bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and characteristics of adverse drug reactions in a cohort of patients treated with PD-1/PD-L1 inhibitors in real-world practice
Authors: Sabaté Gallego Mònica , Pérez Esquirol Eulàlia , Garcia Doladé Núria , Vidal Guitart Xavier , Carreras Soler Maria-Josep , Farriols Danés Anna , Felip Enriqueta , Braña Irene , Carles Galceran Joan , Morales Barrera Rafael , Muñoz-Couselo Eva , Agustí Escasany Antònia 
Published: August 2022

BackgroundData related to adverse drug reactions (ADRs), specifically immune-related adverse events (irAEs), in long-term treatment with immunotherapy in real-world practice is scarce, as is general information regarding the management of ADRs.ObjectivesTo characterize and describe the incidence of ADRs in patients who began immunotherapy treatment in clinical practice.MethodsIn a prospective observational study cancer patients ≥18 years of age who were treated with a monotherapy regime of PD-1/PD-L1 inhibitors were evaluated. The study period was from November 2017 to June 2019 and patients were followed up until June 2021. Patients were contacted monthly by telephone and their electronic health records were reviewed. Each ADR was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).ResultsOut of 99 patients, 86 met the inclusion criteria. Most were male (67.4%), with a median age of 66 (interquartile range, IQR: 59–76). The most frequent cancer was non-small cellular lung cancer (46 cases, 53.5%), followed by melanoma (22, 25.6%). A total of 74 patients (86%) were treated with anti-PD-1 drugs and 12 (14%) were treated with anti-PD-L1 drugs. The median treatment durations were 4.9 (IQR: 1.9–17.0) and 5.9 months (IQR: 1.2–12.3), respectively. Sixty-three patients (73%) developed from a total of 156 (44% of the total number of ADR) irADRs, wherein the most frequent were skin disorders (50 cases, 32%, incidence = 30.5 irADRs/100 patients per year [p-y]), gastrointestinal disorders (29, 19%, 17.7 irADRs/100 p-y), musculoskeletal disorders (17, 11%, 10.4 irADRs/100 p-y), and endocrine disorders (14, 9%, 8.6 irADRs/100 p-y). A total of 22 irADRs (14%) had a latency period of ≥12 months. Twelve irADRs (7.7%) were categorized as grade 3–4, and while 2 (1.3%) were categorized as grade 5 (death). Sixty-one irADRs (39.1%) in 36 patients required pharmacological treatment and 47 irADRs (30.1%) in 22 patients required treatment with corticosteriods.ConclusionThe majority of patients treated with anti-PD1/PDL1-based immunotherapy experienced adverse reactions. Although most of these reactions were mild, 11.5% were categorized as grade 3 or above. A high percentage of the reactions were immune-related and occurred throughout the treatment, thereby indicating that early identification and close monitoring is essential.
Prognostic value of proadrenomedullin in patients with COVID-19 pneumonia
Authors: Astapovskii Aleksandr A. , Drozdov Vladimir N. , Shikh Evgenia V. , Melkonyan George G. , Sizova Zhanna M. , Zakharova Valeria L. , Shindryaeva Natalia N. , Lapidus Natalia I. 
Published: August 2022

