bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the fate and regenerative mechanism of zebrafish melanocyte progenitor cells and melanocytes after laser‐induced pigment ablation
Authors: Park Ji Hyun , Koun Soonil , Kim Ko Eun , Kim Il‐Hwan
Published: July 2021

Background and Objectives

Lasers are known to be the most effective treatment modality for pigmentary skin diseases. However, melanocytes and melanin pigment often recur or leave post‐inflammatory hyperpigmentation after the laser procedure. Studies have reported on the role of progenitor cells in pigment cell regeneration, which can be constantly replenished through mitosis. However, the response of unpigmented melanocyte progenitor cells to laser treatment is poorly understood. In this study, we used adult zebrafish skin as the melanocyte regenerative system and examined the response of melanocyte progenitor cells to laser photothermolysis.

Materials and Methods

The two groups of adult zebrafish were irradiated with 1064 nm wavelength laser system of Q‐switched neodymium:yttrium–aluminum–garnet (Nd:YAG) laser with 0.3 or 0.7 J·cm−2. We compared the regeneration of pigment at different energy levels by measuring new melanocyte counts and pigment area. We traced and quantitatively compared the melanocyte lineage cells by immunohistochemical staining using specific markers such as sox10, mitfa, and dct during the regeneration process. Three repetitive laser ablations were also held to test the postinflammatory hyperpigmentation.

Results

After the laser ablation of melanocytes, most of the new melanocytes appeared between Days 5 and 10. In high‐energy irradiation of 0.7 J·cm−2, the unpigmented mitfa‐expressing cells showed significant decrease (p < 0.05) and showed delay in the differentiation process of melanocyte lineage cells. After repeated laser irradiation, hyperpigmentation did not appear and the final recovery ratio of the pigmented area was 87.5% and 75.3% at the 0.3 and 0.7 J·cm−2 energy levels, respectively.

Conclusion

We suggest that laser treatment overcoming the recurrence should be planned based on the adequate energy level targeting the melanocyte progenitor cells. High‐energy irradiation may induce apoptosis of progenitor cells and delay their process of differentiation. Short‐term repetitive sessions of laser therapy can reduce the pigmentation in the long‐term observation.
Fast Optical‐Thermal Responsive Intelligent Glass Realized by Hydrated Poly(N‐Isopropylacrylamide) Film
Authors: Tang Shuangxi , Sang Xiao , Zhu Shicai , Ma Liran , Tian Yu , Luo Jianbin
Published: July 2021

Glass is widely applied in fields of architecture, automobiles, optics and instruments due to its light transmission, wind resistance, sound and heat insulation. However, the light transmittance of traditional glass cannot change after the glass is formed, which limits the practicability of glass. In this study, an intelligent glass that can quickly and freely switch between transparency and opacity based on an optical‐thermal responsive hydrated poly(N‐isopropylacrylamide) film triggered by white light, infrared light, and direct thermal stimuli is developed. The fastest response time is ≈21 s under white light or 5 s by hand touch. A fatigue test of 250 cycles showed no obvious performance degradation. The transmittance of the intelligent glass changed reversibly between 88.5%–93.2% (transparent) and 25.5%–41.6% (opaque). The optical‐thermal response of the intelligent glass is attributed to the reversible phase transition of the hydrated poly(N‐isopropylacrylamide) film. This intelligent glass not only has obvious advantages in energy savings and emission reduction but also may be very useful for privacy protection, for example, in car windows, house windows, and office windows.
Schiff bases of sulphonamides as a new class of antifungal agent against multidrug‐resistant Candida auris
Authors: Hamad Asad , Chen Yiyuan , Khan Mohsin A. , Jamshidi Shirin , Saeed Naima , Clifford Melanie , Hind Charlotte , Sutton J. Mark , Rahman Khondaker Miraz
Published: July 2021

Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug‐resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole‐resistant C. auris strains, with MICs of 4–16 µg/ml. The drug‐like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre‐clinical evaluation.
Georgia advocates seek better result for legislative initiatives in 2022
Authors: Enos Gary
Published: July 2021

After a disappointing year in which no major mental health reform initiatives cleared the Georgia state legislature, can advocates expect a better outcome in 2022? That's the question many are asking at a time when subjects such as the COVID‐19 crisis and state election reform have eclipsed mental health in the legislative discourse.
States look to lift barriers to care for patients with MH/DD needs
Authors: Enos Gary
Published: July 2021

