bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: The evolving phenotype of ESCO2 spectrum disorder in a 15-year-old Malaysian child
Authors: Tae Sok-Kun , RA Mazlan , Thong Meow-Keong
Published: January 2024

ESCO2 spectrum disorder is an autosomal recessive developmental disorder characterized by growth retardation, symmetrical mesomelic limb malformation, and distinctive facies with microcephaly, with a wide phenotypic continuum that ranges from Roberts syndrome (MIM #268300) at the severe end to SC phocomelia (MIM #269000) at the milder end. ESCO2 encodes a 601-amino acid protein belonging to the Eco1/Ctf7 family of acetyltransferases that is involved in the establishment of sister chromatid cohesion, which is essential for accurate chromosome segregation and genomic stability and thus belongs to a group of disorders called “cohesinopathies”. We describe a 15-year-old Malaysian female who presented with the characteristic triad of ESCO2 spectrum disorder, with an equivocal chromosomal breakage study and normal karyotyping findings. She was initially suspected to have mosaic Fanconi anemia but whole exome sequencing (WES) showed a likely pathogenic homozygous splice variant c.955 + 2_955+5del in the ESCO2 gene. During the 15-year diagnostic odyssey, she developed type 2 diabetes mellitus, primary ovarian insufficiency, increased optic cup-to-disc ratio with tortuous vessels bilaterally, and an evolving but distinct facial and skin hypopigmentation phenotype. Of note, there was an absence of learning disabilities. Our findings provide further evidence for ESCO2 spectrum disorder in an Asian child and contribute to defining the clinical and radiographic spectrum.
Mitochondrial dynamics and metabolic regulation control T cell fate in the thymus
Authors: Elhage Rima , Kelly Mairead , Goudin Nicolas , Megret Jérôme , Legrand Agnès , Nemazanyy Ivan , Patitucci Cécilia , Quellec Véronique , Wai Timothy , Hamaï Ahmed , Ezine Sophie
Published: January 2024

Several studies demonstrated that mitochondrial dynamics and metabolic pathways control T cell fate in the periphery. However, little is known about their implication in thymocyte development. Our results showed that thymic progenitors (CD3-CD4-CD8- triple negative, TN), in active division, have essentially a fused mitochondrial morphology and rely on high glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). As TN cells differentiate to double positive (DP, CD4+CD8+) and single positive (SP, CD4+ and CD8+) stages, they became more quiescent, their mitochondria fragment and they downregulate glycolysis and OXPHOS. Accordingly, in vitro inhibition of the mitochondrial fission during progenitor differentiation on OP9-DL4 stroma, affected the TN to DP thymocyte transition by enhancing the percentage of TN and reducing that of DP, leading to a decrease in the total number of thymic cells including SP T cells. We demonstrated that the stage 3 triple negative pre-T (TN3) and the stage 4 triple negative pre-T (TN4) have different metabolic and functional behaviors. While their mitochondrial morphologies are both essentially fused, the LC-MS based analysis of their metabolome showed that they are distinct: TN3 rely more on OXPHOS whereas TN4 are more glycolytic. In line with this, TN4 display an increased Hexokinase II expression in comparison to TN3, associated with high proliferation and glycolysis. The in vivo inhibition of glycolysis using 2-deoxyglucose (2-DG) and the absence of IL-7 signaling, led to a decline in glucose metabolism and mitochondrial membrane potential. In addition, the glucose/IL-7R connection affects the TN3 to TN4 transition (also called β-selection transition), by enhancing the percentage of TN3, leading to a decrease in the total number of thymocytes. Thus, we identified additional components, essential during β-selection transition and playing a major role in thymic development.
Case report: Immune pressure on hematopoietic stem cells can drastically expand glycosylphosphatidylinositol-deficient clones in paroxysmal nocturnal hemoglobinuria
Authors: Shingai Naoki , Mizumaki Hiroki , Najima Yuho , Yamada Yuta , Tran Dung Cao , Haraguchi Kyoko , Toya Takashi , Okuyama Yoshiki , Doki Noriko , Nannya Yasuhito , Ogawa Seishi , Nakao Shinji
Published: January 2024

Introduction

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) genes, what drives PNH clones to expand remains elusive.

Case description

We present a case of a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol-anchored protein deficient (GPI[-]) cells. The patient was diagnosed with PNH with non-severe aplastic anemia. Deep-targeted sequencing covering 390 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the patient’s serum lactate dehydrogenase level decreased, she remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After four years, the patient’s blood count remained normal without any signs of hemolysis. However, the peripheral blood still contained 0.2% GPI (-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at similar proportions to those before transplantation (p.I69fs, VAF 36.1%; p.T192P, VAF 3.7%; p.V300fs, VAF 8.6%) in the small PNH clones that persisted after transplantation.