ObjectiveThe aim of the study was to assess the role of mid-regional proadrenomedullin (MR-proADM) in comparison with routine laboratory tests in patients with COVID-19.Materials and methods140 hospitalized patients aged 18 and older with COVID-19 pneumonia were included in prospective single-center study. Routine analyses were performed, and MR-proADM level was measured within the first and the third hospital days using Human MR pro-ADM (Mid-regional pro-adrenomedullin) ELISA Kit with a sensitivity of 0.469 pmol/L (immunofluorescence assay). National Early Warning Score (NEWS) was used for primary assessment of the disease severity. According to disease outcome the patients were divided into two groups: discharged patients (n = 110, 78.6%) and deceased patients (n = 30, 21.4%). Results: The groups had no statistically significant difference in sex, comorbidity, body temperature, oxygen saturation level, heart rate, respiratory rate, and C-reactive protein (CRP) level and procalcitonin (PCT). The deceased patients had statistically significant difference in age (median, 76 years; interquartile range, 73.2–78.2 vs. median, 66 years; interquartile range, 62–67; p &lt; 0.0001), NEWS value (median, 5; interquartile range, 3–8 vs. median, 2; interquartile range, 0–6; p &lt;0.05), hospitalization period (median, 17; interquartile range, 7–35 vs. median, 6; interquartile range, 3–14), quantitative CT extent of lung damage &gt; 50% [n = 26 (86.7%) vs. n = 9 (8.2%) p &lt; 0.0001], level of leukocytes (median, 11.4 ×109/L; interquartile range, 6.2–15.5 vs. median, 5.3 ×109/L; interquartile range, 4.7–6.4; p = 0.003), level of neutrophils (median, 80.9%; interquartile range, 73.6–88.6 vs. median, 72.6%; interquartile range, 68.7–76.9; p = 0.027), level of MR-proADM at the first hospital day (median, 828.6 pmol/L; interquartile range, 586.4–1,184.6 vs. median, 492.6 pmol/L; interquartile range, 352.9–712.2; p = 0.02), and level of MR-proADM at the third hospital day (median, 1,855.2 pmol/L; interquartile range, 1,078.4–2,596.5 vs. median, 270.7 pmol/L; interquartile range, 155.06–427.1).ConclusionMid-regional proadrenomedullin has a higher prognostic value in patients with COVID-19 in comparison with routine inflammatory markers (leukocyte and neutrophils levels, CRP, and PCT) and NEWS.
Decolonization of carbapenem-resistant Klebsiella pneumoniae from the intestinal microbiota of model mice by phages targeting two surface structures
Authors: Liu Ju-Yun , Lin Tzu-Lung , Chiu Ching-Yu , Hsieh Pei-Fang , Lin Yi-Tsung , Lai Li-Yin , Wang Jin-Town 
Published: August 2022

BackgroundKlebsiella pneumoniae is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant K. pneumoniae (CRKP), has been increasing.Materials and methodsWe attempted to specifically eliminate CRKP from a mouse model with the human intestinal microbiota. To establish humanized microbiota-colonized mice, we administered K64 CRKP-containing human microbiota to germ-free mice by fecal microbiota transplantation. Then, we used two phages, one targeting the capsule (φK64-1) and one targeting O1 lipopolysaccharide (φKO1-1) of K64 K. pneumoniae, to eliminate CRKP.ResultsIn untreated control and φKO1-1-treated K64-colonized mice, no change in CRKP was observed, while in mice treated with φK64-1, a transient reduction was observed. In half of the mice treated with both φKO1-1 and φK64-1, CRKP was undetectable in feces by PCR and culture for 60 days. However, in the other 50% of the mice, K. pneumoniae was transiently reduced but recovered 35 days after treatment.ConclusionCombination treatment with φK64-1 and φKO1-1 achieved long-term decolonization in 52.3% of mice carrying CRKP. Importantly, the composition of the intestinal microbiota was not altered after phage treatment. Therefore, this strategy may be useful not only for eradicating drug-resistant bacterial species from the intestinal microbiota but also for the treatment of other dysbiosis-associated diseases.
Predicting progression to dementia with “comprehensive visual rating scale” and machine learning algorithms
Authors: Park Chaeyoon , Jang Jae-Won , Joo Gihun , Kim Yeshin , Kim Seongheon , Byeon Gihwan , Park Sang Won , Kasani Payam Hosseinzadeh , Yum Sujin , Pyun Jung-Min , Park Young Ho , Lim Jae-Sung , Youn Young Chul , Choi Hyun-Soo , Park Chihyun , Im Hyeonseung , Kim SangYun 
Published: August 2022

