bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexity in core argument marking and population size
Authors: Ki Kaius SinnemÄ
Published: November 2023

A widely accepted presupposition among linguists is that language structure has nothing to do with its geographical or sociocultural setting (e.g. Kaye 1989: 48).1 However, this claim has not been supported by empirical evidence. On the contrary, there seems to be a growing body of evidence indicating a relationship between, for example, structural complexity of language and its geographical or sociocultural setting. Nichols (1992), for one, has argued that morphological complexity varies geographically. Perkins (1992) has argued that grammatical complexity of deictic categories correlates negatively with cultural complexity. Sociolinguistic aspects of the speech community have also been suggested as causing complexity variation (Nettle 1999; Kusters 2003; Trudgill 1996b, 2004a, b). This chapter develops the ideas of Johanna Nichols (in Chapter 8 above and other recent writing) by studying whether a specific morphosyntactic area, core argument marking, shows complexity varying with speech community size.
Introduction: A Guided Tour of Metametaphysics
Authors: Manley David
Published: November 2023

Metaphysics is concerned with the foundations of reality. It asks questions about the nature of the world, such as: Aside from concrete objects, are there also abstract objects like numbers and properties? Does every event have a cause? What is the nature of possibility and necessity? When do several things make up a single bigger thing? Do the past and future exist? And so on.
Composition, Colocation, and Metaontology1
Authors: Bennett Karen
Published: November 2023

Some of the things we metaphysicians think about strike others — and, in some moods, ourselves— as a trifile silly. Are there numbers? If I say that my shirt is blue, am I committed to the existence of a universal, namely blueness? If you have two objects, are you guaranteed to also have a third object entirely composed of the first two? And so on and so forth.
Ethical issues around evidence-based patient choice and shared decision-making
Authors: Holm Søren , Davies Myfanwy
Published: November 2023

Evidence-based patient choice brings together the movements to promote evidence-based medicine and patient-centred medicine. While proponents of evidence-based medicine contend that interventions need to be based on evidence of effectiveness, patient-centred medicine is concerned with emphasizing the central role of patients in decisions about their care (Parker, 2001). Evidence-based patient choice may help to address the power imbalance inherent in many medical consultations and may serve to promote more effective patient care (Hope, 1997).
Conceptual variation and iteration in shared decision-making: The need for clarity
Authors: Clayman Marla L , Gregory Makoul
Published: November 2023

The medical encounter is filled with potential decision points. How best to make decisions about tests, medications, procedures, referrals, or behaviours and whom to involve in these decisions are questions that have received increasing attention over the last several decades. Shared decision-making (SDM) is frequently advocated in teaching and research about the provider – patient interaction. Interest in SDM, in particular, has grown over the last several years (Makoul and Clayman, 2006), and recent articles have highlighted the conceptual variation that has become evident as educators and researchers grapple with the topic (Makoul and Clayman, 2006; Moumjid et al., 2007b).
What’s happening around the world?
Authors: Coulter Angela
Published: November 2023

In democracies, those responsible for health care must ensure that they retain public support for the way health care is organized and delivered. For many governments and health authorities, this means searching for ways to ensure that health services are sufficiently responsive to patients’ needs and preferences. Often there is a perceived need to respond to ‘consumer pressure’ and make health care more like other consumer experiences. But the need for ‘patient engagement’, where the patient is encouraged to take an active role as a key player in choosing appropriate treatments for episodes of ill-health and managing chronic disease, has often been ignored in the past. As other chapters in this volume show, substantial evidence now exists that this not only improves patients’ experience and satisfaction, but can also be clinically and economically effective. As a result, the issue is creeping up the health policy agenda. This chapter looks at approaches adopted in a number of countries to promote and support shared decision-making.
Decision aids in diabetes
Authors: Lenz Matthias , Mühlhauser Ingrid
Published: November 2023

Diabetes is usually not considered a typical disease for shared decision-making (SDM) even by protagonists of SDM (O’Connor et al., 2003). The belief is still widely held that control of blood glucose and other cardiovascular risk factors is beyond any doubt beneficial, and therefore, supporting patients in adherence increasing behaviour rather than SDM has been standard procedure in diabetes care (IDF, 2005; Nathan et al., 2006; ADA, 2008).
Population-Level Bioethics: Mapping a New Agenda
Authors: Wikler Daniel , Brock Dan W
Published: November 2023

Bioethics was long focused on ethical issues arising in the relationships and interactions of individual patients and their physicians, as well as individual investigators and their research subjects. Ethical issues arising at the population level are no less acute, but are much less visible to lay people, to health professionals, and to many bioethicists. The issues come into focus only when one adopts a bird’s-eye view that looks at populations. From this perspective, new issues become visible, and their close kinship to long-debated ethical questions in other fields such as population policy, environmental health, and political philosophy becomes apparent. Even as investigation, debate, and education continue in the clinical settings in which bioethics has been most at home, an extensive, new, and largely unexplored region of bioethics is coming into view. The bird’s-eye perspective of this population-level bioethics includes consideration not only of health care but of other social determinants of health, including socio-economic standing, environmental and working conditions, and social exclusion. Its subject therefore is health rather than health care alone, insofar as health can be affected by conditions and interventions in any of these domains.
Global Norms, Informed Consensus, and Hypocrisy in Bioethics
Authors: Harris John
Published: November 2023

