bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short‐Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B‐Cell Acute Lymphoblastic Leukemia: A Retrospective Single‐Center Study
Authors: Yin Jin , Cai Xiaoya , Qian Bingxin , Liu Ying , Li Dengju 
Published: December 2024

ABSTRACTBackgroudThe high cost of blinatumomab in full doses of full treatments has led to dose reduction and fewer treatment cycles for most patients in China. With current needs for cost‐efficiency and resource management in health care, we retrospectively evaluated the clinical effects of short‐course blinatumomab treatment for R/R Ph‐ B‐ALL at our center.MethodsBlinatumomab was administered with 24‐h continuous intravenous infusion (9 μg/day for the first 3 days and 28 μg/day for 6–10 days). The clinical data of 30 R/R B‐ALL patients were collected and analyzed.ResultsA total of 25 patients (83.3%) including 13 (43.3%) with a high leukemic load (> 50%) achieved morphological CR. Twelve patients (40%) were MRD‐negative. The estimated 2‐year OS rate was 82.62%. The 2‐year PFS rate was 78.35%. The estimated 2‐year OS and PFS were significantly better in patients receiving further treatment.ConclusionsOur findings provide novel insights into the optimization of blinatumomab therapy, proposing a viable treatment alternative that aligns with current needs for cost‐efficiency and resource management in health care.
Structural Diversity and Mutational Challenges of Toll‐Like Receptor 4 Antagonists as Inflammatory Pathway Blocker
Authors: Batin Rahaman S. K. , Nandi Sandip K. , Mandal Sudip Kumar , Debnath Utsab 
Published: December 2024

ABSTRACTToll‐like receptor 4 (TLR4) is an important mediator that activates bacterial inflammation through its signaling pathway. It binds lipopolysaccharide (LPS) in the presence of myeloid differentiation protein 2 (MD2) to dimerise the TLR4‐MD2‐LPS complex. The TLR4 mediated signaling pathway stimulates cytokine production in humans, initiating inflammatory responses. Overactivation of the TLR4 pathway can trigger binding of LPS to the TLR4‐MD2 complex, which may lead to the development of several inflammatory disorders. Therefore, the TLR4‐MD2 complex is a potential therapeutic target for the identification of new and effective anti‐inflammatory agents. Various biologically active TLR4 and MD2 targeting natural and synthetic molecules are explored with anti‐inflammatory activity in micromolar ranges. But no FDA‐approved drugs are available in the market as of now, and some are discontinued in clinical trials due to drug resistance and severe side effects. In this review, we have assessed recent molecular advancements in TLR4‐MD2 antagonists which are showing direct inhibition in lower micro and nanomolar levels. Along with it, protein informatics analysis of the binding pockets of wild type and mutated TLR4‐MD2 proteins are also discussed here to give a new insight about the changes in physicochemical properties of the ligand binding area. We have also pointed out several important residues in three different sites of the large LPS binding pocket of TLR4‐MD2 complex to understand probable binding affinity of small molecule inhibitors (SMIs). In addition, the present status of clinical trials for TLR4 antagonists is also reviewed. The current assessment will pave a future perspective to design different small molecules as a direct inhibitor of TLR4‐MD2 complex for anti‐inflammatory activities.
A Tale of Two Lakes: Divergent Evolutionary Trajectories of Two Daphnia Populations Experiencing Distinct Environments
Authors: Wersebe Matthew J. , Günther Torsten , Morton Philip K. , Weider Lawrence J. , Frisch Dagmar 
Published: December 2024

ABSTRACTMost studies of local adaptation substitute the correlation between spatial distance and environmental heterogeneity for the temporal dynamics over which local adaptation evolves. The availability of detailed ecological and genomic information from lake sediments provides an opportunity to study local adaptation with unparalleled clarity from the temporal perspective. Inference can be further enhanced by including multiple lakes along ecological axes to further isolate the effects of ecological change in driving local adaptation. Lakes throughout the world face the impact of numerous anthropogenically induced environmental changes. Top among these is the eutrophication of freshwaters from agriculture, development, and land‐use change. Here, we use the genetic information recorded in lake sediments of two lakes experiencing contrasting histories of land‐use change to study the evolution of local adaptation in the lakes’ Daphnia pulicaria populations. Utilizing nextRAD derived single‐nucleotide polymorphisms (SNPs) in resurrected clonal lineages, we studied the evolutionary trajectories of Daphnia pulicaria in both lakes. Using gene–environment correlations and Fst tests for selection, we found SNPs that appear to be under selection in both lakes. Specifically, we found more outlier SNPs in the highly impacted lake using Fst‐based tests for selection. Conversely, gene–environment tests revealed the reverse pattern. We discuss numerous facets of experimental design that must be considered when using resurrection ecology to study local adaptation and critically evaluate how they may have impacted the of this investigation.
Study on the Improvement of Cognitive Impairment Induced by Scopolamine in Mice by Forsythia suspensa Essential Oil
Authors: Wang Wei , Huang Liujing , Niu Xuyang , Li Shanshan , Liu Huimin , Xia Lan , Chen Xuewu , Liu Qinglei 
Published: December 2024

