bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Methods for Individual Killing of Broiler Chickens: A Matter of Animal Welfare and On-Farm Feasibility
Authors: Watteyn Anneleen , Garmyn An , Ampe Bart , Jacobs Leonie , Moons Christel P. H. , Tuyttens Frank A. M.
Published: May 2022

The humane killing of individual broiler chickens on-farm requires a minimum of suffering. In this regard, rapid and irreversible loss of consciousness are important determinants. This can be verified by cerebral and spinal reflexes. Also, on-farm feasibility determines whether producers will apply the method. The aim of the study was to compare the effectiveness and animal welfare impact of two different methods for killing individual broilers of varying ages (2, 4, and 6 weeks): manual cervical dislocation (CD) and captive bolt (CB). The evaluation of CD and CB was based on effectiveness and on time to onset (convulsions) or cessation (pain response, pupillary light reflex, convulsions, heartbeat) of non-invasive indicators. In addition, a pilot study was conducted on-farm to assess the feasibility of two alternative methods, CB and nitrogen gasification (N2), and to survey farmers’ opinions on them. The onset of convulsions was almost immediate for both methods in the first study. No differences between CD and CB were observed for the cessation of pain response for chickens at age of 2 weeks (5.0 and 7.5 s, respectively) and 6 weeks (14.0 and 14.1 s, respectively). However, at 4 weeks a longer pain response was measured after CD (11.3 s) than after CB (4.7 s). For the three age categories, the pupillary light reflex disappeared later after CD (54.9 - 80.7 s) compared to CB (8.3 - 13.7 s). The same was observed for cessation of convulsions in 2- and 6-week-old chickens (185.3 and 172.0 s for CD and 79.0 and 82.9 s for CB). This suggests that brain death occurred faster after CB compared to CD. No difference between the methods was found for the cessation of the heartbeat. After the pilot study, the producers preferred N2 over CB in terms of animal-friendliness, time-efficiency, ease of use, and effectiveness. However, both methods were found rather expensive and required some experience. CB and N2 are good killing alternatives to CD due to rapid and irreversible insensibility. However, more information and support for chicken producers will be needed for these to become routine killing methods.
Case Report: Primary Aldosteronism and Subclinical Cushing Syndrome in a 49-Year-Old Woman With Hypertension Plus Hypokalaemia
Authors: Hu Lihua , Ji Wenjun , Guo Meiyu , Yi Tieci , Wang Jie , Bao Minghui , Gao Yusi , Jin Han , Lu Difei , Ma Wei , Han Xiaoning , Li Jianping , Yuan Zhenfang
Published: May 2022

Background

Coexisting primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) caused by bilateral adrenocortical adenomas have occasionally been reported. Precise diagnosis and treatment of the disease pose a challenge to clinicians due to its atypical clinical manifestations and laboratory findings.

Case Summary

A 49-year-old woman was admitted to our hospital due to fatigue, increased nocturia and refractory hypertension. The patient had a history of severe left hydronephrosis 6 months prior. Laboratory examinations showed hypokalaemia (2.58 mmol/L) and high urine potassium (71 mmol/24 h). Adrenal computed tomography (CT) showed bilateral adrenal masses. Undetectable ACTH and unsuppressed plasma cortisol levels by dexamethasone indicated ACTH-independent Cushing's syndrome. Although the upright aldosterone-to-renin ratio (ARR) was 3.06 which did not exceed 3.7, elevated plasma aldosterone concentrations (PAC) with unsuppressed PAC after the captopril test still suggested PA. Adrenal venous sampling (AVS) without adrenocorticotropic hormone further revealed hypersecretion of aldosterone from the right side and no dominant side of cortisol secretion. A laparoscopic right adrenal tumor resection was performed. The pathological diagnosis was adrenocortical adenoma. After the operation, the supine and standing PAC were normalized; while the plasma cortisol levels postoperatively were still high and plasma renin was activated. The patient's postoperative serum potassium and 24-h urine potassium returned to normal without any pharmacological treatment. In addition, the patient's blood pressure was controlled normally with irbesartan alone.

Conclusion

Patients with refractory hypertension should be screened for the cause of secondary hypertension. AVS should be performed in patients in which PA is highly suspected to determine whether there is the option of surgical treatment. Moreover, patients with PA should be screened for hypercortisolism, which can contribute to a proper understanding of the AVS result.
Artificial Intelligence in Predicting Systemic Parameters and Diseases From Ophthalmic Imaging
Authors: Betzler Bjorn Kaijun , Rim Tyler Hyungtaek , Sabanayagam Charumathi , Cheng Ching-Yu
Published: May 2022

Artificial Intelligence (AI) analytics has been used to predict, classify, and aid clinical management of multiple eye diseases. Its robust performances have prompted researchers to expand the use of AI into predicting systemic, non-ocular diseases and parameters based on ocular images. Herein, we discuss the reasons why the eye is well-suited for systemic applications, and review the applications of deep learning on ophthalmic images in the prediction of demographic parameters, body composition factors, and diseases of the cardiovascular, hematological, neurodegenerative, metabolic, renal, and hepatobiliary systems. Three main imaging modalities are included—retinal fundus photographs, optical coherence tomographs and external ophthalmic images. We examine the range of systemic factors studied from ophthalmic imaging in current literature and discuss areas of future research, while acknowledging current limitations of AI systems based on ophthalmic images.
Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials
Authors: Liu Ying , Chen Hongbo , Li Hui , Li Liman , Wu Jin , Li Hong
Published: May 2022

Background

The role of metformin in the treatment of adolescents with type 1 diabetes mellitus (T1DM) remains controversial. We conducted this updated meta-analysis to generate a comprehensive assessment regarding the effect and safety of metformin in treating adolescents with T1DM.

