bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in socioeconomic inequalities in self-rated health and mental distress during four decades in a Norwegian population: a HUNT Study
Authors: Vonen Hanne Dahl , Sund Erik R , Ariansen Inger , Krokstad Steinar
Published: June 2024

Background

Socioeconomic inequalities constitute an important focus area for public health, and it has long been established that higher educational level and longer lifespan are correlated. Little is known about decennial time trends in poor self-rated health and mental distress.

Methods

This study linked decennial cross-sectional survey data on self-rated health and mental distress from the Trøndelag Health Study (HUNT) from 1984 to 2019 with educational registry data using personal identification numbers. Survey participation ranged from 50 807 to 77 212. Slope index of inequality (SII) and relative index of inequality (RII) were calculated using generalized linear models in Stata. Analyses were stratified by sex and age, using the age categories of 30–59 years and 60–80 years.

Results

Absolute inequalities in self-rated health and mental distress between educational groups have stayed relatively stable throughout all rounds of HUNT. Relative inequalities in self-rated health and mental distress have generally increased, and both men and women with the lowest education level were more likely to experience poor self-rated health and mental distress relative to those with the highest education level. RII in self-rated health increased over time for both sexes and both age groups. RII for mental distress increased in both sexes and both age groups, except for men and women aged 60–80.

Discussion

This study shows that relative inequalities in self-rated and mental health in the Norwegian population are still persistent and have increased. Further knowledge about groups with a disadvantageous health situation should have implications for health care resource allocation.
Association Between Cognitive Trajectories and Subsequent Health Status, Depressive Symptoms, and Mortality Among Older Adults in the United States: Findings From a Nationally Representative Study
Authors: Zang Emma , Zhang Yunxuan , Wang Yi , Wu Bei , Fried Terri R , Becher Robert D , Gill Thomas M
Published: June 2024

Background

Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort.

Methods

Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes.

Results

Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates.

Conclusions

Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes.
Deformation of solid earth by surface pressure: equivalence between Ben-Menahem and Singh’s formula and Sorrells’ formula
Authors: Tanimoto Toshiro
Published: June 2024

Atmospheric pressure changes on Earth’s surface can deform the solid Earth. Sorrells derived analytical formulae for displacement in a homogeneous, elastic half-space, generated by a moving surface pressure source with speed $c$. Ben-Menahem and Singh derived formulae when an atmospheric P wave impinges on Earth’s surface. For a P wave with an incident angle close to the grazing angle, which essentially meant a slow apparent velocity $c_a$ in comparison to P- ($\alpha ^{\prime }$) and S-wave velocities ($\beta ^{\prime }$) in the Earth ($c_a \ll \beta ^{\prime } \lt \alpha ^{\prime }$), they showed that their formulae for solid-Earth deformations become identical with Sorrells’ formulae if $c_a$ is replaced by $c$. But this agreement was only for the asymptotic cases ($c_a \ll \beta ^{\prime }$). The first point of this paper is that the agreement of the two solutions extends to non-asymptotic cases, or when $c_a /\beta ^{\prime }$ is not small. The second point is that the angle of incidence in Ben-Menahem and Singh’s problem does not have to be the grazing angle. As long as the incident angle exceeds the critical angle of refraction from the P wave in the atmosphere to the S wave in the solid Earth, the formulae for Ben-Menahem and Singh’s solution become identical to Sorrell’s formulae. The third point is that this solution has two different domains depending on the speed $c$ (or $c_a$) on the surface. When $c/\beta ^{\prime }$ is small, deformations consist of the evanescent waves. When $c$ approaches Rayleigh-wave phase velocity, the driven oscillation in the solid Earth turns into a free oscillation due to resonance and dominates the wavefield. The non-asymptotic analytical solutions may be useful for the initial modelling of seismic deformations by fast-moving sources, such as those generated by shock waves from meteoroids and volcanic eruptions because the condition $c / \beta ^{\prime } \ll 1$ may be violated for such fast-moving sources.
The 2013 Mw 6.2 Shonbeh (Kaki) earthquake (Zagros-Iran): seismo-tectonic implications for the Kazerun shear transition zone from high-resolution aftershock and InSAR data analysis
Authors: Yamini-Fard F , Tatar M , Fathian A
Published: June 2024

The aim of this study is to investigate the aftershock sequence data recorded by a dense temporary seismological network deployed in the epicentral area of the 2013 April 9 Shonbeh (Kaki) earthquake, located in the south of the Simply Folded Belt of the Zagros (Iran). For a comprehensive understanding, coseismic displacements of the Shonbeh earthquake have been investigated using Interferometric Synthetic Aperture Radar (InSAR) data. The epicentral distribution of high-resolution relocated aftershocks shows NW–SE and N–S trending of seismicity. The aftershocks are confined between ∼3 and ∼14 km depth, which implies that the rupture occurred mostly within the sedimentary cover beside the fault parameters retrieved from InSAR modelling. Projection of precisely located aftershocks on NE-oriented section and InSAR ground displacement data are consistent with both NW-trending NE- and SW-dipping fault segments. We observe a NNW–SSE right-lateral strike-slip motions that accommodate oblique convergence and differential motion between the North and Central Zagros. The spatial pattern and focal mechanisms of aftershocks are consistent with a distributed deformation between NW–SE trending reverse and N–S trending right-lateral strike-slip fault segments in the south of the Kazerun transition zone that accommodates a wide shear zone.
Deep learning for deep earthquakes: insights from OBS observations of the Tonga subduction zone
Authors: Xi Ziyi , Wei S Shawn , Zhu Weiqiang , Beroza Gregory C , Jie Yaqi , Saloor Nooshin
Published: June 2024

