bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the Diagnosis and Follow‐Up of Chronic Myeloid Leukemia Using Conventional and Molecular Techniques
Authors: Bahar Noor Al‐Huda A. , Al‐Ouqaili Mushtak T. S. , Talib Nabeel M. 
Published: February 2025

ABSTRACTBackgroundThe Philadelphia chromosome (Ph) represented a finding of chronic myeloid leukemia (CML) in most cases which formed from t (9; 22) (q34; q11) resulting in the Breakpoint cluster region‐Abelson tyrosine‐protein kinase1 (BCR‐ABL1) fusion gene. Assuming CCE's inaccuracies in diagnosing CML and FISH's limitations with low BCR‐ABL1 percentages, a Predicted‐FISH (Pred‐FISH) was developed. This model predicts treatment response during follow‐up by integrating qRT‐PCR results, White Blood Cell (WBC) counts, and Cytogenetic Response data.MethodsQuantitative Real‐Time Polymerase Chain Reaction Analysis (qRT‐PCR), fluorescence in situ hybridization (FISH), and Conventional Cytogenetic Examination (CCE or Karyotyping) have been used in the detection and follow‐up of CML patients. The study included 110 individuals, divided into three groups: 31.82% (35 individuals) were newly diagnosed CML patients, another 22.73% (25 individuals) were healthy control samples, and the remaining 45.45% (50 individuals) were previously diagnosed CML patients.ResultsInclude BCR‐ABL1 fusion gene levels detected by qRT‐PCR, Ph chromosome presence t (9; 22) (q34; q11) observed by CCE, and WBC counts. The FISH test, used to confirm disease in new patients before treatment, was compared to CCE results due to its insensitivity in certain conditions. Data from CCE, FISH, qRT‐PCR, and WBC for newly diagnosed patients provided a standard for evaluating the Predicted‐FISH.ConclusionThe FISH technique excels in disease detection with over 98% accuracy and high sensitivity. QRT‐PCR is effective for monitoring CML and BCR‐ABL1 gene levels, indicating MMR and DMR. CCE, while useful for posttreatment monitoring, is less accurate in measuring treatment response over time.
Navigating First‐in‐Human and Early‐Phase Patient Studies: Study Designs, Risk Mitigation, and Population Selection Challenges
Authors: Courville Jocelyn , Barber Amanda , Fura Aberra 
Published: February 2025

AbstractFirst–in‐human (FIH) and early‐phase clinical studies have increasingly become an integral part of the entire clinical development process, applying integrated protocols and robust risk mitigation strategies to enhance participant safety and development efficiency. This manuscript focuses on the diverse study designs employed in FIH studies, strategies for effective risk mitigation, suitable study population selection, and the methodologies and considerations unique to early‐phase patient trials. FIH studies typically include single ascending dose (SAD) and multiple ascending dose (MAD) cohorts that may be conducted in healthy volunteers (HVs) or with relevant patient populations. An analysis of 193 compounds approved by the FDA's Center for Drug Evaluation and Research between 2020 and 2023 revealed that 47.7% (92 out of 193) conducted FIH or initial SAD/MAD studies in healthy volunteers, while 39.4% (76 out of 193) initiated their FIH studies in the relevant patient population. The status for 12.9% (25 out of 193) was unknown. Among the programs that did not involve healthy volunteers for FIH or initial SAD/MAD studies, 65.8% (50 out of 76) were developed for oncology indications, whereas the remaining 34.2% (26 out of 76) were involved in therapeutic areas such as rare disease, genetic disorders, and ophthalmology. This manuscript highlights the importance of tailoring scientific and operational approaches to specific molecules, indications, and patient relevance. It provides tools, strategies, and a mind map to effectively navigate challenges during this phase of the development.
Dynamic control of reactive pressure‐swing distillation process for separating tetrahydrofuran/methanol/water
Authors: Yang Kun , Wang Shangkun , Li Zeng , Liu Xiaojing , Zhang Fangkun , Shan Baoming , Cui Peizhe , Xu Qilei 
Published: February 2025

