bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence‐Based Teaching Strategies for Assessing Pressure Injuries in Older Nursing Home Residents With Darker Skin Tones
Authors: Sugathapala R D Udeshika Priyadarshani , Balasuriya Aindralal , Gillespie Brigid M. , Chaboyer Wendy , Latimer Sharon
Published: January 2025

Aim

To describe the development and implementation of evidence‐based teaching strategies for assessing and classifying pressure injuries in older nursing home individuals ≥ 60 years old with darker skin tones.

Design

Pressure injury assessment learning interventions based on pre‐ and post‐test assessments.

Methods

The learning interventions were developed by experts in pressure injury education and were based on empirical evidence, international clinical practice guidelines, and underpinned by social constructivism theory and the integrated interactive teaching model. The teaching strategy was developed to educate research assistants in the assessment of pressure injuries in darker skin tone individuals. The content included requisite knowledge and skills for pressure injury assessment and classification in darker skinned individuals. Using evidence‐based teaching strategies, the content was delivered through face‐to‐face lectures, small group discussions, and practical application sessions delivered using classroom and practical‐based activities. Photographic images were used to assess their knowledge and skills in classifying pressure injuries. Four Bachelor of Nursing‐qualified registered nurses in Sri Lanka were recruited as research assistants using the new education resource. Using scores from 1 to 20 points, mastery of the theory and practice components was assessed.

Results

The mean pre‐test score was 9 ± 1.6 (95% confidence interval 6.4–11.6), demonstrating that assessment and classification of pressure injury knowledge were lacking. The mean post‐test score was 16 ± 0.8 (95% confidence interval 14.7–17.3) indicating an improvement in the participants' ability to assess and staging pressure injuries.

Conclusion

Early pressure injury detection among older individuals with darker skin tones is challenging. This evidence‐based teaching approach can be used to educate clinical nurses and research assistants in assessing pressure injuries in individuals with darker skin tones.

Clinical Relevance

This study contributes to the body of knowledge by improving the early detection and accurate classification of pressure injuries in older nursing home residents with darker skin tones, addressing a significant gap in current nursing practice.
Maternal differential treatment and adult children's well‐being when mothers have cognitive impairment
Authors: Suitor J. Jill , Gilligan Megan , Frase Robert T. , He Ranran , Ogle Destiny
Published: January 2025

Objectives

Our goal was to examine the role of perceptions of mothers' cognitive impairment (CI) in shaping the impact of maternal differential treatment on adult children's psychological well‐being.

Background

The detrimental impact of mothers' differential treatment on adult children's psychological well‐being has been well‐documented; however, little is known about whether this association is moderated by mothers' CI.

Methods

Mixed‐methods data were collected from 287 adult children (mean age = 59 years) nested within 142 families as part of the Within‐Family Differences Study. Analytic approaches were multilevel regression and in‐depth qualitative analyses.

Results

Perceiving oneself as the child to whom one's mother was most emotionally close or with whom she had the most conflict was associated with lower psychological well‐being among adult children who did not report that their mothers had symptoms of CI; however, such perceptions were not associated with well‐being when children perceived that mothers showed symptoms of CI. Qualitative analyses revealed that when children reported that mothers did not have CI, children attributed their greater closeness and conflict to unique characteristics of themselves or their mother–child ties. However, when children perceived that mothers showed symptoms of CI, attributions for mothers' differentiation focused on contextual factors surrounding mothers' cognitive health, and thus did not reflect on the children themselves. Thus, the negative impact of perceptions of mothers' differential treatment on well‐being was muted.

Conclusion

This study sheds light on conditions under which perceptions of maternal differential treatment affect adult children's psychological well‐being, and the role of cognitive health in these processes.
High‐Field‐Blinded Assessment of Portable Ultra‐Low‐Field Brain MRI for Multiple Sclerosis
Authors: Okar Serhat V. , Nair Govind , Kawatra Karan D. , Thommana Ashley A. , Donnay Corinne A. , Gaitán María I. , Stein Joel M. , Reich Daniel S.
Published: January 2025

Background and Purpose

MRI is crucial for multiple sclerosis (MS), but the relative value of portable ultra‐low field MRI (pULF‐MRI), a technology that holds promise for extending access to MRI, is unknown. We assessed white matter lesion (WML) detection on pULF‐MRI compared to high‐field MRI (HF‐MRI), focusing on blinded assessments, assessor self‐training, and multiplanar acquisitions.

Methods

Fifty‐five adults with MS underwent pULF‐MRI following their HF‐MRI. Two neuroradiologists independently assessed pULF‐MRI images in an evaluation process, including initial assessment blinded to HF‐MRI, self‐training with reference to HF‐MRI and evaluation of 20 cases with additional T2‐fluid‐attenuated inversion recovery in an additional plane. A third rater conducted cross‐referenced analysis with HF‐MRI data to determine true‐positive lesions, false‐positive areas, and case‐level sensitivity and positive predictive value.

