Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences of the Structure of Immune Regulatory Cell Populations between Cellular Material from Sonographically Detected Focal Thyroid Lesions and Peripheral Blood in Humans

Focal thyroid lesions are common ultrasound findings with the estimated prevalence up to 67% of the population. They form characteristically enveloped regions with individual encapsulated microenvironment that may involve the specific distribution of immune system compounds—especially antigen presenting cells (APC). We analyzed and compared the most potent APC—plasmacytoid and conventional dendritic cells (DCs) subpopulations and three monocyte subpopulations as well as other immune cells—in peripheral blood and local blood of thyroid gland obtained parallelly in patients with focal thyroid lesions using flow cytometry. The analysis revealed significant differences in the distribution of main subsets of assessed cells between peripheral blood and biopsy material. The results support the existence of local, organ-specific immune reaction control networks within thyroid nodules.
Patient perception of obesity versus physician documentation of obesity: A quality improvement study

As the prevalence of obesity increases, the prevalence of associated comorbid diseases, obesity‐related mortality rates and healthcare costs rise concordantly. Two main factors that hinder efforts to treat obesity include a lack of recognition by patients and documentation by physicians. This study evaluates the relationship between patient perception of obese weight and physician documentation of obesity. This quality improvement observational study surveyed patients of an academic internal medicine clinic on their perception of obesity. Responses were compared to longitudinal physician documentation of obesity and body mass index (BMI). A total of 59.9% of patients with obesity perceived their weight as obese. While 33.7% of patients with a BMI of 30 to 34.9 kg/m2 perceived themselves as having obesity, 71.4% of patients with a BMI of 45 to 49.9 kg/m2 perceived themselves as having obesity. A total of 42.4% of patients with obesity had physician documentation of obesity in the last year. While 25% of patients with a BMI of 30 to 34.9 kg/m2 had physician documentation of obesity, 85.7% of patients with a BMI of 45 to 49.9 kg/m2 had physician documentation of obesity. For patients with a BMI ≥50 kg/m2, 52.9% perceived their weight to be obese and 76.5% had physician documentation of obesity in the last year. Both patient perception and physician documentation of obesity were significantly less than the prevalence of obesity. Patient perception of obesity and provider documentation of obesity increased as BMI increased until a BMI ≥50 kg/m2. Both patients and providers must improve recognition of this disease.
PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis

ABSTRACT A centrosome consists of a pair of centrioles and pericentriolar material (PCM). We manipulated expression of PCNT, a key PCM protein, and investigated roles of PCM in centriole behavior during mitosis. Deletion of PCNT had little effect on interphase centrosomes. However, centrioles in PCNT-deleted mitotic cells prematurely separated and frequently amplified, revealing that centrioles are limited within the spindle poles by PCNT during mitosis. It is known that specific cleavage of PCNT is necessary for centriole separation during mitotic exit. We observed delayed centriole separation in the G0 phase when a non-cleavable mutant form of PCNT was removed or when PCNT was artificially cleaved by TEV protease. Furthermore, a daughter centriole converts to a mother centriole only after experiencing both mitotic exit and specific PCNT cleavage. Based on these results, we propose that a centriole pair disengages upon entering mitosis but remains associated with the surrounding PCM proteins throughout mitosis. During mitotic exit, specific cleavage of PCNT induces PCM disintegration. As a result, a daughter centriole separates from the mother centriole and converts to a young mother centriole. Summary: Entering mitosis, centriole pairs disengage but remain associated with surrounding PCM proteins. On mitotic exit, specific cleavage of PCNT induces PCM disintegration, allowing separation of mother and daughter centrioles.
Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study

In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double‐blinded, placebo‐controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients ≥50 years with type 2 diabetes receiving anti‐diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of ≥50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow‐up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
Maternal and Congenital Toxoplasmosis: Diagnosis and Treatment Recommendations of a French Multidisciplinary Working Group

Women infected with toxoplasmosis during pregnancy do not present symptoms in most cases, but the consequences of the congenital infection may be severe for the unborn child. Fetal damage can range from asymptomatic to severe neurological alterations to retinal lesions prone to potential flare up and relapses lifelong. Despite the possible severity of outcome, congenital toxoplasmosis (CT) is a neglected disease. There is no consensus regarding screening during pregnancy, prenatal/postnatal treatment or short or medium term follow-up. Since 1992, France has offered systematic serological testing to non-immune pregnant women, monthly until delivery. Any maternal infection is thus detected; moreover, diagnosis of congenital infection can be made at birth and follow-up can be provided. “Guidelines” drawn up by a multidisciplinary group are presented here, concerning treatment, before and after birth. The recommendations are based on the regular analysis of the literature and the results of the working group. The evaluation of the recommendations takes into account the robustness of the recommendation and the quality of the evidence.
Targeting ALK in Cancer: Therapeutic Potential of Proapoptotic Peptides

ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more. This makes ALK an attractive target for cancer therapy. Since ALK–driven tumors are dependent for their proliferation on the constitutively activated ALK kinase, a number of tyrosine kinase inhibitors have been developed to block tumor growth. While some inhibitors are under investigation in clinical trials, others are now approved for treatment, notably in ALK-positive lung cancer. Their efficacy is remarkable, however limited in time, as the tumors escape and become resistant to the treatment through different mechanisms. Hence, there is a pressing need to target ALK-dependent tumors by other therapeutic strategies, and possibly use them in combination with kinase inhibitors. In this review we will focus on the therapeutic potential of proapoptotic ALK-derived peptides based on the dependence receptor properties of ALK. We will also try to make a non-exhaustive list of several alternative treatments targeting ALK-dependent and independent signaling pathways.
Beyond Opioids for Pain Management in Adult Critically Ill Patients

Critically ill patients commonly experience pain, and the provision of analgesia is an essential component of intensive care unit (ICU) care. Opioids are the mainstay of pain management in the ICU but are limited by their adverse effects, risk of addiction and abuse, and recent drug shortages of injectable formulations. A multimodal analgesia approach, utilizing nonopioid analgesics as adjuncts to opioid therapy, is recommended since they may modulate the pain response and reduce opioid requirements by acting on multiple pain mediators. Nonopioid analgesics discussed in detail in this article are acetaminophen, α-2 receptor agonists, gabapentinoids, ketamine, lidocaine, and nonsteroidal anti-inflammatory drugs. This literature review describes the clinical pharmacology, supportive ICU and relevant non-ICU data, and practical considerations associated with the administration of nonopioid analgesics in critically ill adult patients.
Direct Intramyocardial Mesenchymal Stromal Cell Injections in Patients with Severe Refractory Angina: One-Year Follow-Up

In patients with stable coronary artery disease (CAD) and refractory angina, we performed direct intramyocardial injections of autologous mesenchymal stromal cells (MSC) and followed the safety and efficacy of the treatment for 12 months. A total of 31 patients with stable CAD, moderate to severe angina, normal left ventricular ejection fraction, and no further revascularization options were included. Bone marrow MSCs were isolated and culture expanded for 6–8 weeks and then stimulated with vascular endothelial growth factor (VEGF) for 1 week. The 12-month follow-up demonstrated that it was safe to culture expand MSCs and use the cells for clinical treatment. The patients' maximal metabolic equivalent (MET) during exercise increased from 4.23 MET at baseline to 4.72 MET at 12-month follow-up (p < 0.001), Canadian Cardiovascular Society Class (CCS) was reduced from 3.0 to 0.8 (p < 0.001), angina attacks per week from 13.8 to 3.2 (p < 0.001), and nitroglycerin consumption from 10.7 to 3.4 per week (p < 0.001). In addition, Seattle Angina Questionnaire (SAQ) evaluations demonstrated highly significant improvements in physical limitation, angina stability, angina frequency, and quality of life (p < 0.001 for all). It is safe in the intermediate/long term to treat patients with stable CAD using autologous culture expanded MSCs. Previously reported, early and highly significant improvements in exercise capacity and clinical symptoms persist after 12 months. The results are encouraging, and a larger controlled study is warranted.
A Microfluidic Micropipette Aspiration Device to Study Single-Cell Mechanics Inspired by the Principle of Wheatstone Bridge

The biomechanical properties of single cells show great potential for early disease diagnosis and effective treatments. In this study, a microfluidic device was developed for quantifying the mechanical properties of a single cell. Micropipette aspiration was integrated into a microfluidic device that mimics a classical Wheatstone bridge circuit. This technique allows us not only to effectively alter the flow direction for single-cell trapping, but also to precisely control the pressure exerted on the aspirated cells, analogous to the feature of the Wheatstone bridge that can precisely control bridge voltage and current. By combining the micropipette aspiration technique into the microfluidic device, we can effectively trap the microparticles and Hela cells as well as measure the deformability of cells. The Young’s modulus of Hela cells was evaluated to be 387 ± 77 Pa, which is consistent with previous micropipette aspiration studies. The simplicity, precision, and usability of our device show good potential for biomechanical trials in clinical diagnosis and cell biology research.
Systematic scoping review of frameworks used to develop rehabilitation interventions for older adults

