bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Norovirus in the First 2 Years of Life in an Australian Community-based Birth Cohort
Authors: El-Heneidy Asmaa , Grimwood Keith , Mihala Gabor , Lambert Stephen , Ware Robert S
Published: October 2022

Background:

Noroviruses are a leading cause of acute gastroenteritis across all age groups in Australia. We explored the epidemiology of symptomatic and asymptomatic norovirus infection and assessed risk factors and the related healthcare burden in Australian children during their first 2 years of life.

Methods:

Participants in the Observational Research in Childhood Infectious Diseases birth cohort provided weekly stool swabs, daily gastrointestinal symptoms (vomiting and loose stools) observations and healthcare data. Swabs were batch-tested for norovirus genogroups (GI and GII) using real-time polymerase chain reaction assays.

Results:

Overall, 158 children returned 11,124 swabs. There were 221 infection episodes, of which 183 (82.8%) were GII. The incidence rate was 0.90 infections per child-year [95% confidence interval (CI): 0.74–1.09]. The symptomatic infection incidence rate was 0.39 per child-year (95% CI: 0.31–0.48), peaking between ages 6 and 11 months [0.58 (95% CI: 0.41–0.81)]. Incidence increased significantly with age and childcare attendance. Of 209 episodes with symptom diary data, 82 (39.2%) were symptomatic; of these 70 (85.4%) were associated with vomiting and 29 (35.4%) with diarrhea. Forty-one percent of symptomatic episodes required healthcare, including 4 emergency department presentations and 1 hospitalization. Children with initial infections had almost twice the risk of seeking primary healthcare compared to subsequent infections (adjusted risk ratio 1.92; 95% CI: 1.01–3.65).

Conclusions:

Norovirus infections, particularly GII, are common in Australian children 6–23 months of age. Estimates of norovirus incidence, including symptomatic infections and healthcare utilization in community settings in young children, are crucial for planning norovirus vaccine programs and determining vaccine effectiveness.
Smart healthcare: A prospective future medical approach for COVID-19
Authors: Yang De-Ming , Chang Tai-Jay , Hung Kai-Feng , Wang Mong-Lien , Cheng Yen-Fu , Chiang Su-Hua , Chen Mei-Fang , Liao Yi-Ting , Lai Wei-Qun , Liang Kung-Hao
Published: October 2022

COVID-19 has greatly affected human life for over 3 years. In this review, we focus on smart healthcare solutions that address major requirements for coping with the COVID-19 pandemic, including (1) the continuous monitoring of severe acute respiratory syndrome coronavirus 2, (2) patient stratification with distinct short-term outcomes (eg, mild or severe diseases) and long-term outcomes (eg, long COVID), and (3) adherence to medication and treatments for patients with COVID-19. Smart healthcare often utilizes medical artificial intelligence (AI) and cloud computing and integrates cutting-edge biological and optoelectronic techniques. These are valuable technologies for addressing the unmet needs in the management of COVID. By leveraging deep learning/machine learning capabilities and big data, medical AI can perform precise prognosis predictions and provide reliable suggestions for physicians’ decision-making. Through the assistance of the Internet of Medical Things, which encompasses wearable devices, smartphone apps, internet-based drug delivery systems, and telemedicine technologies, the status of mild cases can be continuously monitored and medications provided at home without the need for hospital care. In cases that develop into severe cases, emergency feedback can be provided through the hospital for rapid treatment. Smart healthcare can possibly prevent the development of severe COVID-19 cases and therefore lower the burden on intensive care units.
ON Path: outpatient nonunion pathway for lower-extremity nonunions
Authors: Rice Olivia M. , Ganta Abhishek , Bailey Gisele , Seymour Rachel B. , Hsu Joseph R.
Published: October 2022

Objectives:

The purpose of this study was to assess the safety and efficacy of outpatient and short-stay surgical nonunion treatment by incorporating minimally invasive surgical techniques, multimodal pain control, and a modernized postoperative protocol.

Design:

Retrospective case series.

Setting:

Tertiary referral hospital and hospital outpatient department.

Patients:

All consecutive nonunion surgeries performed by 1 surgeon between 2014 and 2019 were identified. Outpatient and short-stay surgeries for patients with nonunion of the tibia and femur were eligible (n = 50).

Intervention:

Outpatient and short-stay surgical nonunion treatment by incorporating minimally invasive surgical techniques, multimodal pain control, and a modernized postoperative protocol.

Main Outcome Measurements:

Length of stay, postoperative emergency department visits, all complications, reoperations, and time to union.

Results:

Fifty patients were eligible, with 32 male patients (64%) and an average age of 46.5 years. The patient cohort consisted of 28 femur (56%) and 22 tibia (44%) nonunions. The average length of stay was 0.36 days. Seven patients (14%) required reoperation, 6 patients because of deep infection and 1 patient because of painful implant removal. Four patients (8%) presented to the emergency department within 1 week of surgery. One patient requiring amputation and patients lost to follow-up were excluded from the union rate calculation. For the remaining patients (46/50), 100% (46/46) united their nonunion. The average time to radiographic union was 7.82 months.

