bluuebunny/crossref_metadata_2025 huggingface dataset:
Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes
Authors: Jiménez-Kaufmann Andrés , Chong Amanda Y. , Cortés Adrián , Quinto-Cortés Consuelo D. , Fernandez-Valverde Selene L. , Ferreyra-Reyes Leticia , Cruz-Hervert Luis Pablo , Medina-Muñoz Santiago G. , Sohail Mashaal , Palma-Martinez María J. , Delgado-Sánchez Gudalupe , Mongua-Rodríguez Norma , Mentzer Alexander J. , Hill Adrian V. S. , Moreno-Macías Hortensia , Huerta-Chagoya Alicia , Aguilar-Salinas Carlos A. , Torres Michael , Kim Hie Lim , Kalsi Namrata , Schuster Stephan C. , Tusié-Luna Teresa , Del-Vecchyo Diego Ortega , García-García Lourdes , Moreno-Estrada Andrés
Published: January 2022

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.
Construction of Genetic Linkage Maps From a Hybrid Family of Large Yellow Croaker (Larimichthys crocea)
Authors: Yu Xinxiu , Joshi Rajesh , Gjøen Hans Magnus , Lv Zhenming , Kent Matthew
Published: January 2022

Consensus and sex-specific genetic linkage maps for large yellow croaker (Larimichthys crocea) were constructed using samples from an F1 family produced by crossing a Daiqu female and a Mindong male. A total of 20,147 single nucleotide polymorphisms (SNPs) by restriction site associated DNA sequencing were assigned to 24 linkage groups (LGs). The total length of the consensus map was 1757.4 centimorgan (cM) with an average marker interval of 0.09 cM. The total length of female and male linkage map was 1533.1 cM and 1279.2 cM, respectively. The average female-to-male map length ratio was 1.2 ± 0.23. Collapsed markers in the genetic maps were re-ordered according to their relative positions in the ASM435267v1 genome assembly to produce integrated genetic linkage maps with 9885 SNPs distributed across the 24 LGs. The recombination pattern of most LGs showed sigmoidal patterns of recombination, with higher recombination in the middle and suppressed recombination at both ends, which corresponds with the presence of sub-telocentric and acrocentric chromosomes in the species. The average recombination rate in the integrated female and male maps was respectively 3.55 cM/Mb and 3.05 cM/Mb. In most LGs, higher recombination rates were found in the integrated female map, compared to the male map, except in LG12, LG16, LG21, LG22, and LG24. Recombination rate profiles within each LG differed between the male and the female, with distinct regions indicating potential recombination hotspots. Separate quantitative trait loci (QTL) and association analyses for growth related traits in 6 months fish were performed, however, no significant QTL was detected. The study indicates that there may be genetic differences between the two strains, which may have implications for the application of DNA-information in the further breeding schemes.
VTP-Identifier: Vesicular Transport Proteins Identification Based on PSSM Profiles and XGBoost
Authors: Gong Yue , Dong Benzhi , Zhang Zixiao , Zhai Yixiao , Gao Bo , Zhang Tianjiao , Zhang Jingyu
Published: January 2022

Vesicular transport proteins are related to many human diseases, and they threaten human health when they undergo pathological changes. Protein function prediction has been one of the most in-depth topics in bioinformatics. In this work, we developed a useful tool to identify vesicular transport proteins. Our strategy is to extract transition probability composition, autocovariance transformation and other information from the position-specific scoring matrix as feature vectors. EditedNearesNeighbours (ENN) is used to address the imbalance of the data set, and the Max-Relevance-Max-Distance (MRMD) algorithm is adopted to reduce the dimension of the feature vector. We used 5-fold cross-validation and independent test sets to evaluate our model. On the test set, VTP-Identifier presented a higher performance compared with GRU. The accuracy, Matthew’s correlation coefficient (MCC) and area under the ROC curve (AUC) were 83.6%, 0.531 and 0.873, respectively.
The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Authors: König Rahel S. , Albrich Werner C. , Kahlert Christian R. , Bahr Lina Samira , Löber Ulrike , Vernazza Pietro , Scheibenbogen Carmen , Forslund Sofia K.
Published: January 2022

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.
Application of Machine Learning for Cytometry Data
Authors: Hu Zicheng , Bhattacharya Sanchita , Butte Atul J.
Published: January 2022

