bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat infiltration in the thigh muscles is associated with symptomatic spinal stenosis and reduced physical functioning in adults with achondroplasia
Authors: Fredwall Svein O. , Linge Jennifer , de Vries Olga , Leinhard Olof Dahlqvist , Eggesbø Heidi Beate , Weedon-Fekjær Harald , Petersson Mikael , Widholm Per , Månum Grethe , Savarirayan Ravi 
Published: February 2023

Abstract
Background
Symptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning.

Methods
MFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning.

Results
Symptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference − 0.9 pp, 95% CI − 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = − 0.81, − 0.83, and − 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = − 0.56, − 0.57, and − 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group.

Conclusion
Increased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.
Beyond lymphopenia, unraveling radiation-induced leucocyte subpopulation kinetics and mechanisms through modeling approaches
Authors: Pham Thao-Nguyen , Coupey Julie , Candeias Serge M. , Ivanova Viktoriia , Valable Samuel , Thariat Juliette 
Published: February 2023

AbstractLeucocyte subpopulations in both lymphoid and myeloid lineages have a significant impact on antitumor immune response. While radiation-induced lymphopenia is being studied extensively, radiation effects on lymphoid and myeloid subtypes have been relatively less addressed. Interactions between leucocyte subpopulations, their specific radiation sensitivity and the specific kinetics of each subpopulation can be modeled based on both experimental data and knowledge of physiological leucocyte depletion, production, proliferation, maturation and homeostasis. Modeling approaches of the leucocyte kinetics that may be used to unravel mechanisms underlying radiation induced-leucopenia and prediction of changes in cell counts and compositions after irradiation are presented in this review. The approaches described open up new possibilities for determining the influence of irradiation parameters both on a single-time point of acute effects and the subsequent recovery of leukocyte subpopulations. Utilization of these approaches to model kinetic data in post-radiotherapy states may be a useful tool for further development of new treatment strategies or for the combination of radiotherapy and immunotherapy.
Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety (ME-SMART): a monocentric, controlled, randomized, crossover trial
Authors: Scholz Michael , Lakaemper Stefan , Keller Kristina , Dobay Akos , Steuer Andrea Eva , Landolt Hans-Peter , Kraemer Thomas 
Published: February 2023

Abstract
Background
Too little sleep and the consequences thereof are a heavy burden in modern societies. In contrast to alcohol or illicit drug use, there are no quick roadside or workplace tests for objective biomarkers for sleepiness. We hypothesize that changes in physiological functions (such as sleep–wake regulation) are reflected in changes of endogenous metabolism and should therefore be detectable as a change in metabolic profiles. This study will allow for creating a reliable and objective panel of candidate biomarkers being indicative for sleepiness and its behavioral outcomes.

Methods
This is a monocentric, controlled, randomized, crossover, clinical study to detect potential biomarkers. Each of the anticipated 24 participants will be allocated in randomized order to each of the three study arms (control, sleep restriction, and sleep deprivation). These only differ in the amount of hours slept per night. In the control condition, participants will adhere to a 16/8 h wake/sleep regime. In both sleep restriction and sleep deprivation conditions, participants will accumulate a total sleep deficit of 8 h, achieved by different wake/sleep regimes that simulate real-life scenarios. The primary outcome is changes in the metabolic profile (i.e., metabolome) in oral fluid. Secondary outcome measures will include driving performance, psychomotor vigilance test, d2 Test of Attention, visual attention test, subjective (situational) sleepiness, electroencephalographic changes, behavioral markers of sleepiness, changes in metabolite concentrations in exhaled breath and finger sweat, and correlation of metabolic changes among biological matrices.

Discussion
This is the first trial of its kind that investigates complete metabolic profiles combined with performance monitoring in humans over a multi-day period involving different sleep–wake schedules. Hereby, we aim to establish a candidate biomarker panel being indicative for sleepiness and its behavioral outcomes. To date, there are no robust and easily accessible biomarkers for the detection of sleepiness, even though the vast damage on society is well known. Thus, our findings will be of high value for many related disciplines.

