Core Clinical Data Elements for Cancer Genomic Repositories: A Multi-stakeholder Consensus.

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

Controlling laser-dressed resonance line shape using attosecond extreme-ultraviolet pulse with a spectral minimum.

High-harmonic generation from a gas target exhibits sharp spectral features and rapid phase variation near the Cooper minimum. By applying spectral filtering, shaped isolated attosecond pulses can be generated where the pulse is split into two in the time domain. Using such shaped extreme-ultraviolet (XUV) pulses, we theoretically study attosecond transient absorption (ATA) spectra of helium [Formula: see text] autoionizing state which is resonantly coupled to the [Formula: see text] dark state by a time-delayed infrared laser. Our simulations show that the asymmetric [Formula: see text] Fano line shape can be readily tuned into symmetric Lorentzian within the time delay of a few tens of attoseconds. Such efficient control is due to the destructive interference in the generation of the [Formula: see text] state when it is excited by a strongly shaped XUV pulse. This is to be compared to prior experiments where tuning the line shape of a Fano resonance would take tens of femtoseconds. We also show that the predicted ATA spectral line shape can be observed experimentally after propagation in a gas medium. Our results suggest that strongly shaped attosecond XUV pulses offer the opportunity for controlling and probing fine features of narrow resonances on the few-ten attoseconds timescale.

Discovery of a pathway for terminal-alkyne amino acid biosynthesis.

Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1-4. However, biologically 'rare' functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15-17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(I)-catalysed azide-alkyne cycloaddition 'click' reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that L-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.

PigmentHunter: A point-and-click application for automated chlorophyll-protein simulations.

Chlorophyll proteins (CPs) are the workhorses of biological photosynthesis, working together to absorb solar energy, transfer it to chemically active reaction centers, and control the charge-separation process that drives its storage as chemical energy. Yet predicting CP optical and electronic properties remains a serious challenge, driven by the computational difficulty of treating large, electronically coupled molecular pigments embedded in a dynamically structured protein environment. To address this challenge, we introduce here an analysis tool called PigmentHunter, which automates the process of preparing CP structures for molecular dynamics (MD), running short MD simulations on the nanoHUB.org science gateway, and then using electrostatic and steric analysis routines to predict optical absorption, fluorescence, and circular dichroism spectra within a Frenkel exciton model. Inter-pigment couplings are evaluated using point-dipole or transition-charge coupling models, while site energies can be estimated using both electrostatic and ring-deformation approaches. The package is built in a Jupyter Notebook environment, with a point-and-click interface that can be used either to manually prepare individual structures or to batch-process many structures at once. We illustrate PigmentHunter's capabilities with example simulations on spectral line shapes in the light harvesting 2 complex, site energies in the Fenna-Matthews-Olson protein, and ring deformation in photosystems I and II.

TFCP2L1, a potential differentiation regulator, predicts favorable prognosis and dampens thyroid cancer progression.

PURPOSE: Thyroid cancer has an overwhelming incidence in the population. Thus, there is an urgent need to understand the underlying mechanism of its occurrence and development, which may provide new insights into therapeutic strategies. The role and mechanism of TFCP2L1 in regulating the progression of thyroid cancer remains unclear. METHODS: Public databases and clinical samples were used to detect the expression of TFCP2L1 in cancer and non-cancer tissues. Kaplan-Meier and Cox regression analyses were used to compare the differences in survival probability of the TFCP2L1 highly expressing group and the TFCP2L1 lowly expressing group. Functional assays were used to evaluate the biological effect of TFCP2L1 on thyroid cancer cells. RNA sequencing and enrichment analyses were used to find out pathways that were activated or inactivated by TFCP2L1. RESULTS: We demonstrated that TFCP2L1 was significantly downregulated in thyroid cancer. Decreased expression of TFCP2L1 was associated with malignant clinicopathological characteristics. Kaplan-Meier and Cox regression analyses indicated that thyroid tumor patients with low TFCP2L1 expression presented shorter disease-free interval and progression-free interval. Additionally, TFCP2L1 expression was positively correlated with thyroid differentiation degree. Overexpression of TFCP2L1 in thyroid cancer cells inhibited cell growth and motility in vitro, and tumorigenicity and metastasis in vivo. Mechanistically, the NF-κB signaling pathway was found inactivated by overexpressing TFCP2L1. CONCLUSION: Our results suggest that TFCP2L1 is a tumor suppressor and potential differentiation regulator, and might be a potential therapeutic target in thyroid cancer.

