Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular Risk Factors and Benign Paroxysmal Positional Vertigo in Community Otolaryngology–Head and Neck Surgery

Objective Cardiovascular risk factors have been associated with benign paroxysmal positional vertigo (BPPV), possibly causing degeneration of the utricular epithelium and subepithelium, but supportive evidence is mixed. This is the first study to examine the association between cardiovascular risk factors and BPPV as they present in the community practice of comprehensive otolaryngology–head and neck surgery. Study Design Cross-sectional case-matched case-control series. Setting A community practice of otolaryngology–head and neck surgery with 3 clinical offices and a socioeconomically diverse patient population. Subjects and Methods Clinical data were collected retrospectively from the electronic health records of a continuous 4-year series of 628 patients with BPPV and age- and sex-matched controls. Results There were no statistically significant associations found between BPPV and diabetes, hypertension, dyslipidemia, or body mass index in the study population in pairwise comparisons or multivariable modeling. Conclusion This study suggests that BPPV as encountered in a community ear, nose, and throat practice is not generally associated with cardiovascular risk factors. The possibility that these or other cardiovascular risk factors may be causative in some cases cannot be excluded, though most cases of BPPV appear to be caused primarily by shedding of otoconia from the utricle that is idiopathic or at least in part by unconfirmed noncardiovascular factors.
Meibomian Gland Morphology: The Influence of Structural Variations on Gland Function and Ocular Surface Parameters.

PURPOSE To objectively and quantitatively characterize meibomian gland morphology and to investigate the influence of morphological variations on gland function and ocular surface and tear film parameters. METHODS One hundred fifty subjects were enrolled. The examinations included tear osmolarity, tear meniscus height, bulbar conjunctival hyperemia, noninvasive tear film breakup time, lid margin thickness, foam secretion, meibomian gland expressibility, count of functioning glands, corneal and conjunctival staining, fluorescein breakup time, lid wiper epitheliopathy, and Schirmer test. Patient symptoms were assessed using the Ocular Surface Disease Index questionnaire. Images from noncontact meibography were analyzed using an automated method that objectively estimates dropout area, number of glands, gland length and width, and gland irregularity. RESULTS Gland irregularity highly correlated with dropout area (r = -0.4, P < 0.001) and showed significant partial correlations with fluorescein breakup time (r = 0.162, P = 0.049) and the Ocular Surface Disease Index questionnaire (r = -0.250, P = 0.002) Subjects with dropout area <32% were divided into 2 groups: high and low irregularity. Gland expressibility was statistically significantly different between the 2 groups (U = 319.5, P = 0.006). In the high irregularity group, gland irregularity correlated with the Schirmer test (r = 0.530, P = 0.001) and corneal fluorescein staining (r = -0.377, P = 0.021). CONCLUSIONS Automated morphological analysis of meibomian gland structure provides additional quantitative and objective information regarding gland morphology. The link between dropout area and gland function is not clear. Assessment of gland irregularity might better predict gland function and its effects on ocular surface and tear film parameters.
Constraint-induced or multi-modal personalized aphasia rehabilitation (COMPARE): A randomized controlled trial for stroke-related chronic aphasia

