Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel tyrosine kinase inhibitor can augment radioactive iodine uptake through endogenous sodium/iodide symporter (NIS) expression in anaplastic thyroid cancer.

Background Radioactive iodine (RAI) therapy is an important strategy in the treatment of thyroid cancer. However, anaplastic thyroid cancer (ATC), a rare malignancy, exhibits severe de-differentiation characteristics along with a lack of sodium iodide symporter (NIS) expression and function. Therefore, RAI therapy is ineffective and contributes toward poor prognosis of these patients. Recently, small-molecule tyrosine kinase inhibitors (TKIs) have been used to treat thyroid cancer patients for restoring NIS expression and function and RAI uptake capacity. However, most results reported thus far are associated with differentiated thyroid cancer. Here, we identified a new TKI and investigated its effects on cell re-differentiation, NIS function, and RAI therapy in ATC. Methods We identified a new TKI, "5-(5- {4H, 5H,6H-cyclopenta[b]thiophen-2-yl}-1,3,4-oxadiazol-2-yl)-1-methyl-1,2-dihydropyridin-2-one" (CTOM-DHP) using a high-throughput screening system. CTOM-DHP was exposed to 8505C ATC cells at different concentrations and timepoints. Concentrations of 12.5 µM and 25 µM and an incubation time of 72 hours, were chosen as the conditions for subsequent NIS promoter assays and NIS mRNA and protein expression experiments. Additionally, we examined factors related to iodide metabolism after CTOM-DHP treatment as well as the signaling pathways mediating the effects of CTOM-DHP on endogenous NIS expression. RAI uptake and 131I cytotoxicity effects caused by CTOM-DHP pre-treatment were also evaluated in vitro and in vivo. Results Promoter assays as well as mRNA and protein expression analyses confirmed that NIS expression was augmented by treatment of 8505C ATC cells with CTOM-DHP. Moreover, CTOM-DHP treatment robustly increased the expression of other thyroid-specific proteins and thyroid transcription factors related to iodide metabolism. Enhancement of NIS function was demonstrated by an increase in 125I uptake and 131I cytotoxicity. Increased endogenous NIS expression was associated with the inhibition of PI3K/Akt and MAPK signaling pathways. In vivo results also demonstrated an increase in NIS promoter activity and RAI avidity in response to CTOM-DHP treatment. Furthermore, 131I-mediated therapeutic effects preferentially improved in a tumor xenograft mice model. Conclusions CTOM-DHP, a new TKI identified in this study, enhances endogenous NIS expression and thereby is a promising compound for restoring RAI avidity in ATC.
Sexual and Reproductive Health Web Sites: An Analysis of Content for Sexual and Gender Minority Youth

Purpose: Sexual and gender minority (SGM) youth face risks for negative sexual and reproductive health (SRH) outcomes; it is critical to provide these populations with health education that is both inclusive of and specific to their needs. We sought to characterize the strengths and weaknesses of SGM-related messages from web sites that address SRH for young people. We considered who is included, what topics are discussed, and how messages are framed. Methods: A systematic Google search and screening process was used to identify health promotion web sites with SRH content for adolescents and young adults. Using MAXQDA, we thematically coded and analyzed SGM content qualitatively. Results: Of 32 SRH web sites identified, 23 (71.9%) contained SGM content. Collectively, the sites included 318 unique SGM codes flagging this content. Approximately two-thirds of codes included messages that discussed SGM youth in aggregate (eg, lesbian, gay, bisexual, and transgender)—specific content about the diverse subpopulations within this umbrella term (eg, transgender youth) was more limited. In addition to SRH topics, most web sites had messages that addressed a broad array of other health issues including violence, mental health, and substance use (n = 17, 73.9%) and SGM-specific topics, for example coming out (n = 21, 91.3%). The former were often risk-framed, yet affirmational messages were common. Most web sites (n = 16; 69.6%) presented information for SGM youth both in stand-alone sections and integrated into broader content. Yet, integrated information was slightly more common (56.6% of all codes) than stand-alone content. Conclusions: Challenges of developing SRH content related to SGM youth include: (1) aggregate terms, which may not represent the nuances of sexual orientation and gender, (2) balancing risk versus affirmational messages, and (3) balancing stand-alone versus integrated content. However, SGM-related content also offers an opportunity to address diverse topics that can help meet the needs of these populations.
Questioning the Effort Hypothesis That Depressed Patients Perform Disproportionately Worse on Effortful Cognitive Tasks

