Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic equivalence of ivermectin 1% and two novel formulations combined of ivermectin 1% + fluazuron 12.5% for the control of Rhipicephalus (Boophilus) microplus in beef cattle from Uruguay

Background: Novel combinations of ivermectin (IVM) and fluazuron (FLU) are presented as an alternative for the control of ticks in cattle. Applying a combination of drugs with the aim to affect different stages of the parasite’s life cycle is established as a potential measure to achieve the control of ticks in cattle. Aim: To determine the therapeutic equivalence between two novel formulations of IVM 1% combined with FLU 12.5% tested on bovines naturally infested with Rhipicephalus (Boophilus) microplus. Methods: Forty adult beef cattle were randomized into four groups (n = 10): IVM [1% (0.2 mg/kg)], combinations groups A and B [IVM 1% (0.2 mg/kg) + FLU 12.5% (2.5 mg/kg), each], and control [untreated]). On days 14, 27, and 49 after administration, the presence of ticks was ranked as null, low, medium, and high; a cumulative link model was adjusted to evaluate treatment response. Results: Although all groups had some animals with the presence of ticks until day 27, on day 14 IVM [odds ratios (OR) 0.013, CI95%: 0.001–0.014, p < 0.01], A (OR 0.01, CI95%: 0.00–0.07, p < 0.01) and B (OR 0.01, CI95%: 0.00–0.148, p < 0.01) groups were different when compared to the control group, unlike on day 27 where only groups A (OR 0.02, CI95%: 0.00–0.17, p < 0.01) and B (OR 0.06, CI95%: 0.00–0.46, p < 0.01) remained different from the control group. On day 49 post-administration, IVM and B did not differ from the control group, with 0.95 probability (CI95% 0.92–1.02) of high parasite burden. At day 49 post-administration, group A was the only group free of ticks (OR 0.01, CI95%: 0.00–0.13, p < 0.01). Conclusions: Pharmacotechnical differences in combined formulations should be considered in therapeutic equivalence studies.
Role of Regulatory Cells in Immune Tolerance Induction in Hemophilia A

The main complication of hemophilia A treatment is the development of neutralizing antibodies (inhibitors) against factor VIII (FVIII). Immune tolerance induction (ITI) is the prescribed treatment for inhibitor eradication, although its working mechanism remains unresolved. To clarify this mechanism, we compared blood samples of hemophilia A patients with and without inhibitors for presence of immunoregulatory cells and markers, including regulatory B-cells (Bregs), regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and expression of regulatory markers on T-cells (programmed cell death protein 1 [PD1], inducable T-cell costimulator, cytotoxic T-lymphocyte-associated protein 4 [CTLA4]), by use of flow cytometry. By cross-sectional analysis inhibitor patients (N = 20) were compared with inhibitor-negative (N = 28) and ex-inhibitor (N = 17) patients. In another longitudinal study, changes in immunoregulatory parameters were evaluated during ITI (N = 12) and compared with inhibitor-negative hemophilia A patients (N = 36). The frequency of Bregs, but not of Tregs nor MDSCs, was significantly reduced in inhibitor patients (3.2%) compared with inhibitor-negative (5.9%) and ex-inhibitor patients (8.9%; P < 0.01). CTLA4 expression on T-cells was also reduced (mean fluorescence intensity 133 in inhibitor versus 537 in inhibitor-negative patients; P < 0.01). Fittingly, in patients followed during ITI, inhibitor eradication associated with increased Bregs, increased Tregs, and increased expression of CTLA4 and PD1 on CD4+ T-cells. In conclusion, inhibitor patients express significantly lower frequency of Bregs and Tregs marker expression, which are restored by successful ITI. Our findings suggest that an existing anti-FVIII immune response is associated with deficits in peripheral tolerance mechanisms and that Bregs and changes in immunoregulatory properties of CD4+ T-cells likely contribute to ITI in hemophilia A patients with inhibitors.
LncRNA MIAT enhances systemic lupus erythematosus by upregulating CFHR5 expression via miR-222 degradation