Applications of machine learning in seismology have greatly improved our capability of detecting earthquakes in large seismic data archives. Most of these efforts have been focused on continental shallow earthquakes, but here we introduce an integrated deep-learning-based workflow to detect deep earthquakes recorded by a temporary array of ocean-bottom seismographs (OBSs) and land-based stations in the Tonga subduction zone. We develop a new phase picker, PhaseNet-TF, to detect and pick P- and S-wave arrivals in the time–frequency domain. The frequency-domain information is critical for analysing OBS data, particularly the horizontal components, because they are contaminated by signals of ocean-bottom currents and other noise sources in certain frequency bands. PhaseNet-TF shows a much better performance in picking S waves at OBSs and land stations compared to its predecessor PhaseNet. The predicted phases are associated using an improved Gaussian Mixture Model Associator GaMMA-1D and then relocated with a double-difference package teletomoDD. We further enhance the model performance with a semi-supervised learning approach by iteratively refining labelled data and retraining PhaseNet-TF. This approach effectively suppresses false picks and significantly improves the detection of small earthquakes. The new catalogue of Tonga deep earthquakes contains more than 10 times more events compared to the reference catalogue that was analysed manually. This deep-learning-enhanced catalogue reveals Tonga seismicity in unprecedented detail, and better defines the lateral extent of the double-seismic zone at intermediate depths and the location of four large deep-focus earthquakes relative to background seismicity. It also offers new potential for deciphering deep earthquake mechanisms, refining tomographic models, and understanding of subduction processes.
Residual Disease Burden Among European Patients With Inflammatory Bowel Disease: A Real-World Survey
Authors: Burisch Johan , Hart Ailsa , Sturm Andreas , Rudolph Christine , Meadows Rachael , Jus Anna , Dawod Fatima , Patel Haridarshan , Armuzzi Alessandro
Published: June 2024

Background

Understanding disease burden is imperative for improving inflammatory bowel disease (IBD) management. This real-world survey investigated residual disease burden and treatment satisfaction among European patients with moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

The Adelphi Real World IBD Disease Specific Programme was a multinational, cross-sectional survey with retrospective collection of patient- and physician-reported data on disease burden and management. Between October 2020 and March 2021, participating gastroenterologists recruited their next 7 (UC) and 8 (CD) eligible patients and reported demographics and clinical characteristics. Patients completed symptom, health-related quality of life (HRQoL), and treatment satisfaction questionnaires. Data were adjusted for confounding variables and compared between patients in remission (clinical remission, endoscopic remission, or both) and not in remission.

Results

Overall, 1040 patients (UC, n = 502; CD, n = 538) were included. Although most patients were in remission (UC, 66.1%; CD, 69.5%), most still reported symptoms (UC, 63.7%; CD, 74.1%), including flatulence, fatigue/tiredness, and abdominal pain/distension. In UC, there were no significant differences in the likelihood of experiencing 7 of 23 symptoms between patients in remission and not in remission. In CD, there was no significant difference in 19 of 23 symptoms between patients in remission and not in remission. Several symptoms were significantly associated with reduced HRQoL. HRQoL was significantly better among patients in remission than not in remission.

Conclusions

Patients with IBD, both in remission and not in remission, experience residual symptoms that impair HRQoL. Comprehensive endpoints, incorporating HRQoL and patients’ perspectives, and improved treatments are needed to address residual disease and patients’ needs.
Challenges of Mediating Investor-State Disputes
Authors: Gotsiridze Mariam
Published: June 2024

Mediation has gained a lot of traction in the context of ISDS in the past few years. There are many who truly believe that this could be an alternative to highly costly and lengthy investor-State arbitrations and litigations. States have started to include mediation in their investment treaties; institutions have designed separate mediation rules and procedures specifically for investor-State disputes. The 2022 International Dispute Resolution Survey from the Singapore International Dispute Resolution Academy (SIDRA) is a testament to this positive trend towards investor-State mediation. In the 2022 SIDRA Survey, the respondents signal increased acceptance of mediation in ISDS.

Despite these trends, the use of mediation in investor-State disputes appears to be very limited. During the 2022 SIDRA Survey qualitative interviews, the SIDRA tried to enquire about the users’ perspective on the Survey results on mediation and the prospect of the use of mediation for investor-State matters.

