bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking nanoparticulate polymer–drug conjugates for cancer theranostics
Authors: Wang Yaoqi , Xia Heming , Chen Binlong , Wang Yiguang
Published: June 2022

Polymer–drug conjugates (PDCs) fabricated as nanoparticles have hogged the limelight in cancer theranostics in the past decade. Many researchers have devoted to developing novel and efficient polymeric drug delivery system since the first generation of poly(N‐[2‐hydroxypropyl]methacrylamide) copolymer–drug conjugates. However, none of them has been approved for chemotherapy in clinic. An ideal PDC nanoparticle for cancer theranostics should possess several properties, including prolonged circulation in blood, sufficient accumulation and internalization in tumors, and efficient drug release in target sites. To achieve these goals, it is important to rationally design the nanoparticulate PDCs based on circulation, accumulation, penetration, internalization, and drug release (CAPIR) cascade. Specifically, CAPIR cascades are divided into five steps: (1) circulation in the vascular compartment without burst release, (2) accumulation in tumors via enhanced permeability and retention effect, (3) subsequent penetration into the deep regions of tumors, (4) internalization into tumor cells, and (5) release of drugs as free molecules to exert their pharmacological effects. In this review, we focus on the development and novel approaches of nanoparticulate PDCs based on CAPIR cascade, and provide an outlook on future clinical application.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Admission and Discharge Planning
Authors: Feijo Isabelle , Hoare Steve , Sarmiento Karen
Published: June 2022

It is essential that staff of an adolescent inpatient psychiatry unit have the capacity and authority to ensure parents and treating community clinicians support the admission, families participate in the treatment, and community clinicians participate in discharge planning and assertive follow up since these are features known to improve clinical outcomes. The chapter outlines, through the use of a hypothetical case example, the processes involved in admission to and discharge from the Walker Unit.
Immunreaktion nach perforierender Keratoplastik in Abhängigkeit von der Transplantatgröße und -zentrierung
Authors: Tischer N. , Zemova E. , Maamri A. , Pfeiffer M. , Reinert U. , Sideroudi H. , Seitz B.
Published: June 2022

Hintergrund

Die Immunreaktion (IR) nach perforierender Keratoplastik (PKP) stellt eine schwerwiegende Komplikation mit hohem Risiko des Transplantat(TPL)-Verlustes dar. Ziel dieser Studie ist es, insbesondere den Einfluss der TPL-Größe und -Zentrierung auf das Auftreten einer IR mithilfe präziser Messmethoden zu analysieren und zu bewerten.

Patienten und Methoden

In diese retrospektive Studie wurden insgesamt 2133 Patienten eingeschlossen, welche im Zeitraum von Januar 2009 bis Juli 2019 eine PKP erhalten haben. Es wurden folgende Zielgrößen analysiert: Häufigkeit einer IR, TPL-Herkunft, Spender- und Patientenalter, Diagnose, Hornhaut(HH)-Durchmesser, Flächenverhältnisse von TPL zu Empfänger-HH und die Rolle der TPL-Zentrierung mithilfe von Abstandsmessungen zum vaskularisierten Limbusrand an 4 verschiedenen Stellen.

Ergebnisse

Insgesamt erlitten 8,25 % der Patienten eine IR im Beobachtungszeitraum. Die Häufigkeit einer IR korrelierte signifikant (p < 0,001) positiv mit dem Verhältnis von TPL-Größe und Empfänger-HH-Größe. Außerdem konnte eine signifikante Korrelation zwischen dem Auftreten einer IR und einem geringen Abstand des TPL-Randes zum Limbus in der y‑Achse (oben und unten) festgestellt werden. Insbesondere zeigte sich anhand des Korrelationskoeffizienten ein stärkerer Zusammenhang für den unteren Limbusrand (p < 0,001).

Schlussfolgerung

Eine IR nach PKP ist eine nicht seltene Komplikation, die signifikant mit der TPL-Größe und -Zentrierung zusammenhängt. Ein im Verhältnis zur Empfänger-HH groß gewähltes TPL sowie die Nähe des TPL-Randes zum vaskularisierten Limbus oben und unten korrelieren signifikant mit dem Auftreten einer IR. Es handelt sich dabei um bedeutende Risikofaktoren für das TPL-Überleben, welche von mikrochirurgischer Seite aus beeinflussbar sind und sich zukünftig möglicherweise weiter optimieren lassen.
A review on advanced numerical methods for free-surface hydrodynamics
Authors: Casulli Vincenzo , Zanolli Paola
Published: June 2022

Environmental hydrodynamics is typically characterized by free-surface hydrostatic flows. Within such a framework a set of simplified models are derived from the Reynolds averaged Navier–Stokes equations under various simplifying assumptions. Numerically, a simple method for the 1D open channel flow is derived first. This method is then extended to the $$2D_{xz}$$

