Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene polymorphism and prediction of toxicity to platinum‐based chemotherapy in patients with gynecologic cancer

The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum‐based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first‐line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi‐square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi‐square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT‐treated patients with gynecologic cancer.
Colonisation of Group B Streptococcus and its effects on pregnancy outcomes in pregnant women in Guangzhou, China: a retrospective study

Objectives This study was to investigate the colonisation rate of Group B Streptococcus (GBS) during pregnancy, and to evaluate the influence of GBS colonisation on pregnancy outcomes. Design A retrospective cohort study. Setting Data of 47 380 pregnant women from 2016 to 2022 were collected from the Maternal and Child Health Hospital of Huadu District, Guangzhou City, China. Participants A total of 15 040 pregnant women were eligible for this study, of which 32 340 were excluded due to non-native pregnant women, in vitro fertilization infants, malformed fetuses, habitual abortion, abortions due to poor reproductive or obstetrical history, artificial insemination, umbilical cord torsion, and other diseases during pregnancy. Primary outcome measures The incidence rates of GBS colonisation and premature delivery, fetal distress, premature rupture of membranes (PROM), low birth weight (LBW), abortion and stillbirth. Results Of the 15 040 pregnant women included in this study, 1445 developed GBS colonisation, with a prevalence of 9.61% (95% CI, 9.15 to 10.09). Advanced maternal age (≥35 years) predisposed women to GBS colonisation, and the occurrence of GBS colonisation varied among different ethnic groups. Our data revealed that fetal distress, PROM and LBW were more common in pregnant women colonised with GBS than in pregnant women not colonised with GBS. The incidence for premature delivery, fetal distress, PROM and LBW in infants of pregnant women colonised with GBS was 41.0% (OR=1.410, 95% CI, 1.134 to 1.753), 282.5% (OR=3.825, 95% CI, 3.185 to 4.593), 14.9% (OR=1.149, 95% CI, 1.005 to 1.313), and 29.7% (OR=1.297, 95% CI, 1.010 to 1.664), respectively. Conclusions GBS colonisation was relatively low in pregnant women in Guangzhou. Women of advanced maternal age were more prone to GBS colonisation, and pregnant women colonised with GBS were more predisposed to fetal distress, PROM and LBW.
p16/Ki67 dual stain triage versus cytology in primary human papillomavirus‐based cervical cancer screening with limited genotyping

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high‐grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high‐risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual‐stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18‐positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV‐positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18‐positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2–55.8; p < 0.0001) and very high NPV in all HPV‐positive cases regardless of detected genotype (96.3%–100.0%). The risk (1‐NPV) for CIN3+ in HRHPV16/18‐positive/p16/Ki67‐negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual‐immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.
MASLD may inappropriately exclude lean female NAFLD patients with significant liver fibrosis.

AIM It remains unclear whether the newly defined concept of metabolic dysfunction-associated steatotic liver disease (MASLD) appropriately includes patients with nonalcoholic fatty liver disease (NAFLD) with significant liver fibrosis. METHODS A total of 4,112 patients in whom NAFLD was diagnosed by ultrasonography during medical check-ups were enrolled. We defined a fibrosis-4 (FIB-4) index ≥1.3 aged <65 years and ≥2.0 aged ≥65 years as significant liver fibrosis. RESULTS he numbers of patients with a low, intermediate, and high probability of advanced ﬁbrosis based on the FIB-4 index were 3,360 (81.7%), 668 (16.2%), and 84 (2.0%). There were 3,828 (93.1%) and 284 (6.9%) patients diagnosed with MASLD and non-MASLD. The non-MASLD group, compared to the MASLD group, was significantly younger (44 versus 55 years) and had a higher percentage of females (62.3% versus 27.7%). Significant fibrosis, defined based on the FIB-4 index, was present in 18.5% of the MASLD group and 15.5% of the non-MASLD group. In a multivariable analysis, female sex (odds ratio [OR], 6.170; 95% conﬁdence interval [CI], 3.180-12.000; p<0.001) was independently associated with non-MASLD in patients with a significant fibrosis. Among non-MASLD patients with a significant fibrosis (n=44), body mass index was significantly lower in females than in males (p<0.001). In a multivariable analysis of patients aged <65 years, female sex (OR, 7.700; 95% CI, 3.750-15.800; p<0.001) remained independently associated with non-MASLD in patients with a significant fibrosis. CONCLUSIONS MASLD may inappropriately exclude patients with significant fibrosis, especially lean females with NAFLD. This article is protected by copyright. All rights reserved.
Chapter 12 Conflicts in stratigraphic classification of the Puranas of the Pranhita–Godavari Valley: review, recommendations and status of the ‘Penganga’ sequence

