bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Perioperative Tasks for Women Undergoing Anti-incontinence Surgery
Authors: Erekson Elisabeth , Whitcomb Emily L. , Kamdar Neil , Swift Steve , Cundiff Geoffrey W. , Yaklic Jerome , Strohbehn Kris , Adam Rony , Danford Jill , Willis-Gray Marcella G. , Maxwell Rose , Edenfield Autumn , Pulliam Samantha , Gong Merry , Malek Mackenzie , Hanissian Paul , Towers Geoffrey , Guaderrama Noelani M. , Slocum Paul , Morgan Daniel
Published: July 2023

Objectives

Surgery for the correction of stress urinary incontinence is an elective procedure that can have a dramatic and positive impact on quality of life. Anti-incontinence procedures, like inguinal hernia repairs or cholecystectomies, can be classified as high-volume/low-morbidity procedures. The performance of a standard set of perioperative tasks has been suggested as one way to optimize quality of care in elective high-volume/low-morbidity procedures. Our primary objective was to evaluate the performance of 5 perioperative tasks—(1) offering nonsurgical treatment, (2) performance of a standard preoperative prolapse examination, (3) cough stress test, (4) postvoid residual test, and (5) intraoperative cystoscopy for women undergoing surgery for stress urinary incontinence—compared among surgeons with and without board certification in female pelvic medicine and reconstructive surgery (FPMRS).

Study Design

This study was a retrospective chart review of anti-incontinence surgical procedures performed between 2011 and 2013 at 9 health systems. Cases were reviewed for surgical volume, adverse outcomes, and the performance of 5 perioperative tasks and compared between surgeons with and without FPMRS certification.

Results

Non-FPMRS surgeons performed fewer anti-incontinence procedures than FPMRS-certified surgeons. Female pelvic medicine and reconstructive surgery surgeons were more likely to perform all 5 perioperative tasks compared with non-FPMRS surgeons. After propensity matching, FPMRS surgeons had fewer patients readmitted within 30 days of surgery compared with non-FPMRS surgeons.

Conclusions

Female pelvic medicine and reconstructive surgery surgeons performed higher volumes of anti-incontinence procedures, were more likely to document the performance of the 5 perioperative tasks, and were less likely to have their patients readmitted within 30 days.
Rubellimicrobium arenae sp. nov., isolated from desert soil
Authors: Han Jia-Rui , Li Shuai , Lu Chun-Yan , Lian Wen-Hui , Shi Guo-Yuan , Feng Chu-Ying , Li Wen-Jun , Dong Lei
Published: July 2023

Two Gram-stain-negative strains, designated as SYSU D00286T and SYSU D00782, were isolated from a sand sample collected from the Kumtag Desert in Xinjiang, north-west China. Cells were aerobic, non-motile and positive for both oxidase and catalase. Growth occurred at 4–37 °C (optimum, 28–30 °C), pH 6.0–7.0 (optimum, pH 7.0) and NaCl concentration of 0–1.5 % (w/v; optimum, 0%). Growth was observed on Reasoner’s 2A agar and nutrient agar, but not on Luria–Bertani agar and trypticase soy agar. The polar lipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified aminolipids, one unidentified glycolipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-10 and the major fatty acids (>10 %) were C16 : 0 and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c). The 16S rRNA gene sequence similarity between strains SYSU D00286T and SYSU D00782 was 100%, and their average nucleotide identity (ANI), average amino acid identity and (AAI) digital DNA–DNA hybridization (dDDH) values were all 100.0 %. Phylogenetic analysis indicated that these two strains belong to the same species of the genus

Rubellimicrobium

and show the highest sequence similarity to

Rubellimicrobium rubrum

KCTC 72461T (98.2 %) and

Rubellimicrobium roseum

CCTCC AA 208029T (97.5 %). The ANI, AAI and dDDH values between SYSU D00286T (as well as SYSU D00782) and the other five

Rubellimicrobium

type strains were all less than or equal to 83.2, 80.1 and 23.6 %, respectively. Based on their phylogenetic, phenotypic and chemotaxonomical features, strains SYSU D00286T and SYSU D00782 represent a novel species of the genus

Rubellimicrobium

, for which the name Rubellimicrobium arenae sp. nov. is proposed. The type strain is SYSU D00286T (=MCCC 1K04981T=CGMCC 1.8626T=KCTC 82271T).
Magnitude Of Birth Outcome After Induced Labor Among Mothers Delivered In Nigist Eleni Mohammed Memorial Comprehensive Specialized Hospital, Hosanna Town, Hadiya Zone, Southern Ethiopia. Cross-Sectional Study
Authors: Worku Dereje , Assebe Tesfaye , Gobena Tesfaye , Kechine Temesgen
Published: July 2023

Background

“Induction of labor is not risk free, despite its importance for ending risky pregnancy compare to spontaneous onset of labor it has potential harms and it increases the rate of different maternal and neonatal complications.” Due to this WHO recommends IOL with only clear medical indications when the benefit more significant than potential harms. Even though there is a few study on IOL that address magnitude of birth outcome after IOL no study is found that determine the contributing factors to birth outcomes after IOL in Ethiopia especially in my study area, therefore the factors that affect the birth outcome after IOL need to be clearly understood.

