bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined analytical approach empowers precise spectroscopic interpretation of subcellular components of pancreatic cancer cells
Authors: Szymoński Krzysztof , Skirlińska-Nosek Katarzyna , Lipiec Ewelina , Sofińska Kamila , Czaja Michał , Wilkosz Natalia , Krupa Matylda , Wanat Filip , Ulatowska-Białas Magdalena , Adamek Dariusz 
Published: October 2023

AbstractThe lack of specific and sensitive early diagnostic options for pancreatic cancer (PC) results in patients being largely diagnosed with late-stage disease, thus inoperable and burdened with high mortality. Molecular spectroscopic methodologies, such as Raman or infrared spectroscopies, show promise in becoming a leader in screening for early-stage cancer diseases, including PC. However, should such technology be introduced, the identification of differentiating spectral features between various cancer types is required. This would not be possible without the precise extraction of spectra without the contamination by necrosis, inflammation, desmoplasia, or extracellular fluids such as mucous that surround tumor cells. Moreover, an efficient methodology for their interpretation has not been well defined. In this study, we compared different methods of spectral analysis to find the best for investigating the biomolecular composition of PC cells cytoplasm and nuclei separately. Sixteen PC tissue samples of main PC subtypes (ductal adenocarcinoma, intraductal papillary mucinous carcinoma, and ampulla of Vater carcinoma) were collected with Raman hyperspectral mapping, resulting in 191,355 Raman spectra and analyzed with comparative methodologies, specifically, hierarchical cluster analysis, non-negative matrix factorization, T-distributed stochastic neighbor embedding, principal components analysis (PCA), and convolutional neural networks (CNN). As a result, we propose an innovative approach to spectra classification by CNN, combined with PCA for molecular characterization. The CNN-based spectra classification achieved over 98% successful validation rate. Subsequent analyses of spectral features revealed differences among PC subtypes and between the cytoplasm and nuclei of their cells. Our study establishes an optimal methodology for cancer tissue spectral data classification and interpretation that allows precise and cognitive studies of cancer cells and their subcellular components, without mixing the results with cancer-surrounding tissue. As a proof of concept, we describe findings that add to the spectroscopic understanding of PC.
Graphical Abstract
MRI characteristics and oncological follow-up of patients with ISUP grade group 4 or 5 prostate cancer
Authors: Boschheidgen M. , Schimmöller L. , Kastl R. , Drewes L. R. , Jannusch K. , Radke K. L. , Kirchner J. , Ullrich T. , Niegisch G. , Albers P. , Antoch G. , Radtke J. P. 
Published: October 2023

Abstract
Objectives
To analyze multiparametric MRI (mpMRI) characteristics of patients with International Society of Urological Pathology (ISUP) grade group (GG) 4 or 5 prostate cancer (PC) and to correlate MRI parameters with the occurrence of biochemical recurrence (BCR) after radical prostatectomy (RPE).

Methods
In this single-center cohort study consecutive patients with mpMRI and ISUP GG 4 or 5 PC were retrospectively analyzed. Clinical, MR-guided biopsy, and diagnostic mpMRI parameter were assessed. A subcohort of patients with RPE and follow-up was analyzed separately. A univariate and multivariate analyses were performed to determine parameters that are associated to patients with BCR after RPE.

Results
145 patients (mean age 70y, median PSA 10.9 ng/ml) were analyzed. 99% had a PI-RADS classification of 4 or 5, 48% revealed MRI T3 stage, and median diameter of the MRI index lesion (IL) was 15 mm. IL showed a median ADC value of 668 ×10−6 mm2/s and exhibited contrast enhancement in 94% of the cases. For patients with follow-up after RPE (n = 82; mean follow-up time 68 ± 27 m), MRI parameters were significantly different for contact length of the IL to the pseudocapsule (LCC), MRI T3 stage, and IL localization (p < 0.05). Higher PSAD and MRI T3 stage were independent parameters for the risk of BCR when incorporating clinical, biopsy, and MRI parameters.

Conclusion
ISUP GG 4 or 5 PC has distinctive characteristics on mpMRI and were detected on MRI in all cases. In addition, higher PSAD and MRI T3 stage were significant predictors for BCR after RPE.
Are novel oral oncolytics underdosed in obese patients?
Authors: Lin Lishi , van der Meer Ellen K. O. , Steeghs Neeltje , Beijnen Jos H. , Huitema Alwin D. R. 
Published: October 2023

Abstract
Purpose
Data on the effects of obesity on drug exposure of oral targeted oncolytics is scarce. Therefore, the aim of this study was to investigate the influence of body weight and body mass index (BMI) on trough levels of oral oncolytics with an exposure–response relationship. The oral oncolytics of interest were abiraterone, alectinib, cabozantinib, crizotinib, imatinib, pazopanib, sunitinib and trametinib.

