bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator
Authors: Schaefer Noah , Lindner Holger A. , Hahn Bianka , Schefzik Roman , Velásquez Sonia Y. , Schulte Jutta , Fuderer Tanja , Centner Franz-Simon , Schoettler Jochen J. , Himmelhan Bianca S. , Sturm Timo , Thiel Manfred , Schneider-Lindner Verena , Coulibaly Anna 
Published: December 2023

BackgroundPneumonia develops frequently after major surgery and polytrauma and thus in the presence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. Immune checkpoints balance self-tolerance and immune activation. Altered checkpoint blood levels were reported for sepsis. We analyzed associations of pneumonia incidence in the presence of SIRS during the first week of critical illness and trends in checkpoint blood levels.Materials and methodsPatients were studied from day two to six after admission to a surgical intensive care unit (ICU). Blood was sampled and physician experts retrospectively adjudicated upon the presence of SIRS and Sepsis-1/2 every eight hours. We measured the daily levels of immune checkpoints and inflammatory markers by bead arrays for polytrauma patients developing pneumonia. Immune checkpoint time series were additionally determined for clinically highly similar polytrauma controls remaining infection-free during follow-up. We performed cluster analyses. Immune checkpoint time trends in cases and controls were compared with hierarchical linear models. For patients with surgical trauma and with and without sepsis, selected immune checkpoints were determined in study baseline samples.ResultsIn polytrauma patients with post-injury pneumonia, eleven immune checkpoints dominated subcluster 3 that separated subclusters 1 and 2 of myeloid markers from subcluster 4 of endothelial activation, tissue inflammation, and adaptive immunity markers. Immune checkpoint blood levels were more stable in polytrauma cases than controls, where they trended towards an increase in subcluster A and a decrease in subcluster B. Herpes virus entry mediator (HVEM) levels (subcluster A) were lower in cases throughout. In unselected surgical patients, sepsis was not associated with altered HVEM levels at the study baseline.ConclusionPneumonia development after polytrauma until ICU-day six was associated with decreased blood levels of HVEM. HVEM signaling may reduce pneumonia risk by strengthening myeloid antimicrobial defense and dampening lymphoid-mediated tissue damage. Future investigations into the role of HVEM in pneumonia and sepsis development and as a predictive biomarker should consider the etiology of critical illness and the site of infection.
Inhibition of ERO1a and IDO1 improves dendritic cell infiltration into pancreatic ductal adenocarcinoma
Authors: Tay Apple Hui Min , Cinotti Riccardo , Sze Newman Sui Kwan , Lundqvist Andreas 
Published: December 2023

IntroductionPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and treatment resistant cancers. Due to its desmoplastic and hypoxic nature along with an abundance of myeloid cell infiltration and scarce T cell infiltration, PDAC is considered a cold tumor.MethodsHere we sought to investigate myeloid cell infiltration and composition in PDAC spheroids by targeting the hypoxia-associated pathways endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) and indoleamine 2,3-dioxygenase 1 (IDO1). Using MiaPaCa2 spheroids with hypoxic core, we assessed the roles of ERO1a and IDO1 inhibition in modulating monocyte infiltration and differentiation, followed by characterizing immunomodulatory factors secreted using LC-MS/MS.ResultsInhibition of ERO1a and IDO1 significantly improved monocyte infiltration and differentiation into dendritic cells. LC-MS/MS analysis of the PDAC spheroid secretome identified downregulation of hypoxia and PDAC pathways, and upregulation of antigen presentation pathways upon inhibition of ERO1a and IDO1. Furthermore, immunomodulatory factors involved in immune infiltration and migration including interleukin-8, lymphocyte cytosolic protein 1, and transgelin-2, were upregulated upon inhibition of ERO1a and IDO1.DiscussionCollectively, our results show that inhibition of ERO1a and IDO1 modulates the tumor microenvironment associated with improved monocyte infiltration and differentiation into dendritic cells to potentially influence therapeutic responses in patients with PDAC.
Gemtuzumab ozogamicin for relapsed or primary refractory acute myeloid leukemia in children—the Polish Pediatric Leukemia and Lymphoma Study Group experience
Authors: Pawinska-Wasikowska Katarzyna , Czogala Malgorzata , Skoczen Szymon , Surman Marta , Rygielska Monika , Ksiazek Teofila , Pac Agnieszka , Wieczorek Aleksandra , Skalska-Sadowska Jolanta , Samborska Magdalena , Wachowiak Jacek , Chaber Radoslaw , Tomaszewska Renata , Szczepanski Tomasz , Zielezinska Karolina , Urasinski Tomasz , Moj-Hackemer Malgorzata , Kalwak Krzysztof , Kozlowska Marta , Irga-Jaworska Ninela , Balwierz Walentyna , Bukowska-Strakova Karolina 
Published: December 2023

