Energy Barrier and Gaps between Two Excited States in a Dual-Emissive Carborane.

A thorough understanding of the internal conversion process between excited states is important for designing ideal multiple emissive materials. However, it is hard to experimentally measure both the energy barrier and energy gaps between the excited states of a compound. For a long time, it is dubious if what was measured is the energy gap or energy barrier between two excited states. In this paper, we designed 1-(pyren-2'-yl)-9,12-di(p-tolyl)-o-carborane (2), which shows dual emission in solution. Temperature-dependent fluorescence measurements show that the two emission bands in hexane are corresponding to two different excited states. The ratio of the emission bands is controlled by thermodynamics at higher temperatures and by kinetics at lower temperatures. Thus, the energy barrier and energy gaps between the two excited states of 2 can be experimentally estimated.

Inhibition of palmitoyltransferase ZDHHC12 sensitizes ovarian cancer cells to cisplatin through ROS-mediated mechanisms.

Platinum-based therapies have revolutionized the treatment of high-grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells. Analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed significantly elevated ZDHHC12 expression, demonstrating the strongest positive association with ROS pathways among all ZDHHC enzymes. Transcriptomic analysis of independent ovarian cancer datasets and the SNU119 cell model corroborated this association, highlighting a strong link between ZDHHC12 expression and signature pathways involving mitochondrial oxidative metabolism and ROS regulation. Knockdown of ZDHHC12 disrupted this association, leading to increased cellular complexity, ATP levels, mitochondrial activity, and both mitochondrial and cellular ROS. This dysregulation, achieved by the siRNA knockdown of ZDHHC12 or treatment with the general palmitoylation inhibitor 2BP or the fatty acid synthase inhibitor C75, significantly enhanced cisplatin cytotoxicity in 2D and 3D spheroid models of HGSOC through ROS-mediated mechanisms. Markedly, ZDHHC12 inhibition significantly augmented the anti-tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites-derived organoid line of platinum-resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum-based chemotherapy.

Lung-PNet: An Automated Deep Learning Model for the Diagnosis of Invasive Adenocarcinoma in Pure Ground-Glass Nodules on Chest CT.

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

In vitro and in vivo evaluation of immune response of poly(lactic acid) nanoparticles with different end groups.

Poly(lactic acid) (PLA) has excellent properties of biodegradability and biocompatibility, which is a US Food and Drug Administration (FDA) approved biopolymer for the preparation of safe and effective vaccines, drugs, and gene delivery systems. However, there still exists a great problem whether and how the end group affects the immune response of PLA vaccines. Therefore, the aim of this study was to evaluate the in vitro and in vivo of immune response of PLA nanoparticles (NPs) with carboxyl (COOH) and ester (COOR) end groups. In vitro experiments suggested COOH NPs could promote the higher phagocytosis and activation of bone marrow dendritic cells (BMDCs) with a lower cytotoxicity. In vivo experiments showed that COOR NPs and COOH NPs could strongly elicit IgG, IgG1, and IgG2a responses both in the short and long-terms. However, the highest T cell and B cell activation, and central memory T cells response was induced by COOH NPs. In addition, the COOH NPs could significantly enhance splenocytes proliferation and cytokines secretion. Thus, the PLA with the COOH end group shows greater potential as efficient carrier materials of NPs for enhancing cellular and humoral immune responses.

The sustained attention characteristics of flight crews on exempt and non-exempt flights.

We analyzed the characteristics of sustained attention changes in flight crews during exempt and non-exempt flights. Fourteen pilots (aged 30-43 y) participated in this study, with seven involved in each flight type, all of which were intercontinental (China to North America). Pilots completed continuous performance tests (CPT) at the required flight stages without compromising safety while on duty. No significant differences in sleep and sustained attention emerged between the exempt and non-exempt flight crews. Pilots' fatigue was highest in the early morning hours. Their general stability of efficiency increased during the day and decreased at night. Non-exempt flight crews appeared to sacrifice reaction rate to improve accuracy. Exempt crews appeared to increase their test proficiency. The task stability time of the non-exempt flight crews was better than that of the exempt ones. Short-term stability was better for exempt inbound flights rather than for outbound ones. Pilots were more prone to error runs as their total time awake increased, especially on non-exempt flights. The addition of crew members to exempt flights, allowance for more in-flight rest shifts, and over-stop rest on non-exempt flights may alleviate pilot fatigue and preserve alertness.

