bluuebunny/crossref_metadata_2025 huggingface dataset:
Applied Statistics with R
Authors: Touchon Justin C.
Published: August 2021

Whether at the undergraduate, graduate, or post-graduate level, Applied Statistics with R: A Practical Guide for the Life Sciences teaches readers to properly analyze data in an efficient, accessible, plainspoken, frank, and occasionally humorous manner. Readers will come away with the knowledge of which analyses they should use and when they should use them, an important skill in an age when the statistical analyses used in the life-sciences are becoming increasingly advanced. This book uses the statistical language R, which is the choice of ecologists worldwide and is rapidly becoming the ‘go-to’ stats program throughout the life-sciences. Written around a single real-world dataset, Applied Statistics with R which encourages readers to become deeply familiar with an imperfect but realistic set of data, much like they themselves might collect. Early chapters are designed to teach basic data manipulation skills and build good habits in preparation for learning more advanced analyses. This approach also demonstrates the importance of viewing data through different lenses, facilitating an easy and natural progression from linear and generalized linear models through to mixed effects versions of those same analyses. Readers will also learn advanced plotting and data-wrangling techniques, and gain an introduction to writing their own functions. Applied Statistics with R is suitable for senior undergraduate and graduate students, professional researchers, and practitioners throughout the life-sciences, whether in the fields of ecology, evolution, environmental studies, or computational biology.
On the Coherence of Vague Predicates
Authors: Wright Crispin
Published: August 2021

This chapter is concerned to diagnose, and defuse, the plausibility of the universally quantified major premises in standard Sorites paradoxes. The two constituent theses of what is termed the ‘governing view’—that linguistic competence consists in mastery of semantic and syntactic rules and that aspects of these rules for particular expressions may be uncovered by reflection on our characteristic linguistic training in their use, limitations of our senses and memories, and our conception of the role and interest of the classifications they effect—are shown to force the attribution to a variety of expressions of an inconsistent semantics. It is argued that that one class of predicate to which the governing view attributes such semantic incoherence is, in a certain sense, ineliminable; more specifically, that the precisification of these predicates would spawn further Sorites-prone concepts. It is concluded that the governing view must be abandoned.
The Epistemic Conception of Vagueness
Authors: Wright Crispin
Published: August 2021

This chapter challenges Epistemicism. It rebuts Williamson’s arguments for unrestricted Bivalence, based on the Disquotational Scheme for the truth predicate, and Sorensen’s arguments that the idea of a predicate’s being of limited sensitivity is itself incoherent. The chapter nevertheless proposes a broadly epistemic conception of what a definite case of a vague predicate is—namely, a case where at least one of two conflicting verdicts about a vague predication must involve some kind of cognitive shortcoming, and proposes a corresponding notion of a borderline case—one where each of a pair of conflicting verdicts can be unexceptionable—and sides with Epistemicism in rejecting the idea of such cases as truth-value gaps. It is contended that Williamson’s explanation of why we cannot know where the putative sharp cut-offs in Sorites series come at best explains too little, since it has nothing plausible to say about our ignorance throughout a borderline area, nor about vagueness induced by deliberate approximation—‘roughly six feet tall’, ‘about a metre long’.
Vagueness
Authors: Wright Crispin
Published: August 2021

This chapter centres on what it terms the Vagueness Trilemma: that what may impress as the only three possible types of view about what vagueness is—namely, that it is a matter of semantic indeterminacy, that it originates in rebus, and the epistemicist idea that it is a matter of our ineluctable ignorance about fully determinate matters— are each open to serious, indeed arguably fatal, objections. The chapter is organized about the possible attitudes to three interrelated, nodal theses. Bivalence—are borderline statements bivalent? Third possibility—do they possess some third alethic status—lack of truth value or some third truth value? And Verdict Exclusion: is knowledge of truth value precluded in borderline cases? It is argued that there are five consistent combinations of acceptance and non-acceptance of the three nodal issues, and that an attitude of agnosticism to all three, and a consequent broadly intuitionistic attitude to vagueness, is the way out of the Trilemma.
The Illusion of Higher-Order Vagueness
Authors: Wright Crispin
Published: August 2021

It is near orthodoxy among philosophers interested in vagueness in natural language not merely to acknowledge higher-order vagueness but to take its existence as a basic datum; so that views that lack the resources to account for it, or that put obstacles in the way, are regarded as deficient just on that score. This chapter aims to loosen the hold of this deeply misconceived idea. Its dialectic is complex and defies short summary. The upshot is that higher-order vagueness is no basic datum but an illusion, fostered by misunderstandings of the nature of ordinary (if you will, ‘first-order’) vagueness itself. To see through the illusion is to take a step that is prerequisite for a correct understanding of vagueness, and for any satisfying dissolution of its attendant paradoxes.
On the Characterization of Borderline Cases
Authors: Wright Crispin
Published: August 2021

