bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia
Authors: van Gils Aniek M. , Tolonen Antti , van Harten Argonde C. , Vigneswaran Sinthujah , Barkhof Frederik , Visser Leonie N. C. , Koikkalainen Juha , Herukka Sanna-Kaisa , Hasselbalch Steen Gregers , Mecocci Patrizia , Remes Anne M. , Soininen Hilkka , Lemstra Afina W. , Teunissen Charlotte E. , Jönsson Linus , Lötjönen Jyrki , van der Flier Wiesje M. , Rhodius-Meester Hanneke F. M. 
Published: November 2024

Abstract
Background
The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods
We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer’s disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN). Tests included digital cognitive screening (cCOG), neuropsychological and functional assessment (NP), MRI with automated quantification, and CSF biomarkers. Sequential testing followed a predetermined order, guided by diagnostic certainty. Diagnostic certainty was determined using a clinical decision support system (CDSS) that generates a disease state index (DSI, 0–1), indicating the probability of the syndrome diagnosis or underlying etiology. Diagnosis was confirmed if the DSI exceeded a predefined threshold based on sensitivity/specificity cutoffs relevant to each clinical scenario. Diagnostic accuracy and the need for additional testing were assessed at each step.

Results
Using cCOG as a prescreener for 1) syndrome diagnosis has the potential to accurately reduce the need for extensive NP (42%), resulting in syndrome diagnosis in all patients, with a diagnostic accuracy of 0.71, which was comparable to using NP alone. For 2) etiological diagnosis, stepwise testing resulted in an etiological diagnosis in 80% of patients with a diagnostic accuracy of 0.77, with MRI needed in 77%, and CSF in 37%. When 3) determining DMT eligibility, stepwise testing (100% cCOG, 83% NP, 75% MRI) selected 60% of the patients for confirmatory CSF testing and eventually identified 90% of the potentially eligible patients with AD dementia.

Conclusions
Different diagnostic pathways are accurate and efficient depending on the setting. As such, a data-driven tool holds promise for assisting clinicians in selecting tests of added value across different clinical contexts. This becomes especially important with DMT availability, where the need for more efficient diagnostic pathways is crucial to maintain the accessibility and affordability of dementia diagnoses.
Early reduction in gut microbiota diversity in critically ill patients is associated with mortality
Authors: Wozniak Hannah , Gaïa Nadia , Lazarevic Vladimir , Le Terrier Christophe , Beckmann Tal Sarah , Balzani Eleonora , Urner Martin , Pugin Jérôme , Schrenzel Jacques , Heidegger Claudia-Paula ,   Gut Microbiota working group, Fröhlich Lorin , Negro Tommaso Rochat , Soccorsi Tania , Suh Noémie , Perret Aurélie , Chaabane Chiraz 
Published: November 2024

Abstract
Background
Critical illness is associated with an altered gut microbiota, yet its association with poor outcomes remains unclear. This study evaluates the early gut microbiota diversity changes in intensive care unit patients and its association with mortality. Additionally, it explores fecal pH as a potential biomarker for these changes.

Methods
In this prospective observational cohort study, fecal samples were collected at two time points: S1, the first stool passed upon intensive care unit admission, and S2, the first stool passed at least 24 h after S1. Full-length 16S rRNA gene sequencing was performed for gut microbiota analysis, with α-diversity measured using the Shannon index. Bayesian joint models were used to estimate the association between time-varying changes in gut microbiota diversity and 60-day mortality, as well as the association between daily changes in stool pH and in diversity.

Results
Twenty-four of 96 patients overall died during follow-up. Daily Shannon index decreased on average by −0.1 points [95% Credible Intervals (CrI) −0.20 to −0.10]. Every point decrease in Shannon index was associated with a 1.99-fold increase in the hazard of death (95% CrI, 1.04 to 4.51). Time-varying fecal pH levels were not associated with changes in Shannon index.

