bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications
Authors: Darzentas Franziska , Szczepanowski Monika , Kotrová Michaela , Hartmann Alina , Beder Thomas , Gökbuget Nicola , Schwartz Stefan , Bastian Lorenz , Baldus Claudia Dorothea , Pál Karol , Darzentas Nikos , Brüggemann Monika
Published: April 2023

Introduction

The malignant transformation leading to a maturation arrest in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occurs early in B-cell development, in a pro-B or pre-B cell, when somatic recombination of variable (V), diversity (D), and joining (J) segment immunoglobulin (IG) genes and the B-cell rescue mechanism of VH replacement might be ongoing or fully active, driving clonal evolution. In this study of newly diagnosed BCP-ALL, we sought to understand the mechanistic details of oligoclonal composition of the leukemia at diagnosis, clonal evolution during follow-up, and clonal distribution in different hematopoietic compartments.

Methods

Utilizing high-throughput sequencing assays and bespoke bioinformatics we identified BCP-ALL-derived clonally-related IGH sequences by their shared ‘DNJ-stem’.

Results

We introduce the concept of ‘marker DNJ-stem’ to cover the entirety of, even lowly abundant, clonally-related family members. In a cohort of 280 adult patients with BCP-ALL, IGH clonal evolution at diagnosis was identified in one-third of patients. The phenomenon was linked to contemporaneous recombinant and editing activity driven by aberrant ongoing DH/VH-DJH recombination and VH replacement, and we share insights and examples for both. Furthermore, in a subset of 167 patients with molecular subtype allocation, high prevalence and high degree of clonal evolution driven by ongoing DH/VH-DJH recombination were associated with the presence of KMT2A gene rearrangements, while VH replacements occurred more frequently in Ph-like and DUX4 BCP-ALL. Analysis of 46 matched diagnostic bone marrow and peripheral blood samples showed a comparable clonal and clonotypic distribution in both hematopoietic compartments, but the clonotypic composition markedly changed in longitudinal follow-up analysis in select cases. Thus, finally, we present cases where the specific dynamics of clonal evolution have implications for both the initial marker identification and the MRD monitoring in follow-up samples.

Discussion

Consequently, we suggest to follow the marker DNJ-stem (capturing all family members) rather than specific clonotypes as the MRD target, as well as to follow both VDJH and DJH family members since their respective kinetics are not always parallel. Our study further highlights the intricacy, importance, and present and future challenges of IGH clonal evolution in BCP-ALL.
The association of systemic inflammation and cognitive functions of pre-school aged children residing in a Schistosoma haematobium endemic area in Zimbabwe
Authors: Kasambala Maritha , Mukaratirwa Samson , Vengesai Arthur , Mduluza-Jokonya Tariro , Jokonya Luxwell , Midzi Herald , Makota Rutendo Birri , Mutemeri Arnold , Maziti Emmanuel , Dube-Marimbe Bazondlile , Chibanda Dixon , Mutapi Francisca , Mduluza Takafira
Published: April 2023

Background

Cognitive function is negatively impacted by schistosomiasis and might be caused by systemic inflammation which has been hypothesized to be one of the mechanisms driving cognitive decline, This study explored the association of systemic inflammatory biomarkers; interleukin (IL)-10, IL-6, IL-17, transforming growth factor (TGF-β), tumor necrosis factor (TNF-α), C-reactive protein (CRP) and hematological parameters with cognitive performance of preschool-aged children (PSAC) from an Schistosoma haematobium endemic area

Methods

The Griffith III tool was used to measure the cognitive performance of 136 PSAC. Whole blood and sera were collected and used to quantify levels of IL-10, TNF-α, IL-6, TGF-β, IL-17 A and CRP using the enzyme-linked immunosorbent assay and hematological parameters using the hematology analyzer. Spearman correlation analysis was used to determine the relationship between each inflammatory biomarker and cognitive performance. Multivariate logistic regression analysis was used to determine whether systemic inflammation due to S. haematobium infection affected cognitive performance in PSAC.

Results

Higher levels of TNF-α and IL-6, were correlated with lower performance in the Foundations of Learning domain (r = -0.30; p < 0.001 and r = -0.26; p < 0.001), respectively. Low cognitive performance in the Eye-Hand-Coordination Domain was observed in PSAC with high levels of the following inflammatory biomarkers that showed negative correlations to performance; TNF-α (r = -0.26; p < 0.001), IL-6 (r = -0.29; p < 0.001), IL-10 (r = -0.18; p < 0.04), WBC (r = -0.29; p < 0.001), neutrophils (r = -0.21; p = 0.01) and lymphocytes (r = -0.25; p = 0.003) The General Development Domain correlated with TNF-α (r = -0.28; p < 0.001) and IL-6 (r = -0.30; p < 0.001). TGF-β, L-17A and MXD had no significant correlations to performance in any of the cognitive domains. The overall general development of PSAC was negatively impacted by S. haematobium infections (OR = 7.6; p = 0.008) and (OR = 5.6; p = 0.03) where the PSAC had higher levels of TNF-α and IL-6 respectively.