Abstract Understanding of the incompatibility of King's three-fold classification of the Proterozoic (‘Purana’) rocks of the Pranhita–Godavari Valley, south India, and renewed mapping and stratigraphic studies, reveal that syn-depositional basin dynamics, with differential uplift and subsidence, was the major control on basin evolution and the development of multiple unconformity-bound successions. The unconformities demarcate six major successions, the Mallampalli/Devalmari, Somanpalli, Mulug, Penganga, Albaka and Sullavai groups, each with a very distinctive set of sedimentological attributes. There are at least five different conflicting classification schemes so far. The major problems in the classification of the succession appear to lie in the recognition of unconformities and unconformity-bound successions, and in stratigraphic nomenclature. Based on field geology, available age data and the concept of the megasequence, the Mallampali, Devalmari, Mulug and Somanpalli groups have been grouped into the Pakhal Supergroup. The question of combining the rest of the groups has been deferred until the resolution of the Albaka–Penganga relationship is achieved beyond doubt. The relationships between different stratigraphic units have been critically examined to reconstruct the stratigraphic history, events of sea-level change and palaeogeographical evolution.
Genetic mechanisms and biological processes underlying host response to ophidiomycosis (snake fungal disease) inferred from tissue‐specific transcriptome analyses

Emerging infectious diseases in wildlife species caused by pathogenic fungi are of growing concern, yet crucial knowledge gaps remain for diseases with potentially large impacts. For example, there is detailed knowledge about host pathology and mechanisms underlying response for chytridiomycosis in amphibians and white‐nose syndrome in bats, but such information is lacking for other more recently described fungal infections. One such disease is ophidiomycosis, caused by the fungus Ophidiomyces ophidiicola, which has been identified in many species of snakes, yet the biological mechanisms and molecular changes occurring during infection are unknown. To gain this information, we performed a controlled experimental infection in captive Prairie rattlesnakes (Crotalus viridis) with O. ophidiicola at two different temperatures: 20 and 26°C. We then compared liver, kidney, and skin transcriptomes to assess tissue‐specific genetic responses to O. ophidiicola infection. Given previous histopathological studies and the fact that snakes are ectotherms, we expected highest fungal activity on skin and a significant impact of temperature on host response. Although we found fungal activity to be localized on skin, most of the differential gene expression occurred in internal tissues. Infected snakes at the lower temperature had the highest host mortality whereas two‐thirds of the infected snakes at the higher temperature survived. Our results suggest that ophidiomycosis is likely a systemic disease with long‐term effects on host response. Our analysis also identified candidate protein coding genes that are potentially involved in host response, providing genetic tools for studies of host response to ophidiomycosis in natural populations.
Length-frequency estimation for yellowfin tuna (Thunnus albacares) caught by commercial fishing gear in the Eastern Pacific Ocean