Objective

To assess the magnitude birth outcome after induced labor and associated factor among child bearing mother who deliver in NEMMCSH in the last two years (January 01, 2019 to December 31, 2020 GC). Data was collected from June 25 to July 09, 2021 GC.

Methods

Hospital based retrospective cross-sectional study was conducted on 778 study participants selected by systematic random sampling technique among all child bearing mothers delivered by induction in NEMMCSH from January 01, 2019 to December 31, 2020 GC. Data was collected from patient cards, delivery registration log books and operation note books. Then data were entered and coded using EPI data version 3.1 and analyzed using SPSS version 25. Bivariate and multivariate logistic regression analysis was carried out to determine the association different potential factors with the birth outcome after IOL. Independent predictors were determined using adjusted odd ratio with 95% CL at p value < 0.05 in multivariate logistic regression analysis.

Results

In this study the magnitude of still birth after IOL was 9.6%. Rural residence [AOR=3.59; 95%CI:(1.32, 9.80)], maternal chronic medical diseases [AOR=3.58; 95% CL: (1.23, 10.41)], history of previous still birth [AOR=7.45; 95%CI: (2.45, 22.38)], Partograph use [AOR=0.034; 95%CI: 0.01,0.09)], delivering ˂8 hours[AOR=0.13; 95%CI: (0.03,0.56)] and delivering within 8-16[AOR=0.28; 95%CI:(0.10, 0.76)] hours were significant predictors for still birth.

Conclusions

The magnitude of still birth after IOL was relatively high in the study area. Variables which increase the likelihood of still birth were, living in rural area and previous history of still birth. The recommendations also forwarded for health care provider, NEMMCSH, different stakeholders and for researchers.
Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI
Authors: Zhang Jiahe , Chen Danlei , Deming Philip , Srirangarajan Tara , Theriault Jordan , Kragel Philip A. , Hartley Ludger , Lee Kent M. , McVeigh Kieran , Wager Tor D. , Wald Lawrence L. , Satpute Ajay B. , Quigley Karen S. , Whitfield-Gabrieli Susan , Barrett Lisa Feldman , Bianciardi Marta
Published: July 2023

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, called allostasis. In support of allostasis, the brain continually models the sensory state of the body, called interoception. We replicated and extended a large-scale system supporting allostasis and interoception in the human brain using ultra-high precision 7 Tesla functional magnetic resonance imaging (fMRI) (N =90), improving the precision of subgenual and pregenual anterior cingulate topography combined with extensive brainstem nuclei mapping. We observed over 90% of the anatomical connections published in tract-tracing studies in non-human animals. The system also included regions of dense intrinsic connectivity broadly throughout the system, some of which were identified previously as part of the backbone of neural communication across the brain. These results strengthen previous evidence for a whole-brain system supporting the modeling and regulation of the internal milieu of the body.
Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking
Authors: Wilkinson Courtney S. , Blount Harrison L. , Davis Shane , Rojas Giselle , Wu Lizhen , Murphy Niall P. , Schwendt Marek , Knackstedt Lori A.
Published: July 2023

Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with access to either alcohol (20% v/v) and water or only water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent extinction training and brains were processed for c-fos mRNA expression immediately following a cue-primed reinstatement test. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, female oxycodone+alcohol rats exhibited decreased demand elasticity for intravenous oxycodone and increased cue-primed reinstatement while male rats did not. Spontaneous withdrawal signs were correlated with oxycodone intake while alcohol intake was correlated with anxiety-like behavior. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor containing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and alters the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.
Neural filtering of physiological tremor oscillations to spinal motor neurons mediates short-term acquisition of a skill learning task
Authors: Cabral Hélio V. , Cudicio Alessandro , Bonardi Alberto , Del Vecchio Alessandro , Falciati Luca , Orizio Claudio , Martinez-Valdes Eduardo , Negro Francesco
Published: July 2023

