bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 related outcomes among individuals with neurodegenerative diseases: a cohort analysis in the UK biobank
Authors: Hu Yihan , Yang Huazhen , Hou Can , Chen Wenwen , Zhang Hanyue , Ying Zhiye , Hu Yao , Sun Yajing , Qu Yuanyuan , Feychting Maria , Valdimarsdottir Unnur , Song Huan , Fang Fang
Published: January 2022

Background

An increased susceptibility to COVID-19 has been suggested for individuals with neurodegenerative diseases, but data are scarce from longitudinal studies.

Methods

In this community-based cohort study, we included 96,275 participants of the UK Biobank who had available SARS-CoV-2 test results in Public Health England. Of these, 2617 had a clinical diagnosis of neurodegenerative diseases in the UK Biobank inpatient hospital data before the outbreak of COVID-19 (defined as January 31st, 2020), while the remaining participants constituted the reference group. We then followed both groups from January 31st, 2020 to June 14th, 2021 for ascertainment of COVID-19 outcomes, including any COVID-19, inpatient care for COVID-19, and COVID-19 related death. Logistic regression was applied to estimate the association between neurogenerative disease and risks of COVID-19 outcomes, adjusted for multiple confounders and somatic comorbidities.

Results

We observed an elevated risk of COVID-19 outcomes among individuals with a neurodegenerative disease compared with the reference group, corresponding to a fully adjusted odds ratio of 2.47 (95%CI 2.25–2.71) for any COVID-19, 2.18 (95%CI 1.94–2.45) for inpatient COVID-19, and 3.67 (95%CI 3.11–4.34) for COVID-19 related death. Among individuals with a positive test result for SARS-CoV-2, individuals with neurodegenerative diseases had also a higher risk of COVID-19 related death than others (fully adjusted odds ratio 2.08; 95%CI 1.71–2.53).

Conclusion

Among UK Biobank participants who received at least one test for SARS-CoV-2, a pre-existing diagnosis of neurodegenerative disease was associated with a subsequently increased risk of COVID-19, especially COVID-19 related death.
Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report
Authors: Nan Haitian , Wu Yunqing , Cui Shilei , Sun Houliang , Wang Jiawei , Li Ying , Meng Lingchao , Nagasaka Takamura , Wu Liyong
Published: January 2022

Background

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary neuropathy, and CMT1A is the most common form; it is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Mutations in the transient sodium channel Nav1.4 alpha subunit (SCN4A) gene underlie a diverse group of dominantly inherited nondystrophic myotonias that run the spectrum from subclinical myopathy to severe muscle stiffness, disabling weakness, or frank episodes of paralysis.

Case presentation

We describe a Chinese family affected by both CMT1A and myotonia with concomitant alterations in both the PMP22 and SCN4A genes. In this family, the affected proband inherited the disease from his father in an autosomal dominant manner. Genetic analysis confirmed duplication of the PMP22 gene and a missense c.3917G > C (p. Gly1306Ala) mutation in SCN4A in both the proband and his father. The clinical phenotype in the proband showed the combined involvement of skeletal muscle and peripheral nerves. Electromyography showed myopathic changes, including myotonic discharges. MRI revealed the concurrence of neurogenic and myogenic changes in the lower leg muscles. Sural nerve biopsies revealed a chronic demyelinating and remyelinating process with onion bulb formations in the proband. The proband’s father presented with confirmed subclinical myopathy, very mild distal atrophy and proximal hypertrophy of the lower leg muscles, pes cavus, and areflexia.

Conclusion

This study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations.
Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson’s disease patients
Authors: Wu Gang , Jiang Zhengli , Pu Yaling , Chen Shiyong , Wang Tingling , Wang Yajing , Xu Xiaoping , Wang Shanshan , Jin Minya , Yao Yangyang , Liu Yang , Ke Shaofa , Liu Suzhi
Published: January 2022

Background

Parkinson’s disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson’s symptoms.

Methods

50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson’s symptoms and the potential effects of medications on the serum SCFAs was analyzed.

Results

Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson’s Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid.