States are overcoming a variety of structural and financial barriers to make inroads in meeting the mental health needs of persons with intellectual and developmental disabilities, a new report suggests. No one model has emerged as the ideal approach, though in all cases there has been a need to improve coordination of effort across multiple organizational silos.
Annapolis Coalition celebrates 20 years of workforce promotion
Authors: Canady Valerie A.
Published: July 2021

COVID‐19 has only exacerbated the need for an increased behavioral health workforce. As the Annapolis Coalition, a nonprofit organization dedicated to improving the recruitment, retention and training of the behavioral health workforce, celebrates 20 years, its executive director, in an interview with Mental Health Weekly last week, discussed the ongoing challenges the workforce is facing and the important next steps.
Statin‐associated anti–3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) myopathy: Imaging findings on thigh‐muscle magnetic resonance imaging (MRI) in six patients
Authors: Lee Kam‐Ho , Gao Yuan , Lau Vince
Published: July 2021

Introduction/Aims

Anti–3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) myopathy is a rare but serious complication of statin use. The aim of this study was to describe the imaging features of statin‐associated anti‐HMGCR myopathy on thigh muscle magnetic resonance imaging (MRI).

Methods

Thigh muscle MRI images of six patients with statin‐associated anti‐HMGCR myopathy were reviewed for muscle edema, fatty replacement, and fascial edema in four compartments of each thigh: gluteal, anterior, medial, and posterior. Signal intensity ratio (SIR) was calculated in 17 muscles in both thighs on T2‐weighted fat‐suppressed images. Intracompartmental comparison of T2 SIRs of different muscles were performed.

Results

All patients demonstrated bilateral symmetrical pan‐compartmental muscle edema. Three patients had fatty infiltration, involving gluteal and/or posterior compartments. In the anterior compartment, rectus femoris and vastus lateralis most frequently demonstrated the highest T2 SIR. In the posterior compartment, semimembranosus most frequently demonstrated the highest T2 SIR. The long head of the biceps femoris always had a higher T2 SIR than the short head.

Discussion

Statin‐associated anti‐HMGCR myopathy commonly demonstrates bilateral symmetrical pan‐compartmental edema on thigh muscle MRI, with anterolateral predilection in the anterior compartment, and greater involvement of the semimembranosus with relative sparing of the short head of the biceps femoris in the posterior compartment. These observations can contribute to the diagnosis of statin‐associated anti‐HMGCR myopathy.
Neuropharmacology of Antiseizure Drugs
Authors: Hakami Tahir
Published: July 2021

Background

Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non‐neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents.

Methods

Randomized controlled trials, observational studies, and evidence‐based meta‐analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology.

Results

The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new‐onset and drug‐resistant epilepsy were recently published. The guidelines have shown that the newer‐generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first‐line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first‐line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first‐line treatment, for example, vigabatrin, felbamate, and rufinamide.

Conclusions

Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug‐drug interactions, and adverse effects.
DNA‐PKc inhibition overcomes taxane resistance by promoting taxane‐induced DNA damage in prostate cancer cells
Authors: Chao Olivia S. , Goodman Oscar B.
Published: July 2021

Background

Overcoming taxane resistance remains a major clinical challenge in metastatic castrate‐resistant prostate cancer (mCRPC). Loss of DNA repair proteins is associated with resistance to anti‐microtubule agents. We propose that alterations in DNA damage response (DDR) pathway contribute to taxane resistance, and identification of these alterations may provide a potential therapeutic target to resensitize docetaxel‐refractory mCRPC to taxane‐based therapy.

Methods

Alterations in DDR gene expression in our prostate cancer cell line model of docetaxel‐resistance (DU145‐DxR) derived from DU‐145 cells were determined by DDR pathway‐specific polymerase chain reaction array and immunoblotting. The PRKDC gene encoding DNA‐PKc (DNA‐dependent protein kinase catalytic unit), was noted to be overexpressed and evaluated for its role in docetaxel resistance. Cell viability and clonogenic survival of docetaxel‐treated DU145‐DxR cells were assessed after pharmacologic inhibition of DNA‐PKc with three different inhibitors—NU7441, LTURM34, and M3814. Response to second‐line cytotoxic agents, cabazitaxel and etoposide upon DNA‐PKc inhibition was also tested. The impact of DNA‐PKc upregulation on DNA damage repair was evaluated by comet assay and analysis of double‐strand breaks marker, γH2AX and Rad51. Lastly, DNA‐PKc inhibitor's effect on MDR1 activity was assessed by rhodamine 123 efflux assay.

