bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Sense of Early Modern Modal Theory
Authors: Dodds Michael R.
Published: November 2023

The transition from modes to keys, so often described as a path, might more accurately be characterized as a network of paths. Religion, region, and close associations between modal systems and repertories, to say nothing of the interplay of tradition and innovation, created widely diverse views within modal theory, especially in the seventeenth century. Theorists differed on the number and disposition of the modes, on their graphic representation, on the relative importance of specific modal parameters, and on their ontology. We can make sense of this seemingly chaotic state of affairs by recognizing that early modern modal theory was shaped by the ongoing interplay of three historical layers or theoretical polarities. The first of these, originating in the Middle Ages, concerns a conceptual continuum between melodic and scalar conceptions of mode, reflected in contrasting connotations of the terms tonus and modus. The second layer, arising in the Renaissance, involves a distinction between modal parameters already established for monophony and new parameters relevant to polyphony. The third layer concerns a shift from vocal to keyboard ways of conceptualizing tonal space accelerated by the introduction of basso continuo c. 1600. The relationship between these three dimensions of modal theory is fluid and dynamic; in Baroque music theory they are simultaneously at play in forms both old and new.
Organizing Schemes for the Two Modes, 1687–1722
Authors: Dodds Michael R.
Published: November 2023

+It is the two modes’ organization that makes them a system. This chapter considers the organization of major–minor key listings in twenty-four treatises between Speer’s 1687 Grundrichtiger Unterricht, the first continental treatise listing the major and minor keys apart from another modal scheme, and Rameau’s 1722 Traité de l’harmonie, a book inaugurating a new era in harmonic theory. In these two-mode treatises, we encounter three organizing schemes: (1) stepwise by final, whether diatonic or chromatic (2) first by type of key, and then stepwise by final; and (3) by increasing signature and/or the circle of fifths. In all three organizing schemes, major and minor keys are sometimes integrated and sometimes listed separately. If the north German theorists Werckmeister and Heinichen led the way in circular organization between and within keys, their French counterparts Ozanam and Saint-Lambert clarified the notion of the two modes as abstract, freely transposable scales, with Loulié uniting signature, heptachordal syllables, and key in the conventions still used today. Heinichen’s circle of fifths and Campion’s rule of the octave produced new conceptions of tonal space, premised on transpositional equivalent of keys and consolidation of voice-leading norms, as well as identification of chord functions. Tonal circularity, which since antiquity had reflected music’s kinship with the spatial-temporal disciplines of the quadrivium, now became instrumental in the creation of a new musical grammar, and indeed new expressions of musical logic and rhetoric. Thus the shift from modes to keys corresponds to a complete transformation of the language of Western music.
Changing Concepts of Tonal Space
Authors: Dodds Michael R.
Published: November 2023

From ladder to circle: this is the essence of the shift that took place in the Baroque era as keyboard eclipsed voice as the main referent for organizing tonal space. In music theory treatises from the Middle Ages through the seventeenth century, representations of the gamut on a single oversized staff are ubiquitous: they reflect a ladder-like, low-to-high mapping of the human vocal range, navigable via the system of overlapping hexachords. In telling contrast, many treatises from the Baroque era graphically organize tonal content in circular form. In some cases, it is the keyboard itself that is circular, or the major and minor keys. The rise of circularity parallels the gradual dissolution of the hexachordal system, including its dual littera-vox nomenclature, and its replacement with heptachordal solmization (requiring no mutation) or letter names. While circles in medieval and renaissance music theory are preeminently symbolic, in the Baroque they begin to reflect practical and even empirical ways of representing musical space. Among the most sophisticated musical circles are volvelles, revolving paper wheels permitting musical patterns such as intervals, triads, modes, and scales to be transposed to any chromatic degree by turning the wheel. Especially apt for relating circular or cyclical constructs of time and space, volvelles are common in Renaissance books in disciplines such as astronomy, navigation, and calendrical reform.
Musical Circles and Labyrinths
Authors: Dodds Michael R.
Published: November 2023

Perhaps no metaphor was more strongly associated with the rise of tonal circularity than the labyrinth. Numerous Baroque theorists and composers invoked the Cretan labyrinth as a metaphor in relation to the proliferation of keys and to their organization. The analogy of the labyrinth to musical circles is apt in many ways. While labyrinths come in many shapes, most are circular. Modulation through remote and unfamiliar keys brings bewilderment like that of a person in a maze, while sequential circle-of-fifths progressions provide an Ariadne’s thread back to the starting point. Moreover, like the history of music theory, the history of horticultural labyrinths reflects the shifting epistemologies of the early modern era. If the monocursal (one-route) labyrinth of the Middle Ages required faith and hope to exit, then the multicursal (multi-route) labyrinth of the Renaissance and Baroque pleasure garden called for reason and memory. Both of these episteme, faith and reason, are invoked in the titles and explanations of musical labyrinths. Inevitably tied to the ascendancy of circulating temperaments, musical circles and labyrinths epitomized the potential of the new two-mode system.
Lotic Primary Producers
Authors: Mallin Michael A.
Published: November 2023