Conclusions

The PNH clones that had increased excessively before BMT decreased, but persisted at low percentages for more than four years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that as opposed to conventional theory, immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA-mutated HSCs to clonally expand to develop PNH.
Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota
Authors: Zhang Haonan , Shi Yulu , Lin Chanchan , He Chengcheng , Wang Shanping , Li Qingyuan , Sun Yan , Li Mingsong
Published: January 2024

Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn’s disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.
Advancements in innate immune regulation strategies in islet transplantation
Authors: Duan Kehang , Liu Jiao , Zhang Jian , Chu Tongjia , Liu Huan , Lou Fengxiang , Liu Ziyu , Gao Bing , Wei Shixiong , Wei Feng
Published: January 2024

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research.
Moving beyond fish: working towards integrating human dimensions into sustainable seafood guides from South African perspectives
Authors: Ward Catherine Dale , Pillay Pavitray , Norton Marieke
Published: January 2024

Traditionally, seafood assessments and subsequent ratings have guided choice and responsible sourcing of sustainable seafood based primarily on environmental concerns, with limited to no consideration to multi-faceted human dimensions that form an integral part of these complex social-ecological systems. For wild-capture marine fisheries around the world, and particularly in developing countries, human dimensions remain underrepresented in sustainability ratings, where the focus has traditionally been on larger, data-rich commercial fishery components that report predominantly on ecological and management considerations. Yet, addressing the diverse and complex nature of marine social-ecological systems remains critical to achieve global sustainable seafood systems that balance ecological and societal needs to benefit both nature and people. This paper champions the integration of human elements into seafood sustainability guides, building on work reviewing how best to integrate human dimensions into traditional seafood assessments under the World Wide Fund for Nature (WWF) – drawing on examples from South Africa. While the paper does not prescribe a blueprint for implementation, this review highlights challenges and opportunities to include human rights violations and small-scale fisheries in existing sustainable seafood guides from a South African perspective. There is a need for sustainability considerations to move beyond fish to better represent how these social-ecological systems feed into oceanic cultural norms and nutrition. This translates to shifting from an ecological focus to include human dimensions to better represent complex marine social-ecological systems and drive equitable change within local and global seafood industries.
Using marine mammal necropsy data in animal health surveillance: the case of the harbor porpoise in the Southern North Sea
Authors: IJsseldijk Lonneke L. , van den Broek Jan , Kik Marja J. L. , Leopold Mardik F. , Bravo Rebolledo Elisa , Gröne Andrea , Heesterbeek Hans
Published: January 2024

Rapid changes of marine ecosystems resulting from human activities and climate change, and the subsequent reported rise of infectious diseases in marine mammals, highlight the urgency for timely detection of unusual health events negatively affecting populations. Studies reporting pathological findings in the commonly stranded harbor porpoise (Phocoena phocoena) on North Atlantic coastlines are essential to describe new and emerging causes of mortality. However, such studies often cannot be used as long-term health surveillance tools due to analytical limitations. We tested 31 variables gained from stranding-, necropsy-, dietary- and marine debris data from 405 harbor porpoises using applied supervised and unsupervised machine learning techniques to explore and analyze this large dataset. We classified and cross-correlated the variables and characterized the importance of the different variables for accurately predicting cause-of-death categories, to allow trend assessment for good conservation decision. The variable ‘age class’ seemed most influential in determining cause-of-death categories, and it became apparent that juveniles died more often due to acute causes, including bycatch, grey-seal-predation and other trauma, while adults of infectious diseases. Neonates were found in summer, and mostly without prey in their stomach and more often stranded alive. The variables assigned as part of the external examination of carcasses, such as imprints from nets and lesions induced by predators, as well as nutritional condition were most important for predicting cause-of-death categories, with a model prediction accuracy of 75%. Future porpoise monitoring, and in particular the assessment of temporal trends, should predominantly focus on influential variables as determined in this study. Pathogen- and contaminant assessment data was not available for all cases, but would be an important step to further complete the dataset. This could be vital for drawing population-inferences and thus for long-term harbor porpoise population health monitoring as an early warning tool for population change.
The non-uniformity characteristics of the evaporation duct in the South China Sea based on CLDAS data
Authors: Yang Ning , Zou Xiaohai , Sun Luyao , Su Debin , Wang Tao
Published: January 2024