AbstractBACKGROUNDReactive pressure‐swing distillation (RPSD) is an innovative and promising technology for the separation of azeotropic systems, offering high integration and efficiency. However, the dynamic control of RPSD processes presents significant challenges due to complex coupling and nonlinearity. This paper investigates the practical control structures for the RPSD processes, and the dynamic control structure was first designed for the RPSD system for separating tetrahydrofuran/methanol/water.RESULTThree practical control structures based on PID control were developed for existing separation processes, both with and without heat integration. The results demonstrated that all designed control structures effectively withstand disturbances of ±20% in feed flow rate and composition, exhibiting strong anti‐interference capabilities. Furthermore, an advanced intelligent control strategy was designed, integrating PID control with Back Propagation Neural Networks (BPNN) to enhance the performance of the product composition controllers.CONCLUSIONThe results indicated that the BPNN can accurately predict temperature setpoints using easily measurable variables, facilitating stable control of product concentrations without the necessity for direct composition measurements. This proposed control strategy offers an efficient and reliable alternative for the control of RPSD processes. © 2025 Society of Chemical Industry (SCI).
The minimal clinically important difference changes greatly based on the patient's baseline clinical status
Authors: Franceschini Marco , Boffa Angelo , Di Martino Alessandro , Pignotti Elettra , Andriolo Luca , Zaffagnini Stefano , Filardo Giuseppe 
Published: February 2025

AbstractPurposeTo quantify the influence of baseline values of a specific patient‐reported outcome measure (PROM) on the minimal clinically important difference (MCID) calculation in a homogeneous series of knee osteoarthritis patients treated with platelet‐rich plasma (PRP) injections.MethodsA data set of 312 patients with knee osteoarthritis treated with intra‐articular PRP injections was used. Patients were evaluated through the International Knee Documentation Committee (IKDC) subjective score at 6 months after treatment. According to the baseline IKDC score, the study population was stratified into eight clusters in the first phase (<20, 20–29, 30–39, 40–49, 50–59, 60–69, 70–79 and ≥80) and in three macro clusters in the second phase (<40, 40–69 and ≥70). MCID for the IKDC score was calculated through an anchor‐based method in both phases.ResultsThe MCID calculation was performed for the eight clusters according to the baseline IKDC values, obtaining values from 16.2 to −3.1. Afterwards, further MCID calculation was performed after unifying patients in three major clusters based on the similarity of the previously obtained MCID values. Ninety‐six patients reported a baseline IKDC score <40, 173 patients between 40 and 70, and 43 patients ≥70. MCID values for the three macro clusters were: 14.6 for patients with baseline IKDC score <40, 7.2 for patients with values between 40 and 69, while patients with values ≥70 reported an MCID value of −2.8.ConclusionsThis study demonstrated that the baseline patient clinical status influences the improvement needed to be perceived as clinically relevant. Patients with a worse baseline clinical status presented higher MCID levels, while MCID lost significance in patients with high baseline clinical values. These findings warrant applying general thresholds to a patients' cohort, showing the remarkable impact of the baseline clinical status. Patient stratification ensures a proper quantification of MCID values and the identification of patients benefiting from the studied treatment.Level of EvidenceLevel 4.
Greater anterior pelvic tilt and lumbar mobility in females compared to males undergoing periacetabular osteotomy: A matched cohort study
Authors: Fischer Maximilian , Nonnenmacher Lars , Nitsch Andreas , Mühler Matthias R. , Hofer Andre , Wassilew Georgi I. 
Published: February 2025

AbstractPurposeThe functional hip–spine interaction is increasingly noted in hip preservation by periacetabular osteotomy (PAO), while potentially affecting the impingement‐free acetabular reorientation. However, the clinically relevant sex‐related differences in lumbopelvic alignment have been poorly studied. Thus, the purpose of this study was to evaluate a matched PAO patient cohort for sex‐related differences in lumbopelvic alignment.MethodsOut of 138 patients undergoing PAO between January 2024 and September 2024 at one high‐volume centre, there were 68 data sets (34 male, 34 female) included. The data sets of this diagnostic cohort study were prospectively collected, and the patients were matched in a 1:1 ratio for sex, age and acetabular morphology (hip dysplasia, borderline hip dysplasia, acetabular retroversion). Lumbopelvic alignment was assessed with serial sagittal lumbopelvic radiographs in standing, relaxed‐seated and deep‐seated positions. Each radiograph was reviewed for pelvic tilt (PT), lumbar lordosis and sacral slope.ResultsFemales showed a significantly lower PT in standing (7.8 vs. 14.3°, p < 0.001), relaxed‐seated (28.1 vs. 34.9°, p = 0.012) and deep‐seated (3.7 vs. 11.0°, p = 0.013) positions. Furthermore, females had a significantly increased lumbar mobility (Δ relaxed‐seated − deep‐seated position − 35.4° vs. 27.0°, p = 0.003), while there was no sex‐related difference in sacral mobility (p > 0.05).ConclusionThere are sex‐related differences in functional lumbopelvic alignment across various positions of daily living in patients undergoing PAO. With a greater anterior PT, females are at risk of an anterior hip impingement. Thus, the intraoperative anterior and posterior wall reorientation by PAO should be adapted to the sex‐related lumbopelvic alignment to ensure an impingement‐free surgical outcome.Level of EvidenceLevel IV, case series.
Recurrence of arthroscopic treatment of pigmented villonodular synovitis of the knee: A systematic review and meta‐analysis
Authors: Keyhani Sohrab , Soleymanha Mehran , Vosoughi Fardis , Nikibakhsh Ali , Zadgari Ervin , Mousavi Maryam , LaPrade Robert F. 
Published: February 2025

