Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Expression of HER2 and SKP2 in Benign and Malignant Colorectal Lesions

Background: Colorectal cancer (CRC) is the fourth most common cancer worldwide. Both HER2 and SKP2 have a carcinogenic role in CRC making them attractive targets for tailored treatment. This work aims to correlate HER2 and SKP2 protein expression as well as HER2 gene amplification with clinicopathological parameters aiming at identifying potential candidates for targeted therapy. Methods: This Study was conducted on 127 paraffin-embedded tissue samples of different colorectal lesions [controls, chronic colitis, ulcerative colitis (UC), hyperplastic polyps (HPs), adenomas and CRCs] to investigate HER2 and SKP2 expression by immunohistochemistry (IHC), Selected CRC cases [equivocal (2+) and positive (3+) by IHC] were further evaluated by ISH (CISH and SISH ) to assess HER2 gene amplification. Results: Chronic colitis, UC, HPs and adenomas were HER2-negative. HER2 positivity (scores 2+ and 3+) was found only in15% of CRCs. Both SISH and CISH showed the same results with high concordance as 66.7% of equivocal and 100% of positive cases showed amplification of HER2 gene. SKP2 positivity was detected in 26.7% and 45% of adenomas and CRCs respectively, while other studied groups were negative. A significant correlation was noted between HER2 and SKP2 expression. Conclusion: A small percent of CRCs exhibited HER2 gene amplification, which would be potential candidates for anti HER2 therapy whereas IHC could be a primary screening test for patient selection. A potential carcinogenic role of SKP2 was suggested by the findings that SKP2 expression was undetectable in normal colonic mucosa but significantly increases from adenoma to carcinoma, hoping adenoma patients to get benefit from targeted therapy.
Adaptation of the WHO group interpersonal therapy for people living with HIV/AIDS in Northwest Ethiopia: A qualitative study

Background Psychological treatments improve depressive symptoms in people living with HIV/AIDS (PLWHA). Adaptation of treatments should be based on explanatory models of depression and other elements within the given context. Aim This study aimed to examine explanatory models of depression and acceptable approaches for implementation of group IPT in Northwest Ethiopia. Methods Qualitative data were collected from April to May 2019 from case managers, adherence supporters and service users using focus group discussion and analysed thematically. Results PLWHA attributed depression to psychosocial problems, spiritual factors and biological factors. Depression had several impacts at individual and family level. Group-based interpersonal therapy (IPT) was acceptable if provided by trained peer counselors. Conclusion The current study findings informed how to conduct feasibility and acceptability trials of group IPT in the HIV population in Ethiopia.
Dental Workforce Trends: A National Study of Gender Diversity and Practice Patterns

The dental workforce is increasingly gender diverse. This study analyzed gender differences in dental practice using the American Dental Association’s 2010-2016 Masterfile and the 2017 Survey of Dental Practice. Between 2010 and 2016, the proportion of women working in dentistry increased from 24.5% to 29.8%. Overall, female dentists were more racially/ethnically diverse, more likely to be foreign-trained, and more likely to work in pediatric dentistry than male dentists. The likelihood of female dentists working as employees, part-time, and/or in metropolitan areas was 1.2 to 4.2 times greater compared with male dentists. Female solo practitioners were 1.2 to 1.8 times more likely to provide services to children and patients covered by public insurance than male solo practitioners. Gender diversification in dentistry and other factors, including generational differences and changes in the dental service delivery system and public policy, will continue to reshape the delivery of oral health services.
Coral reef species assemblages are associated with ambient soundscapes

