Miracle-dz/UniFAR-FTUs huggingface dataset:
Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males

Significance Transfer of sperm-producing stem cells isolated from a donor male into testes of a recipient male has important applications for preserving germplasm and as a conduit for widespread dissemination of desirable genetics in livestock production. A key aspect is surrogate males that lack endogenous germline but are otherwise physiologically normal. Here we demonstrate that male mice, pigs, and goats rendered genetically sterile by CRISPR-Cas9 editing of the NANOS2 gene support donor-derived spermatogenesis following allogeneic stem cell transplantation. In addition, we show that CRISPR-Cas9 editing of the NANOS2 gene in cattle leads to male germline ablation. These findings represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals. Spermatogonial stem cell transplantation (SSCT) is an experimental technique for transfer of germline between donor and recipient males that could be used as a tool for biomedical research, preservation of endangered species, and dissemination of desirable genetics in food animal populations. To fully realize these potentials, recipient males must be devoid of endogenous germline but possess normal testicular architecture and somatic cell function capable of supporting allogeneic donor stem cell engraftment and regeneration of spermatogenesis. Here we show that male mice, pigs, goats, and cattle harboring knockout alleles of the NANOS2 gene generated by CRISPR-Cas9 editing have testes that are germline ablated but otherwise structurally normal. In adult pigs and goats, SSCT with allogeneic donor stem cells led to sustained donor-derived spermatogenesis. With prepubertal mice, allogeneic SSCT resulted in attainment of natural fertility. Collectively, these advancements represent a major step toward realizing the enormous potential of surrogate sires as a tool for dissemination and regeneration of germplasm in all mammalian species.
Increased red blood cell distribution width might predict left ventricular hypertrophy in patients with atrial fibrillation

Abstract The presence of left ventricular hypertrophy has been confirmed to be an independent risk factor for stroke and death in patients with atrial fibrillation. This retrospective study aimed to evaluate the potential risk factors for left ventricular hypertrophy in patients with atrial fibrillation. A series of consecutive patients diagnosed with atrial fibrillation between June 2018 and December 2019 were included. The patients’ clinical data were analyzed. The cut-off values, sensitivity and specificity of the independent risk factors were calculated using a receiver operating characteristic curve. Among 87 patients with atrial fibrillation, 39 patients with left ventricular hypertrophy and 48 patients without left ventricular hypertrophy were included. Multivariate logistic regression analysis showed that red blood cell distribution width (odds ratio [OR] 4.89, 95% confidence interval [CI]: 1.69–14.13, P < .05) was an independent risk factor, while the concentration of low-density lipoprotein (OR 0.37, 95% CI: 0.17–0.83, P < .05) and left ventricular ejection fraction (OR 0.88, 95% CI: 0.82–0.95, P < .05) were inversely associated with left ventricular hypertrophy in atrial fibrillation patients. The receiver operating characteristic curve demonstrated that the area under the curve was 0.80 (95% CI: 0.71–0.90, P < .05) with a cut-off value of 13.05, and the red blood cell distribution width predicted left ventricular hypertrophy status among atrial fibrillation patients with a sensitivity of 72.1% and a specificity of 76.9%. Red blood cell distribution width was associated with left ventricular hypertrophy in patients with atrial fibrillation.
The Longitudinal Relationship Between Screen Time, Sleep and a Diagnosis of Attention-Deficit/Hyperactivity Disorder in Childhood

Objective: To evaluate longitudinal associations between recreational screen time and sleep in early childhood, and attention-deficit/hyperactivity disorder (ADHD) at age 8 to 10 years. Method: Questionnaires from 2,768 mother-child pairs from the Dutch KOALA Birth Cohort Study were used. General estimating equation logistic regression analyses examined associations between screen time and sleep at age 2, 4, and 6, and ADHD at age 8 to 10. Linear regression analysis examined associations between television time, sleep and CBCL/2-3 scores at age 2. Results: Longitudinally, neither screen time nor sleep were associated with ADHD. Cross-sectionally, CBCL/2-3 externalizing symptom scores increased by 0.03 with every hour television time (95% CI 0.002–0.05) and increased by 0.02 per hour of less sleep (95% CI −0.03–−0.01). Conclusion: Despite an association with externalizing symptoms at age 2, screen time and sleep in early childhood were not associated with ADHD. Carefulness is warranted when extrapolating cross-sectional associations at early age to an ADHD diagnosis.
Liquid biopsy technologies for hematological diseases

