Mapping electronic decoherence pathways in molecules.

Establishing the fundamental chemical principles that govern molecular electronic quantum decoherence has remained an outstanding challenge. Fundamental questions such as how solvent and intramolecular vibrations or chemical functionalization contribute to the decoherence remain unanswered and are beyond the reach of state-of-the-art theoretical and experimental approaches. Here we address this challenge by developing a strategy to isolate electronic decoherence pathways for molecular chromophores immersed in condensed phase environments that enables elucidating how electronic quantum coherence is lost. For this, we first identify resonance Raman spectroscopy as a general experimental method to reconstruct molecular spectral densities with full chemical complexity at room temperature, in solvent, and for fluorescent and non-fluorescent molecules. We then show how to quantitatively capture the decoherence dynamics from the spectral density and identify decoherence pathways by decomposing the overall coherence loss into contributions due to individual molecular vibrations and solvent modes. We illustrate the utility of the strategy by analyzing the electronic decoherence pathways of the DNA base thymine in water. Its electronic coherences decay in [Formula: see text]30 fs. The early-time decoherence is determined by intramolecular vibrations while the overall decay by solvent. Chemical substitution of thymine modulates the decoherence with hydrogen-bond interactions of the thymine ring with water leading to the fastest decoherence. Increasing temperature leads to faster decoherence as it enhances the importance of solvent contributions but leaves the early-time decoherence dynamics intact. The developed strategy opens key opportunities to establish the connection between molecular structure and quantum decoherence as needed to develop chemical strategies to rationally modulate it.

A Stool DNA-Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population: A Multicenter Prospective Randomized Trial.

INTRODUCTION: Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations. METHODS: This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards. RESULTS: Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P < 0.01), and sensitivity was not associated with CRC stage (P = 0.864). DISCUSSION: The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

General framework for quantifying dissipation pathways in open quantum systems. II. Numerical validation and the role of non-Markovianity.

In the previous paper [C. W. Kim and I. Franco, J. Chem. Phys. 160, 214111-1-214111-13 (2024)], we developed a theory called MQME-D, which allows us to decompose the overall energy dissipation process in open quantum system dynamics into contributions by individual components of the bath when the subsystem dynamics is governed by a Markovian quantum master equation (MQME). Here, we contrast the predictions of MQME-D against the numerically exact results obtained by combining hierarchical equations of motion (HEOM) with a recently reported protocol for monitoring the statistics of the bath. Overall, MQME-D accurately captures the contributions of specific bath components to the overall dissipation while greatly reducing the computational cost compared to exact computations using HEOM. The computations show that MQME-D exhibits errors originating from its inherent Markov approximation. We demonstrate that its accuracy can be significantly increased by incorporating non-Markovianity by exploiting time scale separations (TSS) in different components of the bath. Our work demonstrates that MQME-D combined with TSS can be reliably used to understand how energy is dissipated in realistic open quantum system dynamics.

General framework for quantifying dissipation pathways in open quantum systems. I. Theoretical formulation.

We present a general and practical theoretical framework to investigate how energy is dissipated in open quantum system dynamics. This is performed by quantifying the contributions of individual bath components to the overall dissipation of the system. The framework is based on the Nakajima-Zwanzig projection operator technique, which allows us to express the rate of energy dissipation into a specific bath degree of freedom by using traces of operator products. The approach captures system-bath interactions to all orders, but is based on second-order perturbation theory on the off-diagonal subsystem's couplings and a Markovian description of the bath. The usefulness of our theory is demonstrated by applying it to various models of open quantum systems involving harmonic oscillators or spin baths and connecting the outcomes to existing results such as our previously reported formula derived for locally coupled harmonic baths [Kim and Franco, J. Chem. Phys. 154, 084109 (2021)]. We also prove that the dissipation calculated by our theory rigorously satisfies thermodynamic principles such as energy conservation and detailed balance. Overall, the strategy can be used to develop the theory and simulation of dissipation pathways to interpret and engineer the dynamics of open quantum systems.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering.

