Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and Functional Characteristics of a Novel KLF11 Cys354Phe Variant Involved in Maturity-Onset Diabetes of the Young

Background Mutations in human KLF11 may lead to the development of maturity-onset diabetes of the young 7 (MODY7). This occurs due to impaired insulin synthesis in the pancreas. To date, the clinical and functional characteristics of the novel KLF11 mutation c.1061G > T have not yet been reported. Methods Whole-exon sequencing was used to screen the proband and family members with clinical suspicion of the KLF11 variant. Luciferase reporter assays were used to investigate whether the KLF11 variant binds to the insulin promoter. Real-time PCR, western blotting, and glucose-stimulated insulin secretion (GSIS) analysis were used to analyze the KLF11 variant that regulates insulin expression and insulin secretion activity in beta cell lines. The Freestyle Libre H (Abbott Diabetes Care Ltd) was used to dynamically monitor the proband daily blood glucose levels. Results Mutation screening for the whole exon genes identified a heterozygous KLF11 (c.1061G > T) variant in the proband, her mother, and her maternal grandfather. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed that the KLF11 (c.1061G > T) variant had impaired insulin promoter regulation activity. Moreover, this variant was found to impair insulin expression and insulin secretion in pancreatic beta cells. The proband had better blood glucose control without staple food intake (p < 0.05). Conclusions Herein, for the first time, we report a novel KLF11 (c.1061G > T) monogenic mutation associated with MODY7. This variant has impaired insulin promoter regulation activity and impairs insulin expression and secretion in pancreatic beta cells. Therefore, administering oral antidiabetic drugs along with dietary intervention may benefit the proband.
Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Heat shock proteins (HSPs) are molecular chaperones produced in response to oxidative stress (OS). These proteins are involved in the folding of newly synthesized proteins and refolding of damaged or misfolded proteins. Recent studies have been focused on the regulatory role of HSPs in OS and ischemia/reperfusion injury (I/R) where reactive oxygen species (ROS) play a major role. ROS perform many functions, including cell signaling. Unfortunately, they are also the cause of pathological processes leading to various diseases. Biological pathways such as p38 MAPK, HSP70 and Akt/GSK-3β/eNOS, HSP70, JAK2/STAT3 or PI3K/Akt/HSP70, and HSF1/Nrf2-Keap1 are considered in the relationship between HSP and OS. New pathophysiological mechanisms involving ROS are being discovered and described the protein network of HSP interactions. Understanding of the mechanisms involved, e.g., in I/R, is important to the development of treatment methods. HSPs are multifunctional proteins because they closely interact with the antioxidant and the nitric oxide generation systems, such as HSP70/HSP90/NOS. A deficiency or excess of antioxidants modulates the activation of HSF and subsequent HSP biosynthesis. It is well known that HSPs are involved in the regulation of several redox processes and play an important role in protein-protein interactions. The latest research focuses on determining the role of HSPs in OS, their antioxidant activity, and the possibility of using HSPs in the treatment of I/R consequences. Physical exercises are important in patients with cardiovascular diseases, as they affect the expression of HSPs and the development of OS.
Brownian dynamics studies on DNA gel electrophoresis. I. Numerical method and “periodic” behavior of elongation-contraction motions

The dynamics of a DNA molecule which is undergoing constant field gel electrophoresis (CFGE) is studied by a Brownian dynamics simulation method we have developed. In the method a DNA molecule is modeled as a chain of spherical electrolyte beads and the gel as a three-dimensional array of immobile beads. With the constraint for the separation of each pair of bonded beads to be less than a certain fixed value, as well as with the excluded volume effect, the simultaneous Langevin equations of motion for the beads are solved by means of the Lagrangian multiplier method. The resultant mobilities μ as a function of electric field coincide satisfactorily with the corresponding experimental results, once the time, the length, and the field of the simulation are properly scaled. In relatively strong fields “periodic” behavior is found in the chain dynamics and is examined through the time evolution of the radius of the longer principal axis, Rl(t). It is found that the mean width of a peak in Rl(t), or a period o.
Information technology challenges in a public hospital during the COVID-19 pandemic