AbstractPurposeThe purpose of this study was to assess the efficacy of arthroscopic intervention on the treatment of pigmented villonodular synovitis (PVNS) patients, with a focus on the potential advantages of this approach in lowering the risk of disease recurrence.MethodsWe performed a systematic review and meta‐analysis following the PRISMA 2020 protocol. Our search encompassed five databases, namely PubMed, Embase, Scopus, Web of Science and Cochrane Library. Statistical analysis was conducted on the extracted data by using the R ver. 4.4.0 software. This study included English‐language observational studies (case series and cohort studies) published up to 31 March 2024, focusing on in vivo human subjects with at least 2 years of follow‐up. Studies with less than 2 years of follow‐up, non‐arthroscopic treatment methods or addressing PVNS in structures other than the knee were excluded.ResultsWe identified 24 articles, comprising 7 case series and 17 cohort studies, based on title, abstract, and quality assessments. Approximately 16% (95% confidence interval [CI]: 10.4%–24.75%) of knees that underwent arthroscopic surgery were found to be at risk of recurrence. In line with our expectations, sub‐group analysis comparing recurrence rates among different subtypes of PVNS found that the diffuse subtype exhibited a higher recurrence rate of 19.4% (95% CI: 10.01%–34.15%), compared to the local subtype, which had a recurrence rate of 9.5% (95% CI: 4.47%–19.01%). Based on the meta‐regression analysis, no significant association was found between the recurrence rate and the publication year or patient mean age. However, there was a noticeable rise in the recurrence rate with a longer follow‐up period, indicating a probable correlation between extended follow‐up and increased recurrence rates.ConclusionOur findings suggest that arthroscopic surgery for PVNS, particularly for the diffuse subtype, results in a higher recurrence rate compared to the localized subtype. However, the inherent challenges in achieving complete resection through arthroscopy, particularly in cases with extensive disease involvement, may contribute to the observed recurrence rates.Level of EvidenceLevel III systematic review and meta‐analysis.
Immune Signatures Identify Patient Subsets Deriving Long‐Term Benefit From First‐Line Rituximab in Follicular Lymphoma
Authors: Lolli Ginevra , Davini Alessandro , Tabanelli Valentina , Sapienza Maria Rosaria , Melle Federica , Motta Giovanna , Del Corvo Marcello , Calleri Angelica , Vanazzi Anna , Nierychlewska Paulina , Maraglino Alessio Maria Edoardo , Castelli Marta , Quattrocchi Maria Chiara , Chiarle Roberto , Pileri Stefano , Tarella Corrado , Derenzini Enrico 
Published: February 2025