It has been said that morality is the science of the good. If it is, then surely ethics is the study of that science. Usually ‘ ‘moral and ethical ‘ ‘ are words that are linked almost as synonyms, and few would be able to articulate any supposed differences between them. I shall continue this somewhat lazy tradition and try to say something about moral and/or ethical decision- making. This chapter has two central themes. The first is the nature of ethical reasoning; the second will concern some of the main influences or pressures upon the way in which we do that reasoning in contemporary society.
Integer Programming Methods for Reserve Selection and Design
Authors: Haight Robert G , Snyder Stephanie A
Published: November 2023

How many nature reserves should there be? Where should they be located? Which places have highest priority for protection? Conservation biologists, economists, and operations researchers have been developing quantitative methods to address these questions since the 1980s. The first formulations (Kirkpatrick 1983; Margules et al. 1988; Chapters 3 and 19) focused on species protection and efficiency – select the minimum number of reserves from a list of candidate sites to represent all species – and were solved using iterative heuristics, which guarantee only an approximation of the optimal solution (Chapter 5). Researchers later formulated the problem as a 0–1 linear integer programming (IP) model and found mathematically proven optimal solutions using the branch and bound (B&B) method available in commercial optimization software (Saetersdal et al. 1993; Underhill 1994). The main advantage of formulating a reserve selection problem as an IP model is the availability of solution methods such as B&B that guarantee finding the optimal solution. Researchers quickly recognized this advantage and have formulated reserve selection problems with a remarkable array of objectives and constraints.
Accounting for Habitat Dynamics in Conservation Planning
Authors: Possingham Hugh P , Moilanen Atte , Wilson Kerrie A
Published: November 2023

The ‘conservation prioritization problem’ has traditionally been formulated as a static problem (Chapter 3). This involves determining the priority of different planning units under the assumption that most of the high-priority planning units will eventually be added to the reserve network, and the low priority planning units will not. Such an approach can be valid, especially in marine systems or in areas where a single entity has property rights over the entire region of interest, for example, the government. However a static approach does not accurately represent the conservation system if system attributes change before the conservation plan can be fully implemented, which is frequently the case for terrestrial conservation planning (McDonaldMadden et al. 2008).
Conservation Prioritization and Uncertainty in Planning Inputs
Authors: Regan Helen M , Ensbey Michelle J , Burgman Mark A
Published: November 2023

Uncertainty is pervasive in conservation decisions (Regan et al. 2002a; Harwood and Stokes 2003) and failing to account for it can lead to suboptimal decisions or actions that damage biodiversity (Rabinowitz 1995; Grand et al. 2007). Nevertheless, there is an imperative to make decisions for conservation planning and postponing decisions to wait for more data (hence greater certainty) can lead to unnecessary and avoidable biodiversity losses (Slooten et al. 2000). Decisions in the face of uncertainty should allow for opportunities to learn from mistakes and to update existing knowledge as new information becomes available. In this review, we outline the sources of uncertainty that typically arise in conservation planning exercises, and we identify appropriate treatments for the different kinds of uncertainty. We then assess spatial conservation planning software platforms against a set of criteria to evaluate which kinds of uncertainty are treated explicitly, and which are ignored. We identify potential areas for development and methods that may be usefully implemented in these platforms.
‘Things that Undermine Each Other’: Occasionalism, Freedom, and Attention in Malebranche
Authors: Greenberg Sean
Published: November 2023

It is natural to suppose that Malebranche’s commitments to occasionalism and human freedom undermine each other. According to Malebranche’s occasionalism, no finite being has the causal power to bring anything about or effect any change in the natural world, either in the physical or the mental realm.(Finite beings are merely occasional causes; God is the only real cause.) Since, according to occasionalism, agents have no real causal power, it would seem that they do not have the active power necessary to determine their own free choices.
Leibniz as Idealist
Authors: Rutherford Donald
Published: November 2023

Leibniz has long been held to be an idealist.Minimally, this involves the claim that, in his late writings at least, Leibniz’s fundamental ontology— his inventory of the ultimately real, independently existing things — is limited to mind-like, simple substances, or monads. This fixes one meaning of the term ‘idealism’, and considerable evidence confirms that in his late writings Leibniz is, in this sense, an idealist.
A Theory of Hedged Moral Principles
Authors: Väyrynen Pekka
Published: November 2023

Moral theories have explanatory aspirations. They purport not merely to tell us which things are right and wrong, good and bad, and just and unjust, but also to explain why those things have the moral features that they do. Many theorists think that explanations which help us understand or make sense of morality must in some way rely on general moral principles. Suppose, for instance, that Anna ought to help Adam who is very badly off. Views which are “generalist” in this sense hold that Anna ought to do whatever it is that she ought to do in some sense because of some moral principles with suitable content, such as that one ought to help the badly off.
Gods
Authors: Oppy Graham
Published: November 2023

