Miracle-dz/UniFAR-FTUs huggingface dataset:
Liraglutide overdose: A case report and an updated review

Little is known about liraglutide overdose and in particular its association with hypoglycemia. The aim of this study was to report on an accidental case of liraglutide overdose and to review similar cases in the literature. Here, we report a case of a young female presented with an accidental injection of 18 mg of liraglutide subcutaneously. She presented with relative hypoglycemia with gastrointestinal symptoms that resembled pancreatitis. We concluded with several implications and policies targeting accidental injections from the use of such medication and similar subcutaneous medications in clinical practice.
A rare condition in the third trimester of pregnancy: Ovarian torsion

Ovarian torsion (OT) during pregnancy is a rare condition that can cause maternal and fetal morbidity. Although the etiology of the disease is not fully understood, predisposing factors include increased ovarian size, free mobility, and long pedicle. The incidence of the disease increases after ovarian stimulation for the treatment of fertility. Diagnostic imaging modalities include ultrasonography and magnetic resonance imaging (MRI). A 28-year-old woman with a 33-week pregnancy presented to our emergency department with acute, severe left groin pain. According to the patient's declaration, she had her first pregnancy, which was acquired by intrauterine insemination in another center. Her vital signs were unremarkable except for tachycardia. Physical examination revealed guarding (défense musculaire) and rebound tenderness on the left lower quadrant of the abdomen. Laboratory and imaging studies were performed for the preliminary diagnosis of acute abdomen. She was diagnosed with OT and admitted to the department of obstetrics and gynecology. OT should be included in the differential diagnosis of patients with suspected acute abdomen in advanced stages of pregnancy. In addition, MRI should be used as an alternative diagnostic modality in patients with normal sonographic findings.
Perception of postgraduate students in pharmacology toward animal simulation model

OBJECTIVE: The objective of the study is to evaluate the perception of postgraduate pharmacology students toward computer-simulated method (CSM) in comparison to the prevalent isolated live tissue-based bioassay method. MATERIALS AND METHODS: A questionnaire-based survey was conducted in 30 postgraduate pharmacology students who had used the animal simulation software and had completed at least five isolated tissue experiments. Students' opinions on the usage, logistics, advantages, disadvantages, and usefulness of CSM compared to live animal experiments (LAE) were analyzed. RESULTS: Four tissues were used for LAE, whereas with CSM, students could perform experiments using 11 different tissues. Of the total nine bioassay methods, students had performed six assay methods using both LAE and CSM. Majority of the students (23/30) agreed that CSM reduces anxiety, technical errors and is less time consuming when used before LAE. Most of the students agreed that CSM can be used for difficult, lengthy experiments (19/30), and for UG/PG teaching (19/30). However, opinions regarding replacing LAE with CSM in PG teaching were divided (agree: 7, neutral: 12, and disagree: 12). CONCLUSION: CSM should be integrated alongside LAE to complement, reinforce, and enhance learning from other techniques.
Invasive aspergillosis of tympanomastoid cavity

Invasive aspergillosis of the tympanomastoid cavity is an extremely rare clinical incidence in comparison to the invasive fungal infections of the paranasal sinus and other parts of the body. Delay in the diagnosis and treatment of this rare clinical entity often leads to fatal complications such as skull base osteomyelitis and progressive multiple cranial nerve palsies. The invasive aspergillosis of the tympanomastoid region should be considered as a differential diagnosis for atypical mastoiditis in immunocompromised patients. Here, we report a case of invasive aspergillosis of the tympanomastoid region in a 60-year-old diabetic patient with facial nerve palsy. The diagnosis was done by the demonstration of fungi in the tissue with Gomori methenamine silver staining and confirmed with molecular diagnosis. Surgical debridement of the tympanomastoid region was done along with long-term voriconazole therapy.
DUROPHAGOUS FISH PREDATION TRACES VERSUS TUMBLING-INDUCED SHELL DAMAGE—A PALEOBIOLOGICAL PERSPECTIVE

