bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 Induced Glycolysis and Apoptosis Regulator and Monocarboxylate Transporter 4 drive metabolic reprogramming with c‐MYC and NFkB activation in breast cancer
Authors: Roche Megan E. , Ko Ying‐Hui , Domingo‐Vidal Marina , Lin Zhao , Whitaker‐Menezes Diana , Birbe Ruth C. , Tuluc Madalina , Győrffy Balázs , Caro Jaime , Philp Nancy J. , Bartrons Ramon , Martinez‐Outschoorn Ubaldo 
Published: July 2023

AbstractBreast cancer is composed of metabolically coupled cellular compartments with upregulation of TP53 Induced Glycolysis and Apoptosis Regulator (TIGAR) in carcinoma cells and loss of caveolin 1 (CAV1) with upregulation of monocarboxylate transporter 4 (MCT4) in fibroblasts. The mechanisms that drive metabolic coupling are poorly characterized. The effects of TIGAR on fibroblast CAV1 and MCT4 expression and breast cancer aggressiveness was studied using coculture and conditioned media systems and in‐vivo. Also, the role of cytokines in promoting tumor metabolic coupling via MCT4 on cancer aggressiveness was studied. TIGAR downregulation in breast carcinoma cells reduces tumor growth. TIGAR overexpression in carcinoma cells drives MCT4 expression and NFkB activation in fibroblasts. IL6 and TGFB drive TIGAR upregulation in carcinoma cells, reduce CAV1 and increase MCT4 expression in fibroblasts. Tumor growth is abrogated in the presence of MCT4 knockout fibroblasts and environment. We discovered coregulation of c‐MYC and TIGAR in carcinoma cells driven by lactate. Metabolic coupling primes the tumor microenvironment allowing for production, uptake and utilization of lactate. In sum, aggressive breast cancer is dependent on metabolic coupling.
Reimbursement of elective egg freezing from health care systems: Beyond simplistic claims
Authors: Santulli Pietro , Viganò Paola , Somigliana Edgardo 
Published: July 2023

SynopsisFrance is the first country to offer elective egg freezing for nonmedical reasons under public health coverage. However, this decision deserves in‐depth scrutiny in the future because the cost‐beneficial profile is yet unknown.
Predicting partitioning from low density polyethylene to blood and adipose tissue by linear solvation energy relationship models
Authors: Ulrich Nadin , Böhme Alexander , Strobel Adrian Benedict , Egert Thomas 
Published: July 2023

AbstractThe variety of polymers utilized in medical devices demands for testing of extractables and leachables according to ISO 10993‐18:2020 in combination with ISO 10993‐1:2018. The extraction of the materials involves the use of organic solvents as well as aqueous buffers to cover a wide range of polarity and pH‐values, respectively. To estimate patient exposure to chemicals leaching from a polymer in direct body contact, simulating solvents are applied to best mimic the solubilization and partitioning behavior of the related tissue or body fluid. Here we apply linear solvation energy relationship (LSER) models to predict blood/water and adipose tissue/water partition coefficients. We suggest this predictive approach to project levels of potential leachables, design extraction experiments, and to identify the optimal composition of simulating extraction solvents. We compare our predictions to LSER predictions for commonly applied surrogates like ethanol/water mixtures, butanol, and octanol as well as olive oil, butanone, 1,4‐dioxane for blood and adipose tissue, respectively. We therefore selected a set of 26 experimentally determined blood/water partition coefficients and 33 adipose tissue/water partition coefficients, where we demonstrate that based on the root mean squared error rmse the LSER approach performs better than surrogates like octanol or butanol and equally well as 60:40 ethanol/water for blood. For adipose tissue/water partitioning, the experimentally determined octanol/water partition coefficient performs best but the rmse is at the same range as our LSER approach based on experimentally determined descriptors. Further, we applied our approach for 248 extractables where we calculated blood/low density polyethylene (LDPE) and adipose tissue/LDPE partition coefficients. By this approach, we successfully identified chemicals of potential interest to a toxicological evaluation based on the total risk score.
Development and Verification of a Japanese Pediatric Physiologically Based Pharmacokinetic Model with Emphasis on Drugs Eliminated by Cytochrome P450 or Renal Excretion
Authors: Johnson Trevor N. , Abduljalil Khaled , Pan Xian , Emoto Chie 
Published: July 2023