There are many different views that have been held about the content of the idea or concept of God, and many different suggestions that have been made about how to define or analyse the name “God”. In this chapter, I defend the suggestion that to be God is just to be the one and only god, where to be a god is to be a supernatural being or force that has and exercises power over the natural world but that is not, in turn, under the power of any higher-ranking or more powerful category of beings or forces. While many will take this to be a rather radical suggestion, it seems to me that there are many good reasons for adopting this proposal, and that there are no telling reasons that speak against it.
A Non-Extensional Notion of Conversion in the Organon
Authors: Malink Marko
Published: November 2023

This paper is about a special notion of conversion found in Prior Analytics 2. 22, 68a16–21. I hope to show that the notion is worth studying for two reasons: firstly because it is interesting in itself, and secondly because it has implications for the semantics of a propositions (that is, assertoric universal affirmative propositions).

Let us say that A is a-predicated of B if and only if the a-proposition ‘A belongs to all B’ is true. The notion of conversion in question is: A converts with B if and only if A is a-predicated of everything of which B is a-predicated including B itself, while B is a-predicated of everything of which A is a-predicated except of A itself. We may call this asymmetric conversion.
Isolation and characterization of nuclei and nuclear subfractions
Authors: Rickwood David , Messent, Anthea , Patel Dipak
Published: November 2023

The nucleus is the centre of a wide range of diverse activities that. are essential for the survival of the cell. The development of methods for the isolation and purification of functional nuclei, nuclear subfractions, and individual components have been central to understanding how the nucleus functions in the cell. However, given the space limitations of a single chapter, it is only possible to focus on a selection of the methods used for isolating and characterizing the various components of the nucleus and analyzing their functions. The reader will be referred to other, relevant practical manuals for details of other types of technique as appropriate.
In vitro selection of nucleic acid ligands
Authors: Conrad Richard C , Bell Sabine , Ellington Andrew D
Published: November 2023

The molecular biology explosion of the last three decades has been capped by the finding that nucleic acids have extraordinary functionality. Once thought to be mere repositories or carriers of information, the discovery of structural complexity in tRNA and catalysis in group I self-splicing intrans and eubacte rial RNase P RNAs prompted the realization that nucleic acids may harbour biochemistries as complex as those of protein enzymes. The discovery that functional nucleic acids could be generated by natural selection led directly to the notion that researchers might themselves design or select nucleic acids with novel functions. For example, researchers have modified the functions of existing ribozymes, much as protein chemists engineered the physical and catalytic properties of known protein enzyme. In addition, researchers have selected binding or catalytic nucleic acid species de novo from pools of nucleic acid molecules that contained literally trillions of different sequences.
Proteases in peptide synthesis
Authors: Kasche Volker
Published: November 2023

The basis for the classification of proteases as enzymes is their biological function as hydrolases. As catalysts, the proteases must also catalyze the reverse reaction, i.e. the formation of a peptide bond (1,2). For some time this was treated as a curiosity rather than a property that could be used to gain more knowledge of the catalytic function of proteases, or for peptide synthesis in vitro. Recently, their potential use for the latter has led to a marked increase in studies on the synthetic function of proteases.
Generic techniques for fluorescence measurements of protein-ligand interactions; real-time kinetics and spatial imaging
Authors: Cladera Josep , O’Shea Paul
Published: November 2023

The non-covalent interactions of small molecules (i.e. the ‘ligand’) with a larger molecule (the ‘receptor’—usually a protein or nucleic acid) underlies much of the ‘process’ of cell biology and physiology as illustrated by the broad range of examples covered in this volume. Whilst there are techniques available that offer very accurate quantitative and unequivocal measurements of ligand-receptor interactions (see, e.g. ref. 1, and other chapters in the present volumes), many such techniques are highly specialized and/or dedicated to a particular biological phenomenon. A number of more simple and routine techniques have also evolved to measure or indicate this behaviour and have tended to be grouped within one or more of the following general areas: The ligand-receptor interaction leads to a biological response that is assayed; examples include signalling responses (e.g. intracellular Ca mobilization), i.e. the ligand-receptor association is inferred from the response. Strictly, this is then more of a dose-response reaction rather than a ligand-receptor binding reaction. With localized or non-linear signalling behaviour, however, the binding reactions may be difficult to disentangle from the response.
Protein-protein complexes formed by electron transfer proteins
Authors: Scott Mathews F , Grant Mauk A , Moore Geoffrey R
Published: November 2023

Transfer of an electron from one protein to another is one of the most common biochemical reactions (1). Not only are such reactions a primary feature of respiratory chains, such as the aerobic pathways terminating with the reduction of O2 to H2O by cytochrome c oxidase, but they are also critical to many other metabolic processes. Two examples of such processes are the conversion of non-functional methaemoglobin to deoxyhaemoglobin by cytochrome b5 and cytochrome b5 reductase (2), and the complex organic biotransformations catalysed by cytochrome P450 (3). The widespread occurrence of protein-protein electron transfer reactions and their apparent simplicity has provided an attractive subject for extensive theoretical and experimental studies. A major objective of many such studies concerns the structural definition of the electron transfer process and identification of those mechanistic factors that are rate-limiting.
Adenosine deaminases that act on RNA
Authors: Hough Ronald F , Bass Brenda L
Published: November 2023

