bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study
Authors: Waliszewska-Prosół Marta , Montisano Danilo Antonio , Antolak Mariola , Bighiani Federico , Cammarota Francescantonio , Cetta Ilaria , Corrado Michele , Ihara Keiko , Kartamysheva Regina , Petrušić Igor , Pocora Maria Magdalena , Takizawa Tsubasa , Vaghi Gloria , Martelletti Paolo , Corso Barbara , Raggi Alberto ,   On behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)
Published: March 2024

Abstract
Background
The burden and disability associated with headaches are conceptualized and measured differently at patients’ and populations’ levels. At the patients’ level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0–1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients’ disability which might inform future GBD definitions of DW for headache disorders.

Methods
We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females’ percentage in the sample, and age). We developed a 0–1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium.

Results
A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake.

Conclusions
Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.
Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis
Authors: Habib Tito N. , Altonsy Mohammed O. , Ghanem Salah A. , Salama Mohamed S. , Hosny Mai A. 
Published: March 2024

Abstract
Background
Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of combining the chemotherapeutic agent Paclitaxel (PTX) with Sulforaphane (SFN), a natural compound primarily found in cruciferous vegetables, to enhance treatment efficacy in prostate cancer.

Methods
Two prostate cancer cell lines, PC-3 and LNCaP, were treated with varying concentrations of PTX, SFN, and their combination. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay to determine the EC50 values. Western blot analysis was conducted to evaluate the expression of Bax, Bcl2, and Caspase-3 activation proteins in response to individual and combined treatments of PTX and SFN. Fluorescent microscopy was employed to observe morphological changes indicative of apoptotic stress in cell nuclei. Flow cytometry analysis was utilized to assess alterations in cell cycle phases, such as redistribution and arrest. Statistical analyses, including Student’s t-tests and one-way analysis of variance with Tukey’s correction, were performed to determine significant differences between mono- and combination treatments.

Results
The impact of PTX, SFN, and their combination on cell viability reduction was evaluated in a dose-dependent manner. The combined treatment enhanced PTX’s effects and decreased the EC50 values of both drugs compared to individual treatments. PTX and SFN treatments differentially regulated the expression of Bax and Bcl2 proteins in PC-3 and LNCaP cell lines, favoring apoptosis over cell survival. Our data indicated that combination therapy significantly increased Bax protein expression and the Bax/Bcl2 ratio compared to PTX or SFN alone. Flow cytometry analysis revealed alterations in cell cycle phases, including S-phase arrest and an increased population of apoptotic cells. Notably, the combination treatments did not have a discernible impact on necrotic cells. Signs of apoptotic cell death were confirmed through Caspase-3 cleavage, and morphological changes in cell nuclei were assessed via western blot and fluorescent microscopy.

Conclusion
This combination therapy of PTX and SFN has the potential to improve prostate cancer treatment by minimizing side effects while maintaining efficacy. Mechanistic investigations revealed that SFN enhances PTX efficacy by promoting apoptosis, activating caspase-3, inducing nuclear morphology changes, modulating the cell cycle, and altering Bax and Bcl2 protein expression. These findings offer valuable insights into the synergistic effects of PTX and SFN, supporting the optimization of combination therapy and providing efficient therapeutic strategies in preclinical research.
RpoS role in antibiotic resistance, tolerance and persistence in E. coli natural isolates
Authors: Valencia Estela Ynés , de Moraes Gomes Felipe , Ospino Katia , Spira Beny 
Published: March 2024

Abstract
Background
The intrinsic concentration of RpoS, the second most abundant sigma factor, varies widely across the E. coli species. Bacterial isolates that express high levels of RpoS display high resistance to environmental stresses, such as temperature, pH and osmolarity shifts, but are less nutritional competent, making them less capable of utilising alternative nutrient sources. The role of RpoS in antibiotic resistance and persistence in standard laboratory domesticated strains has been examined in several studies, most demonstrating a positive role for RpoS.

Results
Using disk diffusion assays we examined bacterial resistance to 15 different antibiotics, including $$\upbeta$$
β
-lactams (penicillins, monobactams, carbapenems and cephalosporins), aminoglycosides, quinolones and anti-folates, in a representative collection of 328 E. coli natural isolates displaying a continuum of different levels of RpoS. There was an overall trend that isolates with higher levels of RpoS were slightly more resistant to these antibiotics. In addition, the effect of RpoS on bacterial tolerance and persistence to 3 different antibiotics - ampicillin, ciprofloxacin and kanamycin was evaluated through time-kill curves. Again, there was a small beneficial effect of RpoS on tolerance and persistence to these antibiotics, but this difference was not statistically significant. Finally, a K-12 strain expressing high levels of RpoS was compared with its isogenic RpoS-null counterpart, and no significant effect of RpoS was found.

