bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentation of Perforator Flap Blood Supply with Vascular Supercharge or Flap Prefabrication: Evaluation in a Rat Model
Authors: Huang Xin , Liu Daiming , Gu Shuchen , Pu Lee L. Q. , Xu Xiangwen , Khoong Yimin , Wang Zi , Zhao Yixuan , Gao Yashan , Zan Tao 
Published: April 2021

Background:
Vascular supercharge and flap prefabrication are two surgical maneuvers to improve flap blood supply. Although these techniques have been studied intensively, few studies have focused on the differences between supercharge and prefabricated flaps regarding their flap survival areas, vasculatures, and hemodynamics.

Methods:
In this study, 21 male Sprague-Dawley rats were divided into three groups as follows: group A, single perforator flap; group B, supercharge flap; and group C, prefabricated flap. Flap survival was measured 1 week after flap elevation. Indocyanine green angiography was applied to visualize flap vascularity and to analyze flap hemodynamics. Von Willebrand factor immunohistochemical staining was applied to assess the number of microvessels in the choke zone of the abdominal wall.

Results:
The flap survival areas were expanded significantly in the arteriovenous supercharge group and the vascular bundle prefabricated group compared with that in the single-perforator group (81.34 ± 8.12 percent and 75.51 ± 8.08 percent versus 46.27 ± 10.01 percent, respectively; p < 0.05). Hemodynamic analysis suggested that although a significant increase in arterial infusion could be achieved with flap prefabrication, the venous effusion of the prefabricated flap was the worst among the three groups, indicating greater susceptibility to compromised venous return. Active neovascularization was confirmed by an increased number of microvessels in group C. Specifically, the dilatation of choke vessels and the newly formed vessels of the prefabricated pedicle could be appreciated by indocyanine green angiographic mapping.

Conclusions:
Both vascular supercharge and flap prefabrication can augment the blood supply of the perforator flap but by means of different mechanisms. Because a supercharge flap is less susceptible to venous compromise, it is suggested to first consider the use of vascular supercharging when feasible.
Effect of Reduction Mammoplasty on Pulmonary Function Tests
Authors: Guliyeva Gunel , Cheung Joseph Y. , Avila Francisco R. , Huayllani Maria T. , Boczar Daniel , Broer Peter N. , Forte Antonio Jorge 
Published: April 2021

Abstract
In patients with breast hypertrophy, excessive breast weight applies pressure on the thorax, which may disrupt the normal breathing. The purpose of this study is to evaluate the impact of the breast hypertrophy and reduction mammoplasty on respiratory function. A comprehensive search of 3 databases, PubMed, Ovid, and Scopus databases, was performed. “Mammoplasty” and “respiration or pulmonary function tests” were the keywords used to search for relevant articles. Ten studies involving 280 patients with breast hypertrophy were included in the final review. Seven articles demonstrated an increase in at least 1 pulmonary function test value after the surgery. This systematic review revealed that, preoperatively, pulmonary function test values of the patients are usually in the normal range. Nonetheless, reduction mammoplasty still improves lung function parameters. Additionally, patients with respiratory complaints felt improvement in their symptoms after the surgery. However, future studies are needed, as heterogeneity among studies was observed.
Outcomes of Living Kidney Donor Candidate Evaluations in the Living Donor Collective Pilot Registry
Authors: Kasiske Bertram L. , Ahn Yoon Son , Conboy Michael , Dew Mary Amanda , Folken Christian , Levan Macey , Israni Ajay K. , Lentine Krista L. , Matas Arthur J. , Newell Kenneth A. , LaPointe Rudow Dianne , Massie Allan B. , Musgrove Donald , Snyder Jon J. , Taler Sandra J. , Wang Jeffrey , Waterman Amy D. 
Published: April 2021

Background.
Gaps in our knowledge of long-term outcomes affect decision making for potential living kidney donors.

Methods.
The Scientific Registry of Transplant Recipients was asked to determine the feasibility of a candidate registry.

Results.
Ten living kidney donor programs evaluated 2107 consecutive kidney donor candidates; 2099 of 2107 (99.6%) completed evaluations, 1578 of 2099 (75.2%) had a decision, and 790 of 1578 (50.1%) were approved to donate as of March 12, 2020. By logistic regression, candidates most likely to be approved were married or had attended college or technical school; those least likely to be approved had ≥1 of the following characteristics: Black race, history of cigarette smoking, and higher blood pressure, higher triglycerides, or higher urine albumin-to-creatinine ratios. Reasons for 617 candidates not being approved included medical issues other than chronic kidney disease risk (25.3%), chronic kidney disease risk (18.5%), candidate withdrawal (15.2%), recipient reason (13.6%), anatomical risk to the recipient (10.3%), noneconomic psychosocial (10.3%), economic (0.5%), and other reasons (6.4%).

