Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunoglobulin G: A useful outcome marker in the follow‐up of cystic fibrosis patients?

Hypergammaglobulinemia (hyper‐IgG) and hypogammaglobulinemia (hypo‐IgG) have been reported in patients with cystic fibrosis (CF). Although the clinical respiratory course is paradoxically different, depending on the IgG status, this association remains elusive. Therefore, we performed a longitudinal study to assess the annual evolution of IgG profiles in a cohort of pediatric patients with CF, from their diagnosis until 2016. We then compared clinical findings with the patients’ IgG status to determine whether IgG status could reflect the respiratory clinical course of patients with CF.
The effect of the food environment on fresh produce served in family child care homes

Background: Higher produce consumption in childhood decreases risks of short- and long-term malnutrition, obesity, and disease. Children in early care programs, including family child care homes (FCCHs), receive 50–67% of daily nutrition while in care. Procuring nutritious foods requires grocer access, which is absent in food deserts (FDs). Aim: To determine if FCCH food environment (FE) impacted distance to grocers and amount of fresh produce served. Methods: Using a cross-sectional design, Modified Retail Food Environment Index scores determined census tract FD status. FCCH and grocer addresses were geocoded and distance to the nearest grocers was calculated. Fresh produce was observed during two lunches. Results: FE did not influence distance to grocers or fresh produce served. Non-desert FCCHs tended to serve fresh produce more frequently. The amount of fresh produce served was overall low. Conclusion: Further studies are warranted to inform policies aimed to reduce provider barriers regarding service of fresh produce.
ZYP1 is required for obligate cross-over formation and cross-over interference in Arabidopsis

Significance The synaptonemal complex (SC) is a meiosis-specific proteinaceous ultrastructure required to ensure cross-over (CO) formation in the majority of sexually reproducing eukaryotes. It is composed of two lateral elements adjoined by transverse filaments. Even though the general structure of the SC is conserved throughout kingdoms, phenotypic differences between mutants perpetuate the enigmatic role of the SC. Here, we have used genetic and cytogenetic approaches to show that the transverse filament protein, ZYP1, acts on multiple pathways of meiotic recombination in Arabidopsis. ZYP1 is required for CO assurance, thus ensuring that every chromosome pair receives at least one CO. ZYP1 limits the number of COs and mediates CO interference, the phenomenon that reduces the probability of multiple COs forming close together. The synaptonemal complex is a tripartite proteinaceous ultrastructure that forms between homologous chromosomes during prophase I of meiosis in the majority of eukaryotes. It is characterized by the coordinated installation of transverse filament proteins between two lateral elements and is required for wild-type levels of crossing over and meiotic progression. We have generated null mutants of the duplicated Arabidopsis transverse filament genes zyp1a and zyp1b using a combination of T-DNA insertional mutants and targeted CRISPR/Cas mutagenesis. Cytological and genetic analysis of the zyp1 null mutants reveals loss of the obligate chiasma, an increase in recombination map length by 1.3- to 1.7-fold and a virtual absence of cross-over (CO) interference, determined by a significant increase in the number of double COs. At diplotene, the numbers of HEI10 foci, a marker for Class I interference-sensitive COs, are twofold greater in the zyp1 mutant compared to wild type. The increase in recombination in zyp1 does not appear to be due to the Class II interference-insensitive COs as chiasmata were reduced by ∼52% in msh5/zyp1 compared to msh5. These data suggest that ZYP1 limits the formation of closely spaced Class I COs in Arabidopsis. Our data indicate that installation of ZYP1 occurs at ASY1-labeled axial bridges and that loss of the protein disrupts progressive coalignment of the chromosome axes.
Hearing Impairment Increases Economic Inequality

Objectives We evaluated changes in income levels in a hearing-impaired population. Methods The study subjects were selected from the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 of Koreans ≥40 years old. In total, 5,857 hearing-impaired subjects were matched with 23,428 comparison participants. Differences between the initial income level and income levels at 1, 2, 3, 4, and 5 years post-enrollment were compared between the hearing-impaired and comparison groups. The interaction of time and hearing impairment/comparison was estimated. Results Both the hearing-impaired group and the comparison group showed increased income levels over time. In the hearing-impaired group, the income levels at 4 and 5 years post-enrollment were higher than the initial income level (each P<0.001). In the comparison group, the income levels of all the participants after 1–5 years were higher than the initial income level (each P<0.001). The interaction of time and hearing impairment was statistically significant (P=0.021). Conclusion The increase in income over time was relatively lower in the hearing-impaired adult population; therefore, the income gap widened between this population and the normal-hearing population.
Discovery of a Novel Respiratory Syncytial Virus Replication Inhibitor