Conclusions
Gut microbiota diversity decreased over time, associated with increased mortality. Fecal pH is an unreliable marker of gut microbiota change. Future studies on gut microbiota and related biomarkers should focus on the initial days in the intensive care unit to detect and mitigate a decline in gut microbiota diversity.
Prevalence, risk factors and molecular identification of paramphistomid species in sheep from a Spanish endemic area
Authors: García-Dios David , Díaz Pablo , Remesar Susana , Viña Miguel , Martínez-Calabuig Néstor , Saldaña Ana , Díez-Baños Pablo , Panadero Rosario , Morrondo Patrocinio , López Ceferino Manuel 
Published: November 2024

Abstract
Background
Paramphistomids are ruminal trematodes that cause important losses in tropical and subtropical regions. However, their presence in Europe has increased significantly in recent decades. In northwestern Spain, this trend has been confirmed in cattle, but data in sheep are scarce and not updated. Moreover, the paramphistomid species affecting sheep in the area have never been molecularly identified. To evaluate the prevalence of paramphistomid infections in sheep from northwestern Spain, 826 faecal samples from 25 sheep farms were collected and analysed via coproscopic techniques. In addition, the rumens of 85 roe deer from the same area were examined to detect adult paramphistomids. The species present were molecularly identified. Multivariate analyses for identifying the risk factors affecting the prevalence and egg shedding of rumen flukes were also performed.

Results
Overall, 14% of the animals and 44% of the flocks were positive; the mean egg count was 20.5 eggs per gram of faeces. In contrast, no adult paramphistomids were found in roe deer. Older sheep, those from farms located in the central climatic area, without water throughs available on pastures and using their own manure to fertilize, were considered significantly more susceptible to infection with paramphistomids. With respect to egg shedding, animals from 37 to 72 months of age, farms under semiextensive management, and those coinfected with Fasciola hepatica presented significantly greater egg counts. Molecular identification revealed 100% similarity with Calicophoron daubneyi sequences from other European and Mediterranean countries.

Conclusions
The present study confirms the increase in the prevalence of paramphistomid infections in sheep in the area with high dissemination of the parasite, as previously reported in cattle, and represents the first molecular identification of C. daubneyi in sheep from Spain. Our results demonstrate that special attention should be given to adult animals since they are the main carriers and are responsible for environmental contamination. In addition, detecting risk areas and applying effective control management measures such as the installation of watering points on pastures seems essential for limiting infections in livestock, especially in sheep, since they are susceptible to developing clinical paramphistomidosis at any time in their lives. The absence of adult flukes in roe deer suggests that they represent less suitable hosts for this trematode than cattle and sheep, although more robust studies monitoring the situation in sympatric areas with domestic ruminants are needed.
Modelling the impact of past and future land-use changes on land cover degradation at territorial level in Eastern DR Congo
Authors: Nacishali Nteranya Jean , Kiplagat Andrew , Ucakuwun Elias K. , Nzabandora Chantal Kabonyi 
Published: November 2024