Conclusion

Systemic inflammation and S. haematobium infections are negatively associated with cognitive function. We recommend the inclusion of PSAC into mass drug treatment programs.
The role of protein arginine deiminase 4-dependent neutrophil extracellular traps formation in ulcerative colitis
Authors: Wang Ping , Liu Dan , Zhou Ziqi , Liu Fangjun , Shen Yiming , You Qi , Lu Shiping , Wu Jie
Published: April 2023

Background

Neutrophil extracellular traps (NETs) play an important role in the development and progression of ulcerative colitis (UC). Peptidyl arginine deiminase 4 (PAD4) is essential for the formation of NETs via catalyzing histone citrullination. This study mainly to explore the role of PAD4-mediated NETs in intestinal inflammation of dextran sulfate sodium (DSS)-induced UC.

Methods

Acute and chronic colitis mouse models were established by supplementing DSS in drinking water. Colon tissues from colitis mice were analyzed for the level of PAD4 expression, citrullinated histone H3(Cit-H3), intestinal histopathology, and inflammatory cytokines secretion. Serum samples were tested for systemic neutrophil activation biomarkers. Colitis mice administered with Cl-amidine, a PAD4 inhibitor, and PAD4 knockout mice were investigated to detect NETs formation, intestinal inflammation, and barrier function.

Result

We found the formation of NETs significantly increased in DSS-induced colitis mice and was correlated with disease markers. Blocking NETs formation by Cl-amidine or PAD4 genetic knockout could alleviate clinical colitis index, intestinal inflammation, and barrier dysfunction.

Conclusion

This study provided a research basis for the role of PAD4-mediated NETs formation in the pathogenesis of UC and suggested that inhibition of PAD4 activity and the formation of NETs may be helpful for the prevention and treatment of UC.
Dsg3 epitope-specific signalling in pemphigus
Authors: Schmitt Thomas , Hudemann Christoph , Moztarzadeh Sina , Hertl Michael , Tikkanen Ritva , Waschke Jens
Published: April 2023

Introduction

Pemphigus is an autoantibody driven disease that impairs the barrier function of the skin and mucosa by disrupting desmosomes and thereby impeding cellular cohesion. It is known that the different clinical phenotypes of pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are dependent on the autoantibody profile and target antigens that, amongst others, are primarily desmoglein (Dsg)1 and/or Dsg3 for PV and Dsg1 for PF. However, it was reported that autoantibodiesagainst different epitopes of Dsg1 and Dsg3 can be pathogenic or not. The underlying mechanisms are very complex and involve both direct inhibition of Dsg interactions and downstream signalling. The aim of this study was to find out whether there is target-epitope-specific Dsg3 signalling by comparing the effects of the two pathogenic murine IgGs, 2G4 and AK23.

Methods

Dispase-based dissociation assay, Western Blot analysis, Stimulated emission depletion microscopy, Fura-based Ca2+ flux measurements, Rho/Rac G-Protein-linked immunosorbent assay, Enzyme-linked immunosorbent assay.

Results

The IgGs are directed against the EC5 and EC1 domain of Dsg3, respectively. The data show that 2G4 was less effective in causing loss of cell adhesion, compared to AK23. STED imaging revealed that both autoantibodies had similar effects on keratin retraction and reduction of desmosome number whereas only AK23 induced Dsg3 depletion. Moreover, both antibodies induced phosphorylation of p38MAPK and Akt whereas Src was phosphorylated upon treatment with AK23 only. Interestingly, Src and Akt activation were p38MAPK-dependent. All pathogenic effects were rescued by p38MAPK inhibition and AK23-mediated effects were also ameliorated by Src inhibition.

Discussion

The results give first insights into pemphigus autoantibody-induced Dsg3 epitope-specific signalling which is involved in pathogenic events such as Dsg3 depletion.
Identificationof a novel linear epitope on the porcine reproductive and respiratory syndrome virus nucleocapsid protein, as recognized by a specific monoclonal antibody
Authors: Cheng Yuening , Wu Miaoli , Xiao Li , Zhang Mengdi , Huang Bihong , Cong Feng , Yi Li
Published: April 2023

Introduction

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most threatening pathogens of swine. The nucleocapsid (N) protein is the major structural protein of the virus and has been used as a PRRSV diagnostic antigen due to its high level of inherent immunogenicity.

Methods

The recombinant PRRSV N protein was generated by the prokaryotic expressing system and used to immunized mice. Monoclonal antibodies against PRRSV were produced and validated by western blot analysis and indirect immunofluorescence analysis. In this study, the linear epitope of a specific monoclonal antibody mAb (N06) was subsequently identified by enzyme-linked immunosorbent assays (ELISA) using the synthesized overlapping peptides as antigens.

Results

According to the results of western blot analysis and indirect immunofluorescence analysis, mAb (N06) was capable of recognizing the native form as well as the denatured form of PRRSV N protein. The results of ELISA showed that mAb N06 recognized the epitope NRKKNPEKPHFPLATE, which was consistent with BCPREDS predictions of antigenicity.

