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The tera-electronvolt (TeV) light curve of gamma-ray burst 221009A exhibits an unprecedentedly rapid rise at its start. This phenomenon could be due to the strong absorption of photons and electrons within the emitting region. As the external shock expands outward and the radius increases, the volume of matter also grows, resulting in a gradual reduction of the optical depth for TeV photons. We investigate several potential explanations for the early TeV light curves. We calculate the optical depth for TeV photons, considering both annihilation with lower energy photons in the external shock and their scattering by electrons generated through the cascading of the TeV emission. Even under the favourable assumptions, we have determined that the optical depths for these processes are orders of magnitude too small to explain the observed light curve. Additional sources of absorbers, including electrons in the ejecta or external shock, also do not result in sufficient optical depths. Hence, the cause behind the early peculiar TeV light curve remains unclear. [ABSTRACT FROM AUTHOR]

Fast radio bursts (FRBs) are millisecond radio signals from cosmological distances. As they propagate, FRBs can interact with ambient photons and initiate a quantum cascade that can limit the electric field strength. This paper examines whether some observed bright and brief FRBs may challenge this limit if the source is not relativistic. The size of a static FRB source is estimated as R ∼ ct , where t is the time-scale of the FRB and c denotes the speed of light. But for a relativistic source moving at the Lorentz factor Γ, the size is R ∼ 2Γ2 ct. Using an FRB catalogue, we plot the luminosity–duration distribution. Most FRBs fall below the limit for a static source, but two events have higher luminosity and shorter duration. This suggests these bursts may originate from relativistic sources, although more data are needed to confirm this. [ABSTRACT FROM AUTHOR]

Magnetars are believed to be neutron stars (NSs) with strong magnetic fields. X-ray flares and fast radio bursts (FRBs) have been observed from the magnetar (soft gamma-ray repeater, SGR J1935+2154). We propose that the phase transition of the NS can power the FRBs and SGRs. Based on the equation of state provided by the MIT bag model and the mean field approximation, we solve the Tolman–Oppenheimer–Volkoff equations to get the NS structure. With the spin-down of the NS, the hadronic shell gradually transfers to the quark shell. The gravitational potential energy released by one time of the phase transition can be achieved. The released energy, time interval between two successive phase transitions, and glitch are all consistent with the observations of the FRBs and the X-ray flares from SGR J1935 + 2154. We conclude that the phase transition of an NS is a plausible mechanism to power the SGRs as well as the repeating FRBs. [ABSTRACT FROM AUTHOR]

Background: There is little information concerning futile liver resection for patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC). This study aimed to establish a predictive model of futile liver resection for patients with BCLC stage B/C HCC.Methods: The outcomes of 484 patients with BCLC stage B/C HCC who underwent liver resection at our centre between 2010 and 2016 were reviewed. Patients were randomised and divided 2:1 into training and validation sets. A novel risk-scoring model and prognostic nomogram were developed based on the results of multivariate analysis.Results: Fifty-seven futile operations were observed. Multivariate analyses revealed tumour numbers > 3, Vp4 portal vein tumour thrombosis (PVTT) and alpha-fetoprotein (AFP) > 400 ng/ml independently associated with futile liver resection. A risk-scoring model based on the above-mentioned factors was developed (predictive risk score = 1 × (if AFP > 400 ng/ml) + 2 × (if tumour number > 3) + 3 × (if with Vp4 PVTT)). The area under the receiver-operating characteristic curve of this model was 0.845, with a sensitivity of 60.0% and a specificity of 94.8%. A prognostic nomogram was also developed and achieved a C-index of 0.831. The validation studies optically supported these results.Conclusion: A risk-scoring model and predictive nomogram for futile liver resection were developed in the present study. T`he BCLC stage B/C HCC patients with a high risk obtained no benefit from liver resection. [ABSTRACT FROM AUTHOR]