Rationale The comparative efficacy and cost-effectiveness of constraint-induced and multi-modality aphasia therapy in chronic stroke are unknown. Aims and hypotheses In the COMPARE trial, we aim to determine whether Multi-Modal Aphasia Treatment (M-MAT) and Constraint-Induced Aphasia Therapy Plus (CIAT-Plus) are superior to usual care (UC) for chronic post-stroke aphasia. Primary hypothesis: CIAT-Plus and M-MAT will reduce aphasia severity (Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ)) compared with UC: CIAT-Plus superior for moderate aphasia; M-MAT superior for mild and severe aphasia. Sample size estimates A total of 216 participants (72 per arm) will provide 90% power to detect a 5-point difference on the WAB-R-AQ between CIAT-Plus or M-MAT and UC at α = 0.05. Methods and design Prospective, randomized, parallel group, open-label, assessor blinded trial. Participants: Stroke >6 months; aphasia severity categorized using WAB-R-AQ. Computer-generated blocked and stratified randomization by aphasia severity (mild, moderate, and severe), to 3 arms: CIAT-Plus, M-MAT (both 30 h therapy over two weeks); UC (self-reported usual community care). Study outcomes WAB-R-AQ immediately post-intervention. Secondary outcomes: WAB-R-AQ at 12-week follow-up; naming scores, discourse measures, Communicative Effectiveness Index, Scenario Test, and Stroke and Aphasia Quality of Life Scale-39 g immediately and at 12 weeks post-intervention; incremental cost-effectiveness ratios compared with UC at 12 weeks. Discussion This trial will determine whether CIAT-Plus and M-MAT are superior and more cost-effective than UC in chronic aphasia. Participant subgroups with the greatest response to CIAT-Plus and M-MAT will be described.
Exogenous Isoprene Confers Physiological Benefits in a Negligible Isoprene Emitter (Acer monspessulanum L.) under Water Deficit

Isoprene, the main volatile released by plants, is known to protect the photosynthetic apparatus in isoprene emitters submitted to oxidative pressures caused by environmental constraints. Whether ambient isoprene contributes to protect negligible plant emitters under abiotic stress conditions is less clear, and no study has tested if ambient isoprene is beneficial during drought periods in plant species that naturally release negligible isoprene emissions. This study examines the effect of exogenous isoprene (20 ppbv) on net photosynthesis, stomatal conductance and production of H2O2 (a reactive oxygen species: ROS) in leaves of Acer monspessulanum (a negligible isoprene emitter) submitted to three watering treatments (optimal, moderate water stress and severe water stress). Results showed that A. monspessulanum exhibited a net photosynthesis increase (+30%) and a relative leaf H2O2 decrease when saplings were exposed to an enriched isoprene atmosphere compared to isoprene-free conditions under moderate water deficit. Such physiological improvement under isoprene exposure was not observed under optimal watering or severe water stress. These findings suggest that when negligible isoprene emitters are surrounded by a very high concentration of isoprene in the ambient air, some plant protection mechanism occurs under moderate water deficit probably related to protection against ROS damage eventually impeding photosynthesis drop.
HDAC6—An Emerging Target Against Chronic Myeloid Leukemia?

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.
Is dyschloremia a marker of critical illness or euchloremia an interventional target to improve outcomes?

Despite chloride being the most abundant extracellular anion, its significance in clinical practice was undervalued for years. In the past decade this has dramatically changed to the point of chloride receiving the distinction of “queen” of electrolytes (1); with several observational and interventional studies focused on the chloride content of crystalloid solutions used for fluid resuscitation.
The Moral Psychology of Raceless, Genderless Strangers

Moral psychology uses tightly controlled scenarios in which the identities of the characters are either unspecified or vague. Studies with raceless, genderless strangers help to highlight the important structural elements of moral acts (e.g., intention, causation, harm) but may not generalize to real-world judgments. As researchers have long shown, social judgments hinge on the identities (e.g., race, gender, age, religion, group affiliation) of both target and perceiver. Asking whether people generally condemn “shooting someone” is very different from asking whether liberals as opposed to conservatives condemn “a White police officer shooting a Black suspect. ” We argue for the importance of incorporating identity into moral psychology. We briefly outline the central role of identity in social judgments before reviewing current theories in moral psychology. We then advocate an expanded person-centered morality—synthesizing moral psychology with social cognition—to better capture everyday moral judgments.
Detection methods for influenza A H1N1 virus with special reference to biosensors: a review