Modern cytometry technologies present opportunities to profile the immune system at a single-cell resolution with more than 50 protein markers, and have been widely used in both research and clinical settings. The number of publicly available cytometry datasets is growing. However, the analysis of cytometry data remains a bottleneck due to its high dimensionality, large cell numbers, and heterogeneity between datasets. Machine learning techniques are well suited to analyze complex cytometry data and have been used in multiple facets of cytometry data analysis, including dimensionality reduction, cell population identification, and sample classification. Here, we review the existing machine learning applications for analyzing cytometry data and highlight the importance of publicly available cytometry data that enable researchers to develop and validate machine learning methods.
Effect of Bone Marrow Mesenchymal Stromal Cell Therapies in Rodent Models of Sepsis: A Meta-Analysis
Authors: Ge Lite , Zhao Jing , Deng Huiyin , Chen Chunli , Hu Zhiping , Zeng Liuwang
Published: January 2022

Background

Multiple preclinical studies have demonstrated that bone‐marrow derived mesenchymal stromal (stem) cells [MSC(M)] positively influence the severity of sepsis symptoms and mortality in rodent models. However, this remains an inconclusive finding.

Objective

To review the effect of naïve MSC(M) in rodent models of sepsis.

Methods

The PubMed, EMBASE, and Web of Science databases were searched up to August 31, 2021. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified MSC(M); (3) comparison: not specified; (4) primary outcome: the effects of MSC(M) cell therapy on the mortality of rodent models of sepsis and endotoxemia; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.The inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).

Results

twenty-four animal studies met the inclusion criteria. Our results revealed an overall OR difference between animals treated with naïve MSC(M) and controls for mortality rate was 0.34(95% confidence interval: 0.27-0.44; P < 0.0001). Significant heterogeneity among studies was observed.

Conclusions

The findings of this meta-analysis suggest that naïve MSC(M) therapy decreased mortality in rodent models of sepsis. Additionally, we identified several key knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis. Before MSC(M) treatment can advance to clinical trials, these knowledge gaps must be addressed.
The cGAS/STING Pathway: A Novel Target for Cancer Therapy
Authors: Gan Yu , Li Xiaoying , Han Shuangze , Liang Qi , Ma Xiaoqian , Rong Pengfei , Wang Wei , Li Wei
Published: January 2022

As a DNA receptor, cyclic GMP-AMP synthase (cGAS) plays a crucial role in the immune system by recognizing abnormal DNA in the cytoplasm and activating the stimulator of interferon genes (STING) signaling pathway. This signaling cascade reaction leads to an immune response produced by type I interferon and other immune mediators. Recent advances in research have enhanced our current understanding of the potential role of the cGAS/STING pathway in anticancer therapy; however, in some cases, chronic STING activation may promote tumorigenesis. The present review article discusses the biological mechanisms of the cGAS/STING pathway, its dichotomous role in tumors, and the latest advances with respect to STING agonists and antagonists.
Antibody Responses to Phlebotomus papatasi Saliva in American Soldiers With Cutaneous Leishmaniasis Versus Controls
Authors: Aronson Naomi E. , Oliveira Fabiano , Gomes Regis , Porter William D. , Howard Robin S. , Kamhawi Shaden , Valenzuela Jesus G.
Published: January 2022

Leishmania major, transmitted in Iraq by the bite of a sand fly Phlebotomus papatasi, causes cutaneous leishmaniasis (CL). The sand fly saliva is immunogenic, with both systemic humoral and cellular human immune responses resulting from natural exposure. 248 Americans who developed L. major infection in Iraq were sex, race/ethnicity, year of Iraq deployment-matched to controls without CL. Using a case-control study design, we compared sand fly saliva-specific human IgG levels and recognized antigens between the two groups. Serologic responses to Ph. papatasi salivary gland homogenate were studied with ELISA and Western blot, using serial samples obtained from before travel, during CL treatment (CL) or at time of return to US (controls), as well as (for CL cases) six to 24 months after return to non-endemic US. The mean change in optical density (MCOD), reflecting the change in sand fly saliva-specific IgG before and after exposure in Iraq, was 0.296 (range -0.138 to 2.057) in cases and 0.151 (range -0.454 to1.085) in controls, p<0.001. Low levels of sand fly saliva specific antibody were noted in CL cases by 7-8 months after return to the US. The most frequently recognized Ph. papatasi salivary antigens were MW30 (PpSP32) and MW64, although other salivary proteins recognized were MW12/14, 15, 18, 28, 32, 36, 42, 44, 46, 52. Logistic regression suggested that MW15, 28 and 42 were associated with the largest effect on the MCOD. MW30 was the most frequently recognized antigen suggesting a role as biomarker for sand fly exposure and CL risk. Anti-Ph. papatasi saliva IgG waned within months of return to the US. We also discuss vector antigenic saliva proteins in the context of CL presentation and identify some salivary antigens that may correlate with less lesion area, ulcer versus papule/plaque, race among those with CL.
Physical Responses of Pinctada fucata to Salinity Stress
Authors: Yang Jingru , Yang Jinling , Chen Mingqiang , Fu Zhengyi , Sun Jing , Yu Gang , Wang Aimin , Ma Zhenhua , Gu Zhifeng
Published: January 2022