2

D

xz

laterally averaged model and to the $$2D_{xy}$$

2

D

xy

vertically averaged model. Next, a semi-implicit method for the 3D model is described and discussed.
Neural activities during the Processing of unattended and unseen emotional faces: a voxel-wise Meta-analysis
Authors: Qiu Zeguo , Lei Xue , Becker Stefanie I. , Pegna Alan J.
Published: June 2022

Voxel-wise meta-analyses of task-evoked regional activity were conducted for healthy individuals during the unconscious processing of emotional and neutral faces with an aim to examine whether and how different experimental paradigms influenced brain activation patterns. Studies were categorized into sensory and attentional unawareness paradigms. Thirty-four fMRI studies including 883 healthy participants were identified. Across experimental paradigms, unaware emotional faces elicited stronger activation of the limbic system, striatum, inferior frontal gyrus, insula and the temporal lobe, compared to unaware neutral faces. Crucially, in attentional unawareness paradigms, unattended emotional faces elicited a right-lateralized increased activation (i.e., right amygdala, right temporal pole), suggesting a right hemisphere dominance for processing emotional faces during inattention. By contrast, in sensory unawareness paradigms, unseen emotional faces elicited increased activation of the left striatum, the left amygdala and the right middle temporal gyrus. Additionally, across paradigms, unconsciously processed positive emotions were found associated with more activation in temporal and parietal cortices whereas unconsciously processed negative emotions elicited stronger activation in subcortical regions, compared to neutral faces.
Bayes factors for peri-null hypotheses
Authors: Ly Alexander , Wagenmakers Eric-Jan
Published: June 2022

A perennial objection against Bayes factor point-null hypothesis tests is that the point-null hypothesis is known to be false from the outset. We examine the consequences of approximating the sharp point-null hypothesis by a hazy ‘peri-null’ hypothesis instantiated as a narrow prior distribution centered on the point of interest. The peri-null Bayes factor then equals the point-null Bayes factor multiplied by a correction term which is itself a Bayes factor. For moderate sample sizes, the correction term is relatively inconsequential; however, for large sample sizes, the correction term becomes influential and causes the peri-null Bayes factor to be inconsistent and approach a limit that depends on the ratio of prior ordinates evaluated at the maximum likelihood estimate. We characterize the asymptotic behavior of the peri-null Bayes factor and briefly discuss suggestions on how to construct peri-null Bayes factor hypothesis tests that are also consistent.
Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: a consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology
Authors: Trigo José , García-Cosío Mónica , García-Castaño Almudena , Gomà Montserrat , Mesia-Nin Ricard , Ruiz-Bravo Elena , Soria-Rivas Ainara , Castillo Paola , Braña-García Irene , Alberola-Ferranti Margarita
Published: June 2022

The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.
A comparison between different methods to fill gaps in early precipitation series
Authors: Camuffo Dario , Becherini Francesca , della Valle Antonio , Zanini Valeria
Published: June 2022

The aim of this work is to analyse and compare different methodologies to fill gaps in early precipitation series, and to evaluate which time resolution is reachable, i.e. monthly or daily one. The following methods are applied and tested to fill the 1764–1767 gap in the precipitation series of Padua: (1) using a relationship between monthly amounts and frequencies; (2) transforming a daily log with visual observations into numerical values through analysis, classification, and calibration; (3) substituting the missing values with an instrumental record from a nearby, contemporary station in the same climatic area. To apply the second method, the descriptions reported in the Morgagni Logs are grouped in 37 classes and transformed into numerical values, using for calibration the observed amounts in the Poleni record over the 24-year common period. As a third method, the series of Temanza and Pollaroli in Venice is used to fill the gap, and the application of a factor scale based on the ratio Padua/Venice tempted. The results of these three methods are discussed and commented.
Empathy for the health professional in online asynchronous graduate education: an initial design thinking approach to program improvement
Authors: Bayer Ilana , Elma Asiana , Nasser Muhammadhasan , Grierson Lawrence
Published: June 2022

Introduction

Health professionals engage in continuous professional development through higher education. As traditional university learning environments pose a challenge to working health professionals, distance education allows these learners to engage in higher education in alignment with their learning preferences and needs. Literature on health professional learners’ experiences in online learning environments report findings at the course level and/or focus on a singular aspect of the online learning experience.

Objectives

In this initial study, we aim to understand the health professional learner’s perspective in a distance graduate education program and make normative recommendations to improve the health professional learner experience in an online environment.

Methods

Within the context of theEmpathyarm of Deitte and Omary’s (Deitte and Omary in Acad Radiol 26:1417–1420, 2019) Design Thinking methodology, we conducted a two-part sequential explanatory qualitative study. Part 1 involved focus groups with stakeholders (n = 14) of the Health Science Education (HSED) Graduate Program at McMaster University (Hamilton, Canada). Part 2 entailed semi-structured interviews with learners (n = 11) in the HSED Program. An unconstrained approach to directed content analysis was used to analyze the data and construct themes.