Safety and feasibility of preferential manual bronchoplasty in 2-3 cm single-port video-assisted thoracoscopic lobectomy.

BACKGROUND: This retrospective study aimed to compare preferential manual bronchoplasty (PMB) and mechanical stapler closure (MSC) of the bronchial stump after 2-3 cm single-port (SP) video-assisted thoracoscopic surgery (VATS) lobectomy in patients with pathological T1 (pT1) stage lung cancer. METHODS: Between January 2019 and March 2022, patients with pulmonary neoplasms who underwent 2-3 cm SP VATS lobectomy were retrospectively screened. After propensity-matched analysis, we compared perioperative outcomes and analyzed the safety and feasibility of PMB and MSC of the bronchial stump while performing VATS lobectomy. RESULTS: In this study, 280 and 832 patients were enrolled in the PMB and MSC groups, respectively. Propensity score matching produced 280 pairs. The operation time was shorter in the PMB group, whereas the average number of lymph nodes dissected was higher in the PMB group. The conversion rate was significantly lower in the PMB group. The following were similar between the PMB and MSC groups, respectively: average blood loss volume, postoperative hospital stay, and chest tube removal time. Postoperatively, the incidence of atelectasis was significantly higher in the MSC group. As per subgroup analyses, PMB was associated with a shorter operation time in left and right upper lobectomies. Particularly in left upper lobectomy, PMB had more lymph node dissections and less conversion to open and postoperative atelectasis. CONCLUSIONS: In comparison with MSC of the bronchial stump, PMB showed better safety and feasibility in 2-3 cm SP VATS left and right superior lobectomies in patients with pT1 stage lung cancer.

Versatile gold-silver-PB nanojujubes for multi-modal detection and photo-responsive elimination against bacteria.

Bacterial infections have become a serious threat to global public health. Nanomaterials have shown promise in the development of bacterial biosensing and antibiotic-free antibacterial modalities, but single-component materials are often less functional and difficult to achieve dual bacterial detection and killing. Herein, we report a novel strategy based on the effective integration of multi-modal bacterial detection and elimination, by constructing the versatile gold-silver-Prussian blue nanojujubes (GSP NJs) via a facile template etching method. Such incorporation of multi-components involves the utilization of cores of gold nanobipyramids with strong surface-enhanced Raman scattering (SERS) activity, the shells of Prussian blue as both an efficient bio-silent SERS label and an active peroxidase-mimic, and functionalization of polyvinyl pyrrolidone and vancomycin, respectively endowing them with good colloidal dispersibility and specificity against S. aureus. The GSP NJs show operational convenience in the SERS detection and excellent peroxidase-like activity for the sensitive colorimetric detection. Meanwhile, they exhibit robust near-infrared photothermal/photodynamic effects, and the photo-promoted Ag+ ions release, ultimately achieving a high antibacterial efficiency over 99.9% in 5 min. The NJs can also effectively eliminate complex biofilms. The work provides new insights into the design of multifunctional core-shell nanostructures for the integrated bacterial detection and therapy.

High-quality super-resolution mapping using spatial deep learning.

Super-resolution mapping (SRM) is a critical technology in remote sensing. Recently, several deep learning models have been developed for SRM. Most of these models, however, only use a single stream to process remote sensing images and mainly focus on capturing spectral features. This can undermine the quality of the resulting maps. To address this issue, we propose a soft information-constrained network (SCNet) for SRM that leverages spatial transition features represented by soft information as a spatial prior. Our network incorporates a separate branch to process prior spatial features for feature enhancement. SCNet can extract multi-level feature representations simultaneously from both remote sensing images and prior soft information and hierarchically incorporate features from soft information into image features. Experimental results on three datasets demonstrate that SCNet generates more complete spatial details in complex areas, providing an effective means for producing high-quality and high-resolution mapping products from remote sensing images.

Comparison between radical surgery and chemoradiotherapy in patients with cervical esophageal cancer: a propensity score matched analysis.