Conclusion
Based on a representative collection of the species E. coli, RpoS was found to have a very small impact on antibiotic resistance, tolerance, or persistence.
Gastric point-of-care ultrasonography in patients undergoing radical gastrointestinal surgery before anesthetic induction: an observational cohort study
Authors: Huang Siming , Cao Shumei , Sun Xia , Zhang Jun 
Published: March 2024

Abstract
Background
Pulmonary aspiration of gastric contents is a serious perioperative complication. Patients with gastric cancer may experience delayed gastric emptying. However, the role of qualitative and quantitative gastric ultrasound assessments in this patient population before anesthesia induction has not yet been determined.

Methods
Adult patients with gastrointestinal cancer were recruited and examined using gastric point-of-care ultrasound (POCUS) before anesthetic induction from March 2023 to August 2023 in a tertiary cancer center. Three hundred patients with gastric cancer were conducted with POCUS prior to induction, and three hundred patients with colorectal cancer were included as controls. The cross-sectional area (CSA) of the gastric antrum and gastric volumes (GV) were measured and calculated. We determined the nature of the gastric contents and classified the antrum using a 3-point grading system. A ratio of GV to body weight > 1.5mL/Kg was defined as a high risk of aspiration.

Results
In patients with gastric cancer, 70 patients were classified as grade 2 (23%, including 6 patients with solid gastric contents) and 63 patients (21%) were identified as having a high risk of aspiration. Whereas in patients with colorectal cancer, only 11 patients were classified as grade 2 (3.7%), and 27 patients (9.7%) were identified as having a high risk of aspiration. A larger tumor size (OR:1.169, 95% CI 1.045–1.307, P = 0.006), tumor located in antrum (OR:2.304, 95% CI 1.169–4.539,P = 0.016), gastrointestinal obstruction (OR:21.633, 95% CI 4.199–111.443, P < 0.0001) and more lymph node metastasis (OR:2.261, 95% CI 1.062–4.812, P = 0.034) were found to be positively while tumor site at cardia (OR:0.096, 95% CI 0.019–0.464, P = 0.004) was negatively associated with high aspiration risk in patients with gastric cancer.

Conclusion
The Gastric POCUS prior to induction provides an assessment of the status of gastric emptying and can identify the patients at high risk of aspiration, especially those with gastric cancer.

Trial registration
Chinese Clinical Trial Registry (www.chictr.org.cn) identifier: ChiCTR2300069242; registered 10 March 2023.
Effectiveness of a tailored communication intervention to improve physical activity in hypertensive patients: a twelve-month randomized controlled trial
Authors: Adorni Roberta , Zanatta Francesco , Cappelletti Erika Rosa , Greco Andrea , Steca Patrizia , D’Addario Marco 
Published: March 2024

Abstract
Background
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally. Arterial hypertension is one of the main cardiovascular risk factors. Despite this, individuals with hypertension often fail to follow medical advice to counteract cardiovascular risks. A physically active lifestyle is one of the most challenging behaviors to adopt. This study aimed to preliminarily investigate the effectiveness of a tailored print message intervention to increase physical activity in patients with arterial hypertension.

Methods
A sample of 188 patients with hypertension (mean age = 63 years; SD = 10.9; 50% men) participated in a theory-based tailored health communication intervention. Participants were randomly assigned to three parallel groups: (1) the tailored group, which received tailored health brochures; (2) the non-tailored group, which received non-tailored health brochures; or (3) the usual care group, which received no informative print materials. The longitudinal physical activity trajectories (baseline, 6- and 12-month follow-ups) were examined using repeated measures ANOVA and growth curve models.

Results
At the baseline, 38.8% of patients achieved the target physical activity. This percentage rose to 43.0% at 6-month follow-up and 46.0% at 12-month follow-up. The descriptive statistics divided in function of the experimental group suggested differences in the longitudinal trend of the mean physical activity depending on the experimental group. However, statistical significance using repeated measures ANOVA did not support this observation. The analysis of the growth curves suggested that the tailored group showed a progressive increase in physical activity over twelve months (the model that best described the longitudinal trajectory was a linear growth model). The non-tailored group showed an increase in physical activity six months after the beginning of the intervention, followed by a decrease (free time score model). The usual care group did not change over time (no-growth model).

Conclusions
Findings suggest the effectiveness of the tailored intervention proposed. However, further investigations and empirical confirmations are required.

Trial registration
ISRCTN13415993 (https://doi.org/10.1186/ISRCTN13415993). Registration date: 08/04/2019.
A rapid multi-parametric quantitative MR imaging method to assess Parkinson’s disease: a feasibility study
Authors: Duan Min , Pan Rongrong , Gao Qing , Wu Xinying , Lin Hai , Yuan Jianmin , Zhang Yamei , Liu Lindong , Tian Youyong , Fu Tong 
Published: March 2024

Abstract
Background
MULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson’s disease (PD).

Methods
27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs.

