bluuebunny/crossref_metadata_2025 huggingface dataset:
Laryngeal contrasts in Hadza occlusives
Authors: Coburn Jeremy R.
Published: April 2023

Laryngeal contrasts in consonants are found in nearly all languages. Two-way laryngeal contrasts are common in western European languages, and three- and four-way systems are attested, for example, in many South Asian languages. The current study presents acoustic data on laryngeal contrasts in Hadza, a language isolate spoken by ∼1200 people (Brian Wood, pc.) in Tanzania. Hadza contains multiple complex consonant types, including clicks and ejectives, as well as aspiration and prenasalization. Some previous descriptions suggested a three-way contrast in stops (e.g., /t tʰ d/) and affricates (e.g., t⌢s t⌢sʰ d⌢z), and also a two-way contrast in clicks (e.g., /! !ʰ/) (Tucker et al., 1977; de Voogt, 1992), but did not offer corroborating phonetic evidence. Sands et al. (1996) documented the expected distinction in Voice Onset Time (VOT) between voiceless unaspirated and aspirated stops, but they did not find VOT differences for clicks or affricates. Using wordlist data collected in 2022, this study presents temporal measurements, including VOT, to examine the phonetic properties of laryngeal contrasts in Hadza occlusives and, especially, to evince an aspiration contrast in affricates and clicks previously unsubstantiated in the literature. These results resolve discrepancies between past research and further elucidate the laryngeal system of Hadza.
Revisiting listener evaluations of creaky voice
Authors: Bellavance Sarah R. , Levi Susannah V.
Published: April 2023

In U.S. English, nonpathological creaky voice is a common and natural voice quality that contributes meaningful linguistic information. However, it is also a target of gender-based prejudice, with studies suggesting that speakers with creak sound less hirable and less pleasant. Unfortunately, the stimuli in these studies were often problematic (e.g., creak present in both creaky and modal stimuli; unusually high proportions of creak). To address these problems, we carefully selected naturallyproduced, low predictability sentences. Half of these contained creak on the final word (a common location for creak in both men and women speakers) and half did not. Listeners rated half of the sentences on a hirability scale and half on a pleasantness scale. They then completed an implicit association task regarding gender and career roles. Consistent with previous research, sentences with creak were rated as being produced by speakers who were less hirable than those without creak. Similar to previous findings, older listeners rated stimuli with creak as less pleasant than stimuli without creak. Implicit association scores did not predict ratings on either rating scale. Contrary to our expectations, less favorable evaluations of creak were found despite using naturallyproduced sentences with only sentence-final creak.
Studying the glottal vibration onset and offset using laryngeal high-speed videoendoscopy in connected speech
Authors: Naghibolhosseini Maryam , Henry Trent M. , Zacharias Stephanie R. , Deliyski Dimitar
Published: April 2023

Laryngeal high-speed videoendoscopy (HSV) is a powerful tool to study the detailed vibratory characteristics of the vocal folds. The use of HSV in connected speech enables us to study the transitory behaviors of the vocal folds during different vocalizations. The onset and offset of voicing contain critical information about the health and function of the vocal folds. In this work, HSV is used to study how the voicing begins/ends at the laryngeal level at the onset/offset of phonation. HSV data were obtained during production of connected speech from participants with non-pathological voices and patients with different neurogenic voice disorders. The data collection was performed using a Photron FASTCAM mini AX200 high-speed camera coupled with a flexible nasolaryngoscope. The glottal attack time and glottal offset time were measured at the onset and offset of different vocalizations, respectively, from the HSV data. The findings show differences in the onset and offset measures between the two groups of participants. The vocal fold vibratory behaviors will be discussed qualitatively and quantitatively using these measures. The use of HSV in connected speech could help us develop accurate voice assessment procedures to assess the vocal folds function during connected speech.
Applying machine learning algorithms for stuttering detection
Authors: Filipowcz Piotr , Kostek Bozena
Published: April 2023

This work aims to develop algorithms designed to detect stuttering in speech signals effectively. The background of this speech disorder is given with particular attention paid to its subcategories, i.e., extensions, blocks, sound repetitions, word repetitions, and interjections. A review of state-of-the-art machine learning-based approaches to detect and classify stuttering is presented. A deep model capable of detecting stuttering in the speech signal at the f1 measure level of 0.93 for the general class is built. Also, two baseline algorithms, i.e., Support vector machine (SVM) and k-nearest neighbors (kNN), are implemented to compare their efficiency with a residual neural network outcome. In addition, a series of experiments are conducted to study the impact of elements such as model architecture, data partitioning, amount of data, or use of individual features. The results obtained for the different categories of stuttering differ significantly due to the size of each subclass in the datasets used for the study and the annotation quality.
Leveling of /o/ in Raleigh
Authors: Lundergan Sean
Published: April 2023