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Complement factor H related protein 5 (CFHR5) may contribute to dysfunctional complement activation, thus predisposing to SLE. The expression levels of anti-dsDNA, C3 and CFHR5 in blood samples from 50 SLE patients and 50 healthy individuals were evaluated, and also their expression levels were measured in an MRL/lpr mouse model and control MRL/MPJ mice. The results showed that CFHR5 expression increased in SLE patients together with the increase of anti-dsDNA in comparison with the healthy control. Furthermore, CFHR5 expression was inversely correlated with C3, down-regulation of which was associated with worse SLE. Previous studies indicated that long noncoding RNA (lncRNA) regulates mRNA synthesis via microRNA (miRNA) inhibition. The present bioinformatics analysis revealed that the target miRNA (miR-222) was combined with both lncRNA MIAT and mRNA CFHR5. H&E staining of the kidney tissues of the MRL/lpr mice revealed that lncRNA MIAT, as a competitive inhibitor of miR-222, enhanced SLE by upregulating CFHR5 expression through the degradation of miR-222 in vivo. Thus, our study revealed for the first time the role of lncRNA MIAT in regulating CFHR5 expression in SLE in vivo and provided new insights into the role of lncRNA in regulation and complement function of SLE pathogenesis.
Impact of COVID-19 on household food insecurity and interlinkages with child feeding practices and coping strategies in Uttar Pradesh, India: a longitudinal community-based study

Objectives The COVID-19 pandemic has profound negative impacts on people’s lives, but little is known on its effect on household food insecurity (HFI) in poor setting resources. This study assessed changes in HFI during the pandemic and examined the interlinkages between HFI with child feeding practices and coping strategies. Design A longitudinal survey in December 2019 (in-person) and August 2020 (by phone). Setting Community-based individuals from 26 blocks in 2 districts in Uttar Pradesh, India. Participants Mothers with children <2 years (n=569). Main outcomes and analyses We measured HFI by using the HFI Access Scale and examined the changes in HFI during the pandemic using the Wilcoxon matched-pairs signed-rank tests. We then assessed child feeding practices and coping strategies by HFI status using multivariable regression models. Results HFI increased sharply from 21% in December 2019 to 80% in August 2020, with 62% households changing the status from food secure to insecure over this period. Children in newly or consistently food-insecure households were less likely to consume a diverse diet (adjusted OR, AOR 0.57, 95% CI 0.34 to 0.95 and AOR 0.51, 95% CI 0.23 to 1.12, respectively) compared with those in food-secure households. Households with consistent food insecurity were more likely to engage in coping strategies such as reducing other essential non-food expenditures (AOR 2.2, 95% CI 1.09 to 4.24), borrowing money to buy food (AOR 4.3, 95% CI 2.31 to 7.95) or selling jewellery (AOR 5.0, 95% CI 1.74 to 14.27) to obtain foods. Similar findings were observed for newly food-insecure households. Conclusions The COVID-19 pandemic and its lockdown measures posed a significant risk to HFI which in turn had implications for child feeding practices and coping strategies. Our findings highlight the need for further investment in targeted social protection strategies and safety nets as part of multisectoral solutions to improve HFI during and after COVID-19.
Personal and perceptual factors associated with the use of electronic cigarettes among university students in northern Thailand

INTRODUCTION Although Thailand has banned the import of electronic cigarettes (e-cigarettes) into the kingdom, a range of evidence has revealed the widespread use of these illegal products, especially among university students. Too little is known about personal and perceptual factors for such behavior. This study aimed to investigate the prevalence and factors associated with the use of e-cigarettes among university students in Northern Thailand METHODS A cross-sectional study was conducted with 792 university students in Northern Thailand between June and July 2020. An anonymous, self-administered questionnaire was implemented to collect relevant information. Bivariate and multivariate logistic regression analyses were applied to identify factors associated with the use of e-cigarettes in the last 30 days. RESULTS The study revealed that 18.1% of the participants used e-cigarettes in the past 30 days. The personal factors associated with e-cigarette use among Thai university students included: studying in non-health related faculties (AOR=11.21; 95% CI: 4.88–25.71); having a friend using e-cigarettes (AOR=10.48; 95% CI: 5.96–18.41); having a lower GPA than the mean (AOR=1.93; 95% CI: 1.14– 3.28); and having a monthly income higher than the mean (AOR=1.74; 95% CI: 1.09–2.78). Regarding perceptual factors, there was a significant link between e-cigarette use and the perception that these modern cigarettes are less harmful than conventional cigarettes (AOR=2.47; 95% CI: 1.50–4.07), and perception that using e-cigarettes in public is not illegal (AOR=1.93; 95% CI: 1.19–3.15). CONCLUSIONS E-cigarette use is widespread among Thai university students. Maintaining the enforcement policy on banning the importation of e-cigarettes into the country is thus needed. Also, further communication and public relations on the risks and legal prohibitions of e-cigarette use are needed among university students in the Northern Thailand.
The occurrence of osteosarcoma after tibial fracture repair in a dog

