bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Differences Between the Sexes in a Fish Species Seen Through Satellite DNAs
Authors: Crepaldi Carolina , Martí Emiliano , Gonçalves Évelin Mariani , Martí Dardo Andrea , Parise-Maltempi Patricia Pasquali
Published: September 2021

Neotropical fishes have highly diversified karyotypic and genomic characteristics and present many diverse sex chromosome systems, with various degrees of sex chromosome differentiation. Knowledge on their sex-specific composition and evolution, however, is still limited. Satellite DNAs (satDNAs) are tandemly repeated sequences with pervasive genomic distribution and distinctive evolutionary pathways, and investigating satDNA content might shed light into how genome architecture is organized in fishes and in their sex chromosomes. The present study investigated the satellitome of Megaleporinus elongatus, a freshwater fish with a proposed Z1Z1Z2Z2/Z1W1Z2W2 multiple sex chromosome system that encompasses a highly heterochromatic and differentiated W1 chromosome. The species satellitome comprises of 140 different satDNA families, including previously isolated sequences and new families found in this study. This diversity is remarkable considering the relatively low proportion that satDNAs generally account for the M. elongatus genome (around only 5%). Differences between the sexes in regards of satDNA content were also evidenced, as these sequences are 14% more abundant in the female genome. The occurrence of sex-biased signatures of satDNA evolution in the species is tightly linked to satellite enrichment associated with W1 in females. Although both sexes share practically all satDNAs, the overall massive amplification of only a few of them accompanied the W1 differentiation. We also investigated the expansion and diversification of the two most abundant satDNAs of M. elongatus, MelSat01-36 and MelSat02-26, both highly amplified sequences in W1 and, in MelSat02-26’s case, also harbored by Z2 and W2 chromosomes. We compared their occurrences in M. elongatus and the sister species M. macrocephalus (with a standard ZW sex chromosome system) and concluded that both satDNAs have led to the formation of highly amplified arrays in both species; however, they formed species-specific organization on female-restricted sex chromosomes. Our results show how satDNA composition is highly diversified in M. elongatus, in which their accumulation is significantly contributing to W1 differentiation and not satDNA diversity per se. Also, the evolutionary behavior of these repeats may be associated with genome plasticity and satDNA variability between the sexes and between closely related species, influencing how seemingly homeologous heteromorphic sex chromosomes undergo independent satDNA evolution.
Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed
Authors: Shibata Takeo , Shah Sumit , Evans Teresa , Coleman Hannah , Lieblong Benjamin J. , Spencer Horace J. , Quick Charles M. , Sasagawa Toshiyuki , Stephens Owen W. , Peterson Erich , Johann Donald , Lu Yong-Chen , Nakagawa Mayumi
Published: September 2021

Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) β deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR β bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.
Proton Pump Inhibitors Increase the Risk of Autoimmune Diseases: A Nationwide Cohort Study
Authors: Lin Sheng-Hong , Chang Yu-Sheng , Lin Tzu-Min , Hu Li-Fang , Hou Tsung-Yun , Hsu Hui-Ching , Shen Yu-Chuan , Kuo Pei-I , Chen Wei-Sheng , Lin Yi-Chun , Chen Jin-Hua , Chang Chi-Ching
Published: September 2021

Background

Previous study revealed proton pump inhibitors (PPIs) have an effect on gut microbiota. Alteration of the microbiome causes changes of the host immune system and then induces the development of autoimmune diseases (ADs). This study aimed to explore the possible association between PPIs use and ADs.

Methods

This study was conducted using data from the Taiwan National Health Insurance Research Database in the period between 2002 and 2015. We performed multivariate and stratified analysis through the Kaplan-Meier method and Cox proportional hazard models to estimate the association between proton pump inhibitor use and the risk of autoimmune diseases.

Results

Of the 297,099 patients treated with PPI identified, the overall mean (SD) age was 49.17 (15.63) years and 56.28% of the subjects was male. As compared with the non-PPI group, the adjusted hazard ratio (aHR) were higher for incident organ specific ADs such as Graves disease (aHR=3.28), Hashmoto thyroiditis (aHR=3.61), autoimmune hemolytic anemia (aHR=8.88), immune thrombocytopenic purpura (aHR=5.05) Henoch-Schonlein pupura (aHR=4.83) and Myasthenia gravis (aHR=8.73). Furthermore, the adjusted hazard ratio (aHR) were also higher for incident systemic ADs such as ankylosing spondylitis (aHR=3.67), rheumatoid arthritis (aHR=3.96), primary Sjogren syndrome (aHR=7.81), systemic lupus erythemtoasus (aHR=7.03). systemic vasculitis (aHR=5.10), psoriasis (aHR=2.57), systemic scleroderma (aHR=15.85) and inflammatory myopathy (aHR=37.40). Furthermore, we observed no dose-dependent effect between PPI use and the risk of ADs.

