Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clinical Relevance of the Cervical Disc Prosthesis

Small differences in NDI with narrow confidence intervals found in this study demonstrate an absence of clinical benefit for ACDA, when compared to ACDF or ACD two years after surgery. Neither for the entire group of patients, nor a subset of patients. Mean NDI differences varied from 0.4 to 1.1 out of 100. Study Design. Retrospective analysis was performed on data from 251 patients that were included in two randomized, double-blinded clinical trials comparing clinical results of anterior cervical discectomy and arthroplasty (ACDA) to anterior cervical discectomy and fusion (ACDF), and anterior cervical discectomy (ACD), for single-level disc herniation. Objective. This study aimed to investigate whether the ACDA procedure offers superior clinical results 2 years after surgery, to either ACDF or ACD without instrumentation, in the entire group of patients or in a particular subgroup of patients. Summary of Background Data. The cervical disc prosthesis was introduced to provide superior clinical outcomes after ACD. Methods. Neck Disability Index (NDI), and subscales of the 36-item short-form health survey (SF-36) and McGill pain score were collected at baseline, 1 year and 2 years after surgery. Reoperations and complications were also evaluated. A preliminary subgroup analysis was performed for age, disc height, body mass index (BMI), smoking, and sex. Results. The NDI decreased comparably in all treatment arms to circa 50% of the baseline value and marginal mean NDI differences varied from 0.4 to 1.1 on a 100 point NDI scale, with confidence intervals never exceeding the 20-point minimal clinical important difference (MCID). Secondary outcome parameters showed comparable results. Preliminary subgroup analysis could not demonstrate clinically relevant differences in NDI between treatments after 2 years. Conclusion. After combining data from two Randomized Controlled Trials it can be concluded that there is no clinical benefit for ACDA, when compared with ACDF or ACD 2 years after surgery. Preliminary subgroup analysis indicated outcomes were similar between treatment groups, and that no subgroup could be appointed that benefited more from either ACD, ACDF, or ACDA. Level of Evidence: 1
Bladder Stimulation for Clean Catch Urine Collection

Objectives Previous studies have demonstrated the efficacy of fluid intake with suprapubic and lumbar paravertebral massage for clean catch urine (CCU) collection in infants. We investigated the acceptability and feasibility of integrating this bladder stimulation technique (BST) into routine care in the pediatric emergency department (PED). Methods This was a prospective cohort study. Infants less than 6 months of age requiring a urinalysis and urine culture as part of their PED visit were recruited. All PED nurses and technicians received a standardized training outlining the BST using a video module and print materials. Success rates, bacterial contamination, parental perception of patient distress, and parent and provider satisfaction with the BST for CCU collection were compared with urethral catheterization. Results A total of 124 patients were recruited. The BST was successful in 38% (47/124) with a median time to void of 73 seconds (interquartile range: 19, 151). The BST was more likely to be successful in infants less than 90 days (53%; 95% confidence interval, 0.075–0.046; P = 0.005). A urinary tract infection was diagnosed in 4% of patients, with no significant differences between BST (1/47; 2%) and catheterization (4/59; 7%; P = 0.65). Patients experienced less discomfort during the BST compared with catheterization (mean numeric rating scale score, 2/10 vs 6/10; P < 0.001), and the BST was viewed positively by both parents and providers. Compared with catheterization, parents were significantly more satisfied with the BST (BST, 98%; catheterization, 58%; P < 0.001) and were more likely to consent to the BST in the future (BST, 98%; catheterization, 69%; P < 0.001). Most providers reported that the BST was well tolerated by participants (46/47; 98%), and providers felt that the BST improved parental satisfaction with the clinical encounter (46/47; 98%). Conclusion The BST for CCU collection is a well-tolerated and well-received approach that can easily be implemented into clinical practice with minimal training.
Evidence‐based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology

Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1‐associated protein 1 (BAP1), methylthioadenosine (MTAP), 5‐hydroxymethylcitosine (5‐hmC), glucose transporter 1 (GLUT1), insulin like‐growth factor II messenger RNA–binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin‐dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta‐analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy‐one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59‐0.71) and a specificity of 0.99 (CI, 0.93‐1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38‐0.57) and 0.62 (CI, 0.53‐0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78‐0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70‐0.90) and 0.65 (CI, 0.41‐0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68‐0.77) and a specificity of 0.90 (CI, 0.84‐0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
Phylogenetic and phylogenomic analyses reveal two new genera and three new species of ophiostomatalean fungi from termite fungus combs