AbstractPhysiologically based pharmacokinetic (PBPK) models are useful in bridging drug exposure in different ethnic groups, and there is increasing regulatory application of this approach in adults. Reported pediatric PBPK models tend to focus on the North European population, with few examples in other ethnic groups. This study describes the development and verification of a Japanese pediatric PBPK population. The development of the model was based on the existing North European pediatric population. Japanese systems and clinical data were collated from public databases and the literature, and the underlying demographics and equations were optimized so that physiological outputs represented the Japanese pediatric population. The model was tested using 14 different small molecule drugs, eliminated by a variety of pathways, including cytochrome P450 3A4 (CYP3A4) metabolism and renal excretion. Given the limitations of the clinical data, the overall performance of the model was good, with 44/62 predictions for PK parameters (area under the plasma drug concentration–time curve, AUC; maximum serum concentration, Cmax; clearance, CL) being within 0.8‐ to 1.25‐fold, 56/62 within 0.67‐ to 1.5‐fold, and 61/62 within 0.5‐ to 2.0‐fold of the observed values. Specific results for the 5 CYP3A4 substrates showed 20/31 cases were predicted within 0.8‐ to 1.25‐fold, 27/31 within 0.67‐ to 1.5‐fold, and all were within 0.5‐ to 2.0‐fold of the observed values. Given the increased regulatory use of pediatric PBPK in drug development, expanding these models to other ethnic groups are important. Considering qualifying these models based on the context of use, there is a need to expand on the current research to include a larger range of drugs with different elimination pathways. Collaboration among academic, industry, model providers, and regulators will facilitate further development.
Self‐Assembly of Glycolipid Epimers: Their Supramolecular Morphology Control and Immunoactivation Function
Authors: Xu Xuyang , Li Long , Ye Linfei , Liu Xiaomei , Feng Yingle , Chen Guosong 
Published: July 2023

AbstractAlthough advances have been made in carbohydrate‐based macromolecular self‐assembly, harnessing epimers of carbohydrates to perform molecular assembly and further investigating the properties of supramolecular materials remain little explored. Herein, two classes of stereoisomeric glycolipid amphiphiles based on d‐N‐acetylgalactosamine (GalNAc) are reported, and they can aggregate into ribbon‐like structures in the aqueous solution due to amphiphilic property, which allow to obtain glycocalyx‐mimicking supramolecular materials. The subtle distinction in glycoside configuration of GalNAc‐α‐SSA and GalNAc‐β‐SSA dictates the different molecular packing in self‐assembled structures. Since driven by the distinguishing carbohydrate–carbohydrate interactions, the ribbon‐like architectures transform into spherical nanostructures via mixing GalNAc‐α‐SSA and GalNAc‐β‐SSA. The resulting spherical micelles fabricated by blending glycolipid epimers can potentiate the macrophage‐ and dendritic cell‐mediated immune responses in vitro. Such glycolipid epimers will pave the way to create glycocalyx‐mimicking immune modulators by incorporating stereochemistry into supramolecular self‐assembly.
Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
Authors: Oladayo Abimbola , Gowans Lord Jephthah Joojo , Awotoye Waheed , Alade Azeez , Busch Tamara , Naicker Thirona , Eshete Mekonen A. , Adeyemo Wasiu L. , Hetmanski Jacqueline B. , Zeng Erliang , Adamson Olawale , Adeleke Chinyere , Li Mary , Sule Veronica , Kayali Sami , Olotu Joy , Mossey Peter A. , Obiri‐Yeboah Solomon , Buxo Carmen J. , Beaty Terri , Taub Margaret , Donkor Peter , Marazita Mary L. , Odukoya Oluwakemi , Adeyemo Adebowale A. , Murray Jeffrey C. , Prince Anya , Butali Azeez 
Published: July 2023

AbstractIntroductionThe frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large‐scale population genomic studies. The availability of data from the first whole‐genome sequencing for orofacial clefts in an African population motivated this investigation.MethodsIn total, 130 case‐parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM).ResultsWe identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP.ConclusionThis study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations.
Effect of bladder outlet procedures on urodynamic assessments in men with an acontractile or underactive detrusor: A systematic review and meta‐analysis
Authors: van Merode Nadine A. M. , Nijholt Ingrid M. , Heesakkers John P. , van Koeveringe Gommert A. , Steffens Martijn G. , Witte Lambertus P. W. 
Published: July 2023

