Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycoprotein C of Herpes Simplex Virus 1 Shields Glycoprotein B from Antibody Neutralization

HSV-1 causes lifelong infection in the human population and can be fatal in neonatal and immunocompromised individuals. There is no vaccine or cure, in part due to the ability of HSV to escape the host immune response by various mechanisms. The HSV particle contains at least 15 envelope proteins, four of which are required for entry and replication. This work suggests a novel role for gC in shielding the HSV entry glycoproteins. gC may function to help HSV escape neutralization by antibodies. ABSTRACT Viruses have evolved strategies to avoid neutralization by the host antibody response. Herpes simplex virus (HSV) glycoprotein C (gC) functions in viral entry and binds to complement component C3b, inhibiting complement-mediated immunity. We investigated whether gC protects HSV from antibody neutralization. HSV-1 that lacks gC was more sensitive to complement-independent neutralization by a panel of gB monoclonal antibodies than a wild-type gC rescuant virus. The presence of gC decreased neutralization by 2- to 16-fold. The gB in the native envelope of HSV-1 had reduced reactivity with antibodies in comparison to gB from the gC-null virus, suggesting that gC hampers the recognition of gB epitopes in the viral particle. The protein composition of the gC-null virus, including the surface glycoproteins essential for entry, was equivalent to that of the wild type, suggesting that gC is directly responsible for the reduced antibody recognition and neutralization. The neutralizing activity of antibodies to gD and gH antibodies was also increased in HSV lacking gC. Together, the data suggest that HSV-1 gC protects the viral envelope glycoproteins essential for entry, including gB, by shielding them from neutralization as a potential mechanism of immune evasion. IMPORTANCE HSV-1 causes lifelong infection in the human population and can be fatal in neonatal and immunocompromised individuals. There is no vaccine or cure, in part due to the ability of HSV to escape the host immune response by various mechanisms. The HSV particle contains at least 15 envelope proteins, four of which are required for entry and replication. This work suggests a novel role for gC in shielding the HSV entry glycoproteins. gC may function to help HSV escape neutralization by antibodies.
Inconsistent condom use between serodifferent sexual partnerships to the human immunodeficiency virus*

Objective: to analyze predictors of inconsistent condom use among HIV-positive people with sexual immunodeficiency virus serodifferent sexual partnership. Method: cross-sectional, analytical study with a consecutive non-probabilistic sample consisting of people living with the human immunodeficiency virus with serodifferent sexual partnership and who were in outpatient clinical follow-up. Data were collected through individual interviews guided by a semi-structured questionnaire and subsequently analyzed with bivariate analysis and logistic regression. Results: Seven variables were independently associated with inconsistent condom use. Schooling less than 11 years of schooling (4.9 [2.4-10.1]), having multiple partnerships (5.0 [1.3-19.6]), using alcohol (2.1 [1.1 -4.4]) or other drugs (2.8 [1.2-6.3]), do not receive advice from a healthcare professional (2.0 [1.1-3.9]), have no knowledge of treatment as prevention (3.0 [1,2-6,9]) and not knowing that undetectable viral load reduces the risk of human immunodeficiency virus transmission (3.8 [1,1-13,7]) were predictors for inconsistent condom use. Conclusion: The study showed that psychosocial factors interfere with consistent condom use between serodifferent partnerships. Thus, it is highlighted that there is a need for comprehensive interventions that include the integration of clinical and psychosocial care.
CXCR4/TGF-β1 mediated hepatic stellate cells differentiation into carcinoma-associated fibroblasts and promoted liver metastasis of colon cancer

ABSTRACT Background: Liver metastasis of colon cancer is strongly affected by the tumor microenvironment (TME), with interactions between tumor cells and cancer-associated fibroblasts (CAFs) in particular. TGF-β is well known for its ability to mediate the CAF phenotype, and CXCR4 expression is closely correlated to poor prognosis in CRC. The relationship between these two signaling pathways remains to be delineated in liver metastasis of colon cancer. Methods: Immunohistochemistry was employed to investigate CXCR4 expression in 45 human specimens of primary colorectal cancer (CRC) and liver metastasis. The functions of SDF-1 released by hepatic stellate cells (HSCs) on CXCR4 and TGF-β1 in CRC cells were investigated in vitro. The effects of CRC on HSCs differentiation into CAFs were confirmed using co-culture technology and expression analysis of CAFs markers by qPCR, western blot and immunofluorescence. The involvement of CXCR4 and TGF-β1 was verified with addition of CXCR4 inhibitor AMD3100 and TGF-β1 inhibitor cyclophosphamide (Cy) both in vitro and in vivo. Results: There were more CXCR4-positive cells at the liver metastatic tissues compared to the primary sites. CRC cells activated and transformed HSCs to CAFs after co-cultivating with HSCs. Activated HSCs stimulated TGF-β1 secretion from CRC cells after co-culture with CRC cells in vitro. Moreover, the expression of CAFs markers was increasing in the activated HSCs. In a mouse hepatic metastasis model, treated with AMD3100 or Cy blocked the metastatic potential of HCT116 cells and the hepatic CAFs differentiation. Conclusions: These results indicated that CXCR4/TGF-β1 axis plays an important role in CRC liver metastasis through mediating HSCs differentiation into CAFs, providing preclinical evidences that blockade of the axis might be beneficial for anti-metastasis therapy in CRC.
Hemophilia A in Females: Considerations for Clinical Management