The RNA editing enzymes now known as adenosine deaminases that act on RNA (ADARs) comprise a unique protein family with members throughout the metazoa. Discovered in 1987 in Xenopus laevis, the enzymes were first characterized as doublestranded RNA (dsRNA) unwinding activities (1, 2) and later shown to be dsRNA adenosine-to-inosine modifying activities (3, 4). The observed ‘unwinding’ of the RNA turned out to be a consequence of the modification which, in the context of dsRNA, converts AU base-pairs to the less stable IU mismatch.
Identification and Characterization of Colletotrichum truncatum and C. destructivum Causing Stem Rot of White Clover in China
Authors: Tuluhong Muzhapaer , Mu Meiqi , Wang Shuni , Li Yonggang , Cui Guowen
Published: November 2023

White clover (Trifolium repens L.) is an excellent quality forage legume species with superior planting efficiency, which reduces the cost of artificial weeding and nitrogen fertilizer inputs, and has feeding and economic value. However, from June to September 2022, severe stem rot affected the yield and quality of white clover crops in Harbin, Heilongjiang Province, China. The aim of this study was to identify the causative agents of the disease. Overall, Colletotrichum truncatum (6 isolates) and C. destructivum (10 isolates) were obtained from rotten white clover stems and identified based on morpho-molecular characteristics and phylogenetic analyses. Pathogenicity tests of the isolates revealed that C. destructivum had a higher pathogenicity to white clover than C. truncatum. In addition, all isolates were highly pathogenic to broad bean, fodder soybean, soybean, pak choi, and chickpea, were pathogenic to mint, and did not infect corn, wheat, or cilantro. C. destructivum and C. truncatum isolates were very sensitive to tebuconazole and pyraclostrobin, with EC50 values of 0.54 to 0.70 μg/ml and 0.42 to 0.62 μg/ml, respectively, efficacies ranging between 93.2 to 94.9% and 90.2 to 95.2% at 600 μg/ml and 450 μg/ml, respectively, and EC90 values of 1.88 to 13.36 μg/ml and 1.32 to 23.39 μg/ml, respectively. Therefore, intercropping of host and nonhost plants and chemicals can be considered to control stem rot in white clover. These results provide a basis for controlling C. destructivum and C. truncatum in white clover in China.
Plate Fixation of Hamate Fractures in Fourth and Fifth Carpometacarpal Fracture Dislocations
Authors: Eswaran Sanju P. , Schreck Michael J. , Harley Brian J.
Published: November 2023

Traumatic dislocations of the fourth and fifth metacarpals, in conjunction with dorsal hamate fractures, are a common entity that can lead to the instability of the fourth and fifth carpometacarpal (CMC) joints. The fracture of the hamate, usually in a coronal dorsal shear configuration, can lead to the dorsal subluxation of the hamatometacarpal joint. Open reduction and internal fixation of the hamate bone with a dorsally applied buttress plate can re-establish a stable and congruent joint surface and anatomically align the articular surfaces of the small and ring finger CMC joints. We present a technique of internal fixation of the hamate to facilitate the reduction of the hamatometacarpal joints. Using a dorsal approach centered over the fourth and fifth CMC joints, the joint surfaces are directly visualized and subsequent fixation of the hamate is performed using a 1.3-mm T-plate to securely buttress its articular surface. This technique presents an approach to the multifaceted injury pattern of fourth and fifth CMC dislocations associated with a hamate fracture.
Artificial intelligence for OCTA-based disease activity prediction in age-related macular degeneration.
Authors: Heinke Anna , Zhang Haochen , Deussen Daniel , Galang Carlo Miguel B. , Warter Alexandra , Paguiligan Kalaw Fritz Gerald , Bartsch Dirk-Uwe G. , Cheng Lingyun , An Cheolhong , Nguyen Truong , Freeman William R.
Published: November 2023

Purpose:

We hypothesize that OCTA-visualized vascular morphology may be a predictor of CNV status in AMD. We thus evaluated the use of AI to predict different stages of AMD disease based on OCTA en-face 2D projections scans.

Methods:

Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active and wet-AMD in remission with no signs of activity. Two human experts graded the same test set and a consensus grading between 2 experts was used for the prediction of 4 categories.

Results:

The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was: 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was: 0.4286 active CNV, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, 0.9762 respectively. The overall AI classification prediction was significantly better than the human (odds ratio=1.95, p=0.0021).

