Efficacy of befotertinib in non-small cell lung cancer harboring uncommon compound EGFR mutations G719X and S768I: a case report.

The discovery of epidermal growth factor receptor (EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC). p.G719X and p.S768I mutations, often present in the form of complex mutations, are considered rare. This study firstly reported the treatment outcome of a locally advanced unresectable NSCLC patient with a rare complex EGFR p.G719X/p.S768I mutations who received befotertinib. After treatment, the patient achieved partial response (PR), and no severe adverse events were observed. This case report supported befotertinib as a promising treatment option for advanced NSCLC patients with the rare p.G719X/p.S768I complex mutations.

Raman Spectroscopy of Conical Intersections Using Entangled Photons.

Ultrafast Raman spectroscopy with attosecond pulses in the extreme ultraviolet and X-ray regime has been proposed theoretically for tracking the non-adiabatic dynamics of molecules in great detail. The large bandwidth of these pulses, which span several electronvolts within a couple of femtoseconds, provides a unique tool for tracking non-adiabatic phenomena. However, spectroscopy with classical light is limited by the time-bandwidth product of the probe laser pulse. In this work, we theoretically investigate an ultrafast Raman spectroscopy scheme that utilizes pairs of entangled photons. Our model simulations demonstrate that the dynamics in the vicinity of a conical intersection can be resolved with unprecedented resolution in the time and frequency domain.

Multidimensional Coherent Spectroscopy of Molecular Polaritons: Langevin Approach.

We present a microscopic theory for nonlinear optical spectroscopy of N molecules in an optical cavity. Using the Heisenberg-Langevin equation, an analytical expression is derived for the time- and frequency-resolved signals accounting for arbitrary numbers of vibrational excitations. We identify clear signatures of the polariton-polaron interaction from multidimensional projections of the signal, e.g., pathways and timescales. Cooperative dynamics of cavity polaritons against intramolecular vibrations is revealed, along with a crosstalk between long-range coherence and vibronic coupling that may lead to localization effects. Our results further characterize the polaritonic coherence and the population transfer that is slower.

Long-term follow-up of persistent pulmonary subsolid nodules: Natural course of pure, heterogeneous, and real part-solid ground-glass nodules.

BACKGROUND: Previous studies have suggested the applicability of three classifications of subsolid nodules (SSNs). However, few studies have unraveled the natural history of the three types of SSNs. METHODS: A retrospective study from two medical centers between November 2007 and November 2017 was conducted to explore the long-term follow-up results of three different types of SSNs, which were divided into pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (hGGNs), and real part-solid nodules (rPSNs). RESULTS: A total of 306 consecutive patients, including 361 SSNs with long-term follow-up, were reviewed. The median growth times of pGGNs, hGGNs, and rPSNs were 7.7, 6.0, and 2.0 years, respectively. For pGGNs, the median period of development into rPSNs was 4.6 years, while that of hGGNs was 1.8 years, and the time from pGGNs to hGGNs was 3.1 years (p < 0.05). In SSNs with an initial lung window consolidation tumor ratio (LW-CTR) >0.5 and mediastinum window (MW)-CTR >0.2, all cases with growth were identified within 5 years. Meanwhile, in SSNs whose LW-CTR and MW-CTR were 0, it took over 5 years to detect nodular growth. Pathologically, 90.6% of initial SSNs with LW-CTR >0 were invasive carcinomas (invasive adenocarcinoma and micro-invasive adenocarcinoma). Among patients with rPSNs in the initial state, 100.0% of the final pathological results were invasive carcinoma. Cox regression showed that age (p = 0.038), initial maximal diameter (p < 0.001), and LW-CTR (p = 0.002) were independent risk factors for SSN growth. CONCLUSIONS: pGGNs, hGGNs, and rPSNs have significantly different natural histories. Age, initial nodule diameter, and LW-CTR are important risk factors for SSN growth.

The natural growth history of persistent pulmonary subsolid nodules: Radiology, genetics, and clinical management.

The high detection rate of pulmonary subsolid nodules (SSN) is an increasingly crucial clinical issue due to the increased number of screening tests and the growing popularity of low-dose computed tomography (LDCT). The persistence of SSN strongly suggests the possibility of malignancy. Guidelines have been published over the past few years and guide the optimal management of SSNs, but many remain controversial and confusing for clinicians. Therefore, in-depth research on the natural growth history of persistent pulmonary SSN can help provide evidence-based medical recommendations for nodule management. In this review, we briefly describe the differential diagnosis, growth patterns and rates, genetic characteristics, and factors that influence the growth of persistent SSN. With the advancement of radiomics and artificial intelligence (AI) technology, individualized evaluation of SSN becomes possible. These technologies together with liquid biopsy, will promote the transformation of current diagnosis and follow-up strategies and provide significant progress in the precise management of subsolid nodules in the early stage of lung cancer.

