Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population

The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.
Phylogenetic analysis based on the complete mitochondrial genome of Discogobio brachyphysallidos (Cypriniformes: Cyprinidae) suggests the need for taxonomic revision at the genus level

Abstract Discogobio brachyphysallidos Huang 1989 is a Cyprinidae fish species that is endemic to the upper Pearl River. In the present study, the complete mitochondrial genome of D. brachyphysallidos collected from the Nanpanjiang River was sequenced and annotated. The mitochondrial genome encompassed 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and the control region (D-loop). The total length of the mitochondrial genome was determined to be 16,594 base pairs (bp), with a GC content of 41.7%. Phylogenetic analyses revealed that D. brachyphysallidos may be a sister to D. longibarbatus and D. macrophysallidos. These findings provide insight into the genetic information and phylogenetic relationships of D. brachyphysallidos.
The Speciation and Potential Bioavailability of Zinc, Manganese, and Lead in Soils of Automobile Workshops in Sapele, Nigeria

This paper presents the result of speciation of three heavy metals (Zn, Mn, & Pb) in soils from ten automobile workshops in Sapele, Nigeria. Soil samples were taken from depth 0 – 60cm and heavy metal concentration were determined. Higher concentrations of these metals were found in soils in the vicinity of the automobile mechanics workshops compared to that of the control. On speciating, 20 to 28% Zn, 23 to 39% Mn, and 15 to 23% Pb, were potentially mobile and bio-available. Keywords: soils, heavy metals, automobile workshops, speciation, bio-available.
Performance of Denitrifying Bioreactors at Reducing Agricultural Nitrogen Pollution in a Humid Subtropical Coastal Plain Climate

Denitrifying bioreactors are an agricultural best management practice developed in the midwestern United States to treat agricultural drainage water enriched with nitrate‐nitrogen (NO3N). The practice is spreading rapidly to agricultural regions with poor water quality due to nutrient enrichment. This makes it imperative to track bioreactor NO3‐N reduction efficiency as this practice gets deployed to new regions. This study evaluated the application and performance of denitrifying bioreactors in the humid subtropical coastal plain environment of the Chesapeake Bay catchment to provide data about regionally specific NO3‐N reduction efficiencies. NO3‐N samples were taken before and after treatment at three denitrifying bioreactors, in addition to other nutrients (orthophosphate‐phosphorus, PO4‐P; ammonium‐nitrogen, NH4‐N; total nitrogen, TN; total phosphorus, TP) and water quality parameters (dissolved oxygen, DO; oxidation reduction potential, ORP; pH; specific conductance, SPC). Total removal ranged drastically between bioreactors from 10 to 133 kg N, with removal efficiencies of 9.0% to 62% and N removal rates of 0.21 to 5.36 g N removed per m3 of bioreactor per day. As the first bioreactor study in the humid subtropical coastal plain, this data provides positive proof of concept that denitrifying bioreactor is another tool for reducing N loads in agricultural tile drainage in this region.
Genome characterization of influenza A and B viruses in New South Wales, Australia, in 2019: A retrospective study using high‐throughput whole genome sequencing