Background: There are few detailed reports on implant-associated sarcoma in dogs; however, loose implants, metal type, and infection have not been shown as specific risk factors for this condition. Case Description: A 14-year-old spayed female Labrador retriever was referred to our hospital with a main complaint of chronic right hind lameness after previous tibial fracture repair. On radiographs, rupture of the bone plate and screws with swelling of the surrounding soft tissue was observed, and osteosarcoma (OSA) was diagnosed after histopathological examinations. During amputation surgery, a plastic band was found associated with the implant. Conclusion: Veterinary surgeons should be aware of implant-associated OSA and refrain from using non-medical materials in the implants. Furthermore, they should recommend the removal of orthopedic implants after fracture repair.
Optical Coherence Tomographic Finding in a Case of Congenital Macular Coloboma at King Abdulaziz University Hospital, Jeddah

Macular coloboma is a rare eye condition that affects around 0.5-0.7/10,000 of live births. Macular coloboma appears as a well-demarcated atrophic lesions that could affect one eye or both eyes on fundus examination. This is a case of a 33-year-old male patient who presented to the outpatient clinic with a history of poor vision in the left eye since childhood. He had a history of strabismus surgery for sensory exotropia (XT) in the left eye. Anterior segment examination of both eyes was normal while the fundus examination of both eyes revealed bilateral chorioretinal lesions in the macula which was larger in the left eye (OS) than the right eye (OD), representing bilateral chorioretinal coloboma. Congenital coloboma is a rare eye condition that leads to non-progressive decrease in visual acuity. Optical coherence tomography (OCT) is the modality of choice in diagnosing and describing macular coloboma.
Seminal pro-inflammatory cytokines and pH are affected by Chlamydia infection in asymptomatic patients with teratozoospermia

Introduction Infection and inflammation of the reproductive tract by Chlamydia trachomatis (CT) are recognized as significant risk factors for male infertility. This study aimed to evaluate CT infection and its effects on seminal parameters and cytokines in asymptomatic patients with teratozoospermia. Material and methods Semen samples from one hundred four male patients were collected, and CT detection was performed by polymerase chain reaction (PCR). The quality (volume, sperm concentration, pH, motility, morphology, and leucocytes) of the semen was measured by standard procedures recommended by the World Health Organization (WHO). Pro-inflammatory cytokines [interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ)], as well as anti-inflammatory cytokines (IL-4, IL-10), were determined by using enzyme-linked immunosorbent assay (ELISA). The frequency of CT infection was expressed as a percentage. Descriptive statistics were used for comparison of cytokines from infertile men, and then the Mann-Whitney U test was applied for the contrast of seminal parameters and cytokines from CT-infected versus non-CT infected men. Results A ratio of 33/104 (31.7%) patients were positive for CT infection. The ejaculate of positive CT infection was found to have increased pH (pH = 7.65 in non-CT infected vs. 7.94 CT-infected men; p = 0.026). High levels of pro-inflammatory cytokines were found in the population studied; however, infected males were noted to have high levels of IL-1 β [184.66 (0-3985.33 pg/ml), p = 0.001] and IL-6 [87.8 (0-1042.8 pg/ml), p = 0.001]. Conclusions CT infection increased seminal pH, as well as IL-1 β and IL-6 cytokines, suggesting a potential role of infection and inflammation in asymptomatic patients with teratozoospermia.
Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis

Objective Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in the developed world. 10% of KD patients are resistant to front-line therapy, and no interventions exist to address secondary complications such as myocardial fibrosis. We sought to identify proteins and pathways associated with disease and anti-IL-1 treatment in a mouse model of KD. Methods Vasculitis was induced via Lactobacillus casei cell wall extract (LCWE) injection in 5-week-old male mice. Groups of mice were injected with LCWE alone, LCWE and IL-1 receptor antagonist anakinra, or saline for controls. Upper heart tissue was assessed by quantitative mass spectrometry analysis. Expression and activation of STAT3 was assessed by immunohistochemistry, immunofluorescence and Western blot, and IL-6 expression by RNA-seq and ELISA. A STAT3 small molecular inhibitor and anti-IL-6R antibody were used to evaluate the role of STAT3 and IL-6 in disease development. Results STAT3 was highly expressed and phosphorylated in cardiac tissue of LCWE-injected mice, and reduced following anakinra treatment. Il6 and Stat3 gene expression was enhanced in abdominal aorta of LCWE-injected mice and reduced with Anakinra treatment. IL-6 serum levels were enhanced in LCWE-injected mice and normalized by anakinra. However, neither inhibition of STAT3 nor blockade of IL-6 altered disease development. Conclusion Proteomic analysis of cardiac tissues demonstrates differential protein expression between KD-like, control and anakinra treated cardiac tissue. STAT3 and IL-6 were highly upregulated with LCWE and normalized by anakinra treatment. However, both STAT3 and IL-6 were dispensable for disease development indicating they may be bystanders of inflammation.
Age-related differences of genetic susceptibility to patients with acute lymphoblastic leukemia

Inherited predispositions to acute lymphoblastic leukemia have been well investigated in pediatric patients, but studies on adults, particularly Chinese patients, are limited. In this study, we conducted a genome-wide association study in 466 all-age Chinese patients with Acute lymphoblastic leukemia (ALL) and 1,466 non-ALL controls to estimate the impact of age on ALL susceptibility in the Chinese population. Among the 17 reported loci, 8 have been validated in pediatric and 1 in adult patients. The strongest association signal was identified at ARID5B locus and gradually decreased with age, while the signal at GATA3 exhibited the opposite trend and significantly impact on adult patients. With genome-wide approaches, germline variants at 2q14.3 rank as the top inherited predisposition to adult patients (e.g., rs73956024, P = 4.3 × 10-5) and separate the genetic risk of pediatric vs. adult patients (P = 3.6 × 10-6), whereas variants at 15q25.3 (e.g., rs11638062) have a similar impact on patients in different age groups (overall P = 2.9 × 10-7). Our analysis highlights the impact of age on genetic susceptibility to ALL in Chinese patients.
A review on traditional uses, phytochemistry, pharmacology, and clinical research of dietary spice Cuminum cyminum L.

Cuminum cyminum L. is a versatile spice belonging to family Apiaceae. Though the plant has pan‐tropical distribution but it is indigenous to Egypt, the Mediterranean, and South Asian countries. It exhibits numerous culinary, traditional, and pharmacological attributes. Its traditional uses also validate its immense pharmacological potential. Cuminum cyminum is the hub of numerous bioactives such as alkaloids, flavonoids, terpenoids, and so forth. Cuminaldehyde is the major bioactive, rendered to most of its pharmacological as well as clinical significance. The present study comprised of current knowledge on its taxonomy, nutritional, traditional, phytochemistry, pharmacology (antimicrobial, antioxidant, anti‐inflammation, antidiabetic, wound healing, anticancer, etc.), toxicology, and clinical attributes. Besides, the mechanism of action is also well explained. The present study provides a rationale for further bioprospection of this wonder plant. Future studies are needed to fill the research gaps, particularly on relevant phytocompound isolation, their pre‐clinical and clinical characterization, evaluation, and structure–activity relationship. Moreover, well‐designed and highly appropriate clinical and placebo trials are still needed to demonstrate the trustworthy role of cumin on human health.
Adenine-induced chronic kidney disease induces a similar skeletal phenotype in male and female C57BL/6 mice with more severe deficits in cortical bone properties of male mice