Impact of Social Determinants of Health on Outcomes for Patients with Adult Congenital Heart Disease.

PURPOSE OF REVIEW: The study of adults with congenital heart disease (ACHD) is a rapidly growing field; however, more research is needed on the disparities affecting outcomes. With advances in medicine, a high percentage of patients with congenital heart disease (CHD) are advancing to adulthood, leading to an increase in the number of ACHD. This creates a pressing need to evaluate the factors, specifically the social determinants of health (SDOH) contributing to the outcomes for ACHD. RECENT FINDINGS: A myriad of factors, including, but not limited to, race, education, and socioeconomic status, have been shown to affect ACHD outcomes. Existing data from hospitalizations, mortality and morbidity, advanced care planning, patient and physician awareness, financial factors, and education alongside race and socioeconomic status present differences in ACHD outcomes. With SDOH having a significant impact on ACHD subspecialty care outcomes, ACHD centers need to be constantly adapting and innovating, incorporating SDOH into patient management, and providing additional healthcare resources to manage the care of ACHD.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Swallowing performance in older adults: Associated cognitive, neuroanatomical and demographic factors.

BACKGROUND: Swallowing problems are frequently seen in older adults, especially in individuals with cognitive impairment (CI). The brain plays a crucial role in both cognition and swallowing. Using magnetic resonance imaging (MRI) data, researchers identified regions associated with swallowing. However, it is not yet fully elucidated which factors influence the swallowing performance in older adults. OBJECTIVES: The current study investigated which factors, such as cognitive function, neuroanatomical factors (e.g., the cortical thickness and volume of specific brain regions) and demographical factors are associated with swallowing performance in older adults. Secondly, it was investigated whether there is a difference in neuroanatomical factors between individuals with and without CI. RESEARCH DESIGN AND METHODS: In total, 15 CI individuals (73.1 ± 9.1 years; 46.7% male) and 48 non-CI controls (69.0 ± 5.1 years; 29.2% male) were included. The repetitive saliva swallowing test (RSST) was performed, and an MRI scan was acquired from the participants. RESULTS: Multivariate linear regression analysis showed that the cortical thickness of the right supramarginal gyrus and female gender were positively associated, and a higher age was negatively associated with the RSST in older adults (p < .05). CI was not significantly associated with swallowing performance. Furthermore, it was found that the cortical volume differs more frequently between CI and non-CI than the cortical thickness. CONCLUSION: A thinner cortex of the right supramarginal gyrus and being an older female are associated with poorer swallowing performance. Secondly, cortical volume was more often found to differ between CI and non-CI individuals than cortical thickness.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

Enabling ultra-low-voltage switching in BaTiO3.

Single crystals of BaTiO3 exhibit small switching fields and energies, but thin-film performance is considerably worse, thus precluding their use in next-generation devices. Here, we demonstrate high-quality BaTiO3 thin films with nearly bulk-like properties. Thickness scaling provides access to the coercive voltages (<100 mV) and fields (<10 kV cm-1) required for future applications and results in a switching energy of <2 J cm-3 (corresponding to <2 aJ per bit in a 10 × 10 × 10 nm3 device). While reduction in film thickness reduces coercive voltage, it does so at the expense of remanent polarization. Depolarization fields impact polar state stability in thicker films but fortunately suppress the coercive field, thus driving a deviation from Janovec-Kay-Dunn scaling and enabling a constant coercive field for films <150 nm in thickness. Switching studies reveal fast speeds (switching times of ~2 ns for 25-nm-thick films with 5-µm-diameter capacitors) and a pathway to subnanosecond switching. Finally, integration of BaTiO3 thin films onto silicon substrates is shown. We also discuss what remains to be demonstrated to enable the use of these materials for next-generation devices.

Role of the Porras factor in phase matching of high-order harmonic generation driven by focused few-cycle laser pulses.

We investigate the role of the Porras factor (or laser focusing effect) on the macroscopic high-order harmonic generation (HHG) driven by a focused broadband few-cycle laser beam. By employing a non-adiabatic phase-matching analysis method, we reveal that phase mismatch due to the induced-dipole phase varies with the Porras factor, which is dominant in phase matching at low gas pressure. We also find that in a strongly ionized medium when gas pressure is high, the nonlinear propagation is dominated by a plasma effect such that the focusing effect is mitigated, resulting in similar poor phase matching of HHG regardless of the Porras factor. Our results are expected to assist experimentalists identifying optimal conditions for HHG using ultrashort laser pulses.

Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Blazar spectral variability as explained by a twisted inhomogeneous jet.

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

Differentiation between normal and abnormal kidneys using 99mTc-DMSA SPECT with deep learning in paediatric patients.

AIM: To investigate the feasibility of using deep learning (DL) to differentiate normal from abnormal (or scarred) kidneys using technetium-99m dimercaptosuccinic acid (99mTc-DMSA) single-photon-emission computed tomography (SPECT) in paediatric patients. MATERIAL AND METHODS: Three hundred and one 99mTc-DMSA renal SPECT examinations were reviewed retrospectively. The 301 patients were split randomly into 261, 20, and 20 for training, validation, and testing data, respectively. The DL model was trained using three-dimensional (3D) SPECT images, two-dimensional (2D) maximum intensity projections (MIPs), and 2.5-dimensional (2.5D) MIPs (i.e., transverse, sagittal, and coronal views). Each DL model was trained to determine renal SPECT images into either normal or abnormal. Consensus reading results by two nuclear medicine physicians served as the reference standard. RESULTS: The DL model trained by 2.5D MIPs outperformed that trained by either 3D SPECT images or 2D MIPs. The accuracy, sensitivity, and specificity of the 2.5D model for the differentiation between normal and abnormal kidneys were 92.5%, 90% and 95%, respectively. CONCLUSION: The experimental results suggest that DL has the potential to differentiate normal from abnormal kidneys in children using 99mTc-DMSA SPECT imaging.

Novel Electronic Health Records-Based Consultation Workflow Improves Time to Operating Room for Vascular Surgery Patients in an Acute Setting.

BACKGROUND: Inefficient clinical workflows can have downstream effects of increased costs, poor resource utilization, and worse patient outcomes. The surgical consultation process can be complex with unclear communication, potentially delaying care for patients requiring time-sensitive intervention in an acute setting. A novel electronic health records (EHR)-based workflow was implemented to improve the consultation process. After implementation, we assessed the impact of this initiative in patients requiring vascular surgery consultation. METHODS: An EHR-driven consultation workflow was implemented at a single institution, standardizing the process across all consulting services. This order-initiated workflow automated notification to clinicians of consult requests, communication of patient data, patient addition to consultants' lists, and tracking consult completion. Preimplementation (1/1/2020-1/31/2022) and postimplementation (2/1/2022-12/4/2022) vascular surgery consultation cohorts were compared to evaluate the impact of this initiative on timeliness of care. RESULTS: There were 554 inpatient vascular surgery consultations (255 preimplementation and 299 postimplementation); 45 and 76 consults required surgery before and after implementation, respectively. The novel workflow resulted in placement of a consult note 32 min faster than preimplementation (preimplementation: 462 min, postimplementation: 430 min, P = 0.001) for all vascular surgery consults. Furthermore, vascular surgery patients with ASA class III or IV status requiring an urgent or emergent operation were transported to the operating room 63.3% faster after implementation of the workflow (preimplementation: 284 min, postimplementation: 180 min, P = 0.02). There were no differences in procedure duration, postoperative disposition, or intraoperative complication rates. CONCLUSIONS: We implemented a novel workflow utilizing the EHR to standardize and automate the consultation process in the acute inpatient setting. This institutional initiative significantly improved timeliness of care for vascular surgery patients, including decreased time to operation. Innovations such as this can be further disseminated across shared EHR platforms across institutions, representing a powerful tool to increase the value of care in vascular surgery and healthcare overall.

Lychnophora pinaster in endangered campos rupestres: phenolic compounds and population ecogeography.

Lychnophora pinaster, known as arnica-mineira, is endemic to campos rupestres, at risk of extinction. The present study aimed to characterize the ecogeography and phenolic constituents of 11 L. pinaster populations collected in the mesoregions North, Jequitinhonha, Metropolitan of Belo Horizonte and Campos das Vertentes in the state of Minas Gerais, Brazil. Phenolic constituents were identified and quantified by Ultra-high performance liquid chromatography- mass spectrometry. Lychnophora pinaster occurs in sites at high altitude (700 and 1498 m), annual rainfall of up to 1455 m, soils with low fertility and predominantly loamy texture. Therefore, it can be considered tolerant to acidic soils, with low availability of nutrient. The most abundant substances in all populations were vitexin (18 - 1345 ng/g) and chlorogenic acid (60 - 767 ng/g). The 11 populations formed four groups in relation to the phenolic constituents, with group 1 consisting of the populations of the North Mesoregion (GM, OD) and Jetiquinhonha (DIMa), group 2, the Metropolitan of Belo Horizonte (SRM, NLSC, SM, RPS, CTRA), group 3, the North Mesoregion (ODMa and DI), and group 4, the Campos das Vertentes (CC). Among the populations, only those from the Metropolitan of Belo Horizonte showed correlation of soil properties with phenolic constituents.

