bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mecom mutation related to radioulnar synostosis with amegakaryocytic thrombocytopenia reduces HSPCs in mice
Authors: Nagai Koki , Niihori Tetsuya , Muto Akihiko , Hayashi Yoshikazu , Abe Taiki , Igarashi Kazuhiko , Aoki Yoko 
Published: April 2023

Abstract
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome characterized by the congenital fusion of the forearm bones. RUSAT is largely caused by missense mutations that are clustered in a specific region of the MDS1 and EVI1 complex locus (MECOM). EVI1, a transcript variant encoded by MECOM, is a zinc finger transcription factor involved in hematopoietic stem cell maintenance that induce leukemic transformation when overexpressed. Mice with exonic deletions in Mecom show reduced hematopoietic stem and progenitor cells (HSPCs). However, the pathogenic roles of RUSAT-associated MECOM mutations in vivo have not yet been elucidated. To investigate the impact of the RUSAT-associated MECOM mutation on the phenotype, we generated knockin mice harboring a point mutation (translated into EVI1 p.H752R and MDS1-EVI1 p.H942R), which corresponds to an EVI1 p.H751R and MDS1-EVI1 p.H939R mutation identified in a patient with RUSAT. Homozygous mutant mice died at embryonic day 10.5 to 11.5. Heterozygous mutant mice (Evi1KI/+ mice) grew normally without radioulnar synostosis. Male Evi1KI/+ mice, aged between 5 and 15 weeks, exhibited lower body weight, and those aged ≥16 weeks showed low platelet counts. Flow cytometric analysis of bone marrow cells revealed a decrease in HSPCs in Evi1KI/+ mice between 8 and 12 weeks. Moreover, Evi1KI/+ mice showed delayed leukocyte and platelet recovery after 5-fluorouracil–induced myelosuppression. These findings suggest that Evi1KI/+ mice recapitulate the bone marrow dysfunction in RUSAT, similar to that caused by loss-of-function Mecom alleles.
25(OH)Vitamin D and autism spectrum disorder: genetic overlap and causality
Authors: Yu GuoSheng , Xu MinZhi , Chen Yao , Ke HaiYan 
Published: April 2023

Abstract
Objective
To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD).

Methods
Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits. A bidirectional Mendelian randomization (MR) analysis was applied to investigate whether there is a causal relationship between 25(OH)D and ASD.

Results
The linkage disequilibrium score regression (LDSC) showed a negative genetic correlation between 25(OH)D and ASD (rg = − 0.227, P < 0.05), and PLACO analysis identified 20 independent pleiotropic loci matched to 24 pleiotropic genes, of which the function reveals an underlying mechanism on 25(OH)D and ASD. In Mendelian randomization analysis, the inverse variance-weighted (IVW) method with OR = 0.941 (0.796, 1.112) and p < 0.474 did not show a causal relationship between 25(OH)D and ASD, while, in the reverse Mendelian randomization analysis, IVW method showed OR = 1.042 (0.930, 1.169), indicating no causal relationship either.

Conclusion
This study provides evidence for a shared genetic overlap between 25(OH)D and ASD. Bidirectional MR analysis also did not show a definite causal relationship between 25(OH)D and ASD.
Priors, population sizes, and power in genome-wide hypothesis tests
Authors: Cai Jitong , Zhan Jianan , Arking Dan E. , Bader Joel S. 
Published: April 2023

Abstract
Background
Genome-wide tests, including genome-wide association studies (GWAS) of germ-line genetic variants, driver tests of cancer somatic mutations, and transcriptome-wide association tests of RNAseq data, carry a high multiple testing burden. This burden can be overcome by enrolling larger cohorts or alleviated by using prior biological knowledge to favor some hypotheses over others. Here we compare these two methods in terms of their abilities to boost the power of hypothesis testing.

Results
We provide a quantitative estimate for progress in cohort sizes and present a theoretical analysis of the power of oracular hard priors: priors that select a subset of hypotheses for testing, with an oracular guarantee that all true positives are within the tested subset. This theory demonstrates that for GWAS, strong priors that limit testing to 100–1000 genes provide less power than typical annual 20–40% increases in cohort sizes. Furthermore, non-oracular priors that exclude even a small fraction of true positives from the tested set can perform worse than not using a prior at all.