One of the most challenging tasks in biological science is to understand how a protein folds. In theoretical studies, the hypothesis adopting a funnel-like free-energy landscape has been recognized as a prominent scheme for explaining protein folding in views of both internal energy and conformational heterogeneity of a protein. Despite numerous experimental efforts, however, comprehensively studying protein folding with respect to its global conformational changes in conjunction with the heterogeneity has been elusive. Here we investigate the redox-coupled folding dynamics of equine heart cytochrome c (cyt-c) induced by external electron injection by using time-resolved X-ray solution scattering. A systematic kinetic analysis unveils a kinetic model for its folding with a stretched exponential behavior during the transition toward the folded state. With the aid of the ensemble optimization method combined with molecular dynamics simulations, we found that during the folding the heterogeneously populated ensemble of the unfolded state is converted to a narrowly populated ensemble of folded conformations. These observations obtained from the kinetic and the structural analyses of X-ray scattering data reveal that the folding dynamics of cyt-c accompanies many parallel pathways associated with the heterogeneously populated ensemble of unfolded conformations, resulting in the stretched exponential kinetics at room temperature. This finding provides direct evidence with a view to microscopic protein conformations that the cyt-c folding initiates from a highly heterogeneous unfolded state, passes through still diverse intermediate structures, and reaches structural homogeneity by arriving at the folded state.

Long-term oncologic outcomes of single-incision laparoscopic surgery for colon cancer.

BACKGROUND: Studies find similar perioperative outcomes between single-incision laparoscopic surgery (SILS) and conventional laparoscopic surgery (CLS) for colon cancer. However, few have reported long-term outcomes of SILS versus CLS. We aimed to compare long-term postoperative and oncologic outcomes as well as perioperative outcomes between SILS and CLS for colon cancer. METHODS: A total of 641 consecutive patients who underwent laparoscopic surgery for colon cancer from July 2009 to September 2014 were eligible for the study. Data from 300 of these patients were used for analysis after propensity score-matching (n = 150 per group). Variables associated with short- and long-term outcomes were analyzed. RESULTS: The SILS group had a shorter mean total incision length, less postoperative pain, and a similar mean rate of incisional hernia (2.7% versus 3.3%) compared with the CLS group. The 7-year overall and disease-free survival rates were 92.7% versus 94% (p = 0.673) and 85.3% versus 84.7% (p = 0.688) in the SILS and CLS groups, respectively. CONCLUSIONS: Compared with CLS, SILS for colon cancer appeared to be safe in terms of perioperative and long-term postoperative and oncologic outcomes. The results suggested that SILS is a reasonable treatment option for colon cancer for a selected group of patients.

Laparoscopic repair of perforated peptic ulcer: a multicenter, propensity score matching analysis.

BACKGROUND: Perforated peptic ulcer (PPU) is a common emergency condition requiring surgery using laparoscopy or open repair of the perforated site. The aim of this study was to assess the role of laparoscopic surgery (LS) based on the safety and efficacy for PPU. METHODS: Medical records of the consecutive patients who underwent LS or open surgery (OS) for PPU at five hospitals between January 2009 and December 2019 were retrospectively reviewed. After propensity score matching, short-term perioperative outcomes were compared between LS and OS in selected patients. RESULTS: Among the 598 patients included in the analysis, OS was more frequently performed in patients with worse factors, including older age, a higher American Society of Anesthesiologists score, more alcohol use, longer symptom duration, a higher Boey score, a higher serum C-reactive protein level, a lower serum albumin level, and a larger-diameter perforated site. After propensity score matching, 183 patients were included in each group; variables were well-balanced between-groups. Postoperative complications were not different between groups (24.6% LS group vs. 31.7% OS group, p = 0.131). However, postoperative length of hospital stay (10.03 vs. 12.53 days, respectively, p = 0.003) and postoperative time to liquid intake (3.75 vs. 5.26 days, p < 0.001) were shorter in the LS group. CONCLUSIONS: LS resulted in better functional recovery than OS and can be safely performed for treatment of PPU. When performed by experienced surgeons, LS is an alternative option, even for hemodynamically unstable patients.

Short-term Outcomes of Single-port Versus Multiport Laparoscopic Surgery for Colon Cancer: The SIMPLE Multicenter Randomized Clinical Trial.