Trial registration
ClinicalTrials.gov Identifier NCT05585515, released on 18.10.2022; Swiss National Clinical Trial Portal SNCTP000005089, registered on 12 August 2022.
Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease
Authors: Green Rebecca E. , Lord Jodie , Scelsi Marzia A. , Xu Jin , Wong Andrew , Naomi-James Sarah , Handy Alex , Gilchrist Lachlan , Williams Dylan M. , Parker Thomas D. , Lane Christopher A. , Malone Ian B. , Cash David M. , Sudre Carole H. , Coath William , Thomas David L. , Keuss Sarah , Dobson Richard , Legido-Quigley Cristina , Fox Nick C. , Schott Jonathan M. , Richards Marcus , Proitsi Petroula ,   The Insight 46 study team
Published: February 2023

AbstractBackgroundIdentifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46—the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer’s disease (AD).MethodsFollowing quality control, levels of 1019 metabolites—detected with liquid chromatography-mass spectrometry—were available for 1740 participants at age 60–64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69–71). Regression analyses tested relationships between metabolite measures—modules and hub metabolites—and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex,APOEgenotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding theAPOEregion, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).ResultsIn the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume:ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume:ß =  − 0.072, 95%CI = [− 0.12, − 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume:ß =  − 0.066, 95% CI = [− 0.11, − 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.ConclusionsOur findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.
Spinal nerve root sleeve cysticercosis: a case report and review of the literature
Authors: Tao Benzhang , Li Teng , Ji Kaipeng , Shang Aijia 
Published: February 2023

AbstractBackgroundNeurocysticercosis is a parasitic infection of the central nervous system by tapeworm larvae. Spinal cysticercosis is thought to be relatively rare, and spinal nerve root sleeve cysticercosis have not been reported previously.Case presentationA 46-year-old Chinese Han female patient presented with low back pain and radicular pain of the right lower limb. The visual analog scale was 6. Magnetic resonance imaging showed a subarachnoid cyst at the S1 level, with a slight enhanced rim. The patient underwent surgical treatment. During surgery, we found the cyst located mainly in the subarachnoid space and partly in a sacral nerve root sleeve. Cysticercosis was also confirmed by postoperative pathological examination. Postoperative drug therapy was performed after cysticercosis was confirmed. Postoperatively, the patient was treated with oral albendazole (15 mg/kg) for 1 month. Only mild sensory impairment was left when she was discharged. After 3 years of follow-up, the visual analog scale reduced from 6 to 2, and the patient’s sensory function completely recovered. Magnetic resonance imaging showed no recurrence of cysticercosis.ConclusionSubarachnoid cysticercosis may extend to nerve root sleeve causing back pain and radiculopathy, which may present with similar magnetic resonance imaging manifestations to Tarlov cysts. Hence, spinal subarachnoid cysticercosis should be considered as an important differential diagnosis of arachnoid cyst and sacral Tarlov cyst. Combined treatment with surgical removal and drug therapy is effective to manage spinal subarachnoid cysticercosis.
Identification and phylogenetic analysis of Enterococcus isolates using MALDI-TOF MS and VITEK 2
Authors: Kim Se-Hyung , Chon Jung-Whan , Jeong Hyo-Won , Song Kwang-Young , Kim Dong-Hyeon , Bae Dongryeoul , Kim Hyunsook , Seo Kun-Ho 
Published: February 2023

AbstractThe bacterial genus Enterococcus encompasses 38 species. Two of the most common species are E. faecalis and E. faecium. Recently, however, there has been an increase in clinical reports concerning less prevalent Enterococcus species, such as E. durans, E. hirae, and E. gallinarum. Rapid and accurate laboratory methods are needed to facilitate the identification of all these bacterial species. In the present study, we compared the relative accuracy of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS), VITEK 2, and 16S rRNA gene sequencing using 39 enterococci isolates from dairy samples, and compared the resultant phylogenetic trees. We found that MALDI-TOF MS correctly identified all isolates at the species level except for one, whereas the VITEK 2 system, which is an automated identification system using biochemical characteristics of species, misidentified ten isolates. However, phylogenetic trees constructed from both methods showed all isolates in similar positions. Our results clearly showed that MALDI-TOF MS is a reliable and rapid tool for identifying Enterococcus species with greater discriminatory power than the biochemical assay method of VITEK 2.
Experimental study on disaster mechanism of completely weathered granite landslide induced by extreme rainfall
Authors: Liu Honghua , Yu Peng , Lu Haitao , Xie Yongjian , Wang Zhongsheng , Hao Shengyou , Liu Hongjun , Fu Yunxia 
Published: February 2023

Abstract
Background
With the increased frequency of extreme weather, landslides induced by extremely heavy rainfall pose a major threat to human lives and property safety. In July 2020, a landslide occurred in the strongly weathered Laoshan Scenic Spot in Qingdao, China, and a short period of heavy rainfall was the main factor inducing the landslide.

