bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota develop towards an adult profile in a sex-specific manner during puberty
Authors: Korpela Katri , Kallio Sampo , Salonen Anne , Hero Matti , Kukkonen Anna Kaarina , Miettinen Päivi J. , Savilahti Erkki , Kohva Ella , Kariola Laura , Suutela Maria , Tarkkanen Annika , de Vos Willem M. , Raivio Taneli , Kuitunen Mikael 
Published: December 2021

AbstractAccumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006—Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337. The adult-comparison cohort (HELMi) is NCT03996304.
Non-monotonic variation of the Kramers point band gap with increasing magnetic doping in BiTeI
Authors: Shikin A. M. , Rybkina A. A. , Estyunin D. A. , Klimovskikh I. I. , Rybkin A. G. , Filnov S. O. , Koroleva A. V. , Shevchenko E. V. , Likholetova M. V. , Voroshnin V. Yu. , Petukhov A. E. , Kokh K. A. , Tereshchenko O. E. , Petaccia L. , Di Santo G. , Kumar S. , Kimura A. , Skirdkov P. N. , Zvezdin K. A. , Zvezdin A. K. 
Published: December 2021

AbstractPolar Rashba-type semiconductor BiTeI doped with magnetic elements constitutes one of the most promising platforms for the future development of spintronics and quantum computing thanks to the combination of strong spin-orbit coupling and internal ferromagnetic ordering. The latter originates from magnetic impurities and is able to open an energy gap at the Kramers point (KP gap) of the Rashba bands. In the current work using angle-resolved photoemission spectroscopy (ARPES) we show that the KP gap depends non-monotonically on the doping level in case of V-doped BiTeI. We observe that the gap increases with V concentration until it reaches 3% and then starts to mitigate. Moreover, we find that the saturation magnetisation of samples under applied magnetic field studied by superconducting quantum interference device (SQUID) magnetometer has a similar behaviour with the doping level. Theoretical analysis shows that the non-monotonic behavior can be explained by the increase of antiferromagnetic coupled atoms of magnetic impurity above a certain doping level. This leads to the reduction of the total magnetic moment in the domains and thus to the mitigation of the KP gap as observed in the experiment. These findings provide further insight in the creation of internal magnetic ordering and consequent KP gap opening in magnetically-doped Rashba-type semiconductors.
Preclinical therapeutics ex ovo quail eggs as a biomimetic automation-ready xenograft platform
Authors: Rasmussen Samuel V. , Berlow Noah E. , Price Lisa Hudson , Mansoor Atiya , Cairo Stefano , Rugonyi Sandra , Keller Charles 
Published: December 2021

AbstractPreclinical cancer research ranges from in vitro studies that are inexpensive and not necessarily reflective of the tumor microenvironment to mouse studies that are better models but prohibitively expensive at scale. Chorioallantoic membrane (CAM) assays utilizing Japanese quail (Coturnix japonica) are a cost-effective screening method to precede and minimize the scope of murine studies for anti-cancer efficacy and drug toxicity. To increase the throughput of CAM assays we have built and optimized an 11-day platform for processing up to 200 quail eggs per screening to evaluate drug efficacy and drug toxicity caused by a therapeutic. We demonstrate ex ovo concordance with murine in vivo studies, even when the in vitro and in vivo studies diverge, suggesting a role for this quail shell-free CAM xenograft assay in the validation of new anti-cancer agents.
The association between gut microbiome affecting concomitant medication and the effectiveness of immunotherapy in patients with stage IV NSCLC
Authors: Verschueren M. V. , van der Welle C. M. Cramer - , Tonn M. , Schramel F. M. N. H. , Peters B. J. M. , van de Garde E. M. W. 
Published: December 2021

AbstractSeveral observational studies suggested that gut microbiome-affecting-medication impairs the effectiveness of immunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is affected by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. In a retrospective matched cohort study, immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding rather than disturbing the composition of the microbiome.
New statistical model for misreported data with application to current public health challenges
Authors: Moriña David , Fernández-Fontelo Amanda , Cabaña Alejandra , Puig Pedro 
Published: December 2021

