bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning for a Heterogeneous Water Modeling Framework
Authors: Frame Jonathan M. , Araki Ryoko , Bhuiyan Soelem Aafnan , Bindas Tadd , Rapp Jeremy , Bolotin Lauren , Deardorff Emily , Liu Qiyue , Haces‐Garcia Francisco , Liao Mochi , Frazier Nels , Ogden Fred L.
Published: February 2025

This technical note describes recent efforts to integrate machine learning (ML) models, specifically long short‐term memory (LSTM) networks and differentiable parameter learning conceptual hydrological models (δ conceptual models), into the next‐generation water resources modeling framework (Nextgen) to enhance future versions of the U.S. National Water Model (NWM). We address three specific methodology gaps of this new modeling framework: (1) assess model performance across many ungauged catchments, (2) diagnostic‐based model selection, and (3) regionalization based on catchment attributes. We demonstrate that an LSTM trained on CAMELS catchments can make large‐scale predictions with Nextgen across the New England region and match the average flow duration curve observed by stream gauges for streamflow with low exceedance probability (high flows), but diverges from the mean in high exceedance probability (low flows). We demonstrate improvements in peak flow predictions when using δ conceptual model, but results also suggest that performance increases may come at a cost of accurately representing hydrologic states within the conceptual model. We propose a novel approach using ML to predict the most performant mosaic modeling approach and demonstrate improved distributions of efficiency scores throughout the large sample of basins. Our findings advocate for the future development of ML capabilities within Nextgen for advancing operational hydrological modeling.
Associations of Healthcare Utilization and Health Expenditures in Older Adults With Osteoarthritis: Korean Health Panel Survey Study
Authors: Kim Yejin , Kim Bomgyeol , Park Jun Su , Rajaguru Vasuki , Chang Hyuk‐Jae , Lee Sang Gyu , Kim Tae Hyun
Published: February 2025

Background

This study investigated the association between healthcare utilization and expenditures, including non‐covered services in Korean older adults with osteoarthritis (OA).

Methods

This cross‐sectional study used data from the 2019 Korean Health Panel (KHP) annual data of participants aged ≥ 60 years who had OA. Healthcare utilization and expenditures were determined by hospitalization, outpatient, and emergency visits. A generalized linear model was used to examine healthcare utilization and expenditures associated with OA.

Results

Among the 5877 participants, 1645 (27.9%) had OA. Participants with OA had higher healthcare utilization (Increment = 6.5 visits, SE = 0.8, p < 0.0001) and expenditures (Increment = USD 432.8, SE = 111.8, p = 0.0001) compared to those without OA. The increase in utilization was primarily in outpatient visits (Increment = 6.4 visits, SE = 0.8, p < 0.0001), especially at clinics (Increment = 5.6 visits, SE = 0.9, p < 0.0001). Healthcare expenditures were also higher for both inpatient (Increment = USD 200.9, SE = 89.8, p = 0.0254) and outpatient visits (Increment = USD 236.6, SE = 51.7, p < 0.0001). Male with OA spent higher cost (USD 242.9) on outpatient visits than non‐OA participants. In contrast, females with OA reported higher expenditures for both inpatient (USD 301.3) and outpatient (USD 259.6) visits than those without OA.

Conclusions

OA was associated with a significant increase in healthcare utilization and expenditure. Appropriate strategies are required to reduce the burden of OA. Further study is required to explore how various healthcare facilities might be used together to provide safe and cost‐efficient treatment for OA patients within the healthcare system and in the community.
AMMonitor 2: Remote monitoring of biodiversity in an adaptive framework in R
Authors: Clarfeld Laurence , Tang Caroline , Huber Kaitlin , Balantic Cathleen , Donovan Therese
Published: February 2025

Wildlife face a myriad of challenges due to changing climate and land use regimes that necessitate efficient monitoring methods on large geospatial scales. This monitoring is increasingly accomplished with remotely deployed trail cameras and automated recording units.

However, remote wildlife monitoring comes with data management challenges, such as storing, organizing and analysing large volumes of digital data. Data management tools can assist biologists in managing projects to reduce the barriers between data collection and dissemination of results.

AMMonitor is an R package for remote wildlife monitoring with greatly increased functionality in the version 2 release, including a new database structure, support for both photographs and audio monitoring, a rich graphical user interface (Shiny) that includes media labelling tools, integration of machine learning classification outputs and 20 in‐depth tutorials.

As a fully open‐source data management solution, AMMonitor is highly accessible, extensible and customizable, making it especially useful for students and users with some coding experience who desire a standardized yet flexible data management framework.

AMMonitor project data can be released to the public via the USGS ScienceBase data repository, where released projects can be reconstituted by AMMonitor functions.
Repairing gaps in ecological time series
Authors: Carpenter Delia , Deyle Ethan , Park Joseph , Saberski Erik , Sugihara George
Published: February 2025

Missing values are ubiquitous in ecological time series. Methods like linear interpolation, k‐nearest neighbour (kNN) imputation or regression‐based imputation are commonly used to repair these gaps, but may be unsuitable when the data are infrequently sampled or have nonlinear dynamics.

We introduce multiview cross‐mapping (MVCM), a novel method based in empirical dynamic modelling (EDM) that exploits shared information between dynamically coupled time series. Rather than using points nearby in time, MVCM uses similar system states on an attractor to estimate the value of a missing data point. MVCM works best where other dynamically coupled variables have been observed, but it can also predict into short gaps where all variables are missing (data void).

