bluuebunny/crossref_metadata_2025 huggingface dataset:
Nominal number in Cushitic
Authors: Mous Maarten
Published: August 2021

Cushitic languages have a number of interesting properties in the category of number. None of these are valid for all Cushitic languages. Number is not obligatorily expressed in various Cushitic languages which have a general number form that is unspecified for number. Nonetheless morphological number marking in the noun is often complex in two ways: there are many competing lexically determined morphological markers and many different constellations of derived singular and derived plurals. Number and gender show complex interactions in Cushitic. Number formatives impose gender and hence different gender values for different number forms in the same lexeme, sometimes apparent gender polarity (singular and plural having opposite values for gender). A theoretically challenging property of some languages is that that there is a third gender, here labelled ‘plural’ because it takes the agreement morphology of 3pl pronouns.
Number in Sign Languages
Authors: Pfau Roland , Steinbach Markus
Published: August 2021

In sign languages, just as in many spoken languages, number can be marked on nouns, pronouns, and verbs, and quantifiers are used to specify quantity within noun phrases. The chapter does not address the expression of grammatical number in one specific sign language, but rather describes patterns found in various sign languages, focusing on modality-independent and modality-specific properties of number marking. As for the former, nominal and verbal plurals are commonly realized by reduplication. As for number-marking strategies specific to visual–spatial languages, it is found that sign languages employ the two hands (e.g. lexical plurality), the signing space in front of the signer's body (e.g. plural marking on predicates), and specific reduplication types that are not attested in spoken languages (e.g. sideward reduplication of certain nouns). In addition, the choice of pluralization strategy is determined by modality-specific phonological features, and we are thus dealing with phonologically conditioned allomorphy.
Number in Marori
Authors: Arka I Wayan
Published: August 2021

The number system in Marori shows a three-way distinction (singular–dual–plural) with distributed and often underspecified (plural vs nonplural, or singular vs non-singular) marking. Nominal number is expressed via marking of free pronouns and certain nouns and their associated verbal indexing, with a three-way distinction in first and second bound pronominals, and a two-way underspecified distinction elsewhere. Verbal number is expressed by suppletive verbal root alternations, typically singular vs non-singular. Dual number/duactional can be expressed by a combination of non-singular and nonplural exponents. Number agreement is semantic in nature, with mismatches possibly expressing an inclusory meaning or a small plural/paucal meaning. While radically different from English in its number system, Marori is similar to English and other European languages in terms of the distribution of plural meanings under negation and other contexts.
Number and Quantity Expressions
Authors: Doetjes Jenny
Published: August 2021

This chapter examines the interactions between quantity expressions and number across languages. Quantity expressions may require the presence of specific number markers on the noun or noun phrase they combine with. They may also trigger a singular or plural interpretation for the noun phrase as a whole, as in one N or several N. An important criterion used to distinguish classes of quantity expressions is the way these expressions interact with countability. While some quantity expressions depend on the presence of countable units in order to be interpreted, others do not. Examples of the former type are numerals, vague cardinal quantity expressions (several), and distributive universal quantifiers (each, every), while non-cardinal quantity expressions (a lot) and non-distributive universal quantifiers (all) belong to the second category. The chapter mainly focuses on the nominal domain. The use of quantity expressions in relation to verbal plurality is considered briefly.
The Natural World and the Anthropocene
Authors: Mak Cliff
Published: August 2021

This chapter situates Woolf at the intersection of different ‘natural world’ discourses, including the typological ethics explored by her father Leslie Stephen and the fly-fishing writing of her brother-in-law John Waller Hills (often taken to be the real-world model for Richard Dalloway himself). Woolf’s descriptions of characters evince an epistemophilic propensity to reveal subjectivity most readily through animalistic, physiognomic imagery and thus ask to be contextualized within these other discourses and beyond modernist aesthetics alone. In her later works, moreover, Woolf recognized the problematic politics of such human–animal equivalence, especially when it was the feminist representation of the nonverbal interiority that was at stake. This chapter thus outlines Woolf’s efforts to move away from an epistemology of transparency and instinct and towards one of opacity and type, with attendant consequences for any understanding of Woolf’s post- and anti-humanist politics in the age of the Anthropocene.
Creative Non-fiction and Poetry
Authors: D’Erasmo Stacey
Published: August 2021

This chapter considers Woolf’s significant influence on feminist writers working in the essay, creative non-fiction, and poetry. Woolf’s radical transformation of narrative design is emphasized. Woolf developed an aesthetic of patterning, repetition, and decentralization that transformed not only fiction, but also creative non-fiction and poetry. In Woolf’s work, every life is exquisitely enclosed in an overall pattern of life and death, of colour and light and movement, over which no single consciousness is master. Woolf’s method suffuses the work of writers such as Susan Sontag, Rebecca Solnit, Leslie Jamison, and Eula Biss, among others. It revolutionizes our ideas not only about the nature of perception, but also about the construction of reality, narrative, and the self.
Introduction
Authors: Fernald Anne E.
Published: August 2021