Method
Based on the similarity criterion, three groups of laboratory model tests under different extreme rainfall conditions were conducted using a large landslide model test box. The rainfall infiltration responses under different rainfall intensities, deformation processes, and failure modes of the slope were analyzed. The inducing mechanism and rainfall disaster process of granite landslides induced by extreme rainfall in strongly weathered areas were summarized.

Result
The results showed that (1) a completely weathered granite landslide induced by rainfall had four stages, i.e., infiltration erosion, surface deformation, damage deepening, and overall instability, and the landslide was characterized by "sheet slip". (2) With greater rainfall intensities, the rainfall infiltration rate was higher, the changes in soil pressure, pore water pressure, water content, and matrix suction were faster, and the hysteresis effect was weaker. (3) A certain spatial distribution pattern was observed between slope deformation/damage and rainfall infiltration, and the research results could provide references for landslide warning and treatment in strongly weathered granite areas.
Predictor of adverse pathology in patients who underwent deferred radical prostatectomy following active surveillance: Results from multi-institutional prospective observational cohort in the PRIAS-JAPAN.
Authors: Tohi Yoichiro , Ishikawa Ryou , Kato Takuma , Miyakawa Jimpei , Matsumoto Ryuji , Mori Keiichiro , Mitsuzuka Koji , Inokuchi Junichi , Matsumura Masafumi , Shiga Kenichiro , Naito Hirohito , Kohjimoto Yasuo , Kawamura Norihiko , Inoue Masaharu , Akamatsu Shusuke , Terada Naoki , Miyazawa Yoshiyuki , Narita Shintaro , Haba Reiji , Sugimoto Mikio ,   PRIAS-JAPAN
Published: February 2023

350 Background: Intraductal carcinoma of the prostate (IDC-P) and invasive cribriform are key prognostic pathologies among early stage prostate cancer patients; however, predictors of adverse pathology, including these types, remain unknown. In men who opted for active surveillance (AS), we aimed to examine the association between adverse pathology and patient characteristics, utilizing radical prostatectomy (RP) specimens. Methods: We re-reviewed available RP specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on RP specimen as Gleason grade group of ≥3, pT-stage≥T3, pN positivity, or the presence of IDC-P or invasive cribriform. And, we examined the predictive factors associated with adverse pathology, using factors at AS enrollment and before RP. Results: Out of 162 men underwent RP, available 137 RP specimens were analyzed. The percentage of adverse pathology was 48.9% (67 patients), including 8.8% in IDC-P and 29.9 % in invasive cribriform. Men with adverse pathology had lower prostate specific antigen recurrence-free survival than those without them (log rank P = 0.0189). On multivariate logistic regression analyses, increasing age at AS enrollment and before RP were the predictive factors for adverse pathology (Odds ratio [OR], 1.1; 95% confidence interval [CI]: 1.02-1.19, P = 0.0178, OR, 1.12; 95% CI: 1.02-1.22, P=0.0126), not magnetic resonance imaging findings. Conclusions: Aging is significantly associated with adverse pathology including IDC-P or cribriform. The results suggest that relaxing scheduled examinations during AS depending on age is not practical. Clinical trial information: UMIN000048095 .
Preliminary results from a phase II study of tislelizumab combined with radiotherapy as bladder-preserving treatment for patients with high-risk non-muscle-invasive bladder cancer (HR NMIBC) unresponsive to bacillus Calmette-Guerin (BCG).
Authors: Li Zhiyong , He Liru , Li Xiangdong , Yao Kai , Liu Yang , Qin Zike , Ye Yunlin , Zhou Fangjian , Liu Zhuowei 
Published: February 2023