ABSTRACTIn this study, the mechanism of Forsythia suspensa essential oil (FSEO) on cognitive disorders was investigated based on network pharmacology and animal experiments. The common targets of AD diseases and the main components of FSEO were collected through GeneCards, PubChem, STRING and other databases, and protein–protein interaction (PPI) network maps were established. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using DAVID and Metascape databases, and the enrichment results were verified using the scopolamine (SCO) cognitive impairment mouse model. The results of network pharmacological analysis showed that FSEO involved 107 potential therapeutic targets, among which MAPK1, MAPK3 and ESR1 were the core targets, which were closely related to the regulatory pathways of MAPK cascade, 5‐hydroxytryptaminergic synapses, dopaminergic synapses and oxidoreductase activity. The results of animal experiments showed that FSEO improved cognitively impaired behaviours, reduced central cholinergic neuron damage and oxidative stress in the mouse brain and increased the content of monoamine transmitters in the mouse brain. Animal experiments further validated the results of the FSEO network pharmacology analysis.
Medial opening low tibial osteotomy shifts the load laterally not only at the ankle joint but also at the knee joint
Authors: Wanezaki Yoshihiro , Kurokawa Hiroaki , Ueno Yuki , Tablante Adrian , Mei Nan , Yinghao Li , Taniguchi Akira , Suzuki Akemi , Takakubo Yuya , Takagi Michiaki , Tanaka Yasuhito 
Published: December 2024

AbstractPurposeThe purpose of this study was to determine the effects of medial opening low tibial osteotomy (LTO) on lower limb alignment, including the knee joint, 1 year after low tibial osteotomy.MethodsThis study included 20 legs of 20 patients (mean age, 66.8 ± 5.4 years) who underwent LTO for medial ankle osteoarthritis and evaluated the changes in the hip–knee–ankle angle (HKA), percentage hip‐to‐ankle line (%HA), percentage hip‐to‐calcaneal line (%HC), medial proximal tibial angle (MPTA), knee joint line convergence angle (K‐JLCA), tibio‐calcaneal angle (TCA), tibial anterior surface angle (TAS), tibio‐plafond inclination (TPI), talar inclination (TI), ankle joint line convergence angle (A‐JLCA), mechanical ankle joint axis point (MAJAP) on radiographs and the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale before and 1 year after low tibial osteotomy.ResultsThe mean preoperative/postoperative measured values showed the following: HKA (degrees) of 1.0 ± 3.7/−0.8 ± 3.7; %HC of 38.8 ± 10.0/53.8 ± 16.1; MPTA (degrees) of 85.6 ± 2.4/87.6 ± 2.1; and A‐JLCA (degrees) of 4.2 ± 2.9/1.1 ± 2.3 respectively. Including other measurements, a significant increase in the %HA, %HC, MPTA, TCA, TAS, MAJAP and JSSF ankle/hindfoot scale was observed postoperatively, whereas a significant decrease in the HKA, TPA, TI and A‐JLCA was observed postoperatively (p < 0.05). With the numbers available, no significant differences were observed between the preoperative and postoperative values of K‐JLCA (n.s.).ConclusionAfter LTO, the entire lower limb alignment became valgus, and the loading points of the knee and ankle joints shifted laterally. These changes must be considered when performing LTO, especially in patients with lateral knee OA.Level of EvidenceⅣ
Double‐bundle versus single‐bundle medial patellofemoral ligament reconstruction for recurrent patellar dislocation: A meta‐analysis
Authors: Wu Yiheng , Li Junran , Zhao Hongbo , Zhou Hongyan , Wang Bokai , Zhang Jinlong , Zhao Shengkun 
Published: December 2024

