bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipocalin-2 and neutrophil activation in pancreatic cancer cachexia
Authors: Deng Min , Aberle Merel R. , van Bijnen Annemarie A. J. H. M. , van der Kroft Gregory , Lenaerts Kaatje , Neumann Ulf P. , Wiltberger Georg , Schaap Frank G. , Olde Damink Steven W. M. , Rensen Sander S. 
Published: March 2023

BackgroundCancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients.MethodsPlasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (≥26.9 ng/mL, n=34) or low (&lt;26.9 ng/mL, n=34) circulating lipocalin-2 levels. Patients’ nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level.ResultsCirculating lipocalin-2 levels did not differ between cachectic and non-cachectic PDAC patients (median 26.7 (IQR 19.7-34.8) vs. 24.8 (16.6-29.4) ng/mL, p=0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than non-cachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) vs. 457.5 (213.3-606.9), p=0.448 vs. 366.5 (294.5-478.5) ng/mL, p=0.009; myeloperoxidase: 30.3 (22.1-37.9) vs. 16.3 (12.0-27.5), p=0.021 vs. 20.2 (15.0-29.2) ng/mL, p=0.011; elastase: 137.1 (90.8-253.2) vs. 97.2 (28.8-215.7), p=0.410 vs. 95.0 (72.2-113.6) ng/mL, p=0.006; respectively). The CRP/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), p=0.041). Lipocalin-2 concentrations correlated with those of calprotectin (rs=0.36, p&lt;0.001), myeloperoxidase (rs=0.48, p&lt;0.001), elastase (rs=0.50, p&lt;0.001), and BPI (rs=0.22, p=0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index (rs=-0.25, p=0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) vs. 19.9 (13.4-26.4) ng/mL, p=0.058).ConclusionsThese data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status.
Artificial intelligence in colposcopic examination: A promising tool to assist junior colposcopists
Authors: Wu Aiyuan , Xue Peng , Abulizi Guzhalinuer , Tuerxun Dilinuer , Rezhake Remila , Qiao Youlin 
Published: March 2023

IntroductionWell-trained colposcopists are in huge shortage worldwide, especially in low-resource areas. Here, we aimed to evaluate the Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) to detect abnormalities based on digital colposcopy images, especially focusing on its role in assisting junior colposcopist to correctly identify the lesion areas where biopsy should be performed.Materials and methodsThis is a hospital-based retrospective study, which recruited the women who visited colposcopy clinics between September 2021 to January 2022. A total of 366 of 1,146 women with complete medical information recorded by a senior colposcopist and valid histology results were included. Anonymized colposcopy images were reviewed by CAIADS and a junior colposcopist separately, and the junior colposcopist reviewed the colposcopy images with CAIADS results (named CAIADS-Junior). The diagnostic accuracy and biopsy efficiency of CAIADS and CAIADS-Junior were assessed in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+), CIN3+, and cancer in comparison with the senior and junior colposcipists. The factors influencing the accuracy of CAIADS were explored.ResultsFor CIN2 + and CIN3 + detection, CAIADS showed a sensitivity at ~80%, which was not significantly lower than the sensitivity achieved by the senior colposcopist (for CIN2 +: 80.6 vs. 91.3%, p = 0.061 and for CIN3 +: 80.0 vs. 90.0%, p = 0.189). The sensitivity of the junior colposcopist was increased significantly with the assistance of CAIADS (for CIN2 +: 95.1 vs. 79.6%, p = 0.002 and for CIN3 +: 97.1 vs. 85.7%, p = 0.039) and was comparable to those of the senior colposcopists (for CIN2 +: 95.1 vs. 91.3%, p = 0.388 and for CIN3 +: 97.1 vs. 90.0%, p = 0.125). In detecting cervical cancer, CAIADS achieved the highest sensitivity at 100%. For all endpoints, CAIADS showed the highest specificity (55–64%) and positive predictive values compared to both senior and junior colposcopists. When CIN grades became higher, the average biopsy numbers decreased for the subspecialists and CAIADS required a minimum number of biopsies to detect per case (2.2–2.6 cut-points). Meanwhile, the biopsy sensitivity of the junior colposcopist was the lowest, but the CAIADS-assisted junior colposcopist achieved a higher biopsy sensitivity.ConclusionColposcopic Artificial Intelligence Auxiliary Diagnostic System could assist junior colposcopists to improve diagnostic accuracy and biopsy efficiency, which might be a promising solution to improve the quality of cervical cancer screening in low-resource settings.
Combination of organic acids benzoate, butyrate, caprylate, and sorbate provides a novel antibiotics-independent treatment option in the combat of acute campylobacteriosis
Authors: Du Ke , Foote Minnja S. , Mousavi Soraya , Buczkowski Agnes , Schmidt Sebastian , Peh Elisa , Kittler Sophie , Bereswill Stefan , Heimesaat Markus M. 
Published: March 2023

