bluuebunny/crossref_metadata_2025_split huggingface dataset:
An improved limit on the neutrinoless double-electron capture of $$^{36}$$Ar with GERDA
Authors:   GERDA Collaboration, Agostini M. , Alexander A. , Araujo G. R. , Bakalyarov A. M. , Balata M. , Barabanov I. , Baudis L. , Bauer C. , Belogurov S. , Bettini A. , Bezrukov L. , Biancacci V. , Bossio E. , Bothe V. , Brudanin V. , Brugnera R. , Caldwell A. , Cattadori C. , Chernogorov A. , Comellato T. , D’Andrea V. , Demidova E. V. , Marco N. Di , Doroshkevich E. , Fischer F. , Fomina M. , Gangapshev A. , Garfagnini A. , Gooch C. , Grabmayr P. , Gurentsov V. , Gusev K. , Hakenmüller J. , Hemmer S. , Hofmann W. , Huang J. , Hult M. , Inzhechik L. V. , Csáthy J. Janicskó , Jochum J. , Junker M. , Kazalov V. , Kermaïdic Y. , Khushbakht H. , Kihm T. , Kilgus K. , Kirpichnikov I. V. , Klimenko A. , Kneißl R. , Knöpfle K. T. , Kochetov O. , Kornoukhov V. N. , Korošec M. , Krause P. , Kuzminov V. V. , Laubenstein M. , Lindner M. , Lippi I. , Lubashevskiy A. , Lubsandorzhiev B. , Lutter G. , Macolino C. , Majorovits B. , Maneschg W. , Manzanillas L. , Marshall G. , Misiaszek M. , Morella M. , Müller Y. , Nemchenok I. , Pandola L. , Pelczar K. , Pertoldi L. , Piseri P. , Pullia A. , Ransom C. , Rauscher L. , Redchuk M. , Riboldi S. , Rumyantseva N. , Sada C. , Salamida F. , Schönert S. , Schreiner J. , Schütt M. , Schütz A.-K. , Schulz O. , Schwarz M. , Schwingenheuer B. , Selivanenko O. , Shevchik E. , Shirchenko M. , Shtembari L. , Simgen H. , Smolnikov A. , Stukov D. , Vasenko A. A. , Veresnikova A. , Vignoli C. , Sturm K. von , Wester T. , Wiesinger C. , Wojcik M. , Yanovich E. , Zatschler B. , Zhitnikov I. , Zhukov S. V. , Zinatulina D. , Zschocke A. , Zsigmond A. J. , Zuber K. , Zuzel G. 
Published: January 2024

AbstractThe GERmanium Detector Array (Gerda) experiment operated enriched high-purity germanium detectors in a liquid argon cryostat, which contains 0.33% of $$^{36}$$

36

Ar, a candidate isotope for the two-neutrino double-electron capture (2$$\nu $$
ν
ECEC) and therefore for the neutrinoless double-electron capture (0$$\nu $$
ν
ECEC). If detected, this process would give evidence of lepton number violation and the Majorana nature of neutrinos. In the radiative 0$$\nu $$
ν
ECEC of $$^{36}$$

36

Ar, a monochromatic photon is emitted with an energy of 429.88 keV, which may be detected by the Gerda germanium detectors. We searched for the $$^{36}$$

36

Ar 0$$\nu $$
ν
ECEC with Gerda data, with a total live time of 4.34 year (3.08 year accumulated during Gerda Phase II and 1.26 year during Gerda Phase I). No signal was found and a 90% CL lower limit on the half-life of this process was established $$T_{1/2} >1.5\cdot 10^{22} $$

T

1
/
2

>
1.5
·

10
22

year.
Bifurcation diagrams for spacetime singularities and black holes
Authors: Cotsakis Spiros 
Published: January 2024

AbstractWe reexamine the focusing effect crucial to the theorems that predict the emergence of spacetime singularities and various results in the general theory of black holes in general relativity. Our investigation incorporates the fully nonlinear and dispersive nature of the underlying equations. We introduce and thoroughly explore the concept of versal unfolding (topological normal form) within the framework of the Newman–Penrose–Raychaudhuri system, the convergence-vorticity equations (notably the first and third Sachs optical equations), and the Oppenheimer–Snyder equation governing exactly spherical collapse. The findings lead to a novel dynamical depiction of spacetime singularities and black holes, exposing their continuous transformations into new topological configurations guided by the bifurcation diagrams associated with these problems.
Alarm or emotion? intranasal oxytocin helps determine information conveyed by dog barks for adult male human listeners
Authors: Pongrácz Péter , Lugosi Csenge Anna , Szávai Luca , Gengeliczky Atina , Jégh-Czinege Nikolett , Faragó Tamás 
Published: January 2024