With thirty-nine original chapters from internationally prominent scholars, The Oxford Handbook of Virginia Woolf is designed for scholars and graduate students. Feminist to the core, each chapter examines an aspect of Woolf’s achievement and legacy. Each contribution offers an overview that is at once fresh and thoroughly grounded in prior scholarship. Virginia Woolf (1882–1941) wrote prolifically and experimentally. In all she wrote and did, she strove for the rights of women artists: she was a feminist. This volume’s six parts take her feminism and her experiments in language as foundational to her legacy: the opening Part I has a biographical focus; then the chapters in Part II examine her career, holistically and chronologically; Part III offers more detail on the extent of her experimental and aesthetic practices, taking aspects of her innovation across multiple genres, examining each along the span of her career; Part IV invites readers to consider how Woolf worked in cultural fields including and extending beyond the Hogarth Press and the TLS and Part V ‘Contexts’ moves beyond writing to depict her engagement with expectations of class and gender, the natural world, as well as the political, artistic, and popular culture of her time. Finally, ‘Afterlives’ demonstrates the many ways Woolf’s reputation continues to grow, across the globe, and across media, in ideas and in artistic expression. Chapters on Woolf’s engagement with feminism and suffrage are followed by chapters on Woolf’s posthumous influence on conversations around queer and feminist theory. Of particular note is that chapters explore three distinct Woolfian traditions in fiction: the novel of manners, magical realism, and the feminist novel.
Mature Works I (1924–1927)
Authors: McIntire Gabrielle
Published: August 2021

Between 1924 and 1927 Woolf was at an apex of her career, publishing some of her best-known works, including Mrs Dalloway (1925), The Common Reader (1925), and To the Lighthouse (1927). She also wrote prolific letters, diary entries, short stories, and essays whose co-extensiveness with her major work remains to be fully scrutinized. This chapter considers some the connections, traces, and shared themes across these multiple genres of Woolf’s writing to argue that Woolf consistently emphasizes (1) literature as a vehicle of ethics that changes us as we read; (2) the necessity of breaking with formal literary conventions in order to render the ambivalences and uncertain ontological and psychological terrain of modernist ‘truth(s);’ (3) poetry as both the highest form of literary art and as way of being that traverses her characters; (4) a duty to render, despite her atheism, what she persistently calls ‘the soul’.
Mature Works II (1928–1932)
Authors: Högberg Elsa
Published: August 2021

This chapter engages Woolf’s writings from the prolific years 1928–1932, with particular focus on her hybrid novels Orlando: A Biography (1928) and The Waves (1931) as well as her feminist essay A Room of One’s Own (1929) and 1927 manifesto ‘Poetry, Fiction and the Future’. Woolf’s literary journalism during this period evinces a persistent concern with the poetic and prosaic impulses of fiction, and frequently privileges poetic detachment from prosaic, socio-political causes. While recent scholarship has demonstrated how her aesthetic experiments undermine such distinctions between poetic and committed writing, we have yet to fully appreciate how the lyricism and formal-generic hybridity that lie at the heart of Woolf’s work in these years become the very site for her socio-political commitments. Taking this premise as its starting point, the present chapter illuminates connections between her fictional and non-fictional writings in this extraordinarily creative period.
Economic and Social Rights in Ireland
Authors: Murray Thomas
Published: August 2021

This chapter examines the law and politics of contesting economic and social rights in Ireland. Civil society mobilizations for the constitutional recognition of socio-economic rights provoke disagreement about the feasibility, legitimacy, and effectiveness of using such rights to de-commodify labour and social reproduction. The chapter situates these debates in their socio-legal context. It examines why state actors have opposed socio-economic rights in the past, and why enhanced constitutional protection of such rights will not radically alter structural inequalities today. At best, public interest litigation may prompt the political system to address the needs of minority groups in highly specific instances. Internationally, contemporary constitution-making experiments advance alternative models of socio-economic rights enforcement more decisively premised on social solidarity. Any similar realization of economic and social rights in Ireland will likely depend on civil society capacities to foster the requisite political will for social solidarity and constitutional change.
The Political Economy of Housing in Ireland
Authors: Norris Michelle , Byrne Michael
Published: August 2021

This chapter examines the political economy of housing in Ireland since the turn of the nineteenth century. It identifies three phases. The early and mid-twentieth century saw enormous state intervention, with the Irish welfare state becoming property based and home ownership being socialized. The closing years of the twentieth century saw state intervention diminish, and the consequent shaping of housing dynamics by financial markets. This drove a house price and building boom, before bust in the mid-2000s. The years since the financial crisis have seen an intensification of neoliberalization and financialization, through the ever greater marketization of housing and the development of links between global capital and urban development, asset ownership, and housing. This analysis shows the central role that housing has played in the Irish political economy. It also demonstrates significant long-term continuity in housing policy, and the importance of taking into account national institutional, political, and cultural contexts.
Paul and Sacred Space
Authors: Økland Jorunn
Published: August 2021