BackgroundGemtuzumab ozogamicin (GO), one of the first targeted drugs used in oncology, consists of an anti-cluster of differentiation 33 (CD33) monoclonal antibody bound to a derivative of cytotoxic calicheamicin. After the drug withdrawn in 2010 due to a significantly higher rate of early deaths, GO regained approval in 2017 for the treatment of newly diagnosed, refractory, or relapsed acute myeloid leukemia (AML) in adults and children over 15 years of age. The objective of the study was a retrospective analysis of clinical characteristics, treatment outcomes, and GO toxicity profile in children with primary refractory or relapsed (R/R) AML treated in Poland from 2008 to 2022.MethodsData were collected through the Polish Registry of Acute Myeloid Leukemia. From January 2008 to December 2022, 35 children with R/R AML were treated with GO in seven centers of the Polish Pediatric Leukemia and Lymphoma Study Group.ResultsMost of the children (30 of 35) received only one GO cycle in combination with various chemotherapy cycles (IDA-FLA, DOXO-FLA, FLA, FLAG, and others). Eighteen children (51%) achieved complete remission (CR), 14 did not respond to treatment, and three progressed. GO therapy was followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 18 children in CR. The 5-year overall survival (OS) after GO therapy was 37.1% ± 8.7% for the total cohort. There was a trend toward a superior outcome in patients with strong expression of CD33 expression (over 50% positive cells) compared with that in patients with lower expression of CD33 (OS, 41.2% ± 11.9% versus 27.8% ± 13.2%; p = 0.5; 5-year event-free survival, 35.4% ± 11.6% versus 25.7% ± 12.3%; p = 0.5, respectively). Children under 15 years have better outcome (OS, 34.9% ± 10.4% versus 30% ± 14.5%, p = 0.3). The most common adverse events were bone marrow aplasia, fever of unknown origin, infections, and elevated liver enzyme elevation. Sinusoidal obstruction syndrome occurred in two children.ConclusionsThe use of GO in severely pretreated children, including those under 15 years of age, with previous failure of AML treatment is a feasible and effective bridging therapy to allo-HSCT with an acceptable toxicity profile.
Improved prevention of female genital schistosomiasis: piloting integration of services into the national health system in Côte d’Ivoire
Authors: Preston Ashley , Vitolas Carlos Torres , Kouamin Alain Claver , Nadri Johara , Lavry Suzanne Lobohon , Dhanani Neerav , Dje Norbert , Toh Alain , Fleming Fiona M. , Meite Aboulaye 
Published: December 2023

