Abstract
Spin-valley locking in monolayer transition metal dichalcogenides has attracted enormous interest, since it offers potential for valleytronic and optoelectronic applications. Such an exotic ...electronic state has sparsely been seen in bulk materials. Here, we report spin-valley locking in a Dirac semimetal BaMnSb
2
. This is revealed by comprehensive studies using first principles calculations, tight-binding and effective model analyses, angle-resolved photoemission spectroscopy measurements. Moreover, this material also exhibits a stacked quantum Hall effect (QHE). The spin-valley degeneracy extracted from the QHE is close to 2. This result, together with the Landau level spin splitting, further confirms the spin-valley locking picture. In the extreme quantum limit, we also observed a plateau in the
z
-axis resistance, suggestive of a two-dimensional chiral surface state present in the quantum Hall state. These findings establish BaMnSb
2
as a rare platform for exploring coupled spin and valley physics in bulk single crystals and accessing 3D interacting topological states.
Objective
To assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer ...(EEC).
Design
A randomised, single‐centre, open‐label, controlled trial conducted between October 2013 and December 2017.
Setting
Shanghai OBGYN Hospital of Fudan University, China.
Population
A total of 150 patients (18–45 years old) with primary AEH or well‐differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).
Methods
Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).
Main outcomes and measures
The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w‐CR rate); the secondary efficacy parameters were 30w‐CR rate and adverse events.
Results
The 16w‐CR rate was higher in the metformin plus MA group than in the MA‐only group (34.3 versus 20.7%, odds ratio OR 2.0, 95% confidence interval CI 0.89–4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06–6.21, P = 0.04). This effect of metformin was also significant in non‐obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22–8.84, P = 0.02) and insulin‐sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03–8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.
Conclusion
As a fertility‐sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve a higher early CR rate compared with MA alone.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve higher early CR rate compared with MA alone.
IMPORTANCE: Time spent in outdoor activities has decreased owing to home confinement for the coronavirus disease 2019 (COVID-19) pandemic. Concerns have been raised about whether home confinement may ...have worsened the burden of myopia owing to substantially decreased time spent outdoors and increased screen time at home. OBJECTIVE: To investigate the refractive changes and prevalence of myopia in school-aged children during the COVID-19 home confinement. DESIGN, SETTING, AND PARTICIPANTS: A prospective cross-sectional study using school-based photoscreenings in 123 535 children aged 6 to 13 years from 10 elementary schools in Feicheng, China, was conducted. The study was performed during 6 consecutive years (2015-2020). Data were analyzed in July 2020. EXPOSURES: Noncycloplegic photorefraction was examined using a photoscreener device. MAIN OUTCOMES AND MEASURES: The spherical equivalent refraction was recorded for each child and the prevalence of myopia for each age group during each year was calculated. The mean spherical equivalent refraction and prevalence of myopia were compared between 2020 (after home confinement) and the previous 5 years for each age group. RESULTS: Of the 123 535 children included in the study, 64 335 (52.1%) were boys. A total of 194 904 test results (389 808 eyes) were included in the analysis. A substantial myopic shift (approximately −0.3 diopters D) was found in the 2020 school-based photoscreenings compared with previous years (2015-2019) for younger children aged 6 (−0.32 D), 7 (−0.28 D), and 8 (−0.29 D) years. The prevalence of myopia in the 2020 photoscreenings was higher than the highest prevalence of myopia within 2015-2019 for children aged 6 (21.5% vs 5.7%), 7 (26.2% vs 16.2%), and 8 (37.2% vs 27.7%) years. The differences in spherical equivalent refraction and the prevalence of myopia between 2020 and previous years were minimal in children aged 9 to 13 years. CONCLUSIONS AND RELEVANCE: Home confinement during the COVID-19 pandemic appeared to be associated with a significant myopic shift for children aged 6 to 8 years according to 2020 school-based photoscreenings. However, numerous limitations warrant caution in the interpretation of these associations, including use of noncycloplegic refractions and lack of orthokeratology history or ocular biometry data. Younger children’s refractive status may be more sensitive to environmental changes than older ages, given the younger children are in a critical period for the development of myopia.
A retrospective observational study was performed to assess the relationship between diagnostic method (traditional work-up TW, multiplex PCR panel with < 12 target pathogens PCR < 12, or multiplex ...PCR panel with ≥ 12 target pathogens PCR12), and diagnostic yield, health care resource use (HRU), and cost in adult outpatients visiting U.S. hospitals for acute infectious gastroenteritis (AGE). Using data from PINC AI Healthcare Database during January 1, 2016-June 30, 2021, we analyzed adult patients with an AGE diagnosis and stool testing performed during an outpatient visit. Detection rates for different pathogens were analyzed for those with microbiology data available. Among 36,787 patients, TW was most often performed (57.0%). PCR12 testing was more frequent in patients from large, urban, and teaching hospitals, compared to TW (all
< 0.01). PCR12 was associated with a higher mean index visit cost (by $97) but lower mean 30-day AGE-related follow-up cost (by $117) than TW. Patients with PCR12 had a lower 30-day AGE-related hospitalization risk than TW (1.7% versus 2.7%
< 0.01). Among the 8,451 patients with microbiology data, PCR12 was associated with fewer stool tests per patient (mean 1.61 versus 1.26), faster turnaround time (mean 6.3 versus 25.7 h) and lower likelihood of receiving in-hospital antibiotics (39.4% versus 47.1%, all
< 0.01) than TW. A higher percentage of patients with PCR12 had a target pathogen detected (73.1%) compared to PCR < 12 (63.6%) or TW (45.4%,
< 0.01). Thus, we found that large multiplex PCR panels were associated with lower 30-day AGE-related follow-up cost and risk of AGE-related hospitalization, and increased diagnostic yield compared to TW.
Identification of the specific cell types expressing CFTR (cystic fibrosis CF transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full ...characterization of CFTR expression in normal human airway epithelia is missing.
To identify the cell types that contribute to
expression and function within the proximal-distal axis of the normal human lung.
Single-cell RNA (scRNA) sequencing (scRNA-seq) was performed on freshly isolated human large and small airway epithelial cells. scRNA
hybridization (ISH) and single-cell qRT-PCR were performed for validation.
culture systems correlated CFTR function with cell types. Lentiviruses were used for cell type-specific transduction of wild-type CFTR in CF cells.
scRNA-seq identified secretory cells as dominating
expression in normal human large and, particularly, small airway superficial epithelia, followed by basal cells. Ionocytes expressed the highest
levels but were rare, whereas the expression in ciliated cells was infrequent and low. scRNA ISH and single-cell qRT-PCR confirmed the scRNA-seq findings. CF lungs exhibited distributions of
and ionocytes similar to those of normal control subjects. CFTR mediated Cl
secretion in cultures tracked secretory cell, but not ionocyte, densities. Furthermore, the nucleotide-purinergic regulatory system that controls CFTR-mediated hydration was associated with secretory cells and not with ionocytes. Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl
secretion in CF airway secretory cells but not in ciliated cells.
Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.
Plasma-based accelerators have made impressive progress in recent years. However, the beam energy spread obtained in these accelerators is still at the ∼1% level, nearly one order of magnitude larger ...than what is needed for challenging applications like coherent light sources or colliders. In plasma accelerators, the beam energy spread is mainly dominated by its energy chirp (longitudinally correlated energy spread). Here we demonstrate that when an initially chirped electron beam from a linac with a proper current profile is sent through a low-density plasma structure, the self-wake of the beam can significantly reduce its energy chirp and the overall energy spread. The resolution-limited energy spectrum measurements show at least a threefold reduction of the beam energy spread from 1.28% to 0.41% FWHM with a dechirping strength of ∼1 (MV/m)/(mm pC). Refined time-resolved phase space measurements, combined with high-fidelity three-dimensional particle-in-cell simulations, further indicate the real energy spread after the dechirper is only about 0.13% (FWHM), a factor of 10 reduction of the initial energy spread.
