bluuebunny/crossref_metadata_2025 huggingface dataset:
IL12/18/21 Preactivation Enhances the Antitumor Efficacy of Expanded γδT Cells and Overcomes Resistance to Anti–PD-L1 Treatment
Authors: Teo Huey Yee , Song Yuan , Yong Kylie Su Mei , Liu Yonghao , Mei Yu , Hanafi Zuhairah Binte , Zhu Ying , Chua Yen Leong , Gascoigne Nicholas R.J. , Chen Qingfeng , Liu Haiyan
Published: April 2023

γδT cells are promising candidates for cellular immunotherapy due to their immune regulation through cytokine production and MHC-independent direct cytotoxicity against a broad spectrum of tumors. However, current γδT cell-based cancer immunotherapy has limited efficacy, and novel strategies are needed to improve clinical outcomes. Here, we report that cytokine pretreatment with IL12/18, IL12/15/18, IL12/18/21, and IL12/15/18/21 effectively enhanced the activation and cytotoxicity of in vitro–expanded murine and human γδT cells. However, only adoptive transfer of IL12/18/21 preactivated γδT cells significantly inhibited tumor growth in a murine melanoma model and a hepatocellular carcinoma model. Both IL12/18/21 preactivated antibody-expanded and zoledronate-expanded human γδT cells effectively controlled tumor growth in a humanized mouse model. IL12/18/21 preactivation promoted γδT cell proliferation and cytokine production in vivo and enhanced IFNγ production and activation of endogenous CD8+ T cells in a cell–cell contact- and ICAM-1–dependent manner. Furthermore, the adoptive transfer of IL12/18/21 preactivated γδT cells could overcome the resistance to anti–PD-L1 therapy, and the combination therapy had a synergistic effect on the therapeutic outcomes. Moreover, the enhanced antitumor function of adoptively transferred IL12/18/21 preactivated γδT cells was largely diminished in the absence of endogenous CD8+ T cells when administered alone or in combination with anti–PD-L1, suggesting a CD8+ T cell–dependent mechanism. Taken together, IL12/18/21 preactivation can promote γδT cell antitumor function and overcome the resistance to checkpoint blockade therapy, indicating an effective combinational cancer immunotherapeutic strategy.
Figure S4 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: April 2023

APOBEC-related kataegis event.
Data from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: April 2023

Abstract
Gynecologic carcinosarcomas (CS), are biphasic neoplasms composed of carcinomatous (C) epithelial and sarcomatous (S) malignant components. Due to their rarity and histological complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown.
Whole genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS. Reconstructions of the evolutionary history of each tumor further reveal that C and S samples are composed of both ancestral cell populations and component-specific sub-clones, supporting a common origin followed by distinct evolutionary trajectories. However, while we do not find any recurrent genomic features associated with phenotypic divergence, transcriptomic and methylome analyses identify a common mechanism across the cohort, the epithelial-to-mesenchymal transition (EMT), suggesting a role for non-genetic factors in inflicting changes to cellular fate. Altogether, these data accredit the hypothesis that CS tumors are driven by both clonal evolution and transcriptomic reprogramming, essential for susceptibility to transdifferentiation upon encountering environmental cues, thus linking CS heterogeneity to genetic, transcriptomic and epigenetic influences.
Injuries, Poisonings, and Other External Causes of Morbidity among Drug Crime Offenders: A Follow-Up Study of Former Adolescent Psychiatric Inpatients
Authors: Kontu Mikaela , Hakko Helina , Riala Kaisa , Riipinen Pirkko
Published: April 2023

Introduction: Criminal offenders have high incidences of injury- and substance-related emergency department visits. Very few studies focus on drug crime offenders or the medical specialties involved in treating these offenders. We aimed to study how drug crime offenders’ treatment events in specialized health care due to injuries, poisonings, or other external causes of morbidity differed from treatment of non-criminal controls and which of the medical specialties were involved in their care. Methods: The study population included 508 former adolescent psychiatric inpatients (age 13–17 years), who were followed up through Finnish national registers. A total of 60 had committed a drug crime during the 10–15 years’ follow-up. They were matched with 120 non-criminal controls from the study population. Hazard ratios (HRs) with 95% confidence intervals (Cl) for drug crime offending were assessed using a Cox regression model. Results: Almost 90% of drug crime offenders had treatment events in specialized health care due to injuries, poisonings, and other external causes of morbidity, compared to 50% of non-criminals. The majority of the drug crime offenders had been treated for accidental injuries (65% vs. 29%; p < 0.001) in comparison to non-criminal controls. More drug crime offenders had been treated for intentional poisonings (42% vs. 11%; p < 0.001) than non-criminal controls. For drug crime offenders, the lifetime probability of a treatment event due to poisoning was almost doubled (HR: 1.89, 95% CI: 1.26–2.84; p = 0.002), and for treatments due to injury, there was a 2.5-fold increase (HR: 2.54, 95% CI: 1.69–3.82; p < 0.001) in comparison to non-criminal controls. Conclusion: In emergency care, substance use screening and referral for appropriate psychiatric and substance abuse treatment services should be considered for all adolescents and young adults attending hospitals due to injuries or poisonings.
The avian diversity of Chemmattamvayal Wetlands and adjacent areas of Kasaragod District, Kerala, India
Authors: Mohan Sreehari K. , R. Anjitha  , K. Maxim Rodrigues
Published: April 2023