This chapter analyses the terms with which Paul of Tarsus designates various sacred spaces—hieron, naos, eidoleion, ekklesia—in conversation with the archaeology of sacred spaces, research on the Pauline house churches, and with the help of theories of space, new materialism, and the sacred. The chapter starts with an introduction of the analytical frameworks and ends with ideas about ‘monumentalization’: that the social-structural relations between people in a sacred space tended to materialize over time into purpose-built buildings—hence the double meanings of synagogue, ekklesia, and hieron as designations both of assemblies and later of the buildings accommodating the respective assemblies. A central argument is that Paul’s letters constitute a special case in the development of the early Christian ekklesia and the parallel development of the synagogue, because in Paul’s time the temple in Jerusalem was still standing and was a self-evident part of his religious universe.
Long-term repetitive exposure to excess iodine induces mitochondrial apoptosis, and alters monoamine neurotransmitters in hippocampus of rats of different genders
Authors: Cui Yushan , Zhang Bin , Zhang Zushan , Nie Junyan , Liu Hongliang
Published: August 2021

The influence of excess iodine on human health has been paid more and more attention. Although numerous studies have reported that excess iodine may cause deleterious effects, the mental damage and its mechanism is yet to be identified. Using Sprague-Dawley rats exposed to excess iodine from pregnancy to 6 months post-delivery as in vivo model, this study explored the impacts of long-term repetitive excess iodine administration on the hippocampus of offspring rats, focusing on mitochondrial apoptosis pathway, with changes in monoamine neurotransmitters. The results showed that excess iodine could increase urinary iodine and brain organ coefficient in offspring of both genders, change the hippocampal cell structure, and damage the spatial learning and memory capacities. Poly ADP-ribose polymerase (PARP), P53, Cleaved Caspase-3, and cytochrome C proteins expression increased and Bcl2 protein expression decreased in hippocampus of excess iodine-treated offspring, indicating that excess iodine could activate the mitochondrial apoptosis pathway. Besides, excess iodine showed different effects on monoamine neurotransmitter in different gender. Collectively, our experimental data indicated that the learning and memory impairment induced by excess iodine may be mediated via mitochondrial apoptotic pathway. Long-term repetitive excess iodine exposure affected monoamine neurotransmitters in hippocampus of offspring rats.
Auxin concentration and xylem production of Pinus massoniana in a subtropical forest in south China
Authors: Guo Xiali , Huang Jian-Guo , Buttò Valentina , Luo Dawei , Shen Chunyu , Li Jingye , Liang Hanxue , Zhang Shaokang , Hou Xingliang , Zhao Ping , Rossi Sergio
Published: August 2021

Auxin is involved in various developmental processes of plants, including cell division in cambium and xylem differentiation. However, most studies linking auxin and xylem cell production are performed in environments with a strong seasonality (i.e., temperate and boreal climates). The temporal dynamics of auxin and cambial activity of subtropical trees remain basically unknown. In this study, we sampled four microcores weekly in three individuals of Chinese red pine (Pinus massoniana Lamb.) from February to December 2015–16 to compare xylem formation with auxin concentration in subtropical China. During the entire period of sampling, the number of cambial cells varied from 2 to 7, while the number of cells in the enlarging zone ranged from 1 to 4 and from 1 to 5 in the wall-thickening zone. In 2015, the average auxin concentration was 3.46 ng g−1, with 33 xylem cells being produced at the end of the year. In 2016, a lower auxin concentration (2.59 ng g−1) corresponded to a reduced annual xylem production (13.7 cells). No significant relationship between auxin concentration and number of xylem cells in differentiation was found at the weekly scale. Unlike in boreal and temperate forests, the lack of wood formation seasonality in subtropical forests makes it more difficult to reveal the relationship between auxin concentration and number of xylem cells in differentiation at the intra-annual scale. The frequent and repeated samplings might have reduced auxin concentration in the developing cambium and xylem, resulting in a lower xylem cell production.
Poacic acid, a β‐1,3‐glucan–binding antifungal agent, inhibits cell‐wall remodeling and activates transcriptional responses regulated by the cell‐wall integrity and high‐osmolarity glycerol pathways in yeast
Authors: García Raúl , Itto‐Nakama Kaori , Rodríguez‐Peña José Manuel , Chen Xiaolin , Sanz Ana Belén , de Lorenzo Alba , Pavón‐Vergés Mónica , Kubo Karen , Ohnuki Shinsuke , Nombela César , Popolo Laura , Ohya Yoshikazu , Arroyo Javier
Published: August 2021

As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits β‐1,3‐glucan synthesis inSaccharomyces cerevisiaeand has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to β‐1,3‐glucan, its affinity for which is ~30‐fold that for chitin. Besides its effect on β‐1,3‐glucan synthase activity, PA inhibited the yeast glucan‐elongating activity of Gas1 and Gas2 and the chitin–glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co‐regulation was mediated by parallel activation of the cell‐wall integrity (CWI) and high‐osmolarity glycerol signaling pathways. Despite targeting β‐1,3‐glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.
Atypic SUMOylation of Nor1/NR4A3 regulates neural cell viability and redox sensitivity
Authors: Gagnon Jonathan , Caron Véronique , Gyenizse Laurent , Tremblay André
Published: August 2021