Full text
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CMK, CTK, FMFMET, NUK, UL
All hepatitis E virus (HEV) variants reported to infect humans belong to the species Orthohepevirus A (HEV-A). The zoonotic potential of the species Orthohepevirus C (HEV-C), which circulates in rats ...and is highly divergent from HEV-A, is unknown. We report a liver transplant recipient with hepatitis caused by HEV-C infection. We detected HEV-C RNA in multiple clinical samples and HEV-C antigen in the liver. The complete genome of the HEV-C isolate had 93.7% nt similarity to an HEV-C strain from Vietnam. The patient had preexisting HEV antibodies, which were not protective against HEV-C infection. Ribavirin was an effective treatment, resulting in resolution of hepatitis and clearance of HEV-C viremia. Testing for this zoonotic virus should be performed for immunocompromised and immunocompetent patients with unexplained hepatitis because routine hepatitis E diagnostic tests may miss HEV-C infection. HEV-C is also a potential threat to the blood product supply.
Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women ...with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes.
We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival.
A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio HR, 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors.
The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.
A major challenge for organic solar cell (OSC) research is how to minimize the tradeoff between voltage loss and charge generation. In early 2019, we reported a non-fullerene acceptor (named Y6) that ...can simultaneously achieve high external quantum efficiency and low voltage loss for OSC. Here, we use a combination of experimental and theoretical modeling to reveal the structure-property-performance relationships of this state-of-the-art OSC system. We find that the distinctive π-π molecular packing of Y6 not only exists in molecular single crystals but also in thin films. Importantly, such molecular packing leads to (i) the formation of delocalized and emissive excitons that enable small non-radiative voltage loss, and (ii) delocalization of electron wavefunctions at donor/acceptor interfaces that significantly reduces the Coulomb attraction between interfacial electron-hole pairs. These properties are critical in enabling highly efficient charge generation in OSC systems with negligible donor-acceptor energy offset.
Metformin, a well‐known antidiabetic drug, has been repurposed for cancer treatment; however, recently observed drug resistance and tumor metastasis have questioned its further application. Here, we ...found that long‐term metformin exposure led to metabolic adaptation of hepatocellular carcinoma (HCC) cells, which was characterized by an obvious epithelial–mesenchymal transition (EMT) phenotype and compensatory elevation of oxidative phosphorylation (OXPHOS). TOMM34, a translocase of the outer mitochondrial membrane, was upregulated to promote tumor metastasis in response to metformin‐induced metabolic stress. Mechanistically, TOMM34 interacted with ATP5B to preserve F1FO‐ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preference for OXPHOS suggested a large requirement of energy supply by cancer cells to survive and spread in response to therapeutic stress. Notably, disturbing the interaction between TOMM34 and ATP5B using Gboxin, a specific OXPHOS inhibitor, increased sensitivity to metformin and suppressed tumor progression both in vitro and in vivo. Overall, this study demonstrates a molecular link of the TOMM34/ATP5B‐ATP synthesis axis during metformin adaptation and provides promising therapeutic targets for metformin sensitization in cancer treatment.
Synopsis
Adaptation to metformin is frequently observed during long‐term tumor treatment. Here, during this adaptation process, TOMM34 was upregulated to enhance OXPHOS by interacting with ATP5B. Disruption of the TOMM34‐ATP5B interaction using Gboxin synergized with metformin to suppress HCC.
HCC cells exhibited an EMT phenotype and a compensatory elevation of respiration rate during metformin adaptation.
TOMM34 upregulation preserved OXPHOS and ATP production during metformin adaptation.
TOMM34 interacted with ATP5B to maintain OXPHOS and ATP production.
Gboxin disrupted TOMM34/ATP5B interaction and prevented metformin adaptation.
Adaptation to metformin is frequently observed during long‐term tumor treatment. Here, during this adaptation process, TOMM34 was upregulated to enhance OXPHOS by interacting with ATP5B. Disruption of the TOMM34‐ATP5B interaction using Gboxin synergized with metformin to suppress HCC.
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