bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
Authors: Huang Manling , He Minghui , Guo Yu , Li Heping , Shen Shunli , Xie Yubin , Li Xiaoxing , Xiao Han , Fang Lujing , Li Dongming , Peng Baogang , Liang Lijian , Yu Jun , Kuang Ming , Xu Lixia , Peng Sui
Published: June 2020

Purpose:

Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.

Experimental Design:

We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti–programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated.

Results:

The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti–PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti–PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma.

Conclusions:

The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti–PD-1 therapy.
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?
Authors: Khasraw Mustafa , Reardon David A. , Weller Michael , Sampson John H.
Published: June 2020

Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood–brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intratumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for future basic and clinical research and to provide a novel perspective to further stimulate preclinical and clinical research to ultimately help patients with glioma, including glioblastoma, which is arguably one of the greatest areas of unmet need in cancer. Moving forward, we need to build on our existing knowledge by conducting further fundamental glioma immunobiology research in parallel with innovative and methodologically sound clinical trials.
Tumor Endothelial Cell–Mediated Antigen-Specific T-cell Suppression via the PD-1/PD-L1 Pathway
Authors: Taguchi Kazuhiro , Onoe Takashi , Yoshida Tomoaki , Yamashita Yoshinori , Tanaka Yuka , Ohdan Hideki
Published: June 2020

Tumor endothelial cells (TEC) play multiple roles in the regional specialization of vascular structure and physiology. Because TECs in the tumor microenvironment come in contact with circulating immune cells, they might influence not only trafficking but also the antitumor cellular immune response. In a mouse tumor implantation model with B16 melanoma cells, TECs expressed MHC class II, costimulating molecules, and programmed death-ligand 1 (PD-L1), suggesting that they are antigen (Ag)-presenting cells with suppressive activity. Furthermore, TECs were able to take up and present tumor-derived ovalbumin (OVA) peptide on MHC class I molecules. In functional assays, B16-OVA tumor–derived TECs significantly suppressed the proliferation and Ag-specific cytotoxicity of OVA-specific CD8+ T cells relative to those of B16 tumor–derived TECs. This suppressive activity required cell–cell contact and was abrogated by PD-L1 blockade. TECs impaired proinflammatory cytokine production of CD8+ T cells, including IL2, TNFα, and IFNγ. B16-OVA tumor–derived TECs induced immunosuppressive CD4+ T cells that suppressed OVA-specific CD8+ T-cell proliferation via inhibitory cytokines, including IL10 and TGFβ. Deficiency of PD-L1 in TECs, but not in hematopoietic cells, impaired suppression and apoptosis of tumor-infiltrating CD8+ T cells, resulting in inhibition of tumor development in vivo model. These data suggest that TECs might regulate the immune response of tumor Ag–specific CD8+ T cells via the PD-1/PD-L1 pathway and induce immune suppressive CD4+ T cells in an Ag-specific manner, contributing to tumor immune evasion.

Implications:

The findings of this study might encourage the further development of novel anticancer therapies and strategies.
The Protective Effect of Pre-Moxibustion on Reproductive Hormones Profile of Rats with Tripterygium Glycosides-Induced Ovarian Damage
Authors: Zhu Shipeng , Wang Yaoshuai , Chang Xiaoxia , Chen Huan , Jin Xun
Published: June 2020

Background: Acupuncture and moxibustion have been proven to be conducive to improving the ovarian reserve. However, the mechanism of pre-moxibustion on Tripterygium glycosides (TG)-induced ovarian damage has not been previously reported. Method: Female rats were randomly divided into 5 groups: control, model (75 mg/kg TG, 14 days), preventive moxibustion 1 (PM1, receiving moxibustion for 4 weeks before TG administration), preventive moxibustion 2 (PM2, receiving moxibustion for 2 weeks before TG administration and another 2 weeks during TG administration), and preventive moxibustion 3 (PM3, receiving 4 weeks of moxibustion during TG administration). The estrous cycle of the animal was recorded after TG administration. Rats were sacrificed 14 days after TG administration. The reproductive hormones profiles in serum, ovary, and hypothalamic tissues were analyzed. Result: Pre-moxibustion could revert abnormal estrous cycles, relieve follicle damage, and improve abnormal secretion of reproductive hormones resulting from ovarian damage. However, both PM2 and PM3 were more effective than PM1. In addition, PM2 disclosed more advantages in regulating reproductive hormones abnormalities, while PM3 performed better in follicular development. Conclusion: In combination, the findings of this study suggest that pre-moxibustion is effective in protecting the ovary from damage in TG-induced ovarian damage rats. But different time points correspond to different modulation targets and mechanisms.
Effect and Molecular Mechanisms of Collateral Vessel Growth Mediated by Activation of Transient Receptor Potential Vanilloid Type 1
Authors: Zhao Shuang , Liu Weiqing , Feng Chengan , Zhang Xingping , Cai Weijun , Luo Mingying
Published: June 2020