Conclusion:

Our data shows that CNV morphology can be used to predict disease activity by AI; Longitudinal studies are needed to better understand the evolution of CNV and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.
Preoperative upper lid skin tear: a rare and unique complication of retrobulbar anesthesia before cataract surgery
Authors: Hura Arjan S. , Osher Robert H. , Henson Ginger L.
Published: November 2023

Retrobulbar anesthesia is commonly administered before cataract surgery or other intraocular and intraorbital ophthalmic procedures. The main benefits of retrobulbar anesthesia include rapid onset of action, low volume required to achieve analgesia, and complete akinesia. Retrobulbar anesthesia has a low risk for complications, and those complications are well known and have been extensively documented. A unique complication of an upper lid skin tear secondary to a retrobulbar block is presented.
A cross-sectional study of contact allergens in feminine hygiene wipes: a possible cause of vulvar contact dermatitis
Authors: Newton Jazmin , Richardson Sophie , van Oosbre Annika M. , Yu Jiade , Silence Channi
Published: November 2023

Background:

Feminine hygiene wipes marketed toward women for maintaining freshness and cleanliness of the vulva and perineum are abundant both in-store and online. Many of these products boast being “fragrance free,” “gentle,” and “for sensitive skin,” which is attractive to consumers. However, these claims do not necessarily mean they are free of potential allergens.

Objective:

The present study aims to investigate the presence and prevalence of potential allergens in the most used feminine hygiene wipes.

Methods:

An internet-based search was performed to identify best-selling name brand and generic feminine hygiene wipes. Each unique wipe was analyzed and compared to the North American Contact Dermatitis Group 80 allergens.

Results:

We found contact allergens are frequently present in feminine hygiene wipes, most commonly fragrances, other scented botanicals in the form of essences, oils, and fruit juices, and vitamin E (tocopherol). All wipes analyzed in this study contained potential allergens.

Limitations:

The inability to eliminate commercial names from analysis could have introduced bias.

Conclusions:

Vaginal and vulvar epithelia are highly susceptible to contact allergens, often found in products marketed for feminine hygiene and cleanliness. Providers should caution patients against trusting product labeling claims to avoid incidental contact allergy and encourage simply cleansing the vulva with water.
Roadmaps to green nephrology: a mediterranean point of view
Authors: Ben Hmida Mohamed , Torreggiani Massimo , Berman-Parks Nathan , Salomone Mario , Piccoli Giorgina Barbara
Published: November 2023

Purpose of review

Green nephrology is a movement whose aim is to find ways to reduce the environmental impact of kidney care. The question is of particular concern in this field since haemodialysis is one of the major contributors to waste generation, energy use and water consumption in healthcare. Although several ways for improving sustainability have been advocated, they are all context sensitive. This review aims to analyse the interventions that have been proposed to improve the ecologic sustainability and reduce the carbon footprint of nephrology care adapting to specific settings, and taking advantage of local expertise.

Recent findings

Green hospitals are becoming a reality in several high-income settings, thanks to new building guidelines, with greater awareness of climate change and users’ demands. Water saving is feasible, and is increasingly done, in different ways (improving hardware, reducing and adapting dialysate flows). Recycling noncontaminated plastic waste is feasible, but is still rarely performed. However, ecological transition has been slow even in high-income countries, while in low and middle-income countries lack of resources limit the ability to cope with the planet's urgent needs. Conversely, where man-power cost is low, some time-consuming tasks, such as separation of various components for recycling may be affordable. Theoretically, implementation of all clinical tasks aiming to avoid or retard dialysis, should be a priority.

There is no single roadmap for achieving green nephrology. Each setting should start from those feasible interventions most in line with its specific needs and priorities.
Percutaneous Ultrasound Cholangiography With Microbubbles in Children With Biliary Diseases
Authors: Chen Meixi , Zhang Xiaoer , Zhou Wenying , Zhang Nan , Wang Guotao , Zhou Luyao
Published: November 2023

The application of intracavity contrast-enhanced ultrasound in the evaluation of biliary disease has been confirmed valuable among pediatric population. This pictorial essay aims to demonstrate the role of percutaneous ultrasound cholangiography (PUSC) with microbubbles in the diagnosis of different pediatric biliary diseases in our center. The biliary system's morphologic characteristics in PUSC mode of neonatal hepatitis, biliary atresia, choledochal cysts, and biliary complications of hepatobiliary surgery are presented.
In Vivo Sonoporation Effect Under the Presence of a Large Amount of Micro-Nano Bubbles in Swine Liver
Authors: Ueno Yutaka , Kariya Shuji , Ono Yasuyuki , Maruyama Takuji , Nakatani Miyuki , Komemushi Atsushi , Tanigawa Noboru
Published: November 2023

Objectives

Sonoporation as a method of intracellular drug and gene delivery has not yet progressed to being used in vivo. The aim of this study was to prove the feasibility of sonoporation at a level practical for use in vivo by using a large amount of carbon dioxide micro-nano bubbles.

Methods

The carbon dioxide micro-nano bubbles and 100 mg of cisplatin were intra-arterially injected to the swine livers, and ultrasound irradiation was performed from the surface of the liver under laparotomy during the intra-arterial injection. After the intra-arterial injection, ultrasound-irradiated and nonirradiated liver tissues were immediately excised. Tissue platinum concentration was measured using inductively coupled plasma mass spectrometry. Liver tissue platinum concentrations were compared between the irradiated tissue and nonirradiated tissue using the Wilcoxon signed rank test.

