bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipocalin 2 attenuates oligodendrocyte loss and immune cell infiltration in mouse models for multiple sclerosis
Authors: Gasterich Natalie , Bohn Amelie , Sesterhenn Anika , Nebelo Frederik , Fein Lena , Kaddatz Hannes , Nyamoya Stella , Kant Sebastian , Kipp Markus , Weiskirchen Ralf , Zendedel Adib , Beyer Cordian , Clarner Tim 
Published: July 2022

AbstractMultiple sclerosis (MS) is a central nervous system disease characterized by both degenerative and inflammatory processes. Various mediators are involved in the interplay of degeneration and innate immunity on one hand and peripheral adaptive immunity on the other hand. The secreted protein lipocalin 2 (LCN2) is an inflammatory modulator in a variety of pathologies. Although elevated intrathecal levels of LCN2 have been reported in MS patients, it's functional role is widely unknown. Here, we identified a subpopulation of astrocytes as a source of LCN2 in MS lesions and respective animal models. We investigated the functional role of LCN2 for both autoimmune and degenerative aspects in three MS mouse models including both wild type (WT) and Lcn2−/− mouse strains. While the experimental autoimmune encephalomyelitis (EAE) model reflects primary autoimmunity, the cuprizone model reflects selective oligodendrocyte loss and demyelination. In addition, we included a combinatory Cup/EAE model in which primary cytodegeneration is followed by inflammatory lesions within the forebrain. While in the EAE model, the disease outcome was comparable in between the two mouse strains, cuprizone intoxicated Lcn2−/− animals showed an increased loss of oligodendrocytes. In the Cup/EAE model, Lcn2−/− animals showed increased inflammation when compared to WT mice. Together, our results highlight LCN2 as a potentially protective molecule in MS lesion formation, which might be able to limit loss of oligodendrocytes immune‐cell invasion. Despite these findings, it is not yet clear which glial cell phenotype (and to which extent) contributes to the observed neuroprotective effects, that is, microglia and/or astroglia or even endothelial cells in the brain.
Longitudinal effect of dementia carers' sense of coherence on burden
Authors: Turró‐Garriga Oriol , Viñas‐Díez Vanesa , Zacarias‐Pons Lluís , Conde‐Sala Josep‐Lluís , Garre‐Olmo Josep ,   SOC & DEM Study Group
Published: July 2022

AbstractBackgroundA sense of coherence (SOC) could help us better understand why there are individuals who cope better than others in similar situations. The study aimed to assess the effect of SOC on the course of burden reports in relatives of persons with dementia.MethodsThis was a prospective cohort study of 156 dementia carers. The SOC was assessed by the Orientation to Life Questionnaire (OLQ‐13), burden by Burden Interview, and personal and contextual characteristics were collected via ad hoc questions. The main dementia symptoms, including functional difficulties (Disability Assessment for Dementia), neuropsychiatric symptoms (Neuropsychiatric Inventory), and cognitive impairment (Mini‐Mental State Examination), were also assessed. A general linear model was adjusted to determine the effect of SOC and other covariates on burden throughout the follow‐up. Burden differences between baseline and 12 and 24 months were analysed, and the baseline OLQ‐13 score was grouped by quartiles.ResultsThe global burden reported increased after 24 months (F = 9.98; df = 2; p < 0.001), but not equally for all carers; daughters reported the greatest increase. SOC, functional disability, and neuropsychiatric disorders showed a significant effect on burden, but time did not. Carers with higher SOC at baseline tend to remain with lower burden levels, whereas carers with low SOC reported higher burden at each visit.ConclusionsThis study reports evidence of the effect of SOC on burden at baseline, 12 and 24 months of follow‐up. Burden scores differ by carers' SOC; those with higher SOC showed lower burden levels, whereas the low‐SOC group reported a greater burden at each visit.
Network structure of time‐varying depressive symptoms through dynamic time warp analysis in late‐life depression
Authors: van Zelst Denise C. R. , Veltman Eveline M. , Rhebergen Didi , Naarding Paul , Kok Almar A. L. , Ottenheim Nathaly Rius , Giltay Erik J. 
Published: July 2022