The acquisition of a motor skill involves adaptations of spinal and supraspinal pathways to alpha motoneurons. In this study, we estimated the shared synaptic contributions of these pathways to understand the neural mechanisms underlying the short-term acquisition of a new force-matching task. High-density surface electromyography (HDsEMG) was acquired from the first dorsal interosseous (FDI; 7 males and 6 females) and tibialis anterior (TA; 7 males and 4 females) during 15 trials of an isometric force-matching task. For two selected trials (pre-andpost-skillacquisition), we decomposed the HDsEMG into motor unit spike trains, tracked motor units between trials, and calculated the mean discharge rate and the coefficient of variation of inter-spike interval (CoVISI). We also quantified thepost/preratio of motor units’ coherence within delta, alpha, and beta bands. Improvements in force-matching were accompanied by a significant increase in the mean discharge rate and a decrease in CoVISIfor both muscles. Moreover, the area under the curve within alpha band decreased by ∼22% and ∼13% for the TA and FDI muscles, respectively, with no changes in the delta or beta bands. These reductions correlated significantly with increased coupling between force/neural drive and target oscillations. These results suggest that the short-term acquisition of a new force-matching skill is mediated by the attenuation of tremor oscillations in the shared synaptic inputs. In other words, the central nervous system acts as a matched filter to modulate the synaptic weights of shared inputs and suppress neural components unrelated to the specific task. Supported by simulations, a plausible mechanism behind these alpha band reductions may involve spinal interneurons’ phase-cancelling descending oscillations.
Brain and circulating steroids in an electric fish: relevance for non-breeding aggression
Authors: Zubizarreta Lucia , Jalabert Cecilia , Silva Ana C. , Soma Kiran K. , Quintana Laura
Published: July 2023

Steroids play a crucial role in modulating brain and behavior. While traditionally it is considered that the brain is a target of peripheral hormones produced in endocrine glands, it has been discovered that the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in brain regions involved in the regulation of social behaviors and can act locally regulating behaviors like reproduction and aggression. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain. We use the weakly electric fishGymnotus omarorum, a species which shows non-breeding aggression in both sexes, to characterize these hormonal profiles in wild non-breeding adults. We show that: 1) systemic steroids in the non-breeding season are similar in both sexes, although only males have circulating 11-KT, 2) brain steroid levels are sexually dimorphic, as females display higher levels of AE, T and E1, and only males had 11-KT, 3) systemic androgens such as AE and T in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data fall in line with previous reports inG. omarorumwhich show that non-breeding aggression is dependent on the estrogenic pathway, as has also been shown in bird and mammal models. Overall, our results constitute a fundamental groundwork to understanding the complexity of hormonal modulation, its potential sex differences, the role of neurosteroids and the interplay between central and peripheral hormones in the regulation of behaviors.
RNAi-based screen for cuticle pigmentation inDrosophila melanogasterreveals novel regulators of brain dopamine
Authors: Deal Samantha L , Bei Danqing , Gibson Shelley B , Delgado-Seo Harim , Fujita Yoko , Wilwayco Kyla , Seto Elaine S , Yamamoto Shinya
Published: July 2023

The dopaminergic system has been extensively studied for its role in behavior in various animals as well as human neuropsychiatric and neurological diseases. However, we still know little about how dopamine levels are tightly regulatedin vivo. In order to identify novel regulators of dopamine levels, we utilizedDrosophila melanogastercuticle pigmentation as a readout, where dopamine is used as a precursor to melanin. First, we measured dopamine from classical mutants of genes that are known to be important for cuticle pigmentation to understand the relationship between dopamine levels and cuticle color. We then performed an RNAi-based screen to identify novel regulators of cuticle pigmentation. We identified 153 genes that were not only enriched for conserved homologs and disease-associated genes, but were unexpectedly enriched for multiple developmental signaling pathways and mitochondria-associated proteins. Upon measuring dopamine from 35 prioritized candidates from this cohort, we found 10 that caused significant reduction in dopamine in the head while one caused an increase. While most of these 11 genes are expressed in the fly brain, only two of them,cluandmask,altered dopamine levels specifically in the brain upon knockdown in dopaminergic cells. Interestingly,maskmay act as a hub of dopamine regulation since it is associated with three nodes found in our screen (Receptor tyrosine kinase/EGF signaling, Hippo signaling, and mitochondrial dynamics). Further examination suggests that Mask likely acts on dopamine synthesis by regulating transcription of the rate-limiting dopamine synthesis enzyme,tyrosine hydroxylase. In conclusion, this screen identified 11 new regulators of dopamine levels and provides molecular handles to investigate how dopamine levels are controlledin vivo, as well as revealed an unexpected relationship between fly pigmentation genes, developmental signaling and human neurological and neurodevelopmental disease genes.
Image Analysis Techniques for In Vivo Quantification of Cerebrospinal Fluid Flow
Authors: Kim Daehyun , Gan Yiming , Nedergaard Maiken , Kelley Douglas H. , Tithof Jeffrey
Published: July 2023

