bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Testing and Self-Reported Diagnoses of Sexually Transmitted Infections in Gay and Bisexual Men in Australia, 2017-2021: Analysis of National Behavioural Surveillance Surveys
Authors: Chan Curtis , Holt Martin , Broady Timothy R. , Traeger Michael , Mao Limin , Grulich Andrew E. , Prestage Garrett , MacGibbon James , Rule John , Bavinton Benjamin R.
Published: October 2023

Background

Gay, bisexual, and other men who have sex with men (GBM) are overrepresented in diagnoses of sexually transmitted infections (STI) relative to their population size. This study assessed trends in STI testing and diagnoses among GBM in Australia.

Methods

The Gay Community Periodic Surveys are repeated cross-sectional behavioural surveillance surveys of GBM. Participants reported the number of anal swabs, throat swabs, urine samples, and blood tests for syphilis they undertook in the last year. ‘Frequent comprehensive testing’ was defined as ≥3 of each test in the previous year. Participants reported STI diagnoses of chlamydia, gonorrhoea, syphilis, and other STIs in the last year. Trends in testing and diagnoses from 2017-2020 and 2020-2021 were assessed with logistic regression models.

Results

We analysed 24,488 survey responses from participants reporting casual sex in the last 6 months. Between 2017-2020, frequent comprehensive STI testing decreased among HIV-negative GBM on PrEP from 71.7% to 68.9% and declined further to 58.6% in 2021. Frequent comprehensive STI testing was stable during 2017-2020 among HIV-negative/untested GBM not on PrEP (17.4% to 14.6%) and HIV-positive GBM (30.4% to 35.1%) but declined in 2021 to 7.5% among non-PrEP-users and 25.7% among HIV-positive participants. There were minimal changes in STI diagnoses during 2017-2020, but diagnoses declined in 2021.

Conclusions

Many GBM do not meet Australian STI testing guidelines that recommend quarterly testing. Further evaluation of whether this recommendation is realistic or necessary to reduce STIs among GBM is recommended.
Cardiac Enlargement in a Medicolegal Autopsy Setting
Authors: Beer Torfinn , Eriksson Anders , Wingren Carl Johan
Published: October 2023

A key element for diagnosing cardiac enlargement in an autopsy setting is relevant heart weight references. However, most available references are to a large extent not representative of a medicolegal autopsy population, implying that reference weights are likely lower than those in the relevant population.

To establish more applicable heart weight references in a medicolegal autopsy population, we designed a heart weight model that accounts for undiagnosed cardiac enlargement using data from 11,897 nontraumatic Swedish medicolegal autopsy cases autopsied between 2010 and 2019. The model was validated in 296 nonobese young adult suicidal hanging cases.

For a decedent of average height (174 cm), the evidence that a heart weight was enlarged reached weak support at approximately 430 g, substantial support at approximately 480 g, and strong support at 520 g. The modeled prevalence of cardiac enlargement was very high among elderly and obese decedents.

We believe that our model is more applicable in a medicolegal setting than those previously published. The presented quantification of the degree of uncertainty regarding diagnosis can help the pathologist in diagnosing cardiac enlargement. To facilitate the use of this model, we also made it available through a simple online tool (https://formedum.shinyapps.io/HeartWeightCalc/).
Association of Complex Repetitive Discharges With Chronicity and Clinical Symptoms in Radiculopathies
Authors: Skolka Michael P. , Hass Reece M. , Rubin Devon I. , Laughlin Ruple S.
Published: October 2023

Purpose:

Complex repetitive discharges (CRDs) are incompletely understood needle electromyography (EMG) waveforms seen in both myopathic and neurogenic disorders including radiculopathies. This study aimed to clarify the significance of CRDs in patients with radiculopathies.

Methods:

This case–control study randomly identified 100 patients with needle EMG evidence of radiculopathy demonstrating at least one CRD in the electrodiagnostically involved myotome between January 2017 and January 2022. These patients were compared with 100 randomly selected patients with EMG evidence of radiculopathy without CRDs controlled for sex, age at EMG testing, and affected nerve root segment. Patient clinical symptoms, neurologic examination, EMG features, and imaging were analyzed. A paired sample t-test for categorial data and χ2 test for nonparametric data were used for statistical analysis with significance defined as P < 0.05.

Results:

Patients with radiculopathies with CRDs had longer disease duration averaging 59 months (range 1–480) compared with patients with radiculopathies without CRDs averaging 26 months (range 1–192, P < 0.01). Clinical symptoms of paresthesias and weakness were both significantly more common in patients with radiculopathies with CRDs than those without CRDs (P < 0.01 and 0.01, respectively). Needle EMG demonstrated a greater average number of muscles with neurogenic motor unit potentials per radiculopathy in patients with radiculopathies with CRDs compared with those without CRDs. Imaging studies of patients with radiculopathies with CRDs were more likely to reveal evidence of nerve root compression (P < 0.01).

