Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecules with ALMA at Planet-forming Scales (MAPS). XI. CN and HCN as Tracers of Photochemistry in Disks

UV photochemistry in the surface layers of protoplanetary disks dramatically alters their composition relative to previous stages of star formation. The abundance ratio CN/HCN has long been proposed to trace the UV field in various astrophysical objects; however, to date the relationship between CN, HCN, and the UV field in disks remains ambiguous. As part of the ALMA Large Program MAPS (Molecules with ALMA at Planet-forming Scales), we present observations of CN N = 1–0 transitions at 0. ″3 resolution toward five disk systems. All disks show bright CN emission within ∼50–150 au, along with a diffuse emission shelf extending up to 600 au. In all sources we find that the CN/HCN column density ratio increases with disk radius from about unity to 100, likely tracing increased UV penetration that enhances selective HCN photodissociation in the outer disk. Additionally, multiple millimeter dust gaps and rings coincide with peaks and troughs, respectively, in the CN/HCN ratio, implying that some millimeter substructures are accompanied by changes to the UV penetration in more elevated disk layers. That the CN/HCN ratio is generally high (>1) points to a robust photochemistry shaping disk chemical compositions and also means that CN is the dominant carrier of the prebiotically interesting nitrile group at most disk radii. We also find that the local column densities of CN and HCN are positively correlated despite emitting from vertically stratified disk regions, indicating that different disk layers are chemically linked. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.
The substitution spectra of coronavirus genomes

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has triggered an unprecedented international effort to sequence complete viral genomes. We leveraged this wealth of information to characterize the substitution spectrum of SARS-CoV-2 and to compare it with those of other human and animal coronaviruses. We show that, once nucleotide composition is taken into account, human and most animal coronaviruses display a mutation spectrum dominated by C to U and G to U substitutions, a feature that is not shared by other positive-sense RNA viruses. However, the proportions of C to U and G to U substitutions tend to decrease as divergence increases, suggesting that, whatever their origin, a proportion of these changes is subsequently eliminated by purifying selection. Analysis of the sequence context of C to U substitutions showed little evidence of apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-mediated editing and such contexts were similar for SARS-CoV-2 and Middle East respiratory syndrome coronavirus sampled from different hosts, despite different repertoires of APOBEC3 proteins in distinct species. Conversely, we found evidence that C to U and G to U changes affect CpG dinucleotides at a frequency higher than expected. Whereas this suggests ongoing selective reduction of CpGs, this effect alone cannot account for the substitution spectra. Finally, we show that, during the first months of SARS-CoV-2 pandemic spread, the frequency of both G to U and C to U substitutions increased. Our data suggest that the substitution spectrum of SARS-CoV-2 is determined by an interplay of factors, including intrinsic biases of the replication process, avoidance of CpG dinucleotides and other constraints exerted by the new host.
Promoting Physical Activity Through Conversational Agents: Mixed Methods Systematic Review

Background Regular physical activity (PA) is crucial for well-being; however, healthy habits are difficult to create and maintain. Interventions delivered via conversational agents (eg, chatbots or virtual agents) are a novel and potentially accessible way to promote PA. Thus, it is important to understand the evolving landscape of research that uses conversational agents. Objective This mixed methods systematic review aims to summarize the usability and effectiveness of conversational agents in promoting PA, describe common theories and intervention components used, and identify areas for further development. Methods We conducted a mixed methods systematic review. We searched seven electronic databases (PsycINFO, PubMed, Embase, CINAHL, ACM Digital Library, Scopus, and Web of Science) for quantitative, qualitative, and mixed methods studies that conveyed primary research on automated conversational agents designed to increase PA. The studies were independently screened, and their methodological quality was assessed using the Mixed Methods Appraisal Tool by 2 reviewers. Data on intervention impact and effectiveness, treatment characteristics, and challenges were extracted and analyzed using parallel-results convergent synthesis and narrative summary. Results In total, 255 studies were identified, 7.8% (20) of which met our inclusion criteria. The methodological quality of the studies was varied. Overall, conversational agents had moderate usability and feasibility. Those that were evaluated through randomized controlled trials were found to be effective in promoting PA. Common challenges facing interventions were repetitive program content, high attrition, technical issues, and safety and privacy concerns. Conclusions Conversational agents hold promise for PA interventions. However, there is a lack of rigorous research on long-term intervention effectiveness and patient safety. Future interventions should be based on evidence-informed theories and treatment approaches and should address users’ desires for program variety, natural language processing, delivery via mobile devices, and safety and privacy concerns.
The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis

Visual Abstract Significance Statement In ANCA-associated vasculitis (AAV), noninvasive biomarkers of active renal inflammation, such as urinary soluble CD163, are needed for early detection of active disease before irreversible end organ damage occurs. Clinical translation requires a diagnostic-grade assay, prospective assessment of its diagnostic utility in AAV flare, and assessment of its utility in proteinuric states. The authors report use of an accredited, diagnostic-grade assay for urinary soluble CD163, derivation of cutoff values, and application of the assay to a prospective cohort of patients with potential renal vasculitis flare. They found that urinary soluble CD163 displays high precision in separating RV flare from flare mimics. They also observed increased false-positive results in the setting of high-grade proteinuria, which they demonstrated can be effectively corrected by normalization to the urine protein value, thereby restoring diagnostic accuracy. Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163’s specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a “positive” usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.
Evaluation of knowledge, awareness and attitudes towards breast cancer risk factors and early detection among females in Bangladesh: A hospital based cross-sectional study

Background Breast cancer (BCa) is a leading cause of mortality among women in Bangladesh. Many young women in Bangladesh have poor knowledge about breast cancer screening, including risk factors, warning signs/symptoms, diagnosis and early detection. We investigated awareness about breast cancer risk factors as a screening tool among women at the Sheikh Hasina Medical College (SHMC) of Tangail district in Bangladesh. Methods A cross sectional survey was conducted to collect data via a structured questionnaire from SHMC during the period of February to December 2019. A total of 1,007 participants (aged 33.47 (±12.37 years)) was considered for data analysis. Results Of the 1,007 women, about 50% were knowledgeable about the risk factors. Pain in the breast was identified as the most commonly warning sign/symptom of breast cancer. Only 32.2% of respondents knew at least one breast cancer screening method. The mean knowledge was scored 3.43 ± 2.25 out of a total possible score of 8. Awareness of BCa was associated with residence, family history of breast cancer, marital, literacy and socio-economic status (p <0.05). Only 14.7% of women who knew about BSE said they were conducting regular breast self-examination. Unmarried women (aOR: 2.971; 95% CI: 1.108–7.968) were more likely to have performed BSE compared to married women (p <0.05). Conclusion Although most participants were aware of breast cancer; knowledge about risk factors, warning signs/symptoms, early diagnosis and detection was relatively poor. Knowledge about performing BSE was particularly low. This highlights the importance of increasing awareness about breast cancer risk factors and early detection among young women in Bangladesh.
Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonia. Some miRNAs may be associated with IPF and may affect the occurrence and development of IPF in various pathways. Many miRNAs and genes that may be involved in the development of IPF have been discovered using chip and high throughput technologies. Methods: We analyzed one miRNA and four mRNA databases. We identified hub genes and pathways related to IPF using GO, KEGG enrichment analysis, gene set variation analysis (GSVA), PPI network construction, and hub gene analysis. A comprehensive analysis of differentially expressed miRNAs (DEMs), predicted miRNA target genes, and differentially expressed genes (DEGs) led to the creation of a miRNA-mRNA regulatory network in IPF. Results: We found 203 DEGs and 165 DEMs that were associated with IPF. The findings of enrichment analyses showed that these DEGs were mainly involved in antimicrobial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptide, extracellular matrix organization, cell killing, and organ or tissue specific immune response. The VEGFA, CDH5, and WNT3A genes overlapped between hub genes and the miRNA-mRNA regulatory network. The miRNAs including miR-199b-5p, miR-140-5p, miR-199a-5p, miR-125A-5p, and miR-107 that we predicted would regulate the VEGFA, CDH5, and WNT3A genes, which were also associated with IPF or other fibrosis-related diseases. GSVA indicated that metabolic processes of UTP and IMP, immune response, regulation of Th2 cell cytokine production, and positive regulation of NK cell-mediated immunity are associated with the pathogenesis and treatment of IPF. These pathways also interact with VEGFA, CDH5, and WNT3A. Conclusion: These findings provide a new research direction for the diagnosis and treatment of IPF.
Screening and prevention of colorectal cancer

Abstract Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.
Effect of a Nurse-Led Education Program for Stroke Patients on Sleep Quality and Quality of Life: A Randomized Controlled Study

Nurse-led education and follow-up for stroke patients may facilitate management and improve quality of life. This study investigated the effect of a nurse-led education program for stroke patients on sleep and life quality. A total of 92 stroke patients (46 in the intervention group, 46 in the control group) aged 18 to 75 years who were independently mobile (less than or equal to one assistive device) and had no other neurologic or psychiatric disorders or history of sleep disorder prior to stroke were included. Patients randomized to the intervention group completed a 20-week education and follow-up program including information about stroke, rehabilitation, adaptation to daily life, and the importance of sleep quality. In the posttest, the intervention group had significantly higher sleep quality and stroke-specific quality of life scores than the control group. This study may serve as a guide for nurses who work with stroke patients.
LIM Homeodomain (LIM-HD) Genes and Their Co-Regulators in Developing Reproductive System and Disorders of Sex Development

LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the LIM-HD proteins are regulated by the co-regulators LIM only (LMO) and LIM domain-binding (LDB). In the mouse genome, there are 13 LIM-HD genes (Lhx1–Lhx9, Isl1–2, Lmx1a–1b), 4 Lmo genes (Lmo1–4), and 2 Ldb genes (Ldb1–2). Amongst these, Lhx1 is required for the development of the müllerian duct epithelium and the timing of the primordial germ cell migration. Lhx8 is necessary for oocyte differentiation and Lhx9 for somatic cell proliferation in the genital ridges and control of testosterone production in the Leydig cells. Lmo4 is involved in Sertoli cell differentiation. Mutations in LHX1 are associated with müllerian agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. LHX9 gene variants are reported in cases with disorders of sex development (DSD). Mutations in LHX3 and LHX4 are reported in patients with combined pituitary hormone deficiency having absent or delayed puberty. A transcript map of the Lhx, Lmo, and Ldb genes reveal that multiple LIM-HD genes and their co-regulators are expressed in a sexually dimorphic pattern in the developing mouse gonads. Unraveling the roles of LIM-HD genes during development will aid in our understanding of the causes of DSD.
Hypocalcemia in a Patient With Metastatic Prostate Cancer From Denosumab Treatment

Denosumab is a humanized monoclonal antibody that binds RANKL to inhibit osteoclast activity. It is indicated for the prevention of skeletal-related events (SRE) in patients with solid tumors who have bone metastasis and in patients with multiple myeloma. Hypocalcemia is one of the known side effects of denosumab, which can be prevented with calcium supplementation. We present a case of a 72-year-old male with diagnosed metastatic prostate cancer who had received one dose of denosumab 10 days prior to presentation with fatigue, insomnia, and somnolence. His labs showed severe (Grade 4) hypocalcemia, which improved with intravenous calcium supplementation. This case highlights a known but life-threatening side effect of denosumab and the potential need for prolonged calcium monitoring in patients placed on the drug.
Bluefin tuna reveal global patterns of mercury pollution and bioavailability in the world's oceans

Significance Bluefin tuna (BFT) is an apex predatory, long-lived, migratory pelagic fish that is widely distributed throughout the world's oceans. These fish have very high concentrations of neurotoxic methylmercury (MeHg) in their tissues, which increase with age. Our study shows that Hg accumulation rates (MARs) in BFT as a global pollution index can reveal global patterns of Hg pollution and bioavailability in the oceans and further reflect both natural and anthropogenic emissions and regional environmental features. Overall, MARs provide a means to compare Hg bioavailability among geographically distinct populations of upper trophic level marine fish across ocean subbasins, to investigate trophic dynamics of Hg in marine food webs, and furthermore, to improve public health risk assessments of Hg exposure from seafood. Bluefin tuna (BFT), highly prized among consumers, accumulate high levels of mercury (Hg) as neurotoxic methylmercury (MeHg). However, how Hg bioaccumulation varies among globally distributed BFT populations is not understood. Here, we show mercury accumulation rates (MARs) in BFT are highest in the Mediterranean Sea and decrease as North Pacific Ocean > Indian Ocean > North Atlantic Ocean. Moreover, MARs increase in proportion to the concentrations of MeHg in regional seawater and zooplankton, linking MeHg accumulation in BFT to MeHg bioavailability at the base of each subbasin's food web. Observed global patterns correspond to levels of Hg in each ocean subbasin; the Mediterranean, North Pacific, and Indian Oceans are subject to geogenic enrichment and anthropogenic contamination, while the North Atlantic Ocean is less so. MAR in BFT as a global pollution index reflects natural and human sources and global thermohaline circulation.
Morphological canalization, integration, and plasticity in response to population density in Abutilon theophrasti: Influences of soil conditions and growth stages

Abstract Phenotypic integration and developmental canalization have been hypothesized to constrain the degree of phenotypic plasticity, but little evidence exists, probably due to the lack of studies on the relationships among the three processes, especially for plants under different environments. We conducted a field experiment by subjecting plants of Abutilon theophrasti to three densities, under infertile and fertile soil conditions, and analyzing correlations among canalization, integration, and plasticity in a variety of measured morphological traits after 50 and 70 days, to investigate the relationships among the three variables in response to density and how these responses vary with soil conditions and growth stages. Results showed trait canalization decreased and phenotypic integration and the degree of plasticity (absolute plasticity) in traits increased with density. Phenotypic integration often positively correlated with absolute plasticity, whereas correlations between trait canalization and plasticity were insignificant in most cases, with a few positive ones between canalization and absolute plasticity at low and medium densities. As plants grew, these correlations intensified in infertile soil and attenuated in fertile soil. Our findings suggested the complexity of the relationship between canalization and plasticity: Decreased canalization is more likely to facilitate active plastic responses under more favorable conditions, whereas increased level of integration should mainly be an outcome of plastic responses. Soil conditions and growth stage may affect responses of these correlations to density via modifying plant size, competition strength, and plastic responses in traits. We also predicted that decreased canalization can be advantageous or disadvantageous, and the lack of response to stress may demonstrate a stronger ability of adaptation than passive response, thus should be adaptive plasticity as active response.
Prevalence and Multiplicity of Thrombophilia Genetic Polymorphisms of FV, MTHFR, FII, and PAI-I: A Cross-Sectional Study on a Healthy Jordanian Population

Background FV, MTHFR, II, and PAI-I are the most common genes associated with thrombophilia genetic variants, which vary among different populations and ethnic groups. Little is known about the prevalence and multiplicity of these variants in Jordan. The aim of this study was to estimate the prevalence and multiplicity of the FV G1691A, FV H1299R, MTHFR 1298A>C, MTHFR 677C>T, II 20210G>A, and PAI-I 675 4G/5G variants among healthy Jordanians. Methods This cross-sectional study was conducted on randomly selected healthy Jordanian participants. Non-Jordanians and those with a history of arterial/venous thrombosis, atherosclerosis, or a history of recurrent abortions were excluded from the study. PCR was used to detect variants in DNA extracted from participants’ blood samples. Results A total of 300 subjects were screened: 170 (56.7%) females with an average age of 27.78±9.32 years and 130 (43.3%) males with an average age of 29.88±8.55 years. Genetic variants (at least one) were found in 75% of the subjects (81.2% among females and 66.9% among men), while 64.7%, 52%, and 12% were found to have at least two, three, and four variants, respectively. Overall, 21%, 29%, 54.3%, 27.3%, 7.7%, and 66% of participants were found to have FV G1691A, FV H1299R, MTHFR 1298A>C, MTHFR 677C>T, II 20210G>A, and PAI-I 675 4G/5G gene variants, respectively. Conclusion Three-quarters of our population had at least one of the thrombophilia genetic variants, and most had more than one variant. The most common variants detected were associated with MTHFR, followed by PAI-I, FV, and then II. We observed that females had higher prevalence estimates than males. However, multiplicity among males was significantly higher than females. Our findings indicated noticeable differences in prevalence estimates compared with other populations.
Understanding the Significance of the Hypothalamic Nature of the Subthalamic Nucleus

Abstract The subthalamic nucleus (STN) is an essential component of the basal ganglia and has long been considered to be a part of the ventral thalamus. However, recent neurodevelopmental data indicated that this nucleus is of hypothalamic origin which is now commonly acknowledged. In this work, we aimed to verify whether the inclusion of the STN in the hypothalamus could influence the way we understand and conduct research on the organization of the whole ventral and posterior diencephalon. Developmental and neurochemical data indicate that the STN is part of a larger glutamatergic posterior hypothalamic region that includes the premammillary and mammillary nuclei. The main anatomic characteristic common to this region involves the convergent cortical and pallidal projections that it receives, which is based on the model of the hyperdirect and indirect pathways to the STN. This whole posterior hypothalamic region is then integrated into distinct functional networks that interact with the ventral mesencephalon to adjust behavior depending on external and internal contexts.