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.
The Alternative Model of Personality Disorders (AMPD) from the Perspective of the Five-Factor Model
Authors: Widiger Thomas A. , McCabe Gillian A.
Published: June 2020

The fifth edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders(DSM-5; American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington: American Psychiatric Association; 2013) includes an Alternative Model of Personality Disorders (AMPD). The AMPD includes two components: the Criterion A level of personality functioning (i.e., impairments or deficits in the sense of self and interpersonal relatedness) and the Criterion B five-domain maladaptive trait model. The purpose of the current paper is to discuss the AMPD from the perspective of the Five-Factor Model (FFM) of general personality structure. The conclusion of this review is that both the Criterion A self-other deficits and the Criterion B traits can be understood as maladaptive variants of the FFM.
Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms
Authors: Mahmoudi Narges , Kiasalari Zahra , Rahmani Tayebeh , Sanaierad Ashkan , Afshin-Majd Siamak , Naderi Gholamali , Baluchnejadmojarad Tourandokht , Roghani Mehrdad
Published: June 2020

Objective: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation.Methods:Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. Results: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon­dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. Conclusions: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential.
Secondary Alopecia Neoplastica Mimicking Alopecia Areata following Breast Cancer
Authors: Skafida Efthymia , Triantafyllopoulou Ioanna , Flessas Ioannis , Liontos Michael , Koutsoukos Konstantinos , Zagouri Flora , Dimopoulos Athanasios-Meletios
Published: June 2020

Cutaneous metastases from visceral carcinomas are relatively uncommon, with an overall incidence ranging from 0.7 to 9%. Diagnosis of scalp metastases usually escapes clinicians and dermatologists due to the fact that these metastases are mimicking other benign dermatological conditions. Herein, we present an uncommon case of scalp alopecia neoplastica mimicking alopecia areata due to breast cancer; a 43-year-old woman diagnosed with lobular cancer 3 years previously presented with acute loss of hair in well-circumscribed areas of the scalp and was diagnosed with alopecia areata by a private-practice dermatologist. She was then reevaluated, and due to her history of breast cancer, a biopsy from the scalp was performed and revealed alopecia neoplastica. At the same time that the skin lesions were recognized as disease involvement, the patient presented with dyspepsia, and endoscopy of the upper and lower gastrointestinal tract also revealed metastasis to the stomach and bowel. Gastrointestinal metastasis may occur with several types of cancer, but the stomach and bowel are rare metastatic sites for breast cancer.
Studium zur Psychotherapie-Approbation als Herausforderung und Chance: Praktische Hochschullehrkonzepte in der klinischen Psychologie und Psychotherapie
Authors: Wilhelm Marcel , Rief Winfried , Haberkamp Anke , von Blanckenburg Pia , Glombiewski Julia Anna
Published: June 2020

Die Psychotherapiereform verändert die Ausbildung von Psychotherapeutinnen und -therapeuten in Deutschland: Zukünftig sollen klinisch-psychologische Masterstudiengänge mit einer staatlichen Approbationsprüfung in Psychotherapie abgeschlossen werden. Die hochschulische Lehre muss entsprechend psychotherapeutische Basisfertigkeiten praktisch vermitteln. Dieser Artikel stellt Modelle praxisorientierter Lehrveranstaltungen der klinischen Psychologie der Phi­lipps-Universität Marburg vor, die größtenteils seit Jahren erprobt sind. Bei den praktischen Übungen “Interventionspraktikum 1 und 2” machen Studierende erste Erfahrungen mit therapeutischen Techniken an persönlich relevanten Problemen. Im Fallseminar wird das Gelernte an einem Fall aus der ambulanten Versorgung vertieft und eine Translation des Grundlagenwissens auf einen individualisierten Behandlungsplan gefördert. Während hier mit einem Fall intensiv gearbeitet wird, bietet das Seminar “Unterschiedliche Ansätze der Psychotherapie in der Praxis” die Gelegenheit, 6 verschiedene Fälle aus wechselnden Behandlungssettings nach vorgegebenen Gruppenthemen zu explorieren und Unterschiede herauszuarbeiten. Die Veranstaltungen werden regelmäßig evaluiert. Eine Übersicht über verschiedene Lehrpersonen hinweg zeigt eine sehr hohe Zufriedenheit der Studierenden mit den Veranstaltungskonzepten. Die bestehenden Veranstaltungen setzen viele Forderungen der neuen Approbationsordnung um, v.a. im Hinblick auf die berufsqualifizierende Tätigkeit II und III sowie die Selbstreflexion. Notwendige Anpassungen sowie zusätzliche Anforderungen an die Hochschullehre werden diskutiert und Lösungsvorschläge gemacht. Werden die Anforderungen der Approbationsordnung entsprechend umgesetzt, scheint Approbation im Anschluss an das Masterstudium gerechtfertigt.
Ultrasound Measurements of Intracranial Structures in Growth-Restricted Neonates with Fetal Blood Flow Redistribution: A Pilot Observational Study
Authors: Pharande Pramod , Krishnamurthy Mohan , Whiteley Gillian , Sasi Arun , Malhotra Atul
Published: June 2020