AbstractLand use and land cover (LULC) changes are recognized as drivers of environmental changes at the local, regional, and global levels. Detecting these changes is essential in developing land management plans and strategies. More particularly, the LULC changes constitute one of the sub-indicators used for setting the baseline for land degradation neutrality (LDN) planning and assessing the progress toward the sustainable development goal 15.3. This study aims to determine the implication of LULC dynamics on land cover degradation in Eastern DR Congo. This region has been subjected to uncontrolled LULC changes over the last three decades but the impact of these changes on land degradation has not been assessed yet at the territorial level. To fill this gap, the territory of Kalehe has been used as a case study to monitor the LULC changes during the 1987–2020 period based on the classification of Landsat images, to forecast the future LULC for the 2030–2070 period through the hybrid Markov-Support Vector Machine modeling, to determine the extent of land cover degradation associated with these changes and to assess the impact of biophysical and socio-economic factors on the occurrence of land cover degradation using the binary logistic regression model. The results reveal that the overall trends of LULC changes during the 1987–2020 period are the increasing of built-up area, shrubland, and cropland at the expense of forestland, wetland, and grassland. This situation is expected to continue in the future and contribute to the degradation of land cover within the study area. Under the current situation of LULC changes, 34.17% of the land has been subjected to potential degradation. Furthermore, under the business-as-usual scenario 28.28%, 27.28%, and 33.65% of the land will be degraded by 2030, 2050, and 2070 respectively. This land cover degradation is more likely to occur in the proximity of roads, localities, highly populated areas, mining concessions, and high-altitudinal zones. Since the current land use system is unsustainable, there is a necessity to implement sustainable land management strategies that take into account the biophysical and socio-economic specificities of this region to reverse the problem of land cover degradation.
The role of fluids in earthquake swarms in northeastern Noto Peninsula, central Japan: insights from source mechanisms
Authors: Takano Sayaka , Hiramatsu Yoshihiro , Yukutake Yohei 
Published: November 2024

AbstractA prolonged earthquake swarm has persisted since June 2018 in northeastern Noto Peninsula (central Japan), with activity focused into distinct southern, western, northern, and eastern clusters. To explore the role of fluids in the occurrence of this swarm, we analyzed the focal mechanisms of the earthquakes occurring from 1 January 2018 to 30 November 2022 and performed stress tensor inversions. The western, northern, and eastern clusters were dominated by a reverse fault-type mechanism with a horizontal P-axis oriented NW–SE. One of the nodal planes of those mechanisms aligns closely with the precisely relocated hypocenter distribution. The stress fields in these three clusters, as determined by stress tensor inversion, have maximum principal stresses oriented horizontally in the NW–SE direction and minimum principal stresses oriented vertically, aligning with the regional stress field. From these focal mechanisms and this stress field, we derived small misfit angles and large slip tendencies. These findings suggest that, in these three clusters, fluids diffused into faults largely aligned with the regional stress field, resulting in earthquakes with compatible focal mechanisms. Conversely, normal and strike-slip fault-type focal mechanisms, which are unfavorable to the regional stress field, dominated in the southern cluster. The estimated stress fields, deviating from the regional stress field, have maximum principal stresses closer to vertical and minimum principal stress oriented horizontally in the ENE–WSW direction. For earthquakes deeper than 15 km, this local stress field results in relatively larger misfit angles and lower slip tendency than the other clusters. These results suggest that those earthquakes in the southern cluster occurred on misoriented fault planes due to elevated pore fluid pressures. These findings provide strong evidence of the ascent of high-pore-pressure fluids from depth in the southern cluster and their subsequent diffusion into a southeast-dipping fault zone.
Graphical Abstract
Challenging the significance of SUV-based parameters in a large-scale retrospective study on lung lesions
Authors: Pini Cristiano , Kirienko Margarita , Gelardi Fabrizia , Bossi Paola , Rahal Daoud , Toschi Luca , Ninatti Gaia , Rodari Marcello , Marulli Giuseppe , Antunovic Lidija , Chiti Arturo , Voulaz Emanuele , Sollini Martina 
Published: November 2024

Abstract
Background
Although many well-known factors affect the maximum standardized uptake value (SUVmax), it remains the most requested and used parameter, especially among clinicians, despite other parameters, such as the standardized uptake value corrected for lean body mass and the metabolic tumor volume, being proven to be less sensitive to the same factors, more robust, and eventually more informative. This study intends to provide robust evidence regarding the diagnostic and prognostic value of SUVmax in a large cohort of subjects with suspected malignant lung nodules imaged by [18F]FDG PET/CT.

Materials and methods
We performed a retrospective analysis of patients with suspected/confirmed primary lung tumours undergoing [18F]FDG PET/CT. The sample size was 567 patients. Demographics, imaging, surgical, histological, and follow-up data were collected. SUVmax was analysed according to histology, stage, scanner, and outcome. The impact on measured values of different reconstruction protocols was assessed. All potential predictors of patients’ outcome were assessed.