Methods

We systematically searched PubMed, Embase, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from their inception to November 2021 to identify randomized controlled trials evaluating the efficacy of metformin in the treatment of adolescents with T1DM. The primary outcome was the HbA1c level, and secondary outcomes included the body mass index (BMI), total insulin daily dose (TIDD) (unit/kg/d), hypoglycemia events, diabetes ketoacidosis (DKA) events, and gastrointestinal adverse events (GIAEs). Statistical analysis was conducted using RevMan 5.4 and STATA 14.0.

Results

Ten studies enrolling 539 T1DM adolescents were included. Results suggested that metformin significantly decreased the HbA1c level at 12 months (mean difference [MD])=-0.50, 95% confidence interval [CI]=-0.61 to -0.39, P < 0.01); BMI (kg/m2) at 3 months (MD=-1.05, 95%CI=-2.05 to -0.05, P=0.04); BMI z-score at 6 months (MD=-0.10, 95%CI=-0.14 to -0.06, P<0.01); and TIDD at 3 (MD=-0.13, 95%CI=-0.20 to -0.06, P<0.01), 6 (MD=-0.18, 95%CI=-0.25 to -0.11, P<0.01), and 12 (MD=-0.42, 95%CI=-0.49 to -0.35, P<0.01) months but significantly increased the risk of hypoglycemia events (risk ratio [RR]=3.13, 95%CI=1.05 to 9.32, P=0.04) and GIAEs (RR=1.64, 95%CI=1.28 to 2.10, P<0.01). For remaining outcomes at other time points, no statistical difference was identified. Sensitivity analysis confirmed the robustness of all pooled results.

Conclusions

The use of metformin might result in decreased BMI (kg/m2), BMI z-score, and TIDD and increased risk of hypoglycemia events and GIAEs in adolescents with T1DM. However, future studies are required to further confirm the optimal dose and duration of metformin therapy.
Therapeutic Potential of Targeting Periostin in the Treatment of Graves’ Orbitopathy
Authors: Jang Sun Young , Kim Jinjoo , Park Jung Tak , Liu Catherine Y. , Korn Bobby S. , Kikkawa Don O. , Lee Eun Jig , Yoon Jin Sook
Published: May 2022

Periostin is a matricellular protein that is ubiquitously expressed in normal human tissues and is involved in pathologic mechanism of chronic inflammatory and fibrotic disease. In this study we investigate periostin in the pathogenesis of Graves’ orbitopathy (GO) using human orbital adipose tissue obtained from surgery and primary cultured orbital fibroblasts in vitro. POSTN (gene encoding periostin) expression in Graves’ orbital tissues and healthy control tissues was studied, and the role of periostin in GO pathologic mechanism was examined through small-interfering RNA (siRNA)-mediated silencing. POSTN gene expression was significantly higher in Graves’ orbital tissues than healthy control tissues in real-time PCR results, and immunohistochemical staining revealed higher expression of periostin in Graves’ orbital tissues than normal tissues. Silencing periostin using siRNA transfection significantly attenuated TGF-β-induced profibrotic protein production and phosphorylated p38 and SMAD protein production. Knockdown of periostin inhibited interleukin-1 β -induced proinflammatory cytokines production as well as phosphorylation of NF-κB and Ak signaling protein. Adipocyte differentiation was also suppressed in periostin-targeting siRNA transfected GO cells. We hypothesize that periostin contributes to the pathogenic process of inflammation, fibrosis and adipogenesis of GO. Our study provides in vitro evidence that periostin may be a novel potential therapeutic target for the treatment of GO.
Battery Life Prediction Based on a Hybrid Support Vector Regression Model
Authors: Chen Yuan , Duan Wenxian , Ding Zhenhuan , Li Yingli
Published: May 2022

An accurate state of health and remaining useful life prediction is important to provide effective judgment for the lithium-ion battery and reduce the probability of battery effectiveness. This article proposes a hybrid model for the prediction by combining an improved decomposition algorithm, an improved parameterization algorithm, and a least squares support vector regression algorithm. The capacity signal is decomposed by the improved complete ensemble empirical mode decomposition with an adaptive noise algorithm to solve the backward problem. Then, the least squares support vector regression algorithm is used to predict each decomposition component separately. To obtain better parameters of the prediction model, a good point set principle and inertia weights are introduced to optimize a sparrow search algorithm. Experimental results confirm that the proposed hybrid prediction model has high accuracy, good stability, and strong robustness, which achieves a minimum 0.3% mean absolute error of the B0005 battery. The impact of prediction steps on accuracy is also discussed in this article. The results verified the capacity accuracy of the batteries predicted by eight steps.
Vertical and Horizontal Plastic Litter Distribution in a Bend of a Tidal River
Authors: Blondel Elise , Buschman Frans A.
Published: May 2022