Results

The mean age of participants was 50 years (standard deviation: 11; 74% women). Initially, Rater 2 marked more false‐positive areas than Rater 1 (p = 0.003). After self‐training, both raters embraced a conservative approach, with Rater 2 marking fewer false‐positive areas (p = 0.01). Both raters maintained 100% case‐level sensitivity and positive predictive value for detecting at least one WML, particularly in periventricular areas. Multiplanar acquisitions reduced both false‐positive areas and true‐positive lesions. True‐positive lesions and false‐positive areas had similar contrast‐to‐noise ratios in the juxtacortical region (p = 0.73) but not in periventricular, deep parenchymal regions (p = 0.004, p = 0.01).

Conclusion

With adequate training, radiological interpretation of pULF‐MRI has high sensitivity and positive predictive value for MS lesions but should be approached conservatively. These results suggest utility for patient triage, potentially reducing diagnostic delay, and screening high‐risk individuals.
We Were Meant to be: Do Implicit Theories of Relationships and Perceived Partner Fit Help Explain Post‐Relationship Contact and Tracking Behaviors Following a Breakup?
Authors: Thompson Ashley E. , Gooch Katie , Willhite Rachel M. , O'Sullivan Lucia F.
Published: January 2025

Those experiencing relationship termination often report using efforts to contact and/or track their ex‐partner, frequently with the intent of re‐establishing connection. Implicit beliefs about relationships as being predestined (destiny beliefs) or requiring cultivation for success (growth beliefs) appear to be linked to concepts of partner fit and attempts to re‐establish connection. Combining findings across four studies, this mixed‐methods research explored how beliefs about relationships and perceptions of partner fit were linked to post‐relationship contact and tracking (PRCT). Study 1 demonstrated that stronger endorsement of destiny (but not growth) beliefs was linked to recall of higher levels of PRCT. Study 2 replicated these findings and indicated that partner fit moderated the link between destiny beliefs and PRCT. Using an experimental design, Studies 3 and 4 showed it was possible to manipulate anticipated use of PRCT, particularly destiny beliefs. This work adds information to our understanding of how relationship beliefs impact adjustment following relationship loss, with implications for those supporting individuals in distress and highlighting the possibility of altering destiny beliefs to improve adjustment.
Stimulate to Remember? The Effects of Short Burst of Transcutaneous Vagus Nerve Stimulation (taVNS) on Memory Performance and Pupil Dilation
Authors: Ludwig Mareike , Betts Matthew J. , Hämmerer Dorothea
Published: January 2025

The decline in noradrenergic (NE) locus coeruleus (LC) function in aging is thought to be implicated in episodic memory decline. Transcutaneous auricular vagus nerve stimulation (taVNS), which supports LC function, might serve to preserve or improve memory function in aging. However, taVNS effects are generally very heterogeneous, and it is currently unclear whether taVNS has an effect on memory. In this study, an emotional memory task with negative events involving the LC‐NE system was combined with the short burst of event‐related taVNS (3 s) in younger adults (N = 24). The aim was to investigate taVNS‐induced changes in pupil dilation during encoding and possible taVNS‐induced improvements in (emotional) memory performance for early and delayed (24 h) recognition. Negative events were associated with increased pupil dilation and better memory performance. Additionally, real as compared to sham or no stimulation selectively increased memory for negative events. Short bursts of stimulation, whether real or sham, led to an increase in pupil dilation and an improvement in memory performance over time, likely due to the attention‐inducing sensory modulation of electrical stimulation.
Single‐Cell RNA Sequencing Analysis Reveals Exercise‐Induced Transcriptional Dynamics in Half‐Marathon Runners
Authors: Veschetti Laura , Patuzzo Cristina , Treccani Mirko , Moron Dalla Tor Lucas , Deiana Michela , Cheri Samuele , Griggio Francesca , Lippi Giuseppe , Schena Federico , De Santis Daniele , Dalle Carbonare Luca , Tarperi Cantor , Trabetti Elisabetta , Valenti Maria Teresa , Malerba Giovanni
Published: January 2025

Previous studies in sports science suggested that regular exercise has a positive impact on human health. However, the effects of endurance sports and their underlying mechanisms are still not completely understood. One of the main debates regards the modulation of immune dynamics in high‐intensity exercise. As part of the “Run 4 Science” project in Verona, Italy, we conducted a single‐cell RNA sequencing analysis on half‐marathon amateur runners to investigate the transcriptional dynamics of peripheral blood mononuclear cells following endurance exercise. Blood samples were collected from four participants before and after running a half‐marathon to carry out a comprehensive transcriptomic analysis of immune cells at the single‐cell level. Our analysis revealed significant alterations in the transcriptional profiles following endurance physical exercise. Modulations in myeloid cells suggested the activation of stress response (6 related pathways, p < 0.04) and pathways related to viral processes (4 related pathways, p < 0.03), while in lymphoid cells they hinted to a shift towards immune activation (24 related pathways, p < 0.01). Additionally, transcriptional changes in platelets point to an activation of the coagulation process (5 related pathways, p < 0.005). Single‐cell data was also analyzed following a pseudo‐bulk approach (i.e., simulating a bulk RNAseq experiment) to gain further biological insights. Our findings suggest that a pseudo‐bulk analysis could offer complementary findings to classical single‐cell analysis methods and demonstrate that endurance physical exercise, such as running a half‐marathon, induces substantial changes in the transcriptional dynamics of immune cells. These insights contribute to a better understanding of the immune modulation mediated by endurance exercise and may inform future training routines or nutritional guidelines based on individual gene expression levels.
Clostridioides difficile
colonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an
in vitro
model
Authors: Huang Xiaoyun , Johnson April E. , Brehm Joshua N. , Do Thi Van Thanh , Auchtung Thomas A. , McCullough Hugh C. , Lerma Armando I. , Haidacher Sigmund J. , Hoch Kathleen M. , Horvath Thomas D. , Sorg Joseph A. , Haag Anthony M. , Auchtung Jennifer M.
Published: January 2025