Results
91% cases were primary lung tumours. Lung benign nodules or metastases accounted for 5% and 4% of cases. Most patients presented with adenocarcinoma (70%) and stage I disease (51%); 144 patients relapsed and 55 died. SUVmax failed to effectively differentiate benign lesions from primary tumours or metastases. Stage I patients presented lower SUVmax. SUVmax significantly correlated with patient weight, injected [18F]FDG activity, and lesion size and differed between reconstructions’ protocols. Survival analyses revealed no independent prognostic significance for SUVmax in progression-free after adjusting for other variables. SUVmax correlated with overall survival, disease stage and tumour histotype.

Conclusion
Our study confirms that SUVmax, though widely employed, present relevant limitations in discriminating between benign lesion and lung cancer, in classifying cancer histotypes, and in predicting patient outcomes independently. Known influencing factors significantly impact on numerical values, thus SUV values should be regarded with caution in clinical practice.
Female prediabetic rats are protected from vascular dysfunction: the role of nitroso and sulfide signaling
Authors: Cacanyiova Sona , Berenyiova Andrea , Malinska Hana , Huttl Martina , Markova Irena , Aydemir Basak G. , Garaiova Veronika , Cebova Martina 
Published: November 2024

Abstract
Background
The activity of perivascular adipose tissue (PVAT), a specific deposit of adipose tissue surrounding blood vessels, could contribute to sex differences in vascular tone control, particularly in dyslipidemic disorders; however, the mutual associations remain unclear. This study aimed to evaluate the relationships among sex, PVAT and vascular function in Wistar and hereditary hypertriglyceridemic (HTG) rats. Vasoactive responses of the isolated thoracic aorta with preserved or removed PVAT were compared in adult male and female Wistar and HTG rats, and the roles of nitric oxide (NO), hydrogen sulfide (H2S), cyclooxygenase (COX) and inflammatory signaling in vascular function were monitored in females.

Results
HTG rats were hypertensive, but females less than males. Increased 2-h glycemia was observed in HTG rats regardless of sex; however, HTG females exhibited better glucose utilization than males did. Females, independent of strain, had better preserved endothelial function than males did. PVAT inhibited endothelium-dependent relaxation in all the rats except HTG females. In HTG males, pathologically increased aortic contractility was noted; however, in HTG females, the contractile responses were lower, thus approaching physiological levels despite the pro-contractile action of COX products. In HTG females, NO contributed to endothelial function to a lesser extent than it did in controls, but the presence of PVAT eliminated this difference, which corresponded with increased NO synthase activity. Although increased protein expression of several proinflammatory factors (TNFα, IL-6, iNOS, and NfκB) was confirmed in the aortic and PVAT tissue of HTG females, the protein expression of factors regulating the adhesion and infiltration of monocytes (ICAM-1 and MCP-1) was decreased in PVAT. Moreover, in HTG females, unlike in controls, H2S produced by PVAT did not inhibit endothelial relaxation, and regardless of PVAT, endogenous H2S had beneficial anticontractile effects, which were associated with increased protein expression of H2S-producing enzymes in both aortic and PVAT tissues.

Conclusions
Despite increased inflammation and the pathological impact of cyclooxygenase signaling in female HTG rats, protective vasoactive mechanisms associated with milder hypertension and improved endothelial function and contractility linked to PVAT activity were triggered. Sulfide and nitroso signaling represent important compensatory vasoactive mechanisms against hypertriglyceridemia-associated metabolic disorders and may be promising therapeutic targets in prediabetic females.
Phage-induced disturbance of a marine sponge microbiome
Authors: Steiner Leon X. , Schmittmann Lara , Rahn Tanja , Lachnit Tim , Jahn Martin T. , Hentschel Ute 
Published: November 2024

Abstract
Background
Bacteriophages are known modulators of community composition and activity in environmental and host-associated microbiomes. However, the impact single phages have on bacterial community dynamics under viral predation, the extent and duration of their effect, are not completely understood. In this study, we combine morphological and genomic characterization of a novel marine phage, isolated from the Baltic sponge Halichondria panicea, and report on first attempts of controlled phage-manipulation of natural sponge-associated microbiomes.