ABSTRACT The Ophiostomatales (Ascomycota) accommodates more than 300 species characterized by similar morphological adaptations to arthropod dispersal. Most species in this order are wood-inhabiting fungi associated with bark or ambrosia beetles. However, a smaller group of species occur in other niches such as in soil and Protea infructescences. Recent surveys of Termitomyces fungus gardens (fungus combs) of fungus-growing termites led to the discovery of characteristic ophiostomatalean-like fruiting structures. In this study, these ophiostomatalean-like fungi were identified using morphological characteristics, conventional molecular markers, and whole genome sequencing. In addition, the influence of the extracts derived from various parts of Termitomyces combs on the growth of these fungi in culture was considered. Based on phylogenomic analyses, two new genera (Intubia and Chrysosphaeria) were introduced to accommodate these ophiostomatalean species. Phylogenetic analyses revealed that the isolates resided in three well-supported lineages, and these were described as three new species (Intubia macrotermitinarum, I. oerlemansii, and Chrysosphaeria jan-nelii). Culture-based studies showed that these species do not depend on the Termitomyces comb material for growth.
Safety and immunogenicity of a quadrivalent influenza vaccine in adults aged 60 years or above: a phase III randomized controlled clinical study

ABSTRACT To control seasonal influenza epidemics in elders, a quadrivalent, inactivated, split-virion influenza vaccine (IIV4) comprising A and B lineages is produced for young individuals and adults aged ≥60 years. In this phase III, randomized, double-blind, active-controlled trial, we compared safety and immunogenicity of IIV4 with a licensed quadrivalent inactivated vaccine (IIV4-HL) produced by Hualan Biological Engineering during the 2019 influenza season. Participants were randomly assigned to receive IIV4 (n = 959) or IIV4-HL (n = 959). Compared to IIV4-HL, geometric mean titers (GMT) of hemagglutination inhibition (HAI) titers and seroconversion rate (SCR) of IIV4 demonstrated better antibody responses in A lineages (H1N1 and H3N2) (P < .01) and equivalent antibody responses in B lineages (B/Yamagata and B/Victoria) (P > .01) in both age groups. After immunization, IIV4 provided a satisfactory SCR and seroprotection rate (SPR) in elders. No discernible variation in immunogenicity was observed between the two age cohorts. In both age groups, IIV4 and IIV4-HL recipients experienced similar levels of solicited and unsolicited adverse events (AEs), and the incidence of AEs was low in both vaccine groups. Most AEs were of mild-to-moderate severity and no grade 3 AEs in IIV4 group, but AEs in adults aged 60–65 were little higher than in adults over 65 years in IIV4 and IIV4-HL groups (IIV4: 14.66% vs. 10.36%; IIV4-HL:14.67% vs. 11.43%). Totally, IIV4 was generally well tolerated and induced high antibody titers against all four influenza strains in elderly, making it a compelling alternative for the elderly aged ≥60 years. Trial registration: Clinical Trials.gov: 2015L00649-2.
Ankyrin‐repeat and SOCS box‐containing protein 9 (ASB9) regulates ovarian granulosa cells function and MAPK signaling

Ankyrin‐repeat and SOCS box‐containing proteins (ASB) interact with the elongin B‐C adapter via their SOCS box domain and with the cullin and ring box proteins to form E3 ubiquitin ligase complexes within the protein ubiquitination pathway. ASB9 in particular is a differentially expressed gene in ovulatory follicles (OFs) induced by the luteinizing hormone (LH) surge or hCG injection in ovarian granulosa cells (GC) while downregulated in growing dominant follicles. Although ASB9 has been involved in biological processes such as protein modification, the signaling network associated with ASB9 in GC is yet to be fully defined. We previously identified and reported ASB9 interactions and binding partners in GC including PAR1, TAOK1, and TNFAIP6/TSG6. Here, we further investigate ASB9 effects on target binding partners regulation and signaling in GC. CRISPR/Cas9‐induced inhibition of ASB9 revealed that ASB9 regulates PAR1, TAOK1, TNFAIP6 as well as genes associated with proliferation and cell cycle progression such as PCNA, CCND2, and CCNE2 while CCNA2 was not affected. Inhibition of ASB9 was also associated with increased GC number and decreased caspase3/7 activity, CASP3 expression, and BAX/BCL2 ratio. Furthermore, ASB9 induction in OF in vivo 24 h post‐hCG is concomitant with a significant decrease in phosphorylation levels of MAPK3/1 while pMAPK3/1 levels increased following ASB9 inhibition in GC in vitro. Together, these results provide strong evidence for ASB9 as a regulator of GC activity and function by modulating MAPK signaling likely through specific binding partners such as PAR1, therefore controlling GC proliferation and contributing to GC differentiation into luteal cells.
The bladder microbiome and interstitial cystitis: is there a connection?

