinger Annelise , Klaus Maggie , Jenkinson Elizabeth
Published: January 2024

Background

Before COVID-19, people with rare diseases (RD) experienced numerous disparities in quality of life and healthcare access and quality, yet little is known about the experiences of this underserved group during the pandemic.

Results

During the first wave of the COVID-19 pandemic in the United States, spring and summer of 2020, 759 participants representing 231 unique RDs responded to open-ended questions about the impact of the pandemic on life with a RD, healthcare access, and coping. Qualitative conventional content analysis was used to analyze responses. Identified themes represented positive and negative dimensions of change, including a shock to the (health) system, coping with uncertainty, and the value of social support while isolated.

Conclusions

Limitations in healthcare access and quality were the most frequently described as impacts of COVID-19. Other major negative impacts included exacerbation of symptoms, psychological distress, and a lack of usual social support and reliable information. However, participants also noted silver linings, especially in healthcare. For some, expanded telehealth enhanced their ability to access medical and mental health providers and RD specialists. Finally, many participants hoped that, by highlighting social and health inequities faced by people with RDs and other minorities, the pandemic would prompt greater understanding and policies that could improve the quality of life of the RD community.