Surgical management of primary mediastinal mature teratoma: A single-center 20 years' experience.

Background: This study aims to investigate the clinical efficacy of video-assisted thoracic surgery (VATS) in treating mediastinal mature teratoma (MMT) and explore the clinical factors that increase the difficulties associated with VATS. Method: We retrospectively reviewed 101 consecutive patients with MMT who underwent surgical excision between November 2001 and June 2021. Follow-up was done by telephone or at an outpatient clinic. The deadline for follow-up was February 2022. Results: The operative time, the chest tube indwelling time, and the hospital stay duration were significantly shorter in the VATS group compared with the thoracotomy group. The intraoperative and postoperative complication rates in the VATS group were lower than that of the thoracotomy group (P < .05). In thoracoscopic surgery, the clinical symptoms during the course of the disease were significantly associated with bleeding loss increasing [odds ratio (OR) = 3.562; 95% confidence interval (CI) 1.180-10.753, P = .024] and operation time extension (OR = 5.697; 95% CI 1.529-21.221, P = .010). The relationship between lesions and superior vena cava or innominate vein from preoperative CT imaging was significantly associated with bleeding loss increasing (OR = 4.629; 95% CI 1.463-14.639, P = .009). A maximal lesion diameter greater than 7 cm was significantly associated with increased risks of operation time extension (OR = 5.019; 95% CI 1.641-15.348, P = .005). Conclusion: Compared with traditional thoracotomy surgery, VATS can be performed safely in selected patients with MMT. A surgical method for complete resection needs to be determined according to preoperative imaging and intraoperative conditions to reduce the unnecessary damage.

Entangled photons enabled time-frequency-resolved coherent Raman spectroscopy and applications to electronic coherences at femtosecond scale.

Quantum entanglement has emerged as a great resource for spectroscopy and its importance in two-photon spectrum and microscopy has been demonstrated. Current studies focus on the two-photon absorption, whereas the Raman spectroscopy with quantum entanglement still remains elusive, with outstanding issues of temporal and spectral resolutions. Here we study the new capabilities provided by entangled photons in coherent Raman spectroscopy. An ultrafast frequency-resolved Raman spectroscopy with entangled photons is developed for condensed-phase molecules, to probe the electronic and vibrational coherences. Using quantum correlation between the photons, the signal shows the capability of both temporal and spectral resolutions not accessible by either classical pulses or the fields without entanglement. We develop a microscopic theory for this Raman spectroscopy, revealing the electronic coherence dynamics even at timescale of 50fs. This suggests new paradigms of optical signals and spectroscopy, with potential to push detection below standard quantum limit.

Plasmonic Nanocavity Induced Coupling and Boost of Dark Excitons in Monolayer WSe2 at Room Temperature.

Spin-forbidden excitons in monolayer transition metal dichalcogenides are optically inactive at room temperature. Probing and manipulating these dark excitons are essential for understanding exciton spin relaxation and valley coherence of these 2D materials. Here, we show that the coupling of dark excitons to a metal nanoparticle-on-mirror cavity leads to plasmon-induced resonant emission with the intensity comparable to that of the spin-allowed bright excitons. A three-state quantum model combined with full-wave electrodynamic calculations reveals that the radiative decay rate of the dark excitons can be enhanced by nearly 6 orders of magnitude through the Purcell effect, therefore compensating its intrinsic nature of weak radiation. Our nanocavity approach provides a useful paradigm for understanding the room-temperature dynamics of dark excitons, potentially paving the road for employing dark exciton in quantum computing and nanoscale optoelectronics.

Surgical treatment for esophageal neurofibroma: report of two cases and review of literature.