AbstractObjectiveTo review the effect of bladder outlet procedures on urodynamic outcomes and symptom scores in males with detrusor underactivity (DU) or acontractile detrusors (AD).Materials and MethodsWe performed a systematic review and meta‐analysis of research publications derived from PubMed, Embase, Web of Science, and Ovid Medline to identify clinical studies of adult men with non‐neurogenic DU or AD who underwent any bladder outlet procedure. Outcomes comprised the detrusor pressure at maximum flow (PdetQmax), maximum flow rate (Qmax), international prostate symptom score (IPSS), and quality of life (QoL). This study is registered under PROSPERO CRD42020215832.ResultsWe included 13 studies of bladder outlet procedures, of which 6 reported decreased and 7 reported improved PdetQmax after the procedure. Meta‐analysis revealed an increase in the pooled mean PdetQmax of 5.99 cmH20 after surgery (95% CI: 0.59−11.40; p = 0.03; I2 95%). Notably, the PdetQmax improved in all subgroups with a preoperative bladder contractility index (BCI) <50 and decreased in all subgroups with a BCI ≥50. All studies reported an improved Qmax after surgery, with a pooled mean difference of 5.87 mL/s (95% CI: 4.25−7.49; I2 93%). Only three studies reported QoL, but pooling suggested significant improvements after surgery (mean, −2.41 points; 95% CI: −2.81 to −2.01; p = 0.007). All seven studies reporting IPSS demonstrated improvement (mean, −12.82; 95% CI: −14.76 to −10.88; p < 0.001).ConclusionsThis review shows that PdetQmax and Qmax increases after surgical bladder outlet procedures in men with DU and AD. Bladder outlet procedures should be discussed as part of the shared decision‐making process for this group. The evidence was of low to very low certainty.
On the excessive use of coefficient of variation as a metric of quantitation quality in proteomics
Authors: Ivanov Mark V. , Garibova Leyla A. , Postoenko Valeriy I. , Levitsky Lev I. , Gorshkov Mikhail V. 
Published: July 2023

AbstractThe coefficient of variation (CV) is often used in proteomics as a proxy to characterize the performance of a quantitation method and/or the related software. In this note, we question the excessive reliance on this metric in quantitative proteomics that may result in erroneous conclusions. We support this note using a ground‐truth Human‐Yeast‐E. coli dataset demonstrating in a number of cases that erroneous data processing methods may lead to a low CV which has nothing to do with these methods’ performances in quantitation.
The European (Green?) Deal: a systematic analysis of environmental sustainability
Authors: Hereu‐Morales Joan , Segarra Alba , Valderrama César 
Published: July 2023

AbstractTransitioning towards a sustainable society is at the core of public planning in the EU through the European Green Deal (EGD). However, is the EGD a master plan for actual sustainable development in the EU? This work aims to answer this question through an analysis of the environmental sustainability within the EGD's plans through the method of critical discourse analysis, and discussing the results with previous efforts for sustainable development in the EU and in the UN. The results of the analysis identify fundamental flaws in the environmental sustainability of the EGD, which seems to repeat mistakes of previous efforts for sustainability planning in the EU. This work concludes that economic growth is the predominant focus in public planning and that the EGD needs a review of various environmental aspects to be considered the master plan for a transition towards a sustainable EU.
Patient‐reported outcomes and satisfaction after revisions of medial unicompartmental knee arthroplasties for unexplained pain vs aseptic loosening
Authors: Arndt Kristine Bollerup , Schrøder Henrik Morville , Troelsen Anders , Lindberg‐Larsen Martin 
Published: July 2023

