bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: An analysis from the Japan Stroke Data Bank
Authors: Arakaki Yoshito , Yoshimura Sohei , Toyoda Kazunori , Sonoda Kazutaka , Wada Shinichi , Nakai Michikazu , Nakahara Jin , Shiozawa Masayuki , Koge Junpei , Ishigami Akiko , Miwa Kaori , Torii-Yoshimura Takako , Miyazaki Junji , Miyamoto Yoshihiro , Minematsu Kazuo , Koga Masatoshi 
Published: October 2024

Background and aim: Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Methods: Patients with intracerebral hemorrhage admitted within 24 h after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5–6 at discharge. Results: Of a total 9810 patients with intracerebral hemorrhage (4267 females; mean age = 70 ± 15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5–22), 13 (5–26), 15 (5–30), and 13 (6–24), respectively, in the four groups. In multivariable analysis, the prestroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio = 1.09 (95% confidence interval (CI) = 1.06–1.13), with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 (95% CI = 0.98–1.02)) and DOAC group (0.98 (95% CI = 0.95–1.01)) were not. The rate of mRS 5–6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, prestroke warfarin use was associated with mRS 5–6 (adjusted odds ratio = 1.90 (95% CI = 1.28–2.81), with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 (95% CI = 0.91–1.37)) and DOAC group (1.25 (95% CI = 0.88–1.77)) were not. Conclusion: Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.
Association between handgrip strength and small airway disease in patients with stable chronic obstructive pulmonary disease
Authors: Keawon Thanapon , Saiphoklang Narongkorn 
Published: October 2024

Background: Chronic obstructive pulmonary disease (COPD) is associated with airflow limitation resulting from a combination of small airway disease (SAD) and parenchymal destruction. Although various diagnostic methods for SAD exist, access to these tools can be limited. Objectives: This study aimed to explore the correlation between handgrip strength (HGS) and SAD in COPD patients. Design: Cross-sectional prospective study. Methods: HGS was measured using a hand dynamometer. SAD was evaluated using impulse oscillometry, with results reported as the difference between respiratory resistance at 5 and 20 Hz (R5–R20). SAD was defined as R5–R20 ⩾0.07 kPa/L/s. The receiver operator characteristic (ROC) curves, sensitivity, and specificity values were calculated to determine the optimal cutoff value of HGS for predicting SAD. Results: Sixty-four patients (90.6% male) were included. The average age was 72.1 ± 8.3 years, and body mass index was 23.4 ± 4.2 kg/m2. FEV1 was 71.6 ± 21.3%, and HGS was 30.2 ± 8.1 kg. R5–R20 was 0.11 ± 0.08 kPa/L/s. SAD was found in 64.1% of patients. A negative correlation between HGS and R5–R20 was observed ( r = −0.332, p = 0.007). The best cutoff value for HGS in detecting SAD was determined to be 28.25 kg, with a sensitivity of 73.9%, specificity of 65.9%, and an area under ROC curve of 0.685 (95% CI 0.550–0.819, p = 0.015). Conclusion: SAD is common in COPD patients, and HGS is significantly negatively correlated with SAD. This tool might serve as an alternative or adjunctive assessment for small airway dysfunction in COPD patients. Registration: This study was registered with ClinicalTrials.gov with number NCT06223139.
The Deceptive Reassurance of a “Negative” Test – A Difficult Case Highlighting the BioFire© Meningitis/Encephalitis Panel and Medical Heuristics
Authors: Hoang Hai E. 
Published: October 2024

Purpose: Neurolisteriosis is a difficult neurologic infectious disease to diagnose. Here, we present a case in which the diagnosis was suspected, but repeated testing for the pathogen was negative. Ultimately the diagnosis was made after the patient iatrogenically worsened. Results: This prompted an investigation into the widely used diagnostic test, the BioFire© Meningitis/Encephalitis Panel. Although the company reports high sensitivities and specificities for the panel, real world studies have demonstrated insufficient evidence that all 14 pathogens tested on the panel have similar results. Conclusion: This case is a reminder of the heuristics involved in medicine and how with every medical advancement, clinicians should always go back to the fundamentals of history-taking and physical examinations to ensure no steps have been overlooked in the diagnosis and management of challenging cases.
Outcomes of haploidentical transplants with PT-CY vs 10/10 MUD transplants with ATG in Germany
Authors: Arslan Aysenur , Labuhn Svenja , Sala Elisa , Ringhoffer Mark , Schetelig Johannes , Schröder Thomas , Bug Gesine , Franke Georg-Nikolaus , Stelljes Matthias , Dreger Peter , Zeiser Robert , Teschner Daniel , Bethge Wolfgang , Eder Matthias , Edinger Matthias , Amann Elisa Maria , Neuchel Christine , Schmid-Möglich Amelie , Schmeller Sandra , Beyersmann Jan , Schrezenmeier Hubert , Mytilineos Joannis , Kröger Nicolaus , Fürst Daniel 
Published: October 2024

Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the best curative treatment modality for many malignant hematologic disorders. In the absence of a matched related donor, matched unrelated donors (MUDs) and haploidentical donors are the most important stem cell sources. In this registry-based retrospective study, we compared the outcomes of allo-HSCTs from 10/10 MUDs with antithymocyte globulin (ATG)–based regimens (n = 7050) vs haploidentical transplants (Haplo-Tx) using posttransplant cyclophosphamide (PT-CY Haplo; n = 487) in adult patients with hematologic malignancies between 2010 and 2020. Cox proportional hazard-and competing risks regression models were formed to compare the outcomes. Overall survival (OS), Disease-free survival (DFS), and graft-versus-host disease (GVHD)–free and relapse-free survival (GRFS) were superior for 10/10 MUDs (OS [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.10-1.47; P = .001]; DFS [HR, 1.17; CI, 1.02-1.34; P = .022]; GRFS [HR, 1.34; CI, 1.19-1.50; P &lt; .001]). The risk of acute GVHD (aGVHD) grade 2 to 4, aGVHD grade 3 to 4, and chronic GVHD (cGVHD) was higher in the PT-CY Haplo group than the 10/10 MUD group (aGVHD grade 2-4 [HR, 1.46; CI, 1.25-1.71; P &lt; .001]; aGVHD grade 3-4 [HR, 1.74; CI, 1.37- 2.20; P &lt; .001]; cGVHD [HR, 1.30; CI, 1.11-1.51; P = .001]). A lower incidence of relapse was observed in the PT-CY Haplo group (relapse: HR, 0.83; CI, 0.69-0.99; P = .038). Unrelated 10/10 matched transplantation with ATG leads to lower GVHD rates and improved survival rates compared with PT-CY Haplo transplantation in Germany.
Identification of factors predicting low-risk febrile neutropenia admissions in adults with acute myeloid leukemia
Authors: Pal Khushboo V. , Othus Megan , Ali Zahra , Russell Katherine , Shaw Carole , Percival Mary-Elizabeth M. , Hendrie Paul C. , Appelbaum Jacob S. , Walter Roland B. , Halpern Anna B. 
Published: October 2024

Abstract
Febrile neutropenia (FN) is the most common reason for hospital readmission after chemotherapy for acute myeloid leukemia (AML) and is a major driver of health care resource utilization. Although FN risk models exist, they have largely been developed and validated for solid tumors. We therefore examined whether baseline characteristics could predict which patients with AML and FN have a lower risk of progression to severe illness. We identified adults with high-grade myeloid neoplasms (≥10% blasts in the blood/marrow) who received intensive chemotherapy and who were admitted for FN between 2016 and 2023. We collected baseline clinical and disease variables. Outcomes were: infections identified, hospital length of stay (LOS), intensive care unit (ICU) admission, and survival. A lower-risk (LR) outcome was defined as LOS &lt;72 hours without ICU admission or inpatient death. Univariate and multivariable (MV) logistic regression models were used to assess covariate associations with outcomes. We identified 397 FN admissions in 248 patients (median age, 61; [range, 29-77] years). The median hospital LOS was 6 days (range, 1-56) days; 10% required ICU admission, and 3.5% died inpatient. Only 15% of admissions were LR. Infection was identified in 59% of admissions. Physiologic parameters, including heart rate, blood pressure, and fever height, were the best predictors of LR admission and infection. We developed MV models to predict LR admission and infection with area under the curve (AUC) of 0.82 and 0.72, respectively. Established FN and critical illness models were not predictive of outcomes in AML, and we could not identify a LR group; thus, an AML-specific FN risk model requires further development and validation.
Recruitment of emergency department patients to a prospective observational study
Authors: Shubeck Claire , Reyes Garay Hans , Nelson Bret P. , Wilder Marcee , Degtyar Aleksandra , Lukas Megan , Gordon Lauren , Loo George T. , Coleman Bernice , Richardson Lynne D. , Souffront Kimberly 
Published: October 2024