Conclusions:

An outpatient pathway is safe and effective for medically appropriate patients undergoing nonunion surgery. Outpatient nonunion surgery is a reasonable alternative that achieves similar outcomes compared with inpatient nonunion studies in the published literature.

Level of Evidence:

IV.
Staffing Up and Sustaining the Public Health Workforce
Authors: Leider Jonathon P. , McCullough J. Mac , Singh Simone Rauscher , Sieger Annie , Robins Moriah , Fisher Jessica Solomon , Kuehnert Paul , Castrucci Brian C.
Published: October 2022

Objectives:

Estimate the number of full-time equivalents (FTEs) needed to fully implement Foundational Public Health Services (FPHS) at the state and local levels in the United States.

Methods:

Current and full implementation cost estimation data from 168 local health departments (LHDs), as well as data from the Association of State and Territorial Health Officials and the National Association of County and City Health Officials, were utilized to estimate current and “full implementation” staffing modes to estimate the workforce gap.

Results:

The US state and local governmental public health workforce needs at least 80 000 additional FTEs to deliver core FPHS in a post–COVID-19 landscape. LHDs require approximately 54 000 more FTEs, and states health agency central offices require approximately 26 000 more.

Conclusions:

Governmental public health needs tens of thousands of more FTEs, on top of replacements for those leaving or retiring, to fully implement core FPHS.

Implications for Policy and Practice:

Transitioning a COVID-related surge in staffing to a permanent workforce requires substantial and sustained investment from federal and state governments to deliver even the bare minimum of public health services.
Optimization of protocols using neuromuscular electrical stimulation for paralyzed lower-limb muscles to increase energy expenditure in people with spinal cord injury
Authors: Ma Yiming , de Groot Sonja , Vink Ad , Harmsen Wouter , Smit Christof A.J. , Stolwijk-Swuste Janneke M. , Weijs Peter J.M. , Janssen Thomas W.J.
Published: October 2022

Objective

To evaluate if using surface neuromuscular electrical stimulation (NMES) for paralyzed lower-limb muscles results in an increase in energy expenditure and if the number of activated muscles and duty cycle affect the potential increase.

Design

Cross-sectional study.

Results

Energy expenditure during all NMES protocols was significantly higher than the condition without NMES (1.2 ± 0.2 kcal/min), with the highest increase (+ 51%; +0.7 kcal/min, 95% CI: 0.3 - 1.2) for the protocol with more muscles activated and the duty cycle with a shorter rest period. A significant decrease in muscle contraction size during NMES was found with a longer stimulation time, more muscles activated or the duty cycle with a shorter rest period.

Conclusion

Using NMES for paralyzed lower-limb muscles can significantly increase the energy expenditure compared to sitting without NMES with the highest increase for the protocol with more muscles activated and the duty cycle with a shorter rest period. Muscle fatigue occurred significantly with the more intense NMES protocols which might cause a lower energy expenditure in a longer protocol. Future studies should further optimize the NMES parameters and investigate the long-term effects of NMES on weight management in people with SCI.
High Prevalence of Long-COVID Among Kidney Transplant Recipients: A Longitudinal Cohort Study
Authors: Amorim Carlos Eduardo Neves , Gomes Vinicius Lafico Teixeira , Cristelli Marina Pontello , Viana Laila Almeida , de Luca Correa Hugo , Lima Gierisson Brenno Borges , de Sousa Silva Flaviana Santos , de Castro Lima Gabriel Santos , Rosa Thiago dos Santos , Nakamura Monica Rika , Quintino Priscilla Monteiro , Tedesco-Silva Helio , Medina-Pestana José
Published: October 2022

Background.

Kidney transplant recipients are at a higher risk to develop more severe clinical forms of coronavirus disease 2019 (COVID-19), perhaps increasing the risk of presenting its long-term clinical complications, labeled as Long-COVID.

Methods.

This single-center, observational, prospective study included adult kidney transplant recipients with COVID-19 confirmed by reverse transcription polymerase chain reaction between March 20, 2020, and May 31, 2021, who were alive and with functioning graft 3 mo after the onset of symptoms. The prevalence of Long-COVID was investigated by a phone survey using a structured questionnaire of organic symptoms. Adjusted multivariable logistic regression models were used to investigate independent risk factors.

Results.

Of 1741 patients who developed COVID-19, 465 died, and 37 returned to dialysis. Of the 1239 eligible patients, 780 (63%) answered the survey during the window period. The mean age was 48 ± 12 y, 41% were women, and the mean time from transplantation was 8 ± 6 y. During acute illness, 45% needed hospitalization. Long-COVID was identified in 214 (27%) of the subjects, with body aches being the most prevalent symptom (44%). Of 233 who provided working status, 17% did not return to work within 3 mo. No baseline characteristics or infection-related variables predicted Long-COVID; actually, the number of symptoms in the acute illness was the only independent risk factor identified (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22).