Results

DDR pathway‐specific gene profiling revealed significant upregulation of PRKDC and CDK7, and downregulation of MSH3 in DU145‐DxR cells. Compared to parental DU145, DU145‐DxR cells sustained significantly less DNA damage when exposed to etoposide and docetaxel. Pharmacologic inhibition of DNA‐PKc, a component of NHEJ repair machinery, with all three inhibitors, significantly resensitized DU145‐DxR cells to docetaxel. Furthermore, DNA‐PKc inhibition also resensitized DU145‐DxR to cabazitaxel and etoposide, which demonstrated cross‐resistance. Inhibition of DNA‐PKc led to increased DNA damage in etoposide‐ and docetaxel‐treated DU145‐DxR cells. Finally, DNA‐PKc inhibition did not affect MDR1 activity, indicating that DNA‐PKc inhibitors resensitized taxane‐resistant cells via an MDR1‐independent mechanism.

Conclusion

This study supports a role of DDR genes, particularly, DNA‐PKc in promoting resistance to taxanes in mCRPC. Targeting prostatic DNA‐PKc may provide a novel strategy to restore taxane sensitivity in taxane‐refractory mCRPC.
Technical aspects of paediatric robotic pancreatic enucleation based on a case of an insulinoma
Authors: Schulte am Esch Jan , Krüger Martin , Barthlen Winfried , Förster Christine , Mohnike Konrad , Empting Susann , Benhidjeb Tahar , Vossschulte Hendrik
Published: July 2021

Background

Insulinomas are rare insulin‐producing pancreatic neuroendocrine tumours leading to severe episodes of hypoglycaemia. Surgery is the predominant curative therapy.

Methods

We report here the first paediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10‐year‐old male with multiple endocrine neoplasia type 1. The port set‐up was adapted for the narrowed dimensions of the paediatric peritoneal space. We comment on technical key steps for the organ‐preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted.

Results

Following an uneventful post‐operative course, the boy was discharged on day 11 with normalised glucose‐metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting.

Conclusions

The applicability of a robotic surgical system in limited space conditions such as found in the paediatric abdominal cavity is demonstrated here for pancreatic surgery.
An explicit formula for minimizing the infected peak in an SIR epidemic model when using a fixed number of complete lockdowns
Authors: Sontag Eduardo D.
Published: July 2021

Careful timing of nonpharmaceutical interventions such as social distancing may avoid high “second waves” of infections of COVID‐19. This article asks what should be the timing of a set of K complete‐lockdowns of prespecified lengths (such as two weeks) so as to minimize the peak of the infective compartment. Perhaps surprisingly, it is possible to give an explicit and easily computable rule for when each lockdown should commence. Simulations are used to show that the rule remains fairly accurate even if lockdowns are not perfect.
Long‐term effect of tillage and straw retention in conservation agriculture systems on soil carbon storage
Authors: Gómez‐Muñoz Beatriz , Jensen Lars Stoumann , Munkholm Lars , Olesen Jørgen Eivind , Møller Hansen Elly , Bruun Sander
Published: July 2021

The main principles of conservationagriculture (CA) are minimal soil disturbance, permanent soil cover, diversification of crop rotations, and retention of crop residues. Tillage has been implicated with increased soil organic C (SOC) mineralization, but recently this has been contested. Residue retention and cover crops result in higher soil C inputs and are therefore expected to increase SOC. This study aimed to evaluate the effect of 17 yr of residue retention (with and without) and tillage (plowing and no‐till) on soil C storage on two Danish sandy loam soils with different clay and SOC content under cool temperate humid climate conditions. Straw retention reduced bulk density at both sites. It also increased the C concentration with 0.47 mg C g–1 dry soil on average from 2002 to 2019, and SOC stocks in 2019 with 23 tonnes C ha–1, on average, at the site with higher initial SOC content. The effect of straw retention on soil C was higher when the soil was plowed, and no significant effect was observed in no‐till soils. Straw retention did not significantly affect C concentration at the site with low initial SOC. Tillage altered the C distribution in the soil profile, so that the C concentration in the upper layer (0–25 cm) was higher in the no‐till soils, but did not significantly increase total C concentration in deeper layers (0–50 cm). Use of no‐till and straw retention did not consistently affect crop yield across site‐years, but the interannual variability was large, obscuring possible differences in yields.
The representation of gender in England's sexuality education policy
Authors: Mukoro Jude
Published: July 2021

