Miracle-dz/UniFAR-FTUs huggingface dataset:
Does ischaemia-modified albumin level predict clomiphene citrate resistant polycystic ovary syndrome patients?

Abstract This study aims to examine the role of ischaemic-modified albumin (IMA) in predicting clomiphene citrate (CC) resistance in patients with CC-resistant and CC-sensitive infertile polycystic ovary syndrome (PCOS). Sixty women patients admitted to the infertility clinic were evaluated. The patients were divided into two groups. Group 1 comprised 30 infertile PCOS patients with CC resistance; group 2 was the control group comprising 30 infertile PCOS patients with CC sensitivity. Serum IMA levels of PCOS patients with CC resistance were significantly higher than CC sensitivity patients (p < .001). The independent variables BMI and age effects were adjusted according to the logistic regression method with groups. Significant differences were observed between the two groups in the levels of IMA (p = .0005), HOMA-IR (p = .0045), insulin (p = .022), free testosterone (p = .0001) and total testosterone (p = .03) values. By using ROC curve analysis for IMA between study and control groups, cut off point of IMA was calculated as 0.505 U/mL, sensitivity was 80% and specificity was 63%. The area under the curve was 0.926. This shows us that more oxidative stress (OS) occurs in the CC-resistant group. As a reflection of OS in the follicular endocrine, microenvironment may be linked with impaired oocyte developmental competence and embryo quality in association with increased IMA, free testosterone, total testosterone, insulin and HOMA-IR levels. Impact statement What is already known on this subject? In previous studies, IMA was compared between PCOS and control groups. In this study, serum IMA levels were measured in infertile PCOS patients resistant to CC for the first time. What the results of this study add? Serum IMA levels were significantly higher in resistant infertile PCOS patients compared to the control group. This shows us that more OS occurs in the CC-resistant group. What the implications are of these findings for clinical practice and/or further research? IMA will be a guide for PCOS management in patients with CC-resistant PCOS.
Characterisation of neurogenesis and neuronal subtypes in the embryonic zebrafish telencephalon.

The telencephalon is the embryonic structure that in mammals gives rise to the cerebral cortex and the basal ganglia. Despite the manifest differences in size, structure and function of telencephalic derivatives in different vertebrate species, the underlying patterning of the embryonic telencephalon is highly conserved. Very little is known about the development of the zebrafish telencephalon beyond the earliest embryonic stages of neural induction and patterning. One major outstanding question is the mechanism underlying telencephalic eversion, a process that is peculiar to ray-finned fish and that results in the dorsal telencephalon folding out laterally rather than evaginating as it does in most other vertebrate species. I used a range of techniques to monitor proliferation, neurogenesis, and axon extension over the entire period of embryogenesis. This led me to propose a mechanism for an observed rearrangement within the telencephalon between 2 and 3 days post fertilisation (dpf) that may also underlie the eversion process. To characterise the neuronal populations of the dorsal telencephalon I made a careful expression analysis of three LIM-homeobox (Lhx) genes, genes that are involved in neuronal subtype specification in a variety of systems. The Lhx genes lhx1a, lhx1b and lhx5 are expressed in spatially co-ordinated overlapping domains in the dorsal telencephalon and some of these genes are later expressed in the telencephalon-derived olfactory bulb. This suggested a dorsal origin of some olfactory bulb neurons. To further probe the morphogenetic movements and cell migrations that shape the zebrafish telencephalon I performed a fate map of the 1dpf telencephalon. I developed a cell labelling technique that uses the Kaede protein, a green fluorescent protein that is converted to a red fluorescent form on irradiation with UV light. By labelling small groups of cells in the 1dpf telencephalon and following them to their positions at 5dpf I established that the most posterior regions of the dorsal telencephalon contribute to the OB at 5dpf. In addition I identified two populations of migratory cells in the ventral telencephalon, contributing cells to the OB and the dorsal telencephalon respectively. These populations may reveal a previously unknown conservation between fish and tetrapods.
Basilar artery origin of an orbital artery – A rare variant and review of the embryology of the orbital arterial supply

We present a patient with separation of the arterial supply to the globe and the extra-ocular muscles. The ophthalmic artery originates from the typical adult location and supplies only the globe. Arising from the basilar artery was a branch that supplies the extra-ocular muscles. There was no apparent connection between these vessels around the optic nerve and no evidence of supply from the external carotid artery. We discuss the embryology of the ophthalmic artery from the point of view of Padget and Lasjaunias and offer our opinion on the on-going controversy. We believe this is the first case to highlight the trigeminal-primitive maxillary-stapedial anastamotic pathway.
Increased Morbidity and Mortality in Hypertensive Patients With Substance Use Disorders: Electronic Health Record Findings.