Phytoplankton communities are usually sparse in smaller headwaters streams, limited by light and current. However, phytoplankton can be abundant and diverse in larger rivers and estuaries, with seeding from numerous sources along the river continuum, such as farm ponds, oxbow lakes, and drainage ditches. Phytoplankton-based food webs occur in many large rivers and estuaries. In large, nutrient-rich rivers nuisance and toxic blooms can form, especially in heavily regulated rivers; this can have severe impacts on river animals and human drinking-water users. The major microscopic primary producers in headwaters or middle-order streams are often periphytic microalgae, living on rocky substrata or macrophyte stems and leaves. This is an important food source to grazers, which supports fish and other vertebrates, mollusks, and crustaceans. Periphyton can also form nuisance blooms fueled by a constant nutrient source, overgrow macrophytes on occasion, and disrupt stream ecology and human usage.
Lotic Primary Producers
Authors: Mallin Michael A.
Published: November 2023

Stream and river aquatic macrophytes occur in several functional forms, including emergent, loosely attached, submersed, and free-floating. Macrophyte growth in moderation enhances stream animal life by providing a direct food source, or substrata for periphyton, or cover and habitat for invertebrates, fish, and other vertebrates. Macrophyte beds can also reduce turbidity, sequester excess nutrients from the water column, and reduce erosion. Unfortunately, some macrophytes are highly invasive and once established out of their native range can cause major disruptions to ecosystems. Macroalgae are highly visible algae (nonvascular plants) that can have many of the same positive attributes that aquatic macrophytes do, again provided they occur in moderation. However, in eutrophic situations macrophytes can cover stream beds in long trailing masses, altering stream physical habitat, and upon dying create a BOD load that leads to severe hypoxia.
Feeding the River
Authors: Mallin Michael A.
Published: November 2023

The stream invertebrate community is nourished by both dissolved and particulate carbon, the latter of various size ranges, both living organisms and decaying matter. The invertebrate communities conform to the geomorphic and hydrologic conditions of the river as it transforms from small headwaters streams to large river channels far downstream. The River Continuum Concept is a unifying concept that details these relationships and is valid in many types of rivers. Exceptions would be in nonforested headwaters regions and in the abundant blackwater river systems in the US Southeast. The flood-pulse concept describes how, at least in relatively unaltered rivers, there are annual, natural floods that fish evolutionarily take advantage of to access the rich food resources of the floodplain, where younger and smaller fish can find refuge from larger, channel-based predatory fish. Unfortunately, the flood pulse is diminished or absent in dammed or otherwise fragmented river systems, which are now found worldwide.
Stream Pollution from Human Sewage and Animal Wastes
Authors: Mallin Michael A.
Published: November 2023

Stream pollution from human sewage is one of the oldest types of pollution, yet is pervasive today in both highly industrialized and less-developed nations. Pollutants include microbial pathogens, nutrients, suspended solids, BOD, pharmaceuticals, and other compounds. In this chapter the design of wastewater treatment plants is explained, what is treated and what isn’t, and results of failures described. Some human waste is treated by septic systems, which may operate well in proper circumstances but are sources of groundwater and surface water pollution where soils are porous and the water table high. Industrial-scale livestock production is a large source of stream pollution (microbial, nutrient, BOD) in selected areas, because the concentrated animal waste receives minimal treatment (often in waste lagoons) and is discharged into the air and/or onto surrounding soils. The waste pollutes streams from surface runoff, from groundwater movement through porous soils, and by atmospheric deposition of ammonia and fecal microbes.
Species Loss and Impacts of Invasive Species
Authors: Mallin Michael A.
Published: November 2023

Non-native species, also called invasive species, alien species, exotic species, and less complimentary terms, are both plant and animal. Those invading from a different continent are often brought in and released in ballast water exchanges; some are deliberately brought in as aquarium species. Within a given continent invasives are spread by canal construction, in boat bilges, or on boat trailers or propellers, released as unwanted pets, carried by animals, or deliberately released somewhere as a fish or game animal. Successful invasives can alter whole riverine and lentic ecosystems, cause havoc to water intakes, cause native species losses, ruin fisheries, and cost industries and governments millions if not billions of dollars in control schemes. Some useful means of reducing successful invasions include exchanging ballast water offshore, using various ballast water chemical and physical treatments, having strong, enforceable plant and animal importation regulations, signage and required inspections at boat ramps, and public education regarding invasives, the problems they cause, and what to do to prevent such problems.
The Time-Independent Schrödinger Equation
Authors: Bertlmann Reinhold A. , Friis Nicolai
Published: November 2023