A good representation of gender issues in sexuality education not only enriches the contents of sexuality education but makes it more effective. To unravel if and how gender is represented in England's policy on sexuality education, two important policy documents: Sex and Relationship Education (SRE) Guidance 2000 and Guidance for Relationships Education, Relationships and Sex Education (RSE) and Health Education 2019 were thematically analyzed. The results indicate that gender is presented as a characteristic to be respected, as a diverse reality to be included, as a social reality laced with stereotypes and needs. These representations indicate that England's policy on sexuality education is gender‐sensitive and seeks to be gender‐transformative. There are also indications that policy has evolved to include diverse gender understandings.
Desire/Desirability: Gender Asymmetries in Heterosexual Erotic Attention
Authors: LaFleur Gabrielle
Published: July 2021

This article proposes to synthesize sexual social constructionism, radical feminism, and cognitive sociology in order to identify and analyze “gender asymmetries” in heterosexual erotic attention. These gender asymmetries are evident in widely circulating androcentric imagery and prevailing linguistic conventions used to denote heterosexual activity, in erotic schematizations that differentially ascribe erotic meaning (and thereby erotic attention) to bodies that have been classified as “female,” and in interactional dynamics and constructions of sexual‐selfhood that perceptually foreground the desires and somatic sensations (subjective embodiment) of men and background those of women. Irreconcilable accounts of sexual interactions from the #MeToo Movement are cited to illustrate the analytic purchase of the proposed conceptual framework for clarifying issues of pleasure parity and consent.
Design of energy‐efficient intermittently connected sensor networks
Authors: Kimura Tomotaka , Fukuoka Masahiro , Hirata Kouji , Muraguchi Masahiro
Published: July 2021

This paper introduces the concept of intermittently connected sensor networks where sensors are sleep most of time and become active randomly and rarely. In the networks, packet collision probability and power consumption can be reduced. Meanwhile, the delivery delay increases with the use of the low activation values. In this paper, we design the energy‐efficient intermittently connected sensor networks, considering this trade‐off of activation control. We first provide the algorithm that computes the optimal packet forwarding rule achieving the minimum delivery delay, which can be calculated using the activation rates. We then propose the activation rate control methods, which control the activation rates of the sensors based on the density of the sensors and/or the number of wake‐ups of sensors having relay packets. By doing this, we can improve the delay performance, while suppressing the increase in the packet collision probability and the power consumption of sensors. Through simulation experiments, we demonstrate the effectiveness of our activation control methods in the intermittently connected sensor networks. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Gustav Nikolaus Specht (1860–1940)
Authors: Braun Birgit , Kornhuber Johannes
Published: July 2021

Hinführung

Gustav Specht steht am Anfang der Erlanger Universitätspsychiatrie. 80 Jahre nach seinem Tod untersucht der vorliegende Artikel insbesondere die Rolle Spechts bei der von Kraepelin ausgehenden psychopathologisch-nosologischen Diskussion. Trotz spärlicher Datenlage unternehmen die Autoren erstmals eine Annäherung an Spechts Positionen innerhalb der nationalsozialistischen Psychiatrie.

Methode

Relevantes archivalisches Material sowie Primär- und Sekundärliteratur wurden ausgewertet.

Ergebnisse

Specht wurde 1897 zum außerplanmäßigen Professor und 1903 zum ersten Ordinarius für Psychiatrie in Erlangen ernannt. Specht arbeitete die Bedeutung des manischen Elementes in der Paranoia heraus. Specht ergänzte den sog. „exogenen Reaktionstypus“ Bonhoeffers 1913 um die depressiven Zustandsbilder; er selbst war – bei fremddiagnostischem Verdacht auf zyklothymes Temperament – zweimalig exogen reaktiv depressiv erkrankt.

Diskussion

Durch seine Forschungsarbeiten zum pathologischen Affekt in der chronischen Paranoia beeinflusste Specht die zeitgenössische psychopathologische Diskussion nachhaltig. Spechts Perspektivenwechsel in puncto „Erbgesundheit“ lässt sich interpretieren als Anpassung an das NS-Regime.

Schlussfolgerung

Das Werk Gustav Spechts kann u. a. dazu anregen, einen interdisziplinären psychopathologischen Diskurs zu kultivieren.
Using uniform design and regression methodology of turning parameters study of nickel alloy
Authors: Chen Shao-Hsien , Hsu Chih-Hung
Published: July 2021