The debate over Hasher and Zacks’ effort hypothesis—that performance on effortful tasks by patients with depression will be disproportionately worse than their performance on automatic tasks—shows a need for additional research to settle whether or not this notion is “clinical lore. ” In this study, we categorized 285 outpatient recipients of neuropsychological evaluations into three groups—No Depression, Mild-to-Moderate Depression, and Severe Depression—based on their Beck Depression Inventory-2 self-reports. We then compared these groups’ performances on both “automatic” and “effortful” versions of the Ruff 2 & 7 Selective Attention Test Total Speed and Total Accuracy Indices, the Digit Span subtest from the Wechsler Adult Intellectual Scale—Fourth Edition, and Trail Making Test Parts A and B, using a two-way (3 × 2) mixed multivariate analysis of variance. Patients with Mild-to-Moderate Depression or Severe Depression performed disproportionately worse than patients with No Depression in our sample on more effortful versions of only one of the four attention or executive functioning measures (Trail Making Test). Thus, these data failed to fully support a hypothesis of disproportionately worse performance on more effortful tasks. While this study failed to negate the effort hypothesis in some specific instances, particularly for use in the Trail Making Test, there is cause for caution in routinely applying the effort hypothesis when interpreting test findings in most clinical settings and for most measures.
Digestive tract microbiota of beef cattle that differed in feed efficiency.

We hypothesized cattle that differed in BW gain had different digestive tract microbiota. Two experiments were conducted. In both experiments steers received a diet that consisted of 8.0% chopped alfalfa hay, 20% wet distillers grain with solubles, 67.75% dry-rolled corn, and 4.25% vitamin/mineral mix (including monensin) on a dry matter basis. Steers had ad libitum access to feed and water. In Exp. 1, 144 steers (age = 310 ± 1.5 d; BW = 503 ± 37.2 kg) were individually fed for 105 d. Ruminal digesta samples were collected from 8 steers with the greatest (1.96 ± 0.02 kg/d) and 8 steers with the least ADG (1.57 ± 0.02 kg/d) that were within ± 0.32 SD of the mean (10.1 ± 0.05 kg/d) dry matter. In Exp. 2, 66 steers (age = 396 ± 1 d; BW = 456 ± 5 kg) were individually fed for 84 d. Rumen, duodenum, jejunum, ileum, cecum, and colon digesta samples were collected from 8 steers with the greatest (2.39 ± 0.06 kg/d) and 8 steers with the least ADG (1.85 ± 0.06 kg/d) that were within ± 0.55 SD of the mean dry matter intake (11.9 ± 0.1 kg/d). In both studies, DNA was isolated and the V1 to V3 regions of the 16S rRNA gene were sequenced. Operational taxonomic units were classified using 0.03 dissimilarity and identified using the Greengenes 16S rRNA Gene Database. In Exp.1, there were no differences in the Chao1, Shannon, Simpson, and InvSimpson diversity indexes or the PERMANOVA (P = 0.57). The hierarchical test returned 6 clades as being differentially abundant between steer classifications (P < 0.05). In Exp. 2, Chao1, Shannon, Simpson, and InvSimpson diversity indexes and PERMANOVA between steer classified as less or greater ADG did not differ (P > 0.05) for the rumen, duodenum, ileum, cecum, and colon. In the jejunum, there tended to be a difference in the Chao1 (P = 0.09) and Simpson diversity (P = 0.09) indexes between steer classifications, but there was no difference in the Shannon (P = 0.14) and InvSimpson (P = 0.14) diversity indexes. Classification groups for the jejunum differed (P = 0.006) in the PERMANOVA. The hierarchical dependence false discovery rate procedure returned 11 clades as being differentially abundant between steer classifications in the jejunum (P < 0.05). The majority of the OTU were in the Families Corynebacteriaceae and Coriobacteriaceae. This study suggests that intestinal differences in microbiota of ruminants may be associated with animal performance.
Molecular structure of a U•A-U-rich RNA triple helix with 11 consecutive base triples

Abstract Three-dimensional structures have been solved for several naturally occurring RNA triple helices, although all are limited to six or fewer consecutive base triples, hindering accurate estimation of global and local structural parameters. We present an X-ray crystal structure of a right-handed, U•A-U-rich RNA triple helix with 11 continuous base triples. Due to helical unwinding, the RNA triple helix spans an average of 12 base triples per turn. The double helix portion of the RNA triple helix is more similar to both the helical and base step structural parameters of A′-RNA rather than A-RNA. Its most striking features are its wide and deep major groove, a smaller inclination angle and all three strands favoring a C3′-endo sugar pucker. Despite the presence of a third strand, the diameter of an RNA triple helix remains nearly identical to those of DNA and RNA double helices. Contrary to our previous modeling predictions, this structure demonstrates that an RNA triple helix is not limited in length to six consecutive base triples and that longer RNA triple helices may exist in nature. Our structure provides a starting point to establish structural parameters of the so-called ‘ideal’ RNA triple helix, analogous to A-RNA and B-DNA double helices.
Transcriptome profile and association study revealed STAT3 gene as a potential quality marker of bovine gametes