Conclusions

Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson’s symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.
Identification of an at-risk subpopulation with high immune infiltration based on the peroxisome pathway and TIM3 in colorectal cancer
Authors: Yin Jinwen , Wang Hao , Hong Yuntian , Ren Anli , Wang Haizhou , Liu Lan , Zhao Qiu
Published: January 2022

Background

Peroxisomes are pivotal metabolic organelles that exist in almost all eukaryote cells. A reduction in numbers and enzymatic activities of peroxisomes was found in colon adenocarcinomas. However, the role of peroxisomes or the peroxisome pathway in colorectal cancer (CRC) is not defined.

Methods

In the current study, a peroxisome score was calculated to indicate the activity of the peroxisome pathway using gene set variant analysis based on transcriptomic datasets. CIBERSORTx was chosen to infer enriched immune cells for tumors among subgroups. The SubMap algorithm was applied to predict its sensitivity to immunotherapy.

Results

The patients with a relatively low peroxisome score and high level of T-cell immunoglobulin and mucin domain 3 (TIM-3) presented the worse overall survival than others. Moreover, low peroxisome scores were associated with high infiltration of lymphocytes and poor prognosis in those CRC patients. Thus, a PERLowTIM3High CRC risk subpopulation was identified and characterized by high immune infiltration. The results also showed that CD8 T cells and macrophages highly infiltrated tumors of the PERLowTIM3High group, regardless of consortium molecular subtype and microsatellite instability status. This subgroup had the highest tumor mutational burden and overexpression of immune checkpoint genes. Further, the PERLowTIM3High group showed a higher probability of responding to programmed cell death protein-1-based immunotherapy. In addition, genes involved in peroxisomal metabolic processes in CRC were also investigated since peroxisome is a rather pleiotropic and highly metabolic organelle in cell. The results indicated that only those genes involved in fatty acid alpha oxidation could be used to stratify CRC patients as similar as peroxisome pathway genes.

Conclusions

We revealed the favorable prognostic value of the peroxisome pathway in CRC and provided a new CRC stratification based on peroxisomes and TIM3, which might be helpful for CRC diagnostics and personalized treatment.
HIV-child with disseminated Talaromyces Marneffei (Penicillium marneffei) infection: a rare severe case report
Authors: Hu Wei , Yu Xiao-hong , Wei Wei-qin , Xiang Xuan
Published: January 2022

Background

Talaromyces Marneffei (Penicillium marneffei, T.marneffei) has been frequently reported in patients with adult acquired immunodeficiency syndrome. Still, cases of children with HIV combined with T.marneffei infection are very rare. This report describes the case of a HIV-child who is a girl from China. Her special clinical manifestations and laboratory diagnosis results can provide clinicians with the basis for diagnosis and treatment of T.marneffei related rare diseases.

Case presntation

We reported a single case of 7-year-old Chinese female patient who presented with fever, abdominal pain, multiple lymphadenopathy, hepatosplenomegaly, left lower extremity ecchymosis, and bloody stool. The patient received anti-inflammatory therapy; however, her symptoms did not improve. Consequently, she was diagnosed with T.marneffei and HIV infection; it was also confirmed that her mother did not undergo HIV blocking therapy during pregnancy. Yet, the child’s family refused all treatment, after which the child was discharged from the hospital. The patient died a few days later.

Conclusion

This case suggested that children with AIDS suffering from fever, lymphadenopathy and coagulation dysfunction, penicilliosis should be suspected. Clinicians should diagnose the disease early through laboratory and imaging results, which can help reduce the mortality, prolong the survival time and improve the quality of life of children.
The prevalence of sexual compulsivity and its correlates among adults living with HIV/AIDS attending antiretroviral therapy clinic in Gambella town, Southwest Ethiopia, 2020
Authors: Shumye Seid , Kassaw Chalachew , Melaku Getnet
Published: January 2022

Introduction

Sexual compulsivity is a concealed psychiatric disease marked by intrusive thoughts followed by ritualized sexual acts. In Ethiopia, the prevalence of HIV/AIDS has recently increased. Furthermore, sexual compulsivity among adults living with HIV/AIDS receives less attention, particularly in Ethiopia. Therefore, this study aimed to assess the prevalence of sexual compulsivity and its correlates among adults living with HIV/AIDS attending ART clinic in Gambella town, Southwest Ethiopia, 2020.

Method

A hospital-based study employing cross-sectional design and simple random sampling technique was used to select the study participants. Data were collected by using interview technique. A 10 item Sexual Compulsivity Scale (SCS) questionnaire was used to assess sexual compulsivity. The translated version of the questionnaire was used for data collection. Bivariate and multivariable logistic regression was conducted to determine factors associated with the outcome variable at p-value < 0.05 with a 95% confidence interval.