We discuss the procedure of solving the time-dependent Schrödinger equation via a separation ansatz that leads to the time-independent Schrödinger equation. The resulting equation is in the form of an eigenvalue problem for the Hamiltonian, whose solutions are the stationary states. We derive and discuss the bound states and corresponding energy levels for several one-dimensional potentials of interest, including the finite and infinite potential well, the Dirac-delta potential, and the square double-well modelling the spatial configuration of the ammonia molecule. We then turn to the scattered solutions and discuss reflection from and transmission through a finite potential barrier, thus encountering the tunnel effect, which we in turn formulate more generally using the Gamow factor. This leads us to the interesting phenomenon of tunnelling resonances
Hidden-Variable Theories
Authors: Bertlmann Reinhold A. , Friis Nicolai
Published: November 2023

In chapter 12 we give an overview of the historical development of hidden-variable theories aiming to attribute ‘hidden’ definite outcomes to any potential measurement on a quantum system. We start with a discussion of von Neumann’s assumption on hidden-variable models, which was later realized not to hold by Hermann, Kochen, Specker, and Bell, going into detail on Bell’s refutation of von Neumann’s arguments. We then turn to the notion of contextuality, which severely restricts hidden-variable models: we discuss Gleason’s theorem before stating and proving the famous Kochen-Specker theorem, as well as the simpler versions of Peres’ nonet and Mermin’s pentagram. These results show that quantum mechanics is not compatible with the assignment of definite measurement outcomes to all possible measurements, and such assignments can hence only be made once a restricted set of observables, a context, is selected
Quantification and Conversion of Entanglement
Authors: Bertlmann Reinhold A. , Friis Nicolai
Published: November 2023

In this chapter the quantification of entanglement is discussed. Beginning with the pure-state entanglement measure called the entropy of entanglement, we discuss the paradigm of local operations and classical communication (LOCC) and its relation to majorization via Nielsen’s majorization theorem. We then turn to the asymptotic setting and discuss the formation and distillation of entanglement and the related entanglement measures: entanglement cost and distillable entanglement, and we examine the notions of distillability and bound entanglement. This brings us to a more general discussion of entanglement measures and monotones, and their desired properties, during which we present the entanglement of formation and concurrence, squashed entanglement, as well as the tangle and its relation to monogamy of entanglement, but also quantities like the relative entropy of entanglement, the Hilbert-Schmidt measure, and the (logarithmic) negativity. Finally we turn to the construction of entanglement witnesses and their geometric interpretation via the Bertlmann-Narnhofer-Thirring theorem
Quantum Channels and Quantum Operations
Authors: Bertlmann Reinhold A. , Friis Nicolai
Published: November 2023

In this chapter we visit the ‘church of the larger Hilbert space’: we take a closer look at the relationship of pure and mixed quantum states via purification, and discuss a similar connection between completely positive and trace-preserving (CPTP) maps and unitary dynamics on a larger Hilbert space. We show that such CPTP maps, which represent quantum channels, are equivalent to operations admitting a Kraus decomposition, as well as to unitary dynamics on a larger Hilbert space with factoring initial condition, the famous Stinespring dilation of quantum operations. In this context we introduce the Choi-Jamiołkowski isomorphism, which expresses a duality between maps between two Hilbert spaces and states on tensor products of these Hilbert spaces, and we review several important examples of quantum channels such as the dephasing channel, amplitude-damping channel, and depolarizing channel. Finally, we examine operations that are not possible in quantum theory, focusing on the no-cloning theorem.
Treatment delay from onset of occipital neuralgia symptoms to treatment with nerve decompression surgery: a prospective cohort study
Authors: Hazewinkel Merel H J , Remy Katya , Black Grant , Tseng Sierra , Mathew Paul G , Schoenbrunner Anna , Janis Jeffrey E , Austen William G , Jotwani Rohan , Gfrerer Lisa
Published: November 2023

Background

The aims of this study were to (1) evaluate the time between onset of occipital neuralgia symptoms and nerve decompression surgery, (2) perform a cost comparison analysis between surgical and nonsurgical treatment of occipital neuralgia, and (3) report postoperative results of nerve decompression for occipital neuralgia.

Methods

Subjects (n = 1112) who underwent screening for nerve decompression surgery were evaluated for occipital neuralgia. Of those, 367 patients (33%) met the inclusion criteria. Timing of occipital neuralgia symptom onset and pain characteristics were prospectively collected. Cost associated with the nonsurgical treatment of occipital neuralgia was calculated for the period between onset of symptoms and surgery.