Conclusions.
These results suggest that a comprehensive living donor registry is both feasible and necessary to assess long-term outcomes that may inform decision making for future living donor candidates. There may be socioeconomic barriers to donation that require more granular identification so that active measures can address inequities. Some candidates who did not donate may be suitable controls for discerning the appropriateness of acceptance decisions and the long-term outcomes attributable to donation. We anticipate that these issues will be better identified with modifications to the data collection and expansion of the registry to all centers over the next several years.
Integrative molecular and clinical profiling of acral melanoma identifies LZTR1 as a key tumor promoter and therapeutic target
Authors: Farshidfar Farshad , Peng Cong , Levovitz Chaya , Knight James , Bacchiocchi Antonella , Su Juan , Rhrissorrakrai Kahn , Yin Mingzhu , Sznol Mario , Ariyan Stephan , Clune James , Olino Kelly , Parida Laxmi , Nikolaus Joerg , Zhang Meiling , Zhao Shuang , Wang Yan , Huang Gang , Wan Miaojian , Li Xianan , Cao Jian , Yan Qin , Chen Xiang , Newman Aaron M. , Halaban Ruth 
Published: April 2021

ABSTRACTAcral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we performed integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We found that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 – a known tumor suppressor in other cancers – is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide new insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.
Early immune pressure imposed by tissue resident memory T cells sculpts tumour evolution in non-small cell lung cancer
Authors: Weeden Clare E , Gayevskiy Velimir , Trussart Marie , Marceaux Claire , Ribera Nina Tubau , Batey Daniel , Teh Charis E , Mitchell Andrew J , Antippa Phillip , Leong Tracy , Steinfort Daniel , Irving Louis , Gordon Claire L , Swanton Charles , Speed Terence P , Gray Daniel HD , Asselin-Labat Marie-Liesse 
Published: April 2021

AbstractTissue-resident memory T cells (TRM) provide immune defence against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRMactivation and how the immune pressure exerted by TRMaffects developing tumours in humans. We performed deep profiling of lung cancers arising in never-smokers (NS) and ever-smokers (ES), finding evidence of enhanced TRMimmunosurveillance in ES lung. Only tumours arising in ES patients underwent clonal immune escape, even when evaluating cancers with similar tumour mutational burden to NS patients, suggesting that the timing of immune pressure exerted by TRMis a critical factor in the evolution of tumour immune evasion. Tumours grown in T cell quiescent NS lungs displayed little evidence of immune evasion and had fewer neoantigens with low diversity, paradoxically making them amenable to treatment with agonist of the costimulatory molecule, ICOS. These data demonstrate local environmental insults enhance TRMimmunosurveillance of human tissue, shape the evolution of tumour immunogenicity and that this interplay informs effective immunotherapeutic modalities.
Decreased overall neuronal activity in a rodent model of impaired consciousness during absence seizures
Authors: McCafferty Cian , Gruenbaum Benjamin , Tung Renee , Li Jing-Jing , Salvino Peter , Vincent Peter , Kratochvil Zachary , Ryu Jun Hwan , Khalaf Aya , Swift Kohl , Akbari Rashid , Islam Wasif , Antwi Prince , Johnson Emily Ann , Vitkovskiy Petr , Sampognaro James , Freedman Isaac , Kundishora Adam , Sanganahalli Basavaraju G. , Herman Peter , Hyder Fahmeed , Crunelli Vincenzo , Depaulis Antoine , Blumenfeld Hal 
Published: April 2021

AbstractAbsence seizures are characterized by a brief behavioural impairment including apparent loss of consciousness. Neuronal mechanisms determining the behavioural impairment of absence seizures remain unknown, and their elucidation might highlight therapeutic options for reducing seizure severity. However, recent studies have questioned the similarity of animal spike-wave-discharges (SWD) to human absence seizures both behaviourally and neuronally. Here, we report that Genetic Absence Epilepsy Rats from Strasbourg recapitulate the decreased neuroimaging signals and loss of consciousness characteristic of human absence seizures. Overall neuronal firing is decreased but rhythmic in the somatosensory cortex and thalamus during these seizures. Interestingly, individual neurons in both regions tend to consistently express one of four distinct patterns of seizure-associated activity. These patterns differ in firing rate dynamics and in rhythmicity during seizure. One group of neurons showed a transient initial peak in firing at SWD onset, accounting for the brief initial increase in overall neuronal firing seen in cortex and thalamus. The largest group of neurons in both cortex and thalamus showed sustained decreases in firing during SWD. Other neurons showed either sustained increases or no change in firing. These findings suggest that certain classes of cortical and thalamic neurons may be particularly responsible for the paroxysmal oscillations and consequent loss of consciousness in absence epilepsy.
Developmental stage- and site-specific transitions in lineage specification and gene regulatory networks in human hematopoietic stem and progenitor cells
Authors: Roy Anindita , Wang Guanlin , Iskander Deena , O’Byrne Sorcha , Elliott Natalina , O’Sullivan Jennifer , Buck Gemma , Heuston Elisabeth F. , Wen Wei Xiong , Meira Alba Rodriguez , Hua Peng , Karadimitiris Anastasios , Mead Adam J , Bodine David , Roberts Irene , Psaila Bethan , Thongjuea Supat 
Published: April 2021

