bluuebunny/crossref_metadata_2025_split huggingface dataset:
The occurrence of asthma in an extensive-stage small-cell lung cancer patient after combination therapy with atezolizumab and anlotinib: a case report
Authors: Deng Wang , Chen Juan , Deng Xin-Yu 
Published: February 2024

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events.Case presentationA 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade.ConclusionsThis is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.
Immunoproteomics enable broad identification of new Aspergillus fumigatus antigens in severe equine asthma
Authors: Jentsch Maria-Christin , Lübke Sabrina , Schrödl Wieland , Volke Daniela , Krizsan Andor , Hoffmann Ralf , Kaiser-Thom Sarah , Gerber Vinzenz , Marti Eliane , Wagner Bettina , Schnabel Christiane L. 
Published: February 2024

IntroductionSevere equine asthma (SEA) is a common chronic disease of adult horses with characteristic recurrent airway obstruction and similarities to neutrophilic asthma in humans. As an extrinsic stimulus, hay dust exposure is a major risk factor and induces acute exacerbation in susceptible horses. However, single inducing agents of SEA have hardly been identified on a molecular basis. Aspergillus fumigatus (A. fumigatus) is a common mold species in hay and has been described as a major provoking agent of SEA.MethodsAiming to identify disease-relevant antigens, we analyzed A. fumigatus using an immunoproteomics approach on two-dimensional immunoblots of A. fumigatus protein probed with serum from environmentally matched asthmatic and healthy horses (n=5 pairs). A. fumigatus binding serum immunoglobulins (Pan-Ig), and the isotypes IgG4/7 and IgG3/5 were quantified for each protein spot and then compared between asthmatic and healthy horses.Results and discussionFor 21 out of 289 spots serum immunoglobulin (Ig) binding was different between the two groups for Pan-Ig or the isotypes. If differences were detected, Pan-Ig and IgG4/7 binding to the proteins were lower, while IgG3/5 binding was higher in asthmatic than healthy horse sera. Proteins were extracted from the 21 spots of interest and analyzed by liquid chromatography mass spectrometry. Eight prioritized proteins (candidate antigens) were expressed as recombinant proteins. Some of these have been previously described as major or minor A. fumigatus allergens, alongside other proteins, most with hydrolase activity. Recombinant candidate antigens were tested on 1D immunoblots to confirm their relevance as antigens by serum antibody binding. Four proteins (beta-hexosaminidase, class II aldolase/adducin domain protein, glucoamylase, peptide hydrolase B0XX53) showed different antibody binding characteristics between asthmatic and healthy horses and are likely relevant antigens in SEA. Their identification can provide the basis for innovative diagnostics, prevention, or therapeutic approaches. Additionally, a more profound understanding of SEA and its potential underlying mechanisms can be established. Elevated serum IgG3/5 antibodies correlate with T helper cell 2 responses in other equine pathologies, and the recombinant SEA antigens developed here can become instrumental in analyzing the involvement of SEA-specific T cell responses and Ig responses in future studies.
Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy
Authors: Bar Jair , Leibowitz Raya , Reinmuth Niels , Ammendola Astrid , Jacob Eyal , Moskovitz Mor , Levy-Barda Adva , Lotem Michal , Katsenelson Rivka , Agbarya Abed , Abu-Amna Mahmoud , Gottfried Maya , Harkovsky Tatiana , Wolf Ido , Tepper Ella , Loewenthal Gil , Yellin Ben , Brody Yehuda , Dahan Nili , Yanko Maya , Lahav Coren , Harel Michal , Raveh Shoval Shani , Elon Yehonatan , Sela Itamar , Dicker Adam P. , Shaked Yuval 
Published: February 2024

IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.
Distribution and influencing factors of macrobenthos on three seagrass beds in the intertidal zone of Shandong province, China
Authors: Ji Yinglu , Song Bo , Xu Jiangling , Jiang Shaoyu , Chen Linlin , Li Baoquan 
Published: February 2024