BACKGROUND: The prognostic value of radical surgery (RS) and chemoradiotherapy (CRT) for cervical esophageal cancer (CEC) was estimated using the Surveillance, Epidemiology and End Results (SEER) database after 1:1 propensity score matching (PSM). METHODS: This retrospective study used SEER data of CEC patients between 2004 and 2015. The prognostic effects on cancer-specific survival (CSS) were evaluated using multivariate cox regression analysis following radical surgery or CRT before and after PSM. The subgroup analysis of CSS is carried out according to T stages. RESULTS: A total of 440 patients met the eligibility criteria. Three hundred and fifty-six(80.9%)patients underwent chemoradiotherapy, and eighty-four (19.1%) patients underwent radical surgery. There were significant differences between patients of radical surgery and CRT groups with regard to the tumor grade, histology and N stage. After PSM, 80 matched pairs (A total of 160 patients) were selected. Multivariable cox regression analysis revealed no difference in the CSS of patients that underwent either radical surgery or CRT before [hazard ratio (HR): 0.955, 95% CI: 0.704-1.295, P = 0.766] and after PSM (HR: 0.767, 95% CI: 0.512-1.149, P = 0.198). Subgroup analysis revealed no significant difference in CSS between patients with radical surgery and CRT groups for all T stages (T 1-4, all P > 0.05). CONCLUSIONS: This analysis revealed that the prognostic outcomes in patients with cervical esophageal cancer were comparable between radical surgery and CRT.

Visualized concentration sensors based on fluorescence indication in a dye-doped polymer microwire.

We demonstrate visualized microwire sensors based on fluorescence indication for detecting the concentrations of the aqueous solutions. The single Rhodamine (RhB) doped polymer microwires (PMWs) which are excited by the waveguiding excitation method are used as the sensory area. According to the fluorescent microimages of the PMWs, stable periodic oscillations could be observed in the RhB-doped PMWs. The fluorescent period which is dependent on the concentration is further analyzed by image processing and information extraction algorithms. Corresponding to a 1.0% change, the period length change of the visualized sensor reaches ∼380 nm, ∼270 nm, and ∼300 nm in NaCl, KCl, and sucrose solutions, respectively. The dection limits of the three solutions are estimated to be around 1.5 × 10-4%. The dye-doped PMW sensors by fluorescence indication and image analysis proposed here realize the direct visualized detection in concentration sensing, making it possible to avoid the challenges of stability and weak signal detection and offer a potentially stable and cost-effective approach for micro/nanofiber sensor application.

Reconstruction of the hourly fine-resolution apparent temperature (Humidex) with the aerodynamic parameters.

Apparent temperature is the preferred measure of hotness or coldness expressed to depict the human sense. Spatially explicit measurement of the hourly apparent temperature is essential for capturing the threats to bioclimatic comfort and preventing potential mortality/morbidity risk from heat or cold. However, existing apparent temperature products only provide daily observations at the spatial resolution of several dozen kilometers, resulting in some substantial underestimations for some life-threatening thermal stresses highly localized in space and time. Furthermore, some data-driven models lack mechanical constraints on the turbulent exchange between the surface and the atmosphere, making some unsatisfactory accuracy. Here, we propose Humidex reconstruction model incorporating atmospheric dynamics theory and aerodynamic parameters (i.e., heat and momentum roughness lengths for natural surfaces and three urban canopy geometry parameters for artificial surfaces), capable of developing an hourly dataset at fine-grained spatial resolution (0.01° × 0.01°). In this study, a total of 2952 h in four seasons were selected to test the seasonal performance of this model, taking the Yangtze River Delta as an example. The results show that the Humidex products from this model generally outperform the existing comparable products, with the hourly population root mean square error (RMSE) ranging from 1 to 2 °C in winter and autumn and 2-3 °C in spring and summer. Moreover, the constraint of aerodynamic parameters can reduce RMSE with a significant margin for each season, up to 2 °C, especially in areas with dense woodlands or buildings. In addition, the results demonstrate the excellent performance of this model in capturing short-lived thermal health threats, which are easily overlooked when observed data only provides a daily variation. This indicates that the model can allow researchers and practitioners investigate the fine-grained spatial and temporal evolution of thermal stress and its impact on public health, tourism, learning, and work performance.

Uniportal VATS lobectomy versus thoracotomy lobectomy for NSCLC larger than 5 cm: A propensity score-matched study.