The non-uniformity of the evaporation duct has a significant impact on the propagation of electromagnetic waves. Based on the near real-time dataset from the China Meteorological Administration Land Data Assimilation System (CLDAS) and the National Centers for Environmental Prediction (NCEP) Climate Forecast System Reanalysis (CFSR) datasets, the non-uniformity characteristics of evaporation duct height (EDH) in the South China Sea (SCS) region at different distances of electromagnetic propagation and the main influencing factors of EDH non-uniformity are analyzed. The findings are given as follows. First, the SCS monsoon has a significant impact on the spatial and temporal distribution of EDH, particularly in the western coastal areas of Luzon Island and the eastern coastal areas of the Indochina Peninsula. Secondly, the non-uniformity of EDH is more pronounced in the western part of Luzon Island, the eastern coast of the Indochina Peninsula, and the sea-land boundary area of the Beibu Gulf. Besides, the non-uniformity of EDH in the western part of Luzon Island and the eastern part of the Indochinese Peninsula is greatly influenced by air-sea temperature difference and relative humidity. Finally, it is advisable to consider the influence of the non-uniformity of EDH when the distance of electromagnetic propagation in coastal areas exceeds 50 km. However, it can be disregarded within a range of 100 km on the broad ocean.
The current situation of hereditary angioedema patients in Germany: results of an online survey
Authors: Magerl Markus , Martinez-Saguer Inmaculada , Schauf Lucia , Pohl Sven , Brendel Klaus
Published: January 2024

Introduction

Hereditary angioedema (HAE) is a rare hereditary disease with an estimated prevalence of approximately 1 in 50,000.

Methods

An online survey was performed between January and June 2021 on a total of 99 HAE patients (with 92 of them aged 15 years and older and 7 of them being parents of patients under the age of 15 years). They were asked about their current situation, with a focus on the disease.

Results

The survey results show that HAE has a strong influence on the patients’ quality of life. In particular, the anxiety and uncertainty of not knowing when a swelling attack will occur is considered burdensome by the patients. In addition, there can be physical problems during an attack (depending on its severity) that severely burden and limit patients in their everyday lives. Only one-third of the patients surveyed stated that no or only very minor physical limitations occurred during their most recent swelling attack. Almost three-quarters of all patients receive regular treatment at an HAE center. The patients are mostly satisfied with the therapy and particularly with long-term prophylactics (LTPs). When an LTP was used, the frequency and severity of the swelling attacks, and their duration, were significantly lower and/or shorter than when no LTP was used.

Discussion

Despite the high level of satisfaction with their current medication, 62% of patients expressed a strong/very strong interest in an oral LTP. In the group of patients already using an LTP, 74% reported a strong/very strong interest in an oral medication for long-term prophylaxis. The simplicity and minimal time involved in LTP use are considered beneficial to patients’ quality of life.
Unraveling the genetic evolution of SARS-CoV-2 Recombinants using mutational dynamics across the different lineages
Authors: Ravi Varsha , Shamim Uzma , Khan Md Abuzar , Swaminathan Aparna , Mishra Pallavi , Singh Rajender , Bharali Pankaj , Chauhan Nar Singh , Pandey Rajesh
Published: January 2024

Introduction

Recombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events during the viral evolution. This study introspects the phenomenon of genome recombination by tracing the footprint of prominent lineages of SARS-CoV-2 at different time points in the context of on-going evolution and emergence of Recombinants.

Method

Whole genome sequencing was carried out for 2,516 SARS-CoV-2 (discovery cohort) and 1,126 (validation cohort) using nasopharyngeal samples collected between the time period of March 2020 to August 2022, as part of the genomic surveillance program. The sequences were classified according to the different lineages of SARS-CoV-2 prevailing in India at respective time points.

Results

Mutational diversity and abundance evaluation across the 12 lineages identified 58 Recombinant sequences as harboring the least number of mutations (n = 111), with 14 low-frequency unique mutations with major chunk of mutations coming from the BA.2. The spontaneously/dynamically increasing and decreasing trends of mutations highlight the loss of mutations in the Recombinants that were associated with the SARS-CoV-2 replication efficiency, infectivity, and disease severity, rendering them functionally with low infectivity and pathogenicity. Linkage disequilibrium (LD) analysis revealed that mutations comprising the LD blocks of BA.1, BA.2, and Recombinants were found as minor alleles or as low-frequency alleles in the LD blocks from the previous SARS-CoV-2 variant samples, especially Pre-VOC. Moreover, a dissipation in the size of LD blocks as well as LD decay along with a high negative regression coefficient (R squared) value was demonstrated in the Omicron and BA.1 and BA.2 lineages, which corroborated with the breakpoint analysis.

