Miracle-dz/UniFAR-FTUs huggingface dataset:
Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming

Induction of pluripotent stem cells (iPSC) by OCT4 (octamer-binding transcription factor 4), SOX2 (SR box 2), KLF4 (Krüppel-Like Factor 4), and MYC (cellular Myelocytomatosis, c-MYC or MYC) (collectively OSKM) is revolutionary, but very inefficient, slow, and stochastic. It is unknown as to what underlies the potency aspect of the multi-step, multi-pathway, and inefficient iPSC reprogramming. Mesenchymal-to-epithelial (MET) transition is known as the earliest pathway reprogrammed. Using the recently established concepts of reprogramome and reprogramming legitimacy, the author first demonstrated that ribosome biogenesis (RB) is globally enriched in terms of human embryonic stem cells in comparison with fibroblasts, the popular starting cells of pluripotency reprogramming. It is then shown that the RB network was reprogrammed quickly in a coordinated fashion. Human iPSCs also demonstrated a more robust ribosome biogenesis. The quick and global reprogramming of ribosome biogenesis was also observed in an independent fibroblast line from a different donor. This study additionally demonstrated that MET did not initiate substantially at the time of proper RB reprogramming. This quick, coordinated and authentic RB reprogramming to the more robust pluripotent state by the OSKM reprogramming factors dramatically contrasts the overall low efficiency and long latency of iPSC reprogramming, and aligns well with the potency aspect of the inefficient OSKM reprogramming.
Silencing KIF14 reverses acquired resistance to sorafenib in hepatocellular carcinoma

For nearly a decade, sorafenib has served as a first-line chemotherapeutic drug for the treatment of hepatocellular carcinoma (HCC), but it displays only limited efficacy against advanced drug-resistant HCC. Regorafenib, the first second-line drug approved for treatment after sorafenib failure, can reverse resistance to sorafenib. We used bioinformatics methods to identify genes whose expression was differentially induced by sorafenib and regorafenib in HCC. We identified KIF14 as an oncogene involved in the acquired resistance to sorafenib in HCC and investigated its potential as a target for reversing this resistance. Sustained exposure of resistant HCC cells to sorafenib activated the AKT pathway, which in turn upregulated KIF14 expression by increasing expression of the transcription factor ETS1. Silencing KIF14 reversed the acquired resistance to sorafenib by inhibiting AKT activation and downregulating ETS1 expression by blocking the AKT–ETS1–KIF14 positive feedback loop. Moreover, injection of siKIF14 with sorafenib suppressed growth of sorafenib-resistant HCC tumors in mice. These results demonstrate that targeting KIF14 could be an effective means of reversing sorafenib failure or strengthening sorafenib’s antitumor effects.
Novel 1-Amidino-4-Phenylpiperazines as Potent Agonists at Human TAAR1 Receptor: Rational Design, Synthesis, Biological Evaluation and Molecular Docking Studies

Targeting trace amine-associated receptor 1 (TAAR1) receptor continues to offer an intriguing opportunity to develop innovative therapies in different pharmacological settings. Pursuing our endeavors in the search for effective and safe human TAAR1 (hTAAR1) ligands, we synthesized a new series of 1-amidino-4-phenylpiperazine derivatives (1–16) based on the application of a combined pharmacophore model/scaffold simplification strategy for an in-house series of biguanide-based TAAR1 agonists. Most of the novel compounds proved to be more effective than their prototypes, showing nanomolar EC50 values in functional activity at hTAAR1 and low general cytotoxicity (CC50 > 80 µM) when tested on the Vero-76 cell line. In this new series, the main determinant for TAAR1 agonism ability appears to result from the appropriate combination between the steric size and position of the substituents on the phenyl ring rather than from their different electronic nature, since both electron-withdrawing and electron donor groups are permitted. In particular, the ortho-substitution seems to impose a more appropriate spatial geometry to the molecule that entails an enhanced TAAR1 potency profile, as experienced, in the following order, by compounds 15 (2,3-diCl, EC50 = 20 nM), 2 (2-CH3, EC50 = 30 nM), 6 (2-OCH3, EC50 = 93 nM) and 3 (2-Cl, EC50 = 160 nM). Apart from the interest in them as valuable leads for the development of promising hTAAR1 agonists, these simple small molecules have further allowed us to identify the minimal structural requirements for producing an efficient hTAAR1 targeting ability.
PREVALENCE OF TRYPANOSOMA CRUZI IN BACKYARD MAMMALS FROM A RURAL COMMUNITY OF YUCATAN, MEXICO