This article examines the challenges of using mediation in ISDS to propose possible solutions to overcome these challenges. Section II presents the 2022 SIDRA Survey results. Section III outlines and examines user insights collected during qualitative interviews. Section IV proposes possible measures to eliminate the obstacles hindering the use of mediation by States. Section V draws final conclusions.
A high-performance lithium-ion batteries state of charge estimation strategy for photovoltaics application
Authors: Cai Ying , Ding Haochuan , Yu Zhiwen , Li Jun , Cao Renwei , Tang Dayuan , Li Li
Published: June 2024

Virtual power plants (VPPs) can realize the aggregation and coordinated optimization of distributed generation (DG), such as renewable energy (e.g. photovoltaic (PV), wind power) and energy storage systems (ESSs), which is considered an up-and-coming technology. The lithium-ion battery is widely used in VPPs as a high-quality energy storage. Meanwhile, the battery state of charge (SOC) estimation is fundamental, which characterizes the remaining energy, and obtaining an accurate battery SOC is essential for the safe and reliable operation of the ESS. This article proposes a SOC estimation technique for lithium-ion batteries in VPPs containing PV. Considering that the extended Kalman filtering (EKF) can obtain a more accurate battery SOC, it is further optimized based on the EKF to improve the accuracy of its SOC estimation. First, the principle of the general method and its deficiencies are analyzed, and then the proposed improved method is analyzed in detail. Finally, the advantages of the proposed method and the feasibility of applying it to PV-ESSs are analyzed in detail. A test platform is built for validation, and the results show that the SOC estimation errors of the proposed strategy are 1.8%, 2.1%, and 2.3%, respectively, with better performance.
Model updating of highway slope under seismic intensity conditions considering spatially varying soils
Authors: Zhang Yongjuan , Liu Yong , Wang Ruohan
Published: June 2024

Understanding the mechanisms underlying earthquake-induced landslides and assessing seismic responses are crucial for effective mitigation strategies. Earthquakes typically involve a mainshock followed by aftershocks, posing challenges to structures weakened by the mainshock. Highway slope structures, especially those in unsaturated soft-soil slopes, are vulnerable to aftershocks, amplifying the damage caused by the mainshock-aftershock (MSAS) sequence. While existing research primarily focuses on the effects of mainshocks on certain structures, there is a notable gap regarding the damage sustained by unsaturated slope structures under MSAS conditions. Addressing this gap is vital for comprehensive risk assessment and mitigation. To address these challenges, we propose a stochastic model updating approach for seismic reliability analysis. This approach integrates subset simulation with adaptive Bayesian updating and dimensionality reduction using the Karhunen–Lòeve expansion. Shaking table tests on a slope structure with unsaturated red clay soil are conducted to investigate the effects of matrix suction on performance degradation and failure mechanisms. The results reveal spatial variability in soil property parameters, underscoring the need to incorporate this variability into inverse analyses. Traditional deterministic methods or probability-based approaches may overlook such variability. Also, the results indicated our proposed approach enables effective prediction of seismic responses for unsaturated slopes subjected to MSAS sequences. By considering spatial variability and the effects of matrix suction, our method offers a comprehensive framework for seismic reliability analysis of unsaturated slope structures.
A National Mandate for Thermal Fuses for Home Oxygen Users is Cost-Effective in the Prevention of Burn Morbidity, Mortality, and Property Loss
Authors: Sheckter Clifford C , Coffey Rebecca
Published: June 2024

Smoking while using home oxygen leads to explosions, which cause cutaneous burns, death, and loss of property. Thermal fuses interrupt the propagation of ignited oxygen lines and reduce the risk of injury. Prior to mandating thermal fuses for all home oxygen users in the United States, cost-effectiveness analysis should be performed. A Markov model was constructed for suffering a thermal injury while smoking on home oxygen. Societal and Medicare perspectives were adopted, evaluating the costs of a federal policy, including purchasing/shipping thermal fuses to all home oxygen users. Costs included the healthcare required to treat burn patients and extend lives in advanced chronic obstructive pulmonary disease. Cost savings included the avoided property loss. Effectiveness was measured in gains in quality adjusted life years (QALYs). In the status quo, the 10-year societal cost was $28.67 billion compared to $28.36 billion in the policy mandate (saving $305.40 million at 10 years). 1812 QALYs were gained with the policy mandate, yielding, and incremental cost-effectiveness ratio (ICER) of −$160 317. From the Medicare payor perspective, the ICER was $64 981. Deterministic and probabilistic sensitivity analyses showed little variation in the ICER under multiple scenarios. The discrepancy between the dominant ICER for a societal perspective and the cost-effective ICER for a Medicare perspective reflected savings from averted property loss not realized by Medicare. A national policy mandating and paying for thermal fuses for all home oxygen users is dominant from a societal perspective and cost-effective from a Medicare perspective. The US government should adopt such a policy.
Characterization of haying behavior by the Ladakh Pika (Ochotona ladacensis) and the Nubra Pika (Ochotona nubrica) from the Changthang, Ladakh, India
Authors: Kumar Harsha , D’Souza Senan , Dhanesh Ponnu , Nandini Rajamani
Published: June 2024