Since the discovery of circulating tumor cells in 1869, technological advances in studying circulating biomarkers from patients' blood have made the diagnosis of nonhematologic cancers less invasive. Technological advances in the detection and analysis of biomarkers provide new opportunities for the characterization of other disease types. When compared with traditional biopsies, liquid biopsy markers, such as exfoliated bladder cancer cells, circulating cell‐free DNA (cfDNA), and extracellular vesicles (EV), are considered more convenient than conventional biopsies. Liquid biopsy markers undoubtedly have the potential to influence disease management and treatment dynamics. Our main focuses of this review will be the cell‐based, gene‐based, and protein‐based key liquid biopsy markers (including EV and cfDNA) in disease detection, and discuss the research progress of these biomarkers used in conjunction with liquid biopsy. First, we highlighted the key technologies that have been broadly adopted used in hematological diseases. Second, we introduced the latest technological developments for the specific detection of cardiovascular disease, leukemia, and coronavirus disease. Finally, we concluded with perspectives on these research areas, focusing on the role of microfluidic technology and artificial intelligence in point‐of‐care medical applications. We believe that the noninvasive capabilities of these technologies have great potential in the development of diagnostics and can influence treatment options, thereby advancing precision disease management.
Leaflet immobility and thrombosis in transcatheter aortic valve replacement

Abstract Transcatheter aortic valve replacement (TAVR) has grown exponentially worldwide in the last decade. Due to the higher bleeding risks associated with oral anticoagulation and in patients undergoing TAVR, antiplatelet therapy is currently considered first-line antithrombotic treatment after TAVR. Recent studies suggest that some patients can develop subclinical transcatheter heart valve (THV) thrombosis after the procedure, whereby thrombus forms on the leaflets that can be a precursor to leaflet dysfunction. Compared with echocardiography, multidetector computed tomography is more sensitive at detecting THV thrombosis. Transcatheter heart valve thrombosis can occur while on dual antiplatelet therapy with aspirin and thienopyridine but significantly less with anticoagulation. This review summarizes the incidence and diagnostic criteria for THV thrombosis and discusses the pathophysiological mechanisms that may lead to thrombus formation, its natural history, potential clinical implications and treatment for these patients.
Limited genetic parallelism underlies recent, repeated incipient speciation in geographically proximate populations of an Arctic fish (Salvelinus alpinus)

