bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway-Associated Complications With and Without Primary Tracheotomy in Oral Squamous Cell Carcinoma Surgery
Authors: Riekert Maximilian , Rempel Vadim , Keilwerth Stefanie , Zöller Joachim E. , Kreppel Matthias , Schick Volker C.
Published: August 2022

Purpose:

This study analyzes postoperative airway management, tracheotomy strategies, and airway-associated complications in patients with oral squamous cell carcinoma in a tertiary care university hospital setting.

Material and Methods:

After institutional approval, airway-associated complications, tracheotomy, length of hospital stay (LOHS), and length of intensive care unit stay were retrospectively recorded. Patients were subdivided in primarily tracheotomized and not-primarily tracheotomized. Subgroup analyses dichotomized the not-primarily tracheotomized patients into secondary tracheotomized and never tracheotomized. Associations were calculated using regression analyses. A multivariate regression model was used to determine risk factors for secondary tracheotomy.

Results:

A total of 207 patients were included. One hundred fifty-three patients (73.9%) were primarily tracheotomized. Primarily tracheotomized patients showed longer LOHS [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.07, P=0.008] but decreased need for reventilation within the intensive care unit stay (OR 0.39, 95% CI 0.15–0.99, P=0.05) compared with not-primarily tracheotomized patients. Within the not-primarily tracheotomized patients, secondary tracheotomized during the hospital stay was needed in 15 of 54 patients (27.8%). In secondary tracheotomized patients, airway management due to respiratory failure was required in 6/15 (40%) patients resulting in critical airway situations in 3/6 (50%) patients. Multivariate regression model showed secondary tracheotomy-associated with bilateral neck dissection (OR 5.93, 95% CI 1.22–28.95, P=0.03) and pneumonia (OR 16.81, 95% CI 2.31–122.51, P=0.005).

Conclusion:

Primary tracheotomy was associated with extended LOHS, whereas secondary tracheotomy was associated with increased complications rates resulting in extended length of intensive care unit stay. Especially in not-primarily tracheotomized patients, careful individualized patient evaluation and critical re-evaluation during intensive care unit stay is necessary to avoid critical airway events.
Birk-Barel Intellectual Disability Dimorphism and KCNK9 Imprinting Syndrome: Craniofacial Surgery Considerations for an Exceedingly Rare Syndrome
Authors: Villavisanis Dillan F. , Blum Jessica D. , Taylor Jesse A.
Published: August 2022

Birk-Barel intellectual disability dimorphism syndrome, also referred to as KCNK9 imprinting syndrome, is an exceedingly rare condition described in under 20 cases that presents with intellectual disability, hypotonia, scoliosis, dysphonia, dysphagia, and craniofacial dysmorphic features. The condition follows an autosomal dominant pattern of inheritance in the maternally expressed KCNK9 gene on chromosome 8. Due to the complexity of presentation, patients with Birk-Barel syndrome are optimally managed by a multidisciplinary team including a craniofacial surgeon. Previously described craniofacial dysmorphic features include micrognathia, cleft palate, dolichocephaly, broad nasal tip, and broad philtrum, among others. Here the authors describe a genetically confirmed case that has been managed in our institution’s multidisciplinary cleft and craniofacial clinic. The authors aim to discuss Birk-Barel syndrome for a surgical and craniofacial audience with considerations for operative management in the context of a multidisciplinary team.
Insights into the human gut virome by sampling a population from the Indian subcontinent
Authors: Bhardwaj Kanchan , Garg Anjali , Pandey Abhay Deep , Sharma Himani , Kumar Manish , Vrati Sudhanshu
Published: August 2022

Gut virome plays an important role in human physiology but remains poorly understood. This study reports an investigation of the human gut DNA-virome of a previously unexplored ethnic population through metagenomics of faecal samples collected from individuals residing in Northern India. Analysis shows that, similar to the populations investigated earlier, majority of the identified virome belongs to bacteriophages and a smaller fraction (<20 %) consists of viruses that infect animals, archaea, protists, multiple domains or plants. However, crAss-like phages, in this population, are dominated by the genera VI, VII and VIII. Interestingly, it also reveals the presence of a virus family, Sphaerolipoviridae, which has not been detected in the human gut earlier. Viral families, Siphoviridae, Myoviridae, Podoviridae, Microviridae, Herelleviridae and Phycodnaviridae are detected in all of the analysed individuals, which supports the existence of a core virome. Lysogeny-associated genes were found in less than 10 % of the assembled genomes and a negative correlation was observed in the richness of bacterial and free-viral species, suggesting that the dominant lifestyle of gut phage is not lysogenic. This is in contrast to some of the earlier studies. Further, several hundred high-quality viral genomes were recovered. Detailed characterization of these genomes would be useful for understanding the biology of these viruses and their significance in human physiology.
Excess mortality in Cyprus during the COVID-19 pandemic and its lack of association with vaccination rates
Authors: Lytras Theodore , Athanasiadou Maria , Demetriou Anna , Stylianou Despina , Heraclides Alexandros , Kalakouta Olga
Published: August 2022

Background

It has been claimed that COVID-19 vaccination is associated with excess mortality during the COVID-19 pandemic, a claim that contributes to vaccine hesitancy. We examined whether all-cause mortality has actually increased in Cyprus during the first two pandemic years, and whether any increases are associated with vaccination rates.