Conclusion
Our results provide a theoretical explanation for the continued dominance of simple, unbiased univariate hypothesis tests for GWAS: if a statistical question can be answered by larger cohort sizes, it should be answered by larger cohort sizes rather than by more complicated biased methods involving priors. We suggest that priors are better suited for non-statistical aspects of biology, such as pathway structure and causality, that are not yet easily captured by standard hypothesis tests.
Biocontrol of multi-drug resistant pathogenic bacteria in drainage water by locally isolated bacteriophage
Authors: Soliman Rabab M. , Othman Badawi A. , Shoman Sahar A. , Azzam Mohamed I. , Gado Marwa M. 
Published: April 2023

AbstractIn areas with limited water resources, the reuse of treated drainage water for non-potable purposes is increasingly recognised as a valuable and sustainable water resource. Numerous pathogenic bacteria found in drainage water have a detrimental impact on public health. The emergence of antibiotic-resistant bacteria and the current worldwide delay in the production of new antibiotics may make the issue of this microbial water pollution even more challenging. This challenge aided the resumption of phage treatment to address this alarming issue. In this study, strains of Escherichia coli and Pseudomonas aeruginosa and their phages were isolated from drainage and surface water from Bahr El-Baqar and El-Manzala Lake in Damietta governorate, Egypt. Bacterial strains were identified by microscopical and biochemical examinations which were confirmed by 16 S rDNA sequencing. The susceptibility of these bacteria to several antibiotics revealed that most of the isolates had multiple antibiotic resistances (MAR). The calculated MAR index values (> 0.25) categorized study sites as potentially hazardous to health. Lytic bacteriophages against these multidrug-resistant strains of E. coli and P. aeruginosa were isolated and characterized. The isolated phages were found to be pH and heat stable and were all members of the Caudovirales order as recognized by the electron microscope. They infect 88.9% of E. coli strains and 100% of P. aeruginosa strains examined. Under laboratory conditions, the use of a phage cocktail resulted in a considerable reduction in bacterial growth. The removal efficiency (%) for E. coli and P. aeruginosa colonies increased with time and maximized at 24 h revealing a nearly 100% reduction after incubation with the phage mixture. The study candidates new phages for detecting and controlling other bacterial pathogens of public health concern to limit water pollution and maintain adequate hygiene.
Genome-wide comparative analysis of the valine glutamine motif containing genes in four Ipomoea species
Authors: Si Zengzhi , Wang Lianjun , Ji Zhixin , Qiao Yake , Zhang Kai , Han Jinling 
Published: April 2023

AbstractBackgroundGenes with valine glutamine (VQ) motifs play an essential role in plant growth, development, and resistance to biotic and abiotic stresses. However, little information on theVQgenes in sweetpotato and otherIpomoeaspecies is available.ResultsThis study identified 55, 58, 50 and 47VQgenes from sweetpotato (I. batatas),I.triflida,I. trilobaandI. nil, respectively. The phylogenetic analysis revealed that theVQgenes formed eight clades (I–VII), and the members in the same group exhibited similar exon–intron structure and conserved motifs distribution. The distribution of theVQgenes among the chromosomes ofIpomoeaspecies was disproportional, with noVQgenes mapped on a few of each species' chromosomes. Duplication analysis suggested that segmental duplication significantly contributes to their expansion in sweetpotato,I.trifida, andI.triloba, while the segmental and tandem duplication contributions were comparable inI.nil.Cis-regulatory elements involved in stress responses, such as W-box, TGACG-motif, CGTCA-motif, ABRE, ARE, MBS, TCA-elements, LTR, and WUN-motif, were detected in the promoter regions of theVQgenes. A total of 30 orthologous groups were detected by syntenic analysis of theVQgenes. Based on the analysis of RNA-seq datasets, it was found that theVQgenes are expressed distinctly among different tissues and hormone or stress treatments. A total of 40 sweetpotato differentially expressed genes (DEGs) refer to biotic (sweetpotato stem nematodes andCeratocystis fimbriatapathogen infection) or abiotic (cold, salt and drought) stress treatments were detected. Moreover,IbVQ8,IbVQ25andIbVQ44responded to the five stress treatments and were selected for quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis, and the results were consistent with the transcriptome analysis.ConclusionsOur study may provide new insights into the evolution ofVQgenes in the fourIpomoeagenomes and contribute to the future molecular breeding of sweetpotatoes.
Association of frailty with influenza and hospitalization due to influenza among independent older adults: a longitudinal study of Japan Gerontological Evaluation Study (JAGES)
Authors: Iwai-Saito Kousuke , Sato Koryu , Aida Jun , Kondo Katsunori 
Published: April 2023