AbstractThe main goal of this work is to present a new model able to deal with potentially misreported continuous time series. The proposed model is able to handle the autocorrelation structure in continuous time series data, which might be partially or totally underreported or overreported. Its performance is illustrated through a comprehensive simulation study considering several autocorrelation structures and three real data applications on human papillomavirus incidence in Girona (Catalonia, Spain) and Covid-19 incidence in two regions with very different circumstances: the early days of the epidemic in the Chinese region of Heilongjiang and the most current data from Catalonia.
A novel paper MAP method for rapid high resolution histological analysis
Authors: Lee Mirae , Woo Jiwon , Kim Doh-Hee , Yang Yu-Mi , Lee Eunice Yoojin , Kim Jung-Hee , Kang Seok-Gu , Shim Jin-Kyung , Park Jeong-Yoon 
Published: December 2021

AbstractThree-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer’s disease and glioma.
PCBP1 regulates the transcription and alternative splicing of metastasis‑related genes and pathways in hepatocellular carcinoma
Authors: Huang Shuai , Luo Kai , Jiang Li , Zhang Xu-Dong , Lv Ying-Hao , Li Ren-Feng 
Published: December 2021

AbstractPCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.
A single dose of Ultraviolet-A induces proteome remodeling and senescence in primary human keratinocytes
Authors: Valerio Hellen Paula , Ravagnani Felipe Gustavo , Ronsein Graziella Eliza , Di Mascio Paolo 
Published: December 2021

AbstractEpidermal photoaging contributes to skin fragility over time and it is a risk factor for skin cancer. Photoaging has been associated for a long time with exposure to Ultraviolet-A (UVA) light, the predominant component of the solar ultraviolet radiation. While the cellular mechanisms underlying UVA-induced photoaging in the dermis have been well characterized, UVA’s action on the epidermis remains elusive. Here, proteomic analysis was conducted to derive the cellular responses induced by an environmentally relevant dose of UVA in primary human keratinocytes. We also investigated the effects of UVA on non-transformed immortalized keratinocytes (HaCaT cells), bearing potentially oncogenic mutations. We showed that UVA induces proteome remodeling and senescence in primary keratinocytes, eliciting potent antioxidant and pro-inflammatory responses. Additionally, we showed that UVA modulates the secretory phenotype of these cells to the extent of inducing paracrine oxidative stress and immune system activation in pre-malignant keratinocytes. These observations offer insights into the cellular mechanisms by which UVA drives photoaging in the skin.
A machine learning pipeline revealing heterogeneous responses to drug perturbations on vascular smooth muscle cell spheroid morphology and formation
Authors: Vaidyanathan Kalyanaraman , Wang Chuangqi , Krajnik Amanda , Yu Yudong , Choi Moses , Lin Bolun , Jang Junbong , Heo Su-Jin , Kolega John , Lee Kwonmoo , Bae Yongho 
Published: December 2021

AbstractMachine learning approaches have shown great promise in biology and medicine discovering hidden information to further understand complex biological and pathological processes. In this study, we developed a deep learning-based machine learning algorithm to meaningfully process image data and facilitate studies in vascular biology and pathology. Vascular injury and atherosclerosis are characterized by neointima formation caused by the aberrant accumulation and proliferation of vascular smooth muscle cells (VSMCs) within the vessel wall. Understanding how to control VSMC behaviors would promote the development of therapeutic targets to treat vascular diseases. However, the response to drug treatments among VSMCs with the same diseased vascular condition is often heterogeneous. Here, to identify the heterogeneous responses of drug treatments, we created an in vitro experimental model system using VSMC spheroids and developed a machine learning-based computational method called HETEROID (heterogeneous spheroid). First, we established a VSMC spheroid model that mimics neointima-like formation and the structure of arteries. Then, to identify the morphological subpopulations of drug-treated VSMC spheroids, we used a machine learning framework that combines deep learning-based spheroid segmentation and morphological clustering analysis. Our machine learning approach successfully showed that FAK, Rac, Rho, and Cdc42 inhibitors differentially affect spheroid morphology, suggesting that multiple drug responses of VSMC spheroid formation exist. Overall, our HETEROID pipeline enables detailed quantitative drug characterization of morphological changes in neointima formation, that occurs in vivo, by single-spheroid analysis.
Correlation between elastic modulus and clinical severity of pathological scars: a cross-sectional study
Authors: Hang Jing , Chen Jie , Zhang Weixin , Yuan Tao , Xu Yang , Zhou Bingrong 
Published: December 2021