IntroductionThe food-borne Gram-negative bacterial pathogenCampylobacter jejunimay cause the acute enterocolitis syndrome campylobacteriosis in infected humans. Given that humanC. jejuniinfections are rising globally which hold also true for resistance rates against antibiotic compounds such as macrolides and fluoroquinolones frequently prescribed for the treatment of severe infectious enteritis, novel antibiotics-independent therapeutic strategies are needed. Distinct organic acids are well known for their health-beneficial including anti-microbial and immunomodulatory properties. In our present study, we investigated potential pathogen-lowering and anti-inflammatory effects of benzoic acid, butyric acid, caprylic acid, and sorbic acid either alone or in combination during acute murine campylobacteriosis.MethodsTherefore, secondary abiotic IL-10–/–mice were perorally infected withC. jejunistrain 81–176 and subjected to a 4-day-course of respective organic acid treatment.Results and discussionOn day 6 post-infection, mice from the combination cohort displayed slightly lower pathogen loads in the duodenum, but neither in the stomach, ileum nor large intestine. Remarkably, the clinical outcome ofC. jejuniinduced acute enterocolitis was significantly improved after combined organic acid treatment when compared to the placebo control group. In support, the combinatory organic acid treatment dampened both, macroscopic and microscopic inflammatory sequelae ofC. jejuniinfection as indicated by less colonic shrinkage and less pronounced histopathological including apoptotic epithelial cell changes in the colon on day 6 post-infection. Furthermore, mice from the combination as compared to placebo cohort exhibited lower numbers of innate and adaptive immune cells such as neutrophilic granulocytes, macrophages, monocytes, and T lymphocytes in their colonic mucosa and lamina propria, respectively, which also held true for pro-inflammatory cytokine secretion in the large intestines and mesenteric lymph nodes. Notably, the anti-inflammatory effects were not restricted to the intestinal tract, but could also be observed systemically given pro-inflammatory mediator concentrations inC. jejuniinfected mice from the combination organic acid treatment that were comparable to basal values. In conclusion, ourin vivostudy provides first evidence that an oral application of distinct organic acids in combination exhibits pronounced anti-inflammatory effects and hence, constitutes a promising novel antibiotics-independent therapeutic strategy in the combat of acute campylobacteriosis.
Remnant cholesterol and mild cognitive impairment: A cross-sectional study
Authors: Zhang Qiaoyang , Huang Shan , Cao Yin , Dong Guanzhong , Chen Yun , Zhu Xuanyan , Yun Wenwei , Zhang Min 
Published: March 2023