The avian diversity of Chemmattamvayal Wetlands and adjacent areas, in Kasaragod District, Kerala State, was recorded from December 2014 to March 2018. The methodology followed was mainly incidental observations using binoculars. Findings presented here are also based on the data collected from eBird, a citizen science based online platform. A total of 145 bird species, belonging to 17 orders and 50 families were recorded during the study. Among them, 42 species were winter migrants and 97 were seen throughout the year. The highest number of birds were recorded during the month of January and the lowest in June. The present work gains importance as a literature on the avian fauna of the district. White-throated Kingfisher Halcyon smyrnensis, Indian Pond Heron Ardeola grayii, and Spotted Dove Spilopelia chinensis were recorded highest in terms of relative abundance. The importance of these wetlands and adjacent areas as the stepping stone for trans-continental migrants is discussed.
Mammalian diversity of Debrigarh Wildlife Sanctuary, Odisha, India
Authors: Nimain Charan Palei  , Bhakta Padarbinda Rath  , Sudeep Nayak
Published: April 2023

Camera traps were deployed at 123 stations in an area of 346.91 km2 in Debrigarh Wildlife Sanctuary between 25 August 2018 and 29 December 2019 that provided the effort of 3,150 trap-days. Of the 2,767 photo captures, 1,304 were mammals belonging to 13 families and 27 large and medium-sized mammals were recorded in the study area. Carnivores were especially diverse, with 11 species recorded with particular four felidae including Tiger Pantera tigris, Leopard Panthera pardus, and globally threatened Rusty-spotted Cats which extended the range of this species. Leopard was the most captured species with the highest relative abundance (RAI = 5.68) among the carnivore species, whereas the Indian Pangolin Manis crassicaudata (RAI = 0.06) had the lowest abundance. We provide photographic evidence of mammalian species and highlight the importance of conservation of dry deciduous forests for threatened and vulnerable species in the study area. The current camera trap survey is expected to help in the formulation of management strategies for long-term conservation of mammalian species in Debrigarh Wildlife Sanctuary.
The giant clam commensal shrimp Anchistus miersi (de Man, 1888) (Decapoda: Palaemonoidae) new to Lakshadweep Sea, India
Authors: Madhavan Manu , Paramasivam Purushothaman , S. Akash  , T.T. Ajith Kumar  , Kuldeep Kumar Lal
Published: April 2023

The genus Anchistus Borradaile, 1898 is a colourful shrimp from the commensal group. In this study, we are reporting a new occurrence of Giant Clam commensal shrimp Anchistus miersi (de Man, 1888 [in de Man, 1887–1888]) caught from Agatti Island, Lakshadweep Sea during February 2020. The present specimens (one each matured male and female) were collected from the mantle cavity of the Giant Clam, Tridacna maxima (Roding, 1798) in the coral lagoon at a depth of 4 m. Anchistus miersi is morphologically very similar to Anchistus demani, which is easily distinguished by the presence of a strong antennal spine and conspicuous accessory spinules in the third─fifth pereopods and presence of small blue spots all over the body. The molecular analysis confirms that, the morphological identification of the present Indian specimens displays an intraspecific genetic divergence of 0.3─1.2%.  Besides, the remarkable taxonomic features and colour patterns, distributional ranges are also attested with the report of the species from the present area.
Vertebrate road kills on State Highway 26 in Khandwa Forest Division, central India
Authors: Husain Kamran , Mehta Prachi
Published: April 2023