Beginning in the late 1950s, Raleigh, North Carolina, experienced high levels of in-migration from areas outside of the South. The resulting dialect contact led to leveling of many Southern features, including the Southern Vowel Shift. Change in the front vowel system of Raleigh has been the subject of many studies, but back vowels get less attention. Back vowel fronting is a widespread phenomenon in American English, but whereas back vowels in other regions are back-gliding, much of the South also fronted glides. This study investigates the change in /o/ (GOAT) in Raleigh during the 20th century, using sociolinguistic interview data from NC State’s Raleigh corpus. The findings suggest that where previously /o/ was front- and upgliding, it now has a backward trajectory with little vertical movement. This is in line with previous findings of southern and non-southern variants of back vowels in the urban South and adds to our understanding of leveling in Raleigh. It also suggests future directions for research into the drivers of back vowel fronting.
Syllable position effects on English dark and light /l/ in comparison to /s/
Authors: Lombardo Danilo A. , Whalen D. H. , Chen Wei-Rong , Shadle Christine H.
Published: April 2023

Effects of syllable position on the acoustic structure of speech sounds have been explored for different consonants, particularly for the lateral approximant /l/ in American English (AE). Sproat and Fujimura [J. Phonetics 21, 291–311 (1993)] reported that /l/’s spectral properties vary between initial (light) and final (dark) position, as in [l]ease vs. sea[ɫ]; this has been replicated in other studies. A similar effect was found for the fricative /s/ [Lombardo et al., J. Acoust. Soc. Am. 151, A45 (2022)], though the acoustic measures necessarily differed. We explored whether the magnitude of a light/dark difference varies by syllable position in AE words with both /s/ and /l/. Preliminary results show that the magnitude of positional differences for /l/ was uncorrelated with that of the /s/. Like previous studies, the positional effect for /l/ occurred with all vowels. Our measures are distinct acoustically (formants during the lateral resonance versus both peak frequency and the amplitude of mid-to-high frequencies during the fricative); therefore, the inconsistency may be due to measurement factors. Alternatively, the physiological mechanism may differ enough that speakers themselves differ; or, indeed, /l/ differences may be phonologized while the /s/ differences are not.
Gasp! The reality of ingressive speech in contemporary French
Authors: Gilbert Jane
Published: April 2023

Pulmonic ingressive speech, the use of an inhalation airstream in speech, serves a set of similar paralinguistic functions in a wide variety of languages (Eklund, 2007). This phenomenon is most closely associated with Swedish and related languages (Eklund, 2008), affirmative particles (Eklund, 2007), and female speakers (Clarke andMelchers, 2005). It is known to be highly interactive and therefore difficult to elicit (Eklund, 2002). While acknowledged to exist in French, particularly used by women on the word oui “yes” when expressing “reticence” (Léon, 1992), this mode of articulation and its uses have yet to be described systematically in that language. In this study, we extracted all tokens of ingressive oui produced spontaneously over one season (338 min) of the reality television series L’Agence, yielding 14 tokens. A detailed analysis of each in context, combined with observations from native speaker use and additional discourse-pragmatic observations from the study data, suggests that ingressive oui is used more often by men, is restricted to a semi-professional middle register, and is associated with final vowel devoicing, another known French phenomenon (Dalola, 2014). These data further indicate that, though rarer, ingressive oui is more perceptually salient when pronounced by a female speaker.
Effect of speaking style and word length on V-to-V coarticulation in child and adult speech
Authors: Redford Melissa A. , Diantoro Carissa A.
Published: April 2023

Anticipatory vowel-to-vowel coarticulation indexes both the coherence of adjacent syllables in the speech plan and the relative “segmentalness” of articulation. In this study, speaking style and word length were manipulated to disrupt default production strategies and thereby identify age-related differences in planning and articulation between adults’ and 8-year-old children’s speech. Preliminary results indicate an anticipatory effect on schwa F1 and F2 in adults’ speech across styles. The same effect was also observed on F1 in children’s speech regardless of style, but the effect on schwa F2 was stronger when the target was in focus. There were also systematic effects of word length on F1 and F2 across both groups. For F1, unstressed vowels before one- and two-syllable words were more similar (more closed) than within four-syllable words; whereas, for F2, unstressed vowels were more similar (less fronted) before two-syllable words or within four-syllable words than before one-syllable words. Overall, neither speaking style nor word length appears to significantly disrupt the articulatory coherence of adjacent syllables in child or adult speech, but there is some indication ofgreater underlying coherence between syllables in children’s speech compared to adults’ speech. [Work supported by NICHD grant #R01HD087452.]
Improving signal-to-noise ratio in ultrasound video pixel difference
Authors: Palo Pertti , Lulich Steven M.
Published: April 2023

Pixel difference is a holistic change measure for ultrasound videos and other image sequences. It is based on Euclidean distance (l2 norm) which is calculated by interpreting each frame as a vector of pixels. Recently, we found that 3D/4D ultrasound data producesignificantly worse signal-to-noise ratio in Pixel Difference curves, which appears to be primarily due to the lower frame rate of 3D/4D ultrasound when compared with 2D ultrasound. We also found that the signal-to-noise ratio is improved when we limit the analysis to tongue-internal pixels. In this study, we seek to quantify the timing behavior of tongue gestures obtained from whole-image and tongue-internalPD. If the timing behavior is similar in both cases, we can increase the signal to noise ratio of 3D/4D ultrasound at the same time as we increase its frame rate, because imaging to a shallower depth requires less time per frame. We also examine the signal-to-noise behavior of PD curves calculated with other norms (e.g., l1, and l3 norms).
An exploration of mixed race and the California Vowel Shift
Authors: Fong Kaela
Published: April 2023