Results

A total of 226 patients (73%) underwent occipital nerve decompression. The average time between onset of occipital neuralgia and surgery was 19 years (7.1–32). Postoperatively, the median number of pain days per month decreased by 17 (0–26, 57%) (P < .001), the median pain intensity decreased by 4 (2–8, 44%) (P < .001), and median pain duration in hours was reduced by 12 (2–23, 50%) (P < .001). The annual mean cost of nonsurgical occipital neuralgia treatment was $28 728.82 ($16 419.42–$41 198.41) per patient. The mean cost during the 19-year time frame before surgery was $545 847.75($311 968.90–$782 769.82).

Conclusion

This study demonstrates that patients suffer from occipital neuralgia for an average of 19 years before undergoing surgery. Nerve decompression reduces symptom severity significantly and should be considered earlier in the treatment course of occipital neuralgia that is refractory to conservative treatment to prevent patient morbidity and decrease direct and indirect health care costs.
Assessment of interleukin 1 receptor antagonist (IL-1RA) levels in children with and without community acquired pneumonia: a hospital based case–control study
Authors: Verma Neha , Awasthi Shally , Pandey Anuj K , Gupta Prashant
Published: November 2023

The primary objective was to compare serum interleukin-1 receptor antagonist (IL-1RA) levels in cases of community acquired pneumonia (CAP) and healthy age–gender-matched controls. The secondary objective was to compare serum IL-1RA levels in cases which were positive or negative for Streptococcus pneumoniae in the blood by real-time-polymerase chain reaction (RT-PCR). Hospitalized children with World Health Organization defined CAP, aged 2–59 months, were included as cases. Healthy controls were recruited from the immunization clinic of the hospital. Enzyme-linked immunosorbent assay (ELISA) test was used to detect serum IL-1RA levels. Identification of S.pneumoniae in blood was done by RT-PCR. From October 2019 to October 2021, 330 cases (123, 37.27% female) and 330 controls (151, 45.75% females) were recruited. Mean serum IL-1RA levels (ng/ml) were 1.36 ± 0.95 in cases and 0.25 ± 0.25 in controls (p < 0.001). Within cases, serum IL-1RA levels were significantly higher in those whose RT-PCR was positive for S.pneumoniae. Thus serum IL-1RA levels may be evaluated as a surrogate marker of S.pneumoniae in future studies.
Neurovascular dysfunction associated with erectile dysfunction persists after long‐term recovery from simulations of weightlessness and deep space irradiation
Authors: Andrade Manuella R. , Azeez Tooyib A. , Montgomery McLane M. , Caldwell Jacob T. , Park Hyerim , Kwok Andy T. , Borg Alexander M. , Narayanan S. Anand , Willey Jeffrey S. , Delp Michael D. , La Favor Justin D.
Published: November 2023

There has been growing interest within the space industry for long‐duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long‐term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty‐six adult male Fisher‐344 rats were randomized into six groups and exposed to 4‐weeks of hindlimb unloading (HLU) or weight‐bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground‐based GCR simulator at the NASA Space Radiation Laboratory. Following a 12–13‐month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium‐dependent and ‐independent relaxation that was tissue type specific. GCR impaired non‐adrenergic non‐cholinergic (NANC) nerve‐mediated relaxation in the dIPA and CC, while follow‐up experiments of the CC showed restoration of NANC‐mediated relaxation of GCR tissues following acute incubation with the antioxidants mito‐TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long‐term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.
Mutual Mistrust: The Multilayered Experiences at the Intersection of Healthcare and Early Parenting Among Mothers With Opioid Use Disorder
Authors: Schiff Davida M. , Muftu Serra , MacMillan Kathryn Dee L. , Work Erin C. , Hoeppner Bettina B. , Greenfield Shelly F. , Schwartz Leah , Chaiyachati Barbara , Wilens Timothy E. , Bernstein Judith A.
Published: November 2023

Objective

The aim of the study is to explore the early parenting experiences among a cohort of postpartum individuals with opioid use disorder (OUD) both during and after the delivery hospitalization to identify areas of intervention to strengthen bonding and attachment.

Methods

Semistructured qualitative interviews with recently pregnant people with OUD assessed parenting needs, supports, and goals in the context of the demands of addiction treatment and early motherhood. Probes explored the relationship between early parenting experiences, addiction, and recovery, as well as enabling factors and barriers to mother-infant bonding. Interviews were completed between 2019 to 2020. A constant comparative methods approach was used for codebook development and analysis.

Results

Twenty-six women completed interviews a mean of 10.1 months postpartum. Twenty-four women were receiving methadone or buprenorphine treatment at delivery for OUD. Four interrelated themes emerged. Women experienced the following: (1) increased surveillance from healthcare workers who doubted their parenting ability; (2) a desire for a “normal” early parenting experience that was not disrupted by increased medical monitoring and surveillance; (3) complex and intersecting identities of being both a mother and a person in recovery; and (4) the importance of support from and advocacy by clinicians and peers to developing maternal confidence and connection.