Conclusion

All the data suggested that the mAb (N06) can be used as diagnostic reagents for PRRSV detection, while the recognized linear epitope can be useful in epitope-based vaccines development, which is helpful for the control of local PRRSV infections in swine.
Source, distribution, and transformation of dissolved and particulate organic matters in Qinzhou Bay, Northern Beibu Gulf
Authors: Cai Shangjun , Wang Chao , Zhu Qingmei , Lao Qibin
Published: April 2023

Both dissolved and particulate organic matters (DOM and POM) provide a reduced carbon pool of considerable size in coastal ecosystems, and the two are closely linked. Currently, however, the integrated study of DOM and POM remains limited, precluding a more in-depth understanding of their interaction in coastal regions. In April 2021, 13 surface water samples were collected from Qinzhou Bay, in the northern Beibu Gulf. The DOM samples were characterized using dissolved organic carbon (DOC) analysis and UV-visible and fluorescence spectroscopy techniques. We determined the POM for the particulate organic carbon and nitrogen (POC and PN) and also isotopic composition (δ13C and δ15N). The weak to negligible relationships found between the DOC, colored and fluorescent DOM, salinity, and chlorophyll a together suggested that DOM’s distribution in Qinzhou Bay is concurrently shaped by various processes, namely, hydrological and in situ biological processes. A high C/N ratio of ~17, high POC/chlorophyll a ratio (253 ± 112), and depleted δ13C (−25.7 ± 1.6‰) confirmed that POM is highly degraded and originates mainly from allochthonous input, to which the terrigenous organic matter and freshwater phytoplankton each contributes 35%. The total organic carbon (TOC = DOC + POC) was positively correlated with the humic-like peak M, revealing the transformation of labile DOM and POM into recalcitrant DOM components. The in situ production efficiency of peak M in surface waters of Qinzhou Bay is one order of magnitude greater than that in inland waters or open oceans, indicating that not only temperature but also the activity of substrate is a key factor controlling the in situ production of recalcitrant DOM in Qinzhou Bay. High levels of TOC and humic-like fluorescent DOM suggest the mass coexistence of organic matter differing in its reactivity, highlighting the large potential for photochemical as well as microbial degradation in the future.
The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease
Authors: Belcher John D. , Nataraja Selvaraj , Abdulla Fuad , Zhang Ping , Chen Chunsheng , Nguyen Julia , Ruan Conglin , Singh Maneet , Demes Shilpa , Olson Lyndsay , Stickens Domi , Stanwix Jeff , Clarke Emer , Huang Yongzhao , Biddle Margaret , Vercellotti Gregory M.
Published: April 2023

In sickle cell disease (SCD), heme released during intravascular hemolysis promotes oxidative stress, inflammation, and vaso-occlusion. Conversely, free heme can also activate expression of antioxidant and globin genes. Heme binds to the transcription factor BACH1, which represses NRF2-mediated gene transcription. ASP8731, is a selective small molecule inhibitor of BACH1. We investigated the ability of ASP8731 to modulate pathways involved in SCD pathophysiology. In HepG2 liver cells, ASP8731 increased HMOX1 and FTH1 mRNA. In pulmonary endothelial cells, ASP8731 decreased VCAM1 mRNA in response to TNF-α and blocked a decrease in glutathione in response to hemin. Townes-SS mice were gavaged once per day for 4 weeks with ASP8731, hydroxyurea (HU) or vehicle. Both ASP8731 and HU inhibited heme-mediated microvascular stasis and in combination, ASP8731 significantly reduced microvascular stasis compared to HU alone. In Townes-SS mice, ASP8731 and HU markedly increased heme oxygenase-1 and decreased hepatic ICAM-1, NF-kB phospho-p65 protein expression in the liver, and white blood cell counts. In addition, ASP8731 increased gamma-globin expression and HbF+ cells (F-cells) as compared to vehicle-treated mice. In human erythroid differentiated CD34+ cells, ASP8731 increased HGB mRNA and increased the percentage of F-cells 2-fold in manner similar to HU. ASP8731 and HU when given together induced more HbF+ cells compared to either drug alone. In CD34+ cells from one donor that was non-responsive to HU, ASP8731 induced HbF+ cells ~2-fold. ASP8731 and HU also increased HBG and HBA, but not HBB mRNA in erythroid differentiated CD34+ cells derived from SCD patients. These data indicate that BACH1 may offer a new therapeutic target to treat SCD.
Nursing management of treatment-related venous thromboembolism in patients with multiple myeloma
Authors: Yang Bianhong , Liu Chao , Lin Zeyu , Geng Chuanying , Zhang Zhiyao
Published: April 2023

Objectives

Venous thromboembolism (VTE) is a common complication among patients with newly diagnosed multiple myeloma (NDMM). Therefore, this study aimed to analyze the incidence and risk factors associated with VTE in the current era of thromboprophylaxis and to propose appropriate nursing measures.

Methods

A total of 1,539 NDMM patients were retrospectively analyzed. All patients underwent VTE risk assessment and received aspirin or low molecular weight heparin (LMWH) to prevent thrombosis, followed by appropriate care based on their individual thrombosis risk. The incidence of VTE and its related risk factors were then analyzed.

Results

All patients received at least four cycles of therapy containing immunomodulators (IMiDs) and/or proteasome inhibitors (PIs). We assigned 371 patients (24.1%) to the moderate-risk thrombosis group, who received daily aspirin (75 mg) for thrombosis prevention and 1,168 patients (75.9%) to the high-risk group, who received daily low molecular weight heparin (3,000 IU) for thrombosis prevention two times a day. Among all the patients, 53 (3.4%) experienced lower extremity venous thromboembolism events, with three of those patients experiencing a concurrent pulmonary embolism. A multivariate analysis indicated that bed rest lasting more than 2 months and plasma cells of ≥60% were independent factors associated with thrombosis.

