bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-bacterial thrombotic endocarditis: a clinical and pathophysiological reappraisal
Authors: Ahmed Omair , King Nicholas E , Qureshi Muhammad Ahmad , Choudhry Abira Afzal , Osama Muhammad , Zehner Carl , Ali Abdelrahman , Hamzeh Ihab R , Palaskas Nicolas L , Thompson Kara A , Koutroumpakis Efstratios , Deswal Anita , Yusuf Syed Wamique
Published: November 2024

Non-bacterial thrombotic endocarditis (NBTE), formerly recognized as marantic endocarditis, represents a rare cardiovascular pathology intricately linked with hypercoagulable states, notably malignancy and autoimmune disorders. Characterized by the development of sterile vegetations comprised of fibrin and platelets on cardiac valves, NBTE poses a diagnostic challenge due to its resemblance to infective endocarditis. Therapeutic endeavours primarily revolve around addressing the underlying aetiology and instituting anticoagulant regimens to forestall embolic events, with surgical intervention seldom warranted. Non-bacterial thrombotic endocarditis frequently coexists with malignancies and autoimmune conditions, such as lupus and antiphospholipid antibody syndrome, and, more recently, has been associated with COVID-19. Its pathogenesis is underpinned by a complex interplay of endothelial dysfunction, hypercoagulability, hypoxia, and immune complex deposition. Clinical manifestations typically manifest as embolic phenomena, particularly cerebrovascular accidents, bearing substantial mortality rates. Diagnosis necessitates a high index of suspicion and meticulous exclusion of infective endocarditis, often facilitated by advanced cardiac imaging modalities. Anticoagulation, typically employing low molecular weight heparin or warfarin, constitutes the cornerstone of pharmacological intervention. Surgical recourse may be warranted in instances of refractory heart failure or recurrent embolic events. Given its multifaceted nature, the management of NBTE mandates a multidisciplinary approach, with prognosis contingent upon individual clinical intricacies. Future endeavours should prioritize further research to refine therapeutic strategies and enhance patient outcomes.
Prevalent findings on low-dose CT scan lung cancer screening: a French prospective pilot study
Authors: Grenier Philippe A , Arutkin Maxence , Brun Anne Laure , Métivier Anne-Cécile , Sage Edouard , Haziza Franck , Ackermann Félix , Mellot François , Vallée Alexandre
Published: November 2024

Despite significant therapeutic advances, lung cancer remains the biggest killer among cancers. In France, there is no national screening program against lung cancer. Thus, in this perspective, the Foch Hospital decided to implement a pilot and clinical low-dose CT screening program to evaluate the efficiency of such screening. The purpose of this study was to describe the prevalent findings of this low-dose CT screening program. Participants were recruited in the screening program through general practitioners (GPs), pharmacists, and specialists from June 2023 to June 2024. The inclusion criteria included male or female participants aged 50 to 80 years, current smokers or former smokers who had quit less than 15 years prior, with a smoking history of over 20 pack-years. Chest CT scans were conducted at Foch Hospital using a low-dose CT protocol based on volume mode with a multi-slice scanner (≥60 slices) without contrast injection. In total, 477 participants were recruited in the CT scan screening, 235 (49%) were males with a median age of 60 years [56–67] and 35 smoke pack-years [29–44] and 242 females (51%) with a median age of 60 years [55–60] and 30 smoke pack-years [25–40]. Eight participants showed positive nodules on CT scan, as a 1.7% rate. 66.7% of diagnosed cancers were in early stages (0-I). It is feasible to implement structured lung cancer screening using low-dose CT in a real-world setting among the general population. This approach successfully identifies most early-stage cancers that could be treated curatively.
Variation in general practitioners’ follow-up of depressed patients starting antidepressant medication: a register-based cohort study
Authors: Hansen Anneli B , Hetlevik Øystein , Baste Valborg , Haukenes Inger , Smith-Sivertsen Tone , Ruths Sabine
Published: November 2024

Background

Guidelines recommend follow-up within 2 weeks for patients starting medication for depression. Knowledge is lacking about how general practitioners’ (GPs) follow-up varies with patients’ sociodemographic characteristics.

Objective

To describe follow-up by GP and specialist in mental healthcare provided to men and women with depression within 3 months of starting drug therapy. Furthermore, to examine whether follow-up varied according to patients’ age and education.

Methods

Registry-based cohort study comprising all patients aged ≥18 years in Norway with a new depression episode in 2014 who started on antidepressants within 12 months from diagnosis. Patients’ age and educational level were the exposures. Outcomes were follow-up by GP and/or mental healthcare specialist, and talking therapy with GP, within 90 days of first prescription. Cox proportional hazard models were used to estimate the likelihood of having follow-up contacts. Log binomial regression analysis was performed to explore the likelihood of having talking therapy with a GP. Time to first contact was illustrated by Kaplan–Meier survival curves.