Conclusion

Together, the findings help to understand the evolution and emergence of Recombinants after the Omicron lineages, for sustenance and adaptability, to maintain the epidemic spread of SARS-CoV-2 in the host population already high in immunity levels.
General practice management of chronic post-surgical pain in patients with hip fracture: a qualitative study
Authors: Cao Wenshu , Ye Jizhong , Yan Yini , Xu Cheng , Lv Qiwei
Published: January 2024

Background

Hip fractures are common among elderly people and often lead to chronic post-surgical pain (CPSP). Effective CPSP management when patients transition from hospital to community settings is essential, but has not been sufficiently researched. This study examined general practitioner (GP) perspectives on managing patients with CPSP after hip fractures in Shanghai, China.

Methods

A descriptive qualitative study was performed wherein semi-structured interviews were conducted with GPs practicing in Shanghai who volunteered to participate. This study was initiated after a regional survey of general practice care for patients with CPSP following hip fracture.

Results

Six key themes emerged: (1) GPs’ care priorities for patients with CPSP varied; (2) pharmacological management posed challenges in terms of selecting appropriate medications; (3) consultation time constraints hindered comprehensive management; (4) GPs desired better communication from hospitals at discharge; (5) limited access to services, such as pain specialists and allied health, obstructed optimal care delivery; and (6) patient nonadherence to CPSP treatment was an issue.

Conclusion

Multiple patient-, provider-, and system-level factors affected GP care for patients with CPSP after hip fracture. Improved interdisciplinary communication and education on evidence-based CPSP guidelines are needed to address the knowledge gaps among GPs. Barriers to healthcare access must be minimized to facilitate guideline-based care.
The optimal timing of frozen-thawed embryo transfer: delayed or not delayed? A systematic review and meta-analysis
Authors: Gao Yu-Qi , Song Jing-Yan , Sun Zhen-Gao
Published: January 2024

Background

The use of frozen embryo transfer (FET) has grown exponentially over the past few years. However, in clinical practice, there are no specific criteria as to whether a delay of at least one menstrual cycle is required for an FET after a failed fresh ET or a freeze-all cycle.

Objective

Through the effects on live birth rate (LBR), clinical pregnancy rate (CPR) and pregnancy loss rate (PLR), to determine whether FET requires a delay of at least one menstrual cycle after fresh ET failure or a freeze-all cycle.

Methods

The search was conducted through PubMed, Web of Science, CNKI, and Wanfang databases for terms related to FET timing as of April 2023. There are no restrictions on the year of publication or follow-up time. Women aged 20 to 46 with any indication for in vitro fertilization and embryo transfer (IVF-ET) treatment are eligible for inclusion. Oocyte donation studies are excluded. Except for the case report, study protocol, and abstract, all original studies are included.

Results

In 4,124 search results, 19 studies were included in the review. The meta-analysis includes studies on the adjusted odds ratio (OR) and 95% confidence interval (CI) of reported live birth rate (LBR), clinical pregnancy rate (CPR), and pregnancy loss rate (PLR), 17 studies were retrospective cohort study, and 2 studies were randomized controlled trial, a total of 6,917 immediate FET cycles and 16,105 delayed FET cycles were involved. In this meta-analysis, the combined OR of LBR was [OR = 1.09, 95% CI (0.93–1.28)], the combined OR of CPR was [OR = 1.05, 95% CI (0.92–1.20)], and the combined OR of PLR was (OR = 0.96, 95% CI 0.75–1.22). There was no statistical significance between the two groups.

Conclusion

Overall, delaying FET by at least one menstrual cycle has no advantage in LBR, CPR, or PLR. So, flexible scheduling of FETs is available to both doctors and patients.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020161648.
In vitro characterization and molecular epidemiology of Cryptococcus spp. isolates from non-HIV patients in Guangdong, China
Authors: Wang Penglei , Li Yongming , Gao Lei , Tang Xiang , Zheng Dandian , Wu Kuihai , Wang Luxia , Guo Penghao , Ye Feng
Published: January 2024

Background

The burden of cryptococcosis in mainland China is enormous. However, the in vitro characterization and molecular epidemiology in Guangdong, a key region with a high incidence of fungal infection in China, are not clear.

Methods

From January 1, 2010, to March 31, 2019, clinical strains of Cryptococcus were collected from six medical centres in Guangdong. The clinical information and characteristics of the strains were analysed. Furthermore, molecular types were determined.