BACKGROUND: The performance of uniportal VATS lobectomy (uVATS) for non-small cell lung cancer (NSCLC) larger than 5 cm is uncertain due to a lack of evidence. Here, we present a retrospective, propensity-score matched cohort study to evaluate the safety and effectiveness of uVATS for patients with locally advanced NSCLC. METHODS: The data of patients with NSCLC larger than 5 cm diameter who underwent curative resection via uVATS or thoracotomy lobectomy between January 2015 and December 2020 was collected. Propensity-score matching was utilized to control the observable biases. RESULTS: Seventy-two patients underwent uVATS lobectomy, while 38 received thoracotomy lobectomy. No conversion to open surgery or perioperative death occurred. uVATS lobectomy achieved similar total lymph node dissection counts compared to thoracotomy and even yielded a higher amount of lymph node dissection in pTNM stage II patients. The long-term overall and recurrence-free survival rates were also similar between the two groups. Results from the propensity-score matching generated cohort agreed with those from the full cohort. CONCLUSIONS: uVATS lobectomy is feasible and effective for curative lobectomy for NSCLC larger than 5 cm in diameter in selected patients. Further validations from well-designed prospective studies are required for uVATS lobectomy for patients with locally advanced NSCLC.

Mo@ZIF-8 nanozyme preparation and its antibacterial property evaluation.

Types of nanozymes can produce free radicals and/or reactive oxygen species (ROS) to serve as broad spectrum antibacterial materials. Developing nanozyme-based antibacterial materials with good biocompatibility exhibits promising application prospects. In this study, we doped Mo to ZIF-8 (both components have good biocompatibility) to prepare a new nanozyme, Mo@ZIF-8, which can produce hydroxyl radicals (•OH) triggered by a low dosage of hydrogen peroxide (H2O2), exhibiting effective antibacterial capability against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). This work provides a reference for the design of antibacterial nanozymes with good biocompatibility.

Left versus right approach for middle and lower esophageal squamous cell carcinoma: A propensity score-matched study.

Background: Despite superior short-term outcomes, there is considerable debate about the oncological efficacy of the left approach esophagectomy for middle and lower squamous esophageal carcinoma (ESCC). A propensity score-matched retrospective study was conducted to evaluate the left approach's short- and long-term effects. Methods: We recorded data from patients with ESCC who underwent curative resection via the left or right approach between January 2010 and December 2015. Propensity score matching (PSM) was performed, and maximally selected rank statistics (MSRS) were utilized to determine the appropriate number of lymph nodes to resect during esophagectomy. Results: One hundred and forty-eight ESCC patients underwent esophagectomy via the right approach, and 108 underwent the left approach esophagectomy. After PSM, the left approach esophagectomy showed statistically significant superiority in operative time and time to oral intake, and there was a trend toward a shorter length of hospital stay. Fewer cervical, upper thoracic, and recurrent laryngeal nerve lymph nodes were harvested via the left approach than the right approach; the total number of lymph nodes harvested via the left and right approaches was similar. Similar long-term survival outcomes were achieved. MSRS suggested that at least 25 lymph nodes are needed to be resected during esophagectomy to improve survival in N0 patients. Conclusions: The left approach esophagectomy might facilitate postoperative recovery in patients with middle and lower ESCC. With adequate lymphadenectomy, the left approach esophagectomy might achieve similar long-term outcomes for middle and lower ESCC patients.

Effects of total sleep deprivation on execution lapses during vigilance tasks.

Total sleep deprivation (TSD) results in reduced efficiency of cognitive resources. Moreover, when the available cognitive resources are less than required, individuals exhibit lapses in responsiveness. Accordingly, this study explored the effects of TSD on executive function and the characteristics of execution lapses. Functional near-infrared spectroscopy was used to monitor the prefrontal cortex's functional connections in resting and tasking states for various sleep deprivation durations. Data from participants' attentional performance test and self-reported fatigue were collected over 30 hours of wakefulness. Task performance was compared based on time of day, time on task, and reaction time. The results show that participants' arousal level significantly decreased post 14 hours (P < .05), while sleepiness increased. The prefrontal cortex connection and attentional performance dropped at the Window of Circadian Low (3:00 ~ 6:00). The number of execution lapses was higher during the initiation, inhibition, and fatigue phases and rose markedly post 14 hours of wakefulness. We conclude that maintaining better inhibition control requires a reasonable extension of the reaction time. Moreover, subjective perception is significantly correlated with task performance and right prefrontal connection strength. This study presents the scientific evidence for measures to address consistently long working hours and disrupted circadian rhythms.

Plasmon-enhanced photothermal properties of Au@Ti3C2Tx nanosheets for antibacterial applications.