The California Vowel Shift (CVS) has been the study of much acoustic linguistic inquiry since it was first noted in the 1980s. It has since been grouped in with other like patterns which have arisen independently under the name, Low-Back-Merger-Shift (LBMS), though California will be the focus of the present study. The current study builds on previous literature by investigating acoustic vowel quality within a neighborhood in San Francisco, while also working to fill the gap of studies which take into account and specifically highlight mixed race peoples. Using vowel F1 and F2 measurements taken from informal interviews with 27 speakers from The Sunset district in San Francisco, a primarily white and Asian neighborhood, the vowel spaces of these speakers were examined. The aim of this project was to determine if racial/ethnic status as monoracial (Asian or White) or mixed-race had a significant effect on speakers' vowel quality and their level of participation in the CVS. Quantitative analysis found that speakers' vowel systems do exhibit the characteristics of CVS. For the back vowels /ɑ/, /ɔ/, /ʌ/, /ʊ/, /u/, and /o/ difference between speakers of mixed race and their white counterparts were found to be statistically significant.
ALMA 2022 experiment : Source paramater estimation comparison betweenLFM and MLS waveforms
Authors: Real Gaultier , Gemba Kay L. , Lamy Kathrine , Kacel Thomas
Published: April 2023

For underwater source localization, accurate estimation of the time of flight (or travel time) is required and the observed waveform may include Doppler (waveform dilation). The source waveform, thus, needs to be sensitive to estimate both time of flight and Doppler. In this study, we compare two waveforms : Linear Frequency Modulated sweeps (LFMs) and Maximum Length Sequences (MLSs) with identical center frequency (6 kHz) and bandwidth (2 kHz). During an at-sea experiment conducted in March 2022 near in the Mediterranean Sea, near the coast of Toulon, a mobile source transmitted the two waveforms, recorded by a 192-hydrophone moored bilboard array. The source-array distance ranged from 2.5 to 8 km, and the source was towed at a constant speed (∼1.5 m/s) and depth (∼50m). The analysis of the gathered data shows that the MLS waveform outperforms the LFM waveform for estimating time of flight (uncertainty reduced by a factor 4) and radial velocity (uncertainty reduced by a factor 20). Preliminary results focus on single hydrophone processing, but possible applications to 2D array processing are discussed for localizing the source in range-dependent environments.
An architecture for passive joint localization and environment learning in shallow-water underwater acoustic settings
Authors: Arikan Toros , Weiss Amir , Vishnu Hari , Deane Grant B. , Singer Andrew C. , Wornell Greg
Published: April 2023

Passive localization and tracking of a mobile emitter, and joint learning of its reverberant 3D environment, is a challenging task in various application domains. In underwater acoustic monitoring with a receiver array, for example, a submarine may need to be tracked in a setting with natural and man-made obstacles, such as seamounts or piers. If such obstacles occlude the line of sight from this vessel to the receivers, then the non-line of sight reflected arrivals from the reverberant environment must be leveraged for localization. Hence, we need to precisely map these reflective features in order to deliver robust performance. We propose a multi-stage global optimization and tracking architecture to approach this problem. Each stage of this architecture establishes domain knowledge such as synchronization and occluder mapping, which are inputs for the following stages of more refined algorithms. This approach is generalizable to different physical scales, and improves on methods that do not exploit emitter motion. We further introduce a robust neural network-based reflector estimation method that outperforms its alternatives in realistic application settings. The performance of this holistic approach is analyzed and its reliability is demonstrated both in simulation and in a real-life reverberant watertank, which models shallow-water acoustic environments.
Subsurface acoustic ducts in the Northern California Current System
Authors: Xu Guangyu , Harcourt Ramsey R. , Tang Dajun , Hefner Brian T. , Thorsos Eric I. , Mickett John B.
Published: April 2023

A survey of sound speed profiles obtained from archived mooring and glider observations over the continental shelf, slope, and further offshore along the U.S. Pacific Northwest coastline reveals a shallow subsurface duct that appears at depths below the mixed layer. Sound propagation simulations using parabolic equation techniques demonstrate that the presence of the duct has a strong impact on sound propagation at 3.5 kHz. The duct is more prevalent in summer to fall than in winter to spring and extends to at least 200 km offshore from the shelf break. The depth of the minimum sound speed of the duct decreases onshore from between 80 m and 100 m offshore of the continental slope to less than 60 m over the shelf. The duct is also more prevalent offshore of the shelf break than over the shelf. Two processes potentially contribute to the formation of the subsurface duct: (1) differential advection of water masses driven by large-scale circulation within the northern California Current Systemand (2) wintertime surface cooling and convective deepening of the surface mixed layer. Data analysis conducted in this study suggests that the former is likely the dominant mechanism. [Work supported by the Office of Naval Research.]
Modal structure of the sound field in a shallow-water waveguide with a gassy sediment layer: Experiment and theory
Authors: Yarina Marina , Katsnelson Boris , Godin Oleg A.
Published: April 2023