Plastic litter transported in rivers may enter the marine environment. Due to the durability of plastic, the residence times in the aquatic environment are decades to millennia. Plastic litter items come in a wide variety. The density of the item and the flow velocity largely determine the vertical distribution of the plastic litter, although the litter shape and wind can also play a role in a river. Estimates of plastic transport in a river are usually based on observations of visible litter items in the near-surface layer alone. Only a very limited number of studies have observed the vertical distribution in rivers or estuaries. We have carried out 28 sampling surveys in a river bend located in the lower part of the Rhine-Meuse delta that is under the influence of tides. To observe the vertical distribution, we sampled with three nets simultaneously up to 5 m water depth, at both sides of the river bend. In total, almost 90% of the collected debris was organic matter. Plastic litter represented the large majority of the non-organic litter: about 80% by mass, having an average concentration of 0.5 mg/m3, and more than 90% by number. We observed that by mass and by number the plastic mass concentration in the middle net was generally lower than in the lower and upper nets. In total, more plastic litter was present in the two nets lower in the water column than in the surface net. A higher plastic concentration was found at the downwind side of the channel than at the upwind side of the fairway. It was found that the plastic litter mass concentrations were of the same order of magnitude during ebb than during flood tide. The litter size that contributed most to the mass concentration (around 65%) were items in between 25 and 500 mm, which were mostly soft plastics (i.e. foils). In the lower net, relatively more small hard plastic items were found. It was observed that these plastic items were sometimes entangled in organic matter. The plastic flux lower in the water column may follow the transport of organic matter like aquatic plants.
Baseline of Surface and Column-Integrated Aerosol Loadings in the Pearl River Delta Region, China
Authors: Fan Xuehua , Xia Xiangao , Chen Hongbin , Zhu Yanliang , Li Jun , Yang Honglong , Luo Hongyan
Published: May 2022

Much attention has been paid to the rapid variation of aerosol loading in the urban areas of the Pearl River Delta (PRD) region. The baseline of aerosol loading in this rapidly developing region is critical in evaluating how and why the aerosol level has evolved, which absolutely requires long-term observations. Based on long-term observations of aerosol optical depth (AOD), visibility, and particulate matter (PM) mass concentrations at Xichong (114.56°E, 22.49°N), a background site in the PRD region, the variabilities of aerosol loading at multiple temporal scales are revealed. The means (±σ) of AOD, visibility, PM10, PM2.5, and PM1 are 0.38 ± 0.07, 12.6 ± 2.3 km, 23.7 ± 12.6 μg/m3, 19.7 ± 11.0 μg/m3, and 16.1 ± 10.1 μg/m3, respectively, which show that aerosol loading at the Xichong site is much lower than that in urban and suburban sites. Significant decreases in PM10, PM2.5, and PM1 mass concentrations are observed with magnitudes up to −2.13, −1.82, and −1.37 yr−1, respectively, at a 95% confidence level. The decrease in aerosol loadings at Xichong is attributed to the strict environmental regulations for improving air quality. Higher AOD and PM (lower visibility) values are observed during the early spring months as a result of long-range transport of biomass burning from Southeastern Asia. Diurnal variations of PM and visibility are dominantly determined by those of boundary layer height and relative humidity. PM mass concentrations show a generally negative (positive) correlation with visibility (AOD) at Xichong, but the correlations are weak with the R2 of 0.22 and 0.54, respectively. Low visibility and high aerosol loading are generally associated with very weak easterly and southerly winds. Understanding of variability of surface particle concentration and column-integrated aerosol loading at this background site in the PRD region would provide a scientific basis for the adoption of pollution prevention and control measures.
An Insight Into Pentatricopeptide-Mediated Chloroplast Necrosis via microRNA395a During Rhizoctonia solani Infection
Authors: Srikakulam Nagesh , Guria Ashirbad , Karanthamalai Jeyalakshmi , Murugesan Vidya , Krishnan Vignesh , Sundaramoorthy Kasthuri , Saha Shakkhar , Singh Rudransh , Victorathisayam Thiveyarajan , Rajapriya Veeraputhiran , Sridevi Ganapathi , Pandi Gopal
Published: May 2022

Sheath blight (ShB) disease, caused by Rhizoctonia solani, is one of the major biotic stress-oriented diseases that adversely affect the rice productivity worldwide. However, the regulatory mechanisms are not understood yet comprehensively. In the current study, we had investigated the potential roles of miRNAs in economically important indica rice variety Pusa Basmati-1 upon R. solani infection by carrying out in-depth, high-throughput small RNA sequencing with a total data size of 435 million paired-end raw reads from rice leaf RNA samples collected at different time points. Detailed data analysis revealed a total of 468 known mature miRNAs and 747 putative novel miRNAs across all the libraries. Target prediction and Gene Ontology functional analysis of these miRNAs were found to be unraveling various cellular, molecular, and biological functions by targeting various plant defense-related genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate the miRNAs and their putative target genes. Out of the selected miRNA-specific putative target genes, miR395a binding and its cleavage site on pentatricopeptide were determined by 5’ RACE-PCR. It might be possible that R. solani instigated chloroplast degradation by modulating the pentatricopeptide which led to increased susceptibility to fungal infection.
Case Report: MYO5B Homozygous Variant c.2090+3A>T Causes Intron Retention Related to Chronic Cholestasis and Diarrhea
Authors: Zheng Yu , Peng Yuming , Zhang Shuju , Zhao Hongmei , Chen Weijian , Yang Yongjia , Hu Zhengmao , Yin Qiang , Peng Yu
Published: May 2022

Background: Biallelically mutated MYO5B is associated with microvillus inclusion disease (MVID, MIM: 251850), cholestasis, or both. This study aims at validating the splicing alteration and clinical features of an intron variant for diagnosis.