Conclusions

Our retrospective population-based cohort study showed that the prescription of proton pump inhibitors is associated with a higher risk of ADs.
Novel Combination of Surface Markers for the Reliable and Comprehensive Identification of Human Thymic Epithelial Cells by Flow Cytometry: Quantitation and Transcriptional Characterization of Thymic Stroma in a Pediatric Cohort
Authors: Haunerdinger Veronika , Moccia Maria Domenica , Opitz Lennart , Vavassori Stefano , Dave Hitendu , Hauri-Hohl Mathias M.
Published: September 2021

Thymic epithelial cells (TECs) are essential in supporting the development of mature T cells from hematopoietic progenitor cells and facilitate their lineage-commitment, proliferation, T-cell receptor repertoire selection and maturation. While animal model systems have greatly aided in elucidating the contribution of stromal cells to these intricate processes, human tissue has been more difficult to study, partly due to a lack of suitable surface markers comprehensively defining human TECs. Here, we conducted a flow cytometry based surface marker screen to reliably identify and quantify human TECs and delineate medullary from cortical subsets. These findings were validated by transcriptomic and histologic means. The combination of EpCAM, podoplanin (pdpn), CD49f and CD200 comprehensively identified human TECs and not only allowed their reliable distinction in medullary and cortical subsets but also their detailed quantitation. Transcriptomic profiling of each subset in comparison to fibroblasts and endothelial cells confirmed the identity of the different stromal cell subsets sorted according to the proposed strategy. Our dataset not only demonstrated transcriptional similarities between TEC and cells of mesenchymal origin but furthermore revealed a subset-specific distribution of a specific set of extracellular matrix-related genes in TECs. This indicates that TECs significantly contribute to the distinct compartmentalization – and thus function – of the human thymus. We applied the strategy to quantify TEC subsets in 31 immunologically healthy children, which revealed sex-specific differences of TEC composition early in life. As the distribution of mature CD4- or CD8-single-positive thymocytes was correspondingly altered, the composition of the thymic epithelial compartment may directly impact on the CD4-CD8-lineage choice of thymocytes. We prove that the plain, reliable strategy proposed here to comprehensively identify human TEC subpopulations by flow cytometry based on surface marker expression is suitable to determine their frequency and phenotype in health and disease and allows sorting of live cells for downstream analysis. Its use reaches from a reliable diagnostic tool for thymic biopsies to improved phenotypic characterization of thymic grafts intended for therapeutic use.
Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults
Authors: Petrara Maria Raffaella , Bonfante Francesco , Costenaro Paola , Cantarutti Anna , Carmona Francesco , Ruffoni Elena , Di Chiara Costanza , Zanchetta Marisa , Barzon Luisa , Donà Daniele , Da Dalt Liviana , Bortolami Alessio , Pagliari Matteo , Plebani Mario , Rossi Paolo , Cotugno Nicola , Palma Paolo , Giaquinto Carlo , De Rossi Anita
Published: September 2021

Background

The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.

Methods

Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1–3.7) and 6.1 (5.3–7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).

Results

Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.

Conclusions

Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.
Th1-Biased Hepatitis C Virus-Specific Follicular T Helper-Like Cells Effectively Support B Cells After Antiviral Therapy
Authors: Zoldan Katharina , Ehrlich Sabine , Killmer Saskia , Wild Katharina , Smits Maike , Russ Marissa , Globig Anna-Maria , Hofmann Maike , Thimme Robert , Boettler Tobias
Published: September 2021