Background: Fetal growth restriction (FGR) is associated with neonatal and long-term neuro-morbidity. Preferential redistribution of blood flow to the brain is a common antenatal adaptation in FGR. The impact of this “brain sparing,” which may signify severity of FGR, on the growth of brain structures has not been studied. Aim: To compare corpus callosum (CC), cerebellar, and ventricular measurements of FGR neonates with evidence of fetal blood flow redistribution with those of gestation-matched appropriately grown (AGA) neonates. Methods: This was a pilot, prospective observational study conducted at a tertiary level neonatal unit in Melbourne, Australia. Cranial ultrasound was done between days 1 and 3 of life in FGR and AGA neonates. Results: Cranial ultrasound on 20 FGR, gestation (mean ± SD) 31.4 ± 3.1 weeks, weight 1,205 ± 463 g, and 20 AGA neonates, 31.1 ± 3.0 weeks, 1,668 ± 490 g, was performed. CC length was significantly decreased in FGR neonates as compared to AGA neonates (35.28 ± 3.47 vs. 38.83 ± 4.05 mm, p = 0.0002). CC was significantly thinner at genu (3.36 ± 0.66 vs. 4.04 ± 0.83 mm, p = 0.007), body (1.97 ± 0.36 vs. 2.27 ± 0.39 mm, p = 0.02), and splenium (4.07 ± 0.76 vs. 4.72 ± 0.75 mm, p = 0.003) in FGR vs. AGA neonates. CC-fastigium length was also significantly decreased (39.65 ± 3.87 vs. 41.96 ± 4.50 mm, p = 0.04). Similarly, FGR neonates showed decreased transverse cerebellar diameter (36.15 ± 5.51 vs. 38.81 ± 7.21 mm, p = 0.02), but ventricular measurements were comparable. In multivariate analysis, these differences were evident independent of the birth weight. Conclusions:CC and cerebellar measurements are significantly smaller in FGR neonates with fetal blood flow redistribution, which warrants further study.
Dermoscopic Features of Nail Psoriasis: An Observational, Analytical Study
Authors: Chauhan Ankita , Singal Archana , Grover Chander , Sharma Sonal
Published: June 2020

Introduction: Nail involvement in psoriasis occurs in up to 30–50% of patients, and 5–10% may have isolated nail disease. Onychoscopy, a noninvasive tool, might obviate the need for nail biopsy, which is a diagnostic gold standard. Objective: The aim of this study was to evaluate onychoscopic features of nail unit in patients with nail psoriasis. Methods: Fifty-five patients with clinically diagnosed and histologically documented nail psoriasis were recruited. Onychoscopy was performed for each nail (excluding the 5th toenail). Clinically, 443/550 fingernails and 101/440 toenails were involved. The frequency distributions of various onychoscopic features was assessed and compared using the χ2 test (p value <0.05 was considered significant). Results: With onychoscopy, additional 52 fingernails and 64 toenails showed psoriatic involvement. Pitting was the commonest finding in fingernails (60.5%) followed by subungual hyperkeratosis (SUH) (52.8%), onycholysis (40.8%), and dotted capillaries in hyponychium, proximal, and lateral nail folds (38.6 vs. 35.8 vs. 35.8%). In toenails, we observed SUH (85.1%), nail plate thickening (82.1%), onycholysis (77.2%), and dotted capillaries in hyponychium and nail folds (59.4 vs. 53.4 vs. 45.5%). Fuzzy lunula was a novel onychoscopic finding noted in 33.6% fingernails and 4.95% toenails (p < 0.00001). Limitations: Small sample size. Conclusions: Onychoscopy may aid in diagnosing nail lesions even before the clinical signs are apparent.
Specific Management of Patients with Acute Abdomen during the COVID-19 Pandemic: A Surgical Perspective from Germany
Authors: Kühn Florian , Klein Matthias , Laven Henning , Börner Nikolaus , Weinberger Tobias , Streitparth Florian , Werner Jens , Schiergens Tobias S.
Published: June 2020

