bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin improves cancer immunotherapy by directly rescuing tumor-infiltrating CD8 T lymphocytes from hypoxia-induced immunosuppression
Authors: Finisguerra Veronica , Dvorakova Tereza , Formenti Matteo , Van Meerbeeck Pierre , Mignion Lionel , Gallez Bernard , Van den Eynde Benoit J 
Published: May 2023

BackgroundDespite their revolutionary success in cancer treatment over the last decades, immunotherapies encounter limitations in certain tumor types and patients. The efficacy of immunotherapies depends on tumor antigen-specific CD8 T-cell viability and functionality within the immunosuppressive tumor microenvironment, where oxygen levels are often low. Hypoxia can reduce CD8 T-cell fitness in several ways and CD8 T cells are mostly excluded from hypoxic tumor regions. Given the challenges to achieve durable reduction of hypoxia in the clinic, ameliorating CD8 T-cell survival and effector function in hypoxic condition could improve tumor response to immunotherapies.MethodsActivated CD8 T cells were exposed to hypoxia and metformin and analyzed by fluorescence-activated cell sorting for cell proliferation, apoptosis and phenotype. In vivo, metformin was administered to mice bearing hypoxic tumors and receiving either adoptive cell therapy with tumor-specific CD8 T cells, or immune checkpoint inhibitors; tumor growth was followed over time and CD8 T-cell infiltration, survival and localization in normoxic or hypoxic tumor regions were assessed by flow cytometry and immunofluorescence. Tumor oxygenation and hypoxia were measured by electron paramagnetic resonance and pimonidazole staining, respectively.ResultsWe found that the antidiabetic drug metformin directly improved CD8 T-cell fitness in hypoxia, both in vitro and in vivo. Metformin rescued murine and human CD8 T cells from hypoxia-induced apoptosis and increased their proliferation and cytokine production, while blunting the upregulation of programmed cell death protein 1 and lymphocyte-activation gene 3. This appeared to result from a reduced production of reactive oxygen species, due to the inhibition of mitochondrial complex I. Differently from what others reported, metformin did not reduce tumor hypoxia, but rather increased CD8 T-cell infiltration and survival in hypoxic tumor areas, and synergized with cyclophosphamide to enhance tumor response to adoptive cell therapy or immune checkpoint blockade in different tumor models.ConclusionsThis study describes a novel mechanism of action of metformin and presents a promising strategy to achieve immune rejection in hypoxic and immunosuppressive tumors, which would otherwise be resistant to immunotherapy.
On black hole surface gravity
Authors: Pugliese Daniela , Quevedo Hernando 
Published: May 2023

AbstractWe analyze the properties of the black hole surface gravity by using an alternative approach based upon the use of light surfaces that are represented by certain characteristic frequencies. To this end, we rewrite the Kerr line element in terms of the characteristic frequencies, which allows us to obtain copies of the Kerr geometries (black hole–clusters) as the parameters vary. In particular, we replace the spin parameter $$a=J/M$$

a
=
J
/
M

with the corresponding characteristic frequencies so that the line element describes only black holes. This new representation is particularly adapted to analyze how the surface gravity behaves as the black hole passes from one state to another. It turns out that the spins $$a={\sqrt{3}}/{2} M$$

a
=

3

/
2
M

and $$a=1/\sqrt{2} M$$

a
=
1
/

2

M

for black holes and $$a/M=\sqrt{9/8}$$

a
/
M
=

9
/
8

for naked singularities are of particular relevance for the analysis of the surface gravity properties.
Four-directional controlled quantum teleportation by using a nine-qubit entangled state as the quantum channel
Authors: Verma Vikram 
Published: May 2023

In this paper, we propose a four-directional controlled quantum teleportation (CQT) by using a nine-qubit entangled state as the quantum channel. In 2020, a scheme for four-directional controlled quantum teleportation by using a 10-qubit state as the quantum resource had been proposed in X. W. Zha and K. Li [Mod. Phys. Lett. B 34, 2050412 (2020)] in which the controller has no control over the two teleportation processes. In this study, it is also shown that two receivers cannot reconstruct the original state sent from the respective senders and hence the teleportation processes cannot be completed in the previous scheme. However, these problems have been resolved in our proposed scheme in which the controller has control over all the teleportation processes and none of the receivers can reconstruct the original state sent from the respective senders without the permission of the controller. Thus, our proposed scheme reduces the consumption of quantum resource and is more secure and successful as compared to the previous scheme.
Optimization of Microwave-Assisted Extraction of Mucilage from Ocimum basilicum var. album (L.) Seed
Authors: Shiehnezhad Mahdiye , Zarringhalami Soheila , Malekjani Narjes 
Published: May 2023