Result

Out of 300 respondents, 27% (24.3, 29.2) of them were scored above the mean score of the Sexual Compulsivity Scale. Age less than 31 years old, widowed, involving in risky sexual behaviors, current substance use, not received any skill training about safer sex behaviors, and not attending support group discussion on HIV prevention were significantly associated with sexual compulsivity.

Conclusion

Almost one fourth of the respondents have high score for Sexual Compulsivity Scale score. Therefore, there is a need of routine sexual behavior screening program and collaboration with mental health workers for addressing the problem. Furthermore, the emphasis should be given on the identified high-risk categories.
Burden of disease study of overweight and obesity; the societal impact in terms of cost-of-illness and health-related quality of life
Authors: Hecker J. , Freijer K. , Hiligsmann M. , Evers S. M. A. A.
Published: January 2022

Background

Little is known about the burden that overweight and obesity impose on Dutch society. The aim of this study is to examine this burden in terms of cost-of-illness and health-related quality of life.

Method

A bottom-up, prevalence-based burden of disease study from a societal perspective was performed. Cost-of-illness information including healthcare costs, patient and family costs, and other costs was obtained via the Treatment Inventory of Costs in Patients with psychiatric disorders (TiC-P) questionnaire. Health-related quality of life was assessed through the EuroQol (EQ-5D-5L) and the BODY-Q instruments. Non-parametric bootstrapping was applied to test for significant differences in costs. Subgroup analyses were performed on all outcomes.

Results

A total of 97 people with overweight and obesity completed the survey. Per respondent, mean healthcare costs were €2907, patient and family costs were €4037, and other costs were €4519, leading to a total societal cost of €11,463 per respondent per year. Total costs were significantly higher for respondents with obesity versus overweight and between low & intermediate versus highly educated respondents. The mean utility score of our population was 0.81. A significantly lower utility score was found for respondents with obesity in comparison with respondents with overweight. BODY-Q results show that respondents with obesity scored a significantly lower Rasch-score than did respondents with overweight in three scales. Respondents with a high education level and having paid work scored significantly higher Rasch-scores in two scales than did those with a low education level and without having paid work. The age group 19–29 have significantly higher Rasch-scores in three scales than respondents in the other two age categories.

Conclusions

Overweight and obesity have a considerable impact on the societal costs and on health-related quality of life. The results show that the impact of overweight and obesity go beyond the healthcare sector, as the other costs have the biggest share of the total costs. Another interesting finding of this study is that obesity leads to significant higher costs and lower health-related quality of life than overweight. These findings draw attention to policy making, as collective prevention and effective treatment are needed to reduce this burden.
Social determinants of malnutrition in Chilean children aged up to five
Authors: Alvear-Vega Sandra , Vargas-Garrido Héctor
Published: January 2022

Background

This study aimed to ascertain the Social Determinants (SDs) of malnutrition (over and undernutrition) of Chilean children aged up to five.

Methods

The study was carried out using a sample of children from zero to five years old (n = 1,270,485; 52.2% female) from the National Socioeconomic Characterization Survey (CASEN) 2017. A multinomial logistic regression model was used, where the “child nutritional status” outcome variable assumed three possible values: normal nutrition, overnutrition, and undernutrition, while taking those variables reported in previous literature as independent variables.

Results

The model, by default, set normal nutrition as the reference group, Count R2 = 0.81. Results show a higher likelihood of both overnutrition and undernutrition among male children from the lowest quintiles, with native ethnic backgrounds, reporting health problems, having public health insurance, and who attend kindergarten. Additionally, higher probabilities of undernutrition in younger than two and living in the north of the country, while overnutrition is more likely in the south.

Conclusions

Socioeconomic variables are fundamentally related to both over and undernutrition; the current single schema program to prevent malnutrition should consider SDs such as ethnicity and geographical location, among others; moreover, successful nutritional programs—which focused on the lowest quintiles, need to be expanded to other vulnerable groups and pay more attention to overnutrition.
Fixation of intraoperative proximal femoral fractures during THA using two versus three cerclage wires - a biomechanical study
Authors: Wendler Toni , Edel Melanie , Möbius Robert , Fakler Johannes , Osterhoff Georg , Zajonz Dirk
Published: January 2022

Background

Intraoperative proximal femoral fractures (IPFF) are relevant complications during total hip arthroplasty. Fixation using cerclage wires (CW) represents a minimally-invasive technique to address these fractures through the same surgical approach. The goal of treatment is to mobilise the patient as early as possible, which requires high primary stability. This study aimed to compare different cerclage wire configurations fixing IPFF with regard to biomechanical primary stability.

