Miracle-dz/UniFAR-FTUs huggingface dataset:
A multimillion-year-old record of Greenland vegetation and glacial history preserved in sediment beneath 1.4 km of ice at Camp Century

Significance Understanding Greenland Ice Sheet history is critical for predicting its response to future climate warming and contribution to sea-level rise. We analyzed sediment at the bottom of the Camp Century ice core, collected 120 km from the coast in northwestern Greenland. The sediment, frozen under nearly 1.4 km of ice, contains well-preserved fossil plants and biomolecules sourced from at least two ice-free warm periods in the past few million years. Enriched stable isotopes in pore ice indicate precipitation at lower elevations than present, implying ice-sheet absence. The similarity of cosmogenic isotope ratios in the upper-most sediment to those measured in bedrock near the center of Greenland suggests that the ice sheet melted and re-formed at least once during the past million years. Understanding the history of the Greenland Ice Sheet (GrIS) is critical for determining its sensitivity to warming and contribution to sea level; however, that history is poorly known before the last interglacial. Most knowledge comes from interpretation of marine sediment, an indirect record of past ice-sheet extent and behavior. Subglacial sediment and rock, retrieved at the base of ice cores, provide terrestrial evidence for GrIS behavior during the Pleistocene. Here, we use multiple methods to determine GrIS history from subglacial sediment at the base of the Camp Century ice core collected in 1966. This material contains a stratigraphic record of glaciation and vegetation in northwestern Greenland spanning the Pleistocene. Enriched stable isotopes of pore-ice suggest precipitation at lower elevations implying ice-sheet absence. Plant macrofossils and biomarkers in the sediment indicate that paleo-ecosystems from previous interglacial periods are preserved beneath the GrIS. Cosmogenic 26Al/10Be and luminescence data bracket the burial of the lower-most sediment between <3.2 ± 0.4 Ma and >0.7 to 1.4 Ma. In the upper-most sediment, cosmogenic 26Al/10Be data require exposure within the last 1.0 ± 0.1 My. The unique subglacial sedimentary record from Camp Century documents at least two episodes of ice-free, vegetated conditions, each followed by glaciation. The lower sediment derives from an Early Pleistocene GrIS advance. 26Al/10Be ratios in the upper-most sediment match those in subglacial bedrock from central Greenland, suggesting similar ice-cover histories across the GrIS. We conclude that the GrIS persisted through much of the Pleistocene but melted and reformed at least once since 1.1 Ma.
Culture clash of female Somali adolescents and sexual and reproductive health services in Oslo, Norway

Abstract Objective Culture influences an individual’s perception of health needs. The influence of culture also applies to Somali individuals’ perception of their sexual and reproductive health (SRH) and uptake of related services. An understanding of female Somali adolescents’ SRH needs is vital to achieve inclusive health coverage. No research has, however, been conducted to explore the SRH needs of this population group in Oslo; hence, the aim of this qualitative study was to minimise the knowledge gap. Methods Fourteen young women aged 16–20 years were recruited using the snowball technique with purposive sampling. In-depth interviews using a semi-structured interview guide were used to collect data, and thematic analysis was applied. Results Participants perceived SRH as a very private matter and open discussion of SRH was extremely limited owing to certain Somali cultural beliefs and values. As the participants intend to practise chastity before marriage, they believed that existing SRH services were largely irrelevant and inappropriate. Where they felt the need to access SRH services, participants wished to do so in a way they considered culturally appropriate. Conclusion Somali culture markedly influences individuals’ perceptions of SRH services. It is recommended to modify existing SRH services by increasing confidentiality and anonymity in order to take into account the cultural requirements of female Somali adolescents.
Variation of stroke-associated pneumonia in stroke units across England and Wales: A registry-based cohort study

