Background
The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G‐NECs) or mixed ...adenoneuroendocrine carcinomas (G‐MANECs).
Methods
The study included patients with G‐NECs or G‐MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan–Meier method.
Results
In total, 804 patients with resectable G‐NECs or G‐MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no‐chemotherapy group. Among patients with G‐NECs, survival in the fluorouracil (5‐FU)‐based chemotherapy group and the non‐5‐FU‐based chemotherapy group was similar to that in the no‐chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G‐NECs. Among patients with G‐MANECs, OS in the non‐5‐FU‐based chemotherapy group was worse than that in the no‐chemotherapy group. Patients with G‐MANECs did not have better OS when platinum‐based chemotherapy was
used.
Conclusion
There was no survival benefit in patients who received adjuvant chemotherapy for G‐NECs or G‐MANECs.
Antecedentes
El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G‐NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G‐MANECs).
Métodos
Se incluyeron pacientes con G‐NECs y G‐MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan‐Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento.
Resultados
En total, se incluyeron en el estudio 804 pacientes con G‐NECs y G‐MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G‐NECs, la supervivencia en los grupos con quimioterapia basada en 5‐FU (fluorouracilo) y de quimioterapia sin 5‐FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G‐NECs. En pacientes con G‐MANECs, la OS del grupo con quimioterapia sin 5‐FU fue peor que la del grupo sin quimioterapia. Los pacientes con G‐MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos.
Conclusión
La administración de quimioterapia adyuvante en pacientes con G‐NECs y G‐MANECs no mejoró la supervivencia.
This multicentre study enrolled 804 patients with resectable gastric neuroendocrine carcinomas and gastric mixed adenoneuroendocrine carcinomas. In propensity score matching analysis, there were no associations between the use of adjuvant chemotherapy and improved overall survival. Similar results were obtained in stratified analysis according to different chemotherapy regimens.
No benefit
Aims
The objective of this study was twofold: (i) to examine the effect of Clostridium butyricum on intestinal barrier function and (ii) to elucidate the mechanisms involved in enhanced intestinal ...barrier function.
Methods and Results
Forty‐eight weaned piglets were assigned randomly to either a basal diet or a C. butyricum‐supplemented diet. On day 15, all pigs were orally challenged with enterotoxigenic Escherichia coli (ETEC) K88 or saline. Clostridium butyricum decreased serum diamine oxidase activity and d‐lactic acid concentration, as well as increased intestinal tight junction proteins (ZO‐1, claudin‐3 and occludin) expression in ETEC K88‐infected pigs. Moreover, C. butyricum decreased IL‐1β and IL‐18 levels in serum and gut, whereas it increased IL‐10 levels. Furthermore, C. butyricum downregulated NLRP3 and caspase‐1 expression in ETEC K88‐challenged pig gut, but did not affect apoptosis‐associated speck‐like protein expression.
Conclusions
Clostridium butyricum enhanced intestinal barrier function and inhibited apoptosis‐associated speck‐like protein‐independent NLRP3 inflammasome signalling pathway in weaned piglets after ETEC K88 challenge.
Significance and Impact of the Study
The novelty of this study lies in the beneficial effects of C. butyricum on intestinal health, likely by improving intestinal barrier function and alleviating inflammatory reactions.
Intracranial aneurysms, a rare complication of radiation therapy, have been reported mainly in case reports or case series. We performed a multicenter, retrospective cohort study to investigate the ...characteristics of radiation-induced intracranial aneurysms.
Data on 2641 patients with intracranial aneurysms were retrospectively collected from 3 hospitals between January 2005 and June 2014. An additional 1519 patients were recruited from a single center between July 2014 and March 2020. Aneurysms in patients with a history of radiation therapy for at least 6 months were defined as radiation-related aneurysms. Patients' demographic profiles, clinical characteristics, and aneurysm parameters detected on CTA were compared between radiation-related and control groups.
Of the 4160 patients, the average age was 57.9 (SD, 13.5) years, 2406 (57.8%) were women, 477 (11.5%) had multiple aneurysms, 3009 (72.3%) had SAH, and 34 (0.8%) had radiation-related aneurysms. The male-to-female ratio in the radiation-related group was significantly higher than that in the control group (2.4:1 versus 0.72:1,
= .001). The mean age of the radiation-related group was significantly younger than in the control group (51.4 SD, 15.0 years versus 58.2 SD, 13.5 years,
= .003). More patients in the radiation-related group presented with SAH than in the control group (without age and sex matching, 88.2% versus 72.2%,
= .037; with age and sex matching, 88.2% versus 58.8%,
= .006). Of the 4813 intracranial aneurysms, only 43 (0.9%) aneurysms were categorized as in the radiation-related group, whereas 4770 (99.1%) aneurysms constituted the control group. Compared with the control group, there was a significantly higher proportion of sidewall aneurysms (46.5% versus 32.3%,
= .048) and a predilection for aneurysms involving the ICA and posterior circulation arteries (72.1% versus 52.2%,
= .046) in the radiation-related group.
