bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty estimation in diagnosis generation from large language models: next-word probability is not pre-test probability
Authors: Gao Yanjun , Myers Skatje , Chen Shan , Dligach Dmitriy , Miller Timothy , Bitterman Danielle S , Chen Guanhua , Mayampurath Anoop , Churpek Matthew M , Afshar Majid
Published: January 2025

Objective

To evaluate large language models (LLMs) for pre-test diagnostic probability estimation and compare their uncertainty estimation performance with a traditional machine learning classifier.

Materials and Methods

We assessed 2 instruction-tuned LLMs, Mistral-7B-Instruct and Llama3-70B-chat-hf, on predicting binary outcomes for Sepsis, Arrhythmia, and Congestive Heart Failure (CHF) using electronic health record (EHR) data from 660 patients. Three uncertainty estimation methods—Verbalized Confidence, Token Logits, and LLM Embedding+XGB—were compared against an eXtreme Gradient Boosting (XGB) classifier trained on raw EHR data. Performance metrics included AUROC and Pearson correlation between predicted probabilities.

Results

The XGB classifier outperformed the LLM-based methods across all tasks. LLM Embedding+XGB showed the closest performance to the XGB baseline, while Verbalized Confidence and Token Logits underperformed.

Discussion

These findings, consistent across multiple models and demographic groups, highlight the limitations of current LLMs in providing reliable pre-test probability estimations and underscore the need for improved calibration and bias mitigation strategies. Future work should explore hybrid approaches that integrate LLMs with numerical reasoning modules and calibrated embeddings to enhance diagnostic accuracy and ensure fairer predictions across diverse populations.

Conclusions

LLMs demonstrate potential but currently fall short in estimating diagnostic probabilities compared to traditional machine learning classifiers trained on structured EHR data. Further improvements are needed for reliable clinical use.
Bone turnover markers predict changes in bone mineral density in men treated with abaloparatide: results from the abaloparatide for the treatment of men with osteoporosis (ATOM) study
Authors: Eastell Richard , Brown Jacques P , Adler Robert A , Lewiecki E Michael , Binkley Neil , Orwoll Eric S , Kendler David , Mitlak Bruce H , Wang Yamei
Published: January 2025

Early increases in bone turnover markers (BTMs) in response to anabolic therapy correlate with 18-mo BMD increases in postmenopausal women with osteoporosis; however, this relationship has not been assessed in men. In this analysis, the correlation between changes from baseline in fasting intact serum procollagen type I N propeptide (PINP) and serum CTX at 1, 3, 6, and 12 mo and percent increase from baseline in BMD at 12 mo in men from the randomized phase 3 ATOM study (NCT03512262) were evaluated using Pearson’s correlation coefficients. The uncoupling index (UI), a measure of the balance between markers of bone formation (PINP) and bone resorption (CTX), with positive UI favoring bone formation, was calculated. Results in men were compared to 12-mo results for women from the ACTIVE study using the z score test after Fisher’s Z transformation. In abaloparatide-treated men, PINP increases at 1 mo (r = 0.485), 3 mo (r = 0.614), 6 mo (r = 0.632), and 12 mo (r = 0.521) were highly correlated (p < .0001) with 12-mo LS BMD increases. The mean UI for abaloparatide-treated men was greater than placebo as early as 1 mo (2.26 vs −0.25). At month 3, the mean UI for men was greater (1.32) than for women (0.88) (p < .001). There was a significant correlation between 3-mo UI and LS BMD at 12 mo in both men (r = 0.453; p < .001) and women (r = 0.252; p < .01). UI at months 6 and 12 were also significantly correlated with 12-mo LS BMD in men and women, but the correlation was stronger in men than women. These data support that early changes in BTMs in men treated with abaloparatide are associated with subsequent changes in BMD similar to what has been reported in women.
Ethanol release patterns and captures of Xylosandrus spp. (Coleoptera: Curculionidae) in ornamental nursery
Authors: Govindaraju Ramkumar , Joseph Shimat V
Published: January 2025

Xylosandrus crassiusculus Motschulsky and Xylosandrus germanus Blandford are serious ambrosia beetle pests in ornamental nurseries. Three ethanol baits, AgBio low release (LR), AgBio high release (HR), and Trécé are commercially available for use in bottle traps to determine flight activity of adult Xylosandrus spp. However, release patterns of ethanol from these baits under varying temperatures and captures of Xylosandrus spp. are poorly understood. Thus, the objectives of this study were (i) to determine ethanol release rates from these baits under constant and variable temperatures and (ii) to compare relative adult Xylosandrus spp. captures using these baits in ornamental nurseries. When 3-d difference (3-d difference) bait weights were recorded under constant 15.6, 21.1, 26.7, and 32.2 °C, an increase in release rates was recorded with an increase in temperature from 15.6 to 32.2 °C for LR bait. At 32.2 °C, no increase or reduction in the 3-d-difference weights was found for the HR and Trécé baits, respectively, compared to LR bait. The 3-d-difference weights were steady with all 3 baits when temperatures gradually increased and decreased in variable sequence for 30 d. In 2022, 2023, and 2024, although all 3 baits captured adult X. crassiusculus and X. germanus, LR bait captured significantly more numbers of X. crassiusculus than the other 2 baits in 2022 and 2023, and in 2024, X. crassiusculus captures were greater in traps with the Trécé bait than the other 2 baits. Thus, ethanol baits can effectively detect the early flight activity of Xylosandrus spp. adults in ornamental nurseries.
The Book of Malachi: Its Place in the Twelve Minor Prophets, in Jewish and in Christian Canon
Authors: Kalimi Isaac
Published: January 2025