Background Pneumonia is common in stroke patients and is associated with worse clinical outcomes. Prevalence of stroke-associated pneumonia varies between studies, and reasons for this variation remain unclear. We aimed to describe the variation of observed stroke-associated pneumonia in England and Wales and explore the influence of patient baseline characteristics on this variation. Methods Patient data were obtained from the Sentinel Stroke National Audit Programme for all confirmed strokes between 1 April 2013 and 31 December 2018. Stroke-associated pneumonia was defined by new antibiotic initiation for pneumonia within the first seven days of admission. The probability of stroke-associated pneumonia occurrence within stroke units was estimated and compared using a multilevel mixed model with and without adjustment for patient-level characteristics at admission. Results Of the 413,133 patients included, median National Institutes of Health Stroke Scale was 4 (IQR: 2–10) and 42.3% were aged over 80 years. Stroke-associated pneumonia was identified in 8.5% of patients. The median within stroke unit stroke-associated pneumonia prevalence was 8.5% (IQR: 6.1–11.5%) with a maximum of 21.4%. The mean and variance of the predicted stroke-associated pneumonia probability across stroke units decreased from 0.08 (0.68) to 0.05 (0.63) when adjusting for patient admission characteristics. This difference in the variance suggests that clinical characteristics account for 5% of the observed variation in stroke-associated pneumonia between units. Conclusions Patient-level clinical characteristics contributed minimally to the observed variation of stroke-associated pneumonia between stroke units. Additional explanations for the observed variation in stroke-associated pneumonia need to be explored which could reduce variation in antibiotic use for stroke patients.
Bad Timing for Epileptic Networks: Role of Temporal Dynamics in Seizures and Cognitive Deficits

The precise coordination of neuronal activity is critical for optimal brain function. When such coordination fails, this can lead to dire consequences. In this review, I will present evidence that in epilepsy, failed coordination leads not only to seizures but also to alterations of the rhythmical patterns observed in the electroencephalogram and cognitive deficits. Restoring the dynamic coordination of epileptic networks could therefore both improve seizures and cognitive outcomes.
Frondoside A Inhibits an MYC-Driven Medulloblastoma Model Derived from Human-Induced Pluripotent Stem Cells

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MYC-driven MBs, commonly found in the group 3 MB, are aggressive and metastatic with the worst prognosis. Modeling MYC-driven MB is the foundation of therapeutic development. Here, we applied a synthetic mRNA-driven strategy to generate neuronal precursors from human-induced pluripotent stem cells (iPSCs). These neuronal precursors were transformed by the MYC oncogene combined with p53 loss of function to establish an MYC-driven MB model recapitulating the histologic and transcriptomic hallmarks of group 3 MB. We further show that the marine compound Frondoside A (FA) effectively inhibits this MYC-driven MB model without affecting isogenic neuronal precursors with undetectable MYC expression. Consistent results from a panel of MB models support that MYC levels are positively correlated with FA's antitumor potency. Next, we show that FA suppresses MYC expression and its downstream gene targets in MB cells, suggesting a potential mechanism underlying FA's inhibitory effects on MYC-driven cancers. In orthotopic xenografts of MYC-driven MB, intratumoral FA administration potently induces cytotoxicity in tumor xenografts, significantly extends the survival of tumor-bearing animals, and enhances the recruitment of microglia/macrophages and cytotoxic T lymphocytes to tumors. Moreover, we show that MYC levels also predict FA potency in glioblastoma and non–small cell lung cancer cells. Taken together, this study provides an efficient human iPSC-based strategy for personalizable cancer modeling, widely applicable to mechanistic studies (e.g., genetic predisposition to cancer) and drug discovery. Our preclinical results justify the clinical translation of FA in treating MYC-driven MB and other human cancers.
Proteomic analysis of urinary and tissue‐exudative extracellular vesicles to discover novel bladder cancer biomarkers

Proteomic analysis of urinary extracellular vesicles (EVs) is a powerful approach to discover potential bladder cancer (BCa) biomarkers, however urine contains numerous EVs derived from the kidney and normal urothelial epithelium, which can obfuscate information related to BCa cell‐derived EVs. In this study, we combined proteomic analysis of urinary EVs and tissue‐exudative EVs (Te‐EVs), which were isolated from culture medium of freshly resected viable BCa tissues. Urinary EVs were isolated from urine samples of 11 individuals (7 BCa patients and 4 healthy individuals), and Te‐EVs were isolated from 7 BCa tissues. We performed tandem mass tag (TMT)‐labeling liquid chromatography (LC‐MS/MS) analysis for both urinary EVs and Te‐EVs and identified 1960 proteins in urinary EVs and 1538 proteins in Te‐EVs. Most of the proteins identified in Te‐EVs were also present in urinary EVs (82.4%), with 55 of these proteins showing upregulated levels in the urine of BCa patients (fold change > 2.0; P < .1). Among them, we selected 22 membrane proteins as BCa biomarker candidates for validation using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis on urine samples from 70 individuals (40 BCa patients and 30 healthy individuals). Six urinary EV proteins (heat‐shock protein 90, syndecan‐1, myristoylated alanine‐rich C‐kinase substrate (MARCKS), MARCKS‐related protein, tight junction protein ZO‐2, and complement decay‐accelerating factor) were quantified using SRM/MRM analysis and validated as significantly upregulated in BCa patients (P < .05). In conclusion, the novel strategy that combined proteomic analysis of urinary EVs and Te‐EVs enabled selective detection of urinary BCa biomarkers.
Medical Malpractice Allegations in Nasal Turbinate Surgery

Background Despite studies showing most patients significantly improve their nasal congestion with surgical management of nasal turbinates, not all achieve acceptable results. Rarely, patients report substantial worsening of symptoms leading to litigation risk. Objective Document the United States medicolegal environment for nasal turbinate surgery. Methods We searched the Westlaw database for turbinate related terms for 1987- July 2019, recording demographics, claims, legal arguments, and outcomes in legal cases related to nasal turbinate surgery. We assessed prevalence and correlations with case outcomes. Results Of the 39 cases identified, the most common complaint was nose/facial pain (53.8% of cases). Surgeons prevailed in 87.2% of cases, with total liabilities of $3,224,606 [mean $97,715.3, ±$283,900.8]. Surgeons had statistically significant favorable outcomes when patients claimed dryness, headache, congestion, crusting, breathing problems, and disfigurement (all p < 0.05). Revision surgery was indicated in 23.1% of cases and was claimed in 40.0% of patient awards. Surgical negligence was claimed in 40.0% of patient awards versus 67.9% of surgeon awards (p = 0.333). Lack of informed consent was claimed in 20.0% of patient awards versus 32.1% of surgeon awards (p = 0.601). Conclusions There are inherent litigation risks for surgeons when performing nasal turbinate surgery. Most claims against surgeons, are resolved in favor of the surgeon. Understanding the types of claims and legal arguments that are made by patients could help assessing the risks of a proposed litigation. Documenting clear indications for surgery and written informed consent may reduce litigations against surgeons.
Interim Singapore guidelines for basic and advanced life support for paediatric patients with suspected or confirmed COVID-19

The COVID-19 pandemic has resulted in significant challenges for the resuscitation of paediatric patients, especially for infants and children who are suspected or confirmed to be infected. Thus, the paediatric subcommittee of the Singapore Resuscitation and First Aid Council developed interim modifications to the current Singapore paediatric guidelines using extrapolated data from the available literature, local multidisciplinary expert consensus and institutional best practices. It is hoped that this it will provide a framework during the pandemic for improved outcomes in paediatric cardiac arrest patients in the local context, while taking into consideration the safety of all community first responders, medical frontline providers and healthcare workers.
AFExNet: An Adversarial Autoencoder for Differentiating Breast Cancer Sub-Types and Extracting Biologically Relevant Genes

Technological advancements in high-throughput genomics enable the generation of complex and large data sets that can be used for classification, clustering, and bio-marker identification. Modern deep learning algorithms provide us with the opportunity of finding most significant features in such huge dataset to characterize diseases (e.g., cancer) and their sub-types. Thus, developing such deep learning method, which can successfully extract meaningful features from various breast cancer sub-types, is of current research interest. In this paper, we develop dual stage (unsupervised pre-training and supervised fine-tuning) neural network architecture termed AFExNet based on adversarial auto-encoder (AAE) to extract features from high dimensional genetic data. We evaluated the performance of our model through twelve different supervised classifiers to verify the usefulness of the new features using public RNA-Seq dataset of breast cancer. AFExNet provides consistent results in all performance metrics across twelve different classifiers which makes our model classifier independent. We also develop a method named ‘TopGene’ to find highly weighted genes from the latent space which could be useful for finding cancer bio-markers. Put together, AFExNet has great potential for biological data to accurately and effectively extract features. Our work is fully reproducible and source code can be downloaded from Github: https://github.com/NeuroSyd/breast-cancer-sub-types.
Animal models of pulmonary hypertension: Getting to the heart of the problem