Methods

We calculated weekly excess mortality for Cyprus between January 2020 and June 2022, overall and by age group, using both a Distributed Lag Nonlinear Model (DLNM) adjusted for mean daily temperature, and the EuroMOMO algorithm. Excess deaths were regressed on the weekly number of confirmed COVID-19 deaths and on weekly first-dose vaccinations, also using a DLNM to explore the lag-response dimension.

Results

552 excess deaths were observed in Cyprus during the study period (95%CI: 508–597) as opposed to 1306 confirmed COVID-19 deaths. No association between excess deaths and vaccination rates was found overall and for any age group except 18-49 years, among whom 1.09 excess deaths (95%CI: 0.27–1.91) per 10,000 vaccinations were estimated during the first 8 weeks post-vaccination. However, detailed cause-of-death examination identified just two such deaths potentially linked to vaccination, therefore this association is spurious and attributable to random error.

Conclusions

Excess mortality was moderately increased in Cyprus during the COVID-19 pandemic, primarily as a result of laboratory-confirmed COVID-19 deaths. No relationship was found between vaccination rates and all-cause mortality, demonstrating the excellent safety profile of COVID-19 vaccines.
How Efficient is the k-means Clustering to Analyze the CT images of Pyogenic and Amoebic Liver Abscess?
Authors: Chattopadhyay Subhagata
Published: August 2022

Liver abscesses are well-delineated pus-filled lesions. Two common types are Amoebic liver abscesses (ALA), caused by protozoa called entamoeba histolytica while several pus-forming bacteria cause pyogenic liver abscesses (PLA). Both cause debilitating morbidities and are diagnosed by pus culture-sensitivity tests. A contrast CT abdomen shows well-demarcated lesions in the liver. The telemedicine practice is on the rise where image processing is becoming a part and parcel of teleradiology to fill the gap between the number of radiologists versus the large patient pool. Cluster-based image segmentation is a useful step in grouping the image into the desired number of clusters. The k-means clustering (k-MC) technique is one popular method, used in this study on ALA and PLA contrast CT images. it observes that with the desired 2-clusters – a) normal liver tissue and b) the pus-filled tissue) parameters, the algorithm gives better results in PLA.
The Maine Vein of Marshall Ethanol Experience: Learning Curve, Efficacy, and Safety
Authors: Leyton-Mange Jordan S , Tandon Kunal , Sze Edward Y , Carpenter Charles M , Sesselberg Henry W
Published: August 2022

Background

The marginal benefit of ethanol infusion into the VOM as an adjunct to atrial fibrillation ablation has shown promise in a single randomized study and case series from very experienced centers. However, adoption has not been widespread and the impact on real-world outcomes outside of leading centers is not established.

Objective

To understand the learning curve, and explore procedural outcomes and safety with VOM ethanol infusion from a large single medical center.

Methods

All atrial ablation cases wherein VOM ethanol infusion was attempted were identified from the time of the program’s inception in 2019 at Maine Medical Center (Portland, ME). Our technical approach, procedural success and efficacy rates, and complications were adjudicated from the medical record.

Results

The overall VOM ethanol infusion success was 90%. Infusion success rates improved and fluoroscopy utilization decreased with experience. Arrhythmia recurrence was 86% after a mean follow-up of 9.5 months, with an arrhythmia-freedom probability of 80% at 12 months. Complications occurred in 5.4% of patients, including a 3.1% risk of delayed tamponade.

Conclusion

In our single center experience, VOM ethanol infusion was feasible with a high technical success rate and excellent arrhythmia freedom in follow-up. These positive results are balanced against a concerning rate of delayed tamponade.
A key role of the hippocampal P3 in the attentional blink
Authors: Derner M , Reber TP , Faber J , Surges R , Mormann F , Fell J
Published: August 2022

The attentional blink (AB) refers to an impaired identification of target stimuli (T2), which are presented shortly after a prior target (T1) within a rapid serial visual presentation (RSVP) stream. It has been suggested that the AB is related to a failed transfer of T2 into working memory and that hippocampus (HC) and entorhinal (EC) cortex are regions crucial for this transfer. Since the event-related P3 component has been linked to inhibitory processes, we hypothesized that the hippocampal P3 elicited by T1 may impact on T2 processing within HC and EC. To test this hypothesis, we reanalyzed microwire data from 21 patients, who performed an RSVP task, during intracranial recordings for epilepsy surgery assessment (Reber et al., 2017). We identified T1-related hippocampal P3 components in the local field potentials (LFPs) and determined the temporal onset of T2 processing in HC/EC based on single-unit response onset activity. In accordance with our hypothesis, T1-related single-trial P3 amplitudes at the onset of T2 processing were clearly larger for unseen compared to seen T2-stimuli. Moreover, increased T1-related single-trial P3 peak latencies were found for T2[unseen] versus T2[seen] trials in case of lags 1 to 3, which was in line with our predictions. In conclusion, our findings support inhibition models of the AB and indicate that the hippocampal P3 elicited by T1 plays a central role in the AB.
Ethylene impact on grapevine pistil temperature and fruit set
Authors: Chervin Christian , Geffroy Olivier
Published: August 2022