Results

The study population comprised 17 000 patients, mean age 45.7 years, 60.6% women. Only 27.8% of the patients were followed up by GP and/or specialist within 2 weeks of the first drug dispensing, 67.1% within 90 days. Older or less educated men and women received less and later contacts than the younger or more highly educated.

Conclusions

Differences in age and educational level were associated with follow-up of depressed patients who started medication. This may indicate unwarranted variation in depression care that GPs should consider when prescribing antidepressants.
Accessing microbial natural products of the past
Authors: Klapper Martin , Stallforth Pierre
Published: November 2024

Microbial natural products—low molecular weight compounds biosynthesized by microorganisms—form the foundation of important modern therapeutics, including antibiotics, immunomodulators, and anti-cancer agents. This perspective discusses and contrasts two emerging approaches for uncovering natural products of the past. On the one hand, ancestral sequence reconstruction allows recreating biosynthetic pathways that date back hundreds of millions of years. On the other hand, sequencing and de novo assembly of ancient DNA reveals the biosynthetic potential of ancient microbial communities up to 100 000 years. Together, these approaches unveil an otherwise hidden reservoir of functional and structural molecular diversity. They also offer new opportunities to study the biological function and evolution of these molecules within an archaeological context.
Higher-Order Disease Interactions in Multimorbidity Measurement: Marginal Benefit Over Additive Disease Summation
Authors: Wei Melissa Y , Tseng Chi-Hong , Kang Ashley J
Published: November 2024

Background

Current multimorbidity measures often oversimplify complex disease interactions by assuming a merely additive impact of diseases on health outcomes. This oversimplification neglects clinical observations that certain disease combinations can exhibit synergistic effects. Thus, we aimed to incorporate simultaneous higher-order disease interactions into the validated ICD-coded multimorbidity-weighted index, to assess for model improvement.

Methods

Health and Retirement Study participants with linked Medicare data contributed ICD-9-CM claims, 1991–2012. Top 20 most prevalent and impactful conditions (based on associations with decline in physical functioning) were assessed through higher-order interactions (2-way, 3-way). We applied the least absolute shrinkage and selection operator and bootstrapping to identify and retain statistically significant disease interactions. We compared model fit in multimorbidity-weighted index with and without disease interactions in linear models.

Results

We analyzed 73 830 observations from 18 212 participants (training set N = 14 570, testing set N = 3 642). Multimorbidity-weighted index without interactions produced an overall R2 = 0.26. Introducing 2-way interactions for the top 10 most prevalent and impactful conditions resulted in a R2 = 0.27, while expanding to top 20 most prevalent and impactful conditions yielded a R2 = 0.26. When adding 3-way interactions, the same top 10 conditions produced a R2 = 0.26, while expanding to top 20 conditions resulted in a R2 = 0.24.

Conclusions

We present novel insights into simultaneous higher-order disease interactions for potential integration into multimorbidity measurement. Incorporating 2-way disease interactions for the top 10 most prevalent and impactful conditions showed a minimal improvement in model fit. A more precise multimorbidity index may incorporate both the main effects of diseases and their significant interactions.
Body waves from train noise correlations: potential and limits for monitoring the San Jacinto Fault, CA
Authors: Higueret Quentin , Sheng Yixiao , Mordret Aurelien , Brenguier Florent , Boué Pierre , Fichtner Andreas , Vernon Frank , Krischer Lion , Hollis Dan , Aubert Coralie , Ben-Zion Yehuda
Published: November 2024

A large portion of the stress release on seismic faults remains silent and undetected, requiring the development of novel observation techniques. Measuring traveltime perturbations from the correlation of ambient seismic noise at different stations is a well-known approach to assess temporal changes in seismic velocities, which can provide insights into hydrologic, tectonics and volcanic dynamic processes. In this work, we study the specific case of a P-wave phase retrieved from the correlation of freight train noise in Southern California and evaluate its potential to detect localized velocity changes along the San Jacinto Fault. We use a full waveform modelling approach to simulate this P-wave interference and further assess its sensitivity to the position of the train source, near-surface velocity changes and localized velocity changes in the fault zone. Our results show that the uncertainty in trains location can induce large traveltime biases which can be mitigated by averaging over many trains. Our results also highlight the weak sensitivity of these correlation P waves to near-surface velocity changes, while they show significant sensitivity to localized changes at depth. This modelling highlights the potential of monitoring traveltime perturbations of this ballistic P-wave interference to detect hidden slow-slip events on the San Jacinto Fault, particularly in identifying subtle velocity anomalies associated with fault zone changes that may otherwise go unnoticed by conventional seismic monitoring techniques.
Gravity data inversion of the Pyrenees range using Taguchi sensitivity analysis and ADMM bound constraints based on seismic data
Authors: Martin Roland , Ogarko Vitaliy , Giraud Jérémie , Plazolles Bastien , Angrand Paul , Rousse Sonia , Macouin Melina
Published: November 2024

