Nodeless electron pairing in CsV3Sb5-derived kagome superconductors.

The newly discovered kagome superconductors represent a promising platform for investigating the interplay between band topology, electronic order and lattice geometry1-9. Despite extensive research efforts on this system, the nature of the superconducting ground state remains elusive10-17. In particular, consensus on the electron pairing symmetry has not been achieved so far18-20, in part owing to the lack of a momentum-resolved measurement of the superconducting gap structure. Here we report the direct observation of a nodeless, nearly isotropic and orbital-independent superconducting gap in the momentum space of two exemplary CsV3Sb5-derived kagome superconductors-Cs(V0.93Nb0.07)3Sb5 and Cs(V0.86Ta0.14)3Sb5-using ultrahigh-resolution and low-temperature angle-resolved photoemission spectroscopy. Remarkably, such a gap structure is robust to the appearance or absence of charge order in the normal state, tuned by isovalent Nb/Ta substitutions of V. Our comprehensive characterizations of the superconducting gap provide indispensable information on the electron pairing symmetry of kagome superconductors, and advance our understanding of the superconductivity and intertwined electronic orders in quantum materials.

The ion channel TRPA1 is a modulator of the cocaine reward circuit in the nucleus accumbens.

Drug addiction therapies commonly fail because continued drug use promotes the release of excessive and pleasurable dopamine levels. Because the connection between pleasure and drug use becomes hard-wired in the nucleus accumbens (NAc), which interfaces motivation, effective therapies need to modulate this mesolimbic reward system. Here, we report that mice with knockdown of the cation channel TRPA1 (transient receptor potential ankyrin 1) were resistant to the drug-seeking behavior and reward effects of cocaine compared to their wildtype litter mates. In our study, we demonstrate that TRPA1 inhibition in the NAc reduces cocaine activity and dopamine release, and conversely, that TRPA1 is critical for cocaine-induced synaptic strength in dopamine receptor 1-expressing medium spiny neurons. Taken together, our data support that cocaine-induced reward-related behavior and synaptic release of dopamine in the NAc are controlled by TRPA1 and suggest that TRPA1 has therapeutic potential as a target for drug misuse therapies.

Gba1 E326K renders motor and non-motor symptoms with pathologic α-syn, tau and glial activation.

Mutations in the GBA1 gene are common genetic risk factors for Parkinson's disease (PD), disrupting enzymatic activity and causing lysosomal dysfunction, leading to elevated α-synuclein (α-syn) levels. While GBA1's role in synucleinopathy is well-established, recent research underscores neuroinflammation as a significant pathogenic mechanism in GBA1 deficiency. This study investigates neuroinflammation in Gba1 E326K knock-in mice, a model associated with increased PD and dementia risk. At 9 and 24 months, we assessed GBA1 protein and activity, α-synuclein pathology, neurodegeneration, motor deficits, and gliosis in the ventral midbrain and hippocampus using immunohistochemistry (IHC), Western blot (WB), and GCase assays. Additionally, primary microglia from WT and GBA1E326K/E326K mice were treated with α-syn preformed fibrils (PFF) to study microglia activation, pro-inflammatory cytokines, reactive astrocyte formation, and neuronal death through qPCR, WB, and immunocytochemistry analyses. We also evaluated the effects of gut inoculation of α-syn PFF in Gba1 E326K mice at 7 months and striatal inoculation at 10 months, assessing motor/non-motor symptoms, α-syn pathology, neuroinflammation, gliosis, and neurodegeneration via behavioural tests, IHC, and WB assays. At 24 months, Gba1 E326K knock-in mice showed reduced GCase enzymatic activity and glucosylceramide build-up in the ventral midbrain and hippocampus. Increased pro-inflammatory cytokines and reactive astrocytes were observed in microglia and astrocytes from Gba1 E326K mice treated with pathologic α-syn PFF. Gut inoculation of α-syn PFF increased Lewy body accumulation in the hippocampal dentate gyrus, with heightened microglia and astrocyte activation and worsened non-motor symptoms. Intrastriatal α-syn preformed fibril injection induced motor deficits, reactive glial protein accumulation, and tauopathy in the prefrontal cortex and hippocampus of Gba1 E326K mice. GBA1 deficiency due to the Gba1 E326K mutation exacerbates neuroinflammation and promotes pathogenic α-synuclein transmission, intensifying disease pathology in PD models. This study enhances our understanding of how the Gba1 E326K mutation contributes to neuroinflammation and the spread of pathogenic α-syn in the brain, suggesting new therapeutic strategies for PD and related synucleinopathies.