During the current COVID-19 pandemic, the triage, assessment, and management of patients presenting to the emergency department with critical conditions has become ­challenging. The clinical features of COVID-19 are heterogeneous and subtle in many cases. They may easily be overlooked in the case of other acute diseases. Gastrointestinal symptoms are common in patients with COVID-19 as SARS-CoV-2 is able to enter gastrointestinal epithelial cells. However, these complaints can also be caused by a COVID-19-independent concomitant abdominal pathology. Therefore, patients with acute abdominal pain and fever need to be assessed very thoroughly. Based on a clinical case, we present our approach of managing emergency patients with acute abdomen and concomitant suspicion of ­COVID-19.
ADAM (a Disintegrin and Metalloproteinase) 15 Deficiency Exacerbates Ang II (Angiotensin II)–Induced Aortic Remodeling Leading to Abdominal Aortic Aneurysm
Authors: Jana Sayantan , Chute Michael , Hu Mei , Winkelaar Gerrit , Owen Caroline A. , Oudit Gavin Y. , Kassiri Zamaneh
Published: June 2020

Objective:

ADAM (a disintegrin and metalloproteinase) 15—a membrane-bound metalloprotease from the ADAM (disintegrin and metalloproteinase) family—has been linked to endothelial permeability, inflammation, and metastasis. However, its function in aortic aneurysm has not been explored. We aimed to determine the function of ADAM15 in the pathogenesis of aortic remodeling and aneurysm formation.

Approach and Results:

Male
Adam15
-deficient and WT (wild type) mice (10 weeks old), on standard laboratory diet, received Ang II (angiotensin II; 1.5 mg/kg per day) or saline (Alzet pump) for 2 or 4 weeks. Ang II increased ADAM15 in WT aorta, while
Adam15
-deficiency resulted in abdominal aortic aneurysm characterized by loss of medial smooth muscle cells (SMCs), elastin fragmentation, inflammation, but unaltered Ang II–mediated hypertension. In the abdominal aortic tissue and primary aortic SMCs culture,
Adam15
deficiency decreased SMC proliferation, increased apoptosis, and reduced contractile properties along with F-actin depolymerization to G-actin. Ang II triggered a markedly greater increase in THBS (thrombospondin) 1 in
Adam15
-deficient aorta, primarily the medial layer in vivo, and in aortic SMC in vitro; increased SSH1 (slingshot homolog 1) phosphatase activity and cofilin dephosphorylation that promoted F-actin depolymerization and G-actin accumulation. rhTHBS1 (recombinant THBS1) alone was sufficient to activate the cofilin pathway, increase G-actin, and induce apoptosis of aortic SMCs, confirming the key role of THBS1 in this process. Further, in human abdominal aortic aneurysm specimens, decreased ADAM15 was associated with increased THBS1 levels and loss of medial SMCs.

Conclusions:

This study is the first to demonstrate a key role for ADAM15 in abdominal aortic aneurysm through regulating the SMC function, thereby placing ADAM15 in a critical position as a potential therapeutic target for abdominal aortic aneurysm.
The Emaciated Soul: Four Women’s Self-Inscriptions on Their Portraits in Late Imperial China
Authors: Wang Yuanfei
Published: June 2020

This article examines the emaciated self-images of four women’s self-inscription poems on their own portraits. They are Huang Hong (early seventeenth century), Xi Peilan (1760­­­–after 1829), Tan Yinmei (fl. mid-eighteenth to early nineteenth century) and Zheng Lansun (1819-61). These women similarly describe their self-images as qiaocui (emaciated), alluding to the legendary girl poet Feng Xiaoqing. Inherently ambivalent, qiaocui could imply sexual and erotic appeal, the virtuous mind of a recluse, sickness, ordinariness, melancholy, as well as aging and death. The article argues for the importance of the rhetoric of qiaocui and the topoi of Feng Xiaoqing in the self-inscriptions by women in Hangzhou and the broader Jiangnan region as a medium to construct their female subjectivity. This article suggests that, initially a persona publicly circulated in the late Ming, the topoi of Feng Xiaoqing came to define the women’s personhood in private spaces in late eighteenth and early nineteenth centuries.
Masculinity, Femininity, Sacrifice, and Celebrity during China’s War of Resistance: Telling the Lives of the Aviators Yan Haiwen (1916-37) and Lee Ya-Ching (1912-98)
Authors: Baumler Alan
Published: June 2020

