bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal models and prediction in cell line perturbation experiments
Authors: Long James P. , Yang Yumeng , Shimizu Shohei , Pham Thong , Do Kim-Anh 
Published: January 2025

AbstractIn cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for predicting responses: a Linear Regression (LR) estimator and a causal structure learning estimator that we term Causal Structure Regression (CSR). The CSR estimator requires more assumptions than LR, but can predict the effects of drugs that were not applied in the training data. Next we present Cellbox, a recently proposed system of ordinary differential equations (ODEs) based model that obtained the best prediction performance on a Melanoma cell line perturbation data set (Yuan et al. in Cell Syst 12:128–140, 2021). We derive analytic results that show a close connection between CSR and Cellbox, providing a new causal interpretation for the Cellbox model. We compare LR and CSR/Cellbox in simulations, highlighting the strengths and weaknesses of the two approaches. Finally we compare the performance of LR and CSR/Cellbox on the benchmark Melanoma data set. We find that the LR model has comparable or slightly better performance than Cellbox.
Intranasal racemic ketamine maintenance therapy for patients with treatment-resistant depression: a naturalistic feasibility study
Authors: Halpape Katelyn , Pashovitz Raelle , Wanson Annabelle , Hooper Monika , Peters Evyn M. 
Published: January 2025

Abstract
Background
Ketamine is a promising therapy for treatment-resistant depression due to its rapid onset, although benefits are often transitory, with patients needing maintenance therapy to prevent relapse. Most data supporting ketamine for treatment-resistant depression refers to the intravenous route of administration, leaving alternative routes lacking in data, especially as maintenance regimens. Moreover, the safety of ketamine maintenance therapy is poorly defined. This report aims to describe and evaluate a novel hospital-to-outpatient intranasal racemic ketamine maintenance therapy program.

Methods
This was an observational program evaluation study. Participants were adult inpatients with treatment-resistant depression who had been successfully treated with intranasal racemic ketamine in hospital and were being referred for outpatient maintenance therapy with an intranasal racemic ketamine spray, administered at a specialized community treatment centre. Effectiveness was assessed with the Self-Report Quick Inventory of Depressive Symptomatology, the Quality of Life Scale, and the Clinical Global Impression-Improvement scale.

Results
Five patients were enrolled, completing up to 14 treatment sessions over 192 days. The mean dose administered throughout treatment was 220 mg (100 to 400 mg). All patients had decreased (or stable) depressive symptoms and increased (or stable) quality of life. There were no serious adverse events or discontinuations due to adverse effects. Reported adverse effects included anxiety and nausea. Slight blood pressure increases were seen during treatment, none of which required intervention.

Conclusions
Intranasal racemic ketamine maintenance therapy for treatment-resistant depression appeared to be feasible and well tolerated, although effectiveness conclusions cannot be drawn from this small pilot study. Further investigations regarding the safety and effectiveness of intranasal ketamine maintenance therapy are warranted.
Practice of self-medication to manage oral health issues in a community setting of Nepal
Authors: Shrestha Ashish , Bhagat Tarakant , Agrawal Santosh Kumari , Gautam Ujwal , Joshi Naresh Prasad 
Published: January 2025

Abstract
Background
Self-medication has been defined as the practice of self-diagnosis and medication use without seeking professional healthcare advice. Its prevalence for alleviating dental problems in Nepali communities has not been explored. This study was conducted to assess self-medication for oral health problems in a community setting in Nepal.

Methods
A community-based cross-sectional study was conducted in two conveniently selected wards of Baraha Municipality of Sunsari district in August 2021 using a pre-validated questionnaire in the Nepali language. The prevalence of self-medication for oral health problems was assessed. The chi-square and Mann-Whitney U tests were used to check its association with demographic variables.

Results
The prevalence of self-medication was found to be 43.3%. The most common health problem leading to self-medication was toothache (78.5%). Around half of the respondents (55.1%) replied achieving temporary relief after its use while around a quarter (25.1%) thought that self-medication was effective in taking care of their problems. Three-quarters of the respondents (75.7%) knew that they had to visit a dentist if their problems persisted. The annual family income was significantly associated with the practice of self-medication for oral health problems. (p = 0.013)

Conclusion
Self-medication was found to be frequently utilized by the people of Baraha municipality with almost every second person with oral health problems reporting using it to solve their problems. This phenomenon is disproportionately seen in those with lower economic status.

