bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights into the influence of pre-culture on robust solvent production of C. acetobutylicum
Authors: Oehlenschläger Katharina , Volkmar Marianne , Stiefelmaier Judith , Langsdorf Alexander , Holtmann Dirk , Tippkötter Nils , Ulber Roland 
Published: January 2024

Abstract
Clostridia are known for their solvent production, especially the production of butanol. Concerning the projected depletion of fossil fuels, this is of great interest. The cultivation of clostridia is known to be challenging, and it is difficult to achieve reproducible results and robust processes. However, existing publications usually concentrate on the cultivation conditions of the main culture. In this paper, the influence of cryo-conservation and pre-culture on growth and solvent production in the resulting main cultivation are examined. A protocol was developed that leads to reproducible cultivations of Clostridium acetobutylicum. Detailed investigation of the cell conservation in cryo-cultures ensured reliable cell growth in the pre-culture. Moreover, a reason for the acid crash in the main culture was found, based on the cultivation conditions of the pre-culture. The critical parameter to avoid the acid crash and accomplish the shift to the solventogenesis of clostridia is the metabolic phase in which the cells of the pre-culture were at the time of inoculation of the main culture; this depends on the cultivation time of the pre-culture. Using cells from the exponential growth phase to inoculate the main culture leads to an acid crash. To achieve the solventogenic phase with butanol production, the inoculum should consist of older cells which are in the stationary growth phase. Considering these parameters, which affect the entire cultivation process, reproducible results and reliable solvent production are ensured.

Key points
• Both cryo- and pre-culture strongly impact the cultivation of C. acetobutylicum
• Cultivation conditions of the pre-culture are a reason for the acid crash
• Inoculum from cells in stationary growth phase ensures shift to solventogenesis

Graphical Abstract
Amino acid PET vs. RANO MRI for prediction of overall survival in patients with recurrent high grade glioma under bevacizumab therapy
Authors: Chaban Artem , Waschulzik Birgit , Bernhardt Denise , Delbridge Claire , Schmidt-Graf Friederike , Wagner Arthur , Wiestler Benedikt , Weber Wolfgang , Yakushev Igor 
Published: January 2024

Abstract
Purpose
To summarize evidence on the comparative value of amino acid (AA) PET and conventional MRI for prediction of overall survival (OS) in patients with recurrent high grade glioma (rHGG) under bevacizumab therapy.

Methods
Medical databases were screened for studies with individual data on OS, follow-up MRI, and PET findings in the same patient. MRI images were assessed according to the RANO criteria. A receiver operating characteristic curve analysis was used to predict OS at 9 months.

Results
Five studies with a total of 72 patients were included. Median OS was significantly lower in the PET-positive than in the PET-negative group. PET findings predicted OS with a pooled sensitivity and specificity of 76% and 71%, respectively. Corresponding values for MRI were 32% and 82%. Area under the curve and sensitivity were significantly higher for PET than for MRI.

Conclusion
For monitoring of patients with rHGG under bevacizumab therapy, AA-PET should be preferred over RANO MRI.
The spatial extent of tauopathy on [18F]MK-6240 tau PET shows stronger association with cognitive performances than the standard uptake value ratio in Alzheimer’s disease
Authors: Gérard Thomas , Colmant Lise , Malotaux Vincent , Salman Yasmine , Huyghe Lara , Quenon Lisa , Dricot Laurence , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard 
Published: January 2024

Abstract
Purpose
[18F]MK-6240, a second-generation tau PET tracer, is increasingly used for the detection and the quantification of in vivo cerebral tauopathy in Alzheimer’s disease (AD). Given that neurological symptoms are better explained by the topography rather than by the nature of brain lesions, our study aimed to evaluate whether cognitive impairment would be more closely associated with the spatial extent than with the intensity of tau-PET signal, as measured by the standard uptake value ratio (SUVr).

Methods
[18F]MK6240 tau-PET data from 82 participants in the AD spectrum were quantified in three different brain regions (Braak ≤ 2, Braak ≤ 4, and Braak ≤ 6) using SUVr and the extent of tauopathy (EOT, percentage of voxels with SUVr ≥ 1.3). PET data were first compared between diagnostic categories, and ROC curves were computed to evaluate sensitivity and specificity. PET data were then correlated to cognitive performances and cerebrospinal fluid (CSF) tau values.