The nickel alloy has good mechanical strength and corrosion resistance at high temperature; it is extensively used in aerospace and biomedical and energy industries, as well as alloy designs of different chemical compositions to achieve different mechanical properties. However, for high mechanical strength, low thermal conductivity, and surface hardening property, the nickel alloy has worse cutting tool life and machining efficiency than general materials. Therefore, how to select the optimum machining parameters will influence the workpiece quality, cost, and machining time. This research will be using a new experimental design methodology to the cutting parameter planning for nickel-based alloy cutting test, and used the uniform design methodology to cutting test to reduce the number of experiments. Three independent variable parameters are set up, including cutting speed, feed rate, and cutting depth, and four dependent variable parameters are set up, including cutting tool wear, surface roughness, machining time, and cutting force. A nickel alloy turning parameter model is built by using regression analysis to further predict the I/O relationship among various combinations of variables. The errors between actual values and prediction values are validated. When the cutting tool wear (VB) is 2.72~6.18%, the surface roughness (Ra) is 4.10~7.72%, the machining time (T) is 3.75~8.82%, and the cutting force (N) is 1.54~7.42%; the errors of various dependent variables are approximately less than 10%, so a high precision estimation model is obtained through a few experiments of uniform design method.
Harnessing beliefs to optimally disclose contestants’ types
Authors: Serena Marco
Published: July 2021

A contestant’s effort depends on her knowledge of her rival’s type. This knowledge is often limited in real-life contests. We propose a model where the principal of a contest has commitment power to verifiably disclose contestants’ types. We investigate the optimal disclosure policy to stimulate contestants’ efforts. Full disclosure stimulates more (less) effort than full concealment if high-types are more (less) likely than low-types. However, regardless of the likelihood of types, the optimal policy is that of contingent disclosure; it is optimal to commit to disclosing if both contestants are high types and concealing otherwise.
Automated alternate cover test for ‘HINTS’ assessment: a validation study
Authors: Morrison Miranda , Kerkeni Hassen , Korda Athanasia , Räss Simone , Caversaccio Marco D. , Abegg Mathias , Schneider Erich , Mantokoudis Georgios
Published: July 2021

Objective

The alternate cover test (ACT) in patients with acute vestibular syndrome is part of the ‘HINTS’ battery test. Although quantitative, the ACT is highly dependent on the examiner’s experience and could theoretically vary greatly between examiners. In this study, we sought to validate an automated video-oculography (VOG) system based on eye tracking and dedicated glasses.

Methods

We artificially induced a vertical strabismus to simulate a skew deviation on ten healthy subjects, aged from 26 to 66, using different press-on Fresnel prisms on one eye while recording eye position with VOG of the contralateral eye. We then compared the system’s performance to that of a blinded trained orthoptist using conventional, semi-quantitative method of skew measurement known as the alternate prism cover test (APCT) as a gold standard.

Results

We found a significant correlation between the reference APCT and the Skew VOG (Pearson’s R2 = 0.606, p < 0.05). There was a good agreement between the two tests (intraclass correlation coefficient 0.852, 95 CI 0.728–0.917, p < 0.001). The overall accuracy of the VOG was estimated at 80.53% with an error rate of 19.46%. There was no significant difference in VOG skew estimations compared with the gold standard except for very small skews.

Conclusions

VOG offers an objective and quantitative skew measurement and proved to be accurate in measuring vertical eye misalignment compared to the ACT with prisms. Precision was moderate, which mandates a sufficient number of tests per subject.
Modern Chiral Forces Applied to the Neutron-Deuteron Breakup Reaction
Authors: Skibiński Roman , Golak Jacek , Soloviov Volodymyr , Topolnicki Kacper , Volkotrub Yuriy , Witała Henryk
Published: July 2021

We report on applications of the recent chiral potentials from the Bochum-Bonn group to the description of the neutron induced deuteron breakup observables. Specifically, we discuss the convergence of predictions with respect to the chiral order and the dependence of our results on the value of the regularization parameter. To that end we use the chiral forces with semi-local coordinate or momentum space regularization up to the N$$^4$$

4

LO$$^+$$

+

order of chiral expansion. We find a satisfactory picture revealing high quality of the chiral forces used.
Brain metastases in gastroesophageal cancers—an underestimated complication
Authors: Brunner Marius , Soll Dominik , Adler Kathrin , Sasse André , König Ute , Mekolli Ardian , Lowes Kristina , Reinecke Johanna , Ellenrieder Volker , König Alexander
Published: July 2021

Background

Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs.

Methods

We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs.

Results

From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091).

