Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffuse Optical Biomarkers Of Breast Cancer

DIFFUSE OPTICAL BIOMARKERS OF BREAST CANCER Jeffrey M. Cochran Jr. Arjun G. Yodh Diffuse optical spectroscopy/tomography (DOS/DOT) and diffuse correlation spectroscopy (DCS) employ near-infrared light to non-invasively monitor the physiology of deep tissues. These methods are well-suited to investigation of breast cancer due to their sensitivity to physiological parameters, such as hemoglobin concentration, oxygen saturation, and blood flow. This thesis utilizes these techniques to identify and develop diffuse optical biomarkers for the diagnosis and prognosis of breast cancer. Notably, a novel DOS prognostic marker for predicting pathologic complete response to neoadjuvant chemotherapy using z-score normalization and logistic regression was developed and demonstrated. This investigation found that tumors that were not hypoxic relative to the surrounding tissue were more likely to achieve complete response. Thus, the approach could enable dynamic feedback for the optimization of chemotherapy. Similar logistic regression models based on other optical parameters distinguished tumors from the surrounding normal tissue and diagnosed whether a lesion was malignant or benign. These diagnostic markers improve the ability of DOS/DOT to accurately localize tumors and could serve as a type of optical biopsy to classify suspicious lesions. Another study carried out the first longitudinal DCS blood flow monitoring over a full course of neoadjuvant chemotherapy in humans; this work explored initial correlations between blood flow and response to therapy and showed how DCS and DOS together can more accurately probe tumor physiology than either modality alone. Finally, still other thesis research included the final construction and initial imaging tests of a DOT instrument incorporated into a clinical MRI suite and the optimization of the DOT reconstruction algorithm. In total, these instrumental and algorithmic advances improved DOT image quality, helped to increase contrast between malignant and normal tissue, and eventually could lead to better understanding of tumor microvasculature. These contributions represent important steps towards the translation of diffuse optics into the clinic, demonstrating significant roles for optics to play in the diagnosis, prognosis, and physiological understanding of breast cancer.
Clinical and MRI phenotypes of sarcoidosis-associated myelopathy

Objective To determine the characteristic clinical and spinal MRI phenotypes of sarcoidosis-associated myelopathy (SAM), we analyzed a large cohort of patients with this disorder. Methods Patients diagnosed with SAM at a single center between 2000 and 2018 who met the established criteria for definite and probable neurosarcoidosis were included in a retrospective analysis to identify clinical profiles, CSF characteristics, and MRI lesion morphology. Results Of 62 included patients, 33 (53%) were male, and 30 (48%) were African American. SAM was the first clinical presentation of sarcoidosis in 49 patients (79%). Temporal profile of symptom evolution was chronic in 81%, with sensory symptoms most frequently reported (87%). CSF studies showed pleocytosis in 79% and CSF-restricted oligoclonal bands in 23% of samples tested. Four discrete patterns of lesion morphology were identified on spine MRI: longitudinally extensive myelitis (n = 28, 45%), short tumefactive myelitis (n = 14, 23%), spinal meningitis/meningoradiculitis (n = 14, 23%), and anterior myelitis associated with areas of disc degeneration (n = 6, 10%). Postgadolinium enhancement was seen in all but 1 patient during the acute phase. The most frequent enhancement pattern was dorsal subpial enhancement (n = 40), followed by meningeal/radicular enhancement (n = 23) and ventral subpial enhancement (n = 12). In 26 cases (42%), enhancement occurred at locations with coexisting structural changes (e.g., spondylosis). Conclusions Recognition of the clinical features (chronically evolving myelopathy) and distinct MRI phenotypes (with enhancement in a subpial and/or meningeal pattern) seen in SAM can aid diagnosis of this disorder. Enhancement patterns suggest that SAM may have a predilection for areas of the spinal cord susceptible to mechanical stress.
Vitamin D, Covid-19 and Children.