Conclusion

More effective risk assessment models are needed to predict thrombosis accurately. In addition, nurses involved in the treatment and management of thrombosis should continually engage in professional development to enhance their knowledge and skills.
Bacterial coinfections in hospitalized children with COVID-19 during the SARS-CoV-2 Omicron BA.2 variant pandemic in Taiwan
Authors: Lai Huan-Cheng , Hsu Yu-Lung , Lin Chien-Heng , Wei Hsiu-Mei , Chen Jiun-An , Low Yan-Yi , Chiu Yu-Ting , Lin Hsiao-Chuan , Hwang Kao-Pin
Published: April 2023

Background

Bacterial coinfections have been widely recognized in adults with coronavirus disease 2019 (COVID-19). However, bacterial coinfections in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been sufficiently researched. This study aimed to determine the clinical presentations and risk factors for bacterial coinfections of pediatric inpatients during the SARS-CoV-2 Omicron BA.2 variant pandemic.

Methods

This retrospective, observational study included patients younger than 18 years of age who were hospitalized for COVID-19 confirmed by polymerase chain reaction (PCR) or antigen rapid tests during the SARS-CoV-2 Omicron BA.2 variant pandemic. Data and outcomes of these patients with or without bacterial coinfections were compared.

Results

During this study period, 161 children with confirmed COVID-19 were hospitalized. Twenty-four had bacterial coinfections. The most frequently reported concurrent diagnosis was bacterial enteritis, followed by lower respiratory tract infections. Children with bacterial coinfections had higher white blood cell (WBC) counts and PCR cycle threshold values. The bacterial coinfection group comprised a relatively greater proportion of patients who required high-flow nasal cannula oxygen and remdesivir. The length of stay in the hospital and that in the intensive care unit were longer for children with COVID-19 with bacterial coinfections. Mortality was not observed in either group. Abdominal pain, diarrhea, and comorbidity with neurologic illnesses were risk factors for bacterial coinfections with COVID-19.

Conclusion

This study provides clinicians with reference points for the detection of COVID-19 in children and its possible association with bacterial infections. Children with COVID-19 and neurologic diseases who present with abdominal pain or diarrhea are at risk of bacterial coinfections. Prolonged fever duration and higher PCR test cycle threshold values, WBC levels, and high-sensitivity C-reactive protein (hsCRP) levels may indicate bacterial coinfections in children with COVID-19.
Exploring the Therapeutic Potentials of Exopolysaccharides Derived From Lactic Acid Bacteria and Bifidobacteria: Antioxidant, Antitumor, and Periodontal Regeneration
Authors: Khalil Maha A. , Sonbol Fatma I. , Al-Madboly Lamiaa A. , Aboshady Tamer A. , Alqurashi Abeer S. , Ali Sameh S.
Published: April 2023

Graphical Abstract

Therapeutic applications of exopolysaccharides derived from lactic acid bacteria and bifidobacteria.
Isolation and identification of ligninolytic bacterium (Bacillus cereus) from buffalo (Bubalus bubalis) rumen and its effects on the fermentation quality, nutrient composition, and bacterial community of rape silage
Authors: Zhong Huimin , Zhou Jiayan , Wang Fan , Wu Wenqing , Xiong Haiqian , Yin Huaihui , Li Xiang
Published: April 2023

This study aimed to isolate and identify a ligninolytic bacterium from the rumen of buffalo (Bubalus bubalis) and investigate its effects as a silage additive for whole-plant rape. Three lignin-degradation strains were isolated from the buffalo rumen, with AH7-7 being chosen for further experiments. Strain AH7-7, with acid tolerance and a 51.4% survival rate at pH 4, was identified as Bacillus cereus. It exhibited a lignin-degradation rate of 20.5% after being inoculated in a lignin-degrading medium for 8 days. We divided the rape into four groups according to the various additive compositions to examine the fermentation quality, nutritional value, and bacterial community after ensiling: Bc group (inoculated with B. cereus AH7-7 3.0 × 106 CFU g FW−1), Blac group (inoculated with B. cereus AH7-7 1.0 × 106 CFU g FW−1, L. plantarum 1.0 × 106 CFU g FW−1, and L. buchneri 1.0 × 106 CFU g FW−1), Lac group (inoculated with L. plantarum 1.5 × 106 CFU g FW−1 and L. buchneri 1.5 × 106 CFU g FW−1), and Ctrl group (no additives). After 60 days of fermentation, the application of B. cereus AH7-7 was potent in modulating the fermentation quality of silage, especially when combined with L. plantarum and L. buchneri, as indicated by lower dry matter loss and higher contents of crude protein, water-soluble carbohydrate, and lactic acid. Furthermore, treatments with the B. cereus AH7-7 additive decreased the contents of acid detergent lignin, cellulose, and hemicellulose. The B. cereus AH7-7 additive treatments reduced the bacterial diversity and optimized the bacterial community compositions of silage, with an increase in the relative abundance of beneficial Lactobacillus and a decrease in the relative abundance of undesirable Pantoea and Erwinia. Functional prediction revealed that inoculation with B. cereus AH7-7 could increase the cofactors and vitamins metabolism, amino acid metabolism, translation, replication and repair, and nucleotide metabolism, while decreasing the carbohydrate metabolism, membrane transport, and energy metabolism. In brief, B. cereus AH7-7 improved the microbial community, fermentation activity, and ultimately the quality of silage. The ensiling with B. cereus AH7-7, L. plantarum, and L. buchneri combination is an effective and practical strategy to improve the fermentation and nutrition preservation of rape silage.
The role of gut microbiota in diabetic peripheral neuropathy rats with cognitive dysfunction
Authors: Huang Wei , Lin Ziqiang , Sun Ailing , Deng JieMin , Manyande Anne , Xiang Hongbing , Zhao Gao Feng , Hong Qingxiong
Published: April 2023