Objectives Rehabilitation interventions for older adults are complex as they involve a number of interacting components, have multiple outcomes of interest and are influenced by a number of contextual factors. The importance of rigorous intervention development prior to formal evaluation has been acknowledged and a number of frameworks have been developed. This review explored which frameworks have been used to guide the development of rehabilitation interventions for older adults. Design Systematic scoping review. Setting Studies were not limited for inclusion based on setting. Participants Studies were included that featured older adults (>65 years of age). Interventions Studies were included that reported the development of a rehabilitation intervention. Primary and secondary outcome measures Data were extracted on study population, setting, type of intervention developed and frameworks used. The primary outcome of interest was the type of intervention development framework. Results Thirty-five studies were included. There was a range of underlying medical conditions including mild cognitive impairment and dementia (n=5), cardiac (n=4), stroke (n=3), falls (n=3), hip fracture (n=2), diabetes (n=2), breast cancer (n=1), Parkinson’s disease (n=1), depression (n=1), chronic health problems (n=1), osteoarthritis (n=1), leg ulcer (n=1), neck pain (n=1) and foot problems (n=1). The intervention types being developed included multicomponent, support based, cognitive, physical activities, nursing led, falls prevention and occupational therapy led. Twelve studies (34%) did not report using a framework. Five frameworks were reported with the Medical Research Council (MRC) framework for developing and evaluating complex interventions being the most frequently cited (77%, n=17). Conclusion At present, the MRC framework is the most popular for developing rehabilitation interventions for older adults. Many studies do not report using a framework. Further, specific guidance to assist this complex field of rehabilitation research is required.
Nanoemulsions for “Nose-to-Brain” Drug Delivery

The blood–brain barrier (BBB) plays a fundamental role in protecting the brain from toxic substances and therefore also controls and restricts the entry of therapeutic agents. The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB. Through the nasal route, the drug can access the brain directly along the trigeminal and olfactory nerves, which are located in the upper part of the nasal cavity. Nanoemulsions are formulations belonging to the field of nanomedicine. They consist of emulsions (commonly oil in water) stabilized by one or more surfactants—and eventually co-surfactants—delivered in droplets of small dimensions (sizes of 100–300 nm or less) with a high surface area. A mucoadhesive polymer such as chitosan can be added to the formulation to impair rapid nasal clearance. Nanoemulsions represent promising formulations to deliver drugs directly into the brain through the intranasal route. Therefore, they can be used as a possible alternative to oral administration, avoiding problems such as low solubility in water, poor bioavailability, enzymatic degradation and slow onset of action. This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.
Transactivation domain of Krüppel‐like factor 15 negatively regulates angiotensin II–induced adventitial inflammation and fibrosis

Krüppel‐like factor (KLF) 15 has emerged as a critical regulator of fibrosis in cardiovascular diseases. However, the precise role that KLF15 and its functional domain played in adventitial inflammation and fibrosis remains unclear. This study aims to investigate the role of the transactivation domain (TAD) of KLF15 in angiotensin II (Ang II)–induced adventitial pathologic changes. KLF15 expression was decreased in the vascular adventitia of Ang II–infused mice (1000 ng/kg/min, 14 d) and in adventitial fibroblasts (AFs) stimulated by Ang II (10−7 M). Adenovirus‐mediated KLF15 overexpression normalized Ang II–induced vascular hypertrophy, increased collagen deposition, macrophage infiltration, and CCL2 and VCAM‐1 expression. Interestingly, KLF15‐ΔTAD (KLF15 with deletion of TAD at amino acids 132–152) overexpression showed no effect on the above pathologic changes. Similarly, perivascularly over‐expression of KLF15 but not KLF15‐ΔTAD in carotid arteries also attenuated Ang II–induced vascular inflammation and fibrosis. Furthermore, KLF15 overexpression after Ang II infusion rescued Ang II–induced vascular remodeling. CCL2 or VCAM‐1–mediated monocyte and macrophage migration or adhesion to AFs in response to Ang II was negatively regulated by KLF15 through TAD. Ang II–enhanced Smad2/3 activation and adventitial migration, proliferation, and differentiation of AFs were suppressed by KLF15 but not KLF15‐ΔTAD overexpression. Conversely, small interfering RNA knockdown of KLF15 aggravated Ang II–induced Smad2/3 activation and dysfunction of AFs. Luciferase, coimmunoprecipitation, and chromatin immunoprecipitation assay were used to demonstrate that interaction of KLF15 with Smad2/3 suppressed CCL2 expression through TAD. Mechanistically, activation of Ang II type 1 receptor/phospholipase Cγ 1/ERK1/2 signaling resulted in a decrease of KLF15 expression. In conclusion, these results demonstrate that KLF15 negatively regulates activation of AFs through TAD, which plays an important role in Ang II–induced adventitial inflammation and fibrosis. —Lu, Y. ‐Y. , Li, X. ‐D. , Zhou, H. ‐D. , Shao, S. , He, S. , Hong, M. ‐N. , Liu, J.‐C. , Xu, Y. ‐L. , Wu, Y. ‐J., Zhu, D. ‐L. , Wang, J.‐G. , Gao, P.‐J. Transactivation domain of Krüppel‐like factor 15 negatively regulates angiotensin II–induced adventitial inflammation and fibrosis. FASEB J. 33, 6254–6268 (2019). www.fasebj. org
Depression Remission Rates Among Older Black and White Adults: Analyses From the IRL-GREY Trial.