Trypanosoma cruzi the causative agent of Chagas disease, can be found in more than 150 different species of domestic and wild mammals in the American continent. Domestic mammals like dogs, and commensal rodents, have been frequently implicated as hosts and/or reservoirs in the domestic and peridomestic cycle of transmission, however, little attention have been paid to backyard mammals as potential maintaining hosts of T. cruzi in the peridomicile. In the present work, we reported the first data of prevalence of infection with T. cruzi in the backyard mammals of households in a rural community of Yucatan, Mexico. A total of 84 animals, including swine, sheep, horses, cattle and rabbits, were sampled. Blood samples were collected and processed for DNA extraction of parasite and analyzed by PCR technique. From all animals tested, 75% of the pigs (21/28), 85.71% of the sheep (6/7) and 100% of the horses (8/8), were positive for T. cruzi. Cattle (28) and rabbits (13) were negative. The results obtained constitute an important preliminary evidence to implicate backyard mammals as potential maintaining hosts of T. cruzi in the peridomestic habitat of rural communities in Yucatan.
Molecular Characteristics of Rickettsia in Ticks Collected along the Southern Border of Mongolia

Tick-borne infections are a significant threat to public health, particularly in regions where individuals frequently enter tick habitats. Roughly 26% of the population in Mongolia practice nomadic pastoralism and are considered at high risk of exposure to ticks and the diseases they carry. This study tested ticks from Mongolia’s southern border for Rickettsia spp. to better understand the epidemiology of tick-borne diseases in the region. Dermacentor nuttalli and Hyalomma asiaticum ticks (n = 4022) were pooled and tested for Rickettsia spp. by real-time PCR. Melt-curve analyses and Sanger sequencing were used to identify Rickettsia species. Approximately 64% of the 786 tick pools tested positive for Rickettsia bacteria. Melt curve analyses identified four different Rickettsia species circulating in these tick pools. Amplicon sequencing of the ompA gene identified Rickettsia spp. that closely resembled R. raoultii and R. sibirica. Dermacentor nuttalli ticks from Govi-Altai had the highest maximum likelihood estimation infection rate 48.4% (95% CI: 41.7–56.5%), while Hyalomma asiaticum collected in Omnogovi had a rate of 7.6% (95% CI: 6.2–9.2%). The high detection of Rickettsia suggests a substantial risk of infection in southern Mongolia. Further studies are necessary to investigate the clinical burden of tick-borne diseases in Mongolia.
Psychological Capital and Burnout in Teachers: The Mediating Role of Flourishing

In keeping with the growth in the development of healthy environments in organizational contexts, in recent years, there has also been increasing interest in the identification of personal psychological resources that contribute to improved worker mental health. From this proactive approach, this study examines the mediating role of flourishing in the relationship between psychological capital (PsyCap) and burnout in teachers, a professional group that is particularly prone to suffering from this syndrome. A total of 1379 teachers from pre-school, primary, secondary, and vocational education systems participated in the study. The mediating effect of flourishing was determined via mediation analysis using the PROCESS macro. The results showed that flourishing partially mediates the negative effect of PsyCap on the three symptoms of burnout (emotional exhaustion, depersonalization, and lack of professional accomplishment). These findings indicate that both PsyCap and flourishing may be effective personal resources in reducing teacher burnout. Therefore, in order to prevent burnout, it is advisable to design interventions that combine PsyCap and flourishing.
Monitoring Culicine Mosquitoes (Diptera: Culicidae) as a Vector of Flavivirus in Incheon Metropolitan City and Hwaseong-Si, Gyeonggi-Do, Korea, during 2019