Motivated by a series of experiments in the Lake Kinneret (Israel), the paper investigates low-frequency sound propagation in the three-layer model of the shallow water waveguide, where a thin layer of gas-saturated sediment is situated between a homogeneous fluid sub-bottom and a continuously stratified water column. Typical values of the thickness and sound speed in the gassy layer are 1 m and 250 m/s. The layer is thin compared to typical water depth of about 40 m. Normal mode structure of the acoustic field is analyzed. It is shown that with increasing frequency each normal mode transforms into a mode trapped in the gassy layer. These modes have unusually small phase and group speeds that are significantly less than the sound speed in water. Theoretically predicted normal mode dispersion curves are compared to the dispersion curves retrieved from observations of shipping noise. Phase speeds of normal modes are measured by cross-correlatingthe noise recorded on two sparse vertical arrays. A technique is proposed for solving the inverse problem of determining the parameters of a gas-saturated layer by matching the measured and modeled frequency dependencies of the normal mode phase speed.
Scattering statistics of nonstationary seafloors: Mixture models and choosing the number of components
Authors: Olson Derek
Published: April 2023

Modern high resolution synthetic aperture sonars are capable of resolving the structure of patchy seafloors, defined as seafloors having non-stationarygeoacoustic and roughness properties. Within each patch, it is often possible to model the amplitude statistics using commonly used physics based statistical models, such as the K-distribution. However, it is impossible to use on a large scale because either the parameters change from patch to patchor the imaging sonar alters the scattering statistics at different ranges. Here, we propose a method to segment different patches in a sonar image using a mixture of physicallymotivated statistical models. We detail how the number of components can be chosen using Bayesian model selection techniques, such as the deviance information criterion. The tradeoff between model accuracy and robustness is explored using a dataset provided by the Norwegian Defence Research Establishment.
Comparison of imaging techniques for the analysis of bubble distribution in ship wakes
Authors: Bae Ho Seuk , Kim Won-Ki , Son Su-Uk
Published: April 2023

Ship wakes, which are inevitably caused by ship movement, are a subject of great interest for military purposes. In this study, we created an underwater acoustic signal measuring device to characterize the distribution of wakes from a ship maneuvering in a real ocean environment. Two sets of multi-array sonar systems consisting of multiple projectors and multiple hydrophones were fabricated to acquire underwater acoustic signals. The systems were then placed vertically at a certain distance from each other in the sea. Afterward, we stably acquired the transmitted and scattered signals from the bubble wake generated by an actual ship. The distribution of bubbles in the ship's wake was then imaged by applying the RTM (reverse-time migration) and WI (waveform inversion) numerical analysis techniques to image the bubble distribution in the ship wake. Finally, the results obtained using the two aforementioned techniques were analyzed and compared.
Mechanisms Underlying Menstrual Cycle Effects on Exercise Performance: A Scoping Review
Authors: Bernstein Christine , Behringer Michael
Published: April 2023

This scoping review aims to provide a comprehensive overview of biological mechanisms underlying the menstrual cycle’s impact on various performance-determining anatomical and physiological parameters. It is intended to identify the various proposed vital concepts and theories that may explain performance changes following hormonal fluctuations. The review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol. A framework of six groups was built such as skeletal muscle physiology, muscle damage, tendons and ligaments, neuromuscular control, cardiovascular system, and exercise metabolism to cluster studies thematically and to specify the concept of “performance.” Original research studies published between 1970 and 2021 that were conducted with a naturally menstruating population were considered. Changes in performance regarding the menstrual cycle phase were crucial for inclusion. Topic-specific reviews and systematic reviews were included if they addressed the impact of female steroid hormones on any structure or part of the human body. The review indicates that the impact of estrogen and progesterone is primarily responsible for observed changes in athletic performance during the menstrual cycle. Estrogen seems capable of fostering protein synthesis, diminishing collagen metabolism, preventing muscle damage due to its antioxidant effects, and restraining inhibitory, while promoting excitatory, control by interacting with neurotransmitters. Progesterone is assumed to increase thermoregulation and enhance ventilatory drive by interacting with hypothalamic pathways and may further amplify inhibitory control by interacting with neurotransmitters. The female steroid hormones and the endocrinologic system collaborate in complex interrelationships with biological systems to maintain homeostasis. However, proposed mechanisms are often derived from animal studies and studies conducted in vitro and still remain to be proven true in the human regularly menstruating population. In the future, it is crucial to rely on studies that followed the methodology for cycle monitoring recommendations thoroughly. Otherwise, it is not possible to determine whether hormonal fluctuations cause observed changes in performance or not.
Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish
Authors: Patterson Victoria , Ullah Farid , Bryant Laura , Li Dong , Griffin John N. , Sidhu Alpa , Saliganan Sheila , Blaile Mackenzie , Saenz Margarita S. , Smith Rosemarie , Ellingwood Sara , Grange Dorothy K. , Hu Xuyun , Mireguli Maimaiti , Luo Yanfei , Shen Yiping , Mulhern Maureen , Zackai Elaine , Ritter Alyssa , Izumi Kosuke , Hoefele Julia , Wagner Matias , Riedhammer Korbinian M. , Seitz Barbara , Robin Nathaniel H. , Goodloe Dana , Mignot Cyril , Keren Boris , Cox Helen , Jarvis Joanna , Hempel Maja , Gibson Cynthia Forster , Tran Mau-Them Frederic , Vitobello Antonio , Bruel Ange-Line , Sorlin Arthur , Mehta Sarju , Raymond F. Lucy , Gilmore Kelly , Powell Bradford C. , Weck Karen , Li Chumei , Vulto-van Silfhout Anneke T. , Giacomini Thea , Mancardi Maria Margherita , Accogli Andrea , Salpietro Vincenzo , Zara Federico , Vora Neeta L. , Davis Erica E. , Burdine Rebecca D. , Bhoj Elizabeth
Published: April 2023

