bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of an automated method for the isolation and purification of fat-soluble vitamins and cholesterol for chromatographic analysis
Authors: van Aardt Marleen , Komarek Andrew R , Roche Michael , Ivarsen Elise 
Published: February 2025

Abstract

Background
The isolation and purification of vitamins A, E, D and cholesterol from food and feed test materials, for quantitation, is currently a time consuming and labor-intensive process. It includes separate steps for saponification, extraction, purification, and solvent evaporation. A new instrument (FLEX) was developed which improves and automates all steps involved, and which uses solid phase extraction (SPE). This study validates the FLEX automated method.

Objectives
The objective of this study was to validate the automated method by recovery of standards, analysis of reference materials, comparison against proficiency test materials, and comparison against manual reference methods.

Methods
The FLEX instrument automatically adds reagents, mixes and heats to saponify test materials, filters the digestate, extracts with SPE, and evaporates solvent.

Results
The accuracy of the automated FLEX Instrument method was confirmed by the agreement with NIST reference materials for retinol, α-tocopherol, cholecalciferol, ergocalciferol, and cholesterol. Accuracy also was compared against manual reference methods on 11 different food types that ranged from 4–100% fat, 0–75% protein, and 0–85% carbohydrates. The automated and manual methods were highly correlated with no bias or distortion over the range of test materials. Precision was similar to the manual methods for retinol recovery but improved for α-tocopherol and cholecalciferol analysis. The accuracy of the automated method also was confirmed for feed analysis. Eleven different animal feeds were analyzed in the FLEX and results were highly correlated with Association of American Feed Control Officials proficiency test results.

Conclusions
The automated method accurately and efficiently performed the multiple analytical steps necessary for the isolation and purification of the analytes in preparation for chromatographic analysis.

Highlights
The automated method was compared against industry standard methods and yielded equivalent results and improved precision. SPE technology was optimized to efficiently elute non-polar analytes, while retaining protein and other medium-polar analytes.
Involvement of a NIMA-related kinase in cell division in a liverwort Marchantia polymorpha
Authors: Mase Hikari , Sumiura Aoi , Yoshitake Yoshihiro , Kohchi Takayuki , Takahashi Taku , Motose Hiroyasu 
Published: February 2025

Abstract
NIMA-related kinases (NEKs) regulate a series of mitotic events in fungi and animals, whereas plant NEKs have been shown to control the growth direction of cells and organs. Plant NEKs are highly expressed in the meristem, but whether they regulate meristematic activity remains unknown. The liverwort Marchantia polymorpha has a single functional MpNEK1 gene, and its knockout results in twisted rhizoid growth. For a gain-of-function approach, we generated lines for the inducible expression of MpNEK1 using an estrogen receptor mediated system. Estradiol treatment effectively induced the accumulation of MpNEK1 mRNA and MpNEK1-Citrine fusion protein throughout the plant. MpNEK1 overexpression severely suppressed rhizoid and thallus growth, ultimately leading to the lethality of juvenile plants. This severe effect was observed even at the nanomolar level of estradiol. EdU staining and microtubule imaging clearly indicated suppression of cell division by estradiol-induced MpNEK1. MpNEK1 induction also reduced cortical microtubule density and dynamics, but not severely affected cell growth and morphology in thalli. Overexpression of kinase-deficient MpNEK1 also suppressed thallus and rhizoid growth, although to a slightly lesser extent than wild-type MpNEK1, indicating a phosphorylation-independent mechanism of growth suppression. Furthermore, Mpnek1 mutants exhibited growth suppression in their reproductive organs, the gametangiophores. This supports the role of MpNEK1 in cell division, as observed in both fungi and animals.
Sitting Together and Reaching to Play (START-Play) Physical Therapy Affects Dyadic Emotional Availability in Children and with Neuromotor Delay and their Families
Authors: Molinini Rebecca , Stuyvenburg Corri , Koziol Natalie A , Harbourne Regina T , Hsu Lin-Ya , Lobo Michele A , Willett Sandra L , Bovaird James A , Chu Virginia W , Price Sarah K , Shall Mary S , Dusing Stacey C 
Published: February 2025

Abstract

Objective
Emotional availability (EA) describes caregiver-child emotional attunement and is critical to fostering adaptive development. Although early physical therapist interventions adopt a family-centered approach, the impact of interventions on families is often not quantified. This study compares EA in dyads receiving usual care–early intervention (UC-EI) versus sitting together and reaching to play (START-Play) in addition to UC-EI.

