bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Term Effectiveness and Safety of Intracavernosal Botulinum Toxin A as an Add-on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 Injections for Erectile Dysfunction
Authors: Giuliano Francois , Joussain Charles , Denys Pierre 
Published: December 2021

ABSTRACTBackgroundSome evidence suggests that intracavernosal botulinum toxin A (BTX-A IC) injections administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandin E1 intracavernosal injections (PGE1 ICI) could effectively treat erectile dysfunction (ED) in non–responders, or insufficient responders to these pharmacologic treatments.AimTo determine the long-term effectiveness and safety of combined treatment involving a single injection of BTX-A IC as an add on therapy to PDE5-Is or PGE1-ICI for the treatment of ED of different etiologies.MethodsA retrospective, uncontrolled, single center study was conducted. Data from 123 consecutive patients with ED who were insufficient responders to PDE5-Is or PGE1-ICI and who received onabotulinumtoxinA 100 U, abobotulinumtoxinA 250 U or 500 U IC as an add on to their current pharmacologic treatment were analyzed. All analyses were exploratory. Qualitative data were compared using the Fisher’s exact test. Univariate and multivariate analysis were performed using logistic regression with Odds Ratios (OR). Only variables with P &lt; .05 in the univariate analysis were selected for multivariate analysis.ResultsThe minimally clinically important difference (relative to baseline severity of ED) in the International Index of Erectile Function-Erectile function domain (IIEF-EF) score was achieved in 50% of patients at 34 (27–42) days and in 41% at 5.9 (3.9 – 8.1) months following BTX-A IC in combination with PDE5-Is or PGE1 ICI. The severity of ED influenced response to BTX-A IC according to the multivariate analysis (OR = 0.3, IC(95%]) = (0.16 – 0.56). Neither being post prostatectomy nor the type of BTX-A affected the response. Effectiveness tended to decrease more over time with abobotulinumtoxinA 250 U than 500 U.The only side-effects were mild penile pain on injection (n = 1) and mild penile pain for 3 days following injection (n = 1); no systemic effects were reported.Clinical implicationsBTX-A IC (all types) administered as an add on to registered pharmacologic treatments improved erectile function for at least 6 months in 41% of patients with ED of varying etiologies, and was safe.Strengths & LimitationsA relatively large cohort of patients with ED was included, with a long follow-up period, however the study was retrospective, and uncontrolled.ConclusionThis study provides preliminary evidence that BTX-A IC administered as an add-on therapy for ED that is insufficiently responsive to standard therapy is effective for at least 6 months, and is safe. Randomized clinical trials are now needed to fully confirm these results.
The privatisation of remembering practices in contemporary inpatient mental healthcare: going beyond Agnes's Jacket
Authors: Brown Steven D. , Reavey Paula 
Published: December 2021

Abstract
In this paper, we consider changes to memorial practices for mental health service users during the asylum period of the mid-nineteenth up to the end of the twentieth century and into the twenty-first century. The closing of large asylums in the UK has been largely welcomed by professionals and service-users alike, but their closure has led to a decrease in continuous and consistent care for those with enduring mental health challenges. Temporary and time-limited mental health services, largely dedicated to crisis management and risk reduction have failed to enable memory practices outside the therapy room. This is an unusual case of privatised memories being favoured over collective memorial activity. We argue that the collectivisation of service user memories, especially in institutions containing large numbers of long-stay patients, would benefit both staff and patients. The benefit would be in the development of awareness of how service users make sense of their past in relation to their present stay in hospital, how they might connect with others in similar positions and how they may connect with the world and others upon future release. This seems to us central to a project of recovery and yet is rarely practised in any mental health institution in the UK, despite being central to other forms of care provision, such as elderly and children's care services. We offer some suggestions on how collective models of memory in mental health might assist in this project of recovery and create greater visibility between past, present and future imaginings.
Between Qum and Qayrawān: Unearthing early Shii ḥadı̄th sources
Authors: Rajani Kumail 
Published: December 2021

AbstractIn this article, I develop and test a new methodology of unearthing early Shii ḥadı̄th sources that served as the basis for the later collections of the fourth/tenth century. This method, besides answering the question of historicity, enables us to understand the dissemination of texts across times and regions. As a case-study, I examine what is alleged to have been the first Shii legal ḥadı̄th collection, a work attributed to ʿUbaydullāh b. ʿAlī al-Ḥalabī (d. c. 148/765). By comparing the reports transmitted on the authority of al-Ḥalabī in the Twelver ḥadı̄th compendium originating in Qum, al-Kulaynī's al-Kāfī, and an Ismaili legal ḥadı̄th composition, al-Qāḍī al-Nuʿmān's al-Īḍāḥ, composed in Qayrawān, I demonstrate that both works trace their material to an earlier Kūfan source of the second/eighth century, with each work drawing on the same material independently. A cross-regional textual analysis of later ḥadı̄th compendia, in this case composed by contemporaneous scholars, residing in different regions, affiliated to dissimilar religious persuasions, reveals the transmission of identical material; this finding contributes to our understanding of both geographical transmission of early sources and compositional arrangements of the later ḥadı̄th compendia.
Mechanisms Controlling the Distribution of Net Water Transport in Estuarine Networks
Authors: Wang Jinyang , Dijkstra Yoeri M. , de Swart Huib E. 
Published: December 2021