Conclusions

Interventions are needed to improve the early parenting experiences of opioid-exposed mother-infant dyads, to address the mutual mistrust between health care providers and parents, and to provide additional supports to families. Promotion of positive attachment and parental self-efficacy should be prioritized over increased surveillance and scrutiny to sustain maternal recovery trajectories into early childhood and foster family well-being.
The Effect of Rho Kinase Inhibitors on In Vitro Human Orbital Preadipocytes
Authors: Yoo David , Horacek Meredith , Chae Min Kyung , Kim Ji Young , Bu Ping , Yoon Jin Sook
Published: November 2023

Purpose:

To identify the effects of Rho Kinase (ROCK) inhibitor medications on human orbital adipogenesis, fibroblast proliferation, and fibrosis.

Methods:

Orbital adipose tissue was obtained from patients with Graves’ ophthalmopathy (GO) as well as controls (non-GO or normal) after informed consent was done. These tissue samples were cultured and adipogenesis was initiated. Levels of Rho Kinase as well as cellular mediators of orbital inflammation and fibrosis. The same cultures and measurements were then repeated with the use of a ROCK inhibitor (KD025-ROCK2) to assess for changes in adipogenesis as well as markers associated with inflammation and fibrosis.

Results:

Rho Kinase levels in GO tissue were more highly expressed than in controls. These levels were suppressed with the use of the ROCK inhibitor KD025. There was a dose-dependent reduction in differentiation of orbital adipocytes with the use of KD025. KD025 reduced the levels of fibrosis-related gene expression. Finally, there was a significant reduction of transforming growth factor beta mediated phosphorylation signaling pathways in the KD025-treated GO tissue.

Conclusion:

This study shows that the ROCK inhibitor, KD025, helps to reduce the expression of ROCK in GO tissue along with reducing orbital adipocyte differentiation as well as cell mediators involved in fibrosis that occurs in GO.
New Insights Into the Anatomy of the Eyelashes With Regard to Ethnic Differences Against a Clinical Background
Authors: Singh Swati , Hammer Christian M. , Paulsen Friedrich
Published: November 2023

Background:

To investigate the root depth, root angle, and light and scanning electron microscopical anatomy of human eyelashes relevant to eyelash ablation.

Methods:

Eyelash root depth, the angle between eyelash root and skin epithelium, spatial relationship, and scanning electron microscopical features of the eyelashes were studied on 4 upper and 4 lower eyelids of Caucasian (n = 4) and Indian (n = 4) cadaver heads according to a set protocol.

Results:

There were significant differences in the mean eyelash root depth between Indians (2.3 ± 0.38 mm) and Caucasians (1.9 ± 0.26 mm; p = 0.007), as well as between upper eyelids and lower eyelids (1.9 ± 0.2 mm vs. 1.8 ± 0.1 mm). The mean angle between the lash follicle root and the skin epithelium was 75 ± 11 degrees and similar in both ethnic groups. The eyelash bulb was located close to the tarsal plate and meibomian glands and formed an angle of less than 15 degrees with the eyelash root. Scanning electron microscopy studies revealed that the eyelash bulb was 202 ± 12 μm wide in Indians and 170.6 ± 16.8 μm wide in Caucasian eyelids (p = 0.08). The eyelashes were placed more closely in Indian eyelids than in Caucasian eyelids (p = 0.03). The width of the cuticle layer varied between the hair shaft and the inner eyelid segment.

Conclusions:

There are differences in eyelash root depth, inter-eyelash distance, and cuticle thickness between Indian and Caucasian eyelids. The oblique orientation of the eyelash root and close proximity of the eyelash bulb to the tarsal plate should be kept in mind while doing the electroepilation procedure.
Interpreting coagulation mixing study results in the era of direct oral anticoagulants
Authors: Kim Moon Joo , Salazar Eric , Philips Bonnie , Rice Lawrence , Castillo Brian , Leveque Christopher , Chen Jian
Published: November 2023

Interpretation of coagulation mixing studies is complicated by interference arising from direct oral anticoagulants (DOACs), which are increasingly prescribed. In this retrospective study, we reviewed 1035 consecutive coagulation mixing studies performed from 2017 to 2021. Three hundred and ninety-nine cases with normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) were excluded. aPTT mixing studies were performed at time 0 and after 60 min of incubation. We confirmed the presence of interfering factors with additional laboratory testing, medication records, and medical history. Mixing corrected most prolonged PT samples (93%), but 32 cases showed incomplete correction. Of these 32 cases, 18 were confounded by DOAC use, and 3 by factor V (FV) inhibitor. We observed an unusual pattern of prolongation of aPTT after incubation, which was previously considered a characteristic of specific factor inhibitors, most commonly FVIII inhibitor. However, we found that lupus anticoagulant (28%) and DOAC (25%) contributed to this pattern similarly as specific factor inhibitors (28%). Coagulation laboratories should be aware of interference arising from DOACs and other factors in PT/aPTT mixing studies, especially in some unusual correction patterns.
Impact of Facility Dog and Certified Child Life Specialist Dyad on Children’s Pain and Anxiety During Needlestick Procedures in a Pediatric Hematology Oncology Clinic Setting
Authors: Spikestein Ali , Musante Jordan , Huang Hsin-Hui , Stojanowski Morgan , Rode Diane , Pillai Pallavi , Crouch Gary D.
Published: November 2023