Abstract H1N1 (Swine flu) is caused by influenza A virus, which is a member of Orthomyxoviridae family. Transmission of H1N1 occurs from human to human through air or sometimes from pigs to humans. The influenza virus has different RNA segments, which can reassert to make new virus strain with the possibility to create an outbreak in unimmunized people. Gene reassortment is a process through which new strains are emerging in pigs, as it has specific receptors for both human influenza and avian influenza viruses. H1N1 binds specifically with an α-2,6 glycosidic bond, which is present in human respiratory tract cells as well as in pigs. Considering the fact of fast multiplication of viruses inside the living cells, rapid detection methods need an hour. Currently, WHO recommended methods for the detection of swine flu include real-time PCR in specific testing centres that take 3–4 h. More recently, a number of methods such as Antigen–Antibody or RT-LAMP and DNA biosensors have also been developed that are rapid and more sensitive. This review describes the various challenges in the diagnosis of H1N1, and merits and demerits of conventional vis-à-vis latest methods with special emphasis on biosensors.
Riboflavin-Targeted Drug Delivery

Active targeting can improve the retention of drugs and drug delivery systems in tumors, thereby enhancing their therapeutic efficacy. In this context, vitamin receptors that are overexpressed in many cancers are promising targets. In the last decade, attention and research were mainly centered on vitamin B9 (folate) targeting; however, the focus is slowly shifting towards vitamin B2 (riboflavin). Interestingly, while the riboflavin carrier protein was discovered in the 1960s, the three riboflavin transporters (RFVT 1-3) were only identified recently. It has been shown that riboflavin transporters and the riboflavin carrier protein are overexpressed in many tumor types, tumor stem cells, and the tumor neovasculature. Furthermore, a clinical study has demonstrated that tumor cells exhibit increased riboflavin metabolism as compared to normal cells. Moreover, riboflavin and its derivatives have been conjugated to ultrasmall iron oxide nanoparticles, polyethylene glycol polymers, dendrimers, and liposomes. These conjugates have shown a high affinity towards tumors in preclinical studies. This review article summarizes knowledge on RFVT expression in healthy and pathological tissues, discusses riboflavin internalization pathways, and provides an overview of RF-targeted diagnostics and therapeutics.
Evaluation of image quality and task performance for a mobile C-arm with a complementary metal–oxide semiconductor detector

Abstract. We assessed interventional radiologists’ task-based image quality preferences for two- and three-dimensional images obtained with a complementary metal–oxide semiconductor (CMOS) flat-panel detector versus a hydrogenated amorphous silicon (a-Si:H) flat-panel detector. CMOS and a-Si:H detectors were implemented on identical mobile C-arms to acquire radiographic, fluoroscopic, and cone-beam computed tomography (CBCT) images of cadavers undergoing simulated interventional procedures using low- and high-dose settings. Images from both systems were displayed side by side on calibrated, diagnostic-quality displays, and three interventional radiologists evaluated task performance relevant to each image and ranked their preferences based on visibility of pertinent anatomy and interventional devices. Overall, CMOS images were preferred in fluoroscopy (p = 0.002) and CBCT (p = 0.004), at low-dose settings (p = 0.001), and for tasks associated with high levels of spatial resolution [e.g., fine anatomical details (p = 0.006) and assessment of interventional devices (p = 0.015)]. No significant difference was found for fluoroscopic imaging tasks emphasizing temporal resolution (p = 0.072), for radiography tasks (p = 0.825), when using high-dose settings (p = 0.360), or tasks involving general anatomy (p = 0.174). The image quality preferences are consistent with reported technical advantages of CMOS regarding finer pixel size and reduced electronic noise.
T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven that T-2 toxin caused hepatotoxicity in chicken, but the regulatory mechanism is unclear. In the present study, we assessed the toxicological effect of T-2 toxin on apoptosis and autophagy in hepatocytes. The total of 120 1-day-old healthy broilers were allocated randomly into four groups and reared for 21 day with complete feed containing 0 mg/kg, 0.5 mg/kg, 1 mg/kg or 2 mg/kg T-2 toxin, respectively. The results showed that the apoptosis rate and pathological changes degree hepatocytes were aggravated with the increase of T-2 toxin. At the molecular mechanism level, T-2 toxin induced mitochondria-mediated apoptosis by producing reactive oxygen species, promoting cytochrome c translocation between the mitochondria and cytoplasm, and thus promoting apoptosomes formation. Meanwhile, the expression of the autophagy-related protein, ATG5, ATG7 and Beclin-1, and the LC3-II/LC3-I ratio were increased, while p62 was downregulated, suggesting T-2 toxin caused autophagy in hepatocytes. Further experiments demonstrated that the PI3K/AKT/mTOR signal may be participated in autophagy induced by T-2 toxin in chicken hepatocytes. These data suggest a possible underlying molecular mechanism for T-2 toxin that induces apoptosis and autophagy in chicken hepatocytes
Small Molecules Targeting the Specific Domains of Histone-Mark Readers in Cancer Therapy