Conclusions:

The presence of CRDs in patients with radiculopathies is consistent with clinically more symptomatic radiculopathies and a longer duration of nerve root compromise.
ICTV Virus Taxonomy Profile: Yueviridae 2023
Authors: Krupovic Mart , Wolf Yuri I. , Koonin Eugene V. , Kuhn Jens H.
Published: October 2023

Yueviridae is a family of negative-sense RNA viruses with genomes of 7.8–8.2 kb that have been associated with crustaceans, insects, stramenopiles and plants. The yuevirid genome consist of two segments, each with at least one ORF. The large (L) segment ORF encodes a large protein containing an RNA-directed RNA polymerase domain. The small (S) segment ORF encodes a nucleocapsid protein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Yueviridae, which is available at http://www.ictv.global/report/yueviridae.
The Positive F Wave in Lead V1 of Typical Atrial Flutter is Caused by Activation of the Right Atrial Appendage: Insight from Mapping During Entrainment from the Right Atrial Appendage
Authors: Yamashita Shu , Mizukami Akira , Ono Maki , Hiroki Jiro , Miyakuni Shota , Miyamoto Hina , Ishizu Hiroki , Arashiro Takumi , Noguchi Soichi , Ueshima Daisuke , Matsumura Akihiko , Miyazaki Shinsuke , Sasano Tetsuo
Published: October 2023

Background

Typical atrial flutter (AFL) is a macroreentrant tachycardia in which intra-cardiac conduction rotates counterclockwise around the tricuspid annulus. Typical AFL has specific electrocardiographic characteristics of a negative sawtooth-like wave in the inferior lead and a positive F wave in lead V1.

Objective

This study analyzed the source of the positive F wave in lead V1, which has not been well elucidated.

Methods

This study included 10 patients who underwent radiofrequency catheter ablation for a typical AFL. Electroanatomical mapping was performed both during typical AFL and entrainment from the right atrial appendage (RAA). The 12-lead electrocardiogram and three-dimensional (3D) electroanatomical maps were analyzed.

Results

The positive F wave in lead V1 changed during entrainment from the RAA in all the cases. The 3D map during entrainment from the RAA showed an area of antidromic capture around the RAA, which collided with the orthodromic wave in the anterior right atrium. This area of antidromic capture around the RAA was the only difference from the 3D electroanatomical map of tachycardia and is thought to be the cause of the disappearance of the F wave in lead V1 during entrainment.

Conclusion

The analysis of the differences in the 12-lead ECG and 3D maps between tachycardia and entrainment from the RAA clearly showed that activation around the RAA is responsible for the generation of the positive F wave in lead V1 of typical AFL.
Transactional sex and age-disparate sexual partnerships among adolescent girls and young women in Tanzania
Authors: Rucinski Katherine B. , Mbita Gaspar , Atkins Kaitlyn , Majani Esther , Komba Albert , Casalini Caterina , Drake Mary , Makyao Neema , Galishi Anthony , Mlawa Yeronimo , Wamoyi Joyce , Schwartz Sheree , Baral Stefan , Curran Kelly
Published: October 2023

Adolescent girls and young women (AGYW) continue to experience a high incidence of HIV in southern and eastern Africa, even in the context of large-scale HIV prevention interventions. In Tanzania, AGYW account for the largest proportion of new infections and have a higher risk of HIV acquisition than males of comparable age. We used routinely collected data from the PEPFAR/USAID-funded Sauti Project, a large combination HIV prevention program, to examine the relationship between transactional sex and sex with older partners among AGYW in Tanzania (2015-2020). Out-of-school AGYW 15-24 years completed a vulnerability index and were tested for HIV. We estimated weighted prevalence ratios (PR) and 95% confidence intervals (CI) for the associations of transactional sex (sex exchanged for money/services/gifts outside of sex work) and sex with older partners (≥5-years older, ≥10-years older) with prevalent HIV. We assessed potential synergism between exposures, and subgroup analyses explored associations among girls 15-19. 67,357 AGYW completed the vulnerability index and 14,873 had captured HIV testing records. Median age was 20 years (IQR 18-22). Transactional sex and age-disparate sex were common (35% and 28%, respectively); 13% of AGYW reported both behaviors. HIV prevalence was associated with both transactional sex (PR:1.28; 95% CI 1.00-1.63) and age-disparate sex (PR:1.26, 95% CI 0.99-1.60). In common referent analysis, transactional sex remained strongly associated with HIV, even in the absence of age-disparate sex (PR 1.41; 95% CI 1.02-1.94). Evidence of statistical synergism was not present, suggesting both transactional sex and age-disparate sex operate through similar pathways to increase HIV risk. Increased specificity within HIV prevention programs is needed to better meet the sexual and reproductive health needs of AGYW at high risk of HIV in Tanzania, including investment in tailored youth-friendly strategies for AGYW who have been marginalized from the current HIV response.
Transient brain activity dynamics discriminate levels of consciousness during anesthesia
Authors: Ensel Scott , Uhrig Lynn , Ozkirli Ayberk , Hoffner Guylaine , Tasserie Jordy , Dehaene Stanislas , Van De Ville Dimitri , Jarraya Béchir , Pirondini Elvira
Published: October 2023