This study was conducted to understand the changes of physiological and biochemical indexes of black and red shell Pinctada fucata under acute high and low salt stress. In this study, the salinity of 35‰ was used as the control, while the salinities of 20 and 50% salinity were used as the low and high salt treatment groups, respectively. The osmotic pressure (OSM) and ion concentration in the hemolymph, Na+-K+ -ATPase (NKA) activity and respiratory metabolism in gills, and antioxidant and immune (non) enzymes in the hepatopancreas of P. fucata with two shell colors were compared and analyzed at the time periods of 1.5 and 3 h post-salinity stress. The results showed that the OSM and inorganic ion (Na+, Ca2+, and Cl–) concentration in the hemolymph of the black and red P. fucata increased significantly with the increase of salinity after the time periods of 1.5 and 3 h. At 3 h, the black P. fucata NKA activity decreased significantly with the increase of salinity, while red P. fucata reached the highest value at high salinity. The succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities of red P. fucata showed U-shaped and inverted U-shaped distributions with the increase of salinity after 1.5 h, respectively. With the increase of salinity, the phenoloxidase (POX) activity of red and black P. fucata showed inverted U-shaped and U-shaped distributions, respectively. The contents of glutathione (GSH) and vitamin C (VC) in black P. fucata decreased significantly with the increase of salinity at 1.5 and 3 h. Red P. fucata GSH and VC reached their maximum value in the 1.5-h low salinity group and 3-h high salinity group. The vitamin E (VE) content in black P. fucata increased significantly with the increase of salinity at 1.5 h, and reached the maximum at 3 h in the control group. Red P. fucata VE reached the maximum at 1.5 and 3 h in the control group. The results obtained from the present study revealed that the sensitivity of P. fucata to salinity varied in shell color. Compared to black P. fucata, red P. fucata responds more quickly to sharp salinity changes, thereby reducing more likely damage. Compared with a high salt environment, P. fucata was more adaptable to the changes of acute low salt environment. The results obtained from the present study provide the physical references for subsequent selective breeding of this species.
Overall and Cancer-Specific Survival in Patients With Renal Pelvic Transitional Cell Carcinoma: A Population-Based Study
Authors: Hu Tingting , You Shengjie
Published: January 2022

Background: Renal pelvic transitional cell carcinoma (TCC) is a relatively rare tumor. This study aimed to develop two prognostic nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in renal pelvic TCC patients.

Methods: Clinicopathological and follow-up data of renal pelvic TCC patients diagnosed between 2010 and 2015 were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regression analyses were used to screen the independently prognostic factors. These independently prognostic factors were then utilized to build nomograms for predicting 3-, 4-, and 5- years OS and CSS of patients with renal pelvic TCC. The nomograms were assessed by calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA).

Results: A total of 1,979 renal pelvic TCC patients were enrolled. Age, tumor size, histological type, American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, bone metastasis and liver metastasis were confirmed as independently prognostic factors for both OS and CSS. The areas under the ROC curves (AUCs) of OS nomogram at 3-, 4- and 5-years in the training cohort were 0.797, 0.781, and 0.772, respectively, and the corresponding AUCs in the validation cohort were 0.813, 0.797, and 0.759, respectively. The corresponding AUCs of CSS nomogram were all higher than 0.800. The calibration curves and DCA indicated that both nomograms had favorable performance. Subgroup analyses showed that both nomograms perform in well and poorly differentiated patients.