Background:

Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied.

Methods:

Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children’s Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures.

Results:

A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention (P=0.033).

Conclusions:

Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone.
Structure-decoupled functional connectome-based brain age prediction provides higher association to cognition
Authors: Chen Huan , Wang Haiyan , Yu Mingxia , Duan Bin
Published: November 2023

Brain age prediction as well as the prediction difference has been well examined to be a potential biomarker for brain disease or abnormal aging process. However, less knowledge was reported for the cognitive association within normal population. In this study, we proposed a novel approach to brain age prediction by structure-decoupled functional connectome. The original functional connectome was decomposed and decoupled into a structure-decoupled functional connectome using structural connectome harmonics. Our method was applied to a large dataset of normal aging individuals and achieved a high correlation between predicted and chronological age (r = 0.77). Both the original FC and structure-decoupled FC could be well-trained in a brain age prediction model. Significant remarkable relationships between the brain age prediction difference (predicted age minus chronological age) and cognitive scores were discovered. However, the brain age-predicted difference driven by structure-decoupled FC showed a stronger correction to the two cognitive scores (MMSE: r = −0.27, P-value = 0.002; MoCA: r = −0.32, P-value = 0.0003). Our findings suggest that our structure-decoupled functional connectivity approach could provide a more individual-specific functional network, leading to improved brain age prediction performance and a better understanding of cognitive decline in aging.
Detection of aac3IIc, aac(6)Ib and armA gene encoding aminoglycoside resistance in Klebsiella pneumoniae in Burkina Faso.

Authors: DJAGBARE Pamane , NADEMBEGA Christelle , ANDOGNABA Ursule Wendkèta , OBIRI-YEBOAH Dorcas , SIMPORE Jacques
Published: November 2023

BackgroundKlebsiella pneumoniae is the second most frequently isolated bacterium in medical bacteriology laboratory after Escherichia coli. It can be responsible for many infections including urinary tract infections and pneumonia. The treatment of these infections is often prolonged because of the resistance of this bacterium to antibiotics. The production of aminoglycoside-modifying enzymes and the production of RNA methylases confer resistance to aminoglycosides. In Burkina Faso, studies on bacterial resistance to aminoglycosides, an antibiotic regularly prescribed and consumed by patients, are limited, hence the purpose of this study was to determine the prevalence of aminoglycoside resistance genes in K. pneumoniae isolated from urine and pus samples.Methods and FindingsA total of 150 Klebsiella strains from pus and urine cultures were collected from October 2018 to June 2019 in two hospitals in Ouagadougou and were included in this study. After plating on Muller Hinton (MH) medium to obtain pure colonies, antibiotic susceptibility testing was performed with aminoglycosides, β-lactams, fluoroquinolones and sulfonamides. PCR testing for the phoE gene allowed genotypic identification of Klebsiella pneumoniae. PCRs were then performed on strains with at least one aminoglycoside resistance for identification of the aac(6')-Ib, aac(3)-IIc, and armA resistance genes.Antibiotic susceptibility testing showed that 38.67% (58/150) of the strains were resistant to Tobramycin, 28.67% (43/150) to Gentamicin, 10.00% (15/150) to Netilmicin, 8.67% (13/150) to Kanamycin, 4.67% (7/150) to Amikacin and 0.67% (1/150) to Neomycin. Of the 63 strains (42.66%) with at least one aminoglycoside resistance, the resistance genes, aac(3)-IIc and aac(6')-Ib were detected in 49 strains (77.77%) and 39 strains (61.90%), respectively; and 34 strains (53.97%) had both genes. Among the 16S rRNA genes, the armA gene was present in 19.04% of the strains (12/63).ConclusionAminoglycoside resistance in K. pneumoniae strains in this study is primarily due to aac(3)-IIc and aac(6')-Ib acetyltransferases. Although armA RNA methylases genes are less frequent, increased surveillance is necessary due to the high level of aminoglycoside resistance conferred by this gene.
dFLASH; dual FLuorescent transcription factor Activity Sensor for Histone integrated live-cell reporting and high-content screening
Authors: Allen Timothy P. , Roennfeldt Alison E. , Reckdharajkumar Moganalaxmi , Liu Miaomiao , Quinn Ronald J. , Russell Darryl L. , Peet Daniel J. , Whitelaw Murray L. , Bersten David C.
Published: November 2023