Using model data from a coupled five‐species system, and observational data from a long‐term plankton survey in Lake Zurich, Switzerland, we show that MVCM is robust and performs significantly better than linear methods (linear interpolation, linear regression‐based imputation) and kNN imputation.

Crucially, this approach differs from methods based on a purely statistical paradigm because it assumes that the time series are generated by underlying deterministic rules. This dynamical framework allows us to exploit information shared between time series from a mechanistically coupled system, making complexity an asset for the analysis of imperfect observational data.
Oral Citrate Supplementation Mitigates Age‐Associated Pathologic Intervertebral Disc Calcification in LG/J Mice
Authors: Ottone Olivia K. , Mundo Jorge J. , Kwakye Boahen N. , Slaweski Amber , Collins John A. , Wu Qinglin , Connelly Margery A. , Niaziorimi Fatemeh , van de Wetering Koen , Risbud Makarand V.
Published: February 2025

Despite the high prevalence of age‐dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. We investigated the efficacy of long‐term oral K3Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age‐associated disc calcification. K3Citrate reduced the incidence of disc calcification without affecting the vertebral bone structure, knee calcification, plasma chemistry, or locomotion in LG/J mice. Notably, a positive effect on grip strength was evident in treated mice. FTIR spectroscopy of the persisting calcified nodules indicated K3Citrate did not alter the mineral composition. Mechanistically, activation of an endochondral differentiation in the cartilaginous endplates and nucleus pulposus (NP) compartment contributed to LG/J disc calcification. Importantly, K3Citrate reduced calcification incidence by Ca2+ chelation throughout the disc while exhibiting a differential effect on NP and endplate cell differentiation. In the NP compartment, K3Citrate reduced the NP cell acquisition of a hypertrophic chondrocytic fate, but the pathologic endochondral program was unimpacted in the endplates. Overall, this study for the first time shows the therapeutic potential of oral K3Citrate as a systemic intervention strategy to ameliorate disc calcification.
Recent decline in Chinese alcohol production and consumption: Potential contributing factors and the role of globally recommended measures
Authors: Tang Yi‐lang , Wang Xuyi , Hao Wei
Published: February 2025

Background and aim

Alcohol consumption in China poses significant public health challenges. Between 2005 and 2010, alcohol production and by implication, consumption, surged, leading to increased alcohol‐related harms due to weak regulatory frameworks. This study examined recent patterns of alcohol consumption in China using public production data as a proxy.

Method

Statistical analysis was conducted using data from the National Bureau of Statistics of China on the production of beer, wine, and liquor, from the years 2009 to 2023.

Results

The production of liquor and wine in China increased from 7.1 and 0.96 million tons in 2009 to 13.6 and 1.14 million tons in 2016, respectively. Inferred alcohol per capita consumption (APC) rose from 4.38 L in 2009 to 6.45 L in 2016, representing a 47% increase. However, from 2016 onwards, alcohol production declined to 4.5 and 0.14 million tons for liquor and wine in 2023, respectively. Consequently, inferred APC decreased from 6.45 L to 2.85 L, an overall reduction of 55.8%.

Conclusions

Alcohol production and inferred consumption in China appear to have substantially declined since 2016. Potential factors contributing to this decline include stricter government policies, stricter market regulation and tax enforcement, public health campaigns, and demographic and cultural shifts. However, many global measures such as higher taxes, price controls, advertising restrictions, and a legal drinking age, have not been (adequately) implemented in China.
Personalized chat‐based support for smoking cessation among smokers with mental health symptoms in the workplace: A randomized controlled trial
Authors: Yao Ying , Luk Tzu Tsun , Lau Oi Sze , Wu Yongda Socrates , Weng Xue , Ng Chak Hang , Cheung Yee Tak Derek , Lam Tai Hing , Wang Man Ping
Published: February 2025

Aims

Smoking rates are disproportionately high among people with mental health issues. We evaluated the effectiveness of a chat‐based intervention paired with psychological support for workplace smokers with mental health symptoms.

Design and setting

A pragmatic, two‐arm, randomized controlled trial in 65 companies in Hong Kong, China.

Participants

300 employees who smoked daily (84.3% male) with stress (Perceived Stress Scale‐4 ≥ 6), anxiety (General Anxiety Disorder‐2 ≥ 3) or depressive symptoms (Patient Health Questionnaire‐2 ≥ 3).

Interventions

Participants were randomly allocated to either the intervention group (n = 144) or the control group (n = 156). The intervention group received 20 instant messages and chat‐based support delivered by trained counselors over 3 months, using Acceptance and Commitment Therapy. The control group received 6 messages on general health. Both groups received a health talk and self‐help booklet at baseline, brief phone advice at follow‐ups and full‐course nicotine replacement therapy for continuing smokers at 6 months.

Measurements

The primary outcome was self‐reported 7‐day point prevalence abstinence (PPA) at 6 months after intervention initiation. Secondary outcomes included PPA at 1, 3, 9 and 12 months, changes in mental health symptoms and intervention engagement (chatting with counsellors).