AbstractPurposeTo compare the clinical efficacy of single‐bundle versus double‐bundle reconstruction of the medial patellofemoral ligament (MPFL) for recurrent patellar dislocation (RPD) regarding knee function scores, postoperative complications, and imaging assessments.MethodsA computerized search of PubMed, Cochrane Library, Embase, China Biomedical Literature Database (CBM), China National Knowledge Network (CNKI), and VIP Database was performed for single‐bundle versus double‐bundle reconstruction of the medial patellofemoral ligament for treatment of RPD. Randomized controlled trials (RCTs) were evaluated for quality using the risk‐of‐bias evaluation tool recommended by the Cochrane Collaboration Network, and Cohort studies (CSs) were assessed using the Newcastle‐Ottawa Scale (NOS) scale. Meta‐analysis was performed using RevMan 5.3 software and STATA 16.0.ResultsThirteen studies were included, four randomized controlled studies, and nine cohort studies. The level of evidence for the four randomized controlled studies was Ⅰ, and the nine cohort studies were Ⅲ. A total of 862 (891 knees) patients were included, of which 448 (465 knees) underwent double‐bundle MPFL reconstruction and 414 (426 knees) underwent single‐bundle MPFL reconstruction. Kujala score (MD = 2.06, 95% confidence interval [CI] [0.11, 4.01], p < 0.05), Tegner score (MD = 0.39, 95% CI [0.11, 0.68], p < 0.05), International Knee Documentation Committee (IKDC) score (MD = 4.88, 95% CI [1.46, 8.31], p < 0.05), and postoperative recurrence instability (odds ratio [OR] = 0.12, 95% CI [0.04, 0.44], p < 0.05) were better in the double‐bundle group than in the single‐bundle group. Lysholm score (MD = 0.86, 95% CI [−0.76, 2.48], p = n.s), patellar tilt angle (MD = −0.22, 95% CI [−0.54, 0.10], p = n.s), patellar lateral shift rate (MD = −0.16, 95% CI [−0.41, 0.09], p = n.s), congruence angle (MD = 0.06, 95% CI [−0.41, 0.52], p = n.s), postoperative knee pain (OR = 0.39, 95% CI [0.14, 1.11], p = n.s), and additional postoperative surgical treatment (OR = 0.20, 95% CI [0.01−6.25], p = n.s) had no statistically significant differences.ConclusionsDouble‐bundle reconstruction of the medial patellofemoral ligament for RPD was superior to single‐bundle reconstruction in both knee function scores and postoperative recurrent patellar instability, and double‐bundle reconstruction of the medial patellofemoral ligament for RPD had better clinical outcomes.Level of EvidenceLevel Ⅲ, Ⅰ and Ⅲ studies.
Beyond neuropsychological tests: AI speech analysis in PKU
Authors: Waisbren Susan E. , Norel Raquel , Agurto Carla , Singh Shifali , Connor Zoe A. , Ebrahim Marina G. , Cecchi Guillermo A. 
Published: December 2024

AbstractPhenylketonuria (PKU) is a rare inherited metabolic disorder characterized by toxic phenylalanine (Phe) concentrations in blood and brain. State‐of‐the‐art analyses of speech detected a dimension of verbal discourse providing insights that extend beyond those captured by existing paradigms to measure performance associated with biochemical markers in PKU. The Cookie Theft Picture Task provided a standardized stimulus for eliciting spontaneous speech from 42 adults with PKU and 41 adults without PKU. Subtests measuring language and memory from the Wechsler Adult Intelligence Scale‐Fourth Edition showed no differences between the groups and no correlations with biomarkers in PKU. In contrast, AI analyses of responses to the Cookie Theft Task revealed significant differences between the PKU and non‐PKU groups on 23 linguistic features. Using multidimensional scaling (MDS), these features were aggregated into a single quantifiable Dimension 1 that significantly correlated with biomarkers. When extreme examples of Dimension 1 were presented to chatGPT, the differences noted reflected attention to detail, clarity in word choice, expression cohesion, contextual awareness and emotion recognition. We subsequently defined Dimension 1 as Proficiency in Verbal Discourse. This novel measure elucidated discourse styles possibly associated with suboptimal achievement and learning disabilities, often reported in PKU. In summary, AI captured a characteristic associated with metabolic status undetectable through traditional neuropsychological measures. Future studies will expand upon this novel paradigm, leveraging speech AI to quantify meaningful aspects of everyday functioning and possibly provide information for management decisions. Once validated, this measure holds promise for extension to other rare diseases and incorporation into clinical trials.
Culture and Sketching: Comparative Analysis of UK and Chinese Designers
Authors: Tang Pinyan , Lawson Glyn , Sun Xu , Sharples Sarah 
Published: December 2024