This chapter was originally written for Gary Ostertag’s edition of the festschrift for Stephen Schiffer, Meanings and Other Things (Oxford University Press, 2016). It centres on Schiffer’s treatment of the characterization problem: the problem of saying what being a borderline case of a concept expressed by a vague expression consists in. While broadly sympathetic to Schiffer’s approach, the chapter takes issue with two aspects of it. Schiffer endorses Verdict Exclusion: the doctrine that a ‘polar verdict’ about a borderline case cannot be an expression of knowledge. This endorsement comes at too high a cost: among other things, it conflicts with the entitlement intuition—the intuition that there will be no point in a Sorites sequence at which it is mandatory to return neither of the polar verdicts. The chapter argues for agnosticism about Verdict Exclusion (‘Liberalism’). It also rejects Schiffer’s idea that a special genre of partial belief—vagueness-related partial belief—plays an essential role in characterizing the possession conditions for vague concepts.
First-Year Trajectories of Medical Cannabis Use Among Adults Taking Opioids for Chronic Pain: An Observational Cohort Study
Authors: Ross Jonathan , Slawek Deepika E , Zhang Chenshu , Starrels Joanna L , Levin Frances R , Sohler Nancy L , Minami Haruka , Arnsten Julia H , Cunningham Chinazo O
Published: August 2021

Objective

To describe first-year trajectories of medical cannabis use and identify characteristics associated with patterns of use in a cohort of adults using opioids for chronic pain.

Design

Latent class trajectory analysis of a prospective cohort study using data on the 14-day frequency of medical cannabis use.

Setting

A large academic medical center and four medical cannabis dispensaries in the New York City metropolitan area.

Subjects

Adults with chronic pain using opioids and newly certified for medical cannabis in New York between 2018 and 2020.

Methods

Using latent class trajectory analysis, we identified clusters of participants based on the 14-day frequency of medical cannabis use. We used logistic regression to determine factors associated with cluster membership, including sociodemographic characteristics, pain, substance use, and mental health symptoms.

Results

Among 99 participants, the mean age was 53 years; 62% were women, and 52% were White. We identified three clusters of medical cannabis use: infrequent use (n = 30, mean use = 1.5 days/14-day period), occasional use (n = 28, mean = 5.7 days/14-day period), and frequent use (n = 41, mean = 12.1 days/14-day period). Within clusters, use patterns did not vary significantly over 52 weeks. Differences were observed in two sociodemographic variables: Frequent (vs infrequent) use was associated with non-Hispanic White race/ethnicity (adjusted odds ratio 4.54, 95% confidence interval 1.49–14.29), while occasional (vs infrequent) use was associated with employment (adjusted odds ratio 13.84, 95% confidence interval 1.21–158.74).

Conclusions

Three clusters of medical cannabis use patterns emerged and were stable over time. Results suggest that structural factors related to race/ethnicity and employment may be major drivers of medical cannabis use, even among adults certified for its use.
Responding to the Public during a Pandemic: Perceptions of ‘Satisfactory’ and ‘Unsatisfactory’ Policing
Authors: Ghaemmaghami Aram , Inkpen Rob , Charman Sarah , Ilett Camille , Bennett Stephanie , Smith Paul , Newiss Geoff
Published: August 2021

As part of a substantial research project on policing the Covid-19 pandemic, a public survey was conducted in Hampshire and the Isle of Wight in England. Four open-ended questions provided participants with the opportunity to produce unlimited free-text responses regarding their perception of policing during the pandemic. Responses were coded and thematically analysed to identify themes concerning public compliance and policing during the lockdown. Subthemes surrounding communication, efficiency, and equity emerged from participant’s perceptions of what they considered to be ‘satisfactory’ and ‘unsatisfactory’ forms of policing during the pandemic. A common sub-theme regarding the public’s confusion over the role of the police was countered by an acknowledgement that the police were ‘doing their best.’ The pandemic has thrown into sharper relief pre-crisis public perceptions of appropriate policing. The free-text responses highlight the ongoing tensions between normative and instrumental approaches to policing and public expectations of police actions.
The Costs and Benefits of Liquidity Regulations: Lessons from an Idle Monetary Policy Tool
Authors: Curfman Christopher J , Kandrac John
Published: August 2021

We investigate how liquidity regulations affect banks by examining a dormant monetary policy tool that functions as a liquidity regulation. For causal inference, we use a regression kink design that relies on the variation in a marginal high-quality liquid asset requirement around an exogenous threshold. We show that mandated increases in liquidity cause banks to reduce credit supply. Liquidity requirements also depress banks’ profitability, though some of the regulatory costs are passed on to liability holders. We document a prudential benefit of liquidity requirements by showing that banks subject to a higher requirement just before the financial crisis had lower odds of failure.
Cultural Sidelining: How Campus Cultures across University Contexts Shortchange Working-Class Hispanic Students
Authors: Garza Alma Nidia
Published: August 2021