Case Presentation: A homozygous variant of MYO5B, NM_001080467.2:c.2090+3A > T (NP_001073936.1:p.?) in intron 17, was identified in a patient suffering from chronic cholestasis and diarrhea. Functional validation showed that this variant caused 185 bp of intron retention in its mRNA and was predicted to present a premature translation termination site for myoVb (p.Arg697fs*47) in the head motor domain. In addition, bowel biopsy revealed decreased microvilli and local lesions of microvillus inclusion in the duodena of the patient. The patient was presented with neonatal cholestasis leading to cirrhosis, intractable diarrhea, cholelithiasis, hepatic cyst, corneal opacity, and failure to thrive.

Conclusion: Our study demonstrated an intronic homozygous variant of MYO5B that affected an intron, subsequently altering splicing and leading to combined cholestasis and MVID. Our results further supported the underlying genotype–phenotype correlations and extended clinical practices toward its diagnosis and management.
How the Replication and Transcription Complex Functions in Jumping Transcription of SARS-CoV-2
Authors: Liang Jianguang , Shi Jinsong , Chen Shunmei , Duan Guangyou , Yang Fan , Cheng Zhi , Li Xin , Ruan Jishou , Mi Dong , Gao Shan
Published: May 2022

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC). Ascertaining all the RTC components and the arrangement of them is an indispensably step for the eventual determination of its global structure, leading to completely understanding all of its functions at the molecular level.

Results: The main results include: 1) hairpins containing the canonical and non-canonical NSP15 cleavage motifs are canonical and non-canonical transcription regulatory sequence (TRS) hairpins; 2) TRS hairpins can be used to identify recombination regions in CoV genomes; 3) RNA methylation participates in the determination of the local RNA structures in CoVs by affecting the formation of base pairing; and 4) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design.

Conclusions: In the present study, we proposed the theoretical arrangement of NSP12-15 and METTL3 in the global RTC structure and constructed a model to answer how the RTC functions in the jumping transcription of CoVs. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.
Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
Authors: Kawabe Takeshi , Ciucci Thomas , Kim Kwang Soon , Tayama Shunichi , Kawajiri Akihisa , Suzuki Takumi , Tanaka Riou , Ishii Naoto , Jankovic Dragana , Zhu Jinfang , Sprent Jonathan , Bosselut Rémy , Sher Alan
Published: May 2022

Under steady-state conditions, conventional CD4+T lymphocytes are classically divided into naïve (CD44loCD62Lhi) and memory (CD44hiCD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+T lymphocytes are divided into CD127hiSca1lo, CD127hiSca1hi, CD127loSca1hi, and CD127loSca1losubpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hiSca1hiBcl2hi. We further show that among the four MP subsets, CD127hiSca1hilymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hiSca1hiMP cells.
Case Report: A Severe Paediatric Presentation of COVID-19 in APDS2 Immunodeficiency
Authors: Sanchez Clemente Nuria , Penner Justin , Breuer Judith , Ip Winnie , Booth Claire
Published: May 2022

Critical respiratory manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are rare in children, and little is known about how immunocompromised children respond to the infection. We report a case of a 4-year-old boy with activated PI3K delta syndrome type 2 (APDS2) with a protracted and severe COVID-19 course with both inflammatory and acute respiratory features. He was treated with remdesivir, nitazoxanide, high-dose corticosteroids, and tocilizumab and made a full recovery. We propose that remdesivir may be used in combination with nitazoxanide to improve viral clearance and reduce the chance of resistance in treating acute SARS-CoV-2 infection.
Higher Affinity Antibodies Bind With Lower Hydration and Flexibility in Large Scale Simulations
Authors: Wong Mabel T. Y. , Kelm Sebastian , Liu Xiaofeng , Taylor Richard D. , Baker Terry , Essex Jonathan W.
Published: May 2022

We have carried out a long-timescale simulation study on crystal structures of nine antibody-antigen pairs, in antigen-bound and antibody-only forms, using molecular dynamics with enhanced sampling and an explicit water model to explore interface conformation and hydration. By combining atomic level simulation and replica exchange to enable full protein flexibility, we find significant numbers of bridging water molecules at the antibody-antigen interface. Additionally, a higher proportion of interactions excluding bulk waters and a lower degree of antigen bound CDR conformational sampling are correlated with higher antibody affinity. The CDR sampling supports enthalpically driven antibody binding, as opposed to entropically driven, in that the difference between antigen bound and unbound conformations do not correlate with affinity. We thus propose that interactions with waters and CDR sampling are aspects of the interface that may moderate antibody-antigen binding, and that explicit hydration and CDR flexibility should be considered to improve antibody affinity prediction and computational design workflows.
Wave Attenuation Over Mangroves in the Nanliu Delta, China
Authors: Zhou Xiaoyan , Dai Zhijun , Pang Wenhong , Wang Jie , Long Chuqi
Published: May 2022