AbstractThough widely used to assess pathological scars, the modified Vancouver Scar Scale (mVSS) is neither convenient nor objective. Shear wave elastography (SWE) is used to evaluate the stiffness of pathological scars. We aimed to determine the correlation between mVSS score and elastic modulus (EM) measured by SWE for pathological scars. Clinical information including ultrasound (US) results of the enrolled patients with pathological scars was analyzed. The clinical severity of the pathological scars was evaluated by mVSS. Skin stiffness, as represented by EM, was calculated using SWE. The average EM of the whole scar (EMWHOLE), hardest part of the scar (EMHARDEST), and normal appearance of the skin around the scar (EMNORMAL) were also recorded. Enrolled in this study were 69 pathological scars, including 28 hypertrophic scars and 41 keloids. The univariable regression analyses showed that the EM of pathological scars was closely related to mVSS score, while the linear multivariable regression analyses showed no significantly correlation. Curve fitting and threshold effect analysis revealed that when EMWHOLE was less than 166.6 kPa or EMHARDEST was less than 133.07 kPa, EM was positively correlated with mVSS score. In stratified analysis, there was no significant linear correlation and threshold effect between EMWHOLE and mVSS score in hypertrophic scars or keloids. However, the fully adjusted smooth curves presented a linear association between mVSS score and EMHARDEST in keloids (the adjusted β [95% CI] was 0.010 [0.001, 0.018]), but a threshold and nonlinear association were found in hypertrophic scars. When EMHARDEST was less than 156.13 kPa, the mVSS score increased along with the hardest scar part stiffness; the adjusted β (95% CI) was 0.024 (0.009, 0.038). In conclusion, EM of pathological scars measured by SWE were correlated with mVSS within a threshold range, and showed different association patterns in hypertrophic scars and keloids.
The agglomeration and dispersion dichotomy of human settlements on Earth
Authors: Strano Emanuele , Simini Filippo , De Nadai Marco , Esch Thomas , Marconcini Mattia 
Published: December 2021

AbstractHuman settlements on Earth are scattered in a multitude of shapes, sizes and spatial arrangements. These patterns are often not random but a result of complex geographical, cultural, economic and historical processes that have profound human and ecological impacts. However, little is known about the global distribution of these patterns and the spatial forces that creates them. This study analyses human settlements from high-resolution satellite imagery and provides a global classification of spatial patterns. We find two emerging classes, namely agglomeration and dispersion. In the former, settlements are fewer than expected based on the predictions of scaling theory, while an unexpectedly high number of settlements characterizes the latter. To explain the observed spatial patterns, we propose a model that combines two agglomeration forces and simulates human settlements’ historical growth. Our results show that our model accurately matches the observed global classification (F1: 0.73), helps to understand and estimate the growth of human settlements and, in turn, the distribution and physical dynamics of all human settlements on Earth, from small villages to cities.
Impact of reducing day 1 dexamethasone dose in anthracycline-containing regimens on acute gastrointestinal symptoms associated with breast cancer treatment
Authors: Saito Yoshitaka , Takekuma Yoh , Takeshita Takashi , Sugawara Mitsuru 
Published: December 2021