Treatment with antibiotics is a major risk factor for
Clostridioides difficile
infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit
C. difficile
colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to
C. difficile
growth and competition between the microbiota and
C. difficile
for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to
C. difficile
infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate with
C. difficile
susceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate. However, changes in bile salt did not correlate with increased
C. difficile
susceptibility. Furthermore, bile salts were not required to inhibit
C. difficile
colonization. We tested whether amino acid fermentation contributed to the persistence of
C. difficile
in antibiotic-treated communities.
C. difficile
mutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (
prdB
−) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. The inability to ferment glycine or leucine as electron acceptors, however, was not sufficient to limit colonization in any communities. The data provide further support for the importance of bile salt-independent mechanisms in regulating the colonization of
C. difficile
.

IMPORTANCE

Clostridioides difficile
is one of the leading causes of hospital-acquired infections and antibiotic-associated diarrhea. Several potential mechanisms through which the microbiota can limit
C. difficile
infection have been identified and are potential targets for new therapeutics. However, it is unclear which mechanisms of
C. difficile
inhibition represent the best targets for the development of new therapeutics. These studies demonstrate that in a complex
in vitro
model of
C. difficile
infection, colonization resistance is independent of microbial bile salt metabolism. Instead, the ability of
C. difficile
to colonize is dependent upon its ability to metabolize proline, although proline-dependent colonization is context dependent and is not observed in all disrupted communities. Altogether, these studies support the need for further work to understand how bile-independent mechanisms regulate
C. difficile
colonization.
Decision rules in the diagnostic work-up of aortic dissection
Authors: Jaconelli Tom , Crane Steven
Published: January 2025

A short cut review of the literature was carried out to examine whether a decision rule in conjunction with a D-dimer can be used to rule out aortic dissection. 117 unique papers were found of which three systematic reviews included data on patients relevant to the clinical question; these are discussed in the paper. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. The clinical bottom line is that in low-risk patients (aortic dissection detection risk score 0 or 1) who present to the Emergency Department with chest pain, a negative D-dimer level makes aortic dissection unlikely. However, further prospective validation studies are needed to optimally define the patient group that warrants investigation, the threshold for investigation and the clinical effectiveness of such a diagnostic strategy before it can be widely adopted.
Longitudinal cardiac imaging for assessment of myocardial injury in non-hospitalised community-dwelling individuals after COVID-19 infection: the Rotterdam Study
Authors: van den Heuvel Frederik , Aribas Elif , Tilly Martijn J , Geurts Sven , Yang Shuyue , Lu Zuolin , de Groot Natasja M S , van den Bosch Annemien E , Eijsvogels Thijs M H , Peeters Robin , Rutten Frans , Geersing Geert-Jan , van Rosmalen Joost , Ikram M Arfan , Nijveldt Robin , Hirsch Alexander , Kavousi Maryam
Published: January 2025

Background

The aim of this study was to assess the presence of myocardial injury after COVID-19 infection and to evaluate the relation between persistent cardiac symptoms after COVID-19 and myocardial function in participants with known cardiovascular health status before infection.

Methods

In the prospective population-based Rotterdam Study cohort, echocardiography and cardiovascular magnetic resonance (CMR) were performed among participants who recovered from COVID-19 at home within 2 years prior to inclusion in the current study. Persistent cardiac symptoms comprised only self-reported symptoms of chest pain, dyspnoea or palpitations lasting >4 weeks after COVID-19 infection. We used linear regression and linear mixed models to estimate and test age-adjusted and sex-adjusted mean differences (95% CIs) of (1) post-COVID-19 CMR-derived and echocardiographic-derived parameters among participants with and without persistent post-COVID-19 symptoms and (2) pre-COVID-19 and post-COVID-19 echocardiographic assessments.

Results

92 participants were included, with a mean age of 59±8 years of whom 52% were male. Normal post-COVID-19 CMR-derived left ventricular (LV) function and right ventricular ejection fraction were observed in 92% and 98% of participants, respectively. We observed normal native T1 relaxation times in 100%, normal extracellular volume in 98% and normal T2 relaxation times in 98% of the participants. Comparison of pre-COVID-19 and post-COVID-19 echocardiography revealed a significant but small decline in left ventricular ejection fraction (adjusted mean change −1.37% (95% CI −2.57%, –0.17%)) and global longitudinal strain (1.32% (95% CI 0.50%, 2.15%)). Comparing participants with and without persistent symptoms, there were no significant differences in adjusted CMR-derived ventricular volumes, LV function or presence of myocardial injury.