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in
mitogen-activated protein kinase kinase kinase kinase 4
(
MAP4K4
). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects. Furthermore, MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. Together, our data demonstrate that MAP4K4 negatively regulates RAS signaling in the early embryo and that variants identified in affected humans abrogate its function, establishing
MAP4K4
as a causal locus for individuals with syndromic neurodevelopmental differences.
High-temperature low-humidity proton exchange membrane with “stream-reservoir” ionic channels for high-power-density fuel cells
Authors: Guan Panpan , Zou Yecheng , Zhang Ming , Zhong Wenkai , Xu Jinqiu , Lei Jianlong , Ding Han , Feng Wei , Liu Feng , Zhang Yongming
Published: April 2023

The perfluorosulfonic acid (PFSA) proton exchange membrane (PEM) is the key component for hydrogen fuel cells (FCs). We used in situ synchrotron scattering to investigate the PEM morphology evolution and found a “stream-reservoir” morphology, which enables efficient proton transport. The short-side-chain (SSC) PFSA PEM is fabricated under the guidance of morphology optimization, which delivered a proton conductivity of 193 milliSiemens per centimeter [95% relativity humidity (RH)] and 40 milliSiemens per centimeter (40% RH) at 80°C. The improved glass transition temperature, water permeability, and mechanical strength enable high-temperature low-humidity FC applications. Performance improvement by 82.3% at 110°C and 25% RH is obtained for SSC-PFSA PEM FCs compared to Nafion polymer PEM devices. The insights in chain conformation, packing mechanism, crystallization, and phase separation of PFSAs build up the structure-property relationship. In addition, SSC-PFSA PEM is ideal for high-temperature low-humidity FCs that are needed urgently for high-power-density and heavy-duty applications.
On-skin biosensors for noninvasive monitoring of postoperative free flaps and replanted digits
Authors: Wu Hao , Li Zhuo , Xu Zhao , Huang Xin , Guo Wei , Zhao Jun , Zhang Jinwen , Liu Shaoyu , Tang Miao , Qiu Yuqi , Yang Ganguang , Zhu Juntong , Liu Lili , Wu Yingjie , Lei Wei , Zhou Pan , Yin Zhouping , Chen Zhenbing , Liu Yutian
Published: April 2023

Severe soft tissue defects and amputated digits are clinically common injuries. Primary treatments include surgical free flap transfer and digit replantation, but these can fail because of vascular compromise. Postoperative monitoring is therefore crucial for timely detection of vessel obstruction and survival of replanted digits and free flaps. However, current postoperative clinical monitoring methods are labor intensive and highly dependent on the experience of nurses and surgeons. Here, we developed on-skin biosensors for noninvasive and wireless postoperative monitoring based on pulse oximetry. The on-skin biosensor was made of polydimethylsiloxane with gradient cross-linking to create a self-adhesive and mechanically robust substrate that interfaces with skin. The substrate was shown to exhibit appropriate adhesion on one side for both high-fidelity measurements of the sensor and low risk of peeling injury to delicate tissues. The other side demonstrated mechanical integrity to facilitate flexible hybrid integration of the sensor. Validation studies using a model of vascular obstruction in rats demonstrated the effectiveness of the sensor in vivo. Clinical studies indicated that the on-skin biosensor was accurate and more responsive than current clinical monitoring methods in identifying microvascular conditions. Comparisons with existing monitoring techniques, including laser Doppler flowmetry and micro-lightguide spectrophotometry, further verified the sensor’s accuracy and ability to identify both arterial and venous insufficiency. These findings suggest that this on-skin biosensor may improve postoperative outcomes in free flap and replanted digit surgeries by providing sensitive and unbiased data directly from the surgical site that can be remotely monitored.
Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a
TREM2
-dependent manner in mice
Authors: Parhizkar Samira , Gent Grace , Chen Yun , Rensing Nicholas , Gratuze Maud , Strout Gregory , Sviben Sanja , Tycksen Eric , Zhang Qiang , Gilmore Petra Erdmann , Sprung Robert , Malone Jim , Chen Wei , Remolina Serrano Javier , Bao Xin , Lee Choonghee , Wang Chanung , Landsness Eric , Fitzpatrick James , Wong Michael , Townsend Reid , Colonna Marco , Schmidt Robert E. , Holtzman David M.
Published: April 2023