IntroductionThe macrobenthos plays a vital role within the ecosystem of seagrass beds, with its characteristics and spatial distribution serving as indicators of the well-being of the seagrass beds.MethodsIn August 2018, three seagrass beds located in the Yellow River Estuary of Dongying, the west coast of Yantai, and Swan Lake of Weihai, were investigated to compare the ecological influences of seagrass habitat on the benthic environment and macrobenthic community. Within each seagrass bed, porewater, sediment, and macrobenthos were sampled from three separate stations (center of seagrass bed, edge of seagrass bed and bare area).Results and discussionOne-way ANOVA showed significant differences (p &lt; 0.05) in environmental factors and macrobenthos species, abundance, biomass and diversity indices among the three seagrass beds. The present data did not show significant impacts on habitat and macrobenthos in the different coverage areas of seagrass beds at the investigated spatial scales, though crustacea and some carnivores were relatively more inclined to inhabit areas with higher seagrass densities. Aquaculture and eutrophication may trigger the loss of seagrass bed habitats, that affects macrobenthic biodiversity, and conservation measures are needed to protect seagrass bed habitats.
Potential role of physical labor and cultural views of menstruation in high incidence of pelvic organ prolapse in Nepalese women: a comparative study across the menstrual cycle
Authors: Biswokarma Yvonne , Brandon Karen , Lohman Everett , Stafford Ryan , Daher Noha , Petrofsky Jerold , Thapa Uma , Berk Lee , Hitchcock Robert , Hodges Paul W. 
Published: February 2024

IntroductionPelvic organ prolapse (POP) is a significant health concern for young Nepali women, with potential risk factors including pelvic floor trauma from vaginal delivery and heavy lifting. The prevalence of symptomatic POP (SPOP) among nulliparous women in Nepal is 6%, while the general population of Nepali women aged 15–49 years reports a prevalence of 7%. Surprisingly, the average age of SPOP onset in Nepal is 27 years, challenging the assumption that postmenopausal age and vaginal delivery are the sole risk factors. This study aims to investigate the influence of increased intra-abdominal pressure (IAP) during lifting tasks on pelvic organ descent in Nepali women across different menstrual cycle stages.MethodsThe study included 22 asymptomatic Nepali women aged 18–30 years who regularly engage in heavy lifting. Intra-abdominal pressure was measured intra-vaginally during typical and simulated lifting tasks, which encompassed various scenarios such as ballistic lifting, ramped lifting, and pre-contraction of pelvic floor muscles, as well as coughing, Valsalva maneuver, and pelvic floor contractions. Pelvic floor displacement was recorded using transperineal ultrasound during menstruation, ovulation, and the mid-luteal phase.ResultsResults indicated that pelvic floor displacement was greater during menstruation than ovulation when performing a simulated ballistic lifting task (6.0 ± 1.6 mm vs. 5.1 ± 1.5 mm, p = 0.03, d = 0.6). However, there was no significant difference in pelvic floor displacement during lifting when the pelvic muscles were pre-contracted.ConclusionThese findings suggest that lifting heavy loads during menstruation may increase the risk of stretching and injuring pelvic floor supportive tissues, potentially contributing to SPOP in young Nepali women. Pre-contracting pelvic floor muscles during lifting tasks may offer a protective effect. Understanding these factors could aid in developing targeted preventive measures and raising awareness about the impact of heavy lifting on pelvic floor health among Nepali women.
Efficacy of vestibular rehabilitation and its facilitating and hindering factors from real-world clinical data
Authors: Kim Min-Ku , Yun So-Yeon , Lee Seonkyung , Lee Ja-Ok , Sung Soo-Yun , Lee Ju-Young , Kim Hyo-Jung , Park Hye Youn , Choi Jeong-Yoon , Song Jae-Jin , Choi Byung Yoon , Koo Ja-Won , Kim Ji-Soo 
Published: February 2024

Background and purposeCustomized vestibular rehabilitation improved dizziness and imbalance in several randomized controlled trials. In the present study, we determined the efficacy of customized vestibular rehabilitation using real-world observational data.MethodsIn this retrospective observational study, we recruited 64 patients (median age = 60, interquartile range = 48–66.3) who completed the customized vestibular rehabilitation from January to December 2022. The outcomes of rehabilitation were evaluated using the dizziness handicap inventory (DHI) or vestibular disorders activities of daily living scale (VADL). The factors associated with outcomes were assessed with a generalized linear model, of which covariates included patients’ age, sex, duration of illness, type of vestibular disorders, initial DHI and VADL scores, exercise compliance, and initial hospital anxiety and depression scale (HADS) scores.ResultsAfter the median of 6 (4–6) weeks of rehabilitation, DHI and VADL scores significantly improved in patients with either peripheral or central vestibular disorders (Wilcoxon signed-rank test, p &lt; 0.05). The initial DHI and VADL scores showed a positive while the sum of HADS scores showed a negative correlation with the outcome. In contrast, the age, sex, duration of illness, types of vestibular disorders, and exercise compliance did not affect the outcome.Discussion and conclusionCustomized vestibular rehabilitation is effective for central as well as peripheral disorders, especially when the symptoms are severe and the psychological distress is mild.
Establishing an MSU service in a medium-sized German urban area—clinical and economic considerations
Authors: Rink Johann S. , Tollens Fabian , Tschalzev Andrej , Bartelt Christian , Heinzl Armin , Hoffmann Jens , Schoenberg Stefan O. , Marzina Annika , Sandikci Vesile , Wiegand Carla , Hoyer Carolin , Szabo Kristina 
Published: February 2024

