bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity
Authors: Gregersen Emil , Betzer Cristine , Kim Woojin S. , Kovacs Gergo , Reimer Lasse , Halliday Glenda M. , Thiel Steffen , Jensen Poul Henning 
Published: August 2021

AbstractBackgroundSynucleinopathies are characterized by neurodegeneration and deposition of the presynaptic protein α-synuclein in pathological protein inclusions. Growing evidence suggests the complement system not only has physiological functions in the central nervous system, but also is involved in mediating the pathological loss of synapses in Alzheimer’s disease. However, it is not established whether the complement system has a similar role in the diseases Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy (MSA) that are associated with α-synuclein aggregate pathology.MethodsTo investigate if the complement system has a pathological role in synucleinopathies, we assessed the effect of the complement system on the viability of an α-synuclein expressing cell model and examined direct activation of the complement system by α-synuclein in a plate-based activation assay. Finally, we investigated the levels of the initiator of the classical pathway, C1q, in postmortem brain samples from MSA patients.ResultsWe demonstrate that α-synuclein activates the classical complement pathway and mediates complement-dependent toxicity in α-synuclein expressing SH-SY5Y cells. The α-synuclein-dependent cellular toxicity was rescued by the complement inhibitors RaCI (inhibiting C5) and Cp20 (inhibiting C3). Furthermore, we observed a trend for higher levels of C1q in the putamen of MSA subjects than that of controls.Conclusionα-Synuclein can activate the classical complement pathway, and the complement system is involved in α-synuclein-dependent cellular cytotoxicity suggesting the system could play a prodegenerative role in synucleinopathies.
Factors associated with testing for HIV and hepatitis C among behaviorally vulnerable men in Germany: a cross-sectional analysis upon enrollment into an observational cohort
Authors: Crowell Trevor A. , Qian Haoyu , Tiemann Carsten , Lehmann Clara , Boesecke Christoph , Stoehr Albrecht , Hartikainen Jukka , Esser Stefan , Bickel Markus , Spinner Christoph D. , Schneeweiß Stephan , Cordes Christiane , Brockmeyer Norbert , Jessen Heiko , Robb Merlin L. , Michael Nelson L. , Jansen Klaus , Streeck Hendrik ,   for the BRAHMS Study Team
Published: August 2021

Abstract
Background
HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM.

Methods
From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months.

Results
Among 1017 participants with median age 33 (interquartile range 28–39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing.

Conclusion
Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.
Investigation of the clinical inter-observer bias in prostate fiducial marker image registration between CT and MR images
Authors: Persson Emilia , Emin Sevgi , Scherman Jonas , Jamtheim Gustafsson Christian , Brynolfsson Patrik , Ceberg Sofie , Gunnlaugsson Adalsteinn , Olsson Lars E. 
Published: August 2021

Abstract
Background and purpose
Inter-modality image registration between computed tomography (CT) and magnetic resonance (MR) images is associated with systematic uncertainties and the magnitude of these uncertainties is not well documented.
The purpose of this study was to investigate the potential uncertainty of gold fiducial marker (GFM) registration for localized prostate cancer and to estimate the inter-observer bias in a clinical setting.

Methods

Four experienced observers registered CT and MR images for 42 prostate cancer patients. Manual GFM identification was followed by a landmark-based registration. The absolute difference between observers in GFM identification and the displacement of the clinical target volume (CTV) was investigated. The CTV center of mass (CoM) vector displacements, DICE-index and Hausdorff distances for the observer registrations were compared against a clinical baseline registration. The time allocated for the manual registrations was compared.

Results
Absolute difference in GFM identification between observers ranged from 0.0 to 3.0 mm. The maximum CTV CoM displacement from the clinical baseline was 3.1 mm. Displacements larger than or equal to 1 mm, 2 mm and 3 mm were 46%, 18% and 4%, respectively. No statistically significant difference was detected between observers in terms of CTV displacement. Median DICE-index and Hausdorff distance for the CTV, with their respective ranges were 0.94 [0.70–1.00] and 2.5 mm [0.7–8.7].

Conclusions
Registration of CT and MR images using GFMs for localized prostate cancer patients was subject to inter-observer bias on an individual patient level. A CTV displacement as large as 3 mm occurred for individual patients. These results show that GFM registration in a clinical setting is associated with uncertainties, which motivates the removal of inter-modality registrations in the radiotherapy workflow and a transition to an MRI-only workflow for localized prostate cancer.
68Ga-DOTATATE PET-CT as a tool for radiation planning and evaluating treatment responses in the clinical management of meningiomas
Authors: Kowalski Emily S. , Khairnar Rahul , Gryaznov Anton A. , Kesari Vivek , Koroulakis Antony , Raghavan Prashant , Chen Wengen , Woodworth Graeme , Mishra Mark 
Published: August 2021

Abstract
Background and purpose
Meningiomas express the somatostatin receptor (SSTR), which normal bone and brain lack. PET imaging with SSTR ligands such as 68 Ga-DOTATATE have been recently shown to aid in the imaging and identification of menginiomas. We hypothesize that 68 Ga-DOTATATE PET/CT in conjunction with MRI aids in radiation (RT) target volume delineation and evaluating treatment response.