Abstract
Background
It is unknown that whether frailty is a risk factor of influenza and the hospitalization among older adults, although it has been shown that frailty was associated with poor recovery from the hospitalization among those. We examined the association of frailty with influenza and the hospitalization and the effect by sex among independent older adults.

Methods
We used the longitudinal data from the Japan Gerontological Evaluation Study (JAGES), performed in 2016 and 2019 and conducted in 28 municipalities in Japan. The target population comprised 77,103 persons aged ≥ 65 years who did not need assistance from the public long-term care insurance. Primary outcome measures were influenza and hospitalization due to influenza. Frailty was evaluated with the Kihon check list. We estimated the risk of influenza, the hospitalization, those risks by sex, and the interaction for frailty and sex using Poisson regression adjusting for covariates.

Results
Frailty was associated with both influenza and the hospitalization among the older adults compared with nonfrail individuals after adjusting for covariates (influenza, frail: risk ratio {RR}: 1.36, 95% confidence interval {95% CI}: 1.20 − 1.53, and prefrail: RR: 1.16, 95% CI: 1.09 − 1.23; the hospitalization, frail: RR: 3.18, 95% CI: 1.84 − 5.57, and prefrail: RR: 2.13, 95% CI: 1.44 − 3.16). Male was associated with the hospitalization, but not associated with influenza compared to female (the hospitalization: RR: 1.70, 95% CI: 1.15 − 2.52 and influenza: RR: 1.01, 95% CI: 0.95 − 1.08). The interaction for frailty and sex was significant neither in influenza nor in the hospitalization.

Conclusion
These results suggest that frailty is a risk of influenza and the hospitalization, that risks of the hospitalization are different by sex, but that the sex difference does not cause the effect heterogeneity of frailty on the susceptibility and severity among independent older adults.
Ceftriaxone resistant Salmonella enterica serovar Paratyphi A identified in a case of enteric fever: first case report from Pakistan
Authors: Irfan Seema , Hasan Zahra , Qamar Farah , Ghanchi Najia , Ashraf Javaria , Kanji Akbar , Razzak Safina Abdul , Greig David , Nair Satheesh , Hasan Rumina 
Published: April 2023

Abstract
Background
Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global burden of 14.3 million cases. Cases of enteric fever or paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A (S. Para A) have been found to rise in many endemic and non-endemic countries. Drug resistance is relatively uncommon in S. Para A. Here we report a case of paratyphoid fever caused by ceftriaxone resistant S. Para A from Pakistan.

Case presentation
A 29-year-old female presented with a history of fever, headache, and shivering. Her blood culture revealed a S. Para A isolate (S7), which was resistant to ceftriaxone, cefixime, ampicillin and ciprofloxacin. She was prescribed oral Azithromycin for 10 days, which resulted in resolution of her symptoms.
Two other isolates of S. Para A (S1 and S4), resistant to fluoroquinolone were also selected for comparison. DST and whole genome sequencing was performed for all three isolates. Sequence analysis was performed for identification of drug resistance and phylogeny. Whole Genome Sequencing (WGS) of S7 revealed the presence of plasmids, IncX4 and IncFIB(K). blaCTX-M-15 and qnrS1 genes were found on IncFIB(K). The gyrA S83F mutation conferring fluoroquinolone resistance was also found present. Multi-locus sequence typing (MLST) showed the S7 isolate to belong to ST129. S1 and S4 had the gyrA S83Y and S83F mutations respectively.