Ethylene is known to stimulate plant respiration, and this later is always associated with heat generation. The grapevine fruit set is dependent upon pistil temperature, controlling the pollen germination and ovule fertilization. This led us to test whether ethylene would be able to impact fruit set often limited in cool climate conditions, particularly in the case ofVitis vinifera L. cv. Malbec, a variety prone to poor fruit set. With this cultivar, we ran trials in growth chambers using the ethylene gas, and field trials using ethephon as an ethylene precursor. At 14.5 °C ambient temperature, we observed that ethylene at 1 and 10 ppm increased the stigma and pistil temperature to 15 °C, compared to 14.7 °C in controls. This minor temperature rise was associated with an increase of fruit set from 10 to 25 %. The field trials, conducted in the South West of France, confirmed this trend. Indeed, spraying a concentration as low as 216 mg/ha of ethephon onto Malbec at full bloom at 16 °C in the shade, led to an increase of fruit set from 35 % to 45 %. These experiments suggest that spraying ultra-low concentrations of ethylene precursors onto the grapevines prone to poor fruit set, during cool mornings, could improve fruit set and reduce crop losses.
Gene fate spectrum as a reflection of local genomic properties
Authors: Hara Yuichiro , Kuraku Shigehiro
Published: August 2022

Functionally indispensable genes are likely to be retained and otherwise to be lost during evolution. This evolutionary fate of a gene can also be affected by neutral factors, including the mutability of genomic positions, but such features have not been examined well. To uncover the genomic features associated with gene loss, we investigated the characteristics of genomic regions where genes have been independently lost in multiple lineages. With a comprehensive scan of gene phylogenies of vertebrates with a careful inspection of evolutionary gene losses, we identified 1,081 human genes whose orthologs were lost in multiple mammalian lineages: designated ‘elusive genes.’ These elusive genes were located in genomic regions with rapid nucleotide substitution, high GC content, and high gene density. A comparison of the orthologous regions of such elusive genes across vertebrates revealed that these features had been established before the radiation of the extant vertebrates more than 500 million years ago. The association of human elusive genes with transcriptomic and epigenomic characteristics illuminated that the genomic regions containing such genes were subject to repressive transcriptional regulation. Thus, the heterogeneous genomic features driving gene fates toward loss have been in place since the ancestral vertebrates and may sometimes have relaxed the functional indispensability of such genes.
Facilitation-inhibition control of motor neuronal persistent inward currents in young and older adults
Authors: Orssatto Lucas B. R. , Fernandes Gabriel L. , Blazevich Anthony J. , Trajano Gabriel S.
Published: August 2022

A well-coordinated control of motor neuronal persistent inward currents (PICs) via diffuse neuromodulation and local inhibition is essential to ensure motor units discharge at required times and frequencies. Current best estimates indicate that PICs are reduced in older adults; however, it is not yet known whether PIC facilitation-inhibition control is also altered with ageing. We investigated the responses of PICs to i) a remote handgrip contraction, which is believed to diffusely increase serotonergic input onto motor neurones, and ii) tendon vibration of the antagonist muscle, which elicits reciprocal inhibition, in both young and older adults. High-density surface electromyograms were collected from soleus and tibialis anterior of 18 young and 26 older adults during triangular-shaped plantar and dorsiflexion contractions to 20% (handgrip experiments) and 30% (vibration experiments) of maximum torque (rise-decline rate of 2%/s). The paired-motor-unit analysis was used to calculate ΔF, which is assumed proportional to PIC strength. ΔF increased in both soleus (0.55pps, 16.0%) and tibialis anterior (0.42pps, 11.4%) during the handgrip contraction independent of age. However, although antagonist tendon vibration reduced ΔF in soleus (0.28pps, 12.6%) independent of age, less reduction was observed in older (0.42pps, 10.7%) than young adults (0.72pps, 17.8%) in tibialis anterior. Our data indicate a preserved ability of older adults to amplify PICs following a remote handgrip contraction, during which increased serotonergic input onto the motor neurones is expected, in both lower leg muscles. However, PIC deactivation in response to reciprocal inhibition was impaired with ageing in tibialis anterior despite being preserved in soleus.

KEYPOINTS

Motor neuronal persistent inward currents (PICs) are amplified via diffuse neuromodulation and deactivated by local inhibition to ensure motor units discharge at required times and frequencies, allowing a normal motor behaviour.