Food caching and haying can help species to survive extreme environmental conditions and cope with seasonal fluctuations in resource availability. We documented the food caching/haying behavior of the Ladakh Pika (Ochotona ladacensis) and the Nubra Pika (O. nubrica) from the cold desert of the Changthang biotic province, Ladakh, India, and contrasted their haying strategies under differing conditions of sociality and niche occupation. We found that the more social and larger species, O. ladacensis—which lives in open microhabitats—built larger and more conspicuous haypiles compared to O. nubrica—which built smaller, concealed haypiles in less open microhabitats. Ochotona ladacensis collected a different set of plants with greater overall richness than O. nubrica. Both species collected distasteful, toxic plants that are known to discourage herbivory. Ochotona nubrica placed haypiles closer to burrows in comparison to O. ladacensis. Haypiles in O. ladacensis colonies were clumped rather than uniformly distributed, not meeting predictions of the theory of cache defensibility associated with theft by conspecifics. The present study provides insights into haypile characteristics and associated behavioral responses of high-elevation pikas to variation in the availability of resources.
The Ambivalent Elegies of Gwendolyn Brooks
Authors: Gargaillo Florian
Published: June 2024

This essay addresses the significance of the elegy in the early verse of Gwendolyn Brooks and the importance of her elegies to the form’s evolution in the twentieth century. To describe those who have passed, Brooks layers a variety of ambiguities, paradoxes, and contradictions within a single poem, resulting in an attitude that can best be described as ambivalent. For Brooks, it was crucial to depict the deceased ambivalently because of white culture’s tendency to moralize on the death of Black Americans. By juxtaposing competing views of the dead, she resists the notion that a life can be summarily evaluated in retrospect. Thus, Brooks participates in a broader shift among twentieth-century elegists who came to view the genre’s ability to console with a skeptical eye. At the same time, she extends that skepticism to the genre’s capacity to form singular, coherent narratives out of past lives. This article considers a range of poems in Brooks’s early work, from her debut collection A Street in Bronzeville (1945) to In the Mecca (1968).
Low-luminosity accretion of Be/X-ray pulsar MAXI J1409−619
Authors: Ghimiray Monika , Sharma Pankaj , Subba Nishika
Published: June 2024

This paper used Nuclear Spectroscopic Telescope Array observations to examine the temporal and spectral features of the Be/X-ray binary pulsar MAXI J1409−619. The timing analysis of the light curve finds the pulsation of the source at $(501.23\,\,\pm \,\,0.01)$ s. The pulse profile of the source in various energy bands was analysed and showed weak dependence on energy exhibiting asymmetric character and generally suggests a source accretion in the subcritical regime. The variation of pulse fraction with photon energy in general shows an increasing trend. Assuming a distance of 14.5 kpc, we calculated the 3–30 keV source luminosity to be $\sim 6.13\,\,\times \,\,10^{34}\,\,$ erg s$^{-1}$. The long-term spin evolution of the source was carried out, where the source underwent torque reversal.
Accelerating heat pump diffusion in the UK: emergent tensions and priority areas for change
Authors: Barnes Jake , Silvonen Taru , Taylor Mike , Rosenow Jan
Published: June 2024

Energy efficiency is essential to meeting international carbon reduction ambitions. Shifting how energy services are delivered through the adoption of strategic technologies, like heat pumps for domestic heating, offers one important route to deliver efficiency gains if associated infrastructures, markets, cultures, and practices around broader systems can be transformed as well. Transformative Innovation Policy calls for new, reflexive, multi-actor governance practices capable of guiding such transformative change in particular directions whilst remaining open and responsive to system developments as they unfold. Yet seldom are stakeholders afforded the chance to deliberate on progress towards system transformation and offer insights on what is needed to expediate change. In this paper, we draw on data from three deliberative workshops carried out in 2023 in which experts from across industry, manufacturing, policy and research explored what is required to accelerate the diffusion of heat pumps in the UK. Our findings suggest decision theatres are a promising tool for reflexive evaluation of policy and identify five priority areas for change: (i) fostering a clear narrative, (ii) developing and delivering a coherent, long-term policy, (iii) increasing affordability, (iv) building installer capacity and (v) improving customer journeys. Although individual policies remain important, these priority areas shift the focus from policy instruments to broader considerations about the coherence of policy mixes and strategy for system transformations. Our work affirms how tensions arise in reflexive governance practices and supports the use of decision theatres as a method for exploring their implications in practice.
Developing attributes and attribute-levels for subacromial pain syndrome: A systematic review and qualitative study
Authors: Tróndarson Tróndur Frídi , Storgaard Filip Sandberg , Larsen Mikkel Bjerre , Rathleff Michael Skovdal , Clausen Mikkel Bek , Lyng Kristian Damgaard
Published: June 2024

Background

Subacromial pain syndrome (SAPS), the most common cause of shoulder pain, can be treated through different treatments with similar effects. Therefore, in terms of deciding on the right treatment fit, patient preferences need to be understood. We aimed to identify treatment characteristics that delineate interventions (attributes) and corresponding sets of specific categorical range (attribute-levels) for SAPS.