Conclusion: In conclusion, we successfully developed and validated two valuable nomograms to predict the OS and CSS for renal pelvic TCC patients. The nomograms incorporating various clinicopathological indicators can provide accurate prognostic assessment for patients and help clinicians to select appropriate treatment strategies.
Predictors of a Minimal Clinically Important Difference Following Omalizumab Treatment in Adult Patients With Severe Allergic Asthma
Authors: Huang Wei-Chang , Fu Pin-Kuei , Chan Ming-Cheng , Chin Chun-Shih , Huang Wen-Nan , Lai Kuo-Lung , Wang Jiun-Long , Hung Wei-Ting , Wu Yi-Da , Hsieh Chia-Wei , Wu Ming-Feng , Chen Yi-Hsing , Hsu Jeng-Yuan
Published: January 2022

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m2, odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/μL (<300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment.
Association Between Neutrophil–Lymphocyte Ratio and Frailty: The Chinese Longitudinal Healthy Longevity Survey
Authors: Xu Weihao , Liang Yuanfeng , Lin Zhanyi
Published: January 2022

Background: Inflammation has been reported to play an important role in frailty syndrome. The neutrophil–lymphocyte ratio (NLR) has recently emerged as an informative marker for systematic inflammation. However, few studies have examined the association between NLR and frailty. This study aims to examine the association between NLR and frailty in community-dwelling older adults.

Methods: Community-dwelling older adults aged ≥ 65 years in the 2011 (n = 2,354) and 2014 (n = 2,458) waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included. Frailty status was determined using the 38-item frailty index (FI) and categorized into “robust” (FI ≤ 0.1), “pre-frail” (0.1 < FI ≤ 0.21), or “frail” (FI > 0.21). NLR was calculated using a derived formula: NLR = (white blood cell–lymphocyte)/lymphocyte.

Results: A total of 3,267 participants were finally included. In cross-sectional analyses, participants with higher NLR levels had increased likelihood of frailty [the 3rd quartile: adjusted odds ratio (OR) = 1.29; 95% confidence interval (CI): 1.02–1.63; the 4th quartile: OR = 1.59; 95% CI: 1.23–2.02) compared with those in the 1st quartile group. During the 3-year follow-up, 164 of the 1,206 participants, robust or pre-frail at baseline, developed frailty, and 197 of the 562 participants, robust at baseline, developed pre-frailty or frailty. Among the robust and pre-frail participants in 2011, after multivariate adjustment, those in the 4th quartile group had a higher frailty incidence than those in the 1st quartile group (OR = 2.06; 95% CI: 1.18–3.59). Among the robust participants in 2011, those in the 4th quartile group also had a higher pre-frailty or frailty incidence than those in the 1st quartile group (OR = 1.95; 95% CI: 1.07–3.55).

Conclusion: Among community-dwelling older adults, higher NLR levels were found to be associated with increased odds of prevalent and incident frailty.
Impaired Spontaneous Baroreceptor Reflex Sensitivity in Patients With COPD Compared to Healthy Controls: The Role of Lung Hyperinflation
Authors: Mayr Anna Katharina , Wieser Victoria , Funk Georg-Christian , Asadi Sherwin , Sperk Irene , Urban Matthias Helmut , Valipour Arschang
Published: January 2022

Background and Objectives: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular disease. This study aimed to investigate the relationship between pulmonary hyperinflation and baroreceptor reflex sensitivity (BRS), a surrogate for cardiovascular risk.

Methods: 33 patients with COPD, free from clinical cardiovascular disease, and 12 healthy controls were studied. Participants underwent pulmonary function and non-invasive hemodynamic measurements. BRS was evaluated using the sequence method during resting conditions and mental arithmetic stress testing.

Results: Patients with COPD had evidence of airflow obstruction [forced expiratory volume in 1 s predicted (FEV1%) 26.5 (23.3–29.1) vs. 91.5 (82.8–100.8); P < 0.001; geometric means (GM) with 95% confidence interval (CI)] and lung hyperinflation [residual volume/total lung capacity (RV/TLC) 67.7 (64.3–71.3) vs. 41.0 (38.8–44.3); P < 0.001; GM with 95% CI] compared to controls. Spontaneous mean BRS (BRSmean) was significantly lower in COPD, both during rest [5.6 (4.2–6.9) vs. 12.0 (9.1–17.6); P = 0.003; GM with 95% CI] and stress testing [4.4 (3.7–5.3) vs. 9.6 (7.7–12.2); P < 0.001; GM with 95% CI]. Stroke volume (SV) was significantly lower in the patient group [−21.0 ml (−29.4 to −12.6); P < 0.001; difference of the means with 95% CI]. RV/TLC was found to be a predictor of BRS and SV (P < 0.05 for both), independent of resting heart rate.