Abstract
Background
Barks play an important role in interspecific communication between dogs and humans, by allowing a reliable perception of the inner state of dogs for human listeners. However, there is growing concern in society regarding the nuisance that barking dogs cause to the surrounding inhabitants. We assumed that at least in part, this nuisance effect can be explained by particular communicative functions of dog barks. In this study we experimentally tested two separate hypotheses concerning how the content of dog barks could affect human listeners. According to the first hypothesis, barks that convey negative inner states, would especially cause stress in human listeners due to the process called interspecific empathy. Based on the second hypothesis, alarm-type dog barks cause particularly strong stress in the listener, by capitalizing on their specific acoustic makeup (high pitch, low tonality) that resembles to the parameters of a baby’s cry. We tested 40 healthy, young adult males in a double-blind placebo controlled experiment, where participants received either intranasal oxytocin or placebo treatment. After an incubation period, they had to evaluate the (1) perceived emotions (happiness, fear and aggression), that specifically created dog bark sequences conveyed to them; and (2) score the annoyance level these dog barks elicited in them.

Results
We found that oxytocin treatment had a sensitizing effect on the participants’ reactions to negative valence emotions conveyed by dog barks, as they evaluated low fundamental frequency barks with higher aggression scores than the placebo-treated participants did. On the other hand, oxytocin treatment attenuated the annoyance that noisy (atonal) barks elicited from the participants.

Conclusions
Based on these results, we provide first-hand evidence that dog barks provide information to humans (which may also cause stress) in a dual way: through specific attention-grabbing functions and through emotional understanding.
Classification of bruxism based on time-frequency and nonlinear features of single channel EEG
Authors: Wang Chunwu , Verma Ajay K. , Guragain Bijay , Xiong Xin , Liu Chunling 
Published: January 2024

Abstract
Background
In the classification of bruxism patients based on electroencephalogram (EEG), feature extraction is essential. The method of using multi-channel EEG fusing electrocardiogram (ECG) and Electromyography (EMG) signal features has been proved to have good performance in bruxism classification, but the classification performance based on single channel EEG signal is still understudied. We investigate the efficacy of single EEG channel in bruxism classification.

Methods
We have extracted time-domain, frequency-domain, and nonlinear features from single EEG channel to classify bruxism. Five common bipolar EEG recordings from 2 bruxism patients and 4 healthy controls during REM sleep were analyzed. The time domain (mean, standard deviation, root mean squared value), frequency domain (absolute, relative and ratios power spectral density (PSD)), and non-linear features (sample entropy) of different EEG frequency bands were analyzed from five EEG channels of each participant. Fine tree algorithm was trained and tested for classifying sleep bruxism with healthy controls using five-fold cross-validation.

Results
Our results demonstrate that the C4P4 EEG channel was most effective for classification of sleep bruxism that yielded 95.59% sensitivity, 98.44% specificity, 97.84% accuracy, and 94.20% positive predictive value (PPV).

Conclusions
Our results illustrate the feasibility of sleep bruxism classification using single EEG channel and provides an experimental foundation for the development of a future portable automatic sleep bruxism detection system.
Scaffold-based 3D cell culture models in cancer research
Authors: Abuwatfa Waad H. , Pitt William G. , Husseini Ghaleb A. 
Published: January 2024

AbstractThree-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions between cancer cells and their surrounding stroma. Tumors consist not only of cancer cells but also various other cell types, including stromal cells, immune cells, and blood vessels. These models bridge traditional 2D cell cultures and animal models, offering a cost-effective, scalable, and ethical alternative for preclinical research. As the field advances, 3D cell cultures are poised to play a pivotal role in understanding cancer biology and accelerating the development of effective anticancer therapies. This review article highlights the key advantages of 3D cell cultures, progress in the most common scaffold-based culturing techniques, pertinent literature on their applications in cancer research, and the ongoing challenges.
Graphical Abstract
Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases
Authors: Sun Yuchen , Saito Kosuke , Ushiki Atsuhito , Abe Mitsuhiro , Saito Yoshinobu , Kashiwada Takeru , Horimasu Yasushi , Gemma Akihiko , Tatsumi Koichiro , Hattori Noboru , Tsushima Kenji , Takemoto Kazuhisa , Ishikawa Rika , Momiyama Toshiko , Matsuyama Shin-ichiro , Arakawa Noriaki , Akane Hirotoshi , Toyoda Takeshi , Ogawa Kumiko , Sato Motonobu , Takamatsu Kazuhiko , Mori Kazuhiko , Nishiya Takayoshi , Izumi Takashi , Ohno Yasuo , Saito Yoshiro , Hanaoka Masayuki 
Published: January 2024

Abstract
Background
Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need.

