Miracle-dz/UniFAR-FTUs huggingface dataset:
Working with Patients at risk for Hereditary Degenerative Brain Disorders

Dedication To my grandmother, Marilyn White, and my late grandfather, Clifford White. Both developed Alzheimer disease, and have since become my inspiration toward the study of hereditary degenerative brain disorders. They lived and loved with no cure. May the next generation take courage from their examples and continue to hope for the day Alzheimer disease is cured. iv Acknowledgements Thank you to Jill Goldman for being the first to listen to my ideas about this project back when I was just an unknown student in another state. Thank you for your time, patience, and for giving me the feedback to make this thesis work. Thank you to Michelle Fox for putting excitement and vigor into this project. Your encouragement and ideas have been greatly appreciated. Thank you to Ruth Abramson for the time you gave so gladly to me, often while sharing some candy and refreshments. You brought smiles to a difficult task, and for that (and many other things), I am grateful for our friendship. Thank you to Peggy Walker for aiding me in this process of creating a thesis. I could always tell you cared about me and my successful completion of this project despite all your other duties. Thank you. v Abstract Hereditary degenerative brain disorders (HDBDs) are a unique class of genetic conditions that result in progressive loss of function within the nervous system, many of which present during adulthood. Given this, the diagnosis of a HDBD can be daunting for both the patient and the genetic counselor assisting in medical care. The purpose of this study was to find themes among genetic counselors who see this patient population and help provide a framework to counselors entering this field by recognizing verified methods of HDBD counseling. Sixteen genetic counselors who routinely see patients at-risk for HDBDs were interviewed concerning how they prepared for and engaged with their patients, how they handled the complex emotions frequently associated with presymptomatic HDBD counseling, and how they perceived the stress levels and coping mechanisms of their patients. The results of this study showed that genetic counselors who see patients at-risk for HDBDs utilize agendas and/or protocols in preparing for and directing sessions. Additionally, these genetic counselors perceive their HDBD patients as capable of coping with their own presymptomatic testing results. There was not enough evidence from this study to determine if genetic counselors who see patients at risk for HDBDs …
Four Generations Working Together in the Workforce and in Higher Education.

The purpose of this study was to help the reader hear and begin to understand each of the 4 generations, resulting in an awareness of how each generation perceived the world in general, and specifically its perception of work in an academic setting. The researcher studied 4 participants currently or formerly involved in the higher education environment; each represented one of the 4 generations examined and was studied through stories, autobiography, notes, conversations, interviews, family stories, and life experiences. Today's American workforce is unique in that never before has there been such a diverse group of individuals working together. Research suggests that the mixing of race, gender, ethnicity, and generation in the workforce of today is remarkable. First, the 4 generations in this qualitative study were identified. For this study, the generations were known as The Veterans or Traditionalists born approximately between 1922 and 1945, The Baby Boomers born approximately between 1946 and 1964, Generation X born approximately between 1965 and 1980, and Generation Y born approximately between 1981 and 2000. After the collection and analysis of the 3 sets of data (interactive interviewing, written descriptions, and descriptive observations), the researcher created a coding and catalog content analysis. Much of the researcher's work consisted of a process method of analysis to discover characteristics and patterns similar to the 4 generations represented in the qualitative Narrative Inquiry methodology. Through the narrative inquiry method of this qualitative study, the examination of multiple generations within the workforce produced more similarities than differences. Common ground spanning over 80 years was evident more often than not. All 4 generations ultimately wanted the same thing with regard to their jobs: an enjoyable job, fulfillment and purpose, good benefits and pay, a perspective on what is important, respect, stability in the company and job, validation, and appreciation (Gibson, 2009).
Comparative Volume Analysis of Alveolar Defects by 3D Simulation