Abstract: Durophagous (shell-crushing) fish predation is considered to have been a major force of evolutionary change in the history of marine communities. However, because fish predators are very rarely preserved in the act of predation, fossil evidence of such interactions is commonly indirect. For instance, it has been argued that shell fragments with sharp margins constitute a good proxy for durophagy. However, drawing a distinction between predation- and abiotic-induced shell damage can be challenging. Notably, experimental data on shell fragmentation by marine durophagous fishes are almost lacking. In this study, we explore whether shell breakage caused by durophagous marine fishes versus physical factors can be distinguished. Aquarium experiments involving commercially available predatory fishes (Diodon) and thin-shelled invertebrate preys (gastropods Nassarius and brachiopods Frenulina) show that the predation by some fish produces shell fragments displaying extremely low roundness and varying degree of sphericity. Importantly, these fragments typically display sharp and jagged margins, and reveal distortion of individual crystal fibers. Tumbling experiments showed that the disintegration of brachiopod shells proceeds much more rapidly than that of gastropods, which may suggest that abiotic-induced fragmentation of brachiopods may be eventually confused with predation. However, the tumbling-induced fragmentation and damage in both groups are typically characterized by the presence of spherical or discoidal and rounded shell fragments displaying smooth edges (without any microstructural distortion), and numerous abrasive scratches and wear scars on the surface. These data underscore that the shell fragments produced by a durophagous fish, if not subsequently abraded by physical factors, can be recognized in the fossil record.
Management Considerations for Recalcitrant Hyperemesis.

Importance Hyperemesis gravidarum (HEG) affects 0.3% to 3% of pregnancies and requires additional therapies beyond those commonly used for less severe instances of nausea and vomiting of pregnancy (NVP). Differentiating between NVP and HEG is a vital yet challenging function for any obstetrician. The literature for management of HEG is lacking compared with that of NVP. Objective Review etiology of NVP/HEG highlights key considerations in the workup of HEG as they compare to NVP and explore management options for recalcitrant HEG focusing principally on how they affect maternal and fetal outcomes and secondarily on where data are nonprescriptive. Evidence Acquisition This was a literature review primarily using PubMed and Google Scholar. Results Short-course corticosteroids and treatment for Helicobacter pylori have the most favorable risk-reward profiles of the 4 pharmacologic therapies evaluated. Mirtazapine and diazepam may have a place in highly selected patients. If nutritional supplementation is required, enteral nutrition is strictly preferred to parenteral nutrition. Postpyloric feeding approaches are less likely to induce vomiting. Surgically placed feeding tubes are less likely to be dislodged and may be worth the invasive insertion procedure if nasogastric or nasojejunal tubes are not tolerated. Conclusions and Relevance Hyperemesis gravidarum is a diagnosis reserved for refractory cases of NVP and therefore by definition poses treatment challenges. Any clinical presentation that lent itself to prescriptive, algorithmic management would likely fall short of the diagnostic criteria for HEG. However, data can inform management on a patient-by-patient basis or at least help patient and provider understand risks and benefits of therapies reserved for refractory cases.
Tunable metamaterial beam using negative capacitor for local resonators coupling

This article presents a theoretical study of a tunable metamaterial beam for low-frequency broadband vibration suppression. First, the mechanism of employing the shunt circuit technique to realize the internal coupling between two adjacent local resonators is introduced. The working principle of the proposed metamaterial beam by integrating the shunt circuit technique is demonstrated. The stability of the proposed metamaterial beam is then analysed, and the corresponding criterion is proposed. Subsequently, analytical models of the proposed metamaterial beam are developed. The band structures and the transmittances are calculated. The analytical study demonstrates the generation of multiple band gaps using a shunt negative capacitance circuit, which is equivalent to a coupling spring. A parametric study is conducted to investigate the effect of the equivalent coupling stiffness on the band gaps and the corresponding suppression regions. It is found that the band gaps are controllable by varying the equivalent coupling stiffness. Finally, to verify the analytical solutions, a finite-element model of the proposed metamaterial beam is developed. The simulation results confirm the existence of multiple band gaps, which are tunable through modification of the negative capacitance. The broadband vibration-suppression ability of the proposed metamaterial beam is thus confirmed.
Mechanical behavior and pore integration density optimization of switchable hydrogel composite membranes

Switchable hydrogel-layered composite membranes can be used for the analysis of particle size distributions. This functionality is provided by pores with controllable diameter. In order to obtain a device that can be used to measure the cell size distribution in native biological samples, lots of switchable pores are required. In the current work, we model and simulate the mechanical behavior of active composite membranes with switchable pores. This is done in order to find the maximum number of pores that can be integrated into a membrane without cross-influencing effects on the actuation of the pores. Therefore, we investigate (1) the interaction of active pores inside the multifunctional composite and (2) the membrane bending under microfluidic pressure load. We show that through miniaturization, sufficient pores can be added to a permeation control membrane for processing native blood samples. The envisioned device allows a parallelized measurement of cell sizes in a simple lab-on-a-chip setup.
Unsuspected Involvement of Spinal Cord in Alzheimer Disease

