Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity and Efficacy of Insulin Glargine Biosimilar Ezelin versus Originator Insulin Glargine in Patients with Type 2 Diabetes

Purpose To compare the immunogenicity and efficacy of insulin glargine biosimilar Ezelin (EZL) versus originator insulin glargine Lantus (LAN) as a reference basal insulin in patients with type 2 diabetes (T2D). Patients and Methods This was a randomized, multicenter, open-label, 24-week study in insulin-naïve patients with T2D, with HbA1c of >7.0%. We randomly assigned 133 eligible patients to receive either EZL or LAN. Baseline characteristics, including insulin autoantibody (IAA), zinc transporter 8 (ZnT8) antibody, HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), AST, ALT, BUN, eGFR, and oral antidiabetic drugs, were obtained before starting insulin treatment. After starting treatment, insulin dose was titrated to achieve FPG target along with oral antidiabetic drugs. Patients were given home glucometer and assisted to record plasma glucose measurement and adverse event (AE). Every month, patients came to the diabetes clinic and performed a regular physical examination and intensifying treatment if needed. Out of the 133 randomized patients, only 122 completed the study and can be examined for their IAA and ZnT8 after 6 months of treatment. The study was registered in clinicaltrials.gov, NCT03352674. Results There is a similar proportion of patients with changes of IAA from baseline: 1 out of 58 (1.7%) patients receiving EZL versus 1 out of 64 (1.6%) patients receiving LAN (p = 1.000). One patient in the EZL group (1.7%) versus none in the LAN group experienced a change of ZnT8 antibody from baseline. Similar glucose control in EZL versus LAN was determined by the change in HbA1c, FPG, and 2hPPG (−2.0%, −67.46 mg/dL, and −76.51 mg/dL in the EZL group versus −1.7%, −58.11 mg/dL, and −70.03 mg/dL in the LAN group). There were six events of documented hypoglycemia in the EZL group versus five events in the LAN group. No patients experienced diabetic ketoacidosis during the study. Conclusion Overall, insulin glargine biosimilar EZL and originator insulin glargine LAN have shown a similar immunogenicity profile, as well as efficacy in providing glucose control and safety findings in T2D populations.
Comparison of Different Ultrasound Classification Systems of Thyroid Nodules for Identifying Malignant Potential: A Cross-sectional Study

OBJECTIVE: In our organization, it has been necessary in our organization to calculate the risk categories according to the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) classification systems for each patient, from the year 2019; these are also required to be registered in the database. This creates a barrier to medical collaboration in everyday radiological practice because using multiple rating systems can be confusing for both readers and patients. For the change in routine practice, this study aimed to compare diagnostic parameters of the ATA, AACE/ACE/AME, and ACR TIRADS classification systems for the detection of suspicious thyroid nodule(s) considering the results of fine-needle aspiration cytopathology as the reference standard. METHODS: Data on ultrasound characteristics (2,000 nodules) and fine-needle aspiration cytopathology (39 nodules) were included in the analysis. The decision making of fine-needle aspiration biopsies was evaluated from the ultrasound characteristics as per the ATA, AACE/ACE/AME, and ACR TIRADS classification systems. RESULTS: The ATA, AACE/ACE/AME, and ACR TIRADS recommended 26, 32, and 37 nodules for fine-needle aspiration biopsies, respectively. Considering the results of fine-needle aspiration cytopathology as the reference standard, the ATA, AACE/ACE/AME, and ACR TIRADS classification systems had 0.993, 0.996, and 0.998 sensitivity, respectively. The accuracies were 0.641, 0.795, and 0.923, respectively. CONCLUSION: The ACR TIRADS classification system is less invasive and can identify suspicious nodules more accurately than that of ATA and AACE/ACE/AME.
Effects of Raloxifene Combined with Low-dose Conjugated Estrogen on the Endometrium in Menopausal Women at High Risk for Breast Cancer