A precise volumetric assessment of maxillary alveolar defects in patients with cleft lip and palate can reduce donor site morbidity or allow accurate preparation of bone substitutes in future applications. However, there is a lack of agreement regarding the optimal volumetric technique to adopt. This study measured the alveolar bone defects by using two cone-beam computed tomography (CBCT)-based surgical simulation methods. Presurgical CBCT scans from 32 patients with unilateral or bilateral clefts undergoing alveolar bone graft surgery were analyzed. Two hands-on CBCT-based volumetric measurement methods were compared: the 3D real-scale printed model-based surgical method and the virtual surgical method. Different densities of CBCT were compared. Intra- and inter-examiner reliability was assessed. For patients with unilateral clefts, the average alveolar defect volumes were 1.09 ± 0.24 and 1.09 ± 0.25 mL (p > 0.05) for 3D printing- and virtual-based models, respectively; for patients with bilateral clefts, they were 2.05 ± 0.22 and 2.02 ± 0.27 mL (p > 0.05), respectively. Bland–Altman analysis revealed that the methods were equivalent for unilateral and bilateral alveolar cleft defect assessment. No significant differences or linear relationships were observed between adjacent different densities of CBCT for model production to obtain the measured volumes. Intra- and inter-examiner reliability was moderate to good (intraclass correlation coefficient (ICC) > 0.6) for all measurements. This study revealed that the volume of unilateral and bilateral alveolar cleft defects can be equally quantified by 3D-printed and virtual surgical simulation methods and provides alveolar defect-specific volumes which can serve as a reference for planning and execution of alveolar bone graft surgery.
Functional contribution of sphingosine‐1‐phosphate to airway pathology in cigarette smoke‐exposed mice

A critical role for sphingosine kinase/sphingosine‐1‐phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD).
A Yersinia ruckeri TIR Domain-Containing Protein (STIR-2) Mediates Immune Evasion by Targeting the MyD88 Adaptor

TIR domain-containing proteins are essential for bacterial pathogens to subvert host defenses. This study describes a fish pathogen, Yersinia ruckeri SC09 strain, with a novel TIR domain-containing protein (STIR-2) that affects Toll-like receptor (TLR) function. STIR-2 was identified in Y. ruckeri by bioinformatics analysis. The toxic effects of this gene on fish were determined by in vivo challenge experiments in knockout mutants and complement mutants of the stir-2 gene. In vitro, STIR-2 downregulated the expression and secretion of IL-6, IL-1β, and TNF-α. Furthermore, the results of NF-κB-dependent luciferase reporter system, co-immunoprecipitation, GST pull-down assays, and yeast two-hybrid assay indicated that STIR-2 inhibited the TLR signaling pathway by interacting with myeloid differentiation factor 88 (MyD88). In addition, STIR-2 promoted the intracellular survival of pathogenic Yersinia ruckeri SC09 strain by binding to the TIR adaptor protein MyD88 and inhibiting the pre-inflammatory signal of immune cells. These results showed that STIR-2 increased virulence in Y. ruckeri and suppressed the innate immune response by inhibiting TLR and MyD88-mediated signaling, serving as a novel strategy for innate immune evasion.
Portable Skin Analyzers with Simultaneous Measurements of Transepidermal Water Loss, Skin Conductance and Skin Hardness

Simultaneous measurement of skin physiological and physical properties are important for the diagnosis of skin diseases and monitoring of human performance, since it provides more comprehensive understanding on the skin conditions. Current skin analysis devices, however, require each of probes and unique protocols for the measurement of individual skin properties, resulting in inconvenience and increase of measurement uncertainty. This paper presents a pen-type skin analyzing device capable tomeasure three key skin properties at the same time: transepidermal water loss (TEWL), skin conductance, and skin hardness. It uses a single truncated hollow cone (THC) probe integrated with a humidity sensor, paired electrodes, and a load cell for the multimodal assessment of the skin properties. The present device measured TEWL with a sensitivity of 0.0068 (%/s)/(g/m2/h) and a linearity of 99.63%, conductance with a sensitivity of 1.02 µS/µS and a linearity of 99.36%, and hardness with a sensitivity of 0.98 Shore 00/Shore 00 and a linearity of 99.85%, within the appropriate ranges for the human skin. The present pen-type device has a high potential for the skin health diagnosis as well as the human performance monitoring applications.
Validation of the San Diego Early Test Score for early HIV infection among Amsterdam men who have sex with men.