Results

An overarching theme of ‘the learner experience is an autonomous-supportive online learning environment’ was constructed, with two sub-themes: learner autonomy and building community.

Conclusion

Learners valued an autonomous-supportive online learning environment wherein they could tailor their educational experiences while also fostering a sense of community in the online environment. Future research should consider how a balance between maintaining autonomy in pacing learning and building community can be achieved to enhance the health professional learner experience in an online environment.
Gender Distribution Associated With the Journal Wilderness & Environmental Medicine
Authors: Keyes Linda E. , Schlein Sarah M. , Brown Alainna B. , Polukoff Natalya E. , Byrne Alicia , Pollock Neal W.
Published: June 2022

Introduction

Publication and peer review are fundamental to career advancement in science and academic medicine. Studies demonstrate that women are underrepresented in science publishing. We evaluated the gender distribution of contributors to Wilderness & Environmental Medicine ( WEM) from 2010 through 2019.

Methods

We extracted author data from ScienceDirect, reviewer data from the WEM Editorial Manager database, and editorial board data from journal records. Gender (female and male) was classified using automated probability-based assessment with Genderize.io software.

Results

A total of 2297 unique authors were published over the 10-y span, generating 3613 authorships, of which gender was classified for 96% (n=3480). Women represented 26% (n=572) of all authors, which breaks down to 22% of all, 19% of first, 28% of second, and 18% of last authorships. Women represented 20% of peer reviewers (508/2517), 20% of reviewers-in-training (19/72), and 16% of editorial board members (7/45). The proportion of female authors, first authors, and reviewers increased over time. Women received fewer invitations per reviewer than men (mean 2.1 [95% CI 2.0-2.3] vs 2.4 [95% CI 2.3-2.5]; P=0.004), accepted reviews at similar rates (mean 73 vs 71%; P=0.214), and returned reviews 1.4 d later (mean 10.4 [CI 9.5-11.3] vs 9.0 d [95% CI 8.5-9.6]; P=0.005).

Conclusions

While female representation increased over the study period, women comprise a minority of WEM authors, peer reviewers, and editorial board members. Gender equity could be improved by identifying and eliminating barriers to participation, addressing any potential bias in review processes, implementing strategies to increase female-authored submissions, and increasing mentorship and training.
Gender Equity in Membership, Leadership, and Award Recognition in the Wilderness Medical Society
Authors: Schlein Sarah M. , Pollock Neal W. , Polukoff Natalya E. , Brown Alainna B. , Byrne Alicia , Keyes Linda E.
Published: June 2022

Introduction

Despite near gender parity for women entering medical careers, women remain underrepresented in medical societies. This study evaluated the gender distribution associated with Wilderness Medical Society (WMS) activities.

Methods

A retrospective review was performed on the gender breakdown of the following WMS members: a single-day 2020 snapshot, conference attendees 2012 through 2020, conference presenters from winter 2017 through winter 2021, and leadership and awards data from 1984 through 2021. Genderize.io was used to generate probability-based gender categorizations (male/female) based on first names or pronoun associations.

Results

Gender was assigned in 91% (4043/4461) of 2020 WMS members, 92% (6179/6720) of 2012-2020 conference attendees, and 100% of remaining categories. Women represented 28% (1143/4043) of members, 27% (1679/6179) of conference attendees, 31% (143/465) of all conference presenters, 20% (62/303) of mainstage presenters, 23% (17/75) of all board members, 38% (14/37) of committee chairs, and 10% (2/20) of board presidents. Women received 18% (42/228) of recognition awards and 31% (15/48) of research grants issued.

Conclusions

Although women comprise a minority of WMS participants, gender distribution was similar across categories for membership, conference presenters, total board positions, and research grant awards. Relative underrepresentation was seen in the highest leadership levels, in recognition awards, and in mainstage presenters. Ongoing auditing may help to identify and address sources of bias and/or barriers to participation. Although it is only one of many components of equity, identifying successes and future opportunities for gender balance can strengthen the base of the WMS, promote growth, and ensure a strong leadership pipeline.
The Cambridge Centenary Ulysses: The 1922 Text with Essays and Notes
Authors: Joyce James , Flynn Catherine
Published: June 2022

James Joyce's Ulysses is considered one of the greatest novels of the twentieth century. This new edition - published to celebrate the book's first publication - helps readers to understand the pleasures of this monumental work and to grapple with its challenges. Copiously equipped with maps, photographs, and explanatory footnotes, it provides a vivid and illuminating context for the experiences of Leopold Bloom, Stephen Dedalus, and Molly Bloom, as well as Joyce's many other Dublin characters, on June 16, 1904. Featuring a facsimile of the historic 1922 Shakespeare and Company text, this version also includes Joyce's own errata as well as references to amendments made in later editions. Each of the eighteen chapters of Ulysses is introduced by a leading Joyce scholar. These richly informative pieces discuss the novel's plot and allusions, while also explaining crucial questions that have puzzled and tantalized readers over the last hundred years.
Leo Strauss and Islamic Political Thought
Authors: Namazi Rasoul
Published: June 2022