OBJECTIVES: To compare the effects of low-dose conjugated estrogen (CE), raloxifene, and the combination thereof on the endometrium of postmenopausal women. METHODS: Postmenopausal women between 45 and 60 years of age, with Gail score≥1.67 and no endometrial disorders, were randomly assigned to receive low-dose CE (0.3 mg), raloxifene (60 mg), or combined therapy for 1 year. Transvaginal ultrasound was performed at baseline and every 3 months; the Kupperman Index was assessed at baseline and every 6 months. Endometrial biopsies were performed if endometrial thickness (ET) was ≥5 mm or if vaginal bleeding occurred. The primary outcome was the occurrence of ET≥5 mm over the one-year period. RESULTS: Seventy-three women were randomly assigned and analyzed on an intent-to-treat basis. Eight, three, and four women in the CE, raloxifene, and combination groups, respectively, exhibited ET≥5 mm. No genital bleeding was reported in the combination group. Endometrial biopsy revealed atrophy or polyps in all groups, with one patient in the CE group exhibiting a proliferative endometrium without atypia. At 6 months, there was a progressive increase in mean ET in the CE group, but not in the other two groups, with statistically significant differences at 6, 9, and 12 months. Mean scores for vasomotor symptoms and Kupperman Index favored the CE and combination groups over raloxifene. CONCLUSION: Combined raloxifene and low-dose CE decreased the severity of menopausal symptoms to a similar extent as CE alone and had similar effects as raloxifene alone on the endometrium.
Validation of ICD-10-CM Diagnosis Codes for Identification of Patients with Acute Hemorrhagic Stroke in a National Health Insurance Claims Database

Purpose The performance of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for identifying acute hemorrhagic stroke in Taiwan’s National Health Insurance claims database has not been assessed. This study aimed to construct and validate the case definitions for acute hemorrhagic stroke based on ICD-10-CM diagnostic codes. Patients and Methods From January 2018 to December 2019, all inpatient records with ICD-10-CM code of I60 or I61 in any field of the discharge diagnoses were retrieved from the hospitalization claims data and all hospitalizations with a final diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) were identified from the stroke registry databases. The clinical diagnosis in the stroke registry was treated as the reference standard. For hospitalizations not recorded in the stroke registry, manual review of the medical records and images was done to ascertain the diagnosis. The positive predictive value (PPV) and sensitivity of various case definitions for acute hemorrhagic stroke were estimated. Results Among the 983 hospitalizations, 860, 111, and 12 were determined to be true-positive, false-positive, and false-negative episodes of acute hemorrhagic stroke, respectively. The PPV and sensitivity of the ICD-10-CM codes of I60 or I61 for identifying acute hemorrhagic stroke were 88.6% and 98.6%, respectively. The PPV increased to 98.2%, whereas the sensitivity decreased to 93.1% when acute hemorrhagic stroke was defined as hospitalizations in which the primary diagnosis field contained I60 or I61. Hemorrhagic transformation of ischemic stroke and concomitant cerebrovascular diseases other than SAH or ICH were the main reasons for a false-positive and false-negative diagnosis of acute hemorrhagic stroke, respectively. Conclusion This study demonstrated the performance of ICD-10-CM codes for identifying acute hemorrhagic stroke and may offer a reference for future claims-based stroke studies.
Chronic Obstructive Pulmonary Disease Treatment and Pharmacist-Led Medication Management

Abstract Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death across the globe. Its repeated exacerbation will seriously worsen the quality of life, aggravate the patients’ symptoms, and bring a heavy burden on the patients and the society. Understanding the current status of drug therapy and the role of pharmaceutical care is essential for the management of COPD. In addition to the drugs already on the market, recent clinical trials also show that emerging novel drugs for treating COPD are being developed to prevent the symptoms, reduce the frequency of acute exacerbation, and improve the quality of life. Recent progress in new drug research should lead to novel treatment options for COPD patients in future clinical practice. The pharmaceutical care has shown significantly favourable impacts on addressing drug-related problems, supporting its vital role in the management of COPD, especially when there are a wide range of therapeutic agents. This review not only provides an overview of current treatment strategies but also further underlines the importance of new drug development and pharmaceutical care for patients with COPD.
Clinical Manifestations, Fluid Changes and Neuroimaging Alterations in Patients with General Paresis of the Insane