Coral reefs provide a wide array of ecosystem services and harbor some of the highest levels of biodiversity on the planet, but many reefs are in decline worldwide. Tracking changes is necessary for effective resource management. Biological sounds have been suggested as a means to quantify ecosystem health and biodiversity, but this requires an understanding of natural bioacoustic variability and relationships to the taxa present. This investigation sought to characterize spatial and temporal variation in biological sound production within and among reefs that varied in their species assemblages. Multiple acoustic recorders were deployed for intensive 24 h periods and longer-term (~4 mo) duty-cycled deployments on 3 reefs that varied in coral cover and fish density. Short-term results suggest that while there were statistically significant acoustic differences among recorders on a given reef, these differences were relatively small, indicating that a single sensor may be suitable for acoustic characterization of reefs. Analyses of sounds recorded over approximately 4 mo indicated that the strength of diel trends in a low frequency fish band (100 to 1000 Hz) was correlated with coral cover and fish density but the strength of highfrequency snapping shrimp (2 to 20 kHz) trends was not, suggesting that low-frequency recordings may be better indicators of the species assemblages present. Power spectra varied within reefs over the deployment periods, underscoring the need for long-duration recordings to characterize these trends. These findings suggest that, in spite of considerable spatial and temporal variability within reef soundscapes, diel trends in low-frequency sound production correlate with reef species assemblages.
Validation and utility of a body condition scoring system for chimpanzees (Pan troglodytes)

Obesity is a problem in captive chimpanzee colonies that can lead to increased risk for disease; therefore, implementation of effective weight management strategies is imperative. To properly implement a weight management program, captive managers should be able to noninvasively identify and assess overweight or obese individuals. Traditional means of categorizing obese individuals involve sedating the animals to obtain body weights or skin fold measurements. The current study aimed to validate a noninvasive, subjective body condition score (BCS) system for captive chimpanzees. The system utilizes a 10‐point scale, with one rated as “emaciated,” five as “normal,” and 10 as “extremely obese. ” Between 2013 and 2014, 158 chimpanzees were weighed and scored using this system (a) while sedated and (b) while awake in their social group within 1–3 days of sedation (“In‐group” ratings). We found high inter‐rater reliability between In‐group raters, as well as between sedated and In‐group scores. BCSs, which require observation only, were significantly positively correlated with weight (an objective measure of obesity often requiring anesthetization), supporting the scale's validity. The BCS system identified 36 individuals as “overweight,” while the use of weights alone identified only 26 individuals as “overweight. ” Furthermore, the BCS system was able to classify individuals of the same sex and weight as having different BCSs, ranging from normal to overweight. Lastly, using focal animal behavioral observations from 2016 to 2018 (N = 120), we found that In‐group BCS predicted individual levels of inactive behavior more than 2 years later, demonstrating the predictive validity of the scale. These results illustrate the utility of the BCS system as a noninvasive, reliable, and valid technique that may be more sensitive than traditional methods in identifying and quantifying obesity in chimpanzees. This system can be a useful tool for captive managers to monitor and manage the weight of chimpanzees and other nonhuman primates.
Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens

Significance Conformational diversity of foreign antigens and cross-reactivity with self are implicated in the failure to generate effective antibody responses against many challenging pathogens, but few studies directly address how these two factors affect antibody formation. Here we address this question from biophysical, structural, and immunological perspectives using structurally related lysozyme proteins. The results show germinal centers have remarkable ability to select antibody producing cells along novel hypermutation trajectories, transmuting an antibody with no capacity to differentiate foreign from self into highly foreign-specific antibody derivatives, exploiting conformational flexibility in antigen and antibody. These findings address a central issue for developing vaccines against HIV and other chronic infections and represent a prime example of stepwise, evolutionary adaptation of protein–protein interfaces. Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.
The role of p53 in normal development and teratogen-induced apoptosis and birth defects in mouse embryos