Objective: Brain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and vice-versa, it is indeed a very interesting question to assess whether it is affected by atrophy due to a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We, therefore, hypothesize that in Alzheimer’s disease (AD), severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia. Methods: 3DT1 images of 31 AD and 35 healthy control (HC) subjects were processed to calculate volume of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord [per vertebra as well as the C2-C3 pair (CSA23 and CSV23)]. Correlated features (ρ > 0.7) were removed, and the best subset identified for patients’ classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p ≤ 0.05). Linear regression was implemented to assess the explained variance of the Mini-Mental State Examination (MMSE) score as a dependent variable with the best features as predictors. Results: Spinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and gray matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance. Discussion: Our findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. The results show that CSA23, calculated from the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD.
Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

Calreticulin (CALR) has anti-tumor effects by increasing dendritic cell maturation and tumor antigen presentation. However, whether CALR affects macrophages and modulates progression of acute respiratory distress syndrome/acute lung injury (ARDS/ALI) remains unknown. In this study, we discovered that CALR protein was highly expressed in the mice with LPS-induced ALI and CALR expression level was positively correlated to the severity of ALI. Commercial anti-CALR antibody (aCALR) can neutralize recombinant CALR (rCALR) and suppress the expression of TNF-alpha and IL-6 in the rCALR-treated macrophages. Blocking CALR activity by intraperitoneal (i.p.) administration of aCALR significantly suppressed ALI, accompanied with lower total cell counts, neutrophil and T cell infiltration in bronchoalveolar lavage (BAL) and lung tissues. The expression of CXCL15, IL-6, IL-1beta, TNF-alpha, and CALR were significantly reduced, in association with more polarization of Siglec F+CD206+M2 subtype macrophages in the aCALR-treated mice. Pre-depletion of circulating monocytes did not abolish the aCALR-mediated suppression of ALI. Further analysis in bone marrow-derived macrophages (BMDMs) showed that aCALR suppressed the expression of CD80, IL-6, IL-1beta, IL-18, NLRP3, and p-p38 MAPK; but enhanced the expression of CD206 and IL-10. In addition, we observed more expression and phosphorylation of STAT6 in the aCALR-treated BMDM. Lack of STAT6 resulted in comparable and slightly higher expression of CALR, TNF-alpha and IL-6 in the aCALR-treated STAT6-/- BMDMs than the untreated cells. Therefore, we conclude that CALR is a novel biomarker in the evaluation of ALI. Blocking CALR activity by aCALR effectively suppressed ALI independent of circulating monocytes. Siglec F+CD206+M2 subtype macrophages and p38 MAPK/STAT6 signaling pathway played important role in the immune regulation of aCALR. Blocking CALR activity is a promising therapeutic approach in the treatment of ARDS/ALI.
Implementation of a Physiologically Based Pharmacokinetic Modeling Approach to Guide Optimal Dosing Regimens for Imatinib and Potential Drug Interactions in Paediatrics

Long-term use of imatinib is effective and well-tolerated in children with chronic myeloid leukaemia (CML) yet defining an optimal dosing regimen for imatinib in younger patients is a challenge. The potential interactions between imatinib and coadministered drugs in this “special” population also remains largely unexplored. This study implements a physiologically based pharmacokinetic (PBPK) modeling approach to investigate optimal dosing regimens and potential drug interactions with imatinib in the paediatric population. A PBPK model for imatinib was developed in the Simcyp Simulator (version 17) utilizing in silico, in vitro drug metabolism, and in vivo pharmacokinetic data and verified using an independent set of published clinical pharmacokinetic data. The model was then extrapolated to children and adolescents (aged 2–18 years) by incorporating developmental changes in organ size and maturation of drug-metabolising enzymes and plasma protein responsible for imatinib disposition. The PBPK model described imatinib pharmacokinetics in adult and paediatric populations and predicted drug interaction with carbamazepine, a cytochrome P450 (CYP)3A4 and 2C8 inducer, with a good accuracy (evaluated by visual inspections of the simulation results and predicted pharmacokinetic parameters that were within 1.25-fold of the clinically observed values). The PBPK simulation suggests that the optimal dosing regimen range for imatinib is 230–340 mg/m2/d in paediatrics, which is supported by the recommended initial dose for treatment of childhood CML. The simulations also highlighted that children and adults being treated with imatinib have similar vulnerability to CYP modulations. A PBPK model for imatinib was successfully developed with an excellent performance in predicting imatinib pharmacokinetics across age groups. This PBPK model is beneficial to guide optimal dosing regimens for imatinib and predict drug interactions with CYP modulators in the paediatric population.
Epigenetic Agents Trigger the Production of Bioactive Nucleoside Derivatives and Bisabolane Sesquiterpenes From the Marine-Derived Fungus Aspergillus versicolor

Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marine-derived fungus Aspergillus versicolor XS-20090066. By HPLC and 1H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K (1) and L (2) were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (7), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds 1 and 7 displayed antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus with the MIC values of 8–16 μg/mL. Our study revealed that the fungus A. versicolor XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.
Desmetramadol Is Identified as a G-Protein Biased µ Opioid Receptor Agonist

Tramadol is widely used globally and is the second most prescribed opioid in the United States. It treats moderate to severe pain but lethal opioid-induced respiratory depression is uncommon even in large overdose. It is unknown why tramadol spares respiration. Here we show its active metabolite, desmetramadol, is as effective as morphine, oxycodone and fentanyl in eliciting G protein coupling at the human µ opioid receptor (MOR), but surprisingly, supratherapeutic concentrations spare human MOR-mediated βarrestin2 recruitment thought to mediate lethal opioid-induced respiratory depression.
Association Between Reduced Daily Steps and Sarcopenic Obesity in Treatment-Seeking Adults With Obesity

Objectives: Understanding the condition that describes the coexistence of obesity and sarcopenia, termed sarcopenic obesity (SO), is becoming a scientific and clinical priority. In this study, we aimed to assess the prevalence of SO in treatment-seeking adults with obesity and investigate any potential association between SO and a sedentary lifestyle, expressed in terms of daily steps. Methods: In this cross-sectional, prospective observational study, body composition and daily steps measurements were obtained using a segmental body composition analyser (Tanita BC-418) and an Omron HJ-320 pedometer, respectively, in 111 adults of both genders with obesity (body mass index; BMI ≥ 30 kg/m2), referred to the Outpatient Clinic in the Department of Nutrition and Dietetics at Beirut Arab University (BAU) in Lebanon. The participants were then categorized according to the presence of absence of SO, defined as an appendicular lean mass divided by body weight (ALM/weight) × 100%) of less than 23.40 and 29.60 in females and males, respectively. Results: Fifty-five of the 111 participants with obesity, with a mean age of 39.62 ± 16.55 years and a mean BMI of 38.05 ± 5.33 kg/m2 met the criteria for SO and displayed a significantly higher prevalence of inactivity (<5,000 daily steps), i.e., nearly double (54.5% vs. 32.1%; p = 0.017) and they had a lower mean number of daily steps than those in the group without SO (5,279 ± 2,641 vs. 6,732 ± 2,989; p = 0.008). Linear regression analysis showed that SO is associated with a lower number of daily steps by 1,421 (β = −1421.4; −2508.9, −333.9; p = 0.011) after adjusting for age, gender employment and the presence of cardiometabolic disease. Conclusion: Sarcopenic obesity affects nearly 50% of treatment-seeking adults with obesity. Moreover, it seems to be associated with a lower number of daily steps and a sedentary lifestyle. Future studies are needed to clarify whether this may influence clinical outcomes. If this is shown to be the case, weight management programmes should incorporate additional physical activity strategies in this population.
Differential Expression of HERV-W in Peripheral Blood in Multiple Sclerosis and Healthy Patients in Two Different Ethnic Groups

Overexpression of the Human endogenous retrovirus W (HERV-W) group of inherited retroviruses has been consistently linked with Multiple Sclerosis (MS). However most of the studies on this link have focused on European genetic groups with a very high risk of MS and it is not clear that this relationship holds for all ethnic groups. This study examined via qPCR the RNA expression in peripheral blood of HERV-W (the multiple sclerosis associated retrovirus variant MSRV) of MS patients and healthy controls from two ethnic groups with very different risk rates of MS. Population one was derived from the UK with a Northern European genetic background and an MS risk rate of 108/100,000, population two was derived from the republic of Tatarstan, Russian Federation, with a mixed Russian (Eastern European) and Tartar (Turkic or Volga/Urals) population with an MS risk rate of 21-31/100,000. The Russian population displayed a significantly higher basal level of expression of MSRV in both healthy and MS individuals when compared to the British control population with a trend in the Russian population towards higher expression levels in MS patients than healthy patients.