bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice expressing nonpolymerizable fibrinogen have reduced arterial and venous thrombosis with preserved hemostasis
Authors: Hur Woosuk S. , Kawano Tomohiro , Mwiza Jean Marie N. , Paul David S. , Lee Robert H. , Clark Emily G. , Bouck Emma G. , Dutta Ananya , Cai Can , Baker Stephen R. , Guthold Martin , Mackman Nigel , Mangin Pierre , Wolberg Alisa S. , Bergmeier Wolfgang , Flick Matthew J. 
Published: October 2023

Abstract
Elevated circulating fibrinogen levels correlate with increased risk for both cardiovascular and venous thromboembolic diseases. In vitro studies show that formation of a highly dense fibrin matrix is a major determinant of clot structure and stability. Here, we analyzed the impact of nonpolymerizable fibrinogen on arterial and venous thrombosis as well as hemostasis in vivo using FgaEK mice that express normal levels of a fibrinogen that cannot be cleaved by thrombin. In a model of carotid artery thrombosis, FgaWT/EK and FgaEK/EK mice were protected from occlusion with 4% ferric chloride (FeCl3) challenges compared with wild-type (FgaWT/WT) mice, but this protection was lost, with injuries driven by higher concentrations of FeCl3. In contrast, fibrinogen-deficient (Fga−/−) mice showed no evidence of occlusion, even with high-concentration FeCl3 challenge. Fibrinogen-dependent platelet aggregation and intraplatelet fibrinogen content were similar in FgaWT/WT, FgaWT/EK, and FgaEK/EK mice, consistent with preserved fibrinogen–platelet interactions that support arterial thrombosis with severe challenge. In an inferior vena cava stasis model of venous thrombosis, FgaEK/EK mice had near complete protection from thrombus formation. FgaWT/EK mice also displayed reduced thrombus incidence and a significant reduction in thrombus mass relative to FgaWT/WT mice after inferior vena cava stasis, suggesting that partial expression of nonpolymerizable fibrinogen was sufficient for conferring protection. Notably, FgaWT/EK and FgaEK/EK mice had preserved hemostasis in multiple models as well as normal wound healing times after skin incision, unlike Fga−/− mice that displayed significant bleeding and delayed healing. These findings indicate that a nonpolymerizable fibrinogen variant can significantly suppress occlusive thrombosis while preserving hemostatic potential in vivo.
The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma
Authors: Di Ciaccio Pietro R. , Polizzotto Mark N. , Cwynarski Kate , Gerrie Alina S. , Burton Catherine , Bower Mark , Kuruvilla John , Montoto Silvia , McKay Pam , Fox Christopher P. , Milliken Samuel , Jiamsakul Awachana , Osborne Wendy , Collins Graham P. , Manos Kate , Linton Kim M. , Iyengar Sunil , Kassam Shireen , Limei Michelle Poon , Kliman David , Wong Doo Nicole , Watson Anne-Marie , Fedele Pasquale , Yannakou Costas K. , Hunt Stewart , Ku Matthew , Sehn Laurie H. , Smith Alexandra , Renshaw Hanna , Maxwell Alice , Liu Qin , Dhairyawan Rageshri , Ferguson Graeme , Pickard Keir , Painter Daniel , Thakrar Nisha , Song Kevin W. , Hamad Nada 
Published: October 2023

Abstract
Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus–negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.
Identifying quantitatively differential chromosomal compartmentalization changes and their biological significance from Hi-C data using DARIC
Authors: Kai Yan , Liu Nan , Orkin Stuart H. , Yuan Guo-Cheng 
Published: October 2023

Abstract
Background
Chromosomal compartmentalization plays a critical role in maintaining proper transcriptional programs in cell differentiation and oncogenesis. However, currently the prevalent method for comparative analysis of compartmentalization landscapes between different cell types is limited to the qualitative switched compartments.

Results
To identify genomic regions with quantitatively differential compartmentalization changes from genome-wide chromatin conformation data like Hi-C, we developed a computational framework named DARIC. DARIC includes three modules: compartmentalization quantification, normalization, and differential analysis. Comparing DARIC with the conventional compartment switching analysis reveals substantial regions characterized by quantitatively significant compartmentalization changes without switching. These changes are accompanied by changes in gene expression, chromatin accessibility, H3K27ac intensity, as well as the interactions with nuclear lamina proteins and nuclear positioning, highlighting the functional importance of such quantitative changes in gene regulation. We applied DARIC to dissect the quantitative compartmentalization changes during human cardiomyocyte differentiation and identified two distinct mechanisms for gene activation based on the association with compartmentalization changes. Using the quantitative compartmentalization measurement module from DARIC, we further dissected the compartment variability landscape in the human genome by analyzing a compendium of 32 Hi-C datasets from 4DN. We discovered an interesting correlation between compartmentalization variability and sub-compartments.