The Role of p53 in Normal Development and Teratogen-Induced Apoptosis and Birth Defects in Mouse Embryos. (December 2008) Hiromi Hosako, B.S., Texas State University – San Marcos Co-Chairs of Advisory Committee, Dr. Philip E. Mirkes Dr. Stephen H. Safe In the studies described in this dissertation, we investigated the roles of p53 in normal development, teratogen-induced apoptosis, and birth defects. In the first study, the activation of p53 and its target genes, p21, NOXA, and PUMA, were examined during neural tube closure in mouse embryos exposed to hyperthermia (HS) or 4peroxycyclophosphamide (4CP), teratogens known to induce neural tube defects (NTDs). In the second study, using p53-deficient mice, we examined the expression of mRNAs and microRNAs (miRNAs) during neural tube closure. In the third study, the incidence of NTDs was investigated in p53and p21-deficient mouse embryos exposed to HS. Finally, we examined the induction of apoptosis in p53-deficient mouse embryos exposed to HS. HS and 4CP induced the activation of p53 by phosphorylation and accumulation of the protein, leading to an increase in p21 proteins and mRNAs. Although HS and 4CP also induced the expression of Noxa and Puma mRNAs, no significant increases in NOXA and PUMA proteins were observed, suggesting a possible role of transcriptionindependent apoptosis. In the second study, we showed that the expression of 388 genes and 5 miRNAs were significantly altered in p53 -/compared to p53 +/+ embryos. Finally, we showed that 10% of p53 -/pups exhibit exencephaly, spina bifida, and/or preaxial polydactyly, whereas no malformations were observed among p21 -/offspring in the absence of HS. HS resulted in an increased incidence of exencephaly in both p53 and p21 null mice indicating that these two proteins act as teratogen suppressors. Our
Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose

Metabolic signals from gut microbes The gut is a stretchy, glandular, and highly innervated tube packed at its distal end with microorganisms. Disruption of the microbial community can lead to metabolic disorders such as obesity and diabetes. Muller et al. investigated how the microbiota interacts with the enteric nervous system to induce a metabolic outcome. A population of autonomous enteric neurons called CART+ neurons are enriched in the ileum and colon, where most of the microbiota resides. Stimulation or ablation of the CART+ neurons alters blood glucose levels, insulin, and feeding behavior. Furthermore, by manipulating the microbiota, the density of enteric neurons responds plastically in an inducible and reversible manner. Science, this issue p. 314 The gut microbiota regulates regionally defined intrinsic enteric neurons in mice, thereby modulating feeding and glucose metabolism. The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEANs) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are polysynaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6- and caspase 11–dependent loss of CART+ neurons and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.
Cancer Bereavement and Depression Symptoms in Older Spouses: The Possible Modifying Role of the Circadian Rest-Activity Rhythm

ABSTRACT Objectives This study examines the associations of cancer death and aspects of the 24-h circadian rest-activity rhythm (RAR) on depression symptoms in older spouses. Methods Participants included 46 adults aged 60–94 years (M = 73 years) who experienced the death of a spouse. We tested a multivariate model using cancer death (vs. non-cancer death) and RAR variables as correlates of depression symptoms while controlling for age, sex, physical illness burden, and preparedness for death. We also present a case example to describe the behavioral activity patterns of a participant bereaved by cancer. Results Cancer death was associated with elevated levels of depression symptoms. However, the timing of the RAR moderated this association. Cancer bereavement was associated with depression symptoms when participants “settled-down” after 11:00 PM. The case example illustrates how intrusive thoughts about death quality impacts a widower’s drive to stay busy with daily activities. Conclusions Settling down earlier in the evening is important for older spouses bereaved by cancer, in terms of fewer symptoms of depression. Clinical implications Objectively specifying the activity patterns of older spouses bereaved by cancer is a promising avenue for interventions that aim to reduce depression symptoms.
Effects of Simulated Winter Browsing by Moose on Morphology and Biomass of Two Birch Species

(1) Morphological responses and biomass changes of birches (Betula pendula and B. pubescens) following simulated moose browsing were studied on trees which were 8 and 5 years old, respectively, at the beginning of the study. (2) The current annual long-shoots were removed at different clipping intensities in March-April 1981. The treatments were repeated on the same trees for another three years and at the same time control (earlier unclipped) trees were clipped. Plant responses were studied in all three years. (3) An increased clipping intensity induced the following morphological changes: the number of long-shoots decreased; the frequency of branched shoots increased; the base diameter, length and dry weight of individual shoots increased; the number of buds per long-shoot increased, but the total number of buds on all current annual long-shoots decreased. Rate of increase in tree size, measured as height and main stem diameter, decreased with clipping. (4) Simulated browsing during four years caused the long-shoot biomass to increase at a lower rate on treated trees than on control trees. The long-shoot biomass decreased during the last two years only for the highest clipping intensity on B. pubescens. The values never fell below those at the beginning of the trial. (5) The number of female catkins decreased with higher clipping intensities, but individual viable seeds increased in weight.
The Gender Gap: Who Is (and Is Not) Included on Graduate-Level Syllabi in Social/Personality Psychology

We contacted a random sample of social/personality psychologists in the United States and asked for copies of their graduate syllabi. We coded more than 3,400 papers referenced on these syllabi for gender of authors as well as other characteristics. Less than 30% of the papers referenced on these syllabi were written by female first authors, with no evidence of a trend toward greater inclusion of papers published by female first authors since the 1980s. The difference in inclusion rates of female first-authored papers could not be explained by a preference for including classic over contemporary papers in syllabi (there was evidence of a recency bias instead) or the relative availability of female first-authored papers in the published literature. Implications are discussed.
Sex specific inflammatory profiles of cerebellar mitochondria are attenuated in Parkinson’s disease

Response to inflammation is a key determinant in many diseases and their outcomes. Diseases that commonly affect older people are frequently associated with altered inflammatory processes. Neuroinflammation has been described in Parkinson's disease (PD) brain. PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and at the sub-cellular level, mitochondrial dysfunction is a key feature. However, there is evidence that a different region of the brain, the cerebellum, is involved in the pathophysiology of PD. We report relative levels of 40 pro- and anti-inflammatory cytokines measured in PD and control cerebellar mitochondria. These data were obtained by screening cytokine antibody arrays. In parallel, we present concentrations of 29 oxylipins and 4 endocannabinoids measured in mitochondrial fractions isolated from post-mortem PD cerebellum with age and sex matched controls. Our oxylipin and endocannabinoid data were acquired via quantitation by LC-ESI—MS/MS. The separate sample sets both show there are clearly different inflammatory profiles between the sexes in control samples. Sex specific profiles were not maintained in cerebellar mitochondria isolated from PD brains.
Influence of Cultivation Regime Upon Buried Weed Seeds in Arable Cropping Systems

(1) The effects of cultivation on the number of seeds of different species in arable land were investigated at four sites over several years. Soil cores were obtained from uncultivated and ploughed plots, and the seed content determined by germinating the seeds and counting and identifying the emerged seedlings. (2) Distribution of seeds was not uniform in the soil profile, and fluctuated annually on ploughed plots. Seed decline, although not markedly different between treatments, was more rapid in ploughed soil. The rate of seed decline at different depths was similar for both uncultivated and ploughed plots. Successful germination alone could not account for the rate of seed decline reported,4indicating that losses from other causes were substantial. (3) A considerable number of species were recorded in the seed bank (23-30), but only a few (3-4) comprised the majority. A number of species present in the seed bank of uncultivated soil were absent from the seedling flora.
A Double-Edged Sword: Neurologic Complications and Mortality in Extracorporeal Membrane Oxygenation Therapy for COVID-19–Related Severe Acute Respiratory Distress Syndrome at a Tertiary Care Center

SUMMARY: In this clinical case series, we report our experience to date with neurologic complications of extracorporeal membrane oxygenation therapy for COVID-19 Acute Respiratory Distress Syndrome. We have found an unexpectedly increased rate of complications as demonstrated by neuroimaging compared with meta-analysis data in extracorporeal membrane oxygenation therapy for all Acute Respiratory Distress Syndrome etiologies over the past few decades and compared with the most recent baseline data describing the incidence of neurologic complication in all patients with COVID-19. For our 12-patient cohort, there was a rate of intracranial hemorrhage of 41.7%. Representative cases and images of devastating intracranial hemorrhage are presented. We hypothesize that the interplay between hematologic changes inherent to extracorporeal membrane oxygenation and inflammatory and coagulopathic changes that have begun to be elucidated as part of the COVID-19 disease process are responsible. Continued analysis of extracorporeal membrane oxygenation therapy in this disease paradigm is warranted.
Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population

Background: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. Methods: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. Results: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. Conclusions: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.