Findings

By intention to treat, there was no evidence of a difference in 7‐day PPA between intervention and control group at 6 months [16.0% vs. 13.5%, odds ratio (OR) = 1.22, 95% confidence interval (CI) = 0.64–2.32]. At 12 months, there was weak evidence of an intervention benefit (21.5% vs. 13.5%, 1.76, 0.96–3.24), which was statistically significant after adjusting for baseline factors (adjusted OR = 2.61, 1.22–5.58, P = 0.01). A greater reduction in anxiety symptoms over a 12‐month period in the intervention group was observed (adjusted b = −0.28, 95% CI = −0.56 to −0.00, P = 0.05).

Conclusions

There appears to be weak evidence for a benefit of a personalised chat‐based smoking cessation intervention plus psychological support on promoting smoking abstinence among workplace smokers with mental health symptoms.
Lithium Ore Tailings May Increase the Invasion Potential of Melinis minutiflora in Native Areas Around to Mining Sites
Authors: Melo Nayara Magry Jesus , Souza João Paulo
Published: February 2025

The growing demand for lithium has led to an increased focus on understanding the impact of mining waste on ecosystems in the surrounding area. This study aimed to investigate the effect of lithium ore tailings (LOT) on the growth and establishment of an invasive C4 herbaceous species (Melinis minutiflora) and a native C3 herbaceous species (Stylosanthes capitata) from native areas of Brazil. We grow plants in three substrates: soil without LOT, a mixture of 50% soil and 50% LOT (soil + LOT) and only LOT. Melinis minutiflora plants grown in the soil + LOT treatment showed higher growth and vegetative biomass production than S. capitata plants in the same treatment. Also, M. minutiflora plants grown in soil + LOT and LOT had a higher chlorophyll b index than S. capitata plants. The findings suggest that invasive M. minutiflora plants may benefit from soils contaminated with LOT. In areas surrounding LOT, M. minutiflora could establish, grow and spread faster, potentially affecting ecosystem processes. Understanding the impact of environmental disturbances on native areas and their consequences for the growth of invasive and native species is crucial for ecosystem management and preservation.
Systematic Review of Rare Major Adverse Cardiovascular Events Associated With the Treatment of Acne With Isotretinoin
Authors: Cowan Timothy L. , Stark Madeleine , Sarmiento Simona , Miller Andrew
Published: February 2025

Acne vulgaris is a common inflammatory condition that is often treated by dermatologists with isotretinoin. Isotretinoin has a number of effects on inflammatory pathways, with clear efficacy in managing acne vulgaris. There are also well‐documented side effects of isotretinoin, including hyperlipidemia; however, the overall cardiovascular risk is unclear. This systematic review revealed low evidence for major adverse cardiovascular events associated with the use of isotretinoin in acne patients. Despite this low evidence, rare events may be associated and should still be considered when using isotretinoin in acne patients.
An Integrative Approach of Taxonomic, Morphometric and Ecological Research to Solve the Status of Cryptic Chelonian Taxa—A Case Study With Pelomedusa kobe in Rwanda
Authors: Umulisa Christella , Djurakic Marko , Bantlin Drew , Müller Anke , Vamberger Melita
Published: February 2025

Using genetic data, we confirm for the first time the presence of the Tanzanian helmeted terrapin Pelomedusa kobe in Akagera National Park, Rwanda, extending their known distribution. Our study provides the first natural history observations, population and morphological data for this species from a wild population. As species in the genus Pelomedusa are morphologically difficult to distinguish, we gain the first insights into intraspecific and interspecific patterns of size and shape variation of plastron morphology between two morphologically‐similar species living in Eastern Africa, P. kobe and P. subrufa, using geometric morphometrics. Species affiliation, rather than sex, is the dominant factor influencing size and shape variation. P. kobe exhibits female‐based sexual size dimorphism (SSD), while P. subrufa shows a tendency toward male‐based SSD. Furthermore, sexual shape dimorphism (SShD) was observed in P. kobe but not in P. subrufa. Our results provide the first integrative data (genetic, morphological and natural history) on P. kobe, however further information on their distribution in the park is needed for effective conservation of this data‐deficient species. Our findings lay the groundwork for future ecological studies on P. kobe, potentially revealing unique adaptations and conservation needs previously overlooked due to its cryptic nature.
The Effect of Acupoint Sticking Therapy on Serum Estrogen Levels and Endometrial Polyp Tissue Receptor Expression in Postmenopausal Patients With Endometrial Polyps
Authors: Zhang Da , Chen Ying , Zhang Liangyu , Wang Yang
Published: February 2025

Background

Postmenopausal women with endometrial polyps (EPs) often experience hormonal imbalances. Acupoint application, a traditional Chinese medicine (TCM) approach, shows the potential to influence hormonal levels. This study investigated the impact of acupoint application on hormone levels and receptors in postmenopausal women with EP, comparing its efficacy and safety to surgery.

Methods

We conducted a retrospective analysis of 170 postmenopausal patients with EP. Eighty‐four patients received surgery alone, while 86 received surgery combined with acupoint application. Hormone levels, hormone receptor expression, TCM symptom scores, and adverse effects were compared between the two groups.

Results

The acupoint application group demonstrated a significantly higher total effective rate than the control group (p < 0.05). After treatment, the acupoint application group exhibited a significantly greater reduction in serum progesterone levels and vaginal pH compared to the control group (p < 0.05). Additionally, the acupoint application group showed a significant increase in endometrial estrogen receptor expression after treatment (p < 0.05). TCM symptom scores related to vaginal bleeding volume, duration, facial complexion, dry mouth, and thirst significantly improved in the acupoint application group post‐treatment (p < 0.01). Furthermore, the acupoint application group demonstrated a notably lower incidence of adverse effects (including nausea, headache, breast tenderness, and dizziness) compared to the control group (p < 0.05).

Conclusion

Our study suggests acupoint application, alongside surgery, enhances clinical outcomes, hormonal balance, and symptom relief in postmenopausal women with EPs, compared to surgery alone. Its safety and sustained benefits support its use as a complementary treatment.
How Is Chronic Pain Managed in Rural Australia? A Qualitative Study Exploring Rural Healthcare Professional and Consumer Experiences
Authors: Grant Ashley R. , Westhorp Gill , Mardon Amelia , White Monique , Hibbert Peter D. , Karran Emma L. , Roeger Christopher , Moseley G. Lorimer
Published: February 2025

Introduction

Guideline‐based care for chronic pain is variably provided. Existing data on chronic pain management in Australia come primarily from metropolitan samples. As the initial investigations for a wider needs assessment, we sought to understand how chronic pain is managed in rural Australia, focused on investigating the gap between guideline‐recommended care and provided care.

Methods

We conducted semistructured interviews with rural healthcare professionals who treat patients with chronic pain and rural consumers affected by chronic pain. We asked healthcare professionals what treatments they deliver to patients with chronic pain. We asked consumers to describe the healthcare service providers they had accessed for pain care and the treatments they received from these providers. We utilised content analysis to gain an understanding of what care for chronic pain is being provided and compared these findings to guideline recommendations.

Results

We interviewed 15 healthcare professionals and 27 consumers. Both healthcare professionas and consumers reported minimal use of most first‐line management strategies. We also found differences between healthcare professional and consumer reports of pain care. Healthcare professionals frequently described delivering guideline‐aligned pain care and consumers frequently described receiving care that contradicted guidelines. We identified challenges with rural access to pain care services, including minimal usage of telehealth services.

Conclusions

Given the identified gaps in care, future research may consider ways of improving rural access to pain care services, including investigating ways to increase uptake of telehealth services, and how to shift consumer expectations of pain care.
Outcomes of after‐hours surgeries performed under general anaesthesia: a South Korean nationwide cohort study
Authors: Oh Tak Kyu , Song In‐Ae
Published: February 2025

Introduction

The day of the week or time of day that surgery is performed may influence postoperative mortality or complications. We aimed to examine whether surgery under general anaesthesia performed after‐hours was associated with increased rates of mortality and morbidity, compared with surgery performed in‐hours.

Methods

This population‐based cohort study obtained data for patients who underwent surgery under general anaesthesia from the National Health Insurance Service of South Korea. Propensity score‐matched groups of patients who underwent surgery either in‐hours (weekdays between 9.00 and 18.00) or after‐hours (weekdays between 18.00 and 09.00 or on a weekend/holiday) were compared for 90‐day and 1‐year mortality, and the incidence postoperative complications.

Results

A total of 1,416,844 patients were considered (63,567 in the after‐hours group and 1,353,277 in the in‐hours group) and after a 1:5 propensity score matching, 281,717 were included (57,497 in the after‐hours group and 224,220 in the in‐hours group). Patients in the after‐hours group showed 3.58‐fold (OR 3.58, 95%CI 3.47–3.69, p < 0.001) and 2.51‐fold (hazard ratio 2.51, 95%CI 2.46–2.57, p < 0.001) higher 90‐day and 1‐year all‐cause mortality rates, respectively, compared with those in the in‐hours group. Patients in the after‐hours group had a 2.14‐fold (OR 2.14, 95%CI 2.10–2.19, p < 0.001) greater incidence of postoperative complications compared with those in the in‐hours group.

Discussion

After‐hours surgery was associated with a higher risk of death within 90 days, an increase in all‐cause mortality after 1‐year and a higher incidence of postoperative complications.
Simultaneous clustering of individuals and covariates for high‐dimensional longitudinal data
Authors: Han Chao , Wu Jiaqi , Zhang Weiping
Published: February 2025

This paper considers identifying and estimating high‐dimensional longitudinal data models with latent subgroups and clustered covariates. We propose a regularised approach to recover group structures while simultaneously detecting clusters of significant covariates. The consistency and asymptotic normality are established for the estimator under mild conditions. Besides, we develop an effective algorithm based on local quadratic approximation to optimise the objective function. The finite‐sample performance is illustrated through extensive simulations, and the proposed method is applied to study the shift in the economic structure of European countries before and after the debt crisis.
Predictors for regression and progression of actively surveilled cervical intraepithelial neoplasia grade 2: A prospective cohort study
Authors: Bergqvist Laura , Virtanen Anni , Kalliala Ilkka , Bützow Ralf , Jakobsson Maija , Heinonen Annu , Louvanto Karolina , Dillner Joakim , Nieminen Pekka , Aro Karoliina
Published: February 2025

Introduction

To evaluate predicting clinical factors for regression and progression of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) in young women during two years of active surveillance.

Material and Methods

This was a single‐center prospective observational cohort study. Women under 31 years of age giving written informed consent with histologically confirmed CIN2 were followed with colposcopy, cytology, and biopsies every 6 months up to 24 months. At baseline, HPV genotyping was performed on cervical samples. The rates of regression and progression were recorded for every timepoint and at the end of study overall and stratified according to clinical factors and HPV genotypes at baseline. Risk ratio (RR) was used to estimate the relative risks for regression and progression. The study was registered in the ISRCTN registry (ISRCTN91953024).

Results

In total, 205/243 (84.4%) women completed the study. Complete regression (normal histology and/or normal or atypical squamous cells of undetermined significance (ASC‐US) cytology) was detected in 64.4.% (n = 132) while 16.1% (n = 33) of the lesions progressed to CIN grade 3 (CIN3) or worse including 31 CIN3 cases, one adenocarcinoma in situ and one cervical cancer case. Factors associated with progression were initial large (>50% of the transformation zone) lesion size, risk ratio (RR) 3.06 (95% confidence interval (CI) 1.40–6.69), and high‐grade referral cytology RR 4.73 (95% CI 1.18–19.03). Compared with baseline HPV negativity or having only low‐risk HPV genotypes present, high‐risk HPV (hrHPV) positivity was associated with lower likelihood of regression RR 0.74 (95% CI 0.60–0.91). Age, cigarette smoking, use of combined oral contraceptives or baseline high‐risk HPV genotype, including HPV16, were not associated with the outcomes.

Conclusions

The majority of CIN2 lesions regress in young women. Women with large lesions and/or high‐grade referral cytology should perhaps more often be treated instead of active surveillance. Initial hrHPV genotype does not appear to predict outcomes while not harboring hrHPV favors regression.
Comparison of Extracorporeal Membrane Oxygenation Initiation in Cardiogenic Shock During Work‐Hours Versus After‐Hours
Authors: Li Chenglong , Wang Xiaomeng , Du Zhongtao , Lu Andong , Lyv Liwen , Zhang Sheng , Liu Jianling , Liu Yan , Zuo Liuer , Huang Yue , Li Binfei , Chang Ping , Yang Yi , Liu Jianhua , Huang Man , Xie Haixiu , Wang Liangshan , Yang Feng , Wang Hong , Hou Xiaotong ,   Chinese Society of Extracorporeal Life Support (CSECLS)
Published: February 2025

Background

Extracorporeal membrane oxygenation (ECMO) as rescue therapy for cardiogenic shock (CS) is highly dependent on timeliness and medical resources.

Objectives

Aimed to assess ECMO management and outcomes in adult patients with CS in terms of on‐ and after‐hour ECMO initiation from a national ECMO registry.

Methods

Adult patients diagnosed with CS and those who received ECMO were enrolled in the study. The population was divided into the work‐hours and the after‐hours group based on the time of ECMO initiation. In‐hospital mortality and ECMO management were compared between them. Electronic data in this research were provided by Chinese Society of Extracorporeal Life Support.

Results

In a cohort of 1862 patients, 552 (29.6%) received ECMO during work‐hours, whereas 1310 (70.4%) received ECMO during after‐hours. After‐hour ECMO had more patients with elective cardiac procedures (35.1% vs. 26.3%, p < 0.001) and higher severity (p < 0.001), with more patients with Society for Cardiovascular Angiography and Interventions shock stage D (29.6% vs. 24.5), E (60.0% vs. 51.8%), and fewer B (3.6% vs. 13.2%) and C (6.8% vs. 10.5%). A high proportion underwent intra‐aortic balloon pump (IABP) implantation before ECMO (28.4% vs. 23.0%, p = 0.016) and mechanical ventilation (92.1% vs. 87.0%, p < 0.001) during after‐hours. The in‐hospital mortality in patients with after‐hour ECMO initiation was higher than that in patients with work‐hour ECMO initiation (51.8% vs. 45.3%, p = 0.011).

Conclusion

In this cohort, 70% were initiated during after‐hours and showed higher in‐hospital mortality than patients with work‐hour ECMO initiation. After‐hour ECMO initiation should be a concern for ECMO programs.
A distal convoluted tubule‐specific isoform of murine SLC41A3 extrudes magnesium
Authors: Franken Gijs A. C. , Bosman Willem , Jung Hyun Jun , Bos Caro , Latta Femke , Knepper Mark , Hoenderop Joost G. J. , de Baaij Jeroen H. F.
Published: February 2025

Background

The distal convoluted tubule (DCT) plays an indispensable role in magnesium (Mg2+) reabsorption in the kidney. Yet, the extrusion mechanism of Mg2+ has not been identified. The solute carrier 41A3 (SLC41A3) has been suggested to be involved in Mg2+ extrusion, but this has never been conclusively demonstrated.

Methods

Using available RNA‐sequencing data and real‐time quantitative PCR, expression of two alternative Slc41a3 transcripts, encoding isoform (Iso) 1 or 2, were assessed in kidney and isolated DCT tubules. HEK293 or HAP1 cells were transfected with plasmids expressing either of the isoforms, followed by 25Mg2+ transport studies. Identification of cis‐regulatory elements (CRE) was achieved by combining data from publicly available ATAC sequencing data and luciferase assays.

Results

Gene expression studies revealed a distinct transcript of Slc41a3 in the DCT with an alternative promoter, leading to a protein with a unique N‐terminus; SLC41A3‐Iso 2. HEK293 cells overexpressing SLC41A3‐Iso 2, but not ‐Iso 1, exhibited 2.7‐fold and 1.6‐fold higher 25Mg2+ uptake and extrusion, compared to mock, respectively. The transport was independent of Na+, of the Mg2+ channel TRPM7 or of transporters CNNM3 and ‐4. We identified a CRE accessible in the DCT, ±2.8kb upstream of the transcript. The presence of the CRE increased the Slc41a3‐Iso 2 promoter activity 3.8‐fold following luciferase assays, indicating the CRE contains an enhancer function.