OBJECTIVE: To compare short-term perioperative outcomes of single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for colon cancer. SUMMARY BACKGROUND DATA: Although many studies reported short- and long-term outcomes of SPLS for colon cancer compared with MPLS, few have reported results of randomized controlled trials. METHODS: This was a multicenter, prospective, randomized controlled trial with a noninferiority design. It was conducted between August 2011 and June 2017 at 7 sites in Korea. A total of 388 adults (aged 19-85 yrs) with clinical stage I, II, or III adenocarcinoma of the ascending or sigmoid colon were enrolled and randomized. The primary endpoint was 30-day postoperative complication rates. Secondary endpoints were the number of harvested lymph nodes, length of the resection margin, postoperative pain, and time to functional recovery (bowel movement and diet). Patients were followed for 30 days after surgery. RESULTS: Among 388 patients, 359 (92.5%) completed the study (SPLS, n = 179; MPLS, n = 180). The 30-day postoperative complication rate was 10.6% in the SPLS group and 13.9% in the MPLS group (95% confidence interval, -10.05 to 3.05 percentage points; P < 0.0001). Total incision length was shorter in the SPLS group than in the MPLS group (4.6 cm vs 7.2 cm, P < 0.001), whereas the length of the specimen extraction site did not differ (4.4 cm vs 4.6 cm, P = 0.249). There were no significant differences between groups for all secondary endpoints and all other outcomes. CONCLUSIONS: Even though there was no obvious benefit to SPLS over MPLS when performing colectomy for cancer, our data suggest that SPLS is noninferior to MPLS and can be considered an option in selected patients, when performed by experienced surgeons.Trial registration: ClinicalTrials.gov Identifier: NCT01480128.

Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial.

BACKGROUND: Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. METHODS: All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer's protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer's instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). DISCUSSION: This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. TRIAL REGISTRATION: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1 .

Quality of life and patient satisfaction after single- and multiport laparoscopic surgery in colon cancer: a multicentre randomised controlled trial (SIMPLE Trial).

BACKGROUND: The clinical benefits of single-port laparoscopic surgery (SPLS) in patients with colon cancer patients are unclear because only a few studies have reported on the quality of life (QoL) of such patients. This study aimed to compare the QoL and patient satisfaction between SPLS and multiport laparoscopic surgery (MPLS) in colon cancer. METHODS: The multicentre randomised controlled SIngle-port versus MultiPort Laparoscopic surgEry (SIMPLE) trial included patients with colon cancer who underwent radical surgery at seven hospitals in South Korea. We performed a pre-planned secondary analysis of the QoL data of 359 patients from that trial. The QoL was surveyed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 preoperatively and at 1, 3, 6, and 12 months postoperatively. Patient satisfaction was measured with a 5-point questionnaire at these postoperative time points. RESULTS: Overall, 145 and 147 patients were included in the SPLS and MPLS groups, respectively. Most QoL domains were similar between the groups. In the subgroup analysis of patients without adjuvant chemotherapy, patients in the SPLS group presented with significantly better global health status (p = 0.017), fatigue (p = 0.047), and pain (p = 0.005) scores and tended to have improved physical (p = 0.055), emotional (p = 0.064), and social (p = 0.081) functioning, with marginal significance at 1 month postoperatively, compared to those in the MPLS group. Patient satisfaction regarding surgery (p = 0.002) and appearance of the abdominal scar (p = 0.002) was significantly higher with SPLS than with MPLS at 12 months postoperatively. CONCLUSION: Patients who underwent SPLS without adjuvant chemotherapy had better global health status, fatigue status, and pain at 1 month postoperatively; however, these improvements were minimal and temporary. In the near future, the effect of SPLS on postoperative QoL should be confirmed through a randomised controlled trial targeting the QoL in colon cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01480128.

Theory of dissipation pathways in open quantum systems.

We introduce a simple and effective method to decompose the energy dissipation in the dynamics of open quantum systems into contributions due to individual bath components. The method is based on a vibronic extension of the Förster resonance energy transfer theory that enables quantifying the energy dissipated by specific bath degrees of freedom. Its accuracy is determined by benchmarking against mixed quantum-classical simulations that reveal that the method provides a semi-quantitative frequency-dependent decomposition of the overall dissipation. The utility of the method is illustrated by using a model donor-acceptor pair interacting to a thermal harmonic bath with different coupling strengths. The method can be used to identify the key features of a bath that leads to energy dissipation as required to develop a deep understanding of the dynamics of open quantum systems and to engineer environments with desired dissipative features.

Stercoral re-perforation after colostomy takedown: a case report.

BACKGROUND: Stercoral perforation (SP) is a rare surgical condition that is associated with high morbidity and mortality. Most of these patients undergo emergent surgery, including colostomy, and some undergo colostomy takedown after recovery. Stercoral re-perforation after colostomy takedown followed by colostomy for SP has not yet been reported. CASE PRESENTATION: A 79-year-old woman presented with abdominal pain for one day. Abdominal-pelvis computed tomography revealed pneumoperitoneum with diffuse mesenteric fat haziness of the left abdomen. During laparoscopic exploration, a 3-cm-sized perforated site was found at the sigmoid-descending colon, with fecal material and reactive fluid outside the colon. Loop colostomy formation was performed, and a takedown was completed after 3 months. Two years 4 months after the initial procedure, the patient was re-admitted to our hospital with abdominal pain. She underwent a second laparoscopic colostomy formation and was discharged, although the postoperative clinical course was poorer than that after the first surgery. CONCLUSIONS: This case of stercoral re-perforation after colostomy takedown followed by colostomy formation for SP has important clinical implications and can be a reference for physicians. When the first colostomy formation was performed for SP, the decision on performance of a colostomy takedown should be made after carefully considering several factors.