Methods

Standardised IPFF (type II, Modified Mallory Classification) were created in human fresh frozen femora and were fixed either by two or three CW (1.6 mm, stainless steel). All cadaveric specimens (n = 42) were randomised to different groups (quasi-static, dynamic) or subgroups (2 CW, 3 CW) stratified by bone mineral density determined by Dual Energy X-ray Absorptiometry. Using a biomechanical testing setup, quasi-static and dynamic cyclic failure tests were carried out. Cyclic loading started from 200 N to 500 N at 1 Hz with increasing peak load by 250 N every 100 cycles until failure occurred or maximum load (5250 N) reached. The change of fracture gap size was optically captured.

Results

No significant differences in failure load after quasi-static (p = 0.701) or dynamic cyclic loading (p = 0.132) were found between the experimental groups. In the quasi-static load testing, all constructs resisted 250% of the body weight (BW) of their corresponding body donor. In the dynamic cyclic load testing, all but one construct (treated by 3 CW) resisted 250% BW.

Conclusions

Based on this in vitro data, both two and three CW provided sufficient primary stability according to the predefined minimum failure load (250% BW) to resist. The authors recommend the treatment using two CW because it reduces the risk of vascular injury and shortens procedure time.
Shear bond strength of ceramic laminate veneers to finishing surfaces with different percentages of preserved enamel under a digital guided method
Authors: Zhu Jiakang , Gao Jing , Jia Luming , Tan Xin , Xie Chenyang , Yu Haiyang
Published: January 2022

Background

The purpose of this in vitro study was to evaluate the effect of the percentages of preserved enamel on ceramic laminate veneers’ (CLVs) shear bond strength (SBS).

Methods

Seventy extracted human maxillary central incisors were scanned and reconstructed into three-dimensional models. The extracted teeth were then embedded and randomly divided into seven groups (n = 10 per group). Based on digital analyses of the three-dimensional models, guided tooth preparation and bonding procedures were performed individually to form seven different percentages (100%, 80%, 60% 50%, 40%, 20% and 0%) of remaining enamel thickness on the bonding surface. Finally, the SBS test was performed, and the data were statistically analysed by one-way ANOVA with LSD post hoc test (α = 0.05).

Results

The complete enamel surface exhibited the highest SBS (19.93 ± 4.55 MPa), followed by 80% enamel (19.03 ± 3.66 MPa), 60% enamel (18.44 ± 3.65 MPa), 50% enamel (18.18 ± 3.41 MPa), 40% enamel (17.83 ± 3.01 MPa) and 20% enamel (11.32 ± 3.42 MPa) group. The lowest SBS (9.63 ± 3.46 MPa) was detected in 0% enamel group. No significant difference was observed among the 40–100% enamel groups, while the 20% or 0% enamel group demonstrated a significantly lower mean SBS than the 40% enamel group (p < 0.05).

Conclusion

The SBS value of CLVs bonded to 100% enamel on the finishing surfaces (nearly 20 MPa) was twice that which bonded to 0% enamel (nearly 10 MPa). Bonding to 100% enamel is the most reliable treatment. When dentin exposure is inevitable, enamel should be preserved as much as possible to maintain good bonding. In addition, 40% of preserved enamel on the bonding surface was the minimal acceptable value to fulfil the requirements of good bonding strength.
E-learning and the virtual transformation of histopathology teaching during COVID-19: its impact on student learning experience and outcome
Authors: Waugh Samantha , Devin James , Lam Alfred King-Yin , Gopalan Vinod
Published: January 2022

Background

Medical and pathology education has gone through an immense transformation from traditional face-to-face teaching mode to virtual mode during the COVID-19 pandemic. This study evaluated the effectiveness of online histopathology teaching in medical education during the 2020 COVID-19 pandemic in Griffith University, Australia.