Methods
This retrospective cohort study included patients treated with the selected oral oncolytics at the standard dose, with a measured trough level at steady state and with available body weight. The Spearman’s correlation test was used to determine the correlation between body weight and trough levels. The Fisher’s exact text was used to compare the frequency of inadequate trough levels between BMI categories.

Results
1265 patients were included across the different oral oncolytics. A negative correlation coefficient was observed between weight and trough levels for crizotinib (n = 75), imatinib (n = 201) and trametinib (n = 310), respectively, ρ = − 0.41, ρ = − 0.24 and ρ = − 0.23, all with a p-value < 0.001. For crizotinib, a higher percentage of patients with a body weight > 100 kg had inadequate trough levels. No statistically significant differences were observed in the frequency of inadequate trough levels between BMI categories.

Conclusion
Higher body weight was only correlated with lower plasma trough levels for crizotinib, imatinib, and trametinib. Therefore, patients with a high body weight may require dose escalation to obtain adequate target levels when treated with these oral oncolytics.
Predicting estimated glomerular filtration rate after partial and radical nephrectomy based on split renal function measured by radionuclide: a large-scale retrospective study
Authors: Zheng Wanxiang , Hou Guangdong , Ju Dongen , Yan Fei , Liu Kepu , Niu Zhiping , Huang Luguang , Xing Zibao , Kong Lingchen , Liu Pengfei , Zhang Geng , Wei Di , Yuan Jianlin 
Published: October 2023

Abstract
Purpose
The purpose of this study was to develop predictive models for postoperative estimated glomerular filtration rate (eGFR) based on the split glomerular filtration rate measured by radionuclide (rGFR), as choosing radical nephrectomy (RN) or partial nephrectomy (PN) for complex renal masses requires accurate prediction of postoperative eGFR.

Methods
Patients who underwent RN or PN for a single renal mass at Xijing Hospital between 2008 and 2022 were retrospectively included. Preoperative split rGFR was evaluated using technetium-99 m-diethylenetriaminepentaacetic acid (Tc-99 m DTPA) renal dynamic imaging, and the postoperative short-term (< 7 days) and long-term (3 months to 5 years) eGFRs were assessed. Linear mixed-effect models were used to predict eGFRs, with marginal R2 reflecting predictive ability.

Results
After excluding patients with missing follow-up eGFRs, the data of 2251 (RN: 1286, PN: 965) and 2447 (RN: 1417, PN: 1030) patients were respectively included in the long-term and short-term models. Two models were established to predict long-term eGFRs after RN (marginal R2 = 0.554) and PN (marginal R2 = 0.630), respectively. Two other models were established to predict short-term eGFRs after RN (marginal R2 = 0.692) and PN (marginal R2 = 0.656), respectively. In terms of long-term eGFRs, laparoscopic and robotic surgery were superior to open surgery in both PN and RN.

Conclusions
We developed novel tools for predicting short-term and long-term eGFRs after RN and PN based on split rGFR that can help in preoperative decision-making.
Prognostic factors in patients with high-risk stage II colon cancer after curative resection: a post hoc analysis of the JFMC46-1201 trial
Authors: Sugimoto Kiichi , Sakamoto Kazuhiro , Tsuchiya Takashi , Takahashi Takao , Ohge Hiroki , Sato Toshihiko , Taguri Masataka , Morita Satoshi , Sadahiro Sotaro 
Published: October 2023

Abstract
Purpose
The goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer.

Methods
The subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783).

Results
1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases.

Conclusion
This study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer.
Ocrelizumab exposure in relapsing–remitting multiple sclerosis: 10-year analysis of the phase 2 randomized clinical trial and its extension
Authors: Kappos Ludwig , Traboulsee Anthony , Li David K. B. , Bar-Or Amit , Barkhof Frederik , Montalban Xavier , Leppert David , Baldinotti Anna , Schneble Hans-Martin , Koendgen Harold , Sauter Annette , Wang Qing , Hauser Stephen L. 
Published: October 2023