IntroductionFemale genital schistosomiasis (FGS) is a neglected gynecological condition, putting women at-risk of poor sexual and reproductive health (SRH), including pregnancy complications or infertility. Early treatment of schistosomiasis with praziquantel is important to avoid disease progression to FGS as it is not always possible to reverse these symptoms. However, prevention programs with praziquantel have historically focused on school-aged children. Therefore, there is a gap to provide prevention services for young women in endemic areas, including Côte d’Ivoire.MethodsWe piloted integration of FGS prevention services into routine SRH care in seven health centers (Soubré district, Côte d’Ivoire, November 2020 to April 2021) and enrolled 56 health workers. We used mixed methods including key informant interviews, focus group discussions, and questionnaires to determine effectiveness, feasibility and acceptability of integration across health system decision makers, health workers and female patients (15 to 29 years old). For qualitative data, we used an inductive coding process to analyze themes. We used descriptive statistics to analyze quantitative data.ResultsInterviewed health workers perceived that the integrated services increased access and improved health outcomes for women (15 to 29 years old) due to the more comprehensive approach, although barriers to access included lack of transportation. Female patients surveyed at baseline (n=448) indicated there were no routine FGS prevention services. During the pilot, FGS prevention services were provided to &gt;8500 women at-risk. Health workers interviewed at the end of the pilot indicated they could feasibly provide FGS prevention services as part of routine patient consultations, and they maintained knowledge from training on the key FGS health education points and the consultation processes to follow. The greatest challenge expressed by health workers was the high workload.DiscussionProvision of integrated healthcare in the health center setting is an effective and acceptable way to increase access to prevention services and provide holistic care for women (15 to 29 years old) in this setting in Côte d’Ivoire. Future scale-up will require further streamlining of the strategy, building on existing platforms, whilst ensuring reduced impact on workload and consideration of how to overcome barriers to accessing health centers.
The association between research design and the perceived treatment effectiveness: a cross-sectional study
Authors: Bralić Nensi , Buljan Ivan 
Published: December 2023

ObjectiveTo evaluate the impact of research design on the perceived medical treatment effectiveness among researchers, healthcare workers (HCWs) and consumers in Croatia.MethodsA cross-sectional study was conducted from November 2021 to February 2022 using an online survey. The participants were researchers, HCWs and consumers from Croatia. The survey had six scenarios about the same medical treatment presented within different study designs and in random order. Participants were asked to assess on a scale from 1 to 10 if the descriptions presented a sufficient level of evidence to conclude that the treatment was effective.ResultsFor researchers (n = 97), as the number of participants and degree of variable control in the study design increased, the perceived level of sufficient evidence also increased significantly. Among consumers (n = 286) and HCWs (n = 201), no significant differences in scores were observed between the cross-sectional study, cohort study, RCT, and systematic review.ConclusionThere is a need to implement educational courses on basic research methodology in lower levels of education and as part of Continuing Medical Education for all stakeholders in the healthcare system. Trial registration: this study has been registered on the Open Science Framework prior to study commencement (https://osf.io/t7xmf).
Comparison of the gut microbiota and metabolism in different regions of Red Swamp Crayfish (Procambarus clarkii)
Authors: Liu Songyi , Wang Ziyan , Wang Ze , Wu Qiaoli , Zhou Jun , Wang Rixin , Han Jiaojiao , Su Xiurong 
Published: December 2023

BackgroundThe gut microbiota is very important for maintaining the homeostasis and health of crustaceans. Many factors affect the gut microbiota of crustaceans, one of which is temperature. However, it is currently unclear how temperature affects the gut microbiota and metabolites of Procambarus clarkii.MethodsUsing metagenomic sequencing and gas chromatography–mass spectrometry (GC–MS) techniques, the gut microbiota and metabolites of P. clarkii from Hubei (HB), Jiangsu (JS), Shandong (SD), and Zhejiang (ZJ) in China were investigated.ResultsUnder the impact of temperature, the gut microbiota and metabolites of P. clarkii exhibit a specific trend of change. The primary pathogenic bacteria affecting P. clarkii are Citrobacter, Enterobacterium, and Aeromonas, which are affected by temperature. Two metabolites, namely, sugars and amino acids, are regulated by temperature.ImplicationThis study demonstrated that the gut microbiota and gut metabolites of P. clarkii were considerably affected by temperature. It provides a theoretical basis for the systematic study of P. clarkii and provides a basis for a healthy culture of P. clarkii.
Uncovering differences in the composition and function of phage communities and phage-bacterium interactions in raw soy sauce
Authors: Tan Guiliang , Qi Shaohan , Wang Yi , Li Xueyan , Li Xiangli , Li Mei , Li Lin , Zhao Lichao , Hu Min 
Published: December 2023