Purpose We aim to study the clinical manifestations, fluid changes and neuroimaging alterations in patients with general paresis of the insane (GPI). Methods A total of 119 patients suffering from GPI recruited in Beijing Ditan Hospital, Capital Medical University from 2010 to 2020 were retrospectively analyzed. Results In 119 GPI patients, 103 cases (86.6%) were male. Misdiagnosed rate was up to 83.2%, schizophrenia and mood disorders were the most common misdiagnosed diseases. Duration from symptom onset to the final confirmed diagnosis was 10.4±12.9 months. The main clinical manifestations included cognitive impairment (114 cases, 95.8%) and neuropsychiatric symptoms (107 cases, 90.0%). The cognitive domains including the delayed recall, visuospatial/executive function and language ability indicated by MoCA score were damaged severely. Rapid plasma regain (RPR) of all GPI patients was 100% positive in serum and 89.9% positive in cerebral spinal fluid (CSF). The white blood cell (WBC) number in CSF was between 6 and 50/μL in 73 GPI patients (61.3%). The protein level was between 45.1 and 70mg/dL in 47 cases (39.5%). In the 110 cases, 96 cases (87.3%) were abnormal indicated by cerebral atrophy mostly located in the anterior brain and abnormal signals distributed in various regions of the brain mostly in the frontal lobe and temporal lobe. Conclusion The symptoms of GPI were complex and easy to misdiagnose. The clinicians were still short of vigilance for neurosyphilis. We should expand serologic testing for syphilis especially in patients with cognitive impairment and neuropsychiatric symptoms. We suggest syphilis curricula in the training program of the clinicians especially for neurologist and psychiatrist.
Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092

Background: Severe acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM. Materials and methods: Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing. Intensive PK sampling was performed at weeks 1, 12, and 24. Plasma drug concentrations were measured using liquid chromatography tandem mass spectrometry. Steady-state mean area under the curve (AUC0–12h) and clearance (CL/F) for each drug were compared. Grade ≥3 adverse events were compared between cohorts. Results: Fifty-two children were enrolled across 5 sites in Africa with 44% (23/52) female, median age 19 months (Q1, Q3: 13, 25). Twenty-five children had SAM with entry median weight-for-height Z-score (WHZ) −3.4 (IQR −4.0, −3.0) and 27 non-SAM had median WHZ −1.0 (IQR −1.8, −0.1). No significant differences in mean AUC0–12h or CL/F were observed (P ≥ 0.09) except for lower 3TC AUC0–12h (GMR, 0.60; 95% CI, 0.4–1.0; P = 0.047) at week 12, higher ZDV AUC0–12h (GMR, 1.52; 1.2–2.0; P = 0.003) at week 24 in the SAM cohort compared with non-SAM cohort. Treatment-related grade ≥3 events did not differ significantly between cohorts (24.0% vs. 25.9%). Conclusion: PK and safety findings for ZDV, 3TC, and LPV/r support current WHO weight band dosing of syrup formulations in children with SAM.
Ultraviolet Absorption Cross-Sections of Ammonia at Elevated Temperatures for Nonintrusive Quantitative Detection in Combustion Environments