Gravity inversion methods are able to recover density distributions in the Earth but they require strong constraints based on various prior information. In the present study, our aim is to invert gravity anomalies using existing geological models and density information in orogenic areas like the extensively studied Pyrenees region. Geophysical exploration for resource assessment using gravity and seismic data already accessible in this area has been performed to identify potential fluid/gas reservoirs of economic significance. For a given pre-existing model defined by different geological units and summarizing our knowledge of the area, we aim at retrieving the density distribution within each unit. For this, we use an Alternate Direction Multiplier Method to perform gravity data inversion by constrained by Interval Bound Constraints (IBC-ADMM) defined as bounding distribution intervals of possible density values. To estimate these bounding intervals, we first use a prior density model geologically compatible and obtained using geological information, gravity modelling, seismological data and seismic models. In a second step, we apply a Taguchi statistical analysis on representative density variations inside each unit of the prior density model to estimate their impact on data residuals, and reduce the parameter space prior to inversion. We perform the gravity data inversion constrained by these Taguchi-derived density intervals and we estimate model uncertainties for these density intervals. We apply the technique to the entire Pyrenees range at 2 km resolution. The sensitivity analysis shows that the strongest variations on gravity data are obtained essentially in the Axial Zone, in the middle and lower crust, and in the Upper mantle. Inverted densities are compared to the prior model. They are increased in the central part of the Pyrenees Axial Zone while, in the deeper structures (from middle crust down to upper mantle), they are decreased in the Southern (Spanish) Iberian upper mantle and increased in the Northern (French) Eurasian Upper mantle. A possible shortening of the Iberian lower crust–upper mantle system can be assumed below the western part of the Axial Zone.
On the variability of the site-response parameters of the active rock slope in Brienz/Brinzauls (Switzerland)
Authors: Borgeat X , Glueer F , Häusler M , Hobiger M , Fäh D
Published: November 2024

Unstable rock slopes, prone to collapse, pose an increasingly severe threat to both people and infrastructures, necessitating effective monitoring for risk mitigation. While many techniques rely on surface displacements to assess slope stability, seismic indicators such as resonance frequency, variations in seismic wave velocity and site amplification offer valuable insights into the structural integrity of the slope, aspects not captured by surface deformation alone. Research has demonstrated that these site-response parameters can serve as monitoring tools to detect precursory signs of failure, such as a drop in resonance frequency and relative seismic wave velocity prior to collapse. Still, environmental factors like temperature, precipitation, snow melt, earthquakes and freeze-thaw cycles transiently influence the seismic response. Our main objective is to understand the correlations and drivers between environmental parameters and seismic response, distinguishing between reversible and irreversible changes in dynamic behaviour. Over a 5-yr monitoring period, we continuously recorded ambient vibration data at the Brienz/Brinzauls instability and monitored three different site-response parameters (resonance frequency, site amplification, relative seismic wave velocity variation) using enhanced frequency domain decomposition, site-to-reference spectral ratio and single station ambient vibrations correlation techniques. Our results highlight a long-term increase in site amplification and a long-term decrease in first and second resonance frequencies, indicating ongoing structural weakening. Temperature was found to correlate with seasonal variations of seismic wave velocity with a few day’s time lag. Snow melting and rainfalls exerted a secondary influence, temporarily reducing relative seismic wave velocity during snowmelt and rainfall. Our findings suggest that single-station relative seismic velocity variations are mainly influenced by the shallow subsurface (depth of about 30 m), limiting its application to study the stability this deep structure.
ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats
Authors: Grillo Giacomo , Boyarchuk Ekaterina , Mihic Seed , Ivkovic Ivana , Bertrand Mathilde , Jouneau Alice , Dahlet Thomas , Dumas Michael , Weber Michael , Velasco Guillaume , Francastel Claire
Published: November 2024

Since its discovery as a causative gene of the Immunodeficiency with Centromeric instability and Facial anomalies syndrome, ZBTB24 has emerged as a key player in DNA methylation, immunity and development. By extensively analyzing ZBTB24 genomic functions in ICF-relevant mouse and human cellular models, we document here its multiple facets as a transcription factor, with key roles in immune response-related genes expression and also in early embryonic development. Using a constitutive Zbtb24 ICF-like mutant and an auxin-inducible degron system in mouse embryonic stem cells, we showed that ZBTB24 is recruited to centromeric satellite DNA where it is required to establish and maintain the correct DNA methylation patterns through the recruitment of DNMT3B. The ability of ZBTB24 to occupy centromeric satellite DNA is conserved in human cells. Together, our results unveiled an essential and underappreciated role for ZBTB24 at mouse and human centromeric satellite repeat arrays by controlling their DNA methylation and transcription status.
Evaluation of Immunoglobulin A Enzyme Immunoassays to Detect Primary Respiratory Syncytial Virus Infection in Infants and Young Children
Authors: Sankaranarayanan Ranjini , Ha Binh , Sun Heying , Liu Katie , Jadhao Samadhan , Hussaini Laila , McCracken Courtney , Gibson Theda , Yildirim Inci , Yi Jumi , Stephens Kathy , Korski Chelsea , Kao Carol , Rostad Christina A , Anderson Evan J , Anderson Larry J
Published: November 2024

Background

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children <2 years of age. Prior infection in a child is usually determined by RSV antibodies; however, in young children, persisting maternal immunoglobulin G antibodies can incorrectly indicate past RSV infection. We developed and evaluated 4 immunoglobulin A (IgA) antibody enzyme immunoassays (EIAs) with the RSV F, subgroup G (Ga or Gb proteins) or RSV lysate antigens to distinguish infection induced from persisting maternal RSV antibodies.