Neuron‐derived orphan receptor 1, NR4A3 (Nor1)/NR4A3 is an orphan nuclear receptor involved in the transcriptional control of developmental and neurological functions. Oxidative stress‐induced conditions are primarily associated with neurological defects in humans, yet the impact on Nor1‐mediated transcription of neuronal genes remains with unknown mechanism. Here, we demonstrate that Nor1 is a non‐conventional target of SUMO2/3 conjugation at Lys‐137 contained in an atypic ψKxSP motif referred to as the pSuM. Nor1 pSuM SUMOylation differs from the canonical process with the obligate phosphorylation of Ser‐139 by Ras signaling to create the required negatively charged interface for SUMOylation. Additional phosphorylation at sites flanking the pSuM is also mediated by the coordinated action of protein kinase casein kinase 2 to function as a small ubiquitin‐like modifier enhancer, regulating Nor1‐mediated transcription and proteasomal degradation. Nor1 responsive genes involved in cell proliferation and metabolism, such as activating transcription factor 3, cyclin D1, CASP8 and FADD‐like apoptosis regulator, and enolase 3 were upregulated in response to pSuM disruption in mouse HT‐22 hippocampal neuronal cells and human neuroblastoma SH‐SY5Y cells. We also identified critical antioxidant genes, such as catalase, superoxide dismutase 1, and microsomal glutathione S‐transferase 2, as responsive targets of Nor1 under pSuM regulation. Nor1 SUMOylation impaired gene transcription through less effective Nor1 chromatin binding and reduced enrichment of histone H3K27ac marks to gene promoters. These effects resulted in decreased neuronal cell growth, increased apoptosis, and reduced survival to oxidative stress damage, underlying the role of pSuM‐modified Nor1 in redox homeostasis. Our findings uncover a hierarchical post‐translational mechanism that dictates Nor1 non‐canonical SUMOylation, disrupting Nor1 transcriptional competence, and neuroprotective redox sensitivity.
Ablation of PDE4B protects from Pseudomonas aeruginosa‐induced acute lung injury in mice by ameliorating the cytostorm and associated hypothermia
Authors: Abou Saleh Lina , Boyd Abigail , Aragon Ileana V. , Koloteva Anna , Spadafora Domenico , Mneimneh Wadad , Barrington Robert A. , Richter Wito
Published: August 2021

Pseudomonas aeruginosa is a frequent cause of hospital‐acquired lung infections characterized by hyperinflammation, antibiotic resistance, and high morbidity/mortality. Here, we show that the genetic ablation of one cAMP‐phosphodiesterase 4 subtype, PDE4B, is sufficient to protect mice from acute lung injury induced by P aeruginosa infection as it reduces pulmonary and systemic levels of pro‐inflammatory cytokines, as well as pulmonary vascular leakage and mortality. Surprisingly, despite dampening immune responses, bacterial clearance in the lungs of PDE4B‐KO mice is significantly improved compared to WT controls. In wildtypes, P aeruginosa‐infection produces high systemic levels of several cytokines, including TNF‐α, IL‐1β, and IL‐6, that act as cryogens and render the animals hypothermic. This, in turn, diminishes their ability to clear the bacteria. Ablation of PDE4B curbs both the initial production of acute response cytokines, including TNF‐α and IL‐1β, as well as their downstream signaling, specifically the induction of the secondary‐response cytokine IL‐6. This synergistic action protects PDE4B‐KO mice from the deleterious effects of the P aeruginosa‐induced cytostorm, while concurrently improving bacterial clearance, rather than being immunosuppressive. These benefits of PDE4B ablation are in contrast to the effects resulting from treatment with PAN‐PDE4 inhibitors, which have been shown to increase bacterial burden and dissemination. Thus, PDE4B represents a promising therapeutic target in settings of P aeruginosa lung infections.
Disruption of lateral hypothalamic calorie detection by a free choice high fat diet
Authors: Koekkoek Laura L. , Slomp Margo , Castel Julien , Mutersbaugh Michael , Linville Ian , Serlie Mireille J. , Luquet Serge H. , la Fleur Susanne E.
Published: August 2021

During the last few decades, the consumption of low‐calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low‐calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two‐photon calcium imaging, we investigated how drinking sucrose or sucralose (a low‐calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free‐choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free‐choice high fat diet shifts the glutamatergic neuronal response from sucrose‐specific to sucralose‐specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.
Modern Medicine Is a Colonial Artifact: Introducing Decoloniality to Medical Education Research
Authors: Naidu Thirusha
Published: August 2021