Microwave-assisted extraction (MAE) is an effective green extraction method of value-added and bioactive compounds. The impact of different extraction times (2-7 min), microwave power (360-760 W), and solvent-to-sample ratio (20 : 1-40 : 1 ml/g) on the extraction yield of Ocimum basilicum var. album L. using MAE was investigated. Maximum extraction yield (

17.00
±
0.14

%) was obtained at optimal conditions for extraction using response surface methodology, including extraction time of 4.33 min, power of 570.32 W, and the solvent-to-sample ratio of 40 : 1 ml/g, which was very close to the model prediction (17.01%). The yield of the conventional extraction (CE) method (50°C, 100 rpm, 1 h extraction time, and solvent-to-sample ratio of 40 : 1 ml/g) was

14.53
±
0.25

%. Comparisons were made between the functional and structural characteristics of the mucilage extracted under optimal conditions and the CE method. Fourier transforms infrared (FTIR) spectroscopy was utilized to study the changes in functional groups, and scanning electron microscopy (SEM) was used to determine the morphological characteristics. Emulsion stability against heat, water absorption capacity, foaming capacity, and foaming stability of the extracted mucilage under optimal conditions were

80.73
±
0.08

%,

48.71
±
0.32

g/g,

24.55
±
0.42

%, and

91.6
±
0.49

%, respectively, which were higher than the CE method. SEM results showed a more porous structure in mucilage obtained by the MAE method, while no changes were observed by FTIR analysis between the functional groups of extracted mucilage obtained from the utilized extraction methods. Therefore, the application of the MAE method was superior to CE in terms of yield, structural and functional characteristics, and significantly shorter extraction time. The findings show the great potential of microwave processing in commercial and laboratory extraction of mucilage without deteriorative effects on the structural and functional properties of the extracted material.
Linking Body Composition and Nutritional Status with CAR T-cell Efficacy
Authors: Nawas Mariam T. , Scordo Michael 
Published: May 2023

Obesity and its attendant pathophysiological alterations have long been implicated in promoting cancer development and in the modulation of antitumor immunologic responses, but little is known about their impact on outcomes after cellular immunotherapy. In this issue, Rejeski and colleagues report that intrinsic host factors including body composition and nutritional status may predict response after chimeric antigen receptor T-cell therapy in patients with relapsed lymphomas. These data highlight the clinical relevance of these factors on treatment outcomes and will hopefully motivate interventional studies of prehabilitation and nutritional optimization in these patients.See related article by Rejeski et al., p. 707 (1).
Characterisation of an endospore population of Pasteuria that adheres to the plant-parasitic nematode Heterodera schachtii
Authors: Hirschfield Ramona , Mohan Sharad , Davies Keith G. 
Published: May 2023

Summary
Selected strains of Pasteuria species from the endospore-forming Gram-positive bacteria group have the potential to be developed into control agents for plant-parasitic nematodes. If Pasteuria is to be deployed successfully as a control agent, endospores of the bacterium initially have to adhere to the cuticle of the infective juvenile. Studies of the bacteria isolated from root-knot nematodes have suggested that collagen-like fibres on the endospore surface interact with a cuticle receptor on the second-stage juvenile through a host specific ‘Velcro-like’ mechanism. However, very little is known regarding the biochemical nature of the mechanism in Pasteuria strains isolated from cyst nematodes. Here, using several polyclonal antibodies raised to whole endospores and to synthetic collagen-like peptides, we compare two Pasteuria populations, one a strain from a root-knot nematode, Meloidogyne javanica, and another from cowpea cyst nematode, Heterodera cajani. We demonstrate that there is differential adhesion of endospores to the beet cyst nematode H. schachtii and that the sugar moieties on the endospore surface may protect the collagen-like fibres on the endospore from proteolytic digestion and be involved in the endospore’s specificity.
Is There a Duty to Mitigate Damages in Civil Law? Should We Introduce Such a Duty? The Case of Qatar
Authors: Al-Kaabi Mohammed Hassan 
Published: May 2023