As organizations that privilege the interests and behaviors of a White middle class, universities institutionalize processes that undermine both the preparation and contributions of students from working-class backgrounds and racial/ethnic minoritized groups such as Hispanics. While studies have documented how universities carry out forms of class or racial exclusion, how racial exclusion is embedded in university class cultural practices is less understood. Understanding how class processes that are linked to racial objectives inhibit Hispanic student development is important not solely due to the group’s growing representation in college but also because such information facilitates an understanding of how universities legitimize racial hierarchies. Drawing on theories of racialized organizations and cultural reproduction, I compare how working-class Hispanic students attending a moderately selective institution and their co-ethnic counterparts attending a less selective, regional university contend with class cultural hierarchies that impact their growth and inclusion. I propose that universities engage in a practice of cultural sidelining. Students are unable to exercise elements of sidelined class cultures depending on the set of behaviors endorsed on campus. Sidelining enables organizations to draw on social class practices to carry out divergent forms of racial exclusion.
Determination of therapeutic agents efficiencies of microsatellite instability high colon cancer cells in post‐metastatic liver biochip modeling
Authors: Bayir Garbioglu Duygu , Demir Nazan , Ozel Ceren , Avci Hüseyin , Dincer Murat
Published: August 2021

Two distinct genetic mutational pathways characterized by either chromosomal instability or high‐frequency microsatellite instability (MSI‐H) are recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI‐H have a significant, stage‐independent, multivariate survival advantage. Biological properties of CMS1 (MSI‐H type) can affect therapeutic efficiencies of agents used in the treatment of CRC, and therefore become a new predictive factor of the treatment. But, the predictive impact of MSI‐H status for adjuvant chemotherapy remains controversial. This study will assess whether there is any unnecessary or inappropriate use of treatment agents recommended for adjuvant therapy of stage 2 and 3 of disease and for palliative or curative treatment of liver metastatic disease in microsatellite instability high group, a molecular subtype of colon cancer. Within this scope, the efficiencies of fluorouracil‐ and oxaliplatin‐based chemotherapeutic agents will be shown on stage 3 microsatellite instability high colon tumor cell lines first, and then a microfluidic model will be created, imitating the metastasis of colon cancer to the liver. In the microfluidic chip model, we will create in liver tissue, where the metastasis of microsatellite instability high colon cancer will be simulated; the effectiveness of chemotherapeutic agents, immunotherapy agents, and targeted agents on tumor cells as well as drug response will be assessed according to cell viability through released biomarkers from the cells. The proposed hypothesis study includes the modeling and treatment of patient‐derived post‐metastatic liver cancer in microfluidics which has priority at the global and our region and consequently develop personal medication.
Regional anesthesia in coronavirus disease 2019 pandemic
Authors: Heijnen Tyler , Vandebergh Vincent , Vandepitte Catherine , Buck Robbert
Published: August 2021

Purpose of review

Coronavirus disease 19 (COVID-19) has presented numerous challenges to healthcare systems worldwide. The virus is highly contagious and infectious since transmission can occur via multiple routes. General measures to prevent viral transmission to patients and healthcare personnel, such as a reduction in clinical load and routine testing, must be coupled with multiple additional safety measures in perioperative services.

Recent findings

Regional anesthesia preserves respiratory function and reduces aerosol-generating procedures typically associated with airway management in general anesthesia, making it the first choice for a suspected or confirmed COVID-19 patient in need of surgery with anesthesia. A well thought out regional anesthetic plan, implementation of hygiene and (personal) safety measures are necessary to ensure the best possible outcome for both the patient and the healthcare staff.

The present review addresses both practical and recommended measures for performing regional anesthesia in the pandemic, to ensure patient and staff safety, and equipment protection. Further research and evidence-based guidelines are necessary to devise an established standard of care during the current COVID-19 and possible future pandemics.
Impact of Women’s Domination in Plastic Surgery Residency Program in Indonesia
Authors: Aulia Indri , Mustika Rita , Menaldi Sri L.
Published: August 2021

Background:

A shift in gender dominance from man to woman in the medical field has occurred from time to time globally, including in Indonesia’s plastic surgery community. This shift may alter the education and clinical settings of plastic surgery. This study aimed to explore the effect of the phenomenon of women’s dominance in plastic surgery residency programs in Indonesia.

Methods:

This qualitative study was conducted using a phenomenological approach on three plastic surgery residency programs in Indonesia. Academic report review, focus group discussions, and in-depth interviews of residents, lecturers, residency program managers, and alumni user groups were selected using the maximum variation sampling method. Data obtained were analyzed and processed thematically.

Results:

Three themes emerged based on the educational process timeline: pre-education, intra-education, and post-education. Each timeline had several themes that mutually influenced the educational process. In the pre-educational process, residents’ personal characters were affected by societies’ positive and negative perceptions. The working environment, impact of women’s dominance, and cultural dimension affected the intra-educational process. When entering the career life, residents expected an ideal working environment and had particular workplace preferences to achieve their well-being.