PIC amplitudes appear to be reduced with ageing, however it is not known whether PIC facilitation-inhibition control is also altered.

Remote handgrip contraction, which should diffusely increase serotonergic input onto motor neurones, amplified PICs similarly in both soleus and tibialis anterior of young and older adults.

Antagonist tendon vibration, which induces reciprocal inhibition, reduced PICs in soleus in both young and older adults but had less effect in tibialis anterior in older adults.

Our data suggest that older adults have preserved soleus PIC facilitation during lowintensity contractions, equivalent to activities such as standing and walking. However, a reduced reciprocal inhibition of PICs in tibialis anterior may contribute to locomotion impairments, such as increases in soleus-tibialis anterior co-activation during propulsion.
Enteric glia adopt an activated pro-inflammatory state in response to human and bacterial amyloids
Authors: Verstraelen Peter , Van Remoortel Samuel , De Loose Nouchin , Verboven Rosanne , Garcia-Diaz Barriga Gerardo , Christmann Anne , Gries Manuela , Tükel Cagla , Ibiza Martinez Sales , Schäfer Karl-Herbert , Timmermans Jean-Pierre , De Vos Winnok H.
Published: August 2022

Mounting evidence suggests a role for the microbiome-gut-brain axis in amyloid-associated neurodegeneration, but the pathogenic changes induced by amyloids in the gastro-intestinal tract remain elusive. To scrutinize the early response to amyloids of human and bacterial origin, we challenged primary murine myenteric networks with Aβ1-42 (vs a scrambled version of Aβ1-42) and curli (vs culture medium), respectively, and performed shotgun RNA sequencing. Both amyloid types induced a transcriptional signature of DNA damage and cell cycle dysregulation. Using in vitro neurosphere-derived cultures and in vivo amyloid injections we found that enteric glia and smooth muscle cells were the most responsive cell types, showing increased proliferation, γH2AX burden and SOD2 levels after amyloid challenge. Consistent with this activated state, we identified a pro-inflammatory hub in the transcriptional profile of amyloid-stimulated myenteric networks. Enteric glia were the principal source of the associated cytokines, and in vivo, this was accompanied by an influx of immune cells. Together, these results shed new light on the intrinsic vulnerability of ENS cells to both amyloid species and position enteric glial cell activation as an early driver of neurodegenerative disease progression.

Significance statement

The increasing socio-economic impact of Alzheimer’s disease (AD), long sub-clinical disease progression window, and failure of drug candidates demand mechanistic insight into the early stages of disease development. Epidemiological associations and experimental studies in rodents suggest that the gut may be vulnerable to amyloids and mediate their transfer to the brain. However, whether and how amyloids induce local pathology in the gastro-intestinal wall is not known. We identified a pathogenic program that becomes activated in the gastro-intestinal tract after exposure to amyloid β and curli (the main bacterial amyloid), and show that enteric glia are responsible for creating an amyloid-induced pro-inflammatory environment. This insight of an early response in a distant, more accessible organ than the brain, may have important implications for both disease diagnosis and therapy.
Relationship Between Prediction Accuracy and Feature Importance Reliability: an Empirical and Theoretical Study
Authors: Chen Jianzhong , Ooi Leon Qi Rong , Kiat Tan Trevor Wei , Zhang Shaoshi , Li Jingwei , Asplund Christopher L. , Eickhoff Simon B , Bzdok Danilo , Holmes Avram J , Yeo B.T. Thomas
Published: August 2022

There is significant interest in using neuroimaging data to predict behavior. The predictive models are often interpreted by the computation of feature importance, which quantifies the predictive relevance of an imaging feature. Tian and Zalesky (2021) suggest that feature importance estimates exhibit low split-half reliability, as well as a trade-off between prediction accuracy and feature importance reliability across parcellation resolutions. However, it is unclear whether the trade-off between prediction accuracy and feature importance reliability is universal. Here, we demonstrate that, with a sufficient sample size, feature importance (operationalized as Haufe-transformed weights) can achieve fair to excellent split-half reliability. With a sample size of 2600 participants, Haufe-transformed weights achieve average intra-class correlation coefficients of 0.75, 0.57 and 0.53 for cognitive, personality and mental health measures respectively. Haufe-transformed weights are much more reliable than original regression weights and univariate FC-behavior correlations. Original regression weights are not reliable even with 2600 participants. Intriguingly, feature importance reliability is strongly positively correlated with prediction accuracy across phenotypes. Within a particular behavioral domain, there is no clear relationship between prediction performance and feature importance reliability across regression models. Furthermore, we show mathematically that feature importance reliability is necessary, but not sufficient, for low feature importance error. In the case of linear models, lower feature importance error is mathematically related to lower prediction error. Therefore, higher feature importance reliability might yield lower feature importance error and higher prediction accuracy. Finally, we discuss how our theoretical results relate with the reliability of imaging features and behavioral measures. Overall, the current study provides empirical and theoretical insights into the relationship between prediction accuracy and feature importance reliability.
Predicting Mycoplasma tissue and host specificity from genome sequences
Authors: Zondervan Niels A. , dos Santos Vitor A. P. Martins , Suarez-Diez Maria
Published: August 2022