Abstract
In common law, the non-breaching party of a contract should mitigate damages or risk a reduction in recovery for the breach. The party must take measures to reduce the loss arising from the breach by making a cover purchase, reselling the goods, or taking other actions. The breaching party may claim a reduction in the damages that would be awarded to the injured party up to the amount in which reasonable mitigation measures would have reduced the loss or injury to the injured party. Unlike in common law countries, some civil law countries do not contain a general duty to mitigate damages upon the non-breaching party. However, the concept of damage mitigation has gradually expanded beyond its original sphere of influence. The questions to be answered in this article are as follows: Why is there no duty to mitigate damages in civil law? Should we introduce such a duty?
Effect of Wave Directions on Orientation and Magnitude of Surface Wind Stress under Typhoon Megi (2010)
Authors: Hsu Je-Yuan 
Published: May 2023

Abstract
The relationship between the wind-wave spectrum and surface wind stress τ in tropical cyclones, especially for the misalignment |ϕ| between the wind and τ, was investigated using data from three Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats deployed in Super Typhoon Megi (2010). The floats measured τ by integrating downward momentum flux in the ocean and, in a recent development, directional spectra of surface waves. The wind was captured by aircraft surveys. At wind speeds from 25 to 40 m s−1, the |ϕ| increased with the increasing angle between the wind and dominant waves. The |ϕ| was small near the eyewall, where wave energy concentrated in a narrow frequency band. At the location far away from the eyewall, where most spectra were bimodal in directions with similar frequencies, the stress direction might be similar to the high-frequency waves. The misalignment between the wind and propagating swell might affect the growth and directional spreading of wind waves under tropical cyclones. The resulting wave breaking might then release wave momentum into the ocean as most stress clockwise from the wind direction. C‖, the downwind drag coefficient, increased with increasing inverse wave age of dominant waves. |C⊥|, the magnitude of the crosswind drag coefficient, was significant when low-frequency waves deviated from the wind by more than 90°. The wave directions are used in the inverse wave age for scaling drag coefficients. The new parameterization based on wave dynamics can be useful for improving the prediction of wind stress curl under storms.

Significance Statement
Tropical cyclones can impact the maximum sea surface temperature cooling through the curl of surface wind stress τ, which causes divergence under the storm eye. To investigate the effect of surface waves on τ, measurements of downward momentum flux and surface waves from three EM-APEX floats deployed under Typhoon Megi in 2010 are used. The inverse wave age involving wind forcing on the wave directions of dominant waves and swells can significantly influence the momentum transfer efficiency in the downwind and crosswind directions, respectively. That is, the propagating swell under storms should play a crucial role in the downward momentum flux during its interaction with high-frequency waves and wind. Incorporating wave directions to parameterize the magnitude and orientation of τ will improve future models’ ability to predict wind stress curl and thereby the heat fluxes to storm intensification.
The remoulding of dietary effects on the fecundity / longevity trade-off in a social insect
Authors: Rau Veronika , Flatt Thomas , Korb Judith 
Published: May 2023

AbstractBackgroundIn many organisms increased reproductive effort is associated with a shortened life span. This trade-off is reflected in conserved molecular pathways that link nutrient-sensing with fecundity and longevity. Social insect queens apparently defy the fecundity / longevity trade-off as they are both, extremely long-lived and highly fecund. Here, we have examined the effects of a protein-enriched diet on these life-history traits and on tissue-specific gene expression in a termite species of low social complexity.ResultsOn a colony level, we did not observe reduced lifespan and increased fecundity, effects typically seen in solitary model organisms, after protein enrichment. Instead, on the individual level mortality was reduced in queens that consumed more of the protein-enriched diet – and partially also in workers – while fecundity seemed unaffected. Our transcriptome analyses supported our life-history results. Consistent with life span extension, the expression of IIS (insulin/insulin-like growth factor 1 signalling) components was reduced in fat bodies after protein enrichment. Interestingly, however, genes involved in reproductive physiology (e.g., vitellogenin) were largely unaffected in fat body and head transcriptomes.ConclusionThese results suggest that IIS is decoupled from downstream fecundity-associated pathways, which can contribute to the remoulding of the fecundity/longevity trade-off in termites as compared to solitary insects.
A systematic review and meta-analysis: the therapeutic and preventive effect of Lactobacillus reuteri DSM 17,938 addition in children with diarrhea
Authors: Sun Xiaoqi , Kong Juan , Zhu Shuotong , Liu Chengjiang 
Published: May 2023

AbstractObjectiveTo summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease.MethodsSearch for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators.Results963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78–0.97) and day 2 (RR = 0.61, 95%CI: 0.44–0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68–1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78–2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77–4.05), and diarrhea (RR = 1.35, 95%CI: 0.95–1.92).ConclusionAddition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention.
Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis
Authors: Ma J-B , Zeng L-C , Ren F , Dang L-Y , Luo H , Wu Y-Q , Yang X-J , Li R , Yang H , Xu Y 
Published: May 2023

Abstract
Background
The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB).