Results

A total of 84 strains were collected, mostly from male and young or middle-aged adult patients. Pulmonary and cerebral infections (82.1%) were most common. All strains were Cryptococcus neoformans, grew well at 37°C and had capsules around their cells. One melanin- and urea- and one melanin+ and urea- variants were found. Although most strains exhibited a low minimum inhibitory concentration (MIC) value for voriconazole (mean: 0.04 μg/mL) and posaconazole (mean: 0.12 μg/mL), the results for these isolates showed a high degree of variation in the MIC values of fluconazole and 5-fluorocytosine, and resistance was observed for 4 out of 6 drugs. A significant proportion of these strains had MIC values near the ECV values, particularly in the case of amphotericin B. The proportion of strains near the clinical breakpoints was as follows: fluconazole: 3.66%; voriconazole: 3.66%; itraconazole: 6.10%; posaconazole: 13.41%; amphotericin B: 84.15%; 5-fluorocytosine: 2.44%. These strains were highly homogeneous and were dominated by the Grubii variant (95.2%), VNI (94.0%), α mating (100%), and ST5 (89.3%) genotypes. Other rare types, including ST4, 31, 278, 7, 57 and 106, were also found.

Conclusion

Phenotypically variant and non-wild-type strains were found in Guangdong, and a significant proportion of these strains had MIC values near the ECV values towards the 6 antifungal drugs, and resistance was observed for 4 out of 6 drugs. The molecular type was highly homogeneous but compositionally diverse, with rare types found. Enhanced surveillance of the aetiology and evolution and continuous monitoring of antifungal susceptibility are needed to provide references for decision-making in the health sector and optimization of disease prevention and control.
Recent advances in infectious disease research using cryo-electron tomography
Authors: Asarnow Daniel , Becker Vada A. , Bobe Daija , Dubbledam Charlie , Johnston Jake D. , Kopylov Mykhailo , Lavoie Nathalie R. , Li Qiuye , Mattingly Jacob M. , Mendez Joshua H. , Paraan Mohammadreza , Turner Jack , Upadhye Viraj , Walsh Richard M. , Gupta Meghna , Eng Edward T.
Published: January 2024

With the increasing spread of infectious diseases worldwide, there is an urgent need for novel strategies to combat them. Cryogenic sample electron microscopy (cryo-EM) techniques, particularly electron tomography (cryo-ET), have revolutionized the field of infectious disease research by enabling multiscale observation of biological structures in a near-native state. This review highlights the recent advances in infectious disease research using cryo-ET and discusses the potential of this structural biology technique to help discover mechanisms of infection in native environments and guiding in the right direction for future drug discovery.
Association between inflammatory bowel disease and Parkinson’s disease: a prospective cohort study of 468,556 UK biobank participants
Authors: Wang Hai-li , Wang Zhi-yun , Tian Jie , Ma Dong-rui , Shi Chang-he
Published: January 2024

Introduction

Inflammatory Bowel Disease (IBD) and Parkinson’s disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database.

Methods

We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023.

Results

The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941–1.955, p = 0.103), and the effect remained consistent in specific Crohn’s disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032–3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401–4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128–3.697, p = 0.018) was associated with an increased risk of PD.

Conclusion

In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.
Development and implementation of a Dependable, Simple, and Cost-effective (DSC), open-source running wheel in High Drinking in the Dark and Heterogeneous Stock/Northport mice
Authors: Grigsby Kolter , Usmani Zaynah , Anderson Justin , Ozburn Angela
Published: January 2024

Maintaining healthy and consistent levels of physical activity (PA) is a clinically proven and low-cost means of reducing the onset of several chronic diseases and may provide an excellent strategy for managing mental health and related outcomes. Wheel-running (WR) is a well-characterized rodent model of voluntary PA; however, its use in biomedical research is limited by economical and methodical constraints. Here, we showcase the DSC (Dependable, Simple, Cost-effective), open-source running wheel by characterizing 24-h running patterns in two genetically unique mouse lines: inbred High Drinking in the Dark line 1 [iHDID-1; selectively bred to drink alcohol to intoxication (and then inbred to maintain phenotype)] and Heterogeneous Stock/Northport (HS/Npt; the genetically heterogeneous founders of iHDID mice). Running distance (km/day), duration (active minutes/day) and speed (km/hour) at 13-days (acute WR; Experiment 1) and 28-days (chronic WR; Experiment 2) were comparable to other mouse strains, suggesting the DSC-wheel reliably captures murine WR behavior. Analysis of 24-h running distance supports previous findings, wherein iHDID-1 mice tend to run less than HS/Npt mice in the early hours of the dark phase and more than HS/Npt in the late hours of dark phase/early light phase. Moreover, circadian actograms were generated to highlight the broad application of our wheel design across disciplines. Overall, the present findings demonstrate the ability of the DSC-wheel to function as a high-throughput and precise tool to comprehensively measure WR behaviors in mice.
Aspiration thrombectomy versus stent retriever thrombectomy as a first-line approach for cardiogenic cerebral embolism and cryptogenic stroke in large vessels of the anterior circulation
Authors: Zhiqiang Peng , Junchen Chen , Wenying Cao , Dongqing Zhao , Mi Ma , Qiaowei Li , Zhenzhen Zhu , Wanyi He , Biqing Yang , Minqi Cao
Published: January 2024

Subject

This study aims to compare the clinical efficacy of aspiration thrombectomy and stent retriever thrombectomy as first-line approaches for anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke.