OBJECTIVE Substance use disorder (SUD) management by medical providers may be important for patients with comorbid health conditions exacerbated by SUD. This study evaluated potential associations of SUD with morbidity and mortality in a large sample of hypertensive patients. METHOD Analysis of a limited data set was obtained through IBM Watson Health Explorys, a platform integrating data from electronic health records. Matched controls were defined for each of five SUDs: tobacco use disorder (TUD), alcohol use disorder (AUD), cocaine use disorder (COUD), opioid use disorder (OUD), and cannabis use disorder (CUD) using Mahalanobis distance within propensity score calipers. All patients were from The MetroHealth System (Cleveland, OH) and had diagnosed hypertension. SUD group participants had diagnosed abuse/dependence for the substance of interest. Controls for each SUD group had no diagnosis code related to the substance of interest and were selected to match the SUD patients on several factors. Total sample sizes for each SUD-control comparison ranged from 3,176 (CUD) to 49,696 (TUD); proportions of female patients ranged from 31.7% (AUD) to 51.2% (TUD). Outcomes were diagnosis (yes/no) of the following: cerebrovascular accident, myocardial infarction, renal failure, and all-cause mortality. RESULTS Logistic regressions revealed that SUD was significantly associated with cerebrovascular accident (odds ratios [ORs]: TUD = 2.23; AUD = 1.68; COUD = 2.53; OUD = 1.87; CUD = 2.20), renal failure (ORs: TUD = 1.46; COUD = 2.09; OUD = 1.77), myocardial infarction (ORs: TUD = 2.96; AUD = 1.92; COUD = 3.00), and mortality (ORs: TUD = 1.34; AUD = 1.60; COUD = 1.83; OUD = 1.35; CUD = 1.39). CONCLUSIONS Among patients with hypertension, those with SUDs appear to have significantly greater risk for morbidity and mortality, suggesting the importance of managing SUD in hypertensive patients.
Recovery from High pH Exposure in the Rainbow Trout: White Muscle Ammonia Storage, Ammonia Washout, and the Restoration of Blood Chemistry

The physiological responses of rainbow trout were followed during 48 h of high pH (pH 9.5) exposure and a further 48 h of recovery at pH 8.0. High pH exposure temporarily inhibited ammonia excretion (JAmm) and led to a sixfold increase in plasma total ammonia (TAmm) concentration. By 24 h at pH 9.5, JAmm had returned to preexposure (control) rates but plasma TAmm concentration remained elevated. The fish also developed a transient metabolic alkalosis (increased metabolic base) and a sustained respiratory alkalosis (decreased plasma CO₂ tension [PaCO₂]). Plasma Na⁺ and Cl⁻ concentrations were reduced by 5% after 48 h at pH 9.5. An "ammonia washout, " of about 5,000 μmol ․ kg⁻¹ occurred during the first 12 h of the recovery period, with fivefold elevations in JAmm during the first few hours. This ammonia washout was accompanied by a return of plasma TAmm concentration to preexposure levels after 3 h. The amount of excess TAmm excreted by the fish during the washout was about 50-fold greater than extracellular fluid (ECF) TAmm stores. Subsequent experiments indicated the white muscle (WM) intracellular fluid (ICF) compartment had stored at least 40% of the excess TAmm. The TAmm concentrations in the WM ICF were 2.5-fold greater in fish held at pH 9.5 for 48 h than in those held at pH 8.0. Estimates of the ECF and WM ICF pH, NH₃ partial pressures (PNH₃), and NH⁺₄ concentrations indicated the development of favorable ECF:ICF electrochemical gradients for NH⁺₄ uptake, and PNH₃ gradients for NH₃ uptake, by the WM during the initial period of high pH exposure. There was a partial return toward steady state by 48 h. Thus, the WM serves as an "ammonia reservoir" for rainbow trout when plasma TAmm increases owing to temporary reductions in branchial ammonia excretion. The rapid return of other physiological indices such as arterial pH (pHa), PaCO₂, and plasma Na⁺ and Cl⁻ to control levels during recovery (in 3-8 h), as well as constant arterial O₂, tension (Pao₂), suggested that high-pH-induced physiological disturbances are reversible and that there is no high-pH-induced gill histopathology during such short-term exposures.
Resolution of eicosanoid/cytokine storm prevents carcinogen and inflammation-initiated hepatocellular cancer progression