The San Diego Early Test (SDET) score is a simple risk-assessment tool for acute and early HIV-infection. Validation in a prospective cohort of Amsterdam men who have sex with men showed fair prediction of HIV seroconversion (AUC 0.701). Use of this score can help prioritise and target HIV prevention strategies.
Cardiovascular Risk/Benefit Profile of MHT

Background and Objectives: Data emerging from the Women’s Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the way to a better understanding of the relationship between estrogen and CV risk. The aim of this review was to revise the current literature and evaluate the CV risk or benefit following administration of MHT considering several factors such as MHT timing, dose, route of administration, and formulation. Materials and Methods: An electronic databases search of MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) was performed, with the date range from each database’s inception until June 2019. All the studies evaluating MHT and cardiovascular risk, including thromboembolism or stroke, were selected. Results: Timing of MHT initiation was shown to be a critical factor in CV risk assessment. In concordance with the “timing hypothesis”, healthy symptomatic women who initiated MHT when aged younger than 60 years, or who were within 10 years of menopause onset, have demonstrated a reduction in both coronary heart disease (CHD) risk and all-cause mortality. In particular, MHT therapy was associated with improvement of subclinical signs of atherosclerosis. Venous thromboembolism (VTE) risk is reduced when low doses of oral estrogen are used. Moreover, transdermal hormonal application significantly reduces CV risk compared with oral administration. MHT impact on the CV system is influenced by either factors inherent to the specific regimen, or factors inherent to the specific patient. Hence, individualization of care is necessary. Conclusion: CV risk calculation should be considered by clinicians in order to exclude patients with high CV risk, in whom MHT is contraindicated. Assessing risks and benefits in a patient-centered approach according to individual’s features, health status, and personal preferences is important in order to realize a safe and effective treatment.
Construction of pseudomolecule sequences of Brassica rapa ssp. pekinensis inbred line CT001 and analysis of spontaneous mutations derived via sexual propagation

Chinese cabbage (Brassica rapa ssp. pekinensis) is a major crop that is widely cultivated, especially in Korea, Japan, and China. With the advent of next generation sequencing technology, the cost and time required for sequencing have decreased and the development of genome research accelerated. Genome sequencing of Chinese cabbage was completed in 2011 using the variety Chiifu-401-42, and since then the genome has been continuously updated. In the present study, we conducted whole-genome sequencing of Chinese cabbage inbred line CT001, a line widely used in traditional or molecular breeding, to improve the accuracy of genetic polymorphism analysis. The constructed CT001 pseudomolecule represented 85.4% (219.8 Mb) of the Chiifu reference genome, and a total of 38,567 gene models were annotated using RNA-Seq analysis. In addition, the spontaneous mutation rate of CT001 was estimated by resequencing DNA obtained from individual plants after sexual propagation for six generations to estimate the naturally occurring variations. The CT001 pseudomolecule constructed in this study will provide valuable resources for genomic studies on Chinese cabbage.
Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant

Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.
Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II/LC3I ratio, p62/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.
Expertentreffen COPD: Lunge und Herz – ziemlich oft gemeinsam krank!