This study discusses the establishment of the corpus of the Twelve Minor Prophets into which the book of Malachi is integrated. The grouping of the Twelve in one body was known prior to the second century bce, and the Baraita explains the necessity of putting them together. After exploring the place, literary status, and standing of Malachi within the Twelve and the Prophets more generally, the study examines whether or not the canonicity of the book was disputed among Jews and Christians. Malachi plays a significant role in the Jewish canon: It connects Nebe’im with Torah, serves as a transition from Prophets to Writings, and is the transition point from the Written to the Oral Torah. In the Christian canon, Malachi is located at the end of the Old Testament, just before Matthew that opens the New Testament and recounts the birth of Jesus. That Elijah is forerunner of the Messiah is common to Jewish and Christian tradition. However, while in Judaism he will appear again, in Christianity, he has already appeared and was identified with John the Baptist who announced Jesus as Christ.
Breaking vaccination barriers among migrants? Human rights and crisis preparedness
Authors: Litins’ka Yana
Published: January 2025

Vaccination hesitancy is one of the critical threats to public health. The coronavirus disease pandemic reconfirmed that certain groups of populations are more reluctant to vaccinate than others, particularly migrants. This article examines legal obligations related to protecting the right to health in addressing vaccination barriers among newly arrived adult migrants, taking Ukrainians granted temporary protection as an example. From human rights law requirements delineated by the United Nations and Council of Europe, it maps out a framework of vaccination-related obligations. Furthermore, the article tests the framework created in one national legal system—Sweden—to show where the gaps in transposing obligations into national law still exist. To deepen the analysis, the interview study with Ukrainian refugees in Sweden is presented, which allows reflection on what obligations have not reached their recipients and resulted in vaccination barriers. The article advocates for further specification of obligations related to vaccinations in both national and international laws for better crisis preparedness.
The onset of bar formation in a massive galaxy at z ∼ 3.8
Authors: Amvrosiadis A , Lange S , Nightingale J W , He Q , Frenk C S , Oman K A , Smail I , Swinbank A M , Fragkoudi F , Gadotti D A , Cole S , Borsato E , Robertson A , Massey R , Cao X , Li R
Published: January 2025

We examine the morphological and kinematical properties of SPT-2147, a strongly lensed, massive, dusty, star-forming galaxy at $z = 3.762$. Combining data from JWST, Hubble Space Telescope, and ALMA, we study the galaxy’s stellar emission, dust continuum, and gas properties. The imaging reveals a central bar structure in the stars and gas embedded within an extended disc with a spiral arm-like feature. The kinematics confirm the presence of the bar and of the regularly rotating disc. Dynamical modelling yields a dynamical mass, ${M}_{\rm dyn} = (9.7 \pm 2.0) \times 10^{10}$${\rm M}_{\odot }$, and a maximum rotational velocity to velocity dispersion ratio, $V / \sigma = 9.8 \pm 1.2$. From multiband imaging we infer, via spectral energy distribution fitting, a stellar mass, ${M}_{\star } = (6.3 \pm 0.9) \times 10^{10}$$\rm {M}_{\odot }$, and a star formation rate, ${\rm SFR} = 781 \pm 99$${\rm {\rm M}_{\odot } yr^{-1}}$, after correcting for magnification. Combining these measurements with the molecular gas mass, we derive a baryonic-to-total mass ratio of ${M}_{\rm bar} / {M}_{\rm dyn} = 1.1 \pm 0.3$ within 4.0 kpc. This finding suggests that the formation of bars in galaxies begins earlier in the history of the Universe than previously thought and can also occur in galaxies with elevated gas fractions.
Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology
Authors: Deligne Clémence , Tourbez Arthur , Bénard Flavie , Meyer Swann , Curt Alexis , Gianesello Matteo , Hamadou Maud , Clavier Léna , Coquet Claire , Bocquet Charlotte , Tomine Julia , Diot Thomas , Paraqindes Hermes , Marcel Virginie , Berthelot Clément , Engel Justine , Rochet Isabelle , Barritault Marc , Savary Clara , Gadot Nicolas , Attignon Valéry , Carrere Marjorie , Billaud Marc , Dutour Aurélie , Cordier-Bussat Martine , Beuriat Pierre-Aurélien , Szathmari Alexandru , Di Rocco Federico , Blay Jean-Yves , Tiberi Luca , Vasiljevic Alexandre , Meyronet David , Castets Marie , Leblond Pierre , Broutier Laura
Published: January 2025

Background

Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help define new therapeutic options for pediatric brain tumors.

Methods

Through an integrative approach based on our expertise and a careful review of the literature about glioblastoma 3D primary cultures, we set up a standardized methodological pipeline for the establishment, characterization, and biobanking of PDT-O through direct 3D in vitro culture of the deadliest pediatric glial brain tumors. To assess PDT-O fidelity and validate their preclinical relevance, we performed comprehensive histological, molecular, and drug-response analyses.