Methods

We tested the EIAs against 62 cord blood specimens (group A), 39 plasma specimens from infants not exposed to an RSV season (group B), 102 plasma specimens from infants with a documented RSV infection (group C), and 124 plasma specimens from infants exposed to their first RSV season but without a documented RSV infection (group D).

Results

Among the 2 negative control groups, no group A specimens and 1 of the group B specimens were positive in all 4 IgA EIAs, giving a specificity of 100% and 97%, respectively. The sensitivity of the F, Ga, Gb, and Lysate IgA EIAs were 88%, 31%, 26%, and 61%, respectively, for group C specimens. Forty-four percent of the 124 specimens in group D were positive in the RSV-F IgA EIA.

Conclusions

The RSV-F protein IgA EIA exhibited a high level of sensitivity and specificity for detecting previous RSV infections in the presence of maternal antibodies and can help in RSV clinical trials and epidemiologic studies in young children.
The influence mechanism analysis of family doctor team effectiveness: a mixed-method approach
Authors: He Anning , Guo Zhimin , Zhang Tao , Zhang Meng , Ni Ziling
Published: November 2024

Background

Team-based delivery of family doctor services is associated with improved patient experiences, better health outcomes, and more efficient healthcare utilization. Team effectiveness is related to the team’s output, and family doctor team effectiveness (FDTE) directly impacts the quality and efficiency of contracted family doctor services. We aimed to explore the path and mechanisms influencing FDTE, propose strategies for improvement, and enhance both team effectiveness and service quality.

Methods

The literature review, key informant interviews, expert consultation, and questionnaire survey were employed. The questionnaire, based on the input–mediator–output–input model, was designed to measure FDTE and its influencing factors. Using stratified random sampling, we distributed the questionnaire to family doctors in both developed and underdeveloped areas of Zhejiang Province, China. We performed hierarchical linear regression analysis to examine the relationship between team effectiveness and influencing factors. Subsequently, we used structural equation model (SEM) to explore and validate the relationships and mechanisms of action among “team input factors,” “member input factors,” “team behavioral process,” and “team emotional process” on team effectiveness.

Results

The questionnaire was divided into five main sections: “team input factors,” “member input factors,” “team behavioral process,” “team emotional process,” and “team effectiveness,” with 11 dimensions and 42 items. A total of 508 valid questionnaires were returned. The main factors influencing FDTE are team composition (β = −0.116, P < .01), goals and systems (β = 0.165, P < .01), cooperative attitude (β = 0.123, P < .05), team behavioral process (β = 0.161, P < .001), and team emotional process (β = 0.193, P < .001). SEM analysis revealed that team input factors, member input factors, and team behavioral process had direct and indirect effects on team effectiveness, while the team emotional process had a direct effect.

Conclusions

It is recommended to optimize the basic inputs of family doctor teams, enhance the intrinsic motivation of team members, promote team interaction and cooperation, and foster a positive atmosphere for family doctor teamwork.
Setting standards in residential aged care: identifying achievable benchmarks of care for long-term aged care services
Authors: Schwabe Johannes , Caughey Gillian E , Jorissen Robert , Comans Tracy , Gray Len , Westbrook Johanna , Braithwaite Jeffrey , Hibbert Peter , Wesselingh Steven , Sluggett Janet K , Wabe Nasir , Inacio Maria C
Published: November 2024

Background

Benchmark is an important aspect of quality measurement and evaluation of long-term care services (LTCS) performance. In this study, we aimed to estimate achievable benchmarks of care (ABC©) for 12 quality indicators used to monitor the quality of care in Australian LTCS and to identify LTCS characteristics associated with attaining the estimated ABC.

Methods

A cross-sectional study was conducted using integrated population-based datasets from long-term care, health care, and social welfare sectors within the Registry of Senior Australians (ROSA) National Historical Cohort. All LTCS residents in 2019 were included. Twelve risk-adjusted quality indicators were examined. ABC were defined as the performance level of top-ranked LTCS, including those sequentially from rank 1 onward, until the combined number of residents included at least 10% of all residents nationally. Indicator-specific ABC for 2019 were estimated using Bayesian-adjusted performance fraction ranking. Logistic regressions estimated LTCS characteristics associated with ABC attainment.