ABSTRACTThis research investigates the influence of culture on sketching by comparing UK and Chinese designers. We employed a novel dual‐method approach: machine learning algorithms analyzed a dataset of 2,090 digitized sketches from student designers, while protocol analysis based on shape transformation rules examined the sketching processes of professional designers from both cultures. The machine learning analysis classified sketches by extracting region‐ and shape‐based features, revealing distinctive visual attributes between the two cultures. Concurrently, protocol studies of professional designers' sketches uncovered patterns in their sketching processes. By integrating computational analyses of student sketches with protocol studies of professional designers, we identified significant cultural differences in both visual attributes and sketching processes. The paper discusses potential factors contributing to these disparities, drawing on insights from cross‐cultural comparisons of cognitive styles. This comprehensive mixed‐methods analysis provides new insights into the complex interplay between culture, cognition, and design.
Intestinal histopathology in pediatric PSC‐IBD: Characterization of phenotype and assessment of the Nancy Index
Authors: Little Rebecca , Putra Juan , Kamath Binita M. , Griffiths Anne M. , Ricciuto Amanda , Siddiqui Iram 
Published: December 2024

AbstractObjectivesWe aimed to characterize the histologic gut phenotype of pediatric primary sclerosing cholangitis (PSC)‐associated inflammatory bowel disease (IBD) against non‐PSC colitis, and to assess Nancy Index (NI) performance in pediatric PSC‐IBD.MethodsSingle‐center retrospective cohort study including children diagnosed with PSC‐IBD or non‐PSC colitis (ulcerative colitis [UC] or IBD‐unclassified) from 2000 to 2018, with diagnostic intestinal biopsies. Biopsies were re‐reviewed by two independent pathologists who assessed microscopic disease distribution, NI scores, and specific histological features in the right and left colons, overall and stratified by endoscopic severity (moderate‐severe vs. no more than mild). We examined NI inter‐rater reliability with Fleiss' weighted (quadratic) kappa and NI construct validity against global endoscopic severity (Spearman correlation) and clinical outcomes (logistic regression).ResultsFifty children with PSC‐IBD and 81 colitis controls were included. Histologically, pancolitis (84% vs. 55%), right colon‐predominant colitis (48% vs. 3%), and backwash ileitis (53% vs. 12%) (all p < 0.01) were significantly more common in PSC‐IBD; histologic rectal sparing occurred at similar rates (6% vs. 10%, p = 0.54). Lamina propria‐predominant neutrophils, prominent eosinophilic infiltration (left colon), and surface villiform change (right colon) were more common in PSC‐IBD than colitis controls (p < 0.01). NI showed excellent inter‐rater reliability (kappa > 0.9) and correlated moderately with global endoscopic severity but poorly with clinical activity in PSC‐IBD.ConclusionsPediatric PSC‐IBD has a distinct histologic phenotype that largely mirrors the endoscopic phenotype in distribution and includes a greater frequency of features not included in conventional UC histologic activity indices. Future work should investigate whether a PSC‐IBD‐specific index incorporating these features is warranted.
Distribution and palaeoenvironmental significance of mountain blockstreams in the southern hemisphere
Authors: Grab Stefan , Knight Jasper 
Published: December 2024