Results

The mean (SD) liver tissue platinum concentration was 6.260*103 (2.070) ng/g in the irradiated liver tissue and 3.280*103 (0.430) ng/g in the nonirradiated liver tissue, showing significantly higher concentrations in the irradiated tissue (P = 0.004).

Conclusions

In conclusion, increasing the tissue concentration of administered cisplatin in the livers of living swine through the effect of sonoporation was possible in the presence of a large amount of micro-nano bubbles.
Predictive Ability of Ultrasound on Neonatal Diagnoses and Consequences on Prenatal Care Utilization
Authors: Lunardhi Alicia , Goldrich Alisa , Stohl Hindi E. , Ko Kimberly J. , Dong Fanglong , Galyon Kristina D.
Published: November 2023

Fetal anomalies suspected on fetal ultrasound may cause significant stress for patients. Some findings resolve or have minimal clinical significance for the neonate. Our purpose is to evaluate fetal ultrasound accuracy and false-positive results and determine the clinical impact on maternal counseling. A retrospective review was performed on electronic medical records for women receiving prenatal care at Harbor-UCLA Medical Center who had abnormal findings on fetal ultrasounds between January 2015 and December 2018. Corresponding neonatal medical records were reviewed for the suspected condition(s). χ
2 and Fisher exact tests were conducted to assess associations between fetal ultrasounds and neonatal outcomes. Two hundred eight mothers and 237 babies (including all 29 sets of twins) were included in the final analysis. Fetal ultrasounds were significantly associated with neonatal findings for the following conditions (sensitivity, specificity): anatomical disorder of extremities (0.72, 0.97), anatomical disorder of the face/skull/brain (0.67, 0.91), congenital anomaly of gastrointestinal tract (0.75, 0.98), congenital heart disease (0.75, 0.91), genetic disorder (0.72, 1.00), growth restriction (1.00, 0.85), kidney disorder (0.55, 0.98), and large for gestational age (0.80, 0.98). The highest false-positive rates occurred in congenital heart disease (65.4%), anatomical disorder of the face/skull/brain (64.3%), and growth restriction (54%). Fetal ultrasound highly correlates with neonatal findings for many congenital conditions. However, it can also be associated with a high false-positive rate for certain diagnoses; maternal counseling should include the limitations of ultrasound, including the potential for false-positive results.
Nocardioides cremeus sp. nov., Nocardioides abyssi sp. nov. and Nocardioides oceani sp. nov., three actinobacteria isolated from Western Pacific Ocean sediment
Authors: Wang Wenjing , Ding Yihan , Wei Shiping , Yin Miaomiao , Zhang Gaiyun
Published: November 2023

Three Gram-stain-positive, non-motile, short rod-shaped, catalase-positive and oxidase-negative actinomycete strains (SOB44T, SOB72T and SOB77T) were isolated from a deep-sea sediment sample collected from the Western Pacific Ocean. Cells of the three strains showed optimum growth at 30 °C and pH 7.0. Strains SOB44T, SOB72T and SOB77T could tolerate up to 10, 9 and 9 % (w/v) NaCl concentration and grow at pH 5.0–12.0, 5.0–11.0 and 5.0–11.0, respectively. Phylogenetic results based on 16S rRNA gene sequences showed that the three isolates belonged to the genus

Nocardioides

and were identified as representing three novel species based on 78.0–93.1 % average nucleotide identity and 21.3–50.0 % DNA–DNA hybridization values with closely related reference strains. Strains SOB44T, SOB72T and SOB77T showed highest 16S rRNA gene sequence similarity to

Nocardioides salarius

CL-Z59T (99.2 %),

Nocardioides deserti

SC8A-24T (99.2 %) and Nocardioides marmotae zg-579T (98.5 %), respectively. All three strains had MK-8(H4) as the respiratory quinone, iso-C16 : 0 as the major fatty acid, and phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol as the major polar lipids. The diagnostic diamino acid in the cell-wall peptidoglycan of all three isolates was ll-diaminopimelic acid. The DNA G+C contents of strains SOB44T, SOB72T and SOB77T were 71.1, 72.9 and 72.9 mol%, respectively. Based on the phenotypic, phylogenetic and genotypic data, strains SOB44T, SOB72T and SOB77T clearly represent three novel taxa within the genus

Nocardioides

, for which the names Nocardioides cremeus sp. nov. (type strain SOB44T=JCM 35774T= MCCC M28400T), Nocardioides abyssi sp. nov. (type strain SOB72T=JCM 35775T=MCCC M28318T) and Nocardioides oceani sp. nov. (type strain SOB77T=JCM 35776T=MCCC M28544T) are proposed.
Gardenin A improves cognitive and motor function in A53T-α-syn mice
Authors: Hack Wyatt , Gladen-Kolarsky Noah , Chatterjee Swarnali , Liang Qiaoli , Maitra Urmila , Ciesla Lukasz , Gray Nora E
Published: November 2023

Oxidative stress and neuroinflammation are widespread in the Parkinson’s disease (PD) brain and contribute to the synaptic degradation and dopaminergic cell loss that result in cognitive impairment and motor dysfunction. The polymethoxyflavone Gardenin A (GA) has been shown to activate the NRF2-regulated antioxidant pathway and inhibit the NFkB-dependent pro-inflammatory pathway in aDrosophilamodel of PD. Here, we evaluate the effects of GA on A53T alpha-synuclein overexpressing (A53TSyn) mice.