The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquitoes or tick vectors and are etiological agents of acute zoonotic infections. The viruses are found around the world and account for significant cases of human diseases. We investigated population of culicine mosquitoes in central region of Korean Peninsula, Incheon Metropolitan City and Hwaseong-si. Aedes vexans nipponii was the most frequently collected mosquitoes (56.5%), followed by Ochlerotatus dorsalis (23.6%), Anopheles spp. (10.9%), and Culex pipiens complex (5.9%). In rural regions of Hwaseong, Aedes vexans nipponii was the highest population (62.9%), followed by Ochlerotatus dorsalis (23.9%) and Anopheles spp. (12.0%). In another rural region of Incheon (habitat of migratory birds), Culex pipiens complex was the highest population (31.4%), followed by Ochlerotatus dorsalis (30.5%), and Aedes vexans vexans (27.5%). Culex pipiens complex was the predominant species in the urban region (84.7%). Culicine mosquitoes were identified at the species level, pooled up to 30 mosquitoes each, and tested for flaviviral RNA using the SYBR Green-based RT-PCR and confirmed by cDNA sequencing. Three of the assayed 2,683 pools (989 pools without Anopheles spp.) were positive for Culex flaviviruses, an insect-specific virus, from Culex pipiens pallens collected at the habitats for migratory birds in Incheon. The maximum likelihood estimation (the estimated number) for Culex pipiens pallens positive for Culex flavivirus was 25. Although viruses responsible for mosquito-borne diseases were not identified, we encourage intensified monitoring and long-term surveillance of both vector and viruses in the interest of global public health.
Using Hepatocellular Carcinoma Tumor Burden Score to Stratify Prognosis after Liver Transplantation

Simple Summary Liver transplantation (LT) is an important therapeutic option in selected patients with hepatocellular carcinoma (HCC). Tumor factors such as size and number of tumors define the eligibility criteria for LT through the Milan criteria. The tumor burden score (TBS) incorporates both tumor number and size into a single continuous variable and has been successfully used to differentiate prognosis among patients undergoing resection for HCC. Moreover, the TBS has been included in the complex predictive scores of outcomes after LT for HCC. This study evaluated the role of the TBS as a solitary simple score to predict outcomes after LT for HCC. Abstract Liver transplantation (LT) remains a mainstay of treatment for hepatocellular carcinoma (HCC). Tumor factors such as size and number of tumors define eligibility for LT using the Milan criteria. The tumor burden score (TBS) incorporates both tumor number and size into a single continuous variable and has been used to differentiate prognosis among patients undergoing resection for HCC. The objective of the present study was to evaluate the ability of the TBS to predict overall and recurrence-free survival in patients undergoing LT for HCC. The Scientific Registry of Transplant Recipients (SRTR) was used to analyze all liver transplants for HCC, with initial tumor size data from 2004 to 2018. There were 12,486 patients in the study period. In the unadjusted analyses, patients with a high TBS had worse overall (p < 0.0001) and recurrence-free (p < 0.0001) survival. In the adjusted analyses, a high TBS was associated with a greater hazard ratio (HR) of death (HR = 1.21; 95%CI, [1.13–1.30]; p < 0.001) and recurrence (HR = 1.49; 95%CI [1.3–1.7]; p < 0.001). When we superimposed the TBS on the Milan criteria, we saw that a higher TBS was associated with a higher hazard of recurrence at values that were either all within (HR = 1.20; 95%CI, [1.04–1.37]; p = 0.011) or variably within (HR = 1.53; 95%CI, [1.16–2.01]; p = 0.002) the Milan criteria. In conclusion, the TBS is a promising tool in predicting outcomes in patients with HCC after LT.
Effects of Dietary Supplementation of Humic Acid Sodium and Zinc Oxide on Growth Performance, Immune Status and Antioxidant Capacity of Weaned Piglets