Purpose of review Interstitial cystitis/painful bladder syndrome (PBS) is a debilitating condition, the etiology of which remains unclear and for which there are variable and often unsatisfactory treatment options. Within the last decade, evolving knowledge regarding the presence and role of the urinary microbiome has led to investigations regarding its impact on symptoms and severity of interstitial cystitis PBS. Recent findings Since 2017, five studies have investigated differences between the microbiome of female patients with interstitial cystitis /PBS to asymptomatic controls. While varied in methodology, specifically with regard to urine collection processing and microbial detection, the majority of studies (4/5) found no association between urinary microbiota and interstitial cystitis /PBS. Summary Research regarding the role of the urinary microbiome and lower urinary tract function and dysfunction, including interstitial cystitis /BPS, remains in preliminary stages. While data regarding the role of lactobacillus in lower urinary tract homeostasis is inconclusive, further research is warranted.
Discrimination between the exogenous and endogenous origin of thiouracil in farm animals, the final chapter?

ABSTRACT Thiouracil (2-thiouracil) is a thyreostatic compound that can be used as an illegal growth promoter. In bovine, porcine and other farm animals, low concentrations of thiouracil are detected in urine. There is much debate on which concentrations can be considered to originate from feed (‘natural’) and which concentrations are caused by the illegal administration of thiouracil for growth-promoting purposes. Currently, a threshold value of 10 µg/L in urine is applied. The threshold value is based on epidemiological data. Data on thiouracil from animals treated with thiouracil is scarce. We conducted a study whereby animals were fed with rapeseed, rapeseed with thiouracil, or regular feed with thiouracil (low and high concentration). It was determined that administration of thiouracil leads to concentrations higher than the current 10 µg/L threshold of thiouracil and its metabolites in urine during treatment. Animals fed with rapeseed showed higher thiouracil concentrations than the control group, mostly above 10 µg/L and in some cases above 30 µg/L. In the discovery study, several biomarkers for thiouracil treatment were tentatively identified and confirmed with reference standards. One metabolite was identified as indicative for thiouracil abuse, namely 6-methyl-thiouracil. Another metabolite, 4-thiouracil, was indicative for endogenous formation and did not increase during 2-thiouracil treatment. 6-Methyl-thiouracil was not found in urine samples from the Dutch routine control programmes that contained (endogenous) 2-thiouracil above the threshold value. However, 4-thiouracil was found at high concentrations in the same samples when 2-thiouracil was present. This study’s overall conclusion is that the threshold value for thiouracil in bovine urine samples should be set at 10 µg/L and for porcine urine samples at 30 µg/L. Also, confirmation of 6-methyl-thiouracil and 4-thiouracil should be used as indicators for exogenous or endogenous origin in routine control monitoring programmes.
Eugenol modulates genomic methylation and inactivates breast cancer‐associated fibroblasts through E2F1‐dependent downregulation of DNMT1/DNMT3A

Active cancer‐associated fibroblasts (CAFs) are major components of the tumor microenvironment, which promote carcinogenesis and modulate response to therapy. Therefore, targeting these cells or reducing their paracrine pro‐carcinogenic effects could be of great therapeutic value. To this end, we sought to investigate the effect of eugenol, a natural phenolic molecule, on active breast CAFs. We have shown that decitabine (5‐Aza‐2′‐deoxycytidine, DAC) and eugenol inhibit the expression of the DNA methyltransferase genes DNMT1 and DNMT3A at both the protein and mRNA levels in breast CAF cells. While the effect of eugenol was persistent, DAC had only a transient inhibitory effect on the mRNA level of both DNMT genes. Furthermore, eugenol and DAC suppressed the invasive/migratory and proliferative potential of CAF cells as well as their paracrine pro‐carcinogenic effects both in vitro and in humanized orthotopic tumor xenografts. Interestingly, these inhibitory effects of decitabine and eugenol were mediated through E2F1 downregulation. Indeed, ectopic expression of E2F1 upregulated both genes and attenuated the effects of eugenol. Additionally, we provide clear evidence that eugenol, like DAC, strongly modulates the methylation pattern in active CAF cells, through methylating several oncogenes and demethylating various important tumor suppressor genes, which affected their mRNA expression levels. Importantly, the E2F1 promoter was also hypermethylated and the gene downregulated in response to eugenol. Together, these findings show that the active features of breast CAF cells can be normalized through eugenol‐dependent targeting of DNMT1/DNMT3A and the consequent modulation in gene methylation.
The effect of trunk training on trunk control, upper extremity, and pulmonary function in children with Duchenne muscular dystrophy: A randomized clinical trial