Methods

This multiple method study systematically reviewed both qualitative and quantitative studies on patient preferences for treatment of SAPS, which informed semi-structured interviews with 9 clinicians and 14 patients. The qualitative data from the interviews was analyzed using the framework analysis formulated by Ritchie and Spencer. Attributes and attribute levels of the systematic review and interviews were summarized and categorized.

Results

The search resulted in 2607 studies, 16 of which met the eligibility criteria. The review identified 120 potential attributes, which were synthesized into 25 potential attributes. Fourteen new potential attributes were identified through the interviews, equaling a total of 39 attributes across 11 categories. Levels for 37 attributes were identified through systematic review and interviews, we were unable to identify levels for 2 attributes.

Conclusions

This study identified attributes and attribute levels for the treatment of SAPS. There was a discrepancy in the frequency of the represented attributes between the literature and interviews. This study may improve the understanding of patient preferences for the treatment of SAPS and help individualize care. Our study informs a future discrete choice experiment and supports shared decision-making in clinical practice.
Dose, dose, dose, but where is the patient dose?
Authors: Rehani Madan M , Xu Xie George
Published: June 2024

The article reviews the historical developments in radiation dose metrices in medical imaging. It identifies the good, the bad, and the ugly aspects of current-day metrices. The actions on shifting focus from International Commission on Radiological Protection (ICRP) Reference-Man–based population-average phantoms to patient-specific computational phantoms have been proposed and discussed. Technological developments in recent years involving AI-based automatic organ segmentation and ‘near real-time’ Monte Carlo dose calculations suggest the feasibility and advantage of obtaining patient-specific organ doses. It appears that the time for ICRP and other international organizations to embrace ‘patient-specific’ dose quantity representing risk may have finally come. While the existing dose metrices meet specific demands, emphasis needs to be also placed on making radiation units understandable to the medical community.
Evaluation of uncertainty in personal dose measured using CaSO4:Dy-based TLD badge at different workplaces
Authors: Pradhan Suresh M , Pathan Munir S , Chakrabarty Shatabdi , Selvam T Palani , Sapra Balvinder K
Published: June 2024

The metrological quality of a measurement is characterised by evaluating the uncertainty in the measurement. In this paper, uncertainty in personal dose measured using individual monitoring CaSO4:Dy-based thermoluminescence dosimeter badge is evaluated by application of the guide to the expression of uncertainty in measurement method. The present dose reporting quantity, whole body dose (WBD) and the proposed quantity, personal dose equivalent, Hp(10) has been used as measurands. The influence of various input quantities on the measurement were analyzed through tests that conform to the requirements of the International Electrotechnical Commission IEC 62387. The study found that the expanded uncertainties for WBD and Hp(10) measurements were 63.4% and 41.4%, respectively, corresponding to a 95% coverage probability for workplace fields covering a wide photon energy range (33–1250 keV). However, the uncertainty estimates were quite lower for the type of workplaces that are identified using the dose evaluation algorithm. The input quantities, namely, the response to a mixture of photon beam qualities and photon energy and angular dependence contribute the most to the total uncertainty.
CarcSeq detection of lorcaserin-induced clonal expansion ofPik3caH1047R mutants in rat mammary tissue
Authors: Faske Jennifer B , Myers Meagan B , Bryant Matthew , He Xiaobo , McLellen Florence , Bourcier Todd , Parsons Barbara L
Published: June 2024

Lorcaserin is a 5-hydroxytryptamine 2C (serotonin) receptor agonist and a nongenotoxic rat carcinogen, which induced mammary tumors in male and female rats in a 2-yr bioassay. Female Sprague Dawley rats were treated by gavage daily with 0, 30, or 100 mg/kg lorcaserin, replicating bioassay dosing but for shorter duration, 12 or 24 wk. To characterize exposure and eliminate possible confounding by a potentially genotoxic degradation product, lorcaserin and N-nitroso-lorcaserin were quantified in dosing solutions, terminal plasma, mammary, and liver samples using ultra-high-performance liquid chromatography-electrospray tandem mass spectrometry. N-nitroso-lorcaserin was not detected, supporting lorcaserin classification as nongenotoxic carcinogen. Mammary DNA samples (n = 6/dose/timepoint) were used to synthesize PCR products from gene segments encompassing hotspot cancer driver mutations, namely regions of Apc, Braf, Egfr, Hras, Kras, Nfe2l2, Pik3ca, Setbp1, Stk11, and Tp53. Mutant fractions (MFs) in the amplicons were quantified by CarcSeq, an error-corrected next-generation sequencing approach. Considering all recovered mutants, no significant differences between lorcaserin dose groups were observed. However, significant dose-responsive increases in Pik3ca H1047R mutation were observed at both timepoints (ANOVA, P < 0.05), with greater numbers of mutants and mutants with greater MFs observed at 24 wk as compared with 12 wk. These observations suggest lorcaserin promotes outgrowth of spontaneously occurring Pik3ca H1047R mutant clones leading to mammary carcinogenesis. Importantly, this work reports approaches to analyze clonal expansion and demonstrates CarcSeq detection of the carcinogenic impact (selective Pik3ca H0147R mutant expansion) of a nongenotoxic carcinogen using a treatment duration as short as 3 months.
In situ measurements of dissolved gases in xylem sap as tracers in plant physiology
Authors: Marion Capucine , Gharun Mana , Brennwald Matthias S , Kipfer Rolf
Published: June 2024