510 Background: Radical cystectomy (RC) was recommended to patients (pts) with HR NMIBC BCG-unresponsive papillary tumors. Clinical unmet need was to explore non-surgical treatment options for pts who were ineligible for or refused RC. Our study aimed to evaluate the efficacy and safety of tislelizumab combined with radiotherapy as bladder-preserving treatment for pts with HR NMIBC unresponsive to BCG. Methods: This open-label, single arm phase II study enrolled pts with HR NMIBC BCG-unresponsive papillary tumors (high-grade Ta or T1 tumors without carcinoma in situ). The papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Within 2 weeks after TURBT, eligible pts received tislelizumab 200 mg in day 1 (D1), every 21 days for eight cycles and a total radiotherapy dose of 60-66 GY in 30-33 fractions over seven weeks. The primary end point was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary end points were bladder-preservation rate, OS and safety. Our study anticipated a DFS rate at 12 months was 45% and the study would enroll 32 pts to meet the primary endpoint. Results: By Sep. 2022, 14 eligible pts were enrolled. Ten pts have completed therapy and were analyzed (male 90.0%; median age 58 years (31-79); pure TCC 100%; median tumor size 1.0 cm (0.5-2.0); 40% multiple papillary tumours; median eGFR, 91.1 mL/(min•1.73m2) (46.1-115.5); high-grade Ta 40.0%, T1 60.0%; median of 11 previous BCG instillations (9-19)). Median follow-up was 20.3 months (9.9-28.1), the median number of tislelizumab cycles was 8 (2-8) and radiotherapy doses was 60 GY (60-66) in 30 fractions. The DFS rate at 12 month was 80.0% (95%CI, 67.4%-92.6%), at 24 month was 60.0% (95%CI, 40.3%-79.7%). Two pts showed reappearance of high-grade Ta and received TURBT, one patient showed stage development from T1N0M0 to M1 disease and received systemic treatment. The bladder-preservation rate at 24 months was 100% (95%CI, 100%-100%). The OS rate at 24 months was 100% (95%CI, 100%-100%). Treatment related adverse events (TRAEs) of any grade were rash (40.0%), neutropenia (10.0%), hyperthyroidism (10.0%), AST/ALT increased (10.0%) and hyperglycaemia (10.0%). 5 pts experienced immune related AEs, including rash (n=4, G1-2), hyperthyroidism (n=1, G2), hyperglycaemia (n=1, G3) and AST/ALT increased (n=1, G3). Conclusions: Our preliminary results supported the use of tislelizumab combined with radiotherapy as a promising bladder-preserving therapy for pts with BCG-unresponsive HR NMIBC who were ineligible for or refused RC. Clinical trial information: ChiCTR2000035275 .
Assessment of Puberty and Hypothalamic–Pituitary–Gonadal Axis Function After Childhood Brain Tumor Treatment
Authors: Rosimont Manon , Kariyawasam Dulanjalee , Samara-Boustani Dinane , Giani Elisa , Beltrand Jacques , Bolle Stephanie , Fresneau Brice , Puget Stephanie , Sainte-Rose Christian , Alapetite Claire , Pinto Graziella , Touraine Philippe , Piketty Marie-Liesse , Brabant Séverine , Abbou Samuel , Aerts Isabelle , Beccaria Kevin , Bourgeois Marie , Roujeau Thomas , Blauwblomme Thomas , Rocco Federico Di , Thalassinos Caroline , Rigaud Charlotte , James Syril , Busiah Kanetee , Simon Albane , Bourdeaut Franck , Lemelle Lauriane , Guerrini-Rousseau Léa , Orbach Daniel , Doz François , Dufour Christelle , Grill Jacques , Polak Michel , Briceño Laura González 
Published: February 2023

Abstract

Context
Endocrine complications are common in pediatric brain tumor patients.

Objective
To describe hypothalamic–pituitary–gonadal axis (HPGA) function in patients treated in childhood for a primary brain tumor more than 5 years earlier, in order to identify risk factors for HPGA impairment.

Methods
We retrospectively included 204 patients diagnosed with a primary brain tumor before 18 years of age and monitored at the pediatric endocrinology unit of the Necker Enfants-Malades University Hospital (Paris, France) between January 2010 and December 2015. Patients with pituitary adenoma or untreated glioma were excluded.

Results
Among patients with suprasellar glioma not treated by radiotherapy, the prevalence of advanced puberty was 65% overall and 70% when the diagnosis occurred before 5 years of age. Medulloblastoma chemotherapy caused gonadal toxicity in 70% of all patients and in 87.5% of those younger than 5 years at diagnosis. In the group with craniopharyngioma, 70% of patients had hypogonadotropic hypogonadism, which was consistently accompanied by growth hormone deficiency.

Conclusion
Tumor type, location, and treatment were the risk main factors for HPGA impairment. Awareness that onset can be delayed is essential to guide information of parents and patients, patient monitoring, and timely hormone replacement therapy.