bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial
Authors: Hoburg Arnd , Niemeyer Philipp , Laute Volker , Zinser Wolfgang , John Thilo , Becher Christoph , Izadpanah Kaywan , Diehl Peter , Kolombe Thomas , Fay Jakob , Siebold Rainer , Fickert Stefan 
Published: January 2022

Background: Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix). Purpose: To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm2), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm2 of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test. Results: A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up ( P < .0001) and 76.9 ± 19.3 at 5-year follow-up ( P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes ( P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9). Conclusion: ACI using spheroids was safe and effective for defect sizes up to 10 cm2 and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated. Registration: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).
HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation
Authors: Dulmovits Brian M. , Tang Yuefeng , Papoin Julien , He Mingzhu , Li Jianhua , Yang Huan , Addorisio Meghan E. , Kennedy Lauren , Khan Mushran , Brindley Elena , Ashley Ryan J. , Ackert-Bicknell Cheryl , Hale John , Kurita Ryo , Nakamura Yukio , Diamond Betty , Barnes Betsy J. , Hermine Olivier , Gallagher Patrick G. , Steiner Laurie A. , Lipton Jeffrey M. , Taylor Naomi , Mohandas Narla , Andersson Ulf , Al-Abed Yousef , Tracey Kevin J. , Blanc Lionel 
Published: January 2022

Abstract
Anemia of inflammation, also known as anemia of chronic disease, is refractory to erythropoietin (EPO) treatment, but the mechanisms underlying the EPO refractory state are unclear. Here, we demonstrate that high mobility group box-1 protein (HMGB1), a damage-associated molecular pattern molecule recently implicated in anemia development during sepsis, leads to reduced expansion and increased death of EPO-sensitive erythroid precursors in human models of erythropoiesis. HMGB1 significantly attenuates EPO-mediated phosphorylation of the Janus kinase 2/STAT5 and mTOR signaling pathways. Genetic ablation of receptor for advanced glycation end products, the only known HMGB1 receptor expressed by erythroid precursors, does not rescue the deleterious effects of HMGB1 on EPO signaling, either in human or murine precursors. Furthermore, surface plasmon resonance studies highlight the ability of HMGB1 to interfere with the binding between EPO and the EPOR. Administration of a monoclonal anti-HMGB1 antibody after sepsis onset in mice partially restores EPO signaling in vivo. Thus, HMGB1-mediated restriction of EPO signaling contributes to the chronic phase of anemia of inflammation.
Lupus anticoagulant test persistence over time and its associations with future thrombotic events
Authors: Colling Meaghan E. , Ay Cihan , Kraemmer Daniel , Koder Silvia , Quehenberger Peter , Pabinger Ingrid , Posch Florian , Gebhart Johanna 
Published: January 2022

Abstract
Data on lupus anticoagulant (LA) test stability in patients persistently positive for LA are limited, and its implications on clinical outcomes are lacking. We investigated the rate and predictors of a negative LA test and whether experiencing a negative test affected a patient’s risk of future thrombotic events or death in a prospective observational study of persistently LA+ patients. We followed 164 patients (84% women) for a median of 9.2 years and a total of 1438 follow-up visits. During the observation period, 50 thrombotic events (23 arterial and 27 venous events) occurred, and 24 patients died. Forty-six of the patients had at least 1 negative LA test during the observation period, corresponding to a 10-year cumulative incidence of a negative LA test of 28% (95% confidence interval, 20-35). The majority of patients with available follow-up after a negative LA test (n = 41) had at least 1 subsequent positive test for LA (n = 28/41, 68%). Vitamin K antagonist (VKA) treatment at baseline was associated with a negative LA test during follow-up. Using a multistate time-to-event model with multivariable adjustment, a negative LA test had no impact on a patient’s prospective risk of thrombosis or mortality. We conclude that a negative LA test during observation cannot be used clinically to stratify a patient’s risk for future events.
Fish health in the Nidda as an indicator for ecosystem integrity: a case study for Central European small streams in densely populated areas
Authors: Schweizer Mona , Dieterich Andreas , Betz Sarah , Leim Dietlinde , Prozmann Viktoria , Jacobs Björn , Wick Arne , Köhler Heinz-R. , Triebskorn Rita 
Published: January 2022