Clinical trial number
Not applicable.
A hyperspectral open-source imager (HOSI)
Authors: Troscianko Jolyon 
Published: January 2025

Abstract
Background
The spatial and spectral properties of the light environment underpin many aspects of animal behaviour, ecology and evolution, and quantifying this information is crucial in fields ranging from optical physics, agriculture/plant sciences, human psychophysics, food science, architecture and materials sciences. The escalating threat of artificial light at night (ALAN) presents unique challenges for measuring the visual impact of light pollution, requiring measurement at low light levels across the human-visible and ultraviolet ranges, across all viewing angles, and often with high within-scene contrast.

Results
Here, I present a hyperspectral open-source imager (HOSI), an innovative and low-cost solution for collecting full-field hyperspectral data. The system uses a Hamamatsu C12880MA micro spectrometer to take single-point measurements, together with a motorised gimbal for spatial control. The hardware uses off-the-shelf components and 3D printed parts, costing around £350 in total. The system can run directly from a computer or smartphone with a graphical user interface, making it highly portable and user-friendly. The HOSI system can take panoramic hyperspectral images that meet the difficult requirements of ALAN research, sensitive to low light around 0.001 cd.m−2, across 320–880 nm range with spectral resolution of ~ 9 nm (FWHM) and spatial resolution of ~ 2 cycles per degree. The independent exposure of each pixel also allows for an extremely wide dynamic range that can encompass typical natural and artificially illuminated scenes, with sample night-time scans achieving full-spectrum peak-to-peak dynamic ranges of > 50,000:1.

Conclusions
This system’s adaptability, cost-effectiveness and open-source nature position it as a valuable tool for researchers investigating the complex relationships between light, environment, behaviour, ecology and biodiversity, with further potential uses in many other fields.
Dystonia caused by ANO3 variants is due to attenuated Ca2+ influx by ORAI1
Authors: Ousingsawat Jiraporn , Talbi Khaoula , Gómez-Martín Hilario , Koy Anne , Fernández-Jaén Alberto , Tekgül Hasan , Serdaroğlu Esra , Ortigoza-Escobar Juan Darío , Schreiber Rainer , Kunzelmann Karl 
Published: January 2025

Abstract
Background
Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.

Methods
We applied electrophysiology, Ca2+ measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca2+ signals and defective activation of K+ channels in patients heterozygous for the ANO3 variants.

Results
Upon expression, emptying of the endoplasmic reticulum Ca2+ store (store release) and particularly store-operated Ca2+ entry (SOCE) were strongly inhibited, leading to impaired activation of KCa3.1 (KCNN) K+ channels, but not of Na+-activated K+ channels (KNa; SLO2). The data provide evidence for a strongly impaired expression of store-operated ORAI1 Ca2+ influx channels in the plasma membrane of cells expressing ANO3 variants.

Conclusions
Dysregulated Ca2+ signaling by ANO3 variants may impair the activation of K+ channels in striatal neurons of the brain, thereby causing dystonia. Furthermore, the data provide a first indication of a possible regulation of protein expression in the plasma membrane by ANO3, as has been described for other anoctamins.
Clinical efficacy and hemodynamic effects of levosimendan in cardiac surgery patients after surgery
Authors: Zhao Meiling , Hou Yunfeng , Yuan Meng , Ma Shuang , Yue Yifeng 
Published: January 2025

Abstract
Objective
To investigate the therapeutic effect of levosimendan on hemodynamics in patients undergoing major cardiac surgery and presenting with acute postoperative heart failure.

Methods
The subjects of the study were 160 patients with severe cardiac conditions who underwent surgery and had acute heart failure. Eighty cases each were assigned to the research and control groups using a random number table. Document the general patient data for each of the two groups; compare the clinical outcomes of the two groups. The hemodynamic states of the two groups were compared both before and after therapy. 48 h after surgery, echocardiography was performed in both groups to determine cardiac function. 48 h after surgery, N-terminal pro-brain B-type natriuretic peptide (NT-Pro-BNP) levels were compared between the two groups.

