Miracle-dz/UniFAR-FTUs huggingface dataset:
A proposal for a new classification of “unfavorable risk criteria” in patients with stage I endometrial cancer

Background Randomized trials describe differing sets of high–intermediate risk criteria. Objective To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of “unfavorable risk. ” Methods Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high–intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification. Results We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001). Conclusion Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB disease.
Cyclin F‐dependent degradation of E2F7 is critical for DNA repair and G2‐phase progression

E2F7 and E2F8 act as tumor suppressors via transcriptional repression of genes involved in S‐phase entry and progression. Previously, we demonstrated that these atypical E2Fs are degraded by APC/CCdh1 during G1 phase of the cell cycle. However, the mechanism driving the downregulation of atypical E2Fs during G2 phase is unknown. Here, we show that E2F7 is targeted for degradation by the E3 ubiquitin ligase SCFcyclin F during G2. Cyclin F binds via its cyclin domain to a conserved C‐terminal CY motif on E2F7. An E2F7 mutant unable to interact with SCFcyclin F remains stable during G2. Furthermore, SCFcyclin F can also interact and induce degradation of E2F8. However, this does not require the cyclin domain of SCFcyclin F nor the CY motifs in the C‐terminus of E2F8, implying a different regulatory mechanism than for E2F7. Importantly, depletion of cyclin F causes an atypical‐E2F‐dependent delay of the G2/M transition, accompanied by reduced expression of E2F target genes involved in DNA repair. Live cell imaging of DNA damage revealed that cyclin F‐dependent regulation of atypical E2Fs is critical for efficient DNA repair and cell cycle progression.
Dopamine replacement remediates risk aversion in Parkinson’s disease in a value-independent manner

Introduction Clinical evidence suggests that Parkinson’s Disease (PD) patients are risk averse. Dopaminergic therapy has been reported to increase risk tolerance, but the underlying mechanisms are unclear. Some studies have suggested an amplification of subjective reward value, consistent with the role of dopamine in reward value coding. Others have reported value-independent risk enhancement. We evaluated the value-dependence of the effects of PD and its therapy on risk using tasks designed to sensitively measure risk over a wide range of expected values. Method 36 patients with idiopathic PD receiving levodopa monotherapy and 36 healthy matched controls performed two behavioural economic tasks aimed at quantifying 1) risk tolerance/ aversion in the gain frame and 2) valuation of potential gains relative to losses. PD patients performed the tasks on and off their usual dose of levodopa in randomized order; controls performed the same tasks twice. Results Relative to the controls, unmedicated PD patients showed significant value-independent risk aversion in the gain frame, which was normalized by levodopa. PD patients did not differ from controls in their valuation of gains relative to losses. However, across both tasks and regardless of medication, choices of the patients were more determined by expected values of the prospects than those of controls. Conclusion Dopamine deficiency in PD was associated with risk aversion, and levodopa promoted riskier choice in a value-independent manner. PD patients also showed an increased sensitivity to expected value, which was independent of levodopa and does not appear to result directly from dopamine deficiency.
Optimal systolic blood pressure in noncritically ill patients with acute kidney injury: A retrospective cohort study

Background Few data showed the optimal blood pressure (BP) in noncritically ill patients with acute kidney injury (AKI) relative to mortality or severe AKI. We therefore sought to analyze the data that exist for the ideal target range for BP in noncritically ill patients with AKI. Methods We performed a retrospective cohort study involving 1,612 hospitalized patients who were diagnosed with AKI using the Kidney Disease: Improving Global Outcomes definition based on serum creatinine measurements for a period of 1 year. The average systolic BP (SBP) was categorized into 10-mmHg increments (within 48 hours after the development of AKI). The primary outcome was a composite of severe AKI or 90-day mortality. Results The composite outcome rate in patients was 18.7% (302/1,612). The relationship between BP and the composite outcome followed a U-shaped curve, with an increased event rate observed at both low and high BP values. The average SBP after AKI predicted the composite outcome after adjusting for baseline variables (reference SBP: 120–129 mmHg; < 100 mmHg: hazard ratio [HR] 1.84, P = 0.015; 100–109 mmHg: HR 1.56, P = 0.038; 110–119 mmHg: HR 1.15, P = 0.483; 130–139 mmHg: HR 1.51, P = 0.045; ≥ 140 mmHg: HR 1.73, P = 0.005). Conclusion Among noncritically ill patients with AKI, a U-shaped curve association was observed between the average SBP within 48 hours after AKI and the composite primary outcome of this study, with the lowest event rate for SBP ranging from approximately 110 to 129 mmHg.
Patients' and partners' views of care and treatment provided for metastatic castrate-resistant prostate cancer in the UK.