Abstract Background During the 2019 severe influenza season, New South Wales (NSW) experienced the highest number of cases in Australia. This study retrospectively investigated the genetic characteristics of influenza viruses circulating in NSW in 2019 and identified genetic markers related to antiviral resistance and potential virulence. Methods The complete genomes of influenza A and B viruses were amplified using reverse transcription‐polymerase chain reaction (PCR) and sequenced with an Illumina MiSeq platform. Results When comparing the sequencing data with the vaccine strains and reference sequences, the phylogenetic analysis revealed that most NSW A/H3N2 viruses (n = 68; 94%) belonged to 3C.2a1b and a minority (n = 4; 6%) belonged to 3C.3a. These viruses all diverged from the vaccine strain A/Switzerland/8060/2017. All A/H1N1pdm09 viruses (n = 20) showed genetic dissimilarity from vaccine strain A/Michigan/45/2015, with subclades 6B.1A. 5 and 6B.1A. 2 identified. All B/Victoria‐lineage viruses (n = 21) aligned with clade V1A.3, presenting triple amino acid deletions at positions 162–164 in the hemagglutinin protein, significantly diverging from the vaccine strain B/Colorado/06/2017. Multiple amino acid substitutions were also found in the internal proteins of influenza viruses, some of which have been previously reported in hospitalized influenza patients in Thailand. Notably, the oseltamivir‐resistant marker H275Y was present in one immunocompromised patient infected with A/H1N1pdm09 and the resistance‐related mutation I222V was detected in another A/H3N2‐infected patient. Conclusions Considering antigenic drift and the constant evolution of circulating A and B strains, we believe continuous monitoring of influenza viruses in NSW via the high‐throughput sequencing approach provides timely and pivotal information for both public health surveillance and clinical treatment.
The space-time variations of PM10 concentration in major cities of China during 2000-2007

Using data of PM10 concentration in 83 major cities of China during 2000-2007,the space-time variations of PM10 concentration in China in latest 8 years were analyzed.Simultaneously,the seasonal variations of PM10 concentration were also analyzed.The results indicated that in the latest 8 years,the PM10 concentration was decreased in the major cities of China.The seasonal variations showed that the PM10 concentration in summer was the lowest,which meant that precipitation could eliminate the particulate matter in some degree.While the PM10 concentration in winter was the highest,which maybe caused by coal burning in north China and led to the high concentration.
African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. Methods: Transplant-free survival and hepatic decompensation–free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. Results: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4–15.2 vs. 15.1, 14.1–15.7, p=0.002), but Mayo risk score (0.03, −0.8 to 1.1 vs. 0.02, −0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8–10.7 vs. 6.4, 2.6–10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02–1.06, p<0.0001), total bilirubin (1.06, 1.04–1.08, p<0.0001), and albumin (0.44, 0.33–0.61, p<0.0001). AA race did not affect the performance of prognostic models. Conclusions: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.
The Lived Experience of Ethiopian Women After Mastectomy due to Breast Cancer: A Qualitative Study

Background: The impact of breast absence on women’s lived experiences is not well studied in Sub-Saharan Africa particularly in Ethiopia, with implications for service design. This study aimed to explore the lived experiences of Ethiopian women after mastectomy due to breast cancer. Methods: A qualitative study approach was used to explore the experiences of women who underwent a mastectomy at the oncology unit of Tikur Anbessa Specialized Hospital. Before the commencement of the study, consent was obtained from each respondent. An in-depth interview was conducted with twelve post-mastectomy women using a semi-structured interview guide. Audio-recorded data were transcribed verbatim and translated into English. Data were coded, sorted, and themes were developed manually based on the thematic analysis. Results: Five themes illustrating the impact on the women’s life after mastectomy were identified and categorized into (1) Perceived alteration in physical and psychosocial aspects, (2) Perceived social support, and adapting to life after mastectomy. Conclusion: Our finding suggests that women who underwent mastectomy need holistic care including physical, psychosocial, and emotional support from their family, society, and healthcare professionals.
Schmidt‐hammer exposure ages from periglacial patterned ground (sorted circles) in jotunheimen, norway, and their interpretative problems

Abstract Periglacial patterned ground (sorted circles and polygons) along an altitudinal profile at Juvflya in central Jotunheimen, southern Norway, is investigated using Schmidt‐hammer exposure‐age dating (SHD). The patterned ground surfaces exhibit R‐value distributions with platycurtic modes, broad plateaus, narrow tails, and a negative skew. Sample sites located between 1500 and 1925 m a.s. l. indicate a distinct altitudinal gradient of increasing mean R‐values towards higher altitudes interpreted as a chronological function. An established regional SHD calibration curve for Jotunheimen yielded mean boulder exposure ages in the range 6910 ± 510 to 8240 ± 495 years ago. These SHD ages are indicative of the timing of patterned ground formation, representing minimum ages for active boulder upfreezing and maximum ages for the stabilization of boulders in the encircling gutters. Despite uncertainties associated with the calibration curve and the age distribution of the boulders, the early‐Holocene age of the patterned ground surfaces, the apparent cessation of major activity during the Holocene Thermal Maximum (HTM) and continuing lack of late‐Holocene activity clarify existing understanding of the process dynamics and palaeoclimatic significance of large‐scale sorted patterned ground as an indicator of a permafrost environment. The interpretation of SHD ages from patterned ground surfaces remains challenging, however, owing to their diachronous nature, the potential for a complex history of formation, and the influence of local, non‐climatic factors.
Prognostic effect of systematic geriatric assessment on patients with acute heart failure