Results
We used culture-based and culture-independent (16S rRNA gene amplicon sequencing) methods to investigate bacterial community composition and dynamics in sponge microbiomes with and without the addition of phages. Upon application of a novel Maribacter specialist phage Panino under controlled conditions, we were able to detect community-wide shifts in the microbiome composition and load after 72 h. While bacterial community composition became more dissimilar over time in the presence of phages, species evenness and richness were maintained. Upon phage exposure, we observed the loss of several low-abundance constituent taxa of the resident microbiota, while other originally underrepresented taxa increased. Virulent phages likely induce community-wide disturbances, evident in changes in the total sponge microbial profile by specific elimination of constituent taxa, which leads to an increase in bacterial abundance of opportunistic taxa, such as the genera Vibrio, Pseudoalteromonas, and Photobacterium.

Conclusions
Our findings suggest that sponge microbiome diversity and, by extension, its resilience depend on the maintenance of resident bacterial community members, irrespective of their abundance. Phage-induced disturbances can significantly alter community structure by promoting the growth of opportunistic bacteria like Vibrio and shifting the microbiome to a dysbiotic state. These insights highlight the role of bacteriophages in shaping microbiome dynamics and underscore the potential for phage application in managing bacterial community composition in marine host-associated environments.
Navigating the implementation gap for Trastuzumab's journey from health insurance to patient access: a preliminary study in a hospital in China
Authors: Yang Xingxia , Jia Yufei , Xu Jianhong , Zhou Qin , Long Qian , Yang Yi , Liu Yunguo , Zhu Juanying , Zhang Xiaochen 
Published: November 2024

Abstract
Background
Trastuzumab, a monoclonal antibody for breast cancer, faces global accessibility challenges, primarily due to high costs. This study examines how changes in medical insurance policies and price adjustments influence Trastuzumab utilization in China, focusing on implementation challenges and their impact on drug accessibility and affordability.

Methods
This retrospective study investigated Trastuzumab utilization among HER2-positive breast cancer patients at a tertiary hospital from May 2013 to December 2022 in JX, a prefecture-level city in eastern China. Patients were stratified based on their CerbB2 indicator, because those with a 2 + CerbB2 status require further FISH testing to confirm Trastuzumab eligibility. We analyzed the utilization rates of both FISH test and Trastuzumab using logistic regressions, identifying factors that influence their usage.

Results
766 patients were included. The utilization rate of Trastuzumab among patients with CerbB2 3+ rose from 40.40 to 77.94% in September 2017 following the expansion of insurance coverage, and further increased to 90.41% after a price reduction in 2020. The FISH test was not covered by health insurance, and it was not available in the local hospital until Trastuzumab became available in JX city. For patients with CerbB2 2+, the proportion undergoing the FISH test increased dramatically from 8.89 to 82.08% after the price reduction in 2020. The mere inclusion into basic medical insurance, regardless of insurance types, significantly increased the utilization of Trastuzumab and the FISH test. However, rural patients in JX city are still facing financial burdens with Trastuzumab's out-of-pocket cost accounting for 62.9% of their annual disposable income in 2020.

Conclusions
Our findings indicate that insurance coverage and price reduction significantly increased Trastuzumab utilization. However, failure to improve the accessibility of the FISH test can pose challenges in enhancing the uptake of Trastuzumab among eligible patients. With the expiration of Trastuzumab's patent and the development of affordable biosimilars, there are now greater opportunities to enhance treatment access globally. These insights can inform policy makers of implementation guidance about providing financial support for breast cancer patients in other LMICs.