Significance Eicosanoid and cytokine storms are poorly characterized in cancer. Our study demonstrates the environmental carcinogen aflatoxin B1 (AFB1) promotes hepatocellular carcinoma (HCC) by triggering a debris-stimulated proinflammatory and proangiogenic “eicosanoid and cytokine storm” in the tumor microenvironment. The dual COX-2/sEH inhibitor PTUPB prevents AFB1-stimulated HCC growth by increasing macrophage phagocytosis of debris and suppressing the eicosanoid and cytokine storm, thus promoting resolution of inflammation. Enhancing endogenous clearance of debris via eicosanoid regulation, such as dual inhibition of COX-2/sEH, is a strategy to stifle inflammation and thus suppress tumor progression driven by carcinogens. sEH and dual COX-2/sEH inhibitors are in clinical development for multiple inflammatory diseases and thus may be rapidly translated for the prevention and treatment of carcinogen-induced cancers. Toxic environmental carcinogens promote cancer via genotoxic and nongenotoxic pathways, but nongenetic mechanisms remain poorly characterized. Carcinogen-induced apoptosis may trigger escape from dormancy of microtumors by interfering with inflammation resolution and triggering an endoplasmic reticulum (ER) stress response. While eicosanoid and cytokine storms are well-characterized in infection and inflammation, they are poorly characterized in cancer. Here, we demonstrate that carcinogens, such as aflatoxin B1 (AFB1), induce apoptotic cell death and the resulting cell debris stimulates hepatocellular carcinoma (HCC) tumor growth via an “eicosanoid and cytokine storm. ” AFB1-generated debris up-regulates cyclooxygenase-2 (COX-2), soluble epoxide hydrolase (sEH), ER stress-response genes including BiP, CHOP, and PDI in macrophages. Thus, selective cytokine or eicosanoid blockade is unlikely to prevent carcinogen-induced cancer progression. Pharmacological abrogation of both the COX-2 and sEH pathways by PTUPB prevented the debris-stimulated eicosanoid and cytokine storm, down-regulated ER stress genes, and promoted macrophage phagocytosis of debris, resulting in suppression of HCC tumor growth. Thus, inflammation resolution via dual COX-2/sEH inhibition is an approach to prevent carcinogen-induced cancer.
RSA reactivity to parent-child conflict as a predictor of dysregulated emotion and behavior in daily life

Abstract Background Individual variability in tonic (resting) and phasic (reactivity) respiratory sinus arrhythmia (RSA) may underlie risk for dysregulated emotion and behavior, two transdiagnostic indicators that permeate most psychological disorders in youth. The interaction between tonic and phasic RSA may specify unique physiological profiles during the transition to adolescence. The current study utilized clinically referred youth (Mage = 12.03; s.d. = 0.92) to examine baseline RSA, RSA reactivity, and their interaction as predictors of dysregulated emotion and behavior in daily life. Method Participants were 162 youth (47% female; 60% minority) in psychiatric treatment for any mood or behavior problem. RSA was assessed during three, 2-minute baselines and an 8-minute parent-child conflict discussion task. Dysregulated emotion and behavior were assessed during a 4-day ecological momentary assessment protocol that included 10 time-based prompts over a long weekend. Results Greater RSA withdrawal to the conflict was associated with dysregulated basic emotion (sadness, anger, nervousness, stress) in daily life. Two distinct interactions also emerged, such that baseline RSA was related to dysregulated complex emotion (shame, guilt, loneliness, emptiness) and dysregulated behavior as a function of RSA reactivity to conflict. Lower baseline RSA and greater RSA withdrawal were associated with dysregulated complex emotion, while higher baseline RSA and greater RSA withdrawal were associated with dysregulated behavior. Conclusions Findings point to physiological profiles that increase the risk of dysregulated emotion and behavior during the transition to adolescence. Excessive RSA withdrawal uniquely, and in combination with baseline RSA, increased risk for dysregulation in daily life, underscoring the role of autonomic stress responding as a risk factor for psychopathology.
Diffuse Intrinsic Pontine Glioma Cells Are Vulnerable to Mitotic Abnormalities Associated with BMI-1 Modulation

Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor with a median survival of less than 1 year. No effective therapy is currently available, and no therapeutic advances have been made in several decades. We have previously identified BMI-1 as a potential therapeutic target in DIPG and have shown that BMI-1 is highly expressed in DIPG tumors regardless of histone 3 subtype. In the present study, we show that the modulation of BMI-1 leads to DNA damage, M phase cell-cycle arrest, chromosome scattering, and cell death. Interestingly, EZH2 inhibition did not alter these effects. Furthermore, modulation of BMI-1 sensitizes DIPG patient-derived stem-like cells to ionizing radiation (IR). Treatment of DIPG stem-like cells with PTC596, a BMI-1 modulator, and IR impairs the kinetics of DNA damage response (DDR). Both DDR foci formation and resolution were delayed, resulting in further reduction in cell viability compared with either treatment alone. In vivo, treatment of mice bearing DIPG xenografts with PTC596 leads to decreased tumor volume and growth kinetics, increased intratumoral apoptosis, and sustained animal survival benefit. Gene expression analysis indicates that BMI-1 expression correlates positively with DIPG stemness and BMI-1 signature. At the single-cell level, the analysis reveals that BMI-1 pathway is upregulated in undifferentiated cells and positively correlates with stemness in DIPG tumors. Implications: Together, our findings indicate that BMI-1 modulation is associated with mitotic abnormalities, impaired DDR, and cell death, supporting the combination of BMI-1 modulation and radiation as a promising novel therapy for children with DIPG.
Detection of esophageal and glandular stomach calcification in cow (Bos taurus)

Aim: The aims of this study were first to estimate calcification in the esophagus and abomasum of cows and second to quantify its appearance with increasing age using histopathological and immunohistochemical techniques. Materials and Methods: Esophageal and abomasal samples from 24 healthy cows (Bos taurus) were collected. Hematoxylin and eosin, alizarin red, and von Kossa stains were used for histopathological analysis. Histopathological changes were confirmed with immunohistochemical staining, followed by digital image analysis. Results: Histological findings revealed the esophagus and abomasum wall comprised four fundamental layers, the mucosa, submucosa, muscularis, and serosa or adventitia. At 1 year old, calcification was beginning to appear as fine diffused points in mucosa, submucosa, and muscularis of both esophagus and abomasum, appearing as small spots at 2 years old. With advancing age in all animals, this calcification began to appear as medium spots spread throughout all wall layers of these organs at 3 years old. By 4 years old, calcification had evolved into large dark foci spread substantially throughout the tunica submucosa and tunica muscularis. Immunohistochemical results exhibited positive immunoreaction to calcium salts in the esophagus and abomasum layers in all animals, which increased with age. Conclusion: The current study concluded that calcification is a pathological event appearing spontaneously in various types of soft tissue, significantly increasing with age, either because of hypercalcemia and hyperphosphatemia or secondary to other diseases.
In silico molecular investigations of pyridine N-Oxide compounds as potential inhibitors of SARS-CoV-2: 3D QSAR, molecular docking modeling, and ADMET screening

Abstract The new coronavirus SARS-CoV-2 virus is causing a severe pneumonia in human, provoking the serious outbreak epidemic CoV-2. Since its appearance in Wuhan, China on December 2019, CoV-2 becomes the biggest challenge the world is facing today, including the discovery of antiviral drug for SARS-CoV-2. In this study, the potential inhibitory of a class of human SARS inhibitors, namely pyridine N-oxide derivatives, against CoV-2 was addressed by quantitative structure-activity relationship 3 D-QSAR. The reliable CoMSIA developed model of 110 pyridine N-oxide based-antiviral compounds, showed Q2= 0.54 and The molecular surflex-docking was applied to identify the crystal structure of CoV-2 main protease 3CLpro (PDB: 6LU7) and two potentially and largely used antiviral molecules, namely chloroquine, hydroxychloroquine. The obtained free energy affinity and ADMET properties indicate that among the series of model antiviral compounds examined, the new antiviral compound A5 could be an excellent antiviral drug inhibitor against COVID-19. The inhibition activity of pyridine N-oxyde compounds against CoV-2 was compared with the activity of two common antiviral drug, namely chloroquine (CQ) and hydroxychloroquine (HCQ). DFT method was also used to define the sites of reactivity of pyridine N-oxyde derivatives as well as CQ and HCQ. Communicated by Ramaswamy H. Sarma
The Effect of Age and Type of Media on Growth Kinetics of Human Amniotic Fluid Stem cells.