AbstractThe potential of steroid sparing from day 2 onward is reported in anthracycline-containing regimens for breast cancer treatment. We evaluated whether the reduction of dexamethasone (DEX) dose from 9.9 to 6.6 mg on day 1 is possible in anthracycline-containing treatments. Patients receiving anthracycline-containing regimens were divided into control (9.9 mg DEX on day 1) and reduced (6.6 mg DEX on day 1) groups, and retrospectively evaluated. The complete response (CR) rate and the incidence and severity of nausea, vomiting, anorexia, and fatigue were evaluated. The CR rate in the acute phase (day 1) was 63.1% and 38.1% in the control and reduced groups, respectively, with significant difference (P = 0.01) between the groups. However, no difference was found in the delayed phase (days 2–7). The incidence of anorexia and vomiting during treatment was not statistically different. Severity of nausea tended to, but not statistically, worsen while anorexia significantly worsened in the reduced group. Multivariate analysis suggested that patients < 55 years, with non- or less-alcohol drinking habit (< 5 days/week), and administered reduced-DEX dosage on day 1, have a higher risk of acute nausea development. Thus, reducing day 1 DEX dose in anthracycline-containing regimens is not suitable for acute nausea management.
Oscillatory electroencephalographic patterns of arithmetic problem solving in fourth graders
Authors: Brunner Clemens , Koren Nikolaus A. , Scheucher Judith , Mosbacher Jochen A. , De Smedt Bert , Grabner Roland H. , Vogel Stephan E. 
Published: December 2021

AbstractNumerous studies have identified neurophysiological correlates of performing arithmetic in adults. For example, oscillatory electroencephalographic (EEG) patterns associated with retrieval and procedural strategies are well established. Whereas fact retrieval has been linked to enhanced left-hemispheric theta ERS (event-related synchronization), procedural strategies are accompanied by increased bilateral alpha ERD (event-related desynchronization). It is currently not clear if these findings generalize to children. Our study is the first to investigate oscillatory EEG activity related to strategy use and arithmetic operations in children. We assessed ERD/ERS correlates of 31 children in fourth grade (aged between nine and ten years) during arithmetic problem solving. We presented multiplication and subtraction problems, which children solved with fact retrieval or a procedure. We analyzed these four problem categories (retrieved multiplications, retrieved subtractions, procedural multiplications, and procedural subtractions) in our study. In summary, we found similar strategy-related patterns to those reported in previous studies with adults. That is, retrieval problems elicited stronger left-hemispheric theta ERS and weaker alpha ERD as compared to procedural problems. Interestingly, we observed neurophysiological differences between multiplications and subtractions within retrieval problems. Although there were no response time or accuracy differences, retrieved multiplications were accompanied by larger theta ERS than retrieved subtractions. This finding could indicate that retrieval of multiplication and subtraction facts are distinct processes, and/or that multiplications are more frequently retrieved than subtractions in this age group.
Dogs (canis familiaris) underestimate the quantity of connected items: first demonstration of susceptibility to the connectedness illusion in non-human animals
Authors: Lõoke Miina , Marinelli Lieta , Agrillo Christian , Guérineau Cécile , Mongillo Paolo 
Published: December 2021

AbstractIn humans, numerical estimation is affected by perceptual biases, such as those originating from the spatial arrangement of elements. Different animal species can also make relative quantity judgements. This includes dogs, who have been proposed as a good model for comparative neuroscience. However, dogs do not show the same perceptual biases observed in humans. Thus, the exact perceptual/cognitive mechanisms underlying quantity estimations in dogs and their degree of similarity with humans are still a matter of debate. Here we explored whether dogs are susceptible to the connectedness illusion, an illusion based on the tendency to underestimate the quantity of interconnected items. Dogs were first trained to choose the larger of two food arrays. Then, they were presented with two arrays containing the same quantity of food, of which one had items interconnected by lines. Dogs significantly selected the array with unconnected items, suggesting that, like in humans, connectedness determines underestimation biases, possibly disrupting the perceptual system’s ability to segment the display into discrete objects. The similarity in dogs’ and humans’ susceptibility to the connectedness, but not to other numerical illusions, suggests that different mechanisms are involved in the estimation of quantity of stimuli with different characteristics.