Conclusion: We herewith provide evidence of impaired BRS in patients with COPD. Hyperinflation may influence BRS through alteration of mechanosensitive vagal nerve activity.
Differences in Clinical Characteristics Between Delta Variant and Wild-Type SARS-CoV-2 Infected Patients
Authors: Hu Zhenkui , Huang Xing , Zhang Jianguo , Fu Shixiang , Ding Daoyin , Tao Zhimin
Published: January 2022

Background: As delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevailed in the current coronavirus disease 2019 (COVID-19) pandemic, its clinical characteristics with the difference from those of wild-type strains have been little studied.

Methods: We reported one cohort of 341 wild-type patients with COVID-19 admitted at Wuhan, China in 2020 and the other cohort of 336 delta variant patients with COVID-19 admitted at Yangzhou, China in 2021, with comparisons of their demographic information, medical history, clinical manifestation, and hematological data. Furthermore, within the delta variant cohort, patients with none, partial, and full vaccination were also compared to assess vaccine effectiveness.

Findings: For a total of 677 patients with COVID-19 included in this study, their median age was 53.0 years [interquartile range (IQR): 38.0–66.0] and 46.8% were men. No difference was found in age, gender, and percentage of patients with the leading comorbidity between wild-type and delta variant cohorts, but delta variant cohort showed a lessened time interval between disease onset to hospitalization, a reduced portion of patients with smoking history, and a lowered frequency of clinical symptoms. For hematological parameters, most values demonstrated significant differences between wild-type and delta variant cohorts, while full vaccination rather than partial vaccination alleviated the disease condition. This reflected the viremic effect of delta variant when vaccination succeeds or fails to protect.

Interpretation: Delta variant of SARS-CoV-2 may cause severe disease profiles, but timely diagnosis and full vaccination could protect patients with COVID-19 from worsened disease progression.
The Diagnostic Accuracy of Syndromic Management for Genital Ulcer Disease: A Systematic Review and Meta-Analysis
Authors: Loh Andre J. W. , Ting Ee Lynn , Wi Teodora E. , Mayaud Philippe , Chow Eric P. F. , Santesso Nancy , Falconer Jane , Ofori-Asenso Richard , Ong Jason J.
Published: January 2022

Objectives: Genital Ulcer Disease (GUD) carries a significant disease burden globally. With limited access to diagnostics, the 2001 World Health Organization (WHO) sexually transmitted illnesses (STI) guidelines proposed a syndromic management algorithm that required a clinical decision to determine the management of GUD. We assessed the diagnostic accuracy of this algorithm.

Methods: We conducted a systematic review (Prospero: CRD42020153294) using eight databases for publications between 1995 and January 2021 that reported primary data on the diagnostic accuracy of clinical diagnosis to identify aetiological agents of GUD. Titles and abstracts were independently assessed for eligibility, and data were extracted from full texts for sensitivity/specificity. A hierarchical logistic regression model was used to derive pooled sensitivity and specificity. We used GRADE to evaluate the certainty of evidence.

Results: Of 24,857 articles, 151 full texts were examined and 29 included in the analysis. The majority were from middle-income countries [(14/29 (48%) lower middle, 10/29 (34%) upper middle)]. We pooled studies where molecular testing was using to confirm the aetiology of GUD: 9 studies (12 estimates) for herpes, 4 studies (7 estimates) for syphilis, and 7 studies (10 estimates) for chancroid. The pooled sensitivity and specificity of GUD for the detection of herpes was 43.5% [95% confidence interval (CI): 26.2–62.4], and 88.0% (95% CI: 67.0–96.3), respectively (high certainty evidence); and for syphilis were 52.8% (95% CI: 23.0–80.7), and 72.1% (95% CI: 28.0–94.5) (moderate certainty evidence); and for chancroid were 71.9% (95% CI: 45.9–88.5) and 53.1% (95% CI: 36.6–68.9) (moderate certainty evidence), respectively.

Conclusion: Algorithms requiring a clinical diagnosis to determine and treat the aetiology of GUD have poor sensitivities for syphilis and herpes simplex virus, resulting in significant numbers of missed cases. There is an urgent need to improve access to affordable and efficient diagnostics (e.g., point-of-care tests) to be incorporated into GUD algorithms to better guide appropriate management.