Abstract Aims Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. Methods and results We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel < 100) was observed in 65 (32.2%) patients (mean Barthel index: 94.38 ± 11.21). Frailty and dependence showed a significant association with both prognostic events at 1 and 6 months. In the multivariable analysis, frailty was associated with higher mortality at 1 month [hazard ratio (HR) 12.61, 95% confidence interval (CI) 1.57–101.47, P = 0.017] but not at 6 months (HR 2.25, 95% CI 0.61–8.26, P = 0.224) or with the combined endpoint at neither 1 month (HR 1.64, 95% CI 0.54–5.03, P = 0.384) nor 6 months (HR 1.35, 95% CI 0.75–2.46, P = 0.320). Dependence was related to higher mortality at 1 month (HR 13.04, 95% CI 1.62–104.75, P = 0.016) and 6 months (HR 7.18, 95% CI 1.99–25.86, P = 0.003) and to higher incidence of the combined event at 1 month (HR 5.93, 95% CI 1.63–21.50, P = 0.007) and 6 months (HR 2.62, 95% CI 1.49–4.61, P = 0.001). Conclusions In AHF patients, frailty and dependence implied a worse prognosis, rising mortality, readmissions, and ER visits for AHF.
Young lives : Perú round 2 survey

This report presents initial findings from the second round of data collection in Peru between late 2006 and early 2007. It provides a broad outline of key child poverty indicators, as well as changes that have taken place since the first round of research in 2002. Although the economic and policy context in Peru has become more favourable – following recent economic growth and increased awareness of the importance of early childhood – inequalities between different groups persist. The findings show that rural and ethnic minority children are more likely to experience poorer nutrition and educational outcomes, and have lower levels of access to electricity, safe water and sanitation facilities. The data also show how such inequalities interrelate, for example, poor access to services appears to influence nutritional patterns of stunting and being underweight. Interestingly, urban children report higher levels of subjective wellbeing than their rural counterparts, and ethnic minority children lower levels, perhaps due to perceptions of discrimination. Evidence of gender inequalities is also found with faltering growth and lower levels of pre-school enrolment among girls, especially in rural areas. Primary school enrolment is more equal but boys are already at an advantage in learning and making the transition to school, following their time at pre-school. Similarly, differences in nutritional status between urban and rural children seem to be defined in the early stages of life. All these findings underline the importance of investing in early childhood. Future Young Lives research will continue to investigate the inequalities in Peru with particular reference to socio-economic status, the urban-rural divide, gender and ethnicity. It is hoped that empirical evidence of this kind will play a greater role in shaping child-related policies in future.
The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients

Background: Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. Methods: This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. Results: During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. Conclusion: The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.
Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma

Background: As the variable clinical outcome of patients with hepatoblastoma (HB) cannot be explained by genetics alone, the identification of drugs with the potential to effectively reverse epigenetic alterations is a promising approach to overcome poor therapy response. The gene ubiquitin like with PHD and ring finger domains 1 (UHRF1) represents an encouraging epigenetic target due to its regulatory function in both DNA methylation and histone modifications and its clinical relevance in HB. Methods: Patient-derived xenograft in vitro and in vivo models were used to study drug response. The mechanistic basis of CM-272 treatment was elucidated using RNA sequencing and western blot experiments. Results: We validated in comprehensive data sets that UHRF1 is highly expressed in HB and associated with poor outcomes. The simultaneous pharmacological targeting of UHRF1-dependent DNA methylation and histone H3 methylation by the dual inhibitor CM-272 identified a selective impact on HB patient-derived xenograft cell viability while leaving healthy fibroblasts unaffected. RNA sequencing revealed downregulation of the IGF2-activated survival pathway as the main mode of action of CM-272 treatment, subsequently leading to loss of proliferation, hindered colony formation capability, reduced spheroid growth, decreased migration potential, and ultimately, induction of apoptosis in HB cells. Importantly, drug response depended on the level of IGF2 expression, and combination assays showed a strong synergistic effect of CM-272 with cisplatin. Preclinical testing of CM-272 in a transplanted patient-derived xenograft model proved its efficacy but also uncovered side effects presumably caused by its strong antitumor effect in IGF2-driven tumors. Conclusions: The inhibition of UHRF1-associated epigenetic traces, such as IGF2-mediated survival, is an attractive approach to treat high-risk HB, especially when combined with the standard-of-care therapeutic cisplatin.
Explicit ion modeling predicts physicochemical interactions for chromatin organization

Molecular mechanisms that dictate chromatin organization in vivo are under active investigation, and the extent to which intrinsic interactions contribute to this process remains debatable. A central quantity for evaluating their contribution is the strength of nucleosome-nucleosome binding, which previous experiments have estimated to range from 2 to 14 kBT. We introduce an explicit ion model to dramatically enhance the accuracy of residue-level coarse-grained modeling approaches across a wide range of ionic concentrations. This model allows for de novo predictions of chromatin organization and remains computationally efficient, enabling large-scale conformational sampling for free energy calculations. It reproduces the energetics of protein-DNA binding and unwinding of single nucleosomal DNA, and resolves the differential impact of mono- and divalent ions on chromatin conformations. Moreover, we showed that the model can reconcile various experiments on quantifying nucleosomal interactions, providing an explanation for the large discrepancy between existing estimations. We predict the interaction strength at physiological conditions to be 9 kBT, a value that is nonetheless sensitive to DNA linker length and the presence of linker histones. Our study strongly supports the contribution of physicochemical interactions to the phase behavior of chromatin aggregates and chromatin organization inside the nucleus.
Phase 2, open-label, rollover study of cenicriviroc for liver fibrosis associated with metabolic dysfunction–associated steatohepatitis

Background: Cenicriviroc (CVC) is a novel, orally administered antagonist of chemokine receptor types 2/5 that has demonstrated antifibrotic activity in a phase 2b study of patients with NASH. This phase 2, open-label, rollover study investigated the long-term safety and tolerability of CVC in patients with NASH and stage 0–4 liver fibrosis. Methods: Eligible patients who completed the phase 2 CENTAUR study or reached a predefined endpoint in the phase 3 AURORA study were rolled over and received open-label CVC 150 mg once daily. Safety assessments were conducted at the start of the study, and patients were seen in the clinic every 3 months until the study sponsor terminated CVC development. Safety endpoints included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, adverse event severity, and clinical laboratory assessments. Results: A total of 167 patients were enrolled, with a median treatment duration of 33.6 months. Before study termination, 36 patients (21.6%) prematurely discontinued the study. Treatment-related TEAEs were reported in 28 patients (16.8%). The most common treatment-related TEAEs were 4 cases of diarrhea (2.4%) and 2 cases each (1.2%) of abdominal pain, nausea, alanine aminotransferase increased, aspartate aminotransferase increased, hypertriglyceridemia, myalgia, pruritus, and rash. The majority of these treatment-related events were mild in intensity, and none were life-threatening. There were no clinically meaningful changes in hepatic function, chemistry, or liver parameters from baseline to the end of the study. Conclusions: In this rollover study, CVC 150 mg once daily was well tolerated in patients with NASH and stage 0–4 liver fibrosis. No new safety signals were reported, and these data further support the safety and tolerability of CVC.