Trees transport gases from the ground into the atmosphere through the process of transpiration. Tracing gases transported through this mechanism continuously and under field conditions remains an experimental challenge. Here we measured gases dissolved in the tree sap in situ and in real time, aiming to simultaneously analyse the transport of several gases (He, Ar, Kr, N2, O2 and CO2) from the soil, through the trees, into the atmosphere. We constructed and inserted custom-made semi-permeable membrane probes in the xylem of a fir tree and measured gas abundances at different heights using a portable gas equilibrium membrane-inlet mass spectrometer (‘miniRUEDI’). With this method, we were able to continuously measure the abundances of He, Ar, Kr, N2, O2 and CO2 in sap over several weeks. We observed diurnal variations of CO2 and O2 concentrations that reflected tree physiological activities. As a proof of the concept that trees do uptake dissolved gases in soil water, we irrigated the tree with He-enriched water in a tracer experiment and were able to determine upward sap flow velocity. Measurements of inert gases together with reactive species, such as CO2 and O2, allowed separation of the physical transport and exchange of gases derived from the soil or atmosphere from biological reactions. We discuss the opportunities that our technique provides for continuous in situ measurements of gases in the tree sap.
Transcriptome and metabolome reveal the effects of ABA promotion and inhibition on flavonoid and amino acid metabolism in tea plant
Authors: Gao Chenxi , Wang Zhihui , Wu Weiwei , Zhou Zhe , Deng Xuming , Chen Zhidan , Sun Weijiang
Published: June 2024

Flavonoids (especially anthocyanins and catechins) and amino acids represent a high abundance of health-promoting metabolites. Although we observed abscisic acid accumulation in purple leaves and low levels in albino tea leaves, the specific mechanism behind its impact on flavor compounds remains unclear. In this study, we treated tea leaves with exogenous abscisic acid and abscisic acid biosynthesis inhibitors (Flu), measured physiological indicators and conducted comprehensive transcriptomic and metabolomic analyses to elucidate the potential mechanisms underlying color change. Our results demonstrate that abscisic acid treatment induces purple coloration, while Flu treatment causes discoloration in tea leaves. Metabolomic analysis revealed higher levels of four anthocyanins and six catechins in the group treated with abscisic acid in comparison with the control group. Additionally, there was a notable increase in 15 amino acids in the Flu-treated group. Notably, the levels of flavonoids and amino acids showed an inverse relationship between the two treatments. Transcriptomic comparison between the treatments and the control group revealed upregulation of differentially expressed genes encoding dihydroflavonol reductase and uridine diphosphate-glycose flavonoid glycosyltransferase in the abscisic acid-treated group, leading to the accumulation of identified anthocyanins and catechins. In contrast, differentially expressed genes encoding nitrate reductase and nitrate transporter exhibited elevated expression in the group treated with Flu, consequently facilitating the accumulation of amino acids, specifically L-theanine and L-glutamine. Furthermore, our co-expression network analysis suggests that MYB and bHLH transcription factors may play crucial roles in regulating the expression of differentially expressed genes involved in the biosynthesis of flavonoids and amino acids. This study provides insights for targeted genetic engineering to enhance the nutritional and market value of tea, together with the potential application of purple and albino tea leaves as functional beverages. It also offers guidance for future breeding programs and production.
The Impact of the Preoperative Mental Health Component Summary (MCS) Score on Short-Term Outcomes After Lumbar Fusion
Authors: Ezeonu Teeto , Narayanan Rajkishen , Heard Jeremy C. , Lee Yunsoo A. , Mazmudar Aditya , Zucker Jeffrey , Shaer Alexander , Dulitzki Yoni , Resnick Dylan , Canseco Jose A. , Kurd Mark F. , Kaye Ian D. , Hilibrand Alan S. , Vaccaro Alexander R. , Kepler Christopher , Schroeder Gregory D.
Published: June 2024

Study Design.

Retrospective cohort study.

Objective.

The purpose of this study is to characterize the relationship between preoperative MCS and surgical outcomes after lumbar spine surgery including inpatient complications, length of stay, readmissions, and reoperations.

Summary of Background Data.