Over the last decade, there has been a tremendously increased interest in understanding the neuro-physiology of cerebrospinal fluid (CSF) flow, which plays a crucial role in clearing metabolic waste from the brain. This growing interest was largely initiated by two significant discoveries: the glymphatic system (a pathway for solute exchange between interstitial fluid deep within the brain and the CSF surrounding the brain) and meningeal lymphatic vessels (lymphatic vessels in the layer of tissue surrounding the brain that drain CSF). These two CSF systems work in unison, and their disruption has been implicated in several neurological disorders including Alzheimer’s disease, stoke, and traumatic brain injury. Here, we present experimental techniques forin vivoquantification of CSF flow via direct imaging of fluorescent microspheres injected into the CSF. We discuss detailed image processing methods, including registration and masking of stagnant particles, to improve the quality of measurements. We provide guidance for quantifying CSF flow through particle tracking and offer tips for optimizing the process. Additionally, we describe techniques for measuring changes in arterial diameter, which is an hypothesized CSF pumping mechanism. Finally, we outline how these same techniques can be applied to cervical lymphatic vessels, which collect fluid downstream from meningeal lymphatic vessels. We anticipate that these fluid mechanical techniques will prove valuable for future quantitative studies aimed at understanding mechanisms of CSF transport and disruption, as well as for other complex biophysical systems.
Altered Fhod3 Expression Involved in Progressive High-Frequency Hearing Loss via Dysregulation of Actin Polymerization Stoichiometry in The Cuticular Plate
Authors: Boussaty Ely Cheikh , Ninoyu Yuzuru , Andrade Leo , Li Qingzhong , Takeya Ryu , Sumimoto Hideki , Ohyama Takahiro , Wahlin Karl J , Manor Uri , Friedman Rick A
Published: July 2023

Age-related hearing loss (ARHL) is a common sensory impairment with complex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results. We observed Fhod3 expression in auditory hair cells (HCs) and primarily localized at the cuticular plate (CP). To understand the functional implications of Fhod3 in the cochlea, we generated Fhod3 overexpression mice (Pax2-Cre+/-; Fhod3Tg/+) (TG) and HC-specific conditional knockout mice (Atoh1-Cre+/-; Fhod3fl/fl) (KO). Audiological assessments in TG mice demonstrated progressive high-frequency hearing loss, characterized by predominant loss of outer hair cells, and a decreased phalloidin intensities of CP. Ultrastructural analysis revealed shortened stereocilia in the basal turn cochlea. Importantly, the hearing and HC phenotype in TG mice were replicated in KO mice. These findings indicate that Fhod3 plays a critical role in regulating actin dynamics in CP and stereocilia. Further investigation of Fhod3 related hearing impairment mechanisms may facilitate the development of therapeutic strategies for ARHL in humans.
Tumor-reactive clonotype dynamics underlying clinical response to TIL therapy in melanoma
Authors: Chiffelle Johanna , Barras David , Pétremand Rémy , Orcurto Angela , Bobisse Sara , Arnaud Marion , Auger Aymeric , Rodrigo Blanca Navarro , Ghisoni Eleonora , Sauvage Christophe , Saugy Damien , Michel Alexandra , Murgues Baptiste , Fahr Noémie , Imbimbo Martina , Ochoa de Olza Maria , Latifyan Sofiya , Crespo Isaac , Benedetti Fabrizio , Genolet Raphael , Queiroz Lise , Schmidt Julien , Homicsko Krisztian , Zimmermann Stephan , Michielin Olivier , Bassani-Sternberg Michal , Kandalaft Lana E. , Dafni Urania , Corria-Osorio Jesus , Trueb Lionel , Laniti Denarda Dangaj , Harari Alexandre , Coukos George
Published: July 2023

The profiles, specificity and dynamics of tumor-specific clonotypes that are associated with clinical response to adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) remain unclear. Using single-cell RNA/TCR-sequencing, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients treated with TIL-ACT. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, which were more effectively mobilized uponin vitroexpansion, yielding products with higher numbers of tumor-specific CD8+cells, which also preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes, and with cell products mostly composed of blood-borne clonotypes mainly persisting in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost the specific signatures of states originally exhibited in tumors, including exhaustion, and in responders acquired an intermediate exhausted effector state after tumor engraftment, revealing important functional cell reinvigoration.
Addressing persistent challenges in digital image analysis of cancerous tissues
Authors: Prabhakaran Sandhya , Yapp Clarence , Baker Gregory J. , Beyer Johanna , Chang Young Hwan , Creason Allison L. , Krueger Robert , Muhlich Jeremy , Patterson Nathan Heath , Sidak Kevin , Sudar Damir , Taylor Adam J. , Ternes Luke , Troidl Jakob , Xie Yubin , Sokolov Artem , Tyson Darren R. ,   the Cell Imaging Hackathon 2022 Participants (Alphabetical authorship, apart from primary contributors)
Published: July 2023