Summary The present study was aimed to investigate differences in molecular signatures in oocytes derived from Holstein-Friesian heifers with different genetic merit for fertility, euthanized during day 0 or day 12 of the estrous cycle. Moreover, association between single nucleotide polymorphisms (SNPs) of ODC1 and STAT3 genes and bull fertility traits was investigated. The gene expression patterns were analyzed using cDNA array and validated with quantitative real-time polymerase chain reaction (PCR). The result revealed that several genes have shown not only to be regulated by fertility merit but also by the day of oocyte recovery during the estrous cycle. The STAT3 gene was found to be upregulated in oocytes recovered from animals with high fertility merit at both day 0 and day 12. Some other genes like PTTG1, ODC1 and TUBA1C were downregulated at day 0 and upregulated at day 12 in high, compared with low, fertility merit recovered oocytes. In contrast, the transcript abundance of TPM3 was upregulated at day 0 and downregulated at day 12 in high, compared with low, fertility merit recovered oocytes. In addition, ODC1 and STAT3 were found to be associated (P < 0.05) with sperm quality traits as well as flow cytometry parameters. Therefore, the expression of several candidate genes including ODC1 and STAT3 was related to the genetic merit of the cow. In addition polymorphisms in these two genes were found to be associated with bull semen quality.
Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling

Tissue homeostasis and regeneration in the Drosophila midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation by sequestering the transcription co-factor Yorkie (Yki) in the cytoplasm, a factor required for rapid ISC proliferation under injury-induced regeneration. Nonetheless, the mechanism of Hippo-mediated midgut homeostasis and whether canonical Hippo signaling is involved in ISC basal proliferation are less characterized. Here we identify Lola as a transcription factor acting downstream of Hippo signaling to restrict ISC proliferation in a Yki-independent manner. Not only that Lola interacts with and is stabilized by the Hippo signaling core kinase Warts (Wts), Lola rescues the enhanced ISC proliferation upon Wts depletion via suppressing Dref and SkpA expressions. Our findings reveal that Lola is a non-canonical Hippo signaling component in regulating midgut homeostasis, providing insights on the mechanism of tissue maintenance and intestinal function.
Description and characterization of the artisanal elasmobranch fishery on Guatemala’s Caribbean coast

Small-scale shark and ray fisheries are conducted throughout Central America’s Caribbean coast. Yet, there is limited information regarding catch composition and diversity of these fisheries, especially in Guatemala. Surveys of catch landings were conducted in two of Guatemala’s primary Caribbean coastal shark and ray fishing communities, El Quetzalito and Livingston, between January 2015 and July 2017. Biological data from 688 landed chondrichthyans were collected, with 31 species (24 sharks, six rays and one chimaera) identified. The four most frequently captured species included Carcharhinus falciformis (30.2%), Sphyrna lewini (12.7%), Hypanus guttatus (12%) and Rhizoprionodon spp. (6.7%). Landed sharks contained most size classes with a high proportion of juveniles of species with low productivity. The large-bodied species C. falciformis and S. lewini were often recorded at sizes below known maturity; 96.6% and 85.1%, of the captured individuals were immature, respectively. This study can serve as a baseline to determine future trends in the elasmobranch fisheries conducted by Guatemala’s Caribbean coastal communities and support assessments on the persistence of the fisheries.
Prevalence and Factors Associated With Intimate Partner Violence Among Women in Haiti: Understanding Household, Individual, Partner, and Relationship Characteristics