ABSTRACTBackgroundThe role of first‐line single‐agent rituximab immunotherapy in follicular lymphoma (FL) remains debated, as most patients eventually undergo chemotherapy.MethodsIn this study, we retrospectively analyzed 81 FL patients treated with first‐line single‐agent rituximab monotherapy with (n = 53) or without (n = 28) consolidation. Fifty‐one patients (63%) were high‐tumor burden according to Group d'Etude des Lymphomes Folliculaires (GELF) criteria.ResultsAfter a median follow‐up of 11 years, overall survival (OS) and progression‐free survival (PFS) rates were 85% and 32%, respectively. Targeted gene expression profiling (T‐GEP) was performed in 40 patients, revealing a 26‐gene expression signature distinguishing complete responders and non‐responders. This signature included genes involved in T‐regulatory (Treg) and natural‐killer cell activity, and interleukin‐17 signaling. A simplified 14‐gene prognostic score (ImSig) enabled accurate outcome stratification in terms of PFS. These data were validated in silico using two independent publicly available cohorts of FL patients treated with chemoimmunotherapy. Deconvolution analyses demonstrated an enrichment in Treg cells in high‐risk ImSig patients, which was validated by immunohistochemistry.ConclusionsThese findings demonstrate that the efficacy of front‐line anti‐CD20 immunotherapy may depend on microenvironment‐related factors, and that specific immune signatures could identify patient subsets obtaining long‐term benefit from a chemo‐free immunotherapeutic approach.Trial RegistrationThe authors have confirmed clinical trial registration is not needed for this submission.
In Vitro Discovery of a Therapeutic Lead for HFMD From a Library Screen of Rocaglates/Aglains
Authors: Oo Adrian , Borge Angel , Lee Regina Ching Hua , Salim Cyrill Kafi , Wang Wenyu , Ricca Michael , Fong Deborah Yuhui , Alonso Sylvie , Brown Lauren E. , Porco John A. , Chu Justin Jang Hann 
Published: February 2025

ABSTRACTThe lack of effective antiviral treatments for enteroviruses, including human enterovirus A71 (EV‐A71), have resulted in an immense global healthcare burden associated with hand‐foot‐and‐mouth disease (HFMD). Rocaglates and aglains belong to a family of compounds produced by Aglaia genus plants. Since the initial discovery of rocaglates in 1982, various rocaglates and aglains have been synthesized and extensively studied mainly as anticancer agents. Here, we report the discovery of a novel aglain derivative as a potential EV‐A71 inhibitor. From an immunofluorescence‐based phenotypic screen of a library of 296 rocaglate and aglain derivatives, we identified a lead aglain which effectively suppressed EV‐A71 replication by 2.3 log fold at a non‐cytotoxic concentration, with a host cell CC50 of 21.78 µM, an EV‐A71 infection EC50 of 3.57 µM, and a selectivity index of 6.1. Further validation revealed inhibition of EV‐A71 across multiple human cell types and a pan‐enterovirus inhibitory spectrum against other enteroviruses. Subsequent mechanistic investigation revealed interference with EV‐A71 intracellular post‐entry events including viral RNA transcription and translation. Findings from this study have established a strong foundation for development of aglain scaffolds as much needed antiviral agents for HFMD, paving the way for future medicinal chemistry optimization and in vivo studies.
Klf10 Regulates the Emergence of Glial Phenotypes During Hypothalamic Development
Authors: Garduño‐Tamayo Norma Angelica , Almazán Jorge Luis , Romo‐Rodríguez Rubí , Valle‐García David , Meza‐Sosa Karla F. , Pérez‐Domínguez Martha , Pelayo Rosana , Pedraza‐Alva Gustavo , Pérez‐Martínez Leonor 
Published: February 2025

ABSTRACTGlial cells play a pivotal role in the Central Nervous System (CNS), constituting most brain cells. Gliogenesis, crucial in CNS development, occurs after neurogenesis. In the hypothalamus, glial progenitors first generate oligodendrocytes and later astrocytes. However, the precise molecular mechanisms governing the emergence of glial lineages in the developing hypothalamus remain incompletely understood. This study reveals the pivotal role of the transcription factor KLF10 in regulating the emergence of both astrocyte and oligodendrocyte lineages during embryonic hypothalamic development. Through transcriptomic and bioinformatic analyses, we identified novel KLF10 putative target genes, which play important roles in the differentiation of neurons, astrocytes, and oligodendrocytes. Notably, in the absence of KLF10, there is an increase in the oligodendrocyte population, while the astrocyte population decreases in the embryonic hypothalamus. Strikingly, this decline in the number of astrocytes persists into adulthood, indicating that the absence of KLF10 leads to an extended period of oligodendrocyte emergence while delaying the appearance of astrocytes. Our findings also unveil a novel signaling pathway for Klf10 gene expression regulation. We demonstrate that Klf10 is a target of CREB and that its expression is upregulated via the BDNF‐p38‐CREB pathway. Thus, we postulate that KLF10 is an integral part of the hypothalamic developmental program that ensures the correct timing for glial phenotypes' generation. Importantly, we propose that the Klf10−/− mouse model represents a valuable tool for investigating the impact of reduced astrocyte and microglia populations in the homeostasis of the adult hypothalamus.
Comparing Surface Mass Balance and Surface Temperatures From Regional Climate Models and Reanalyses to Observations Over the Antarctic Ice Sheet
Authors: Wang Xiaofeng , Langen Peter L. , Li Rongxing , Qiao Gang , Fan Xiaopeng , Dou Yinke , Cui Xiangbin 
Published: February 2025