The awake mammalian brain is functionally organized in terms of large-scale distributed networks that are constantly interacting. Loss of consciousness might disrupt this temporal organization leaving patients unresponsive. We hypothesized that characterizing brain activity in terms of transient events may provide a signature of consciousness. For this, we analyzed temporal dynamics of spatiotemporally overlapping functional networks obtained from fMRI transient activity across different states of consciousness. We first show a striking homology in spatial organization of networks between monkeys and humans, indicating cross-species similarities in resting- state fMRI structure. We then tracked how network organization shifts under different anesthesia conditions in macaque monkeys. While the spatial aspect of the networks was preserved, their temporal dynamics were highly affected by anesthesia. Networks expressed for longer durations and co-activated in an anesthetic-specific configuration. Additionally, hierarchical brain organization was disrupted with a consciousness-level- signature role of the default mode network. In conclusion, network temporal dynamics is a reliable and robust cortical signature of consciousness, paving the way to its clinical translation.
Developmentally regulated generation of a systemic signal for long-lasting defence priming in tomato
Authors: Stevens Katie , Roberts Michael R , Jeynes-Cupper Katie , Catoni Marco , Luna Estrella
Published: October 2023

Tomato plants can be chemically primed to express long-lasting induced resistance (IR) for the protection of fruit against pathogen infection. Here, we determined that priming results in maintenance of IR in fruit and progeny of tomato plants only when initiated at an early developmental stage. Global DNA methylation analysis revealed seedling-specific changes, which occurred in the context of lower basal methylation, suggesting a greater epigenetic imprinting capacity of young plants. Remarkably, IR was found to be transmissible from primed rootstock to grafted unprimed scions. In these scions, we identified a subset of mobile 24 nt small RNAs associated with genes with enhanced expression in response toBotrytis cinereainfection in fruit, suggesting the functional association of a systemic signal with long-lasting IR and priming. Through integrated omics approaches we have identified markers of long-lasting priming in tomato fruit which could also serve as targets for durable resistance in other crops.
Comparison of genomic DNA isolation methods inPereskia aculeata Mill. (Ora-pro-nóbis)
Authors: Silva Neta Joselina Barbosa da , Silva Neto Amaro Antônio , Magalhães Thaís Correia , Diniz Michely Correia
Published: October 2023

In Brazil, it is estimated that at least 10% of the native flora, which corresponds to about 4 or 5 thousand plant species, are used for food purposes. Among these species,Pereskia aculeataMill, known as ora-pro-nóbis and belonging to the Cactaceae family, stands out. It is considered a Unconventional Food Plant (UFP) and a vegetable of traditional use, playing an important role in the diet and economy of rural and urban families. Due to their high nutrient content, they have both economic and social significance, being a target of interest for scientific research. Despite the potential for human use of this species, there is a lack of knowledge about its diversity and genomic structure, resulting in few genetic and molecular studies that can contribute to the conservation and improvement of this species in general. It is essential to acquire information about its genomic structure, as well as to carry out studies related to the comparison, selection and optimization of protocols for obtaining quality DNA and in sufficient quantity, in order to guarantee the success of molecular and evolutionary analyses. The aim of this research was to evaluate qualitatively and quantitatively methods of isolation of genomic DNA fromPereskia aculeataMill. Significant variations were observed in the DNA extracted and in the purity observed between the different protocols tested, with the isolation by the protocol described by Sambrook et al. (1989) being the most efficient in terms of concentration and purity, followed by the modified method proposed in this work. This work is a pioneer in comparing methods for isolating DNA fromPereskia aculeataMill. in terms of quality and quantity. In addition, it was found that there is still a scarcity of molecular studies on this species, both worldwide and in Brazil, which indicates the existence of a promising gap for the development and realization of scientific research in this field.
Hibernation reduces GABA signaling in the brainstem to enhance motor activity of breathing at cool temperatures
Authors: Saunders Sandy E. , Santin Joseph M.
Published: October 2023

Background

Neural circuits produce reliable activity patterns despite disturbances in the environment. For this to occur, neurons elicit synaptic plasticity during perturbations. However, recent work suggests that plasticity not only regulates circuit activity during disturbances, but these modifications may also linger to stabilize circuits during future perturbations. The implementation of such a regulation scheme for real-life environmental challenges of animals remains unclear. Amphibians provide insight into this problem in a rather extreme way, as circuits that generate breathing are inactive for several months during underwater hibernation and use compensatory plasticity to promote ventilation upon emergence.

Results

Usingex vivobrainstem preparations and electrophysiology, we find that hibernation in American bullfrogs reduces GABAAreceptor (GABAAR) inhibition in respiratory rhythm generating circuits and motor neurons, consistent with a compensatory response to chronic inactivity. Although GABAARs are normally critical for breathing, baseline network output at warm temperatures was not affected. However, when assessed across a range of temperatures, hibernators with reduced GABAAR signaling had greater activity at cooler temperatures, enhancing respiratory motor output under conditions that otherwise strongly depress breathing.

Conclusions

Hibernation reduces GABAAR signaling to promote robust respiratory output only at cooler temperatures. Although animals do not ventilate lungs during hibernation, we suggest this would be beneficial for stabilizing breathing when the animal passes through a large temperature range during emergence in the spring. More broadly, these results demonstrate that compensatory synaptic plasticity can increase the operating range of circuits in harsh environments, thereby promoting adaptive behavior in conditions that suppress activity.
Computational modeling establishes mechanotransduction as a potent modulator of the mammalian circadian clock
Authors: Francis Emmet A. , Rangamani Padmini
Published: October 2023

Mechanotransduction, which is the integration of mechanical signals from the cell’s external environment to changes in intracellular signaling, governs many cellular functions. Recent studies have shown that the mechanical state of the cell is also coupled to the cellular circadian clock. To investigate possible interactions between circadian rhythms and cellular mechanotransduction, we have developed a computational model that integrates the two pathways. We postulated that the translocation of the transcriptional regulators YAP/TAZ and MRTF into the nucleus leads to altered expression of circadian proteins. Simulations from our model predict that lower levels of cytoskeletal activity are associated with longer circadian oscillation periods and higher oscillation amplitudes, consistent with recent experimental observations. Furthermore, accumulation of YAP/TAZ and MRTF in the nucleus causes circadian oscillations to decay. These effects hold both at the single-cell level and within a population-level framework. Finally, we investigated the effects of mutations in YAP or lamin A, the latter of which lead to a class of diseases known as laminopathies. Oscillations in circadian proteins are substantially weaker in populations of cells within silicomutations in YAP or lamin A, suggesting that defects in mechanotransduction can disrupt the circadian clock in certain disease states. However, by reducing substrate stiffness, we were able to restore normal oscillatory behavior, suggesting a possible compensatory mechanism. Thus our study identifies that mechanotransduction could be a potent modulatory cue for cellular clocks and this crosstalk can be leveraged to rescue the circadian clock in disease states.
Analyses of allele age and fitness impact reveal human beneficial alleles to be older than neutral controls
Authors: Pivirotto Alyssa M. , Platt Alexander , Patel Ravi , Kumar Sudhir , Hey Jody
Published: October 2023

A classic population genetic prediction is that alleles experiencing directional selection should swiftly traverse allele frequency space, leaving detectable reductions in genetic variation in linked regions. However, despite this expectation, identifying clear footprints of beneficial allele passage has proven to be surprisingly challenging. We addressed the basic premise underlying this expectation by estimating the ages of large numbers of beneficial and deleterious alleles in a human population genomic data set. Deleterious alleles were found to be young, on average, given their allele frequency. However, beneficial alleles were older on average than non-coding, non-regulatory alleles of the same frequency. This finding is not consistent with directional selection and instead indicates some type of balancing selection. Among derived beneficial alleles, those fixed in the population show higher local recombination rates than those still segregating, consistent with a model in which new beneficial alleles experience an initial period of balancing selection due to linkage disequilibrium with deleterious recessive alleles. Alleles that ultimately fix following a period of balancing selection will leave a modest ‘soft’ sweep impact on the local variation, consistent with the overall paucity of species-wide ‘hard’ sweeps in human genomes.

Impact Statement

Analyses of allele age and evolutionary impact reveal that beneficial alleles in a human population are often older than neutral controls, suggesting a large role for balancing selection in adaptation.
Large genetic analysis of alcohol resistance and tolerance reveals an inverse correlation and suggests ‘true’ tolerance mutants
Authors: Chvilicek Maggie M. , Seguin Alexandra , Lathen Daniel R. , Titos Iris , Cummins-Beebe Pearl N , Pabon Miguel A. , Miscevic Masa , Nickel Emily A. , Merrill Collin B , Rodan Aylin R. , Rothenfluh Adrian
Published: October 2023

Tolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce the same behavioral effects. Tolerance is historically not well-understood, and numerous researchers have turned to model organisms, particularlyDrosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease-causing genes between flies and humans, including those associated with Alcohol Use Disorder. NumerousDrosophilatolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and between labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we have analyzed a large amount of data – our own published and unpublished data and data published by other labs – to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many ‘perceived’ tolerance phenotypes. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. We show that these residuals provide predictive insight into the likelihood of a mutant being a ‘true’ tolerance mutant, and we offer a framework for understanding the relationship between initial resistance and tolerance.
Australian terrestrial environments harbour extensive RNA virus diversity
Authors: Sadiq Sabrina , Harvey Erin , Mifsud Jonathon C. O. , Minasny Budiman , McBratney Alex. B. , Pozza Liana E. , Mahar Jackie E. , Holmes Edward C.
Published: October 2023

Australia is home to a diverse range of unique native fauna and flora. To address whether Australian ecosystems also harbour unique viruses, we performed meta-transcriptomic sequencing of 16 farmland and sediment samples taken from the east and west coasts of Australia. We identified 2,562 putatively novel viruses across 15 orders, the vast majority of which belonged to the microbe-associated phylumLenarviricota. In many orders, the novel viruses identified here comprised entirely new clades, such as theNodamuviralesandGhabrivirales. Novel viruses also fell between established genera or families, such as in theCystoviridaeandPicornavirales, while highly divergent lineages were identified in theMartelliviralesandGhabrivirales. Viral abundance and alpha diversity were influenced by sampling site, soil type and land use, but not by depth from the surface. In sum, Australian soils and sediments are home to remarkable viral diversity, reflecting the biodiversity of local fauna and flora.
Validation of an AI-based solution for breast cancer risk stratification using routine digital histopathology images
Authors: Sharma Abhinav , Lövgren Sandy Kang , Eriksson Kajsa Ledesma , Wang Yinxi , Robertson Stephanie , Hartman Johan , Rantalainen Mattias
Published: October 2023

Background

Stratipath Breast is a CE-IVD marked artificial intelligence-based solution for prognostic risk stratification of breast cancer patients into high- and low-risk groups, using haematoxylin and eosin (H&E)-stained histopathology whole slide images (WSIs). In this validation study, we assessed the prognostic performance of Stratipath Breast in two independent breast cancer cohorts.

Methods

This retrospective multi-site validation study included 2719 patients with primary breast cancer from two Swedish hospitals. The Stratipath Breast tool was applied to stratify patients based on digitised WSIs of the diagnostic H&E-stained tissue sections from surgically resected tumours. The prognostic performance was evaluated using time-to-event analysis by multivariable Cox Proportional Hazards analysis with progression-free survival (PFS) as the primary endpoint.

Results

In the clinically relevant oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patient subgroup, the estimated hazard ratio (HR) associated with PFS between low- and high-risk groups was 2.76 (95% CI: 1.63-4.66, p-value < 0.001) after adjusting for established risk factors. In the ER+/HER2-Nottingham histological grade (NHG) 2 subgroup, the HR was 2.20 (95% CI: 1.22-3.98, p-value = 0.009) between low- and high-risk groups.

Conclusion

The results indicate an independent prognostic value of Stratipath Breast among all breast cancer patients, as well as in the clinically relevant ER+/HER2-subgroup and the NHG2/ER+/HER2-subgroup. Improved risk stratification of intermediate-risk ER+/HER2-breast cancers provides information relevant for treatment decisions of adjuvant chemotherapy and has the potential to reduce both under- and overtreatment. Image-based risk stratification provides the added benefit of short lead times and substantially lower cost compared to molecular diagnostics and therefore has the potential to reach broader patient groups.
The impact of depression and childhood maltreatment experiences on psychological adaptation from lockdown to relaxation periods during the COVID-19 pandemic
Authors: Herpertz Julian , Goltermann Janik , Gruber Marius , Blitz Rogério , Taylor Jacob , Brosch Katharina , Stein Frederike , Straube Benjamin , Meinert Susanne , Kraus Anna , Leehr Elisabeth J , Repple Jonathan , Redlich Ronny , Gutfleisch Lara , Besteher Bianca , Ratzsch Janette , Winter Alexandra , Bonnekoh Linda M. , Emden Daniel , Kircher Tilo , Nenadic Igor , Dannlowski Udo , Hahn Tim , Opel Nils
Published: October 2023

The COVID-19 pandemic has presented a significant challenge to societal mental health. Yet, it remains unknown which factors influence the mental adaptation from lockdown to subsequent relaxation periods, particularly for vulnerable groups.