AbstractPurposeDoes patients revised for unexplained pain after mUKA present the same PROM and satisfaction scores 1–3 years after revision as patients revised for aseptic loosening?”.Methods104 patients undergoing revision of mUKA's for the indications unexplained pain and aseptic loosening were included in the period January 1, 2018 to December 31, 2020.from the Danish Knee Arthroplasty Register. 52 patients were revised for unexplained pain and 52 for aseptic loosening. Patient demographics did not differ between the two groups. PROMs [Oxford Knee Score (OKS), EQ‐5D‐5L, Forgotten Joint Score (FJS)] and questions about satisfaction with the surgery were sent to digitally secured mailboxes. Pearson’s Chi‐square test and Wilcoxon Rank Sum test were used to test for statistical differences between groups.ResultsThe median OKS 1–3 years after revision was 26 (IQR 22) for unexplained pain vs 34 (IQR 12) for aseptic loosening, p = 0.033. The median EQ‐5D‐5L Index after revision was 0.7 (IQR 0.6) for unexplained vs 0.8 (IQR 0.1) for aseptic loosening, p = 0.014. The median FJS after revision was 48 (IQR 10) for unexplained pain vs 52 (IQR 14) for aseptic loosening, p = 0.1. The mean satisfaction with the surgery on a 0–100 scale (100 = not satisfied; 0 = very satisfied) was 55 (IQR 60) for unexplained pain vs 50 (IQR 67) for aseptic loosening, p = 0.087, and patients revised for unexplained pain were less likely to find their knee problem importantly improved (p = 0.032).ConclusionPatients undergoing revision of mUKAs for unexplained pain presented poor postoperative PROM scores, and PROM scores were worse compared to those of patients revised for aseptic loosening. Patients revised for unexplained pain were less likely to find their knee problem importantly improved. This study support the evidence against revisions for unexplained pain.Level of evidenceLevel III.
Bowel wall thickness measured by MRI is useful for early diagnosis of bowel endometriosis
Authors: Zheng Yunxi , Gu Shouxin , Ruan Jingyao , Yi Xiaofang , Xu Congjian 
Published: July 2023

Abstract

Objective
To evaluate MRI features of bowel endometriosis (BE) and verify its clinical significance compared with pathological diagnosis.

Materials and methods
Since 2018, patients clinically diagnosed with deep endometriosis (DE) and planned to undergo surgery were enrolled prospectively. MRI parameters including traction, thickening sign of the rectum, obliteration of the Douglas Pouch, sign of adenomyosis, and pelvic adhesion were extracted. Uni- and multi-variate analyses were performed to explore their association with pathological diagnosis of BE. ROC curve was utilized to ascertain the appropriate cutoff value for predicting the presence and assessing the severity of BE.

Results
A total of 226 patients with DE were recruited, and 154 BE cases were pathologically confirmed. Logistic regression analysis revealed that thickness of the rectal wall, traction sign of the rectum, and obliteration of the Douglas Pouch were independent factors to predict the presence of BE with the OR 1.59 (95% CI: 1.29–1.96), 0.24 (95% CI: 0.09–0.67), and 0.17 (95% CI: 0.07–0.40), respectively (p all < 0.01). A cutoff value of 6.0 mm for the thickness of rectal wall resulted in the highest predictive value of BE (specificity: 90.3%; sensitivity: 78.6%). For patients with measured thickness of the rectal wall over 6.0 mm, 72.1% (93/129) was confirmed BE with lesions infiltrated more than muscular layer.

Conclusion
This prospective study indicates that based on precise definition of visualized features on MRI images, BE could be recognized pre-operatively. DE patients with thickness of rectal wall exceeding 6.0 mm have a greater probability of BE.

Clinical relevance statement
Based on precise definition of visualized features and accurate measurement on MRI images, bowel infiltrating among deep endometriosis patients could be recognized pre-operatively.

Key Points
• Precise definition of measurable MRI parameters made it possible for early detection of bowel endometriosis.
• Thickening sign, traction sign of the rectum, and obliteration of the Douglas Pouch were typical radiological indicators for bowel endometriosis.
• Bowel involvement is more sensitive to be detected among pelvic deep endometriosis patients with the thickness of the rectal wall over 6.0 mm.
Network dysfunction of sadness facial expression processing and morphometry in euthymic bipolar disorder
Authors: Miola Alessandro , Trevisan Nicolò , Salvucci Margherita , Minerva Matteo , Valeggia Silvia , Manara Renzo , Sambataro Fabio 
Published: July 2023