OBJECTIVE Documentations of the experiences of patients with advanced prostate cancer and their partners are sparse. Views of care and treatment received for metastatic castrate-resistant prostate cancer (mCRPC) are presented here. METHODS Structured interviews conducted within 14 days of a systemic therapy for mCRPC starting and 3 months later explored the following: treatment decisions, information provision, perceived benefits and harms of treatment, and effects of these on patients' and partners' lives. RESULTS Thirty-seven patients and 33 partners recruited from UK cancer centres participated. The majority of patients (46%) reported pain was their worst symptom and many wanted to discuss its management (baseline-50%; 3 months-33%). Patients and partners believed treatment would delay progression (>75%), improve wellbeing (33%), alleviate pain (≈12%) and extend life (15% patients, 36% partners). At 3 months, most men (42%) said fatigue was the worst treatment-related side effect (SE), 27% experienced unexpected SEs and 54% needed help with SEs. Most patients received SE information (85% written; 75% verbally); many additionally searched the Internet (33% patients; 55% partners). Only 54% of patients said nurse support was accessible. CONCLUSION Pain and other symptom management are not optimal. Increased specialist nurse provision and earlier palliative care links are needed. Dedicated clinics may be justified.
Differential disruption of autoinhibition and defect in assembly of cytoskeleton during cell division decide the fate of human DIAPH1-related cytoskeletopathy

Background Diaphanous-related formin 1 (DIA1), which assembles the unbranched actin microfilament and microtubule cytoskeleton, is encoded by DIAPH1. Constitutive activation by the disruption of autoinhibitory interactions between the N-terminal diaphanous inhibitory domain (DID) and C-terminal diaphanous autoregulatory domain (DAD) dysregulates DIA1, resulting in both hearing loss and blood cell abnormalities. Methods and results Here, we report the first constitutively active mutant in the DID (p.A265S) of humans with only hearing loss and not blood cell abnormality through whole exome sequencing. The previously reported DAD mutants and our DID mutant (p.A265S) shared the finding of diminished autoinhibitory interaction, abnormally upregulated actin polymerisation activity and increased localisations at the plasma membrane. However, the obvious defect in the DIA1-driven assembly of cytoskeleton ‘during cell division’ was only from the DAD mutants, not from p.A265S, which did not show any blood cell abnormality. We also evaluated the five DID mutants in the hydrophobic pocket since four of these five additional mutants were predicted to critically disrupt interaction between the DID and DAD. These additional pathogenic DID mutants revealed varying degrees of defect in the DIA1-driven cytoskeleton assembly, including nearly normal phenotype during cell division as well as obvious impaired autoinhibition, again coinciding with our key observation in DIA1 mutant (p.A265S) in the DID. Conclusion Here, we report the first mutant in the DID of humans with only hearing loss. The differential cell biological phenotypes of DIA1 during cell division appear to be potential determinants of the clinical severity of DIAPH1-related cytoskeletopathy in humans.
Prevalence of and factors related to microvascular complications in patients with type 2 diabetes mellitus in Tianjin, China: a cross-sectional study.

Background Since chronic hyperglycemia-related damage to small blood vessels results in complications, patients with longer durations of type 2 diabetes mellitus (T2DM) are more likely to develop microvascular complications, such as retinopathy, neuropathy and nephropathy, which are very harmful to the health of humans. Therefore, this study aimed to assess the prevalence of diabetes-related microvascular complications and to explore their risk factors in patients with T2DM in Tianjin, China. Methods This observational, cross-sectional study was conducted at 8 hospitals in urban and suburban regions of Tianjin, China. The information collected from the subjects mainly included demographic characteristics, anthropometric measurements and clinical information. Univariate and multivariate logistic regression was used to identify the possible risk factors for microvascular complications (retinopathy, neuropathy and nephropathy). Results A total of 4,490 patients with T2DM from 8 hospitals in Tianjin, China were selected from November 2015 to January 2016. Of the study subjects, 2,270 (50.6%) were males. The median age was 64.0±13.0 years. The percentage of patients with T2DM who had at least one microvascular complication was 34.5%. The prevalence rates of neuropathy, retinopathy, and nephropathy were 23.5%, 17.4%, and 10.8%, respectively. The results of the multivariate logistic regression showed that the duration of diabetes, insulin use, and the presence of hypertension and dyslipidemia were the main risk factors for developing microvascular complications of T2DM. Conclusions The incidence of diabetes complications in Tianjin is high. Increasing the control of risk factors can reduce the occurrence of complications to reduce the disease burden and improve the quality of life of patients.
Evaluation of cell protection by Psephellus pyrrhoblepharus (Boiss.) Wagenitz extracts in MPP+-induced dopaminergic cell damage