Methods
Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls.

Results
Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients.

Conclusions
The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.
Microaerobic insights into production of polyhydroxyalkanoates containing 3-hydroxyhexanoate via native reverse β-oxidation from glucose in Ralstonia eutropha H16
Authors: Huong Kai-Hee , Orita Izumi , Fukui Toshiaki 
Published: January 2024

Abstract
Background
Ralstonia eutropha H16, a facultative chemolitoautotroph, is an important workhorse for bioindustrial production of useful compounds such as polyhydroxyalkanoates (PHAs). Despite the extensive studies to date, some of its physiological properties remain not fully understood.

Results
This study demonstrated that the knallgas bacterium exhibited altered PHA production behaviors under slow-shaking condition, as compared to its usual aerobic condition. One of them was a notable increase in PHA accumulation, ranging from 3.0 to 4.5-fold in the mutants lacking of at least two NADPH-acetoacetyl-CoA reductases (PhaB1, PhaB3 and/or phaB2) when compared to their respective aerobic counterpart, suggesting the probable existence of (R)-3HB-CoA-providing route(s) independent on PhaBs. Interestingly, PHA production was still considerably high even with an excess nitrogen source under this regime. The present study further uncovered the conditional activation of native reverse β-oxidation (rBOX) allowing formation of (R)-3HHx-CoA, a crucial precursor for poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)], solely from glucose. This native rBOX led to the natural incorporation of 3.9 mol% 3HHx in a triple phaB-deleted mutant (∆phaB1∆phaB1∆phaB2-C2). Gene deletion experiments elucidated that the native rBOX was mediated by previously characterized (S)-3HB-CoA dehydrogenases (PaaH1/Had), β-ketothiolase (BktB), (R)-2-enoyl-CoA hydratase (PhaJ4a), and unknown crotonase(s) and reductase(s) for crotonyl-CoA to butyryl-CoA conversion prior to elongation. The introduction of heterologous enzymes, crotonyl-CoA carboxylase/reductase (Ccr) and ethylmalonyl-CoA decarboxylase (Emd) along with (R)-2-enoyl-CoA hydratase (PhaJ) aided the native rBOX, resulting in remarkably high 3HHx composition (up to 37.9 mol%) in the polyester chains under the low-aerated condition.

Conclusion
These findings shed new light on the robust characteristics of Ralstonia eutropha H16 and have the potential for the development of new strategies for practical P(3HB-co-3HHx) copolyesters production from sugars under low-aerated conditions.

Graphical Abstract
A neural network with a human learning paradigm for breast fibroadenoma segmentation in sonography
Authors: Guo Yongxin , Chen Maoshan , Yang Lei , Yin Heng , Yang Hongwei , Zhou Yufeng 
Published: January 2024

Abstract
Background
Breast fibroadenoma poses a significant health concern, particularly for young women. Computer-aided diagnosis has emerged as an effective and efficient method for the early and accurate detection of various solid tumors. Automatic segmentation of the breast fibroadenoma is important and potentially reduces unnecessary biopsies, but challenging due to the low image quality and presence of various artifacts in sonography.

Methods
Human learning involves modularizing complete information and then integrating it through dense contextual connections in an intuitive and efficient way. Here, a human learning paradigm was introduced to guide the neural network by using two consecutive phases: the feature fragmentation stage and the information aggregation stage. To optimize this paradigm, three fragmentation attention mechanisms and information aggregation mechanisms were adapted according to the characteristics of sonography. The evaluation was conducted using a local dataset comprising 600 breast ultrasound images from 30 patients at Suining Central Hospital in China. Additionally, a public dataset consisting of 246 breast ultrasound images from Dataset_BUSI and DatasetB was used to further validate the robustness of the proposed network. Segmentation performance and inference speed were assessed by Dice similarity coefficient (DSC), Hausdorff distance (HD), and training time and then compared with those of the baseline model (TransUNet) and other state-of-the-art methods.