Mangrove forests grow on tropical and subtropical coastlines and play a significant role in reducing hydrodynamic energy. However, little information is known about the mechanism of wave attenuation caused by mangroves of different ages, even though the effects of mangroves on wave damping have received widespread concern. Here, a series of systemic biohydrological data were collected along a cross-shore transect through mangroves with different ages of native Aegiceras corniculatum (AC) distribution in the Nanliu Delta of China and were analyzed to investigate wave attenuation over mangroves during different tidal conditions. The results showed that the wave height decreased nearly 58.33%, with a transport distance of 275 m in the AC seedling-sapling region, and approximately 80%, with a transport distance of 1,000 m in the sapling-adult region, on average. The largest wave height attenuation rate of 3 × 10−3 was found in the measured time period and occurred in the seedling-sapling section during the neap tide, while the sapling-adult region had a basically constant reduction rate of 0.8 × 10−3 under changing tidal conditions. Moreover, the drag coefficient calculation indicated that an AC seedling with a height of nearly 0.55 m was more effective in attenuating wave energy than the stem part of a grown tree with a height of nearly 1.2 m. AC seedlings and saplings have significant impacts on wave damping, even though the stem part of an adult AC could produce a decline in wave energy. Moreover, differences in the drag coefficient caused by stems and canopies were responsible for wave attenuation, and the degree of AC inundation volume induced by water level fluctuation might affect the wave damping effect. Our results documented distinct differences in the wave attenuation process by mangroves of different ages, which can inform superior designs of mangroves along coasts against a background of sea-level rise and the occurrence of frequent typhoons.
Cold-Season Epidemic Dynamics of COVID-19 in Two Major Metropolitan Areas in Greece: Hypotheses and Implications for Public Health Interventions
Authors: Sapounas Spyros , Bistaraki Angeliki , Jahaj Edison , Kotanidou Anastasia , Lagiou Pagona , Magiorkinis Gkikas
Published: May 2022

Many respiratory viruses, including coronaviruses, follow seasonal transmission dynamics. Analyzing the social and environmental mechanics of the emergence of SARS-CoV-2 over the first cold season provides insight into designing targeted interventions. We analyzed all fully anonymized SARS-CoV-2 case data in two metropolitan areas, Attika and Thessaloniki, diagnosed between September 1st and December 31st, 2020. The emergence of the second wave in Greece occurred in October-November. SARS-CoV-2 diagnoses in Thessaloniki increased quasi-exponentially in mid-October, coinciding with the increase in the proportion of diagnoses in young people aged 18–39. The same pattern was observed in Attika with an almost 2-week delay, even though Attika had a higher prevalence of cases throughout summer until the second wave. Crucially, the nighttime temperature in Thessaloniki dropped below 18°C 3 weeks earlier than that in Attika. Epidemic growth was independently associated with the proportion of cases attributed to the 18–39 age group as well as with the drop in nighttime temperature below 18°C in both metropolitan areas but with a time difference. This pattern can be explained by a shift of nighttime entertainment activities from open-air to closed spaces, which occurs as nighttime temperature drops. Vaccination of young individuals can be crucial in decelerating the cold-season dynamics of SARS-CoV-2.
Metagenomes of Red Sea Subpopulations Challenge the Use of Marker Genes and Morphology to Assess Trichodesmium Diversity
Authors: Koedooder Coco , Landou Etai , Zhang Futing , Wang Siyuan , Basu Subhajit , Berman-Frank Ilana , Shaked Yeala , Rubin-Blum Maxim
Published: May 2022

Trichodesmium are filamentous cyanobacteria of key interest due to their ability to fix carbon and nitrogen within an oligotrophic marine environment. Their blooms consist of a dynamic assemblage of subpopulations and colony morphologies that are hypothesized to occupy unique niches. Here, we assessed the poorly studied diversity of Trichodesmium in the Red Sea, based on metagenome-assembled genomes (MAGs) and hetR gene-based phylotyping. We assembled four non-redundant MAGs from morphologically distinct Trichodesmium colonies (tufts, dense and thin puffs). Trichodesmium thiebautii (puffs) and Trichodesmium erythraeum (tufts) were the dominant species within these morphotypes. While subspecies diversity is present for both T. thiebautii and T. erythraeum, a single T. thiebautii genotype comprised both thin and dense puff morphotypes, and we hypothesize that this phenotypic variation is likely attributed to gene regulation. Additionally, we found the rare non-diazotrophic clade IV and V genotypes, related to Trichodesmium nobis and Trichodesmium miru, respectively that likely occurred as single filaments. The hetR gene phylogeny further indicated that the genotype in clade IV could represent the species Trichodesmium contortum. Importantly, we show the presence of hetR paralogs in Trichodesmium, where two copies of the hetR gene were present within T. thiebautii genomes. This may lead to the overestimation of Trichodesmium diversity as one of the copies misidentified T. thiebautii as Trichodesmium aureum. Taken together, our results highlight the importance of re-assessing Trichodesmium taxonomy while showing the ability of genomics to capture the complex diversity and distribution of Trichodesmium populations.
Single-Channel EEG Features Reveal an Association With Cognitive Decline in Seniors Performing Auditory Cognitive Assessment
Authors: Molcho Lior , Maimon Neta B. , Regev-Plotnik Noa , Rabinowicz Sarit , Intrator Nathan , Sasson Ady
Published: May 2022

Background

Cognitive decline remains highly underdiagnosed despite efforts to find novel cognitive biomarkers. Electroencephalography (EEG) features based on machine-learning (ML) may offer a non-invasive, low-cost approach for identifying cognitive decline. However, most studies use cumbersome multi-electrode systems. This study aims to evaluate the ability to assess cognitive states using machine learning (ML)-based EEG features extracted from a single-channel EEG with an auditory cognitive assessment.