Background and ObjectiveIdentifying biomarkers for predicting progression to dementia in patients with mild cognitive impairment (MCI) is crucial. To this end, the comprehensive visual rating scale (CVRS), which is based on magnetic resonance imaging (MRI), was developed for the assessment of structural changes in the brains of patients with MCI. This study aimed to investigate the use of the CVRS score for predicting dementia in patients with MCI over a 2-year follow-up period using various machine learning (ML) algorithms.MethodsWe included 197 patients with MCI who were followed up more than once. The data used for this study were obtained from the Japanese-Alzheimer's Disease Neuroimaging Initiative study. We assessed all the patients using their CVRS scores, cortical thickness data, and clinical data to determine their progression to dementia during a follow-up period of over 2 years. ML algorithms, such as logistic regression, random forest (RF), XGBoost, and LightGBM, were applied to the combination of the dataset. Further, feature importance that contributed to the progression from MCI to dementia was analyzed to confirm the risk predictors among the various variables evaluated.ResultsOf the 197 patients, 108 (54.8%) showed progression from MCI to dementia. Tree-based classifiers, such as XGBoost, LightGBM, and RF, achieved relatively high performance. In addition, the prediction models showed better performance when clinical data and CVRS score (accuracy 0.701–0.711) were used than when clinical data and cortical thickness (accuracy 0.650–0.685) were used. The features related to CVRS helped predict progression to dementia using the tree-based models compared to logistic regression.ConclusionsTree-based ML algorithms can predict progression from MCI to dementia using baseline CVRS scores combined with clinical data.
Ischemic and haemorrhagic stroke risk estimation using a machine-learning-based retinal image analysis
Authors: Qu Yimin , Zhuo Yuanyuan , Lee Jack , Huang Xingxian , Yang Zhuoxin , Yu Haibo , Zhang Jinwen , Yuan Weiqu , Wu Jiaman , Owens David , Zee Benny 
Published: August 2022

BackgroundStroke is the second leading cause of death worldwide, causing a considerable disease burden. Ischemic stroke is more frequent, but haemorrhagic stroke is responsible for more deaths. The clinical management and treatment are different, and it is advantageous to classify their risk as early as possible for disease prevention. Furthermore, retinal characteristics have been associated with stroke and can be used for stroke risk estimation. This study investigated machine learning approaches to retinal images for risk estimation and classification of ischemic and haemorrhagic stroke.Study designA case-control study was conducted in the Shenzhen Traditional Chinese Medicine Hospital. According to the computerized tomography scan (CT) or magnetic resonance imaging (MRI) results, stroke patients were classified as either ischemic or hemorrhage stroke. In addition, a control group was formed using non-stroke patients from the hospital and healthy individuals from the community. Baseline demographic and medical information was collected from participants' hospital medical records. Retinal images of both eyes of each participant were taken within 2 weeks of admission. Classification models using a machine-learning approach were developed. A 10-fold cross-validation method was used to validate the results.Results711 patients were included, with 145 ischemic stroke patients, 86 haemorrhagic stroke patients, and 480 controls. Based on 10-fold cross-validation, the ischemic stroke risk estimation has a sensitivity and a specificity of 91.0% and 94.8%, respectively. The area under the ROC curve for ischemic stroke is 0.929 (95% CI 0.900 to 0.958). The haemorrhagic stroke risk estimation has a sensitivity and a specificity of 93.0% and 97.1%, respectively. The area under the ROC curve is 0.951 (95% CI 0.918 to 0.983).ConclusionA fast and fully automatic method can be used for stroke subtype risk assessment and classification based on fundus photographs alone.
Phenytoin as seizure prophylaxis in hematopoietic stem cell transplantation with busulfan conditioning
Authors: Germeraad R. S. , Demandt A. M. P. , Rouhl R. P. W. 
Published: August 2022

BackgroundPhenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan. Because of the negative side effects of phenytoin, we abandoned phenytoin use in these patients. To assess the effect of this change, we performed a retrospective cohort study on all patients receiving busulfan.MethodsWe included 139 patients who underwent conditioning with busulfan for hematopoietic stem cell therapy. We registered the use of phenytoin, as well as the occurrence of seizures, until 7 days after busulfan administration. We compared seizure incidence between patients who received phenytoin and those who did not.ResultsOf the 43 patients who received phenytoin prophylaxis, four patients (9.3%) had a seizure during the conditioning regimen, of which two patients had cerebral non-Hodgkin lymphoma. Furthermore, all these 4 patients had very high levels of phenytoin (intoxication). Of the 96 patients that did not receive phenytoin prophylaxis, three patients (3.1%) had a seizure, and one of these patients had an undefined cerebral lesion. Phenytoin did not relate to seizure prevention in a logistic regression analysis.ConclusionWe conclude that phenytoin prophylaxis in patients treated with busulfan is obsolete and possibly harmful, as phenytoin intoxication can occur. We recommend discontinuing the use of phenytoin as primary seizure prophylaxis in these patients.
Lateralized brain activities in subcortical vascular mild cognitive impairment with differential Chinese medicine patterns: A resting-state functional magnetic resonance imaging study
Authors: Wang Jianjun , Kong Fanxin , Zheng Haotao , Cai Dongbin , Liu Lijin , Lian Jie , Lyu Hanqing , Lin Songjun , Chen Jianxiang , Qin Xiude 
Published: August 2022

BackgroundSubcortical vascular mild cognitive impairment (svMCI) is one of the most treatable cognitive impairments, but could be hampered by the high clinical heterogeneities. Further classification by Chinese Medicine (CM) patterns has been proved to stratify its clinical heterogeneities. It remains largely unknown of the spontaneous brain activities regarding deficiency patterns (DPs) and excess patterns (EPs) of svMCI patients based on fMRI data.ObjectiveWe aim to provide neuroimaging evidence of altered resting-state brain activities associated with DPs and EPs in svMCI patients.MethodsThirty-seven svMCI patients (PAs) and 23 healthy controls (CNs) were consecutively enrolled. All patients were categorized into either the EP group (n = 16) and the DP group (n = 21) based on a quantitative CM scale. The fractional amplitude of low-frequency fluctuation (fALFF) value was used to make comparisons between different subgroups.ResultsThe DP group showed significant differences of fALFF values in the right middle frontal gyrus and the right cerebellum, while the EP group showed significant differences in the left orbitofrontal gyrus and the left cerebellum, when compared with the CN group. When compared with the EP group, the DP group had markedly increased fALFF values in the left superior temporal gyrus, right middle temporal gyrus and brainstem. The decreased fALFF values was shown in the right anterior cingulate and paracingulate gyri. Among the extensive areas of frontotemporal lobe, the Montreal Cognitive Assessment (MoCA) scores were significantly correlated with the reduced fALFF value of the right middle frontal gyrus and the left orbitofrontal gyrus.ConclusionOur results indicated that the DPs and EPs presented the lateralization pattern in the bilateral frontal gyrus, which will probably benefit the future investigation of the pathogenesis of svMCI patients.
Short- and long-term outcome of allogeneic stem cell transplantation in infants: A single-center experience over 20 years
Authors: Miśkiewicz-Bujna Justyna , Miśkiewicz-Migoń Izabella , Szmit Zofia , Przystupski Dawid , Rosa Monika , Król Anna , Kałwak Krzysztof , Ussowicz Marek , Gorczyńska Ewa 
Published: August 2022

IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants.Material and methodsIn the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation.ResultsThe probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III–IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (&lt;3rd percentile) in 37.2% and overt hypothyroidism in 35.4%. In the long-term perspective, 83.3% of survivors were able to attend a regular school.ConclusionsImprovements in unrelated donor availability, and better supportive care resulted in better outcomes. Management of infant allo-HSCT recipients requires the formation of multi-disciplinary specialist teams. In addition, the role of parental empowerment must be acknowledged; for example, in speech therapy and rehabilitation.
Physicians’ Knowledge, Altitudes, and Perceived Barriers of Inappropriate Prescribing for Older Patients in Shanghai, China
Authors: Yuan Jing , Yin Guizhi , Gu Meng , Lu Kevin Z. , Jiang Bin , Li Minghui 
Published: August 2022