Circulating Th1-biased follicular T helper (cTfh1) cells have been associated with antibody responses to viral infection and after vaccination but their B cell helper functionality is less understood. After viral elimination, Tfh1 cells are the dominant subset within circulating Hepatitis C Virus (HCV)-specific CD4 T cells, but their functional capacity is currently unknown. To address this important point, we established a clone-based system to evaluate CD4 T cell functionality in vitro to overcome experimental limitations associated with their low frequencies. Specifically, we analyzed the transcription factor expression, cytokine secretion and B cell help in co-culture assays of HCV- (n = 18) and influenza-specific CD4 T cell clones (n = 5) in comparison to Tfh (n = 26) and Th1 clones (n = 15) with unknown antigen-specificity derived from healthy donors (n = 4) or direct-acting antiviral (DAA)-treated patients (n = 5). The transcription factor expression and cytokine secretion patterns of HCV-specific CD4 T cell clones indicated a Tfh1 phenotype, with expression of T-bet and Bcl6 and production of IFN-γ and IL-21. Their B helper capacity was superior compared to influenza-specific or Tfh and Th1 clones. Moreover, since Tfh cells are enriched in the IFN-rich milieu of the HCV-infected liver, we investigated the impact of IFN exposure on Tfh phenotype and function. Type I IFN exposure was able to introduce similar phenotypic and functional characteristics in the Tfh cell population within PBMCs or Tfh clones in vitro in line with our finding that Tfh cells are elevated in HCV-infected patients shortly after initiation of IFN-α therapy. Collectively, we were able to functionally characterize HCV-specific CD4 T cells in vitro and not only confirmed a Tfh1 phenotype but observed superior Tfh functionality despite their Th1 bias. Furthermore, our results suggest that chronic type I IFN exposure supports the enrichment of highly functional HCV-specific Tfh-like cells during HCV infection. Thus, HCV-specific Tfh-like cells after DAA therapy may be a promising target for future vaccination design aiming to introduce a neutralizing antibody response.
Intrapatient Variability in Tacrolimus Trough Levels Over 2 Years Affects Long-Term Allograft Outcomes of Kidney Transplantation
Authors: Park Yohan , Lee Hanbi , Eum Sang Hun , Kim Hyung Duk , Ko Eun Jeong , Yang Chul Woo , Chung Byung Ha
Published: September 2021

This study aimed to determine the impact of tacrolimus (TAC) trough level (C0) intrapatient variability (IPV) over a period of 2 years after kidney transplantation (KT) on allograft outcomes. In total, 1,143 patients with low immunologic risk were enrolled. The time-weighted coefficient variability (TWCV) of TAC-C0 was calculated, and patients were divided into tertile groups (T1: < 24.6%, T2: 24.6%–33.7%, T3: ≥ 33.7%) according to TAC-C0-TWCV up to post-transplant 1st year. They were classified into the low/low, low/high, high/low, and high/high groups based on a TAC-C0-TWCV value of 33.7% during post-transplant 0–1st and 1st–2nd years. The allograft outcomes among the three tertile and four TAC-C0-TWCV groups were compared. The T3 group had the highest rate of death-censored allograft loss (DCGL), and T3 was considered an independent risk factor for DCGL. The low/low group had the lowest and the high/high group had the highest risk for DCGL. Moreover, patients with a mean TAC-C0 of ≥5 ng/ml in the high/high group were at the highest risk for DCGL. Thus, TAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0. Furthermore, to improve allograft outcomes, a low TAC-IPV should be maintained even after the first year of KT.
Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
Authors: Antequera Desiree , Moneo Diego , Carrero Laura , Bartolome Fernando , Ferrer Isidro , Proctor Gordon , Carro Eva
Published: September 2021

In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer’s disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.
Ocular Motor Abnormalities in Anti-IgLON5 Disease
Authors: Macher Stefan , Milenkovic Ivan , Zrzavy Tobias , Höftberger Romana , Seidel Stefan , Berger-Sieczkowski Evelyn , Berger Thomas , Rommer Paulus S. , Wiest Gerald
Published: September 2021

Objective

Anti-IgLON5 disease forms an interface between neuroinflammation and neurodegeneration and includes clinical phenotypes that are often similar to those of neurodegenerative diseases. An early diagnosis of patients with anti-IgLON5 disease and differentiation from neurodegenerative diseases is necessary and may have therapeutic implications.

Methods

In our small sample size study we investigated oculomotor function as a differentiating factor between anti-IgLON5 disease and neurodegenerative disorders. We examined ocular motor and vestibular function in four patients suffering from anti-IgLON5 disease using video-oculography (VOG) and a computer-controlled rotational chair system (sampling rate 60 Hz) and compared the data with those from ten age-matched patients suffering from progressive supranuclear palsy (PSP) and healthy controls (CON).

Results

Patients suffering from anti-IgLON5 disease differed from PSP most strikingly in terms of saccade velocity and accuracy, the presence of square wave jerks (SWJ) (anti-IgLON5 0/4 vs. PSP 9/10) and the clinical finding of supranuclear gaze palsy (anti-IgLON5 1/4). The presence of nystagmus, analysis of smooth pursuit eye movements, VOR and VOR suppression was reliable to differentiate between the two disease entities. Clear differences in all parameters, although not always significant, were found between all patients and CON.