Conclusion

In conclusion, we identified two alternative transcripts of Slc41a3 in mouse. Slc41a3‐Iso 2 is enriched within the DCT using specific gene regulatory elements. We speculate that specifically in the DCT, SLC41A3‐Iso 2 orchestrates Mg2+ extrusion.
Positive changes in daily life? A meta‐analysis of positive psychological ecological momentary interventions
Authors: Tomczyk Samuel , Ewert Christina
Published: February 2025

Positive psychological interventions (PPI) hold promise for boosting well‐being and quality of life in diverse populations, but not much is known about their efficacy as ecological momentary interventions (EMIs, e.g. via mobile applications) in daily life. This meta‐analysis uses random‐effects models to examine the efficacy of PPI‐EMIs compared to control groups (active or passive) and exploring study region, age, gender, and risk of bias as moderators. Overall, 16 studies were included (N = 3397, 69.1% female, Mage = 21.87, SD = 13.02). We observed clinically significant effects in favor of the intervention for positive affect at posttest (k = 6; g = 0.29; p = 0.05) and well‐being at follow‐up (k = 5; g = 0.21; p = 0.13). No significant moderator effects were found. The number of studies was small for each outcome, risk of bias was mixed, and heterogeneity of effects was moderate to high for most outcomes.
Does concurrent validity really estimate predictive validity in psychological testing? Two local studies
Authors: Fine Saul
Published: February 2025

Concurrent validity designs are used widely in applied psychology as proxy estimates of predictive validity in operational settings, although few primary (local) studies have investigated the generalizability of concurrent validity coefficients empirically. The present study compared the same assessment tool and performance criterion between incumbent and applicant consumer samples from two large financial institutions (N = 2942 and N = 2880), without the common issue of range restriction in the applicant groups. The results found no significant differences in the observed validity coefficients between the groups, despite evidence of impression management in the applicant samples. In addition, range restriction corrections in the concurrent samples would have likely overestimated the predictive validities. Practical implications are briefly discussed.
Direct observation of fluorescent proteins in gels: A rapid, cost‐efficient, and quantitative alternative to immunoblotting
Authors: Sanial Matthieu , Miled Ryan , Alves Marine , Claret Sandra , Joly Nicolas , Proux‐Gillardeaux Véronique , Plessis Anne , Léon Sébastien
Published: February 2025

Background Information

The discovery of green fluorescent protein (GFP) and its derivatives has revolutionized cell biology. These fluorescent proteins (FPs) have enabled the real‐time observation of protein localization and dynamics within live cells. Applications of FP vary from monitoring gene/protein expression patterns, visualizing protein‐protein interactions, measuring protein stability, assessing protein mobility, and creating biosensors. The utility of FPs also extends to biochemical approaches through immunoblotting and proteomic analyses, aided by anti‐FP antibodies and nanobodies. FPs are notoriously robust proteins with a tightly folded domain that confers a strong stability and a relative resistance to degradation and denaturation.

Methods and Results

In this study, we report that various green, orange, and red FPs can be maintained in a native, fluorescent state during the entire process of protein sample extraction, incubation with sample buffer, loading, and migration on SDS‐PAGE (sodium dodecyl sulfate‐polyacrylamide gel electrophoresis) with only minor adaptations of traditional protocols. This protocol results in the ability to detect and quantify in‐gel fluorescence (IGF) of endogenously‐expressed proteins tagged with FPs directly after migration, using standard fluorescence‐imaging devices. This approach eliminates the need for antibodies and chemiluminescent reagents, as well as the time‐consuming steps inherent in immunoblotting such as transfer onto a membrane and antibody incubations.

Conclusions and Significance

Overall, IGF detection provides clearer data with less background interference, a sensitivity comparable to or better than antibody‐based detection, a better quantification, and a broader dynamic range. After fluorescence imaging, gels can still be used for other applications such as total protein staining or immunoblotting if needed. It also expands possibilities by allowing the detection of FPs for which antibodies are not available. Our study explores the feasibility, limitations, and applications of IGF for detecting endogenously expressed proteins in cell extracts, providing insights into sample preparation, imaging conditions, and sensitivity optimizations, and potential applications such as co‐immunoprecipitation experiments.
Abnormal Vessels Potentially Accelerate Glioblastoma Proliferation by Inducing the Protumor Activation of Macrophages
Authors: Matsuzaki Hiroaki , Kai Keitaro , Komohara Yoshihiro , Yano Hiromu , Pan Cheng , Fujiwara Yukio , Yamada Rin , Iwauchi Ai , Fukasawa Nei , Tanaka Toshihide , Shimoda Masayuki , Watanabe Hiroshi , Maruyama Toru , Takeo Toru , Mikami Yoshiki , Mukasa Akitake
Published: February 2025