Conclusion.

In this cohort of kidney transplant recipients, Long-COVID was prevalent and associated with a reduced return to work. The burden of acute phase symptoms was the only risk factor associated with Long-COVID.
Neurological adverse events of immune checkpoint blockade: from pathophysiology to treatment
Authors: Cuzzubbo Stefania , Carpentier Antoine F.
Published: October 2022

Purpose of review

We review the recent advances in neurological toxicities of immune checkpoint inhibitors, with a focus on underlying pathophysiologic mechanisms and the implications on their therapeutical management.

Recent findings

A growing number of cancer patients benefit from immune checkpoint agents and oncologists are increasingly confronted with these novel autoimmune syndromes. During the last years, further progresses have occurred in this field, notably in the identification of specific clinical patterns, such as the association of myasthenic syndrome with myositis and myocarditis, and polyradiculoneuropathies accompanied by cerebrospinal fluid lymphocytic pleocytosis. In addition, recent immune-histological studies improved the understanding of the pathophysiologic mechanisms behind immune-related neurotoxicities.

Neurological toxicity is rare compared with other organs and systems, but its potential morbidity and mortality requires a prompt management. If there is a consensus for steroids as a first-line treatment, no exhaustive clinical data exist for other treatments. Recent advances in the knowledge of pathophysiological mechanisms (behind these toxicities) should be taken into account for the management of these patients. Drugs targeting T-cell mediated inflammation should be preferred in patients who are refractory to steroids, whereas therapies targeting humoral mechanisms should be considered in specific cases associated with autoantibodies such as immune-related myasthenic syndrome.
Frustrated ‘run and tumble’ of swimming
Escherichia coli
bacteria in nematic liquid crystals
Authors: Goral Martyna , Clement Eric , Darnige Thierry , Lopez-Leon Teresa , Lindner Anke
Published: October 2022

In many situations, bacteria move in complex environments, as soils, oceans or the human gut-track, where carrier fluids show complex structures associated with non-Newtonian rheology. Many fundamental questions concerning the ability to navigate in such environments remain unsolved. Recently, it has been shown that the kinetics of bacterial motion in structured fluids as liquid crystals (LCs) is constrained by the orientational molecular order (or director field) and that novel spatio-temporal patterns arise. A question unaddressed so far is how bacteria change swimming direction in such an environment. In this work, we study the swimming mechanism of a single bacterium,
Esherichia coli
, constrained to move along the director field of a lyotropic chromonic liquid crystal confined to a planar cell. Here, the spontaneous ‘run and tumble’ motion of the bacterium gets frustrated: the elasticity of the LC prevents flagella from unbundling. Interestingly, to change direction, bacteria execute a reversal motion along the director field, driven by the relocation of a single flagellum, a ‘frustrated tumble’. We characterize this phenomenon in detail experimentally, exploiting exceptional spatial and temporal resolution of bacterial and flagellar dynamics, using a two colour Lagrangian tracking technique. We suggest a possible mechanism accounting for these observations.
Hyperelastic continuum models for isotropic athermal fibrous networks
Authors: Song Dawei , Oberai Assad A. , Janmey Paul A.
Published: October 2022

Many biological materials contain fibrous protein networks as their main structural components. Understanding the mechanical properties of such networks is important for creating biomimicking materials for cell and tissue engineering, and for developing novel tools for detecting and diagnosing disease. In this work, we develop continuum models for isotropic, athermal fibrous networks by combining a single-fibre model that describes the axial response of individual fibres, with network models that assemble individual fibre properties into overall network behaviour. In particular, we consider four different network models, including the affine, three-chain, eight-chain, and micro-sphere models, which employ different assumptions about network structure and kinematics. We systematically investigate the ability of these models to describe the mechanical response of athermal collagen and fibrin networks by comparing model predictions with experimental data. We test how each model captures network behaviour under three different loading conditions: uniaxial tension, simple shear, and combined tension and shear. We find that the affine and three-chain models can accurately describe both the axial and shear behaviour, whereas the eight-chain and micro-sphere models fail to capture the shear response, leading to unphysical zero shear moduli at infinitesimal strains. Our study is the first to systematically investigate the applicability of popular network models for describing the macroscopic behaviour of athermal fibrous networks, offering insights for selecting efficient models that can be used for large-scale, finite-element simulations of athermal networks.
Semen rheology and its relation to male infertility
Authors: Tomaiuolo Giovanna , Fellico Fiammetta , Preziosi Valentina , Guido Stefano
Published: October 2022