Results
The EOT in the Braak ≤ 2 region provided the highest diagnostic accuracies, distinguishing between amyloid-negative and positive clinically unimpaired individuals (threshold = 9%, sensitivity = 79%, specificity = 82%) as well as between prodromal AD and preclinical AD (threshold = 38%, sensitivity = 81%, specificity = 93%). The EOT better correlated with cognition than SUVr (∆R2 + 0.08–0.09) with the best correlation observed for EOT in the Braak ≤ 4 region (R2 = 0.64). Cognitive performances were more closely associated with PET metrics than with CSF values.

Conclusions
Quantifying [18F]MK-6240 tau PET in terms of EOT rather than SUVr significantly increases the correlation with cognitive performances. Quantification in the mesiotemporal lobe is the most useful to diagnose preclinical AD or prodromal AD.
Rescue of NLRC5 expression restores antigen processing machinery in head and neck cancer cells lacking functional STAT1 and p53
Authors: Kinney Brendan L. C. , Gunti Sreenivasulu , Kansal Vikash , Parrish Connor J. , Saba Nabil F. , Teng Yong , Henry Mary Katherine , Su Fang-Yi , Kwong Gabriel A. , Schmitt Nicole C. 
Published: January 2024

AbstractThe antigen processing machinery (APM) components needed for a tumor cell to present an antigen to a T cell are expressed at low levels in solid tumors, constituting an important mechanism of immune escape. More than most other solid tumors, head and neck squamous cell carcinoma (HNSCC) cells tend to have low APM expression, rendering them insensitive to immune checkpoint blockade and most other forms of immunotherapy. In HNSCC, this APM deficiency is largely driven by high levels of EGFR and SHP2, leading to low expression and activation of STAT1; however, recent studies suggest that p53, which is often mutated in HNSCCs, may also play a role. In the current study, we aimed to investigate the extent to which STAT1 and p53 individually regulate APM component expression in HNSCC cells. We found that in cells lacking functional p53, APM expression could still be induced by interferon-gamma or DNA-damaging chemotherapy (cisplatin) as long as STAT1 expression remained intact; when both transcription factors were knocked down, APM component expression was abolished. When we bypassed these deficient pathways by rescuing the expression of NLRC5, APM expression was also restored. These results suggest that dual loss of functional STAT1 and p53 may render HNSCC cells incapable of processing and presenting antigens, but rescue of downstream NLRC5 expression may be an attractive strategy for restoring sensitivity to T cell-based immunotherapy.
Vaccination against neoantigens induced in cross-priming cDC1 in vivo
Authors: Clark Emily S. , Benaduce Ana Paula , Khan Wasif N. , Martinez Olivier , Gilboa Eli 
Published: January 2024

AbstractThe conventional type 1 dendritic cells (cDC1) play a pivotal role in protective immunity against pathogens and cancer. However, their low frequency in the blood and tissues limits their use in immune therapy. We have recently described a method to vaccinate against neoantigens that are induced in tumor cells by targeted delivery of a TAP siRNA to dendritic cells using a TLR9 binding CpG oligonucleotide. Since TLR9 is also expressed in immune suppressive myeloid populations TLR9 targeting could reduce the effectiveness of this approach. Here, we describe a modular multivalent antibody platform to target the TAP siRNA to resident Clec9a expressing cDC1 and show that it leads to selective and sustained TAP downregulation in cDC1 and inhibits tumor growth in mice more effectively than CpG targeted siRNA. To induce DC maturation an agonistic CD40 antibody was administered to the siRNA treated mice. To obviate the need for a second drug formulation and reduce the risk of toxicity, we exploited the multivalent nature of this targeting platform to co-deliver the TAP siRNA and a DC maturation agent, a CpG containing oligonucleotide, to cDC1 in vivo and show that it was more effective than Clec9a targeting of TAP siRNA in combination with CD40 antibody. This study describes a way to manipulate the function of cDC1 cells in vivo using a broadly applicable antibody-based targeting platform to deliver multiple biological agents to specific cells in vivo to potentiate (immune) therapy and to probe the biology of specific cell types in their natural settings.
Development of a cellular model to study CCR8 signaling in tumor-infiltrating regulatory T cells
Authors: Liu Libao , Rangan Laurie , Vanalken Nathan , Kong Qianqian , Schlenner Susan , De Jonghe Steven , Schols Dominique , Van Loy Tom 
Published: January 2024