Results
The ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients.

Conclusions
MULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients’ subcortical nucleus and dopaminergic midbrain regions.
Uric acid in predicting the traumatic rhabdomyolysis induced acute kidney injury; a systematic review and meta-analysis
Authors: Safari Saeed , Ghasemi Mohammadreza , Yousefifard Mahmoud , Ghasemi Alireza , Najafi Iraj 
Published: March 2024

Abstract
Objective
The objective of this systematic review and meta-analysis was to assess the value of uric acid in predicting acute kidney injury caused by traumatic rhabdomyolysis.

Methods
The search was conducted in MEDLINE, Scopus, Embase and Web of Science until November 1, 2023. Based on the inclusion and exclusion criteria, the articles were included by two independent researchers. Data regarding study design, patient characteristics, number of patients with and without AKI, mean and SD of uric acid and prognostic characteristics of uric acid were extracted from relevant studies. STATA version 17.0 was used to compute pooled measures of standardized mean differences, odds ratios, and diagnostic accuracy. I2 and chi-square tests were used to assess heterogeneity between studies.

Results
We found 689 non-redundant studies, 44 of them were potentially relevant. Six articles met the inclusion criteria and were included in the review. The results of the meta-analysis confirmed that there was a significant correlation between serum uric acid levels and the occurrence of AKI (SMD = 1.61, 95% CI = 0.69 to 2.54, I2 = 96.94%; p value = 0.001). There were no significant publication biases.

Conclusion
According to this meta-analysis, uric acid levels could be considered as a predictor of acute kidney injury following traumatic rhabdomyolysis.
Validation of IgA nephropathy diagnosis in the Swedish Renal Registry
Authors: Rehnberg Johanna , Segelmark Mårten , Ludvigsson Jonas F. , Emilsson Louise 
Published: March 2024

Abstract
Aim
The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis.

Methods
In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015–2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis.

Results
A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90–98%). Median age was 46 years (range: 18–85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases.

Conclusion
Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.
Relationship between glycated hemoglobin levels and three-month outcomes in acute ischemic stroke patients with or without diabetes: a prospective Korean cohort study
Authors: Cao Changchun , Wang Tony Bowei , Hu Haofei , Han Yong , Zhang Xiaohua , Wang Yulong 
Published: March 2024

Abstract
Objective
In patients experiencing acute ischemic stroke, there is ongoing debate surrounding the connection between chronic hyperglycemic status and their initial clinical outcomes. Our objective was to examine the connection between glycated hemoglobin (HbA1c) levels and adverse clinical outcomes at both 3-months adverse clinical outcomes in individuals with acute ischemic stroke (AIS) with and without diabetes.

Methods
The present prospective cohort study involved 896 AIS patients without diabetes and 628 with diabetes treated at a South Korean hospital from January 2010 to December 2016. The target independent variable is HbA1c. The outcome variable is a modified Rankin scale score ≥ 3. A binary logistic regression model was applied to assess the connection between HbA1c levels and 3-month poor clinical outcomes in AIS patients with and without diabetes. Additionally, a generalized additive model and smoothed curve fitting were utilized to explore potential nonlinear associations between HbA1c levels and 3-month adverse clinical outcomes in AIS patients with and without diabetes.

Results
The binary logistic regression model could not identify any statistically significant connection between HbA1c and 3-month adverse clinical outcomes in AIS patients, both those with and without diabetes, after correcting for various factors. However, a nonlinear relationship emerged between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. The inflection point for HbA1c was determined to be 6.1%. For HbA1c values ≤ 6.1%, an inverse association was observed between HbA1c and 3-month adverse clinical outcomes in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with an 87% reduction in 3-month adverse clinical outcomes (OR = 0.13, 95% CI: 0.02–0.81). Conversely, when HbA1c exceeded 6.1%, a positive association between HbA1c and 3-month adverse clinical outcomes became apparent in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with a 23% increase in 3-month adverse clinical outcomes (OR = 1.23, 95%CI: 1.03–1.47). However, it’s important to note that no significant linear or nonlinear relationships were observed between HbA1c levels and 3-month adverse clinical outcomes in AIS patients without diabetes.

Conclusion
Our findings suggest a nonlinear connection and threshold effect between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. AIS patients with diabetes had a lower risk of 3-month adverse clinical outcomes when their HbA1c control was close to 6.1%. Our findings may aid treatment decision-making and potentially guide interventions to optimize glycemic control in AIS patients.
Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets
Authors: Dong Zhang , Chong Wan , Chen Chen , Qi Li , Mengke Li , Minghui Dou , Jiawei Yuan , Longxi Quan , Hengchao Liu , Liu Jia , Zhimin Geng 
Published: March 2024

Abstract
Backgrounds
Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC.

Materials and methods
We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 − 8) was also assessed in tumor specimens from 64 patients.

Results
The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels.

Conclusion
These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.