Conclusions

Almost all recovered non-hospitalised COVID-19 participants had normal CMR-derived ventricular volumes and function, without relevant myocardial injury.
Association of weight change with cardiovascular events and all-cause mortality in obese participants with cardiovascular disease: a prospective cohort study
Authors: Zhang Jufen , Schutte Rudolph , Pierscionek Barbara
Published: January 2025

Background

Studies have examined the association between weight change and risk of cardiovascular (CV) outcomes in the general population. However, very few literature reported the association among obese people with established CV disease (CVD) and the factors associated with weight change are not clear. We sought to investigate this using the UK Biobank data.

Methods

In this large prospective population-based cohort study, absolute interval change scores in weight were calculated between weight measurements at baseline and the follow-up. The estimated HRs with 95% CIs were obtained from the Cox regression models to assess the association between weight change and the risk of CV death, cerebrovascular and ischaemic heart diseases and all-cause mortality.

Results

Of the 8297 obese participants who had CVD with repeated weight measurements, 43.1% were female. The mean age was 56.6 (SD: 7.2) years. The overall median follow-up of the study was 13.9 (IQR: 13.1–14.6) years. 52.7% of the participants had stable weight change (weight loss or gain<5 kg), 14.2% had large weight loss (≥10 kg) and 5.1% had large weight gain (≥10 kg). Compared with stable weight, only large weight gain was associated with an increased risk of CV death and all-cause mortality (fully adjusted HR (95% CI): 3.05 (1.40 to 6.67) for CV death and 1.93 (1.15 to 3.26) for all-cause mortality).

Conclusions

Among obese individuals with CVD, large weight gain is associated with a higher risk of CV death and all-cause mortality. Further studies are needed to understand the exact mechanisms underlying the associations between weight loss or weight gain and mortality.
Age-specific prognosis of acute and steady minor elevations in cardiac troponin among non-acute myocardial infarction inpatients: a large real-world cohort study
Authors: Sun Pengfei , Liu Wen-Nan , Qian Xilong , Zhang Zhiqiang , Liu Hangkuan , A Geru , Liu Yuanyuan , Fonarow Gregg , Foo Roger Sik-Yin , Chan Mark Yan-Yee , Wang Lu , Li Yongle , Yang Qing , Zhou Xin
Published: January 2025

Background

The upper reference limit of normal (ULN) of cardiac troponin (cTn) for older adults can be higher than for young adults, while the same ULN is used for both older and young adults in the current clinical practice.

Methods

In this multicentre longitudinal cohort study, non-acute myocardial infarction (non-AMI) inpatients with at least two cTn concentrations hospitalised between 2013 and 2022 in the Tianjin Health and Medical Data Platform were included. Multivariable Cox proportional hazards and landmark regression models were used to estimate the risk of in-hospital, 30-day and 1-year mortality in different cTn groups (normal, stable minor elevation (1–2×ULN with variation ≤20%), acute minor elevation (1–2×ULN with variation >20%) and apparent elevation (>2×ULN)).

Results

A total of 57 117 patients (mean age, 69.6 (13.6) years; 25 037 (43.8%) female) were included. Even minor elevation in cTn was associated with higher mortality risk. Compared with the normal cTn group, the adjusted HRs of in-hospital mortality for patients with steady minor elevation, acute minor elevation and >2× ULN in cTn were 1.70 (95% CI 1.25 to 2.33), 1.92 (95% CI 1.59 to 2.32) and 4.03 (95% CI 3.50 to 4.65), respectively. Similar trends were found for all-cause 30-day and 30-day to 1-year mortality. Among older adults, compared with the steady minor elevation group, patients with acute minor elevation in cTn had higher 30-day mortality risk (HR 1.30, 95% CI 1.02 to 1.65) but similar 30-day to 1-year mortality risk (HR 0.95, 95% CI 0.82 to 1.10), while among non-older adults, differences in short-term and 1-year mortality risks between the two groups were not statistically significant (p>0.05).

Conclusions

In non-AMI inpatients, including older adults, any stable or acute elevation in cTn, even minor, warrants attention. Further studies are needed to assess whether these patients can benefit from more aggressive treatment approaches.
Explanatory capacity of measures of community context for paediatric injury hospitalisations in the USA
Authors: Puls Henry T , Noelke Clemens , Jeffries Kristyn N , Lindberg Daniel M , Austin Anna E , Chaiyachati Barbara H , Hall Matthew
Published: January 2025

Objective

Community context influences children’s risk for injury. We aimed to measure the explanatory capacity of two ZIP code-level measures—the Child Opportunity Index V.3.0 (COI) and median household income (MHHI)—for rates of paediatric injury hospitalisations.