Systematic Review Registration: PROSPERO, identifier: CRD42020153294.
Analysis of mRNA and circRNA Expression Profiles of Bovine Monocyte-Derived Macrophages Infected With Mycobacterium avium subsp. paratuberculosis
Authors: Bao Yanhong , Yao Yu , Wang Zi , Wu Shuiyin , Jiang Xiuyun , Ma Hongxia
Published: January 2022

Mycobacterium aviumsubsp.paratuberculosis(MAP) is the pathogen of Johne’s disease (paratuberculosis), which mainly causes chronic infectious granulomatous enteritis in ruminants and has brought huge economic losses to animal husbandry. As a specific intracellular pathogen, when MAP invades the body, it is internalized by macrophages where it is able to replicate by inhibition of the phagosome maturation, escaping the host immune system and surviving, which leads to the spread of the disease. More recent studies have shown that circRNA is involved in many pathological and physiological processes of the body as the molecular sponge of miRNA, the scaffold of RNA binding protein and having the characteristic of being able to translate into protein. In this study, the mRNA and circRNA expression profiles of MAP-infected bovine monocyte-macrophages and uninfected bovine cells were analyzed by high-throughput sequencing. A total of 618 differentially expressed mRNA were screened out, including 322 upregulated mRNA and 296 downregulated mRNA. In addition, the analysis of circRNA differential expression profile showed 39 differentially expressed genes including 12 upregulated and 27 downregulated genes. Moreover, differential genes belonging to cytokine activity, chemokine activity, inflammatory reaction, apoptosis, and other functional groups related to macrophage immune response were significantly enriched in Gene Ontology (GO). Multiple signal pathways including NF-κB, MAPK, Toll-like receptor, IL-17, JAK-STAT, and other signaling pathways related to activating macrophage immune response were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, RT-qPCR technology verified the accuracy of the mRNA sequencing results. In this study, we have obtained the transcriptome information of mRNA and circRNA of bovine monocyte-macrophage infected with MAP. These results will provide data support for the further study of mRNA–miRNA–circRNA network and immune escape mechanism of MAP and will enrich the knowledge of the molecular immune mechanisms of Johne’s disease as well.
Fungal Indicators of Sensitivity and Resistance to Long-Term Maize Monoculture: A Culture-Independent Approach
Authors: Wolińska Agnieszka , Podlewski Jacek , Słomczewski Andrzej , Grządziel Jarosław , Gałązka Anna , Kuźniar Agnieszka
Published: January 2022

Although fungi are regarded as very important components of soils, the knowledge of their community in agricultural (monocultural) soils is still limited. This indicates that soil fungal communities are investigated less intensively than bacteria. Therefore, the main goal of this paper was to evaluate the fungal mycobiome structure in monoculture soils in a culture-independent approach. Firstly, the study was conducted to identify the core mycobiome composition and its variability at different stages of the maize growing season (spring, summer, and autumn). Secondly, we identified and recommended fungal indicators of both sensitivity and resistance to long-term maize monoculture. Two neighboring fields from the Potulicka Foundation area were selected for the study: K20 sown with a Gorzow mixture (intercropping mixture) to improve soil quality after a maize monoculture in 2020 and K21, where long-term (over 30 years) monoculture cultivation was continued. The basic chemical features [acidity, redox potential, total organic carbon (TOC), and moisture] of soils were determined, fungal genetic diversity was assessed by ITS next generation sequencing (NGS) analyses, and biodiversity indices were calculated. The results of the NGS technique facilitated recognition and classification of the fungal mycobiome to the taxonomic genus level and changes in the fungal structure in the three periods (spring, summer, and autumn) were assessed. It was evidenced that the mycobiome composition was dependent on both the seasons and the agricultural practices. It was also found that even a 1-year break in the monoculture in favor of an intercropping mixture improved soil properties thus contributing to higher biodiversity. Mortierella was recommended as a potential indicator of sensitivity to long-term maize cultivation, whereas Solicoccozyma and Exophiala were proposed as indicators of resistance to long-term maize cultivation. We proved that the precision farming principles applied on the Potulicka Foundation farm had a very positive effect on fungal biodiversity, which was high even in the long-term maize monoculture field. Therefore, the monoculture cultivation carried out in this way does not induce biological degradation of monoculture soils but preserves their good biological quality.
Proteomimetics of Natural Regulators of JAK–STAT Pathway: Novel Therapeutic Perspectives
Authors: La Manna Sara , De Benedictis Ilaria , Marasco Daniela
Published: January 2022