The National Cancer Institute (NCI) supports many research programs and consortia, many of which use imaging as a major modality for characterizing cancerous tissue. A trans-consortia Image Analysis Working Group (IAWG) was established in 2019 with a mission to disseminate imaging-related work and foster collaborations. In 2022, the IAWG held a virtual hackathon focused on addressing challenges of analyzing high dimensional datasets from fixed cancerous tissues. Standard image processing techniques have automated feature extraction, but the next generation of imaging data requires more advanced methods to fully utilize the available information. In this perspective, we discuss current limitations of the automated analysis of multiplexed tissue images, the first steps toward deeper understanding of these limitations, what possible solutions have been developed, any new or refined approaches that were developed during the Image Analysis Hackathon 2022, and where further effort is required. The outstanding problems addressed in the hackathon fell into three main themes: 1) challenges to cell type classification and assessment, 2) translation and visual representation of spatial aspects of high dimensional data, and 3) scaling digital image analyses to large (multi-TB) datasets. We describe the rationale for each specific challenge and the progress made toward addressing it during the hackathon. We also suggest areas that would benefit from more focus and offer insight into broader challenges that the community will need to address as new technologies are developed and integrated into the broad range of image-based modalities and analytical resources already in use within the cancer research community.
Adaptive therapy achieves long-term control of chemotherapy resistance in high grade ovarian cancer
Authors: Hockings Helen , Lakatos Eszter , Huang Weini , Mossner Maximilian , Khan Mohammed Ateeb , Metcalf Stephen , Nicolini Francesco , Smith Kane , Baker Ann-Marie , Graham Trevor A. , Lockley Michelle
Published: July 2023

Drug resistance results in poor outcomes for most patients with metastatic cancer. Adaptive Therapy (AT) proposes to address this by exploiting presumed fitness costs incurred by drug-resistant cells when drug is absent, and prescribing dose reductions to allow fitter, sensitive cells to re-grow and re- sensitise the tumour. However, empirical evidence for treatment-induced fitness change is lacking. We show that fitness costs in chemotherapy-resistant ovarian cancer cause selective decline and apoptosis of resistant populations in low-resource conditions. Moreover, carboplatin AT caused fluctuations in sensitive/resistant tumour population sizein vitroand significantly extended survival of tumour-bearing mice. In sequential blood-derived cell-free DNA and tumour samples obtained longitudinally from ovarian cancer patients during treatment, we inferred resistant cancer cell population size through therapy and observed it correlated strongly with disease burden. These data have enabled us to launch a multicentre, phase 2 randomised controlled trial (ACTOv) to evaluate AT in ovarian cancer.
ChromatinHD connects single-cell DNA accessibility and conformation to gene expression through scale-adaptive machine learning
Authors: Saelens Wouter , Pushkarev Olga , Deplancke Bart
Published: July 2023

1

Machine learning methods that fully exploit the dual modality of single-cell RNA+ATAC-seq techniques are still lacking. Here, we developed ChromatinHD, a pair of models that uses the raw accessibility data, with-out peak-calling or windows, to predict gene expression and determine differentially accessible chromatin. We show how both models consistently outperform existing peak and window-based approaches, and find that this is due to a considerable amount of functional accessibility changes within and outside of putative cis-regulatory regions, both of which are uniquely captured by our models. Furthermore, ChromatinHD can delineate collaborating regions including their preferential genomic conformations that drive gene expression. Finally, our models also use changes in ATAC-seq fragment lengths to identify dense binding of transcription factors, a feature not captured by footprinting methods. Altogether, ChromatinHD, available athttps://deplanckelab.github.io/ChromatinHD, is a suite of computational tools that enables a data-driven understanding of chromatin accessibility at various scales and how it relates to gene expression.
Ultra-high density imaging arrays for diffuse optical tomography of human brain improve resolution, signal-to-noise, and information decoding
Authors: Markow Zachary E. , Trobaugh Jason W. , Richter Edward J. , Tripathy Kalyan , Rafferty Sean M. , Svoboda Alexandra M. , Schroeder Mariel L. , Burns-Yocum Tracy M. , Bergonzi Karla M. , Chevillet Mark. A. , Mugler Emily M. , Eggebrecht Adam T. , Culver Joseph P.
Published: July 2023

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (∼13 mm) than sparse fNIRS (∼30 mm) and therefore provide higher image quality, with spatial resolution ∼1/2 that of fMRI. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30-50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19-35% lower error than previous HD-DOT, throughout occipital cortex.
Conservation implications of diverse demographic histories: the case study of green peafowl (Pavo muticus, Linnaeus 1766)
Authors: Patil Ajinkya Bharatraj , Vijay Nagarjun
Published: July 2023