Results

Our methodological pipeline allowed the rapid and efficient generation of PDT-O recapitulating their parental tumor features, including intratumoral heterogeneity, even after several passages and cryopreservation/revival as 3D cultures. Moreover, we successfully performed preclinical test responses on these PDT-O to standard-of-care therapies and new therapeutic options. Finally, we identified ONC201 as a selective drug for pediatric glial tumor types not restricted to H3K27-altered glial tumors, as well as combination strategies to increase the therapeutic response to ONC201.

Conclusions

Hence, we describe a fast and robust process to biobank PDT-O for pediatric glial brain tumors. These PDT-O models have the potential for patient-specific modeling even after long-term expansion in vitro, and we established the proof-of-concept of their usefulness to support powerful preclinical studies.
Global elevation of algal bloom frequency in large lakes over the past two decades
Authors: Wang Ying , Zhao Dan , Woolway R Iestyn , Yan Haoran , Paerl Hans W , Zheng Yi , Zheng Chunmiao , Feng Lian
Published: January 2025

The recent increase in algal blooms in lakes, potentially exacerbated by climate warming, is of global concern. However, a spatially and temporally detailed characterization of algal bloom trends at a global scale has been lacking, posing challenges to definitively attribute the increase trend to warming as a primary driver. Here, we used daily MODIS satellite observations from 2003 to 2022 to analyze algal bloom trends in 1956 large freshwater lakes worldwide. Among these lakes, 620 have experienced algal bloom events in over half of the years during the past two decades, with an upward trend in bloom frequency observed in 504 lakes. This trend is particularly prominent in subtropical regions and has become most pronounced after 2015. The global median annual bloom frequency has significantly increased at a rate of +1.8%/yr over the past two decades, showing a significant correlation with air temperatures (r2 = 0.43, P < 0.05). Furthermore, in 44.8% of the bloom-affected lakes, we observed a strong correlation between air temperature and bloom frequency. Our study helps clarify the factors contributing to the global expansion of algal blooms and emphasizes the urgent need to recognize and address this growing environmental challenge within the context of climate warming.
Cotinine-Measured Secondhand Smoke Exposure Among Federal Housing Assistance Recipients Without Active Tobacco or Nicotine Use in the United States: NHANES, 2007–2018
Authors: Stierman Bryan , Helms Garrison Veronica , Brody Debra J , Bachand Jacqueline V
Published: January 2025

Introduction

The prevalence of cigarette smoking is high among U.S. Department of Housing and Urban Development (HUD) assistance recipients, putting others at risk for secondhand smoke (SHS) exposure. We evaluated the burden of SHS exposure among HUD-assisted children, adolescents, and adults.

Aims and Methods

Using 2007–2018 National Health and Nutrition Examination Survey (NHANES) data linked with HUD administrative data, we assessed SHS exposure prevalence, defined using serum cotinine, among non-tobacco, non-nicotine-using, HUD-assisted children and adolescents (ages 3–17 years, n = 955) and adults (ages ≥ 18 years, n = 878) and among low-income, HUD-unassisted children and adolescents (n = 5788) and adults (n = 8027). Time trends were evaluated. Unadjusted and adjusted multivariable logistic regression models were created to assess SHS exposure by HUD assistance status.

Results

The prevalence of SHS exposure during 2015–2018 was 73.2% (95% CI = 63.2% to 81.7%) among HUD-assisted children and adolescents and 50.1% (95% CI = 40.1% to 60.1%) among HUD-assisted adults. Decreases in SHS exposure among HUD-assisted individuals from 2007–2010 through 2015–2018 were significant only for ages 12–17 years (78.6% [95% CI = 68.0% to 87.0%] to 64.3% [95% CI = 52.5% to 74.9%]; p = .04). Among low-income individuals, SHS exposure was higher during 2007–2018 among HUD-assisted than HUD-unassisted children and adolescents (OR = 3.39 [95% CI = 2.58 to 4.47]) and adults (2.11 [95% CI = 1.66 to 2.68]). Results remained significant after adjusting for social, demographic, and housing characteristics.

Conclusions

HUD-assisted children, adolescents, and adults had higher exposure to SHS than those not receiving HUD assistance. SHS exposure among HUD-assisted individuals was high for all years studied, compared to published estimates for the general US population, but did decrease among children and adolescents aged 12–17 years.

Implications

This study is the first to provide biomarker-derived prevalence estimates of SHS exposure among recipients of HUD assistance within a nationally representative sample of the United States. The findings suggest that HUD-assisted children, adolescents, and adults are an at-risk population for SHS exposure, independent of known confounding social and demographic factors.
Genome-Wide Association Study of Varenicline-Aided Smoking Cessation
Authors: Coley Kayesha , Wang Qingning , Packer Richard , John Catherine , Abner Erik , Reis Kadri ,   Estonian Biobank Research Team, Bedair Khaled F , Srinivasan Sundararajan , Paciga Sara , Hyde Craig , Free Robert C , Reeve Nicola F , Shepherd David J , Esko Tõnu , Palmer Colin , Pearson Ewan , Malarstig Anders , Tobin Martin D , Batini Chiara
Published: January 2025

Introduction

Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date, no genome-wide association studies of varenicline response have been published.