AbstractObjectivesLate‐life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level.MethodsIn the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30‐item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged ≥ 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses.ResultsThe mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group‐level nomothetic approach, four depressive symptom dimensions were identified: “core symptoms”, “lethargy/somatic”, “sleep”, and “appetite/atypical”. Items of the “internalizing symptoms” dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms.ConclusionsDTW revealed symptom networks and dimensions based on the within‐person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care.
Inhibition of CBP/β‐catenin signaling ameliorated fibrosis in cholestatic liver disease
Authors: Kimura Masamichi , Nishikawa Koji , Osawa Yosuke , Imamura Jun , Yamaji Kenzaburo , Harada Kenichi , Yatsuhashi Hiroshi , Murata Kazumoto , Miura Kouichi , Tanaka Atsushi , Kanto Tatsuya , Kohara Michinori , Kamisawa Terumi , Kimura Kiminori 
Published: July 2022

Abstract
Chronic cholestatic liver diseases are characterized by injury of the bile ducts and hepatocytes caused by accumulated bile acids (BAs) and inflammation. Wnt/β‐catenin signaling is implicated in organ fibrosis; however, its role in cholestatic liver fibrosis remains unclear. Therefore, we explored the effect of a selective cAMP response element‐binding protein‐binding protein (CBP)/β‐catenin inhibitor, PRI‐724, on murine cholestatic liver fibrosis. PRI‐724 suppressed liver fibrosis induced by multidrug resistance protein 2 knockout (KO), bile duct ligation, or a 3.5‐diethoxycarbonyl‐1.4‐dihydrocollidine (DDC) diet; it also suppressed BA synthesis and macrophage infiltration. The expression of early growth response‐1 (Egr‐1), which plays a key role in BA synthesis, was increased in the hepatocytes of patients with cholestatic liver disease. PRI‐724 inhibited Egr‐1 expression induced by cholestasis, and adenoviral shEgr‐1‐mediated Egr‐1 knockdown suppressed BA synthesis and fibrosis in DDC diet–fed mice, suggesting that PRI‐724 exerts its effects, at least in part, by suppressing Egr‐1 expression in hepatocytes. Hepatocyte‐specific CBP KO in mice suppressed BA synthesis, liver injury, and fibrosis, whereas hepatocyte‐specific KO of P300, a CBP homolog, exacerbated DDC‐induced fibrosis. Intrahepatic Egr‐1 expression was also decreased in hepatocyte‐specific CBP‐KO mice and increased in P300‐KO mice, indicating that Egr‐1 is located downstream of CBP/β‐catenin signaling. Conclusion: PRI‐724 inhibits cholestatic liver injury and fibrosis by inhibiting BA synthesis in hepatocytes. These results highlight the therapeutic effect of CBP/β‐catenin inhibition in cholestatic liver diseases.
Comparison of efficacy and safety of ripertamab (SCT400) versus rituximab (Mabthera®) in combination with CHOP in patients with previously untreated CD20‐positive diffuse large B‐cell lymphoma: A randomized, single‐blind, phase III clinical trial
Authors: Shi Yuankai , Zhang Qingyuan , Hong Xiaonan , Wang Zhen , Gao Yuhuan , Zou Liqun , Cen Hong , Gui Lin , Li Yufu , Feng Jifeng , Wang Zhao , Zhang Mingzhi , Jin Chuan , Zhang Weihua , Hu Jianda , Zheng Chengyun , Zheng Zhendong , Zhang Liling , Chen Shaoshui , Huang Yunhong , Tang Yun , Gao Yajie , Hao Miaowang , Li Xiaoling , Chang Chunkang , Yang Haiyan , Wu Hui , Shen Lida , Ke Xiaoyan , Zhang Liangming , Xi Yaming , Yang Linhua , Xie Liangzhi , Gai Wenlin , Ji Yanan 
Published: July 2022