Abstract
Background
The dynamic environment of the emergency department (ED) poses unique challenges to the execution of well-designed research. There is limited investigation into the viability of studies conducted in the ED. This paper offers a systematic evaluation of our recruitment of emergency patients for a prospective observational research study, shedding light on the intricate landscape of research feasibility within the ED setting.

Results
Research coordinators dedicated 2816.83 h to screening, recruiting, and enrolling patients between June 2018 and September 2023, having to stop recruitment twice due to financial constraints and the COVID-19 pandemic. 485 patients were approached and 84 of them were enrolled, resulting in a 31.94% enrollment rate, with approximately 2.8 participants recruited per month. Of those enrolled, 77 completed all study endpoints. Most participants were Hispanic (n = 44; 52.3%) and/or Black (n = 37; 44%), middle-aged (µ = 51.7 years), and female (n = 48; 57.1%). Participant recruitment was challenged by competing mindsets, the COVID-19 pandemic, and high staff turnover.

Conclusions
Recruiting emergency patients for a prospective observational study is feasible given adequate staffing and financial resources. Standardizing feasibility assessments for the recruitment of patients in the emergency department is important to the success of future study.
Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen
Authors: Yang Muh-Hwa , Chen Tien-Hua , Wang Hung-Ming , Hsieh Jason Chia-Hsun , Huang Huai-Cheng , Hsieh Meng-Che , Yen Chia-Jui , Wu Shang-Yin , Hua Chun-Hung , Lien Ming-Yu , Chang Yi-Fang , Wang Hui-Ching , Chien Chih-Yen , Huang Tai-Lin , Lu Hsueh-Ju , Lin Jin-Ching , Wang Chen-Chi , Liu Yi-Chun , Chen Jo-Pai , Lu Wei-Chen , Yiu Ching-Yi , Lin Chien-Liang , Lou Pei-Jen , Chu Pen-Yuan 
Published: October 2024

Abstract
Background
In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population.

Methods
This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS.

Results
A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 – 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44–13.61), 7.5 months (95% CI 7.33–8.17), and 4.01 months (95% CI 3.94–4.08), respectively, with a log-rank test p-value < 0.001.

Conclusion
This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.
How likely are Eastern European and central Asian countries to achieve global NCD targets: multi-country analysis
Authors: Dumcheva Anastasiya , Nevalainen Jaakko , Laatikainen Tiina , Nuorti Pekka 
Published: October 2024

Abstract
Background
In Europe, mortality rates from noncommunicable diseases (NCDs) among persons 30–69 years of age (“NCD premature mortality rates”) have declined significantly, except in twelve countries of Eastern Europe and Central Asia, namely Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan. Data on long-term trends in NCD mortality in these countries are limited. We analyzed NCD premature mortality rates, identified change points in NCD mortality trends and forecasted how likely countries are to achieve the global NCD targets, stratified by gender and NCD type.

Methods
We used the 1990–2019 Global Burden of Disease database to analyze NCD trends and identified country-specific change points by using piecewise linear regression. We assessed the likelihood of achieving the global targets for reducing NCD premature mortality rates among persons 30–69 years of age from four NCDs: cancers, diabetes, cardiovascular and chronic respiratory diseases. The global NCD targets are 25% reduction in mortality from 2010 to 2025 (WHO 25X25 target) and 33%—from 2015 to 2030 (SDG 3.4.1). We applied the analysis to both genders and four NCDs.