This study used smartphone-based monitoring to explore how 74 individuals with major depression (MDD) and 77 healthy controls (HCs) responded to the transition from lockdown to relaxation during the first wave of the COVID-19 pandemic (March 21 to November 01, 2020) regarding interpersonal interactions, COVID-19-related fear (fear of participants’ own health, the health of close relatives, and the pandemics’ economic impact), and the feeling of isolation. Furthermore, we investigated the effect of a diagnosis of MDD and the experience of childhood maltreatment (CM) on adaptive functioning.

During the transition from lockdown to relaxation, we observed an increase in direct contacts and a decrease in indirect contacts and self-perceived isolation in the study population. The diagnosis of MDD and the experience of CM moderated a maintenance of COVID-19-related fear: HCs and participants without the experience of CM showed a decrease in fear, while fear of participants with MDD and with an experience of CM did not change significantly.

The finding that elevated COVID-19-related fear was sustained in vulnerable groups after lockdown measures were lifted could help guide psychosocial prevention efforts in future pandemic emergencies.
“From Preparation to Consumption.” Food Safety Practices among Public Food Handler’s in Enugu Metropolis
Authors: Wilson Kassy Chukwukasi , Chidinma Ojielo Nwadiuto , Victoria Iloabachie Ugenyi , Ndubuisi Ochie Casmir , Juliet Ogugua Ifeoma , Charles Ntat Ibiok , Hope Chime Onyinye , Amarachi Onyedinma Chioma , Chigedu Ndu Prof Anne , Susan Arinze-Onyia Prof Uzoamaka , Emmanuel Aguwa Prof Nwabueze , Theodora Okeke Prof Adaeze
Published: October 2023

Background

Increased demand for public prepared food with numerous food handlers creates uncertainties in the quality of safe foods and possible food contamination. This study aimed to ascertain the food safety hygiene practices and associated factors among public food handlers in Enugu Metropolis, Nigeria.

Methodology

This was a cross-sectional study conducted among 400 public food handlers in Enugu Metropolis, Nigeria. This study took place between January and April 2023. Samples were selected using multistage sampling technique. Data was collected using pretested structured questionnaire and analyzed using proportion, mean and multiple regression. Statistical significance was set at < 0.05.

Results

The mean age of respondents were 31.16 ± 8.242 years. About two – thirds, 66.5% of respondents were found to have good knowledge of food hygiene safety practices. The overall food safety hygiene practice mean score was 80.10 ± 10.25 with 70.5% showing good practice. Environmental safety hygiene had good practice of 35.0% and mean score of 24.17 ± 2.29. The factors which statistically significantly predicted overall food safety practices, F (11, 388) = 42.957, P < 0.0001, R2= 0.536 were educational level (β = 0.148, C.I = 0.860 – 3.082), knowledge level (β = 8.594, C.I = 5.635 – 8.979) and safety trainings (β = 0.517, C.I = 4.102 – 5.474).

Conclusion

There was good knowledge of food safety hygiene practices with high mean scores except on environmental safety hygiene practices component. Safety training, knowledge level and educational level were the predictors of good practices. Frequent trainings are most needed to prevent or control food contamination and consequent food borne diseases.
BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates
Authors: Rueda-Alaña Eneritz , Grillo Marco , Vazquez Enrique , Marco Salas Sergio , Senovilla-Ganzo Rodrigo , Escobar Laura , Quintas Ana , Benguría Alberto , Aransay Ana María , Dopazo Ana , Encinas Juan Manuel , Nilsson Mats , García-Moreno Fernando
Published: October 2023

Embryonic development is a complex and dynamic process that unfolds over time and involves the production of increasing numbers of cells, as well as the diversification of different cell types. The impact of developmental time on the formation of the central nervous system is well-documented, with evidence showing that time plays a critical role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduceBirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows forin vivolabeling of cells, isolation via FACS, and analysis using high-throughput techniques. We demonstrate the effectiveness of BirthSeq for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in brain development across three vertebrate species (mouse, chick, and gecko). Overall, BirthSeq provides a versatile tool for studying any tissue in any vertebrate organism, helping to fill the necessity in developmental biology research by targeting cells and their temporal cues.

SUMMARY STATEMENT

BirthSeqallows the isolation and investigation of alive cells according to their birthdate, in any kind of tissue and vertebrate species.
Human foot outperforms the hand in mechanical pain discrimination
Authors: Ng Kevin K. W. , Lafee Odai , Bouchatta Otmane , Makdani Adarsh D. , Marshall Andrew G. , Olausson Håkan , McIntyre Sarah , Nagi Saad S.
Published: October 2023

Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterised. Here, we measured the capacity for mechanical pain discrimination using a twoalternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterise the relationship between peripheral neural and perceptual processes, we recorded singleunit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of single primary afferents. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences.