BACKGROUND: Neurofibroma of the esophagus, originated from the nerve sheath cells and fibroblasts of the esophageal submucosal plexus or the intestinal intermuscular plexus, is a very rare mesenchymal tumor. Most of the cases are treated by surgical methods. Due to the technical complexity of video-assisted thoracoscopic surgery (VATS), there are few reports in the literature of VATS for esophageal neurofibroma in recent years. CASE PRESENTATION: We report on two rare cases of esophageal neurofibroma, one of which is a 52-year-old male patient diagnosed with a 4.6 × 5.7 cm upper esophageal submucosal tumor in physical examination. He was admitted to our hospital and the tumor was enucleated by VATS combined with intraoperative endoscopy. There were no complications after operation, and the patients was discharged on the 16th postoperative day. The other patient was a 76-year-old man, with the main clinical manifestation of dysphagia for over 1 year, diagnosed with an 8.0 × 6.0 × 8.0 cm giant subepithelial mass in the lower esophagus. As the intraoperative exploration revealed the tumor connected tightly with the wall of the esophagus, this patient treated by transthoracic partial esophagectomy. The patient was discharged on the 14th postoperative day, and no signs of post-operative complication during the 53-month follow-up. The diagnosis of esophageal neurofibroma was based on these patients' postoperative pathological examination. In the latest follow-up, these two patients had no evidence of long-term postoperative complication and recurrence. CONCLUSION: This is the first reported case of 5 cm in diameter esophageal neurofibroma treated by VATS. This technique can be a commendable treatment option for esophageal neurofibroma, and the tumor diameter is not an absolute contraindication for thoracoscopy. To reduce the unnecessary damage, surgical method for complete tumor resection needs to be determined according to preoperative imaging and intraoperative conditions, partial esophagectomy can be performed via thoracotomy or thoracoscopy for removing neurofibroma when necessary.

Noncoding RNAs Act as Tumor-Derived Molecular Components in Inducing Premetastatic Niche Formation.

Cancer metastasis has been demonstrated as it is the culmination of a cascade of priming steps. Increasing evidence has shown that tumor-derived molecular components (TDMCs) are known as extra cellular vesicle and nonvesicle factors and serve as versatile intercellular communication vehicles which can mediate signaling in the tumor microenvironment while creating the premetastatic niche. Noncoding RNAs (ncRNAs) as one of the TDMCs have been proved in participating in the formation of the premetastatic niche. Understanding the premetastatic niche formation mechanisms through TDMCs, especially ncRNAs may open a new avenue for cancer metastasis therapeutic strategies. In this review, recent findings regarding ncRNAs function were summarized, and then the interaction with the premetastatic niche formation was studied, which highlight the potential of using ncRNAs for cancer diagnosis and therapeutic effect.

Polariton-Assisted Cooperativity of Molecules in Microcavities Monitored by Two-Dimensional Infrared Spectroscopy.

Molecular polaritons created by the strong coupling between matter and field in microcavities enable the control of molecular dynamical processes and optical response. Multidimensional infrared spectroscopy is proposed for monitoring the polariton-assisted cooperative properties. The response of molecules to local fluctuations is incorporated and the full dynamics is monitored through the time- and frequency-resolved multidimensional signal. The cooperativity against solvent-induced disorder and its connection to the localization of the vibrational excitations are predicted. New insights are provided for recent 2DIR experiments on vibrational polaritons.

Enhanced signals from chiral molecules via molecular coherence.

One of the most widely used chiroptical spectroscopic methods for studying chiral molecules is Raman optical activity; however, the chiral Raman optical activity signal is extremely weak. Here, we theoretically examine enhanced chiral signals in a system with strongly prepared molecular coherence. We show that the enhanced chiral signal due to strong molecular coherence is up to four orders of magnitude higher than that of the spontaneous Raman optical activity. We discuss several advantages of studying the heterodyned signal obtained by combining the anti-Stokes signal with a local oscillator. The heterodyning allows direct measurement of the ratio of the chiral and achiral parameters. Taking advantage of the molecular coherence and heterodyne detection, the coherent anti-Stokes Raman scattering technique opens up a new potential application for investigation of biomolecular chirality.

Quantum Fluctuations in the Fröhlich Condensate of Molecular Vibrations Driven Far From Equilibrium.

Fröhlich discovered the remarkable condensation of polar vibrations into the lowest frequency mode when the system is pumped externally. For a full understanding of the Fröhlich condensate one needs to go beyond the mean field level to describe critical behavior as well as quantum fluctuations. The energy redistribution among vibrational modes with nonlinearity included is shown to be essential for realizing the condensate and the phonon-number distribution, revealing the transition from quasithermal to super-Poissonian statistics with the pump. We further study the spectroscopic properties of the Fröhlich condensate, which are especially revealed by the narrow linewidth. This gives the long-lived coherence and the collective motion of the condensate. Finally, we show that the proteins such as bovine serum albumin and lysozyme are most likely the candidates for observing such collective modes in THz regime by means of Raman or infrared spectroscopy.