Chronic kidney disease (CKD) causes bone loss, particularly in cortical bone, through formation of cortical pores which lead to skeletal fragility. Animal models of CKD have shown variability in the skeletal response to CKD between males and females suggesting sex may play a role in this variation. Our aim was to compare the impact of adenine-induced CKD on cortical parameters in skeletally mature male and female C57Bl/6 mice. After 10-weeks of adenine-induced CKD, both male and female adenine mice had high serum parathyroid hormone (PTH), high bone turnover, and cortical porosity compared to non-CKD controls. Both sexes had lower cortical thickness, but only male mice had lower cortical bone area. CKD imparted greater deficits in mechanical properties of male mice compared to female mice. These data demonstrate that both male and female mice develop high PTH/high bone turnover in response to adenine-induced CKD and that cortical bone phenotypes are slightly more severe in males, particularly in mechanical properties deficits.
Impact of regulatory light chain mutation K104E on the ATPase and motor properties of cardiac myosin

Rasicci et al. investigate the mechanochemical properties of distinct isoforms of cardiac myosin carrying the K104E regulatory light chain mutation, previously associated with hypertrophic cardiomyopathy. They demonstrate that the mutation does not affect the ATPase or motor properties of human cardiac myosin subfragment-1 (M2β-S1), but the mutation increases the sliding velocity and disrupts RLC incorporation in full-length α-cardiac myosin.
Aspirin in Hepatocellular Carcinoma

Preclinical and clinical studies provide evidence for aspirin as a preventative agent for cancer. Compelling direct evidence supports a chemopreventive effect of aspirin in individuals at high risk of developing colorectal cancer due to Lynch syndrome, while indirect evidence indicates that aspirin may reduce the risk of and mortality from sporadic colorectal cancer. There is weaker evidence for a protective effect of aspirin against all cancers taken as a group. Nevertheless, the results of recent retrospective cohort studies consistently indicate a beneficial effect of aspirin as a chemopreventive or adjuvant chemotherapeutic agent in hepatocellular carcinoma (HCC). Epidemiologic studies conducted in the general population or in selected populations at higher risk for HCC reveal that regular aspirin use is associated with reduced HCC incidence. In addition, aspirin may act as an adjuvant to other therapies in reducing HCC recurrence. According to studies in animal models, the cancer-preventative effect of aspirin may be related to its antiplatelet and anti-inflammatory activities. Prospective studies are warranted to determine whether aspirin should be recommended to diverse populations of patients at risk for HCC.
Probing the binding specificities of human Siglecs by cell-based glycan arrays

Significance Siglecs are immunomodulatory receptors that recognize sialic acid–carrying glycans with important functions in immunity. However, many of their natural ligands are poorly defined. We generated a cell-based glycan array comprised of a library of isogenic human cells displaying the greater complexity of sialic acids on diverse glycan structures and glycoconjugates in the natural context of the cell surface. We applied this array to reveal fine binding specificities of Siglecs for sialoglycans, informed of the underlying required glycosyltransferase genes, and provided evidence for selective binding context provided by glycan presentation on distinct protein sequences. Insight into the fine binding specificities of Siglecs will advance understanding their diverse biological functions and benefit therapeutic targeting in autoimmunity, inflammation, cancer, and Alzheimer’s disease. Siglecs are a family of sialic acid–binding receptors expressed by cells of the immune system and a few other cell types capable of modulating immune cell functions upon recognition of sialoglycan ligands. While human Siglecs primarily bind to sialic acid residues on diverse types of glycoproteins and glycolipids that constitute the sialome, their fine binding specificities for elaborated complex glycan structures and the contribution of the glycoconjugate and protein context for recognition of sialoglycans at the cell surface are not fully elucidated. Here, we generated a library of isogenic human HEK293 cells with combinatorial loss/gain of individual sialyltransferase genes and the introduction of sulfotransferases for display of the human sialome and to dissect Siglec interactions in the natural context of glycoconjugates at the cell surface. We found that Siglec-4/7/15 all have distinct binding preferences for sialylated GalNAc-type O-glycans but exhibit selectivity for patterns of O-glycans as presented on distinct protein sequences. We discovered that the sulfotransferase CHST1 drives sialoglycan binding of Siglec-3/8/7/15 and that sulfation can impact the preferences for binding to O-glycan patterns. In particular, the branched Neu5Acα2–3(6-O-sulfo)Galβ1–4GlcNAc (6′-Su-SLacNAc) epitope was discovered as the binding epitope for Siglec-3 (CD33) implicated in late-onset Alzheimer’s disease. The cell-based display of the human sialome provides a versatile discovery platform that enables dissection of the genetic and biosynthetic basis for the Siglec glycan interactome and other sialic acid–binding proteins.