Conclusions:

The impact of women’s dominance during the educational program affected residents’ daily dynamics. However, this dominance did not affect the quality of education and workloads.
Open Conjunctival Approach for Sub-Tenon’s Xen Gel Stent Placement and Bleb Morphology by Anterior Segment Optical Coherence Tomography
Authors: Dangda Sonal , Radell Jake E. , Mavrommatis Maria A. , Lee Rachel , Do Anna , Sidoti Paul A. , Panarelli Joseph F.
Published: August 2021

Précis:

Sub-Tenon’s implantation of the Xen Gel stent resulted in significant intraocular pressure (IOP) lowering along with a low rate of postoperative bleb needling, and a favorable bleb morphology on anterior segment optical coherence tomography (AS-OCT).

Purpose:

The aim was to assess clinical outcomes and bleb morphology following sub-Tenon’s implantation of the Xen Gel Stent.

Methods:

The medical records of patients who underwent sub-Tenon’s Xen Gel Stent implantation with intraoperative mitomycin-C through an open conjunctival approach were reviewed. Postoperative IOP and number of glaucoma medications at 1, 3, 6, 9, and 12 months were assessed. Bleb morphology was analyzed at various timepoints using AS-OCT (Topcon DRI OCT version 1.1.1).

Results:

Twenty-six eyes were included in the study. Mean age was 69.4±8.0 years. Mean preoperative IOP was 28.1±7.8 mm Hg on an average of 3.5±0.9 glaucoma medications. Mean IOP at postoperative month 12 (n=23 eyes) was 12.9±4.0 mm Hg (P<0.01) on an average of 0.3±0.6 (P<0.01) glaucoma medications. Three eyes (12%) required postoperative needle revision. Bleb morphology in the early postoperative period (≤3 mo) was characterized by multiple small subconjunctival microcysts on AS-OCT. At the intermediate (6 to 12 mo) and long-term (>12 mo) timepoints, reduction in microcysts with multiple internal parallel layers of aqueous flow and a uniform pattern were more frequently noted. All functional blebs were characterized by the presence of a posterior episcleral fluid lake. Failed blebs showed absence of aqueous humor around the distal end of the microshunt.

Conclusion:

Following an open conjunctival approach, sub-Tenon’s placement of the Xen Gel Stent with significant IOP lowering was achieved. In eyes with good shunt function, bleb morphology by AS-OCT showed a posterior episcleral fluid lake similar to findings following trabeculectomy.
The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD
Authors: Bamias Giorgos , Kokkotis Georgios , Christidou Angeliki , Christodoulou Dimitrios K. , Delis Vasileios , Diamantopoulou Georgia , Fessatou Smaragdi , Gatopoulou Anthia , Giouleme Olga , Kafritsa Panagiota , Kalantzis Chrisostomos , Kapsoritakis Andreas , Karatzas Pantelis , Karmiris Konstantinos , Katsanos Konstantinos , Kevrekidou Polyxeni , Kosmidis Charalampos , Mantaka Aikaterini , Mathou Nicoletta , Michalopoulos George , Michopoulos Spyridon , Papaconstantinou Ioannis , Papatheodoridis George , Polymeros Dimitrios , Potamianos Spyros , Poulopoulos Georgios , Protopapas Andreas , Sklavaina Maria , Soufleris Konstantinos , Theocharis Georgios , Theodoropoulou Angeliki , Triantafillidis John K. , Triantafyllou Konstantinos , Tsiolakidou Georgia , Tsironi Eftychia , Tzouvala Maria , Viazis Nikos , Xourgias Vasileios , Zacharopoulou Eirini , Zampeli Evanthia , Mantzaris Gerasimos J.
Published: August 2021

Objectives

COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic.

Methods

Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death).

Results

We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1–1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84–29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16–0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics.

Conclusions

IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.
The impact of undiagnosed primary biliary cholangitis
Authors: Garrido Isabel , Liberal Rodrigo , Cardoso Maria João , Macedo Guilherme
Published: August 2021

Background

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by symptoms with a major impact on the quality of life. The aim of this study was to identify patients with undiagnosed PBC who are not under hepatology follow-up and to assess the clinical impact of lack of adequate treatment and surveillance.

Methods

Adult patients with a positive antimitochondrial antibodies (AMA) titer were identified from local biochemistry records. Patients with probable PBC who were not known by the hepatology services were invited to accurately stage their disease and optimize medical management.

Results

A total of 214 AMA-positive patients were identified, 148 of whom had diagnostic criteria for PBC. Twenty-three patients were not known by the hepatology services, most of them followed by specialties other than gastroenterology. These patients had significantly higher liver stiffness compared to those followed by the hepatology services (14.3 kPa vs. 6.2 kPa; P = 0.009). A large percentage of untreated individuals reported fatigue (72.7%) and pruritus (27.3%).