Approximately 50% of female carriers of hemophilia A have factor VIII (FVIII) levels below 0.5 IU/dL and may be categorized as having mild hemophilia. Females with hemophilia may go undiagnosed for years because the most common symptoms – menorrhagia and bleeding after childbirth – also occur in females without hemophilia. Females with hemophilia can exhibit increased bleeding tendencies despite current guidelines of expected, adequate FVIII levels. The cases described illustrate the clinical variability and presentation of hemophilia in females and highlight the importance of a timely diagnosis, effective management, and monitoring. Prophylactic factor replacement therapy is recommended in females with hemophilia, particularly those with joint disease or gynecologic complications. Affected individuals should receive infusion training and education on treatment options, physical activities, the importance of treatment adherence, and recognizing bleeding symptoms warranting treatment. Further study is needed to increase awareness of hemophilia in females and reassess current guidelines for their management and monitoring.
Bridging the knowledge gap on mycoses in Africa: Setting up a Pan‐African Mycology Working Group

Most African countries have poorly funded and overburdened health systems. Additionally, a high prevalence of HIV in Sub‐Saharan Africa contributes to a high burden of opportunistic fungal infections. Data generated by GAFFI from 15 of 57 African countries revealed that an estimated 47 million Africans suffer from fungal diseases, of whom an estimated 1.7 million suffer from a serious fungal infection annually. Almost all African countries lack a surveillance system for fungal infections with the exception of South Africa. South Africa is also the only African country with a national mycology reference laboratory. Across the continent, there is a pervasive picture of inadequate/poor diagnostic capacity, low level of awareness among healthcare workers and policymakers and unavailability and non‐accessibility to essential antifungal medications. Recent outreach efforts by the International Society for Human and Animal Mycology (ISHAM) and the European Confederation of Medical Mycology (ECMM) have aimed to increase involvement of African countries and experts in global initiatives such as “One World One Guideline” and also the ECMM Academy. Recently, under the auspices of ISHAM, the African sub‐region created a network of mycology experts whose goal is to organise and engage African leaders in the field of medical mycology. The aim of this ISHAM Working Group was to facilitate interaction and synergy among regional leaders in order to develop educational programmes for capacity building to aid in the diagnosis and care of patients with fungal infections in Africa. The working group will also encourage country initiatives to develop clinical guidelines, to support surveys and to support the establishment of reference mycology laboratories.
High-Negative Anti–Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan

Background: Serologic testing of anti–Helicobacter pylori antibody, together with testing of pepsinogen I and II, is now widely used to stratify groups at high risk of gastric cancer in Japan. Those with a negative anti–H. pylori IgG titer, especially “high-negative” (3–<10 U/mL), are speculated to have higher risk of gastric cancer. We aimed to evaluate the association between a high-negative anti–H. pylori IgG titer and the long-term risk of gastric cancer in the Japan Public Health Center-based Prospective Study (JPHC Study) Cohort II. Methods: The study population consisted of 19,106 Japanese men and women who were followed from 1993 to 2013. A Cox proportional hazards model was used to assess the risk of gastric cancer for plasma anti–H. pylori IgG titers, together with the severity of atrophic gastritis by pepsinogen I and II levels. A total of 595 cases of gastric cancer occurred during an average of 18 years of follow-up. Results: Compared with those with a low-negative anti–H. pylori IgG titer (≤3 U/mL), subjects with a high-negative titer (3–<10 U/mL) showed a significantly elevated risk of gastric cancer [HR = 2.81; 95% confidence interval (CI) = 1.62–4.89]. Among those with a high-negative titer, risk increase was observed under moderate or severe atrophic gastritis (HR = 18.73; 95% CI = 8.83–39.70). Conclusions: Our results suggest that those with a high-negative anti–H. pylori IgG titer and moderate and severe atrophic gastritis are at increased long-term risk of gastric cancer. Impact: Development of moderate or severe atrophic gastritis in subjects with high-negative anti–H. pylori IgG titer is suggested to increase risk of gastric cancer.
Shear Stress Regulation of Endothelial Glycocalyx Structure Is Determined by Glucobiosynthesis