Ammonia (NH3) is regarded as an important nitrogen oxides (NOx) precursor and also as an effective reductant for NOx removal in energy utilization through combustion, and it has recently become an attractive non-carbon alternative fuel. To have a better understanding of thermochemical properties of NH3, accurate in situ detection of NH3 in high temperature environments is desirable. Ultraviolet (UV) absorption spectroscopy is a feasible technique. To achieve quantitative measurements, spectrally resolved UV absorption cross-sections of NH3 in hot gas environments at different temperatures from 295 K to 590 K were experimentally measured for the first time. Based on the experimental results, vibrational constants of NH3 were determined and used for the calculation of the absorption cross-section of NH3 at high temperatures above 590 K using the PGOPHER software. The investigated UV spectra covered the range of wavelengths from 190 nm to 230 nm, where spectral structures of the A ∼ 1 A ″ 2 X ∼ 1 A ' 1 transition of NH3 in the umbrella bending mode, v2, were recognized. The absorption cross-section was found to decrease at higher temperatures. For example, the absorption cross-section peak of the (6, 0) vibrational band of NH3 decreases from ∼2 × 10−17 to ∼0.5 × 10−17 cm2/molecule with the increase of temperature from 295 K to 1570 K. Using the obtained absorption cross-section, in situ nonintrusive quantification of NH3 in different hot gas environments was achieved with a detection limit varying from below 10 parts per million (ppm) to around 200 ppm as temperature increased from 295 K to 1570 K. The quantitative measurement was applied to an experimental investigation of NH3 combustion process. The concentrations of NH3 and nitric oxide (NO) in the post flame zone of NH3–methane (CH4)–air premixed flames at different equivalence ratios were measured. Graphical Abstract
Herp knockout protects against nonalcoholic fatty liver disease in mice on a high fat diet

This study aims to discover the role of Homocysteine‐induced ER protein (Herp) deficiency in high‐fat diet (HFD)‐induced nonalcoholic fatty liver disease (NAFLD). After 8 weeks of feeding with normal‐fat diet (NFD) or HFD, WT (wild type) and Herp−/− mice were measured for the body weight, liver weight and serum biochemical parameters. HE, Oil Red O, and Sirius red stainings were used to evaluate the histopathological changes of liver tissues. QRT‐PCR, Western blotting and Immunohistochemistry were employed to detect the mRNA and protein expression. TUNEL staining was used to observe the hepatocyte apoptosis. Herp knockout reduced the liver/body weight ratio of mice fed with HFD with the decreased serum levels of TG, TC, HDL, LDL, GGT, Hcy, ALT, and AST. Besides, WT mice fed with HFD presented obvious steatosis, inflammation and hepatocytes ballooning, which was relieved in Herp−/− mice. HFD‐induce NFALD mice demonstrated increased Oil Red, Sirius red, and α‐SMA staining than NFD‐induced mice, but mice in the Herp−/− + HFD group was lower than the WT + HFD group. HFD‐induce NFALD mice showed up‐regulated expression of Grp78, Chop, and Atf4 in liver tissues when compared with NFD fed mice. However, regarding to the mice fed with HFD, Herp deficiency decrease in the expression of Grp78, Chop, and Atf4 in liver tissues with the reduced hepatocyte apoptosis. Herp was highly expressed in HFD‐induced NAFLD mice. Herp knockout improved liver function and histopathological conditions with the decreased hepatocyte apoptosis and endoplasmic reticulum stress (ERS) of HFD‐induce NFALD mice.
Androgens, the kidney, and COVID-19: an opportunity for translational research

Coronavirus disease 2019 (COVID-19) has reached pandemic proportions affecting millions of people worldwide. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the COVID-19. Epidemiological reports showed that the severity of SARS-CoV-2 infection is associated with preexisting comorbidities such as hypertension, diabetes mellitus, cardiovascular diseases and chronic kidney diseases; all of which are also risk factors for acute kidney injury (AKI). The kidney has emerged as a key organ affected by the SARS-CoV-2. AKI is associated with an increased morbidity and mortality in COVID-19 patients. Male sex is an independent predictor for AKI and increased death rate has been reported in male patients with COVID-19 worldwide. The mechanism(s) that mediate the sex discrepancy in mortality due to COVID-19 remain unknown. ACE2 is the receptor for SARS-CoV-2. Alteration in the ACE/ACE2 ratio had been implicated in renal diseases. The aim of this perspective is to discuss data that suggest that androgens, via alterations in the intra-renal renin angiotensin system, impair renal hemodynamic predisposing patients to AKI during COVID-19 infection, which could explain the higher mortality observed in men with COVID-19. Clinicians should ensure early and effective cardiometabolic control for all patients to ameliorate the compensatory elevation of ACE2 and alterations in the ACE/ACE2 ratio. A better understanding of the role of androgens in SARS-CoV-2 associated AKI and mortality is imperative. The kidney could constitute a key organ that may explain the sex disparities of the higher mortality and worst outcomes associated with COVID-19 in men.
High-Fidelity Numercial Simulations of Impinging Jet Atomization