Methods
Data were drawn from 106 children with neuromotor delay who were 7 to 16 months old at baseline (mean = 10.5 months) and from their caregiver (91% were mothers). The Emotional Availability Scale, Fourth Edition, was scored from 5-minute videotaped interactions collected at baseline and at 3, 6, and 12 months after baseline. Piecewise multilevel modeling controlling for baseline age and motor delay estimated short- and long-term effects between treatment groups. Additionally, within-group change over time was analyzed to understand if groups differed in direction of EA trajectories. Analyses were run aggregated across all participants and stratified by baseline severity of motor delay or caregiver-reported education.

Results
When comparing EA between groups, there were significant positive short- and long-term effects of START-Play on adult EA (gs &gt; 0.38), sensitivity (gs &gt; 0.26), structuring (gs &gt; 0.43), and nonintrusiveness (gs &gt; 0.36). For dyads with mild or significant motor delay or whose parent reported less than a bachelor’s degree at baseline, positive effects of START-Play were observed.

Conclusion
Results support important clinical implications for the positive effect of START-Play on EA. Similar child-level treatment effects highlight that the key difference between START-Play and UC-EI may lie in the way intervention affects caregivers. START-Play may be more beneficial to dyads with higher versus lower risks to EA.

Impact
Early physical therapist interventions can have a significant impact on parents, children, and the parent–child relationship. Measuring the effect of these interventions on the relationship is critical to optimizing the delivery of family-centered care.
Toward Procedural Judicial Review of Constitutional Law-Making Process in Israel
Authors: Ilan Gonen , Rosilio Gal 
Published: February 2025

Abstract
As part of Israel’s 2023 judicial overhaul, the Knesset enacted Amendment No. 3 to the Basic Law: The Judiciary on 24 July 2023. This amendment barred courts from reviewing the reasonableness of decisions made by the government, prime minister, or ministers. In response, numerous petitions were filed with the Israeli High Court of Justice. Given its importance, the High Court of Justice convened all 15 justices for the hearing, and in an 800-plus page ruling, it annulled the amendment citing abuses of the Knesset’s constituent power. This article examines the rulings of former Chief Justice Esther Hayut (acting Chief Justice during the ruling) and her successor Chief Justice Uzi Vogelman, focusing on alleged procedural flaws. After reviewing their rulings, we will propose an analysis of the impact of their judgments on procedural judicial review of the constitutional law-making process. Based on this, we will suggest refining and updating the Doctrine of the Principle of Participation—a doctrine developed in case law as a tool for procedural-constitutional review—to align with the stricter judicial standards of the constitutional process.
Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells
Authors: Motafeghi Farzaneh , Fakhri B Maryam S , Ghassemi Barghi Nasrin 
Published: February 2025

Abstract

Erythropoietin (EPO) is known for its role in hematopoiesis and also exhibits anti-inflammatory, anti-apoptotic, antioxidant, and cytoprotective properties. However, its clinical application is limited by hematopoietic side effects. ARA290, a non-hematopoietic derivative of EPO, selectively activates the innate repair receptor (IRR) and replicates these protective effects without the associated hematopoietic complications. Cadmium (Cd), a prevalent environmental toxin, causes neurotoxic damage through mechanisms such as oxidative stress, genotoxicity, apoptosis, and inflammation. This study explored ARA290’s neuroprotective effects against cadmium-induced toxicity in PC12 cells, an in vitro model for neuronal health. PC12 cells pretreated with ARA290 showed significantly improved cell viability in the MTT assay, indicating reduced cytotoxicity. The comet assay revealed decreased DNA damage, suggesting reduced genotoxicity. ARA290 also alleviated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside increased glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activities. A marker of apoptosis, TUNEL-positive cells, was significantly reduced. Additionally, ARA290 decreased inflammatory markers such as TNF alpha, IL1ß and IL 6. These findings demonstrate that ARA290, via IRR activation, provides robust neuroprotection against cadmium-induced toxicity, suggesting a multi-faceted protective mechanism. This highlights ARA290’s potential therapeutic role in managing heavy metal-induced neurotoxicity and supports further research into its long-term effects and applications in other neurodegenerative diseases or conditions involving environmental toxins.

Highlights
NUP98‐p65 complex regulates DNA repair to maintain glioblastoma stem cells
Authors: Li Feifei , Zhang Ying , Li Jiahui , Jiang Ranran , Ci Shusheng 
Published: February 2025