In the past few decades, academic healthcare centers have positively impacted medical care quality by establishing well-structured information technology (IT) departments to address medical and research issues globally (1,3). However, information technology is not a panacea to solve all problems concerning healthcare; many aspects of applying IT need to be assessed, such as safety, organization, and environment (6). Nevertheless, IT possesses great potential for creatively resolving and answering the challenges that risky situations pose to society. The COVID-19 pandemic is an extraordinary challenge since, unlike the Spanish flu pandemic in 1918, which took approximately a year to spread worldwide, its infection disseminated in a few weeks (5). COVID-19, an acute viral infection caused by the novel coronavirus (SARS-CoV-2), was initially detected in Wuhan, China, in December 2019. Due to the virus’s high transmissibility and the severity of the disease, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern under the International Health Regulations (2005) (8). Healthcare systems around the world utilized various resources, such as science and technology, in preparation to handle the COVID-19 pandemic. Fortunately, several digital technologies that assisted in tackling COVID-19 infections were mature enough at the start of 2020 to be applied to the field of medicine. Ting et al. (12) divided these digital technologies into four groups: Internet of Things (IoT), big data analytics, artificial intelligence (AI), and blockchain technology. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP)—the most extensive university-affiliated hospital in São Paulo City, Brazil— played an essential role in diagnosing and treating the highly complex COVID-19 cases. Since the end of March 2020, the hospital has reserved one of its largest buildings— with 500 beds and 300 adult intensive care unit (ICU) beds— to treat COVID-19 patients exclusively. Furthermore, all of the hospital’s sectors were utilized to deal with COVID-19 patients. According to Ting et al. (12), the HCFMUSP utilized two of the aforementioned four digital technology groups, namely IoT and AI, in addition to telemedicine. Several departments were integral to effectively applying these resources: the IT department, Núcleo Especializado de Tecnologia de Informação (NETI), which manages the central administration systems and electronic health records; the Clinical Engineering Department, which provides and maintains the highly technological facilities and operational services at the hospital; the Clinical Director’s Office, which promotes the development of health actions and services, supports professional training, and strives for comprehensive patient care; and lastly, the Crisis Management Committee, which was mobilized to assist with strategic planning (7,11,13).
Pretreatment Prediction of Relapse Risk in Patients with Osteosarcoma Using Radiomics Nomogram Based on CT: A Retrospective Multicenter Study

Objective To develop and externally validate a CT-based radiomics nomogram for pretreatment prediction of relapse in osteosarcoma patients within one year. Materials and Methods In this multicenter retrospective study, a total of 80 patients (training cohort: 63 patients from three hospitals; validation cohort: 17 patients from three other hospitals) with osteosarcoma, undergoing pretreatment CT between August 2010 and December 2018, were identified from multicenter databases. Radiomics features were extracted and selected from tumor regions on CT image, and then, the radiomics signature was constructed. The radiomics nomogram that incorporated the radiomics signature and clinical-based risk factors was developed to predict relapse risk with a multivariate Cox regression model using the training cohort and validated using the external validation cohort. The performance of the nomogram was assessed concerning discrimination, calibration, reclassification, and clinical usefulness. Results Kaplan-Meier curves based on the radiomics signature showed a significant difference between the high-risk and the low-risk groups in both training and validation cohorts (P < 0.001 and P = 0.015, respectively). The radiomics nomogram achieved good discriminant results in the training cohort (C-index: 0.779) and the validation cohort (C-index: 0.710) as well as good calibration. Decision curve analysis revealed that the proposed model significantly improved the clinical benefit compared with the clinical-based nomogram (P < 0.001). Conclusions This multicenter study demonstrates that a radiomics nomogram incorporated the radiomics signature and clinical-based risk factors can increase the predictive value of the osteosarcoma relapse risk, which supports the clinical application in different institutions.
Detection of zoonotic diarrheagenic pathotypes of Escherichia coli in healthy household dogs

Background and Objectives: Intestinal pathotypes of Escherichia coli belong to the companion animals may poses potential risk to public health following zoonotic transmission. Therefore, this study was proposed to determine the virulence genes associated to diarrheagenic E. coli strains isolated from healthy pet dogs and their owners in the southeast of Iran, Kerman province. Materials and Methods: Totally 168 E. coli isolates were collected from 49 healthy household dogs and their owners. Seventy isolates were obtained from non-pet owners as control group. Presence or absence of the virulence genes including eae, stx1, stx2, st1, lt1, ipaH, cnf1 and cnf2 were screened by conventional polymerase chain reaction (PCR) and dissemination pattern of the genes were studied among the various hosts. Results: PCR examinations showed that the most frequent virulence gene was ipaH (6.1%) in dogs followed by eae in dog owners (6.1%) and in controls (8.6%). The most frequent pathotypes in dogs, their owners and controls were EIEC (6.1%), EHEC (4.08%) and EPEC (8.5%), respectively. In one of studied houses, both of dog and its owner harbored E. coli strains with same virulence profile (stx1/eae) and pathotype (EHEC). Conclusion: These results collectively indicate that healthy household dogs probably are the mild reservoir of potential virulent E. coli strains with possible active transmission to their contact owner. However, even non-pet owners seemed to be a notable source of intestinal pathotypes, especially EPEC, for their environment. Transmission of E. coli pathotypes may occurs by direct contact with the reservoirs or ingestion of contaminated food. These pathotypes are potentially virulent and creates public health hazards. Further studies are needed for better understanding of dissemination mechanisms of E. coli pathotypes among humans and their pets.
Pre-operative physiotherapy following unilateral ankle fractures at a tertiary hospital in South Africa: Perceptions of patients and nurses