Background and purposeMobile stroke units (MSU) have been demonstrated to improve prehospital stroke care in metropolitan and rural regions. Due to geographical, social and structural idiosyncrasies of the German city of Mannheim, concepts of established MSU services are not directly applicable to the Mannheim initiative. The aim of the present analysis was to identify major determinants that need to be considered when initially setting up a local MSU service.MethodsLocal stroke statistics from 2015 to 2021 were analyzed and circadian distribution of strokes and local incidence rates were calculated. MSU patient numbers and total program costs were estimated for varying operating modes, daytime coverage models, staffing configurations which included several resource sharing models with the hospital. Additional case-number simulations for expanded catchment areas were performed.ResultsMedian time of symptom onset of ischemic stroke patients was 1:00 p.m. 54.3% of all stroke patients were admitted during a 10-h time window on weekdays. Assuming that MSU is able to reach 53% of stroke patients, the average expected number of ischemic stroke patients admitted to MSU would be 0.64 in a 10-h shift each day, which could potentially be increased by expanding the MSU catchment area. Total estimated MSU costs amounted to € 815,087 per annum. Teleneurological assessment reduced overall costs by 11.7%.ConclusionThis analysis provides a framework of determinants and considerations to be addressed during the design process of a novel MSU program in order to balance stroke care improvements with the sustainable use of scarce resources.
Slowing gait during turning: how volition of modifying walking speed affects the gait pattern in healthy adults
Authors: Madrid Julian , Benning Leo , Selig Mischa , Ulrich Baptiste , Jolles Brigitte M. , Favre Julien , Benninger David H. 
Published: February 2024

BackgroundTurning during walking and volitionally modulating walking speed introduces complexity to gait and has been minimally explored.Research questionHow do the spatiotemporal parameters vary between young adults walking at a normal speed and a slower speed while making 90°, 180°, and 360° turns?MethodsIn a laboratory setting, the spatiotemporal parameters of 10 young adults were documented as they made turns at 90°, 180°, and 360°. A generalized linear model was utilized to determine the effect of both walking speed and turning amplitude.ResultsYoung adults volitionally reducing their walking speed while turning at different turning amplitudes significantly decreased their cadence and spatial parameters while increasing their temporal parameters. In conditions of slower movement, the variability of certain spatial parameters decreased, while the variability of some temporal parameters increased.SignificanceThis research broadens the understanding of turning biomechanics in relation to volitionally reducing walking speed. Cadence might be a pace gait constant synchronizing the rhythmic integration of several inputs to coordinate an ordered gait pattern output. Volition might up-regulate or down-regulate this pace gait constant (i.e., cadence) which creates the feeling of modulating walking speed.
Caregiver self-efficacy providing nutritional support for pediatric patients undergoing hematopoietic stem cell transplant is associated with psychosocial factors
Authors: LaLonde Leah , Neenan Alexandra , Byrd Michelle , Hoodin Flora , Bouma Sandra , Choi Sung Won 
Published: February 2024

IntroductionCaregiver self-efficacy in providing nutritional support to pediatric hematopoietic stem cell transplantation (HSCT) patients has been little studied despite the increased risk of these children potentially being over- or under-nourished after HSCT, and nutritional status could possibly affect treatment outcomes. The current study aimed to describe caregiver dietary self-efficacy and its associated psychosocial factors and barriers to following dietary recommendations.MethodsCaregivers completed questionnaires pre-HSCT and 30 days, 100 days, and one year post-HSCT. A subset provided a 24-h recall of food intake.ResultsResults showed generally high caregiver confidence and low difficulty supporting their child nutritionally. However, lower confidence was associated with higher caregiver depression, anxiety, and stress 30 days post-HSCT. Further, higher difficulty at various time points was correlated with lower income, higher depression and anxiety, stress, and miscarried helping (i.e., negative caregiver-child interactions surrounding eating), as well as child overweight status and failure to meet protein intake guidelines. Nutritional criteria for protein, fiber, added sugar, and saturated fat were met by 65%, 0%, 75%, and 75%, respectively. Caregiver attitudes and child behavior were the most frequently reported barriers to healthy eating.DiscussionResults suggest that directing resources to caregivers struggling emotionally, economically, or transactionally could support pediatric patients undergoing HSCT in maintaining optimal nutritional status.
Amide proton transfer imaging has added value for predicting extraprostatic extension in prostate cancer patients
Authors: Qin Xiaoyan , Lv Jian , Zhang Jianmei , Mu Ronghua , Zheng Wei , Liu Fuzhen , Huang Bingqin , Li Xin , Yang Peng , Deng Kan , Zhu Xiqi 
Published: February 2024