AbstractThe nuclear pore complex (NPC) is an evolutionarily conserved structure that maintains the traffic between the nucleus and cytoplasm. Here, we profiled the expression of nucleoporins (NUPs) in glioblastoma stem cells (GSCs) and found that NUP98 promoted GSC maintenance and therapeutic resistance. GSCs preferentially expressed NUP98, which is essential for GSC tumorigenesis in vitro and in vivo. RNA sequencing demonstrated that NUP98 regulated the expression of key DNA damage and repair pathways. NUP98 formed a complex with transcription factor p65 to directly activate genes involved in homologous repair. Attenuation of NUP98 or p65 expression induced unrepaired intrinsic DNA damage and sensitized GSC to ionizing radiation. Clinically, overexpression of NUP98 informs poor clinical outcome among glioblastoma (GBM) patients. Collectively, our results demonstrate that NUP98‐p65 represents a novel node in the regulation of DNA repair, suggesting a therapeutic strategy with potential clinical benefits for GBM patients.
A “Totally Different Beast”: The Effect of Time Variability on Clinical Competency Committee Decision-Making
Authors: Kinnear Benjamin , Santen Sally A. , DeCoursey Bailey , Ferris Sarah , Schumacher Daniel J. 
Published: February 2025

Abstract

Purpose
Competency-based, time-variable training (CBTVT) uses educational outcomes rather than time to determine learner readiness to progress through training. Clinical competency committees (CCCs) are critical components of CBTVT because they ultimately render time-variable promotion decisions. However, the effect of time variability on CCC member decision-making remains unclear. In this study, the authors explored the effect of time variability on the decision-making of CCC members at an internal medicine residency program.

Method
The authors used an evaluative case study approach to study the University of Cincinnati internal medicine residency program’s CBTVT pilot, called Transitioning in Internal Medicine Education Leveraging Entrustment Scores Synthesis (TIMELESS), with 2 to 3 residents per postgraduate year participating longitudinally between October 2020 and March 2022. Taking a constructionist worldview, the authors used semistructured interviews with members of the TIMELESS CCC to explore how time variability affected their decision-making about resident promotion. Interviews and observations were completed between February 2021 and January 2022.

Results
In total, the authors completed 16 interviews with 11 unique CCC members. Participants reported that time variability significantly affected their decision-making process. The authors developed 3 related themes. First, time variability created a sense of increased stakes of promotion decisions. Second, the increased perceived stakes of decisions led to more deliberate decision-making. Third, time in training and clinical experience still influenced time-variable promotion decisions.

Conclusions
Time variability changed CCC member perception of the decision-making (more risk, higher stakes), with subsequent change in their behaviors (in-depth review, active decision-making). Although many time-based programs make entrustment determinations that are not linked to tangible consequences (i.e., Would I trust?), TIMELESS asked CCC members to make entrustment decisions that were consequential (i.e., Will I trust?).
A Comparison of Inpatient Versus Ambulatory Lumbar Surgical Care Utilization Among Minority Patients
Authors: Tiao Justin , Alasadi Husni , Herrera Michael M. , Zubizarreta Nicole , Huang Jonathan , Poeran Jashvant , Chaudhary Saad 
Published: February 2025

Study Design:
Retrospective cohort study.

Objectives:
Identify and compare racial/ethnic disparities in ambulatory versus inpatient surgical care utilization for single-level lumbar spine surgery.

Summary of Background Data:
The proportion of spine surgeries performed in the ambulatory setting has dramatically increased over the past 2 decades. However, few studies have investigated whether this shift has resulted in racial/ethnic disparities in surgical care utilization, particularly for outpatient lumbar spine surgery, compared with the inpatient setting.

Materials and Methods:
Utilizing the 2019 National Inpatient Sample and Nationwide Ambulatory Surgical Sample discharge, we included patients who had undergone a single-level lumbar discectomy, laminectomy, and/or fusion, were of Black, White, or Hispanic race/ethnicity, were covered under Medicare, Medicaid, or private insurance, and were aged 18 years or above. The primary outcome was the rate ratio (RR) of patients from the aforementioned 3 racial/ethnic groups undergoing lumbar surgical care, in the ambulatory and inpatient settings. US Bureau of Labor Statistics data were utilized to offset the model for population-based variations in sociodemographic factors utilizing nested coefficients.

Results:
Among 397,173 cases, 220,250 (55.5%) were inpatient, and 176,923 (44.5%) were ambulatory. Compared with White patients, Black (RR: 0.54, 95% CI: 0.53–0.55) and Hispanic (RR: 0.61, 95% CI: 0.60–0.62) patients had lower utilization rates of ambulatory surgical care. More pronounced patterns were observed for Black (RR: 0.44 95% CI: 0.44–0.45) and Hispanic (RR: 0.55, 95% CI: 0.54–0.56) inpatient surgical utilization; all P < 0.001.

Conclusions:
Racial/ethic disparities in single-level lumbar surgical care utilization exist in both the ambulatory and the inpatient setting.

Level of Evidence:
Level 3.
A Meta-analysis on Effects of Chimeric Antigen Receptor T-cell Therapy in Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
Authors: Jamil Abdur , Qureshi Zaheer , Siddique Rimsha , Altaf Faryal , Jamil Rohma , Wali Neehal 
Published: February 2025

Objectives:
This review evaluates the long-term outcomes and adverse events associated with chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Methods:
We conducted the search in relevant databases up to June 2024. We included clinical trials on CAR T-cell therapy for patients with r/r B-ALL. Meta-analyses were conducted using Comprehensive Meta-Analysis V3 and Review Manager 5.4.