Results

2746 LTCS and 244 419 residents (≥65 years) between 1 January 2019 and 31 December 2019 were included. The cohort was mostly female (65%), with a median age of 86 years, and 56% had dementia. The ABC provide performance targets based on the observed levels of top-performing LTCS. The ABC for premature mortality (0.007%), weight loss hospitalizations (0.1%), pressure injuries (0.2%), delirium and dementia hospitalizations (0.2%), and medication-related adverse events (0.4%) were lower than 1% and attained by 17–59% of LTCS. The ABC for fractures (1.3%), falls (3.9%), and emergency department presentations (5.1%) were between 1 and 5% and attained by 7–11% of LTCS. The ABC for antipsychotic use (10.5%), chronic opioid use (12.6%), high sedative load exposure (26.8%), and antibiotic use (47.8%) were between 10 and 50% and met by 6–7% of LTCS. Smaller LTCS and government-owned LTCS were more likely to achieve the ABC compared to medium, larger, private, and not-for-profit LTCS.

Conclusion

This is the first national estimation of ABC for Australian LTCS, identifying real-world examples of LTCS with relatively better national performance. The ABC are realistic goals for LTCS improvement efforts. They can be leveraged as national standards in quality monitoring reports and incentive programs. Smaller and government LTCS were generally more likely to attain ABC.
Exploring the development of safety culture among physicians with text mining of patient safety reports: a retrospective study
Authors: Koike Daisuke , Ito Masahiro , Horiguchi Akihiko , Yatsuya Hiroshi , Ota Atsuhiko
Published: November 2024

Background

Safety culture development is essential for patient safety in healthcare institution. Perceptions of patient safety and cultural changes are reflected in patient safety reports; however, they were rarely investigated. The aim of this study was to investigate the perception of physicians and to explore the development of safety culture using quantitative content analysis for patient safety reports.

Methods

A retrospective analysis of free descriptions of harmful patient safety reports submitted by physicians was performed. Natural language processing and text analysis were conducted using the “KH Coder.” A co-occurrence analysis was performed in each period to identify and analyze the safety concepts. The study period was grouped into three for comparison.

Results

The patient safety reports from physicians were collected between April 2004 and March 2020. Of these, 3351 reports were harmful: 839 reports were included in period 1, 1016 reports in period 2, and 1496 reports in period 3. Natural language processing identified 316 307 words in the free descriptions of 3351 reports. We identified seven concepts from the cluster in co-occurrence analysis as follows: “explanation of adverse event to patients and families,” “central venous catheter,” “intraoperative procedure and injury,” “minimally invasive surgery,” “life-threatening events,” “blood loss,” and “medical emergency team and critical care.” These seven concepts showed significant differences among the three periods, except for “blood loss.” The “explanation of adverse event to patients and families” decreased in proportion from 11.3% to 8.8% (P < .05). The “central venous catheter” decreased from 17.3% to 11.3% (P < .01). Meanwhile, “minimally invasive surgeries” and “intraoperative procedures” increased from 3.9% to 12.9% (P < .01) and from 10.8% to 14.6% (P < .05), respectively. Focusing on patients’ events, “life-threatening events” decreased from 13.0% to 8.1% (P < .01); however, “medical emergency teams and critical care” increased from 3.3% to 10.6% (P < .01).

Conclusion

Free description in patient safety reports is useful for evaluating the safety culture. Co-occurrence analysis revealed multiple concepts of physicians’ perceptions. Quantitative content analysis revealed changes in perceptions and attitudes, and a disclosure policy of adverse events and the priority of patient care appeared with the development of safety culture.
Political Spaces Beyond the Nation State: The Global Commons in International Security Studies
Authors: Graefrath Moritz S , Jahn Marcel
Published: November 2024

The global commons have come to play an increasingly prominent role in the field of international security as scholars seek to better understand the causes and consequences of interstate cooperation, competition, and conflict in political spaces that lie beyond sovereign jurisdiction. In this piece, we make the case that by grouping all extraterritorial spaces into a single, not further differentiated conceptual category, the notion of the “global commons” as it is presently employed obscures important variation in the way these spaces are governed. Specifically, we argue that there exist two distinct types of spaces that legally do not belong to any one state: those that all states are effectively able to freely use for their own strategic purposes; and those that are de facto dominated and thus defy the ideal of universal accessibility their status as a global common supposedly entails. The updated conceptual framework we develop in response—which explicitly distinguishes between two distinct types of extraterritorial spaces—promises to advance security studies research on the global commons in several ways: it helps scholars avoid the issue of causal heterogeneity which current conceptual foundations introduce into causal analysis; it facilitates normative discussions about the global commons and their political future; and it produces novel insights into the governance problems policymakers will confront when seeking to maintain states’ access to extraterritorial spaces in the new age of great power competition.
Trophic modulation of endophytes by rhizosphere protists
Authors: Asiloglu Rasit , Bodur Seda Ozer , Samuel Solomon Oloruntoba , Aycan Murat , Murase Jun , Harada Naoki
Published: November 2024