During the War of Resistance against Japan (1937-1945) the Chinese government publicized heroic pilots to win domestic and international support for the war effort and to raise money. These pilots also helped create a gendered image of China that was used by both state and non-state actors. The male pilot and martyr Yan Haiwen (1916-37) was part of a masculine discourse of sacrifice aimed at domestic audiences. The female pilot Lee Ya-Ching (1912-98) presented a modern, technologized Chinese femininity which assisted in the Chinese war effort by appealing to white audiences, but was also used by Overseas Chinese communities for their own purposes.
The Nature and Limits of the Duty of Rescue
Authors: Miller David
Published: June 2020

Virtually everyone believes that we have a duty to rescue fellow human-beings from serious danger when we can do so at small cost to ourselves – and this often forms the starting point for arguments in moral and political philosophy on topics such as global poverty, state legitimacy, refugees, and the donation of body parts. But how are we to explain this duty, and within what limits does it apply? It cannot be subsumed under a wider consequentialist requirement to prevent harm. Nor can it be understood as a duty of social justice that citizens owe to one another under a social contract for mutual protection. Instead it is a sui generis duty of justice that arises from the direct physical encounter between rescuer and victim, and is accordingly limited in scope. However the simplicity of the duty evaporates when multiple potential rescuers are present. Here responsibility lies with the collective as a whole until it is assigned by a fair procedure to individual members. Each individual is required as a matter of justice to discharge that share, but not more, though in the case that others do not comply, he will have a reason, and sometimes a humanitarian duty, to take up the slack.
All Animals are Equal, but Some More than Others?
Authors: Brouwer Huub , van der Deijl Willem
Published: June 2020

Does the moral badness of pain depend on who feels it? A common, but generally only implicitly stated view, is that it does not. This view, ‘unitarianism’, maintains that the same interests of different beings should count equally in our moral calculus. Shelly Kagan’s project in How to Count Animals, more or less (2019) is to reject this common view, and develop an alternative to it: a hierarchical view of moral status, on which the badness of pain does depend on who feels it. In this review essay, we critically examine Kagan’s argument for status hierarchy. In particular, we reject two of the central premises in his argument: that (1) moral standing is ultimately grounded in agency and (2) that unitarianism is overdemanding. We conclude that moral status may, despite Kagan’s compelling argument to the contrary, not be hierarchical.
Knowledge without “Experience”
Authors: Williams Michael
Published: June 2020

Genia Schönbaumsfeld argues that Cartesian skepticism is an illusion induced by the “Cartesian Picture” of perceptual knowledge, in which knowledge of the “external world” depends on an inference from how things subjectively seem to one to how they actually are. To show its incoherence, she draws on the work of John McDowell, which she sees as elaborating a central theme from Wittgenstein’s On Certainty. I argue that Cartesian skepticism is not an illusion, as Schönbaumsfeld understands ‘illusion’, and that McDowell’s account of perceptual knowledge is both untenable and incompatible with Wittgenstein’s ideas about knowledge. Schönbaumsfeld thinks that, to understand how perception can engender knowledge of the world, we need a non-Cartesian account of perceptual reasons. Wittgenstein offers a much more radical break with the Cartesian Picture: an account of knowledge without ‘experience’.
Scene and Object Violations Cause Subjective Time Dilation
Authors: Clarke Jason , Porubanova Michaela
Published: June 2020

For a given physical duration, certain events can be experienced as subjectively longer than others, an illusion referred to as subjective time dilation. Many factors have been shown to lead to this illusion in perceived duration, including low-level visual properties of the stimulus (e.g., increase in motion, brightness, and flicker), an unexpected stimulus in a sequence of events, as well as affective factors. Here we report the results of two experiments in which we tested for the influence of scene and object knowledge on subjective time dilation. Based on the results of earlier studies, we predicted that visual scenes and objects containing semantic violations would be judged as lasting longer than control stimuli. The findings from both experiments indicate that stimuli containing semantic violations were judged to be present for longer than stimuli without semantic violations. We interpret our results to mean that neural processes that encode for perception of duration can operate on conceptually integrated scene and object representations. We further conjecture that the underlying neural code for duration perception is likely correlated with the amplitude of neural activity expended on the processing of incoming sensory information.
A Bergia in South America: on the neglected, possibly already extinct B. arenarioides (Elatinaceae)