The JAK-STAT pathway is a crucial cellular signaling cascade, including an intricate network of Protein–protein interactions (PPIs) responsible for its regulation. It mediates the activities of several cytokines, interferons, and growth factors and transduces extracellular signals into transcriptional programs to regulate cell growth and differentiation. It is essential for the development and function of both innate and adaptive immunities, and its aberrant deregulation was highlighted in neuroinflammatory diseases and in crucial mechanisms for tumor cell recognition and tumor-induced immune escape. For its involvement in a multitude of biological processes, it can be considered a valuable target for the development of drugs even if a specific focus on possible side effects associated with its inhibition is required. Herein, we review the possibilities to target JAK–STAT by focusing on its natural inhibitors as the suppressor of cytokine signaling (SOCS) proteins. This protein family is a crucial checkpoint inhibitor in immune homeostasis and a valuable target in immunotherapeutic approaches to cancer and immune deficiency disorders.
Factors Contributing to the Severity and Laterality of Pisa Syndrome in Parkinson’s Disease
Authors: Huh Young Eun , Seo Dae-Won , Kim Kunhyun , Chung Won-Ho , Kim Seonwoo , Cho Jin Whan
Published: January 2022

Objective: Pisa syndrome (PS) is a disabling postural deformity in Parkinson’s disease (PD). We aimed to elucidate clinical factors determining the severity and laterality of PS in PD.

Methods: In 54 PD patients with PS, we measured the clinical factors that are previously known to contribute to the occurrence of PS as follows: asymmetry of motor symptoms for the evaluation of asymmetric basal ganglia dysfunction, the degree and direction of subjective visual vertical (SVV) tilt for the misperception of body verticality, the canal paresis for unilateral peripheral vestibulopathy, and the tonic electromyographic (EMG) hyperactivity of paraspinal muscles for dystonia. Multivariable linear and logistic regression analyses were conducted to identify the clinical factors associated with the degree of truncal tilt, for the quantification of the severity of PS, and PS tilting to the less affected side, respectively.

Results: The multivariable linear regression analyses revealed that the larger degree of SVV tilt (β = 0.29, SE = 0.10, p = 0.005), right-sided SVV tilt (β = 2.32, SE = 0.82, p = 0.007), and higher Hoehn and Yahr (HY) stage (β = 4.01, SE = 1.29, p = 0.003) significantly increased the severity of PS. In the multivariable logistic regression analyses, greater asymmetry of motor symptoms [odds ratio (OR) = 2.01, 95% CI = 1.34–3.49] was significantly associated with PS tilting to the less affected side, while right-sided SVV tilt (OR = 0.02, 95% CI = 0.001–0.21), unilateral canal paresis (OR = 0.06, 95% CI = 0.003–0.79), and higher HY stage (OR = 0.04, 95% CI = 0.002–0.46) were associated with PS tilting to the more affected side.

Conclusion: Misperception of verticality, asymmetric basal ganglia dysfunction, unilateral peripheral vestibulopathy, and motor disability are the clinical factors associated with the severity and laterality of PS in patients with PD.
Red Light Optogenetics in Neuroscience
Authors: Lehtinen Kimmo , Nokia Miriam S. , Takala Heikki
Published: January 2022

Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.
Care Gaps and Recommendations in Vestibular Migraine: An Expert Panel Summit
Authors: Mallampalli Monica P. , Rizk Habib G. , Kheradmand Amir , Beh Shin C. , Abouzari Mehdi , Bassett Alaina M. , Buskirk James , Ceriani Claire E. J. , Crowson Matthew G. , Djalilian Hamid , Goebel Joel A. , Kuhn Jeffery J. , Luebke Anne E. , Mandalà Marco , Nowaczewska Magdalena , Spare Nicole , Teggi Roberto , Versino Maurizio , Yuan Hsiangkuo , Zaleski-King Ashley , Teixido Michael , Godley Frederick
Published: January 2022

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.
Is There Any Relationship Between Biochemical Indices and Anthropometric Measurements With Dorsolateral Prefrontal Cortex Activation Among Older Adults With Mild Cognitive Impairment?
Authors: You Yee Xing , Shahar Suzana , Mohamad Mazlyfarina , Rajab Nor Fadilah , Che Din Normah , Lau Hui Jin , Abdul Hamid Hamzaini
Published: January 2022