ObjectiveEmerging evidence suggests that elevated remnant cholesterol (RC) correlates with several health conditions. To explore the association of plasma RC with MCI incidence and the relationship between plasma RC and different domains of cognition in MCI patients.MethodsThirty-six MCI patients and 38 cognitively healthy controls (HC) were enrolled in the present cross-sectional study. Using total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C) as the formula for calculating fasting RC. Cognition was assessed using the Chinese version of the Montreal cognitive assessment (MoCA), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure Test (ROCF).ResultsCompared to healthy controls, MCI patients had a higher level of RC, the median difference in RC levels between these two groups was 8.13 mg/dl (95.0%CI: 0.97–16.1). Concurrently, plasma RC level was positively associated with MCI risk (OR = 1.05, 95%CI: 1.01–1.10). Notably, elevated RC level was correlated with impaired cognition in MCI patients, such as DSST (pr = −0.45, p = 0.008), ROCF- Long Delayed Recall (pr = −0.45, p = 0.008), AVLT-Immediate Recall (pr = −0.38, p = 0.028), and TMT-A (pr = 0.44, p = 0.009). Conversely, no significant correlation was found between RC and the AVLT-Long Delayed Recall test.ConclusionThis study found that plasma remnant cholesterol was associated with MCI. Further large longitudinal studies are needed in the future to confirm the results and clarify the cause-and-effect relationship.
Traditional Chinese Manual Therapy (Tuina) reshape the function of default mode network in patients with lumbar disc herniation
Authors: Chen Xiao-Min , Wen Ya , Chen Shao , Jin Xin , Liu Chen , Wang Wei , Kong Ning , Ling Dong-Ya , Huang Qin , Chai Jin-Er , Zhao Xiao-Lei , Li Jie , Xu Mao-Sheng , Jiang Zhong , Du Hong-Gen 
Published: March 2023

PurposeInvestigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes.MethodsPatients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs.ResultsIn comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs.ConclusionThe present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.
Quantification of tumor induced motor cortical plasticity using navigated transcranial magnetic stimulation in patients with adult-type diffuse gliomas
Authors: Almeida Cesar Cimonari de , Neville Iuri Santana , Hayashi Cintya Yukie , Gomes dos Santos Alexandra , Brunoni André Russowsky , Teixeira Manoel Jacobsen , Paiva Wellingson Silva 
Published: March 2023

IntroductionThe evaluation of brain plasticity can provide relevant information for the surgical planning of patients with brain tumors, especially when it comes to intrinsic lesions such as gliomas. Neuronavigated transcranial magnetic stimulation (nTMS) is a non-invasive tool capable of providing information about the functional map of the cerebral cortex. Although nTMS presents a good correlation with invasive intraoperative techniques, the measurement of plasticity still needs standardization. The present study evaluated objective and graphic parameters in the quantification and qualification of brain plasticity in adult patients with gliomas in the vicinity of the motor area.MethodsThis is a prospective observational study that included 35 patients with a radiological diagnosis of glioma who underwent standard surgical treatment. nTMS was performed with a focus on the motor area of the upper limbs in both the affected and healthy cerebral hemispheres in all patients to obtain data on motor thresholds (MT) and graphical evaluation by three-dimensional reconstruction and mathematical analysis of parameters related to the location and displacement of the motor centers of gravity (ΔL), dispersion (SDpc) and variability (VCpc) of the points where there was a positive motor response. Data were compared according to the ratios between the hemispheres of each patient and stratified according to the final pathology diagnosis.ResultsThe final sample consisted of 14 patients with a radiological diagnosis of low-grade glioma (LGG), of which 11 were consistent with the final pathology diagnosis. The normalized interhemispheric ratios of ΔL, SDpc, VCpc, and MT were significantly relevant for the quantification of plasticity (p &lt; 0.001). The graphic reconstruction allows the qualitative evaluation of this plasticity.ConclusionThe nTMS was able to quantitatively and qualitatively demonstrate the occurrence of brain plasticity induced by an intrinsic brain tumor. The graphic evaluation allowed the observation of useful characteristics for the operative planning, while the mathematical analysis made it possible to quantify the magnitude of the plasticity.
Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol
Authors: Zhai Weihang , Jiao Haoyang , Zhuang Yutong , Yang Yi , Zhang Jinling , Wang Yifei , Wang Yu , Zhao Ya-nan , Zhang Shuai , He Jianghong , Rong Peijing 
Published: March 2023

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes.Methods/designThis prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients’ CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded.DiscussionThe overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients.Clinical trial registrationhttps://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828.
Bioavailability of calcium in an enriched postbiotic system compared to calcium citrate in healthy postmenopausal females; A randomized, double-blind, comparator-controlled, crossover study
Authors: Friling Marina , Haber Adi , Furman-Assaf Sharon , Israel David , Harari Gil , Evans Malkanthi , Crowley David C. , Ouwehand Arthur C. , Ivanir Eran 
Published: March 2023

IntroductionBioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women.MethodsA total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively.ResultsCa-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study.DiscussionThese findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.
Trends in dietary supplement use among athletes selected for doping controls
Authors: Lauritzen Fredrik , Gjelstad Astrid 
Published: March 2023

BackgroundDietary supplements (DS) may be beneficial for athletes in certain situations, whereas incorrect or excessive use may impair performance, pose a risk to the athlete's health and cause positive doping tests by containing prohibited substances. To provide athletes with relevant and tailored information on safe supplement use, a better knowledge about DS trends over time and between sport disciplines are needed.MethodsThis study examines the use of DS among athletes who have participated in doping controls by extracting information derived from 10,418 doping control forms (DCF) collected by Anti-Doping Norway from 2015 to 2019.ResultsOverall, 51% of the DCFs contained information about at least one DS. National level athletes (NLA) more often reported using DS than recreational athletes (RA) (53 vs. 47%, p &lt; 0.001). Athletes in strength and power (71%), VO2max endurance (56%) and muscular endurance sports (55%) had the highest proportion of DCFs with information about DS. Medical supplements were the most used supplement category for both genders and across all sports. Dietary supplements with a high risk of containing doping substances were most common among male, RA in strength and power sports. There were small and non-significant year-to-year variations in the prevalence of athletes using DS, while the number of products used concomitantly peaked in 2017 before declining in 2019 (2.30 vs. 2.08, p &lt; 0.01). The use of medical supplements and ergogenic substances increased slightly for both NLA and RA from 2015 to 2019, while the use of all other supplement categories declined.ConclusionHalf of the 10,418 DCFs contained information about DS, with variations within the athlete population. DS with high risk of containing prohibited substances were mostly seen in sport disciplines requiring a high degree of specialization in strength/power, including powerlifting and weightlifting, as well as in some team sports, such as cheerleading and american football.
Dosiomics and radiomics to predict pneumonitis after thoracic stereotactic body radiotherapy and immune checkpoint inhibition
Authors: Kraus Kim Melanie , Oreshko Maksym , Bernhardt Denise , Combs Stephanie Elisabeth , Peeken Jan Caspar 
Published: March 2023

IntroductionPneumonitis is a relevant side effect after radiotherapy (RT) and immunotherapy with checkpoint inhibitors (ICIs). Since the effect is radiation dose dependent, the risk increases for high fractional doses as applied for stereotactic body radiation therapy (SBRT) and might even be enhanced for the combination of SBRT with ICI therapy. Hence, patient individual pre-treatment prediction of post-treatment pneumonitis (PTP) might be able to support clinical decision making. Dosimetric factors, however, use limited information and, thus, cannot exploit the full potential of pneumonitis prediction.MethodsWe investigated dosiomics and radiomics model based approaches for PTP prediction after thoracic SBRT with and without ICI therapy. To overcome potential influences of different fractionation schemes, we converted physical doses to 2 Gy equivalent doses (EQD2) and compared both results. In total, four single feature models (dosiomics, radiomics, dosimetric, clinical factors) were tested and five combinations of those (dosimetric+clinical factors, dosiomics+radiomics, dosiomics+dosimetric+clinical factors, radiomics+dosimetric+clinical factors, radiomics+dosiomics+dosimetric+clinical factors). After feature extraction, a feature reduction was performed using pearson intercorrelation coefficient and the Boruta algorithm within 1000-fold bootstrapping runs. Four different machine learning models and the combination of those were trained and tested within 100 iterations of 5-fold nested cross validation.ResultsResults were analysed using the area under the receiver operating characteristic curve (AUC). We found the combination of dosiomics and radiomics features to outperform all other models with AUCradiomics+dosiomics, D = 0.79 (95% confidence interval 0.78-0.80) and AUCradiomics+dosiomics, EQD2 = 0.77 (0.76-0.78) for physical dose and EQD2, respectively. ICI therapy did not impact the prediction result (AUC ≤ 0.5). Clinical and dosimetric features for the total lung did not improve the prediction outcome.ConclusionOur results suggest that combined dosiomics and radiomics analysis can improve PTP prediction in patients treated with lung SBRT. We conclude that pre-treatment prediction could support clinical decision making on an individual patient basis with or without ICI therapy.