The green peafowl (Pavo muticus, Linnaeus 1766) is an endangered species native to the forests of tropical Southeast Asia. Although its morphological diversity and subspecies categorization is known and built upon traditional taxonomy, the intraspecific genetic structure has not been comprehensively addressed. To assess if phenotypic diversity is reflected at the molecular level, we used public whole-genome sequencing data of one blue peafowl and 52 green peafowls from multiple countries to characterize their genetic diversity, differentiation, identify Ancestry Informative Markers (AIMs) and compare their demographic histories. We found evidence of substantial population structure, with at least three distinct clusters and diverse demographic histories that may mirror different responses to various biogeoclimatic events. The genetic structure of native populations follows the pattern of the geographic distribution of the green peafowl with the highest autosomal pairwise FSTbetween Yunnan and Vietnam (∼0.1) and intermediate estimates for Thailand comparisons (∼0.077). We identify AIMs to distinguish between these three native populations. The captive green peafowls from Xinxing clustered with Vietnam and those from Qinhuangdao (QHD) formed a separate cluster. The two QHD individuals appear to have varying levels of blue peafowl ancestry based on PCA and admixture analysis and are mirrored in their demographic histories. Our study establishes the occurrence of genetically distinct natural populations of green peafowl that can be considered separate management units (MU) when planning conservation actions. Transboundary cooperation and concerted efforts to foster genetic diversity are imperative for Southeast Asian species at risk.
Linoleic acid supplementation reverses microglial response to diet induced-obesity at hypothalamic, cortical and subcortical level in mice
Authors: Jantzen Lucas , Dumontoy Stéphanie , Ramadan Bahrie , Houdayer Christophe , Haffen Emmanuel , Hichami Aziz , Khan Naim , Van Waes Vincent , Cabeza Lidia
Published: July 2023

Obesity is a major risk factor for neuropsychiatric alterations. Fatty regimes lead to systemic and cerebral inflammation, the latest acting through lipotoxicity on hypothalamic structures controlling energy homeostasis. Since literature points to a protective effect of linoleic acid (LA) on mood disorders through the regulation of systemic inflammation, we investigated how five weeks of LA supplementation modulates emotional behaviour and microglia-related neuroinflammation. C57BL/6j mice were fed with either a high-fat (HFD) or a standard diet for 12 weeks, underwent a battery of behavioural tests and were subsequently sacrificed for immunofluorescence staining targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was approximated in multiple hypothalamic, cortical and subcortical regions. Our results show an anxio-depressive-like effect of sustained HFD that neither was alleviated nor worsen with LA supplementation. Increased IBA-1 expression in the HFD group was substantially reversed with LA supplementation. Thus, our results suggest anti-neuroinflammatory properties of LA not restricted to hypothalamic areas, but also evident at the cortical and subcortical level. This study is therefore relevant in the frame of obesity and neuropsychiatric disorders with a neuroinflammatory basis. Further investigation may provide more information to justify dietary strategies aiming at reducing the impact of obesity associated comorbidities.
Neural network models for the evolution of associative learning
Authors: Salinas Emiliano Méndez , Weissing Franz J. , Kozielska Magdalena
Published: July 2023

The ability to learn from past experience is an important adaptation, but how natural selection shapes learning is not well understood. Here, we investigate the evolution of associative learning (the association of stimuli with rewards) by a modelling approach that is based on the evolution of neural networks (NNs) underlying learning. Individuals employ their genetically encoded NN to solve a learning task with fitness consequences. NNs inducing more efficient learning have a selective advantage and spread in the population. We show that in a simple learning task, the evolved NNs, even those with very simple architecture, outperform well-studied associative learning rules, such as the Rescorla-Wagner rule. During their evolutionary trajectory, NNs often pass a transitional stage where they functionally resemble Rescorla-Wagner learning, but further evolution shapes them to approximate the theoretically optimal learning rule. Networks with a simple architecture evolve much faster and tend to outperform their more complex counterparts on a shorter-term perspective. Also, on a longer-term perspective network complexity is not a reliable indicator of evolved network performance. These conclusions change somewhat when the learning task is more challenging. Then the performance of many evolved networks is not better than that of the Rescorla-Wagner rule; only some of the more complex networks reach a performance level close to the optimal Bayesian learning rule. In conclusion, we show that the mechanisms underlying learning influence the outcome of evolution. A neural-network approach allows for more flexibility and a wider set of evolutionary outcomes than most analytical studies, while at the same time, it provides a relatively straightforward and intuitive framework to study the learning process.
Computational Engineering of a Therapeutic Antibody to Inhibit Multiple Mutants of HER2 Without Compromising Inhibition of the Canonical HER2
Authors: Peled Sapir , Guez-Haddad Julia , Biton Nevet Zur , Nimrod Guy , Fischman Sharon , Fastman Yair , Ofran Yanay
Published: July 2023

Genomic germline and somatic variations may impact drug binding and even lead to resistance. However, designing a different drug for each mutant may not be feasible. In this study, we identified the most common cancer somatic mutations from the Catalogue of Somatic Mutations in Cancer (COSMIC) that occur in structurally characterized binding sites of approved therapeutic antibodies. We found two HER2 mutations, S310Y and S310F, that substantially compromise binding of Pertuzumab, a widely used therapeutics, and lead to drug resistance. To address these mutations, we designed a multi-specific version of Pertuzumab, that retains original function while also bindings these HER2 variants. This new antibody is stable and inhibits HER3 phosphorylation in a cell-based assay for all three variants, suggesting it can inhibit HER2-HER3 dimerization in patients with any of the variants. This study demonstrates how a small number of carefully selected mutations can add new specificities to an existing antibody without compromising its original function, creating a single therapeutic antibody that targets multiple common variants, making a drug that is not personalized yet its activity may be.
Multilayer Label Free Non-Faradic Electrochemical Impedance Immunosensor for Cortisol Detection
Authors: Gupta Chinmay , Pattanayek Sudip Kumar , Mukherjee Biswarup , Kumar Sachin
Published: July 2023