Background Ankle fractures are a common injury because of an increase in levels of physical activity, as well as senescence worldwide. Ankle fractures often require surgical management for optimal stabilisation. Pre-operative physiotherapy is necessary to prepare patients for early mobilisation and home discharge. There is a lack of information on the influence of pre-operative physiotherapy on post-operative rehabilitation success, as well as timeous discharge, in patients with ankle fractures. Objectives To explore the perceptions of patients receiving pre-operative physiotherapy care following a unilateral ankle fracture and the perceptions of nursing staff managing these patients at a tertiary hospital in South Africa. Method A descriptive qualitative design, using semi-structured interviews, including both patients with unilateral ankle fractures and nurses caring for these patients, was adopted. Interviews were recorded and verbatim transcriptions were analysed utilising thematic analysis. Results Four overarching themes emerged: the perceived benefits of pre-operative physiotherapy; inhibitors to physiotherapy rehabilitation; hidden enablers to pre-operative physiotherapy and future initiatives for rehabilitation. Conclusion The perceived benefits included improved functional independence and safety of patients, as well as reduced burden of care for nurses. Patients also believed that pain and fear were two inhibitors to physiotherapy. Furthermore, nurses identified that organisational limitations, such as short-staffing and inadequately trained staff, inhibited pre-operative physiotherapy and continuity of care. Early post-operative discharge was a crucial hidden enabler to the pre-operative physiotherapy protocol. Recommendations included improved health education; the potential role of nursing staff as facilitators in pre-operative rehabilitation and regular, pre-operative in-patient monitoring of physiotherapy intervention. Clinical implications Health education was perceived to have improved patient safety and compliance which subsequently reduced patient safety incidences as well as served as a risk mitigation measure. Furthermore, gait training and muscle strengthening exercises was perceived to have resulted in safe, independent mobility to ensure prompt discharge home. Consequently, a reduced post-operative length of in hospital stay results in major cost savings per patient as well as improved access and bed availability. Future studies may need to explore the effects of pre-operative physiotherapy on post-operative success and return to pre-injury activity.
Sexual Dysfunction: A Neglected and Overlooked Issue in Adult GH Deficiency: The Management of AGHD Study

Abstract Context Although sexuality influences well-being and quality of life (QoL), studies on sexual dysfunction (SD) in adult growth hormone deficiency (AGHD) patients are lacking. Objective To investigate the prevalence of SD in AGHD patients grouped according to recombinant human growth hormone (r-hGH) therapy. Design Prospective, cross-over, 24 months, monocentric study. Setting Real-life clinical setting in a tertiary, endocrinological center. Patients 83 AGHD patients (31 women, 52 men, mean age 56.3 ± 14.7 years) were enrolled according to stringent criteria. Intervention(s) Patients already on long-term r-hGH therapy (Group 1, n = 32) vs untreated (Group 2, n = 51). Main outcome measure(s) Serum hormones, QoL Satisfaction in Hypopituitarism (QLS-H) and QoL Assessment of GHD in Adults (QoL-AGHDA) questionnaires for QoL, Index for Erectile Function-15 (IIEF-15) in men, and Female Sexual Function Index (FSFI) in women for SD. Results The overall prevalence of SD was 71.2% (60% men, 89% women). All IIEF-15 scores were lower (P = 0.001) and erectile dysfunction was more prevalent in Group 2 (75%) than Group 1 (35%). IGF-1 was correlated to scores of all IIEF-15 domains, particularly with that of erectile function (EF) (R2=0.123, P = 0.019). EF domain score correlated with QLS-H (P < 0.005) and QoL-AGHDA (P = 0.001). Despite the high prevalence of female SD also in untreated AGHD women, FSFI scores did not correlate with IGF-1 levels and QoL scores. Conclusions SD is highly prevalent in AGHD patients, especially in those untreated. SD represents an overlooked and neglected issue in AGHD, regardless the contribution of sexual life on QoL. The evaluation of sexual function should be integrated in the global assessment of AGHD patients.
Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma

Abstract Background Better treatments for glioblastoma (GBM) patients, in particular in the recurrent setting, are urgently needed. Clinical trials performed in Brazil indicated that intranasal delivery of perillyl alcohol (POH) might be effective in this patient group. NEO100, a highly purified version of POH, was current good manufacturing practice (cGMP) manufactured to evaluate the safety and efficacy of this novel approach in a Phase I/IIa clinical trial in the United States. Methods A total of 12 patients with recurrent GBM were enrolled into Phase I of this trial. NEO100 was administered by intranasal delivery using a nebulizer and nasal mask. Dosing was 4 times a day, every day. Four cohorts of 3 patients received the following dosages: 96 mg/dose (384 mg/day), 144 mg/dose (576 mg/day), 192 mg/dose (768 mg/day), and 288 mg/dose (1152 mg/day). Completion of 28 days of treatment was recorded as 1 cycle. Adverse events were documented, and radiographic response via Response Assessment in Neuro-Oncology (RANO) criteria was evaluated every 2 months. Progression-free and overall survival were determined after 6 and 12 months, respectively (progression-free survival-6 [PFS-6], overall survival-12 [OS-12]). Results Intranasal NEO100 was well tolerated at all dose levels and no severe adverse events were reported. PFS-6 was 33%, OS-12 was 55%, and median OS was 15 months. Four patients (33%), all of them with isocitrate dehydrogenase 1 (IDH1)-mutant tumors, survived >24 months. Conclusion Intranasal glioma therapy with NEO100 was well tolerated. It correlated with improved survival when compared to historical controls, pointing to the possibility that this novel intranasal approach could become useful for the treatment of recurrent GBM.
Effect of Methylene Blue on White Matter Injury after Ischemic Stroke

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.
Computer Simulations of a Lithium-Ion Polymer Battery and Implications for Higher Capacity Next-Generation Battery Designs

Most commercial lithium-ion polymer cells differ from traditional lithium-ion cells only in their cell construction and packaging. Their use of thinner separators, immobilized gel electrolyte solutions, and metallized plastic laminated packaging potentially allow an improvement in both rate capability and energy density over previous generations of thin prismatic cells. Computer simulations of the performance of a specific commercial lithium-ion polymer cell (Sony's UP383562) are used to examine the capacity, energy density, and rate capability attainable by these systems. The current first-generation commercial cells are studied, and their performance is extrapolated to next-generation designs that are shown to achieve even higher capacities and energy densities. Fundamental limits in the energy density attainable by these systems are described.
Cerebral Microbleeds Detected Using 3.0T Magnetic Resonance Imaging in 2,003 Patients with Ischemic or Hemorrhagic Stroke

Introduction: Compared with 1.5T magnetic resonance imaging (MRI), using 3.0T MRI makes it easier to detect cerebral microbleeds (CMBs). We used 3.0T MRI to investigate the backgrounds, risk factors, and number and location of CMBs in patients with ischemic or hemorrhagic stroke. Methods: We extracted data on clinical characteristics, risk factors, and number and location of CMBs in 2,003 patients treated between January 2010 and December 2014 within one week of stroke occurrence. We then carried out multivariate analysis of the data. Results: CMBs were present in 1,025 patients. The numbers of CMBs in ischemic stroke and hemorrhagic stroke patients were 9,410 and 6,419, respectively. Patients with CMBs showed significantly higher rates of cognitive impairment (p < 0.001, odds ratio [OR] = 1.514), hypertension (p < 0.001, OR = 3.145), previous history of stroke (p < 0.001, OR = 1.782), and presence of hemorrhagic stroke (p < 0.001, OR = 2.066). The use of antithrombotic medication before the stroke did not affect the incidence of CMBs. In ischemic stroke patients, patients with small vessel occlusion had a significantly greater rate of previous history of hemorrhagic stroke (p = 0.046) and number of patients with CMBs (p < 0.001) than those with cardioembolism. Conclusions: CMBs were well observed in patients with small vessel disease, and hypertension was an important factor in ischemic and hemorrhagic stroke. Antithrombotic medication is not associated with the development of CMBs if adequate antihypertensive therapy is provided.
Canine cognitive dysfunction patients have reduced total hippocampal volume compared with aging control dogs: A comparative magnetic resonance imaging study

Background: Hippocampal atrophy is a key pathologic and magnetic resonance imaging (MRI) feature of human Alzheimer’s disease (AD). Hippocampal atrophy has not been documented via MRI in canine cognitive dysfunction (CCD), which is considered as the dog model of human AD. Aim: The purpose of this retrospective comparative volumetric MRI study was to compare total hippocampal volumes between successfully aging (control) dogs and dogs diagnosed with CCD. Methods: Mimics® software was used to derive total hippocampal volumes and total brain volumes from the MRI studies of 42 aging dogs (≥ 9 years): 16 dogs diagnosed with CCD and 26 successfully aging controls. Hippocampal volumes were normalized to total brain volume and these values were compared between groups using Mann–Whitney U tests. Results: Total hippocampal volume normalized to total brain volume was significantly less for CCD patients compared with control dogs (p = 0.04). Conclusion: The results of this study suggest that – similar to human AD – hippocampal atrophy is a pathological feature of CCD. This finding has potential importance for both investigating disease mechanisms related to dementia as well as future hippocampal-targeted therapies.