Despite recent therapeutic advances, pulmonary hypertension (PH) remains a fatal disease due to the development of right ventricular (RV) failure. At present, no treatments targeted at the right ventricle are available, and RV function is not widely considered in the preclinical assessment of new therapeutics. Several small animal models are used in the study of PH, including the classic models of exposure to either hypoxia or monocrotaline, newer combinational and genetic models, and pulmonary artery banding, a surgical model of pure RV pressure overload. These models reproduce selected features of the structural remodelling and functional decline seen in patients and have provided valuable insight into the pathophysiology of RV failure. However, significant reversal of remodelling and improvement in RV function remains a therapeutic obstacle. Emerging animal models will provide a deeper understanding of the mechanisms governing the transition from adaptive remodelling to a failing right ventricle, aiding the hunt for druggable molecular targets.
Development and Evolution of Energetic Cocrystals.

ConspectusIn spite of the importance of energetic materials to a broad range of military (munitions, missiles) and civilian (mining, space exploration) technologies, the introduction of new chemical entities in the field occurs at a very slow pace. This situation is understandable considering the stringent requirements for cost and safety that must be met for new chemical entities to be fielded. If existing manufacturing infrastructure could be leveraged, then this would offer a fundamental shift in the discovery paradigm. Cocrystallization is an approach poised to realize this goal because it can use existing materials and make new chemical compositions through the assembly of multiple unique components in the solid state. This account describes early proof-of-principle studies with widely used energetics in the field, including 2,4,6-trinitrotoluene (TNT) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), forming cocrystals with nonenergetic coformers that alter key properties such as density, sensitivity, and morphology. The evolution of these studies to produce cocrystals between two energetic components is detailed, including those exploiting new intermolecular interaction motifs that drive assembly such as halogen bonding. Implications of cocrystallization for performance, sensitivity to external stimuli, and manufacturability are explored at each stage. The derivation of many of these cocrystals from energetic materials in common use satisfies the goal of using materials already demonstrated to be cost-effective at scale and with well-understood safety profiles. The account concludes with a discussion of cocrystallizing molecules having excess of oxidizing power with those that are oxygen-deficient to push the limits of explosive performance to unprecedented levels. The purposeful production of an arbitrary combination of two solid components into a cocrystal is far from certain, but the studies described motivate the continued exploration of novel materials and the development of predictive models for identifying crystallization partners. When such cocrystals form, many of their most important properties cannot be predicted, pointing to another challenge for the purposeful development of energetic materials based on cocrystallization.
Conophylline Inhibits Hepatocellular Carcinoma by Inhibiting Activated Cancer-associated Fibroblasts Through Suppression of G Protein–coupled Receptor 68

Treatment of hepatocellular carcinoma (HCC) is currently challenging. Cancer-associated fibroblasts (CAFs) promote the malignancy of HCC cells via production of cytokines. Conophylline (CnP), a vinca alkaloid obtained from Ervatamia microphylla leaves, has been reported to suppress activation of hepatic stellate cells and liver fibrosis in rats. We examined the efficacy of CnP in suppressing tumor growth in HCC. Specifically, we investigated whether CnP could inhibit CAFs, which were derived from HCC tissues in vitro and in vivo. Same as previous reports, CAFs promoted proliferative and invasive ability of HCC cells. CnP suppressed α-smooth muscle actin expression of CAFs, and inhibited their cancer-promoting effects. CnP significantly suppressed CAFs producting cytokines such as IL6, IL8, C-C motif chemokine ligand 2, angiogenin, and osteopontin (OPN). Combined therapy with sorafenib and CnP against HCC cells and CAFs in vivo showed to inhibit tumor growth the most compared with controls and single treatment with CnP or sorafenib. Transcriptome analysis revealed that GPR68 in CAFs was strongly suppressed by CnP. The cancer-promoting effects of cytokines were eliminated by knockdown of GPR68 in CAFs. CnP inhibited the HCC-promoting effects of CAFs by suppressing several HCC-promoting cytokines secreted by CAFs expressing GPR68. Combination therapy with CnP and existing anticancer agents may be a promising strategy for treating refractory HCC associated with activated CAFs.
Effect of osimertinib in treating patients with first-generation EGFR-TKI-resistant advanced non-small cell lung cancer and prognostic analysis.