Zusammenfassung Pneumologen sollten immer auch an das Herz denken, wenn sie Patienten mit pulmonalen Erkrankungen diagnostizieren und therapieren. Dies gilt besonders für die COPD, aber auch eine ganze Reihe anderer pneumologischer Krankheitsbilder. Auf dem Workshop „Luftschlösser“, der wieder im Februar 2019 in Wiesbaden abgehalten wurde, diskutierten die Teilnehmer die vielfältigen Interaktionen von Lunge und Herz und deren Bedeutung für die Therapie. Ausgehend von pathophysiologischen Überlegungen wurden die psychosozialen Auswirkungen des Kardinalsymptoms Dyspnoe für Patienten sowohl mit Lungen- als auch Herzerkrankungen deutlich. Eine besondere diagnostische und therapeutische Herausforderung liegt im simultanen Auftreten von pulmonalen und kardialen Krankheiten beim individuellen Patienten. So wurde gezeigt, wie häufig die Komorbidität Herzinfarkt bei COPD übersehen wird – und vice versa. Dass auch Asthmatiker häufiger eine koronare Herzerkrankung oder eine Herzinsuffizienz aufweisen, ist im klinischen Alltag nicht immer präsent. Die Überblähung der Lunge beim Emphysem beeinträchtigt die kardiale Funktion auch beim Herzgesunden. Die medikamentöse Verminderung der Überblähung verbessert so die kardiale Funktion. Biomarker helfen bei der Differenzialdiagnose. Ihre Rolle wird in der großen deutschen Kohorte COSYCONET untersucht. Der schwerergradig herzkranke Lungenpatient stellt therapeutisch eine große Herausforderung dar, insbesondere wenn er intensiv- und beatmungspflichtig wird und das Weaning prolongiert verläuft. Ein „klassisches“ Beispiel der Interaktion von Lunge und Herz stellen die Lungengefäßerkrankungen dar. Sowohl bei der pulmonal-arteriellen Hypertonie als auch der chronisch-thromboembolischen pulmonalen Hypertonie vergeht nicht selten eine zu lange Zeit bis zur Diagnosestellung. Die therapeutischen Möglichkeiten haben sich für beide Gruppen von Lungengefäßerkrankungen in den letzten Jahren erheblich verbessert und stellen eine wichtige Aufgabe für Pneumologen dar. Schlafbezogene Atmungsstörungen und die kardiale Funktion stehen in einer Wechselbeziehung, die nach der SERVE-HF-Studie einer besonderen Aufmerksamkeit bedarf. Unstrittig bleibt, dass die obstruktive Schlafapnoe ein unabhängiger Risikofaktor für kardiovaskuläre Erkrankungen ist und leitlinienkonform behandelt werden muss. Der Workshop zeigte eindrucksvoll die vielfältigen Wechselwirkungen von Herz und respiratorischem System, die zu Problemen in Diagnostik und Therapie führen können. Pneumologische Leitlinien sollten den Aspekt der kardialen Komorbidität stärker in den Fokus nehmen.
Densification and Phase Transformation in Multi-Layered Graded Si3N4–TiN Components Produced by Field-Assisted Sintering

The structural and/or functional design of multiphase ceramics, along with their processing, are timely research topics in the area of field-assisted sintering techniques, such as spark plasma sintering, especially for systems containing both electrically insulating and conductive phases. In the present study, spark plasma sintering of Si3N4–TiN composites was investigated by changing the TiN particle size and electrical current waveform. Their combined effects on both the densification behavior and α-to-β phase conversion of the Si3N4 matrix was studied and compared by means of a thermodynamic approach and dilatometric measurements. Through the control of TiN phase characteristics and heating mode, double-layered Si3N4-based components were also prepared using a one-step spark plasma sintering process, which was compared with conventional hot-pressing. It was shown that the size of the conductive TiN phase has a significant influence on the particle rearrangement, with the formation of a liquid phase, and the solution–diffusion–precipitation process, through the field-induced local heating and electrowetting mechanisms. Moreover, the contribution of current pulsing to the densification and α-to-β conversion of the layered Si3N4-based components was mostly dependent upon the particle size distribution and content of the TiN phase, indicating that the electric-field effect is dependent upon current path.
Impact of ultraviolet radiation on dermal and epidermal DNA damage in a human pigmented bilayered skin substitute

Our laboratory has developed a scaffold‐free cell‐based method of tissue engineering to produce bilayered tissue‐engineered skin substitutes (TESs) from epidermal and dermal cells. However, TES pigmentation is absent or heterogeneous after grafting, due to a suboptimal number of melanocytes in culture. Our objectives were to produce TESs with a sufficient quantity of melanocytes from different pigmentation phototypes (light and dark) to achieve a homogeneous color and to evaluate whether the resulting pigmentation was photoprotective against ultraviolet radiation (UVR)‐induced DNA damage in the dermis and the epidermis. TESs were cultured using different concentrations of melanocytes (100, 200, and 1,500 melanocytes/mm2), and pigmentation was evaluated in vitro and after grafting onto an athymic mouse excisional model. Dermal and epidermal DNA damage was next studied, exposing pigmented TESs to 13 and 32.5 J/cm2 UVR in vitro. We observed that melanocyte cell density increased with culture time until reaching a plateau corresponding to the cell distribution of native skin. Pigmentation of melanocyte‐containing TESs was similar to donor skin, with visible melanin transfer from melanocytes to keratinocytes. The amount of melanin in TESs was inversely correlated to the UVR‐induced formation of cyclobutane pyrimidine dimer in dermal fibroblasts and keratinocytes. Our results indicate that the pigmentation conferred by the addition of melanocytes in TESs protects against UVR‐induced DNA damage. Therefore, autologous pigmented TESs could ensure photoprotection after grafting.