Infertility affects 15% of couples of reproductive age worldwide. In spite of many advances in understanding and treating male infertility, there is still a number of issues that need further investigation and translation to the clinic. Here, we review the current knowledge and practice concerning semen rheology and its relation with pathological states affecting male infertility. Although it is well recognized that altered rheological properties of semen can impair normal sperm movement in the female reproductive tract, routine semen analysis is mostly focused on number, motility and morphology of spermatozoa, and includes only an approximate, operator-dependent measure of semen viscosity. The latter is based on the possible formation of a liquid thread from a pipette where a semen sample has been aspirated, a method that is sensitive not only to viscosity but also to elongational properties and surface tension of semen. The formation of a liquid thread is usually associated with a gel-like consistency of the sample and changes in spermatozoa motility in such a complex medium are still to be fully elucidated. The aim of this review is to point out that a more quantitative and reliable characterization of semen rheology is in order to improve the current methods of semen analysis and to develop additional tools for the diagnosis and treatment of male infertility.
The final size of an epidemic in a heterogeneous society
Authors: de Jong Peter
Published: October 2022

This note describes the outcome of an epidemic in a heterogeneous population with a very simple structure. The population is split into two sections in which the epidemic runs a different course. The reproduction numbers of the two epidemics are unobserved, only the overall reproduction number is known. For such a population the outcome of the epidemic can be as well far worse as far better than expected on the basis of the overall reproduction number.

By considering a very simple model of this population some calculations are feasible under general assumptions on the epidemic itself. These calculations show in which direction models based on the overall reproduction number can misrepresent the real-world situation.
Acupuncture for emotional disorder and quality of life in patients with polycystic ovary syndrome-A protocol for a systematic review and meta-analysis
Authors: Zhang Chunping , Zhang Yiwen , Chen Jian , Yan Chuanzhu
Published: October 2022

Background

Infertility, obesity, hairiness, acne and other symptoms of polycystic ovary syndrome can easily lead to emotional disorders, such as anxiety and depression, and also affect the patients’ quality of life. A large number of studies have shown that acupuncture has a good effect on polycystic ovary syndrome, but there is no evidence that acupuncture can relieve the affective disorders and improve the quality of life in patients with polycystic ovary syndrome.

Objectives

To assess the effectiveness and safety of acupuncture for emotional disorder and quality of life in patients with PCOS.

Methods and analysis

From inception to July 31, 2022, a total of four English-language databases (PubMed, Embase, Web of science and the Cochrane Central Register of Controlled Trials) and four Chinese-language databases (the China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical) were searched. The randomized clinical trial (RCT) of acupuncture for polycystic ovary syndrome was selected for inclusion in the study. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.4) software. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

Results and conclusion

This study will systematically evaluate the efficacy and safety of acupuncture for emotional disorder and quality of life in patients with polycystic ovary syndrome.
Advanced physiological maturation of iPSC-derived human cardiomyocytes using an algorithm-directed optimization of defined media components
Authors: Callaghan Neal I. , Durland Lauren J. , Chen Wenliang , Kuzmanov Uros , Miranda Maria Zena , Mirzaei Zahra , Ireland Ronald G. , Wang Erika Yan , Wagner Karl , Kim Michelle M. , Audet Julie , Santerre J. Paul , Gramolini Anthony O. , Billia Filio , Radisic Milica , Mital Seema , Ellis James , Backx Peter H. , Simmons Craig A.
Published: October 2022

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold tremendous promise for in vitro modeling to assess native myocardial function and disease mechanisms as well as testing drug safety and efficacy. However, current iPSC- CMs are functionally immature, resembling in vivo CMs of fetal or neonatal developmental states. The use of targeted culture media and organoid formats have been identified as potential high-yield contributors to improve CM maturation. This study presents a novel iPSC-CM maturation medium formulation, designed using a differential evolutionary approach targeting metabolic functionality for iterative optimization. Relative to gold-standard reference formulations, our medium significantly matured morphology, Ca2+handling, electrophysiology, and metabolism, which was further validated by multiomic screening, for cells in either pure or co-cultured microtissue formats. Together, these findings not only provide a reliable workflow for highly functional iPSC-CMs for downstream use, but also demonstrate the power of high-dimensional optimization processes in evoking advanced biological function in vitro.
Enhancing Mucosal-Associated Invariant T (MAIT) cell function and expansion with human selective serum
Authors: Labuz Daniel , Cacioppo Jackson , Li Kelin , Aubé Jeffrey , Leung Daniel T.
Published: October 2022