Supplemental Digital Content is available in the text. Objective: Endothelial cells exposed to laminar shear stress express a thick glycocalyx on their surface that plays an important role in reducing vascular permeability and endothelial anti-inflammatory, antithrombotic, and antiangiogenic properties. Production and maintenance of this glycocalyx layer is dependent on cellular carbohydrate synthesis, but its regulation is still unknown. Approach and Results: Here, we show that biosynthesis of the major structural component of the endothelial glycocalyx, hyaluronan, is regulated by shear. Both in vitro as well as in in vivo, hyaluronan expression on the endothelial surface is increased on laminar shear and reduced when exposed to oscillatory flow, which is regulated by KLF2 (Krüppel-like Factor 2). Using a CRISPR-CAS9 edited small tetracysteine tag to endogenous HAS2 (hyaluronan synthase 2), we demonstrated increased translocation of HAS2 to the endothelial cell membrane during laminar shear. Hyaluronan production by HAS2 was shown to be further driven by availability of the hyaluronan substrates UDP-glucosamine and UDP-glucuronic acid. KLF2 inhibits endothelial glycolysis and allows for glucose intermediates to shuttle into the hexosamine- and glucuronic acid biosynthesis pathways, as measured using nuclear magnetic resonance analysis in combination with 13C-labeled glucose. Conclusions: These data demonstrate how endothelial glycocalyx function and functional adaptation to shear is coupled to KLF2-mediated regulation of endothelial glycolysis.
Validation of analytical methods for heterocyclic amines in seven food matrices using high-performance liquid chromatography-tandem mass spectrometry

ABSTRACT Heterocyclic amines (HCAs) are potent mutagens generated by the high temperatures of the cooking process. The purpose of this study was to develop and validate analytical methods for HCAs determination using high-performance liquid chromatography-tandem mass spectrometry in seven food matrices: corn oil, milk, 20% ethanol, pork, flat fish, sea mustard (Undaria pinnatifida), and radish. Six isotopically labelled internal standards were used for quantitation, and Chem Elut and Oasis hydrphilic-liphophilic balance cartridges were applied for sample preparation to remove interferences. Calibration curves showed good linearity (R2 > 0.99) in all matrices. The ranges of the method detection limit and method quantitation limit were 0.009–2.35 ng g−1 and 0.025–7.13 ng g−1, respectively. The recoveries ranged from 67.5% to 119.6%. The coefficients of variation ranged from 0.3% to 15.1% for intra-day and ranged from 0.8% to 19.1% for inter-day. The methods were applied to 24 total diet study samples for HCAs quantitation. These results indicate that the established methods are reliable for determining HCAs in various foods.
Congenital chloride diarrhoea

Congenital chloride diarrhoea is one of the rare causes of diarrhoea during infancy and it is infrequently reported throughout the world. It is an autosomal recessive condition which is more prevalent in Poland, Finland, Saudi Arabia and Kuwait while rarely reported in Pakistan. Our patient was 7.5-month-old baby boy who presented with diarrhoea since neonatal period. He had consanguineous parents. On examination, baby had distended abdomen, hypotonia and hyporeflexia. Investigations revealed hypochloremic hypokalemic metabolic alkalosis. Urinary electrolytes were normal. Stool electrolytes revealed increased stool chloride excretion that confirmed our diagnosis of congenital chloride diarrhoea. Patient was treated with intravenous fluids and electrolyte replacement, followed by oral potassium and sodium replacement. He was also started on butyrate, cholestyramine and proton-pump inhibitors. He started gaining weight during his hospital admission and is being followed up in clinic.
Electron tomography reveals aspects of spindle structure important for mechanical stability at metaphase

Metaphase spindles exert pole-directed forces on still-connected sister kinetochores. The spindle must counter these forces with extensive forces to prevent spindle collapse. In small spindles, kinetochore microtubules (KMTs) connect directly with the poles, and countering forces are supplied either by interdigitating MTs that form interpolar bundles or by astral MTs connected to the cell cortex. In bigger spindles, particularly those without structured poles, the origin of extensive forces is less obvious. We have used electron tomography of well-preserved metaphase cells to obtain structural evidence about interactions among different classes of MTs in metaphase spindles from Chlamydomonas rheinhardti and two strains of cultured mammalian cells. In all these spindles, KMTs approach close to and cross-bridge with the minus ends of non-KMTs, which form a framework that interdigitates near the spindle equator. Although this structure is not pole-connected, its organization suggests that it can support kinetochore tension. Analogous arrangements of MTs have been seen in even bigger spindles, such as metaphase spindles in Haemanthus endosperm and frog egg extracts. We present and discuss a hypothesis that rationalizes changes in spindle design with spindle size based on the negative exponential distribution of MT lengths in dynamically unstable populations of tubulin polymers.
Toxic Theology as a Contributing Factor in Complicated Mourning