Modern medicine is an artifact of colonialism because the science that underpins modern medicine emerged from Western knowledge structures based on a history of colonialism. The author suggests the colonial roots of Western-based modern medicine must be reexamined. While there are various critical theories that may be applied in this reexamination, most do not adequately account for intersectional, intergenerational, and sociohistorical inequities encountered in the multiplicity of global contexts in practice teaching and research within medicine. The author presents decoloniality as a theoretical perspective from which to interrogate sociohistorical, geopolitical, and economic perspectives on gender, race, and heteropaternalistic influences in medicine emanating from a basis in colonially developed systems of knowledge production. The author offers definitions of relevant theoretical terms and suggests that decolonial praxis begins with an initial realization or awareness of one’s position within the colonial matrix of power followed by the reflecting or deliberation, or a grappling with real-life struggles that are encountered in confronting the oppressive operations of the colonial matrix of power. Decolonial praxis involves action through challenging mainstream foundational theories—the questions they generate, the research methods they support, and the writing styles they employ. In medical education, this may involve changing powerful actors, such as medical journal editors and researchers, with historical privilege; shifting the balance of power in research spaces; and dismantling physical and intellectual structures and institutions established on colonial epistemologies.
Differential Gateways, Facilitators, and Barriers to Substance Use Disorder Treatment for Pregnant Women and Mothers: A Scoping Systematic Review
Authors: Choi Sugy , Rosenbloom David , Stein Michael D. , Raifman Julia , Clark Jack A.
Published: August 2021

Objectives

Access to substance use disorder (SUD) treatment is complex, and more so for pregnant women and mothers who experience unique barriers. This scoping systematic review aimed to summarize contemporary findings on gateways, facilitators, and barriers to treatment for pregnant women and mothers with SUD.

Methods

We used the scoping review methodology and a systematic search strategy via MEDLINE/PubMed and Google Scholar. The search was augmented by the similar article lists for sources identified in PubMed. Scholarly and peer-reviewed articles that were published in English from 1996 to 2019 were included. A thematic analysis of the selected studies was used to summarize pathways to SUD treatment and to identify research gaps.

Results

The analysis included 41 articles. Multiple gateway institutions were identified: health care settings, social service agencies, criminal justice settings, community organizations, and employers. Some of the identified facilitators and barriers to SUD treatment were unique to pregnant women and mothers (eg, fear of incarceration for child abuse). Both personal (emotional support and social support) and child-related factors (loss of children, suspension or termination of parental rights, the anticipation of reuniting with children) motivated women to seek treatment. Major access barriers included fear, stigma, charges of child abuse, inconvenience, and financial hardship.

Conclusions

There has been progress in implementing different types of interventions and treatments for that were attentive to pregnant women and mothers’ needs. We developed a conceptual model that characterized women’s pathways to treatment by deciphering women’s potential engagement in gateway settings.
Tibial tubercle avulsion fractures in adolescents: impact on function and quality of life
Authors: Lima Ana S. , Cabral João , Boavida João , Balacó Inês , Sá Cardoso Pedro , Tarquini Oliana , Ling Tah P. , Alves Cristina
Published: August 2021

The objective of the study was to assess functional outcomes and quality of life of patients treated for tibial tubercle avulsion fractures (TTAFs). Retrospective study of patients under 18 years of age treated from June 2011 to May 2018. Demographic data included age, gender, mechanism of injury, side, fracture classification, associated injuries, predisposing factors, and type of treatment. Clinical results included knee range of motion, pain, return to sports, overall satisfaction, functional outcomes, and complications. At final follow-up, Tegner Lysholm Knee Scoring Scale, and Kidscreen-10 were applied. Ten patients were included, all males, with a median age of 15 years. Mechanism of injury: football (three patients), basketball (two patients), running (two patients), handball (one patient), gymnastics (one patient), and fall (one patient). Nine were treated surgically with reduction and fixation with cannulated screws or Kirschner wires, plus treatment of associated injuries (three patellar tendon avulsions, one contralateral proximal tibia epiphyseal fracture, and two prophylactic fasciotomies). One patient developed mild recurvatum and two presented minor decreased knee flexion. Eight patients returned to their previous level of sports activity. Median Tegner Lysholm Knee Score was 100/100 and Kidscreen-10 was 50/50. With appropriate treatment, nearly 100% of TTAFs have good functional outcomes and low impact on quality of life.
A Population-based Study of Treatment Patterns and Survival of Patients With De Novo Stage IV Non–Small Cell Lung Cancer
Authors: Batra Atul , Yusuf Dimas , Hurry Manjusha , Walton Ryan N. , Devost Natalie , Farrer Christie , Cheung Winson Y.
Published: August 2021

Background:

Treatment strategies for metastatic non–small cell lung cancer (NSCLC) are evolving rapidly and can be highly variable. Real-world evidence of treatment patterns and outcomes can provide an understanding of our current practice and offer insights on ways to incorporate emerging therapies into our treatment paradigm. In this population-based study, we investigated treatments and outcomes of stage IV NSCLC patients from a large Canadian province.

Methods:

Patients diagnosed with de novo stage IV NSCLC from April 1, 2010 to March 31, 2015 were identified. Data for baseline characteristics, treatments, and outcomes were obtained from provincial data sources, including the cancer registry and electronic medical records. We classified systemic treatments as chemotherapy, targeted therapy (anti-epidermal growth factor receptor, and anti-anaplastic lymphoma kinase) and immunotherapy (checkpoint inhibitors) and characterized clinical outcomes by treatment type.