Glioblastoma (GBM) involves disruptions in the blood–brain barrier (BBB) and alterations in the immune microenvironment, including the activation of glioma‐associated macrophages (GAMs). Vascular endothelial growth factor inhibitors, commonly used in recurrent GBM treatment, can influence these processes. This study investigates the relationship between BBB disruption and GAM activation, focusing on plasmalemma vesicle‐associated protein (PLVAP), a marker of BBB disruption, and α1‐acid glycoprotein (AGP), an inflammatory protein implicated in tumor progression. PLVAP expression was analyzed by immunohistochemistry (IHC) in human GBM samples to determine correlations with tumor grade, proliferation, and GAM activation. Pre‐ and post‐bevacizumab treatment GBM samples were compared to assess changes in BBB integrity and macrophage activity. AGP's role in GAM activation was studied through in vitro assays and glioma implantation in AGP knockout mice, with assessments of tumor growth and angiogenesis. Results showed elevated PLVAP expression in higher‐grade gliomas, correlating with increased tumor proliferation and GAM activation, particularly around PLVAP‐positive vessels. Bevacizumab treatment reduced PLVAP expression and macrophage activity. AGP localized to regions of BBB disruption, promoting macrophage‐mediated tumor growth in vitro. AGP knockout mice demonstrated reduced angiogenesis and prolonged survival. Spatial analysis revealed increased expression of macrophage‐inducing molecules near PLVAP‐positive vessels. These findings suggest PLVAP as a marker of BBB disruption and glioma malignancy. AGP, associated with BBB leakage, contributes to GAM activation and tumor progression, highlighting its potential as a therapeutic target for GBM.
Potential Modulatory Effects of Hesperidin on the JAK/STAT Pathway in Mesangial Proliferative Glomerulonephritis
Authors: Tang Yingchun , Zhang Jing , Wang Zhengxiang , Dong Xiongjun
Published: February 2025

Mesangial proliferative glomerulonephritis (MsPGN) is a common type of glomerular disease characterized by immune complex deposition and inflammation in the kidney, leading to renal dysfunction. Currently, treatment options for MsPGN are limited, and there is a need for effective therapeutic interventions. Hesperidin (HSP), a natural flavonoid glycoside, has shown promising anti‐inflammatory and antioxidant properties in various disease models. This study aimed to investigate the therapeutic potential of HSP for MsPGN and explore its possible mechanism of action. A male Wistar rat model of MsPGN was established via tail vein injection of Thy‐1 monoclonal antibody, and the rats were divided into four groups: Control, MsPGN, MsPGN + HSP, and MsPGN + Prednisone. After 7 days of intervention, the therapeutic effects of HSP were evaluated through biochemical and histological analyses. Our results demonstrated that HSP treatment significantly reduced the levels of blood urea nitrogen, serum creatinine, total cholesterol, and triglycerides, and improved renal pathology. Additionally, pro‐inflammatory cytokines, including tumor necrosis factor‐α, interleukin‐1β, interleukin‐2, and monocyte chemoattractant protein‐1, were markedly decreased. Immunofluorescence analysis revealed reduced levels of immunoglobulin G and C5b‐9, along with decreased immune complex deposition in the kidneys. Furthermore, HSP downregulated the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), suggesting modulation of the JAK/STAT pathway. In conclusion, HSP might effectively alleviate renal injury, reduce renal inflammatory response, and inhibit renal immune complex deposition, potentially through the suppression of the JAK/STAT pathway.
Progress in Translating Glaucoma Genetics Into the Clinic: A Review
Authors: Kolovos Antonia , Maxwell Giorgina , Souzeau Emmanuelle , Craig Jamie E.
Published: February 2025

Precision medicine is paving the way for personalised risk assessment, and its translation into glaucoma clinics holds potential to change current management paradigms. Our understanding of glaucoma's genetic architecture has expanded in recent years, recognising both monogenic and polygenic contributions. Genetic testing within glaucoma populations can provide additional information for clinicians to support decision‐making. Here, we review the evidence base for genetic variants strongly associated with glaucoma and outline a vision for translating these learnings into the clinic. Integrating clinical and genetic information will provide clinicians and patients with the strongest evidence to deliver personalised glaucoma management.
Vitamin‐D Insufficiency Leads to Interleukin‐10 Reduction in Peri‐Implant Tissues: A Case–Control Study
Authors: Toy Vesile Elif , Sabanci Arife , Dündar Muhammed , Dişli Faruk , Yildiz Sedat , Aral Kübra
Published: February 2025

Objectives

Vitamin D has been reported to be crucial for bone mineralization and to play a significant role in immune and inflammatory responses. Its deficiency has been stated to be highly prevalent and might alter osseointegration of dental implants. Successful osseointegration has been claimed to be a critical aspect of implant survival and the effects of vitamin D on implant osseointegration have not been well documented. This study aimed to evaluate bone markers and cytokine levels of patients with or without vitamin D insufficiency.

Material and Methods

A total of 42 patients were included and divided into two groups: vitamin D insufficient (Group IN‐S; n = 21) and vitamin D sufficient (Group S; n = 21). Besides clinical periodontal parameters and implant stability measurements, the levels of RANKL, OPG, osteocalcin (OC), calcium (Ca), tumor necrosis factor alpha (TNF‐α), IL‐1β, caspase‐1 (CASP1), and IL‐10 in bone biopsy from implant preparation sockets and peri‐implant crevicular fluid (PICF) were determined by enzyme‐linked immunosorbent assay (ELISA). The results were represented as concentration and total amount.