Method

This retrospective observational study included patients with anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke treated with endovascular therapy. Patients were grouped according to the first-line approach they received: aspiration thrombectomy or stent retriever thrombectomy. The primary outcome measure was the change in the National Institute of Health Stroke Scale (NIHSS) score from preoperative to immediate postoperative and from preoperative to discharge. Secondary indicators included the rate of favorable prognosis at discharge [Modified Rankin Scale (mRS) score ≤ 2], successful vessel recanalization rate [modified Treatment in Cerebral Ischemia (mTICI) score ≥ 2b], time from successful femoral artery puncture to successful vessel recanalization, and perioperative complications.

Result

The study included 127 cases, with 1 case withdrawal after enrollment due to a stroke of another determined cause, with 83 in the aspiration thrombectomy group and 43 cases in the stent retriever thrombectomy group. The change in NIHSS score from preoperative to immediate postoperative was 5 (1, 8) in the aspiration thrombectomy group and 1 (0, 4.5) in the stent retriever thrombectomy group. The change from preoperative to discharge was 8 (5, 12) in the aspiration thrombectomy group and 4 (0, 9) in the stent retriever thrombectomy group. The aspiration thrombectomy group exhibited significantly better prognosis rates and shorter time from successful femoral artery puncture to successful vessel recanalization. There were no significant differences between the two groups in terms of successful vessel recanalization rates and perioperative complications.

Conclusion

As a first-line approach for anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke, aspiration thrombectomy leads to better improvement in neurological functional deficits and prognosis rates compared to stent retriever thrombectomy.
Neutrophil/lymphocyte and monocyte/lymphocyte indexes as potential predictors of relapse at 1 year after diagnosis of pediatric multiple sclerosis: a single-center, exploratory and proof-of-concept study
Authors: Palavra Filipe , Geria Leonor , Jorge André , Marques Margarida , dos Santos Constança Soares , Amaral Joana , Ribeiro Joana Afonso , Pereira Cristina , Robalo Conceição
Published: January 2024

Introduction

Early identification of patients with a more unfavorable outcome in Multiple Sclerosis (MS) is crucial to optimize individualized treatment. Neutrophil-lymphocyte index (NLI) and monocyte-lymphocyte index (MLI) have been considered as potential biomarkers for disease prognosis. Our study aims to investigate the usefulness of NLI and MLI as predictors of relapse, disability progression, and lesion accumulation on magnetic resonance imaging (MRI) 1 year after diagnosis and treatment initiation, in pediatric-onset MS.

Methods

A retrospective single-center study was conducted, including patients with diagnosis of MS established in pediatric age (<18 years old), at least 1-year of follow-up, and a complete blood count (CBC) performed at diagnosis. We collected the nearest-to-diagnosis NLI and MLI, as well as clinical and imaging variables, at diagnosis and 12 months later. Our cohort was further dichotomized into two groups, based on the presence of relapses. Statistical significance was considered for p < 0.05.

Results

Eighteen patients (n = 18) were included. The relapsing group had higher mean, minimum, and maximum values for both NLI (5.17 ± 5.85, range: 1.57–11.92) and MLI (0.35 ± 0.22, range: 0.19–0.59), compared to the non-relapsing group (2.19 ± 1.63, range: 1.12–7.32 for NLI, and 0.24 ± 0.09, range: 0.14–0.44 for MLI). A higher percentage of patients in the relapsing group had increased NLI (>1.89, 66.7%) and MLI (>0.21, 66.7%) values than those in the non-relapsing group (46.7%). Patients who presented new T2-hyperintense lesions on MRI after 1 year of follow-up also had higher mean, minimum, and maximum values of both biomarkers. Patients who did not achieve No Evidence of Disease Activity-3 (NEDA-3) state exhibited higher values for both ratios. However, in our sample, no statistically significant correlations were found between MLI and NLI values and the clinical and imaging variables considered.