Significance Statement

Standard clinical practice for diagnosing neuropathies and pain disorders often involves assessing thresholds for pain or light touch. The ability to discriminate between different stimulus intensities is a separate but equally important sensory function, however this is not typically assessed in the clinic, and so studying this may provide insights into pain signalling mechanisms. Here, we investigated the ability of healthy individuals to discriminate between different forces of painful indentation. We found that the foot was better at this than the hand. This difference could not be explained by the firing activity of peripheral nociceptors (pain-signalling neurons) between the two regions, suggesting that mechanisms other than nociceptor sensitivity are involved.
Long-term human organotypic brain slice cultures: a detailed protocol to provide a comprehensive framework for single-neuron and neuronal network investigations
Authors: Bak Aniella , Koch Henner , van Loo Karen M. J. , Schmied Katharina , Gittel Birgit , Weber Yvonne , Schwarz Niklas , Tauber Simone C. , Wuttke Thomas V. , Delev Daniel
Published: October 2023

Background

The investigation of the human brain at cellular and microcircuit level remains challenging due to the fragile viability of neuronal tissue, inter- and intra-variability of the samples and limited availability of human brain material.

New method

Here, we present an optimized work-up to use resected tissue from brain surgeries for live cell experiments in vitro.

Comparison with existing methods

We provide a reworked, detailed protocol of the production, culturing and viral transduction of human organotypic brain slice cultures for research purposes.

Results

We highlight the critical pitfalls of the culturing process of the human brain tissue and present results on viral expression, single-cell Patch-Clamp recordings, as well as multi-electrode array recordings over a prolonged period of time. Additionally, our statistics show that brain tissue from patients of any age and morbidity can be used for organotypic brain slice cultures if carefully selected.

Conclusions

Organotypic brain slice cultures are of great value for basic neuroscience and disease modeling over a time course of three weeks.

Highlights

Long-term human organotypic brain slice cultures are viable for 2-3 weeks and provide a framework for basic neuroscience and disease modeling

We provide a reworked, detailed protocol for organotypic human brain slice culture production and maintenance

We show results of long-term culturing of human organotypic brain slice cultures in terms of viral transduction, whole-cell Patch-Clamp recordings and multi-electrode array recordings

Statistics of 16 surgeries show the correlation between the overall success rates of efficient culturing and viral transduction with the patient age and morbidity

Figure 1, Graphical abstract.

Schematic overview of preparation, maintenance and experimental workup of human organotypic brain slice cultures.

After surgical resection, human brain tissue is prepared, sliced and cultured at air-liquid-interface between human cerebrospinal fluid and defined incubator atmosphere, allowing for week-long viability. This enables extensive experimental workup such as viral transduction, single cell and multi-electrode array electrophysiological recordings.
Identification and organization of a postural anti-gravity module in the cerebellar vermis
Authors: Gouhier Aurélien , Villette Vincent , Mathieu Benjamin , Ayon Annick , Bradley Jonathan , Dieudonné Stéphane
Published: October 2023

The cerebellum is known to control the proper balance of isometric muscular contractions that maintain body posture. Current optogenetic manipulations of the cerebellar cortex output, however, have focused on ballistic body movements, examining movement initiation or perturbations. Here, by optogenetic stimulations of cerebellar Purkinje cells, the output of the cerebellar cortex, we evaluate body posture maintenance. By sequential analysis of body movement, we dissect the effect of optogenetic stimulation into a directly induced movement that is then followed by a compensatory reflex to regain body posture. We identify a module in the medial part of the anterior vermis which, through multiple muscle tone regulation, is involved in postural anti-gravity maintenance of the body. Moreover, we report an antero-posterior and medio-lateral functional segregation over the vermal lobules IV/V/VI. Taken together our results open new avenues for better understanding of the modular functional organization of the cerebellar cortex and its role in postural anti-gravity maintenance.

Highlights

Vermal Purkinje cell activation elicits a graded postural collapse in the standing mouse

The collapse triggers a secondary composite postural reflex

An identified cerebellar module is involved in postural anti-gravity tone maintenance

The anti-gravity function is somatotopically organized within this module
Training biologically plausible recurrent neural networks on cognitive tasks with long-term dependencies
Authors: Soo Wayne W.M. , Goudar Vishwa , Wang Xiao-Jing
Published: October 2023