ENGLISH: Methods of collecting samples for the purpose of estimating the numbers and weights of fish caught, by length interval, are described. Several models for two-stage sampling are described, and the equations for the estimators and their variances are given. The results from a brief simulation study are used to show the differences between estimates made with the different models. Estimators for the average weights of fish in the catch and their variances are also described. These average weights are used to provide improved estimates of the total annual catches of yellowfin taken from the eastern Pacific Ocean, east of 150°W, between 1955 and 1990. SPANISH: Se describen los metodos de recoger de muestreo para estimar el numero o peso de peces capturados, por intervalo de talla. Se describen varios modelos para el muestreo de dos etapas, y se presentan las ecuaciones para los estimadores y sus varianzas. Se usan los resultados de un breve estudio de simulacion para indicar las diferencias entre estimaciones realizadas con los distintosmodelos. Tambien se describe un estimador para el peso promedio de peces en la captura y su varianza. Se usan estos estimadores para calcular estimaciones mejoradas de las capturas anuales totales de aleta amarilla tomadas del Oceano Pacifico oriental, al este de 150°W, entre 1955 y 1990. (PDF contains 41 pages.)
Population pharmacokinetic modeling and target attainment analyses of rezafungin for the treatment of candidemia and invasive candidiasis

ABSTRACT Rezafungin is a chemically and metabolically stable echinocandin with a longer half-life than other echinocandins, allowing for a once-weekly intravenous infusion versus a daily infusion. Rezafungin is approved in the US for the treatment of candidemia and/or invasive candidiasis and is in development for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp. in immunosuppressed patients. A population pharmacokinetic (PPK) model was developed using data from five Phase 1, one Phase 2, and one Phase 3 study. The model found to best describe the available data was a three-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V23), intercompartmental clearance 1, and intercompartmental clearance 2. The variability model included correlated interindividual variability in CL, V1, and V23 and a proportional residual variability model. The following statistically significant covariates were identified: albumin concentrations on V23; body surface area (BSA) on CL, V1, and V23; and disease state on CL and V1. Disease states were defined as patients from the Phase 2 and Phase 3 studies and hepatically impaired subjects. Covariates of BSA, disease state, or albumin, included in the final model, were not associated with clinically meaningful changes in PK, nor were any other patient factors, indicating that a common dose regimen is adequate for all adult patients. Target attainment simulations were performed to estimate the probability of achieving PK/pharmacodynamic targets across the range of minimum inhibitory concentration values for six species of Candida.
LORF9 of Marek’s disease virus is involved in the early cytolytic replication of B lymphocytes and can act as a target for gene deletion vaccine development

ABSTRACT Marek’s disease (MD) is a poultry disease characterized by severe immunosuppression and the development of T cell lymphomas caused by Marek’s disease virus (MDV). Our study focuses on the role of the viral LORF9 gene in MD pathogenesis and vaccine development. We found that a LORF9 gene deletion mutant (Md5BAC ΔLORF9) showed significantly reduced pathogenicity compared with the parental strain. The LORF9 gene is essential for the early cytolytic infection in B cells. Interestingly, Md5BAC ΔLORF9 provided adequate immunological protection against very virulent MDV challenge and induced a distinct host immune response compared with the CVI988/Rispens vaccine strain. Transcriptome analysis revealed that the deletion of LORF9 led to a significantly different expression of innate immunity-associated genes. Overall, our study provides insights into the role of LORF9 in MD pathogenesis and highlights its importance in MDV gene deletion vaccine development. IMPORTANCE Marek’s disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the LORF9 gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the LORF9 deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine. Marek’s disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the LORF9 gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the LORF9 deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.
Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH‐induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half‐life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH‐induced RVF.
Seismic slip history of the Pizzalto fault (central Apennines, Italy) using in situ‐produced 36Cl cosmic ray exposure dating and rare earth element concentrations

Morphological and geological observations reveal that most Apenninic faults are highly segmented and that the majority of the fault segments are less than 10 km long. Although these faults have undergone numerous paleoseismological investigations, quantitative data remain crucially lacking for a large number of fault segments. Because such data are essential to understanding how these faults have ruptured and interacted in the past and how they might behave in the future, we investigated the Holocene seismic history of the Pizzalto normal fault, a 13 km long fault segment belonging to the Pizzalto‐Rotella‐Aremogna fault system in the Apennines. We collected 44 samples from the Pizzalto fault plane exhumed during the Holocene and analyzed the 36Cl and rare earth element (REE) contents. Together, the 36Cl and REE concentrations show that at least six events have exhumed 4.4 m of the fault scarp between 3 and 1 ka, with slip per event values ranging from 0.3 to 1.2 m. No major events have been detected over the last 1 kyr. The Rotella‐Aremogna‐Pizzalto fault system has a clustered earthquake behavior with a mean recurrence time of 1.2 kyr and a low to moderate probability (ranging from 4% to 26%) of earthquake occurrence over the next 50 years.
Latent trajectories of DSM-5-TR-based Prolonged Grief Disorder: findings from a data pooling project MARBLES

ABSTRACT Background: With the release of the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5-TR), criteria for Prolonged Grief Disorder (PGD) were included. This necessitates studying grief trajectories based on these criteria. Objective: This is the first study examining latent trajectories of DSM-5-TR-based PGD symptom levels and testing whether specific risk factors (e.g. cause of death) predicted PGD trajectories. Method: We evaluated latent DSM-5-TR PGD trajectories using pooled existing data collected at 6–12, 13–24, and 25–60 months post-loss in Danish and Dutch bereaved adults (N = 398). Latent Growth Mixture Modelling (LGMM) was employed to determine the trajectories. Multinomial logistic regression analyses were used to examine which risk factors predicted class membership. Results: The four-class LGMM solution with a quadratic term was best-fitting the data. This solution represented four trajectories: High stable PGD (6%), High PGD quick recovery (10%), High PGD slow recovery (35%), and Low PGD symptoms (49%). Participants with a higher educational level were more likely to be assigned to the Low PGD symptoms trajectory compared to High stable PGD and High PGD slow recovery trajectories. Unnatural causes of death increased the likelihood of being in the High stable PGD and High PGD slow recovery trajectories compared to the Low PGD symptoms trajectory. Conclusions: Consistent with prior research, the Low PGD symptoms trajectory was the most common. A significant minority experienced high and stable levels of PGD within five years after the loss. About one-third of participants experienced high acute grief levels that decreased slowly; how slow decreasing symptoms relate to an individual’s functioning requires further attention. This study demonstrates that a significant minority of bereaved people develop acute PGD symptomatology that does not diminish within five years post-loss, emphasizing the need for early screening for PGD to prevent long-lasting complaints. HIGHLIGHTS This is the first latent trajectory study based on DSM-5-TR Prolonged Grief Disorder (PGD) criteria. Data were analysed using latent growth mixture modelling. Stable high (6%), quick recovery (10%), slow recovery (35%), low symptoms (49%) PGD trajectories arose. Early screening and treatment of PGD seems warranted.
VEGETATIVE CHARACTERISTICS AnD GRASSLAnD PASSERInE USE OF COnSERVATIOn PLAnTInGS In EASTERn SOUTH DAKOTA

Vegetative characteristics and grassland passerine use of conservation plantings were studied in eastern South Dakota Game Production Areas, June 2007-2008. Fourteen fields, from 1 to 8 years old at the onset of the study, were surveyed in each year to describe vegetative characteristics and to correlate grassland passerine use. Sites had been planted to a mixture of 5 native warm-season grasses, 3 cool-season grasses, and alfalfa. Grassland passerines were sampled along fixed width transects during June 2007-2008. Vegetation was sampled at 7 points along each of 3 parallel transects within the bird sampling transects. Younger plantings had lower height and percent canopy cover of dead vegetation, greater litter depth, higher coverage of alfalfa and unplanted forbs, and more bare ground than older plantings. Nonmetric multi-dimensional scaling based upon vegetative characteristics showed that sites tended to become more similar with age. A total of fifteen bird species were identified along transects in each year. Six species showed a relationship between abundance and the measured vegetation structure and composition variables. Although research showed that grassland passerines use these plantings, more research is needed to determine nest success of passerines to determine the true conservation value of these plantings and associated management practices.