AbstractThis study compared the efficacy, safety and immunogenicity of ripertamab (SCT400) and rituximab (Mabthera®) combined with CHOP as the first‐line treatment for Chinese patients with CD20‐positive diffuse large B cell lymphoma (DLBCL). This is a randomized, patient‐blind, multicenter, active‐control, non‐inferiority study with parallel design. Patients were randomly (2:1) to receive ripertamab combined with CHOP (S‐CHOP) or rituximab (Mabthera®) combined with CHOP (R‐CHOP) for up to 6 cycles. The primary endpoint was the Independent Review Committee (IRC) assessed objective response rate (ORR) in full analysis set (FAS) and the per protocol set (PPS). A total of 364 patients (243 in the S‐CHOP and 121 in the R‐CHOP groups) were enrolled in this study. In FAS, IRC‐assessed ORRs were 93.8% (95% confidence interval (CI) 90.0%, 96.5%) and 94.2% (95% CI: 88.4%, 97.6%) in the S‐CHOP and R‐CHOP groups (p = 0.9633), respectively. The ORR difference between the two groups −0.4% (95% CI: −5.5%, 4.8%) met the pre‐specified non‐inferiority margin of −12%. There were no significant differences between the S‐CHOP and R‐CHOP groups in 1‐year progression‐free survival rates (81.1% vs. 83.2%, p = 0.8283), 1 year event‐free survival rates (56.2% vs. 58.1%, p = 0.8005), and 3‐year overall survival rates (81.0% vs. 82.8%, p = 0.7183). The results in PPS were consistent with those in FAS. The rates of treatment‐emergent adverse events (TEAEs) and ≥ grade 3 TEAEs were 97.9% and 99.2%, 85.2% and 86.0% in the S‐CHOP and R‐CHOP groups, respectively in safety set. The percentage of anti‐drug antibodies positive patients in the S‐CHOP group was numerically lower than the R‐CHOP group (10.9% vs. 16.0%). This study demonstrated that S‐CHOP was not inferior to R‐CHOP in the first‐line treatment of Chinese patients with CD20‐positive DLBCL in efficacy, safety and immunogenecity. S‐CHOP could be an alternative first‐line standard treatment regimen for this patient population.
Bacterial diversity significantly reduces toward the late stages among filarial lymphedema patients in the Ahanta West District of Ghana: A cross‐sectional study
Authors: Asiedu Samuel O. , Kini Priscilla , Aglomasa Bill C. , Amewu Emmanuel K. A. , Asiedu Ebenezer , Wireko Solomon , Boahen Kennedy G. , Berbudi Afiat , Sylverken Augustina A. , Kwarteng Alexander 
Published: July 2022

AbstractBackgroundLymphatic Filariasis (LF), a neglected tropical disease, has been speculated to be complicated by secondary bacteria, yet a systematic documentation of these bacterial populations is lacking. Thus, the primary focus of this study was to profile bacteria diversity in the progression of filarial lymphedema among LF individuals with or without wounds.MethodsA cross‐sectional study design recruited 132 LF individuals presenting with lymphedema with or without wounds from eight communities in the Ahanta West District in the Western Region, Ghana. Swabs from the lymphedematous limbs, ulcers, pus, and cutaneous surfaces were cultured using standard culture‐based techniques. The culture isolates were subsequently profiled using Matrix‐assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry.ResultsOf the 132 LF participants recruited, 65% (85) had filarial lymphedema with no wounds. In total, 84% (235) of the bacterial isolates were identified. The remaining 16% (46) could not be identified with the method employed. Additionally, 129(55%) of the strains belonged to the phylum Firmicutes, while 61 (26%) and 45 (19%) represented Proteobacteria and Actinobacteria, respectively. Generally, irrespective of the samples type (i.e., wound sample and non‐wound samples), there was a sharp increase of bacteria diversity from Stages 1 to 3 and a drastic decrease in these numbers by Stage 4, followed by another surge and a gradual decline in the advanced stages of the disease. The Shannon Diversity Index and Equitability for participants with and without wounds were (3.482, 0.94) and (3.023, 0.75), respectively. Further, Staphylococcus haemolyticus and Escherichia coli showed resistance to tetracycline, chloramphenicol, and penicillin.ConclusionThe present study reveals a sharp decline in bacterial load at the late stages of filarial lymphedema patients. In addition, we report an emerging antimicrobial resistance trend of S. haemolyticus and E. coli against commonly used antibiotics such as tetracycline, chloramphenicol, and penicillin in communities endemic for LF in the Ahanta West District, Ghana. This could pose a huge challenge to the management of the disease; particularly as current treatments are not quite effective against the infection.
Impact of cancer on cryopreserved sperm quality and fertility: A cohort study
Authors: Pening David , Constant Marnie , Bruynbroeck Manon , Delbaere Anne , Demeestere I. 
Published: July 2022