A high-throughput screen of a Roche internal chemical library based on inhibition of the respiratory syncytial virus (RSV)-induced cytopathic effect (CPE) on HEp-2 cells was performed to identify RSV inhibitors. Over 2,000 hits were identified and confirmed to be efficacious against RSV infection in vitro. ABSTRACT A high-throughput screen of a Roche internal chemical library based on inhibition of the respiratory syncytial virus (RSV)-induced cytopathic effect (CPE) on HEp-2 cells was performed to identify RSV inhibitors. Over 2,000 hits were identified and confirmed to be efficacious against RSV infection in vitro. Here, we report the discovery of a triazole-oxadiazole derivative, designated triazole-1, as an RSV replication inhibitor, and we characterize its mechanism of action. Triazole-1 inhibited the replication of both RSV A and B subtypes with 50% inhibitory concentration (IC50) values of approximately 1 μM, but it was not effective against other viruses, including influenza virus A, human enterovirus 71 (EV71), and vaccinia virus. Triazole-1 was shown to inhibit RSV replication when added at up to 8 h after viral entry, suggesting that it inhibits RSV after viral entry. In a minigenome reporter assay in which RSV transcription regulatory sequences flanking a luciferase gene were cotransfected with RSV N/P/L/M2-1 genes into HEp-2 cells, triazole-1 demonstrated specific and dose-dependent RSV transcription inhibitory effects. Consistent with these findings, deep sequencing of the genomes of triazole-1-resistant mutants revealed a single point mutation (A to G) at nucleotide 13546 of the RSV genome, leading to a T-to-A change at amino acid position 1684 of the L protein, which is the RSV RNA polymerase for both viral transcription and replication. The effect of triazole-1 on minigenome transcription, which was mediated by the L protein containing the T1684A mutation, was significantly reduced, suggesting that the T1684A mutation alone conferred viral resistance to triazole-1.
Should the high prevalence of sessile serrated lesions in patients aged below 50 years influence screening colonoscopy recommendations?

We read the recently published study by Sekiguchi et al., and the accompanying editorial, with interest. The authors had examined the prevalence and risk factors for serrated lesions (SLs) and associations with synchronous advanced colorectal neoplasia. Among the 5218 patients undergoing first-time screening colonoscopies, various patient factors were found to be associated with the presence of SLs, including older age, male sex, family history of colorectal cancer (CRC), body mass index, and smoking. Among the controversies highlighted were the implications of these findings for the age at which screening colonoscopy should be initiated. The data presented demonstrated that although SLs were detected more frequently in older patients, one in six (16.9%) of SLs were detected in patients aged 40–49, which is below the minimum age for many CRC screening programs. These findings challenge the current paradigms of CRC screening programs, particularly when viewed in the context of the new risk classification for SLs (which establish their malignant potential), rising rates of CRC in patients < 50, the fact that fecal immunochemical tests (FIT) are not sensitive for detection of sessile serrated lesions (SSLs), and recent US recommendations lowering the CRC screening age to 45 years. We would like to share our observations from a cross-sectional examination of 2164 patients from a predominantly Caucasian, general colonoscopy population in Perth, Australia, in 2019. We investigated factors associated with the detection of SSLs in a random subset of 499 patients with polypectomy during colonoscopy. We considered the histopathology data to reflect the contemporary diagnostic criteria for SLs, as presented in the 5th edition of the World Health Organisation classification of tumours of the digestive system. Our findings expand on two key issues raised in the editorial: firstly, establishing the clinical significance of SLs according to their subtype/malignant potential;
Antioxidant system biomarkers of freshwater mussel (Unio tigridis) respond to nanoparticle (Al2O3, CuO, TiO2) exposures

Abstract Purpose Mussels are known as the natural filters of the aquatic systems and are accepted as one of the best bioindicator organism. There is no data on the response of Unio tigridis to metal-oxide nanoparticle (NP) exposures. This study aimed to investigate the response of the antioxidant enzymes of U. tigridis following exposure to NPs. Materials and methods The mussels were exposed to different concentrations (0, 1, 3, 9 mg NP/L) of Al2O3, CuO and TiO2 NPs for 14 days and subsequently, the activities of CAT (catalase), SOD (superoxide dismutase), GPx (glutathione peroxidase), GST (glutathione S-transferase) and GR (glutathione reductase) were measured in the gill and digestive gland. Mussels were fed with cultured unicellular algae (Chlorella vulgaris) during experiments. Results Data showed that algae consumptions of mussels were not significantly (p>0.05) altered by NPs. However, all enzyme activities in the digestive gland and gill altered significantly (p<0.05) after NP exposures. The activities of CAT and SOD decreased, while the activities of enzymes belonging to glutathione metabolism (GPx and GST) increased in both tissues. Conclusion This study representing the first record on the antioxidant system response of U. tigridis toward NP exposures suggests that NP toxicity should be investigated thoroughly in organisms and some regulations must be done on their usages.
Effects of the entomopathogenic fungi Metarhizium robertsii, Metarhizium flavoviride, and Isaria fumosorosea on the lipid composition of Galleria mellonella larvae