The road network is spreading rapidly in human dominated as well as forested areas in India. Roads passing through forested areas are known to negatively impact wildlife populations by contributing to wildlife-road kills besides causing habitat fragmentation, soil erosion, and disruption of gene flow. This paper documents encounters of wildlife road kills on the State Highway 26 (SH 26) passing through the forested area of Khandwa Territorial Forests in central India. Between October 2015 and June 2017 and from November 2021 to June 2022 we collected opportunistic data on wildlife mortalities on SH 26. We recorded 61 wildlife mortalities on a stretch of 34 km of SH 26. Of the road kills encountered, 71% were birds, 21% were mammals, and 8% were herpetofauna. Highest among bird kills were members of nightjars (Caprimulgidae) (26%) and owls (Strigidae) (23%).  Among owls, we recorded two road kills of the endangered Forest Owlet Athene blewitti and individuals of five other owl species. Among other taxa, road-hits of Jungle Cat, Indian Palm Civet, Golden Jackal, Central Indian Langur, and a few snakes were recorded. Most bird kills on the road were recorded in February while the highest number of mammal and herpetofauna kills were recorded in the month of November. We report that the land use around the road and species trait contribute to vulnerability of a species to road-hit. Based on the frequency of road kills, we have identified seven hotspots of road kills on SH 26. Since road construction is one of the major mandates of the Government in India, it is suggested to carry out systematic environment impact assessment on existing and proposed roads to understand the patterns of spatio-temporal incidents of road kills. Planting of tall trees and installation of speed bumps and signboards to alert drivers should be planned at the initial stage of road construction. If appropriate mitigation measures to prevent wildlife mortalities are incorporated while the road is being constructed, it may be possible to bridge the gap between development and conservation.
Tongues as of Fire
Authors: Griffiths John D.
Published: April 2023

The coming of the Spirit of God at Pentecost (Acts 2.1-4) is described in dense imagery, involving auditory, visual, and somatic elements. This study outlines the recent scholarship on these theophanic elements, and in particular, the parallels with the temple inauguration theophanies in the Old Testament. While these parallels are increasingly becoming accepted, the implications of the temple inauguration imagery in Acts 2.1-4 remains unresolved. The core issue revolves around whether it is the Spirit or Jesus who now embodies the theophanic presence of God which once resided in the Jerusalem temple. This study concludes that it is the Spirit of God that now embodies the glory of God which resided in the temple, with the early Jesus community being the new eschatological temple of God.
Signal Cost in Digital Diplomacy: A Study of American and Chinese Public Outreach
Authors: Wu Di , Sevin Efe
Published: April 2023

This study looks at how digital technologies disrupted signalling and signal cost calculations in public diplomacy within the context of Covid-19. The pandemic presented a noteworthy opportunity to observe how countries attempt to navigate a relatively unknown communication landscape as a result of external shock and a crisis for states’ images and reputations. We position the communicative outcomes of the pandemic as an exploratory case to discuss how countries use social media to engage with target audiences. We study American and Chinese messaging on Twitter about Covid-19 employing an analytical model of signal cost developed from signalling theory. Using a data set of 1,512 tweets coming from nine different American and Chinese accounts, we investigated their signal cost through content and network analyses. Our findings describe and operationalise signal cost in digital public diplomacy through signaller, signal content and outreach.
A Letter from Algerian Rabbi David Askénazi to Rabbi Kook Advocating for the Use of the Organ in Synagogue Services
Authors: Abensour Gabriel
Published: April 2023

In 1934, David Askénazi, the chief rabbi of Oran, Algeria, responded to a decision by Abraham Kook, at the time chief rabbi of Mandatory Palestine, condemning the use of the organ in synagogue services in Oran. Transcending the typical European dichotomies between Orthodox and Reform, Askénazi’s letter is above all a testimony to the religious and cultural hybridity of Algerian Jews during the colonial era. In a mere few pages, the rabbi developed a religious argument mixing elements of language and arguments typical of Maghrebian rabbis with positions common to liberal European Jews. Aware of the structure of power between the East and the West, Askénazi also criticized Kook’s interventionism in the affairs of his community. In light of what he denounced as a form of Jewish imperialism, Askénazi emphasized the agency of Sephardic rabbis and called for full recognition of their religious tradition.
Secularisms beyond the West
Authors: Igwe Leo
Published: April 2023

In line with Jacques Berlinerblau’s Secularism: The Basics, this commentary highlights manifestations of secularism beyond the west. It argues that state regulation of religion and religious citizens is not one dimensional. Secularism takes different forms and contends with differing sociopolitical realities.
Commentary on Secularism: The Basics
Authors: Zuckerman Phil
Published: April 2023

Berlinerblau’s latest work, Secularism: The Basics, is a thoughtful, insightful, brilliant, and accessible introduction to political secularism—full of global examples, relevant controversies, and ten core principles that underly the entire secularist phenomenon.
Gold Nanoparticles Improve Clinical Parameters and Reduce Neurological Alterations in Sepsis-Induced Mice
Authors: Ferreira João P. , Di Bella Davide , Andreotti Diana Z. , Cortes Bryan F. , Carvalho Maria H. , Kawamoto Elisa M. , Rodrigues Stephen F.
Published: April 2023