BackgroundProstate cancer invades the capsule is a key factor in selecting appropriate treatment methods. Accurate preoperative prediction of extraprostatic extension (EPE) can help achieve precise selection of treatment plans.PurposeThe aim of this study is to verify the diagnostic efficacy of tumor size, length of capsular contact (LCC), apparent diffusion coefficient (ADC), and Amide proton transfer (APT) value in predicting EPE. Additionally, the study aims to investigate the potential additional value of APT for predicting EPE.MethodThis study include 47 tumor organ confined patients (age, 64.16 ± 9.18) and 50 EPE patients (age, 61.51 ± 8.82). The difference of tumor size, LCC, ADC and APT value between groups were compared. Binary logistic regression was used to screen the EPE predictors. The receiver operator characteristic curve analysis was performed to assess the diagnostic performance of variables for predicting EPE. The diagnostic efficacy of combined models (model I: ADC+LCC+tumor size; model II: APT+LCC+tumor size; and model III: APT +ADC+LCC+tumor size) were also analyzed.ResultsAPT, ADC, tumor size and the LCC were independent predictors of EPE. The area under the curve (AUC) of APT, ADC, tumor size and the LCC were 0.752, 0.665, 0.700 and 0.756, respectively. The AUC of model I, model II, and model III were 0.803, 0.845 and 0.869, respectively. The cutoff value of APT, ADC, tumor size and the LCC were 3.65%, 0.97×10−3mm2/s, 17.30mm and 10.78mm, respectively. The sensitivity/specificity of APT, ADC, tumor size and the LCC were 76%/89.4.0%, 80%/59.6%, 54%/78.9%, 72%/66%, respectively. The sensitivity/specificity of model I, Model II and Model III were 74%/72.3%, 82%/72.5% and 84%/80.9%, respectively.Data conclusionAmide proton transfer imaging has added value for predicting EPE. The combination model of APT balanced the sensitivity and specificity.
Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action
Authors: Patrignani Paola , Tacconelli Stefania , Contursi Annalisa , Piazuelo Elena , Bruno Annalisa , Nobili Stefania , Mazzei Matteo , Milillo Cristina , Hofling Ulrika , Hijos-Mallada Gonzalo , Sostres Carlos , Lanas Angel 
Published: February 2024

Background: Low-dose aspirin’s mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin’s action.Methods: We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100 mg/d, 100 mg/BID, or 300 mg/d for 3 ± 1 weeks. Biomarkers were evaluated in blood, urine, and colorectal biopsies at baseline and after dosing with aspirin. Novel biomarkers of aspirin action were assessed in platelets and colorectal tissues using liquid chromatography-mass spectrometry to quantify the extent of cyclooxygenase (COX)-1 and COX-2 acetylation at Serine 529 and Serine 516, respectively.Results: All aspirin doses caused comparable % acetylation of platelet COX-1 at Serine 529 associated with similar profound inhibition of platelet-dependent thromboxane (TX)A2 generation ex vivo (serum TXB2) and in vivo (urinary TXM). TXB2 was significantly reduced in CRC tissue by aspirin 300 mg/d and 100 mg/BID, associated with comparable % acetylation of COX-1. Differently, 100 mg/day showed a lower % acetylation of COX-1 in CRC tissue and no significant reduction of TXB2. Prostaglandin (PG)E2 biosynthesis in colorectal tumors and in vivo (urinary PGEM) remained unaffected by any dose of aspirin associated with the variable and low extent of COX-2 acetylation at Serine 516 in tumor tissue. Increased expression of tumor-promoting genes like VIM (vimentin) and TWIST1 (Twist Family BHLH Transcription Factor 1) vs. baseline was detected with 100 mg/d of aspirin but not with the other two higher doses.Conclusion: In CRC patients, aspirin 300 mg/d or 100 mg/BID had comparable antiplatelet effects to aspirin 100 mg/d, indicating similar inhibition of the platelet’s contribution to cancer. However, aspirin 300 mg/d and 100 mg/BID can have additional anticancer effects by inhibiting cancerous tissue’s TXA2 biosynthesis associated with a restraining impact on tumor-promoting gene expression. EUDRACT number: 2018-002101-65.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT03957902.