Materials and methods
Nineteen patients with meningiomas underwent 68 Ga-DOTATATE PET/CT and MRI for RT planning and/or post-treatment follow-up. Meningiomas were grade I (n = 9) or not biopsied (n = 8) and frequently involved base of skull (n = 10). Ten (53%) patients received post-operative RT and 9 (47%) received fractaionted RT. In the subgroup that underwent both pre- and post-RT 68 Ga-DOTATATE PET as well as MRI (n = 10), ROVER (ABX GmbH, Radeberg, Germany) adaptive thresholding software was utilized to measure total lesion activity (mean and max) before and after treatment. Tumor volume based on MRI was calculated before and after treatment. Total lesion activity and tumor volume changes were compared using Wilcoxon signed rank test.

Results
68 Ga-DOTATATE PET/CT identified intraosseous (n = 4, 22%), falcine (n = 5, 26%) and satellite lesions (n = 3, 19%) and clarified the diagnosis of meningioma, resulting in a change in management in three patients. Mean total lesion activity decreased 14.7% (median), from pre to post-RT 68 Ga-DOTATATE PET [range 97–8.5% (25–75%),S = − 26.5, p = 0.0039]. Max total lesion activity decreased 36% (median) over the same period [range 105–15% (25–75%), S = − 26.5 p = 0.0039]. In contrast, meningioma volumes based on MRI measurements did not significantly change per RECIST criteria and Wilcoxon signed rank test (S = − 3, p = 0.7422).

Conclusion
68 Ga-DOTATATE PET/CT helped confirm suspected diagnoses and delineate target volumes particularly when lesions involved osseous structures and the falx. Mean and max total tumor 68 Ga-DOTATATE activity on PET/CT decreased at three months following RT despite stable tumor volumes on MRI. Future studies are warranted to (1) assess the sensitivity and specificity of 68 Ga-DOTATATE PET/CT, (2) evaluate the impact of 68 Ga-DOTATATE PET/CT-based planning on treatment outcomes, and (3) assess the prognostic significance of these post-treatment imaging changes.
Projected soil organic carbon loss in response to climate warming and soil water content in a loess watershed
Authors: Zhao Fubo , Wu Yiping , Hui Jinyu , Sivakumar Bellie , Meng Xianyong , Liu Shuguang 
Published: August 2021

AbstractBackgroundSoil organic carbon (SOC) plays a crucial role in the global carbon cycle and terrestrial ecosystem functions. It is widely known that climate change and soil water content (SWC) could influence the SOC dynamics; however, there are still debates about how climate change, especially climate warming, and SWC impact SOC. We investigated the spatiotemporal changes in SOC and its responses to climate warming and root-zone SWC change using the coupled hydro-biogeochemical model (SWAT-DayCent) and climate scenarios data derived under the three Representative Concentration Pathways (RCPs2.6, 4.5, and 8.5) from five downscaled Global Climate Models (GCMs) in a typical loess watershed––the Jinghe River Basin (JRB) on the Chinese Loess Plateau.ResultsThe air temperature would increase significantly during the future period (2017–2099), while the annual precipitation would increase by 2.0–13.1% relative to the baseline period (1976–2016), indicating a warmer and wetter future in the JRB. Driven by the precipitation variation, the root-zone SWC would also increase (by up to 27.9% relative to the baseline under RCP4.5); however, the SOC was projected to decrease significantly under the future warming climate. The combined effects of climate warming and SWC change could more reasonably explain the SOC loss, and this formed hump-shaped response surfaces between SOC loss and warming-SWC interactions under both RCP2.6 and 8.5, which can help explain diverse warming effects on SOC with changing SWC.ConclusionsThe study showed a significant potential carbon source under the future warmer and wetter climate in the JRB, and the SOC loss was largely controlled by future climate warming and the root-zone SWC as well. The hump-shaped responses of the SOC loss to climate warming and SWC change demonstrated that the SWC could mediate the warming effects on SOC loss, but this mediation largely depended on the SWC changing magnitude (drier or wetter soil conditions). This mediation mechanism about the effect of SWC on SOC would be valuable for enhancing soil carbon sequestration in a warming climate on the Loess Plateau.
Development and validation of a novel blending machine learning model for hospital mortality prediction in ICU patients with Sepsis
Authors: Zeng Zhixuan , Yao Shuo , Zheng Jianfei , Gong Xun 
Published: August 2021

Abstract
Background
Early prediction of hospital mortality is crucial for ICU patients with sepsis. This study aimed to develop a novel blending machine learning (ML) model for hospital mortality prediction in ICU patients with sepsis.