Monitoring polariton dynamics in the LHCII photosynthetic antenna in a microcavity by two-photon coincidence counting.

The relaxation dynamics of light-harvesting complex II in an optical cavity is explored theoretically by multidimensional photon coincidence counting spectroscopy. This technique reveals the dynamics in both single (e) and double (f) excitation bands. We study how the polariton dynamics are affected by coupling to photon modes and molecular vibrations described by a realistic spectral density at 77 K. Without the cavity, the e- and f-band energy transfer pathways are not clearly resolved due to the line broadening caused by fast exciton dephasing. The strong coupling to cavity photons results in well-resolved polariton modes. The hybrid nature of polaritons slows down their energy transfer rates.

Utilizing Microcavities To Suppress Third-Order Cascades in Fifth-Order Raman Spectra.

Nonlinear optical signals in the condensed phase are often accompanied by sequences of lower-order processes, known as cascades, which share the same phase matching and power dependence on the incoming fields and are thus hard to distinguish. The suppression of cascading in order to reveal the desired nonlinear signal has been a major challenge in multidimensional Raman spectroscopy, that is, the χ(5) signal being masked by cascading signals given by a product of two χ(3) processes. Because cascading originates from the exchange of a virtual photon between molecules, it can be manipulated by performing the experiment in an optical microcavity which modifies the density of radiation field modes. Using a quantum electrodynamical (QED) treatment, we demonstrate that the χ(3) cascading contributions can be greatly suppressed. By optimizing the cavity size and the incoming pulse directions, we show that up to ∼99.5% suppression of the cascading signal is possible.

Origin of long-lived quantum coherence and excitation dynamics in pigment-protein complexes.

We explore the mechanism for the long-lived quantum coherence by considering the discrete phonon modes: these vibrational modes effectively weaken the exciton-environment interaction, due to the new composite (polaron) formed by excitons and vibrons. This subsequently demonstrates the role of vibrational coherence which greatly contributes to long-lived feature of the excitonic coherence that has been observed in femtosecond experiments. The estimation of the timescale of coherence elongated by vibrational modes is given in an analytical manner. To test the validity of our theory, we study the pigment-protein complex in detail by exploring the energy transfer and coherence dynamics. The ground-state vibrational coherence generated by incoherent radiations is shown to be long-survived and is demonstrated to be significant in promoting the excitation energy transfer. This is attributed to the nonequilibriumness of the system caused by the detailed-balance-breaking, which funnels the downhill migration of excitons.

Vibrational and coherence dynamics of molecules.

We analytically investigate the population and coherence dynamics and relaxations in the vibrational energy transport in molecules. The corresponding two time scales t1 and t2 are explored. Coherence-population entanglement is found to considerably promote the time scale t2 for dephasing and the amplitude of coherence. This is attributed to the suppression of the environment-induced drift force by coherence. Moreover the population imbalance (magnetization) is shown to be significantly amplified with the coherence-population entanglement. Contrary to the previous studies, we exactly elucidate a coherent process by showing t1 < t2. We predict the relaxation of vibrational and orientational dynamics of OH-stretching modes in agreement with the recent experiments, when applied to the water molecules dissolved in D2O. Finally we explore the coherence effect on the heat current at the macroscopic level.

Assistance of molecular vibrations on coherent energy transfer in photosynthesis from the view of a quantum heat engine.

Recently, the quantum nature in the energy transport in solar cells and light-harvesting complexes has attracted much attention as being triggered by the experimental observations. We model the light-harvesting complex (i.e., PEB50 dimer) as a quantum heat engine (QHE) and study the effect of the undamped intramolecule vibrational modes on the coherent energy-transfer process and quantum transport. We find that the exciton-vibration interaction has nontrivial contribution to the promotion of quantum yield as well as transport properties of the QHE at steady state by enhancing the quantum coherence quantified by entanglement entropy. The perfect quantum yield over 90% has been obtained, with the exciton-vibration coupling. We attribute these improvements to the renormalization of the electronic couplings effectively induced by exciton-vibration interaction and the subsequent delocalization of excitons. Finally, we demonstrate that the thermal relaxation and dephasing can help the excitation energy transfer in the PEB50 dimer.