Virtual Reality-Incorporated Horse Riding Simulator to Improve Motor Function and Balance in Children with Cerebral Palsy: A Pilot Study.

The horse riding simulator (HRS) reportedly has a beneficial effect on motor function and balance in children with cerebral palsy (CP). However, by itself, the HRS is not a sufficient source of challenge and motivation for children. To address this issue, we combined the HRS with virtual reality (VR) to promote somatosensory stimulation and motivation. Sixteen children (ages: 5-17 years) with CP and presenting Gross Motor Function Classification System (GMFCS) levels I-IV were enrolled in the study. Using a head-mounted display and controllers, interventions were carried out over 30-min periods (two rides lasting 12 min each, along with a six-min rest period) twice a week over a period of eight weeks (16 sessions in aggregate). The Pediatric Balance Scale (PBS), Gross Motor Function measure (GMFM)-88, and GMFM-66 scores of each participant were measured before and after the interventions. Statistically significant improvements were observed in the PBS, GMFM-66, the total GMFM-88 scores, and those corresponding to dimensions D and E of GMFM-88 after the intervention (p < 0.05). This study demonstrates that VR-incorporated HRS is effective in improving motor function and balance in children with CP and that its incorporation in conventional PT programs could yield beneficial results.

Toward monitoring the dissipative vibrational energy flows in open quantum systems by mixed quantum-classical simulations.

In open quantum system dynamics, rich information about the major energy relaxation channels and corresponding relaxation rates can be elucidated by monitoring the vibrational energy flow among individual bath modes. However, such calculations often become tremendously difficult as the complexity of the subsystem-bath coupling increases. In this paper, we attempt to make this task feasible by using a mixed quantum-classical method, the Poisson-bracket mapping equation with non-Hamiltonian modification (PBME-nH) [H. W. Kim and Y. M. Rhee, J. Chem. Phys. 140, 184106 (2014)]. For a quantum subsystem bilinearly coupled to harmonic bath modes, we derive an expression for the mode energy in terms of the classical positions and momenta of the nuclei, while keeping consistency with the energy of the quantum subsystem. The accuracy of the resulting expression is then benchmarked against a numerically exact method by using relatively simple models. Although our expression predicts a qualitatively correct dissipation rate for a range of situations, cases involving a strong vibronic resonance are quite challenging. This is attributed to the inherent lack of quantum back reaction in PBME-nH, which becomes significant when the subsystem strongly interacts with a small number of bath modes. A rigorous treatment of such an effect will be crucial for developing quantitative simulation methods that can handle generic subsystem-bath coupling.

A tiny retraction of the pars flaccida may conceal an attic cholesteatoma.

OBJECTIVE: The purpose of this study was to evaluate the possibility of attic cholesteatomas concealed within a tiny retraction of the pars flaccida (classification of Tos and Poulsen type I or II attic retraction) in patients with an intact pars tensa of the tympanic membrane. METHODS: The clinical records of patients with a tiny retraction of the pars flaccida and an intact pars tensa of the tympanic membrane who presented to the ear clinic of a tertiary care medical center for the first time between March 2012 and February 2015 were retrospectively reviewed. All patients who had an abnormal pars flaccida of the tympanic membrane were recommended to undergo temporal bone computed tomography (CT) scans. In cases of a soft tissue density lesion within Prussak's space, an exploratory operation was recommended. RESULTS: Among 1320 adult patients, 146 patients (n = 168 ears) who had a tiny attic retraction with a normal pars tensa in unilateral or bilateral ears underwent temporal bone CT scans, and 18 ears had a soft tissue density lesion within Prussak's space. Among the ears with a tiny retraction of the pars flaccida and a normal pars tensa, an attic cholesteatoma was suspected in 10.7% (n = 18 ears) of cases based on the CT scans. After exploratory operations, 2% of patients who underwent CT scans (3 out of 146 patients) and 23% of patients who had a soft tissue density lesion within Prussak's space on CT scans (3 out of 13 operations) had an attic cholesteatoma. CONCLUSION: All attic retractions which are even in cases of Tos type I or II should be examined closely using endoscopy, microscopy, and, if necessary, temporal bone CT scan.