Results:

A total of 6438 patients were identified with NSCLC, of whom 3606 (56%) had de novo stage IV disease. The median age of diagnosis was 69 (range: 20 to 100) years and 52.4% were men. First-line palliative treatments included: chemotherapy in 19.5% (n=703), targeted agents in 5.7% (n=204), immunotherapy in 1% (n=1), radiotherapy in 6.8% (n=246), and best supportive care in 74.8% (n=2,698). Median overall survival (mOS) from diagnosis for the whole cohort was 3.8 months. Within subgroups, mOS was 18.0 months for targeted therapies, 9.4 months for chemotherapy, and 2.5 months for best supportive care. Only 1.0% of patients (n=34) received immunotherapy at any line.

Conclusions:

Survival benefit was dependent on type of treatment received, with significantly better mOS observed with the use of small-molecule targeted therapy against epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements, as compared with best supportive care.
Management of Early-Stage Rectal Cancer
Authors: Greco Justin M. , Abelson Jonathan S.
Published: August 2021

Case Summary:

A 59-year-old man underwent screening colonoscopy that identified a 2-cm rectal polyp in the posterior midline, 7 cm from the anal verge. Biopsy revealed a tubular adenoma with high-grade dysplasia. The patient underwent a robotic-assisted transanal minimally invasive surgery with full-thickness excision (Fig. 1). Final pathology confirmed a well-differentiated adenocarcinoma extending into the submucosa (sm2). There was no lymphovascular or perineural invasion, and the radial margin was 5 mm.
Evaluation and usability study of low-cost laparoscopic box trainer “Lap-Pack”: a 2-stage multicenter cohort study
Authors: Chauhan Manish , Sawhney Riya , Da Silva Carolina F. , Aruparayil Noel , Gnanaraj Jesudian , Maiti Sukumar , Mishra Anurag , Quyn Aaron , Bolton William , Burke Joshua , Jayne David , Valdastri Pietro
Published: August 2021

Introduction:

Laparoscopic training is restricted in low resource settings due to limited access to specialist training equipment and financial constraints. This study aimed to evaluate simulation skills and usability of an original low-cost laparoscopic trainer, the “Lap-Pack,” developed at the University of Leeds, UK.

Methods:

Stage I evaluation was conducted in Kolkata (India) between March, 12 and 14, 2019. Laparoscopic simulation training was based on the 5 domains of fundamentals of laparoscopic surgery (FLS), which assessed skill acquisition across 7 rural surgeons from North-East India. The McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) criteria was used to statistically analyze trainee performance between pretraining and posttraining sessions. Also, Lap-Pack was qualitatively compared with a commercial box trainer, Inovus Pyxus HD (IPHD). Stage II involved a multi-center usability study in 2 centers of India and the United Kingdom (2019). Seventy-eight participants performed 2 FLS tasks using Lap-Pack and provided scores on a 25-point questionnaire, including a preestablished Face-Validity Criteria and 4 evaluation categories—Usability, Camera, View, and, Material.

Results:

In stage I, the total posttraining MISTELS score for Lap-Pack was higher, that is 773.37 (SD: 183.67) than pretraining score, that is 351.2 (SD: 471.5). The posttraining scores showed laparoscopic skill acquisition with statistically significant (P<0.05) difference for precision cutting, intracorporeal and extracorporeal knot. In stage II, Lap-Pack scored highly in Face-Validity with a combined mean score of 4.81 [95% confidence interval (CI): 4.52–5.09, P<0.05] out of a possible 6. It scored highest (scale: 1=low to 7=high) in Usability 6.14 (95% CI: 6.05–6.22, P<0.05) and Camera 6.14 (95% CI: 6.01–6.27, P<0.05). The “Lightweight” (6.46, 95% CI: 6.32–6.60, P<0.05) and “Portability” (6.35, 95% CI: 6.18–6.51, P<0.05) features of Lap-Pack were appreciated.

Conclusion:

The Lap-Pack is a suitable low fidelity simulator for laparoscopic training in a low-resource setting.
Opportunities for Closing the Gap in HIV Diagnosis, Treatment, and Viral Load Suppression in Children in Malawi: Results From a 2015–2016 Population-based HIV Impact Assessment Survey
Authors: Jonnalagadda Sasi , Auld Andrew , Jahn Andreas , Saito Suzue , Bello George , Sleeman Katrina , Ogollah Francis M. , Cuervo-Rojas Juliana , Radin Elizabeth , Kayira Dumbani , Kim Evelyn , Payne Danielle , Burnett Janet , Hrapcak Susan , Patel Hetal , Voetsch Andrew C. ,   for the MPHIA Study Team
Published: August 2021

Background:

Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015–2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression.

Methods:

In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection.

Results:

Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1–1.9) and 8.0% (95% CI: 5.6–10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028–149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3–41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8–95.6) were on ART and 57.9% (95% CI: 41.4–74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0–70.5) had unsuppressed VL.