Epigenetic modifications (or epigenetic tags) on DNA and histones not only alter the chromatin structure, but also provide a recognition platform for subsequent protein recruitment and enable them to acquire executive instructions to carry out specific intracellular biological processes. In cells, different epigenetic-tags on DNA and histones are often recognized by the specific domains in proteins (readers), such as bromodomain (BRD), chromodomain (CHD), plant homeodomain (PHD), Tudor domain, Pro-Trp-Trp-Pro (PWWP) domain and malignant brain tumor (MBT) domain. Recent accumulating data reveal that abnormal intracellular histone modifications (histone marks) caused by tumors can be modulated by small molecule-mediated changes in the activity of the above domains, suggesting that small molecules targeting histone-mark reader domains may be the trend of new anticancer drug development. Here, we summarize the protein domains involved in histone-mark recognition, and introduce recent research findings about small molecules targeting histone-mark readers in cancer therapy.
Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi‐ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow‐up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2‐fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5‐fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra‐coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials. gov/. Unique identifier: NCT00005487.
NAD deficiency due to environmental factors or gene–environment interactions causes congenital malformations and miscarriage in mice

Significance Causes for congenital malformations and miscarriages can be genetic, environmental, or a combination of multiple factors; however, in most cases, the underlying reasons are unknown. This study shows that a dietary undersupply of tryptophan and vitamin B3, the metabolic precursors of nicotinamide adenine dinucleotide (NAD), during pregnancy is a cause for frequent multiple birth defects and miscarriages in wild-type mice. When the maternal malnutrition coincided with a genetic variant that impaired NAD synthesis or low oxygen levels as an environmental factor, embryos were more severely affected. Our findings in mice suggest NAD deficiency, due to environmental factors or gene–environment interactions, as a possible cause of congenital malformations in human cases in which no causative gene defect is present. Causes for miscarriages and congenital malformations can be genetic, environmental, or a combination of both. Genetic variants, hypoxia, malnutrition, or other factors individually may not affect embryo development, however, they may do so collectively. Biallelic loss-of-function variants in HAAO or KYNU, two genes of the nicotinamide adenine dinucleotide (NAD) synthesis pathway, are causative of congenital malformation and miscarriage in humans and mice. The variants affect normal embryonic development by disrupting the synthesis of NAD, a key factor in multiple biological processes, from its dietary precursor tryptophan, resulting in NAD deficiency. This study demonstrates that congenital malformations caused by NAD deficiency can occur independent of genetic disruption of NAD biosynthesis. C57BL/6J wild-type mice had offspring exhibiting similar malformations when their supply of the NAD precursors tryptophan and vitamin B3 in the diet was restricted during pregnancy. When the dietary undersupply was combined with a maternal heterozygous variant in Haao, which alone does not cause NAD deficiency or malformations, the incidence of embryo loss and malformations was significantly higher, suggesting a gene–environment interaction. Maternal and embryonic NAD levels were deficient. Mild hypoxia as an additional factor exacerbated the embryo outcome. Our data show that NAD deficiency as a cause of embryo loss and congenital malformation is not restricted to the rare cases of biallelic mutations in NAD synthesis pathway genes. Instead, monoallelic genetic variants and environmental factors can result in similar outcomes. The results expand our understanding of the causes of congenital malformations and the importance of sufficient NAD precursor consumption during pregnancy.
Craniofacial Analysis May Indicate Co-Occurrence of Skeletal Malocclusions and Associated Risks in Development of Cleft Lip and Palate

Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP (n = 30), normocephalic controls (n = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity (n = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft.
Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.