Conclusion

In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.
Lockean Beliefs, Dutch Books, and Scoring Systems
Authors: Rothschild Daniel
Published: July 2021

On the Lockean thesis one ought to believe a proposition if and only if one assigns it a credence at or above a threshold (Foley in Am Philos Q 29(2):111–124, 1992). The Lockean thesis, thus, provides a way of characterizing sets of all-or-nothing beliefs. Here we give two independent characterizations of the sets of beliefs satisfying the Lockean thesis. One is in terms of betting dispositions associated with full beliefs and one is in terms of an accuracy scoring system for full beliefs. These characterizations are parallel to, but not merely derivative from, the more familiar Dutch Book (de Finetti in Theory of probability, vol 1, Wiley, London, 1974) and accuracy (Joyce in Philos Sci 65(4):575–603, 1998) arguments for probabilism.
Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687
Authors: Vanhove Marc , Wagner Jean-Marc , Noppen Bernard , Jonckx Bart , Vermassen Elke , Stitt Alan W.
Published: July 2021

Intravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.
Are Functional Measures Sufficient to Capture Acceptance? A Qualitative Study on Lower Limb Exoskeleton Use for Older People
Authors: del Rio Carral Maria , Bourqui Vanlisa , Vuilleumier Noémie , Ortieb Amalric , Bouri Mohamed
Published: July 2021

Lower limb exoskeletons (LLE) are robotic devices developed to assist walk. In the field of healthcare, this technology has been available for almost a decade, yet it still faces important acceptance issues. While LLE were first developed for patients with spinal cord injuries, we expect their use to expand to everyday settings to benefit other populations, namely that of older people with reduced mobility (RM). We propose a qualitative approach to unearth key psychosocial themes on the acceptance of LLE in daily living for older people. The study analyses perceptions of older people with RM, as well as their entourage, including informal and professional caregivers. Using a grounded theory approach we analysed 12 semi-structured interviews with older people with RM; 2 focus groups with informal caregivers, and 2 focus groups with professional caregivers. LLE were introduced to participants through photo-elicitation. Older people with RM believed that LLE would increase their autonomy. They also perceived that using LLE would make them feel less of a burden for their entourage. Beyond these expected benefits, results captured participants’ ambivalence, dependent on their experiences of the ageing process and perceptions on the human–machine interaction. Informal caregivers highlighted that LLE could provide important relief related to the burden of care. Nonetheless, professional caregivers raised the fear of LLE leading to dehumanization of care. While each group had specific concerns on how LLE use would impact their lives, psychosocial considerations played a key role in LLE acceptance.
Upregulation of TCF21 inhibits migration of adrenocortical carcinoma cells
Authors: Kremer Jean Lucas , Auricino Thais Barabba , dos Santos Passaia Bárbara , Lotfi Claudimara Ferini Pacicco
Published: July 2021

Background

Adrenocortical carcinomas (ACC) are rare and aggressive cancer. Our previous study has revealed that the transcription factor 21, TCF21, is downregulated in ACC and regulates steroidogenic factor 1 (SF-1) binding to the SF-1 E-box promoter. In addition, it could be found that TCF21 is a predictor of overall survival (OS) in adult carcinomas.

Methods

In this study, it was investigated the correlation between TCF21 expression and the promoter methylation status in adrenocortical tumor cells, carcinomas and adenoma. The biological function and potential molecular mechanism of TCF21 restoration in migration and invasion of ACC cells was examined.

Results

We could be demonstrated a negative correlation between the level of TCF21 expression and methylation of its promoter in adenoma and carcinoma cells indicating the epigenetic control of TCF21 expression. It was also demonstrated that the expression of TCF21 inhibits migration and invasion in the ACC cell line, H295R cells, using plasmid transfection to express TCF21. Furthermore, it could be investigated the TCF21 function as tumor suppressor probably through Kisspeptin 1 (KISS-1) expression and epithelial–mesenchymal transition (EMT) reversion, as well as the modulation of several metalloproteinases in ACC cells.

Conclusions

Our results suggest that enhancement of TCF21 expression levels may be a potential strategy to revert invasive abilities in adrenocortical carcinomas.
Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections
Authors: Albadr Alyaa A. , Tekko Ismaiel A. , Vora Lalitkumar K. , Ali Ahlam A. , Laverty Garry , Donnelly Ryan F. , Thakur Raghu Raj Singh
Published: July 2021

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)–based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays’ reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.

Graphical abstract
The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment
Authors: Ahn Jeeyun , Gorin Michael B.
Published: July 2021

Purpose of Review

Obstructive sleep apnea (OSA) patients are at significantly increased risks for cardiovascular and cerebrovascular morbidities. Recently, there has been heightened interest in the association of OSA with numerous ocular diseases and possible improvement of these conditions with the initiation of OSA treatment. We reviewed the current evidence with an emphasis on the overlapping pathogeneses of both diseases.