Methods

This study included data collected from senior participants in different cognitive states (60) and healthy controls (22), performing an auditory cognitive assessment while being recorded with a single-channel EEG. Mini-Mental State Examination (MMSE) scores were used to designate groups, with cutoff scores of 24 and 27. EEG data processing included wavelet-packet decomposition and ML to extract EEG features. Data analysis included Pearson correlations and generalized linear mixed-models on several EEG variables: Delta and Theta frequency-bands and three ML-based EEG features: VC9, ST4, and A0, previously extracted from a different dataset and showed association with cognitive load.

Results

MMSE scores significantly correlated with reaction times and EEG features A0 and ST4. The features also showed significant separation between study groups: A0 separated between the MMSE < 24 and MMSE ≥ 28 groups, in addition to separating between young participants and senior groups. ST4 differentiated between the MMSE < 24 group and all other groups (MMSE 24–27, MMSE ≥ 28 and healthy young groups), showing sensitivity to subtle changes in cognitive states. EEG features Theta, Delta, A0, and VC9 showed increased activity with higher cognitive load levels, present only in the healthy young group, indicating different activity patterns between young and senior participants in different cognitive states. Consisted with previous reports, this association was most prominent for VC9 which significantly separated between all level of cognitive load.

Discussion

This study successfully demonstrated the ability to assess cognitive states with an easy-to-use single-channel EEG using an auditory cognitive assessment. The short set-up time and novel ML features enable objective and easy assessment of cognitive states. Future studies should explore the potential usefulness of this tool for characterizing changes in EEG patterns of cognitive decline over time, for detection of cognitive decline on a large scale in every clinic to potentially allow early intervention.

Trial Registration

NIH Clinical Trials Registry [https://clinicaltrials.gov/ct2/show/results/NCT04386902], identifier [NCT04386902]; Israeli Ministry of Health registry [https://my.health.gov.il/CliniTrials/Pages/MOH_2019-10-07_007352.aspx], identifier [007352].
Effects of Sex on the Relationship Between Apolipoprotein E Gene and Serum Lipid Profiles in Alzheimer’s Disease
Authors: Fu Jiajia , Huang Yan , Bao Ting , Ou Ruwei , Wei Qianqian , Chen Yongping , Yang Jing , Chen Xueping , Shang Huifang
Published: May 2022

Background

Sex is an important factor in studying the relationship between the APOE gene, lipid profiles, and AD. However, few studies have focused on the effect of sex on lipids in AD and normal controls with different APOE genes.

Materials and Methods

A total of 549 participants, including 298 AD patients and 251 body mass index (BMI)-matched healthy controls (HCs), were enrolled. Lipid profiles and APOE genes in both AD patients and HCs were determined.

Results

(1) TC and LDL were higher in AD patients than in HCs, only in APOEε4 carrying populations, but not in non-carrying populations. (2) TC and LDL were higher in APOEε4 allele carriers than in non-carriers, only in AD populations, but not in HCs. (3) The TC of APOEε2 carriers was lower than that of non-carriers in the male AD population, but not in the female AD population, female HCs, and male HCs. (4) The increased LDL level may increase the risk of AD in female people carrying APOEε4.

Conclusion

The TC and LDL levels of APOEε4 carriers were higher than those of non-carriers, and the effect was more significant in the female AD population. The TC levels in APOEε2 carriers were lower than those in non-carriers, which was more significant in the male AD population.
Contrasting Associations Between Heart Rate Variability and Brainstem-Limbic Connectivity in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Pilot Study
Authors: Thome Janine , Densmore Maria , Terpou Braeden A. , Théberge Jean , McKinnon Margaret C. , Lanius Ruth A.
Published: May 2022

Background

Increasing evidence points toward the need to extend the neurobiological conceptualization of posttraumatic stress disorder (PTSD) to include evolutionarily conserved neurocircuitries centered on the brainstem and the midbrain. The reticular activating system (RAS) helps to shape the arousal state of the brain, acting as a bridge between brain and body. To modulate arousal, the RAS is closely tied to the autonomic nervous system (ANS). Individuals with PTSD often reveal altered arousal patterns, ranging from hyper- to blunted arousal states, as well as altered functional connectivity profiles of key arousal-related brain structures that receive direct projections from the RAS. Accordingly, the present study aims to explore resting state functional connectivity of the RAS and its interaction with the ANS in participants with PTSD and its dissociative subtype.

Methods

Individuals with PTSD (n = 57), its dissociative subtype (PTSD + DS, n = 32) and healthy controls (n = 40) underwent a 6-min resting functional magnetic resonance imaging and pulse data recording. Resting state functional connectivity (rsFC) of a central node of the RAS – the pedunculopontine nuclei (PPN) – was investigated along with its relation to ANS functioning as indexed by heart rate variability (HRV). HRV is a prominent marker indexing the flexibility of an organism to react adaptively to environmental needs, with higher HRV representing greater effective adaptation.