AbstractThe human CC chemokine receptor 8 (CCR8) is specifically expressed on tumor-infiltrating regulatory T cells (TITRs) and is a promising drug target for cancer immunotherapy. However, the role of CCR8 signaling in TITR biology and the effectiveness of CCR8 small molecule antagonists as TITR-targeting immunotherapy remain subjects of ongoing debate. In this work, we generated a novel cellular model of TITRs by culturing peripheral blood mononuclear cell-derived regulatory T cells in medium containing tumor cell-conditioned medium, CD3/CD28 activator, interleukin-2 and 1α,25-dihydroxyvitamin D3. This cellular model (named TITR mimics) highly and stably expressed a series of TITR signature molecules, including CCR8, FOXP3, CD30, CD39, CD134, CD137, TIGIT and Tim-3. Moreover, TITR mimics displayed robust in vitro immunosuppressive activity. To unravel the functional role of CCR8 in TITR mimics, a chemotaxis assay was performed showing strong and CCR8-specific migration toward CCL1, the natural chemokine agonist of CCR8. However, either stimulation (with CCL1) or blocking (with the small molecule antagonist NS-15) of CCR8 signaling did not affect the immunosuppressive activity, proliferation and survival of TITR mimics. Collectively, our work provides a method for the generation of TITR mimics in vitro, which can be used to study TITR biology and to evaluate drug candidates targeting TITRs. Furthermore, our findings suggest that CCR8 signaling primarily regulates migration of these cells.
Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment
Authors: Su Shu , Chen Fungjun , Lv Xin , Qi Liang , Ding Zhou , Ren Wei , Wei Ming , Liu Ye , Yu Lixia , Liu Baorui , Wang Lifeng 
Published: January 2024

Abstract
Background
The introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients.

Methods
This single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response.

Results
A total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8+ T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05).

Conclusions
The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8+ T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.
Hidden blood loss and bleeding characteristics in children with congenital scoliosis undergoing spinal osteotomies
Authors: Raitio Arimatias , Heiskanen Susanna , Soini Venla , Helenius Linda , Syvänen Johanna , Helenius Ilkka 
Published: January 2024

Abstract
Purpose
Spinal osteotomies are often essential in the treatment of congenital scoliosis. Risk factors for bleeding in these patients needing extracavitatory approaches, especially hidden blood loss, are sparsely investigated. We aimed to investigate the bleeding characteristics and hidden blood loss in paediatric patients undergoing spinal osteotomies for congenital scoliosis.

Methods
A retrospective analysis identified all patients with congenital scoliosis were retrospectively identified from the prospectively collected spine register from 2010 to 2022. Operative technique, perioperative laboratory results and imaging studies were extracted. The primary outcome was total blood loss including intraoperative, drain output and hidden blood loss.

Results
Fifty-seven children (32 boys) with a mean age of 8.3 years underwent spinal osteotomy for congenital scoliosis. Posterolateral hemivertebrectomy was sufficient in 34 (59%) patients, while vertebral column resection (VCR) was required in 23 patients. Total bleeding averaged 792 (523) ml accounting for 42% of the estimated blood volume. Hidden blood loss accounted for 40% of total bleeding and 21% of estimated blood volume with a mean of 317 (256) ml. VCR was associated with greater intraoperative and total bleeding than hemivertebrectomies (p = 0.001 and 0.007, respectively). After adjusting for patient weight and fusion levels, hidden blood loss was larger in hemivertebrectomies (4.18 vs. 1.77 ml/kg/fused level, p = 0.049). In multivariable analysis, intraoperative blood loss was inversely correlated with preoperative erythrocyte levels. Younger age was associated with significantly greater drain, hidden and total blood loss.

Conclusion
Hidden blood loss constitutes a significant portion (40%) of total bleeding in congenital scoliosis surgery. Younger age is a risk factor for bleeding and the hidden blood loss should be taken into consideration in their perioperative management.
Efficacy of High-Dose Dexamethasone in Reducing the Symptoms of Postembolization Syndrome Following Prostatic Artery Embolization: Results of a Double-Blind Randomized Controlled Trial
Authors: Svarc Petra , Stroomberg Hein Vincent , Taudorf Mikkel , Brasso Klaus , Lonn Lars , Røder Andreas 
Published: January 2024

Abstract
Purpose
To evaluate the efficacy of a single perioperative dose of dexamethasone in reducing postembolization syndrome following prostatic artery embolization.

Materials and Methods
We conducted a single-center double-blind randomized controlled trial from March 2021 to May 2022 (NCT04588857). Participants were randomized to receive either i.v. 24 mg dexamethasone or saline. The primary outcome measures were temperature, pain, and quality of life in the first 5 days following prostatic artery embolization. Sample size of 60 patients was needed for the assessment of primary outcomes. Participants were followed for 6 months and assessed for a variety of secondary outcome measures including inflammatory markers and lower urinary tract symptoms severity.