Abstract
Background
In Germany and the EU, most headwaters are still far from reaching a good chemical and ecological status as it is required by the European Water Framework Directive (WFD), until 2027 the latest. Particularly, in densely populated areas, impacts from municipal and industrial wastewater discharges or diffuse agricultural emissions are still a matter of concern. This also applies to the Nidda River which is considered to be in a moderate to rather poor condition. In our study, we investigated short-term and long-term consequences of anthropogenic pollution on fish health via one monitoring with caged fish (CF) and two field sampling campaigns (FF). In the CF monitoring, rainbow trout (Oncorhynchus mykiss) were caged for seven weeks at four selected sites along the Nidda, whereas in the FF monitoring approach, feral fish, including brown trout (Salmo trutta f. fario), European chub (Leuciscus cephalus) and stone loach (Barbatula barbatula) were caught in June and September 2016.

Results
Histopathological analyses of liver and gills were conducted, accompanied by measurements of hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity to assess the cytochrome P450 (CYP1A1) function, and genotoxicity via the micronucleus assay. Caged as well as field-captured fish exhibited impaired health conditions showing lesions particularly in the liver, and a presumably overwhelmed CYP1A1 system, whereas genotoxicity was not induced. The variation between sampling sites and seasons was rather low, but two trends were recognisable: (a) liver condition was poorest around spawning season and (b) tissue integrity and EROD activity were most affected downstream of industrial dischargers. Furthermore, effects were species dependent: the generally highly sensitive S. trutta f. fario proved to be impacted most, whereas L. cephalus with its pelagic lifestyle was affected less than the benthic B. barbatula, indicating a relevant contamination of sediments.

Conclusion
Our results confirm the impaired ecological state of the Nidda and emphasise that a sustainable improvement of aquatic ecosystem health needs to include both water quality and sediment contamination to approach the ambitious WFD goal.
Plastid phylogenomics of tribe Perseeae (Lauraceae) yields insights into the evolution of East Asian subtropical evergreen broad-leaved forests
Authors: Xiao Tian-Wen , Yan Hai-Fei , Ge Xue-Jun 
Published: January 2022

Abstract
Background
The East Asian subtropical evergreen broad-leaved forests (EBLFs) harbor remarkable biodiversity. However, their historical assembly remains unclear. To gain new insights into the assembly of this biome, we generated a molecular phylogeny of one of its essential plant groups, the tribe Perseeae (Lauraceae).

Results
Our plastid tree topologies were robust to analyses based on different plastid regions and different strategies for data partitioning, nucleotide substitution saturation, and gap handling. We found that tribe Perseeae comprised six major clades and began to colonize the subtropical EBLFs of East Asia in the early Miocene. The diversification rates of tribe Perseeae accelerated twice in the late Miocene.

Conclusions
Our findings suggest that the intensified precipitation in East Asia in the early Miocene may have facilitated range expansions of the subtropical EBLFs and establishment of tribe Perseeae within this biome. By the late Miocene, species assembly and diversification within the EBLFs had become rapid.
Randomized controlled trial of an alternative drainage strategy vs routine chest tube insertion for postoperative pain after thoracoscopic wedge resection
Authors: Wei Shoucun , Zhang Guangyan , Ma Jue , Nong Lidan , Zhang Jiatao , Zhong Wenzhao , Cui Jianxiu 
Published: January 2022

Abstract
Background
Thoracoscopic surgery has greatly alleviated the postoperative pain of patients, but postsurgical acute and chronic pain still exists and needs to be addressed. Indwelling drainage tubes are one of the leading causes of postoperative pain after thoracic surgery. Therefore, the aim of this study was to explore the effects of alternative drainage on acute and chronic pain after video-assisted thoracoscopic surgery (VATS).