In this book, Rasoul Namazi offers the first in-depth study of Leo Strauss' writings on Islamic political thought, a topic that interested Strauss over the course of his career. Namazi's volume focuses on several important studies by Strauss on Islamic thought. He critically analyzes Strauss's notes on Averroes' commentary on Plato's Republic and also proposes an interpretation of Strauss' theologico-political notes on the Arabian Nights. Namazi also interprets Strauss' essay on Alfarabi's enigmatic treatise, The Philosophy of Plato and provides a detailed commentary on his complex essay devoted to Alfarabi's summary of Plato's Laws. Based on previously unpublished material from Strauss' papers, Namazi's volume provides new insights into Strauss' reflections on religion, philosophy, and politics, and their relationship to wisdom, persecution, divine law, and unbelief in the works of key Muslim thinkers. His work presents Strauss as one of the most innovative historians and scholars of Islamic thought of all time.
Seneca's Characters
Authors: Bexley Erica M.
Published: June 2022

Seneca's Characters addresses one of the most enduring and least theorised elements of literature: fictional character and its relationship to actual, human selfhood. Where does the boundary between character and person lie? While the characters we encounter in texts are obviously not 'real' people, they still possess person-like qualities that stimulate our attention and engagement. How is this relationship formulated in contexts of theatrical performance, where characters are set in motion by actual people, actual bodies and voices? This book addresses such questions by focusing on issues of coherence, imitation, appearance and autonomous action. It argues for the plays' sophisticated treatment of character, their acknowledgement of its purely fictional ontology alongside deep – and often dark – appreciation of its quasi-human qualities. Seneca's Characters offers a fresh perspective on the playwright's powerful tragic aesthetics that will stimulate scholars and students alike.
Rise of clathrodictyid stromatoporoids during the Great Ordovician Biodiversification Event: insights from the Upper Ordovician Xiazhen Formation of South China
Authors: Jeon Juwan , Liang Kun , Kershaw Stephen , Park Jino , Lee Mirinae , Zhang Yuandong
Published: June 2022

Clathrodictyids are the most abundant stromatoporoids in the Upper Ordovician Xiazhen Formation (middle to upper Katian) of South China. A total of nine species belonging to four clathrodictyid genera are identified in the formation, includingClathrodictyon idenseWebby and Banks, 1976,Clathrodictyoncf.Cl. microundulatumNestor, 1964,Clathrodictyoncf.Cl.mammillatum(Schmidt, 1858),Clathrodictyon megalamellatumJeon n. sp.,Clathrodictyon plicatumWebby and Banks, 1976,Ecclimadictyon nestoriWebby, 1969,Ecclimadictyon undatumWebby and Banks, 1976,Camptodictyon amzassensis(Khalfina, 1960), andLabyrinthodictyon cascum(Webby and Morris, 1976). The clathrodictyid fauna in the Xiazhen Formation is very similar to those from both New South Wales and Tasmania, although the latter two Australian regions do not share any common clathrodictyid species during the Late Ordovician. The paleobiogeographic pattern indicates that the northward drift of South China resulted in a favorable environment for the migration of clathrodictyids from other peri-Gondwanan terranes to South China. In addition, these peri-Gondwanan clathrodictyid species hosted various endobionts, representing a variety of paleoecological interactions. The high abundance and species-level diversity of clathrodictyid species presumably increased the substrate availability of suitable host taxa, judging from the diverse intergrowth associations between clathrodictyids and other benthic organisms. These paleoecological interactions between stromatoporoid and other organisms are known from the Late Ordovician and became more abundant and widespread in the Siluro–Devonian. Overall, the Late Ordovician clathrodictyid assemblage in South China demonstrates one of the highest species-level diversities among all peri-Gondwanan terranes and represents a precursor of the complex, clathrodictyid-dominated communities of later metazoan reefs during the Great Ordovician Biodiversification Event.

UUID:http://zoobank.org/6063c47d-cb77-4a03-98cf-b2354656dea6
Metazoan parasite communities of the Pacific red snapper,Lutjanus peru(Perciformes: Lutjanidae): interannual variations in parasite communities
Authors: Villalba-Vasquez P.J. , Violante-González J. , Pulido-Flores G. , Monks S. , Rojas-Herrera A.A. , Flores-Rodríguez P. , Cayetano C.V. , Rosas-Acevedo J.L , Santos-Bustos N.G.
Published: June 2022