Methods

In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes. We defined short-term varenicline effectiveness (SVE) and long-term varenicline effectiveness (LVE) by assessing smoking status at 3 and 12 months, respectively, after initiating varenicline treatment. In Stage 1, comprising five European cohort studies, we tested genome-wide associations with SVE (1405 cases, 2074 controls) and LVE (1576 cases, 2555 controls), defining sentinel variants (the most strongly associated variant within 1 Mb) with p-value < 5 × 10−6 to follow up in Stage 2. In Stage 2, we tested association between sentinel variants and comparable smoking cessation endpoints in varenicline randomized controlled trials. We subsequently meta-analyzed Stages 1 and 2.

Results

No variants reached genome-wide significance in the meta-analysis. In Stage 1, 10 sentinel variants were associated with SVE and five with LVE at a suggestive significance threshold (p-value < 5 × 10−6); none of these sentinels were previously implicated in varenicline-aided smoking cessation or in genetic studies of smoking behavior.

Conclusions

We provide initial insights into the biological underpinnings of varenicline-aided smoking cessation, through implicating genes involved in various processes, including gene expression, cilium assembly, and early-stage development.

Implications

Leveraging electronic health records, we undertook the largest genetic study of varenicline-aided smoking cessation to date, and the only such study to test genome-wide associations. We showed distinct genetic variants associated (p-value < 5 × 10−6) with varenicline-aided smoking cessation which implicate diverse cellular functions, including transcriptional regulation, RNA modification, and cilium assembly. These provide insights which, if independently corroborated, will improve understanding of varenicline response. The growing availability of biobank resources with genetic and varenicline response data will provide future opportunities for larger studies using the approach we developed.
Spanish Pistolerismo and Labour Violence in Post-War Europe, 1917–1923
Authors: Zoffmann Rodriguez Arturo
Published: January 2025

Political violence in Europe in 1917–23 has typically been associated with the destabilizing impact of the First World War. However, some forms of violence displayed continuities with the pre-1914 period and were not directly related to the war, as was the case with trade union violence. This article engages with debates about the character and causality of the convulsions that shook the continent in 1917–23 through the case study of labour violence in Spain. This country remained neutral throughout the conflagration but experienced episodes of intense social warfare connected to strikes that came to be known as pistolerismo (the rule of the gunman). Pistolerismo had a complex prehistory, but it crystallized in 1917–19 due to the economic fallout of the war and the radicalizing influence of the Russian Revolution. This study traces the evolution of labour violence in these years, exploring how neutrality shaped pistolerismo, the retaliatory logic of aggressions, the formation and professionalization of trade union armed detachments, and the entanglements between social and political violence. It does so by interweaving social and cultural approaches. Viewed through this prism, trade union violence stands out as an important driver of instability and polarization in post-war Europe.
A regulatory network involving calmodulin controls phytosulfokine peptide processing during drought-induced flower abscission
Authors: Wang Sai , Ge Siqi , Liu Xianfeng , Cheng Lina , Li Ruizhen , Liu Yang , Cai Yue , Meng Sida , Tan Changhua , Jiang Cai-Zhong , Qi Mingfang , Li Tianlai , Xu Tao
Published: January 2025

Drought stress substantially decreases crop yields by causing flowers and fruits to detach prematurely. However, the molecular mechanisms modulating organ abscission under drought stress remain unclear. Here, we show that expression of CALMODULIN2 (CaM2) is specifically and sharply increased in the pedicel abscission zone in response to drought and plays a positive role in drought-induced flower drop in tomato (Solanum lycopersicum). Due to partial functional redundancy with SlCaM6, we generated the Slcam2 Slcam6 double mutant, which showed minimal flower drop under drought. SlCaM2 and SlCaM6 interacted with the transcription factor signal responsive 3L (SlSR3L), with the 3 proteins operating in the same pathway, based on genetic data. We identified Protease inhibitor26 (SlPI26) as a target gene of SlSR3L by DNA affinity purification sequencing and transcriptome analysis. SlPI26 specifically inhibited the activity of the phytaspase SlPhyt2, hence preventing the generation of active phytosulfokine peptide and negatively regulating drought-induced flower drop. SlCaM2 and SlCaM6 enhanced the repression of SlPI26 expression by SlSR3L, promoting drought-induced flower drop. In addition, the nonphototropic hypocotyl3 (SlNPH3)–Cullin3 (SlCUL3) complex, which relies on auxin, interacted with SlSR3L to induce its degradation. However, under drought conditions, SlNPH3–SlCUL3 function is compromised due to lower auxin concentration. These results uncover a regulatory network that precisely controls floral drop in response to drought stress.
Challenges in the transition of care for rare connective tissue diseases: results from the 2023 ERN ReCONNET Transition of Care Task Force survey
Authors: Marrani Edoardo , Zajc Avramovic Mojca , Marinello Diana , Talarico Rosaria , Baldini Chiara , Collado-González Eva , Fonseca João Eurico , Schraven Linda , Oliveira Ramos Filipa , Triggianese Paola , Vissink Arjan , Mosca Marta , Avcin Tadej , Simonini Gabriele
Published: January 2025

Objectives

Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist. We aimed to inventory transitional care programs for rare CTDs across Europe.

Methods

In April 2023, the ERN ReCONNET Transition of Care Task Force, consisting of expert clinicians, patient advocates and coordination team members, created a survey to assess transitional care practices. The survey was distributed to ERN ReCONNET and ERN RITA centres and responses received by 15 March 2024 were analysed.