Sepsis is a grave systemic condition that affects several organs and is caused by an infectious disease. Among the organs targeted by sepsis is the brain, a condition named sepsis-associated encephalopathy (SAE). Epidemiological studies indicate that 25%–70% of sepsis patients develop SAE, presenting acute and chronic symptoms. The main acute symptom is delirium, while chronic symptoms include cognitive impairment, locomotor dysfunction and mood disorders, amongst them, depression. The physiopathology of SAE involves systemic and local actions. Systemically, reduced brain perfusion, hyperglycemia, and activation of the sensory vagus nerve contribute to SAE. Locally, inflammation, enhanced oxidative stress, and enhanced excitotoxicity play vital roles in SAE development. Today, there is no commercially available treatment for SAE. We recently demonstrated that twenty-nanometer citrate-capped gold nanoparticles (cit-AuNP) intravenously injected two or four hours after induction of sepsis could reduce cerebral inflammation in mice. In the present study, we showed that cit-AuNP acutely injected in mice with sepsis exhibited faster clinical symptom resolution and reduced glutamate levels in the brain thirty days after sepsis induction. The acute twenty-nanometer cit-AuNP treatment also prevented depression-like behavior in mice after a sepsis episode. Thus, cit-AuNP therapy may potentially be used to prevent sepsis-induced depression.
Preparation and Evaluation of an Enrofloxacin Self-Micro Emulsion for Veterinary Use
Authors: Wu Hai-Gang , Wu Xian , Liu Jin-Ni , Chen Pei-Rong , Qin Qing-Ming , Deng Kai-Wei
Published: April 2023

We prepared an enrofloxacin self-micro emulsion and optimized the oil, emulsifier and co-emulsifiers using a pseudoternary phase diagram. The ratio of the oil phase to the emulsifier was used as the influencing factor, and the light transmittance was used as the evaluation index. The
formulation was optimized using a star design-effect surface method. We examined the preparation versus enrofloxacin solution as the control group at the recommended clinical dosage of enrofloxacin for 7 days in healthy broiler chickens. The optimal formulation was composed of 2.5% enrofloxacin,
oil phase 22% isopropyl myristate and 8% benzyl alcohol with the emulsifiers (i.e., 39% EL-40 and 13% Tween-80) and 17.5% 1,2-propanediol as co-emulsifier. The average particle size was 72 nm and emulsification time was 23 sec. The size and distribution of the microemulsion were uniform, and
the cumulative dissolution at 30 min was >80%. The mental states, food and water intake of the chickens in the test group were normal as with the blood biochemical indices. Histopathological examination showed no obvious hepatotoxicity. Slight damage to the lung and intestinal mucosa was
observed, but the degree of injury was similar to that of the enrofloxacin control solution. The self-micro emulsifying preparation of enrofloxacin possessed the advantages of simple preparation, good appearance, high emulsifying efficiency and good safety; therefore, it has a good application
value in a veterinary clinic.
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

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

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

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

In 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

Background

Genes 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.

Results

This 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.

Conclusions

Our 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

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

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

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

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

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

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.
Isolated optic neuritis with positive glial fibrillary acidic protein antibody
Authors: Jia Nan , Wang Jiawei , He Yuhong , Li Zhong , Lai Chuntao
Published: April 2023

Background and objectives

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON).

Methods

We performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test.

Results

Four patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms.

Conclusion

GFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.
Two patients with ZAP-70 deficiency in China present with a different genetic, immunological, and clinical phenotype
Authors: Luo Xianze , Liu Qing , Zhou Lina , Tang Xuemei , Zhao Xiaodong , Zhang Zhiyong
Published: April 2023

Zeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare autosomal recessive primary immunodeficiency disease. Little is known about this disease. In this study, we report two patients to extend the range of clinical phenotypes and immunophenotypes associated with ZAP-70 mutations. We describe the clinical, genetic, and immunological phenotypes of two patients with ZAP-70 deficiency in China, and the data are also compared with the literature. Case 1 presented with leaky severe combined immunodeficiency with low to the absence of CD8 + T cells, while case 2 suffered from a recurrent respiratory infection and had a past medical history of non-EBV-associated Hodgkin’s lymphoma. Sequencing revealed novel compound heterozygous mutations in ZAP-70 of these patients. Case 2 is the second ZAP-70 patient presenting a normal CD8 + T cell number. These two cases have been treated with hematopoietic stem cell transplantation. Selective CD8 + T cell loss is an essential feature of the immunophenotype of ZAP-70 deficiency patients, but there are exceptions. Hematopoietic stem cell transplantation can provide excellent long-term immune function and resolution of clinical problems.