Conclusions
DARIC is a useful tool for analyzing quantitative compartmentalization changes and mining novel biological insights from increasing Hi-C data. Our results demonstrate the functional significance of quantitative compartmentalization changes in gene regulation, and provide new insights into the relationship between compartmentalization variability and sub-compartments in the human genome.
Pulsed electric field treatment of seeds altered the endophytic bacterial community and promotes early growth of roots in buckwheat
Authors: Qu Hao , Wang Yi , Wang Baijuan , Li Chengyun 
Published: October 2023

Abstract
Background
Endophytic bacteria provide nutrients and stimulate systemic resistance during seed germination and plant growth and development, and their functional properties in combating various stresses make them a powerful tool in green agricultural production. In this paper we explored the function of the endophyte community in buckwheat seeds in order to provide a theoretical basis for the application and scientific research of endophytes in buckwheat cultivation. We used pulsed electric field (PEF) technology to treat buckwheat seeds, monitored the effect of high-voltage pulse treatment on buckwheat seed germination, and analyzed the diversity of endophytic bacteria in buckwheat seeds using the amplicon sequencing method.

Results
PEF treatment promoted root development during buckwheat seed germination. A total of 350 Operational taxonomic units (OTUs) that were assigned into 103 genera were obtained from control and treatment groups using 16SrRNA amplicon sequencing technology. Additionally, PEF treatment also caused a significant decrease in the abundance of Actinobacteria, Proteobacteria, and Bacteroidetes. The abundance of 28 genera changed significantly as well: 11 genera were more abundant, and 17 were less abundant. The number of associated network edges was reduced from 980 to 117, the number of positive correlations decreased by 89.1%, and the number of negative correlations decreased by 86.6%.

Conclusion
PEF treatment promoted early root development in buckwheat and was able to alter the seed endophytic bacterial community. This study thus makes a significant contribution to the field of endophyte research and to the application of PEF technology in plant cultivation.
Comparative analysis of flavonoid metabolites from different parts of Hemerocallis citrina
Authors: Lv Hongrui , Guo Shang 
Published: October 2023

Abstract
Background
Hemerocallis citrina Baroni is a traditional medical and edible plant. It is rich in flavonoid compounds, which are a kind of important bioactive components with various health benefits and pharmaceutical value. However, the flavonoid metabolomics profile and the comparison of flavonoid compounds from different parts of H. citrina is scarce.

Results
In this study, flavonoid metabolites were investigated from roots, stems, leaves and flowers of H. citrina. A total of 364 flavonoid metabolites were identified by UPLC-MS/MS based widely targeted metabolomics, and the four plant parts showed huge differences at flavonoid metabolic level. Compared to roots, 185, 234, and 119 metabolites accounted for upregulated differential flavonoid metabolites (DFMs) in stems, leaves, and flowers, respectively. Compared to stems, 168 and 29 flavonoid metabolites accounted for upregulated DFMs in leaves and flowers, respectively. Compared to leaves, only 29 flavonoid metabolites accounted for upregulated DFMs in flowers. A number of 35 common flavonoid metabolites were observed among six comparison groups, and each comparison group had its unique differential metabolites. The most abundant flavonoid metabolites in the four parts are flavonols and flavones, followed by flavanones, chalcones, flavanols, flavanonols, anthocyanidins, tannin, and proanthocyanidins. 6,7,8-Tetrahydroxy-5-methoxyflavone, 7,8,3’,4’-tetrahydroxyflavone, 1-Hydroxy-2,3,8-trimethoxyxanthone, Farrerol-7-O-glucoside, 3’,7-dihydroxy-4’-methoxyflavone, 3,3’-O-Dimethylellagic Acid, 5-Hydroxy-6,7-dimethoxyflavone, Nepetin (5,7,3’,4’-Tetrahydroxy-6-methoxyflavone), (2s)-4,8,10-trihydroxy-2-methoxy-1 h,2 h-furo[3,2-a]xanthen-11-one are dominant in roots. Isorhamnetin-3-O-(6’’-malonyl)glucoside-7-O-rhamnoside, 7-Benzyloxy-5-hydroxy-3’,4’-methylenedioxyflavonoid, 3-Hydroxyphloretin-4’-O-glucoside are dominant in stems. Chrysoeriol-7-O-glucoside, Epicatechin glucoside, Kaempferol-3-O-rhamnoside (Afzelin)(Kaempferin)*, Azaleatin (5-O-Methylquercetin), Chrysoeriol-5-O-glucoside, Nepetin-7-O-glucoside(Nepitrin), 3,5,7,2’-Tetrahydroxyflavone; Datiscetin, Procyanidin B2*, Procyanidin B3*, Procyanidin B1, Isorhamnetin-3-O-(6’’-acetylglucoside) are dominant in leaves. kaempferol-3-p-coumaroyldiglucoside, Delphinidin-3-O-sophoroside-5-O-glucoside, Limocitrin-3-O-sophoroside, Kaempferol-3-O-rutinoside(Nicotiflorin), Luteolin-7-O-(6’’-malonyl)glucoside-5-O-rhamnoside are dominant in flowers.