IntroductionAlthough the composition and succession of microbial communities in soy sauce fermentation have been well-characterized, the understanding of phage communities in soy sauce remains limited.MethodsThis study determined the diversity, taxonomic composition, and predicted function of phage communities and the phage-host interactions in two types of raw soy sauce (Cantonese-type fermentation, NJ; Japanese-type fermentation, PJ) using shotgun metagenomics.Results and discussionThese two raw soy sauces showed differences in phage composition (121 viral operational taxonomic units (vOTUs) in NJ and 387 vOTUs in PJ), with a higher abundance of the family Siphoviridae (58.50%) in the NJ phage community and a higher abundance of Myoviridae (33.01%) in PJ. Auxiliary metabolic functional annotation analyses showed that phages in the raw soy sauces mostly encoded genes with unknown functions (accounting for 66.33% of COG profiles), but the NJ sample contained genes mostly annotated to conventional functions related to carbohydrate metabolism (0.74%) and lipid metabolism (0.84%), while the PJ sample presented a higher level of amino acid metabolism functions (0.12%). Thirty auxiliary metabolism genes (AMGs) were identified in phage genomes, which were associated with carbohydrate utilization, cysteine and methionine metabolism, and aspartic acid biosynthesis for the host. To identify phage-host interactions, 30 host genomes (affiliated with 22 genera) were also recruited from the metagenomic dataset. The phage-host interaction analysis revealed a wide range of phage hosts, for which a total of 57 phage contigs were associated with 17 host genomes, with Shewanella fodinae and Weissella cibaria infected by the most phages. This study provides a comprehensive understanding of the phage community composition, auxiliary metabolic functions, and interactions with hosts in two different types of raw soy sauce.
Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson’s disease
Authors: Hu Ling , Lin Changfu , Lin Fabin , Wang Lingling , Li Zhenzhen , Cai Zhijun , Liu Xianghong , Ye Qinyong , Wu Yiwen , Cai Guoen 
Published: December 2023

BackgroundThe course of impulse control disorders (ICD) varies in the early stage of Parkinson’s disease (PD).AimWe aimed to delineate the association between the evolution pattern of ICD and the progression of PD.MethodsA total of 321 de novo PD patients from the Parkinson’s Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD.ResultsThe ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions.ConclusionFour early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.
Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration
Authors: Kaiser-Graf Debora , Schulz Angela , Mangelsen Eva , Rothe Michael , Bolbrinker Juliane , Kreutz Reinhold 
Published: December 2023

Background: Glomerular hyperfiltration (GH) is an important mechanism in the development of albuminuria in hypertension. The Munich Wistar Frömter (MWF) rat is a non-diabetic model of chronic kidney disease (CKD) with GH due to inherited low nephron number resulting in spontaneous albuminuria and podocyte injury. In MWF rats, we identified prostaglandin (PG) E2 (PGE2) signaling as a potential causative mechanism of albuminuria in GH.Method: For evaluation of the renal PGE2 metabolic pathway, time-course lipidomic analysis of PGE2 and its downstream metabolites 15-keto-PGE2 and 13-14-dihydro-15-keto-PGE2 was conducted in urine, plasma and kidney tissues of MWF rats and albuminuria-resistant spontaneously hypertensive rats (SHR) by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS).Results: Lipidomic analysis revealed no dysregulation of plasma PGs over the time course of albuminuria development, while glomerular levels of PGE2 and 15-keto-PGE2 were significantly elevated in MWF compared to albuminuria-resistant SHR. Overall, averaged PGE2 levels in glomeruli were up to ×150 higher than the corresponding 15-keto-PGE2 levels. Glomerular metabolic ratios of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were significantly lower, while metabolic ratios of prostaglandin reductases (PTGRs) were significantly higher in MWF rats with manifested albuminuria compared to SHR, respectively.Conclusion: Our data reveal glomerular dysregulation of the PGE2 metabolism in the development of albuminuria in GH, resulting at least partly from reduced PGE2 degradation. This study provides first insights into dynamic changes of the PGE2 pathway that support a role of glomerular PGE2 metabolism and signaling for early albuminuria manifestation in GH.
Assessing the risk of intracranial aneurysm rupture using computational fluid dynamics: a pilot study
Authors: Zhu Yajun , Zou Rong , Sun Xiaochuan , Lei Xingwei , Xiang Jianping , Guo Zongduo , Su Hai 
Published: December 2023