Conclusions

A substantial number of patients with PBC are not known to have hepatology services with a significant long-term impact from a lack of follow-up and therapy. Strategies must be established to identify these patients and reduce the disease’s progressive nature.
Long-standing effect of cholecystectomy in patients with metabolic-associated fatty liver disease
Authors: Méndez-Sánchez Nahum , Valencia-Rodríguez Alejandro , Cerda-Reyes Eira , Montejo-Velázquez César , Higuera de la Tijera Fátima , Servin-Caamaño Alfredo , Icaza-Chávez María E. , Chi-Cervera Luis A. , Montalvo-Gordon Iaarah , Qi Xingshun , Jiménez-Gutiérrez Carlos
Published: August 2021

Objective

The role of cholecystectomy as a risk factor in patients with metabolic-associated fatty liver disease (MAFLD) remains unclear. This study aimed to investigate if long-standing cholecystectomy is associated with advanced liver fibrosis and cirrhosis in patients with recently diagnosed MAFLD.

Methods

A retrospective observational study was performed in four hospitals in Mexico including patients with recently diagnosed MAFLD and a history of cholecystectomy. Subjects were divided into those with cholecystectomy ≥6 months before MAFLD diagnosis (ChBM), and those with cholecystectomy at the time of MAFLD diagnosis (ChAM). Odds ratios (OR) for the association of advanced liver fibrosis and cirrhosis with the timing of cholecystectomy were calculated.

Results

Mean age of 211 participants was 49.06 ± 15.12 years and the majority were female (72.5%). Patients from the ChBM (n = 70) group were significantly older (53.14 vs. 47.03 years; P = 0.003), had higher BMI (30.54 vs. 28.52 kg/m2; P = 0.011) and lower platelet count (236.23 vs. 266.72 × 103/µL; P = 0.046) compared with patients from ChAM group (n = 141). In multivariable-adjusted analysis, age (OR = 2.37; P = 0.024), dyslipidemia (OR = 4.28; P = 0.005) and severe liver fibrosis (OR = 4.68; P = 0.0) were independent risk factors associated with long-standing cholecystectomy.

Conclusion

Patients with long-standing cholecystectomy (≥6 months) are at increased risk of severe liver fibrosis and cirrhosis at the time of MAFLD diagnosis compared to those with recently done cholecystectomy. Advanced age (>50 years) and dyslipidemia are also commonly found in these subjects.
Assessment of avoidant restrictive food intake disorder, pica and rumination disorder: interview and questionnaire measures
Authors: Dinkler Lisa , Bryant-Waugh Rachel
Published: August 2021

Purpose of review

This article reviews available assessment instruments for three of the feeding and eating disorder diagnostic categories: avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). It includes an overview of the current status of screening tools, questionnaire measures, and diagnostic instruments.

Recent findings

Screening instruments are available for all three disorders; however, for pica and RD, these typically include single screening items only and do not cover any specific features of these presentations. Only one questionnaire suitable for clinical populations is included, covering ARFID only. Standardized diagnostic interviews are limited to two covering both pica and RD, only one of which provides further clinical information. Of the five diagnostic instruments for ARFID described here, two include diagnostic items as well as allowing more detailed assessment of clinical features.

There are a limited number of assessment measures available for all three disorders, with instruments for ARFID being the greatest in number and widest in terms of scope. A commonly encountered difficulty is that many assessment instruments do not adequately cover diagnostic exclusion criteria, which raises the likelihood of false positive findings. All currently available measures require further study to determine their reliability and validity.
Relationships between biodiversity and ecosystem functioning proxies strengthen when approaching chemosynthetic deep-sea methane seeps
Authors: Ashford Oliver S. , Guan Shuzhe , Capone Dante , Rigney Katherine , Rowley Katelynn , Cordes Erik E. , Cortés Jorge , Rouse Greg W. , Mendoza Guillermo F. , Sweetman Andrew K. , Levin Lisa A.
Published: August 2021

As biodiversity loss accelerates globally, understanding environmental influence over biodiversity–ecosystem functioning (BEF) relationships becomes crucial for ecosystem management. Theory suggests that resource supply affects the shape of BEF relationships, but this awaits detailed investigation in marine ecosystems. Here, we use deep-sea chemosynthetic methane seeps and surrounding sediments as natural laboratories in which to contrast relationships between BEF proxies along with a gradient of trophic resource availability (higher resource methane seep, to lower resource photosynthetically fuelled deep-sea habitats). We determined sediment fauna taxonomic and functional trait biodiversity, and quantified bioturbation potential (BPc), calcification degree, standing stock and density as ecosystem functioning proxies. Relationships were strongly unimodal in chemosynthetic seep habitats, but were undetectable in transitional ‘chemotone’ habitats and photosynthetically dependent deep-sea habitats. In seep habitats, ecosystem functioning proxies peaked below maximum biodiversity, perhaps suggesting that a small number of specialized species are important in shaping this relationship. This suggests that absolute biodiversity is not a good metric of ecosystem ‘value’ at methane seeps, and that these deep-sea environments may require special management to maintain ecosystem functioning under human disturbance. We promote further investigation of BEF relationships in non-traditional resource environments and emphasize that deep-sea conservation should consider ‘functioning hotspots' alongside biodiversity hotspots.
Coming together—symbiont acquisition and early development in deep-sea bathymodioline mussels
Authors: Franke Maximilian , Geier Benedikt , Hammel Jörg U. , Dubilier Nicole , Leisch Nikolaus
Published: August 2021