Results

A total of 67 responses from 59 centres across 20 European countries were collected. Paediatric rheumatologists typically initiated the transition process (49% of centres). Twenty centres had joint clinics. Despite positive self-assessments of transitional programs, significant limitations were noted. Transition policies varied, with only 40% of centres having a formal standardized policy and less than half of the centres adhering to available transition of care guidelines. Transfer readiness was evaluated using validated questionnaires in 13% of centres, while 29% transitioned patients based solely on age without any readiness assessments. The main challenges included finding adult-oriented centres and the lack of guidelines or engagement from adult centres. Adult healthcare providers also noted a lack of training in adolescent medicine.

Conclusion

The survey highlighted diverse transition practices and resources across centres, with challenges in readiness evaluation and the use of guidelines. Despite these obstacles, respondents rated ongoing transition processes positively. Enhancing patient perspectives in the transition process is crucial to meet their needs during this critical phase.
Skin of colour dermatology education in US primary care residency programmes: a nationwide cross-sectional survey of programme directors
Authors: LaMonica Lauren C , Hester Thomas , Thomas Reinie , Wang Frank
Published: January 2025

Background

Physicians-in-training report inadequate education in skin of colour (SOC) dermatology during residency. Although dermatology programmes have made progress in teaching SOC dermatology, the status of SOC dermatology education in primary care residency programmes remains unclear.

Objectives

To characterize SOC didactic and clinical training opportunities available to primary care residents, laying the groundwork for future curriculum development of SOC dermatology.

Methods

This cross-sectional study consisted of a nationwide 16-question survey disseminated by email between October 2022 and February 2023 to US primary care residency programmes identified using the Accreditation Council for Graduate Medical Education (ACGME) database.

Results

Of responding programmes (n = 49/1224, 4.0%), 29/49 offered SOC didactic training, most often through integration of content within general dermatology lectures (n = 29/49, 59.2%) and board review sessions (n = 13/49, 26.5%). Over half of programmes (n = 35/49, 71.4%) offered SOC clinical training through rotation in a general dermatology clinic (n = 33/49, 67.3%) and skin-related chief concerns in primary care clinics (n = 29/49, 59.2%). Programmes with directors indicating that they planned to incorporate SOC education into future curricula (n = 20/49, 40.8%) were more likely to already have SOC didactic and clinical training opportunities (P = 0.01 and P = 0.02, respectively). Regarding future directions, programme directors were most interested in integrating SOC topics within dermatology lectures (n = 31/49, 63.3%); identifying an expert (n = 31/49, 63.3%) and allocating lecture time (n = 10/49, 20.4%) were the most frequently cited barriers.

Conclusions

Some primary care programmes provide SOC dermatology didactic and clinical training opportunities, which are influenced by programme directors’ willingness to incorporate such training into curricula, and present opportunities for dermatologists to educate primary care residents.
Evaluation of Biochar Liquid Extract for Control of Boxwood Blight
Authors: Li Xiaoping , Hong Chuan
Published: January 2025

Boxwood blight, caused by the fungal pathogen Calonectria pseudonaviculata, is an emerging disease that has devastated the boxwood industry and private/public gardens. Here, we evaluated the potential of biochar liquid extracts for controlling boxwood blight disease. Three biochar products from pine, eucalyptus, and citrus were tested at 0.5%, 1.5% and 3% (w/v) concentrations on 2-year-old container-grown Buxus sempervirens ‘Justin Brouwers’ plants under controlled conditions. Although none of the three products at three concentrations evaluated were effective in protecting boxwood from the blight pathogen, this study provided insights into use of biochar as a management strategy for foliar diseases.
Low‐intensity pulsed ultrasound enhances the osteogenic potential of PDLSCs‐derived extracellular vesicles through COMP/PI3K/AKT
Authors: Xiang Mingli , Guo Qiushuang , Liu Yulin , Zhang Gengchao , Liao Chengcheng , Xiao Linlin , Xiang Meiling , Long Sicen , Long Qian , Guan Xiaoyan , Liu Jianguo
Published: January 2025

The therapeutic potential of extracellular vesicles (EVs) in bone regeneration is noteworthy; however, their clinical application is impeded by low yield and limited efficacy. This study investigated the effect of low‐intensity pulsed ultrasound (LIPUS) on the therapeutic efficacy of EVs derived from periodontal ligament stem cells (PDLSCs) and preliminarily explored its mechanism. PDLSCs were cultured with osteogenic media and stimulated with or without LIPUS, and then EVs and LIPUS‐stimulated EVs (L‐EVs) were isolated separately. We investigated the biological characteristics and effects of these two EVs on cell proliferation, migration, osteogenic differentiation, and bone regeneration in vivo and in vitro, and explored the potential mechanism by analyzing protein profiles. LIPUS significantly stimulated the secretion of PDLSCs‐EVs, and L‐EVs exhibited stronger efficacy in promoting cell proliferation, migration, and osteogenic differentiation, thereby enhancing new bone formation. LIPUS stimulation affected the protein profile of PDLSCs‐EVs, and 42 proteins were upregulated and 4 proteins downregulated in L‐EVs when compared with EVs. LIPUS significantly upregulated the level of cartilage oligomeric matrix protein (COMP) in EVs, which enhanced EVs' osteogenic ability via the PI3K/AKT pathway. This study proposes that LIPUS has potential as an optimization method for enhancing the therapeutic effects of EVs in tissue regeneration.
Prolonged tamoxifen treatment induces iron deposition and ferroptosis in the liver
Authors: Yang Jianxin , Wang Dongyao , Wang Weili , Wu Chenghua , Li Chenqi , Shi Wenjing , Qian Jianxin , Xie Feng , Shen Hui , Tang Yuxiao
Published: January 2025