AbstractBackgroundSperm quality at cancer diagnosis is often compromised by the disease and any given gonadotoxic treatment will further diminish fertility.ObjectivesHere, we aim to analyze the cryopreserved sperm quality according to the cancer types as well as the fertility outcomes.MethodsOur study included all cancer patients who cryopreserved sperm over 20 years at Erasme Hospital Brussels (from 1999 to 2019). First sperm samples from 111 hematologic, 104 testicular, 19 prostate, 28 gastrointestinal, and 16 neurological cancer patients were compared.ResultsOligozoo‐asthenozoospermia was observed in 30% of the samples, including 19.33% with severe oligozoospermia (<5 million/ml). Our results showed a significant reduction in sperm concentration among testicular cancer (p < 0.01). No significant differences in progressive motility, sperm volume, and number of frozen straws were observed. Significant correlations were found between sperm concentration and cancer type (p <0.01) as well as patients' age (p <0.01). Twenty‐eight cancer survivors returned for using their cryopreserved sperm (9.33%), fertilization rate was 60.5% and implantation rate was 29.6%. There was no correlation between sperm concentration and fertility outcomes.ConclusionOur results confirm the negative impact of cancer on sperm quality without affecting assisted reproductive technology (ART) success rate, which is utterly important as a male reproductive health perspective. All cancer patients should be counselled and offered fertility preservation options as a gold standard.
Home‐ and community‐level predictors of social connection in nursing home residents: A scoping review
Authors: Clemens Sara , Aelick Katelynn , Babineau Jessica , Bretzlaff Monica , Edwards Cathleen , Gibson Josie‐Lee , Hewitt Colborne Debbie , Iaboni Andrea , Lender Dee , Schon Denise , Snowball Ellen , McGilton Katherine S. , Bethell Jennifer 
Published: July 2022

AbstractBackground and AimsSocial connection is associated with better physical and mental health and is an important aspect of the quality of care for nursing home residents. The primary objective of this scoping review was to answer the question: what nursing home and community characteristics have been tested as predictors of social connection in nursing home residents? The secondary objective was to describe the measures of social connection used in these studies.MethodsWe searched MEDLINE(R) ALL (Ovid), CINAHL (EBSCO), APA PsycINFO (Ovid), Scopus, Sociological Abstracts (ProQuest), Embase and Embase Classic (Ovid), Emcare Nursing (Ovid), and AgeLine (EBSCO) for research that quantified associations between nursing home and/or community characteristics and resident social connection. Searches were limited to English‐language articles published from database inception to search date (July 2019) and update (January 2021).ResultsWe found 45 studies that examined small‐scale home‐like settings (17 studies), facility characteristics (14 studies), staffing characteristics (11 studies), care philosophy (nine studies), and community characteristics (five studies). Eight studies assessed multiple home or community‐level exposures. The most frequent measures of social connection were study‐specific assessments of social engagement (11 studies), the Index of Social Engagement (eight studies) and Qualidem social relations (six studies), and/or social isolation (five studies) subscales. Ten studies assessed multiple social connection outcomes.ConclusionResearch has assessed small‐scale home‐like settings, facility characteristics, staffing characteristics, care philosophy, and community characteristics as predictors of social connection in nursing home residents. In these studies, there was no broad consensus on best approach(es) to the measurement of social connection. Further research is needed to build an evidence‐base on how modifiable built environment, staffing and care philosophy characteristics—and the interactions between these factors—impact residents' social connection.
Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP): Results of a Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial
Authors: Pignolo Robert J. , Baujat Geneviève , Hsiao Edward C. , Keen Richard , Wilson Amy , Packman Jeff , Strahs Andrew L. , Grogan Donna R. , Kaplan Frederick S. 
Published: July 2022