Recent Findings

Currently available literature points to a substantial association of OSA with ocular diseases, ranging from those involving the eyelid to optic neuropathies and retinal vascular diseases. Since the retina is one of the highest oxygen-consuming tissues in the body, the intermittent hypoxia and hypercapnia ensuing in OSA can have deleterious effects on ocular function and health. Tissue hypoxia, autonomic dysfunction, microvascular dysfunction, and inflammation all play important roles in the pathogenesis of both OSA and ocular diseases. Whether OSA treatment is capable of reversing the course of associated ocular diseases remains to be determined. It is anticipated that future therapeutic approaches will target the common underlying pathophysiologic mechanisms and promote favorable effects on the treatment of known associated ocular diseases.

Emerging evidence supports the association of ocular diseases with untreated OSA. Future studies focusing on whether therapeutic approaches targeting the common pathophysiologic mechanisms will be beneficial for the course of both diseases are warranted.
Low and non-uniform illumination color image enhancement using weighted guided image filtering
Authors: Mu Qi , Wang Xinyue , Wei Yanyan , Li Zhanli
Published: July 2021

In the state of the art, grayscale image enhancement algorithms are typically adopted for enhancement of RGB color images captured with low or non-uniform illumination. As these methods are applied to each RGB channel independently, imbalanced inter-channel enhancements (color distortion) can often be observed in the resulting images. On the other hand, images with non-uniform illumination enhanced by the retinex algorithm are prone to artifacts such as local blurring, halos, and over-enhancement. To address these problems, an improved RGB color image enhancement method is proposed for images captured under non-uniform illumination or in poor visibility, based on weighted guided image filtering (WGIF). Unlike the conventional retinex algorithm and its variants, WGIF uses a surround function instead of a Gaussian filter to estimate the illumination component; it avoids local blurring and halo artifacts due to its anisotropy and adaptive local regularization. To limit color distortion, RGB images are first converted to HSI (hue, saturation, intensity) color space, where only the intensity channel is enhanced, before being converted back to RGB space by a linear color restoration algorithm. Experimental results show that the proposed method is effective for both RGB color and grayscale images captured under low exposure and non-uniform illumination, with better visual quality and objective evaluation scores than from comparator algorithms. It is also efficient due to use of a linear color restoration algorithm.
Das Versprechen der Architektur: Schaffen Multireligiöse Räume Toleranz?
Authors: Burchardt Marian , Häring Johanna
Published: July 2021

Während interreligiöse Dialoge durch ikonische architektonische Projekte eine größere öffentliche Sichtbarkeit und mediale Aufmerksamkeit erlangt haben, ist deren breitere gesellschaftliche Wahrnehmung und Wirkung weitestgehend unerforscht. Der Beitrag untersucht gruppenspezifische Wahrnehmungen interreligiöser Beziehungen und Positionierungen zu interreligiösen Dialogen. Im Zentrum der Analyse stehen dabei die Debatten zum BerlinerHouse of One, einem derzeit im Bau befindlichen multireligiösen Gebäude. Unter Rückgriff auf soziologische Konzeptualisierungen zum Verhältnis von Religion, Macht und Stadtraum untersucht der Beitrag, welche unterschiedlichen sozialen Positionen religiöser Akteur*innen (Protestant*innen, Alevit*innen und Muslim*innen) in den kulturellen Hierarchien urbaner Räume sich in solchen Wahrnehmungen dokumentieren. Wir argumentieren, dass die in diskursiven Aushandlungsprozessen zu interreligiösen Dialogen vorgenommenen Positionierungen solche kulturellen Hierarchien auf besondere Weise hervortreten lassen und damit auch auf blinde Flecken des Dialog-Paradigmas aufmerksam machen. Der Beitrag basiert auf Gruppendiskussionen und Einzelinterviews.
Eichhornia crassipes (Mart.) Solms (natural or carbonized) as biosorbent to remove pollutants in water
Authors: Lima Herbert de P. , Asencios Yvan J. O.
Published: July 2021

The prolific aquatic herbEichhornia crassipesconsidered a pest in many countries can cause damage such as obstruction of water flows and impair the locomotion of fishing boats. However,E. crassipesis renewable, inexpensive, and widely available in nature, and its ability to adsorb recalcitrant pollutants with mutagenic and carcinogenic properties, including synthetic dyes and heavy metals, has been extensively studied by the scientific community. This review paper analyzes previous reports concerning the use ofE. crassipes(in the natural and carbonized form) as an adsorbent for heavy metal cations and textile dye. The adsorptive capacity ofE. crassipes,the best conditions (adsorbent dosage, pH, and temperature) for the removal of these pollutants, the mechanism of adsorption, and the comparison between natural and carbonized forms (advantages and disadvantages) are discussed. All the results revised in this review indicated that the use ofE. crassipes(and its carbon derived) as adsorbent is promising and is an excellent material to be applied in the water treatment. It could be used in the actual technologies for the treatment of contaminated water by heavy metals and textile dyes; however, more studies need to be made on scale-up, economy projects, and related issues, to be finally implemented in wastewater treatment plants.
Structural insights into the role of DNA-PK as a master regulator in NHEJ
Authors: Chen Siyu , Lees-Miller James P. , He Yuan , Lees-Miller Susan P.
Published: July 2021