Reallocating desk workers' sitting time to standing or stepping: associations with work performance.

BACKGROUND: Studies have suggested that sitting time at work may lead to underperformance but they may underestimate the benefits to desk workers' performance of reducing occupational sitting time without considering the relative effects of the specific activities replaced. AIMS: To estimate differences in work performance (presenteeism, absenteeism and engagement) when occupational sitting time is reallocated to standing/stepping in desk workers. METHODS: Data for middle-aged desk workers were from a Japan-wide online survey (n = 2228). Self-report proportion of occupational sitting and standing/stepping, work hours and work performance indicators, including absolute (ratings relating only to self) and relative (ratings of self, compared to others) presenteeism and absenteeism, and dimensions of work engagement, were collected. Partition and isotemporal substitution models were used to investigate the associations of occupational sitting and standing/stepping time with work performance, including their reallocation effects. RESULTS: In partition models, longer occupational sitting time was associated with a lower absolute presenteeism score (i.e. less productivity), lower absolute absenteeism (i.e. longer-than-expected work hours), and lower engagement. Longer occupational standing/stepping time was associated with lower absolute absenteeism and more engagement. Isotemporal substitution models showed that each hour of occupational sitting reallocated to standing/stepping was favourably associated with overall work engagement (B = 0.087; 95% confidence interval 0.051, 0.122) and its dimensions (B ranged from 0.078 to 0.092), but was not associated with presenteeism or absenteeism. CONCLUSIONS: These findings suggest that management support and practical initiatives to encourage desk workers to replace portions of their sitting time with standing/stepping may contribute to enhanced work engagement.

The applicability of the "surprise question" as a prognostic tool in patients with severe chronic comorbidities in a university teaching outpatient setting.

BACKGROUND: Life expectancy in recent decades has increased the prevalence of chronic diseases in the population, requiring an approach to new health topics, such as discussions on quality of life and expectations about death and dying. The concept of advance directives (ADs) gives individuals the opportunity to make known their decisions about the treatments they would like to receive at the end of life. Despite the recognition of relevance in clinical practice, the applicability of the concept presents challenges, including establishing the appropriate prognosis for each patient and the ideal time to approach the patient. Some prognostic tools were developed, such as the surprise question (SQ): "Would you be surprised if your patient died in 12 months?", which is used in some clinical settings to predict patient deaths and to make decisions regarding ADs. The main objective of the present study was to evaluate the behavior of second-year resident physicians (PGY-2) when the SQ was applied. METHOD: In our observational study, from July 1, 2016, to February 28, 2017, (PGY-2) in the Internal Medicine Residency Program (IMRP) applied SQ to all patients with multiple and varied chronic no communicable comorbidities, who were followed up at the general medicine outpatient clinic (GMOC) of a tertiary university hospital in São Paulo- Brazil. The frequency of the outcome (death or non-death within 12 months) was analyzed by correlating it with the clinical data (impact of the studied variables). RESULTS: Eight hundred forty patients entered the study. Fitfty-two of them (6.2%) died within one year. PGY-2 predicted that two hundred and fourteen patients (25.5% of total) would die within a year (answer No to SQ), of which, 32 (14.9%) did so. The correct residents' prognosis for the subgroup of 626 patients (answer "Yes" to SQ) was NPV = 96.8% (CI = 95.4%-98.2%) and PPV = 14.9% (CI 10.1%-19, 6%). Answering "Yes" to SQ correlated negatively to addressing AD while the outcomes death and the answer No to SQ were positively correlated, according to the number of comorbidities. CONCLUSION: The SQ, in addition to care, contributed to health education, communication and care planning shared by the doctor and patient.

Impact of chemotherapy on surgical outcomes in ileostomy reversal: a propensity score matching study from a single centre.

PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.