Methods

This was a retrospective cross-sectional population-based study of children living in 19 US states in 2017. We examined injury hospitalisation rates for three categories: physical abuse among children <5 years, injuries suspicious for abuse among infants <12 months and unintentional injuries among children <18 years. Hospitalisation counts were obtained from the Healthcare Cost and Utilization Project and population data from the US Census. The COI is a multidimensional measure of communities’ education, health and environment and social and economic characteristics. We used pseudo R2values from Poisson regression models to describe the per cent of variance in rates of each injury category explained by the COI and MHHI.

Results

The COI explained 75.4% of the variability in rates of physical abuse, representing a 13.5% improvement over MHHI. The COI explained 58.5% of the variability in injuries suspicious for abuse, a 20.7% improvement over MHHI. The COI and MHHI explained 85.7% and 85.8% of the variability in unintentional injuries, respectively; results differed when unintentional injuries were stratified by mechanism and age.

Implications

The COI had superior explanatory capacity for physical abuse and injuries suspicious for abuse compared with MHHI and was similar for unintentional injury hospitalisations. COI represents a means of accounting for community advantage in paediatric injury data, research and prevention.
Changes in leaf functional traits of Phoebe chekiangensis underplanted in moso bamboo forests with different densities
Authors: Ni Huijing , Yang Zhenya , Zhao Jiancheng
Published: January 2025

Leaf functional traits are sensitive to environmental changes and are a current hotspot in ecology. The objective of this study was to explore the changes in leaf functional traits of Phoebe chekiangensis underplanted in moso bamboo forests with different densities. Leaf functional traits of P. chekiangensis were determined, and their relationships were investigated. Results showed that leaf area (LA) and specific leaf area (SLA) increased with the increase of bamboo forest density, and they were significantly lower at 1350 individual·ha−1 than that of 2250 individual·ha−1. However, leaf thickness (LT) and leaf mass per unit area (LMA) showed an opposite trend, and they were significantly higher at 1350 individual·ha−1 than that of 2250 individual·ha−1. No significant difference was found in chlorophyll a (Ca), chlorophyll b (Cb), total chlorophyll (Ca + Cb), and total carotenoids (Car) among the three treatments. Ca/Cb showed a decreasing trend, and it was significantly higher at 1350 individual·ha−1 than that of 2250 individual·ha−1. Leaf nitrogen (N) concentration increased with the increase of bamboo forest density, and it was significantly higher at 2250 individual·ha−1 than that of 1350 individual·ha−1. C/N decreased, and it was significantly higher at 1350 individual·ha−1 than that of 2250 individual·ha−1. LT was positively correlated with LMA, and negatively correlated with SLA. N concentration was positively correlated with SLA, and negatively correlated with LMA. Significant positive correlation between Ca + Cb and C concentration was observed. In conclusion, the leaf functional traits of P. chekiangensis could compensate for light deficiency through certain trait variations and combinations and better adapt to the environment.
Motor-manual release changes carbon distribution in soil and tree biomass pools in the short term
Authors: Darquié Léa , Poirier Vincent , DesRochers Annie
Published: January 2025

Despite offering multiple ecosystem services, such as their ability to sequester carbon (C), regenerating mixedwood boreal forests are often only managed to increase their coniferous part by controlling their competition, impacting the ecosystem C stocks. The aim of this study was to compare the short-term effect of motor-manual release treatments of variable intensities: broadcast brushing (brushing), release from below (RFB), and crop tree release on carbon stocks in soil (SOC) and live biomass (aboveground and root C stocks). The stands treated by brushing had twice as much SOC stocks than in the other stands, at the 5–10 cm depth. RFB treatment kept the largest aspen stems in the stands and retained enough total live biomass to compensate for the initial loss. Despite being similar in intensity, stands treated with RFB had more than twice the amount of live biomass than stands treated by brushing. Overall, total C stocks (SOC and live biomass) did not change between the stands but the distribution among the different C pools did, with the live biomass being the most impacted by the treatments. The design of the RFB treatment seemed promising to mitigate C loss during early forest operations while still controlling fast-growing competitors.
The Evolution of Computer Science at the University Level
Authors: Shein Esther
Published: January 2025

Combining computer science with arts disciplines may be the wave of the future for education.
Novelty Not Found: Exploring Input Shadowing in Fuzzing through Adaptive Fuzzer Restarts
Authors: Schiller Nico , Xu Xinyi , Bernhard Lukas , Bars Nils , Schloegel Moritz , Holz Thorsten
Published: January 2025

Greybox fuzzing enhances software security through unprecedented effectiveness in automated fault detection. Its success lies in the coverage feedback extracted from the system under test, guiding the fuzzer to explore different program parts. The most prominent way to use this feedback is
novelty search
, where the fuzzer keeps only new inputs exercising a new program edge. However, this approach—by design—ignores
input shadowing
, in which interesting inputs are discarded if they do not contribute to new coverage. This limits the accepted input space and may overlook bugs that shadowed inputs could trigger with mutations.