Conclusions:

Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions.
Positive affect and distraction enhance whereas negative affect impairs pain modulation in patients with recurrent low back pain and matched controls
Authors: McPhee Megan E. , Graven-Nielsen Thomas
Published: August 2021

Pathophysiological causes of low back pain (LBP) remain generally unclear, so focus has shifted to psychosocial features and central pain processing. Effects of attentional and affective manipulation on conditioned pain modulation and tonic pain perception were examined in 30 patients with recurrent LBP in 2 sessions, one with and one without clinical pain, and compared with healthy participants. Phasic cuff pressure on one leg, scored on a Numerical Rating Scale, was used for test stimuli, and contralateral tonic cuff pain rated on an electronic Visual Analogue Scale was the conditioning stimulus (CS). Test stimuli were assessed before and during (1) control with no manipulation or CS, (2) 3 attentional manipulations (Flanker with or without CS or CS-Only), and (3) 3 affective manipulations (positive, neutral, and negative images) with CS. Greater inhibition of test stimuli Numerical Rating Scale scores was observed in CS-only (P = 0.028), combined CS&attention (P = 0.026), and CS&Positive (P = 0.006) than control paradigms, and greater in CS&Positive (P = 0.019) than CS&Negative paradigms. Electronic Visual Analogue Scale scores of CS pain increased throughout all paradigms with CS (P < 0.05), except the CS&Positive paradigm, and greater facilitation was observed in the CS-Only paradigm than all others (P < 0.02), and lower facilitation was additionally observed in the CS&Positive paradigm compared with CS&Attention and CS&Negative paradigms (P < 0.01). Flanker effects and interruptive effects of CS pain on attention were observed consistent with prior findings, and affective manipulation produced less shift in valence among people with recurrent LBP than controls (P < 0.05). Attention and positive affect with CS pain evoked conditioned pain modulation, and all attentional or affective tasks, especially positive affect, reduced facilitation of CS pain.
Blood pressure management and renal protection: Revisiting hypertensive nephropathy
Authors: Kao Ting-Wei , Huang Chin-Chou
Published: August 2021

Hypertension has traditionally been the most common cardiovascular disease, and epidemiological studies suggest that the incidence continues to rise. Despite a plethora of antihypertensive agents, the management of blood pressure (BP) remains suboptimal. Addressing this issue is paramount to minimize hypertensive complications, including hypertensive nephropathy, a clinical entity whose definition has been challenged recently. Still, accumulating studies endorse poorly managed BP as an independent risk factor for both the onset of renal dysfunction and aggravation of baseline kidney disease. Nevertheless, current recommendations are not only discordant from one another but also offer inadequate evidence for the optimal BP control targets for renal protection, as since the cutoff values were primarily established on the premise of minimizing cardiovascular sequelae rather than kidney dysfunction. Although intense BP management was traditionally considered to compromise perfusion toward renal parenchyma, literature has gradually established that renal prognosis is more favorable as compared with the standard threshold. This review aims to elucidate the renal impact of poorly controlled hypertension, elaborate on contemporary clinical references for BP control, and propose future directions to improve the holistic care of hypertensive individuals.
Extracorporeal Membrane Oxygenation for Pediatric Toxin Exposures: Review of the Extracorporeal Life Support Organization Registry
Authors: Koshel Christine K. , Alexander Peta M.A. , Rycus Peter , Alibrahim Omar
Published: August 2021

Evidence for the use of extracorporeal membrane oxygenation (ECMO) in children with refractory respiratory failure or shock following ingestion or toxin exposure, has been confined to single-center experiences, individual case reports, and extrapolated from adult cohorts; no pediatric multicenter cohorts exist. The objective of this retrospective review of the Extracorporeal Life Support Organization registry is to describe pediatric ECMO use following ingestion or toxin exposure, and define factors associated with mortality. Twenty-eight children between the ages of 30 days and 18 years met inclusion criteria between January 1, 2008 and December 31, 2017. The primary outcome measure was mortality before hospital discharge, which occurred in 32% of patients. Factors associated with in-hospital mortality included pre-ECMO use of inhaled nitric oxide (44.4% vs. 5.3%, p = 0.026), lower pre-ECMO arterial blood gas pH (6.97 [6.80–7.17] vs. 7.20 [7.15–7.32], p = 0.034), and higher pre-ECMO PaCO2 (79 [57–85] vs. 49 [38–63], p = 0.014). Receipt of inotropic support during ECMO was more common in nonsurvivors (66.7% vs. 21.1%, p = 0.035). Extracorporeal membrane oxygenation should be considered in the most severe pediatric toxin exposures as a bridge to recovery, providing time for both toxin elimination and end-organ recovery.
Toward a Servoregulation Controller to Automate CO2 Removal in Wearable Artificial Lungs
Authors: Potkay Joseph A. , Thompson Alex J. , Toomasian John , Lynch William , Bartlett Robert H. , Rojas-Peña Alvaro
Published: August 2021