Methods

Second-year medical students (n = 150) who had previously completed one year of face-to-face histopathology teaching, completed an online questionnaire rating their learning experiences before and during the COVID-19 pandemic after the completion of their histology and pathology practical sessions. The students' histopathology assessment results were then compared to the histopathology results of a prior second-year cohort to determine if the switch to online histopathology teaching had an impact on students' learning outcome.

Results

A thematic analysis of the qualitative comments strongly indicated that online histopathology teaching was instrumental, more comfortable to engage in and better structured compared to face-to-face teaching. Compared to the previous year's practical assessment, individual performance was not significantly different (p = 0.30) and compared to the prior cohort completing the same curriculum the mean overall mark was significantly improved from 65.36% ± 13.12% to 75.83% ± 14.84% (p < 0.05) during the COVID-19 impacted online teaching period.

Conclusions

The transformation of teaching methods during the 2020 COVID-19 pandemic improved student engagement without any adverse effects on student learning outcomes in histology and pathology education.
Two decades of regional trends in vaccination completion and coverage among children aged 12-23 months: an analysis of the Uganda Demographic Health Survey data from 1995 to 2016
Authors: Okello Gerald , Izudi Jonathan , Ampeire Immaculate , Nghania Frehd , Dochez Carine , Hens Niel
Published: January 2022

Background

Childhood vaccination is an important public health intervention but there is limited information on coverage, trends, and determinants of vaccination completion in Uganda at the regional level. We examined trends in regional vaccination coverage and established the determinants of vaccination completion among children aged 12-23 months in Uganda.

Methods

We analyzed data from the women’s questionnaire for the 1995-2016 Uganda Demographic Health Survey (UDHS). Vaccine completion was defined as having received a dose of Bacillus-Calmette Guerin (BCG) vaccine; three doses of diphtheria, pertussis, and tetanus (DPT) vaccine; three doses of oral polio vaccine (OPV) (excluding OPV given at birth); and one dose of measles vaccine. We performed Chi-square tests to compare vaccination completion by socio-demographic factors stratified by 10 sub-regions: Eastern, East Central, Central 1, Central 2, Kampala, Karamoja, North, Western, West Nile, and Southwest. We performed logistic regression analysis for each of the regions to identify factors associated with vaccination completion at 5% level of statistical significance.

Results

Overall vaccination completion was 48.6% (95%CI, 47.2, 50.1) and ranged from 17.3% in Central 1 to 65.9% in Southwest. Vaccination completion rates declined significantly by 10.4% (95% confidence interval (CI), − 16.1, − 4.6) between 1995 and 2000, and increased significantly by 10.0% (95% CI, 4.6, 15.4) between 2000 and 2006, and by 5.4% (95% CI, 0.2, 10.6) between 2006 and 2011. Maternal education (secondary or higher level), receipt of tetanus toxoid (TT) during pregnancy, and possession of a child health card were associated with vaccination completion across all the sub-regions. Other factors like place of residence, religious affiliation, household wealth, maternal age, childbirth order, size of child at birth, and place of delivery were associated with vaccination completion but differed between the 10 sub-regions.

Conclusion

Besides considerable regional variations, the vaccination completion rate among children aged 12-23 months in Uganda remains suboptimal despite the availability of vaccines. Maternal education, receipt of TT, and possession of a child health card are associated with a higher likelihood of vaccination completion among children aged 12-23 months in all the regions of Uganda. Interventions to improve the utilization of vaccination services in Uganda should consider these factors.
Group II intron and repeat-rich red algal mitochondrial genomes demonstrate the dynamic recent history of autocatalytic RNAs
Authors: Kim Dongseok , Lee JunMo , Cho Chung Hyun , Kim Eun Jeung , Bhattacharya Debashish , Yoon Hwan Su
Published: January 2022

Background

Group II introns are mobile genetic elements that can insert at specific target sequences, however, their origins are often challenging to reconstruct because of rapid sequence decay following invasion and spread into different sites. To advance understanding of group II intron spread, we studied the intron-rich mitochondrial genome (mitogenome) in the unicellular red alga, Porphyridium.

Results

Analysis of mitogenomes in three closely related species in this genus revealed they were 3–6-fold larger in size (56–132 kbp) than in other red algae, that have genomes of size 21–43 kbp. This discrepancy is explained by two factors, group II intron invasion and expansion of repeated sequences in large intergenic regions. Phylogenetic analysis demonstrates that many mitogenome group II intron families are specific to Porphyridium, whereas others are closely related to sequences in fungi and in the red alga-derived plastids of stramenopiles. Network analysis of intron-encoded proteins (IEPs) shows a clear link between plastid and mitochondrial IEPs in distantly related species, with both groups associated with prokaryotic sequences.