In this work, we present a comprehensive analysis of input shadowing and demonstrate that multiple fuzzing runs of the same target exhibit a different basic block hit frequency distribution despite overlapping code coverage. We propose
fuzzer restarts
to effectively redistribute basic block hit frequencies and show that this increases the overall achieved coverage on 15 evaluated targets on average by

\(9.5\%\)

and up to

\(25.0\%\)

. Furthermore, restarts help to find more bugs and trigger them more reliably. Overall, our results highlight the importance of considering input shadowing in the fuzzers’ design and the potential benefits of a restart-based strategy to enhance the performance of complex fuzzing methods.
Backsolver: Adapting Preceding Execution Paths to Solve Constraints for Concolic Execution
Authors: Zeng Yicheng , Song Zhanwei , Lv Guo , Zhou Yu , Zhu Hongsong , Sun Limin
Published: January 2025

Concolic execution follows the execution paths of concrete inputs, capable of generating new inputs for unexplored code by solving negated path constraints. However, implicit flows can hinder concolic execution, reducing the code coverage. Implicit flows occur when inputs influence control flow, and the control flow variation affects the values of some variables. During concolic execution, the preceding path selections limit the potential values of these variables. This limitation may result in unsolvable constraints, subsequently restricting the generation of new inputs for unexplored paths. Our insight is that following the same preceding paths is unnecessary, and we can adapt preceding paths to make the latest constraints solvable. We divide states into general states and implicit-flow-solving states (IFSSs). We utilize the general states to perform concolic execution. When solving constraints influenced by implicit flows, we switch to the IFSSs. We use the IFSSs to explore the relevant code region and adapt paths. To mitigate path explosion and construct the relation between inputs and the variables, we merge the IFSSs. State merging does not burden the general states, and we limit the code regions for the IFSSs to minimize the introduced overhead. Finally, we replace the variable symbols in the target constraints with new expressions and attempt to solve the new constraints. We implement our approach in Backsolver and build a test suite to evaluate it. Backsolver successfully identifies all the implicit flows in the test suite and resolves most of them. When evaluated on six real-world binaries, Backsolver resolves the highest number of branches related to implicit flows in total. Besides, Backsolver has the highest code coverage in PlutoSVG and finds a 0-day vulnerability. We reported the vulnerability and obtained a CVE ID.
Novelty Not Found: Exploring Input Shadowing in Fuzzing through Adaptive Fuzzer Restarts—RCR Report
Authors: Schiller Nico , Xu Xinyi , Bernhard Lukas , Bars Nils , Schloegel Moritz , Holz Thorsten
Published: January 2025

This is the Replicated Computational Results (RCR) Report for our ACM TOSEM paper, “Novelty Not Found: Exploring Input Shadowing in Fuzzing through Adaptive Fuzzer Restarts”. In this paper, we demonstrate how input shadowing can impact the fuzzing process and propose a mitigation strategy: restarting the fuzzing process when progress stagnates. As part of this RCR, we provide a replication package to facilitate the reproduction of our results.
Hierarchical Porous Co-Mn Hexacyanoferrate for Advanced Aqueous Sodium-Ion Hybrid Supercapacitors
Authors: Zhao Chunxia , Chen Qiushuang , Jiang Longsheng , Liu Ziyang , Liao Xiaoxue , Qi Yanyuan , Chen Wen
Published: January 2025

Mn-based Prussian blue analogs (Mn-PBAs) have been regarded as promising electrode materials for sodium-ion hybrid supercapacitors (SHSCs) owing to their high specific capacitance and operational potential. However, the cycling stability of Mn-PBAs remains unsatisfactory due to structural deformation during ion insertion/extraction and their high solubility in aqueous electrolytes. Herein, porous Co-Mn Prussian blue nanomaterials (CoMnHCF) have been synthesized via an ethanol-assisted co-precipitation method with subsequent cation-exchange process. CoMnHCF possesses a hierarchical porous structure with high specific surface area up to 637 m2 g−1, which helps to reduce the structural strain during Na+ insertion/extraction and provides more Na+ diffusion channels. It is proposed that high Co/Mn ratio can effectively stabilize the crystal structure and alleviate the dissolution of electrode materials. CoMnHCF-2 exhibits high specific capacitance (242.7 F g−1 at 0.2 A g−1) and remarkable cycling stability (90.4% retention after 3000 cycles at 4 A g−1). Impressively, the aqueous SHSC assembled with CoMnHCF-2 cathode and activated carbon anode manifests a high energy density of 38.2 W·h kg−1 at a power density of 500 W kg−1 and an outstanding retention of 81.6% after 5000 cycles. It demonstrates that hierarchical porous Co-Mn hexacyanoferrate is an excellent candidate for advanced aqueous SHSCs development.
Distinct Molecular and Clinical Features of Specific Variants of KRAS Codon 12 in Pancreatic Adenocarcinoma
Authors: Ardalan Bach , Ciner Aaron , Baca Yasmine , Hinton Andrew , Darabi Sourat , Kasi Anup , Lou Emil , Azqueta Jose Ignacio , Xiu Joanne , Datta Jashodeep , Shields Anthony F. , Aguirre Andrew , Singh Harshabad , Shroff Rachna T. , Pishvaian Michael J. , Goel Sanjay
Published: January 2025

Purpose:

Oncogenic mutations in KRAS have been identified in >85% of pancreatic ductal adenocarcinoma (PDAC) cases, with G12D, G12V, and G12R being the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRASG12D and KRASG12R.