Conclusions
We highlight the occurrence of plasmid-mediated ceftriaxone resistant strain of S. Para A. This is of significance as ceftriaxone is commonly used to treat paratyphoid fever and resistance in S. Para A is not known. Continuous epidemiological surveillance is required to monitor the transmission and spread of antimicrobial resistance (AMR) among Typhoidal Salmonellae. This will guide treatment options and preventive measures including the need for vaccination against S. Para A in the region.
Efficacy of low-dose rituximab in minimal change disease and prevention of relapse
Authors: Zhang Jian , Zhao Hui , Li Xiaoli , Qian Rui , Gao Peijuan , Lu Shouyan , Ma Zhigang 
Published: April 2023

Abstract
Background
Minimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD.

Methods
A total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD.

Results
Of the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9–31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment.

Conclusion
The results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.
99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer
Authors: Murad Vanessa , Suh Minseok , Choi Hongyoon , Cheon Gi Jeong , Na Kwon Joong , Kim Young Tae 
Published: April 2023

Abstract
Background
99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS).

Methods
Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed.

Results
Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2–3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3 cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis.

Conclusion
The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.
Occurrence of circumscribed choroidal hemangioma accompanied by polypoidal choroidal vasculopathy and branch retinal vein occlusion: a case report
Authors: Zhang Qin , Wang Huan , Zhang Yue , Xu Ling 
Published: April 2023

Abstract
Background
Circumscribed Choroidal hemangioma (CCH) is a kind of hamartoma that is caused by congenital vascular malformation. And, polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy. There is no literature indicating that there is a correlation between the occurrences of CCH and PCV.

Case presentation
A 66-year-old male presented with decreased vision of his left eye for 4 years. Fundus photograph showed that the branches of blood vessels at the supratemporal retina were occluded in white lines, an orange lesion could be seen in the subnasal retina and mottled, yellowish white lesions were accompanied by punctate hard exudation in the macular in the left eye. The Fundus autofluorescence (FAF), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and Spectral domain optical coherence tomography (OCT) were done. There was a diagnosis of CCH, PCV and branch retinal vein occlusion accompanied with retinoschisis of the left eye.

Conclusion
This article reports on a case of an elderly male Chinese patient with CCH and PCV accompanied by branch retinal vein occlusion with retinoschisis in the left eye. The common lesions are choroidal vascular abnormalities. Whether hypertension is related to CCH, PCV and branch retinal vein occlusion remains to be further studied.
Quality of life in intermittent exotropia for Korean children and their parents
Authors: Oh Jin Seon , Jung Jae Ho , Shin Hyun Jin 
Published: April 2023

Abstract
Background
Patients with strabismus are more likely to have mental health problems, including high rates of depressive symptoms and social phobia. Intermittent exotropia (IXT) typically occurs in early childhood and is more common in Asian populations. We aim to assess the health-related quality of life (HRQOL) concerns in children with intermittent exotropia (IXT) using the Intermittent Exotropia Questionaire (IXTQ), and their associations with the clinical severity of IXT and the parents’ HRQOL concerns.

Methods
IXT, defined as both distance and near exodeviation ≥ 10 prism diopters were eligible for inclusion. The final IXTQ score is calculated using the mean score for all items, and ranges from 0 (worst HRQOL) to 100 (best HRQOL). The correlations of child IXTQ scores with their deviation angle and stereoacuity were measured, as were those with their parent’s IXTQ scores.

Results
One hundred twenty-two children with IXT (aged 5–17 years) and one parent for each child completed the child and parent IXTQ, respectively. The greatest HRQOL concern for each child with IXT and their parent was “Worry about eyes” (frequency 88%, score 35.0 ± 27.8). Lower child IXTQ scores were associated with a larger distance (r = 0.24, p = 0.007) and near deviation angle (r = 0.2, p = 0.026). “It bothers me because I have to wait for my eyes to clear up” and “Waiting for their eyes to clear up” were more common in children with a larger deviation angle (both p < 0.05). The parent IXTQ scores (52.1 ± 25.3) were lower than the child ones (79.7 ± 15.8) and showed a positive correlation with child IXTQ scores (r = 0.26, p = 0.004). Lower parent IXTQ scores were associated with poor distance stereoacuity (r = 0.23, p = 0.01).

Conclusion
The HRQOL of IXT children was positively related to that of their parents. A larger deviation angle and worse distance stereoacuity function may predict more-negative impacts on children and their parents, respectively.