Conclusion
There was significant difference in flavonoid metabolites among different parts of H. citrina. Leaves had relative higher metabolites contents than other parts. This study provided biological and chemical evidence for the different uses of various plant parts of H. citrina, and these informations are important theoretical basis for the food industry, and medical treatment.
New approaches and technical considerations in detecting outlier measurements and trajectories in longitudinal children growth data
Authors: Massara Paraskevi , Asrar Arooj , Bourdon Celine , Ngari Moses , Keown-Stoneman Charles D. G. , Maguire Jonathon L. , Birken Catherine S. , Berkley James A. , Bandsma Robert H. J. , Comelli Elena M. 
Published: October 2023

AbstractBackgroundGrowth studies rely on longitudinal measurements, typically represented as trajectories. However, anthropometry is prone to errors that can generate outliers. While various methods are available for detecting outlier measurements, a gold standard has yet to be identified, and there is no established method for outlying trajectories. Thus, outlier types and their effects on growth pattern detection still need to be investigated. This work aimed to assess the performance of six methods at detecting different types of outliers, propose two novel methods for outlier trajectory detection and evaluate how outliers affect growth pattern detection.MethodsWe included 393 healthy infants from The Applied Research Group for Kids (TARGet Kids!) cohort and 1651 children with severe malnutrition from the co-trimoxazole prophylaxis clinical trial. We injected outliers of three types and six intensities and applied four outlier detection methods for measurements (model-based and World Health Organization cut-offs-based) and two for trajectories. We also assessed growth pattern detection before and after outlier injection using time series clustering and latent class mixed models. Error type, intensity, and population affected method performance.ResultsModel-based outlier detection methods performed best for measurements with precision between 5.72-99.89%, especially for low and moderate error intensities. The clustering-based outlier trajectory method had high precision of 14.93-99.12%. Combining methods improved the detection rate to 21.82% in outlier measurements. Finally, when comparing growth groups with and without outliers, the outliers were shown to alter group membership by 57.9 -79.04%.ConclusionsWorld Health Organization cut-off-based techniques were shown to perform well in few very particular cases (extreme errors of high intensity), while model-based techniques performed well, especially for moderate errors of low intensity. Clustering-based outlier trajectory detection performed exceptionally well across all types and intensities of errors, indicating a potential strategic change in how outliers in growth data are viewed. Finally, the importance of detecting outliers was shown, given its impact on children growth studies, as demonstrated by comparing results of growth group detection.
Dynamics, association, and temporal sequence of cognitive function and frailty: a longitudinal study among Chinese community-dwelling older adults
Authors: Cui Kai , Meng Weihan , Li Zhiqiang , Zeng Xinning , Li Xiaozhe , Ge Xiaoyan 
Published: October 2023

Abstract
Background
Little is known about the association of longitudinal dynamics between cognitive function and frailty in Chinese older adults. The temporal sequences between cognitive function and frailty remains unclear. Our study investigates this directionality association using longitudinal data.

Methods
Latent growth and multivariate latent growth models were employed to examine dynamics of cognition and frailty and their association among 2824 older adults in China. Cross-lagged panel analyses were used to assess the temporal sequences between frailty and cognition. The relation between cognitive domains and frailty was also examined using aforementioned methods.

Results
Cognitive function was negatively associated with frailty status. Higher initial level of cognition indicated lower baseline level (β=-0.175, P < 0.001) and change rate (β=-0.041, P = 0.002) of frailty. We observed a reciprocal association between frailty and cognitive function rather than a unidirectional causal relationship. The initial cognitive performance for all components were negatively associated with baseline (β ranged between − 0.098 to -0.023) and change rate (β ranged between − 0.007 to -0.024) of frail status. No consistent associations between change rate of cognitive components and either initial level or change rate of frailty were detected.

Conclusions
Our study detected a reciprocal association between cognition and frailty rather than a unidirectional causal relationship. Our results also revealed different connections between cognitive performance and frailty across diverse cognitive domains.
Balance telerehabilitation and wearable technology for people with Parkinson’s disease (TelePD trial)
Authors: Silva-Batista Carla , Wilhelm Jennifer L. , Scanlan Kathleen T. , Stojak Margaret , Carlson-Kuhta Patricia , Chen Siting , Liu William , de la Huerta Tomas Nicolás García , Horak Fay B. , Mancini Martina , King Laurie A. 
Published: October 2023

Abstract
Background
Balance impairments, that lead to falls, are one of the main symptoms of Parkinson’s disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days.

Methods
The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period.

Conclusion
The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments.

Trial registration
This trial was prospectively registered on ClinicalTrials.gov (NCT05680597).
The machine learning methods to analyze the using strategy of antiplatelet drugs in ischaemic stroke patients with gastrointestinal haemorrhage
Authors: Cui Chaohua , Li Changhong , Hou Min , Wang Ping , Huang Zhonghua 
Published: October 2023

Abstract
Background
For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients.

Methods
Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters.

Results
The patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3–6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001).

Conclusions
For ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.
Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study
Authors: Nara Katsuhiko , Yamamoto Takehito , Yamashita Hiroharu , Yagi Koichi , Takada Tappei , Seto Yasuyuki , Suzuki Hiroshi 
Published: October 2023

Abstract
Background
Weekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.

Methods
This retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).

Results
Among 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216–124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052–477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141–137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0–5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8–13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9–15.7 month, P < 0.01 vs RF-2).

Conclusions
Careful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.