Micromechanism for Copper-Deficiency Enhanced Stability: A Quasi In Situ TEM Study of Electric-Induced Structural Evolution in Cu2-x(S, Se) Liquid-Like Thermoelectric Materials.

Cu-based liquid-like thermoelectric materials have garnered tremendous attention due to their inherent ultralow lattice thermal conductivity. However, their practical application is hampered by stability issues under a large current or temperature gradient. It has been reported that introduction of copper vacancies can enhance the chemical stability, whereas the micromechanism behind this macroscopic improvement still remains unknown. Here, we have established a quasi in situ TEM method to examine and compare the structural evolution of Cu2-xS0.2Se0.8 (x = 0, 0.05) under external electric fields. It is then found that the preset Cu vacancies could favor the electric-induced formation of a more stable intermediate phase, i.e., the hexagonal CuSe-type structure in the form of either lamellar defects (majorly) or long-range order (minorly), in which ordering of S and Se also occurred. Thereby, copper and chalcogen atoms could largely be solidified into the matrix, and the elemental deposition and evaporation process is mitigated under an electric field.

Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

Bipolaronic Nature of the Pseudogap in Quasi-One-Dimensional (TaSe4)2I Revealed via Weak Photoexcitation.

The origin of the pseudogap in many strongly correlated materials has been a longstanding puzzle. Here, we present experimental evidence that many-body interactions among small Holstein polarons, i.e., the formation of bipolarons, are primarily responsible for the pseudogap in (TaSe4)2I. After weak photoexcitation of the material, we observe the appearance of both dispersive (single-particle bare band) and flat bands (single-polaron sub-bands) in the gap by using time- and angle-resolved photoemission spectroscopy. Based on Monte Carlo simulations of the Holstein model, we propose that the melting of pseudogap and emergence of new bands originate from a bipolaron to single-polaron crossover. We also observe dramatically different relaxation times for the excited in-gap states in (TaSe4)2I (∼600 fs) compared with another 1D material Rb0.3MoO3 (∼60 fs), which provides a new method for distinguishing between pseudogaps induced by polaronic or Luttinger-liquid many-body interactions.

Incommensurately Modulated Structure in AgCuSe-Based Thermoelectric Materials for Intriguing Electrical, Thermal, and Mechanical Properties.

AgCuSe-based materials have attracted great attentions recently in thermoelectric (TE) field due to their extremely high electron mobility, ultralow lattice thermal conductivity, and abnormal "brittle-ductile" transition at room temperature. However, although the investigation on the crystal structure of AgCuSe low-temperature phase (named as ß-AgCuSe) was started more than half a century before, it is still in controversy yet, which greatly limits the understanding of its intriguing electrical, thermal, and mechanical performance. In this work, via adopting the advanced three-dimensional electron diffraction technique, this study finds that the AgCuSe-based materials crystalize in an incommensurately modulated structure with an orthorhombic Pmmn(0ß1/2)s00 superspace group. The local lattice distortion in the incommensurately modulated structure has weak effects on the conduction band minimum due to the delocalized and isotropic feature of Ag 5s states, leading to high carrier mobility. Likewise, the inhomogeneous, weak, and anisotropic Ag-Se bonds result in the high degree of anharmonicity and ultralow lattice thermal conductivity. Furthermore, alloying S in AgCuSe reinforces the interaction between the adjacent Ag-Se layers, yielding the "brittle-ductile" transition at room temperature. This work well interprets the structure-performance relationship of AgCuSe-based materials and sheds light on the future investigation of this class of promising TE materials.

Intrinsically Low Thermal Conductivity in a Novel Cu-S Modified ZrS2 Compound with Asymmetric Bonding.