Introduction

Owing to advancements in non-invasive magnetic resonance imaging, many studies have repeatedly showed that diabetes affects the central nervous system in the presence of peripheral neuropathy, suggesting a common or interacting pathological mechanism for both complications.

Methods

We aimed to investigate the role of abnormal gut microbiota in rats with diabetic peripheral neuropathy (DPN) combined with cognitive dysfunction. Glucose-compliant rats with nerve conduction deficits were screened as a successful group of DPN rats. The DPN group was then divided into rats with combined cognitive impairment (CD) and rats with normal cognitive function (NCD) based on the results of the Novel object recognition test. Rat feces were then collected for 16S rRNA gene sequencing of the intestinal flora.

Results and Discussion

The results revealed that abnormalities in Firmicutes, Ruminococcaceae, Bacteroidia, and Actinobacteria-like microorganisms may induce DPN complicated by cognitive dysfunction.
Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
Authors: Chen Keping , Sun Huidi , Geng Yu , Yang Chuankun , Shan Chun , Chen Yuxin
Published: April 2023

Introduction

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. The pathophysiology of SFTS remains unclear. Hence, the identification of inflammatory biomarkers for SFTS is crucial for the timely management and prevention of disease severity.

Methods

A total of 256 patients with SFTS were divided into a survivor group and a non-survivor group. Classical inflammatory biomarkers such as ferritin, procalcitonin (PCT), C-reactive protein (CRP), and white blood cells were investigated for their association with viral load and the clinical significance for predicting the mortality of patients with SFTS.

Results

Serum ferritin and PCT showed a positive association with viral load. Ferritin and PCT levels in non-survivors were significantly higher than those in survivors at 7–9 days from symptom onset. The area under the receiver operating characteristic curve (AUC) values of ferritin and PCT for predicting the fatal outcome of SFTS were 0.9057 and 0.8058, respectively. However, the CRP levels and WBC counts exhibited a weak association with viral load. The AUC value of CRP for predicting mortality was more than 0.7 at 13–15 days from symptom onset.

Discussion

Ferritin and PCT levels, especially ferritin, could be potential inflammatory biomarkers for predicting the prognosis of patients with SFTS in its early stages.
Should artificial intelligence be used in conjunction with Neuroimaging in the diagnosis of Alzheimer’s disease?
Authors: Mirkin Sophia , Albensi Benedict C.
Published: April 2023

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder that affects memory, thinking, behavior, and other cognitive functions. Although there is no cure, detecting AD early is important for the development of a therapeutic plan and a care plan that may preserve cognitive function and prevent irreversible damage. Neuroimaging, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), has served as a critical tool in establishing diagnostic indicators of AD during the preclinical stage. However, as neuroimaging technology quickly advances, there is a challenge in analyzing and interpreting vast amounts of brain imaging data. Given these limitations, there is great interest in using artificial Intelligence (AI) to assist in this process. AI introduces limitless possibilities in the future diagnosis of AD, yet there is still resistance from the healthcare community to incorporate AI in the clinical setting. The goal of this review is to answer the question of whether AI should be used in conjunction with neuroimaging in the diagnosis of AD. To answer the question, the possible benefits and disadvantages of AI are discussed. The main advantages of AI are its potential to improve diagnostic accuracy, improve the efficiency in analyzing radiographic data, reduce physician burnout, and advance precision medicine. The disadvantages include generalization and data shortage, lack of in vivo gold standard, skepticism in the medical community, potential for physician bias, and concerns over patient information, privacy, and safety. Although the challenges present fundamental concerns and must be addressed when the time comes, it would be unethical not to use AI if it can improve patient health and outcome.
Higher serum bilirubin levels are associated with hemorrhagic transformation after intravenous thrombolysis in acute ischemic Stroke
Authors: Chen Xiaoqing , Yang Xiangchou , Xu Xia , Fu FangWang , Huang Xiangwei
Published: April 2023

Background

Bilirubin has both antioxidative and prooxidative properties. The study aimed to explore the relationship between serum bilirubin and hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke.

Methods

The patients receiving intravenous thrombolysis with alteplase were retrospectively analyzed. HT was defined as new intracerebral hemorrhage in follow-up computed tomography images within 24–36 h after thrombolysis. Symptomatic intracranial hemorrhage (sICH) was defined as HT accompanied by worsening neurological function. Multivariate logistic regression and spline regression models were performed to investigate the relationship between serum bilirubin levels and the risk of HT and sICH.