Sleep loss is associated with cognitive decline in the aging population and is a risk factor for Alzheimer’s disease (AD). Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-β (Aβ) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice. We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression. Sleep deprivation not only enhanced TREM2-dependent Aβ plaque deposition compared with 5xFAD mice with normal sleeping patterns but also induced microglial reactivity that was independent of the presence of parenchymal Aβ plaques. We investigated lysosomal morphology using transmission electron microscopy and found abnormalities particularly in mice without Aβ plaques and also observed lysosomal maturation impairments in a TREM2-dependent manner in both microglia and neurons, suggesting that changes in sleep modified neuro-immune cross-talk. Unbiased transcriptome and proteome profiling provided mechanistic insights into functional pathways triggered by sleep deprivation that were unique to TREM2 and Aβ pathology and that converged on metabolic dyshomeostasis. Our findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further Aβ deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.
Cecal Microbiota Development and Physiological Responses of Broilers Following Early Life Microbial Inoculation Using Different Delivery Methods and Microbial Sources
Authors: Marcolla Camila S. , Ju Tingting , Willing Benjamin P.
Published: April 2023

The strict biosecurity procedures employed in the poultry industry may inadvertently hinder the transmission of beneficial commensal bacteria that chickens would encounter in natural environments. This research aims at identifying bacteria that can colonize and persist in the chicken gut after a single exposure.
Draft Genome Sequences of Pseudomonas Isolates Derived from Glyphosate-Treated Sediments
Authors: Cadavillo Sabryna C. , Stroud Morgan P. , Newman Madison , Zigic Jovan , Roman Samuel D. , Connors Bernadette J.
Published: April 2023

Reported here are the genome sequences of
Pseudomonas
isolates that were derived from glyphosate-treated sediment microcosms. Genomes were assembled using workflows available through the Bacterial and Viral Bioinformatics Resource Center (BV-BRC). The genomes of eight
Pseudomonas
isolates were sequenced, with genomes ranging from 5.9 to 6.3 Mb.
Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
Authors: Lee Jaewoong , Nguyen Ngoc-Tu , Tran Le-Minh , Kim Yang-Hoon , Min Jiho
Published: April 2023

The phage display method was used to select peptides with high affinity and specificity for
S. aureus
, and these peptides were then induced to be expressed on the surface of yeast vacuoles. These surface-modified vacuoles can act as drug carriers, with drugs such as the lipopeptide antibiotic daptomycin loaded inside.
Insight into the Antibacterial Action of Iodinated Imine, an Analogue of Rafoxanide: a Comprehensive Study of Its Antistaphylococcal Activity
Authors: Krátký Martin , Konečná Klára , Janďourek Ondřej , Diepoltová Adéla , Vávrová Pavlína , Voxová Barbora , Vejsová Marcela , Bárta Pavel , Bősze Szilvia
Published: April 2023

Antibiotic resistance is among the largest threats to global health, with a potentially serious socioeconomic impact. One of the strategies to deal with the predicted catastrophic future scenarios associated with the rapid emergence of resistant infectious agents lies in the discovery and research of new anti-infectives.
New Perspectives on Escherichia coli Signal Peptidase I Substrate Specificity: Investigating Why the TasA Cleavage Site Is Incompatible with LepB Cleavage
Authors: Musik Joanna E. , Poole Jessica , Day Christopher J. , Haselhorst Thomas , Jen Freda E.-C. , Ve Thomas , Masic Veronika , Jennings Michael P. , Zalucki Yaramah M.
Published: April 2023

Signal peptidase I is an important drug target, and understanding its substrate is critically important to develop new bacterium-specific drugs. To that end, we have a unique signal peptide that we have shown is refractory to processing by LepB, the essential signal peptidase I in
E. coli
, but previously has been shown to be processed by a more human-like signal peptidase found in some bacteria.
Mechanisms of the Specificity of the CRISPR/Cas9 System in Genome Editing
Authors: Kulishova L. M. , Vokhtantsev I. P. , Kim D. V. , Zharkov D. O.
Published: April 2023

The CRISPR/Cas9 system, which was discovered recently, utilizes nucleases targeted by sequence complementarity and is originally intended to protect bacteria from foreign genetic elements. The system provided a convenient tool for manipulating the genomes of living cells. The CRISPR/Cas9 genomic editing technology moved beyond the laboratory and already found application in biotechnology and agriculture. However, off-target activity of the CRISPR/Cas9 system can cause oncogenic mutations and thus limits its use for genome editing in human cells for medical purposes. Many studies are therefore aimed at developing variants of the CRISPR/Cas9 system with improved accuracy. The review considers the mechanisms of precise and erroneous actions of Cas9 RNA-guided nuclease, natural and artificial variants of RNA-targeted nucleases, possibilities to modulate their specificity through guide RNA modifications, and other approaches to increasing the accuracy of the CRISPR/Cas9 system in genome editing.
Modern Approaches to Protein Engineering to Create Enzymes with New Catalytic Properties
Authors: Tyugashev T. E. , Fedorova O. S. , Kuznetsov N. A.
Published: April 2023