Aim: This study compared growth kinetics of human amniotic fluid stem cells (hAFSCs) in different maternal age groups and two different media of AmnioMAX and Dulbecco's modified Eagle's medium (DMEM). Materials and Methods: Three milliliters of amniotic fluid (AF) was provided from 16 pregnant women who were referred for amniocentesis from 16 to 18 weeks of gestation. Mothers were divided to 20-29 (n = 5), 30-39 (n = 5) and 40-49 (n = 6) years old age groups. AF was immediately centrifuged and the cell pellet was cultured. Cells were characterized morphologically, by flow cytometry and for osteogenic and adipogenic inductions. Population doubling time (PDT) and growth kinetics were determined. AFSCs cultured in AmnioMAX were compared in various age groups. A comparison of growth kinetics of AFSCs cultured in AmnioMAX and DMEM from 40 to 49 years old pregnant women was undertaken. Results: AFSCs were adherent to culture flasks and were spindle shape, and positive for osteogenic and adipogenic inductions and for expression of CD73, CD90 and CD105 markers, but negative for CD34 and CD45. PDT among 20-29, 30-39, and 40-49 years old women was 30.9, 38.3, and 43.9 hours, respectively showing a higher cell proliferation in younger ages. When comparing AmnioMAX and DMEM, PDT was 53 and 96.9 hours, respectively denoting to a higher cell proliferation in AmnioMAX. Conclusions: Higher proliferation and plasticity of hAFSCs were noted in AmnioMAX and in younger mothers' samples. These findings can be added to the literature and open a new avenue in regenerative medicine, when hAFSCs are targeted for cell therapy purposes.
Astrocytic TSPO Upregulation Appears Before Microglial TSPO in Alzheimer’s Disease

Background: In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-translocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation. Objective: The present study evaluates the cellular origin of TSPO alterations in Alzheimer’s disease (AD). Methods: The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects. Results: In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD. Conclusion: These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes.
Peripheral, Interictal Serum S100B Levels are Not Increased in Chronic Migraine Patients.

BACKGROUND The trigemino-vascular system (TVS) plays a key role in migraine pathophysiology. Glial cells are abundant in the TVS system and mainly in the trigeminal ganglion. S100B protein is a calcium-binding protein, found in the cytoplasm of glial cells in the central nervous system, which is released in response to inflammatory stimuli. Previous works analyzing S100B in migraineurs have offered contradictory results. OBJECTIVE In this case-control study, we analyzed serum levels of S100B as a possible biomarker of the glial TVS activation in chronic migraine (CM). PATIENTS AND METHODS The study group consisted of patients attending our clinic with CM and, as control groups, patients with episodic migraine (EM), cluster headache (CH) outside of a bout and healthy volunteers (HV) with no headache history. S100B levels were determined interictally in peripheral blood samples by ELISA. RESULTS We assessed serum samples from 43 patients with CM, 19 with EM, 29 HV (mostly women), and 22 with (CH). S100B levels in CM (mean 22.9 ± 9.8 pg/mL) were not different (P = .727) when compared to EM patients (21.2 ± 9.3 pg/mL), difference of 1.7 (95% CI -5.7 to 8.9), CH patients (22.4 ± 7.8 pg/mL), difference of 0.5 (-5.7 to 6.7), and HV (20.6 ± 8.3 pg/mL), difference of 2.3 (-3.7 to 8.3). CONCLUSION In contrast to other neuropeptides such as calcitonin gene-related-peptide and vasoactive intestinal peptide, which are increased in CM, interictal serum S100B levels are not elevated in these patients. According to our results, S100B levels do not seem to be a useful peripheral biomarker of the glial TVS activation in CM.