Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphometric analyses of the vertebrae of Ambystoma (Tschudi, 1838) and the implications for identification of fossil salamanders

Ambystoma (Tschudi, 1838) represents a speciose clade of salamanders that are found across much of North America. Fossils referred to Ambystoma are reported from early Cenozoic deposits and are common in Quaternary fossil deposits. Most fossils identified as Ambystoma are isolated vertebrae. Both quantitative and qualitative characters were reported as being useful for identifying fossilized vertebrae of Ambystoma below the genus level. However, there is limited information on intraspecific variation in those characters and previous studies noted intracolumnar variation which affects the utility of those characters for fossil identification. A lack of understanding of variation in modern species of Ambystoma casts uncertainty on our ability to identify fossil vertebrae confidently. We aimed to document intraspecific and intracolumnar variation in vertebral morphology among species of Ambystoma and examine the implications for fossil identification. We assembled one of the largest skeletal data sets for Ambystoma and took linear measurements on 15 species. We used 2D geometric morphometric analyses to characterize atlantal shape variation in Ambystoma. We apply those morphometric data in a case study where we identify fossil vertebrae from Hall's Cave, a Quaternary fossil locality in central Texas. We found patterns of intraspecific and intracolumnar variation that have substantial implications for fossil identification. Classification accuracies for species and clades within Ambystoma varied considerably. Overall classification accuracies based on size‐adjusted measurements and 2D geometric morphometric landmarks were lower compared with classifications from non‐size adjusted linear measurements. We identified fossil vertebrae from our case study as likely belonging to the tiger salamander clade within Ambystoma, but found that some fossils with lower classification probabilities are of uncertain identity. We discuss biogeographic implications for our fossil identifications and comment on challenges and next steps for advancing our understanding of morphological variation in Ambystoma.
Phase II study of durvalumab monotherapy in patients with previously treated microsatellite instability‐high/mismatch repair‐deficient or POLE‐mutated metastatic or unresectable colorectal cancer

The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability‐high/mismatch repair‐deficient (MSI‐H/dMMR) or polymerase epsilon (POLE)‐mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open‐label, multicenter, phase II study enrolled patients with mCRC harboring MSI‐H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI‐H/dMMR and 3 had POLE‐mutated microsatellite stable (MSS) CRC. With a median follow‐up duration of 11.2 months (95% confidence interval [CI]: 7.3‐15.0), the ORR was 42.4% (95% CI: 25.5‐60.8). Among three patients with POLE‐mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non‐exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression‐free survival rate of 12 months was 58.2% (95% CI: 39.0‐73.1) and the 12‐month overall survival rate was 68.3% (95% CI: 48.8‐81.7). Grade 3 treatment‐related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI‐H/dMMR or POLE EDM. In patients with POLE‐mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.
Hemadsorption for removal of ticagrelor and direct oral anticoagulants in cardiac surgery

ABSTRACT Introduction Cardiac patients on antiplatelets or oral anticoagulation undergoing emergent cardiac surgery without appropriate washout periods are at increased risk for developing perioperative bleeding. CytoSorb is a commercially available hemadsorption adsorber that can simultaneously remove a wide range of substances including ticagrelor, and direct oral anticoagulants (DOACs). Areas covered Although CytoSorb has been used to remove various protein-bound substances, this review will specifically evaluate and review current evidence for applying CytoSorb in removing ticagrelor and DOACs using four in vitro studies, three case reports, one retrospective study and two cost analysis studies. Based on limited evidence, CytoSorb may be effective in reducing perioperative bleeding by reducing chest tube output, blood product transfusions, and re-thoracotomy rates. CytoSorb can also reduce length of intensive care unit (ICU) and hospital stay. Although, CytoSorb has an initial upfront cost, it was proven to be cost-effective due to potential health resource savings on both short- and long-term projections. Expert Commentary CytoSorb provides a novel strategy to remove ticagrelor and DOACs in patients requiring emergency cardiac surgery. Although promising results, more solid evidence is required to establish its clinical effectiveness in reducing perioperative bleeding, bleeding-related complications, mortality, and finally, its overall safety.
SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

Introduction Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications. Methods Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po.). Results DAPA decreased blood glucose levels (D: 37±2.7 vs. D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment. Conclusions These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.
Systematic Bias in Medical Algorithms: To Include or Not Include Discriminatory Demographic Information?