DNA-dependent protein kinase catalytic subunit DNA-PKcs/PRKDC is the largest serine/threonine protein kinase of the phosphatidyl inositol 3-kinase-like protein kinase (PIKK) family and is the most highly expressed PIKK in human cells. With its DNA-binding partner Ku70/80, DNA-PKcs is required for regulated and efficient repair of ionizing radiation-induced DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway. Loss of DNA-PKcs or other NHEJ factors leads to radiation sensitivity and unrepaired DNA double-strand breaks (DSBs), as well as defects in V(D)J recombination and immune defects. In this review, we highlight the contributions of the late Dr. Carl W. Anderson to the discovery and early characterization of DNA-PK. We furthermore build upon his foundational work to provide recent insights into the structure of NHEJ synaptic complexes, an evolutionarily conserved and functionally important YRPD motif, and the role of DNA-PKcs and its phosphorylation in NHEJ. The combined results identify DNA-PKcs as a master regulator that is activated by its detection of two double-strand DNA ends for a cascade of phosphorylation events that provide specificity and efficiency in assembling the synaptic complex for NHEJ.
Learning 2-Opt Heuristics for Routing Problems via Deep Reinforcement Learning
Authors: da Costa Paulo , Rhuggenaath Jason , Zhang Yingqian , Akcay Alp , Kaymak Uzay
Published: July 2021

Recent works using deep learning to solve routing problems such as the traveling salesman problem (TSP) have focused on learning construction heuristics. Such approaches find good quality solutions but require additional procedures such as beam search and sampling to improve solutions and achieve state-of-the-art performance. However, few studies have focused on improvement heuristics, where a given solution is improved until reaching a near-optimal one. In this work, we propose to learn a local search heuristic based on 2-opt operators via deep reinforcement learning. We propose a policy gradient algorithm to learn a stochastic policy that selects 2-opt operations given a current solution. Moreover, we introduce a policy neural network that leverages a pointing attention mechanism, which can be easily extended to more generalk-opt moves. Our results show that the learned policies can improve even over random initial solutions and approach near-optimal solutions faster than previous state-of-the-art deep learning methods for the TSP. We also show we can adapt the proposed method to two extensions of the TSP: the multiple TSP and the Vehicle Routing Problem, achieving results on par with classical heuristics and learned methods.
Extracellular Matrix Remodeling in Chronic Liver Disease
Authors: Ortiz Cristina , Schierwagen Robert , Schaefer Liliana , Klein Sabine , Trepat Xavier , Trebicka Jonel
Published: July 2021

Purpose of the Review

This review aims to summarize the current knowledge of the extracellular matrix remodeling during hepatic fibrosis. We discuss the diverse interactions of the extracellular matrix with hepatic cells and the surrounding matrix in liver fibrosis, with the focus on the molecular pathways and the mechanisms that regulate extracellular matrix remodeling.

Recent Findings

The extracellular matrix not only provides structure and support for the cells, but also controls cell behavior by providing adhesion signals and by acting as a reservoir of growth factors and cytokines.

Hepatic fibrosis is characterized by an excessive accumulation of extracellular matrix. During fibrogenesis, the natural remodeling process of the extracellular matrix varies, resulting in the excessive accumulation of its components, mainly collagens. Signals released by the extracellular matrix induce the activation of hepatic stellate cells, which are the major source of extracellular matrix and most abundant myofibroblasts in the liver.

Graphical abstract
Economics of Visual Art
Authors: Whitaker Amy
Published: July 2021

How can arts managers, artists, and art market observers approach the study of economics? Accompanied by hand-drawn illustrations, wide-ranging case studies, and expansive discussion resources, this interdisciplinary microeconomics primer engages with complex – and, at turns, political – questions of value and resourcefulness with the artist or manager as the decision-maker and the gallery, museum or studio as 'the firm'. Whitaker arms the reader with analytic and creative tools that can be used in service to economic sustainability for artists and organizations. By exploring the complexities of economics in application to art, design and creative industries, this book offers ways to approach the larger world as an art project.