Cortisol, a well-known psychological stress biomarker, produced by the hypothalamic-pituitary-adrenal system, tends to intensify with stressors. Prolonged overexpression of cortisol leads to chronic stress that causes disparities in the proper functioning of the human body. Thus, there is a huge demand for developing a rapid cortisol detection system. Several point-of-care diagnostic techniques are available for rapid cortisol detection, such as electrochemical sensing, which works on changes in the electrical properties due to the binding of an analyte with a biorecognition element. Researchers have used different electrochemical methodologies such as cyclic voltammetry (CV), chronoamperometry, and faradic electrochemical impedance spectroscopy (EIS) for the detection of cortisol, but usage of external redox active reagents, low sensitivity, limited dynamic range, and electrode fouling nature limits their use. Hence, we reported a label-free and non-invasive cortisol detection using non-faradic EIS. A novel multilayer immunosensor was fabricated on PEDOT: PSS coated ITO glass by functionalizing with cortisol antibodies. Specific and rapid detection of cortisol was measured by monitoring the change in impedance in a dynamic range from 50-200 ng/mL. We envision the developed immunosensor has the potential for new developments in stress monitoring, disease prognosis, and enable personalized care.

Highlights

Novel PEDOT: PSS based multilayer immunosensor for cortisol detection

Impedance based label free detection of cortisol using non-faradic EIS

Presentation of detailed multilayer immunosensor fabrication, experimental detection, and equivalent circuit model with working mechanism

Cortisol detection in a dynamic range of 50-200 ng/mL

Graphical Abstract
Non-additive genetic components contribute significantly to population-wide gene expression variation
Authors: Tsouris Andreas , Brach Gauthier , Schacherer Joseph , Hou Jing
Published: July 2023

Gene expression variation, an essential step between genomic variation and phenotypic landscape, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence the heritability of expression traits remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originated from genetically divergent yeast isolates. We estimated the broad- and narrow-sense heritability across 5,087 transcript abundance traits and showed that non-additive components account for 36% of the phenotypic variance on average. By comparing allelic expression ratios in the hybrid and the corresponding parental pair, we identified regulatory changes in 25% of all cases, with a majority acting intrans. We further showed thattrans-regulation could underlie coordinated expression variation across highly connected genes, resulting in significantly higher non-additive variance and most likely in some of the missing heritability of gene expression traits.

Highlights

Diallel panel for dissecting genetic components underlying gene expression variation

Non-additive components account for 36% of gene expression trait heritability

Mostcis-regulatory variation is buffered by additionaltrans-acting variants

Genes undertrans-regulation show high non-additive variance and functional coherence
Discovering Immunoreceptor Coupling and Organization Motifs (ICOMs)
Authors: Reth Michael
Published: July 2023

The recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowing the molecular basis of antigen sensing by these receptors, a rational design of optimal vaccines is not possible. The existence of conserved amino acids (AAs) that are not involved in the subunit interaction suggests that antigen receptors form higher complexes and/or have lateral interactors that control their activity. Here, I describe evolutionary conserved leucine zipper (LZ) motifs within the transmembrane domains (TMD) of antigen and coreceptor components that are likely to be involved in the oligomerization and lateral interaction of antigen receptor complexes on T and B cells. These immunoreceptor coupling and organization motifs (ICOMs) are also found within the TMDs of other important receptor types and viral envelope proteins. This discovery suggests that antigen receptors do not function as isolated entities but rather as part of an ICOM-based interactome that controls their nanoscale organization on resting cells and their dynamic remodeling on activated lymphocytes.
One-Shot Random Forest Model Calibration for Hand Gesture Decoding
Authors: Jiang Xinyu , Ma Chenfei , Nazarpour Kianoush
Published: July 2023

Objective

Most existing machine learning models for myoelectric control require a large amount of data to learn user-specific characteristics of the electromyographic (EMG) signals, which is burdensome. Our objective is to develop an approach to enable the calibration of a pre-trained model with minimal data from a new myoelectric user.

Approach

We trained a random forest model with EMG data from 20 people collected during the performance of multiple hand grips. To adapt the decision rules for a new user, first, the branches of the pre-trained decision trees were pruned using the validation data from the new user. Then new decision trees trained merely with data from the new user were appended to the pruned pre-trained model.

Results

Real-time myoelectric experiments with 18 participants over two days demonstrated the improved accuracy of the proposed approach when compared to benchmark user-specific random forest and the linear discriminant analysis models. Furthermore, the random forest model that was calibrated on day one for a new participant yielded significantly higher accuracy on day two, when compared to the benchmark approaches, which reflects the robustness of the proposed approach.