Adenine-DNA-glycosylase MutY is a monofunctional enzyme and catalyzes hydrolysis of N-glycosidic bonds with adenine residues located opposite 8-oxonuanine residues in DNA. Rational design was carried out to construct mutant enzyme forms with altered catalytic activity. Structures of the MutY mutants were calculated by molecular dynamics (MD). Their analysis showed that some of the MutY mutants may have AP lyase activity in addition to hydrolyzing the N-glycosidic bond, as is the case with bifunctional DNA glycosylases. MutY mutants with the A120K or S124K substitution were obtained by site-directed mutagenesis, and their catalytic activities were determined. The S120K substitution was shown to confer additional AP lyase activity, while the A124K substitution completely inactivated the enzyme.
Making sense of the paediatric ECG: ST segments
Authors: Harris Michael , Oakley Chris
Published: April 2023

This is a follow on article on different aspects of paediatric ECG interpretation.
Interstitial ectopic pregnancy successfully treated with methotrexate
Authors: Dunphy Louise , Haresnape Charlotte , Furara Samira
Published: April 2023

An ectopic pregnancy (EP) occurs when the fertilised ovum implants outside the endometrial cavity. An EP has an incidence of 1%, with the majority occurring in the fallopian tube. It has a maternal mortality of 0.2 per 1000, with about two-thirds of these deaths associated with substandard care. An interstitial pregnancy occurs when the EP implants in the interstitial part of the fallopian tube. An interstitial ectopic pregnancy (IEP) shows few early clinical symptoms, hence it is associated with serious or fatal bleeding and a mortality rate up to 2.5%. With the advent of transvaginal ultrasound scan (TV USS), correlated with serum beta human chorionic gonadotropin (BHCG) assay, earlier diagnosis of an EP can be established. An EP is often diagnosed in women who are trying to conceive; therefore, the prognosis of future fertility is one of the main concerns associated with this diagnosis. Management can be surgical, expectant or medical with methotrexate (MTX). However, the best approach is tailored to the woman’s individual case. The authors present the case of a primigravida woman presenting with abdominal pain and vaginal bleeding at 6 weeks gestation following assisted reproduction. Her BHCG showed a suboptimal rise. Her TV USS showed no evidence of an intrauterine pregnancy. There was no evidence of an adnexal mass or free fluid. As her BHCG remained static, she underwent a diagnostic laparoscopy. A right sided IEP was identified. Due to the high risk of bleeding requiring transfusion or hysterectomy and her desire to preserve her fertility, she received medical management with MTX. Indeed, research has shown that women successfully managed expectantly achieve better reproductive outcomes, with the shortest time to achieve a subsequent intrauterine pregnancy. This case acts as a cautionary reminder of the challenges associated with identifying an IEP on TV USS. A high index of clinical suspicion is required to prevent maternal morbidity and mortality.
Refractory bradycardia and hypotension in patients with autonomic dysfunction treated with pseudoephedrine
Authors: Curran Caleigh , Davoudi Farideh , Foster Gabriel , Gordan Patrick
Published: April 2023

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5–C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.
Fatigue outcomes following COVID-19: a systematic review and meta-analysis
Authors: Poole-Wright Kim , Guennouni Ismail , Sterry Olivia , Evans Rachael A , Gaughran Fiona , Chalder Trudie
Published: April 2023

Objectives

Fatigue is a pervasive clinical symptom in coronaviruses and may continue beyond the acute phase, lasting for several months or years. This systematic review and meta-analysis aimed to incorporate the current evidence for postinfection fatigue among survivors of SARS-CoV-2 and investigate associated factors.

Methods

Embase, PsyINFO, Medline, CINAHL, CDSR, Open Grey, BioRxiv and MedRxiv were systematically searched from January 2019 to December 2021. Eligible records included all study designs in English. Outcomes were fatigue or vitality in adults with a confirmed diagnosis of SARS-CoV-2 measured at >30 days post infection. Non-confirmed cases were excluded. JBI risk of bias was assessed by three reviewers. Random effects model was used for the pooled proportion with 95% CIs. A mixed effects meta-regression of 35 prospective articles calculated change in fatigue overtime. Subgroup analyses explored specific group characteristics of study methodology. Heterogeneity was assessed using Cochran’s Q and I2statistic. Egger’s tests for publication bias.

Results

Database searches returned 14 262 records. Following deduplication and screening, 178 records were identified. 147 (n=48 466 participants) were included for the meta-analyses. Pooled prevalence was 41% (95% CI: 37% to 45%, k=147, I2=98%). Fatigue significantly reduced over time (−0.057, 95% CI: −107 to −0.008, k=35, I2=99.3%, p=0.05). A higher proportion of fatigue was found in studies using a valid scale (51%, 95% CI: 43% to 58%, k=36, I2=96.2%, p=0.004). No significant difference was found for fatigue by study design (p=0.272). Egger’s test indicated publication bias for all analyses except valid scales. Quality assessments indicated 4% at low risk of bias, 78% at moderate risk and 18% at high risk. Frequently reported associations were female gender, age, physical functioning, breathlessness and psychological distress.