1. Paediatrics, Trinity College, the University of Dublin. 2. Trinity Translational Medicine Institute (TTMI) & Trinity Research in Childhood Centre (TRICC), Trinity College Dublin. 3. Paediatrics & Neonatology, Children’s Hospital Ireland (CHI) at Tallaght & Crumlin, Dublin. 4. Coombe Women and Infants University Hospital, Dublin. 5. Endocrinology, CHI at Temple St, Dublin. 6. Paediatrics, University College Dublin, Ireland.
Phenotypic and chemotypic characterization of GABA-shunt mutants in Arabidopsis thaliana

Gamma-Aminobutyric acid (GABA) is a four carbon non protein amino acid, and the pathway that involves its production and degradation is called the GABA shunt. The GABA shunt is a short enzymatic pathway that involves three enzymes: glutamate decarboxylase (GAD), GABA transaminase (GABA-T) and succinic semi aldehyde dehydrogenase (SSADH). GABA shunt is conserved almost in all organisms studied so far. The pathway starts in the cytosol and finishes in mitochondria in higher organisms like plants and mammals, whereas, in yeast it is exclusively cytosolic. The presence of GABA in plants has been known since over half a century ago. The induction of its accumulation under biotic and abiotic stresses has been well documented. However, the specificity of the response and the role of GABA and the GABA shunt under stress conditions have been elusive. Several Arabidopsis GABA shunt mutants have been studied and were shown to have defects in vegetative growth, reproductive growth and response to stress. To describe some, gad1 mutant was shown to have a reduced root growth. The pop2-1 mutant, defective in the activity of GABA-T, accumulated a very high level of GABA in the flower and that led to a pollen tube elongation defect. Arabidopsis ssadh mutants exhibited a severe growth phenotype, accumulated high -hydroxybutyric acid (GHB) and H2O2, and were sensitive to high-light conditions. In this work, several mutant lines have been generated and investigated to answer a range of questions; these include study on the specificity of the GABA response during abiotic stress, identifying the reasons for severe ssadh growth phenotype and suppression of the ssadh phenotype. Arabidopsis gad1/2 mutant is depleted in GABA and is unable to induce GABA synthesis under drought, salt and osmotic stress. Hence, the mutant plants were oversensitive to these stresses, indicating that GABA accumulation during abiotic stresses was a specific response. In an attempt to identify the cause of ssadh phenotype, exogenous GHB was fed to wild type and ghbdh1/2 mutants. The GHB application, however, did not elicit the severe ssadh-like phenotype. But, treatment of wild type and ghbdh1/2 mutant with SSA re-produced the ssadh phenotype, suggesting that SSA, but not GHB, was the cause of the severe ssadh phenotype. To suppress the ssadh phenotype, the potential accumulation of SSA was blocked by simultaneous mutation of Gad1/2. This, indeed, partially suppressed the ssadh phenotype. Suppression of ssadh phenotype mediated by ethyl methanesulfonate (EMS) induced mutation was also successful. Based on the range of phenotypes obtained in GABA shunt mutants, further studies on the role of the GABA shunt in plants is important.
Transfusion-associated microchimerism in traumatic patients

Transfusion-associated microchimerism (TA-MC) is the stable persistence of an allogeneic cell population, resulting from allogeneic blood transfusion (often resulting after trauma). Currently TA-MC is not completely understood, needing further study to reveal its underlying mechanism. This article reviews the immune tolerance mechanism of TA-MC; factors which lead to the appearance of TA-MC; clinical implications of microchimerism; and the latest diagnostic methods of TA-MC.
Contribution of males to brood care can compensate for their food consumption from a shared resource

Abstract The sharing of the same food source among parents and offspring can be a driver of the evolution of family life and parental care. However, if all family members desire the same meal, competitive situations can arise, especially if resource depletion is likely. When food is shared for reproduction and the raising of offspring, parents have to decide whether they should invest in self‐maintenance or in their offspring and it is not entirely clear how these two strategies are balanced. In the burying beetle Nicrophorus vespilloides, parents care for their offspring either bi‐ or uniparentally at a vertebrate carcass as the sole food source. The question of whether biparental care in this species offers the offspring a better environment for development compared with uniparental care has been the subject of some debate. We tested the hypothesis that male contribution to biparental brood care has a beneficial effect on offspring fitness but that this effect can be masked because the male also feeds from the shared resource. We show that a mouse carcass prepared by two Nicrophorus beetles is lighter compared with a carcass prepared by a single female beetle at the start of larval hatching and provisioning. This difference in carcass mass can influence offspring fitness when food availability is limited, supporting our hypothesis. Our results provide new insights into the possible evolutionary pathway of biparental care in this species of burying beetles.
Stressors and Their Association with Symptoms of Depression, Anxiety and Stress in Dental Students