Mucosal-associated invariant T (MAIT) cells are promising innate-like lymphocytes with potential for use in anti-tumor immunotherapy. Existing MAIT cell expansion protocols are associated with potentially decremental phenotypic changes, including increased frequency of CD4+ MAIT cells and higher inhibitory receptor expression. In this study, we compared the effect on expansion of human MAIT cells of a serum replacement, Physiologix XF SR (Phx), with traditional serum fetal bovine serum (FBS) for supplementing RPMI-1640 media. Using flow cytometry, we found that Phx supported a significantly higher proliferative capacity for MAIT cells and resulted in a lower frequency of CD4+ MAIT cells, which have been associated with reduced Th1 effector and cytolytic functions. We saw that culturing MAIT cells in Phx led to better survival of MAIT cells and lower frequency of PD-1+ MAIT cells compared to FBS-supplemented media. Functionally, we saw that Phx supplementation was associated with a higher frequency of IFN-γ+ MAIT cells after stimulation withE. colicompared to FBS-supplemented RPMI. In conclusion, we show that MAIT cells cultured in Phx have higher proliferative capacity, lower expression of inhibitory receptors, and have higher capacity to produce IFN-γ afterE. colistimulation, compared to FBS-supplemented RPMI. This work shows that expanding MAIT cells with Phx compared to FBS-supplemented RPMI result in a more functionally desirable MAIT cell for future anti-tumor immunotherapy.
Developing a standardized but extendable framework to increase the findability of infectious disease datasets
Authors: Tsueng Ginger , Alvarado Cano Marco A. , Bento José , Czech Candice , Kang Mengjia , Pache Lars , Rasmussen Luke V. , Savidge Tor C. , Starren Justin , Wu Qinglong , Xin Jiwen , Yeaman Michael R. , Zhou Xinghua , Su Andrew I. , Wu Chunlei , Brown Liliana , Shabman Reed S. , Hughes Laura D. ,   the NIAID Systems Biology Data Dissemination Working Group
Published: October 2022

Biomedical datasets are increasing in size, stored in many repositories, and face challenges in FAIRness (findability, accessibility, interoperability, reusability). As a Consortium of infectious disease researchers from 15 Centers, we aim to adopt open science practices to promote transparency, encourage reproducibility, and accelerate research advances through data reuse. To improve FAIRness of our datasets and computational tools, we evaluated metadata standards across established biomedical data repositories. The vast majority do not adhere to a single standard, such asSchema.org, which is widely-adopted by generalist repositories. Consequently, datasets in these repositories are not findable in aggregation projects like Google Dataset Search. We alleviated this gap by creating a reusable metadata schema based onSchema.organd catalogued nearly 400 datasets and computational tools we collected. The approach is easily reusable to create schemas interoperable with community standards, but customized to a particular context. Our approach enabled data discovery, increased the reusability of datasets from a large research consortium, and accelerated research. Lastly, we discuss ongoing challenges with FAIRness beyond discoverability.
The Genome of the WaspAnastatus disparisReveals Energy Metabolism Adaptations for Extreme Aggression
Authors: Liu Pengcheng , Wang Ziyin , Tao Yumei , Yin Siyu , Wei Jianrong , Wang Jianjun , Hu Haoyuan
Published: October 2022

Extremely aggressive behavior is rare in most species, as contestants can be severely injured or killed. Such high level of aggression can evolve when critical resources are limited, as the benefits of winning outweigh the potential costs of conflict. Currently, studies of extreme aggression are mainly from the perspectives of behavioral ecology and evolutionary biology, displaying distinct results from common nonextreme aggression. Here, we provide a high-quality genome of the generalist endoparasitoidAnastatus disparis, the males of which exhibit extreme mate-competition aggression, to shed light on possible genomic adaptations for extreme aggressive behavior. We combined Nanopore PromethION sequencing with Hi-C technology to assemble a high-quality chromosome-level genome ofA. disparis. The size of the genome of this species (939.58 Mb) is larger than that of most hymenopterans (ranging from 180 Mb to 340 Mb) due to the expansion of repeated sequences (612.90 Mb, 65.23% of the whole genome). With the aid of RNA sequencing, 19,246 protein-coding genes were identified, and a great expansion of genes involved in detoxification was detected, which could represent an adaptation of this species to exploit a diverse range of known hosts. The integrated multiomics analysis highlighted genes involved in energy metabolism (especially from lipids) and antibacterial activity, both of which are possibly major aspects of adaptation for extreme aggression inA. disparis. Our study provides insight into molecular and evolutionary studies of extreme aggression inA. disparisand provides a valuable genomic resource for further research into the molecular basis of trait evolution in Hymenoptera.
A Cre-Driver Rat Model for Anatomical and Functional Analysis of Glucagon(Gcg)-Expressing Cells in the Brain and Periphery
Authors: Zheng Huiyuan , López-Ferreras Lorena , Krieger Jean-Phillipe , Fasul Stephen , Salazar Valentina Cea , Pena Natalia Valderrama , Skibicka Karolina P. , Rinaman Linda
Published: October 2022

Objective

The glucagon gene (Gcg) encodes preproglucagon, which is cleaved to form glucagon-like peptide 1 (GLP1) and other mature signaling molecules implicated in metabolic functions. To date there are no transgenic rat models available for precise manipulation of GLP1-expressing cells in the brain and periphery.