Conclusion

The ease of obtaining NLI and MLI from routine blood tests renders them useful biomarkers as a screening tool in longitudinal follow-up. Our study was based on a very small sample size, but it allowed us to verify the feasibility of the protocol used. It is intended to involve other centers in the next phase of this work, testing the possible usefulness of the indices under analysis on a larger sample.
Natural product based anticancer drug combination discovery assisted by deep learning and network analysis
Authors: Cao Elton L.
Published: January 2024

Drug combination therapies have shown effective performance in treating cancer through increased efficacy and circumvention of drug resistance through synergy. Two avenues can be used to discover drug combinations: a novel approach that utilizes natural products compared with the textbook approach of utilizing existing chemotherapy drug combinations. Many natural products achieve efficacy due to synergistic interactions between the active ingredients. Therefore, the pharmacophore relationships in herbal compounds which synergize can potentially be applied to chemotherapy drugs to drive combination discovery. Machine learning approaches have been developed to identify drug combinations, especially deep neural networks (DNN), which have achieved state-of-the-art performance in many drug discovery tasks. Here, a drug protein interaction (DPI) prediction DNN, DeepDPI, was developed to employ DPI drug representations and achieved state-of-the-art performance using the DrugBank database. Two DNNs were also developed to predict novel drug combinations: DeepNPD, which predicts combinations in natural products, and DeepCombo, which predicts synergy in chemotherapy drugs, using the HERB and DrugCombDB databases respectively. An ensemble architecture enhanced with a novel similarity based weight adjustment (SBWA) approach was used and both models accurately predicted drug combinations for both known and unknown drugs. Lastly, a screening was conducted using each model where DeepNPD predicted combinations where drugs had similar targets, while DeepCombo predicted combinations where one agent potentiated the other, with both models’ predicted combinations investigated through a network-based analysis and identifying as a synergistic combinations in literature. DeepNPD notably identified Thioguanine and Hydroxyurea and DeepCombo discovered Vinblastine and Dasatinib as hits for potential new anticancer drug combinations. DeepNPD illustrates how natural products are a novel path where new drug combinations can be discovered.
A case series exploring the human milk polyclonal IgA1 response to repeated SARS-CoV-2 vaccinations by LC–MS based fab profiling
Authors: de Graaf Sebastiaan C. , Bondt Albert , van Rijswijck Danique M. H. , Juncker Hannah G. , Mulleners Sien J. , Damen Mirjam J. A. , Hoek Max , van Keulen Britt J. , van Goudoever Johannes B. , Heck Albert J. R. , Dingess Kelly A.
Published: January 2024

Introduction

Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC–MS fragment antigen-binding (Fab) clonal profiling approach.

Methods

We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15  days after the second vaccination.

Results

In all donors, we detected a population of 89–191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine.

Discussion

Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses.
Food insecurity among consumers from rural areas in Romania
Authors: Paştiu Carmen Adina , Maican Silvia Ştefania , Dobra Iulian Bogdan , Muntean Andreea Cipriana , Haţegan Camelia
Published: January 2024

Food security has a special relevance in nowadays economies, due to the current crisis, characterized by multiple layers on a social, political, economic, and individual biological level. The present study aims to identify relevant aspects of food insecurity for consumers in rural Romania and the main factors that significantly influence it (food availability, food access, and food consumption). The data were collected from a sample of 875 consumers from rural areas in Romania. The results show that food insecurity is perceived by the consumers of Romanian rural households as being strongly influenced by food availability, but less influenced by food consumption and access. The results have an essential relevance in the development of agri-food marketing strategies and public policies in the field of sustainable development.
Development of RLK-Unet: a clinically favorable deep learning algorithm for brain metastasis detection and treatment response assessment
Authors: Son Seungyeon , Joo Bio , Park Mina , Suh Sang Hyun , Oh Hee Sang , Kim Jun Won , Lee Seoyoung , Ahn Sung Jun , Lee Jong-Min
Published: January 2024

Purpose/objective(s)

Previous deep learning (DL) algorithms for brain metastasis (BM) detection and segmentation have not been commonly used in clinics because they produce false-positive findings, require multiple sequences, and do not reflect physiological properties such as necrosis. The aim of this study was to develop a more clinically favorable DL algorithm (RLK-Unet) using a single sequence reflecting necrosis and apply it to automated treatment response assessment.

Methods and materials

A total of 128 patients with 1339 BMs, who underwent BM magnetic resonance imaging using the contrast-enhanced 3D T1 weighted (T1WI) turbo spin-echo black blood sequence, were included in the development of the DL algorithm. Fifty-eight patients with 629 BMs were assessed for treatment response. The detection sensitivity, precision, Dice similarity coefficient (DSC), and agreement of treatment response assessments between neuroradiologists and RLK-Unet were assessed.

Results

RLK-Unet demonstrated a sensitivity of 86.9% and a precision of 79.6% for BMs and had a DSC of 0.663. Segmentation performance was better in the subgroup with larger BMs (DSC, 0.843). The agreement in the response assessment for BMs between the radiologists and RLK-Unet was excellent (intraclass correlation, 0.84).