Simple Summary Weaning of piglets can destroy the piglet’s intestinal health and immune function, leading to diarrhea and a reduction in growth rate eventually. Considering drug resistance and residues, new alternatives, such as sodium humate (HNa), have attracted considerable research interest over recent decades. Our study was designed to explore the effect of HNa on the growth performance, diarrhea rate, antioxidative, inflammation, and immunity of weaned piglets and the possibility of HNa replacing antibiotics and zinc oxide. The obtained results indicate that HNa reduces stress, protects the intestinal barrier, and improves the performance of weaned piglets. Abstract At present, the widespread use of high-dose zinc oxide and antibiotics to prevent post-weaning diarrhea (PWD) in piglets has caused serious environmental problems. To solve this problem, we studied the effect of HNa as a substitute for zinc oxide (ZnO) and antibiotics on the growth performance, immune status, and antioxidant capacity of piglets. Seventy-two weaned piglets (body weight = 7.42 ± 0.85 kg, 26-d-old) were distributed in a randomized 2 × 3 factorial design (two sexes and three treatments) with six replicates of four piglets each. The three treatments were the control diet (basic diet), HNa diet (basic diet + 2000 mg/kg sodium humate), and ZoA group (basic diet + 1600 mg/kg zinc oxide + 1000 mg/kg oxytetracycline calcium). ANOVA and Chi-square tests were applied to compare the means (p < 0.05) between treatments. The results showed that body weight at 16 and 30 d and the average daily gain of piglets fed with HNa or ZoA were significantly higher (p < 0.05) than the control group. Supplementing HNa or ZoA significantly increased (p < 0.05) the level of immunoglobulin M and G, and reduced (p < 0.05) the concentration of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukins IL-6 and IL-1β, myeloperoxidase (MPO), and diamine oxidase (DAO). Furthermore, dietary HNa or ZnO significantly reduced (p < 0.05) the level of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) compared with the control group. ZoA treatment showed an upward trend of IgA level and a downward trend of the concentration of lipopolysaccharide (LPS) and catalase (CAT). Overall, the study demonstrated that the addition of HNa in the diet partially replaced antibiotics and ZnO to improve the growth performance, immune function, and antioxidant capacity of weaned piglets, and maintained a good preventive effect on piglet diarrhea.
Nursing Home Residents with Dementia: Association Between Place of Death and Patient Safety Culture.

BACKGROUND AND OBJECTIVES Nursing homes (NHs) care for 70% of Americans dying with dementia. Many consider deaths in NHs rather than hospitals as preferable for most of these residents. NH characteristics such as staff teamwork, communication, and other components of patient safety culture (PSC), together with state minimum NH nurse staffing requirements, may influence location of death. We examined associations between these variables and place of death (NH/hospital) among residents with dementia. RESEARCH DESIGN AND METHODS Cross-sectional study of 11,957 long-stay NH residents with dementia, age 65+, who died in NHs or hospitals shortly following discharge from one of 800 US NHs in 2017. Multivariable logistic regression systematically estimated effects of PSC on odds of in-hospital death among residents with dementia, controlling for resident, NH, county, and state characteristics. Logistic regressions also determined moderating effects of state minimum NH nurse staffing requirements on relationships between key PSC domains and location of death. RESULTS Residents with dementia in NHs with higher PSC scores in communication openness had lower odds of in-hospital death. This effect was stronger in NHs located in states with higher minimum NH nurse staffing requirements. DISCUSSION AND IMPLICATIONS Promoting communication openness in NHs across nursing disciplines may help avoid unnecessary hospitalization at the end of life, and merits particular attention as NHs address nursing staff mix while adhering to state staffing requirements. Future research to better understand unintended consequences of staffing requirements is needed to improve end-of-life care in NHs.
Intergenerational Online Health Information Searching and Brokering: Framing Health Literacy as a Family Asset

ABSTRACT Latino populations are disproportionately impacted by health disparities and face both connectivity and health literacy challenges. As evidenced by the current global pandemic, access to reliable online health-related information and the ability to apply that information is critical to achieving health equity. Through a qualitative study on how Latino families collaborate to access online health resources, this work frames health literacy as a family-level mechanism. Interviews with parent-child dyads combined with online search tasks reveal how families integrate their individual skillsets to obtain, process, and understand online information about illnesses, symptoms, and even medical diagnoses. As they engage in intergenerational online health information searching and brokering, families creatively navigate information and communication technologies (ICTs) to address a range of health needs. Bilingual children help immigrant parents obtain urgent and non-urgent health information needed to care for other family members. When children are tasked with addressing a health need critical to their parent’s wellbeing, they collaborate with their parents to obtain, interpret, and apply online health information. Intergenerational online health information searching and brokering thus reveals family-level strengths that can be leveraged to promote both health and digital literacy among marginalized populations.
Quality measures of a multicentre universal newborn hearing screening program in Malaysia