Methods

To visualize and manipulateGcg-expressing cells in rats, CRISPR/Cas9 was used to expressiCreunder control of theGcgpromoter. Gcg-Cre rats were bred with tdTomato reporter rats to tagGcg-expressing cells. Cre-dependent AAVs and RNAscopein situhybridization were used to evaluate the specificity ofiCreexpression by GLP1 neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt), and by intestinal and pancreatic secretory cells. Food intake was assessed in heterozygous (Het) Gcg-Cre rats after chemogenetic stimulation of cNTS GLP1 neurons expressing an excitatory DREADD.

Results

While genotype has minimal effect on body weight or composition in chow-fed Gcg-Cre rats, homozygous (Homo) rats have lower plasma glucose levels. In neonatal and adult Gcg-Cre/tdTom rats, reporter-labeled cells are present in the cNTS and IRt, and in additional brain regions (e.g., basolateral amygdala, piriform cortex) that lack detectableGcgmRNA in adults but display transient developmental or persistently lowGcgexpression. Compared to wildtype (WT) rats, hindbrainGcgmRNA and GLP1 protein in brain and plasma are markedly reduced in Homo Gcg-Cre rats. Chemogenetic stimulation of cNTS GLP1 neurons reduced overnight chow intake in males but not females, the effect in males was blocked by antagonism of central GLP1 receptors, and hypophagia was enhanced when combined with a subthreshold dose of cholecystokinin-8 to stimulate gastrointestinal vagal afferents.

Conclusions

Gcg-Cre rats are a novel and valuable experimental tool for analyzing the development, anatomy, and function ofGcg-expressing cells in the brain and periphery. In addition, Homo Gcg-Cre rats are a unique model for assessing the role ofGcg-encoded proteins in glucose homeostasis and energy metabolism.

Highlights

A transgenic Gcg-Cre rat model expressesiCreunder control of theGcgpromoter

iCreis expressed by GLP1-positive cells in the hindbrain, pancreas, and intestine

Additional brain regions display transient and/or very low levels ofGcgexpression

+/+ Gcg-Cre rats display a marked knockdown ofGcgmRNA and GLP1 protein

Chemogenetic activation ofGcgneurons suppresses food intake in +/- Gcg-Cre rats
The establishment and transmission of novel foraging techniques indicates a capacity for culture in bumblebees (Bombus terrestris)
Authors: Bridges Alice D. , MaBouDi HaDi , Procenko Olga , Lockwood Charlotte , Mohammed Yaseen , Kowalewska Amelia , Romero González José Eric , Woodgate Joseph L. , Chittka Lars
Published: October 2022

The astonishing behavioural repertoires of social insects have been thought largely innate, but these insects have repeatedly demonstrated remarkable capacities for both individual and social learning. Using the bumblebeeBombus terrestrisas a model, we developed a two-option puzzle box task and used open diffusion paradigms to observe the transmission of novel, non-natural foraging behaviours through populations. Box-opening behaviour spread through colonies seeded with a demonstrator trained to perform one of the two possible behavioural variants, and the observers acquired the demonstrated variant. This preference persisted among observers even when the alternative technique was discovered. In control diffusion experiments that lacked a demonstrator, some bees spontaneously opened the puzzle boxes but were significantly less proficient than those that learned in the presence of a demonstrator. This suggested that social learning was crucial to proper acquisition of box-opening. Additional open diffusion experiments where two behavioural variants were initially present in similar proportions ended with a single variant becoming dominant, due to stochastic processes. This could lead to the emergence and maintenance of local cultural variation. These results suggest that bumblebees, like mammals and birds, may have the capacity for culture and to sustain cultural variation.
Annoying noise: effect of anthropogenic underwater sound on the movement and feeding performance in the red cherry shrimp,Neocaridina davidi
Authors: Azarm-Karnagh Sasan , Lopez Greco Laura , Shafiei Sabet Saeed
Published: October 2022

Acoustic pollution in aquatic environments has increased dramatically, with adverse effects on many organisms. Benthic organisms, including many invertebrates, can sense underwater sounds, yet the responses they trigger in these organisms have received little attention. This study investigates the impact of underwater sound on the behaviour of the red cherry shrimpNeocaridina davidias a model of freshwater decapod. The effect of underwater sound exposure on the movement behaviour and feeding performance of individual shrimps was assessed. Movement speed decreased significantly upon opening the divider in both the sound and control treatments. However, there were no significant changes in total minutes between the control and sound treatments, implying no sound-related initial changes for releasing movement. The spatial distribution of shrimps in response to the sound treatment showed significant changes; shrimps spent more time at the farthest point from the sound source. The time to find the food source (latency) also increased in the sound treatment compared to the control. Moreover, in terms of the number of successes and failures in finding the food source in the control treatment, significantly more shrimps succeeded in finding the food source. Besides, the number of revisits to the food source decreased in sound treatment compared to control and more shrimps were significantly distracted in sound treatment. Our study highlights the crustacean’s ability to receive human-made sound. Thus, they are prone to the impacts of anthropogenic sound, causing negative impacts on their movement-swimming activities, and feeding behaviour and exposing them to potential predator threats. Affecting foraging performance in this gregarious species may have detrimental impacts on their reproductive success and, subsequently unexpected fitness consequences.
Inferring disease architecture and predictive ability with LDpred2-auto
Authors: Privé Florian , Albiñana Clara , Arbel Julyan , Pasaniuc Bogdan , Vilhjálmsson Bjarni J.
Published: October 2022