As an educator and spiritual caregiver to the bereaved, I offer supportive companionship and spiritual healing tools for the grief journey. In this capacity, I have encountered certain theological mindsets that can disrupt psychological well-being, and in some cases lead to complicated mourning, depression and even illness. This paper explores these “toxic theologies” and their relationship to complicated mourning, while offering alternative perspectives and cosmologies that may be helpful in supporting grievers who face spiritual challenges.
Neural-Network-Based Adaptive Event-triggered Control for Spacecraft Attitude Tracking

The problem of attitude tracking control for spacecraft with limited communication rate is addressed in this article. To reduce the communication burden, an adaptive event-triggered control scheme is proposed. In the control scheme, only the sampling states at the event-triggering instants are sent to the control module, which can considerably decrease the data transmission rate. To address the inertia uncertainties and external disturbances, a radial basis function neural network (NN) is introduced. The bound of the uncertainties and disturbances is estimated for the proposed control scheme, which can simplify the NN and reduce the computation. Since the event-triggered error signal is discontinuous due to the event-triggered mechanism, the closed-loop system is formulated as an impulsive dynamical system to obtain the stability properties of the system. Finally, simulation results are given to demonstrate the effectiveness of the proposed control scheme.
Role Of The Thyroid Gland In Expression Of The Thyroid Phenotype Of Sbp2 Deficient Mice.

Selenocysteine insertion sequence binding protein 2, SBP2 (SECISBP2), is required for selenoprotein synthesis. Partial SBP2 deficiency syndrome manifests characteristic thyroid function tests. The Sbp2 deficiency mouse model, Sbp2 iCKO, replicates this thyroid phenotype and was used for pathophysiologic investigations. As selenoproteins have antioxidative role in thyroid gland function, their deficiencies have potential to affect thyroid hormone (TH) synthesis. Sbp2 iCKO mice had larger thyroids relative to body weight and increased thyroidal T4 and T3 content while 5' deiodinases enzymatic activities were decreased. Possible mechanisms for the discrepancy between the increased thyroidal T3 and normal circulating T3 were investigated in dynamic experiments. Treatment with bovine TSH resulted in increased delta T4 in Sbp2 iCKO mice, indicating increased availability of preformed thyroidal TH. Next, the recovery of TH levels was evaluated after withdrawal of chemical suppression. At one day, Sbp2 iCKO had higher serum and thyroidal T3 concomitant with lower TSH, confirming increased capacity of TH synthesis in Sbp2 deficiency. Decreased TH secretion was ruled out, as serum and thyroidal TH were high in Sbp2 iCKO mice. Treatment with low-iodine diet also ruled out thyroidal secretion defect as both serum levels and thyroidal TH content similarly declined over time in Sbp2 deficient mice compared to Wt. This study provides evidence for unsuspected changes in thyroid gland that contribute to the thyroid phenotype of Sbp2 deficiency, with increased thyroidal T4 and T3 content in setting of increased TH synthesis capacity contributing to the circulating TH levels while thyroidal secretion is preserved.
Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p‐AMP‐activated protein kinase, light chain‐3‐II, autophagy‐related geness, and Beclin‐1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases.
Forecasting a Fatal Decision: Direct Replication of the Predictive Validity of the Suicide–Implicit Association Test

A previous study by Nock et al. (2010) suggested that people’s implicit identification with “death” or “suicide” can accurately predict whether they will attempt suicide several months in advance. We report the first direct and independent replication of this promising finding. Participants were 165 patients seeking treatment at a psychiatric unit in France. At baseline, patients completed the Suicide–Implicit Association Test (S–IAT), a semistructured interview, and a self-report measure of suicide ideation. Six months later, we contacted participants by phone and examined their hospital medical records to determine whether they had made a new suicide attempt. Results showed that the S–IAT did not distinguish between patients who were admitted to the hospital following suicide attempts and those who were admitted for other reasons. As in the original study, however, the S–IAT predicted suicide attempts within the 6-month follow-up period beyond well-known predictors. The test correctly classified 85% of patients (95% confidence interval = [76.91, 91.53]), supporting its diagnostic value for identifying who will make a suicide attempt.