ABSTRACTHuman hematopoiesis is a dynamic process that startsin utero4 weeks post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartments change during human ontogeny and the underlying gene regulatory mechanisms, we compared 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identified significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Uncommitted stem cells showed progression from cycling to quiescence and increased inflammatory signalling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct timepoints in postnatal life – juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults.
Quantifying ERK-activity in response to inhibition of the BRAFV600E-MEK-ERK cascade using mathematical modelling
Authors: Hamis Sara , Kapelyukh Yury , McLaren Aileen , Henderson Colin J. , Wolf C. Roland , Chaplain Mark A.J. 
Published: April 2021

AbstractBackgroundSimultaneous inhibition of multiple components of the BRAF-MEK-ERK cascade (vertical inhibition) has become a standard of care for treating BRAF-mutant melanoma. However, the molecular mechanism of how vertical inhibition synergistically suppresses intracellular ERK-activity, and consequently cell proliferation, are yet to be fully elucidated.MethodsWe develop a mechanistic mathematical model that describes how the mutant BRAF-inhibitor, dabrafenib, and the MEK-inhibitor, trametinib, affect BRAFV600E-MEK-ERK signalling. The model is based upon a system of chemical reactions that describes cascade signalling dynamics. Using mass action kinetics, the chemical reactions are re-expressed as ordinary differential equations which are parameterised byin vitrodata and solved numerically to obtain the temporal evolution of cascade component concentrations.ResultsThe model provides a quantitative method to compute how dabrafenib and trametinib can be used in combination to synergistically inhibit ERK-activity in BRAFV600E-mutant melanoma cells. The model elucidates molecular mechanisms of vertical inhibition of the BRAFV600E-MEK-ERK cascade and delineates how elevated BRAF concentrations generate drug resistance to dabrafenib and trametinib. The computational simulations further suggest that elevated ATP levels could be a factor in drug resistance to dabrafenib.ConclusionsThe model can be used to systematically motivate which dabrafenib-trametinib dose-combinations, for treating BRAFV600E-mutated melanoma, warrant experimental investigation.
Mesoporous silica particles functionalized with newly extracted fish oil (Omeg@Silica) inhibit lung cancer cell growth
Authors: Di Sano Caterina , D’Anna Claudia , Scurria Antonino , Lino Claudia , Pagliaro Mario , Ciriminna Rosaria , Pace Elisabetta 
Published: April 2021

AbstractOmeg@Silicamicroparticles consisting of whole fish oil rich in omega-3 lipids, vitamin D3and zeaxanthin extracted with biobased limonene from anchovy fillet leftovers (AnchoisOil) encapsulated within mesoporous silica particles are highly effective in modulating oxidative stress, mitochondrial damage or in promoting antitumor effects in lung cancer cells. A panel of three different human non-small cell lung cancer (NSCLC) cell lines (A549, Colo 699 and SKMES) was used. Cancer cells were treated withAnchoisOildispersed in ethanol (10 and 15 μg/ml) or encapsulated in silica, and cell cycle, reactive oxigen species (ROS) and mitochondrial stress (MitoSOX) assessed by flow cytometry. The effects on long-term proliferation (clonogenic assay) were also evaluated. The sub-micronOmeg@Silicamicroparticles were more effective than fish oil alone in increasing ROS and mitocondrial damage, in altering cell cycle as well as in reducing colony formation ability in the tested lung cancer cell lines. These results suggest thatOmeg@Silicamesoporous silica functionalized with whole fish oil has antitumor effects in NSCLC cell lines and support its investigation in lung cancer therapy.
Single-cell analysis reveals MHCII expressing keratinocytes in pressure ulcers with worse healing outcomes
Authors: Li Dongqing , Cheng Shangli , Pei Yu , Sommar Pehr , Kärner Jaanika , Herter Eva K. , Toma Maria A. , Zhang Letian , Pham Kim , Cheung Yuen Ting , Chen Xingqi , Eidsmo Liv , Deng Qiaolin , Landén Ning Xu 
Published: April 2021

AbstractPressure ulcer (PU) is a chronic wound often seen in spinal cord injury patients and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. Here, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds (AWs) in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II (MHCII) expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFNγ in PU-derived wound fluid could induce MHCII expression in keratinocytes and that these wound fluid-treated keratinocytes inhibited autologous T cell activation. In line with this observation, we found that T cells from PUs enriched with MHCII+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared to AW and intact skin, providing new insights into PU pathology and the future development of tailored wound therapy.
A model of the CA1 field rhythms
Authors: I.E. Mysin 
Published: April 2021

AbstractWe propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm, slow, middle, and fast gamma rhythms, and ripples oscillations. We have based this on data obtained from animals behaving freely. We have considered the modes of neuronal discharges and the occurrence of local field potential (LFP) oscillations in the theta and non-theta states at different inputs from the CA3 field, the medial entorhinal cortex, and the medial septum. In our work, we tried to reproduce the main experimental phenomena about rhythms in the CA1 field: the coupling of neurons to the phase of rhythms, cross-rhythm phase-phase and phase-amplitude coupling. Using computational experiments, we have proved the hypothesis that the descending phase of the theta rhythm in the CA1 field is formed by the input from the CA3 field via the Shaffer collaterals, and the ascending phase of the theta rhythm is formed by the inhibitory postsynaptic potentials from CCK basket cells. The slow gamma rhythm is coupled to the descending phase of the theta rhythm, since it also depends on the arrival of the signal via the Shaffer collaterals. The middle gamma rhythm is formed by the excitatory postsynaptic potentials of the principal neurons of the third layer of the entorhinal cortex, corresponds to experimental data. We were able to unite in a single mathematical model several theoretical ideas about the mechanisms of rhythmic processes in the CA1 field of the hippocampus.
Focal DNA hypo-methylation in cancer is mediated by transcription factors binding
Authors: Detilleux Dylane , Spill Yannick G , Balaramane Delphine , Weber Michaël , Bardet Anaïs Flore 
Published: April 2021

ABSTRACTAberrant DNA methylation has emerged as a hallmark of cancer cells and profiling their epigenetic landscape has widely been carried out in many types of cancer. However, the mechanisms underlying changes in DNA methylation remain elusive. Transcription factors, initially thought to be repressed from binding by DNA methylation, have recently emerged as potential drivers of DNA methylation patterns. Here we perform a rigorous bioinformatic analysis integrating the massive amount of data available from The Cancer Genome Atlas to identify transcription factors driving aberrant DNA methylation. We predict TFs known to be involved in cancer as well as novel candidates to drive hypo-methylated regions such as FOXA1 and GATA3 in breast cancer, FOXA1 and TWIST1 in prostate cancer and NFE2L2 in lung cancer. We also predict TFs that lead to hyper-methylated regions upon TF loss such as EGR1 in several cancer types. Finally, we validate experimentally that FOXA1 and GATA3 mediate hypo-methylated regions in breast cancer cells. Our work shows the importance of TFs as upstream regulators shaping DNA methylation patterns in cancer.
Surrogate production of genome edited sperm from a different subfamily by spermatogonial stem cell transplantation
Authors: Zhang Fenghua , Li Xianmei , Hao Yongkang , Li Yi , Ye Ding , He Mudan , Wang Houpeng , Zhu Zuoyan , Sun Yonghua 
Published: April 2021

AbstractThe surrogate reproduction technique provides a powerful tool for production of allogenic or xenogeneic gametes derived from endangered species or those with valuable genetic traits. Production of functional donor-derived gametes through intra- or inter-specific spermatogonial stem cell transplantation (SSCT) has been achieved in many species. However, generation of functional gametes from a phylogenetically distant species such as from a different subfamily by SSCT has never been successful. Here, using two small cyprinid fishes, Chinese rare minnow (gobiocypris rarus, for brief:Gr) and zebrafish (danio rerio), which belong to different subfamilies, as donors and recipients for SSCT, we optimized the SSCT technique and successfully obtainedGr-derived sperm carrying targeted genome modifications in zebrafish. We revealed that the transplantedGrspermatogonia supported the host gonadal development and underwent normal spermatogenesis, resulting in a reconstructed fertile testis containingGrspermatids and zebrafish testicular somatic cells. Interestingly, the surrogate spermatozoa resembled those of host zebrafish but not donorGrin morphology and swimming behavior. Finally, we showed thatGr-derived genome edited sperm was successfully produced in zebrafish by cross-subfamily SSCT, when thepou5f3andchdgene knockoutGrSSCs were used as surrogate donors. This is the first report demonstrating the surrogate production of genome edited sperm from a phylogenetically distant species, and this method is feasible to be applied to future breeding of commercial fishes.