Background: Dental students are exposed to varying levels of stress that may affect their mental and physical health, academic performance and quality of life. This study aim was to determine the prevalence and severity of depression, anxiety and stress (DAS), and the relationships between DAS symptoms and stressors. Methods: This cross-sectional study included 257 dental students at the International Islamic University Malaysia. The prevalence and severity of DAS symptoms was measured by the Depression, Anxiety, Stress Scale (DASS-21). The stressors were self-reported by students from a list, and the relationships with the DAS symptoms were assessed. Results: The overall prevalence of DAS symptoms for depression, anxiety, and stress were 47.5%, 67.3% and 42.8%, respectively. Clinically significant depression was experienced by 9.3% of the students, anxiety by 28.8% and stress by 10.1%. Anxiety was significantly more frequent in women than in men, and anxiety scores were significantly increased in young students. The top five stressors were time management problems, fear of failing, examination and low grades; feeling of incompetence and study pressure. Conclusions: DAS symptoms occurred in dental students. Academic and personal factors produced stress that precipitated psychological distress.
Development and validation of the Mothers of Preterm Babies Postpartum Depression Scale

Postpartum depression, a common complication in childbearing women, is of great public health concern. Previous screening tools have focused on depressed mood, with less attention paid to postpartum anxiety and suicidal ideation. This study developed and validated a tool to measure postpartum depression among mothers of preterm babies. From the clinical interviews and a pilot survey (n=121) the Mothers of Preterm Babies Postpartum Depression Scale was developed. The Mothers of Preterm Babies Postpartum Depression Scale and the Edinburgh Postnatal Depression Scale questionnaires were completed by 152 mothers who delivered preterm babies at Massey Street Children’s Hospital, Lagos. Data were analyzed with use of confirmatory factor analysis, principal component analysis, and Cronbach’s alpha at the P≤0.05 level of significance. The new scale demonstrated a reliability (α) of 0.91. Construct validity with exploratory factor analysis (Kaiser-Meyer-Olkin measure 0.70) yielded three dimensions of cognitive and emotional difficulty (α=0.92), hopelessness and suicidal ideation (α=0.93), and physiological distress (α=0.71). Confirmatory factor analysis demonstrated a good fit: 18 degrees of freedom; goodness of fit index 0.97; adjusted goodness of fit index 0.93; and root mean square error of approximation 0.04. Convergent validity was established with the Edinburgh Postnatal Depression Scale (r=0.66, P=0.00). The new screening tool was demonstrated to have meritorious validity, faster and easier to administer to the obstetric population. Significance statement Having a baby is often marked by disturbance in mood, and the birth of a premature baby can put mothers at greater risk of psychological distress than the birth of a full-term baby. Available screening tools assess postpartum depression symptoms without consideration of mitigating sources of postpartum stress. Edinburgh Post-natal Depression scale is the commonest measure for differential diagnosis in Nigeria but limited in screening women for suicidal ideation and anxiety. This study developed a new tool that improves the efficiency of, and reduces the time spent diagnosing postpartum depression among mothers of preterm babies. Efficiency in diagnosing the pathological reaction of mothers of preterm babies to the child’s condition and the corresponding depression symptoms is highly important for implementation of cost-effective intervention by mental health practitioners.
The measurement of the quality of maternal and newborn care in Malawi: Comparative analyses of health worker performance measurement methods and an exploration of evidence of respectful maternity care

Background: Global evidence suggests that better quality of care is associated with reductions in maternal and newborn mortality. The routine measurement of the quality of care is important to ensure the proper functioning of a health care system but there is no consensus on the best way to measure quality of care, especially relating to the process of care. While the direct observation of clinical care (especially as it relates to labor, delivery and essential newborn care) may be a gold standard, the routine use of this method is not feasible in most resource poor settings. This dissertation examines the relationship between different process quality of care measurement methods for selected maternal and newborn care services in Malawi including adherence to clinical guidelines, consistency and quality of health worker performance, and the provision of respectful maternity care. The results of an analysis of the quality of essential newborn care and respectful maternity care are
Evaluating Applied Suicide Intervention Skills Training with Counselors-in-Training: Enhancing Sensitivity, Awareness, and Intervention Skills with Suicidal and Non-Suicidal Clients