ABSTRACT Galleria mellonella is a pest of the honey bee (Apis mellifera L.) and causes significant losses to the beekeeping industry; therefore, experiments are needed to decode the effects of entomopathogenic fungi on insect physiology. The gas chromatography–mass spectrometry (GC-MS) method was successful for the determination of the organic compounds of Galleria mellonella larvae, noninfected and infected by three fungal species: M. robertsii, M. flavoviride, and I. fumosorosea. A total of 46 compounds were identified in G. mellonella, including fatty acids, other acids, fatty acid methyl esters, monoacylglycerols, amino acids, sterols, and several other organic compounds. The lipids of G. mellonella larvae after M. robertsii, M. flavoviride, and I. fumosorosea exposure contained 40, 35, and 33 organic compounds, respectively. The following organic compounds, present in the noninfected larvae, were absent from the infected larvae: fatty acids C22:0 and C24:0, glutaric acid, urocanic acid, hydroxycinnamic acid, dihydroxycinnamic acid, 10-oxodecanoic acid, glycine, aspartic acid, glutamic acid, lysine, tyrosine, tryptophan, 2-aminobutyric acid, and tyramine. These compounds can be used by fungi as an exogenous source of carbon. The following organic compounds, present in the infected larvae, were absent from the noninfected larvae: fatty acids C10:0, C11:0, C13:0, and C20:0, suberic acid, phenylacetic acid, fatty acid methyl ester (FAME) C16:0, FAME C18:2, FAME C18:1, glycerol 2-monopalmitate, norvaline, proline, sitosterol, and 2-dekanal. These compounds can be synthesized as an insect response to fungal infection.
Equine Cervical Remodeling during Placentitis and the Prepartum Period: A Transcriptomic Approach.

Cervical remodeling is a critical component in both term and preterm labor in eutherian mammals. However, the molecular mechanisms underlying cervical remodeling remain poorly understood in the mare. The current study compared the transcriptome of the equine cervix (cervical mucosa (CM) and stroma (CS)) during placentitis (placentitis group, n=5) and normal prepartum mares (prepartum group, n=3) to normal pregnant mares (control group, n=4). Transcriptome analysis identified differentially expressed genes (DEGs) during placentitis (5310 in CM and 907 in CS) and during the normal prepartum period (189 in CM and 78 in CS). Our study revealed that cervical remodeling during placentitis was dominated by inflammatory signaling as reflected by the overrepresented toll-like receptor signaling, interleukin signaling, T cell activation, and B cell activation pathways. These pathways were accompanied by upregulation of several proteases, including matrix metalloproteinases (MMP1, MMP2, and MMP9), cathepsins (CTSB, CTSC, and CTSD) and a disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1, ADAMTS4, and ADAMTS5), which are crucial for degradation of cervical collagens during remodeling. Cervical remodeling during placentitis was also associated with upregulation of water channel-related transcripts (AQP9 and RLN), angiogenesis-related transcripts (NOS3, ENG1, THBS1, and RAC2), and aggrecan (ACAN), a hydrophilic glucosaminoglycan, with subsequent cervical hydration. The normal prepartum cervix was associated with upregulation of ADAMTS1, ADAMTS4, NOS3 and THBS1, which might reflect an early stage of cervical remodeling taking place in preparation for labor. In conclusion, our findings revealed the possible key regulators and mechanisms underlying equine cervical remodeling during placentitis and the normal prepartum period.
Chronic treatment with acetaminophen protects against liver aging by targeting inflammation and oxidative stress

The liver exhibits a variety of functions that are well-preserved during aging. However, the cellular hallmarks of aging increase the risk of hepatic alterations and development of chronic liver diseases. Acetaminophen (APAP) is a first choice for relieving mild-to-moderate pain. Most of the knowledge about APAP-mediated hepatotoxicity arises from acute overdose studies due to massive oxidative stress and inflammation, but little is known about its effect in age-related liver inflammation after chronic exposure. Our results show that chronic treatment of wild-type mice on the B6D2JRcc/Hsd genetic background with APAP at an infratherapeutic dose reduces liver alterations during aging without affecting body weight. This intervention attenuates age-induced mild oxidative stress by increasing HO-1, MnSOD and NQO1 protein levels and reducing ERK1/2 and p38 MAPK phosphorylation. More importantly, APAP treatment counteracts the increase in Cd8+ and the reduction in Cd4+ T lymphocytes observed in the liver with age. This response was also found in peripheral blood mononuclear cells. In conclusion, chronic infratherapeutic APAP treatment protects mice from age-related liver alterations by attenuating oxidative stress and inflammation.
Deciphering the Association Between Hypothalamus‐Pituitary‐Adrenal Axis Activity and Obesity: A Meta‐Analysis