A53TSyn mice were treated orally for 4 weeks with 0, 25, or 100 mg/kg GA. In the fourth week, mice underwent behavioral testing and tissue was harvested for immunohistochemical analysis of tyrosine hydroxylase (TH) and phosphorylated alpha synuclein (pSyn) expression, and quantification of synaptic, antioxidant and inflammatory gene expression. Results were compared to vehicle-treated C57BL6 mice.

Treatment with 100 mg/kg GA improved associative memory and decreased abnormalities in mobility and gait in A53TSyn mice. GA treatment also reduced cortical and hippocampal levels of pSyn and attenuated the reduction in TH expression in the striatum. Additionally, GA increased cortical expression of NRF2-regulated antioxidant genes and decreased expression of NFkB-dependent pro-inflammatory genes. GA was readily detectable in the brains of treated mice and modulated the lipid profile in the deep gray brain tissue of those animals.

While the beneficial effects of GA on cognitive deficits, motor dysfunction and PD pathology are promising, future studies are needed to further fully elucidate the mechanism of action of GA, optimizing dosing and confirm these effects in other PD models.

Significance Statement

The polymethoxyflavone Gardenin A can improve cognitive and motor function and attenuate both increases in phosphorylated alpha synuclein and reductions in tyrosine hydroxylase expression in A53T alpha synuclein overexpressing mice. These effects may be related to activation of the NRF2-regulated antioxidant response and downregulation of NFkB-dependent inflammatory response by Gardenin A in treated animals. The study also showed excellent brain bioavailability of Gardenin A and modifications of the lipid profile, possibly through interactions between Gardenin A with the lipid bilayer, following oral administration. The study confirms neuroprotective activity of Gardenin A previously reported in toxin inducedDrosophilamodel of Parkinson’s disease.
Critical capillary waves of biomolecular condensates
Authors: Shimobayashi Shunsuke F. , Konishi Kota , Ackerman Paul J. , Taniguchi Takashi , Brangwynne Clifford P.
Published: November 2023

Membraneless compartments known as biomolecular condensates are thought to form through liquid-liquid phase separation (LLPS). When forces are applied to the fluid interfaces of these condensates, surface fluctuation are generated, a phenomenon known as capillary waves. The spatiotemporal dynamics of these fluctuations, characterized by the amplitude and velocity, reflect the physical properties of condensates. Moreover, unraveling the nature of fluctuations near the critical point is crucial for understanding the universal physical underpinnings of phase transitions. Although fluid condensate interfaces are ubiquitous within living cells, little is known about their surface fluctuations. Here, we quantify the interface fluctuations of light-induced synthetic and endogenous nuclear condensates, including nucleoli and nuclear speckles, in real and Fourier space. Measured fluctuations align with a theory assuming thermal driving, which enables measurement of surface tension and effective viscosity. The surface tensions fall within the range of 10−6to 10−5N/m for all tested condensates; in contrast, we find significant difference of fluctuation velocities, highlighting much higher viscosity of nucleoli 104∼Pa ·s, compared to synthetic condensates and nuclear speckles. We further find that the interface fluctuations become enhanced and slower as the system nears the critical point. These findings elucidate key aspects of intracellular condensate properties, and suggest that the critical trend of surface tension is more consistent with theoretical predictions by the mean-field model than those by the 3D Ising model.
Transdiagnostic brain module dysfunctions across sub-types of frontotemporal dementia: a connectome-based investigation
Authors: Xinglin Zeng , Jiangshan He , Kaixi Zhang , Xiaoluan Xia , Shiyang Xu , Yuan Zhen
Published: November 2023

Background

Frontotemporal dementia (FTD) is a complex neurodegenerative disorder encompassing heterogeneous subtypes, including behavioral variant frontotemporal dementia (BV-FTD), semantic variant frontotemporal dementia (SV-FTD), and progressive non-fluent aphasia frontotemporal dementia (PNFA-FTD). Unraveling the shared and distinctive brain module organizations among these subtypes is critical for unraveling the underlying neural basis of the disease. This study aims to explore brain module organization in FTD subtypes, seeking potential biomarkers and insights into their pathophysiology.

Methods

Resting-state functional magnetic resonance imaging data were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative, comprising 41 BV-FTD, 32 SV-FTD, 28 PNFA-FTD, and 94 healthy controls, following exclusion of participants with excessive head motion. Individual functional brain networks were constructed at the voxel level of gray matter and binarized with a 1% density threshold. Using predefined brain modules, we computed the modular segregation index (MSI) for each module, analyzed intermodular and intramodular connections to identify driving modular connections, and calculated the participation coefficient (PC) to detect regions with altered nodal properties associated with module integrity. A machine learning algorithm was employed for FTD subtype classification based on these matrices. Correlations between modular measures and clinical scores in each FTD subtype were examined.