As the prevalence of mental health disorders in the United States increases, it is important to identify risks associated with poor mental health status in the surgical spine patient. The mental health component summary (MCS) of the Short Form-12 has been used extensively as an indication of a patient’s mental health status and psychological well-being.

Patients and Methods.

Adult patients older than or equal to 18 years who underwent primary one to three level lumbar fusion surgery at our academic medical institution from 2017 to 2021 were retrospectively identified. Preoperative MCS score was used to analyze outcomes in patients based on a cutoff (<45.6). A score >45.6 indicated better preoperative mental health and a score ≤45.6 indicated worse preoperative mental health.

Results.

Patients with lower preoperative MCS scores had longer hospital stays (3.86±2.16 vs. 3.55±1.42 d, P=0.010) and were more likely to have inpatient renal complications (3.09% vs. 7.19%, P=0.006). Patients with lower preoperative MCS scores also had lower activity measure for post-acute care (AM-PAC) scores (17.1±2.85 vs. 17.6±2.49, P=0.030). Ninety-day surgical readmissions, medical readmissions, and reoperations were not significantly different between groups (P>0.05).

Conclusion.

Our study suggests that patients with lower preoperative mental health scores (MCS ≤45.6) were independently more likely to experience more renal complications and longer length of stay after primary lumbar fusion. In addition, higher MCS scores may correlate with better postoperative mobility and daily activity scores. Nevertheless, long-term outcomes are not significantly different between patients of better or worse preoperative mental health.

Level of Evidence.

Level IV.
Icotinib in a lung adenocarcinoma patient with acquired EGFR 19del/C797S mutation-mediated resistance to osimertinib: a case report
Authors: Cai Fei , Zhao Yuanyuan , Song Shuxi , Zhao Dong , Zheng Zhendong , Xu Long
Published: June 2024

Based on the FLAURA and AURA III trials, compared to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), osimertinib provides a longer overall survival benefit for patients with untreated EGFR mutated non-small cell lung cancer. Similar to other EGFR-TKIs, drug resistance is, however, inevitable. The most common mechanism of acquired resistance to first-line osimertinib therapy is the C797S mutation, which accounts for 6% of cases. In view of the current challenges of the development of the next generation of EGFR inhibitors, the mechanism of third-generation targeted drug resistances and targeted strategies are key for further exploration. Our case report discusses a female patient with advanced lung adenocarcinoma carrying the EGFR exon19 E746_A750delinsIP mutation who received osimertinib as first-line therapy and acquired C797S resistance during treatment. The patient was then treated with icotinib for 8 months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.
Vitexin Inhibits TNBC Progression and Metastasis by Modulating Macrophage Polarization Through EGFR Signaling
Authors: Lin Yufeng , Li Lin , Huang Huakang , Wen Xiaohong , Zhang Yongcheng , Zhang Rongxin , Huang Wenbin
Published: June 2024

Triple-negative breast cancer (TNBC) lacks sensitivity to endocrine and targeted therapies, exhibiting high recurrence and poor prognosis postchemotherapy. Tumor-associated macrophages (TAMs) play a crucial role in cancer progression. Vitexin, a compound with diverse pharmacological effects including anti-cancer activity, remains unexplored in its impact on TAMs during TNBC development. This study aimed to investigate vitexin’s effect on TNBC, its regulation of macrophage polarization (M1 vs. M2), and the underlying EGFR/PI3K/AKT/mTOR pathway. Our results demonstrated that vitexin suppressed the proliferation and invasion of TNBC cells (MDA-MB-231 and BT549) while inducing macrophage mediators that further inhibited cancer cell migration. Vitexin also promoted M1 polarization and suppressed M2 polarization, affecting EGFR phosphorylation and downstream signaling. In vivo, vitexin inhibited tumor growth, favoring M1 polarization and suppressing M2 polarization, with synergistic effects when combined with doxorubicin (Dox). These findings offer novel insights into vitexin’s potential in TNBC treatment.
Liposomal Bupivacaine Analgesia in Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Retrospective Cohort Study
Authors: Knackstedt Rebecca W. , Lin Jennifer H. , Kakoty Swapnabir
Published: June 2024

Background:

Liposomal bupivacaine (LB) can be used for postsurgical analgesia after breast reconstruction. We examined real-world clinical and economic benefits of LB versus bupivacaine after deep inferior epigastric perforator (DIEP) flap breast reconstruction.

Methods:

This retrospective cohort study used the IQVIA claims databases to identify patients undergoing primary DIEP flap breast reconstruction in 2016–2019. Patients receiving LB and those receiving bupivacaine were compared to assess opioid utilization in morphine milligram equivalents (MMEs) and healthcare resource utilization during perioperative (2 weeks before surgery to 2 weeks after discharge) and 6-month postdischarge periods. A generalized linear mixed-effects model and inverse probability of treatment weighting method were performed.