Results

PICF RANKL levels (both concentration and total amount) were higher in patients with Vitamin D insufficiency compared to sufficient controls (p < 0.05). Concentration and total amount of IL‐10 were significantly lower in vitamin D insufficient participants than those of vitamin D sufficient group (p < 0.05). No differences were detected between the groups in terms of other parameters. Bone levels of all evaluated parameters also did not differ between the groups (p > 0.05).

Conclusion

It may be concluded that a low serum level of vitamin D may affect peri‐implant health through altering IL‐10 and RANKL.
Efficacy of Cleaning Methods for the Trans‐Mucosal Parts of Zirconia Monolithic Crowns
Authors: Roth Deborah , Despontin François , Compere Philippe , Lamy Marc , Hede Dorien V. A. N. , Lambert France
Published: February 2025

Background

Dental crowns have surface pollutants after their manufacturing. We know that these pollutants can be a source of peri‐implant inflammation for some cases. This study aimed to compare two dental crowns cleaning methods that are simple and quick to apply in the dental lab.

Objectives

To characterize qualitatively and quantitatively the pollution of transmucosal parts of zirconia monolithic crowns after supra‐mucosal glazing in the lab and to compare the efficacy of steam versus ultrasonic cleaning protocols.

Material and Methods

Eighteen customized zirconia monolithic crowns were divided into two groups of 9 crowns receiving a different cleaning protocol. The first group was treated with steam cleaning, whereas the second group was initially rubbed with a sterile compress soaked in a detergent and then cleaned in three successive ultrasonic baths containing a detergent, sterile water, and 70% ethanol. The presence and nature of the contaminants were investigated by BSE‐SEM and energy‐dispersive X‐ray spectroscopy microanalysis.

Results

Organic (e.g., paint, sweat) and inorganic (e.g., zirconia fragments, silica, and metals) were identified on the surface of the zirconia crown before the cleaning treatments. At baseline, pollutants cover 0.51% ± 0.26% of the total area. This percentage dropped, respectively, to 0.02% ± 0.03% after steam cleaning (p < 0.0001) and to 0.02% ± 0.01 after the ultrasonic cleaning protocol (p = 0.0026). No difference was observed between the two decontamination techniques (p > 0.9999), but the variance in the steam group was higher compared to the ultrasound group (p = 0.0042).

Conclusions

Both protocols allowed the cleaning of the transmucosal parts of the zirconia crowns to an extent of 99.98% of the studied surface. However, the ultrasound technique displayed less variability in the removal of residual pollutants and therefore should be preferred.
Current surgical practices and attitudes toward pilonidal sinus disease among Russian surgeons: A national survey
Authors: Shlyk Darya , Balaban Vladimir , He Mingze , Pikuza Maria , Tsarkov Petr
Published: February 2025

Aim

Pilonidal sinus disease (PSD), also known as pilonidal disease, is a common chronic disorder in coloproctology and general surgery. It predominantly affects young male patients and is typically located in the sacrococcygeal region. Nowadays, various approaches are used to address this condition, but no consensus on a gold standard has been established. The aim of this study was to analyse and assess current PSD practice, diagnostic and surgical approaches, training and attitudes among Russian surgeons.

Method

A comprehensive online survey comprising 35 structured questions was developed by the Russian Society of Colorectal Surgeons and distributed to its members. The survey targeted colorectal and general surgeons and collected data on demographics, professional experience, surgical training, PSD management practices and both elective and abscess surgery techniques. Categorical data are reported as frequencies and percentages.

Results

Of the 158 respondents, the vast majority were coloproctologists and general surgeons (n = 152, 96%) with over 10 years of experience (n = 110, 69.6%) and performing 10–50 operations per year. The most popular surgical procedures were excision with midline closure (68%), open healing (62%) and marsupialization (59%). PSD‐associated abscesses were managed through incision and drainage by 81 surgeons (51%). About half of surgeons had access to laser therapy for treating PSD, but sinus laser‐assisted closure was used by only 16%. Most surgeons had received training in PSD surgery under specialist supervision and felt sufficiently trained.

Conclusion

Our findings suggest that PSD surgery in Russia has not yet shifted from midline excisions to off‐midline flap procedures and minimally invasive surgery. This study calls for attention to this underprioritized group of patients and underscores the importance of developing national guidelines in Russia.
Preferences for treatment outcomes in rectal cancer: A discrete choice experiment among patients and healthy volunteers
Authors: Miles Anne , Steele Robert James Campbell , Hutton Gemma , Morris Stephen
Published: February 2025

Aim

Treatment for rectal cancer can leave patients with a permanent stoma or bowel dysfunction. In this work we aimed to examine preferences for treatment outcomes among people with and without rectal cancer.

Method

Our discrete choice experiment examined the effect of risk of cancer recurrence, presence of a stoma and bowel dysfunction on treatment preferences in 372 rectal cancer patients without a stoma, 269 with a stoma and 204 people without cancer.

Results

Predictors of treatment preferences differed significantly between all groups (p < 0.0001). Avoiding a stoma was more important to stoma‐naïve groups, while avoiding bowel dysfunction was more important to those with superior function. Reducing the risk of recurrence was valued highly, and equally, across the groups.

Conclusion

Experience of a stoma or bowel dysfunction resulted in higher tolerance of those treatment outcomes. Hearing from patients living with different treatment outcomes could help prepare newly diagnosed patients, and facilitate informed decision‐making where patients have a choice.