Methods
Two ICU databases were employed: eICU Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care III (MIMIC-III). All adult patients who fulfilled Sepsis-3 criteria were identified. Samples from eICU-CRD constituted training set and samples from MIMIC-III constituted test set. Stepwise logistic regression model was used for predictor selection. Blending ML model which integrated nine sorts of basic ML models was developed for hospital mortality prediction in ICU patients with sepsis. Model performance was evaluated by various measures related to discrimination or calibration.

Results
Twelve thousand five hundred fifty-eight patients from eICU-CRD were included as the training set, and 12,095 patients from MIMIC-III were included as the test set. Both the training set and the test set showed a hospital mortality of 17.9%. Maximum and minimum lactate, maximum and minimum albumin, minimum PaO2/FiO2 and age were important predictors identified by both random forest and extreme gradient boosting algorithm. Blending ML models based on corresponding set of predictors presented better discrimination than SAPS II (AUROC, 0.806 vs. 0.771; AUPRC 0.515 vs. 0.429) and SOFA (AUROC, 0.742 vs. 0.706; AUPRC 0.428 vs. 0.381) on the test set. In addition, calibration curves showed that blending ML models had better calibration than SAPS II.

Conclusions
The blending ML model is capable of integrating different sorts of basic ML models efficiently, and outperforms conventional severity scores in predicting hospital mortality among septic patients in ICU.
Recurrence of carcinoma showing thymus-like differentiation (CASTLE) involving the thyroid gland
Authors: Dang N. V. , Son L. X. , Hong N. T. T. , Nhung N. T. T. , Tung N. T. , Quang L. V. 
Published: August 2021

Abstract
Background
Carcinoma showing thymus-like differentiation (CASTLE) in the thyroid gland is a rare disease with generally a favorable prognosis. Treatment with surgery and adjuvant radiotherapy has been shown to improve local control and long-term survival rates. In this report, we present a case of a recurrent thyroid gland CASTLE and review the literature on the diagnosis and treatment of this disease.

Case presentation
A 60-year-old woman, who was diagnosed with a CASTLE thyroid tumor in 2015, had a total thyroidectomy and was maintained on thyroid hormone replacement (levothyroxine). After 5 years, the patient had a recurrence, in an advanced stage unsuitable for surgery. As the patient declined to undergo radiotherapy, she was followed up without intervention and is currently stable after 15 months.

Conclusions
CASTLE is a rare disease, diagnosed based on postoperative pathology and immunohistochemistry analysis, especially upon CD5 marker. In case of relapse, treatment options include surgery and radiotherapy; however conservative management without intervention is an acceptable alternative in some cases.
Symptoms presented during emergency telephone calls for patients with spontaneous subarachnoid haemorrhage
Authors: Sonne Asger , Egholm Sarita , Elgaard Laurits , Breindahl Niklas , Jensen Alice Herrlin , Eskesen Vagn , Lippert Freddy , Waldorff Frans Boch , Lohse Nicolai , Rasmussen Lars Simon 
Published: August 2021

Abstract
Background
A spontaneous subarachnoid haemorrhage (SAH) is one of the most critical neurological emergencies a dispatcher can face in an emergency telephone call. No study has yet investigated which symptoms are presented in emergency telephone calls for these patients. We aimed to identify symptoms indicative of SAH and to determine the sensitivity of these and their association (odds ratio, OR) with SAH.

Methods
This was a nested case–control study based on all telephone calls to the medical dispatch center of Copenhagen Emergency Medical Services in a 4-year time period. Patients with SAH were identified in the Danish National Patient Register; diagnoses were verified by medical record review and their emergency telephone call audio files were extracted. Audio files were replayed, and symptoms extracted in a standardized manner. Audio files of a control group were replayed and assessed as well.

Results
We included 224 SAH patients and 609 controls. Cardiac arrest and persisting unconsciousness were reported in 5.8% and 14.7% of SAH patients, respectively. The highest sensitivity was found for headache (58.9%), nausea/vomiting (46.9%) and neck pain (32.6%). Among conscious SAH patients these symptoms were found to have the strongest association with SAH (OR 27.0, 8.41 and 34.0, respectively). Inability to stand up, speech difficulty, or sweating were reported in 24.6%, 24.2%, and 22.8%. The most frequent combination of symptoms was headache and nausea/vomiting, which was reported in 41.6% of SAH patients. More than 90% of headaches were severe, but headache was not reported in 29.7% of conscious SAH patients. In these, syncope was described by 49.1% and nausea/vomiting by 37.7%.