Methods
This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi’an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model.

Results
Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes.

Conclusions
We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.
Profile of partners who completed HIV testing and received a new HIV diagnosis in Ukraine’s HIV index testing program: a retrospective cohort study to inform program improvement
Authors: Puttkammer Nancy , Ihnatiuk Alyona , Shapoval Anna , Kazanzhy Anna , Secor Andrew , Shotorbani Solmaz , McDowell Misti , Golden Matthew 
Published: May 2023

AbstractBackgroundApproximately one-third of people living with HIV in Ukraine are unaware of their HIV status. Index testing (IT) is an evidence-based HIV testing strategy that supports voluntary notification of partners with HIV risk, so they can receive HIV testing, prevention, and treatment services.MethodsUkraine scaled up IT services in 2019. This observational study of Ukraine’s IT program covered 39 health facilities located in 11 regions with high HIV burden. The study used routine program data from January—December 2020 to describe the profile of named partners and explore index client (IC) and partner factors associated with two outcomes: 1) completing testing; and 2) HIV case finding. Analysis used descriptive statistics and multilevel linear mixed regression models.ResultsThe study included 8,448 named partners, of whom 6,959 had unknown HIV status. Among them,72.2% completed HIV testing and 19.4% of those tested were newly diagnosed with HIV. Two-thirds of all new cases were among partners of ICs who were recently diagnosed and enrolled in care (< 6 months), while one third were among partners of established ICs. In adjusted analysis, partners of ICs with unsuppressed HIV viral load (VL) were less likely to complete HIV testing (adjusted odds ratio [aOR] = 0.11,p < 0.001), but more likely to receive a new HIV diagnosis (aOR = 1.92,p < 0.001). Partners of ICs who cited injection drug use or having a known HIV + partner as their own reason for testing were more likely to receive a new HIV diagnosis (aOR = 1.32,p = 0.04 and aOR = 1.71,p < 0.001 respectively). Involving providers in the partner notification process was associated with completed testing (aOR = 1.76,p = 0.001) and HIV case finding (aOR = 1.64,p < 0.01), compared with notification by ICs.ConclusionHIV case detection was highest among partners of recently diagnosed ICs, but IT participation among established ICs still yielded an important share of all newly-identified HIV cases. Areas for improvement in Ukraine’s IT program include completing testing for partners of ICs with unsuppressed HIV VL, with history of injection drug use or discordant partnerships. Using intensified follow-up for the sub-groups at risk of incomplete testing may be practical. Greater use of provider-assisted notification could also accelerate HIV case finding.
Associations between macular retinal vasculature and severity of idiopathic epiretinal membrane
Authors: Hsia Yun , Hsieh Yi-Ting 
Published: May 2023

Abstract
Background
To demonstrate the associations between the morphology of macular retinal vasculature and disease severity of idiopathic epiretinal membrane (ERM).

Methods
Macular structures were assessed using optical coherence tomography (OCT), and were classified as “with pseudohole” or “without pseudohole”. The 3 × 3 mm macular OCT angiography images were analyzed using the Fiji software to obtain the vessel density, skeleton density, average vessel diameter, vessel tortuosity, fractal dimension, and foveal avascular zone (FAZ)-related parameters. The correlations between these parameters and ERM grading as well as visual acuity were analyzed.

Results
For ERM with or without a pseudohole, increased average vessel diameter, decreased skeleton density, and decreased vessel tortuosity were all associated with inner retinal folding and thickened inner nuclear layer, indicating more severe ERM. In 191 eyes without a pseudohole, the average vessel diameter increased, fractal dimension decreased and vessel tortuosity decreased with increasing ERM severity. The FAZ was not associated with ERM severity. Decreased skeleton density (r = -0.37), vessel tortuosity (r = -0.35), and increased average vessel diameter (r = 0.42) were correlated with worse visual acuity (All P < 0.001). In 58 eyes with pseudoholes, a larger FAZ was associated with a smaller average vessel diameter (r = -0.43, P = 0.015), higher skeleton density (r = 0.49, P < 0.001), and vessel tortuosity (r = 0.32, P = 0.015). However, none of the retinal vasculature parameters correlated with visual acuity and central foveal thickness.

Conclusion
Increased average vessel diameter, decreased skeleton density, decreased fractal dimension and decreased vessel tortuosity were good indicators of ERM severity and associated visual impairment.