Abstract Neurodegenerative diseases affect millions of people. Major reasons behind the onset and progression of these diseases are still under investigation. Therefore, any approach that would treat/prevent progression is important. In this study, we aimed to investigate the potential protective effects of Psephellus pyrrhoblepharus (Boiss.) Wagenitz extracts in MPP+-induced dopaminergic cell damage and compare the effectiveness of different extracts (methanol:water (1:1), chloroform and n-hexane). The cells were pretreated with four different concentrations (10, 50, 100, and 200 µg/ml) of methanol:water (1:1), chloroform and n-hexane extracts of P. pyrrhoblepharus following MPP+ treatment for 12 or 24 h. The changes in cell viability were determined using the MTT assay. Additionally, antioxidant activities and total phenolic/flavonoid contents of the extracts were determined with radical scavenging capacity, Folin–Ciocalteu and aluminum chloride assays, respectively. The extracts at selected concentrations were found to be protective in a dose-dependent manner at 12 and 24 h. Nevertheless, the methanol extract of the plant showed the highest protection both at 100 and 200 µg/ml (115.13%±3.98, 121.87%±1.66; p < 0.05) against dopaminergic damage at 24 h. The results showed that selected concentrations were not toxic and did not affect cell proliferation rate. Besides, the chloroform extract was found to have higher antioxidant activity than the other extracts (p < 0.05). The total phenolic and total flavonoid contents were found consistent with antioxidant activities. Our findings support the neuroprotective and antioxidant potential of P. pyrrhoblepharus. However, further studies on identifying the presence of chemicals in P. pyrrhoblepharus extracts which are responsible for protection should be carried out to confirm their therapeutic potential.
Biocidal Activity of Metal Nanoparticles Synthesized by Fusarium solani against Multidrug-Resistant Bacteria and Mycotoxigenic Fungi

Antibiotic resistance by pathogenic bacteria and fungi is one of the most serious global public health problems in the 21st century, directly affecting human health and lifestyle. Pseudomonas aeruginosa and Staphylococcus aureus with strong resistance to the common antibiotics have been isolated from Intensive Care Unit patients at Zagazig Hospital. Thus, in this study we assessed the biocidal activity of nanoparticles of silver, copper and zinc synthesized by Fusarium solani KJ 623702 against these multidrug resistant-bacteria. The synthesized Metal Nano-particles (MNPs) were characterized by UV-Vis spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and Zeta potential. The Fourier transform infrared spectroscopy (FTIR) result showed the presence of different functional groups such as carboxyl, amino and thiol, ester and peptide bonds in addition to glycosidic bonds that might stabilize the dispersity of MNPs from aggregation. The antimicrobial potential of MNPs by F. solani against the multidrug-resistant (MDR) P. aeruginosa and S. aureus in addition to the mycotoxigenic Aspergillus awamori, A. fumigatus and F. oxysporum was investigated, based on the visual growth by diameter of inhibition zone. Among the synthesized MNPs, the spherical AgNPs (13.70 nm) displayed significant effect against P. aeruginosa (Zone of Inhibition 22.4 mm and Minimum Inhibitory Concentration 21.33 μg/ml), while ZINC oxide Nano-Particles were the most effective against F. oxysporum (ZOI, 18.5 mm and MIC 24.7 μg/ml). Transmission Electron Microscope micrographs of AgNP-treated P. aeruginosa showed cracks and pits in the cell wall, with internalization of NPs. Production of pyocyanin pigment was significantly inhibited by AgNPs in a concentration-dependent manner, and at 5-20 μg of AgNPs/ml, the pigment production was reduced by about 15- 100%, respectively.
Functionalization of Novel Theranostic Hydrogels with Kartogenin Grafted USPIO Nanoparticles to Enhance Cartilage Regeneration.

Here, kartogenin (KGN), an emerging stable nonprotein compound with the ability to promote bone marrow-derived mesenchymal stem cells (BMSCs) differentiation into chondrocytes, was grafted onto the surface of modified ultrasmall superparamagnetic iron-oxide (USPIO), and then integrated into cellulose nanocrystal/dextran (CNC/Dex) hydrogels. The hydrogels served as a carrier for the USPIO-KGN and a matrix for cartilage repair. We carried out in vitro and in vivo studies, the results of which demonstrated that KGN undergoes long-term stable sustained release, recruits endogenous host cells, and induces BMSCs to differentiate into chondrocytes, thus enabling in situ cartilage regeneration. Meanwhile, the USPIO-incorporated theranostics hydrogels exhibited distinct magnetic resonance (MR) contrast enhancement, and maintained a stable relaxation rate, with almost no loss, both in vivo and in vitro. According to noninvasive in vivo observation results and immunohistochemistry analyses, the regenerated cartilage tissue was very similar to natural hyaline cartilage. This innovative diagnosis and treatment system increase the convenience and effectiveness of chondrogenesis.
Combination therapy using non‐ablative fractional laser and intralesional triamcinolone injection for hypertrophic scars and keloids treatment