Effect of Underdamped Vibration on Excitation Energy Transfer: Direct Comparison between Two Different Partitioning Schemes.

We study excitation energy transfer (EET) in a model three-site system with a mixed-quantum classical dynamics method, by focusing on the effect of an underdamped vibration. We construct two types of models where the underdamped vibration mode is included either in the quantum subsystem or in the classical bath. We show that the two models yield practically equivalent results despite the different depictions of the vibration. In particular, both models consistently demonstrate accelerations of population relaxation induced by quasi-resonant vibration. This indicates that intricate features of EET dynamics that have been frequently ascribed to the quantal nature of vibrations, such as vibronic mixing, can be successfully reproduced by using physically equivalent but classically described bath modes. The mechanism behind the observed quantum-classical correspondence is proposed. We also systematically examine how the structure of the spectating continuum phonon modes affects the vibronic resonance and observe that phonon modes with different time scales influence the resonance in different manners.

Korean Society of Coloproctology (KSCP) trial of cONsolidation Chemotherapy for Locally advanced mid or low rectal cancer after neoadjUvant concurrent chemoraDiothErapy: a multicenter, randomized controlled trial (KONCLUDE).

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) has been a standard treatment option for locally advanced rectal cancer with improved local control. However, systemic recurrence despite neoadjuvant CRT remained unchanged. The only significant prognostic factor proven to be important was pathologic complete response (pCR) after neoadjuvant CRT. Several efforts have been tried to improve survival of patients who treated with neoadjuvant CRT and to achieve more pCR including adding cytotoxic chemotherapeutic agents, chronologic modification of chemotherapy schedule or adding chemotherapy during the perioperative period. Consolidation chemotherapy is adding several cycles of chemotherapy between neoadjuvant CRT and TME. It could increase pCR rate, subsequently could show better oncologic outcomes. METHODS: Patients with advanced mid or low rectal cancer who received neoadjuvant CRT will be included after screening. They will be randomized and assigned to undergo TME followed by 8 cycles of adjuvant chemotherapy (control arm) or receive 3 cycles of consolidation chemotherapy before TME, and receive 5 cycles of adjuvant chemotherapy (experimental arm). The primary endpoints are pCR and 3-year disease-free survival (DFS), and the secondary endpoints are radiotherapy-related complications, R0 resection rate, tumor response rate, surgery-related morbidity, and peripheral neuropathy at 3 year after the surgery. The authors hypothesize that the experimental arm would show a 15% improvement in pCR (15 to 30%) and in 3-year DFS (65 to 80%), compared with the control arm. The accrual period is 2 years and the follow-up period is 3 years. Based on the superiority design, one-sided log-rank test with α-error of 0.025 and a power of 80% was conducted. Allowing for a drop-out rate of 10%, 358 patients (179 per arm) will need to be recruited. Patients will be followed up at every 3 months for 2 years and then every 6 months for 3 years after the last patient has been randomized. DISCUSSION: KONCLUDE trial aims to investigate whether consolidation chemotherapy shows better pCR and 3-year DFS than adjuvant chemotherapy alone for the patients who received neoadjuvant CRT for locally advanced rectal cancer. This trial is expected to provide evidence to support clear treatment guidelines for patients with locally advanced rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov NCT02843191 (First posted on July 25, 2016).

Excited state energy fluctuations in the Fenna-Matthews-Olson complex from molecular dynamics simulations with interpolated chromophore potentials.

We analyze the environment-induced fluctuation of pigment excitation energies in the Fenna-Matthews-Olson (FMO) complex from various perspectives, by employing an interpolation-based all-atom potential energy model for describing realistic pigment vibrations. We conduct molecular dynamics simulations on a 100 ns timescale, which is an extent that can enclose the effect of static disorder, and demonstrate its timescale separation from fast dynamic disorder. We extract the spectral densities of the complex by considering both the site and the exciton bases. We show that exciton delocalization reduces the effective environmental fluctuation and rationalize this aspect based on a model of fluctuating molecular aggregates. We also obtained the spectral density of the lowest exciton state under low temperature conditions and show that it reasonably well reproduces the experimental result. Finally, by additionally performing non-equilibrium excited state trajectory simulations, we show that the system lies well within the linear response regime after photo-absorption and that the pigments do not visit anharmonic regions of the potential surface to a significant extent. This indicates that methodologies based on harmonic bath models are indeed reasonable approaches for describing the excited state dynamics of the FMO complex.