The genetic underpinnings of incipient speciation, including the genomic mechanisms which contribute to morphological and ecological differentiation and reproductive isolation, remain poorly understood. The repeated evolution of consistently, phenotypically distinct morphs of Arctic Charr (Salvelinus alpinus) within the Quaternary period offer an ideal model to study the repeatability of evolution at the genomic level. Sympatric morphs of Arctic Charr are found across this species' circumpolar distribution. However, the specific genetic mechanisms driving this morph differentiation are largely unknown despite the cultural and economic importance of the anadromous morph. We used a newly designed 87k SNP chip to investigate the character and consistency of the genomic differences among sympatric morphs within three recently deglaciated and geographically proximate lakes in Labrador, Canada. We found genetically distinct small and large morph Arctic Charr in all three lakes consistent with resident and anadromous morphs, respectively. A degree of reproductive isolation among sympatric morphs is likely given genome‐wide distributions of outlier SNPs and high genome‐wide FSTs. Across all lakes, outlier SNPs were largely nonoverlapping suggesting a lack of genetic parallelism driving morph differentiation. Alternatively, several genes and paralogous copies of the same gene consistently differentiated morphs across multiple lakes suggesting their importance to the manifestation of morphs. Our results confirm the utility of Arctic Charr as a model for investigating the predictability of evolution and support the importance of both genetic parallelism and nonparallelism to the incipient speciation of Arctic Charr morphs.
Awareness of the COVID-19 Outbreak and Resultant Depressive Tendencies in Patients with Severe Alzheimer's Disease.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. However, we found not all Alzheimer's disease (AD) patients were afraid of COVID-19 infection. Therefore, we investigated the association between rate of awareness of COVID-19 and depressive tendency in AD. 126 consecutive outpatients with AD were enrolled in this study from May 25, on the day when the declaration of emergency was lifted in Japan, through June 30, 2020. In addition to routine psychological tests, the participants were asked the following two questions: "Do you know COVID-19? " and "Why are you wearing a face mask? ". Moderate to severe AD patients were found to have a low COVID-19 recognition rate and did not fully understand why they were wearing face masks. In addition, because they did not understand the seriousness of the COVID-19 outbreak, their Geriatric Depression Scale scores were also substantially lower. These results may appear to simply indicate that people with severe dementia are unaware of current events. However, these results provide insights into how to care for patients with dementia and how to allocate the time and support of our limited staff during the COVID-19 outbreak.
Cultural Characteristics,Anamorph and DNA Phylogeny of Botryosphaeria dothidea Causing Poplar Canker

The cultural characteristics and anamorph morphology of poplar canker fungus isolates collecting from Shaanxi and Gansu were observed,the rDNA-ITS,β-tubulin and EF-1α gene sequences of these fungal isolates were sequenced using universal primer ITS1 / ITS4, EF1-728F / EF1-986R and Bt2a / Bt2b respectively, and the phylogenetic trees were constructed after sequence alignment. The results showed that the 62 isolates could be divided into two colonial groups based on the cultural characteristics on PDA medium: groupⅠ showed typical fountain colony,group Ⅱ showed flat colony. Acconding to characteristics of conidium and culture,these isolates are identified as Fusicoccum aesculi,that is anamorph of Botryosphaeria dothidea. Meanwhile tested isolates were clustered into two,three and three groups based on neighbor-joining( NJ) analysis of the rDNA-ITS,β-tubulin and EF-1α gene sequence data respectively. The isolates of groupⅠin three NJ trees,included most tested isolates,were clustered together with B. dothidea retrieved from GenBank,which confirmed the morphological identification of these isolates; the isolate Fldh1 from Long county was classified as one group in the rDNA-ITS gene phylogenetic trees; the isolates Fyxn,Fyrg and Fyxj from Yangling of Shaanxi were all classified as one separate group in the β-tubulin and EF-1α gene phylogenetic trees; three isolates Fxfh, Fxdh1 and Fxdh2 from Xianyang of Shaanxi were classified as group Ⅲ in the EF-1α gene phylogenetic trees,displaying far away phylogenetic relationship from other isolates of B. dothidea. Overall there was no one-to-one relationship among cultural characteristics,sporulation and molecular phylogeny of the tested isolates.
The impact of anastomotic leakage on oncology after curative anterior resection for rectal cancer