To gain insights into the genotype-phenotype relationships in Mycoplasmas, we set to investigate which Mycoplasma proteins are most predictive of tissue and host trophism and to which functional groups of proteins they belong. We retrieved and annotated 430 Mycoplasma genomes and combined their genome information with data on which host and tissue these Mycoplasmas were isolated from. We assessed clustering of Mycoplasma strains from a wide range of hosts and tissues based on different functional groups of proteins. Additionally, we assessed clustering using only a subset of M. pneumoniae strains based on different functional groups of proteins. We found that proteins belonging to the Gene Ontology (GO) Biological process group ‘Interspecies interaction between organisms’ proteins are most important for predicting the pathogenesis of Mycoplasma strains whereas for M. pneumoniae, those belonging to ‘Quorum sensing’ and ‘Biofilm formation’ proteins are most important for predicting pathogenesis.

Two Random Forest Classifiers were trained to accurately predicts host and tissue specificity based on only 12 proteins. For Mycoplasma host specificity CTP synthase complex, magnesium transporter MgtE, and glycine cleavage system are most important for correctly classifying Mycoplasma strains that infect humans, including opportunistic zoonotic strains. For tissue specificity, we found that a) known virulence and adhesions factor Methionine sulphate reductase MetA is predictive of urinary tract infecting Mycoplasmas; b) an extra cytoplasmic thiamine binding lipoprotein is most predictive of gastro-intestinal infecting Mycoplasmas; c) a type I restriction endonuclease is most predictive of respiratory infecting Mycoplasmas, and; d) a branched-chain amino acid transport system is most predictive for blood infecting Mycoplasmas. These findings can aid in predicting host and tissue specific pathogenicity of Mycoplasmas as well as provide insight in which proteins are important for specific host and tissue adaptations. Furthermore, these results underscore the usefulness of deploying genome-wide methodologies for gaining insights into pathogenicity from genome sequences.
Sniffing behavior of semi free-ranging Barbary macaques (Macaca sylvanus)
Authors: Simon Miriam , Widdig Anja , Weiß Brigitte M.
Published: August 2022

Olfaction is one of the evolutionarily oldest senses and plays a fundamental role in foraging and social interactions across mammals. In primates, the role of olfaction is now well recognized, but better investigated in strepsirrhine and platyrrhine primates than in catarrhines. We observed the sniffing behavior of semi-free ranging Barbary macaques,Macaca sylvanus, at Affenberg Salem, Germany, to assess how frequently macaques sniff and in which contexts, and how sniffing is affected by sex and age. Focal observations of 24 males and 24 females aged 1 to 25 years showed that Barbary macaques sniffed, on average, 5.3 times per hour, with more than 80% of sniffs directed at food. Irrespective of the context, younger individuals sniffed more often than older ones. Females’ sniffs were more often directed at food than male sniffs, while males sniffed more often than females in a social context. Sniffs at conspecifics occurred primarily in a sexual context, with 70% of social sniffs directed at female anogenital swellings performed by males. Of the observed 176 anogenital inspections, 51 involved sniffing of the swelling. Olfactory inspections were followed by copulation significantly less often than merely visual inspections, suggesting that anogenital odors provided additional information guiding male mating decisions. In sum, results show that Barbary macaques routinely use olfaction during feeding, but also in a social context. Our study further suggests that odors may guide mating decisions, but the role of olfaction in sexual interactions warrants further investigations.
Bidirectional and reciprocal control of astrocyte free calcium by modest fluctuations in external potassium
Authors: Institoris A. , Shin S. , Weilinger N.L. , Gorzo K. , Mehina E. , Haidey J. , MacVicar B.A. , Gordon G.R.
Published: August 2022

Astrocytes sense and respond to changes in the concentration of extracellular K+, and separately contribute to multiple physiological processes through Ca2+ dependent mechanisms. Yet, whether a modest change in [K+]o impacts astrocyte free Ca2+ remains unclear. Using relative or quantitative two-photon fluorescence Ca2+ imaging in acute brain slices or in vivo in the somatosensory cortex from Sprague Dawley rats and C57Bl/6 mice, we showed that changes to external K+ (+/-1mM to 2.5mM) reciprocally controls the astrocyte Rhod-2 or OGB-1 Ca2+-dependent fluorescence in the soma, major processes and endfeet. The astrocyte Ca2+ decrease when [K+]o was elevated was sensitive to lowering the external concentration of Ca2+, Cl-, and HCO3-, but not Na+. Unexpectedly, the phenomenon was blocked by inhibiting K-Cl cotransport. Picrotoxin induced ictal neural activity drove an analogous decrease of astrocyte Ca2+. K+ mediated cerebral arteriole dilation in brain slices was also sensitive to inhibiting K-Cl cotransport as well as whole-cell patching a peri-arteriole astrocyte which perturbs normal Ca2+, Cl- and HCO3- concentration gradients. These data reveal subtle, bidirectional regulation of astrocyte free Ca2 via fluctuations of [K+]o within the physiological range.
The first gapless, reference-quality, fully annotated genome from a Southern Han Chinese individual
Authors: Chao Kuan-Hao , Zimin Aleksey V , Pertea Mihaela , Salzberg Steven L
Published: August 2022