How and when symbionts are acquired by their animal hosts has a profound impact on the ecology and evolution of the symbiosis. Understanding symbiont acquisition is particularly challenging in deep-sea organisms because early life stages are so rarely found. Here, we collected early developmental stages of three deep-sea bathymodioline species from different habitats to identify when these acquire their symbionts and how their body plan adapts to a symbiotic lifestyle. These mussels gain their nutrition from chemosynthetic bacteria, allowing them to thrive at deep-sea vents and seeps worldwide. Correlative imaging analyses using synchrotron-radiation based microtomography together with light, fluorescence and electron microscopy revealed that the pediveliger larvae were aposymbiotic. Symbiont colonization began during metamorphosis from a planktonic to a benthic lifestyle, with the symbionts rapidly colonizing first the gills, the symbiotic organ of adults, followed by all other epithelia of their hosts. Once symbiont densities in plantigrades reached those of adults, the host's intestine changed from the looped anatomy typical for bivalves to a straightened form. Within the Mytilidae, this morphological change appears to be specific to
Bathymodiolus
and
Gigantidas
, and is probably linked to the decrease in the importance of filter feeding when these mussels switch to gaining their nutrition largely from their symbionts.
Episodic-like memory is preserved with age in cuttlefish
Authors: Schnell Alexandra K. , Clayton Nicola S. , Hanlon Roger T. , Jozet-Alves Christelle
Published: August 2021

Episodic memory, remembering past experiences based on unique what–where–when components, declines during ageing in humans, as does
episodic-like
memory in non-human mammals. By contrast, semantic memory, remembering learnt knowledge without recalling unique what–where–when features, remains relatively intact with advancing age. The age-related decline in episodic memory likely stems from the deteriorating function of the hippocampus in the brain. Whether episodic memory can deteriorate with age in species that lack a hippocampus is unknown. Cuttlefish are molluscs that lack a hippocampus. We test both semantic-like and episodic-like memory in sub-adults and aged-adults nearing senescence (
n
= 6 per cohort). In the semantic-like memory task, cuttlefish had to learn that the location of a food resource was dependent on the time of day. Performance, measured as proportion of correct trials, was comparable across age groups. In the episodic-like memory task, cuttlefish had to solve a foraging task by retrieving what–where–when information about a past event with unique spatio-temporal features. In this task, performance was comparable across age groups; however, aged-adults reached the success criterion (8/10 correct choices in consecutive trials) significantly faster than sub-adults. Contrary to other animals, episodic-like memory is preserved in aged cuttlefish, suggesting that memory deterioration is delayed in this species.
Chinese herbal medicines and nutraceuticals inhibit Pseudomonas aeruginosa biofilm formation
Authors: Hayashi Minami , Kaneko Hiroshi , Yamada Tetsuya , Ikoshi Hideaki , Noguchi Norihisa , Nakaminami Hidemasa
Published: August 2021

Pseudomonas aeruginosa

is a major biofilm-forming, opportunistic pathogen. Tolerance to antimicrobial agents due to biofilm formation may lead to the emergence of antimicrobial-resistant bacterial strains. Thus, adjunctive agents that can inhibit biofilm formation are necessary to enhance the therapeutic efficacy of antimicrobial agents. In this study, we evaluated the anti-biofilm formation activity of selected Chinese herbal medicines and nutraceuticals, which are commercially available in Japan. Among the eight agents evaluated for their potential to inhibit biofilm formation, Eiekikaryu S, Iribakuga and Hyakujunro significantly reduced

P. aeruginosa

biofilm formation (P <0.05) without inhibiting bacterial growth. Additionally, the expression of biofilm-associated genes (rhlR, rhlA and lasB) in

P. aeruginosa

was significantly suppressed by Eiekikaryu S, Iribakuga and Hyakujunro (P <0.001). Our findings indicate that some Chinese herbal medicines and nutraceuticals can be potential adjunctive agents for antimicrobial therapy against

P. aeruginosa

.
Mesonia hitae sp. nov., isolated from the seawater of the South Atlantic Ocean
Authors: Zhou Ying , Gao Xiujun , Xu Jingjing , Li Guizhen , Ma Rui , Yan Peisheng , Dong Chunming , Shao Zongze
Published: August 2021