Conclusion

Our analysis of group II introns in Porphyridium mitogenomes demonstrates the dynamic nature of group II intron evolution, strongly supports the lateral movement of group II introns among diverse eukaryotes, and reveals their ability to proliferate, once integrated in mitochondrial DNA.
Transposon-induced epigenetic silencing in the X chromosome as a novel form of dmrt1 expression regulation during sex determination in the fighting fish
Authors: Wang Le , Sun Fei , Wan Zi Yi , Yang Zituo , Tay Yi Xuan , Lee May , Ye Baoqing , Wen Yanfei , Meng Zining , Fan Bin , Alfiko Yuzer , Shen Yubang , Piferrer Francesc , Meyer Axel , Schartl Manfred , Yue Gen Hua
Published: January 2022

Background

Fishes are the one of the most diverse groups of animals with respect to their modes of sex determination, providing unique models for uncovering the evolutionary and molecular mechanisms underlying sex determination and reversal. Here, we have investigated how sex is determined in a species of both commercial and ecological importance, the Siamese fighting fish Betta splendens.

Results

We conducted association mapping on four commercial and two wild populations of B. splendens. In three of the four commercial populations, the master sex determining (MSD) locus was found to be located in a region of ~ 80 kb on LG2 which harbours five protein coding genes, including dmrt1, a gene involved in male sex determination in different animal taxa. In these fish, dmrt1 shows a male-biased gonadal expression from undifferentiated stages to adult organs and the knockout of this gene resulted in ovarian development in XY genotypes. Genome sequencing of XX and YY genotypes identified a transposon, drbx1, inserted into the fourth intron of the X-linked dmrt1 allele. Methylation assays revealed that epigenetic changes induced by drbx1 spread out to the promoter region of dmrt1. In addition, drbx1 being inserted between two closely linked cis-regulatory elements reduced their enhancer activities. Thus, epigenetic changes, induced by drbx1, contribute to the reduced expression of the X-linked dmrt1 allele, leading to female development. This represents a previously undescribed solution in animals relying on dmrt1 function for sex determination. Differentiation between the X and Y chromosomes is limited to a small region of ~ 200 kb surrounding the MSD gene. Recombination suppression spread slightly out of the SD locus. However, this mechanism was not found in the fourth commercial stock we studied, or in the two wild populations analysed, suggesting that it originated recently during domestication.

Conclusions

Taken together, our data provide novel insights into the role of epigenetic regulation of dmrt1 in sex determination and turnover of SD systems and suggest that fighting fish are a suitable model to study the initial stages of sex chromosome evolution.
Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing
Authors: Bar-Sadeh Ben , Amichai Or E. , Pnueli Lilach , Begum Khurshida , Leeman Gregory , Emes Richard D. , Stöger Reinhard , Bentley Gillian R. , Melamed Philippa
Published: January 2022

Background

Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens.

Results

Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset.

Conclusions

SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.
Occurrence and genetic characterization of Echinococcus granulosus sensu lato from domestic animals in Central Iran
Authors: Hajimohammadi Bahador , Dalimi Abdolhossein , Eslami Gilda , Ahmadian Salman , Zandi Sajad , Baghbani Ahmad , Hosseini Saeedeh Sadat , Askari Vahideh , Sheykhzadegan Maryam , Ardekani Mehrnoosh Nabizadeh , Boozhmehrani Mohammad Javad , Ranjbar Mohammad Javad , Ghoshouni Hamed , Vakili Mahmood
Published: January 2022

Background

The species complex of Echinococcus granulosus sensu lato (s.l.) causes cystic echinococcosis distributed worldwide. There is no genotype information from hydatid cysts in the intermediate hosts in Central Iran. Therefore, in this study, we analyzed the hydatid cysts in livestock slaughtered in an abattoir in this region. Six hundred fifty-seven hydatid cysts were isolated from 97 animals, including sheep, cattle, camels, and goats slaughtered in Yazd abattoir from September 2018 to January 2020. The demographic data was collected as well as cyst location, fertility, and viability. Out of 657 samples, 164 samples were genotyped. Then, phylogenetic analysis was performed using MEGAX. Statistical analyses were done using SPSS version 16.0 by chi-square with a significant difference of less than 0.05.