Materials with low thermal conductivity have received significant attention across various research fields, including thermal insulation materials, thermal barrier coatings, and thermoelectric materials. Exploring novel materials with intrinsically low thermal conductivity and investigating their phonon transport properties, chemical bonding, and atomic coordination are crucial. In this study, a novel ternary sulfide is successfully discovered, Cu2 ZrS3 , which is achieved by introducing copper ions into both the interlayer and intralayer of ZrS2 . The resulting structure encompasses various coordination forms within each layer, such as [CuS4 ], [ZrS6 ], and [CuS3 ], leading to pronounced phonon anharmonicity induced by the asymmetric bonding of tri-coordinated Cu atoms within the [ZrS6 ] layer. As a result, Cu2 ZrS3 exhibits intrinsically low lattice thermal conductivity (κL ) of about 0.83 W m-1 K-1 at 300 K and 0.35 W m-1 K-1 at 683 K, which are in the exceptionally low level among sulfides. In comparison to the conventional approach of inserting guests between layers, the substitution of atoms within layers provides a novel and effective strategy for designing low κL materials in transition metal dichalcogenides (TMDCs).

Direct Observation of Enhanced Electron-Phonon Coupling in Copper Nanoparticles in the Warm-Dense Matter Regime.

Warm dense matter (WDM) represents a highly excited state that lies at the intersection of solids, plasmas, and liquids and that cannot be described by equilibrium theories. The transient nature of this state when created in a laboratory, as well as the difficulties in probing the strongly coupled interactions between the electrons and the ions, make it challenging to develop a complete understanding of matter in this regime. In this work, by exciting isolated ∼8 nm copper nanoparticles with a femtosecond laser below the ablation threshold, we create uniformly excited WDM. Using photoelectron spectroscopy, we measure the instantaneous electron temperature and extract the electron-ion coupling of the nanoparticle as it undergoes a solid-to-WDM phase transition. By comparing with state-of-the-art theories, we confirm that the superheated nanoparticles lie at the boundary between hot solids and plasmas, with associated strong electron-ion coupling. This is evidenced both by a fast energy loss of electrons to ions, and a strong modulation of the electron temperature induced by strong acoustic breathing modes that change the nanoparticle volume. This work demonstrates a new route for experimental exploration of the exotic properties of WDM.

Real-world applications of PARPi maintenance therapy for recurrent ovarian cancer: A single-center study in China.

OBJECTIVE: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). METHODS: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. RESULTS: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036). CONCLUSIONS: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.

Dynamical approach to the atomic and electronic structures of the ductile semiconductor Ag2S.

Silver sulfide in monoclinic phase (α-Ag2S) has attracted significant attention owing to its metal-like ductility and promising thermoelectric properties near room temperature. However, first-principles studies on this material by density functional theory calculations have been challenging as both the symmetry and atomic structure of α-Ag2S predicted from such calculations are inconsistent with experimental findings. Here, we propose that a dynamical approach is imperative for correctly describing the structure of α-Ag2S. The approach is based on a combination of ab initio molecular dynamics simulation and deliberately chosen density functional considering both proper treatment of the van der Waals interaction and on-site Coulomb interaction. The obtained lattice parameters and atomic site occupations of α-Ag2S are in good agreement with experimental data. A stable phonon spectrum at room temperature can be obtained from this structure, which also yields a bandgap in accord with experimental measurements. The dynamical approach thus paves the way for studying this important ductile semiconductor in not only thermoelectric but also optoelectronic applications.

Coherent modulation of the electron temperature and electron-phonon couplings in a 2D material.

Ultrashort light pulses can selectively excite charges, spins, and phonons in materials, providing a powerful approach for manipulating their properties. Here we use femtosecond laser pulses to coherently manipulate the electron and phonon distributions, and their couplings, in the charge-density wave (CDW) material 1T-TaSe2 After exciting the material with a femtosecond pulse, fast spatial smearing of the laser-excited electrons launches a coherent lattice breathing mode, which in turn modulates the electron temperature. This finding is in contrast to all previous observations in multiple materials to date, where the electron temperature decreases monotonically via electron-phonon scattering. By tuning the laser fluence, the magnitude of the electron temperature modulation changes from ∼200 K in the case of weak excitation, to ∼1,000 K for strong laser excitation. We also observe a phase change of π in the electron temperature modulation at a critical fluence of 0.7 mJ/cm2, which suggests a switching of the dominant coupling mechanism between the coherent phonon and electrons. Our approach opens up routes for coherently manipulating the interactions and properties of two-dimensional and other quantum materials using light.