The plant-microbe interactions, which is crucial for plant health and productivity, mainly occur in rhizosphere: a narrow zone of soil surrounding roots of living plants. The rhizosphere hosts one of the most intense habitats for microbial prey–predator interactions, especially between predatory protists and bacteria. Here, based on two key facts, microbial predators modulate rhizobacterial community composition, and the rhizobacterial community is the primary source of root microbiome, endophytes; we hypothesized that predation upon rhizobacteria would modulate the community composition of endophytic bacteria. The effects of three taxonomically distinct axenic protist species (Acanthamoeba castellanii, Vermamoeba vermiformis, and Heteromita globosa) were tested in this study. To examine the robustness of the hypotheses, the experiments were conducted in three soil types characterized by distinct bacterial communities and physicochemical properties. The bacterial community compositions were analyzed with high throughput sequencing. Bacterial gene abundances were estimated with a real-time-PCR method. The results showed that protists modulated endophytic communities, which originated in the rhizosphere soil. The modulation of endophytic communities by protists showed chaotic patterns rather than a deterministic effect under different soil types. The observed chaotic dynamics were further confirmed with an additional experiment, in which chaos was triggered by changes in the dilution rates of soil nutrients. Furthermore, the presence of predators enhanced the root colonization of endophytes. Our findings identify a key mechanism for the modulation of root endophytes and enhance understanding of underground plant-microbe interactions, which can lead to open new avenues for modulating the root microbiome to enhance crop production.
Alternative polyadenylation landscape of longissimus dorsi muscle with high and low intramuscular fat content in cattle
Authors: Li Chenglong , Xu Junjie , Zhang Yanfeng , Ding Yanling , Zhou Xiaonan , Su Zonghua , Qu Chang , Liang Jiahao , Han Yurun , Wang Dingxiang , Shi Yuangang , Li Cong-Jun , Liu George E , Kang Xiaolong
Published: November 2024

Intramuscular fat content is one of the most important factors affecting beef quality. However, the role of alternative polyadenylation (APA) in intramuscular fat deposition remains unclear. We compared APA events in muscle samples from high and low intramuscular fat (IMF) cattle, based on RNA-seq data. A total of 363 significant APAs were identified. Notably, the number of shortened 3ʹUTR events exceeded the number of lengthened 3ʹUTR events, and genes associated with shortened 3ʹUTR events were enriched in fatty acid metabolism-related pathways. Most APA events had alternative 3ʹUTR (aUTR) lengths of 200 to 300 bp. As the 3ʹUTR lengthened, the aUTR also lengthened (R2 = 0.79). These findings indicate that genes with longer 3ʹUTRs are more likely to be regulated by APA in the muscle of cattle with high IMF. To determine whether the identified APA events drove alterations in the expression of fat deposition-related genes, we analyzed the relationship between APA events and differentially expressed genes and identified several genes critical for fat deposition (e.g., PFKL and SLC1A5). Since miRNAs usually bind to the 3’UTR region of protein-coding genes and affect gene expression, we constructed an miRNA-APA network to detect several key miRNAs that may regulate fat deposition. We identified 10 important miRNAs that affect changes in IMF content, which may be gained (gained miRNA-binding sites) or lost (lost miRNA-binding sites) owing to 187 differential APA events. Our study characterized the APA profiles of cattle with high and low intramuscular fat content and provided further insights into the relationship between APA, miRNA, and fat deposition.
Optimization of a disposable pipette tips extraction for the analysis of psychoactive substances in sweat specimens using design of experiments
Authors: Gomes Nayna Cândida , Bigão Vítor Luiz Caleffo Piva , de Campos Eduardo Geraldo , Cabrices Oscar , Costa Bruno Ruiz Brandão da , De Martinis Bruno Spinosa
Published: November 2024

Novel psychoactive substances continue to emerge in the marketplace and are often found as substances in traditional illicit drug materials and users are often unaware of the presence of other drugs. The proper identification and confirmation of the exposure to a drug is made possible when a biological specimen is collected and tested. Sweat is an alternative biological matrix of great interest for clinical and forensic analysis. One of the reasons is attributed to its expanded drug detection window, enabling a greater monitoring capacity, and provision of information on prospective drug use. However, the concentrations of drugs in sweat samples are often low, which requires highly sensitive and selective methods. Disposable pipette tips extraction (DPX) is a new miniaturized solid-phase extraction technique capable of efficiently extracting analytes from biological specimens, providing high recoveries, and requiring minimized solvent use. This study describes the development and optimization of two methods for the extraction of basic and neutral psychoactive substances from sweat samples using gas chromatography–mass spectrometry and Design of Experiments (DoE). The following extraction parameters were optimized by DoE techniques: sample volume, elution solvent volume, washing solvent volume, sample aspiration time, elution solvent aspiration time, and number of cycles performed, including the elution step. It was possible to design a simple extraction protocol that provided optimized recoveries for both basic and neutral compounds. The sum of analyte areas increased at a rate of 54.7% for compounds of basic character and 39.2% for compounds of neutral character. Therefore, our results were satisfactory, demonstrating that DPX can be successfully used for extracting the target drugs from sweat samples.
Thrombopoietic agents enhance bone healing in mice, rats, and pigs
Authors: Childress Paul J , Nielsen Jeffery J , Bemenderfer Thomas B , Dadwal Ushashi C , Chakraborty Nabarun , Harris Jonathan S , Bethel Monique , Alvarez Marta B , Tucker Aamir , Wessel Alexander R , Millikan Patrick D , Wilhite Jonathan H , Engle Andrew , Brinker Alexander , Rytlewski Jeffrey D , Scofield David C , Griffin Kaitlyn S , Shelley W Christopher , Manikowski Kelli J , Jackson Krista L , Miller Stacy-Ann , Cheng Ying-Hua , Ghosh Joydeep , Mulcrone Patrick L , Srour Edward F , Yoder Mervin C , Natoli Roman M , Shively Karl D , Gautam Aarti , Hammamieh Rasha , Low Stewart A , Low Philip S , McKinley Todd O , Anglen Jeffrey O , Lowery Jonathan W , Chu Tien-Min G , Kacena Melissa A
Published: November 2024