A Gram-negative, non-motile, non-spore-forming, aerobic and short rod-shaped bacterial strain R32T, was isolated from seawater of the South Atlantic Ocean. Strain R32Tgrew at 10–40 °C (optimum 28 °C), at pH 6.0–8.0 (optimum 7.0), and in the presence of 3–8 % NaCl (w/v) (optimum 5 %). Cells were oxidase- and catalase-positive. The 16S rRNA gene sequence of strain R32Tshared the highest similarities withMesonia oceanica(98.3 %), followed bySalegentibacter salarius(93.0 %),Salegentibacter mishustinae(92.8 %),Salegentibacter salegens(92.5 %) andMesonia maritima(92.4 %). The dominant fatty acids were iso-C15 : 0(32.7 %) and iso-C17 : 03-OH (21.1 %). Menaquinone-6 (MK-6) was detected as the sole respiratory quinone. The polar lipids found were phosphatidylethanolamine, three aminolipids and three unidentified lipids. The DNA G+C content was 35.0 mol%. The ANI value and dDDH value between strain R32Tand theSalegentibacterandMesoniaspecies were 70.5–85.8 % and 18.7–30.5 %, respectively. Based on the results of the polyphasic characterization, strain R32Tis considered to represent a novel species of the genusMesonia, for which the nameMesonia hitaesp. nov. is proposed. The type strain is R32T(=MCCC 1A09780T=KCTC 72004T).
Association between Neighborhood Socioeconomic Status and Executive System Activation in Youth
Authors: Murtha Kristin , Larsen Bart , Pines Adam , Parkes Linden , Moore Tyler M. , Adebimpe Azeez , Alexander-Bloch Aaron , Calkins Monica E. , Davila Diego G. , Lindquist Martin A. , Mackey Allyson P. , Roalf David R. , Scott J. Cobb , Wolf Daniel H. , Gur Ruben C. , Gur Raquel E. , Barzilay Ran , Satterthwaite Theodore D.
Published: August 2021

Low socioeconomic status has been shown to have detrimental effects on cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may have a particularly strong impact on cognitive outcomes. Here, we sought to examine how neighborhood socioeconomic status (SES) impacts task-related activation of the executive system during adolescence, and to determine whether this effect mediates the relationship between neighborhood SES and WM performance. To address these questions, we studied 1,158 youths (age 8-22) that completed a fractal n-back WM task during fMRI at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that higher neighborhood SES was associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. These associations remained significant when controlling for related factors like parental education and exposure to traumatic events. Furthermore, high dimensional multivariate mediation analysis identified two distinct patterns of brain activity within the executive system that significantly mediated the relationship between neighborhood SES and task performance. Together, these findings underscore the importance of the neighborhood environment in shaping executive system function and WM in youth.
Clinical Metagenomic Sequencing for Species Identification and Antimicrobial Resistance Prediction in Orthopaedic Device Infection
Authors: Street Teresa L. , Sanderson Nicholas D. , Kolenda Camille , Kavanagh James , Pickford Hayleah , Hoosdally Sarah , Cregan Jack , Taunt Carol , Jones Emma , Oakley Sarah , Atkins Bridget L. , Dudareva Maria , McNally Martin A. , O’Grady Justin , Crook Derrick W. , Eyre David W.
Published: August 2021

Background

Diagnosis of orthopaedic device-related infection is challenging, and causative pathogens may be difficult to culture. Metagenomic sequencing can diagnose infections without culture, but attempts to detect antimicrobial resistance (AMR) determinants using metagenomic data have been less successful. Human DNA depletion may maximise the amount of microbial DNA sequence data available for analysis.

Methods

Human DNA depletion by saponin was tested in 115 sonication fluid samples generated following revision arthroplasty surgery, comprising 67 where pathogens were detected by culture and 48 culture-negative samples. Metagenomic sequencing was performed on the Oxford Nanopore Technologies GridION platform. Filtering thresholds for detection of true species versus contamination or taxonomic misclassification were determined. Mobile and chromosomal genetic AMR determinants were identified in Staphylococcus aureus-positive samples.

Results

Of 114 samples generating sequence data, species-level sensitivity of metagenomic sequencing was 49/65 (75%; 95%CI 63-85%) and specificity 103/114 (90%; 95%CI 83-95%) compared with culture. Saponin treatment reduced the proportion of human bases sequenced in comparison to 5µm filtration from a median (IQR) 98.1% (87.0%-99.9%) to 11.9% (0.4%-67.0%), improving reference genome coverage at 10-fold depth from 18.7% (0.30%-85.7%) to 84.3% (12.9%-93.8%). Metagenomic sequencing predicted 13/15 (87%) resistant and 74/74 (100%) susceptible phenotypes where sufficient data were available for analysis.

Conclusions

Metagenomic nanopore sequencing coupled with human DNA depletion has the potential to detect AMR in addition to species detection in orthopaedic device-related infection. Further work is required to develop pathogen-agnostic human DNA depletion methods, improving AMR determinant detection and allowing its application to other infection types.
An ancient dental signalling centre supports homology of an enamel knot in sharks
Authors: Thiery Alexandre P. , Standing Ariane S. I. , Cooper Rory L. , Fraser Gareth J.
Published: August 2021

Development of tooth cusps is regulated by the enamel knot signalling centre. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here we show the conservation and restriction of fgf10 and fgf3 to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling phenotypes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.
Next generation infection prevention clothing: Non-woven Fabrics Coated with Cranberry Extracts Capable of Inactivating Enveloped Viruses such as SARS-CoV-2 and Multidrug-resistant Bacteria
Authors: Tuñón-Molina Alberto , Cano-Vicent Alba , Martí Miguel , Muramoto Yukiko , Noda Takeshi , Takayama Kazuo , Serrano-Aroca Ángel
Published: August 2021