Results
Due to lack of clinical effect and mild symptoms in the control group, the trial was terminated early. 31 participants (16 dexamethasone vs. 15 control) were enrolled and analyzed. A difference in mean temperature was observed on day 1 (37.23 ± 0.64 °C control vs 36.74 ± 0.41 °C dexamethasone, p = 0.02, 95% CI 0.09–0.89). Difference in pain (score out of 10) was seen only on day 5 (1.48 ± 1.2 control vs. 2.9 ± 2.24 dexamethasone, p = 0.04, 95% CI − 2.78–− 0.04). A difference in C-reactive protein values was observed on day 2 (108 [54–161] mg/l control vs 10 [5–33] mg/l dexamethasone, p < 0.01). No significant differences in other outcomes were observed. No side effects were recorded.

Conclusions
Twenty-four milligrams of dexamethasone bolus is safe but does not reduce postembolization syndrome following prostatic artery embolization.

Graphical Abstract
MI-DenseCFNet: deep learning–based multimodal diagnosis models for Aureus and Aspergillus pneumonia
Authors: Liu Tong , Zhang Zheng-hua , Zhou Qi-hao , Cheng Qing-zhao , Yang Yue , Li Jia-shu , Zhang Xue-mei , Zhang Jian-qing 
Published: January 2024

Abstract
Objective
To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP.

Methods
In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected.

Results
The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model.

Conclusion
The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians.

Clinical relevance statement
MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics.

Key points
• MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia.
• The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists.
• This model can enhance a primary radiologist’s diagnostic capacity.
Borate speciation and structural studies of vanadium ion doping in borate bioglass
Authors: Elbasuoni E. G. , Abdelghany A. M. , Moustafa Y. M. , El-Damrawi G. 
Published: January 2024

AbstractDifferent glasses in the system, xV2O5-(45–x)B2O3–24.5Na2O–24.5CaO–6P2O5, (x = 0, 3, 6, 9, 12, 15, 18, 20 and 25 Wt%) were prepared through melt quenching method. X-ray diffraction (XRD) patterns have revealed that the amorphous structure is the dominant type. There is no tendency for crystallization even with higher vanadium content. Crystallization occurred utilizing treating the glasses thermally. FTIR spectral absorption data showed the presence of both BO3 and BO4 structural groups in combination with the presence of VO4 and VO5 structural building units. The deconvolution analysis technique (DAT) was adopted to retrace the conversion progressions of the coordinated boron. At low V2O5 content (up to 10 wt%), it entered as a glass modifier as well as both Na2O and CaO. The high content of the glass modifier (Na2O + CaO + V2O5) could destroy some of the well-formed BO4 units which are transformed into asymmetric BO3. The back conversion of BO4 to asymmetric or loose BO3 can simply reduce the fraction of tetrahedral units (N4). When V2O5 entered as a glass former (> 10 wt%), the N4 fraction increased. The change in the measured densities and estimated molar volumes may assigned to the formation of BO4 units resulting from increasing vanadium oxide content.
Improved catalytic performance of Ag-doped K-OMS-2 for soot oxidation
Authors: Nithya R. , Vikram A. L. , Dasari Harshini , Nethaji S. , Murari M. S. 
Published: January 2024

AbstractThe catalytic behaviours of pure K-OMS-2 and Ag-doped K-OMS-2 catalysts (5% Ag doping) synthesized using the hydrothermal method are the focus of investigation in this study. To characterize the catalytic performance of these synthesized catalysts, a combination of analytical techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and Soot Temperature Programmed Reduction (Soot TPR), were employed. The analysis of the prepared samples via XRD revealed a nanocrystalline tetragonal structure, with crystal sizes measuring approximately 22.4 nm. Further examination of the samples using Field Emission Scanning Electron Microscopy (FESEM) unveiled nanorods with dimensions of 213 nm in length and 32 nm in width for K-OMS-2. In comparison, Ag-doped K-OMS-2 displayed nanorods with dimensions of 290 nm in length and 26 nm in width. Notably, the incorporation of Ag+ ions into the K-OMS-2 framework led to an increase in the intensities of the 771 and 527 cm−1 bands when compared to the pure K-OMS-2. This increase can be attributed to the replacement of K+ ions with Ag+ ions in the structure. Furthermore, the introduction of Ag+ ions into the K-OMS-2 framework significantly influenced its catalytic activity for soot oxidation, as evidenced by the augmentation of surface-adsorbed and lattice oxygen radicals, as observed in the results of Soot TPR. The doped sample exhibited substantially enhanced catalytic activity for soot oxidation, as indicated by its low T50 of 370 °C. In addition, the incorporation of the dopant was found to enhance the thermal stability of the catalyst.
Graphical abstract