Significance

The proposed model calibration procedure is completely source-free, that is, once the base model is pre-trained, no access to the source data from the original 20 people is required. Our work promotes the use of efficient, explainable, and simple models for myoelectric control.
Imperceptible gamma-band sensory stimulation enhances episodic memory retrieval
Authors: Griffiths Benjamin J. , Weinert Daniel E. , Jensen Ole , Staudigl Tobias
Published: July 2023

Enhanced gamma activity (30-100Hz) coincides with the successful recall of episodic memories, but it remains unknown whether this oscillatory activity is a cause or a consequence of the retrieval process. To address this question, we asked human participants to complete a paired associates memory task while undergoing sensory stimulation (at 65Hz, 43.3Hz and 32.5Hz). We observed that 65Hz and 32.5Hz sensory stimulation enhances recall compared to a baseline condition without stimulation. No similar effect was observed following 43.3Hz stimulation. Notably, while almost all participants could perceive 32.5Hz and 43.3Hz sensory stimulation, only a small proportion of participants (∼10%) could perceive the 65Hz visual flicker, suggesting 65Hz sensory stimulation acts as an imperceptible intervention to enhance recall. To understand the dual action of 65Hz and 32.5Hz sensory stimulation on recall, we built three pyramidal-interneuronal network gamma (PING) models and drove them using the same stimulation protocols as in the behavioural task. The behavioural results could be reproduced by stimulating an endogenous ∼32Hz oscillation, but not by stimulating an endogenous ∼65Hz oscillation nor by stimulating a network without an endogenous oscillation. These results suggest that imperceptible 65Hz sensory stimulation enhances recall by harmonically entraining an endogenous ∼32.5Hz oscillation. Based on these findings, we propose that “slow” gamma oscillations play a causal role in episodic memory retrieval.
Human primary motor cortex indexes the onset of subjective intention in brain-machine-interface mediated actions
Authors: Noel Jean-Paul , Bockbrader Marcia , Colachis Sam , Solca Marco , Orepic Pavo , Ganzer Patrick D. , Haggard Patrick , Rezai Ali , Blanke Olaf , Serino Andrea
Published: July 2023

Self-initiated behavior is accompanied by the experience of willing our actions. Here, we leverage the unique opportunity to examine the full intentional chain – from will (W) to action (A) to environmental effects (E) - in a tetraplegic person fitted with a primary motor cortex (M1) brain machine interface (BMI) generating hand movements via neuromuscular electrical stimulation (NMES). This combined BMI-NMES approach allowed us to selectively manipulate each element of the intentional chain (W, A, and E) while performing extra-cellular recordings and probing subjective experience. Our results reveal single-cell, multi-unit, and population-level dynamics in human M1 that encode W and may predict its subjective onset. Further, we show that the proficiency of a neural decoder in M1 reflects the degree of W-A binding, tracking the participant’s subjective experience of intention in (near) real time. These results point to M1 as a critical node in forming the subjective experience of intention and demonstrate the relevance of intention-related signals for translational neuroprosthetics.
Genomic Characterization and Gene Bank Curation ofAegilops: The Wild Relatives of Wheat
Authors: Adhikari Laxman , Raupp John , Wu Shuangye , Koo Dal-Hoe , Friebe Bernd , Poland Jesse
Published: July 2023

Genetic diversity found in crop wild relatives is critical to preserve and utilize for crop improvement to achieve sustainable food production amid climate change and increased demand. We genetically characterized a large collection of 1,041Aegilopsaccessions distributed among 23 different species using more than 45K single nucleotide polymorphisms identified by genotyping-by-sequencing (GBS). The Wheat Genetics Resource Center (WGRC)Aegilopsgermplasm collection was curated through the identification of misclassified and redundant accessions. There were 49 misclassified and 28 sets of redundant accessions within the four diploid species. The curated germplasm sets now have improved utility for genetic studies and wheat improvement. We constructed a phylogenetic tree and PCA cluster for allAegilopsspecies together, giving one of the most comprehensive views ofAegilops. TheSitopsissection and the U genomeAegilopsclade were further scrutinized with in-depth population analysis. The genetic relatedness among the pair ofAegilopsspecies provided strong evidence for the species evolution, speciation and diversification. We inferred genome symbols for two speciesAe.neglectaandAe.columnarisbased on the sequence read mapping and the presence of segregating loci on the pertinent genomes as well as genetic clustering. The high genetic diversity observed amongAegilopsspecies indicated that the genus could play an even greater role in providing the critical need for untapped genetic diversity for future wheat breeding and improvement. To fully characterize theseAegilopsspecies, there is an urgent need to generate reference assemblies for these wild wheats, especially for the polyploidAegilops.

One-sentence summary

GenotypingAegilopsspecies, the wild relatives of wheat, has revealed high genetic diversity and unique evolutionary relationships among theAegilopsand with wheat, giving insight into the effective use of these germplasms for bread wheat improvement.