Experimental Design:

PDAC samples were tested using DNA and RNA sequencing. The MAPK activation score and tumor microenvironment were analyzed from RNA expression data. Real-world overall survival (OS) obtained from insurance claims data was calculated from tissue collection to last contact. Significance was determined by χ2 and Fisher exact tests.

Results:

A total of 3,755 patients with PDAC harboring KRASG12D (n = 1,766), KRASG12V (n = 1,294), KRASG12R (n = 621), or KRASG12C (n = 74) variants were identified. Patients with G12R mutations had longer OS compared with those with G12D overall (12.7 vs. 10.1 months; P value = 0.0001), with similar trends in patients treated with gemcitabine/nab-paclitaxel (13.5 vs. 10.4 months; P value = 0.0002) or FOLFIRINOX (18.3 vs. 14.0 months; P value<0.001). ARID1A and KMT2D mutations were more frequent in the G12D subgroup. Several genes involved in glucose and glutamine metabolism were less expressed in G12R compared with G12D. PD-L1 expression was lower in G12R compared with G12D (13% vs. 19%).

Conclusions:

KRAS G12D tumors exhibited a distinct molecular profile compared with G12R tumors, including genes involved in the MAPK pathway, immune activation, and glucose and glutamine metabolism. Patients with G12D mutations had lower OS compared with those with G12R. Based on these data, future studies should address the KRAS mutation status and explore distinct therapeutic vulnerabilities.
Supplemental Table 1 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Clinical Characteristics of Patient #1093
Supplemental Figure 3 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Immunoglobulin Heavy Chain Genes were the Top Overexpressed Genes in IGH-MM.
Supplemental Figure 2 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Analysis without IGH Genes Still Shows Two Subpopulations.
Figure 7 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Relapse and disease progression associated with dysregulated apoptosis and increasing drug resistance. A, Volcano plot showing the differential gene expression between LCE-multiple myeloma (MM) cells at timepoint 1 (diagnosis) and LCE-MM cells at timepoint 2 (first relapse, with 1,042 genes higher in LCE-MM at diagnosis, 281 genes higher at first relapse, indicated by green dots for l2FC > 0.25, P < 0.05). Tested by linear regression, n = 4,370 cells at diagnosis, n = 281 cells at first relapse. B, Calcium-binding proteins S100A8 and S100A9 transcripts were increased at first relapse compared with diagnosis. C,MYC was decreased at first relapse compared with diagnosis. D, KEGG enrichment analysis of differentially expressed genes identified several pathways including protein processing, apoptosis, and cellular senescence. E, MM at the R/R timepoint showed a reemergence of IGH genes. F, Multidrug resistance was observed ex vivo by My-DST at the R/R timepoint (n = 3, t test, bars show standard deviation. **, P < 0.01; ***, P < 0.001). Chr, chromosome; Dx, diagnosis; Rel, relapse; OR, odds ratio; R/R, relapsed/refractory timepoint.
Figure 1 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Patient with two multiple myeloma (MM) subpopulations correlating separately to monoclonal protein and free light chain detection through the course of disease. A, UMAP clustering analysis of bone marrow biopsy samples from patient #1093 at all three timepoints showed two distinct subpopulations of MM cells (LCE-MM and IGH-MM), along with the expected normal bone marrow cell types. B, Both MM subpopulations displayed transcript expression for the prototypical MM markers including high CD138, CD38, and light chain restricted to kappa only, but only IGH-MM expressed IGH. C, Clinical measurements of serum monoclonal (M) protein and free kappa light chain for patient #1093 from diagnosis through their disease course up to the date of transition to comfort care. D, UMAPs of scRNA-seq data from each timepoint individually, showing the two MM cluster (LCE-MM and IGH-MM) relative contributions from each sample. E, LCE-MM and IGH-MM were present at diagnosis, and only LCE-MM was present at first relapse. ASCT, autologous stem cell transplant; Benda, bendamustine; DCEP, dexamethasone, cyclophosphamide, etoposide, and cisplatin; DPD, daratumumab, pomalidomide, and dexamethasone; Elo, elotuzumab; FKLC, free kappa light chain; HTB, Hematology Tissue Bank; K, carfilzomib; KPD, carfilzomib, pomalidomide, and dexamethasone; MKs, megakaryocytes; Monos, monocytes; NK, natural killer; Progen, progenitors; RBCs, red blood cells; Rel, relapse; RVD, revlimid, velcade, and dexamethasone.
Data from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Abstract
High-risk multiple myeloma is genomically unstable, comprising heterogeneous populations of tumor cells that evolve over time. Light chain escape (LCE) is a clinical phenomenon observed when light chains rise separately from M-spike values, which implies divergent tumor evolution. We sought to understand LCE by performing high-depth transcriptomic and phenotypic studies. We performed single-cell RNA-sequencing (scRNA-seq) and ex vivo drug sensitivity profiling on serial bone marrow biopsies from a patient with LCE at diagnosis, first relapse, and relapsed/refractory timepoints. scRNA-seq revealed distinct transcriptomic subpopulations with phenotypes that could be tracked separately by clinical serum light chain and M-spike values. Genes differentially expressed between subpopulations were assessed for generalizable effects on prognosis from the Multiple Myeloma Research Foundation CoMMpass and GSE24080 datasets. Notably, the LCE subpopulation exhibited gene expression profile featuring prominent LAMP5 overexpression, which was associated with risk for osteolytic bone lesions. Ex vivo drug sensitivity testing displayed differential sensitivity of the subpopulations. Copy number variant inference showed that the transcriptomic subpopulation underlying LCE was related to a genetic subclone that evolved over time. Our findings illustrate that malignant subpopulations underly LCE in multiple myeloma. These studies imply that LCE and LAMP5 gene overexpression portends for increased risk of osteolytic bone disease and adverse prognosis, findings that were confirmed in the subset of patients from the CoMMpass database with LCE.
Significance:
scRNA-seq was used to study a patient with high-risk multiple myeloma featuring LCE. LCE was rooted in a transcriptomic subpopulation that corresponded to a genetic subclone and established novel links between LCE and LAMP5 overexpression to osteolysis and prognosis, validated in RNA-seq databases.
Increased Plasma Pyruvate Kinase M2 (PK‐M2) in Heart Failure: A Novel Biomarker Related to Cardiac Function and its Clinical Implications
Authors: Cao Lu , Dong Xiaoyu , Chen Fuzhong , Li Guangjuan , Fang Jiale , Han Zhijun , Wang Junhong
Published: January 2025