AbstractNet water transport (NWT) in estuaries is important for, for example, salt intrusion and sediment dynamics. While NWT is only determined by river runoff in single channels, in estuarine networks, it results from a complex interplay between tides and residual flows. This study aims to disentangle the various contributions of these physical drivers to NWT in estuarine networks and investigate the sensitivities of NWT to variable forcing conditions, interventions, and sea level rise (SLR). To this end, a processes‐based perturbative network model is developed, which accounts for the vertical flow structure to resolve density‐driven flow driven by a vertically uniform along‐channel salinity gradient. Other identified drivers are river discharge and three tidal rectification processes: Stokes transport and its return flow, momentum advection, and velocity‐depth asymmetry. The model is applied to the Yangtze Estuary. NWT due to tidal rectifications and density‐driven flow can be comparable to river discharge. Specifically in the North Branch, the direction of NWT may differ from the direction of river discharge. Varying river discharge mainly affects NWT as tide‐river interaction is weak and density‐driven flow is shown to be insensitive to salt intrusion. Conversely, variations in tidal amplitude strongly affect NWT related to tidal rectification and density‐driven flow. The deepening (narrowing) of one channel (Deep Waterway Project), affected the NWT mostly through the density‐driven flow (advection). Furthermore, NWT distribution in the Yangtze is insensitive to SLR up to 2 m because the effects of SLR on transport due to different drivers compensate each other.
Hydroclimate Variability Affects Habitat‐Specific (Open Water and Littoral) Lake Metabolism
Authors: Scordo Facundo , Lottig Noah R. , Fiorenza Juan E. , Culpepper Joshua , Simmons James , Seitz Carina , Krynak Edward M. , Suenaga Erin , Chandra Sudeep 
Published: December 2021

AbstractLakes integrate the signals of changing hydroclimate in their surrounding basin, which substantially influence gross primary production (GPP), respiration (R), and net ecosystem production (NEP). Most research focuses only on the changes to the open water habitat despite the littoral habitat's importance to lakes and its sensitivity to hydroclimatic variability. We analyze how years with different ice‐out dates and snow water equivalent (SWE) triggered different metabolism responses in the open water and littoral habitats of a subalpine lake. The dry (early ice‐out date and low SWE) and wet (late ice‐out date and high SWE) years had lower GPP and R rates in both habitats compared to the average hydroclimatic year. Furthermore, consumer biomass decreased during dry and wet years. GPP and R reduced the most in the littoral habitat. Consequently, the relative contribution to total lake GPP and R of the littoral habitat decreased, and the contribution of the open water habitat increased during the dry and wet years. We demonstrate that hydroclimatic conditions affect productivity and consumer biomass and show that within‐lake habitats do not experience equivalent responses to climate forcing. Our study has implications for how ecosystem scientists and managers quantify the absolute and relative contributions of the littoral habitat to whole lake production in the context of climate variation.
CDK5RAP2 loss-of-function causes premature cell senescence via the GSK3β/β-catenin-WIP1 pathway
Authors: Wang Xidi , Sipila Patrick , Si Zizhen , Rosales Jesusa L. , Gao Xu , Lee Ki-Young 
Published: December 2021