We used long-read DNA sequencing to assemble the genome of a Southern Han Chinese male. We organized the sequence into chromosomes and filled in gaps using the recently completed CHM13 genome as a guide, yielding a gap-free genome, Han1, containing 3,099,707,698 bases. Using the CHM13 annotation as a reference, we mapped all genes onto the Han1 genome and identified additional gene copies, generating a total of 60,708 genes, of which 20,003 are protein coding. A comprehensive comparison between the genes revealed that 235 protein-coding genes were substantially different between the individuals, with frameshifts or truncations affecting the protein-coding sequence. Most of these were heterozygous variants in which one gene copy was unaffected. This represents the first gene-level comparison between two finished, annotated individual human genomes.
Lower Brain Glucose Metabolism in Normal Ageing is Predominantly Frontal and Temporal: A Systematic Review and Pooled Effect Size and Activation Likelihood Estimates Meta-Analyses
Authors: Deery H.A , Di Paolo R , Moran C. , Egan G.F. , Jamadar S.D.
Published: August 2022

This review provides a qualitative and quantitative analysis of cerebral glucose in ageing. We undertook a systematic review of the literature followed by pooled effect size and Activation Likelihood Estimates (ALE) meta-analyses. Studies were retrieved from PubMed following the PRISMA guidelines. After reviewing 653 records, 22 studies with 24 samples (n = 993 participants) were included in the pooled effect size analyses. Eight studies with 11 samples (n = 713 participants) were included in the ALE analyses. Pooled effect sizes showed significantly lower cerebral metabolic rates of glucose for older versus younger adults for the whole brain, as well as for the frontal, temporal, parietal and occipital lobes. Among the sub-cortical structures, the caudate showed a lower metabolic rate among older adults. In sub-group analyses controlling for changes in brain volume or partial volume effects, the lower glucose metabolism among older adults in the frontal lobe remained significant, whereas confidence intervals crossed zero for the other lobes and structures. The ALE identified nine clusters of lower glucose metabolism among older adults, ranging from 200mm3 to 2,640mm3. The two largest clusters were in the left and right inferior frontal and superior temporal gyri and the insula. Clusters were also found in the inferior temporal junction, the anterior cingulate and caudate. Taken together, the results of the meta-analyses are consistent with research showing less efficient glucose metabolism in the ageing brain. The findings are discussed in the context of theories of cognitive ageing and are compared to those found in neurodegenerative disease.
Longitudinal neural and vascular recovery following ultraflexible neural electrode implantation in aged mice
Authors: He Fei , Sun Yingchu , Jin Yifu , Yin Rongkang , Zhu Hanlin , Rathore Haad , Xie Chong , Luan Lan
Published: August 2022

Flexible neural electrodes improve the recording longevity and quality of individual neurons by promoting tissue-electrode integration. However, the intracortical implantation of flexible electrodes inevitably induces tissue damage. Understanding the longitudinal neural and vascular recovery following the intracortical implantation is critical for the ever-growing applications of flexible electrodes in both healthy and disordered brains. Aged animals are of particular interest because they play a key role in modeling neurological disorders, but their tissue-electrode interface remains mostly unstudied. Here we integrate in-vivo two-photon imaging and electrophysiological recording to determine the time-dependent neural and vascular dynamics after the implantation of ultraflexible neural electrodes in aged mice. We find heightened angiogenesis and vascular remodeling in the first two weeks after implantation, which coincides with the rapid increase in local field potentials and unit activities detected by electrophysiological recordings. Vascular remodeling in shallow cortical layers preceded that in deeper layers, which often lasted longer than the recovery of neural signals. By six weeks post-implantation vascular abnormalities had subsided, resulting in normal vasculature and microcirculation. Putative cell classification based on firing pattern and waveform shows similar recovery time courses in fast-spiking interneurons and pyramidal neurons. These results elucidate how structural damages and remodeling near implants affecting recording efficacy, and support the application of ultraflexible electrodes in aged animals at minimal perturbations to endogenous neurophysiology.
The World Is Completely Unprepared For Detecting Emerging Viruses/Bacteria In The Air
Authors: Srikrishna Devabhaktuni
Published: August 2022