Results

Among 557 included patients, 71 (12.7%) were diagnosed with HT and 28 (5.0%) developed sICH. Patients with HT had significant higher baseline serum total bilirubin, direct bilirubin, and indirect bilirubin levels than those without HT. Multivariable logistic regression analysis indicated that patients with higher serum bilirubin levels, including total bilirubin (OR 1.05, 95% CI 1.01–1.08, p = 0.006), direct bilirubin (OR 1.18, 95% CI 1.05–1.31, p = 0.004), and indirect bilirubin (OR 1.06, 95% CI 1.02–1.10, p = 0.005) had increased risk of HT. Furthermore, multiple-adjusted spline regression models excluded nonlinear association between serum bilirubin levels and HT (p > 0.05 for nonlinearity). Similar results were present between serum bilirubin and sICH.

Conclusion

The data showed the positively linearly relationship between serum bilirubin levels and the risk of HT and sICH in patients with acute ischemic stroke undergoing intravenous thrombolysis.
Real-time depth completion based on LiDAR-stereo for autonomous driving
Authors: Wei Ming , Zhu Ming , Zhang Yaoyuan , Wang Jiarong , Sun Jiaqi
Published: April 2023

The integration of multiple sensors is a crucial and emerging trend in the development of autonomous driving technology. The depth image obtained by stereo matching of the binocular camera is easily influenced by environment and distance. The point cloud of LiDAR has strong penetrability. However, it is much sparser than binocular images. LiDAR-stereo fusion can neutralize the advantages of the two sensors and maximize the acquisition of reliable three-dimensional information to improve the safety of automatic driving. Cross-sensor fusion is a key issue in the development of autonomous driving technology. This study proposed a real-time LiDAR-stereo depth completion network without 3D convolution to fuse point clouds and binocular images using injection guidance. At the same time, a kernel-connected spatial propagation network was utilized to refine the depth. The output of dense 3D information is more accurate for autonomous driving. Experimental results on the KITTI dataset showed that our method used real-time techniques effectively. Further, we demonstrated our solution's ability to address sensor defects and challenging environmental conditions using the p-KITTI dataset.
Synergy through integration of digital cognitive tests and wearable devices for mild cognitive impairment screening
Authors: Li Aoyu , Li Jingwen , Zhang Dongxu , Wu Wei , Zhao Juanjuan , Qiang Yan
Published: April 2023

Introduction

Advances in mobile computing platforms and the rapid development of wearable devices have made possible the continuous monitoring of patients with mild cognitive impairment (MCI) and their daily activities. Such rich data can reveal more subtle changes in patients’ behavioral and physiological characteristics, providing new ways to detect MCI anytime, anywhere. Therefore, we aimed to investigate the feasibility and validity of digital cognitive tests and physiological sensors applied to MCI assessment.

Methods

We collected photoplethysmography (PPG), electrodermal activity (EDA) and electroencephalogram (EEG) signals from 120 participants (61 MCI patients, 59 healthy controls) during rest and cognitive testing. The features extracted from these physiological signals involved the time domain, frequency domain, time-frequency domain and statistics. Time and score features during the cognitive test are automatically recorded by the system. In addition, selected features of all modalities were classified by tenfold cross-validation using five different classifiers.

Results

The experimental results showed that the weighted soft voting strategy combining five classifiers achieved the highest classification accuracy (88.9%), precision (89.9%), recall (88.2%), and F1 score (89.0%). Compared to healthy controls, the MCI group typically took longer to recall, draw, and drag. Moreover, during cognitive testing, MCI patients showed lower heart rate variability, higher electrodermal activity values, and stronger brain activity in the alpha and beta bands.

Discussion

It was found that patients’ classification performance improved when combining features from multiple modalities compared to using only tablet parameters or physiological features, indicating that our scheme could reveal MCI-related discriminative information. Furthermore, the best classification results on the digital span test across all tasks suggest that MCI patients may have deficits in attention and short-term memory that came to the fore earlier. Finally, integrating tablet cognitive tests and wearable sensors would provide a new direction for creating an easy-to-use and at-home self-check MCI screening tool.
Expanding radiotherapy access in Sub-Saharan Africa: an analysis of travel burdens and patient-related benefits of hypofractionation
Authors: Patel Saloni , Olatunji Elizabeth , Mallum Abba , Benjika Binsila Bernard , Joseph Adedayo O. , Joseph Shomari , Lasebikan Nwamaka , Mahuna Habiba , Ngoma Mamsau , Ngoma Twalib Athumani , Nnko Godwin , Onwualu Chinelo , Vorster Mariza , Ngwa Wilfred
Published: April 2023

Purpose

The purpose of this project was to examine the travel burdens for radiotherapy patients in Nigeria, Tanzania, and South Africa, and to assess the patient-related benefits of hypofractionated radiotherapy (HFRT) for breast and prostate cancer patients in these countries. The outcomes can inform the implementation of the recent Lancet Oncology Commission recommendations on increasing the adoption of HFRT in Sub-Saharan Africa (SSA) to enhance radiotherapy access in the region.