LDpred2 is a widely used Bayesian method for building polygenic scores (PGS). LDpred2-auto can infer the two parameters from the LDpred model, the SNP heritabilityh2and polygenicityp, so that it does not require an additional validation dataset to choose best-performing parameters. The main aim of this paper is to properly validate the use of LDpred2-auto for inferring multiple genetic parameters. Here, we present a new version of LDpred2-auto that adds an optional third parameterαto its model, for modeling negative selection. We then validate the inference of these three parameters (or two, when using the previous model). We also show that LDpred2-auto provides per-variant probabilities of being causal that are well calibrated, and can therefore be used for fine-mapping purposes. We also derive a new formula to infer the out-of-sample predictive performancer2of the resulting PGS directly from the Gibbs sampler of LDpred2-auto. Finally, we extend the set of HapMap3 variants recommended to use with LDpred2 with 37% more variants to improve the coverage of this set, and show that this new set of variants captures 12% more heritability and provides 6% more predictive performance, on average, in UK Biobank analyses.
OPTIMIZED NEURON TRACING USINGPOST HOCREANALYSIS
Authors: Azzouz Sara , Walker Logan A , Doerner Alexandra , Geisel Kellie L. , Rodríguez Rivera Arianna K. , Li Ye , Roossien Douglas H , Cai Dawen
Published: October 2022

Over the last decade, the advances in Brainbow labeling allowed labeling hundreds of neurons with distinct colors in the same field of view of a brain [1, 2]. Reconstruction (or “tracing”) of the 3D structures of these images has been enabled by a growing set of software tools for automatic and manual annotation. It is common, however, to have errors introduced by heuristics used by tracing software, namely that they assume the “best” path is the highest intensity one, a more pertinent issue when dealing with multicolor microscope images. Here, we reportnCorrect, an algorithm for correcting this error by reanalyzing previously created neuron traces to produce more physiologically-relevant ones. Specifically, we use a four dimensional minimization algorithm to identify a more-optimal reconstruction of the image, allowing us to better take advantage of existing manual tracing results. We define a new metric (hyperspectral cosine similarity) for describing the similarity of different neuron colors to each other. Our code is available in an open source license and forms the basis for future improved neuron tracing software.
Effects of parental verbal abuse experience on the Glutamate response to swear words in the ventromedial prefrontal cortex: A functional1H-magnetic resonance spectroscopy study
Authors: Yoo Jae Hyun , Park Young Woo , Kim Dohyun , Park HyunWook , Jeong Bumseok
Published: October 2022

Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established in humans. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23±4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC.

A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. Furthermore, the total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words (ΔGluSw e). The interaction term of ΔGluSw eand baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between ΔGluSw ein the AMHC and either pVAQ or emotional states.

We conclude that parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.
A suberized exodermis is required for tomato drought tolerance
Authors: Cantó-Pastor Alex , Kajala Kaisa , Shaar-Moshe Lidor , Manzano Concepción , Timilsena Prakash , De Bellis Damien , Gray Sharon , Holbein Julia , Yang He , Mohammad Sana , Nirmal Niba , Suresh Kiran , Ursache Robertas , Mason G. Alex , Gouran Mona , West Donnelly A. , Borowsky Alexander T. , Shackel Kenneth A. , Sinha Neelima , Bailey-Serres Julia , Geldner Niko , Li Song , Franke Rochus Benni , Brady Siobhan M.
Published: October 2022

Plant roots integrate environmental signals and developmental programs using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates the entry and exit of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation, but we find that it is absent in the tomato endodermis during normal development. Instead, suberin is present in the exodermis, a cell type that is absent in the model organismArabidopsis thaliana. Here, we uncover genes driving exodermal suberization and describe its effects on drought responses in tomato, unravelling the similarities and differences with the paradigmatic Arabidopsis endodermis. Cellular resolution imaging, gene expression, and mutant analyses reveal loss of this program from the endodermis, and its co-option in the exodermis. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response. Controlling the degree of exodermal suberization could be a new strategy for breeding climate-resilient plants.
The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study
Authors: Liu Junxi , Richmond Rebecca C , Anderson Emma L , Bowden Jack , Barry Ciarrah-Jane S , Dashti Hassan S , Daghlas Iyas S , Lane Jacqueline M , Kyle Simon D , Vetter Céline , Morrison Claire L , Jones Samuel E , Wood Andrew R , Frayling Timothy M , Wright Alison K , Carr Matthew J , Anderson Simon G , Emsley Richard A , Ray David W , Weedon Michael N , Saxena Richa , Rutter Martin K , Lawlor Deborah A
Published: October 2022

Study Objectives

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar results observed in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other sleep traits, on glycated haemoglobin (HbA1c). Our aims were a) to explore potential effects of accelerometer-derived sleep traits on HbA1c and glucose levels and b) to determine genetic correlations across accelerometer-derived and self-reported sleep traits.