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte (MK) growth factor, thrombopoietin (TPO), and second-generation TPO agents using multiple animal models, including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical-sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (eg, thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells.
Applied deaf aesthetics toward transforming deaf higher education
Authors: Weber Joanne , Hayward Denyse , Skyer Michael , Snively Sarah
Published: November 2024

Deaf aesthetics is a theoretical framework we actualized to enhance interactions in deaf education, particularly via multimodal pedagogy and curricular experiences. Prior research illustrates that deaf aesthetics are desired by deaf teachers and students who are deaf; however, most instructional-delivery formats lack these supports. The present mixed-methodology, multi-method case study is an empirical evaluation of how deaf aesthetics contributed to the process of redesigning a course, including major revisions to instructional slide decks (e.g., PowerPoint, Google Slides, Prezi). The research question we examined is: How can instructional designers and university educators effectively design and use deaf aesthetics and multimodal curricula and pedagogies to prompt and sustain educational interactions with deaf or deafblind learners and teachers?
Bleeding disorders, longer operative time, and nongeneral anesthesia increase are associated with overnight admission after hip arthroscopy
Authors: Zhong Jack , Crutchfield Connor R , Lee Nathan J , Mueller John , Ahmad Christopher , Trofa David , Lynch Thomas Sean
Published: November 2024

Overnight admission is a rare but major complication after hip arthroscopy (HA), and the paucity of data surrounding its causes limits patient education and quality of care. The purpose of this study was to identify risk factors for an unanticipated overnight admission after HA and assess for associated complications. This analysis queried the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes to identify hip arthroscopies from 2005 to 2017. Patient demographics, perioperative variables, and comorbidities were compared between ambulatory and nonambulatory patients [length of stay (LOS) ≥ 1] using bivariate analysis. Multivariate stepwise logistic regression then identified independent risk factors of adverse outcomes. Linear regression analyzed correlation of LOS with age, operative time, modified fragility index (mFI-5), and year of operation. A total of 2420 cases were included in this study with 400 (16.5%) overnight admissions. The mean subject age was 40 ± 13.9 years old (58.1% female). Admitted patients generally had higher American Society of Anesthesiologists (ASA) scores and a higher mFI-5 index. Multivariate logistic regression showed that mFI-5 > 0, bleeding disorders, operative time >1.5 h, and nongeneral anesthesia were independent risk factors for prolonged hospital stay. Patients aged 31–40 years had decreased risk of LOS ≥1. Nonambulatory surgery was associated with significantly increased risk for any complication, readmission, wound complication, and venous thromboembolism. This analysis demonstrates that operations >1.5 h and increased medical comorbidities predispose patients to greater risk of being admitted to the hospital after HA. Surgeons should consider these data to optimize controllable factors and patient selection to reduce the risk of postoperative admission.
Individual survival prediction model for patients with leptomeningeal metastasis
Authors: Jirattikanwong Noraworn , Charoentum Chaiyut , Phenphinan Niphitphon , Pooriwarangkakul Phurich , Ruttanaphol Danusorn , Phinyo Phichayut
Published: November 2024

Background

Survival prediction for patients with leptomeningeal metastasis (LM) is crucial for making proper management plans and counseling patients. Prognostic models in this patient domain have been limited, and existing models often include predictors that are not available in resource-limited settings. Our aim was to develop a practical, individualized survival prediction model for patients diagnosed with LM.

Methods

We collected a retrospective cohort of patients diagnosed with LM from cerebrospinal fluid at Chiang Mai University Hospital from January 2015 to July 2021. Nine candidate predictors included male gender, age > 60 years, presence of extracranial involvement, types of primary cancer, the time between primary cancer and LM diagnosis, presence of cerebral symptoms, cranial symptoms, spinal symptoms, and abnormal CSF profiles. Flexible parametric survival analysis was used to develop the survival prognostic model for predicting survival at 3, 6, and 12 months after diagnosis. The model was evaluated for discrimination and calibration.