Objective To evaluate and discuss the outcomes of the universal newborn hearing screening program conducted at four public hospitals in Malaysia. Method A retrospective analysis of the universal newborn hearing screening database from each hospital was performed. The database consisted of 28,432 and 30,340 screening results of babies born in 2015 and 2016, respectively. Quality indicators (coverage rate, referral rate, return for follow-up rate, and ages at screening and diagnosis) were calculated. Results Overall coverage rate across the four hospitals was 75% in 2015 and 87.4% in 2016. Over the two years, the referral rates for the first screening ranged from 2.7% to 33.93% with only one hospital achieving the recommended benchmark of <4% in both years. The return for follow-up rates for each participating hospital was generally below the recommended benchmark of ≥95%. The mean age at screening was 3.9 ± 1.2 days and 3.3 ± 0.4 days, respectively. The mean age at diagnosis for 70 infants diagnosed with permanent hearing loss was 4.7 ± 0.7 months in 2015 and 3.6 ± 0.9 months in 2016. Conclusions Quality measures for the universal newborn hearing screening program in four public hospitals in Malaysia were lower than the required standards. Nevertheless, some quality indicators showed statistically significant improvements over the two years. Next steps involve identifying and implementing the best practice strategies to improve the outcome measures and thus the quality of the program.
Early presence of Batrachochytrium dendrobatidis in Mexico with a contemporary dominance of the global panzootic lineage

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is a devastating infectious disease of amphibians. Retrospective studies using museum vouchers and genetic samples supported the hypothesis that Bd colonized Mexico from North America and then continued to spread into Central and South America, where it led to dramatic losses in tropical amphibian biodiversity (the epizootic wave hypothesis). While these studies suggest that Bd has been in Mexico since the 1970s, information regarding the historical and contemporary occurrence of different pathogen genetic lineages across the country is limited. In the current study, we investigated the historical and contemporary patterns of Bd in Mexico. We combined the swabbing of historical museum vouchers and sampling of wild amphibians with a custom Bd genotyping assay to assess the presence, prevalence, and genetic diversity of Bd over time in Mexico. We found Bd‐positive museum specimens from the late 1800s, far earlier than previous records and well before recent amphibian declines. With Bd genotypes from samples collected between 1975–2019, we observed a contemporary dominance of the global panzootic lineage in Mexico and report four genetic subpopulations and potential for admixture among these populations. The observed genetic variation did not have a clear geographic signature or provide clear support for the epizootic wave hypothesis. These results provide a framework for testing new questions regarding Bd invasions and their temporal relationship to observed amphibian declines in the Americas.
Body Fat Is a Predictor of Physical Fitness in Obese Adolescent Handball Athletes

We examined the relationships between body fat (BF) and field measures of physical fitness in adolescent handball players. Twenty nine players (age: 16.6 ± 1.72 years; body mass: 79.8 ± 17.0 kg; height: 1.70 ± 0.12 m; body fat: 27.7 ± 8.67%) from Qatar handball first league performed a series of anthropometric and fitness tests related to their performance in sprinting (i.e., 15 m and 30 m sprint), jumping (i.e., countermovement and squat jumps), throwing (i.e., 3 kg medicine ball seated front throw) and running (i.e., agility T-Half and Yo-Yo intermittent recovery level 1 tests). Significant differences between obese and non-obese groups, classified based on age-stratified %BF norms, were found, with the largest difference being attributed to aerobic performance on the Yo-Yo test. Results indicated no significant relationships between anthropometric variables and sprinting or jumping abilities. %BF predicted a significant 8–15% portion in running performances of agility and aerobic capacity, while the latter were mainly explained by body height and mass. %BF was the only and strongest predictor of throwing performance, being an important determinant of performance in handball. Optimizing %BF should be considered as a training and nutrition goal in order to improve sport performance.
Risk factors for anastomotic leakage after laparoscopic low anterior resection: A single‐center retrospective study

Anastomotic leakage (AL) is a serious complication affecting short‐term and long‐term outcomes in rectal cancer surgery. While laparoscopic low anterior resection is a widespread procedure, the risk factors for AL are not well established. This study aimed to evaluate risk factors for AL after laparoscopic low anterior resection with double stapling technique (DST) anastomosis.