Background: Inappropriate medication use is common around the world, particularly among older patients, and, despite potentially being preventable, often leads to adverse clinical and economic outcomes. However, there is a dearth of information regarding this prominent issue in China.Objectives: To evaluate the extent to which the physician can correctly identify potentially inappropriate medication (PIM) in older patients and to understand physicians’ attitudes towards improving PIM knowledge.Methods: An online, cross-sectional survey was conducted anonymously among practicing physicians in China from November through December 2020. Knowledge of PIM was accessed using seven clinical vignettes covering a wide variety of therapeutic areas. Source of information and perceived barriers regarding PIM were also evaluated. We performed the ordinary least square regression analysis to understand the potential factors related to physicians’ knowledge of PIM.Results: A total of 597 study participants were included in the analysis. More than half of them had never heard of any screening tool for PIMs (n = 328, 54.9%) and the most frequently acknowledged tool was the China PIM Criteria (n = 259, 43.4%). For the seven clinical vignettes testing physicians’ knowledge on the medications that should be generally avoided in older patients, the mean score was 2.91 points out of 7 (SD: 1.32), with the median score of three points (IQR: 2–4). Only one-third of the respondents were feeling confident when prescribing for older patients (n = 255, 35.08%). Package inserts have been used as the major source of PIM information (always, n = 177, 29.65%; frequently, n = 286, 47.91%). Perceived barriers to appropriate prescribing include polypharmacy (n = 460, 77.05%), lack of formal education on prescribing for the older patients (n = 428, 71.69%).Conclusion: In this online survey evaluating physicians’ ability to detect PIM for older patients, approximately 40% of PIM were recognized, suggesting an insufficient level of knowledge about appropriate prescribing.
Current situation and future development of the biopharmaceutical industry in China: A mixed-method study
Authors: Yang Ruomeng , Kabba John Alimamy , Yao Xuelin , Yang Caijun , Chang Jie , Ji Wenjing , Jiang Minghuan , Zhao Mingyue , Wen Jun , Fang Yu 
Published: August 2022

Introduction: The biomedical industry has grown significantly both globally and in China; however, there are still challenges. This study aimed at evaluating the biopharmaceutical sector of China, in terms of ability to innovate, current sales volume, investment, and R&amp;D expenditure, as well as providing a case study detailing the progress and challenges of the industry in Shaanxi province.Method: A cross-sectional mixed-method study design was used to generate a comprehensive profile of the nature of biopharmaceutical innovation capacity and development in China by triangulating country-wide survey and interview data from Shaanxi province. Only biopharmaceutical companies that are currently marketing or conducting research and development were eligible for inclusion, and Shaanxi province was selected for conducting the interviews. Categorical and continuous variables were analyzed descriptively. Interviews were thematically analyzed by using NVivo version 12.Results: The analysis includes responses from 77 biopharmaceutical enterprises; the majority (36, 46.8%) are in Eastern China, followed by 26 (33.8%) in Central China. In 2018, the total sales of biological products amounted to 26.28 billion yuan, and in 2019, a slight increase was observed (30.34 billion); the amount doubled in 2020 to about 67.91 billion yuan. The top three biopharmaceutical products on sale in 2020 were Camrelizumab (5.14 billion yuan), human albumin (4.56 billion yuan), and human immunoglobulin for injection (3.78 billion yuan). Expenditure on R&amp;D has also increased; it amounted to 1657.7 million yuan in 2018, which more than doubled in 2019 to 3572.1 million yuan and further increased to 5857.7 million yuan in 2020. Nonetheless, the progress is not uniform across all provinces, as shown from the results from Shaanxi province, because of lack of local government policies that will impact on the funding, incentives, and market share that motivate the producers.Conclusion: China’s biopharmaceutical industry has expand significantly. The increase in sales indicates that there is an increase in demand for biologicals; moreover, R&amp;D funding is increasing. These are key indicators that influence innovation and development. However, the sector’s capacity to innovate and develop needs to be improved, particularly in the western region, where research and production are relatively weak.