The protective effect of 999 XiaoErGanMao granules on the lungs and intestines of influenza A virus-infected mice.

CONTEXT: Gastrointestinal symptoms are a common complication of influenza virus infection in children, which the gut-lung axis become involved in its biological progress. The protective effect of 999 XiaoErGanMao granules (XEGMG) on multi-organ injury in viral pneumonia remains unclear. OBJECTIVE: To investigate the therapeutic effect of XEGMG on lungs and intestines injury in A/FM/1/47 (H1N1) influenza virus-infected mice. MATERIALS AND METHODS: Male BALB/c mice were infected with the 2LD50 H1N1 influenza virus and then treated with XEGMG (6 or 12 g/kg) intragastrically once a day for 4 days. The lung and colon samples were then collected for pathological observation, and assays for inflammatory cytokines and intestinal barrier. Mouse feces were collected to evaluate the intestinal microbiota. RESULTS: Treating with XEGMG (12 g/kg) can mitigate body weight loss caused by 2LD50 H1N1 infection. It can also reduce lung index and pathological damage with the decreased inflammatory cytokines such as IL-6 and IL-1ß. Furthermore, XEGMG (12 g/kg) can maintain the goblet cell number in the colons to protect the intestinal barrier and regulate the major flora such as Firmicutes, Bacteroidetes, and Muribaculaceae back to normal. Meanwhile, the expression of IL-17A in the colon tissues was significantly lower in the group of XEGMG (6, 12 g/kg) compared to H1N1 group. DISCUSSION AND CONCLUSIONS: XEGMG can protect against H1N1 invasion involved in gut-lung axis regulation. The results provide new evidence for the protective effect of XEGMG, which is beneficial to vulnerable children.

High-Throughput Screening for Thermoelectric Semiconductors with Desired Conduction Types by Energy Positions of Band Edges.

The conduction type of semiconductors is vitally important in many fields (e.g., photovoltaics, transistors, and thermoelectrics), but so far, there is no effective and simple indicator to quickly judge or predict the conduction type of various semiconductors. In this work, based on the relationship between the formation energy of charged defect and the Fermi level, we propose a simple and low-cost strategy for high-throughput screening the potential n-type or p-type semiconductors from the material database by using energy positions of band edges as indicators. As a case study, we validate this strategy in searching potential n-type thermoelectric materials from copper (Cu)-containing metal chalcogenides. A new promising thermoelectric material, CuIn5Se8, with potential intrinsic n-type conduction, is successfully screened from 407 Cu-containing metal chalcogenides and validated in the subsequent experiments. Upon doping iodine in CuIn5Se8, a peak thermoelectric figure of merit zT of 0.84 is obtained at 850 K. Beyond thermoelectrics, the strategy proposed in this study also sheds light on the new material development with desired conduction types in photovoltaics, transistors, and other fields.

Impact of clinical and molecular features on efficacy and outcome of patients with non-small cell lung cancer receiving second-line osimertinib.