Metazoan parasite communities can experience temporal structural changes related to seasonal and/or local variations in several biotic and abiotic environmental factors. However, few studies have addressed this issue in tropical regions, where changes in water temperature are less extreme than in temperate regions, so the factors or processes that can generate variations in these parasite communities are as yet unclear. We quantified and analysed the parasite communities of 421Lutjanus peru(Nichols & Murphy, 1922) collected from Acapulco Bay in Guerrero, Mexico, over a four-year period (August 2018 to April 2021), to identify any interannual variation due to local biotic and abiotic factors influenced by natural oceanographic phenomena, such as El Niño–Southern Oscillation, or La Niña. Twenty-five metazoan parasite taxa were recovered and identified: seven Digenea species; two Monogenea; one Cestoda; one Acanthocephala; four Nematoda; and ten of Crustacea (seven Copepoda and three Isopoda). The digeneans and copepods were the best represented parasite groups. The parasite communities were characterized by a high numerical dominance of helminth larvae. Species richness at the component community level (13 to 19 species) was similar to reported richness in otherLutjanusspp. The parasite communities ofL. peruhad a high variability in species composition, but low aggregate variability (e.g. species diversity), suggesting that structure of these communities may be quite stable over time. A clear interannual variation pattern was not observed, suggesting that parasite species of this host may respond differently to variations in environmental factors. Interannual variations were possibly caused by a combination of biotic (i.e. host feeding behaviour and body size) and local abiotic factors (influenced by climatic anomalies) which generated notable changes in the infection levels of several component species.
New records of the Endangered southern river otter Lontra provocax, with notes on its diet, in threatened wetlands of southern Chile
Authors: Fuentes Norka , Arriagada Aldo
Published: June 2022

The wetlands inhabited by the southern river otter Lontra provocax in Chile are subject to anthropogenic disturbances. As a result of the modification and destruction of its habitat, caused by loss of riparian vegetation, and other threats, the species is categorized as Endangered on the IUCN Red List. We monitored the river otter and its diet during September 2020–January 2021 in a swamp forest fragment in southern Chile. We obtained evidence of river otter presence from the upper part of the wetland to the confluence with the Bueno River, suggesting inter-population connectivity of the species in an extensive hydrographic basin. Faeces and food remains showed a predominance of native macrocrustaceans, with introduced fish present at lower levels. The detection of the southern river otter in a fragment of threatened swamp forest suggests a low abundance in environmentally degraded freshwater environments. The identification of subpopulations such as the one reported here provides valuable data to support the conservation of the species in threatened wetlands.
Prevalence of the dissociative subtype of post-traumatic stress disorder: a systematic review and meta-analysis
Authors: White William F. , Burgess Aaron , Dalgleish Tim , Halligan Sarah , Hiller Rachel , Oxley Anna , Smith Patrick , Meiser-Stedman Richard
Published: June 2022

The dissociative subtype of post-traumatic stress disorder (PTSD-DS) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and is characterised by symptoms of either depersonalisation or derealisation, in addition to a diagnosis of post-traumatic stress disorder (PTSD). This systematic review and meta-analysis sought to estimate the point prevalence of current PTSD-DS, and the extent to which method of assessment, demographic and trauma variables moderate this estimate, across different methods of prevalence estimation. Studies included were identified by searching MEDLINE (EBSCO), PsycInfo, CINAHL, Academic Search Complete and PTSDpubs, yielding 49 studies that met the inclusion criteria (N= 8214 participants). A random-effects meta-analysis estimated the prevalence of PTSD-DS as 38.1% (95% CI 31.5–45.0%) across all samples, 45.5% (95% CI 37.7–53.4%) across all diagnosis-based and clinical cut-off samples, 22.8% (95% CI 14.8–32.0%) across all latent class analysis (LCA) and latent profile analysis (LPA) samples and 48.1% (95% CI 35.0–61.3%) across samples which strictly used the DSM-5 PTSD criteria; all as a proportion of those already with a diagnosis of PTSD. All results were characterised by high levels of heterogeneity, limiting generalisability. Moderator analyses mostly failed to identify sources of heterogeneity. PTSD-DS was more prevalent in children compared to adults, and in diagnosis-based and clinical cut-off samples compared to LCA and LPA samples. Risk of bias was not significantly related to prevalence estimates. The implications of these results are discussed further.
Exploring grower strategies and needs for enhancing organic disease management of tomato late blight
Authors: Wu K. Tina , Gevens Amanda J. , Silva Erin M.
Published: June 2022

Late blight, caused by the oomycetePhytophthora infestans, poses a significant challenge to organic tomato and potato production systems across the globe. To enhance education and outreach programming pertaining to tomato organic late blight management in Wisconsin, we sought to identify grower strategies and needs through an online survey conducted during spring 2018. Our findings demonstrated that organic growers emphasized crop diversity, crop rotation and soil health in their late blight management decisions. Grower concerns about biopesticides were identified and suggest that the use of input-based products within integrated management programs could be enhanced by further research on effectiveness and modes of actions. Additionally, stronger emphasis on oomycete pathogen biology and the significance of late blight as a community disease were identified as important areas of emphasis in the development of organic disease management education programming and resources that promote more effective cultural and chemical disease management strategies that adhere to the regulation and principles underlying the USDA National Organic Program. The integration of a live polling questionnaire conducted in winter 2019 allowed us to corroborate findings from the online survey and underscored the importance of two-way learning to enhance outreach efforts between Extension and organic growers in Wisconsin and the surrounding upper Midwestern states.
Analyzing Recharge Dynamics and Storage in a Thick, Karstic Vadose Zone
Authors: Spellman Patricia , Breithaupt Charles , Bremner Paul , Gulley Jason , Jenson John , Lander Mark
Published: June 2022

Karst vadose zone heterogeneity creates complex transmission and storage dynamics that affect the timing and magnitude of aquifer recharge. Young, high‐matrix permeability eogenetic karst aquifers may have significantly higher matrix storage than older, lower matrix permeability counterparts. In vulnerable and water‐limited karst regions, the timescales of storage may be important for seasonal and sub‐seasonal water resource management. We create a framework to quantify storage dynamics in karst aquifers using high‐resolution precipitation and groundwater levels from the Northern Guam Lens Aquifer in the US territory of Guam. We estimate recharge using the Water Table Fluctuation method, and then develop transfer functions between precipitation and recharge to quantify storage and release of water from the vadose zone. The transfer functions are partitioned into different flow pathways including conduit, conduit/matrix, and slowly draining matrix. Probability distributions are fit to each pathway to determine the average travel times of infiltrated waters. The results show that aquifer recharge through secondary porosity features typically occurs within a few hours of a rainfall event, but this rapid recharge accounts for only 12%–28% of total recharge. The majority of aquifer recharge (>70%) occurs within a month of a contributing storm event. An additional 10% of recharge, on average, took longer than a month to reach the water table. The framework established can help improve the hydrological modeling and freshwater management for karst aquifers.
Extreme Nitrate Deficits in the Western Arctic Ocean: Origin, Decadal Changes, and Implications for Denitrification on a Polar Marginal Shelf
Authors: Zhuang Yanpei , Jin Haiyan , Cai Wei‐Jun , Li Hongliang , Qi Di , Chen Jianfang
Published: June 2022

The western Arctic Ocean is known to be nitrate deficient relative to phosphate but the decadal trend and the processes contributing to the deficit are not clear. To investigate changes in this extreme nitrate deficit of over 10 μmol/kg and its causal mechanisms, nutrient concentrations were examined along a transect spanning the Bering Basin, the Bering–Chukchi Shelf, and the western Arctic Ocean Basin over the last two decades (1994–2018). The results show that the extreme nitrate deficit has extended to greater depths and further north during the past two decades, which coincided with the expansion of Pacific water in the western Arctic Ocean. Subsurface nutrient stocks in the basin areas appear to have increased, but are accompanied by a larger nitrate deficit, which may be due to stronger shelf denitrification. This nitrate loss (∆N) caused by shelf denitrification was estimated to be 7.3 ± 0.1 μmol/kg during the interval 2012–2018, which was ∼10% higher than that in 1994. This suggests an intensification of denitrification on this marginal shelf under climatic and environmental change in the Arctic Ocean.
Predictive Capabilities of Corotating Interaction Regions Using STEREO and Wind In‐Situ Observations
Authors: Chi Yutian , Shen Chenglong , Scott Christopher , Xu Mengjiao , Owens Mathew , Wang Yuming , Lockwood Mike
Published: June 2022

Solar wind stream interaction regions (SIRs) and corotating interaction regions (CIRs) can cause geomagnetic storms and change energetic particle environment, ionospheric composition on Earth. Therefore advanced warning of SIRs/CIRs is vital for mitigating the effect of space weather on critical infrastructures in modern society. Recently, several solar missions, for example, Vigil mission (Luntama et al., 2020) and Solar Ring mission (Wang et al., 2020), that can be served as a space weather monitor, have been proposed. To evaluate the capabilities of these future missions of predicting SIRs/CIRs, the Solar Terrestrial Relations Observatory (STEREO‐B) spacecraft is used to investigate the correlation between SIRs/CIRs detected by STEREO‐B and Wind spacecraft. The correlation coefficients of solar wind velocity in SIRs/CIRs are significantly higher than that of magnetic field intensity or plasma density. It indicates that the velocity structure of solar wind is more persistent than magnetic field and ion density. By assuming the SIR/CIR structures are stable and ideal corotation, 58.9% of SIRs/CIRs in the STEREO‐B CIR catalog can be used to predict CIR arrival time in near‐Earth space. With increasing longitudinal and latitudinal separations between STEREO‐B and Wind, the percentage of accurately predicted CIRs decreases gradually from 100% to 20%. If the separation angle between STEREO‐B and Wind is within 30° in longitude and approximately ±5° in latitude, more than 93.2% of SIRs/CIRs can be accurately predicted several days in advance. This demonstrates that a spacecraft situated 30° trailing Earth in its orbit, can optimize our space weather‐predicting capabilities for the Earth and lessen the risk of missing or “false alarms” CIRs.
Dual-color terahertz spatial light modulator for single-pixel imaging
Authors: Li Weili , Hu Xuemei , Wu Jingbo , Fan Kebin , Chen Benwen , Zhang Caihong , Hu Wei , Cao Xun , Jin Biaobing , Lu Yanqing , Chen Jian , Wu Peiheng
Published: June 2022

Spatial light modulators (SLM), capable of dynamically and spatially manipulating electromagnetic waves, have reshaped modern life in projection display and remote sensing. The progress of SLM will expedite next-generation communication and biomedical imaging in the terahertz (THz) range. However, most current THz SLMs are adapted from optical alternatives that still need improvement in terms of uniformity, speed, and bandwidth. Here, we designed, fabricated, and characterized an 8 × 8 THz SLM based on tunable liquid crystal metamaterial absorbers for THz single-pixel compressive imaging. We demonstrated dual-color compressive sensing (CS) imaging for dispersive objects utilizing the large frequency shift controlled by an external electric field. We developed auto-calibrated compressive sensing (ACS) algorithm to mitigate the impact of the spatially nonuniform THz incident beam and pixel modulation, which significantly improves the fidelity of reconstructed images. Furthermore, the complementary modulation at two absorption frequencies enables Hadamard masks with negative element values to be realized by frequency-switching, thereby halving the imaging time. The demonstrated imaging system paves a new route for THz single-pixel multispectral imaging with high reliability and low cost.
Global and seasonal variation of marine phosphonate metabolism
Authors: Lockwood Scott , Greening Chris , Baltar Federico , Morales Sergio E
Published: June 2022

Marine microbial communities rely on dissolved organic phosphorus (DOP) remineralisation to meet phosphorus (P) requirements. We extensively surveyed the genomic and metagenomic distribution of genes directing phosphonate biosynthesis, substrate-specific catabolism of 2-aminoethylphosphonate (2-AEP, the most abundant phosphonate in the marine environment), and broad-specificity catabolism of phosphonates by the C-P lyase (including methylphosphonate, a major source of methane). We developed comprehensive enzyme databases by curating publicly available sequences and then screened metagenomes from TARA Oceans and Munida Microbial Observatory Time Series (MOTS) to assess spatial and seasonal variation in phosphonate metabolism pathways. Phosphonate cycling genes were encoded in diverse gene clusters by 35 marine bacterial and archaeal classes. More than 65% of marine phosphonate cycling genes mapped to Proteobacteria with production demonstrating wider taxonomic diversity than catabolism. Hydrolysis of 2-AEP was the dominant phosphonate catabolism strategy, enabling microbes to assimilate carbon and nitrogen alongside P. Genes for broad-specificity catabolism by the C-P lyase were far less widespread, though enriched in the extremely P-deplete environment of the Mediterranean Sea. Phosphonate cycling genes were abundant in marine metagenomes, particularly from the mesopelagic zone and winter sampling dates. Disparity between prevalence of substrate-specific and broad-specificity catabolism may be due to higher resource expenditure from the cell to build and retain the C-P lyase. This study is the most comprehensive metagenomic survey of marine microbial phosphonate cycling to date and provides curated databases for 14 genes involved in phosphonate cycling.
Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse
Authors: Pujol-Gualdo Natàlia , Läll Kristi , Lepamets Maarja ,   Estonian Biobank Research Team, Metspalu Andres , Nelis Mari , Milani Lili , Esko Tõnu , Hudjashov Georgi , Rossi Henna-Riikka , Arffman Riikka K. , Piltonen Terhi T. , Mägi Reedik , Laisk Triin
Published: June 2022

Pelvic organ prolapse is a common gynecological condition with limited understanding of its genetic background. In this work, we perform a genome-wide association meta-analysis comprising 28,086 cases and 546,291 controls from European ancestry. We identify 19 novel genome-wide significant loci, highlighting connective tissue, urogenital and cardiometabolic as likely affected systems. Here, we prioritize many genes of potential interest and assess shared genetic and phenotypic links. Additionally, we present the first polygenic risk score, which shows similar predictive ability (Harrell C-statistic (C-stat) 0.583, standard deviation (sd) = 0.007) as five established clinical risk factors combined (number of children, body mass index, ever smoked, constipation and asthma) (C-stat = 0.588, sd = 0.007) and demonstrates a substantial incremental value in combination with these (C-stat = 0.630, sd = 0.007). These findings improve our understanding of genetic factors underlying pelvic organ prolapse and provide a solid start evaluating polygenic risk scores as a potential tool to enhance individual risk prediction.
Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation
Authors: Theilgaard-Mönch Kim , Pundhir Sachin , Reckzeh Kristian , Su Jinyu , Tapia Marta , Furtwängler Benjamin , Jendholm Johan , Jakobsen Janus Schou , Hasemann Marie Sigurd , Knudsen Kasper Jermiin , Cowland Jack Bernard , Fossum Anna , Schoof Erwin , Schuster Mikkel Bruhn , Porse Bo T.
Published: June 2022

Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of Cdk1/2/4 inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.
Impact of interannual and multidecadal trends on methane-climate feedbacks and sensitivity
Authors: Cheng Chin-Hsien , Redfern Simon A. T.
Published: June 2022

We estimate the causal contributions of spatiotemporal changes in temperature (T) and precipitation (Pr) to changes in Earth’s atmospheric methane concentration (CCH4) and its isotope ratio δ13CH4 over the last four decades. We identify oscillations between positive and negative feedbacks, showing that both contribute to increasing CCH4. Interannually, increased emissions via positive feedbacks (e.g. wetland emissions and wildfires) with higher land surface air temperature (LSAT) are often followed by increasing CCH4 due to weakened methane sink via atmospheric •OH, via negative feedbacks with lowered sea surface temperatures (SST), especially in the tropics. Over decadal time scales, we find alternating rate-limiting factors for methane oxidation: when CCH4 is limiting, positive methane-climate feedback via direct oceanic emissions dominates; when •OH is limiting, negative feedback is favoured. Incorporating the interannually increasing CCH4 via negative feedbacks gives historical methane-climate feedback sensitivity ≈ 0.08 W m−2 °C−1, much higher than the IPCC AR6 estimate.
Coiled-coil heterodimer-based recruitment of an exonuclease to CRISPR/Cas for enhanced gene editing
Authors: Lainšček Duško , Forstnerič Vida , Mikolič Veronika , Malenšek Špela , Pečan Peter , Benčina Mojca , Sever Matjaž , Podgornik Helena , Jerala Roman
Published: June 2022

The CRISPR/Cas system has emerged as a powerful and versatile genome engineering tool, revolutionizing biological and biomedical sciences, where an improvement of efficiency could have a strong impact. Here we present a strategy to enhance gene editing based on the concerted action of Cas9 and an exonuclease. Non-covalent recruitment of exonuclease to Cas9/gRNA complex via genetically encoded coiled-coil based domains, termed CCExo, recruited the exonuclease to the cleavage site and robustly increased gene knock-out due to progressive DNA strand recession at the cleavage site, causing decreased re-ligation of the nonedited DNA. CCExo exhibited increased deletion size and enhanced gene inactivation efficiency in the context of several DNA targets, gRNA selection, Cas variants, tested cell lines and type of delivery. Targeting a sequence-specific oncogenic chromosomal translocation using CCExo in cells of chronic myelogenous leukemia patients and in an animal model led to the reduction or elimination of cancer, establishing it as a highly specific tool for treating CML and potentially other appropriate diseases with genetic etiology.
Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
Authors: de Jonge Patrick A. , Wortelboer Koen , Scheithauer Torsten P. M. , van den Born Bert-Jan H. , Zwinderman Aeilko H. , Nobrega Franklin L. , Dutilh Bas E. , Nieuwdorp Max , Herrema Hilde
Published: June 2022

There is significant interest in altering the course of cardiometabolic disease development via gut microbiomes. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we show gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants by combined sequencing of bulk whole genome and virus like particle communities. MetS gut viromes exhibit decreased richness and diversity. They are enriched in phages infecting Streptococcaceae and Bacteroidaceae and depleted in those infecting Bifidobacteriaceae. Differential abundance analysis identifies eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of participants. The identification of the temperate Ca. Heliusviridae provides a starting point to studies of phage effects on gut bacteria and the role that this plays in MetS.
Online information analysis on pancreatic cancer in Korea using structural topic model
Authors: Jo Wonkwang , Kim Yeol , Seo Minji , Lee Nayoung , Park Junli
Published: June 2022

Inappropriate information on a deadly and rare disease can make people vulnerable to problematic decisions, leading to irreversible bad outcomes. This study explored online information exchanges on pancreatic cancer. We collected 35,596 questions and 83,888 answers related to pancreatic cancer from January 1, 2003 to May 31, 2020, from Naver, the most popular Korean web portal. We also collected 8495 news articles related to pancreatic cancer during the same period. The study methods employed were structural topic modeling, keyword frequency analysis, and qualitative coding of medical professionals. The number of questions and news articles increased over time. In Naver’s questions, topics on symptoms and diagnostic tests regarding pancreatic cancer increased in proportion. The news topics on new technologies related to pancreatic cancer from various companies increased as well. The use of words related to back pain—which is not an important early symptom in pancreatic cancer—and biomarker tests using blood increased over time in Naver’s questions. Based on 100 question samples related to symptoms and diagnostic tests and an analysis of the threaded answers’ appropriateness, there was considerable misinformation and commercialized information in both categories.