Abstract Background: Anastomotic leakage (AL) is a serious clinical complication after anterior resection for rectal cancer and will lead to an increase in postoperative mortality. However, the effect on long-term oncology outcomes remains controversial. Methods: We searched the PubMed, Embase, and Cochrane library databases for related articles. The included studies assessed local recurrence, distant recurrence, overall survival, cancer-specific survival and disease-free survival. The systematic reviews and meta-analyses was conducted in accordance with the PRISMA guidelines. The combined RRs with 95% CI were then calculated using a fixed effects model or a randomized effect model. Results: A total of 18 cohort studies included 34,487 patients who met the inclusion criteria. The meta-analysis demonstrated that AL was associated with increased local recurrence (RR 1.47, 95% CI 1.14–1.90, I2 = 57.8%). Anastomotic leakage decreased overall survival (RR 0.92, 95% CI 0.88–0.96, I2 = 58.1%), cancer-specific survival (RR 0.96, 95% CI 0.92–1.00, I2 = 30.4%), and disease-free survival (RR 0.85, 95% CI 0.77–0.94, I2 = 80.4%). Distant recurrence may had no significant effects of AL (RR 1.16, 95% CI 0.91–1.46, I2 = 58.4%). Conclusion: AL has a negative effect on local recurrence and long-term survival (including overall survival, cancer-specific survival, and disease-free survival) after anterior resection for rectal cancer, but not related to distant recurrence.
Association of Fine Particulate Matter and Risk of Stroke in Patients With Atrial Fibrillation

Key Points Question What is the association between fine particulate matter measuring 2.5 μm or less (PM2.5) air pollution and ischemic stroke in individuals with prevalent atrial fibrillation (AF)? Findings This cohort study including 31 414 individuals with AF found an association between PM2.5 and prospective ischemic stroke risk in longitudinal, residential-level assessments in a large health care system situated in a region with high industrial activity. In multivariable-adjusted analyses that included relevant covariates and neighborhood-level income and educational level, individuals in the highest quartile of PM2.5 exposure had a 1.2-fold higher risk of stroke compared with the lowest quartile. Meaning The association between residential-level pollution and stroke risk in the presence of AF appears to be an additional public health toll of pollution and suggests that stroke risk assessment in individuals with AF take into account the contributions of environmental exposures.
Longitudinal associations between mother–child conflict and child internalizing problems in mid-childhood

Abstract Several aspects of mother–child relationships are associated with children's internalizing problems. We examined longitudinal associations between mother–child conflict and children's internalizing problems in middle childhood. Specifically, we examined whether conflict and children's internalizing problems predict each other longitudinally in a sample of children from 3rd through 6th grade (N = 1,364) and their mothers using a cross-lagged panel model with random intercepts. In line with expectations, we found stable between-family differences in both mother–child conflict and children's internalizing problems. Contrary to expectations, we did not find that mother–child conflict and children's internalizing problems showed significant cross-lagged associations. However, mother–child conflict and children's internalizing problems had correlated errors at each wave, indicating that these two constructs covary with each other concurrently at multiple times across development, independent of stable between-family associations (i.e., as one increases, so does the other, and vice versa). The results of this study point to the importance of using statistical approaches that can disentangle between-family differences from within-family processes. In future studies, shorter time scales (e.g., weeks or months) may better capture dynamic associations between parent–child conflict and internalizing problems.
Association of Epigenetic Metrics of Biological Age With Cortical Thickness

Key Points Question Are DNA methylation–based metrics of biological age associated with cortical thickness, and does a biological age acceleration index capture unique changes in cortical thinning compared with chronological age measures? Findings In this cross-sectional study of 82 healthy adults, both biological and chronological age were associated with widespread cortical thinning, but biological age acceleration was also associated with additional changes in cortical morphological features. Older biological age relative to chronological age was associated with accentuated thinning within prefrontal and temporal regions. Meaning These findings suggest that DNA methylation–based biological age may yield additional insight into healthy and pathological cortical aging compared with chronological age alone.
Decreased Volume of Lateral and Medial Geniculate Nuclei in Patients with LHON Disease—7 Tesla MRI Study