Live-cell reporting of regulated transcription factor (TF) activity has a wide variety of applications in synthetic biology, drug discovery, and functional genomics. As a result, there is high value in the generation of versatile, sensitive, robust systems that can function across a range of cell types and be adapted toward diverse TF classes. Here we present the dual FLuorescent transcription factor Activity Sensor for Histone integrated live-cell reporting (dFLASH), a modular sensor for TF activity that can be readily integrated into cellular genomes. We demonstrate readily modified dFLASH platforms that homogenously, robustly, and specifically sense regulation of endogenous Hypoxia Inducible Factor (HIF) and Progesterone receptor (PGR) activities, as well as regulated coactivator recruitment to a synthetic DNA-Binding Domain-Activator Domain fusion proteins. The dual-colour nuclear fluorescence produced normalised dynamic live-cell TF activity sensing with facile generation of high-content screening lines, strong signal:noise ratios and reproducible screening capabilities (Z’ = 0.68-0.74). Finally, we demonstrate the utility of this platform for functional genomics applications by using CRISPRoff to modulate the HIF regulatory pathway, and for drug screening by using high content imaging in a bimodal design to isolate activators and inhibitors of the HIF pathway from a ∼1600 natural product library.
Whole-genome Studies of Malagasy People Uncover Novel Body Composition Associations
Authors: Hamid Iman , Stéphie Raveloson Séverine Nantenaina , Spiral Germain Jules , Ravelonjanahary Soanorolalao , Raharivololona Brigitte Marie , Randria José Mahenina , Zafimaro Mosa , Randriambola Tsiorimanitra Aimée , Andriantsoa Rota Mamimbahiny , Andriamahefa Tojo Julio , Laza Rafidison Bodonomena Fitahiana , Mughal Mehreen , Emde Anne-Katrin , Hendershott Melissa , LeBaron von Baeyer Sarah , Wasik Kaja A. , Ranaivoarisoa Jean Freddy , Yerges-Armstrong Laura , Castel Stephane E. , Rakotoarivony Rindra
Published: November 2023

The majority of human genomic research studies have been conducted in European ancestry cohorts, at the loss of detecting potentially novel and globally impactful findings. Here, we present the first whole genome sequence data and genome-wide association study in a cohort of 264 Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands as well as elevated malaria prevalence in the West Coast relative to other sites. We find a number of genetic associations with body composition traits, including many variants that are unique to African populations or populations with admixed African ancestry such as Madagascar. This study highlights the utility of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local Malagasy stakeholders and serves as an example for equitable genomic research with potential impacts on our understanding of human health and disease.
Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso
Authors: Hanley-Cook Giles T. , Bastos-Moreira Yuri , Martens Dries S. , Dailey-Chwalibóg Trenton , Toe Laeticia Celine , de Kok Brenda , Ouédraogo Lionel , Argaw Alemayehu , Tesfamariam Kokeb , Kolsteren Patrick , Huybregts Lieven , Nawrot Tim S. , Saeger Sarah De , De Boevre Marthe , Lachat Carl
Published: November 2023

Background

Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease, such as offspring telomere length (TL) and mitochondrial DNA content (mtDNAc) is unknown.

Objectives

We assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.

Design

We conducted a randomized controlled trial in rural Burkina Faso, among pregnant females (15-40 years old) enrolled at <21 weeks of gestation. Mothers received either MMN-fortified BEP and IFA (intervention) or IFA only (control) throughout pregnancy. Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants, respectively. Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction. Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.

Results

We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL [β = -0.010 (95% CI: -0.057, 0.036);P= 0.662] or mtDNAc [β = 0.065 (95% CI: -0.203, 0.073);P= 0.354], as compared to an IFA tablet alone. These findings were confirmed (P>0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher, but non-significantly different mtDNAc among children born either small-for-gestational age, low birthweight, or preterm.

Conclusions

Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.
How side effects can improve treatment efficacy: a randomized trial
Authors: Schenk Lieven A. , Fadai Tahmine , Büchel Christian
Published: November 2023

While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes.

In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (control). Following the initial phase, participants were randomized to two groups and underwent functional magnetic resonance imaging (fMRI). One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief.

Our results revealed that nasal sprays with a side effect lead to lower pain than control nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. FMRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects.