ABSTRACTOpenwork mountain block deposits (blockfields, blockstreams) have received much research interest globally given their visual appeal as prominent cold‐region landforms. However, studies have shown that these landforms in both glaciated and non‐glaciated environments are probably of considerable age (pre‐Quaternary), yet the environmental conditions of their formation (such as the presence of permafrost) and associated processes remain poorly understood. This paper focuses on consolidating and critically analysing current knowledge on mountain blockstreams found in the southern hemisphere. This is achieved by reviewing past published work on such landforms, from the Falkland Islands, Marion Island, southern Africa and southeastern Australia. By presenting a variety of previously proposed landscape evolutionary models, we demonstrate that southern hemisphere blockstreams are products of a range of weathering and material mobilization processes over long multiple warmer/wetter and colder/drier pre‐Quaternary and Quaternary climatic cycles. Although most southern hemisphere mountain blockstreams have some association with periglacial processes, they are not exclusively periglacial in their developmental history. This can be tested through field geomorphic, sedimentary and ecological methods; the use of remote sensing; radiometric and relative‐age dating; seismic and other subsurface methods; and modelling. However, many research questions remain unanswered, such as the potential role of permafrost in blockstream formation and dynamics, or their sensitivity to ongoing climate change.
Diet shapes and maintains the personalized native gut microbiomes in mice
Authors: Yang Zhihan , Zhang Zeng , Jiang Shuaiming , Li Ao , Song Hainan , Zhang Jiachao 
Published: December 2024

AbstractBACKGROUNDThe gut microbiome plays a critical role in human health and disease. Different dietary backgrounds play an important role in the uniqueness and diversity of the gut microbiota in different individuals, which promotes heterogeneity in disease phenotypes and treatment responses. Here, we explored how diet affects the composition and function of the native gut microbiome of model mice, based on the shotgun metagenomic and metabolomic, by analyzing the gut microbiome of C57B/6J mice in different dietary backgrounds.RESULTSThe gut microbiomes of mice receiving different diets consistently exhibit distinct compositions across bacterial species, strains, fungi and phages. This implies that native microbial communities cannot ‘homogenize’ rapidly becaise of priority effects and unchanging diets. Notably, hotspot bacteria such as Limosilactobacillus reuteri, Parabacteroides distasonis and Akkermansia muciniphila were significantly different among the groups. These species harbor diverse adaptive mutations, reflecting genomic evolutionary diversity. The functional profiles of the gut microbiota also exhibit selective differences, involving the capacity for carbohydrate, branched‐chain amino acid and fatty acid synthesis, as well as virulence factors, carbohydrate‐active enzymes and antibiotic resistance. Furthermore, the differences in the gut microbiota also propagate to the host's serum, where structural and specific metabolite differences were observed. Metabolites that directly impact host health, such as d‐glucosamine 6‐phosphate and testolic acid, also show significant differences between the different dietary groups.CONCLUSIONOur findings underscore the profound influence of different dietary the composition and functionality of the gut microbiome, offering valuable insights into optimizing health outcomes through personalized nutritional interventions. © 2024 Society of Chemical Industry.
Workforce Analysis of Laryngologists in the United States Between 1993 and 2022
Authors: Parikh Neil U. , Zheng Melissa , Merati Albert L , Johns Michael , Shuman Elizabeth A. 
Published: December 2024

IntroductionThis study queries the US laryngology workforce geographic distribution and density and models laryngology workforce trends through 2050.MethodsA national database of fellowship‐trained laryngologists (FTLs) and nonfellowship‐trained laryngologists (nFTLs) practicing primarily laryngology was formed by identifying laryngologists via internet search, with validation by regional laryngologists and senior laryngologists on this manuscript. Demographic variables included residency and/or fellowship graduation year, institutional affiliation, and practice zip code. US Census Bureau population data and projections were grouped by hospital referral region (HRR), as defined by the Dartmouth Healthcare Atlas. The National Resident Matching Program (NRMP) provided annual fellowship match data from 2012 to 2022.ResultsAs of May 2023, there were 349 active laryngologists in the United States, including 303 FTLs. The median practice length for all laryngologists was 11 years. HRRs with the largest number of laryngologists were Manhattan, Boston, and Los Angeles, with 23, 16, and 14 respectively. One hundred and ninety‐four of 306 (63%) HRRs did not have an active, primary laryngologist. The national median density of people per laryngologist including HRRs with at least one laryngologist was 645,160. Assuming a 35‐year practice horizon prior to workforce exit and holding the 2018–2022 NRMP average of 18 fellows constant, the number of forecasted laryngologists by 2040 would be 568—an increase of 66%.ConclusionsTo date, no comprehensive database of practicing US laryngologists nor laryngology workforce forecast exists. Based on current benchmarks, the laryngology workforce would increase by 66% by 2040, ideally addressing the current dearth of laryngologists in low‐density areas.Level of EvidenceNA Laryngoscope, 2024