Methods
Ninety-two patients undergoing lung wedge resection were selected and randomly assigned to the conventional chest tube (CT) group and the 7-Fr central venous catheter (VC) group. Next, the numeric rating scale (NRS) and pain DETECT questionnaire were applied to evaluate the level and characteristics of postoperative pain.

Results
NRS scores of the VC group during hospitalization were significantly lower than those of the CT group 6 h after surgery, at postoperative day 1, at postoperative day 2, and at the moment of drainage tube removal. Moreover, the number of postoperative salvage analgesics (such as nonsteroidal anti-inflammatory drugs [(NSAIDs]) and postoperative hospitalization days were notably reduced in the VC group compared with the CT group. However, no significant difference was observed in terms of NRS pain scores between the two groups of patients during the follow-up for chronic pain at 3 months and 6 months.

Conclusion
In conclusion, a drainage strategy using a 7-Fr central VC can effectively relieve perioperative pain in selected patients undergoing VATS wedge resection, and this may promote the rapid recovery of such patients after surgery.

Trial registration
ClinicalTrials.gov, NCT03230019. Registered July 23, 2017.
Xanthine oxidoreductase activity in platelet-poor and rich plasma as a oxidative stress indicator in patients required renal replacement therapy
Authors: Cecerska-Heryć Elżbieta , Heryć Rafał , Dutkiewicz Grażyna , Michalczyk Anna , Grygorcewicz Bartłomiej , Serwin Natalia , Napiontek-Balińska Sylwia , Dołęgowska Barbara 
Published: January 2022

AbstractBackgroundXanthine oxidoreductase (XOR) is a hydroxylase enzyme involved in the metabolism of purines. XOR activity can vary: the homodimer protein can be converted into two different isoforms XD (antioxidant) and XO (prooxidant). Oxidative stress and inflammation that accompanying chronic kidney disease (CKD), dialysis, and kidney transplantation, resulted in platelet activation. Present study aimed to determine the influence of applied renal replacement therapy on xanthine oxidoreductase and its isoforms activity.Materials and MethodsThe study group consisted of 117 patients, divided into 4 groups: hemodialysis - 30 patients, peritoneal dialysis - 30 patients, kidney transplant patients - 27 and conservative treatment - 30 patients. The control group consisted of 30 healthy volunteers.ResultsSignificant differences were found in XOR activity in platelet-poor plasma (PPP) within the groups studied (p = 0.001). There was a relationship between the type of renal replacement therapy of all oxidoreductase isoforms in PPP (p < 0.001 all isoforms) and XD (p = 0.008), XO (p < 0.001) in platelet rich-plasma (PRP). A relationship was observed between the activity of all oxidoreductase isoforms in PPP and PRP, and the type of renal replacement therapy and the duration of dialysis and the age of patients. The cause of chronic kidney disease was also reflected differences in XD and XO activity in PPP.ConclusionsThe type of renal replacement therapy used in CKD patients, age of patients, duration of dialysis, CKD causes, and stage of progression significantly affect the activity of XOR and its isoforms.
Large tumour volume reduction of IDH-mutated anaplastic glioma involving the insular region following radiotherapy
Authors: Metz Gabrielle , Jayamanne Dasantha , Wheeler Helen , Wong Matthew , Cook Raymond , Little Nicholas , Parkinson Jonathon , Kastelan Marina , Brown Chris , Back Michael 
Published: January 2022

Abstract
Background
The impact of near-total resection of IDH-mutated anaplastic glioma (IDHmutAG) is well-established but there remains uncertainty of benefit in tumours of the insular cortex where the extent of safe resection may be limited. This study aimed to assess tumour volume reduction in patients following IMRT and impact of residual post-surgical volume.

Methods and materials
Patients with IDHmutAG involving insular cortex managed with IMRT from 2008 to 2019 had baseline patient, tumour and treatment factors recorded. Volumetric assessment of residual disease on MRI was performed at baseline, month+ 3 and month+ 12 post-IMRT. Potential prognostic factors were analysed for tumour reduction and relapse-free survival, and assessed by log-rank and Cox regression analyses.