AbstractOpen-label extension (OLE) studies help inform long-term safety and efficacy of disease-modifying therapies in multiple sclerosis (MS). We report exploratory analyses from a phase 2 trial on the longest follow-up to date of ocrelizumab-treated patients with relapsing–remitting MS (RRMS). The primary treatment period (PTP) comprised four 24-week treatment cycles; participants were randomized to double-blind ocrelizumab (2000 mg or 600 mg), placebo, or interferon β-1a (open label) for one cycle, then dose-blinded ocrelizumab 1000 mg or 600 mg for the remaining cycles. The PTP was followed by consecutive assessed and unassessed treatment-free periods (TFPs) and then the OLE (ocrelizumab 600 mg every 24 weeks). Safety and efficacy were prospectively assessed. Of 220 participants randomized, 183 (84%) completed the PTP. After the TFP, 103 entered OLE (median OLE ocrelizumab exposure 6.5 years). Most common adverse events across all periods were infusion-related reactions. MRI activity, annualized relapse rate, and confirmed disability progression (CDP) rates remained low throughout. During the assessed TFP, there was a trend toward less and later B-cell repletion, and later CDP, for patients randomized to ocrelizumab; MRI activity was observed in 16.3% of patients, the earliest 24 weeks after the last ocrelizumab dose. This is the longest follow-up of ocrelizumab-treated patients with RRMS, with no new safety signals emerging during an observation period from 2008 to 2020. Results reinforce the sustained efficacy of long-term ocrelizumab. Reduced disease activity was maintained following interruption of 6-month dosing cycles, with no evidence of rebound.
Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment
Authors: Delgado Silvia R. , Faissner Simon , Linker Ralf A. , Rammohan Kottil 
Published: October 2023

AbstractThe recent success of anti-CD20 monoclonal antibody therapies in the treatment of multiple sclerosis (MS) has highlighted the role of B cells in the pathogenesis of MS. In people with MS, the inflammatory characteristics of B-cell activity are elevated, leading to increased pro-inflammatory cytokine release, diminished anti-inflammatory cytokine production and an accumulation of pathogenic B cells in the cerebrospinal fluid. Rituximab, ocrelizumab, ofatumumab, ublituximab and BCD-132 are anti-CD20 therapies that are either undergoing clinical development, or have been approved, for the treatment of MS. Despite CD20 being a common target for these therapies, differences have been reported in their mechanistic, pharmacological and clinical characteristics, which may have substantial clinical implications. This narrative review explores key characteristics of these therapies. By using clinical trial data and real-world evidence, we discuss their mechanisms of action, routes of administration, efficacy (in relation to B-cell kinetics), safety, tolerability and convenience of use. Clinicians, alongside patients and their families, should consider the aspects discussed in this review as part of shared decision-making discussions to improve outcomes and health-related quality of life for people living with MS.
Composition and dynamics of intestinal fungi during the postnatal 2 months of very low birth weight infants
Authors: Wang Ting , Lu Yanbo , Wu Junhua , Yu Beirong 
Published: October 2023

AbstractIt has been found that intestinal fungi play a role in the composition of the intestinal microecology and in the formation and development of the immunity during childhood. We investigated the gut fungi composition of preterm infants to analysis composition and dynamics of intestinal fungi during the postnatal 2 months of very low birth weight infants. We collected feces from 34 very low birth weight infants (VLBWI) and 28 preterm infants with birth weight >1500 g. We extracted total fungal DNA from feces and analyzed the composition of gut fungus through ITS sequencing. The fungal detectable rate in the experimental group peaked on day 3 (85.19%), then gradually decreased and started to show an increasing trend again by day 28. There were significant differences in the alpha diversity of intestinal fungus between VLBWI and controls, and the VLBWI had its own characteristics at different time points in richness and diversity. A total of 10 phylums and 342 genera were identified in all VLBWI samples. The dominant fungal phylum of the VLBWI group is Ascomycota (50.3%)and Basidiomycota (48.8%). The functional metabolic activity of the experimental group was lower than that of the control group. Conclusion: The composition and abundance of VLBWI intestinal fungal showed several alterations during the first 2 months of life. The prediction of gut microbiota function suggests that intestinal metabolic function may be altered in VLBWI.

What is Known:• A limited number of studies has been found that symbiont fungi may be able to calibrate host immunological responses, promote development of peripheral lymphoid organs, promote T cell responses, and even may be associated with the development of certain diseases, such as inflammatory bowel disease (IBD), NEC, and allergic diseases. However, previous studies on intestinal microecology have mainly focused on adults while neglecting the role of fungi in the gut of children due to the much lower abundance of intestinal fungi than bacteria, limitations of techniques for detecting fungi, the difficulty of obtaining samples, and the absence of largescale reference databases.

What is New:• In recent years, the discovery and development of fungal detection technologies such as 18s rDNA sequencing technology, Internal Transcribed Spacer(ITS), and DNA fingerprinting technology have further broadened the perspective on the impact of intestinal fungal exposure in early life.
Shared decision-making between paediatric haematologists, children with sickle cell disease and their parents: an exploratory study
Authors: Wijngaarde Ricardo , Koning Mijra , Fijnvandraat Karin , Ubbink Dirk 
Published: October 2023