We read the recent article by Barcenas et al who developed a prognostic model for estimating individual prognosis for women with metastatic breast cancer with great interest. We congratulate the authors for providing a robust prognostic model for metastatic breast cancer that may better inform clinical treatment decisions. Although the study was generally well conducted, we have some concerns with potential racial bias introduced to the algorithms. Although the authors report that they included race or ethnicity as covariates in the prognostic models, they did neither discuss possible implications of doing so nor did they evaluate how including these data may affect algorithmic fairness. In this letter, we would like to discuss some of the potential pitfalls of this approach and provide a brief overview of how bias against lessprivileged groups can be revealed and avoided.
Mechanism for Altered Dark-Adapted Electroretinogram Responses in DBA/2J Mice Includes Pupil Dilation Deficits

Abstract Purpose The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. Materials and Methods To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. Results D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. Conclusions These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.
Tumor expression quantitative trait methylation screening reveals distinct CpG panels for deconvolving cancer immune signatures.

DNA methylation signatures in tumors could serve as reliable biomarkers that are accessible in archival tissues for tracking the epigenetic dynamics shaped by both cancer cells and the tumor microenvironment. However, given the ultra-high-dimensionality and non-collapsible nature of the data, it remains challenging to screen all CpG sites to identify the most promising marker panels. In this paper, we introduce the concept of tumor-based expression quantitative trait methylation (eQTM) for the prioritization and systematic mining of predictive biomarkers. In melanoma as a disease model, eQTM CpGs and genes represent new and efficient candidate targets to be investigated for both prognostic and immune status monitoring purposes. Three cis-eQTM CpGs (cg07786657, cg12446199, and cg00027570) were strongly associated with and can serve as surrogate biomarkers for the tumor immune cytolytic activity score (CYT). In addition, multiple eQTM genes could be further exploited for predicting immunoregulatory phenotypes. A targeted gene panel analysis identified one eQTM in TCF7 (cg25947408) as a novel candidate biomarker for uncoupling overall T cell differentiation and exhaustion status in a tumor. The prognostic significance of this eQTM as an independent signature to CYT was validated by both TCGA and Moffitt melanoma cohort data. Overall, eQTMs represent a mechanistically distinct class of potential biomarkers that can be used to predict patient prognosis and immune status.
Effects of increasing levels of orange peel extract on kit growth, feed utilization, and some blood metabolites in the doe rabbits under heat stress conditions

Abstract One of the most severe consequences of climate change on the rabbit production sector is heat stress. Dietary supplementation of phytochemicals could alleviate the negative impact of heat stress on rabbits. Thirty-six V-line rabbit does with average live body weight (LBW) of 2.672 ± 0.031 kg were randomly allocated into three experimental groups as follows: the control group (OPE0) and the OPE2.5 and OPE5 groups were orally administered orange peel extract (OPE) at doses of 2.5 and 5 mL/doe. The increasing OPE levels significantly improved LBW at partum (p = 0.002) and weaning (p = 0.004), daily and total feed intake from pregnancy until weaning (p = 0.007), daily milk yield per doe at 7th and 14th days (p ≤ 0.05), and milk efficiency (p = 0.001). Litter size at 1st–28th days, litter weight gain, survival rate, and kit weight gain at 21st–28th days of heat-stressed doe rabbits were significantly improved with OPE treatments. The treatment of OPE5 significantly decreased serum glucose, triglycerides, and very-low-density lipoprotein-cholesterol levels of rabbits. The increasing OPE levels decreased significantly total lipid and low-density lipoprotein-cholesterol levels and increased (p = 0.001) high-density lipoprotein-cholesterol concentration in heat-stressed rabbits. In conclusion, the treatment of OPE improved feed utilization, milk efficiency, and reproductive performance and alleviated the drastic impacts of heat stress on rabbits.
Contemporary clinical and economic outcomes among oral anticoagulant treated and untreated elderly patients with atrial fibrillation: Insights from the United States Medicare database

Background Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. Objective Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. Methods Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. Results The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68–0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55–0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54–1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). Conclusion For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.
Study of Coefficient of Thermal Expansion and Micro-Structure in Liquid Crystal Polymer Film for Circuit Board

液晶ポリマーフィルム回路板の高温反りを解消することを目的として, フィルムのCTE (熱膨張係数) と微細構造を研究した。 フィルム内部応力の高温緩和が反りの原因である。 この内部応力は, もしフィルムと銅箔の間にCTEの差異があれば, 熱プレス機によるCCL (銅張積層板) の製造における冷却プロセスの間に固定される。 液晶ポリマーフィルムにおけるスメクティック, ネマティック, ランダムの微細構造のCTEはそれぞれ大きく異なっている。 このことは, フィルムのCTEはこれら微細構造の分率を調節することによって, 回路板の高温反りを解消するために, フィルムのCTEは制御可能であることを示している。
Damp heat–stable perovskite solar cells with tailored-dimensionality 2D/3D heterojunctions