Methods

Data were extracted from electronic patient records at the NSIA-LUTH Cancer Center (NLCC) in Lagos, Nigeria and the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa, from written records at the University of Nigeria Teaching Hospital (UNTH) Oncology Center in Enugu, Nigeria, and from phone interviews at Ocean Road Cancer Institute (ORCI) in Dar Es Salaam, Tanzania. Google Maps was used to calculate the shortest driving distance between a patient’s home address and their respective radiotherapy center. QGIS was used to map the straight-line distances to each center. Descriptive statistics were used to compare transportation costs, time expenditures, and lost wages when using HFRT versus conventionally fractionated radiotherapy (CFRT) for breast and prostate cancer.

Results

Patients in Nigeria (n=390) traveled a median distance of 23.1 km to NLCC and 86.7 km to UNTH, patients in Tanzania (n=23) traveled a median distance of 537.0 km to ORCI, and patients in South Africa (n=412) traveled a median distance of 18.0 km to IALCH. Estimated transportation cost savings for breast cancer patients in Lagos and Enugu were 12,895 Naira and 7,369 Naira, respectively and for prostate cancer patients were 25,329 and 14,276 Naira, respectively. Prostate cancer patients in Tanzania saved a median of 137,765 Shillings in transportation costs and 80.0 hours (includes travel, treatment, and wait times). Mean transportation cost savings for patients in South Africa were 4,777 Rand for breast cancer and 9,486 Rand for prostate cancer.

Conclusion

Cancer patients in SSA travel considerable distances to access radiotherapy services. HFRT decreases patient-related costs and time expenditures, which may increase radiotherapy access and alleviate the growing burden of cancer in the region.
The psychosocial impact of microtia and ear reconstruction: A national data-linkage study
Authors: Jovic Thomas H. , Gibson John A. G. , Jovic Matthew , Dobbs Thomas D. , Griffiths Rowena , Akbari Ashley , Whitaker Iain S.
Published: April 2023

Introduction

Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.

Methods

A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.

Results

There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.

Discussion

Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.
Time tracing the earliest case of local pandemic resurgence
Authors: Zhang Jianing , Fang Kexin , Zhu Yinhua , Kang Xiaoyun , Zhang Lin
Published: April 2023

Origin identification of the earliest cases during the pandemic is crucial in containing the transmission of the disease. The high infectiousness of the disease during its incubation period (no symptom yet) and underlying human interaction pattern make it difficult to capture the entire line of the spread. The hidden spreading period is when the disease is silently spreading, for the “silent spreaders” showing no symptoms yet can transmit the infection. Being uncertain of the hidden spreading period would bring a severe challenge to the contact tracing mission. To find the possible hidden spreading period span, we utilized the SEITR (susceptible–exposed–infected–tested positive–recovered) model on networks where the relation between E state and T state can implicitly model the hidden spreading mechanism. We calibrated the model with real local resurgence epidemic data. Through our study, we found that the hidden spreading period span of the possible earliest case of local resurgence could vary according to the people interaction networks. Our modeling results showed the clustering and shortcuts that exist in the human interaction network significantly affect the results in finding the hidden spreading period span. Our study can be a guide for understanding the pandemic and for contact tracing the origin of local resurgence.
Effect of local application of bone morphogenetic protein -2 on experimental tooth movement and biological remodeling in rats
Authors: Wang Menglin , Fan Jiadong , Wang Aoao , Jin Xiang , Zhang Zhenbao , Hu Xiantong , Liu Le , Zhao Yantao , Li Yanfeng
Published: April 2023

Background: This study attempts to detect the potential effects of local bone morphogenetic protein -2 (BMP-2) on orthodontic tooth movement and periodontal tissue remodeling.

Methods: Forty adult SD rats were randomly divided into four groups: blank control group, unilateral injection of BMP-2 on the pressure side or tension side of orthodontic teeth and bilateral injection of BMP-2. Their maxillary first molar was moved by a 30 g constant force closed coil spring. 60 μL of BMP-2 with a concentration of 0.5 μg/mL was injected into each part at a time. In addition, three rats were selected as healthy control rats without any intervention. Fluorescent labeled BMP-2 was used to observe the distribution of exogenous BMP-2 in tissues. Micro-CT was used to measure the microscopic parameters of tooth displacement, trabecular bone and root absorption volume. Three different histological methods were used to observe the changes of tissue remodeling, and then the number of osteoclasts and the content of collagen fibers were calculated.

Results: Compared with the blank control group, BMP-2 injection reduced the movement distance and increased the collagen fiber content and bone mass (p < 0.01). There was no significant difference in tooth movement distance, BV/TV ratio and BMD between injection sites in unilateral injection group (p > 0.05). In the case of bilateral injection of BMP-2, the osteogenesis is enhanced. Unilateral injection of BMP-2 did not promote root resorption, but double injection showed root resorption (p < 0.01).

Conclusion: Our study does show that the osteogenesis of BMP-2 is dose-dependent rather than site-dependent when a certain amount of BMP-2 is applied around orthodontic teeth. Local application of BMP-2 around orthodontic teeth in an appropriate way can enhance bone mass and tooth anchorage without increasing the risk of root absorption volume. However, high levels of BMP-2 may cause aggressive root resorption. These findings are of great significance, that is, BMP-2 is an effective target for regulating orthodontic tooth movement.
Association of oxidative stress, programmed cell death, GSTM1 gene polymorphisms, smoking and the risk of lung carcinogenesis: A two-step Mendelian randomization study
Authors: Wang Yijun , Yang Qiongling , Zheng Lingzhen
Published: April 2023

Aim: We aimed to examine the association of oxidative stress, programmed cell death, smoking, and the GSTM1 gene in the risk of lung carcinogenesis. The two-step Mendelian randomization will reveal evidence supporting the association of the exposure and mediators with the resulting outcome.