AbstractChildren with sickle cell disease (SCD) face various healthcare choices to be made during the disease process that may impact their lives. Shared decision-making (SDM) could improve their health outcomes. We assessed if, and to what extent, paediatricians engage children with SCD and/or their parents in the decision-making process. In this observational cross-sectional study, paediatric SCD patients and their parents visiting the outpatient paediatrics clinic of a university hospital participated in a SDM baseline measurement. Two evaluators independently and objectively analysed the level of patient involvement in decision-making from the audio-recordings of the consultations using the OPTION-5 instrument, a 0–20-point scale from which scores are usually expressed as a percentage of ideal SDM. The level of SDM, as perceived by patients, parents and paediatricians, was appreciated using the SDM-Q-9 and SDM-Q-Doc questionnaires, respectively. Scores could range from 0% (no SDM) to 100% (exemplary SDM). Twenty-four consultations in which a decision needed to be made about SCD treatment were audiotaped and analysed; six were from each paediatrician. The group consisted of 17 male and 7 female patients from various cultural backgrounds between 2 and 17 years old, with a mean age of 9.4 years (SD 4.2). Median OPTION-5 scores were 25.0% [IQR] 20.0–40.0%; range 0–55%). Median SDM-Q-9 and SDM-Q-Doc scores were 56.7% (IQR 39.4–88.9%) and 68.9% (IQR 57.8–77.8%), respectively.Conclusion: Although subjective scores of SDM were fair, the objectively scored level of SDM among children suffering from SCD leaves room for improvement. This may be realized by increasing knowledge about the benefits of SDM, child-centred SDM interventions and SDM-training for paediatricians that takes into account the complexity of intercultural challenges and risk communication between stakeholders.

What is Known:• Children that suffer from sickle cell disease (SCD) are more vulnerable to factors that negatively impact the care that they receive as well as suboptimal health outcomes.• Shared decision-making (SDM) can help children participate in a collaborative decision-making process about their preferred treatment options and improve their health outcomes.

What is New:• The level of participation in the decision-making process for patients suffering from SCD and the families that they belong to leaves room for improvement. The impact of intercultural challenges and the quality and consistency of risk-communication between stakeholders in paediatric SDM needs further exploration.• Paediatricians are more confident about their ability to involve the child and parents compared to how children and their parents experience their level of involvement in a shared decision-making process.
Validation of the maximal cardiopulmonary exercise test in adolescents with major depressive disorder and comparison of cardiorespiratory fitness with sex- and age-related control values
Authors: Wenzel Charlotte , Bongers Bart Chateau , Schlagheck Marit Lea , Reis Daniela , Reinhard Franziska , Schmidt Peter , Bernitzki Stefan , Oberste Max , Wunram Heidrun Lioba , Zimmer Philipp , Fricke Oliver 
Published: October 2023

AbstractEndurance training has been shown to be effective in treating adolescents with major depressive disorder (MDD). To integrate endurance training into the therapeutic setting and the adolescents' daily lives, the current performance status of the adolescents should be accurately assessed. This study aims to examine adolescents with MDD concerning exhaustion criteria during a cardiopulmonary exercise test (CPET), as well as to compare the values obtained thereon with sex- and age-related control values. The study included a retrospective examination of exhaustion criteria ((i) oxygen consumption (V̇O2) plateau, (ii) peak respiratory exchange ratio (RERpeak) > 1.0, (iii) peak heart rate (HRpeak) ≥ 95% of the age-predicted maximal HR, and (iv) peak blood lactate concentration (BLCpeak) > 8.0 mmol⋅L−1) during a graded CPET on a cycle ergometer in adolescents with MDD (n = 57). Subsequently, maximal V̇O2, peak minute ventilation, V̇O2 at the first ventilatory threshold, and peak work rate of participants who met at least two of four criteria were compared with published control values using an independent-sample t-test. Thirty-three percent of the total population achieved a V̇O2 plateau and 75% a RERpeak > 1.0. The HR and BLC criteria were met by 19% and 22%, respectively. T-test results revealed significant differences between adolescents with MDD and control values for all outcomes. Adolescents with MDD achieved between 56% and 83% of control values. Conclusions: The study shows that compared with control values, fewer adolescents with MDD achieve the exhaustion criteria on a CPET and adolescents with MDD have significantly lower cardiorespiratory fitness. Clinical trial registration: No. U1111-1145–1854.

What is Known:• It is already known that endurance training has a positive effect on depressive symptoms.

What is New:• A relevant proportion of adolescents with major depressive disorder do not achieve their V̇O2max during a graded cardiopulmonary exercise test.• Adolescents with major depressive disorder have significantly lower cardiorespiratory fitness compared to sex- and age-related control values.
Emerging markers of cancer cachexia and their relationship to sarcopenia
Authors: Lipshitz Melanie , Visser J. , Anderson R. , Nel D. G. , Smit T. , Steel H. C. , Rapoport B. 
Published: October 2023

Abstract
Purpose
Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored.

Methods
A prospective case–control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured.

Results
Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p =  < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP.

Conclusion
Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined.