bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent verification of circulating miRNA as diagnostic biomarkers for urothelial carcinoma
Authors: Urabe Fumihiko , Matsuzaki Juntaro , Takeshita Fumitaka , Kishida Takeshi , Ochiya Takahiro , Hirai Kotaro 
Published: July 2022

AbstractUrothelial carcinoma (UC) is an umbrella term for bladder cancers (BCa) and upper‐tract urothelial carcinoma (UTUC), with BCa and UTUC sometimes detected concomitantly. The methods of detection for UC are often inaccurate or highly invasive, and, therefore, are thought to be unsatisfactory. Previously, we reported seven serum miRNAs as diagnostic markers for BCa. Here, we re‐evaluated potential diagnostic miRNAs in different institutions. We prospectively analyzed serum samples obtained from 126 UC patients (BCa: 106 samples; UTUC: 14 samples; UTUC with BCa: six samples) and 50 noncancer controls by microarray analysis. We randomly assigned these samples into a training or a validation set. Biomarker candidate miRNAs were selected based on cross‐validation scores in the training set of samples, with diagnostic power confirmed in the validation set. Among the diagnostic miRNAs identified in this way, miR‐1343‐5p and miR‐6087 had been identified as potential diagnostic miRNAs in our previous study. In addition, we evaluated the association between the serum levels of identified miRNAs and the presence of UC risk conditions. The expression levels of several miRNAs correlate with the risk factors in participants without UC, which may be explained by the presence of a microscopic tumor or a precancerous lesion. In conclusion, we identified two robust miRNA diagnostic markers for UC detection. Further functional analysis is required to elucidate the mechanism by which alterations in the expression of these miRNAs occur.
Mechanisms of resistance to immune checkpoint inhibitors
Authors: Nagasaki Joji , Ishino Takamasa , Togashi Yosuke 
Published: July 2022

AbstractImmune checkpoint inhibitors (ICIs) are effective for various types of cancer, and their application has led to paradigm shifts in cancer treatment. While many patients can obtain clinical benefits from ICI treatment, a large number of patients are primarily resistant to such treatment or acquire resistance after an initial response. Thus, elucidating the resistance mechanisms is warranted to improve the clinical outcomes of ICI treatment. ICIs exert their antitumor effects by activating T cells in the tumor microenvironment. There are various resistance mechanisms, such as insufficient antigen recognition by T cells, impaired T‐cell migration and/or infiltration, and reduced T‐cell cytotoxicity, most of which are related to the T‐cell activation process. Thus, we classify them into three main mechanisms: resistance mechanisms related to antigen recognition, T‐cell migration and/or infiltration, and effector functions of T cells. In this review, we summarize these mechanisms of resistance to ICIs related to the T‐cell activation process and progress in the development of novel therapies that can overcome resistance.
Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies
Authors: Seervai Riyad N. H. , Sinha Avilasha , Kulkarni Rajan P. 
Published: July 2022

Abstract
The discovery of immune checkpoint inhibition (ICI) sparked a revolution in the era of targeted anticancer therapy. However, although monoclonal antibodies targeting the cytotoxic T-lymphocyte antigen-4 and programmed death-1 axes have improved survival in patients with advanced cancers, these immunotherapies are associated with a wide spectrum of dermatological immune-related adverse events (irAEs), ranging from mild to life-threatening. Several publications have addressed the clinical and histopathological classification of these skin-directed irAEs, their impact on anti-tumour immunity and survival, and the critical role of supportive oncological dermatology in their management. In this paper, we review the current understanding of the mechanistic drivers of immune-related skin toxicities with a focus on inflammatory, immunobullous and melanocyte/pigment-related reactions. We detail the specific immune-based mechanisms that may underlie different cutaneous reactions. We also discuss potential mechanisms as they relate to extracutaneous irAEs and the lessons learned from these, the potential overlap with cutaneous irAEs, techniques to study differences in immune-related vs. de novo skin reactions, and how treatment of these AEs impacts cancer treatment, patient quality of life and overall survival. An improved understanding of the mechanistic basis of cutaneous irAEs will allow clinicians to develop and use blood-based biomarkers that could help ultimately predict onset and/or severity of these irAEs, and to implement rational mechanistic-based treatment strategies that are targeted to the irAEs while potentially avoiding reducing the anti-tumour effect of ICIs.
Beneficial metabolic effects of recurrent periods of beta‐cell rest and stimulation using stable neuropeptide Y1 and glucagon‐like peptide‐1 receptor agonists
Authors: Tanday Neil , Lafferty Ryan A. , Flatt Peter R. , Irwin Nigel 
Published: July 2022

AbstractAimTo examine whether sequential administration of (d‐Arg35)‐sea lamprey peptide tyrosine tyrosine (1–36) (SL‐PYY) and the glucagon‐like peptide‐1 (GLP‐1) mimetic, liraglutide, has beneficial effects in diabetes.MethodsSL‐PYY is an enzymatically stable neuropeptide Y1 receptor (NPY1R) agonist known to induce pancreatic beta‐cell rest and improve overall beta‐cell health. We employed SL‐PYY and liraglutide to induce appropriate recurrent periods of beta‐cell rest and stimulation, to assess therapeutic benefits in high fat fed (HFF) mice with streptozotocin (STZ)‐induced insulin deficiency, namely HFF‐STZ mice.ResultsPrevious studies confirm that, at a dose of 0.25 nmol/kg, liraglutide exerts bioactivity over an 8‐12 hour period in mice. Initial pharmacokinetic analysis revealed that 75 nmol/kg SL‐PYY yielded a similar plasma drug time profile. When SL‐PYY (75 nmol/kg) and liraglutide (0.25 nmol/kg) were administered sequentially at 08:00 AM and 08:00 PM, respectively, to HFF‐STZ mice for 28 days, reductions in energy intake, body weight, circulating glucose, insulin and glucagon were noted. Similarly positive, but slightly less striking, effects were also apparent with twice‐daily liraglutide‐only therapy. The sequential SL‐PYY and liraglutide treatment also improved insulin sensitivity and glucose‐induced insulin secretory responses, which was not apparent with liraglutide treatment, although benefits on glucose tolerance were mild. Interestingly, combined therapy also elevated pancreatic insulin, decreased pancreatic glucagon and enhanced the plasma insulin/glucagon ratio compared with liraglutide alone. This was not associated with an enhancement of beneficial changes in islet cell areas, proliferation or apoptosis compared with liraglutide alone, but the numbers of centrally stained glucagon‐positive islet cells were reduced by sequential combination therapy.ConclusionThese data show that NPY1R‐induced intervals of beta‐cell rest, combined with GLP‐1R–stimulated periods of beta‐cell stimulation, should be further evaluated as an effective treatment option for obesity‐driven forms of diabetes.
Validation of the new paediatric pulmonary hypertension risk score by CMR and speckle tracking echocardiography
Authors: Hasan Hosan , Chouvarine Philippe , Diekmann Franziska , Diedrich Nikita , Koestenberger Martin , Hansmann Georg 
Published: July 2022

AbstractObjectivesIn 2019, the European Paediatric Pulmonary Vascular Disease Network (EPPVDN) developed a PH risk score to assess the risk and severity of pulmonary hypertension (PH) in children and young adults. We conducted a prospective observational study to validate the EPPVDN paediatric PH risk score by means of cardiac magnetic resonance imaging (CMR) and echocardiography.MethodsDuring the same inpatient stay, the invasive and noninvasive EPPVDN PH risk scores were determined, and a protocol‐driven CMR study was performed on 20 PAH children. Subsequently, we correlated the risk scores with imaging variables derived from CMR and echocardiography, including strain. Further, we applied the risk score to nine children with PAH who received add‐on selexipag therapy. Before and approximately six months after selexipag start, the risk score and echocardiographic RV strain were determined and delta changes of both were correlated.ResultsWe found strong correlations of conventional CMR (r = 0.69–0.88), CMR strain (r = 0.71–0.88), advanced echocardiographic (r = 0.65–0.88) and echocardiographic strain variables (r = 0.67–0.86) with the EPPVDN PH risk scores (p < .006). In the selexipag cohort, the change in echo‐derived RV free wall strain correlated well with the change in the invasive higher risk score (r = 0.72, p = .028).ConclusionsWe demonstrate strong correlations of outcome‐relevant CMR and echocardiographic variables with the EPPVDN PH risk scores, and thus validated the score via independent methods. To achieve broad and easy access, we developed a calculator for the risk score as a web application (www.pvdnetwork.org/pedphriskscore). The novel EPPVDN PH risk score will be useful in routine clinical care and can now be applied in larger paediatric PH studies.
Breaking constraints: The development and evolution of extreme fin morphology in the Bramidae
Authors: Gilbert Michelle C. , Lerose Catherine S. , Conith Andrew J. , Albertson R. Craig 
Published: July 2022

AbstractThe developmental process establishes the foundation upon which natural selection may act. In that same sense, it is inundated with numerous constraints that work to limit the directions in which a phenotype may respond to selective pressures. Extreme phenotypes have been used in the past to identify tradeoffs and constraints and may aid in recognizing how alterations to the Baupläne can influence the trajectories of lineages. The Bramidae, a family of Scombriformes consisting of 20 extant species, are unique in that five species greatly deviate from the stout, ovaloid bodies that typify the bramids. The Ptericlinae, or fanfishes, are instead characterized by relatively elongated body plans and extreme modifications to their medial fins. Here, we explore the development of Bramidae morphologies and examine them through a phylogenetic lens to investigate the concepts of developmental and evolutionary constraints. Contrary to our predictions that the fanfishes had been constrained by inherited properties of an ancestral state, we find that the fanfishes exhibit both increased rates of trait evolution and differ substantially from the other bramids in their developmental trajectories. Conversely, the remaining bramid genera differ little, both among one another and in comparison, to the sister family Caristiidae. In all, our data suggest that the fanfishes have broken constraints, thereby allowing them to mitigate trade‐offs on distinctive aspects of morphology.
Involvement of GABAA receptors containing α6 subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two‐photon uncaging
Authors: Bazzurro Virginia , Gatta Elena , Angeli Elena , Cupello Aroldo , Lange Stefan , Jennische Eva , Robello Mauro , Diaspro Alberto 
Published: July 2022

AbstractThe antisecretory factor (AF) is an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions in vivo. It has been detected in many mammalian tissues and plasma, but its mechanisms of action are largely unknown. To study the pharmacological action of the AF on different GABAA receptor populations in cerebellar granule cells, we took advantage of the two‐photon uncaging method as this technique allows to stimulate the cell locally in well‐identified plasma membrane parts. We compared the electrophysiological response evoked by releasing a caged GABA compound on the soma, the axon initial segment and neurites before and after administering AF‐16, a 16 amino acids long peptide obtained from the amino‐terminal end of the AF protein. After the treatment with AF‐16, we observed peak current increases of varying magnitude depending on the neuronal region. Thus, studying the effects of furosemide and AF‐16 on the electrophysiological behaviour of cerebellar granules, we suggest that GABAA receptors, containing the α6 subunit, may be specifically involved in the increase of the peak current by AF, and different receptor subtype distribution may be responsible for differences in this increase on the cell.
M‐Risk: A framework for assessing global fisheries management efficacy of sharks, rays and chimaeras
Authors: Sherman C. Samantha , Sant Glenn , Simpfendorfer Colin A. , Digel Eric D. , Zubick Patrick , Johnson Grant , Usher Michael , Dulvy Nicholas K. 
Published: July 2022

AbstractFisheries management is essential to guarantee sustainable capture of target species and avoid undesirable declines of incidentally captured species. A key challenge is halting and reversing declines of shark and ray species, and specifically assessing the degree to which management is sufficient to avoid declines in relatively data‐poor fisheries. While ecological risk analyses focus on intrinsic ‘productivity’ and extrinsic ‘susceptibility’, one would ideally consider the influence of ‘fisheries management’. Currently, there is no single management evaluation that can be applied to a combination of fishery types at the scale of individual country or Regional Fisheries Management Organizations (RFMOs). Here, we outline a management‐risk (M‐Risk) framework for sharks, rays and chimaeras used to evaluate species' risk of overfishing resulting from ineffective management. We illustrate our approach with application to one country (Ecuador) and RFMO (Inter‐American Tropical Tuna Commission) and illustrate the variation in scores among species. We found that while both management units assessed had similar overall scores, the scores for individual attributes varied. Ecuador scored higher in reporting‐related attributes, while the IATTC scored higher in attributes related to data collection and use. We evaluated whether the management of individual species was sufficient for their relative sensitivity by combining the management‐risk score for each species with their intrinsic sensitivity to determine a final M‐Risk score. This framework can be applied to determine which species face the greatest risk of overfishing and be used by fisheries managers to identify effective management policies by replicating regulations from countries with lower risk scores.
Family reunification after fathers are released from prison: Perspectives on children's adjustment
Authors: Muentner Luke , Charles Pajarita 
Published: July 2022

AbstractObjectiveThis qualitative study examined adult perspectives on the adjustments children face through the process of paternal incarceration and eventual release.BackgroundWhile the United States leads the world in incarceration, 95% of imprisoned individuals return to community life. Despite poor outcomes for children with incarcerated fathers, less is known as to how they fair after fathers' release. Conceptualizing paternal incarceration and reentry as linked rather than disparate events, this study examines perspectives on family separation, reunification, and children's adjustment when fathers return from prison.MethodThe sample consisted of 38 participants (19 previously incarcerated fathers, nine coparenting mothers, and 10 relatives) who shared perspectives on 63 children's adjustments. The semistructured interviews were analyzed via thematic analysis.ResultsTwo main themes were evident: (a) Paternal incarceration has a lasting toll on children that complicates reunification processes, introduces hurdles to maintaining togetherness, and is tied to changes in children's behaviors; and (b) reentry renews opportunity for father involvement that bolsters resilience despite ongoing systemic vulnerabilities.ConclusionPostrelease family reunification may present challenges for children's adjustment, though supported transitions may curb some concerns. The findings call for strengths‐oriented, needs‐focused, and evidence‐based reentry strategies that support entire family systems.
Collaborative and individual vocabulary learning in the Arabic classroom: The role of engagement and task demands
Authors: Rabie‐Ahmed Amr , Mohamed Ayman 
Published: July 2022

The ChallengeHow can collaborative learning be approached from a processing perspective? Can vocabulary involvement frameworks predict learning gains from collaborative tasks as compared to individual tasks? Are these frameworks relevant to the language classroom settings? This study explores incidental vocabulary acquisition from individual and collaborative tasks in an Arabic online classroom.
Association between the coexistence of premorbid sarcopenia, frailty, and disability and functional outcome in older patients with acute stroke
Authors: Nozoe Masafumi , Noguchi Madoka , Kubo Hiroki , Kanai Masashi , Shimada Shinichi 
Published: July 2022

AimTo investigate the effects of coexisting conditions such as premorbid sarcopenia, frailty, and disability on functional outcomes in older patients with acute stroke.MethodsThis prospective cohort study included older patients (aged ≥65 years) hospitalized for acute stroke at a single neurosurgical hospital. Premorbid sarcopenia, frailty, and disability were diagnosed using the strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC‐F) questionnaire, frailty index, and modified Rankin Scale (mRS) on admission. The primary outcome was the mRS score 3 months after stroke, and a poor outcome was defined as mRS ≥4.ResultsThis study included 317 older patients with acute stroke (median [interquartile range] age: 76 [12] years). Premorbid sarcopenia, frailty, and disability (mRS = 2 or 3) were identified in 59 (19%), 27 (9%), and 54 (17%) patients, respectively. Two coexisting conditions were observed in 26 patients (8%), and three were observed in 18 patients (6%). Adjusted logistic regression analysis revealed that coexisting conditions were independently associated with poor outcomes (one condition, adjusted OR: 3.20 [95%CI: 0.98–10.45]; two conditions, adjusted OR: 6.57 [95%CI: 1.74–24.87]; three conditions, adjusted OR: 12.70 [95%CI: 2.65–60.91]).ConclusionsThe coexistence of premorbid sarcopenia, frailty, and disability was associated with poor functional outcomes in older patients with acute stroke. Geriatr Gerontol Int 2022; 22: 642–647.
Properties of phyllosilicate‐based porous ceramics shaped by conventional tape casting and freeze tape casting
Authors: Barry Kassoum , Lecomte‐Nana Gisèle Laure , Seynou Mohamed , Faucher Michael , Blanchart Philippe , Peyratout Claire 
Published: July 2022

AbstractSilicate ceramics were shaped using tape casting (TC) and freeze tape casting (FTC) processes from three clays labeled HCR, KORS, and KCR. These clays exhibited mass content of 77% halloysite–10 Å, 29% kaolinite, and 98% kaolinite minerals, respectively. After casting the slurries, the dried tapes were sintered at 1200°C. The microstructure changes were characterized before and after sintering using scanning electron microscopy. The apparent porosity of TC samples was lower (36–47 vol.%) compared to values obtained with FTC samples (67–79 vol.%). The latter samples exhibited a highly textured porosity, with micron‐sized pores aligned perpendicular to the tape surfaces. Upon sintering, the porosity of TC samples tended to decrease conversely to the case of FTC samples. Such behavior seemed related to the simultaneous effect of organic additives and ice templating. Consequently, the FTC samples showed a relatively low mechanical strength of 3–7 MPa and thermal conductivity of .14– .22 W m−1 K−1. After sintering, the mullite crystallization contributed to strengthen the bulk materials, helping to compensate for the detrimental effect of porosity on the stress to rupture and on thermal conductivity values.
A novel ZsGreen knock‐in melanoma cell line reveals the function of CD11b in tumor phagocytosis
Authors: Zhang Lichen , Feng Xinyu , Shen Yingzhuo , Wang Yingbin , Liu Zhuangzhuang , Ma Yuang , Gu Yanrong , Guo Guo , Duan Liangwei , Lu Liaoxun , Liang Yinming , Lawrence Toby , Huang Rong 
Published: July 2022

AbstractClustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) is an efficient tool for establishing genetic models including cellular models, and has facilitated unprecedented advancements in biomedical research. In both patients and cancer animal models, immune cells infiltrate the tumor microenvironment and some of them migrate to draining lymph nodes to exert antitumor effects. Among these immune cells, phagocytes such as macrophages and dendritic cells engulf tumor antigens prior to their crosstalk with T cells and elicit adaptive immune response against tumors. Melanoma cells are frequently used as a tumor model because of their relatively high level of somatic mutations and antigenicity. However, few genetic models have been developed using melanoma cell lines to track tumor cell phagocytosis, which is essential for understanding protective immune response in vivo. In this study, we used CRISPR/Cas9‐mediated DNA cleavage and homologous recombination to develop a novel knock‐in tool which expresses the ultra‐bright fluorescent probe ZsGreen in YUMM1.7 melanoma cells. Using this novel tool, we measured the macrophagic engulfment of melanoma cells inside the tumor microenvironment. We also found that in tumor‐grafted mice, a subset of dendritic cells efficiently engulfed YUMM1.7 cells and was preferentially trafficking tumor antigens to draining lymph nodes. In addition, we used this knock‐in tool to assess the impact of a point mutation of CD11b on phagocytosis in the tumor microenvironment. Our results demonstrate that the ZsGreen‐expressing YUMM1.7 melanoma model provides a valuable tool for the study of phagocytosis in vivo.
High‐pressure behavior and phase transition of jadarite, a promising B and Li mineral commodity
Authors: Comboni Davide , Battiston Tommaso , Rumsey Michael S. , Pagliaro Francesco , Lotti Paolo , Hanfland Michael , Gatta G. Diego 
Published: July 2022

AbstractThe high‐pressure behavior of a natural jadarite (ideally LiNaSiB3O7(OH), a ∼ 6.76 Å, b ∼ 13.80 Å, c ∼ 7.69 Å, β = 124.09°, space group P21/c) has been studied by in situ single‐crystal and powder synchrotron X‐ray diffraction up to 20 GPa, with a diamond anvil cell and using He as a hydrostatic pressure‐transmitting fluid. Between 16.57(5) and 17.04(5) GPa, jadarite undergoes a first‐order iso‐symmetric phase transition, which is reconstructive in character, with a ΔV of approximately ‐3%. The structure of the high‐pressure polymorph was solved and refined (to R1 ∼ 4%). The isothermal bulk modulus of the low‐P polymorph of jadarite is KV0 = 55.0(5) GPa (βV0 = 0.0182(2) GPa–1), and its P‐derivative is 3.84(9). The compressional anisotropy, derived along the three main crystallographic directions, is modest, with βa0:βb0:βc0 = 1.23:1:1.23. The P‐induced deformation mechanisms at the atomic scale, which lead to phase transition, are described.