The Coronavirus Disease (COVID-19) pandemic is demanding rapid action of the authorities and scientific community in order to find new antimicrobial solutions that could inactivate the pathogen SARS-CoV-2 that causes this disease. Gram-positive bacteria contribute to severe pneumonia associated with COVID-19, and their resistance to antibiotics is increasing at an alarming rate. In this regard, non-woven fabrics are currently used for the fabrication of infection prevention clothing such as face masks, caps, scrubs, shirts, trousers, disposable gowns, overalls, hoods, aprons and shoe covers as protective tools against viral and bacterial infections. However, these non-woven fabrics are made of materials that do not possess antimicrobial activity. Thus, we have developed here non-woven fabrics with antimicrobial coatings of cranberry extracts capable of inactivating enveloped viruses such as SARS-CoV-2 and the phage phi 6, and two multidrug-resistant bacteria: the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The non-toxicity of these advanced technology was ensured using a Caenorhabditis elegans in vivo model. These results open up a new prevention path using natural and biodegradable compounds for the fabrication of infection prevention clothing in the current COVID-19 and future pandemics.
Leveraging sequences missing from the human genome to diagnose cancer
Authors: Georgakopoulos-Soares Ilias , Barnea Ofer Yizhar , Mouratidis Ioannis , Chan Candace S.Y. , Bradley Rachael , Mahajan Mayank , Sims Jasmine , Cintron Dianne Laboy , Easterlin Ryder , Kim Julia S. , Chen Emmalyn , Pineda Geovanni , Parada Guillermo E. , Witte John S. , Maher Christopher A. , Feng Felix , Vathiotis Ioannis , Syrigos Nikolaos , Panagiotou Emmanouil , Charpidou Andriani , Syrigos Konstantinos , Chapman Jocelyn , Kvale Mark , Hemberg Martin , Ahituv Nadav
Published: August 2021

Cancer diagnosis using cell-free DNA (cfDNA) has potential to improve treatment and survival but has several technical limitations. Here, we show that tumor-associated mutations create neomers, DNA sequences 13-17 nucleotides in length that are predominantly absent from genomes of healthy individuals, that can accurately detect cancer, including early stages, and distinguish subtypes and features. Using a neomer-based classifier, we show that we can distinguish twenty-one different tumor-types with higher accuracy than state-of-the-art methods. Refinement of this classifier using a handcrafted set of kmers identified additional cancer features with greater precision. Generation and analysis of 451 cfDNA whole-genome sequences demonstrates that neomers can precisely detect lung and ovarian cancer with an area under the curve (AUC) of 0.93 and 0.89, respectively. In particular, for early stages, we show that neomers can detect lung cancer with an AUC of 0.94 and ovarian cancer, which lacks an early detection test, with an AUC of 0.93. Finally, testing over 9,000 sequences with either promoter or massively parallel reporter assays, we show that neomers can identify cancer-associated mutations that alter regulatory activity. Combined, our results identify a novel, sensitive, specific and simple diagnostic tool that can also identify novel cancer-associated mutations in gene regulatory elements.
Savor the flavor — a randomized double-blind study on taste-enhanced placebo analgesia in healthy volunteers
Authors: Zunhammer Matthias , Goltz Gerrit , Schweifel Maximilian , Stuck Boris A. , Bingel Ulrike
Published: August 2021

We conducted a randomized, double-blind, between-group study to investigate how the taste of oral medication affects placebo analgesia. Over three sub-studies, 318 healthy volunteers (297 included) were subjected to experimental tonic cold water pain (cold pressor test) before and after receiving taste-neutral (water), bitter (quinine), sweet (saccharine), or no placebo drops. Pain ratings indicated that taste enhances placebo analgesia. This effect was small but accounted for a substantial portion of the overall placebo effect and was comparable to WHO stage 1 analgesic effects. Moreover, placebo treatments were associated with an increase in peak heart rate response to cold water. Adverse effects were minimal. These results indicate that added taste may be an easy-to-implement, cost-effective, and safe way to optimize treatment outcomes and that taste-neutral preparations may reduce placebo-related outcome variance in clinical trials. Further studies are needed to test if these findings can be translated into clinical scenarios.
Cervical Spinal Cord Injury Leads to Injury and Metabolic Dysfunction of the Lung
Authors: Huffman Emily E. , Dong Brittany E. , Clarke Harrison A. , Young Lyndsay E.A. , Allison Derek B. , Sun Ramon C. , Waters Christopher M. , Alilain Warren J.
Published: August 2021

High-cervical spinal cord injury (SCI) often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury (ALI), which predicts substantial mortality rates. While the correlation between ALI and SCI has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap, we performed an experimental cervical SCI and assessed lung injury in adult rats. We demonstrate that animals display signs of ALI two weeks post-SCI. We also observed aberrant N-glycan metabolism determined by matrix-assisted laser desorption/ionization mass spectrometry imaging. Collectively, we establish for the first time a model of ALI after SCI at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate ALI.