Results:
Out of 2659 identified studies, 10 were included in this review. The pooled analysis demonstrated a high minimal residual disease-negative complete remission, with an overall event rate (ER) of 70% (95% CI: 61%-78%, I
2 =8 8.35%). Anti-CD19 CAR T-cell therapy showed the highest efficacy with an ER of 74.75% (95% CI: 61%-80%, I
2 = 89.84%). Combination therapies targeting CD19 and CD22 had an ER of 69% (95% CI: 53%-83%, I
2 = 82.56%). Significant adverse effects included cytokine release syndrome with a mean incidence of 81.8% (95% CI: 76.7%-86.9%), neurotoxicity at 33.2% (95% CI: 28.1%-38.3%), and hematologic toxicities at 71.9% (95% CI: 66.4%-77.4%).

Conclusions:
CAR T-cell therapy is a groundbreaking advancement in treating r/r B-ALL, offering high rates of durable remissions.
Advancements in conventional cancer therapy combined with immunotherapy
Authors: Li Hongxia , Han Songyan , Dong Chunbo , Liu Zhida 
Published: February 2025

Abstract
Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells, reducing the overall tumor burden. Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects. Emerging immunotherapies have revolutionized the clinical management of various cancer types. Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy, leading to numerous ongoing clinical investigations exploring their potential synergistic effects. However, trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy. This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy, chemotherapy, targeted therapy regimens (including dosing, timing, and administration route), and surgery on both cancer cells and the host immune system. Here, we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy. We proposed that optimizing the dosing, timing, and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies, thus offering significant clinical advantages.
Video Grading of Bile Duct Anastomoses During Robotic Pancreatoduodenectomy Predicts Bile Leak and Identifies the Learning Curve
Authors: Zwart Maurice J.W. , van den Broek Bram L.J. , Zwetsloot Sabrina L.M. , Busch Olivier R. , Tran T.C.Khé , Luyer Misha D. , Schreinemakers Jennifer , Wijsman Jan H. , van der Schelling George P. , de Hingh Ignace H.J.T. , Mieog J. Sven D. , Bonsing Bert A. , Takagi Kosei , de Wilde Roeland F. , Zeh Herbert J. , Zureikat Amer H. , Hogg Melissa E. , Groot Koerkamp Bas , Besselink Marc G. ,   for the Dutch Pancreatic Cancer Group
Published: February 2025

Objective:
To determine if video grading using Objective Structured Assessment of Technical Skills (OSATS) could estimate the risk of postoperative bile leak (BL) after robotic pancreatoduodenectomy (RPD) and to identify a learning curve effect.

Summary Background Data:
The hepaticojejunostomy (HJ) bile leak rate after RPD is rather high with 10% and may be improved by structured training and skills. Robotic HJ therefore requires confirmation of adequate performance. Grading of surgical performance during HJ could be used in competency-based surgical training.

Methods:
Post-hoc analysis of patients included the Dutch LAELAPS-3 RPD training program in 6 centers. Technical performance during robotic HJ was graded by two blinded graders using OSATS (attainable scores 6-30). Primary outcome was grade B/C bile leak according to the ISGLS. Logistic regression determined the performance cut-off and CUSUM analysis identified the learning curve.

Results:
Videos from robotic HJ in 259 patients were included with a 6.9% rate of grade B/C bile leak (n=18/259). The median OSATS for the HJ was 25.0 [22–27], with an OSATS score>21 associated with a reduced risk of BL. The rate of BL was 5.1% in patients for OSATS>21 and 12.5% for OSATS ≤21, amounting to a relative reduction of 59.2% and an absolute reduction of 7.4% (8/64 vs. 10/195, OR 0.378, P=0.013). These findings remained similar when only including grade C BL: OR 0.076, P=0.004. On multivariable analysis for grade B/C BL, the only significant predictive factor was OSATS>21: OR 0.273, P=0.025. Stabilization of the CUSUM learning curve for grade B/C BL was reached at 19 RPD procedures, and after 44 procedures the learning curve showed a continuous downward trend. The rate of grade B/C BL was significantly lower beyond 19 RPD: 5.6% versus 8.6% (8/143 vs. 10/116, OR 0.710, P=0.040).

Conclusions:
The risk of postoperative BL after RPD is strongly associated with surgical performance during robotic HJ as objectified using OSATS. This approach can be used for rapid assessment of the learning curve and competency-based surgical training, aiming for a safe implementation RPD.