Results
Most models guided by the human learning paradigm demonstrated improved segmentation on the local dataset with the best one (incorporating C3ECA and LogSparse Attention modules) outperforming the baseline model by 0.76% in DSC and 3.14 mm in HD and reducing the training time by 31.25%. Its robustness and efficiency on the public dataset are also confirmed, surpassing TransUNet by 0.42% in DSC and 5.13 mm in HD.

Conclusions
Our proposed human learning paradigm has demonstrated the superiority and efficiency of ultrasound breast fibroadenoma segmentation across both public and local datasets. This intuitive and efficient learning paradigm as the core of neural networks holds immense potential in medical image processing.
Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome
Authors: Zheng Na , Long Yihao , Bai Zixuan , Li Jianing , Wang Hongyu , Song Dan-Dan , Liu Hong-Lin , Shi Jian-Hong , Zhao Shuli 
Published: January 2024

AbstractBackgroundChimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood.MethodsIn this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells.ResultsOur findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy.ConclusionThe study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.
Update on the association between Helicobacter pylori infection and asthma in terms of microbiota and immunity
Authors: Liu Mengmeng , Wang Yong , Du Bing 
Published: January 2024

AbstractH. pylori is a gram-negative bacterium that is usually acquired in childhood and can persistently colonize the gastric mucosa of humans, affecting approximately half of the world’s population. In recent years, the prevalence of H. pylori infection has steadily reduced while the risk of allergic diseases has steadily climbed. As a result, epidemiological research indicates a strong negative association between the two. Moreover, numerous experimental studies have demonstrated that eradicating H. pylori increases the risk of allergic diseases. Hence, it is hypothesized that H. pylori infection may act as a safeguard against allergic diseases. The hygiene hypothesis, alterations in gut microbiota, the development of tolerogenic dendritic cells, and helper T cells could all be involved in H. pylori’s ability to protect against asthma. Furthermore, Studies on mice models have indicated that H. pylori and its extracts are crucial in the management of asthma. We reviewed the in-depth studies on the most recent developments in the relationship between H. pylori infection and allergic diseases, and we discussed potential mechanisms of the infection’s protective effect on asthma in terms of microbiota and immunity. We also investigated the prospect of the application of H. pylori and its related components in asthma, so as to provide a new perspective for the prevention or treatment of allergic diseases.
Accelerometer-derived sleep metrics in mild and difficult-to-treat asthma
Authors: Sharma Varun , Ricketts Helen Clare , Steffensen Femke , Goodfellow Anna , Buchan Duncan S , Cowan Douglas C 
Published: January 2024

Abstract
Introduction
Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations.

Methods
We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma. Participants wore accelerometers for 24-hours/day for seven days.

Results
Of 124 participants (44 mild, 80 difficult-to-treat), no between-group differences were observed in sleep-window, sleep-time, sleep efficiency or wake time. Sleep-onset time was ~ 40 min later in the difficult-to-treat group (p = 0.019).

Discussion
Broadly, we observed no difference in accelerometer-derived sleep-metrics between mild and difficult-to-treat asthma. This is the largest analysis of accelerometer-derived sleep parameters in asthma and the first comparing groups by asthma severity. Sleep-onset initiation may be delayed in difficult-to-treat asthma but a dedicated study is needed to confirm.
Subcutaneous dirofilariasis in a 25-year-old male patient in Belgium on ultrasonography: a case report
Authors: Klerkx Scott , Venstermans Caroline 
Published: January 2024

Abstract
Background
Subcutaneous dirofilariasis is a parasitic zoonosis commonly described in Canidae but rarely seen in humans. Most physicians are unfamiliar with this disease, especially in nonendemic areas, which can lead to medication error and diagnostic and treatment delay. To the best of our knowledge, no previous case of subcutaneous dirofilariasis preoperatively diagnosed on ultrasound has been described in Western Europe.

Case presentation
A 25-year-old Belgian male patient presented with a subcutaneous nodule in the epigastric region. Ultrasound investigation showed a typical cystic lesion with an internal serpiginous structure with echogenic lines, and there was active twirling movement of this serpentine structure during investigation, pathognomonic for subcutaneous dirofilariasis. Surgical extirpation was performed, and the diagnosis was histopathologically confirmed.

Conclusion
Subcutaneous dirofilariasis has a characteristic appearance on ultrasound but is not well known in nonendemic areas, often leading to diagnostic delay and initial incorrect treatment. More knowledge of this disease and of its characteristic ultrasound appearance will hopefully lead to better patient care.