Training recurrent neural networks (RNNs) has become a go-to approach for generating and evaluating mechanistic neural hypotheses for cognition. The ease and efficiency of training RNNs with backpropagation through time and the availability of robustly supported deep learning libraries has made RNN modeling more approachable and accessible to neuroscience. Yet, a major technical hindrance remains. Cognitive processes such as working memory and decision making involve neural population dynamics over a long period of time within a behavioral trial and across trials. It is difficult to train RNNs to accomplish tasks where neural representations and dynamics have long temporal dependencies without gating mechanisms such as LSTMs or GRUs which currently lack experimental support and prohibit direct comparison between RNNs and biological neural circuits. We tackled this problem based on the idea of specialized skip-connections through time to support the emergence of task-relevant dynamics, and subsequently reinstitute biological plausibility by reverting to the original architecture. We show that this approach enables RNNs to successfully learn cognitive tasks that prove impractical if not impossible to learn using conventional methods. Over numerous tasks considered here, we achieve less training steps and shorter wall-clock times, particularly in tasks that require learning long-term dependencies via temporal integration over long timescales or maintaining a memory of past events in hidden-states. Our methods expand the range of experimental tasks that biologically plausible RNN models can learn, thereby supporting the development of theory for the emergent neural mechanisms of computations involving long-term dependencies.
Air-liquid interface culture of midbrain organoids improves neuronal functionality and integration of microglia
Authors: Kälvälä Sara , Abushik Polina , Dougalis Antonios , Malm Tarja , Pelkonen Anssi , Lehtonen Šárka
Published: October 2023

Midbrain organoids derived from human induced pluripotent stem cells have emerged as a promising in vitro model for studying the molecular and cellular mechanisms in Parkinson’s disease. However, the absence of microglia and the development of a necrotic core in mature organoids have remained key limitations on their utility as functional models of the human midbrain. Here we propose a novel methodology for extended cultivation of midbrain organoid slices, which involves the incorporation of microglia and utilizes an air-liquid culture system. Compared to conventional whole organoids, we found that our model increased the efficacy and consistency of the integration of microglia progenitors. Using single-cell RNA sequencing, we showed that organoid slices maturated in ALI give rise to astrocytes and oligodendrocyte progenitors. Furthermore, the cultivation in air-liquid interface greatly improved neuronal functionality in response to stimulation by NMDA. This stimulation consistently induced robust and stable network activity evaluated by microelectrode array recording. Our newly developed midbrain organoid model with its improved cell type composition and neuronal functionality has potential applications in basic research of Parkinson’s disease and in the development of therapeutics.

Graphical abstract
Gait adaptation to asymmetric hip stiffness applied by a robotic exoskeleton
Authors: Abdikadirova Banu , Price Mark , Moreno Jaramillo Jonaz , Hoogkamer Wouter , Huber Meghan E.
Published: October 2023

Wearable exoskeletons show significant potential for improving gait impairments, such as interlimb asymmetry. However, a more profound understanding of whether exoskeletons are capable of eliciting neural adaptation is needed. This study aimed to characterize how individuals adapt to bilateral asymmetric joint stiffness applied by a hip exoskeleton, similar to split-belt treadmill training. Thirteen unimpaired individuals performed a walking trial on the treadmill while wearing the exoskeleton. The right side of the exoskeleton acted as a positive stiffness torsional spring, pulling the thigh towards the neutral standing position, while the left acted as a negative stiffness spring pulling the thigh away from the neutral standing position. The results showed that this intervention applied by a hip exoskeleton elicited adaptation in spatiotemporal and kinetic gait measures similar to split-belt treadmill training. These results demonstrate the potential of the proposed intervention for retraining symmetric gait.
Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task
Authors: Andrianarivelo Andry , Stein Heike , Gabillet Jeremy , Batifol Clarisse , Jalil Abdelali , Cayco Gajic N Alex , Graupner Michael
Published: October 2023

Locomotion in complex environments depends on the precise timing and active control of single paw movements in order to adapt steps to surface structure and coordinate paws. Such motor control crucially depends on the cerebellum. In turn, cerebellar activity is reported to reflect limb movement kinematics, but how precise action timing in complex environments is controlled by the cerebellar circuit is currently unknown. To address this question, we developed LocoReach: a new task which combines continuous and discrete aspects of motor control by requiring mice to walk on a runged treadmill, where each step involves reaching for the next rung. Over several days of learning, mice became increasingly proficient at LocoReach, so that they made fewer, longer strides with faster swings and fewer missteps. We assessed the cerebellar role during LocoReach learning through pharmacological inhibition as well as real-time optogenetic inhibition of cerebellar activity and electrophysiological recordings of molecular layer interneurons (MLIs), as they are thought to control the timing and gain of the cerebellar cortical output. Inhibiting cerebellar output during the swing phase of a specific paw led to shorter swings of this paw. When analyzing behaviorally-evoked responses in MLIs, we found sharp changes in activity around paw-specific transitions from swing to stance and vice versa. While most MLIs in the left simplex were preferentially modulated by the reach endpoint of the front left paw, a large proportion of cells additionally showed activity variations related to other paws or even multiple paws. Stronger firing rate modulations reflected longer strides made over learning, consistent with previous reports highlighting the role of the intermediate cerebellum in controlling reach endpoint precision. Our results provide the first demonstration that cerebellar inhibitory signals are tuned to specific events in the step cycle which can act as a powerful mechanism for the precise control of paw placements.