Compared with the control group, radiation-related aneurysms are more prone to occur in men and young patients, with a higher percentage of sidewall aneurysms located in the ICA and posterior circulation arteries. Furthermore, SAH is highly prevalent in patients with radiation-induced aneurysms, indicating that dedicated screening for aneurysms after radiation therapy is necessary, but further studies are needed to determine when and how to screen.
Abstract
A quantum thermal machine is an open quantum system coupled to hot and cold thermal baths. Thus, its dynamics can be well understood using the concepts and tools from non-Hermitian quantum ...systems. A hallmark of non-Hermiticity is the existence of exceptional points where the eigenvalues of a non-Hermitian Hamiltonian or a Liouvillian superoperator and their associated eigenvectors coalesce. Here, we report the experimental realization of a single-ion heat engine and demonstrate the effect of Liouvillian exceptional points on the dynamics and the performance of a quantum heat engine. Our experiments have revealed that operating the engine in the exact- and broken-phases, separated by a Liouvillian exceptional point, respectively during the isochoric heating and cooling strokes of an Otto cycle produces more work and output power and achieves higher efficiency than executing the Otto cycle completely in the exact phase where the system has an oscillatory dynamics and higher coherence. This result opens interesting possibilities for the control of quantum heat engines and will be of interest to other research areas that are concerned with the role of coherence and exceptional points in quantum processes and in work extraction by thermal machines.
Sea salt aerosols (SSA) are dominant particles in the Arctic atmosphere and determine the polar radiative balance. SSA react with acidic pollutants that lead to changes in physical and chemical ...properties of their surface, which in turn alter their hygroscopic and optical properties. Transmission electron microscopy with energy-dispersive X-ray spectrometry was used to analyze morphology, composition, size, and mixing state of individual SSA at Ny-Ålesund, Svalbard, in summertime. Individual fresh SSA contained cubic NaCl coated by certain amounts of MgCl2 and CaSO4. Individual partially aged SSA contained irregular NaCl coated by a mixture of NaNO3, Na2SO4, Mg(NO3)2, and MgSO4. The comparison suggests the hydrophilic MgCl2 coating in fresh SSA likely intrigued the heterogeneous reactions at the beginning of SSA and acidic gases. Individual fully aged SSA normally had Na2SO4 cores and an amorphous coating of NaNO3. Elemental mappings of individual SSA particles revealed that as the particles ageing Cl gradually decreased, the C, N, O, and S content increased. 12C- mapping from nanoscale secondary ion mass spectrometry indicates that organic matter increased in the aged SSA compared with the fresh SSA. 12C- line scan further shows that organic matter was mainly concentrated on the aged SSA surface. These new findings indicate that this mixture of organic matter and NaNO3 on particle surfaces likely determines their hygroscopic and optical properties. These abundant SSA as reactive surfaces adsorbing inorganic and organic acidic gases can shorten acidic gas lifetime and influence the possible gaseous reactions in the Arctic atmosphere, which need to be incorporated into atmospheric chemical models in the Arctic troposphere.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
Weyl semimetals are crystalline solids that host emergent relativistic Weyl fermions and have characteristic surface Fermi-arcs in their electronic structure. Weyl semimetals with broken time ...reversal symmetry are difficult to identify unambiguously. In this work, using angle-resolved photoemission spectroscopy, we visualized the electronic structure of the ferromagnetic crystal Co
Sn
S
and discovered its characteristic surface Fermi-arcs and linear bulk band dispersions across the Weyl points. These results establish Co
Sn
S
as a magnetic Weyl semimetal that may serve as a platform for realizing phenomena such as chiral magnetic effects, unusually large anomalous Hall effect and quantum anomalous Hall effect.
In this work, we report the in-orbit demonstration of X-ray pulsar navigation with Insight-Hard X-ray Modulation Telescope (Insight-HXMT) Satellite, which was launched on 2017 June 15. The new pulsar ...navigation method "Significance Enhancement of Pulse-profile with Orbit-dynamics" is adopted to determine the orbit with observations of only one pulsar. In this test, the Crab pulsar is chosen and observed by Insight-HXMT from 2017 August 31 to September 5. Using the five-day long observation data, the orbit of Insight-HXMT is determined successfully with the three telescopes onboard: High Energy X-ray Telescope, Medium Energy X-ray Telescope, and Low Energy X-ray Telescope, respectively. By combining all the data, the position and velocity of the Insight-HXMT are pinpointed to within 10 km (3 ) and 10 m s−1 (3 ), respectively.
Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms ...underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups.
A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation.
Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-β signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01).
This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.