Intimate partner violence (IPV) is a significant public health issue with detrimental consequences for women’s reproductive, mental, and physical health. In Haiti, IPV is a major obstacle to women’s development. Yet, the determinants of IPV victimization are still not well understood. In this study, we utilized the 2016–2017 Haiti Demographic and Health Survey to determine the prevalence of IPV victimization and its subtypes (emotional, physical, and sexual abuse) among married or cohabiting women (N = 3,805) of reproductive age (15–49) by their current husband/partner. Logistic regression was conducted to explore the association between IPV and household, individual, husband/partner, and relationship characteristics. The prevalence of IPV victimization was 32.5% with the majority reporting emotional (24.7%) followed by physical (16.8%) and sexual (10.5%) violence. Increased odds of IPV victimization were found among women with children in the household (adjusted odds ratio [AOR] = 1.45, 95% confidence interval [CI] = [1.03, 2.02]), with attitudinal acceptance of wife-beating (AOR = 1.45, 95% CI = [1.05, 2.02]), and those who witnessed their father beating their mother (AOR = 1.49, 95% CI = [1.18, 2.67]). Higher odds of reporting IPV victimization were also found among women whose partner drank alcohol (AOR = 2.89, 95% CI = [2.29, 3.65]), who were in a polygynous relationship (AOR = 1.76, 95% CI = [1.23, 2.40]), and displayed one or more controlling behaviors (AOR = 1.92, 95% CI = [1.42, 2.59]). Women who reported being afraid of their partner had greater odds of IPV victimization (AOR = 16.22, 95% CI = [8.38, 31.39]). Decreased odds of reporting IPV were associated with women living in rural areas (AOR = 0.73, 95% CI = [0.53, 1.00]) and those unmarried, but living with their partner (AOR = 0.62, 95% CI = [0.43, 0.90]). Our findings identify subgroups of women in Haiti that may be vulnerable to IPV victimization. Thus, we recommend a differentiated approach to IPV prevention strategies and interventions that consider women’s family structure in the household as well as individual, partner, and relationship characteristics.
Unique Characteristics of Intravitreal Silicone Oil on Dual-Energy Computed Tomography

Abstract Silicone oil is used as an intravitreal injection to treat retinal detachment. This material can spread into the subarachnoid space, where it may be mistaken for acute hemorrhage on single-energy computed tomography. This report describes the appearance of intravitreal silicone oil on dual-energy computed tomography, emphasizing unique virtual monoenergetic imaging characteristics that allow for confident differentiation of silicone oil from hemorrhage as well as from other potential single-energy mimics, such as calcium and iodine.
Effective temperature shift strategy development and scale confirmation for simultaneous optimization of protein productivity and quality in Chinese hamster ovary cells

Temperature shifts to lower culture temperatures are frequently employed in the manufacturing of protein therapeutics in mammalian cells to improve productivity, viability, or quality attributes. The direction and extent to which a temperature shift affects productivity and quality may vary depending on the expression host and characteristics of the expressed protein. We demonstrated here that two Chinese hamster ovary (CHO) clones expressing different human monoclonal antibodies responded differently to a temperature shift despite sharing a common parental CHO cell line. Within a single CHO line, we observed a nonlinear response to temperature shift. A moderate shift to 35°C significantly decreased final titer relative to the unshifted control while a larger shift to 32°C significantly increased final titer by 25%. Therefore, we proposed a systematic empirical approach to assess the utility of a temperature shift for faster implementation during process development. By testing multiple shift parameters, we identified optimum shift conditions in shake flasks and successfully translated findings to benchtop bioreactors and 1,000‐L bioreactor scale. Significant differences in final antibody titer and charge variants were observed with temperature shift increments as small as Δ1. 5°C. Acidic charge variants decreased monotonically with decreasing shift temperature in both cell lines; however, final antibody titer required simultaneous optimization of shift day and temperature. Overall, we were able to show that a systematic approach to identify temperature shift parameters at small scales is useful to optimize protein production and quality for efficient and confident translation to large‐scale production.
Value of CT combined with TM detection in diagnosis of non-small cell lung cancer

Objective:To explore the value of CT in combined with serum tumor marker(TM)in determining the diagnosis of non-small cell lung cancer.Methods:A total of 160 patients histopathologically diagnosed with non-small cell lung cancer who were admitted in our hospital were included in the study including 68 cases diagnosed with adenocarcinoma,and 92 patients suffered from squamous carcinoma.All patients underwent CT examination and the serum TM level was determined.The accuracy of CT in combined with TM detection in diagnosis of non-small cell lung cancer was analyzed.Results:The diagnostic coincidence rate of CT in diagnosing adenocarcinoma and squamous carcinoma was higher than that by TM detection,and the diagnostic coincidence rate by the combined examination was significantly higher than that by single examination(P0.05). The serum CYFRA21-1 and CEA mean values in the two types of non-small cell lung cancer patients were significantly higher than the positive standard values(P0.05). The serum CYFRA21-1 value in the squamous carcinoma patients was significantly higher than that in the adenocarcinoma patients(P0.05),while the serum CEA value in the adenocarcinoma patients was significantly higher than that in the squamous carcinoma patients(P0.05). Conclusions:It can be concluded that CT in combined with TM detection can enhance the accuracy of detecting non-small cell lung cancer,which provides a basis for developing a clinical therapeutic schedule.
Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia

Introduction We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. Materials and methods Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. Results Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99–1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81–0.98). Trends toward higher HBsAg-positivity were also seen at ages 30–39 years (AOR, 2.11; 95% CI, 0.96–4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93–3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). Conclusion Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.