Results

161 patients with 133 events were included. The derived individual survival prediction model for patients with LM, or the LMsurv model, consists of three final predictors: types of primary cancer, presence of cerebral symptoms, and presence of spinal symptoms. The model showed acceptable discrimination (Harrell’s C-statistics: 0.72; 95% confidence interval 0.68–0.76) and was well calibrated at 3, 6, and 12 months.

Conclusions

The LMsurv model, incorporating three practical predictors, demonstrated acceptable discrimination and calibration for predicting survival in LM patients. This model could serve as an assisting tool during clinical decision-making. External validation is suggested to confirm the generalizability of the model.
Comparative analysis of oncological outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer utilizing propensity score matching
Authors: Kobayashi Keita , Fujii Nakanori , Shimizu Kosuke , Hitaka Yukihiro , Oka Shintaro , Nakamura Kimihiko , Hiroyoshi Toshiya , Isoyama Naohito , Hirata Hiroshi , Shiraishi Koji
Published: November 2024

Background

Bladder preservation therapy for muscle-invasive bladder cancer is reported to yield outcomes comparable to those of radical cystectomy, although it receives a relatively low recommendation grade in Japanese guidelines. This study aims to compare the outcomes of trimodal therapy versus radical cystectomy in the treatment of muscle-invasive bladder cancer.

Methods

This study is a single-center retrospective analysis that included patients treated with either trimodal therapy or radical cystectomy for muscle-invasive bladder cancer (cT2-4N0-2M0) at our institution between January 1998 and December 2022. Trimodal therapy is administered in cases where radical cystectomy is either unfeasible or declined by the patient, and both treatments are performed with the intent of curative outcomes. Propensity score matching was used to compare cancer-specific survival and overall survival rates.

Results

A total of 93 patients who underwent trimodal therapy and 84 who underwent radical cystectomy for muscle-invasive bladder cancer were analyzed. Using propensity score matching, 66 patients from each treatment group were selected for a comparative analysis of oncological outcomes. The 5-year distant metastasis-free, cancer-specific and overall survival rates were 64.3 and 51.8% (P = 0.096), 83.3 and 69.2% (P = 0.104) and 77.8 and 64.2% (P = 0.274) for trimodal therapy and radical cystectomy, respectively. Subgroup analyses revealed that trimodal therapy for primary tumors significantly improved cancer-specific survival rates compared with radical cystectomy. The two treatment types had similar adverse events related to hematologic toxicity during perioperative chemotherapy.

Conclusion

Trimodal therapy exhibited oncological outcomes comparable to those of radical cystectomy in the treatment of muscle-invasive bladder cancer, indicating that trimodal therapy provides favorable outcomes, particularly in cases of primary muscle-invasive bladder cancer.
Projected outcomes of reduced-biopsy management of Grade Group 1 prostate cancer: implications for relabeling
Authors: Zhao Yibai , Gulati Roman , Yang Zhenwei , Newcomb Lisa , Zheng Yingye , Zhu Kehao , Liu Menghan , Heijnsdijk Eveline A M , Haffner Michael C , Cooperberg Matthew , Eggener Scott E , De Marzo Angelo M , Kibel Adam S , Rizopoulos Dimitris , Hall Ingrid J , Etzioni Ruth
Published: November 2024

Background

Implications of relabeling Grade Group 1 prostate cancer as noncancer will depend on the recommended active surveillance strategy. Whether relabeling should prompt deintensifying, prostate-specific antigen (PSA)–based active monitoring approaches is unclear. We investigated outcomes of biopsy-based active surveillance strategies vs PSA-based active monitoring for Grade Group 1 diagnoses under different patient adherence rates.

Methods

We analyzed longitudinal PSA levels and time to Grade Group 2 or higher reclassification among 850 patients with a diagnosis of Grade Group 1 disease from the Canary Prostate Active Surveillance Study (2008-2013). We then simulated 20 000 patients over 12 years, comparing Grade Group 2 or higher detection under biennial biopsy against 3 PSA-based strategies: (1) PSA (biopsy for PSA change ≥20% per year), (2) PSA plus magnetic resonance imaging (magnetic resonance imaging for PSA change ≥20% per year and biopsy for Prostate Imaging Reporting & Data System ≥3), and (3) predicted risk (biopsy for predicted upgrading risk ≥10%).

Results

Under biennial biopsies and 20% dropout to active treatment, 17% of patients had a 2-year or longer delay in Grade Group 2 or higher detection. The PSA strategy reduced the number of biopsies by 39% but delayed detection in 32% of patients. The PSA plus magnetic resonance imaging strategy reduced the number of biopsies by 52%, with a 34% delay. The predicted risk strategy reduced the number of biopsies by 31%, with only an 8% delay. These findings are robust to biopsy sensitivity and confirmatory biopsy.

Conclusions

Prostate-specific antigen–based active monitoring could substantially reduce biopsy frequency; however, a precision strategy based on an individual upgrading risk is most likely to minimize delays in detection of disease progression. This strategy may be preferred if active surveillance is deintensified under relabeling, provided patient adherence remains unaffected.