ABSTRACT
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO), often heralded by flare-ups, leading to reduced movement and life expectancy. This placebo-controlled, double-blind trial (NCT02190747) evaluated palovarotene, an orally bioavailable selective retinoic acid receptor gamma agonist, for prevention of HO in patients with FOP. Patients experiencing a flare-up were enrolled in two cohorts: (1) patients ≥15 years were randomized 3:1 to palovarotene 10/5 mg (weeks 1–2/3–6) or placebo; (2) patients ≥6 years were randomized 3:3:2 to palovarotene 10/5 mg, palovarotene 5/2.5 mg (weeks 1–2/3–6), or placebo. Cohort data were pooled. The primary endpoint was the proportion of responders (no/minimal new HO at flare-up body region by plain radiograph) at week 6. Change from baseline in HO volume and new HO incidence were assessed by computed tomography (CT) at week 12. Tissue edema was assessed by magnetic resonance imaging (MRI) or ultrasound. Forty patients (aged 7–53 years) were enrolled (placebo: n = 10; palovarotene 5/2.5 mg: n = 9; palovarotene 10/5 mg: n = 21). Disease history was similar between groups. In the per-protocol population, the proportion of responders at week 6 by plain radiograph was 100% with palovarotene 10/5 mg; 88.9% with palovarotene 5/2.5 mg; 88.9% with placebo (Cochran-Armitage trend test: p = 0.17). At week 12, the proportions were 95.0% with palovarotene 10/5 mg; 88.9% with palovarotene 5/2.5 mg; 77.8% with placebo (Cochran-Armitage trend test: p = 0.15). Week 12 least-squares mean (LSmean) new HO volume, assessed by CT, was 3.8 × 103 mm3 with palovarotene 10/5 mg; 1.3 × 103 mm3 with palovarotene 5/2.5 mg; 18.0 × 103 mm3 with placebo (pairwise tests versus placebo: p ≤ 0.12). Palovarotene was well-tolerated. No patients discontinued treatment or required dose reduction; one patient had dose interruption due to elevated lipase. Although these findings were not statistically significant, they support further evaluation of palovarotene for prevention of HO in FOP in larger studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Multiscale segmentation‐ and error‐guided iterative convolutional neural network for cerebral neuron segmentation in microscopic images
Authors: You Zhenzhen , Jiang Ming , Shi Zhenghao , Zhao Minghua , Shi Cheng , Du Shuangli , Hérard Anne‐Sophie , Souedet Nicolas , Delzescaux Thierry 
Published: July 2022

AbstractThis article uses microscopy images obtained from diverse anatomical regions of macaque brain for neuron semantic segmentation. The complex structure of brain, the large intra‐class staining intensity difference within neuron class, the small inter‐class staining intensity difference between neuron and tissue class, and the unbalanced dataset increase the difficulty of neuron semantic segmentation. To address this problem, we propose a multiscale segmentation‐ and error‐guided iterative convolutional neural network (MSEG‐iCNN) to improve the semantic segmentation performance in major anatomical regions of the macaque brain. After evaluating microscopic images from 17 anatomical regions, the semantic segmentation performance of neurons is improved by 10.6%, 4.0%, 1.5%, and 1.2% compared with Random Forest, FCN‐8s, U‐Net, and UNet++, respectively. Especially for neurons with brighter staining intensity in the anatomical regions such as lateral geniculate, globus pallidus and hypothalamus, the performance is improved by 66.1%, 23.9%, 11.2%, and 6.7%, respectively. Experiments show that our proposed method can efficiently segment neurons with a wide range of staining intensities. The semantic segmentation results are of great significance and can be further used for neuron instance segmentation, morphological analysis and disease diagnosis. Cell segmentation plays a critical role in extracting cerebral information, such as cell counting, cell morphometry and distribution analysis. Accurate automated neuron segmentation is challenging due to the complex structure of brain, the large intra‐class staining intensity difference within neuron class, the small inter‐class staining intensity difference between neuron and tissue class, and the unbalanced dataset. The proposed multiscale segmentation‐ and error‐guided iterative convolutional neural network (MSEG‐iCNN) improve the segmentation performance in 17 major anatomical regions of the macaque brain.Highlights
Cell segmentation plays a critical role in extracting cerebral information, such as cell counting, cell morphometry and distribution analysis.
Accurate automated neuron segmentation is challenging due to the complex structure of brain, the large intra‐class staining intensity difference within neuron class, the small inter‐class staining intensity difference between neuron and tissue class, and the unbalanced dataset.
The proposed multiscale segmentation‐ and error‐guided iterative convolutional neural network (MSEG‐iCNN) improve the segmentation performance in 17 major anatomical regions of the macaque brain.