Results
Thirty two patients with IDHmutAG of the insular cortex were managed with median follow-up post-IMRT of 67.2 months. Pathology was anaplastic astrocytoma (AAmut) in 20, and anaplastic oligodendroglioma (AOD) in 12 patients. Median pre-IMRT volume on T1 and T2Flair was 24.3cm3 and 52.2cm3. Twenty-seven patients were alive with 5-year relapse-free survival of 80%. There was a median 67 and 64% reduction from baseline occurring at 3 months post-IMRT for T1 and T2Flair respectively; and subsequent median 78 and 73% at 12 months. At 12 months AOD patients had median 83% T1 volume reduction compared to 63% in AAmut (p < 0.01). There was no difference on T2Flair volume (p = 0.64). No other pathological factors influenced volume reduction at 12 months. No factors were associated with relapse-free survival including baseline T1 (p = 0.52) and T2Flair (p = 0.93) volume.

Conclusion
IMRT provides large tumour volume reduction in IDHmutAG of the insular cortex. While maximal safe debulking remains standard of care when feasible, this patient cohort reported no significant negative impact of residual disease volume on relapse-free survival.
Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol
Authors: Latino Cathy , Gianatti Emily J. , Mehta Shailender , Lo Johnny , Devine Amanda , Christophersen Claus 
Published: January 2022

Abstract
Background
Gestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required.
Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM.

Methods
An open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16 g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks’ gestation), Day 10 and Day 56 (approximately 36 weeks’ gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia.

Discussion
To improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication.

Trial registration
Australian New Zealand Clinical Trial Registry, ACTRN12620000968976p. Registered 28 September 2020
HoSAGE: sarcopenia in older patient with intermediate / high-risk prostate cancer, prevalence and incidence after androgen deprivation therapy: study protocol for a cohort trial
Authors: Couderc Anne-Laure , Villani Patrick , Berbis Julie , Nouguerède Emilie , Rey Dominique , Rossi Dominique , Lechevallier Éric , Badinand Delphine , Bastide Cyrille , Karsenty Gilles , Boissier Romain , Amichi Kahena , Muracciole Xavier 
Published: January 2022

Abstract
Background
Sarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment.

Methods
This cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients.

Discussion
The current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan.

Trial registration
The protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04484246).
The effect of informal caregiving on physical health among non-migrants and Ethnic German Immigrants in Germany: a cohort analysis based on the GSOEP 2000–2018
Authors: Georges Daniela 
Published: January 2022

AbstractBackgroundThe number of people in need of care in Germany has been rising since decades, which is related to an increasing need and relevance of informal caregiving. Likewise, the number of people with a migration background has been increasing. This study aims to analyse the impact of informal caregiving on physical health in comparative perspective for Ethnic German Immigrants (EGI) – the largest and oldest immigrant group in Germany – and non-migrant Germans (NMG).MethodsThe sample was drawn from the years 2000–2018 of the German Socio-Economic Panel (n = 26,354). NMG (n = 24,634) and EGI (n = 1,720) were categorized into non-caregivers (n = 24,379) and caregivers (n = 1,975), where the latter were distinguished by 1) their caregiving status and history (current, former, and never caregiver) and 2) the number of years in the caregiver role. Generalized Estimating Equations were applied to examine main effects and the interaction effects of caregiving status and migration background for changes in physical health (n = 102,066 observations).ResultsAdjusting for socioeconomic, household related, and individual characteristics, NMG and EGI had similar caregiving patterns and physical health. However, the interaction between migration background and caregiving revealed significantly higher declines in physical health for currently caregiving EGI. Sensitivity analyses indicated that particularly socioeconomic resources moderated this effect.ConclusionsFindings suggest that caregiving is associated with declines in physical health, particularly in the long term and for EGI. This implies that care-related disadvantages accumulate over time and that the association of caregiving, health and associated determinants are culturally diverse and shaped by migration background. Both the health disadvantages of caregivers and EGI might be mitigated by a positive social and socioeconomic setting, which highlights the relevance of supporting structures and benefits for these subgroups.