Methods: In step 1, we estimated the impact of smoking exposure on lung carcinogenesis and programmed cell death. Our study involved a total of 500,000 patients of European ancestry, from whom we obtained genotype imputation information. Specifically, we genotyped two arrays: the UK Biobank Axiom (UKBB) which accounted for 95% of marker content, and the UK BiLIEVE Axiom (UKBL). This allowed us to unmask the association between smoking exposure and the incidence of lung carcinogenesis. In step 2, we further examined the effects of smoking on oxidative stress, programmed cell death, and the incidence of lung carcinogenesis.

Results: Different outcomes emerged from the two-step Mendelian randomization. The GSTM1 gene variant was found to be critical in the development of lung carcinogenesis, as its deletion or deficiency can induce the condition. A GWAS study on participant information obtained from the UK Biobank revealed that smoking interferes with the GSTM1 gene, causing programmed cell death in the lungs and ultimately leading to lung carcinogenesis. The relative risk of developing lung carcinogenesis associated with oxidative stress was significantly high among current smokers (a hazard ratio of 17.8, 95% confidence interval of 12.2–26.0) and heavy smokers (a hazard ratio of 16.6 and a 95% confidence interval of 13.6–20.3) compared to individuals who never smoked. The GSTM1 gene polymorphism was found to be 0.006 among participants who have never smoked, <0.001 among ever-smokers, and 0.002 and <0.001 among current and former smokers, respectively.

We compared the effect of smoking within two particular time frames, 6 years and 55 years, and found that smoking’s impact on the GSTM1 gene was highest among participants who were 55 years old. The genetic risk peaked among individuals aged 50 years and above (PRS of at least 80%).

Conclusion: Exposure to smoking is a significant factor in developing lung carcinogenesis, as it is associated with programmed cell death and other mediators involved in the condition. Oxidative stress caused by smoking is also a key mechanism in lung carcinogenesis. The results of the present study highlight the association between oxidative stress, programmed cell death, and the GSTM1 gene in the development of lung carcinogenesis.
Different leafy vegetable cropping systems regulate growth, photosynthesis, and PSII functioning in mono-cropped eggplant by altering chemical properties and upregulating the antioxidant system
Authors: Ghani Muhammad Imran , Ali Ahmad , Atif Muhammad Jawaad , Ali Muhammad , Ahanger Mohammad Abass , Chen Xiaoyulong , Cheng Zhihui
Published: April 2023

Continuous cropping of eggplant threatened regional ecological sustainability by facilitating replanting problems under mono-cropping conditions. Therefore, alternative agronomic and management practices are required to improve crop productivity at low environmental cost for the development of sustainable agricultural systems in different regions. This study examined changes in soil chemical properties, eggplant photosynthesis, and antioxidant functioning in five different vegetable cropping systems over a 2-year period., 2017 and 2018. The results showed that welsh onion-eggplant (WOE), celery-eggplant (CE), non-heading Chinese cabbage-eggplant (NCCE), and leafy lettuce-eggplant (LLE) rotation systems significantly impacted growth, biomass accumulation, and yield than fallow-eggplant (FE). In addition, various leafy vegetable cropping systems, WOE, CE, NCCE, and LLT induced significant increases in soil organic matter (SOM), available nutrients (N, P, and K), and eggplant growth by affecting the photosynthesis and related gas exchange parameters with much evident effect due to CE and NCCE. Moreover, eggplant raised with different leafy vegetable rotation systems showed higher activity of antioxidant enzymes, resulting in lower accumulation of hydrogen peroxide and hence reduced oxidative damage to membranes. In addition, fresh and dry plant biomass was significantly increased due to crop rotation with leafy vegetables. Therefore, we concluded that leafy vegetable crop rotation is a beneficial management practice to improve the growth and yield of eggplant.
Biotization of in vitro oil palm (Elaeis guineensis Jacq.) and its plant-microbe interactions
Authors: Lim Shey-Li , Subramaniam Sreeramanan , Baset Mia Md Abdul , Rahmah Abdul Rahman Siti , Ghazali Amir Hamzah Ahmad
Published: April 2023

Continuous discovery of novel in vitro plant culture practices is always essential to promote better plant growth in the shortest possible cultivation period. An alternative approach to conventional micropropagation practice could be achieved through biotization by inoculating selected Plant Growth Promoting Rhizobacteria (PGPR) into the plant tissue culture materials (e.g., callus, embryogenic callus, and plantlets). Such biotization process often allows the selected PGPR to form a sustaining population with various stages of in vitro plant tissues. During the biotization process, plant tissue culture material imposes developmental and metabolic changes and enhances its tolerance to abiotic and biotic stresses, thereby reducing mortality in the acclimatization and pre-nursery stages. Understanding the mechanisms is, therefore crucial for gaining insights into in vitro plant-microbe interactions. Studies of biochemical activities and compound identifications are always essential to evaluate in vitro plant-microbe interactions. Given the importance of biotization in promoting in vitro plant material growth, this review aims to provide a brief overview of the in vitro oil palm plant-microbe symbiosis system.