PURPOSE To explore the efficacy and safety of the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) Osimertinib in the treatment of patients with first-generation EGFR-TKI-resistant advanced non-small cell lung cancer (NSCLC). METHODS The clinical data of 84 patients with advanced NSCLC treated in our hospital from September 2016 to March 2018 were retrospectively analyzed. All patients had progressive disease (PD) after treatment with first-generation EGFR-TKI, and then they were treated with Osimertinib. The remission of disease was analyzed and evaluated after treatment, and the long-term survival and progression of disease were recorded via follow-up. The influencing factors for the patient's prognosis were explored using univariate and multivariate Cox regression analyses. RESULTS The efficacy was evaluated in all patients at 4 weeks after treatment. There were 0 cases of complete response (CR), 34 cases (40.5%) of partial response (PR), 38 cases (45.2%) of stable disease (SD) and 12 cases (14.3%) of PD. The objective response rate (ORR) and the disease control rate (DCR) were 40.5% (34/84) and 85.7% (72/84), respectively. The main adverse reactions included diarrhea (34.5%), nausea and vomiting (14.3%), constipation (11.9%), rash (27.4%), skin itch (20.2%), loss of appetite (13.1%), oral ulcer (10.7%), hepatic dysfunction (2.4%) and bone marrow suppression, mostly of grade I-II, which could be significantly relieved after symptomatic treatment. The incidence rate of grade III and above adverse reactions was 9.5% (8/84). The dosage of Osimertinib was reduced in 2 cases due to adverse reactions, while other adverse reactions were improved after symptomatic treatment. The levels of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) obviously declined from 247.57±20.72 pg/mL and 11.20±1.38 μg/L before treatment to 134.84±14.37 pg/mL and 6.80±0.54 μg/L after treatment (p<0.05). The median overall survival (mOS) and median progression-free survival (mPFS) were 25.3 and 10.6 months, respectively. The 1-year OS rate was 79.8% (67/84), and the OS rate was 52.3% at the end of follow-up. Subgroup analysis showed found that heart disease and thrombosis complicated before treatment had significant impact on mOS (p=0.007, p=0.019). The results of multivariate Cox regression analysis revealed that heart disease and thrombosis complicated before treatment were independent risk factors affecting the patient's OS [HR=2.339 (95% CI: 1.448-5.674), p=0.031, HR=1.977 (95% CI: 1.152-2.365), p=0.020]. CONCLUSION Osimertinib has definite efficacy in the treatment of patients with first-generation EGFR-TKI-resistant advanced NSCLC, with a low incidence rate of tolerable adverse reactions. The presence or absence of heart disease and thrombosis before treatment are independent influencing factors for the patient OS.
Incidencia de la fertilización nitrogenada sobre la concentración de nutrientes en maíz

-1 . Another treatment consisting of 140 kg N ha -1 plus sulfur, magnesium and zinc (140❖) was also included. Macro and micronutrients were determined in leaf samples collected at flowering (opposite to- and below the ear). The results were interpreted according to critical values (NC) and sufficiency ranges (RSN). Nitrogen availability and tillage system affected significantly nitrogen accumulation, dry matter and grain yield. The higher nitrogen availability in Parana and Rafaela generated luxury consumption of nitrogen, whereas in Balcarce low nitrogen availability caused high nitrogen use efficiency. The addition of nitrogen increased sulfur and manganese leaf concentration in all experiments but did not affect calcium and magnesium concentrations. In Balcarce, this treatment also increased phosphorus, potassium, iron, copper and zinc concentration. The application of magnesium, sulfur and zinc at sowing did not improve corn yield. Under SD there were lower leaf nitrogen, potassium and iron concentration at flowering. The RSN at flowering, indicated that potassium, magnesium, sulfur, copper and zinc were the most limiting nutrients. However, grain yields were close to the potential yield for this locations.