Tamoxifen is an inhibitor of estrogen receptors and was originally developed for breast cancer therapy. Besides, tamoxifen is widely used for Cre‐estrogen receptor‐mediated conditional knockout in transgenic mice. However, we found that the 3‐month feeding of 0.5 g/kg tamoxifen diet dramatically lowered the body weight of mice. The liver fat content and the serum lipid indicators were all decreased. But the liver injuries were identified, as illustrated by liver/body ratio and serum ALT and AST levels. The Sirius red staining and α‐SMA staining even showed fibrosis in the liver. The increased lipid peroxidation indicators MDA and LPO, and ferroptosis markers COX‐2, GPX4, SLC7A11, and ACSL4 implied the tamoxifen‐induced ferroptosis in the liver. We further found that tamoxifen induced hepatic iron deposition. The investigation of iron transporters found that tamoxifen upregulated ferric iron reductase STEAP3, ferrous iron transporter DMT1, and iron storage molecule ferritin, which were probably the reasons for tamoxifen‐induced iron deposition. The downregulation of the transferrin receptor and upregulation of hepcidin were more likely the responses to iron deposition. In conclusion, we found that tamoxifen disturbed the iron metabolism and induced liver injuries and ferroptosis, warranting attention to the applications of tamoxifen in cancer therapy and conditional gene knockout.
The Auditory Environment at Early Intervention Groups for Young Children With Hearing Loss: Signal to Noise Ratio, Background Noise, and Reverberation
Authors: Meijer Annerenée , Benard Michel Ruben , Woonink Aart , Başkent Deniz , Dirks Evelien
Published: January 2025

Objectives:

One important aspect in facilitating language access for children with hearing loss (HL) is the auditory environment. An optimal auditory environment is characterized by high signal to noise ratios (SNRs), low background noise levels, and low reverberation times. In this study, the authors describe the auditory environment of early intervention groups specifically equipped for young children with HL.

Design:

Seven early intervention groups for children with HL were included in the study. A total of 26 young children (22 to 46 months) visiting those groups participated. Language Environmental Analysis recorders were used to record all sounds around a child during one group visit. The recordings were analyzed to estimate SNR levels and background noise levels during the intervention groups. The unoccupied noise levels and reverberation times were measured in the unoccupied room either directly before or after the group visit.

Results:

The average SNR encountered by the children in the intervention groups was +13 dB SNR. The detected speech of the attending professionals achieved the +15 dB SNR recommended by the American Speech-Language-Hearing Association in approximately 42% of the time. The unoccupied noise levels were between 29 and 39 dBA, complying with acoustic norms for classroom environments (≤35 dBA, by ANSI/ASA 12.60-2010 Part 1) for six out of seven groups. Reverberation time was between 0.3 and 0.6 sec for all groups, which complies to the acoustic norms for classroom environments for children without HL (0.6 or 0.7 sec, depending on the room size), while only one group complied to the stricter norm for children with HL (0.3 sec).

Conclusions:

The current findings show characteristics of the auditory environment of a setting that is specifically equipped and designed for groups of children with HL. Maintaining favorable SNRs seems to be the largest challenge to achieve within the constraints of an environment where young children gather, play, and learn. The results underscore the importance of staying attentive to keep spoken language accessible for children with HL in a group setting.
Synergistic effect of anemia and obstructive sleep apnea on hypertension: National Health and Nutrition Examination Survey 2015–2018
Authors: Yao Jiajia , He Xi , Wang Han , Wang Anzi , Zhen Lin
Published: January 2025

Objective:

Anemia, obstructive sleep apnea (OSA), and hypertension are common social health problems. They are interconnected. This study assessed the independent association of anemia and OSA with hypertension and the interaction between anemia and OSA on hypertension in the US population.

Methods:

Data used by this retrospective study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2018. The relative excess risk due to interaction (RERI), weighted logistic regression, and the attributable proportion due to interaction (AP) were used to investigate the interaction above. Its impact was also assessed via subgroup analysis by gender, age, race, diabetes, smoking, alcohol use, education, and marital status.

Results:

After covariate adjustment in 6949 eligible observers, it was found that compared with non-OSA patients, OSA patients were at higher risk of hypertension [odds ratio (OR) = 1.254, 95% confidence interval (CI) 1.099–1.432, P < 0.001). Meanwhile, OSA and anemia had a potential synergistic effect on the incidence of the disease (OR = 1.705, 95% CI: 1.390–2.091, P < 0.01): the RERI was 0.371, and the AP was 0.218. In addition, such effect was observed in the subgroup of other race (AP = 0.48), the nondrinking subgroup (AP = 2.50), the subgroup graduating from high school or above (AP = 0.28), the unmarried subgroup (AP = 0.4), the subgroup without diabetes (AP = 0.24), and the drinking subgroup (AP = 0.41).