A laptop-driven, benchtop control system that automatically adjusts carbon dioxide (CO2) removal in artificial lungs (ALs) is described. The proportional-integral-derivative (PID) feedback controller modulates pump-driven air sweep gas flow through an AL to achieve a desired exhaust gas CO2 partial pressure (EGCO2). When EGCO2 increases, the servoregulator automatically and rapidly increases sweep flow to remove more CO2. If EGCO2 decreases, the sweep flow decreases to reduce CO2 removal. System operation was tested for 6 hours in vitro using bovine blood and in vivo in three proof-of-concept sheep experiments. In all studies, the controller automatically adjusted the sweep gas flow to rapidly (<1 minute) meet the specified EGCO2 level when challenged with changes in inlet blood or target EGCO2 levels. CO2 removal increased or decreased as a function of arterial pCO2 (PaCO2). Such a system may serve as a controller in wearable AL systems that allow for large changes in patient activity or disease status.
Safety and Feasibility of an Early Mobilization Protocol for Patients with Femoral Intra-Aortic Balloon Pumps as Bridge to Heart Transplant
Authors: Chen Stacey , Lester Lynette , Piper Greta L. , Toy Bridget , Saputo Mary , Chan Wendy , Fischer Mary G. , Gidea Claudia , Kon Zachary N. , Moazami Nader , Smith Deane E.
Published: August 2021

Intra-aortic balloon pumps (IABPs) can be used to provide hemodynamic support in patients with end-stage heart failure as a bridge to transplantation (BTT). The IABP is commonly inserted via the common femoral artery, which can limit patients’ mobility. The Ramsey protocol, developed by a critical care physical therapist, allows patients with femoral IABPs to ambulate with the assistance of a tilt table. The aim of this study was to determine the safety and feasibility of a modified Ramsey protocol for early mobilization of patients with femoral IABPs as BTT. This is a retrospective single-center review of patients with femoral IABPs as BTT using a tilt table protocol from May 2019 to May 2020. Primary outcomes were time to successful ambulation, number of successful ambulation events, and ambulation-associated adverse events, including IABP augmentation, waveform, positioning changes, and vascular complications at the insertion site. Twenty-four patients (mean age 55 ± 16 years) underwent femoral IABP insertion as BTT and were mobilized following our protocol. Nineteen patients (79.2%) successfully ambulated with a median of three sessions (interquartile range, 2–4) per patient. The median time from IABP insertion to ambulation was 3 days (interquartile range, 2–5). Twenty-one patients underwent heart transplantation, of which all 19 who ambulated were successfully bridged to transplantation. Early mobilization in select patients with femoral IABPs can be performed safely and successfully, avoiding the deleterious effects of bed rest that have been historically seen in this patient population.
Subjective Changes of Taste and Smell in Conjunction With Anxiety and Depression Are Associated With Symptoms in Globus Patients Without Evidence of Pathologic Acid Reflux
Authors: Liu Jie , Wang Wei , Wang Ying , Wu Dewei , Sun Chenyu , Lv Chaolan , Wu Dandan , Yu Yue
Published: August 2021

Background/Aim:

Patients suffering from globus often report decreased enjoyment when eating as well as a psychological abnormality. Some patients exhibit taste and smell changes (TSCs) when compared with the period before the diagnosis. The main aim of this study was to explore if TSCs and psychological abnormality are present in patients with globus, whether they are associated with the severity of throat symptoms, and the potential risk factors for globus.

Patients and Methods:

A total of 116 included patients who met the Rome IV diagnostic criteria for globus had been performed 24-hour pH monitoring, and the results shown no evidence of pathologic acid reflux. Meanwhile, 125 healthy controls were enrolled in this prospective study. All subjects completed several questionnaires including the Taste and Smell Survey, the Glasgow Edinburgh Throat Scale, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Multiple logistic regression was performed to explore the potential risk factors for globus. The study protocol was registered on the Chinese Clinical Trial Registry (No. ChiCTR-2100044972).

Results:

First, globus patients without evidence of pathologic acid reflux exhibited a 58.62% and 31.03% change in taste and smell, respectively, while their levels of anxiety and depression were 51.72% and 44.83%, respectively. Second, there was a significant difference in the taste score (Z=−4.954, P<0.001) and smell score (Z=−4.552, P<0.001) between globus group patients and healthy controls. Similarly, globus group patients had a higher HAMA score (9.52±2.437 vs. 3.12±1.059, t=6.867, P<0.001) and HAMD score (9.79±2.931 vs. 3.16±1.650, t=6.416, P<0.001) when compared with the healthy controls. Third, in globus group patients, the Glasgow Edinburgh Throat Scale was significantly correlated with the taste score (Spearman ρ=0.782; P<0.001), smell score (Spearman ρ=0.582; P=0.001), HAMA (Spearman ρ=0.676; P<0.001), and HAMD (Spearman ρ=0.672; P<0.001). In addition, the taste score was significantly correlated with HAMA (Spearman ρ=0.532; P=0.004) and HAMD (Spearman ρ=0.681; P<0.001), while the smell score was significantly correlated with HAMD (Spearman ρ=0.392; P=0.035). Finally, multivariate logistic regression revealed that TSCs, anxiety, and depression were significant independent risk factors for globus, with depression exhibiting the highest degree of association (odds ratio: 3.244).

Conclusions:

TSCs and psychological comorbidities are prominent in globus patients without evidence of pathologic acid reflux. The obtained results indicated that there is a strong relationship between TSCs, psychological comorbidities, and globus. Therefore, awareness of this high prevalence of TSCs and psychological disorder may help to better understand the severity of throat symptoms.