Results
Only Kazakhstan and Russia are likely to achieve the global NCD targets. For Kazakhstan, WHO 25X25 and SDG 3.4.1 global targets for mortality rates were 494.3 and 374.8 per 100,000 population respectively; the corresponding predicted values (PVs) were 360.6 [CI 260.1–461.1] and 245.1 [CI 113.4–376.8]. For Russia, WHO 25X25 and SDG 3.4.1 global targets were 560.5 and 442.8 per 100,000 population respectively; the corresponding PVs were 427.7 [CI 270.3–585.1] and 311.0 [CI 102.8–519.1]. Achieving NCD global targets is less likely for Kyrgyzstan, while it is unlikely for the rest of countries. Most countries had higher mortality rates and slower progress among men compared with women. The likelihood of achieving overall global NCD targets was mainly explained by reduction in cardiovascular mortality.

Conclusions
In most Eastern Europe and Central Asia countries, progress towards achieving NCD global targets is slow, or there’s a reverse trend. Further quantitative and qualitative research is needed to understand the underlying reasons. Separate indicators are needed to monitor trends for cancers, diabetes and chronic respiratory diseases.
Chitosan-glucose derivative membrane obtained by Maillard reaction improves cartilage repair in a rabbit model
Authors: Chuang Po-Yao , Chang Shun-Fu , Lu Ying-Chen , Huang Kuo-Chin 
Published: October 2024

Abstract
Background
Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits.

Methods
An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA.

Results
According to histological analysis, CGMR-treated defects showed significantly improved modified O’Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR.

Conclusions
CGMR might improve cartilage regeneration in osteochondral defects.
Heterogeneous impact of Sighs on mortality in patients with acute hypoxemic respiratory failure: insights from the PROTECTION study
Authors: Rezoagli Emanuele , Fornari Carla , Fumagalli Roberto , Grasselli Giacomo , Volta Carlo Alberto , Navalesi Paolo , Knafelj Rihard , Brochard Laurent , Pesenti Antonio , Mauri Tommaso , Foti Giuseppe ,   for the Pleural Pressure Working Group (PLUG), Colombo Riccardo , Cortegiani Andrea , Zhou Jian-Xin , D’Andrea Rocco , Calamai Italo , González Ánxela Vidal , Roca Oriol , Grieco Domenico Luca , Jovaisa Tomas , Bampalis Dimitrios , Becher Tobias , Battaglini Denise , Ge Huiqing , Luz Mariana , Santos Edgard , Constantin Jean-Michel , Ranieri Marco , Guerin Claude , Mancebo Jordi , Pelosi Paolo 
Published: October 2024

Abstract
Background
Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days.

Results
Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH2O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP.

Conclusions
Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch.
Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT03201263.
Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy
Authors: Xu Houshi , Chai Huihui , Chen Ming , Zhu Ruize , Jiang Shan , Liu Xiaoyu , Wang Yue , Chen Jiawen , Wei Junji , Mao Ying , Shi Zhifeng 
Published: October 2024

Abstract
Background
Glioma is the most common primary malignant tumor in the brain, and even with standard treatments including surgical resection, radiotherapy, and chemotherapy, the long-term survival rate of patients remains unsatisfactory. Recurrence is one of the leading causes of death in glioma patients. The molecular mechanisms underlying glioma recurrence remain unclear.

Methods
Our study utilized single-cell sequencing, spatial transcriptomics, and RNA-seq data to identify a subtype of FN1 + tumor-associated macrophages (FN1 + TAMs) associated with glioma recurrence.

Results
This study revealed an increased abundance of FN1 + TAMs in recurrent gliomas, indicating their potential involvement as a critical factor in glioma recurrence. A negative correlation was observed between the abundance of FN1 + TAMs in primary gliomas and the interval time to recurrence, suggesting poor prognosis for glioma patients with high levels of FN1 + TAMs. Further investigation showed that FN1 + TAMs were enriched in hypoxic tumor regions, implying that metabolic changes in tumors drive the production and recruitment of FN1 + TAMs. Additionally, FN1 + TAMs were found to contribute to the regulation of an immunosuppressive microenvironment in gliomas, and their abundance might serve as an indicator of patients’ sensitivity to immunotherapy. Finally, we developed a user-friendly website, PRIMEG (http://www.szflab.site/PRIMEG/), for exploring the immune microenvironment of primary and recurrent gliomas.

Conclusion
Our findings highlight a subtype of FN1 + TAMs associated with glioma recurrence, providing new insights into potential therapeutic targets. Moreover, the abundance of FN1 + TAMs hold promise for predicting immune therapy response and aiding in more precise risk stratification of recurrent glioma patients.