Antibiotic-resistant bacterial strains have become an ever-increasing public concern due to their significant threats to health safety. Nanomaterial-based photothermal treatment has shown potential in antibacterial applications, but many nanomaterials exhibited limited photothermal activity that may compromise their antibacterial efficacies. Herein, we report a novel strategy based on efficient photothermal ablation and physical contact over a supported nanostructure by loading Au nanoparticles (NPs) on few-layered Ti3C2Tx nanosheets (NSs) for antibacterial treatment. Ti3C2Tx NSs are delaminated via etching and sonication, and act as a reductant for the in situ reduction of HAuCl4·xH2O, producing "naked" Au NPs without any stabilizers. Meanwhile, by adjusting the Au/Ti ratio, the size and loading of the Au NPs are finely regulated, thereby providing an ideal model of a surface-clean Au@Ti3C2Tx heterostructure for probing the composition-performance relationship. Upon irradiation with visible light, it exhibits synergistically enhanced photothermal conversion efficiency and stability, owing to the localized surface plasmonic resonance effect of Au NP and Au-NS interactions. Moreover, under visible light irradiation for 10 min, the Au@ Ti3C2Tx heterostructure exhibits excellent antibacterial activity for Gram-positive S. aureus and Gram-negative E. coli, and kills over 99% bacteria with a low dose of the nanomedicine suspension (50 µg mL-1). The work demonstrates that the incorporation of transition metal carbides with plasmonic metal nanostructures is an effective strategy to enhance the photothermal antibacterial efficacy.

Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma.

PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency of these occurrences. Homologous recombination deficiency (HRD) was used to induce particular DNA aberration profiles and related transcriptome alterations. Their presence can identify whether an HR deficiency is present or absent in a particular tumor sample, even without observed HR gene changes. From whole-exome sequencing data in lung adenocarcinoma obtained from TCGA, we obtained several mutational signatures associated with HRD and determined that these HRD-associated mutational signatures are related to genomic installability. We then constructed a prediction model, which found that 11 genes associated with HRD scores could be used as predictors of survival outcomes in LUAD patients. These genes are related to PI3K-Akt, T cell receptors, and the Chemokine pathway. Other GEO datasets validated the survival prediction, which was independent of the PD1/PDL1 treatment. Collectively, our study provides transcriptome biomarkers of lung adenocarcinoma complementary to the HRD score and introduces a novel method of identifying prognostic biomarkers of immunotherapy.

Fatigue during Long-Haul Flights of Different Crew Compositions under Exemption from Layover and Flight Time during COVID-19.

Pilot fatigue and alertness are critical for civil aviation safety. Intercontinental pilots are more prone to fatigue and sleepiness due to jet lag, prolonged workdays, and disrupted rhythms. The Civil Aviation Administration of China excused enlarged flight crews from mandatory layovers and reimposed flight duration restrictions during COVID-19. This study investigates the sleep quality and attentional performance of pilots on intercontinental flights. The fifteen pilots who performed intercontinental flights in different crew compositions wore a body movement recorder, which has been proven to accurately estimate sleep duration and sleep efficiency. The crew's attentional performance and self-report were monitored at specified flight phases. In conclusion, the larger crews slept longer and more efficiently on board, particularly pilots in charge of takeoff and landing responsibilities. Crews on four-pilot layover flights were more alert before the takeoff of the inbound flights than exempt flights, but there was no significant difference towards the end of the mission. The new long-haul flight organization did not result in fatigue or decreased attention in the pilots. This study expands on the research by validating a novel intercontinental flight operation model under the COVID-19 scenario and highlighting critical spots for future fatigue management in various crew compositions.

[Study on homeostasis and circadian rhythm of attention performance of different chronotypes in sleep deprivation].

Difference of chronotypes makes influence to cognitive performance of individuals in routine duties. In this paper, 55 subjects with different chronotypes were subjected to continuous sleep deprivation for 30 h by using the constant routine protocol, during which core body temperature was measured continuously, and subjective sleepiness self-rating and the performance of selective attention were measured hourly. The results showed that the phase difference of core body temperature has no significant difference, yet the amplitude and term difference among the three chronotypes are significant. There was an advance in phase between subjective sleepiness self-rating and core body temperature, and the self-rating sleepiness of evening type came the latest, and the self-rating sleepiness of morning type dissipated the fastest. The response time of selective attention showed a 2 h phase delay with subjective sleepiness self-rating. And the analysis of core body temperature showed that the later the chronotype was, the greater the phase delay was. The correct rate of selective attention of different chronotypes were inconsistent with delay of subjective sleepiness self-rating and core body temperature. We provide reference for industry, aviation, military, medical and other fields to make a more scientific scheduling/ shifting based on cognitive performance characteristics of different chronotypes.