BACKGROUND: Although with the impressive efficacy, several patients showed intrinsic resistance or an unsatisfactory response to Osimertinib. We aim to explore the impact of clinical and molecular features on efficacy and outcome of patients with EGFR T790M-mutation non-small cell lung cancer (NSCLC) receiving second-line Osimertinib. METHODS: Patients with EGFR T790M-mutant NSCLC who had acquired resistance to the first-generation EGFR TKI and then received Osimertinib as second-line treatment were included. Patients' demographic and clinical information, as well as molecular data were extracted from electronic medical records. The impact of clinical and molecular features on treatment response and patients' outcome were assessed. RESULTS: Among the 99 patients, 60 patients were tissue/pleural effusion T790M positive and 69 patients were plasma positive with a median PFS of 12.1 m and 9.9 m (P = 0.25), respectively. In addition, median PFS were similar between patients of plasma T790M + and patients of plasma T790M- (P = 0.94). The Pearson correlation test showed no significant relationship between plasma T790M abundance and PFS (r = 0.074, P = 0.546). In subgroup analyses, PFS was significantly improved in elder patients (P = 0.009) and patients with longer PFS to the first-generation EGFR TKI (P = 0.0008), while smokers tended to have worse PFS compared with non-smokers (P = 0.064). PARP1 mutant-type patients had a worse PFS compared with wild-type group (P = 0.0003). Patients with MYC amplification also had a worse PFS than MYC wild-type patients (P = 0.016). A significant PFS shrinkage was observed in TMB-High group as 6.77 m, compared with 19.10 m in TMB-Low group. The multivariate Cox analysis revealed that years ≥ 65 was an independent positive feature for PFS, while PARP1 mutation and TMB-H were negative features for PFS. CONCLUSION: In conclusion, our findings in this study demonstrated that clinical and molecular features can be served as predictive biomarkers to stratify patients with EGFR T790M-mutant NSCLC receiving second-line Osimertinib.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer.

BACKGROUND: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. METHODS: Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 and 2-3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. RESULT: One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. TRG 2-3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001). CONCLUSION: TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

Complement and Coagulation Cascades are Potentially Involved in Dopaminergic Neurodegeneration in α-Synuclein-Based Mouse Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that results in motor dysfunction and, eventually, cognitive impairment. α-Synuclein protein is known as a central protein to the pathophysiology of PD, but the underlying pathological mechanism still remains to be elucidated. In an effort to understand how α-synuclein underlies the pathology of PD, various PD mouse models with α-synuclein overexpression have been developed. However, systemic analysis of the brain proteome of those mouse models is lacking. In this study, we established two mouse models of PD by injecting α-synuclein preformed fibrils (PFF) or by inducing overexpression of human A53T α-synuclein to investigate common pathways in the two different types of the PD mouse models. For more accurate quantification of mouse brain proteome, the proteins were quantified using the method of stable isotope labeling with amino acids in mammals . We identified a total of 8355 proteins from the two mouse models; ∼6800 and ∼7200 proteins from α-synuclein PFF-injected mice and human A53T α-synuclein transgenic mice, respectively. Through pathway analysis of the differentially expressed proteins common to both PD mouse models, it was discovered that the complement and coagulation cascade pathways were enriched in the PD mice compared to control animals. Notably, a validation study demonstrated that complement component 3 (C3)-positive astrocytes were increased in the ventral midbrain of the intrastriatal α-synuclein PFF-injected mice and C3 secreted from astrocytes could induce the degeneration of dopaminergic neurons. This is the first study that highlights the significance of the complement and coagulation pathways in the pathogenesis of PD through proteome analyses with two sophisticated mouse models of PD.

α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study.

BACKGROUND: Pathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC. METHODS: Three independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC. RESULTS: AFP RNAscope improved the HCC detection sensitivity by 24.7-32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions. CONCLUSIONS: AFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.

The Incidence of Amyotrophic Lateral Sclerosis in Ohio 2016-2018: The Ohio Population-Based ALS Registry.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018. METHODS: We engaged practitioners from 9 Ohio sites to identify newly diagnosed ALS patients and to complete case report forms with demographic and clinical information. ALS was diagnosed according to the Awaji criteria and classified as either definite, probable, or possible. We developed a method to estimate missing cases using a Poisson regression model to impute cases in counties with evidence of undercounting. RESULTS: We identified 333 newly diagnosed ALS patients residing in Ohio during the 2-year index period and found incidence rates varied in the 88 state counties. After incorporating the estimated 27% of missing cases, the corrected crude annual incidence was 1.96/100,000 person-years, and the age- and gender-standardized incidence was 1.71/100,000 person-years (standardized to the 2010 US census). DISCUSSION/CONCLUSION: The estimated Ohio incidence of ALS is overall similar to that reported in other states in the USA. This study reveals a geospatial variation in incidence within the state, and areas with higher rates warrant future investigation.

Dimeric clerodane diterpenoids and antiviral constituents of Dodonaea viscosa.

Three unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro.