Miracle-dz/UniFAR-FTUs huggingface dataset:
Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease

Herpes simplex virus-associated diseases are a complex interaction between cytolytic viral replication and inflammation. Within the normally avascular and immunoprivileged cornea, HSV ocular infection can result in vision-threatening immune-mediated herpetic keratitis, the leading infectious cause of corneal blindness in the industrialized world. Viral replicative processes are entirely dependent upon numerous cellular biosynthetic and metabolic pathways. Consistent with this premise, HSV infection was shown to profoundly alter gene expression associated with cellular amino acid biosynthetic pathways, including key tryptophan metabolism genes. The essential amino acid tryptophan is crucial for pathogen replication, the generation of host immune responses, and the synthesis of neurotransmitters, such as serotonin. Intriguingly, Tryptophan hydroxylase 2 (TPH2), the neuronal specific rate-limiting enzyme for serotonin synthesis, was the most significantly upregulated gene by HSV in an amino acid metabolism PCR array. Despite the well-defined effects of serotonin in the nervous system, the association of peripheral serotonin in disease-promoting inflammation has only recently begun to be elucidated. Likewise, the impact of serotonin on viral replication and ocular disease is also largely unknown. We therefore examined the effect of HSV-induced serotonin-associated synthesis and transport pathways on HSV-1 replication, as well as the correlation between HSV-induced ocular serotonin levels and disease severity. HSV infection induced expression of the critical serotonin synthesis enzymes TPH-1, TPH-2, and DOPA decarboxylase (DDC), as well as the serotonin transporter, SERT. Concordantly, HSV-infected cells upregulated serotonin synthesis and its intracellular uptake. Increased serotonin synthesis and uptake was shown to influence HSV replication. Exogenous addition of serotonin increased HSV-1 yield, while both TPH-1/2 and SERT pharmacological inhibition reduced viral yield. Congruent with these in vitro findings, rabbits intraocularly infected with HSV-1 exhibited significantly higher aqueous humor serotonin concentrations that positively and strongly correlated with viral load and ocular disease severity. Collectively, our findings indicate that HSV-1 promotes serotonin synthesis and cellular uptake to facilitate viral replication and consequently, serotonin’s proinflammatory effects may enhance the development of ocular disease.
Reliability block diagram methods for system reliability analysis of spatial structures

The safety of complex spatial structures in operation depends highly on the reliability of the whole system and its structural components. In order to determine the relationship between system reliability and reliability of its components, reliability block diagram (RBD) method, which emphasises depicting the connection mode among all the components of a system, is employed for system reliability analysis of spatial structures. With the assumption of geometric stability, a new approach, aiming at finding out key elements where damage could lead to overall collapse of the structure, is adopted here for the logic relationship identification among components. The logic relationship, which is considered as the core component of the reliability block diagram, is utilised for reliability analysis of the system and the predetermined components. Finally, a large-span latticed grid spatial structure is investigated to validate the applicability of the RBD method for analysing the system reliability of spatial structures.
Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer

Owing to the ongoing coronavirus disease 2019 (COVID-19) pandemic, we need to pay a particular focus on the impact of coronavirus infection on breast cancer patients. Approximately 70% of breast cancer patients express estrogen receptor (ER), and intervention therapy for ER has been the primary treatment strategy to prevent the development and metastasis of breast cancer. Recent studies have suggested that selective estrogen receptor modulators (SERMs) are a potential therapeutic strategy for COVID-19. With its anti-ER and anti-viral combined functions, SERMs may be an effective treatment for COVID-19 in patients with breast cancer. In this review, we explore the latent effect of SERMs, especially tamoxifen, and the mechanism between ER and virus susceptibility.
A Self-Reference Interference Sensor Based on Coherence Multiplexing

Interferometry has been widely used in biosensing due to its ability to acquire molecular affinity and kinetics in real-time. However, interferometric-based sensors are susceptible to environmental disturbances, including temperature and non-specific binding of target molecules, which reduces their detection robustness. To address this shortcoming, this paper proposes a self-referencing interference sensor based on coherence multiplexing to resist environmental disturbances. The proposed sensor can address temperature and non-specific binding, but it is not limited only to these types of disturbances. In the proposed sensor design, each sensor signal is encoded using a specific optical path difference determined by the optical thickness of a sensor chip. In addition, two sensor signals for disturbances tracking and biomolecule detection are detected simultaneously without additional cost to the second spectrometer and then differenced to achieve real-time self-reference. The temperature fluctuations experiments and specific binding experiments of protein A to IgG are performed to verify the performance of the proposed sensor. The results demonstrate that the proposed sensor can eliminate non-specific binding and temperature disturbances in real-time during biomolecule detection, achieving higher detection robustness. The proposed sensor is suitable for applications that require large-scale testing of biomolecular interactions, such as drug screening.
Analysis of Short-Term Efficacy of Gasless Single-Port Laparoscopic Inguinal Lymphadenectomy Through Vulva Incision for Vulvar Cancer

Objective To investigate the feasibility and short-term efficacy of gasless single-port laparoscopic inguinal lymphadenectomy through vulva incision (VEIL-V). Methods The data of 9 patients diagnosed as vulvar squamous cell carcinoma who underwent single-port laparoscopic inguinal lymph node dissection through vulvectomy incision were retrospectively analyzed. And 13 patients who underwent laparoscopic inguinal lymph node dissection through lower abdominal subcutaneous approach as the control group (VEIL-H). The operation time, blood loss, numbers of unilateral lymph nodes, hospitalization time, and complications between the two groups were compared. Results The operation time of VEIL-V was 56.11 ± 5.94 min, which were shorter than that of VEIL-H (74.62 ± 5.50 min; P = 0.013). Bleeding amount in the VEIL-H was 29.44 ± 2.56, which was significantly lower than that of the VEIL-H group (43.08 ± 4.14 ml; P = 0.021). In the two groups, the numbers of unilateral lymph nodes harvested were similar. The differences in the postoperative hospital stay, skin, and lymphatic complications were not statistically significant. Conclusion Compared with VEIL-H, gasless single-port laparoscopic inguinal lymphadenectomy through vulva incision reduces the difficulty of operation with shorter operation time, and less blood loss, which can be a safe and mini-invasive surgical approach.
Programmed Cell Death May Be Involved in the Seedless Phenotype Formation of Oil Palm

Oil palm (Elaeis guineensis Jacq.) is a well-known vegetable oil-yielding crop. Seedlessness is one of the most prominent traits in oil palm due to its low processing costs and high oil content. Nevertheless, an extensive study on molecular mechanisms regulating seedless phenotype formation in oil palm is very limited so far. In this study, stigma, style, and ovary from seedless and seeded (Tenera and Pisifera) oil palm trees were used to investigate the possible mechanism. Results showed that non-pollination resulted in no fruits, and self- and cross-pollinations resulted in seedless fruits, while boron treatment had no effect on seedless phenotype formation, implying that seedless trees have incomplete self and outcrossing incompatibility. Furthermore, the transcriptome data analysis highlighted eight programmed cell death (PCD) genes and three groups of PCD-related genes: 4-coumarate-CoA ligase (4CL), S-RNase, and MADS-box. The majority of these genes were significantly up-regulated in the stigma and style of Seedless palm trees compared to Tenera and Pisifera. In addition, the co-expression network analysis confirmed the significant correlation among these genes. Moreover, two simple sequence repeats (SSR) markers (S41 and S44) were developed to identify the seedless phenotype. The up-regulation of 4CL and MADS-box TFs activated the expression of PCD genes; on the other hand, S-RNase resulted in pollen tube RNA degradation and triggered PCD. While the link between PCD and seedless phenotype formation in oil palm has not been extensively studied to date, these findings suggest a role of PCD in pollen tube lethality, leading to double fertilization failure and the seedless phenotype.
Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.
Bone Metastasis From Gastric Adenocarcinoma—What Are the Risk Factors and Associated Survival? A Large Comprehensive Population-Based Cohort Study

Background While bone metastasis is not common in gastric adenocarcinoma (GaC), it can have important impacts on prognosis. This large cohort study aimed at exploring factors associated with bone metastasis in GaC and investigating the time-dependent cumulative mortalities and prognostic factors in GaC patients with bone metastasis at the population level. Methods Data on patients with GaC diagnosed in 2010–2016 were retrieved from a large population-based database. We explored factors associated with bone metastasis using the multivariable-adjusted logistic model. We then calculated the time-dependent cancer-specific mortalities in GaC patients with bone metastasis using the cumulative incidence function and compared mortalities across subgroups using Gray’s test. We further assessed factors associated with mortality using the multivariable-adjusted Fine–Gray subdistribution hazard model. Results Together 11,072 eligible patients with metastatic GaC were enrolled, which comprised 1,511 (14%) people with bone metastasis and 9,561 (86%) with other metastasis, encompassing 6,999 person-years of follow-up. Bone metastasis was more frequently detected in 2014 or later, in younger patients, in patients with gastric cardia cancers, in people with signet-ring cell carcinoma, and in those with poorly differentiated/undifferentiated cancers; it was less commonly observed in black patients. Bone metastasis was associated with more frequent brain and lung metastases. The median survival of patients with bone metastasis was 4 months; the 6-month and 3-year cancer-specific cumulative mortalities were 56% and 85%, respectively. In patients receiving chemotherapy, American Indians/Alaskan Natives, patients with gastric antrum/pylorus cancers, and those with positive lymph nodes had higher mortality risks, while those undergoing resection had lower mortality hazards. Conclusion In GaC patients, bone metastasis was associated with various clinicopathologic factors including age, ethnicity, tumor location, histology, differentiation, and metastasis to other sites. Patients with bone metastasis had poor prognosis which was associated with ethnicity, tumor location, lymph node involvement, and treatment. Our findings provide important hints for tailed patient management and for further mechanistic investigations.
Hydrogen Peroxide Can Enhance the Synthesis of Bioactive Compounds in Harvested Broccoli Florets

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) which participates in the signal transduction responses of plants toward biotic and abiotic stresses. Therefore, the objective of this study was to link the exposure of low doses of H2O2 to the improvement of the phytochemical composition of broccoli florets, in particular the content of glucosinolates (GLS), and hydroxy-cinnamates (HCA) without affecting the quality parameters of the vegetable. A dose of 1.25 mM H2O2 applied for 180 min was effective (hormetic) in maintaining the color of broccoli florets, which was also compared with a higher dose of 5.0 mM H2O2 applied for 180 min. The intensity of the treatments was related to respiration rate, which was monitored for 21 d at 4◦C along to weight loss. The initial respiration rate of florets exposed to both doses of H2O2 was significantly (p < 0.0001) higher relative to controls and resulted in weight loss in florets treated with the hormetic dose. The antioxidant capacity of florets, measured indirectly as Oxygen Radical Absorbance Capacity (ORAC) and ascorbic acid (AA), decreased in florets exposed to both doses. The concentration of glucobrassicins, aliphatic GLS, and HCA was consistently higher in florets treated with the two doses, compared to non-exposed florets. The enhancement of these compounds was accompanied by the over expression, immediately (6 h) after treatments, of tryptophan N-hydroxylase 2 (CYP79B3), dihomomethionine N-hydroxylase (CYP79F1), and phenylalanine ammonia-lyase (PAL) genes. Overall, the tested doses of H2O2 positively influenced the augmentation of indole-type and aliphatic GLS, as well as HCA in broccoli florets.
A Detoxification Enzyme for Apis mellifera Newly Characterized by Recombinant Expression: 10-Formyl Tetrahydrofolate Dehydrogenase

Honeybees are important managed pollinators that perform important ecological and economic functions. In recent decades, the obligate ectoparasite Varroa destructor severely affected survival of honeybees as it either feeds on hemolymph and fat bodies or acts as a vector for viruses. A common treatment against the varroa mite is formic acid, which has been used for many years by beekeepers. This treatment is known to be effective, but the therapeutic index is very narrow. Many beekeepers report negative effects of formic acid on bees, which include damage to brood, worker bee mortality, and queen loss. Little is yet known about the molecular mechanisms of formic acid detoxification in honeybees. Our previous study shows the upregulation of predicted 10-formyl tetrahydrofolate dehydrogenase (10-FTHFDH) transcripts in honeybees exposed to formic acid. Here, the predicted honeybee-specific 10-FTHFDH is recombinantly expressed, and its hydrolase and dehydrogenase activities are investigated. As a result, the enzyme shows similar dehydrogenase activity in comparison to known 10-FTHFDHs. This study provides further knowledge to better understand the detoxification mechanisms of formic acid in Apis mellifera.
Volumetric Brain Loss Correlates With a Relapsing MOGAD Disease Course

Background Myelin oligodendrocyte glycoprotein antibody disorders (MOGAD) have evolved as a distinct group of inflammatory, demyelinating diseases of the CNS. MOGAD can present with a monophasic or relapsing disease course with distinct clinical manifestations.However, data on the disease course and disability outcomes of these patients are scarce. We aim to compare brain volumetric changes for MOGAD patients with different disease phenotypes and HCs. Methods Brain magnetic resonance imaging (MRI) scans and clinical data were obtained for 22 MOGAD patients and 22 HCs. Volumetric brain information was determined using volBrain and MDbrain platforms. Results We found decreased brain volume in MOGAD patients compared to HCs, as identified in volume of total brain, gray matter, white matter and deep gray matter (DGM) structures. In addition, we found significantly different volumetric changes between patients with relapsing and monophasic disease course, with significantly decreased volume of total brain and DGM, cerebellum and hippocampus in relapsing patients during the first year of diagnosis. A significant negative correlation was found between EDSS and volume of thalamus. Conclusions Brain MRI analyses revealed volumetric differences between MOGAD patients and HCs, and between patients with different disease phenotypes. Decreased gray matter volume during the first year of diagnosis, especially in the cerebrum and hippocampus of MOGAD patients was associated with relapsing disease course.
Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient’s risk for ALS, provided they have one of the known familial genes. However, the vast majority of ALS cases are sporadic and have no known associated genetic signatures. Our analysis of the whole genome sequencing data from ALS patients and healthy controls from the Answer ALS Consortium has uncovered twenty-three novel mutations in twenty-two protein-coding genes associated with sporadic ALS cases. The results show the majority of patients with the sporadic form of ALS have at least one or more mutation(s) in the 22 genes we have identified with probabilities of developing ALS ranging from 25–99%, depending on the number of mutations a patient has among the identified genes. Moreover, we have identified a subset of the ALS cohort that has >17 mutations in the 22 identified. In this case, a patient with this mutation profile has a 99% chance of developing ALS and could be classified as being at high risk for the disease. These genetic biomarkers can be used as an early ALS disease diagnostic tool with a rapid and non-invasive technique.
Emotion and International Business: Theorising Fear of Failure in the Internationalisation

The road to internationalisation is paved with risk, uncertainty, the possibility of failure, and the Coronavirus Disease-19 (COVID-19) phenomenon. However, the process of internationalisation (IP) theory treats an individual decision-maker as a “black box. ” Emotions are largely ignored by international business (IB) researchers. This study offers conceptual thoughts on the role of fear of failure in the process of internationalisation. It argues that managers experience this emotion in making internationalisation decisions for a firm, which is an area of study that requires further understanding. Following the content analysis method in the literature review and a theory-based adaptation approach to complete the conceptualisation, this manuscript joins the scholarly conversations on “connecting the IP model to people” and “emotion and internationalisation. ” Focussing on fear of failure as a new perspective, this manuscript contributes to IB literature by suggesting new avenues in understanding decision-making about international activities by embracing psychological insights. It also contributes to IB practitioners by offering implications for understanding one’s emotional state and its effect on decision-making about internationalising ventures.
Monoallelic Heb/Tcf12 Deletion Reduces the Requirement for NOTCH1 Hyperactivation in T-Cell Acute Lymphoblastic Leukemia

Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors, together with NOTCH1 and pre-T cell receptor (TCR) signalling. Importantly, perturbations of early T-cell regulatory networks are implicated in leukemogenesis. NOTCH1 gain of function mutations invariably lead to T-cell acute lymphoblastic leukemia (T-ALL), whereas inhibition of E proteins accelerates leukemogenesis. Thus, NOTCH1, pre-TCR, E2A and HEB functions are intertwined, but how these pathways contribute individually or synergistically to leukemogenesis remain to be documented. To directly address these questions, we leveraged Cd3e-deficient mice in which pre-TCR signaling and progression through β-selection is abrogated to dissect and decouple the roles of pre-TCR, NOTCH1, E2A and HEB in SCL/TAL1-induced T-ALL, via the use of Notch1 gain of function transgenic (Notch1ICtg) and Tcf12+/- or Tcf3+/- heterozygote mice. As a result, we now provide evidence that both HEB and E2A restrain cell proliferation at the β-selection checkpoint while the clonal expansion of SCL-LMO1-induced pre-leukemic stem cells in T-ALL is uniquely dependent on Tcf12 gene dosage. At the molecular level, HEB protein levels are decreased via proteasomal degradation at the leukemic stage, pointing to a reversible loss of function mechanism. Moreover, in SCL-LMO1-induced T-ALL, loss of one Tcf12 allele is sufficient to bypass pre-TCR signaling which is required for Notch1 gain of function mutations and for progression to T-ALL. In contrast, Tcf12 monoallelic deletion does not accelerate Notch1IC-induced T-ALL, indicating that Tcf12 and Notch1 operate in the same pathway. Finally, we identify a tumor suppressor gene set downstream of HEB, exhibiting significantly lower expression levels in pediatric T-ALL compared to B-ALL and brain cancer samples, the three most frequent pediatric cancers. In summary, our results indicate a tumor suppressor function of HEB/TCF12 in T-ALL to mitigate cell proliferation controlled by NOTCH1 in pre-leukemic stem cells and prevent NOTCH1-driven progression to T-ALL.