OBJECTIVE This study explored whether older black and white adults with major depressive disorder differed in rates of remission or attrition during open-label treatment with venlafaxine and supportive care. METHODS A total of 47 black (10%) and 412 white (90%) adults age ≥60 were treated with open-label venlafaxine extended-release (≤300 mg per day) for 12-14 weeks during the initial phase of an multisite, randomized, placebo-controlled augmentation trial. Participants were help-seeking older adults with nonpsychotic major depressive disorder (single or recurrent episode) referred from specialty clinics, primary care practices, advertisements, and research programs. Remission was defined as a Montgomery-Asberg Depression Rating Scale score of ≤10 for two consecutive assessments at the end of 12 weeks. Kaplan-Meier curves displayed time to dropout and time to initial remission. Cox proportional hazards models assessed differences in attrition and remission rates. RESULTS Black participants had greater baseline general medical comorbidity, worse physical health-related quality of life, and poorer cognitive function than white participants. White participants were more likely to have received an adequate trial of antidepressant and psychotherapy before study entry. Baseline depression severity, depression duration, age at onset, and recurrence history did not differ between groups. The groups had similar final doses of venlafaxine and similar rates of attrition and remission. Side-effect profiles were comparable between the groups. CONCLUSIONS Despite greater medical comorbidity, lower cognitive function, and less adequate prior exposure to antidepressant treatment and psychotherapy, black participants were no more likely to discontinue antidepressant pharmacotherapy and experienced a rate of remission comparable to white participants.
Risk profile associated with convexity meningioma resection in the modern neurosurgical era.

OBJECT Although meningiomas are commonly found along the supratentorial convexity, the risk profile associated with this subset of lesions in the modern neurosurgical era is unknown. METHODS The authors retrospectively reviewed the clinical course of patients with supratentorial convexity meningiomas treated during the past 10 years. All patients had undergone MR imaging within 72 hours after surgery and at least 1 year of clinical follow-up. Patients with multiple meningiomas, hemangiopericytomas, malignant meningiomas, or tumor-prone syndromes were excluded from analysis. RESULTS Between 1997 and 2007, 141 consecutive patients (median age 48 years, range 18-95 years) underwent resection of a supratentorial convexity meningioma. The most common signs or symptoms at presentation were headache (48%), seizures (34%), and weakness (21%). The mean tumor volume was 146.3 cm3 (range 1-512 cm3). There were no intraoperative complications or deaths. Medical or neurosurgical morbidity was noted in the postoperative course of 14 patients, equating to a 10% overall complication rate. Postoperative surgical complications included hematoma requiring evacuation, CSF leakage, and operative site infection. Medical complications included pulmonary embolus and deep vein thrombosis requiring treatment. A Simpson Grade 0 or 1 resection was achieved in 122 patients (87%). One hundred six tumors (75%) were WHO Grade I, whereas 35 (25%) were WHO Grade II. The median clinical follow-up was 2.9 years (range 1-10 years), and the median radiographic follow-up was 3.7 years (range 1-10 years). Six patients (4%) had radiographic evidence of tumor recurrence, with 3 (2%) undergoing repeat resection. CONCLUSIONS With the conservative recommendations for surgery for asymptomatic meningiomas and the advent of radiosurgery during the past 10 years, microsurgically treated convexity meningiomas are now typically large in size. Nevertheless, the patient's clinical course following microsurgical removal of these lesions is expected to be uncomplicated. The authors' findings provide a defined risk profile associated with the resection of supratentorial convexity meningiomas in the modern neurosurgical era.