Conclusion:

Anemia and OSA had a potential synergistic effect on hypertension. Their relationship needs to be further elucidated by a further study.
Mortality risks in different subtypes of masked hypertension in the Spanish ambulatory blood pressure monitoring registry
Authors: de la Sierra Alejandro , Ruilope Luis M. , Staplin Natalie , Stergiou George S. , Williams Bryan
Published: January 2025

Objective:

We aimed to evaluate the risks of death and cardiovascular death of different subtypes of masked hypertension, defined by either isolated daytime or nighttime blood pressure (BP) elevation, or both, compared with patients with normal both office and 24-h BP.

Methods:

We selected 4999 patients with masked hypertension (normal office BP and elevated 24-h BP). They were divided in three different categories: isolated daytime masked hypertension (elevated daytime BP and normal nighttime BP, 800 patients), isolated nighttime masked hypertension (elevated nighttime BP and normal daytime BP, 1069 patients) and daytime and nighttime masked hypertension (elevation of both daytime and nighttime BP, 2989). All-cause and cardiovascular death (median follow-up 9.7 years) were assessed in each of these subtypes in comparison to 10 006 patients with normal both office and 24-h BP. Hazard ratios from Cox models after adjustment for clinical confounders were used for such comparisons.

Results:

Compared with patients with normal both office and 24-h BP, isolated daytime masked hypertension was not associated with an increased risk of death in models adjusted for clinical confounders [hazard ratio 1.07; 95% confidence interval (CI): 0.80–1.43]. In contrast, isolated nighttime masked hypertension (hazard ratio: 1.39; 95% CI 1.19–1.63) and daytime and nighttime masked hypertension (hazard ratio: 1.22; 95% CI 1.08–1.37) had an increased risk of death in comparison to patients with BP in the normal range. Similar results were observed for cardiovascular death.

Conclusion:

The risk of death in masked hypertension is not homogeneous and requires nocturnal BP elevation, either isolated or with daytime elevation. Isolated daytime masked hypertension is not associated with an increased risk of death.
Prevalence and correlates of uncontrolled hypertension and cardiovascular morbidity among patients with hypertension at the largest tertiary care hospital in Sri Lanka
Authors: Ranasinghe Priyanga , Manchanayake Minura , Perera Thilina , Liyanage Sandamini , Webb David J.
Published: January 2025

Introduction:

Hypertension is the leading preventable cause of cardiovascular morbidity and mortality globally, with a disproportionate impact on low-income and middle-income countries like Sri Lanka. Effective blood pressure (BP) control improves outcomes in patients with hypertension. This study aimed to assess the prevalence of uncontrolled hypertension, and its correlates among Sri Lankan patients with hypertension in clinic settings.

Methods:

A cross-sectional study was done at the largest tertiary care hospital in Sri Lanka and patients with hypertension presenting to its medical clinics over a 6-month period were recruited. An interviewer-administered questionnaire captured sociodemographic, morbidity, and medication details from records. BP measurements were taken following standard guidelines with OMRON-X7 BP monitors. Multivariate logistic regression was used to identify significant associations (P < 0.05).

Results:

Among 600 patients (mean age 64 ± 9 years, 43% men), 55% had uncontrolled hypertension. Most (62%) were on 1 or 2 antihypertensives, primarily renin–angiotensin blockers (91%), with minimal (<10%) thiazide use. Uncontrolled hypertension was less common among furosemide (10.5%) and spironolactone (21.5%) users but frequent among those on alpha-blockers (16.3%). Coronary artery disease (58%), heart failure (9%), and stroke (17%) were more common in men and those with longstanding hypertension. Beta-blockers were favoured in those with cardiac comorbidities, and dihydropyridines in those with stroke. Potential treatment resistance, seen in 11%, was associated with increased cardiac morbidity, while sociodemographic factors and family history had no significant impact on BP control or cardiovascular morbidity.

Conclusion:

Uncontrolled hypertension and cardiovascular morbidity were highly prevalent. The data suggest the need for optimized antihypertensive regimens, with reduced use of alpha-blockers and early and prioritized incorporation of diuretics.
Minimum number of readings necessary for determining long-term visit-to-visit blood pressure variability to predict cardiovascular outcomes in people with diabetes
Authors: Kim Ju Hyeon , Oh Seungmi , Hong Soon Jun , Yu Cheol Woong , Joo Hyung Joon , Kim Yong Hyun , Kim Eung Ju
Published: January 2025

Background:

People with diabetes often have increased blood pressure (BP) variability because of autonomic dysfunction and arterial stiffness, making it a critical factor in predicting clinical outcomes. We investigated the reproducibility of long-term visit-to-visit BP variability (VVV) and the minimum number of BP readings to reliably determine VVV in people with diabetes.

Methods:

This multicenter retrospective study used data from electronic health records of the Korea University Medical Center database. Altogether, 10 475 people with diabetes who had more than nine BP readings during a maximum period of 2 years were identified. This study focused on the coefficient of variation of these readings and their correlation with major adverse cardiovascular events (MACE) over a 3-year follow-up period.

Results:

The mean age of the participants was 65.2 years. Of these, 53.2% were men, and 87.4% had hypertension. The mean coefficient of variation of multiple SBP readings that best predicted the 3-year MACE were 8.4, 9.5, 9.0, 9.0, and 9.7 for three, five, seven, nine, and all readings, respectively. Patients with high VVV (coefficient of variation of five SBP readings >9) exhibited a higher incidence of 3-year MACE (10.1%) than those with low VVV (5.4%, P < 0.001). In the multivariable analysis, high VVV of both SBP and DBP were independently associated with 3-year MACE.