Authors: HASSEMER GUSTAVO
Published: June 2020

The only species of Bergia known from South America, B. arenarioides, was originally described as Merimea arenarioides in 1829 and has been surprisingly neglected in the literature and databases since after the publication of the treatment of the Elatinaceae for Flora brasiliensis in 1872. The species is only known from two gatherings, both from northern Minas Gerais, Brazil, the most recent of which is from 1914. In this work I designate a lectotype for the species, investigate and clarify the location of its type locality and discuss its taxonomy and nomenclature. I present this information aiming at fostering the search and eventual rediscovery of the species.
Updates to the bee fauna of Portugal with the description of three new Iberian Andrena species (Hymenoptera: Apoidea: Anthophila)
Authors: WOOD THOMAS JAMES , CROSS IAN , BALDOCK DAVID W.
Published: June 2020

Portugal is home to a rich but understudied bee fauna that was recently comprehensively documented for the first time. As part of ongoing work to improve the knowledge of Portuguese bees, efforts have been made to survey poorly recorded parts of the country and to continue to review existing material in museum collections. These efforts have resulted in 28 species newly discovered in Portugal, as well as eight species added from the literature and two taxa recently raised to full species status. Three additional species, Andrena (Lepidandrena) baetica spec. nov., Andrena (Micrandrena) omnilaevis spec. nov., and Andrena (Notandrena) foeniculae spec. nov. are described from material collected in southern Iberia, north-western Iberia, and southern Iberia, respectively. Andrena omnilaevis spec. nov. is the new name for north-western Iberian material previously identified as Andrena (Micrandrena) semilaevis Pérez. The male of Stelis hispanica Dusmet, previously only known from the holotype female, was also found and is described here. The taxon Andrena (Melandrena) limata mixtura Warncke has been various treated as a subspecies of A. limata Smith or A. nitida Müller. Examination of the holotype from Portugal shows that it actually belongs in its original combination Andrena limata comb. nov., and that true A. nitida is not present in Portugal. Seven additional species have been removed from the total due to misidentification or uncertainty. We also present discussion on the status of species complexes present in Portugal, and review species doubtfully recorded from the country. Altogether, this work increases the number of bee species recorded from mainland Portugal from 680 to 712, and to 722 for the country as a whole when including the faunas of the Madeira and Azores archipelagos.
Hospital Practices for Parents Following Perinatal Loss
Authors: Kalanlar Bilge
Published: June 2020

The aim of this study is to provide comprehensive and current information on hospital practices following perinatal death. The provinces with the highest number of hospitals in Turkey were selected for the study. To collect data, the questionnaire form of Canadian hospitals maternity policies and practices survey was sent to the appropriate respondents in hospitals. The study showed that encouraging parents to have photos of the deceased baby and preparing a remembrance pack were the most problematic issues and were not available at the majority of hospitals. The most common supportive practices in hospitals were the opportunity to see the deceased baby, assisting with funeral options and autopsies, and support for completing the necessary legal documents. The result indicated that hospitals implement varied practices in assisting the bereaved parents. The study recommended developing hospital policies and practices related to perinatal death and supporting families during their loss and grief.
Effect of knitting structure and yarn composition on thermal comfort properties of bi-layer knitted fabrics
Authors: Yang Yang , Yu Xin , Chen Liqun , Zhang Peihua
Published: June 2020

In this work, nine bi-layer knitted samples with varied knitting structures and made up of different yarn compositions were fabricated, and their thermal comfort properties were investigated. The thermal comfort properties were evaluated by breathability, water transfer properties, thermo-physiology properties and dynamic cooling properties, and their relationship with fabric knitting structure and yarn composition were investigated statistically. It was observed that bi-layer knitted fabrics with meshes at one side had better air permeability, moisture management properties, drying performance, thermo-physiological properties and dynamic cooling function, but lower wicking height than bi-layer knitted fabrics with trim and symmetrical structure (without meshes). The composition of nylon and polyester filaments with varied wettability as outer and inners layer of bi-layer knitted fabrics, respectively, improved the water one-way transport capacity significantly. In particular, bi-layer fabrics with asymmetric structure and made up of yarns with varied hydrophilicity as each layer have excellent moisture management capacity. Moreover, fabrics made up of yarns with finer fibers exhibited better thermal comfort properties.
Platform-mediated short-term rentals and gentrification in Madrid
Authors: Ardura Urquiaga Alvaro , Lorente-Riverola Iñigo , Ruiz Sanchez Javier
Published: June 2020