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder leading to severe and bilateral loss of central vision, with a young male predilection. In recent years, multiple studies examined structural abnormalities in visual white matter tracts such as the optic tract and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect grey matter parts of the visual pathway. This study aimed at improving our understanding of morphometric changes in the lateral (LGN) and medial (MGN) geniculate nuclei and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. A quantitative analysis of the LGN and MGN volume was performed for all individuals. Additionally, morphometric results of LGN and MGN were correlated with variables covering selected aspects of the clinical picture of LHON. In comparison with healthy controls (HC), LHON participants showed a significantly decreased volume of the right LGN and the right MGN. Nevertheless, the volume of the right LGN was strongly correlated with the averaged thickness value of the right retinal nerve fiber layer (RNFL). The abnormalities in the volume of the LHON patients’ thalamic nuclei indicate that the disease can cause changes not only in the white matter areas constituting visual tracts but also in the grey matter structures. Furthermore, the correlation between the changes in the LGN volume and the RNFL, as well as the right optic nerve surface area located proximally to the eyeball, suggest some associations between the atrophy of these structures. However, to fully confirm this observation, longitudinal studies should be conducted.
Developmental cycle, transcriptome and metabolic features of the chlamydial symbiont Protochlamydia amoebophila

Ziel dieser Arbeit war ein besseres Verstandnis der Biologie und der moglichen Pathogenitat der vor etwa 10 Jahren entdeckten und weitverbreiteten Chlamydien-ahnlichen Bakterien. Mittels eines hochempfindlichen PCR-basierten Screenings von Proben aus Patienten mit Lungenentzundung konnte DNA von drei verschiedenen Chlamydiensymbionten nachgewiesen werden. Ob diese Bakterien, die zum ersten Mal in humanen respiratorischen Proben detektiert wurden, tatsachlich krankheitsverursachend sind muss in weiteren Untersuchungen geklart werden. Diese Arbeit beschreibt des Weiteren den viertagigen Entwicklungszyklus von Protochlamydia amoebophila in zwei unterschiedlichen Acanthamoeba Wirts-Zellen und belegt eine stabile symbiotische Beziehung zwischen Symbiont und Wirt. Eisenmangel fuhrte zu einem abnormen Zellwachstum vergleichbar mit persistenten Formen bei pathogenen Chlamydien. In einer weiteren Studie wurde ein DNA-Mikroarray fur die Analyse der Genexpression von P. amoebophila wahrend der Infektion von Amoben entwickelt. Erste Transkriptomanalysen zeigten, dass die Mehrzahl der abgelesenen Gene bei Metabolismus- und Transportvorgangen, bei der Proteinsynthese oder bei der Manipulation des Wirts eine grose Rolle spielen. Neben Transkriptomanalysen wurde die metabolische Aktivitat von P. amoebophila auch auf Einzelzellebene mittels konfokaler Raman Mikrospektroskopie unter Verwendung einer 13C-markierten Aminosaure untersucht. Mittels dieses neuartigen Verfahrens, das erstmals fur die Analyse intrazellularer Bakterien verwendet wurde, konnte gezeigt werden, dass beide Entwicklungsstadien von P. amoebophila nicht nur intrazellular Phenylalanin aus dem Cytoplasma der Wirtszelle aufnehmen sondern auch auserhalb der Wirtszelle uber einen Zeitraum von drei Wochen, uber diesen Zeitraum infektios bleiben und in der Lage sind auserhalb des Wirtes ihr Membranpotential neu aufzubauen. Diese Befunde widerlegen das Dogma, dass alle Chlamydien auserhalb ihres Wirtes unmittelbar ihre Aktivitat verlieren.
Screening of high production strain of β-glucosidase and its enzyme characteristics

Ten β-glucosidase producing strains were isolated from the cellulosic samples.The highest production strain B2 was finally obtained by screening these 10 strains along with the other 9 strains identified previously as β-glucosidase producers.The B2,identified as Aspergillus niger,showed the yield of β-glucosidase of 24.4 U·mL﹣1 under certain conditions.The optimal pH-value of β-glucosidase was 4.5 and the optimal temperature was 65 ℃. The enzyme was stable in the wide range of pH-value 3.0~10.0. It could retain 61.6% relative activity after incubating 120 min at 65℃,indicating it had a good temperature tolerance.The enzyme was activated significantly by 5 mmol·L﹣1 Fe2+ and 5 mmol·L﹣1 Mn2+. The good pH-value stability and thermal stability of this β-glucosidase showed its potential applications in industry.