If perovskite solar cells (PSCs) with high power conversion efficiencies (PCEs) are to be commercialized, they must achieve long-term stability, which is usually assessed with accelerated degradation tests. One of the persistent obstacles for PSCs has been successfully passing the damp-heat test (85°C and 85% relative humidity), which is the standard for verifying the stability of commercial photovoltaic (PV) modules. We fabricated damp heat–stable PSCs by tailoring the dimensional fragments of two-dimensional perovskite layers formed at room temperature with oleylammonium iodide molecules; these layers passivate the perovskite surface at the electron-selective contact. The resulting inverted PSCs deliver a 24.3% PCE and retain >95% of their initial value after >1000 hours at damp-heat test conditions, thereby meeting one of the critical industrial stability standards for PV modules. Description Stabilizing inverted solar cells Although inverted (p-i-n) perovskite solar cells (PSCs) have advantages in fabrication and scaling compared with n-i-p cells, their power conversion efficiencies (PCEs ) are usually lower. Azmi et al. show that by tailoring the number of octahedral inorganic sheets in two-dimensional perovskite (2DP) passivation layers for three-dimensional perovskite active layers, PCEs of more than 24% could be achieved (see the Perspective by Luther and Schelhas). The 2DP layers formed with oleylammonium iodide molecules at the electron-selective interface passivated trap states and suppressed ion migration. These PSCs retained more than 95% of their initial efficiency after 1000 hours of damp-heat testing (85°C and 85% relative humidity), which passes a key industrial stability standard. —PDS Tailored two-dimensional perovskite passivation layers enable efficient, damp-heat stable inverted perovskite solar cells.
Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers

Abstract Background Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. Method 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α. Results Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls. Conclusions The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).
Retracted Article: LncRNA KCNQ1OT1 Promotes Apoptosis and Oxidative Stress of Human Lens Epithelial Cells through Epigenetic Regulation of WRN

We, the authors, Editors and Publisher of the journal Current Eye Research, have retracted the following article: Shengqun Jiang, Yanwen Jia and Ziqing Gao. LncRNA KCNQ1OT1 promotes apoptosis and oxidative stress of human lens epithelial cells through epigenetic regulation of WRN. Current Eye Research 2022; [2022 Feb 18;1–25; Online ahead of print]. doi.org/10.1080/02713683.2022. 2026975. Since publication, the authors have informed the journal that they are unable to provide the original data for the study and are unable to verify the findings after failing to reproduce the results. As this directly impacts the validity of the reported results and conclusions, the authors alerted the issue to the Editors and Publisher and all have agreed to retract the article to ensure the integrity of the scholarly record. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted. ”
The magnetic resonance imaging assessment of optic nerve sheath diameter in pediatric acute liver failure patients.

OBJECTIVE To evaluate the diagnostic value of optic nerve sheath diameter (ONSD) using brain MRI in the pretransplantation period in the pediatric acute liver failure patients, and correlate the ONSD with clinical grade of hepatic encephalopathy (HE) and MRI findings. PATIENTS AND METHODS Forty acute liver failure patients and 40 control group patients were retrospectively analyzed. The high signal intensities in T2W (T2-weighted image), FLAIR (Fluid Attenuated Inversion Recovery) and DWI (diffusion-weighted imaging) sequences were evaluated and ONSD was measured. The patients were grouped first into 5 according to their West Haven score, and HE grade 0 and grade 1 were accepted as low grade HE, HE grade 2, 3 and 4 were accepted as high grade HE. The patients were grouped to 2 according to the MRI findings as low grade and high grade MRI group. RESULTS The mean value of ONSD was 6.0 ± 1.80 and 4.94 ± 1.27 in the all patients and in the control group, respectively. There was statistically significant difference between both the ONSD and the low grade-high grade HE groups (p=0.01), and between the ONSD and the low grade-high grade MRI groups (p<0.001). CONCLUSIONS Although high ONSD values do not make the diagnosis of cerebral edema, it may cause suspicion in the early period. MRI can be helpful in the diagnoses of increased intracranial pressure like ultrasound. Our study is the first study to compare ONSD and MRI findings in addition to HE grades. The widespread use of MRI in children in recent years may help determine the normal range of ONSD values.
[Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways].

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.