AbstractDevelopmental disorders characterized by small body size have been linked to CDK5RAP2 loss-of-function mutations, but the mechanisms underlying which remain obscure. Here, we demonstrate that knocking down CDK5RAP2 in human fibroblasts triggers premature cell senescence that is recapitulated in Cdk5rap2an/an mouse embryonic fibroblasts and embryos, which exhibit reduced body weight and size, and increased senescence-associated (SA)-β-gal staining compared to Cdk5rap2+/+ and Cdk5rap2+/an embryos. Interestingly, CDK5RAP2-knockdown human fibroblasts show increased p53 Ser15 phosphorylation that does not correlate with activation of p53 kinases, but rather correlates with decreased level of the p53 phosphatase, WIP1. Ectopic WIP1 expression reverses the senescent phenotype in CDK5RAP2-knockdown cells, indicating that senescence in these cells is linked to WIP1 downregulation. CDK5RAP2 interacts with GSK3β, causing increased inhibitory GSK3β Ser9 phosphorylation and inhibiting the activity of GSK3β, which phosphorylates β-catenin, tagging β-catenin for degradation. Thus, loss of CDK5RAP2 decreases GSK3β Ser9 phosphorylation and increases GSK3β activity, reducing nuclear β-catenin, which affects the expression of NF-κB target genes such as WIP1. Consequently, loss of CDK5RAP2 or β-catenin causes WIP1 downregulation. Inhibition of GSK3β activity restores β-catenin and WIP1 levels in CDK5RAP2-knockdown cells, reducing p53 Ser15 phosphorylation and preventing senescence in these cells. Conversely, inhibition of WIP1 activity increases p53 Ser15 phosphorylation and senescence in CDK5RAP2-depleted cells lacking GSK3β activity. These findings indicate that loss of CDK5RAP2 promotes premature cell senescence through GSK3β/β-catenin downregulation of WIP1. Premature cell senescence may contribute to reduced body size associated with CDK5RAP2 loss-of-function.
Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging
Authors: Liu Rui , Cui Juanjuan , Sun Yating , Xu Wentao , Wang Ziming , Wu Miaomiao , Dong Huke , Yang Congcong , Hong Shaocheng , Yin Shi , Wang Hua 
Published: December 2021

AbstractAging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.
A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy
Authors: Dromel Pierre C. , Singh Deepti , Andres Eliot , Likes Molly , Kurisawa Motoichi , Alexander-Katz Alfredo , Spector Myron , Young Michael 
Published: December 2021

AbstractBiomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.
Assessments of different batches and dose levels of a two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen
Authors: Bockstal Viki , Gaddah Auguste , Goldstein Neil , Shukarev Georgi , Bart Stephan , Luhn Kerstin , Robinson Cynthia , Anumendem Dickson , Leyssen Maarten , Douoguih Macaya 
Published: December 2021

AbstractTwo phase 3 clinical studies were conducted in the USA to bridge across different Ad26.ZEBOV manufacturing processes and sites, and to evaluate the immunogenicity of different dose levels of Ad26.ZEBOV and MVA-BN-Filo. Study 1 evaluated the immunological equivalence of three batches of Ad26.ZEBOV administered as dose 1, followed by one batch of MVA-BN-Filo as dose 2. In Study 2, immunogenic non-inferiority of intermediate (Ad26.ZEBOV: 2 × 1010 viral particles [vp], MVA-BN-Filo: 5 × 107 infectious units [Inf.U]) and low (8 × 109 vp, 5 × 107 Inf.U) doses of Ad26.ZEBOV and MVA-BN-Filo were evaluated against the full clinical dose (5 × 1010 vp, 1 × 108 Inf.U). In Study 1, equivalence was demonstrated for two of three batch comparisons post-dose 1 and all three batches after the full regimen. Study 2 demonstrated a dose-dependent response; however, non-inferiority against the full clinical dose was not met. All regimens were well tolerated and immune responses were observed in all participants, regardless of manufacturing process or dose. Consistency of immunogenicity of different Ad26.ZEBOV batches was demonstrated and a dose-dependent response was observed after Ad26.ZEBOV, MVA-BN-Filo vaccination. ClinicalTrials.gov identifiers: NCT02543268; NCT02543567.
Pneumococcal capsule blocks protection by immunization with conserved surface proteins
Authors: Zangari Tonia , Zafar M. Ammar , Lees John A. , Abruzzo Annie R. , Bee Gavyn Chern Wei , Weiser Jeffrey N. 
Published: December 2021

AbstractVaccines targetingStreptococcus pneumoniae(Spn) are limited by dependence on capsular polysaccharide and its serotype diversity. More broadly-based approaches using common protein antigens have not resulted in a licensed vaccine. Herein, we used an unbiased, genome-wide approach to find novel vaccine antigens to disrupt carriage modeled in mice. A Tn-Seq screen identified 198 genes required for colonization of which 16 are known to express conserved, immunogenic surface proteins. After testing defined mutants for impaired colonization of infant and adult mice, 5 validated candidates (StkP, PenA/Pbp2a, PgdA, HtrA, and LytD/Pce/CbpE) were used as immunogens. Despite induction of antibody recognizing the Spn cell surface, there was no protection against Spn colonization. There was, however, protection against an unencapsulated Spn mutant. This result correlated with increased antibody binding to the bacterial surface in the absence of capsule. Our findings demonstrate how the pneumococcal capsule interferes with mucosal protection by antibody to common protein targets.
A stroke detection and discrimination framework using broadband microwave scattering on stochastic models with deep learning
Authors: Alon Leeor , Dehkharghani Seena 
Published: December 2021