Working memory is developed in one region of the brain called the dorsolateral prefrontal cortex (DLPFC). The dysfunction of this region leads to synaptic neuroplasticity impairment. It has been reported that several biochemical parameters and anthropometric measurements play a vital role in cognition and brain health. This study aimed to investigate the relationships between cognitive function, serum biochemical profile, and anthropometric measurements using DLPFC activation. A cross-sectional study was conducted among 35 older adults (≥60 years) who experienced mild cognitive impairment (MCI). For this purpose, we distributed a comprehensive interview-based questionnaire for collecting sociodemographic information from the participants and conducting cognitive tests. Anthropometric values were measured, and fasting blood specimens were collected. We investigated their brain activation using the task-based functional MRI (fMRI; N-back), specifically in the DLPFC region. Positive relationships were observed between brain-derived neurotrophic factor (BDNF) (β = 0.494, p < 0.01) and Mini-Mental State Examination (MMSE) (β = 0.698, p < 0.01); however, negative relationships were observed between serum triglyceride (β = −0.402, p < 0.05) and serum malondialdehyde (MDA) (β = −0.326, p < 0.05) with right DLPFC activation (R2 = 0.512) while the participants performed 1-back task after adjustments for age, gender, and years of education. In conclusion, higher serum triglycerides, higher oxidative stress, and lower neurotrophic factor were associated with lower right DLPFC activation among older adults with MCI. A further investigation needs to be carried out to understand the causal-effect mechanisms of the significant parameters and the DLPFC activation so that better intervention strategies can be developed for reducing the risk of irreversible neurodegenerative diseases among older adults with MCI.
From Cell States to Cell Fates: How Cell Proliferation and Neuronal Differentiation Are Coordinated During Embryonic Development
Authors: Belmonte-Mateos Carla , Pujades Cristina
Published: January 2022

The central nervous system (CNS) exhibits an extraordinary diversity of neurons, with the right cell types and proportions at the appropriate sites. Thus, to produce brains with specific size and cell composition, the rates of proliferation and differentiation must be tightly coordinated and balanced during development. Early on, proliferation dominates; later on, the growth rate almost ceases as more cells differentiate and exit the cell cycle. Generation of cell diversity and morphogenesis takes place concomitantly. In the vertebrate brain, this results in dramatic changes in the position of progenitor cells and their neuronal derivatives, whereas in the spinal cord morphogenetic changes are not so important because the structure mainly grows by increasing its volume. Morphogenesis is under control of specific genetic programs that coordinately unfold over time; however, little is known about how they operate and impact in the pools of progenitor cells in the CNS. Thus, the spatiotemporal coordination of these processes is fundamental for generating functional neuronal networks. Some key aims in developmental neurobiology are to determine how cell diversity arises from pluripotent progenitor cells, and how the progenitor potential changes upon time. In this review, we will share our view on how the advance of new technologies provides novel data that challenge some of the current hypothesis. We will cover some of the latest studies on cell lineage tracing and clonal analyses addressing the role of distinct progenitor cell division modes in balancing the rate of proliferation and differentiation during brain morphogenesis. We will discuss different hypothesis proposed to explain how progenitor cell diversity is generated and how they challenged prevailing concepts and raised new questions.
Deep Learning Algorithm Trained on Brain Magnetic Resonance Images and Clinical Data to Predict Motor Outcomes of Patients With Corona Radiata Infarct
Authors: Kim Jeoung Kun , Chang Min Cheol , Park Donghwi
Published: January 2022

The early and accurate prediction of the extent of long-term motor recovery is important for establishing specific rehabilitation strategies for stroke patients. Using clinical parameters and brain magnetic resonance images as inputs, we developed a deep learning algorithm to increase the prediction accuracy of long-term motor outcomes in patients with corona radiata (CR) infarct. Using brain magnetic resonance images and clinical data obtained soon after CR infarct, we developed an integrated algorithm to predict hand function and ambulatory outcomes of the patient 6 months after onset. To develop and evaluate the algorithm, we retrospectively recruited 221 patients with CR infarct. The area under the curve of the validation set of the integrated modified Brunnstrom classification prediction model was 0.891 with 95% confidence interval (0.814–0.967) and that of the integrated functional ambulatory category prediction model was 0.919, with 95% confidence interval (0.842–0.995). We demonstrated that an integrated algorithm trained using patients’ clinical data and brain magnetic resonance images obtained soon after CR infarct can promote the accurate prediction of long-term hand function and ambulatory outcomes. Future efforts will be devoted to finding more appropriate input variables to further increase the accuracy of deep learning models in clinical applications.