In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.
AP-1 regulates heterogeneous cellular dormancy in TNBC
Authors: Dong Yang , Bai Jin , Fu Rong , Su Huilan , Wu Shan , Tang Dean G. , Zhou Jianjun
Published: November 2023

Dormant or slow cycling cells (SSCs) pre-exist in tumor and responsible for chemo-resistant and tumor recurrence. Label retaining is a common method to obtain live SCCs from tumor. Different label retaining methods have been developed, but there still haven’t been reported whether different label retaining methods would result in same or different population of SCCs. We have utilized three label retaining methods simultaneously and identified overlapping but non-identical subpopulations of SCCs. These SCCs have similar yet different phenotypes in cell cycle, detoxification, motility and most importantly chemo-resistance. Gene profile shows three subpopulations of SCCs share similar gene expression pattern, and AP-1 subunit JunB overexpression is a key regulator of cellular dormancy. Inhibition of AP-1 could reduce drug resistance and tumor recurrence caused by SCCs, makes it a potential drug target for SCC elimination that could Improve patients’ survival.
The physiological costs of spatial positioning and leadership in collective movements
Authors: Brandl H. B. , Klarevas-Irby J.A. , Zuniga D. , Wheat C. Hansen , Christensen C. , Omengo F. , Nzomo C. , Cherono W. , Nyaguthii B. , Farine D. R.
Published: November 2023

Forming collectives can generate substantial benefits, but much less is known about the costs that individuals incur in doing so. We simultaneously captured individual movement, within-group position, leadership, and heart rate for each member in a group of wild vulturine guineafowl. Individuals had significantly increased heart rates when moving collectively, occupying more central positions within the group, or attempting to initiate directional movement when consensus among group members was low. Such cardiac system activation can be indicative of physiological stress, entailing increased energy expenditure and long-term physiological damage. Thus, individuals paid the highest physiological costs in situations where theory predicts the benefits of collective behaviours should be greatest, revealing a hidden trade-off of social living.
Fast and accurate disulfide bridge detection
Authors: Heissel Søren , He Yi , Jankevics Andris , Shi Yuqi , Molina Henrik , Viner Rosa , Scheltema Richard A.
Published: November 2023

Recombinant expression of proteins, propelled by therapeutic antibodies, has evolved into a multi-billion-dollar industry. Essential here is quality control assessment of critical attributes such as sequence fidelity, proper folding, and post-translational modifications (PTMs). Errors can lead to diminished bioactivity and, in the context of therapeutic proteins, an elevated risk for immunogenicity. Over the years, many techniques were developed and applied to validate proteins in a standardized and high-throughput fashion. One parameter has, however, so far been challenging to assess. Disulfide bridges, covalent bonds linking two Cysteine residues, assist in the correct folding and stability of proteins and thus have a major influence on their efficacy. Mass spectrometry promises to be an optimal technique to uncover them in a fast and accurate fashion. In this work, we present a unique combination of sample preparation, data acquisition and analysis facilitating the rapid and accurate assessment of disulfide bridges in purified proteins. Through microwave-assisted acid hydrolysis (MAAH), the proteins are digested rapidly and artifact-free into peptides, with a substantial degree of overlap over the sequence. The nonspecific nature of this procedure, however, introduces chemical background which is efficiently removed by integrating ion mobility preceding the mass spectrometric measurement. The nonspecific nature of the digestion step additionally necessitates new developments in data analysis, for which we extended the XlinkX node in Proteome Discoverer (XlinkX/PD) to efficiently process the data and ensure correctness through effective false discovery rate correction. The entire workflow can be completed within one hour, allowing for high-throughput, high-accuracy disulfide mapping.
Can Colpoda travel across oceans? Salinity tolerance of resting cysts may enable global dispersal of the species.
Authors: Saito Ryota , Yamanobe Hiroki , Yabuki Kazuma , Suzuki Tomohirro , Saito Takeru , Hakozaki Shuntaro , Wanner Manfred , Koizumi Ryota , Sakai Tatsuya , Maribet Gamboa , Tanaka Toshihiko , Ono Akiko , Nguyen Hoa Thanh , Saito Yuta , Aoyama Tetsuya , Kojima Katsuhiko , Suizu Futoshi , Watanabe Kozo , Sogame Yoichiro
Published: November 2023

Protist species are distributed worldwide. The processes that enabled this global distribution are unclear. One possible means is through the oceanic dispersal of freshwater protists, although this has not been investigated in detail to date. Here, the ability of resting cysts to tolerate saline conditions is examined as a possible mechanism that enables the oceanic dispersal of protists. Resting cysts of Colpoda cucullus, a freshwater soil protist, can tolerate saline conditions of at least 3.5% NaCl for more than one week. A transcriptome analysis showed that the relative levels of expression of genes associated with membrane function are increased in resting cysts, indicating that salinity tolerance is associated with reconstruction of the cell membrane. Additionally, the outer layer of the cyst wall, a shell-like ectocyst, includes chitin. This may function as a form of biological armor that protects the cell from physical stress during oceanic dispersal.