Objectives: To investigate the effect of trunk training on trunk control, arm, and pulmonary function in children with Duchenne muscular dystrophy. Design: A randomised controlled trial. Settings: Neuromuscular diseases clinic of university hospital. Subjects: Twenty-six children with Duchenne muscular dystrophy aged 5–16 were included in the study. Intervention: Participants were randomly allocated into two groups. The study group (N = 13) exercised with the trunk-oriented exercise program and the conventional exercise program, whereas the control group (N = 13) underwent the conventional exercise program for eight weeks. Main measures: The primary outcomes were trunk control was assessed using the Trunk Control Measurement Scale, the arm function was assessed using Performance of Upper Limb, and respiratory function using the pulmonary function test. Data collection was conducted at baseline, and eighth week. The differences in trunk control scores, arm function scores, and respiratory function values before and after the training were calculated for the intergroup comparison. Results: The mean age of the participants was 11.6 (2.6) in the study group and 10.6 (3.4) in the control group. The changes between trunk control score, arm function score (total and distal level score), and respiratory function value (Forced Vital Capacity, Forced Expiratory Volume in one second, and Peak Expiratory Flow Volume percentage values) were compared and significant differences were found after eight week periods in the study and control groups. Conclusions: Trunk-oriented exercise program in Duchenne muscular dystrophy might be effective for trunk control, arm, and respiratory function.
Clinical characteristics of cirrhosis patients with umbilical vein recanalization

Abstract Umbilical Vein Recanalization (UVR) may occur in patients with long-standing portal hypertension and liver cirrhosis. This study aimed to investigate the clinical significance of UVR. Medical records of a cohort of patients with cirrhosis (n = 247) who were hospitalized at the Digestive Medicine Center of the Second Affiliated Hospital of Nanchang University from January 2012 to October 2015 were accessed. The UVR diagnosis was made by ultrasound examination and was confirmed by computerized tomography scan. The UVR incidence was 20.2% (50/247) in the cohort. The size of UVR was 9.9 ± 4.7 mm (range: 5–26.5 mm) in diameter. The UVR and non-UVR groups showed no difference in grades of hepatic encephalopathy (P = .496), Child-Pugh classification (P = .401), the incidence of moderately severe ascites (26% vs 26%, P = 1), the esophageal variceal bleeding rate (32% vs 39%, P = .402), or portal vein thrombosis (8% vs 12%, P = .580). However, the incidence of cavernous transformation of the portal vein was statistically different, that there was 0 case in the UVR group and 8 cases in the non-UVR group (P < .05). Our results suggested that UVR had little impact on the clinical manifestations of patients with liver cirrhosis, the significance of UVR as an intervention method requires further studies.
Human RecQL4 as a Novel Molecular Target for Cancer Therapy

Human RecQ helicases play diverse roles in the maintenance of genomic stability. Inactivating mutations in 3 of the 5 human RecQ helicases are responsible for the pathogenesis of Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). WS, BS, and RTS patients are at increased risk for developing many age-associated diseases including cancer. Mutations in RecQL1 and RecQL5 have not yet been associated with any human diseases so far. In terms of disease outcome, RecQL4 deserves special attention because mutations in RecQL4 result in 3 autosomal recessive syndromes (RTS type II, RAPADILINO, and BGS). RecQL4, like other human RecQ helicases, has been demonstrated to play a crucial role in the maintenance of genomic stability through participation in diverse DNA metabolic activities. Increased incidence of osteosarcoma in RecQL4-mutated RTS patients and elevated expression of RecQL4 in sporadic cancers including osteosarcoma suggest that loss or gain of RecQL4 expression is linked with cancer susceptibility. In this review, current and future perspectives are discussed on the potential use of RecQL4 as a novel cancer therapeutic target.
Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data

Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data. Applying IPAFinder to 256 pan-cancer tumor/normal pairs across six tumor types, we discovered 490 recurrent dynamically changed IpA events, some of which are novel and derived from cancer-associated genes such as TSC1, SPERD2, and CCND2. Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and m6A modification. In summary, IPAFinder enables the global discovery and characterization of biologically regulated IpA with standard RNA-seq data and should reveal the biological significance of IpA in various processes.