Conclusion
Headache, nausea/vomiting, and neck pain had the highest sensitivity and strongest association with SAH in emergency telephone calls. Unspecific symptoms such as inability to stand up, speech difficulty or sweating were reported in 1 out of 5 calls. Interestingly, 1 in 3 conscious SAH patients did not report headache.
Trial registration NCT03980613 (www.clinicaltrials.gov).
Retrotransposons as pathogenicity factors of the plant pathogenic fungus Botrytis cinerea
Authors: Porquier Antoine , Tisserant Constance , Salinas Francisco , Glassl Carla , Wange Lucas , Enard Wolfgang , Hauser Andreas , Hahn Matthias , Weiberg Arne 
Published: August 2021

AbstractBackgroundRetrotransposons are genetic elements inducing mutations in all domains of life. Despite their detrimental effect, retrotransposons can become temporarily active during epigenetic reprogramming and cellular stress response, which may accelerate host genome evolution. In fungal pathogens, a positive role has been attributed to retrotransposons when shaping genome architecture and expression of genes encoding pathogenicity factors; thus, retrotransposons are known to influence pathogenicity.ResultsWe uncover a hitherto unknown role of fungal retrotransposons as being pathogenicity factors, themselves. The aggressive fungal plant pathogen,Botrytis cinerea, is known to deliver some long-terminal repeat (LTR) deriving regulatory trans-species small RNAs (BcsRNAs) into plant cells to suppress host gene expression for infection. We find that naturally occurring, less aggressiveB. cinereastrains possess considerably lower copy numbers of LTR retrotransposons and had lost retrotransposonBcsRNA production. Using a transgenic proof-of-concept approach, we reconstitute retrotransposon expression in aBcsRNA-lackingB. cinereastrain, which results in enhanced aggressiveness in a retrotransposon andBcsRNA expression-dependent manner. Moreover, retrotransposon expression inB. cinerealeads to suppression of plant defence-related genes during infection.ConclusionsWe propose that retrotransposons are pathogenicity factors that manipulate host plant gene expression by encoding trans-speciesBcsRNAs. Taken together, the novelty that retrotransposons are pathogenicity factors will have a broad impact on studies of host-microbe interactions and pathology.
Anonymous online cognitive behavioral therapy for sleep disorders in shift workers—a study protocol for a randomized controlled trial
Authors: Retzer Lukas , Feil Monika , Reindl Richard , Richter Kneginja , Lehmann Robert , Stemmler Mark , Graessel Elmar 
Published: August 2021

AbstractBackgroundMany shift workers suffer from sleep issues, which negatively affect quality of life and performance. Scientifically evaluated, structured programs for prevention and treatment are scarce. We developed an anonymous online cognitive behavioral therapy for insomnia (CBT-I) program. After successful completion of a feasibility study, we now start this prospective, randomized, controlled superiority trial to compare outcomes of two parallel groups, namely an intervention group and a waiting-list control-group. Additionally, we will compare these outcomes to those of a face-to-face CBT-I outpatient sample.MethodsCollaborating companies will offer our anonymous online intervention to their shift-working employees. Company physicians and counseling services will screen those interested for inclusion and exclusion criteria. Participants will receive access to our online service, where they will complete psychometric assessment and receive random assignment to either the intervention group or the waiting-list control group. Participants and providers will be aware of the group assignment. We aim to allocate at leastN= 60 participants to the trial. The intervention consists of psychoeducation, sleep restriction, stimulus control, relaxation techniques, and individual feedback delivered via four e-mail contacts. During the intervention, as well as during the waiting period, participants will fill out weekly sleep diaries. Immediately after completion of the program, the post-intervention assessment takes place. Participants in the control group will be able to participate in the program after all study assessments. To recruit an additional sample, collaborating outpatient sleep clinics will provide six sessions of standard face-to-face CBT-I to an ad hoc sample of shift working patients. We expect both the online and the face-to-face CBT-I interventions to have beneficial effects compared to the control group on the following primary outcomes: self-reported symptoms of depression and insomnia, sleep quality, and daytime sleepiness.ConclusionsThe online intervention allows shift workers to follow a CBT-I program independently of their working schedule and location. Forthcoming results might contribute to further improvement of prevention and therapy of sleep issues in shift workers.Trial registrationGerman Clinical Trials Register DRKSDRKS00017777. Registered on 14 January 2020—retrospectively registered.