Background Assessing the outcomes of surgeries for hepatocellular carcinoma (HCC) patients who exceed the Milan criteria is necessary. Some studies have demonstrated that preoperative or postoperative alpha fetoprotein (AFP) can predict HCC patients’ prognoses. Methods A total of 280 HCC patients who were positive for AFP and received curative resection were retrospectively analyzed. The patients were classified into three groups according to their preoperative and postoperative AFP levels (group A: normalized AFP; group B: AFP decreases >50%, but continued abnormality; and group C: AFP decreases <50%). Disease-free survival and overall survival rates were analyzed using the Kaplan–Meier method. The factors associated with AFP changes were evaluated by logistic regression. Results AFP dynamic changes were independently associated with disease-free survival and overall survival rates. Group A had better 3- and 5-y survivals than groups B or C (58.7% and 39.5% versus 31.3% and 14.9% versus 17.1% and 8.8%, P < 0.001). Preoperative AFP, tumor differentiation, tumor diameter, microvascular invasion, and satellite nodules remained significant risk factors that were associated with AFP changes. Furthermore, in group A, the disappearances of AFP within and beyond 8 wk resulted in similar overall survival rates ( P > 0.05). Among those with HCC recurrence, the patients treated with resurgery or radiofrequency ablation achieved the best recurrence to death survivals. Those treated with transcatheter arterial chemoembolization achieved the next best survivals. Conclusions AFP changes predicted the prognoses of patients with HCC beyond the predictions of the Milan criteria. Preoperative AFP (>400 ng/mL), tumor differentiation, tumor diameter, and satellite nodules were the risk factors related to AFP normalization. The regular follow-up and early detection of recurrent HCCs that are suitable for curative therapies, such as resurgery and radiofrequency ablation, might improve the prognoses. Other therapies, such as transcatheter arterial chemoembolization, might also be effective. [ABSTRACT FROM AUTHOR]

Abstract Adverse side effects of conventional chemotherapy, acquired resistance and fatal tumor metastasis of human colorectal cancer (CRC) are propelling the exploration for novel selective anticarcinogens. Solasodine is a main active component isolated from Solanum incanum L that exhibited a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells. Colony Spheroid formation assay showed that solasodine dose-dependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by solasodine to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that solasodine impeded HCT116 cell invasion and migration potential strengthened by TGF-β1. Moreover, solasodine attenuated TGF-β1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that solasodine may be a novel therapeutic drug for CRC treatment. Highlights • A component from the Chinese herb solanaceous species has CRC resistance effect. • We explore the induction of TGF-β1 on EMT and cell stemness. • Solasodine shows apparent effect of stemness and EMT reversion in vitro and vivo. • The effect of solasodine on EMT stemness molecules is researched. [ABSTRACT FROM AUTHOR]

Background: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations.Objective: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia.Methods: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings.Results: The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical paroxysmal kinesigenic dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to paroxysmal kinesigenic dyskinesia episodes.Conclusions: Our findings extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish the associations between paroxysmal kinesigenic dyskinesia and genes classically related to other paroxysmal movement disorders. De novo variants might be a cause of sporadic paroxysmal kinesigenic dyskinesia. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson’s disease, though there are still discrepancies among these results. Recently, Gulsuner et al.’s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson’s disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson’s disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson’s disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson’s disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson’s disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson’s disease and essential tremor in China. [ABSTRACT FROM AUTHOR]

Ataxia telangiectasia is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, increased serum alpha-fetoprotein, immunodeficiency, chromosomal instability, and radiation hypersensitivity. Ataxia-telangiectasia mutated gene (ATM) is one of the known genes to be associated with ataxia telangiectasia. We reported the clinical and genetic findings of three early-onset Chinese patients who demonstrated ataxia, oculomotor apraxia, choreoathetosis, myoclonus and telangiectasia of eyes. Sequence analysis of ATM revealed two known nonsense mutations c.8287C > T and c.9139C > T in the siblings. Though the siblings carried the same mutations, they showed different clinical features involving strephenopodia, exotropia, torsion dystonia, myoclonus and extrapyramidal impairments. The other patient was compound heterozygotes for ATM: c.8911C > T and c.7141_7151delAATGGAAAAAT, both of which were not reported previously and not found in 200 control chromosomes. This study widens the spectrum of mutations and phenotypes in ataxia telangiectasia. [ABSTRACT FROM AUTHOR]