Background

The purpose of this study was to investigate whether circulating pyruvate kinase M2 (PK‐M2) levels are elevated in the peripheral blood and to assess their association with diagnosis and prognosis in patients with heart failure (HF).

Methods and Results

We conducted a prospective investigation involving 222 patients with HF and 103 control subjects, measuring PK‐M2 concentrations using ELISA. The primary outcome, assessed over a median follow‐up of 2 years (interquartile range: 776 to 926 days), was the time to the first occurrence of either rehospitalization for worsening HF or cardiovascular death. Patients with HF had higher PK‐M2 levels than controls (17.4±4.1 versus 7.8±2.3 U/mL,
P
<0.001), and these levels correlated with HF severity (New York Heart Association cardiac function class). Patients with reduced left ventricular ejection fraction had higher PK‐M2 concentrations than those with preserved ejection fraction (18.3±4.5 versus 16.7±3.6 U/mL,
P
<0.01). In a subset of patients with HF (n=52), PK‐M2 levels significantly decreased following standardized HF treatment (mean difference, −4.3±0.5 U/mL,
P
<0.001). A high PK‐M2 level had a 1.913‐fold higher risk of the primary outcome (
P
=0.033) after adjusting for multiple cardiovascular risk factors, but not with cardiovascular death. Additionally, PK‐M2 added incremental prognostic value beyond clinical predictors and N‐terminal pro‐brain natriuretic peptide (
P
<0.05).

Conclusions

Elevated PK‐M2 levels are associated with primary outcomes and rehospitalization for worsening heart failure in patients with HF. These findings suggest that PK‐M2 is a potential biomarker for HF diagnosis and prognosis, warranting consideration for serial patient assessment.
Development of an Integrated Modeling Framework for Visibility and Air Quality Forecasting in Delhi
Authors: Jayakumar A. , Anurose T. J. , Bhati Shweta , Hendry Margaret A. , Hayman Garry , Gordon Hamish , Field Paul , Mohandas Saji , Rumbold Heather , Yadav Prafull , Dhangar Narendra Gokul , Parde Avinash , Wagh Sandeep , Ghude Sachin , Ross Andrew N. , Smith Daniel , Dorling Stephen , George John P. , Prasad V. S. , Ravichandran M.
Published: January 2025

Rapid urbanization has subjected the megacities of developing countries to various environmental stresses. Delhi, a major Indian megacity, faces increasing urban stress leading to reduction in air quality and visibility. These challenges necessitate an integrated modeling framework to mitigate adverse environmental impacts on public health. Therefore, we have developed an advanced version of the high-resolution Delhi Model with Chemistry and aerosol framework (DM-Chem) at the National Centre for Medium Range Weather Forecasting (NCMRWF) under the Weather and Climate Science for Service Partnership India (WCSSP India) project. This collaborative initiative between India and the United Kingdom aims to provide real-time forecasts of visibility and fine particulate matter (PM2.5) for Delhi and neighboring regions during the winter season. The DM-Chem framework is unique due to its detailed urban canopy scheme and realistic aerosol representation, making it well suited for city-scale forecasts. It is designed to predict extreme fog and pollution events in the winter season. Here, we discuss the major physical parameterization improvements for the model, along with its skill and deficiencies in predicting extreme events. Notably, irrigation effects on surrounding agricultural areas have significantly improved fog and visibility forecasts, but have degraded the wind forecasts. We demonstrate the applicability of this modeling framework to study aerosol–radiation interaction during fog holes and discuss its potential to be applied or adapted to other megacities worldwide.