High fidelity numerical simulations are performed to study the atomization process of impinging jets over a broad range of operating conditions. An improved volume-of-fluid (VOF) method augmented with adaptive mesh refinement (AMR) is used to simulate the formation and breakup of the liquid sheet formed by two impinging jets. In addition, a thickness-based refinement method is developed and implemented to automatically and efficiently resolve the drastic changing of requested grid resolution. The behaviors in various Reynolds and Weber number regimes are studied systemically. The predicted liquid sheet topology, atomization, and droplet size distribution agree well with experimental measurements. Several different patterns of sheet and rim configurations are obtained, including liquid chain, closed rim, fish-bone, disintegrating sheet, disintegrating rim and impact wave. The instability mechanisms of sheets and rims are studied based on the concepts of absolute and convective instabilities. New knowledge is acquired about the onset of sheet and rim instabilities. This locking-on feature of Strouhal number of impact wave is found based on the previous detailed study. Finally, schematic diagrams of all kinds of instabilities happens in impinging jet atomization are obtained. I. INTRODUCTION Collision between two cylindrical jets is one of the generic configurations for the generation of liquid sheets, the dynamics and stability of which have attracted a great deal of attention due to their relevance to the spray atomization and combustion in liquid propellant engines. [1-4] The impingement of liquid jets is a very efficient method for atomization and mixing whereby the dynamic head of the propellant is used to destabilize an opposing liquid propellant stream. This in turn results in fragmenting the liquid into ligaments and droplets. [5] The oblique collision of two cylindrical laminar jets at low jet velocities leads to the liquid flowing outward from the impingement point, producing a leaf-shaped expanding sheet which lies in a plane perpendicular to the plane containing the two liquid jets,. A rich variety of flow structures, from single oscillating jet obtained at low flow rates, to the violent disintegration of flapping sheets obtained at higher flow rates, have been observed depending on the Weber and Reynolds numbers of the jets. In the specific usage of liquid propellant rocket engine, the liquid sheet shows full-developed violent breakup with quickly growing waves. The liquid sheet destabilizes, breaks and eventually disintegrates into ligaments or droplets under the influence of surface tension, viscous, inertial, and aerodynamic forces. The impinging jets can provide rapid mixing and atomization. This unstable hydrodynamic wave is usually called impact wave[6]. Impact wave dominates the breakup and atomization process in most rocket combustors using impinging jet injectors. [7] Different from another capillary wave, impact wave shows a nonlinear behavior that cannot be described linear stability analysis.
Investigation of COVID-19 Fear, Well-Being and Life Satisfaction in Turkish Society

ABSTRACT This study aims to examine the relationship between the fear of COVID-19, well-being, and life satisfaction perceptions of people aged 18 and over living in Turkey. Another aim of the study is to reveal whether the participants’ COVID-19 fear, well-being, and life satisfaction perceptions change according to various socio-demographic characteristics. In the study, data was collected from 3111 people through a questionnaire created via Google Form on the internet. The data collection process was carried out on April 11–16, 2020. The results obtained from the study showed that COVID-19 fear status and life satisfaction levels of the participants were moderate while the well-being levels were low. According to the result of the regression analysis, it was determined that the fear of COVID-19 explained 11.3% of the total variance on well-being and 1.3% of the total variance on life satisfaction; and well-being explained 19.4% of the total variance on life satisfaction. Furthermore, it was determined that the scores of the participants regarding the fear of COVID-19 showed statistically significant differences according to age, gender, education level, working status, having any chronic diseases, regular drug use, and income level.