Conclusion:

Long-term VVV in the BP is a reproducible and reliable predictor of cardiovascular outcomes in people with diabetes. A minimum of five BP measurements are recommended for effective intraindividual VVV estimation and cardiovascular risk assessment.
Resident-Driven Guideline to Reduce Iatrogenic Pneumothoraxes From Small-Bore Feeding Tubes: A Quality and Safety Improvement Project
Authors: Podder Sourav , Cowan Scott , Koeneman Scott , Pavis Elizabeth , Park Doo , Schleider Christine , Shindle Kathleen , Bowen Matthew , Johnson Adam
Published: January 2025

Small-bore feeding tubes (SBFT) in vulnerable patients carry a risk of iatrogenic pneumothorax by misplacement into the lung. This institution noted a series of iatrogenic pneumothoraxes caused by the placement of these devices. A resident-led, multidisciplinary team developed a hospital guideline through a consensus-driven process. The guideline mandated SBFT placement by approved “super-users” via the CORTRAK Enteral Access System or via non-CORTRAK Methods, including the 2-step X-ray Method, fluoroscopy, or direct visualization techniques. A “super-user” Program for the CORTRAK Enteral Access System was developed to assure competency and consistency. With the development of the guideline and “super-user” program, the authors observed a decrease in the number of SBFT-related iatrogenic pneumothoraxes. Following a brief period of adoption, the three-hospital organization has had no SBFT-related iatrogenic pneumothoraxes. This project demonstrates the effectiveness of developing a resident-driven, evidence-based hospital guideline for the safe passage of SBFTs.
Use of Hearing Aids Embedded with Inertial Sensors and Artificial Intelligence to Identify Patients at Risk for Falling
Authors: Steenerson Kristen K. , Griswold Bryn , Keating Donald P. , Srour Majd , Burwinkel Justin R. , Isanhart Erin , Ma Yifei , Fabry David A. , Bhowmik Achintya K. , Jackler Robert K. , Fitzgerald Matthew B.
Published: January 2025

Objective

To compare fall risk scores of hearing aids embedded with inertial measurement units (IMU-HAs) and powered by artificial intelligence (AI) algorithms with scores by trained observers.

Study Design

Prospective, double-blinded, observational study of fall risk scores between trained observers and those of IMU-HAs.

Setting

Tertiary referral center.

Patients

Two hundred fifty participants aged 55–100 years who were at risk for falls.

Interventions

Fall risk was categorized using the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test battery consisting of the 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests. Performance was scored using bilateral IMU-HAs and compared to scores by clinicians blinded to the hearing aid measures.

Main Outcome Measures

Fall risk categorizations based on 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests obtained from IMU-HAs and clinicians.

Results

Interrater reliability was excellent across all clinicians. The 4-Stage Balance and TUG showed no statistically significant differences between clinician and HAs. However, the IMU-HAs failed to record a response in 12% of TUG trials. For the 30-Second Chair Stand test, there was a significant difference of nearly one stand count, which would have altered fall risk classification in 21% of participants.

Conclusions

These results suggest that fall risk as determined by the STEADI tests was in most instances similar for IMU-HAs and trained observers; however, differences were observed in certain situations, suggesting improvements are needed in the algorithm to maximize accurate fall risk categorization.
Impact of nursing interventions on hemodialysis patients using the integrated theory of health behavior change
Authors: Chen Zhiyu , Ma Jinyan , Ou Hongchun , Pu Li
Published: January 2025

This study investigated the impact of nursing interventions based on the Integrated Theory of Health Behavior Change on hemodialysis patients. A retrospective analysis of 713 hemodialysis patients’ electronic medical records from June 2020 to November 2023 was conducted. Patients were divided into an experimental group, receiving nursing interventions based on the theory, and a control group, receiving regular nursing care. After 1 month, dialysis indices and hospitalization rates were compared. Subgroup analyses based on education level were performed. After basic information matching, the spKt/V values of the experimental group and the control group were 1.62 ± 0.27 and 1.41 ± 0.25, with 198 and 176 individuals meeting the standard, respectively. The urea reduction ratio of the experimental group was 78.26 ± 8.72, with 187 individuals meeting the standard. From the 2 indicators, the dialysis indices of the experimental group were significantly better than those of the control group (P < .05). The numbers of readmissions in the 2 groups were 41 and 61, respectively, with a statistically significant difference (P = .024). We also compared the reasons for readmission between the 2 groups and found significant differences in the reasons. Particularly, the numbers of readmissions due to fluid overload were 13 and 32 in the experimental and control groups, respectively, with significantly fewer in the experimental group than in the control group (P = .033). The education level did not affect the readmission rate of patients, with readmission rates of 12 and 11 in the 2 groups, respectively, with P > .05. The dialysis indices spKt/V and urea reduction ratio increased with increasing BMI, and there was a correlation between the 2, with values of 0.61 and 0.51, respectively, which were statistically significant (P < .05). The extremely satisfied rates were 46% in the experimental group and 36% in the control group, with dissatisfaction rates of 2% and 3% in the 2 groups, respectively, showing a significant statistical difference (P < .01). Nursing interventions based on the Integrated Theory of Health Behavior Change improved dialysis outcomes and patient satisfaction, providing insights for chronic disease management.