Conclusion

RLK-Unet yielded accurate detection and segmentation of BM and could assist clinicians in treatment response assessment.
Potent in vivo efficacy of oral gallium maltolate in treatment-resistant glioblastoma
Authors: Al-Gizawiy Mona M. , Wujek Robert T. , Alhajala Hisham S. , Cobb Jonathan M. , Prah Melissa A. , Doan Ninh B. , Connelly Jennifer M. , Chitambar Christopher R. , Schmainda Kathleen M.
Published: January 2024

Background

Treatment-resistant glioblastoma (trGBM) is an aggressive brain tumor with a dismal prognosis, underscoring the need for better treatment options. Emerging data indicate that trGBM iron metabolism is an attractive therapeutic target. The novel iron mimetic, gallium maltolate (GaM), inhibits mitochondrial function via iron-dependent and -independent pathways.

Methods

In vitro irradiated adult GBM U-87 MG cells were tested for cell viability and allowed to reach confluence prior to stereotactic implantation into the right striatum of male and female athymic rats. Advanced MRI at 9.4T was carried out weekly starting two weeks after implantation. Daily oral GaM (50mg/kg) or vehicle were provided on tumor confirmation. Longitudinal MRI parameters were processed for enhancing tumor ROIs in OsiriX 8.5.1 (lite) with Imaging Biometrics Software (Imaging Biometrics LLC). Statistical analyses included Cox proportional hazards regression models, Kaplan-Meier survival plots, linear mixed model comparisons, and t-statistic for slopes comparison as indicator of tumor growth rate.

Results

In this study we demonstrate non-invasively, using longitudinal MRI surveillance, the potent antineoplastic effects of GaM in a novel rat xenograft model of trGBM, as evidenced by extended suppression of tumor growth (23.56 mm3/week untreated, 5.76 mm3/week treated, P < 0.001), a blunting of tumor perfusion, and a significant survival benefit (median overall survival: 30 days untreated, 56 days treated; P < 0.001). The therapeutic effect was confirmed histologically by the presence of abundant cytotoxic cellular swelling, a significant reduction in proliferation markers (P < 0.01), and vessel normalization characterized by prominent vessel pruning, loss of branching, and uniformity of vessel lumina. Xenograft tumors in the treatment group were further characterized by an absence of an invasive edge and a significant reduction in both, MIB-1% and mitotic index (P < 0.01 each). Transferrin receptor and ferroportin expression in GaM-treated tumors illustrated cellular iron deprivation. Additionally, treatment with GaM decreased the expression of pro-angiogenic markers (von Willebrand Factor and VEGF) and increased the expression of anti-angiogenic markers, such as Angiopoietin-2.

Conclusion

Monotherapy with the iron-mimetic GaM profoundly inhibits trGBM growth and significantly extends disease-specific survival in vivo.
Effects of music on the preoperative and intraoperative anxiety through the assessment of pupil size and vital signs (blood pressure, respiratory, and pulse rates) among cataract surgery patients at UNTH-Enugu
Authors: Ezepue Chukwubuike Obiora , Anyatonwu Obinna Princewill , Duru Christian Chukwuka , Odini Franklin , Nwachukwu Nkiru Zuada , Onoh Chidimma , Nwachukwu Nwamaka , Oguonu Chukwunonso Afam
Published: January 2024

Background/Aim

To examine how music can impact preoperative and intraoperative anxiety via assessment of physiological markers such as pupil size, blood pressure, pulse rate, and respiratory rate.

Methods

This is a randomized interventional study of individuals aged 50 years and above who were scheduled for and undergoing cataract surgery under regional anesthesia, with music (test group) randomly matched with similar individuals undergoing the same procedure but without music (control group). The surgeries were performed in the operating theater of the Department of Ophthalmology, University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu. Using a systematic random sampling method, a total of 98 patients were grouped into two. Both groups completed the State–Trait Anxiety Inventory (STAI) questionnaire at baseline, immediately upon entrance into the preoperative room and 5 min after intervention. Relevant study indices (blood pressure, pulse, respiratory rate, and pupil diameter) were measured and recorded, and these served as baseline parameters. The STAI questionnaire was then administered. Results were analyzed using the SPSS version 20 and analysis of variance was used to compare means of variables measured at baseline, preoperative before intervention, and preoperative after intervention. Categorical variables were compared using the Chi-square test. Student’s t-test was used to analyze the continuous variables.

Results

Our analysis, using the multiple linear regression, showed that music has an effect on preoperative anxiety and intraoperative anxiety by positively affecting the blood pressure, pulse rate, respiratory rate, and pupil diameter (P ≤ 0.001).

Conclusion

Music reduces preoperative and intraoperative anxiety evidenced by its effect on the physiological biomarkers.