Combinations of various treatment modalities were shown to be more effective than monotherapy when treating hypertrophic scars and keloids. This study was conducted to assess the effectiveness of combination therapy with non‐ablative fractional laser and intralesional steroid injection. From May 2015 to June 2017, a total of 38 patients with hypertrophic scars or keloids were evaluated. The control group of 21 patients received steroid injection alone, and 17 patients (the combined group) received 1550‐nm erbium‐glass fractional laser treatment and steroid injection simultaneously. The mean number of treatment sessions was statistically fewer in the combined group than in the control group (6.95 vs 5.47, P = .042). There was a significant difference in the patient's scale in the combined group (14.62 vs 22.82, P = .005); however, the observer's scale was not significantly different (17.92 vs 20.55, P = .549). The recurrence rate was 38.1% (8/21) in the control group and 35.3% (6/17) in the combined groups and showed no significant difference (P = .859). However, the mean remission period was statistically longer in the combined group (3.00 months vs 4.17 months, P = .042). Combination therapy with non‐ablative fractional laser and intralesional steroid injection showed better results for the treatment of hypertrophic scars and keloids with fewer treatment sessions, better patient satisfaction, and longer remission periods.
The PD-1/PD-L1 pathway in advanced prostate cancer-have we milked this cow?

We would like to thank Dr. Fay and Dr. Antonarakis for their insightful comments on immunotherapy (IO) in advanced prostate cancer and specifically their commentary on the recently published KEYNOTE-028 study on the use of pembrolizumab in programmed cell death protein-1 ligand (PD-L1) positive metastatic castrate resistant prostate cancer (mCRPC) (1). As described by the authors, monotherapy with checkpoint inhibitors has not demonstrated the dramatic response rates in mCRPC that were shown in other cancer types such as melanoma and non-small cell lung cancer (NSCLC).
Automatic Identification of Diatoms using Multi-scale Mathematical Morphology

Diatoms are unicellular algae with a great ecological importance. They are ornamented with patterns that are characteristic for the species they belong to. Till now these diatoms are identified by experts, which is a time-consuming and tedious process. For this reason and due to a lack of diatomists, the Automatic Diatom Identification And Classification project ADIAC was started, where various techniques from image analysis are investigated for this use. The goal of this research was to investigate the possibilities of the identification of diatoms using mathematical morphology. Images are considered by this approach as mathematical entities such as sets or functions on which operators are defined. These operators are used to compute pattern spectra that describe the presence or absence of image details with certain characteristics such as size or shape. The idea of this approach is that the patterns on the diatoms can be described by these pattern spectra, so that an identification can be made. Although more research is needed to tackle some problems, some first results of diatom identification using different methods give reason for optimism about the usability of this method especially in combination with other strategies. The results were obtained on a set of 781 images, consisting of 37 different taxa, with the C4.5 decision tree classifier. This method identified 81.4% of the test set correctly.
Severe transient neonatal long QT syndrome due to maternal paroxetine usage: a case report

Abstract A female neonate with in utero selective serotonin reuptake inhibitor exposure presented with bradycardia shortly after birth. Electrocardiography showed severe QT prolongation and second-degree atrioventricular block. Over time QT-times spontaneously normalised and genetic testing did not show mutations associated with long QT syndrome making maternal selective serotonin reuptake inhibitor usage the most likely explanation for the observed severe transient neonatal QT prolongation.
Respondent incentives , interviewer training and survey participation

This paper provides an overview of an experimental study implemented in the German subsample of the Survey of Health, Ageing, and Retirement in Europe (SHARE). We conclude that in our setting pre-paid incentives are effective in increasing response rates, where higher incentives lead to higher response rates in an almost linear fashion. However, pre-paid incentives (regardless of the amount) lead to higher initial refusals even before the interviewer tried to contact the household. In terms of cost-effectiveness, no final conclusion can be drawn – paying the incentive is of course more expensive, but the increases in the response rate and the implied reduction in the initially necessary gross sample may outweigh these costs. Beyond mere monetary conclusions, the incentive groups did not prove to be biased compared to the control group, whereas they are significantly closer to the sampling frame in terms of their age distribution. Furthermore, using a doorstep questionnaire we show that – as far as measurable – there is no non-response bias in key variables of interest. Due to complications during the fieldwork, one initially planned experiment on Refusal Avoidance Training could not be conducted. Still we learned that interviewers do not target those respondents with highest incentive first, leading to the conclusion that their behavior is not much influenced by the incentive the respondents receive. a Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy b University of Mannheim c German Institute for Economic Research, Berlin Address correspondence to Ulrich Krieger, e-mail: Ulrich.Krieger@uni-mannheim.de