Gentrification demands updated frameworks to assess the impact of some major global trends on the local populations’ access to housing. Short-term accommodation using digital platforms in previously gentrified central urban areas is playing a significant role in outlining a new wave of ‘transnational gentrification’ in a number of global cities. Having undergone classical patterns of gentrification over the last two decades, the central district of Madrid and its surroundings are showing patterns of a new wave of gentrification in a context of economic crisis, planetary rent gaps, increasing global tourism and an increase in rental prices in central areas that may be related to the emergence of short-term rentals – making Madrid a relevant case for depicting transnational gentrification in the Southern European capitals. Based on empirical data, this work explores the holiday rental supply in Madrid over three years (2015–2018), verifying a strong association between the growth in tourist arrivals, the settlement of new residents from wealthy economic backgrounds and increasing rental prices. Since this process is accompanied by deregulation of local rental contracts and the growth of transnational Real Estate Investment Trusts (REITs), even in some of the most vulnerable areas located beyond the M-30 ring road, this wave of gentrification has the potential to produce displacement and substitution of residents.
Efficacy of Velopharyngeal Surgery for Positional Obstructive Sleep Apnea Hypopnea Syndrome
Authors: Sun Nian , Ye Jingying , Zhang Junbo , Kang Dan , Tai Jun , Wang Shengcai , Zhang Jie , Ni Xin
Published: June 2020

Background:

Positional obstructive sleep apnea hypopnea syndrome (P-OSAHS) is a distinct OSAHS type. Whether velopharyngeal surgery is efficacious for patients with P-OSAHS remains unclear.

Aim/Objective:

To investigate the efficacy and factors influencing velopharyngeal surgery for treatment of patients with P-OSAHS, defined as the apnea hypopnea index (AHI) in different body postures (supine AHI ≥2*nonsupine AHI).

Materials and Methods:

A total of 44 patients with P-OSAHS who underwent velopharyngeal surgery were retrospectively studied. The clinical data of these patients, including polysomnography (PSG), physical examination, and surgical information, were collected for analysis. All patients underwent a PSG about 6 months after surgery to determine the treatment outcomes.

Results:

The overall AHI of the 44 patients decreased from 40.2 ± 18.7 events/h to 18.5 ± 17.5 events/h after surgery ( P < .001). There were 29 responders (65.9%) according to the classical definition of surgical success. The percentage of sleep time with oxygen saturation below 90% (CT90) was the only predictive parameter for surgical success ( P = .014, odds ratio value = 0.894). There was no significant difference between the change in supine AHI (−55.9 ± 35.2%) and the change in nonsupine AHI (−43.4 ± 74.1%; P = .167), and these 2 parameters were significantly correlated ( r = 0.616, P < .001). Among the 38 patients with residual OSAHS (residual AHI ≥5), 28 had persistent P-OSAHS, and the percentage was as high as 82.4%.

Conclusions and Significance:

Patients with P-OSAHS with a lower CT90 value are more likely to benefit from velopharyngeal surgery. Positional therapy could be indicated for most of the patients who are not cured by such surgery.
Stock Price Crashes and Auditors’ Client-Retention Decisions
Authors: Lee Kyung Yun (Kailey)
Published: June 2020

This study examines auditor resignations around a client firm’s stock price crash. Overall, the study suggests that a firm’s crash risk is one of the key factors influencing auditors’ client-retention decisions. A stock price crash increases the likelihood of lawsuits and financial restatements in the future. After controlling for risk factors that contribute to resignation decisions, I document a positive association between auditor resignations and stock price crashes. Further findings indicate that auditor size affects auditor–client relationship decisions before a crash occurs: Big auditors tend to resign more often from client firms with high crash risk compared with smaller auditors. However, auditor size becomes irrelevant once a crash occurs, as the client firms then become risky clients to both large and small auditors. This study therefore provides evidence that auditors of different sizes face different incentives to alter their relationship prior to a stock price crash and that these incentives change following a crash.
Effects of verb–construction association on second language constructional generalizations in production and comprehension
Authors: Sung Min-Chang , Kim Hyunwoo
Published: June 2020