Suicide is a serious mental health concern, it is the tenth leading cause of death in the United States, the second leading cause of death for young adults (10-34), and the fourth leading cause for persons aged 35 to 54 years (Centers for Disease Control [CDC], 2015). Counselors-intraining (CIT) often encounter clients with suicidal ideation, and they often report feeling, and are found to be, under-prepared to respond effectively (Barrio Minton et al., 2011; Erikson & Abel, 2013). One potential approach to helping augment the skills of counselors-in-training is extending suicide intervention training beyond their formal course work. Applied Suicide Intervention Skills training (ASIST) is a 14hour, 2-day standardized and manualized training designed to train people in the helping professions to identify and effectively intervene with people considering suicide (LivingWorks, 2013). ASIST has been recognized by the Substance Abuse and Mental Health Services Administration (SAMHSA), branches of the US Military, the Center for Disease Control (Rodgers, 2010), and the National Registry of Evidence-based Programs and Practices (NREPP), as an effective training for suicide prevention. However, ASIST has yet to be rigorously evaluated as a systematic means of enhancing CIT preparedness to deal effectively with suicidal clients in a fieldwork setting. It is clear that further research is warranted to evaluate the ability of ASIST to increase the skills of CIT. This study evaluated the use of ASIST by CIT with both suicidal and non-suicidal clients and examined how ASIST may offer a standardized and measurable means of enhancing CITs sensitivity, awareness, and intervention skills in responding to persons-at-risk, for both suicide and other significant mental health issues. This is the first study to evaluate the utilization and generalizability of ASIST by CIT in practice and over time. INDEX WORDS: Suicide, Non-Suicidal, Counselors in Training, Applied Suicide Intervention Skills EVALUATING APPLIED SUICIDE INTERVENTION SKILLS TRAINING WITH COUNSELORS-IN-TRAINING: ENHANCING SENSITIVITY, AWARENESS, AND INTERVENTION SKILLS WITH SUICIDAL AND NON-SUICIDAL CLIENTS
Clinico-pathological and molecular characterization of BRAF mutant metastatic colorectal cancer (mCRC): Are all mutations created equal?

, P Biason, F Cortiula, M Pino, F Urbano, C Antoniotti, S Corallo, , A Orlandi, S Lonardi, F Bergamo, G Munari, U Malapelle, C Mescoli, L Reggiani Bonetti, G Lanza, A Dei Tos, G De Maglio, , F Loupakis, M Fassan Unit 1, Clinical and Experimental Oncology Department, Veneto IOV-IRCCS, Padua, Italy, Oncologia Medica 1, Istituto Oncologico S, Padua, Italy, Oncologia, Azienda Sanitaria Universitaria Integrata di Italy, Medical Oncology, Ospedale Santa Maria Annunziata, Bagno a Department of Radiological, Oncological and Anatomopathological University of Rome, Rome, Italy, Department of Translational New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, iera Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy, IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Modena Cancer Centre, of Oncology/Haematology, University of Modena and Reggio Emilia, Universit a Cattolica del Sacro Cuore Oncologia Medica, Rome, Italy, of Oncology IOV-IRCCS, Padua, Italy, Istituto Oncologico Veneto, Italy, Department of Public Health, University Federico II, Naples, Italy, nt of Medicine, Pathology and Cytopathology Unit, University of Padova, Department of Medicine (DIMED), Pathology Unit, University of Padua, Department of Laboratory Integrated Activities, Anatomic Pathology ne, University of Modena and Reggio Emilia, Modena, Italy, of Ferrara, Ferrara, Italy, Department of Pathology, General Hospital of Italy, University Hospital Udine, Udine, Italy, Oncologia Medica 1, Veneto IRCCS, Padua, Italy
Effect of Open-Ended Coaxial Probe-to-Tissue Contact Pressure on Dielectric Measurements