Both the cortisol awakening response (CAR; corresponding to the state measurement) and hair cortisol concentration (HCC; corresponding to the trait measurement) are considered reliable markers of hypothalamus‐pituitary‐adrenal axis activity. Because cortisol has long been associated with adiposity, this systematic review and meta‐analysis aims to summarize and compare the literature around CAR and HCC and their association with obesity or fat distribution indices.
Efficacy and Complications of External and Internal Pediatric Blepharoptosis Repair Techniques: A Systematic Review

Purpose: To review and evaluate the efficacy and complication rates of external and internal blepharoptosis repair techniques in pediatric patients. Methods: The systematic review protocol was published on PROSPERO (CRD42020197343). Embase, MEDLINE, CENTRAL, and ClinicalTrials.gov were searched without date limitations. Two independent reviewers evaluated the articles for inclusion. Study quality and risk of bias were assessed using GRADE and Cochrane’s ROBINS-I tool, respectively. Results: Of 2,228 articles screened, 23 studies involving 730 patients were included. There were 20 case series and 3 retrospective cohort studies, but no randomized controlled studies. Overall study quality was low with serious risk of bias according to the GRADE and ROBINS-I criteria, respectively. External levator resection was the most studied procedure, evaluated in 18 studies. Seven studies investigated internal approaches including the Fasanella-Servat procedure. There was no standardized evaluation of surgical efficacy. Reoperation rates were 16.6% (range 3.6–50.9%) for external levator resection compared with 22.2% (range 0.0–25.8%) for internal approaches. The commonest postoperative complications were not sight-threatening. The most consistently reported complication was undercorrection, occurring at rates of 8.4% (range 2.4–16.7%) and 15.3% (range 2.7–75.0%) for external levator resection and internal approaches, respectively. There were no consistently applied, validated patient-reported outcomes or cosmetic outcomes. Conclusions: External and internal approaches have been successfully employed in pediatric blepharoptosis repair. However, noncomparative designs and risk-of-bias limit existing studies. Thus, prospectively designed studies with standardized outcome measures are required to minimize reporting bias, facilitate evidence synthesis, and support clinical decision making. Surgical repair of nonsevere blepharoptosis has been achieved with a range of external and internal techniques in the pediatric population, but existing studies are limited by noncomparative designs and nonstandardized outcome measures. Supplemental Digital Content is available in the text.
Tuned to Perfection: Ironing Out the Defects in Metal–Organic Framework UiO-66

Themostdramatic way that a sample may deviate from ideality is thatit may have a signiﬁcantly lower thermal stability than expected,an issue which has not been previously reported. Figure 1(discussed in depth later) demonstrates the surprisingly widevariation in the thermal stabilities of three UiO-66 samplessynthesized at diﬀerent temperatures, highlighting how severelythe material can be aﬀected by alterations to the synthesisconditions.In addition to poor thermal stability, we identify six ways inwhich a UiO-66 sample may deviate from what may beconsidered “ideal” for the material: (1) Symmetry forbiddenreﬂections may appear in its PXRD pattern,
Associations of vitamin D status with colorectal cancer risk and survival

Biological evidence suggests that vitamin D has numerous anticancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season‐standardized 25‐hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360 061 participants, and with survival among 2509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1‐SD increment, 0.95; 95% CI, 0.91‐0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77‐0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65‐0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.
CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update

ABSTRACT Introduction: HEPLISAV-B is a hepatitis B vaccine composed of rHBsAg mixed with a synthetic oligonucleotide containing CpG motifs that stimulate innate immunity through TLR9. This vaccine was recently approved by FDA in view of its superior efficacy. Areas covered: Published literature on HEPLISAV-B was critically reviewed. Four randomized controlled trials among 7,056 subjects receiving 2 doses of HEPLISAV-B and 3,214 subjects receiving 3 doses of Engerix-B showed superior seroprotection rate (SPR) (anti-HBs ≥10 mIU/mL) of 90–100%, compared with 71–90% in those receiving Engerix-B. Furthermore, the seroprotection rate was also significantly higher in HEPLISAV-B compared with Engerix-B recipients in persons with traditionally poor vaccine responses such as older adults, diabetics, and those with chronic kidney disease. The safety profiles among 9,871 subjects were similar between HEPLISAV-B and Engerix-B . Expert opinion: HEPLISAV-B, a CpG adjuvant mixed with HBsAg, is more efficacious and produced earlier seroprotection compared to existing vaccines, with a favorable safety profile. The shorter, two-dose regimen, earlier seroprotection, higher adherence, and a higher seroprotection rate, especially in populations with traditionally poor vaccine response, makes this an important therapeutic option in hepatitis B vaccination.