How strongly a verb is associated with a construction plays a crucial role in the learning of argument structure constructions. We examined the effect of verb–construction association strength on second language (L2) constructional generalization by analysing L2 learners’ production and comprehension of two complex constructions (i.e. ditransitive and resultative), comparable in constructional complexity and input frequency but distinctive in verb–construction association. Using a learner corpus study, we found greater verbal usage variability in the production of ditransitive rather than resultative constructions. The results of an acceptability judgment task indicated that L2 learners accepted the ditransitive sentences regardless of whether they contained high-frequency or low-frequency verbs, but learners were more likely to accept the resultative sentences when they read high-frequency rather than low-frequency verbs. These findings suggest that verb–construction association affects the learning of argument structure constructions, supporting its contribution to the constructional generalization.
Avoiding the cum hoc ergo propter hoc fallacy: Comments and questions regarding Full Transfer Potential
Authors: González Alonso Jorge , Rothman Jason
Published: June 2020

In this commentary to Westergaard (2021), we focus on two main questions. The first, and most important, is what type of L3 data may be construed as supporting evidence–as opposed to a compatible outcome–for the Linguistic Proximity Model. In this regard, we highlight a number of areas in which it remains difficult to derive testable predictions from the model that go beyond compatibility with multiple outcomes that should, in principle, be mutually exclusive. The second part of this commentary deals with Westergaard’s (2021) a priori questioning of wholesale transfer as a tenable hypothesis on the basis of it creating a context for massive unlearning, both in L2 and L3 acquisition, when humans seem to display conservative learning traits from L1 acquisition already. We argue here that decades of accumulated empirical data in L2 and L3 studies have shown enough evidence of L1 transfer and restructuring to render this argument a non sequitur. In connection to this, we discuss some of the issues related to adaptive accounts of linguistic transfer across instances of language acquisition.
Medical cannabis in the UK: From principle to practice
Authors: Schlag Anne Katrin , Baldwin David S , Barnes Michael , Bazire Steve , Coathup Rachel , Curran H Valerie , McShane Rupert , Phillips Lawrence D , Singh Ilina , Nutt David J
Published: June 2020

Background:

In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems.

Aims:

Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes.

Outcomes:

Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions.

Conclusions:

There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.
Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system
Authors: Bèchet Nicholas B , Kylkilahti Tekla M , Mattsson Bengt , Petrasova Martina , Shanbhag Nagesh C , Lundgaard Iben
Published: June 2020

Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.
Evaluation of emergency medical services staff knowledge in breaking bad news to patients
Authors: Rasmus Paweł , Kozłowska Elżbieta , Robaczyńska Katarzyna , Pękala Krzysztof , Timler Dariusz , Lipert Anna
Published: June 2020

Objective

The aim of the study was to investigate knowledge of breaking bad news (BBN) among medical personnel in the emergency medical services (EMS).

Methods

A cross-sectional survey was conducted of 148 individuals employed in EMS. An interview was conducted using a structured questionnaire.

Results

Of study participants, 89.2% were not aware of any formal BBN procedure and 58.1% had not participated in any form of training. Compared with males, females were more likely to report that dealing with the emotional state of the family or the patient was the most difficult aspect of BBN. Only a few participants were aware of the SPIKES protocol for BBN, and none knew what the acronym meant. Sex, educational level, occupation, work experience and workplace were not associated with knowledge of BBN procedures.

Conclusions

Knowledge of BBN in both male and female EMS staff was insufficient. EMS personnel held different opinions about the method of BBN. Even staff who have participated in specific BBN training or have extensive professional experience were pessimistic about BBN skills in self-assessments.
Older Adults’ Perspectives on Fall Risk: Linking Results to the ICF
Authors: de Clercq Hendrika , Naudé Alida , Bornman Juan
Published: June 2020

The aim of this study is to establish the perceptions of older adults in the South African context regarding falls and to link these perceptions to the International Classification of Functioning, Disability and Health (ICF). Data were analyzed by a summative, conventional, and deductive approach. The analysis indicated that the Body Function and Structure codes were most frequently used during the discussions, but the contextual analysis of the most frequently used categories indicated that Activities and Participation were the participants’ main focus. The main focus of fall assessment in older adults should therefore be on Activities and Participation, as this can assist them in decreasing their fall risk, irrespective of whether they had a previous fall. Contrary to the majority of current literature on falls, this study included both participants who had fallen and those who hadn’t, resulting in richer data and themes gathered from the focus groups.