Results
The overall effective rate was significantly higher in the research group (92.5%) compared to the control group (76.25%, P < 0.05). Post-treatment, the research group demonstrated a significant reduction in CVP (9.25 ± 2.11 cmH2O vs. 11.36 ± 3.08 cmH2O, P < 0.001), heart rate (100.30 ± 8.69 bpm vs. 105.74 ± 7.69 bpm, P < 0.001), and lactic acid levels (1.68 ± 0.59 mmol/L vs. 2.69 ± 0.55 mmol/L, P < 0.001). The research group also showed improvements in SBP (117.23 ± 8.74 mmHg vs. 113.25 ± 7.55 mmHg, P = 0.002) and urine output (4.21 ± 1.76 mL/kg/h vs. 3.65 ± 1.23 mL/kg/h, P = 0.021). Cardiac function indicators 48 h after surgery indicated a higher LVEF (55.21 ± 8.04% vs. 47.18 ± 6.60%, P < 0.001) and lower LVEDVi and LVESVi in the research group (P < 0.001 for both). NT-Pro-BNP levels were significantly lower in the research group (6010.19 ± 1208.52 pg/mL vs. 9663.21 ± 2391.34 pg/mL, P < 0.001). The incidence of complications was lower in the research group (5% vs. 22.5%, P = 0.001).

Conclusion
Cardiac surgery patients are prone to complications with acute heart failure after surgery. Treatment with levosimendan can significantly improve clinical efficacy and reduce complications. It can also effectively improve patients' cardiac function and promote hemodynamic stability.
Comprehensive Iranian guidelines for the diagnosis and management of maple syrup urine disease: an evidence- and consensus- based approach
Authors: Rostampour Noushin , Dalili Setila , Moravej Hossein , Afshar Zhila , Yazdani Negar , Mousavi Seyedeh Tahereh , Rostami Parastoo , Zamanfar Daniel , Yahay Maryam , Nikravesh Abdolhossein , Beyzaei Zahra , Davoodi Mohamad Ahangar , Sedaghat Atefeh , Hakemzadeh Tahora , Talea Ali 
Published: January 2025

AbstractMaple Syrup Urine Disease (MSUD) disease is a defect in the function of the Branched-chain 2-ketoacid dehydrogenase complex (BCKDH). It is caused by pathogenic biallelic variants in BCKDHA, BCKA decarboxylase, or dihydrolipoamide dehydrogenase. The brain is the major organ involved in MSUD. MSUD happens in about 1 in 86,800 to 185,000 live births. According to some diversity in the management of Iranian patients with MSUD, the development of a national guideline is essential. This guideline is provided through a literature search on articles in PubMed, Scopus, Web of Sciences, Cochrane, and Embase databases from 2001 to 2022 accompanied by a consensus of physicians of different centers in Iran who are experts in the diagnosis and management of this disease. This article considers pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and monitoring of MSUD patients with limited recourse.
VCP regulates early tau seed amplification via specific cofactors
Authors: Batra Sushobhna , Vaquer-Alicea Jaime , Valdez Clarissa , Taylor Skyler P. , Manon Victor A. , Vega Anthony R. , Kashmer Omar M. , Kolay Sourav , Lemoff Andrew , Cairns Nigel J. , White Charles L. , Diamond Marc I. 
Published: January 2025

Abstract
Background
Neurodegenerative tauopathies may progress based on seeding by pathological tau assemblies, whereby an aggregate is released from one cell, gains entry to an adjacent or connected cell, and serves as a specific template for its own replication in the cytoplasm. Seeding into the complex cytoplasmic milieu happens within hours, implying the existence of unknown factors that regulate this process.

Methods
We used proximity labeling to identify proteins that control seed amplification within 5 h of seed exposure. We fused split-APEX2 to the C-terminus of tau repeat domain (RD) to reconstitute peroxidase activity 5 h after seeded intracellular tau aggregation. Valosin containing protein (VCP/p97) was the top hit. VCP harbors dominant mutations that underlie two neurodegenerative diseases, multisystem proteinopathy and vacuolar tauopathy, but its mechanistic role is unclear. We used immortalized cells and human neurons to study the effects of VCP on tau seeding. We exposed cells to fibrils or brain homogenates in cell culture media and measured effects on uptake and induction of intracellular tau aggregation following various genetic and pharmacological manipulations of VCP.

Results
VCP knockdown reduced tau seeding. Chemical inhibitors had opposing effects on seeding in HEK293T tau biosensor cells and human neurons: ML-240 increased seeding efficiency, whereas NMS-873 decreased it. The inhibitors only functioned when administered within 8 h of seed exposure, indicating a role for VCP early in seed processing. We screened 30 VCP co-factors in HEK293T biosensor cells by genetic knockout or knockdown. Reduction of ATXN3, NSFL1C, UBE4B, NGLY1, and OTUB1 decreased tau seeding, as did NPLOC4, which also uniquely increased soluble tau levels. By contrast, reduction of FAF2 increased tau seeding.