Discussion

We conclude that the use of VOG as a tool for clinical neurophysiological assessment can be helpful in differentiating between patients with PSP and patients with anti-IgLON5 disease. VOG could have particular value in patients with suspected PSP and lack of typical Parkinson’s characteristics. future trials are indispensable to assess the potential of oculomotor function as a biomarker in anti-IgLON5 disease.
Desmoglein2 Regulates Claudin2 Expression by Sequestering PI-3-Kinase in Intestinal Epithelial Cells
Authors: Burkard Natalie , Meir Michael , Kannapin Felix , Otto Christoph , Petzke Maximilian , Germer Christoph-Thomas , Waschke Jens , Schlegel Nicolas
Published: September 2021

Inflammation-induced reduction of intestinal desmosomal cadherin Desmoglein 2 (Dsg2) is linked to changes of tight junctions (TJ) leading to impaired intestinal epithelial barrier (IEB) function by undefined mechanisms. We characterized the interplay between loss of Dsg2 and upregulation of pore-forming TJ protein Claudin2. Intraperitoneal application of Dsg2-stablising Tandem peptide (TP) attenuated impaired IEB function, reduction of Dsg2 and increased Claudin2 in DSS-induced colitis in C57Bl/6 mice. TP blocked loss of Dsg2-mediated adhesion and upregulation of Claudin2 in Caco2 cells challenged with TNFα. In Dsg2-deficient Caco2 cells basal expression of Claudin2 was increased which was paralleled by reduced transepithelial electrical resistance and by augmented phosphorylation of AKTSer473 under basal conditions. Inhibition of phosphoinositid-3-kinase proved that PI-3-kinase/AKT-signaling is critical to upregulate Claudin2. In immunostaining PI-3-kinase dissociated from Dsg2 under inflammatory conditions. Immunoprecipitations and proximity ligation assays confirmed a direct interaction of Dsg2 and PI-3-kinase which was abrogated following TNFα application. In summary, Dsg2 regulates Claudin2 expression by sequestering PI-3-kinase to the cell borders in intestinal epithelium.
Case Report: ANCA-Associated Vasculitis Presenting With Rhabdomyolysis and Pauci-Immune Crescentic Glomerulonephritis After Pfizer-BioNTech COVID-19 mRNA Vaccination
Authors: Hakroush Samy , Tampe Björn
Published: September 2021

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.
Advancing the Interpretation of Shallow Water Marine Soundscapes
Authors: McKenna Megan F. , Baumann-Pickering Simone , Kok Annebelle C. M. , Oestreich William K. , Adams Jeffrey D. , Barkowski Jack , Fristrup Kurt M. , Goldbogen Jeremy A. , Joseph John , Kim Ella B. , Kügler Anke , Lammers Marc O. , Margolina Tetyana , Peavey Reeves Lindsey E. , Rowell Timothy J. , Stanley Jenni A. , Stimpert Alison K. , Zang Eden J. , Southall Brandon L. , Wall Carrie C. , Parijs Sofie Van , Hatch Leila T.
Published: September 2021

Soundscapes offer rich descriptions of composite acoustic environments. Characterizing marine soundscapes simply through sound levels results in incomplete descriptions, limits the understanding of unique features, and impedes meaningful comparisons. Sources that contribute to sound level metrics shift in time and space with changes in biological patterns, physical forces, and human activity. The presence of a constant or chronic source is often interwoven with episodic sounds. Further, the presence and intensity of sources can influence other sources, calling for a more integrated approach to characterizing soundscapes. Here, we illustrate this complexity using data from a national-scale effort, the Sanctuary Soundscape Monitoring Project (SanctSound), an initiative designed to support collection of biological, environmental, and human use data to compliment the interpretation of sound level measurements. Using nine examples from this diverse dataset we demonstrate the benefit of integrating source identification and site features to interpret sound levels across a diversity of shallow water marine soundscapes (<150 m). Sound levels from sites in high human use areas reflect the anthropogenic influences on the soundscape, especially when measuring broad frequency bands, whereas sites with relatively low human activity and high sound levels reveal biological features of the soundscape. At sites with large tidal changes, sound levels correlated with the magnitude of tidal flow, and sound levels during high tidal flow periods were similar to sound levels at sites near commercial shipping lanes. At sites in relatively close proximity (<30 km), sound levels diverge because of the presence of different proximate sound contributors and propagation features of the site. A review of emerging methodologies for integrated soundscape analysis, including acoustic scenes, provides a framework for interpreting soundscapes across a variety of conditions. With a global growth in monitoring efforts collecting standardized measurements over widely distributed arrays, more integrated methods are needed to advance the utility of soundscapes in marine resource management.
Comparative Efficacy Between Trifocal and Bifocal Intraocular Lens Among Patients Undergoing Cataract Surgery: A Systematic Review and Meta-Analysis
Authors: Zhang Ziran , Jiang Haiyang , Zhou Hongwei , Zhou Fang
Published: September 2021