There is an immediate need for efficient networks to detect and control novel/emerging bioaerosol threats. In 2022, the Pentagon Force Protection Agency (PFPA) found detection of emerging bioaerosol threats to be “not feasible for daily operations” due to cost of reagents used for metagenomics, cost of sequencing instruments, and time/cost for labor (subject matter expertise) to analyze bioinformatics. If the Pentagon experiences these operational difficulties, they may also extend to many of the 280,000 buildings (2.3 billion square feet) at 5000 secure US DoD military sites, 250 US Navy ships, and beyond in civilian buildings around the world. These economic barriers can still be addressed in a threat-agnostic manner by dynamically pooling samples from a network of dry filter units (DFUs) to detect spatio-temporally correlated “spikes” in novel pathogen concentrations, termed Spike Triggered Virtualization (STV). In STV, pooling and sequencing depth are automatically modulated in the next cycle in response to novel potential biothreats in the sequencing output of the previous sequencing cycle. By running at a high pooling factor and lower depth unless triggered by a potential pathogen spike, average daily and annual cost per DFU can be reduced by one to two orders of magnitude depending on chosen trigger thresholds. Artificial intelligence (AI) can further enhance sensitivity of STV triggers. Risk of infection remains during the 12-24 hour window between a bioaerosol incident and its detection, but can in some cases be reduced by 80% or potentially more with high-speed indoor air cleaning exceeding 10 air changes per hour (10 ACH) similar to passenger airplanes (Airbus A319, A321 and a Boeing 737-Max8/9) that were tested in flight. Costs of 4 ACH or higher are expected to rise non-linearly with ACH using central HVAC systems and be cost-prohibitive. Whereas 10 ACH or more can be achieved economically by recycling the air in rooms with low-noise, portable air filtration systems tested herein for which costs scale linearly with ACH. For typical ceiling heights (< 10 ‘), the cost per square foot cost for low-noise air filtration exceeding 10 ACH was found to be approximately $0.5 to $1 for Do-It-Yourself (DIY) and $2 to $5 for HEPA.
An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine
Authors: Martín-Sánchez Mario , Wu Peng , Adam Dillon C. , Yang Bingyi , Lim Wey Wen , Lin Yun , Lau Eric H. Y. , Sullivan Sheena G. , Leung Gabriel M. , Cowling Benjamin J.
Published: August 2022

Background

Hong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures.

Methods

We conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values.

Results

There were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; p<0.001) while lower Ct values at isolation were observed in cases infected with Omicron than the ancestral strain or other variants. No Omicron cases were detected beyond 14 days after arrival, and the cases (n=58, 2.6%) detected after 14 days of quarantine more frequently presented without symptoms at isolation and had a higher RT-PCR Ct-value during isolation. At least some of these cases were post-arrival infections.

Conclusions

Testing inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.
Fair Reinforcement Learning for Maternal Sepsis Treatment
Authors: Carey Siân , McInerney Ciarán , Lawton Tom , Habli Ibrahim , Johnson Owen , Fahel Leila , Kotzé Alwyn , de Kamps Marc
Published: August 2022

Objectives

Reinforcement Learning is a branch of artificial intelligence (AI) which has the potential to support significant improvement in patient care. There is concern that such approaches may reinforce existing biases within patient groups. Understanding discrimination in AI models is important for building trust and ensuring fair and safe use. We explore the fairness of a published reinforcement learning model, used to suggest drug dosages for sepsis treatment of patients in critical care, on whether it safe to use with maternal sepsis patients.

Methods

We evaluate the current model using by a) comparing the results for a group of patients with maternal sepsis against a matched control group and b) using random forests to explore feature importance in the model.

Results

Our results show that the original clinicians’ decisions and model suggestions were similar across cohorts. Our feature importance ranking shows high variance for many of the features.

Discussion

In medical settings, different subgroups may have specific clinical needs and require different treatment however, in the absence of a clinical consensus on the most appropriate treatment, AI algorithms that give consistent treatment to patients regardless of subgroup could be judged as the safest and fairest option.

Conclusion

Our experiments showed that the evaluated model gave the same treatment to maternal and non-maternal sepsis patients. The methods developed for evaluating fair reinforcement learning may be more generally applicable to understanding how clinical AI tools can be used for safely and fairly.

What is already known on this topic

The use of reinforcement learning to suggest drug dosages for sepsis patients in critical care is a well-researched area, with multiple open-source models available. It has not previously been considered whether these models can be used on maternal sepsis patients.

What this study adds

The model studied behaves consistently on maternal and non-maternal sepsis patients, and appears to suggest an increased use of vasopressors compared with historical actions.