Conclusions
Divergent effects on tau seeding of chemical inhibitors and cofactor reduction indicate that VCP regulates this process. This is consistent with a cytoplasmic processing complex centered on VCP that directs seeds acutely towards degradation vs. amplification.
Carbohydrate conversion in spent coffee grounds: pretreatment strategies and novel enzymatic cocktail to produce value-added saccharides and prebiotic mannooligosaccharides
Authors: Shaikh-Ibrahim Ali , Curci Nicola , De Lise Federica , Sacco Oriana , Di Fenza Mauro , Castaldi Stefany , Isticato Rachele , Oliveira André , Aniceto José P. S. , Silva Carlos M. , Serafim Luísa Seuanes , M. Krogh Kristian B. R. , Moracci Marco , Cobucci-Ponzano Beatrice 
Published: January 2025

Abstract

Background
Spent coffee grounds (SCG) are the most abundant waste byproducts generated from coffee beverage production worldwide. Typically, these grounds are seen as waste and end up in landfills. However, SCG contain valuable compounds that can be valorized and used in different applications. Notably, they are rich in carbohydrates, primarily galactomannan, arabinogalactan type II, and cellulose. Within the framework of a circular bioeconomy, the targeted degradation of these polysaccharides via a tailored cocktail of carbohydrate-active enzymes offers a promising strategy for producing high-value saccharides from coffee waste.

Results
In this study, various mild pretreatments were evaluated to increase the enzyme accessibility of SCG-derived biomass, reduce lignin content, and minimize hemicellulose loss. Thermostable enzymes were selected to construct an enzymatic cocktail specifically targeting cellulose and hemicelluloses in pretreated SCGs. The approach used achieved a conversion of 52% of the polysaccharide content to oligo- and monosaccharides, producing 17.4 mg of reducing sugars and 5.1 mg of monosaccharides from 50 mg of SCG. Additionally, microwave pretreatment followed by the application of a thermostable endo β-mannanase resulted in the production of 62.3 mg of mannooligosaccharides from 500 mg of SCG. In vitro experiments demonstrated that the produced mannooligosaccharides exhibited prebiotic activity, promoting the growth and biofilm formation of five probiotic bacterial strains.

Conclusions
This study highlights an effective strategy for the valorization of SCG polysaccharides through mild pretreatment and customized enzymatic cocktails in a circular bioeconomic context. The production of both monosaccharides and oligosaccharides with prebiotic activity illustrates the versatility and commercial potential of SCG as a substrate for high-value saccharides. Furthermore, the use of mild pretreatment methods and thermostable enzymes minimizes chemical inputs and energy demands, aligning with sustainable processing practices. The ability to selectively target and degrade specific polysaccharides within SCG not only enhances the yield of desirable products, but also preserves key structural components, reducing waste and promoting resource efficiency.
Substance use recovery needs among college students seeking recovery services: a thematic qualitative analysis
Authors: Nichols Lindsey M. , Brown Tiffany B. , Allmendinger Angela , Hennessy Emily A. , Tanner-Smith Emily E. 
Published: January 2025

Abstract
Background
College students who are in recovery from substance use disorders face challenges related to abstaining from substance use, finding supportive social networks, and achieving their academic goals. These students may therefore seek out various recovery supports at their institutions to meet their needs and goals.

Methods
This study analyzed previously collected data to explore themes related to students’ experiences of recovery, including their recovery needs and challenges while also attending college. We conducted qualitative thematic analysis of written responses to open-ended prompts posed to 92 college students from one university (47% female; M age = 21.5 years, SD = 5.6) who participated in a larger parent study of Collegiate Recovery Programs in the United States. We used a phenomenological approach to guide the current study, to characterize the meaning and experience within the shared phenomenon of recovery processes among college students.

Results
Two broad categories emerged, representing nine total themes that were coded: (a) intrapersonal factors: recovery-specific challenges, self-care and coping, mental and behavioral health, life challenges, and personal motivations and attributes; and (b) interpersonal/social factors: 12-step recovery supports, external supports and community, college environment, and relationships with others.

Conclusions
Findings offer insight into barriers and facilitators to recovery among colleges students and are discussed in terms of their implications for primary stakeholders at institutions of higher education to support college students in substance use recovery.
The burden of Gastric Cancer and possible risk factors from 1990 to 2021, and projections until 2035: findings from the Global Burden of Disease Study 2021
Authors: Qin Niping , Fan Yangyan , Yang Tao , Yang Zhiping , Fan Daiming 
Published: January 2025

Abstract
Background and objective
Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking.

Methods
The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035.

Results
In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs.

Conclusions
Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.