The comparative efficacy of trifocal and bifocal intraocular lenses (IOLs) remained uncertain among patients undergoing cataract surgery. A systematic review and meta-analysis was performed to answer this question. PubMed, Cochrane Library and Embase were searched to capture relevant randomized controlled trials (RCTs). Visual acuity (VA) and patient's satisfaction were regarded as primary outcomes. Secondary outcomes included residual sphere, spherical equivalence, residual cylinder, posterior capsular opacification (PCO), spectacle independence, and other complications. Statistical analysis was done using RevMan 5.2.0. A total of 9 studies (11 RCTs) with 297 participants (558 eyes) were included. Meta-analysis showed significant differences between trifocal and bifocal IOLs in the uncorrected near VA (mean difference [MD], −0.008; 95% confidence interval [Cl], −0.015 to −0.001; P = 0.028) and uncorrected intermediate VA (MD, −0.06; 95% CI, −0.10 to −0.02; P < 0.01). Trifocal IOLs were associated with decreased PCO incidence when compared to bifocal IOLs (relative risk [RR], 0.54; 95% CI, 0.31 to 0.95; P = 0.03). Trifocal IOLs may be superior to bifocal IOLs because of its improved intermediate VA and reduced incidence of PCO.
Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?
Authors: Ceballos Francisco C. , Ryan Pablo , Blancas Rafael , Martin-Vicente María , Vidal-Alcántara Erick Joan , Peréz-García Felipe , Bartolomé Sofía , Churruca-Sarasqueta Juan , Virseda-Berdices Ana , Martínez-González Oscar , Brochado-Kith Oscar , Rava Marta , Vilches-Medkouri Carolina , Blanca-López Natalia , Ramirez Martinez-Acitores Ignacio , Moreira-Escriche Patricia , De Juan Carmen , Resino Salvador , Fernández-Rodríguez Amanda , Jiménez-Sousa María Ángeles
Published: September 2021

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated.

Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality.

Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals.

Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis.

Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death.

Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might “paradoxically” imply a higher risk of progression to severe disease and COVID-19-related mortality.
Cardiovascular Effect of Physical Exercise on Primary Sjogren's Syndrome (pSS): Randomized Trial
Authors: Garcia Ana Beatriz Andrêo , Dardin Luciana Paula , Minali Paulo Alexandre , Trevisani Virginia Fernandes Moça
Published: September 2021

Objective: To evaluate the effects of an exercise program on aerobic capacity, echocardiographic parameters, metabolic profile, quality of life and safety in patients with primary Sjogren's syndrome in a randomized trial.

Methods: 60 women with pSS were evaluated from the SF-36 Short-Form Health Survey (SF-36) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) questionnaires. The participants performed ergospirometry and echocardiography; blood samples were collected to evaluate the metabolic profile. Patients were randomly divided into 2 groups: a training group that participated in the supervised training program and a control group. All variables were analyzed at baseline and after 28 weeks for both groups and we performed an intention-to-treat analysis. The training program consisted of 16 weeks of resistance exercises and, after, the exercise became aerobic. Patients and coaches were not blinded, contrary to the evaluators of all examinations/procedures and data analysts. Statistical analysis included Wilcoxon's rank sum test, chi-square test, and ANOVA test. P values < 0.05 were considered to be statistically significant.

Results: The 2 groups were homogeneous at baseline. The training group showed a significant improvement in oxygen maximum volume (VO2max) and anaerobic threshold (AT). Comparison of the training group and control group after 28 weeks showed a significant difference relating to VO2max and in AT. We did not find statistically significant diference in echocardiographic parameters, metabolic profile and in questionnaires SF-36 and ESSDAI.