AbstractStroke poses an immense public health burden and remains among the primary causes of death and disability worldwide. Emergent therapy is often precluded by late or indeterminate times of onset before initial clinical presentation. Rapid, mobile, safe and low-cost stroke detection technology remains a deeply unmet clinical need. Past studies have explored the use of microwave and other small form-factor strategies for rapid stroke detection; however, widespread clinical adoption remains unrealized. Here, we investigated the use of microwave scattering perturbations from ultra wide-band antenna arrays to learn dielectric signatures of disease. Two deep neural networks (DNNs) were used for: (1) stroke detection (“classification network”), and (2) characterization of the hemorrhage location and size (“discrimination network”). Dielectric signatures were learned on a simulated cohort of 666 hemorrhagic stroke and control subjects using 2D stochastic head models. The classification network yielded a stratified K-fold stroke detection accuracy > 94% with an AUC of 0.996, while the discrimination network resulted in a mean squared error of < 0.004 cm and < 0.02 cm, for the stroke localization and size estimation, respectively. We report a novel approach to intelligent diagnostics using microwave wide-band scattering information thus circumventing conventional image-formation.
An efficient, localised approach for the simulation of elastic blood vessels using the lattice Boltzmann method
Authors: McCullough J. W. S. , Coveney P. V. 
Published: December 2021

AbstractMany numerical studies of blood flow impose a rigid wall assumption due to the simplicity of its implementation compared to a full coupling with a solid mechanics model. In this paper, we present a localised method for incorporating the effects of elastic walls into blood flow simulations using the lattice Boltzmann method implemented by the open-source code HemeLB. We demonstrate that our approach is able to more accurately capture the flow behaviour expected in elastic walled vessels than ones with rigid walls. Furthermore, we show that this can be achieved with no loss of computational performance and remains strongly scalable on high performance computers. We finally illustrate that our approach captures the same trends in wall shear stress distribution as those observed in studies using a rigorous coupling between fluid dynamics and solid mechanics models to solve flow in personalised vascular geometries. These results demonstrate that our model can be used to efficiently and effectively represent flows in elastic blood vessels.
Copper oxalate formation by lichens and fungi
Authors: Frank-Kamenetskaya Olga V. , Zelenskaya Marina S. , Izatulina Alina R. , Vereshchagin Oleg S. , Vlasov Dmitry Yu. , Himelbrant Dmitry E. , Pankin Dmitrii V. 
Published: December 2021

AbstractThe present work focuses on the revealing the patterns of copper oxalates formation under the influence of lichens and fungi by combination of the results of field studies and model experiments. These findings create the scientific basis for the potential microbial technology applications (ore enrichment, monuments conservation, environment bioremediation, etc.). Copper oxalate moolooite Cu(C2O4)·H2O was discovered in saxicolous lichenLecidea inopson the weathered chalcopyrite ore of Voronov Bor deposit (Central Karelia, Russia). Bioinspired syntheses of moolooite and wheatleyite Na2Cu(C2O4)22H2O with the participation of the microscopic fungiAspergillus niger(active producer of oxalic acid) were carried out on weathered Cu-ore from the Voronov Bor deposit. It was shown that morphology of moolooite crystals is controlled both by the underlying rock and by the species composition of microorganisms. Iron ions (sourced from the underlying rock) in the crystallization medium inhibits the moolooite formation. The observed intensive dissolution of moolooite crystals are well explained by washing effect of the intratalline solutions which depends on repeatedly dehydration / rehydration cycles in the lichens. Joint interpretation of original and published data shows that moolooite along with other cooper oxalates are biominerals.
Increased burst coding in deep layers of the ventral anterior cingulate cortex during neuropathic pain
Authors: Kasanetz Fernando , Nevian Thomas 
Published: December 2021

AbstractNeuropathic pain induces changes in neuronal excitability and synaptic connectivity in deep layers of the anterior cingulate cortex (ACC) that play a central role in the sensory, emotional and affective consequences of the disease. However, how this impacts ACC in vivo activity is not completely understood. Using a mouse model, we found that neuropathic pain caused an increase in ACC in vivo activity, as measured by the indirect activity marker c-Fos and juxtacellular electrophysiological recordings. The enhanced firing rate of ACC neurons in lesioned animals was based on a change in the firing pattern towards bursting activity. Despite the proportion of ACC neurons recruited by noxious stimuli was unchanged during neuropathic pain, responses to noxious stimuli were characterized by increased bursting. Thus, this change in coding pattern may have important implications for the processing of nociceptive information in the ACC and could be of great interest to guide the search for new treatment strategies for chronic pain.