Results

Out of 164 samples, the G1-G3 complex genotype had the most frequency in samples, with 135 cases recognized. The G6/G7 was observed in 19 isolates and G5 was reported in nine samples. One sample was detected as Taenia hydatigena.

Conclusions

This study showed that G1-G3 and G6/G7 genotypes were presented in all animals, but G5 was reported only in cattle, goats, and camels. It is the first molecular identification of cystic echinococcosis in Central Iran. Hence, reporting G5 in livestock in this area should be considered due to transmission to humans.
Prediction of long-term mortality by using machine learning models in Chinese patients with connective tissue disease-associated interstitial lung disease
Authors: Sun Di , Wang Yu , Liu Qing , Wang Tingting , Li Pengfei , Jiang Tianci , Dai Lingling , Jia Liuqun , Zhao Wenjing , Cheng Zhe
Published: January 2022

Background

The exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. In the present study, we develop a nomogram to predict 3‑ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients.

Methods

CTD-ILD patients who were diagnosed and treated at the First Affiliated Hospital of Zhengzhou University were enrolled based on a prior well-designed criterion between February 2011 and July 2018. Cox regression with the least absolute shrinkage and selection operator (LASSO) was used to screen out the predictors and generate a nomogram. Internal validation was performed using bootstrap resampling. Then, the nomogram and ILD-GAP model were assessed via likelihood ratio testing, Harrell’s C index, integrated discrimination improvement (IDI), the net reclassification improvement (NRI) and decision curve analysis.

Results

A total of 675 consecutive CTD-ILD patients were enrolled in this study, during the median follow-up period of 50 (interquartile range, 38–65) months, 158 patients died (mortality rate 23.4%). After feature selection, 9 variables were identified: age, rheumatoid arthritis, lung diffusing capacity for carbon monoxide, right ventricular diameter, right atrial area, honeycombing, immunosuppressive agents, aspartate transaminase and albumin. A predictive nomogram was generated by integrating these variables, which provided better mortality estimates than ILD-GAP model based on the likelihood ratio testing, Harrell’s C index (0.767 and 0.652 respectively) and calibration plots. Application of the nomogram resulted in an improved IDI (3- and 5-year, 0.137 and 0.136 respectively) and NRI (3- and 5-year, 0.294 and 0.325 respectively) compared with ILD-GAP model. In addition, the nomogram was more clinically useful revealed by decision curve analysis.

Conclusions

The results from our study prove that the ILD-GAP model may exhibit an inapplicable role in predicting mortality risk in Chinese CTD-ILD patients. The nomogram we developed performed well in predicting 3‑ and 5-year mortality risk of Chinese CTD-ILD patients, but further studies and external validation will be required to determine the clinical usefulness of the nomogram.
Induction and application of ferroptosis in cancer therapy
Authors: Nie Qing , Hu Yue , Yu Xiao , Li Xiao , Fang Xuedong
Published: January 2022

At present, more than one cell death pathways have been found, one of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent and lipid peroxidation-driven regulated cell death pathway. In the past few years, ferroptosis has been shown to induce tumor cell death, providing new ideas for tumor treatment. In this article, we summarize the latest advances in ferroptosis-induced tumor therapy at the intersection of tumor biology, molecular biology, redox biology, and materials chemistry. First, we state the characteristics of ferroptosis in cells, then introduce the key molecular mechanism of ferroptosis, and describes the relationship between ferroptosis and oxidative stress signaling pathways. Finally, we focused on several types of ferroptosis inducers discovered by scholars, and the application of ferroptosis in systemic chemotherapy, radiotherapy, immunotherapy and nanomedicine, in the hope that ferroptosis can exert its potential in the treatment of tumors.
Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis
Authors: Xu Peng , Hu Kang , Zhang Ping , Sun Zhi-Gang , Zhang Nan
Published: January 2022

Background

N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive.

Methods

The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells.

Results

The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN– 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients.

Conclusion

In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.
The characteristic and potential therapeutic effect of isolated multidrug-resistant Acinetobacter baumannii lytic phage
Authors: Sisakhtpour Behnam , Mirzaei Arezoo , Karbasizadeh Vajihe , Hosseini Nafiseh , Shabani Mehdi , Moghim Sharareh
Published: January 2022

Background

Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy.