Conclusions: This study showed significant improvement in aerobic capacity and glycated hemoglobin after a supervised training program in patients with pSS with safety.
Risk Factors for Grade 3 to Grade 4 Adverse Reactions to the ChAdOx1 nCoV-19 Vaccine (AZD1222) Against SARS-CoV-2
Authors: Lee Sang Won , Lee Hyun , Lee Sun-Kyung , Moon Ji-Yong , Moon SeolHwa , Chung Sung Jun , Yeo Yoomi , Park Tai Sun , Won Park Dong , Kim Tae-Hyung , Sohn Jang Won , Yoon Ho Joo , Kim Sang-Heon
Published: September 2021

Objective: Limited data are available regarding the rates and risk factors of severe to serious adverse reactions (ARs) to the ChAdOx1 nCoV-19 vaccine.

Methods: Eligible participants were healthcare workers who received their first dose of the ChAdOx1 nCoV-19 vaccine in either of two university hospitals in Seoul, Korea. We evaluated the type and severity of ARs 7 days after the first dose of the ChAdOx1 nCoV-19 vaccine using a questionnaire survey delivered via a smartphone application link.

Results: Among the 1,603 participants who completed the survey, 684 (42.7%) participants experienced any kind of grade 3 to grade 4 AR. Being young (adjusted odds ratio [OR] for age 21–30 years = 2.49, 95% confidence interval [CI] = 1.75–3.56; adjusted OR for 31–40 years = 1.78, 95% CI = 1.22–2.62; adjusted OR for 41–50 years = 1.47, 95% CI = 1.03–2.11), being female (adjusted OR = 2.16. 95% CI = 1.62–2.89), and being underweight (adjusted OR = 1.61, 95% CI = 1.02–2.55) were identified as risk factors for grade 3 to grade 4 ARs. Among comorbidities, only diabetes mellitus (adjusted OR = 2.36, 95% CI = 1.03–5.53) was identified as a risk factor. When stratified by the type of AR, being young and being female were risk factors for both local and systemic grade 3 to grade 4 ARs.

Conclusions: Being young, female, or underweight and having diabetes mellitus were associated with an increased risk of developing grade 3 to grade 4 ARs after receiving the first dose of the ChAdOx1 nCoV-19 vaccine.
Effects of Sugarcane and Soybean Intercropping on the Nitrogen-Fixing Bacterial Community in the Rhizosphere
Authors: Liu Yue , Ma Wenqing , He Hongliang , Wang Ziting , Cao Yanhong
Published: September 2021

Intercropping between sugarcane and soybean is widely used to increase crop yield and promote the sustainable development of the sugarcane industry. However, our understanding of the soil microenvironment in intercropping systems, especially the effect of crop varieties on rhizosphere soil bacterial communities, remains poor. We selected two excellent sugarcane cultivars, Zhongzhe1 (ZZ1) and Zhongzhe9 (ZZ9), from Guangxi and the local soybean variety GUIZAO2 from Guangxi for field interplanting experiments. These two cultivars of sugarcane have good drought resistance. Rhizosphere soil samples were collected from the two intercropping systems to measure physicochemical properties and soil enzyme activities and to extract total soil DNA for high-throughput sequencing. We found that the diversity of the rhizosphere bacterial community was significantly different between the two intercropping systems. Compared with ZZ1, the ZZ9 intercropping system enriched the nitrogen-fixing bacteria, increasing the available nitrogen content by 18% compared with that with ZZ1. In addition, ZZ9 intercropping with soybean formed a more compact rhizosphere environment than ZZ1, thus providing favorable conditions for sugarcane growth. These results provide guidance for the sugarcane industry, especially for the management of sugarcane and soybean intercropping in Guangxi, China.
Recent Improvements in CRISPR-Based Amplification-Free Pathogen Detection
Authors: Zhang Jian , Lv Hailong , Li Linxian , Chen Minjie , Gu Dayong , Wang Jin , Xu Yong
Published: September 2021

Molecular diagnostic (MDx) methods directly detect target nucleic acid sequences and are therefore an important approach for precise diagnosis of pathogen infection. In comparison with traditional MDx techniques such as PCR, the recently developed CRISPR-based diagnostic technologies, which employ the single-stranded nucleic acid trans-cleavage activities of either Cas12 or Cas13, show merits in both sensitivity and specificity and therefore have great potential in both pathogen detection and beyond. With more and more efforts in improving both the CRISPR trans-cleavage efficiencies and the signal detection sensitivities, CRISPR-based direct detection of target nucleic acids without preamplification can be a possibility. Here in this mini-review, we summarize recent research progresses of amplification-free CRISPR-Dx systems and explore the potential changes they will lead to pathogen diagnosis. In addition, discussion of the challenges for both detection sensitivity and cost of the amplification-free systems will also be covered.
Neural Correlates of Aging-Related Differences in Pro-active Control in a Dual Task
Authors: Yordanova Juliana , Gajewski Patrick D. , Getzmann Stephan , Kirov Roumen , Falkenstein Michael , Kolev Vasil
Published: September 2021

Background: Multi-tasking is usually impaired in older people. In multi-tasking, a fixed order of sub-tasks can improve performance by promoting a time-structured preparation of sub-tasks. How proactive control prioritizes the pre-activation or inhibition of complex tasks in older people has received no sufficient clarification so far.