ABSTRACTThis article assesses the performance of surface mass balance (SMB) and surface temperature products from seven climate models (ERA5, MERRA2, HIRHAM5_ERA‐Interim, HIRHAM5_ERA5, MARv3.11, RACMO2.3p1 and RACMO2.3p2) to be used as inputs to firn densification models (FDMs), crucial for the whole Antarctic mass balance estimation. The evaluation compiles and utilises a new dataset combining existing observations with 184 stake SMB measurements in the Vostok region and two SMB radar transects in Blåskimen Island and Nivlisen Ice Shelf, significantly enhancing the AntSMB dataset. For temperatures at 10 m (T10), 992 observations are included, offering vastly improved spatial coverage. Compared with multi‐year SMB observations, RACMO2.3p1 and ERA5 align closely with observed SMB over the inland and the whole Antarctic, with ERA5 exhibiting superior alignment in coastal areas. However, in terms of temporal SMB variations, ERA5, RACMO2.3p2 and HIRHAM5_ERA‐Interim demonstrate the best consistency with observed SMB, with ERA5 excelling in regression slope comparisons. In our surface temperature evaluation, RACMO2.3p2 and ERA5 have a minimal mean bias from T10 over the whole Antarctic. RACMO2.3p2 performs well with few occurrences of deviations beyond ±3°C in coastal areas, while RACMO2.3p2 and HIRHAM5_ERA5 are both close to T10 in inland areas. In inter‐model SMB comparisons, ERA5, HIRHAM5_Interim, HIRHAM5_ERA5, RACMO2.3p1 and RACMO2.3p2 exhibit similar deviations from the multi‐model mean (MMM), while MARv3.11 and MERRA2 show larger deviations in some coastal areas. For surface temperature, MARv3.11 and ERA5 display larger deviations from the MMM in some coastal areas where ERA5 actually matches the observations well, illustrating that MMM should not be taken to represent the true climate conditions. In conclusion, ERA5 demonstrates the best overall consistency with SMB and T10 observations compared with the other models.
National perspectives of barriers by insurance and pharmacy benefit managers in pediatric inflammatory bowel disease
Authors: Constant Brad D. , Adler Jeremy , Gold Benjamin D. , Dotson Jennifer , Lightdale Jenifer R. , Scott Frank , Saeed Shehzad , Kim Sandra , Moses Jonathan , de Zoeten Edwin F. , Mirea Lucia , Ritchey Andrew , Pasternak Brad 
Published: February 2025

AbstractObjectivesEarly biologic initiation, dose optimization, and therapy modification based on disease phenotype are key to improving outcomes in pediatric inflammatory bowel disease (IBD). Enacting optimized therapy is often impeded by the lack of United States Food and Drug Administration (FDA) approval for pediatric use of newer advanced therapies or intensified dosing regimens. These barriers often result in initial payor denial of coverage and added prior authorization burden on physicians, leading to patient delays in medication initiation and therapy optimization, and development of disease‐related morbidity.MethodsA sample of pediatric patients experiencing payor barriers to IBD biologic treatment, containing data on treatment delays and adverse outcomes, was obtained through a nationwide survey of pediatric gastroenterology providers via a longstanding, widely used pediatric gastroenterology Listserv (housed at University of Vermont) from January 2023 to August 2023.ResultsProviders across the United States reported information for 113 patients experiencing payor barriers for biologics IBD treatment. Ultimately, 77% of initial denials were approved. The median time to receiving medication was 18 days, with administrative time (prior authorization and appeal) requiring a median of 180 min. More than half (60%) of patients experienced adverse outcomes or worsened quality of life due to delays in treatment, including 21% of patients who were hospitalized.ConclusionsThese findings highlight the detrimental impact of payor barriers to treatment for children with IBD. Reforms that minimize delays in care and provider administrative burden are imperative to ensure that children receive timely evidence‐based treatment that improves disease outcomes and prevents adverse events.