ObjectiveThis study compared 2 representative cases with ruptured aneurysms to explore the role of hemodynamic and morphological parameters in evaluating the rupture risk of intracranial aneurysms (IAs).MethodsCTA and 3-dimensional rotational angiography (3DRA) of 3 IAs in 2 patients were retrospectively analyzed in this study. Hemodynamics and morphological parameters were compared between a ruptured IA and an unruptured IA in case1, and between before and after aneurysm rupture in case 2.ResultsIn case 1, the ruptured aneurysm had larger morphological parameters including size ratio (SR), aspect ratio (AR), aneurysm vessel angle (θF), Aneurysm inclination angle (θA), Undulation index (UI), Ellipticity index (EI), and Non-sphericity Index (NSI) than the unruptured aneurysm. And oscillatory shear index (OSI) is also larger. Higher rupture resemblance score (RRS) was shown in the ruptured aneurysm. In case 2, the aneurysm had one daughter sac after 2 years. Partial morphological and hemodynamic parameters including SR, AR, θF, θA, UI, EI, NSI, OSI, and relative residence time (RRT) increased, and normalized wall shear stress (NWSS) was significantly reduced. RRS increased during this period.ConclusionSR and OSI may have predictive values for the risk of intracranial aneurysm rupture. It is possible that WSS Changes before and after IA rupture, yet the influence of high or low WSS on growth and rupture of IA remains unclear. RRS is promising to be used in the clinical assessment of the rupture risk of IAs and to guide the formulation of treatment plans.
Impaired orienting function detected through eye movements in patients with temporal lobe epilepsy
Authors: Wen Shirui , Zhang Huangyemin , Huang Kailing , Wei Xiaojie , Yang Ke , Wang Quan , Feng Li 
Published: December 2023

ObjectivePatients with temporal lobe epilepsy (TLE) often exhibit attention function impairment. The orienting network is the subsystem of the attention network that has not been fully studied. In this study, we used eye-tracking technology with an attention network test (ANT)-based task to assess the orienting function of TLE patients, aiming to characterize their eye movement patterns.MethodsA total of 37 TLE patients and 29 healthy controls (HCs) completed the ANT task based on eye-tracking technology. Orienting function damage was mainly assessed by the ANT orienting effect. Eye movement metrics, such as mean first goal-directed saccade latency (MGSL), total saccades, and saccade amplitudes, were compared between groupsResultsThe TLE patients had a significantly lower ANT orienting effect (HC, 54.05 ± 34.05; TLE, 32.29 ± 39.54) and lower eye-tracking orienting effect (HC, 116.98 ± 56.59; TLE, 86.72 ± 59.10) than those of the HCs. The larger orienting effects indicate that orienting responses are faster when receiving a spatial cue compared with a center cue. In the spatial cue condition, compared with HCs, the TLE group showed a longer first goal-directed saccade latency (HC, 76.77 ± 58.87 ms; TLE, 115.14 ± 59.15 ms), more total saccades (HC, 28.46 ± 12.30; TLE, 36.69 ± 15.13), and larger saccade amplitudes (HC, 0.75° ± 0.60°; TLE, 1.36° ± 0.89°). Furthermore, there was a positive correlation of the orienting-effect score between the ANT task and eye-tracking metrics (r = 0.58, p &lt; 0.05).ConclusionWe innovatively developed a new detection method using eye-tracking technology in combination with an ANT-based task to detect the orienting function in TLE patients. The current research demonstrated that TLE patients had a significant orienting dysfunction with a specific saccade pattern characterized by a longer first goal-directed saccade latency, more total saccades, and larger saccade amplitudes. These oculomotor metrics are likely to be a better indicator of orienting function and may potentially be used for behavioral-based interventions and long-term cognition monitoring in TLE patients.