Objective: To explore the effects of aging on neural proactive control mechanisms in a dual task.

Methodology: To address this question, the psychological refractory period (PRP) paradigm was used. Two 2-alternative-forced-choice reaction tasks with a predefined order (T1 and T2) signaled by a cue had to be executed simultaneously or consecutively by young (mean age 25.1 years, n = 36) and old subjects (mean age 70.4 years, n = 118). Performance indices of dual-task preparation were used to assess the focused preparation of T1 and T2. To compare preparatory mechanisms at the neurophysiologic level, multi-channel electroencephalogram (EEG) was recorded and negative slow cortical potentials (SCPs) were analyzed as objective markers of the amount and localization of cortical pre-activation before sub-task presentation.

Results: Dual-task performance was significantly slower in old adults. T1 performance was facilitated in both age groups, but T2 processing in old adults was not optimized by the temporal structure as efficiently as in young adults. Also, only young adults manifested a stable pattern of focused of negative slow-wave activity increase at medial frontal and right-hemisphere posterior regions, which was associated with a coordinated preparatory T1 pre-activation and T2 deferment, while old adults manifested a broad topographic distribution of negative SCPs associated with a pre-activation of sensory and motor processes.

Conclusions: These observations demonstrate that the proactive preparation for dual tasking is altered with aging. It is suggested that in young adults, attention-based pre-activation of working memory and inhibitory networks in the right hemisphere synchronizes the simultaneous preparation of the two sub-tasks, whereas in old adults, sensory and motor networks appear to be non-specifically pre-activated for subsequent deferred mode of processing.
Diverse Motor Performances Are Related to Incident Cognitive Impairment in Community-Dwelling Older Adults
Authors: Beeri Michal Schnaider , Leurgans Sue E. , Bennett David A. , Barnes Lisa L. , Buchman Aron S.
Published: September 2021

Objective: Late-life cognitive impairment is heterogeneous. This study examined to what extent varied motor performances are differentially associated with incident Alzheimer’s dementia (AD) and incident mild cognitive impairment (MCI) in older adults.

Design: Nested substudy.

Setting: Communities across metropolitan Chicago.

Participants: African American (N = 580) and European American (N = 580) adults without dementia, propensity-balanced by age (mean = 73.2; SD = 6.0), sex (78.4% women), education (mean = 15.6; SD = 3.3) and number of follow ups.

Measurements: Cognitive status was assessed annually and based in part on a composite measure of global cognition including 17 cognitive tests. A global motor score was based on 10 motor performances from which 4 motor domains were computed including hand dexterity, hand strength, gait function, and leg strength.

Results: During 7 years of follow-up, 166 of 1,160 (14.3%) developed AD. In a proportional hazards model controlling for age, sex, education, and race, each 1-SD higher baseline global motor score was associated with about a 20% reduction in the risk of AD (hazard ratio: 0.81; 95% CI: 0.68, 0.97). Higher baseline motor function was also associated with decreased risk of incident MCI (hazard ratio: 0.79; 95% CI: 0.68, 0.92). Hand dexterity, hand strength and gait function but not leg strength were associated with incident AD and MCI. When including all four motor domains in the same model, results remained the same for incident MCI, while for incident AD, the association with hand strength remained significant.

Conclusion: Diverse motor performances are associated with late-life cognitive impairment. Further work is needed to identify specific motor performances that may differentiate adults at risk for future MCI or AD dementia.
Biogenic and Non-Biogenic Waste Utilization in the Synthesis of 2D Materials (Graphene, h-BN, g-C2N) and Their Applications
Authors: Singh Manish Pratap , Bhardwaj Abhishek Kumar , Bharati Keval , Singh Rahul Pratap , Chaurasia Sujeet Kumar , Kumar Santosh , Singh Rishi Pal , Shukla Abhishek , Naraian Ram , Vikram Kunwar
Published: September 2021