Open-ended coaxial probes are widely used to gather dielectric properties of biological tissues. Due to the lack of an agreed data acquisition protocol, several environmental conditions can cause inaccuracies when comparing dielectric data. In this work, the effect of a different measurement probe-to-tissue contact pressure was monitored in the frequency range from 0.5 to 20 GHz. Therefore, we constructed a controlled lifting platform with an integrated pressure sensor to exert a constant pressure on the tissue sample during the dielectric measurement. In the pressure range from 7.74 kPa to 77.4 kPa, we observed a linear correlation of −0.31±0.09% and −0.32±0.14% per kPa for, respectively, the relative real and imaginary complex permittivity. These values are statistically significant compared with the reported measurement uncertainty. Following the literature in different biology-related disciplines regarding pressure-induced variability in measurements, we hypothesize that these changes originate from squeezing out the interstitial and extracellular fluid. This process locally increases the concentration of membranes, cellular organelles, and proteins in the sensed volume. Finally, we suggest moving towards a standardized probe-to-tissue contact pressure, since the literature has already demonstrated that reprobing at the same pressure can produce repeatable data within a 1% uncertainty interval.
Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Immunotherapy has considerably increased the number of anticancer agents in many tumor types including metastatic colorectal cancer (mCRC). Anti-PD-1 (programmed death 1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitors (ICI) have been shown to benefit the mCRC patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, ICI is not effective in mismatch repair proficient (pMMR) colorectal tumors, which constitute a large population of patients. Several clinical trials evaluating the efficacy of immunotherapy combined with chemotherapy, radiation therapy, or other agents are currently ongoing to extend the benefit of immunotherapy to pMMR mCRC cases. In dMMR patients, MSI testing through immunohistochemistry and/or polymerase chain reaction can be used to identify patients that will benefit from immunotherapy. Next-generation sequencing has the ability to detect MSI-H using a low amount of nucleic acids and its application in clinical practice is currently being explored. Preliminary data suggest that radiomics is capable of discriminating MSI from microsatellite stable mCRC and may play a role as an imaging biomarker in the future. Tumor mutational burden, neoantigen burden, tumor-infiltrating lymphocytes, immunoscore, and gastrointestinal microbiome are promising biomarkers that require further investigation and validation.
High sensitivity analysis of BRAF mutations in neoplastic and non-neoplastic thyroid lesions

The clonal distribution of BRAFV600E in papillary thyroid carcinoma (PTC) has been recently debated. No information is currently available about precursor lesions of PTCs. My first aim was to establish whether the BRAFV600E mutation occurs as a subclonal event in PTCs. My second aim was to screen BRAF mutations in histologically benign tissue of cases with BRAFV600E or BRAFwt PTCs in order to identify putative precursor lesions of PTCs. Highly sensitive semi-quantitative methods were used: Allele Specific LNA quantitative PCR (ASLNAqPCR) and 454 Next-Generation Sequencing (NGS). For the first aim 155 consecutive formalin-fixed and paraffin-embedded (FFPE) specimens of PTCs were analyzed. The percentage of mutated cells obtained was normalized to the estimated number of neoplastic cells. Three groups of tumors were identified: a first had a percentage of BRAF mutated neoplastic cells > 80%; a second group showed a number of BRAF mutated neoplastic cells < 30%; a third group had a distribution of BRAFV600E between 30-80%. The large presence of BRAFV600E mutated neoplastic cell sub-populations suggests that BRAFV600E may be acquired early during tumorigenesis: therefore, BRAFV600E can be heterogeneously distributed in PTC. For the second aim, two groups were studied: one consisted of 20 cases with BRAFV600E mutated PTC, the other of 9 BRAFwt PTCs. Seventy-five and 23 histologically benign FFPE thyroid specimens were analyzed from the BRAFV600E mutated and BRAFwt PTC groups, respectively. The screening of BRAF mutations identified BRAFV600E in “atypical” cell foci from both groups of patients. “Unusual” BRAF substitutions were observed in histologically benign thyroid associated with BRAFV600E PTCs. These mutations were very uncommon in the group with BRAFwt PTCs and in BRAFV600E PTCs. Therefore, lesions carrying BRAF mutations may represent “abortive” attempts at cancer development: only BRAFV600E boosts neoplastic transformation to PTC. BRAFV600E mutated “atypical foci” may represent precursor lesions of BRAFV600E mutated PTCs.