AbstractFacial emotion recognition (FER), including sadness, is altered in bipolar disorder (BD). However, the relationship between this impairment and the brain structure in BD is relatively unexplored. Furthermore, its association with clinical variables and with the subtypes of BD remains to be clarified. Twenty euthymic patients with BD type I (BD-I), 28 BD type II (BD-II), and 45 healthy controls completed a FER test and a 3D-T1-weighted magnetic resonance imaging. Gray matter volume (GMV) of the cortico-limbic regions implicated in emotional processing was estimated and their relationship with FER performance was investigated using network analysis. Patients with BD-I had worse total and sadness-related FER performance relative to the other groups. Total FER performance was significantly negatively associated with illness duration and positively associated with global functioning in patients with BD-I. Sadness-related FER performance was also significantly negatively associated with the number of previous manic episodes. Network analysis showed a reduced association of the GMV of the frontal–insular–occipital areas in patients with BD-I, with a greater edge strength between sadness-related FER performance and amygdala GMV relative to controls. Our results suggest that FER performance, particularly for facial sadness, may be distinctively impaired in patients with BD-I. The pattern of reduced interrelationship in the frontal–insular–occipital regions and a stronger positive relationship between facial sadness recognition and the amygdala GMV in BD may reflect altered cortical modulation of limbic structures that ultimately predisposes to emotional dysregulation. Future longitudinal studies investigating the effect of mood state on FER performance in BD are warranted.
Follicular helper T-cell lymphomas: disease spectrum, relationship with clonal hematopoiesis, and mimics. A report of the 2022 EA4HP/SH lymphoma workshop
Authors: Ondrejka Sarah L , Amador Catalina , Climent Fina , Ng Siok-Bian , Soma Lorinda , Zamo Alberto , Dirnhofer Stefan , Quintanilla-Martinez Leticia , Wotherspoon Andrew , Leoncini Lorenzo , de Leval Laurence 
Published: July 2023

AbstractFollicular helper T-cell lymphomas (TFH lymphomas) were discussed in session V of the lymphoma workshop of the European Association for Haematopathology (EA4HP)/Society for Hematopathology (SH) 2022 meeting in Florence, Italy. The session focused on the morphologic spectrum of TFH lymphoma, including its three subtypes: angioimmunoblastic-type (AITL), follicular-type, and not otherwise specified (NOS). The submitted cases encompassed classic examples of TFH lymphoma and unusual cases such as those with early or indolent presentations, associated B-cell proliferations, or Hodgkin/Reed–Sternberg-like cells. The relationship between TFH lymphoma and clonal hematopoiesis was highlighted by several cases documenting divergent evolution of myeloid neoplasm and AITL from shared clonal mutations. The distinction between TFH lymphoma and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), was stressed, and many challenging examples were presented. Various cases highlighted the difficulties of differentiating TFH lymphoma from other established types of lymphoma and reactive conditions. Cutaneous T-cell lymphoma expressing TFH markers, particularly when resulting in lymph node involvement, should be distinguished from TFH lymphomas. Additional immunophenotyping and next-generation sequencing studies were performed on various cases in this session, highlighting the importance of these technologies to our current understanding and classification of TFH lymphomas.
Metastasis pattern and prognosis of large cell neuroendocrine carcinoma: a population-based study
Authors: Jiang Tongchao , Sun Haishuang , Li Na , Jiang Tongcui 
Published: July 2023

Abstract
Purpose
As a rare type of tumor, the metastasis pattern of large cell neuroendocrine carcinoma (LCNEC) is still unclear. Our aim was to investigate metastatic patterns and develop a predictive model of prognosis in patients with advanced LCNEC.

Methods
Patients of LCNEC diagnosed between 2010–2015 from the Surveillance, Epidemiology and End Results (SEER) database were retrospectively included. Chi-square test was used for baseline characteristics analysis. Survival differences were assessed using Kaplan–Meier curves. Independent prognostic factors identified by multivariate Cox proportional risk model were used for the construction of nomogram.

Results
557 eligible patients with metastasis LCNEC (median (IQR), 64 (56 to 72) years; 323 males) were included in this research. Among patients with isolated metastases, brain metastases had the highest incidence (29.4%), and multisite metastases had worse OS (HR: 2.020: 95% CI 1.413–2.888; P < 0.001) and LCSS (HR: 2.144, 95% CI 1.480–3.104; P < 0.001) in all age groups. Independent prognostic indicators including age, race, T stage, N stage, chemotherapy, radiotherapy and metastatic site were used for the construction of nomogram. Concordance index (C-index) and decision-curve analyses (DCAs) showed higher accuracy and net clinical benefit of nomogram compared to the 7th TNM staging system (OS: 0.692 vs 0.555; P < 0.001; LCSS: 0.693 vs 0.555; P < 0.001).

Conclusions
We firstly established a novel comprehensive nomogram to predict the prognosis of metastasis LCNEC. The prognostic model demonstrated excellent accuracy and predictive performance. Chemotherapy and metastasis pattern were the two strongest predictive variables. Close follow-up of patients with LCNEC is necessary to make individualized treatment decisions according to different metastasis patterns.