There is a significant amount of waste generated which creates a huge environmental issue for humanity/earth and a tremendous number of varieties of resources of a different kind are needed globally. In this context, nanoscience technology has shown its potential ability to solve the above issues and provides realistic applications and devices. The beauty of nanotechnology is its multidisciplinary approach, in which green nanotechnology has been translated to focus on waste materials. Waste materials are generally generated from biogenic (rice husk, dead leaves, waste food, etc.) and non-biogenic (several types of plastics waste, lard oil, etc.) materials produced from municipal or industrial waste. Currently, a large number of efforts have been made to utilize the waste materials for the synthesis of 2D materials in a greener way. This green synthetic approach has two advantages 1) it reduces the cost of synthesis and 2) includes minimal use of hazardous chemicals. Biogenic wastes (contains biomolecules) contain several significant constituents such as co-enzymes, enzymes, proteins, terpenoids, etc. These constituents or biomolecules are known to play an energetic role in the formation of a different variety of 2D materials and hence control the protocols of green synthesis of 2D materials. This review focuses on the exploration of the current understanding of 2D-layered material synthesis methods using waste material produce from biogenic and non-biogenic waste. It also investigates the applications of various 2D-layered materials in perspective with synthesis from waste and future challenges along with their limitations to industrial-scale synthesis.
A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling
Authors: Kawatake-Kuno Ayako , Murai Toshiya , Uchida Shusaku
Published: September 2021

Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are far from satisfactory. The antidepressant effect of ketamine is among the most important discoveries in psychiatric research over the last half-century. Neurobiological insights into the ketamine’s effects have shed light on the mechanisms underlying antidepressant efficacy. However, mechanisms underlying the rapid and sustained antidepressant effects of ketamine remain controversial. Elucidating such mechanisms is key to identifying new therapeutic targets and developing therapeutic strategies. Accumulating evidence demonstrates the contribution of the glutamatergic pathway, the major excitatory neurotransmitter system in the central nervous system, in MDD pathophysiology and antidepressant effects. The hypothesis of a connection among the calcium signaling cascade stimulated by the glutamatergic system, neural plasticity, and epigenetic regulation of gene transcription is further supported by its associations with ketamine’s antidepressant effects. This review briefly summarizes the potential mechanisms of ketamine’s effects with a specific focus on glutamatergic signaling from a multiscale perspective, including behavioral, cellular, molecular, and epigenetic aspects, to provide a valuable overview of ketamine’s antidepressant effects.
Subthalamic Peak Beta Ratio Is Asymmetric in Glucocerebrosidase Mutation Carriers With Parkinson's Disease: A Pilot Study
Authors: David Fabian J. , Munoz Miranda J. , Shils Jay L. , Pauciulo Michael W. , Hale Philip T. , Nichols William C. , Afshari Mitra , Sani Sepehr , Verhagen Metman Leo , Corcos Daniel M. , Pal Gian D.
Published: September 2021

Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). Glucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD.

Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non-GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity.

Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non-GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity.

Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.
Systematic Review of the Long-Term Neuroimaging Correlates of Mild Traumatic Brain Injury and Repetitive Head Injuries
Authors: Echlin Holly Victoria , Rahimi Alma , Wojtowicz Magdalena
Published: September 2021

Objective: To systematically review the literature on the long-term neuroimaging findings (≥10 years from exposure) for exposure in adulthood to mild traumatic brain injury (mTBI) and repetitive head impacts (RHIs) using neuroimaging across all available populations.

Data sources: Four electronic databases: MEDLINE, SPORTDiscus, PsycINFO, and EMBASE.

Study selection: All articles were original research and published in English. Studies examined adults with remote exposure to mTBI and/or RHIs from ten or more years ago in addition to any associated neuroimaging findings.

Data extraction: Parameters mainly included participants' population, age, years since head injury, race, sex, education level, and any neuroimaging findings. Scores for the level of evidence and risk of bias were calculated independently by two authors.

Results: 5,521 studies were reviewed, of which 34 met inclusion criteria and were included in this study. The majority of adults in these studies showed positive neuroimaging findings one or more decades following mTBI/RHI exposure. This was consistent across study populations (i.e., veterans, athletes, and the general population). There was evidence for altered protein deposition patterns, micro- and macro-structural, functional, neurochemical, and blood flow-related differences in the brain for those with remote mTBI/RHI exposure.

Conclusion: Findings from these studies suggest that past mTBI/RHI exposure may be associated with neuroimaging findings. However, given the methodological constraints related to relatively small sample sizes and the heterogeneity in injury types/exposure and imaging techniques used, conclusions drawn from this review are limited. Well-designed longitudinal studies with multimodal imaging and in-depth health and demographic information will be required to better understand the potential for having positive neuroimaging findings following remote mTBI/RHI.