Results

Distinct brain module organizations were observed across FTD subtypes, with lower MSI in the subcortical module (SUB), default mode network (DMN), and ventral attention network (VAN) in both BV-FTD and SV-FTD. Specifically, only BV-FTD exhibited disruption in the frontoparietal network (FPN). Notably, the bilateral fusional gyrus, left orbitofrontal cortex, left precuneus, and right insular thalamus showed significant group effects on PC, indicating altered nodal properties associated with module integrity. Our machine learning achieved a multiple classification accuracy of 85%. Correlations between specific network alterations and clinical variables in each FTD subtype were also identified.

Conclusions

These findings illuminate the diverse brain module organization in different FTD subtypes, offering insights into potential neurobiological differences that underlie the clinical heterogeneity of the disease. Regions with altered modular properties may serve as valuable biomarkers for early diagnosis and disease monitoring. Furthermore, understanding disruptions in modular connectivity provides valuable insights into the neuropathological mechanisms of FTD subtypes, paving the way for targeted therapeutic interventions.
Sarand: Exploring Antimicrobial Resistance Gene Neighborhoods in Complex Metagenomic Assembly Graphs
Authors: Kafaie Somayeh , Beiko Robert G. , Maguire Finlay
Published: November 2023

Antimicrobial resistance (AMR) is a major global challenge to human and animal health. The genomic element (e.g., chromosome, plasmid, and genomic islands) and neighbouring genes associated with an AMR gene play a major role in its function, regulation, evolution, and propensity to undergo lateral gene transfer. Therefore, characterising these genomic contexts is vital to effective AMR surveillance, risk assessment, and stewardship. Metagenomic sequencing is widely used to identify AMR genes in microbial communities, but analysis of short-read data offers fragmentary information that lacks this critical contextual information. Alternatively, metagenomic assembly, in which a complex assembly graph is generated and condensed into contigs, provides some contextual information but systematically fails to recover many mobile genetic elements. Here we introduce Sarand, a method that combines the sensitivity of read-based methods with the genomic context offered by assemblies by extracting AMR genes and their associated context directly from metagenomic assembly graphs. Sarand combines BLAST-based homology searches with coverage statistics to sensitively identify and visualise AMR gene contexts while minimising inference of chimeric contexts. Using both real and simulated metagenomic data, we show that Sarand outperforms metagenomic assembly and recently developed graph-based tools in terms of precision and sensitivity for this problem. Sarand (https://github.com/beiko-lab/sarand) enables effective extraction of metagenomic AMR gene contexts to better characterize AMR evolutionary dynamics within complex microbial communities.
A Neanderthal Origin of Genetic Variants Associated with Asthma
Authors: Day Andrew S. H. , Gaulton Kyle J.
Published: November 2023

While genome-wide association studies have implicated a number asthma-associated genes, whether the disease-linked variants originate from ancient genomes has not been explored. Here we show that of the 51 asthma-associated loci that we surveyed, 39 carry variants that were derived in the Neanderthal lineage. The shared sequences suggest that some asthma variants may have originated from the Neanderthal genome after admixture and subsequent introgression into the Eurasian population. Of note, one variant, rs4742170, previously linked to asthma and childhood wheezing, was shown in a recent study to disrupt glucocorticoid receptor binding to a putativeIL33enhancer, and elevate enhancer activity of this key asthma gene. Further analysis of theIL33-associated variant in publicly available single nucleus ATACseq data of the human lung addressed its localization in open chromatin, providing an additional approach to screen for variants that may impact the expression of asthma-associated genes. Together, these findings suggest a possible Neanderthal origin of genetic variants associated with asthma.
High-throughput, label-free detection of DNA origami in single-cell suspensions using origamiFISH-Flow
Authors: Alexander Shana , Wang Wendy Xueyi , Tseng Chung-Yi , Douglas Travis R. , Chou Leo Y.T.
Published: November 2023

Structural DNA nanotechnology enables custom fabrication of nanoscale devices and promises diverse biological applications. However, the effects of design on DNA nanostructure (DN)-cell interactions in vitro and in vivo are not yet well-characterized. origamiFISH is a recently developed technique for imaging DNs in cells and tissues. Compared to the use of fluorescent tags, origamiFISH offers label-free and structure-agnostic detection of DNs with significantly improved sensitivity. Here, we extend the origamiFISH technique to quantifying DNs in single-cell suspensions, including nonadherent cells such as subsets of immune cells, via readout by flow cytometry. This method, referred to as origamiFISH-Flow, is high-throughput (e.g., 10,000 cells per second) and compatible with immunostaining for concurrent cell-type and -state characterization. We demonstrate that origamiFISH-Flow enhances signal-to-noise ratio by up to 20-fold compared to dye labeling approaches, leading to the capture of >25-fold more DN+cells at low, single-picomolar DN uptake concentrations. We additionally show the use of origamiFISH-Flow to profile cell-type and shape-specific DN uptake patterns across cell lines and splenocytes and quantify in vivo DN accumulation in lymphoid organs. Together, origamiFISH-Flow offers a new tool to interrogate DN interactions with cells and tissues, while providing insights for tailoring their designs in bio-applications.