Methods

A novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage.

Results

The morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection.

Conclusion

In this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.
Expanding uncapped translation and emerging function of circular RNA in carcinomas and noncarcinomas
Authors: Wang Yan , Wu Chunjie , Du Yu , Li Zhongwei , Li Minle , Hou Pingfu , Shen Zhigang , Chu Sufang , Zheng Junnian , Bai Jin
Published: January 2022

Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5’ end cap and a 3’ end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.
Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation
Authors: Walker Zachary , Lanes Andrea , Ginsburg Elizabeth
Published: January 2022

Background

The utilization of oocyte cryopreservation (OC) has become popularized with increasing numbers of reproductive-aged patients desiring to maintain fertility for future family building. OC was initially used for fertility preservation in postmenarchal patients prior to gonadotoxic therapies; however, it is now available to patients to circumvent age-related infertility and other diagnoses associated with early loss of ovarian reserve. The primary aim of this paper is to provide a narrative review of the most recent and robust data on the utilization and outcomes of OC in both patient populations.

OC results in similar oocyte yield in patients facing gonadotoxic therapies and patients undergoing planned OC. Available data are insufficient to predict the live birth rates or the number of oocytes needed to result in live birth. However, oocyte yield and live birth rates are best among patients < 37.5 years old or with anti-mullerian hormone levels > 1.995 ng/dL, at the time of oocyte retrieval. There is a high ‘no use’ rate (58.9%) in patients using planned OC with 62.5% returning to use frozen oocytes with a spouse. The utilization rate in medical OC patients is < 10%. There is currently no data on the effects of BMI, smoking, or ethnicity on planned OC outcomes.

Conclusion

It is too early to draw any final conclusions on outcomes of OC in medical OC and planned OC; however, preliminary data supports that utilization of OC in both groups result in preservation of fertility and subsequent live births in patients who return to use their cryopreserved eggs. Higher oocyte yield, with fewer ovarian stimulation cycles, and higher live birth rates are seen in patients who seek OC at younger ages, reinforcing the importance of age on fertility preservation. More studies are needed in medical OC and planned OC to help guide counseling and decision-making in patients seeking these services.
Algebra dissociates from arithmetic in the brain semantic network
Authors: Cheng Dazhi , Li Mengyi , Cui Jiaxin , Wang Li , Wang Naiyi , Ouyang Liangyuan , Wang Xiaozhuang , Bai Xuejun , Zhou Xinlin
Published: January 2022

Background

Mathematical expressions mainly include arithmetic (such as 8 − (1 + 3)) and algebra (such as a − (b + c)). Previous studies have shown that both algebraic processing and arithmetic involved the bilateral parietal brain regions. Although previous studies have revealed that algebra was dissociated from arithmetic, the neural bases of the dissociation between algebraic processing and arithmetic is still unclear. The present study uses functional magnetic resonance imaging (fMRI) to identify the specific brain networks for algebraic and arithmetic processing.

Methods

Using fMRI, this study scanned 30 undergraduates and directly compared the brain activation during algebra and arithmetic. Brain activations, single-trial (item-wise) interindividual correlation and mean-trial interindividual correlation related to algebra processing were compared with those related to arithmetic. The functional connectivity was analyzed by a seed-based region of interest (ROI)-to-ROI analysis.

Results

Brain activation analyses showed that algebra elicited greater activation in the angular gyrus and arithmetic elicited greater activation in the bilateral supplementary motor area, left insula, and left inferior parietal lobule. Interindividual single-trial brain-behavior correlation revealed significant brain-behavior correlations in the semantic network, including the middle temporal gyri, inferior frontal gyri, dorsomedial prefrontal cortices, and left angular gyrus, for algebra. For arithmetic, the significant brain-behavior correlations were located in the phonological network, including the precentral gyrus and supplementary motor area, and in the visuospatial network, including the bilateral superior parietal lobules. For algebra, significant positive functional connectivity was observed between the visuospatial network and semantic network, whereas for arithmetic, significant positive functional connectivity was observed only between the visuospatial network and phonological network.

Conclusion

These findings suggest that algebra relies on the semantic network and conversely, arithmetic relies on the phonological and visuospatial networks.