How this study might affect research, practice or policy

This study shows that it is possible to design models which are consistent across maternal and non-maternal sepsis patients, suggesting that a single model may be appropriate across a variety of patients with sepsis.
Deep learning-based automated lesion segmentation on mouse stroke magnetic resonance images
Authors: An Jeehye , Wendt Leo , Wiese Georg , Herold Tom , Rzepka Norman , Mueller Susanne , Koch Stefan Paul , Hoffmann Christian J. , Harms Christoph , Boehm-Sturm Philipp
Published: August 2022

Magnetic resonance imaging (MRI) is widely used for ischemic stroke lesion detection in mice. A challenge is that lesion segmentation often relies on manual tracing by trained experts, which is labor-intensive, time-consuming, and prone to inter- and intra-rater variability. Here, we present a fully automated ischemic stroke lesion segmentation method for mouse T2-weighted MRI data. As an end-to-end deep learning approach, the automated lesion segmentation requires very little preprocessing and works directly on the raw MRI scans. We randomly split a large dataset of 382 MRI scans into a subset (n = 293) to train the automated lesion segmentation and a subset (n = 89) to evaluate its performance. We compared Dice coefficients and accuracy of lesion volume against manual segmentation, as well as its performance on an independent dataset from an open repository with different imaging characteristics. The automated lesion segmentation produced segmentation masks with a smooth, compact, and realistic appearance that are in high agreement with manual segmentation.
Labeled lines for fat and sugar reward combine to promote overeating
Authors: McDougle Molly , de Araujo Alan , Vergara Macarena , Yang Mingxin , Singh Arashdeep , Braga Isadora , Urs Nikhil , Warren Brandon , de Lartigue Guillaume
Published: August 2022

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits are poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for detection of dietary fats and sugars. Using activity-dependent genetic capture of nutrient-specific vagal neurons activated in response gut infusions, we demonstrate the existence of separate hard-wired reward circuits for fat and sugar that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases overeating compared to fat or sugar alone. This work provides new insight on the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.
Distinct encoding and post-encoding representational formats contribute to episodic sequence memory formation
Authors: Wu Xiongbo , Fuentemilla Lluís
Published: August 2022

In episodic encoding, an unfolding experience is rapidly transformed into a memory representation that binds separate episodic elements into a memory form to be later recollected. However, it is unclear how brain activity changes over time to accommodate the encoding of incoming information. This study aimed to investigate the dynamics of the representational format that contributed to memory formation of sequential episodes. We combined Representational Similarity Analysis and multivariate decoding approaches on EEG data to compare whether “category-level” or “item-level” representations supported memory formation during the online encoding of a picture triplet sequence and offline, in the period that immediately followed encoding. The findings revealed a gradual integration of category-level representation during the online encoding of the picture sequence and a rapid item-based neural reactivation of the encoded sequence at the episodic offset. However, we found that only memory reinstatement at episodic offset was associated with successful memory retrieval from long term memory. These results suggest that post-encoding memory reinstatement is crucial for the rapid formation of unique memory for episodes that unfold over time. Overall, the study sheds light on the dynamics of representational format changes that take place during the formation of episodic memories.
metGWAS 1.0: An R workflow for network-driven over-representation analysis between independent metabolomic and meta-genome wide association studies
Authors: Khan Saifur R. , Obersterescu Andreea , Gunderson Erica P. , Wheeler Michael B. , Cox Brian J.
Published: August 2022

Background

Many diseases may result from disrupted metabolic regulation. Metabolite-GWAS studies assess the association of polymorphic variants with metabolite levels in body fluids. While these studies are successful, they have a high cost and technical expertise burden due to combining the analytical biochemistry of metabolomics with the computational genetics of GWAS. Currently, there are 100s of standalone metabolomics and GWAS studies related to similar diseases or phenotypes. A method that could statically evaluate these independent studies to find novel metabolites-genes association is of high interest. Although such an analysis is limited to genes with known metabolite interactions due to the unpaired nature of the data sets, any discovered associations may represent biomarkers and druggable targets for treatment and prevention.

Methods

We developed a bioinformatics tool, metGWAS 1.0, that generates and statistically compares metabolic and genomic gene sets using a hypergeometric test. Metabolic gene sets are generated by mapping disease-associated metabolites to interacting proteins (genes) via online databases. Genomic gene sets are identified from a network representation of the GWAS Catalog comprising 100s of studies.

Results

The metGWAS 1.0 tool was evaluated using standalone metabolomics datasets extracted from two metabolomics-GWAS case studies. In case-study 1, a cardiovascular disease association study, we identified nine genes (APOA5, PLA2G5, PLA2G2D, PLA2G2E, PLA2G2F, LRAT, PLA2G2A, PLB1, and PLA2G7) that interact with metabolites in the KEGG glycerophospholipid metabolism pathway and contain polymorphic variants associated with cardiovascular disease (P < 0.005). The gene APOA5 was matched from the original metabolomics-GWAS study. In case study 2, a urine metabolome study of kidney metabolism in healthy subjects, we found marginal significance (P = 0.10 and P = 0.13) for glycine, serine, and threonine metabolism and alanine, aspartate, and glutamate metabolism pathways to GWAS data relating to kidney disease.

Conclusion

The metGWAS 1.0 platform provides insight into developing methods that bridge standalone metabolomics and disease and phenotype GWAS data. We show the potential to reproduce findings of paired metabolomics-GWAS data and provide novel associations of gene variation and metabolite expression.