Conclusion

This study revealed that a significant proportion of survivors experienced fatigue following SARS-CoV-2 and their fatigue reduced overtime. Non-modifiable factors and psychological morbidity may contribute to ongoing fatigue and impede recovery.

PROSPERO registration number

CRD42020201247.
Implementing SARS-CoV-2 antigen testing scale-up in Rwanda: retrospective analysis of national programme data and qualitative findings
Authors: Rutayisire Robert , Boeke Caroline E , Joseph Jessica , Bansal Namita , Bigirimana Noella , Demke Owen , Kallarakal Ashley , Karame Prosper , Ndayishimiye Rodrigue , Umumararungu Esperance , Peter Trevor , Khan Shaukat
Published: April 2023

Objectives

Reverse transcriptase PCR is the most sensitive test for SARS-CoV-2 diagnosis. However, the scale-up of these tests in low-income and middle-income countries (LMICs) has been limited due to infrastructure and cost. Antigen rapid diagnostic tests are an alternative option for diagnosing active infection that may allow for faster, easier, less expensive and more widespread testing. We compared the implementation of antigen and PCR testing programmes in Rwanda.

Design

We retrospectively reviewed routinely collected PCR and antigen testing data for all reported tests conducted nationally. We administered semiquantitative surveys to healthcare workers (HCWs) involved in COVID-19 testing and care and clients receiving antigen testing.

Setting

Rwanda, November 2020–July 2021.

Participants

National SARS-CoV-2 testing data; 49 HCWs involved in COVID-19 testing and care; 145 clients receiving antigen testing.

Interventions

None (retrospective analysis of programme data).

Primary and secondary outcome measures

Test volumes, turnaround times, feasibility and acceptability of antigen testing.

Results

Data from 906 204 antigen tests and 445 235 PCR tests were included. Antigen testing increased test availability and case identification compared with PCR and had a median results return time of 0 days (IQR: 0–0). In contrast, PCR testing time ranged from 1 to 18 days depending on the sample collection site/district. Both HCWs and clients indicated that antigen testing was feasible and acceptable. Some HCWs identified stockouts and limited healthcare staff as challenges.

Conclusions

Antigen testing facilitated rapid expansion and decentralisation of SARS-CoV-2 testing across lower tier facilities in Rwanda, contributed to increased case identification, reduced test processing times, and was determined to be feasible and acceptable to clients and providers. Antigen testing will be an essential component of SARS-CoV-2 test and treat programmes in LMICs.
Comparisons of different lymph node staging systems for predicting overall survival of node-positive patients with renal cell carcinoma: a retrospective cohort study using the Surveillance, Epidemiology and End Results database
Authors: Zheng Wenwen , Jiang Wei , Wu Qingna , Chen Jiaojiao , Zhang Zhiyu , Yu Shengqiang , Guo Chenyu
Published: April 2023

Objectives

To compare the prognostic values of three lymph node staging systems in renal cell carcinoma (RCC), including the number of positive lymph nodes (NPLN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS).

Design

A retrospective cohort study using data from the Surveillance, Epidemiology and End Results (SEER) database.

Setting and participants

1904 patients with pathological N1 RCC, diagnosed from 2004 to 2015 and underwent nephrectomy combined with lymph node dissection, were identified from the SEER database.

Primary outcome measure

The primary outcome of this study was overall survival (OS). Restricted cubic spline functions and multivariable Cox regression analyses were employed to characterise the associations of OS with NPLN, LNR and LODDS, respectively.

Results

Data of 1904 eligible RCC patients were extracted from the SEER database. The mortality risks of RCC patients increased with the increasing of NPLN, LNR and LODDS. NPLN (NPLN3 vs NPLN1, HR 1.22, 95% CI 1.05 to 1.43, p=0.001), LNR (LNR3 vs LNR1, HR 1.46, 95% CI 1.28 to 1.67, p<0.001; LNR2 vs LNR1, HR 1.28, 95% CI 1.09 to 1.50, p=0.002) and LODDS (LODDS3 vs LODDS1, HR 1.48, 95% CI 1.28 to 1.72, p<0.001; LODDS2 vs LODDS1, HR 1.34, 95% CI 1.17 to 1.53, p<0.001) were all independent prognostic factors of OS. The predictive abilities of LNR (Akaike information criterion, AIC: 19576.3, optimism-corrected C-index: 0.677) and LODDS (AIC: 19579.2, optimism-corrected C-index: 0.676) were comparable, superior to NPLN (AIC: 19603.7, optimism-corrected C-index: 0.673). In subgroup analyses, the LODDS classification could better stratify survival of RCC patients, in particular for those with the number of dissected lymph nodes <13 or NPLN≤2.

Conclusions

NPLN, LNR and LODDS were all independent predictors of OS in RCC. When compared with NPLN and LNR, LODDS had a better performance in survival prediction and risk stratification. The three metrics all had the potential to be integrated into future versions of the American Joint Committee on Cancer staging manual.