Results:

Weighted baseline characteristics were similar between cohorts (LB, n = 669; bupivacaine, n = 348). The LB cohort received significantly fewer mean MMEs versus the bupivacaine cohort during the perioperative (395 versus 512 MMEs; rate ratio [RR], 0.771 [95% confidence interval (CI), 0.677–0.879]; P = 0.0001), 72 hours after surgery (63 versus 140 MMEs; RR, 0.449 [95% CI, 0.347–0.581]; P < 0.0001), and inpatient (154 versus 303 MMEs; RR, 0.508 [95% CI, 0.411–0.629]; P < 0.0001) periods; postdischarge filled opioid prescriptions were comparable. The LB cohort was less likely to have all-cause inpatient readmission (odds ratio, 0.670 [95% CI, 0.452–0.993]; P = 0.046) and outpatient clinic/office visits (odds ratio, 0.885 [95% CI, 0.785–0.999]; P = 0.048) 3 months after discharge than the bupivacaine cohort; other all-cause healthcare resource utilization outcomes were not different.

Conclusions:

LB was associated with fewer perioperative MMEs and all-cause 3-month inpatient readmissions and outpatient clinic/office visits than bupivacaine in patients undergoing DIEP flap breast reconstruction.
An unsupervised learning model based on CT radiomics features accurately predicts axillary lymph node metastasis in breast cancer patients: diagnostic study
Authors: Qu Limeng , Mei Xilong , Yi Zixi , Zou Qiongyan , Zhou Qin , Zhang Danhua , Zhou Meirong , Pei Lei , Long Qian , Meng Jiahao , Zhang Huashan , Chen Qitong , Yi Wenjun
Published: June 2024

Background:

The accuracy of traditional clinical methods for assessing the metastatic status of axillary lymph nodes (ALNs) is unsatisfactory. In this study, the authors propose the use of radiomic technology and three-dimensional (3D) visualization technology to develop an unsupervised learning model for predicting axillary lymph node metastasis in patients with breast cancer (BC), aiming to provide a new method for clinical axillary lymph node assessment in patients with this disease.

Methods:

In this study, we retrospectively analyzed the data of 350 patients with invasive BC who underwent lung-enhanced computed tomography (CT) and axillary lymph node dissection surgery at the Department of Breast Surgery of the Second Xiangya Hospital of Central South University. The authors used 3D visualization technology to create a 3D atlas of ALNs and identified the region of interest for the lymph nodes. Radiomic features were subsequently extracted and selected, and a prediction model for ALNs was constructed using the K-means unsupervised algorithm. To validate the model, the authors prospectively collected data from 128 BC patients who were clinically evaluated as negative at our center.

Results:

Using 3D visualization technology, we extracted and selected a total of 36 CT radiomics features. The unsupervised learning model categorized 1737 unlabeled lymph nodes into two groups, and the analysis of the radiomic features between these groups indicated potential differences in lymph node status. Further validation with 1397 labeled lymph nodes demonstrated that the model had good predictive ability for axillary lymph node status, with an area under the curve of 0.847 (0.825–0.869). Additionally, the model’s excellent predictive performance was confirmed in the 128 axillary clinical assessment negative cohort (cN0) and the 350 clinical assessment positive (cN+) cohort, for which the correct classification rates were 86.72 and 87.43%, respectively, which were significantly greater than those of clinical assessment methods.

Conclusions:

The authors created an unsupervised learning model that accurately predicts the status of ALNs. This approach offers a novel solution for the precise assessment of ALNs in patients with BC.
Sepsis phenotypes, subphenotypes, and endotypes: are they ready for bedside care?
Authors: Scherger Sias J. , Kalil Andre C.
Published: June 2024

Purpose of review

Sepsis remains a leading global cause of morbidity and mortality, and despite decades of research, no effective therapies have emerged. The lack of progress in sepsis outcomes is related in part to the significant heterogeneity of sepsis populations. This review seeks to highlight recent literature regarding sepsis phenotypes and the potential for further research and therapeutic intervention.

Recent findings

Numerous recent studies have elucidated various phenotypes, subphenotypes, and endotypes in sepsis. Clinical parameters including vital sign trajectories and microbial factors, biomarker investigation, and genomic, transcriptomic, proteomic, and metabolomic studies have illustrated numerous differences in sepsis populations with implications for prediction, diagnosis, treatment, and prognosis of sepsis.

Sepsis therapies including care bundles, fluid resuscitation, and source control procedures may be better guided by validated phenotypes than universal application. Novel biomarkers may improve upon the sensitivity and specificity of existing markers and identify complications and sequelae of sepsis. Multiomics have demonstrated significant differences in sepsis populations, most notably expanding our understanding of immunosuppressed sepsis phenotypes. Despite progress, these findings may be limited by modest reproducibility and logistical barriers to clinical implementation. Further studies may translate recent findings into bedside care.
Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study
Authors: Singh Ritu R. , Gopakumar Harishankar , Dhillon Sonu
Published: June 2024

Goals and Background:

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis.

Methods:

We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching.

Results:

We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59 y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P<0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08–1.18)].

Conclusions:

Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.