Results

Both PTSD and PTSD + DS demonstrated reduced HRV as compared to controls. HRV measures were then correlated with rsFC of the PPN. Critically, participants with PTSD and participants with PTSD + DS displayed inverse correlations between HRV and rsFC between the PPN and key limbic structures, including the amygdala. Whereas participants with PTSD displayed a positive relationship between HRV and PPN rsFC with the amygdala, participants with PTSD + DS demonstrated a negative relationship between HRV and PPN rsFC with the amygdala.

Conclusion

The present exploratory investigation reveals contrasting patterns of arousal-related circuitry among participants with PTSD and PTSD + DS, providing a neurobiological lens to interpret hyper- and more blunted arousal states in PTSD and PTSD + DS, respectively.
sEMG-Based Gesture Classifier for a Rehabilitation Glove
Authors: Copaci Dorin , Arias Janeth , Gómez-Tomé Marcos , Moreno Luis , Blanco Dolores
Published: May 2022

Human hand gesture recognition from surface electromyography (sEMG) signals is one of the main paradigms for prosthetic and rehabilitation device control. The accuracy of gesture recognition is correlated with the control mechanism. In this work, a new classifier based on the Bayesian neural network, pattern recognition networks, and layer recurrent network is presented. The online results obtained with this architecture represent a promising solution for hand gesture recognition (98.7% accuracy) in sEMG signal classification. For real time classification performance with rehabilitation devices, a new simple and efficient interface is developed in which users can re-train the classification algorithm with their own sEMG gesture data in a few minutes while enables shape memory alloy-based rehabilitation device connection and control. The position of reference for the rehabilitation device is generated by the algorithm based on the classifier, which is capable of detecting user movement intention in real time. The main aim of this study is to prove that the device control algorithm is adapted to the characteristics and necessities of the user through the proposed classifier with high accuracy in hand gesture recognition.
Stochastic-HD: Leveraging Stochastic Computing on the Hyper-Dimensional Computing Pipeline
Authors: Morris Justin , Hao Yilun , Gupta Saransh , Khaleghi Behnam , Aksanli Baris , Rosing Tajana
Published: May 2022

Brain-inspired Hyper-dimensional(HD) computing is a novel and efficient computing paradigm. However, highly parallel architectures such as Processing-in-Memory(PIM) are bottle-necked by reduction operations required such as accumulation. To reduce this bottle-neck of HD computing in PIM, we present Stochastic-HD that combines the simplicity of operations in Stochastic Computing (SC) with the complex task solving capabilities of the latest HD computing algorithms. Stochastic-HD leverages deterministic SC, which enables all of HD operations to be done as highly parallel bitwise operations and removes all reduction operations, thus improving the throughput of PIM. To this end, we propose an in-memory hardware design for Stochastic-HD that exploits its high level of parallelism and robustness to approximation. Our hardware uses in-memory bitwise operations along with associative memory-like operations to enable a fast and energy-efficient implementation. With Stochastic-HD, we were able to reach a comparable accuracy with the Baseline-HD. Furthermore, by proposing an integrated Stochastic-HD retraining approach Stochastic-HD is able to reduce the accuracy loss to just 0.3%. We additionally accelerate the retraining process in our hardware design to create an end-to-end accelerator for Stochastic-HD. Finally, we also add support for HD Clustering to Stochastic-HD, which is the first to map the HD Clustering operations to the stochastic domain. As compared to the best PIM design for HD, Stochastic-HD is also 4.4% more accurate and 43.1× more energy-efficient.
A Deep Learning Quantification Algorithm for HER2 Scoring of Gastric Cancer
Authors: Han Zixin , Lan Junlin , Wang Tao , Hu Ziwei , Huang Yuxiu , Deng Yanglin , Zhang Hejun , Wang Jianchao , Chen Musheng , Jiang Haiyan , Lee Ren-Guey , Gao Qinquan , Du Ming , Tong Tong , Chen Gang
Published: May 2022

Gastric cancer is the third most common cause of cancer-related death in the world. Human epidermal growth factor receptor 2 (HER2) positive is an important subtype of gastric cancer, which can provide significant diagnostic information for gastric cancer pathologists. However, pathologists usually use a semi-quantitative assessment method to assign HER2 scores for gastric cancer by repeatedly comparing hematoxylin and eosin (H&E) whole slide images (WSIs) with their HER2 immunohistochemical WSIs one by one under the microscope. It is a repetitive, tedious, and highly subjective process. Additionally, WSIs have billions of pixels in an image, which poses computational challenges to Computer-Aided Diagnosis (CAD) systems. This study proposed a deep learning algorithm for HER2 quantification evaluation of gastric cancer. Different from other studies that use convolutional neural networks for extracting feature maps or pre-processing on WSIs, we proposed a novel automatic HER2 scoring framework in this study. In order to accelerate the computational process, we proposed to use the re-parameterization scheme to separate the training model from the deployment model, which significantly speedup the inference process. To the best of our knowledge, this is the first study to provide a deep learning quantification algorithm for HER2 scoring of gastric cancer to assist the pathologist's diagnosis. Experiment results have demonstrated the effectiveness of our proposed method with an accuracy of 0.94 for the HER2 scoring prediction.
Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives
Authors: Wang Ge , Wu Wenyue , Xu Yuchen , Yang Zhuanyi , Xiao Bo , Long Lili
Published: May 2022

Epilepsy is a neurological network disease with genetics playing a much greater role than was previously appreciated. Unfortunately, the relationship between genetic basis and imaging phenotype is by no means simple. Imaging genetics integrates multidimensional datasets within a unified framework, providing a unique opportunity to pursue a global vision for epilepsy. This review delineates the current knowledge of underlying genetic mechanisms for brain networks in different epilepsy syndromes, particularly from a neural developmental perspective. Further, endophenotypes and their potential value are discussed. Finally, we highlight current challenges and provide perspectives for the future development of imaging genetics in epilepsy.
Prevalence and Trends in Percutaneous Endoscopic Gastrostomy Placement: Results From a 10-Year, Nationwide Analysis
Authors: Folwarski Marcin , Klek Stanislaw , Brzeziński Michał , Szlagatys-Sidorkiewicz Agnieszka , Wyszomirski Adam , Meyer-Szary Jarosław , Skonieczna-Żydecka Karolina
Published: May 2022

Background

Percutaneous endoscopic gastrostomy (PEG) is the most commonly used access for long-term enteral nutrition. Only a few studies report the prevalence and epidemiology of PEG placements. No previous data concentrated on the healthcare system issues influencing the qualification rates and professional nutritional support for individuals with PEG.

Methods

We conducted a retrospective nationwide analysis of PEG placements in Poland from 2010 to 2020. The central data on ICD-10 coding of adult patients with PEG reported to the insurance company were used for the analysis of general and regional prevalence, age, and primary and secondary diseases. Rates of patients with home enteral nutrition (HEN) were calculated with a special focus on patients with cancer. A secondary aim was to determine the causes of regional disparities among administrative regions.

Results

A total number of 90,182 PEGs were placed during the observation period. The number was increasing each year with statistical significance. Malnutrition, dysphagia, and cardiorespiratory/metabolic diseases were the most frequently reported primary diseases. A total of 11.98% of all patients were diagnosed with cancer; 49.9% of oncological patients suffered from head and neck cancer (HNC) and 19.9% from esophageal cancer. In total, 6.61% of HNC and 27.46% of patients with esophageal cancer from the Polish National Cancer Registry (NCR) had PEG. The rates of patients in more advanced ages (65–74 and over 85 years) were growing and decreased in younger groups (18–24, 45–54, and 55–64 years). Overall, 27.6% of all (11.86% of cancer) patients with PEG were reimbursed HEN. A high number of patients in nursing care facilities, lower education of citizens, and lower number of hospital beds were associated with more PEG insertions in the administrative regions.

Conclusion

The number of PEG placements has been increasing, particularly in the elderly. Systemic solutions must be found to address the problems of regional disparities in PEG’s prevalence as well as the lack of inclusion criteria for nutritional support.
Novel Role of Long Non-Coding RNA ASAP1-IT1 in Progression of Hepatocellular Carcinoma
Authors: Liu Yanping , Hu Chengguang , Qu Xiaoyong , Chen Honghui , Liu Logen , Zhou Linlin , Liu Side , Li Guoqing , Zhou Yuanping
Published: May 2022

The long non-coding RNA (lncRNA) ASAP1-IT1 has been recently shown to aberrantly increase in ovarian and bladder cancer, while its role in other malignancies remains unexplored. This study was to characterize the expression and assess the potential role of ASAP1-IT1 in hepatocellular carcinoma (HCC). Fifty-four paired HCC and histologically normal tissues were obtained from HCC patients. Human HCC cell lines (HepG2, Huh7, SMMC-7721, and BEL-7402) and a normal liver cell line (LO2) were used for in vitro studies. ASAP1-IT1-specific siRNAs were used to silence ASAP1-IT1 expression, while the pcDNA-ASAP1-IT1 vector was constructed to up-regulate its expression. In situ hybridization and qRT-PCR were performed to characterize subcellular localization and expression of ASAP1-IT1. Cell proliferation and migration assays were conducted to examine the role of ASAP1-IT1 in the progression of HCC. In silico analysis was conducted to predict putative miRNA binding sites, which were validated by luciferase reporter assays. ASAP1-IT1 levels were significantly increased in HCC tissues and cells compared with controls. Notably, higher ASAP1-IT1 levels were significantly associated with poorer prognosis of HCC patients. In situ hybridization analysis revealed that ASAP1-IT1 was mainly localized in the nucleus of hepatoma cells and differentially expressed in trabecular, compact, and pseudoglandular forms of liver cancer. Furthermore, knockdown of ASAP1-IT1 significantly suppressed cell proliferation and migration, while its overexpression significantly promoted cell proliferation and migration of HCC cells. Mechanistically, ASAP1-IT1 might exert its role in HCC progression, at least in part, by directly interacting with miR-221-3p. In conclusion, ASAP1-IT1 is abnormally elevated in HCC, and higher levels are correlated with poorer prognosis. An underlying mechanism has been proposed for ASAP1-IT1-associated promotion of proliferation and migration in HCC cells. These findings have provided evidence supporting the oncogenic role of ASAP1-IT1 in HCC.