Methods

We used MR methods to explore effects of accelerometer-derived sleep traits (duration, mid-point least active 5-hours, mid-point most active 10-hours, sleep fragmentation, and efficiency) on HbA1c in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 149,054). Cross-trait linkage disequilibrium score regression was also applied to determine genetic correlations across all accelerometer-derived and self-reported sleep traits and HbA1c/glucose.

Results

Main and sensitivity MR analyses showed no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure.

Conclusions

Taken together, these findings suggested accelerometer-derived sleep traits do not causally affect HbA1c levels, and accelerometer-derived measures of sleep duration and sleep quality might not simply be ‘objective’ measures of self-reported sleep duration and insomnia, but rather captured different underlying sleep characteristics.

Statement of Significance

Self-reported and accelerometer-derived sleep disturbance is associated with increased risk of hyperglycaemia and type 2 diabetes in observational analyses. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other self-reported sleep traits, on glycated haemoglobin (HbA1c). This MR study showed little evidence supporting an effect of any accelerometer-derived sleep trait on HbA1c or glucose, but a potential non-linear (e.g., U-shaped) effect cannot be ruled out. The genetic correlation suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different exposures.
Test-retest reliability of functional connectivity in depressed adolescents
Authors: Camp Chris C. , Noble Stephanie , Scheinost Dustin , Stringaris Argyris , Nielson Dylan M.
Published: October 2022

The test-retest reliability of fMRI functional connectivity is a key factor in the identification of reproducible biomarkers for psychiatric illness. Low reliability limits the observable effect size of brain-behavior associations. Despite this important connection to clinical applications of fMRI, few studies have explored reliability in populations with psychiatric illnesses or across age groups. We investigate the test-retest reliability of functional connectivity in a longitudinal cohort of adolescents with and without major depressive disorder (MDD). Measuring reliability is complex and several metrics exist that can offer unique perspectives: for example, univariate metrics capture reliability of a single connection at a time while multivariate metrics reflect stability of the entire connectome. We compare a widely used univariate metric, intraclass correlation coefficient (ICC), and two multivariate metrics, fingerprinting and discriminability. Depressed adolescents were more reliable than healthy adolescents at the univariate level (0.34 > 0.24; Wilcoxon rank-sum:p< .001), and both groups had poor average ICCs (<0.4). Multivariate reliability was high in both groups: fingerprinting (FIHV= 0.53; FIMDD= 0.45; Poisson(1) testp< .001) and discriminability were above chance (DiscrHV= 0.75;DiscrMDD= 0.76; 500-fold permutation testp< .01). Reliability was not associated with symptoms or medication, suggesting that there is not a strong relationship between depression and reliability. These findings support the shift towards multivariate analysis for improved power and reliability.
Inability to make facial expressions dampens emotion perception
Authors: Japee Shruti , Jordan Jessica , Licht Judith , Lokey Savannah ,   Moebius Syndrome Research Consortium, Chen Gang , Snow Joseph , Jabs Ethylin Wang , Webb Bryn D , Engle Elizabeth C , Manoli Irini , Baker Chris , Ungerleider Leslie G.
Published: October 2022

Humans rely heavily on facial expressions for social communication to convey their thoughts and emotions and to understand them in others. One prominent but controversial view is that humans learn to recognize the significance of facial expressions by mimicking the expressions of others. This view predicts that an inability to make facial expressions (e.g., facial paralysis) would result in reduced perceptual sensitivity to others’ facial expressions. To test this hypothesis, we developed a diverse battery of sensitive emotion recognition tasks to characterize emotion perception in individuals with Moebius Syndrome (MBS), a congenital neurological disorder that causes facial palsy. Using computer-based emotion detection tasks we systematically assessed emotion perception thresholds for static and dynamic face and body expressions. We found that while MBS individuals were able to perform challenging perceptual control tasks, they were less efficient at extracting emotion from facial expressions, compared to matched controls. Exploratory analyses of fMRI data from a small group of MBS participants suggested potentially reduced engagement of the amygdala in MBS participants during expression processing relative to matched controls. Collectively, these results support the role of facial mimicry and consequent facial feedback and motor experience in the perception of others’ expressions.