bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between HCAHPS Scores and Survey Response Rate Is Linked to Hospital Size
Authors: Rodriguez-Homs Larissa G , Hammill Bradley G , Ryser Marc D , Phillips Harry R , Mosca Paul J
Published: June 2020

Patient experience is an important dimension of health care quality and is assessed using the standard Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey for inpatients. The HCAHPS scores may vary based on survey response rate and hospital size. The objective of this study was to describe the association between survey response rate and HCAHPS scores and examine whether the relationship varies based on hospital size. Medicare’s Hospital Compare publicly reported HCAHPS data were used. Pearson correlation, controlling for number of staffed beds, and linear regression models were used for the analysis. Hospitals were grouped into quartiles based on number of staffed beds to delineate the effect of increasing hospital size on the relationship between survey response rate and HCAHPS scores. A significant association between HCAHPS survey response rate and all examined HCAHPS domain scores was observed. The effect size across HCAHPS domains varied based on hospital size. The relationship between HCAHPS score and survey response rate differed significantly between hospitals in the smallest and largest size quartiles for discharge information, nurse communication, and hospital quietness. While a causal relationship cannot be inferred from this study, the response rate could be a direct and/or indirect driver of HCAHPS scores. Future research should be aimed to further explore the basis of this relationship and to determine how it may inform the interpretation of HCAHPS results.
Conflicting Notions of a Project: The Battle Between Albert O. Hirschman and Bent Flyvbjerg
Authors: Kreiner Kristian
Published: June 2020

The field of project management has erected an impressive edifice of knowledge that apparently hinders us in learning anything from experience except what we already know. We will use the recent controversy between Hirschman and Flyvbjerg to trace this academic imposition to a narrow notion of a project and to find inspiration in a radically different notion for opening the field to new types of issues and lessons.
Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance
Authors: Clay-Gilmour Alyssa I. , Hildebrandt Michelle A. T. , Brown Elizabeth E. , Hofmann Jonathan N. , Spinelli John J. , Giles Graham G. , Cozen Wendy , Bhatti Parveen , Wu Xifeng , Waller Rosalie G. , Belachew Alem A. , Robinson Dennis P. , Norman Aaron D. , Sinnwell Jason P. , Berndt Sonja I. , Rajkumar S. Vincent , Kumar Shaji K. , Chanock Stephen J. , Machiela Mitchell J. , Milne Roger L. , Slager Susan L. , Camp Nicola J. , Ziv Elad , Vachon Celine M.
Published: June 2020

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.
Ex vivo drug screening defines novel drug sensitivity patterns for informing personalized therapy in myeloid neoplasms
Authors: Spinner Michael A. , Aleshin Alexey , Santaguida Marianne T. , Schaffert Steven A. , Zehnder James L. , Patterson A. Scott , Gekas Christos , Heiser Diane , Greenberg Peter L.
Published: June 2020

Precision medicine approaches such as ex vivo drug sensitivity screening (DSS) are appealing to inform rational drug selection in myelodysplastic syndromes (MDSs) and acute myeloid leukemia, given their marked biologic heterogeneity. We evaluated a novel, fully automated ex vivo DSS platform that uses high-throughput flow cytometry in 54 patients with newly diagnosed or treatment-refractory myeloid neoplasms to evaluate sensitivity (blast cytotoxicity and differentiation) to 74 US Food and Drug Administration–approved or investigational drugs and 36 drug combinations. After piloting the platform in 33 patients, we conducted a prospective feasibility study enrolling 21 patients refractory to hypomethylating agents (HMAs) to determine whether this assay could be performed within a clinically actionable time frame and could accurately predict clinical responses in vivo. When assayed for cytotoxicity, ex vivo drug sensitivity patterns were heterogeneous, but they defined distinct patient clusters with differential sensitivity to HMAs, anthracyclines, histone deacetylase inhibitors, and kinase inhibitors (P < .001 among clusters) and demonstrated synergy between HMAs and venetoclax (P < .01 for combinations vs single agents). In our feasibility study, ex vivo DSS results were available at a median of 15 days after bone marrow biopsy, and they informed personalized therapy, which frequently included venetoclax combinations, kinase inhibitors, differentiative agents, and androgens. In 21 patients with available ex vivo and in vivo clinical response data, the DSS platform had a positive predictive value of 0.92, negative predictive value of 0.82, and overall accuracy of 0.85. These data demonstrate the utility of this approach for identifying potentially useful and often novel therapeutic drugs for patients with myeloid neoplasms refractory to standard therapies.
Prospective multicentre study on the safety and utility of transbronchial lung cryobiopsy with endobronchial balloon
Authors: Inomata Minoru , Kuse Naoyuki , Awano Nobuyasu , Tone Mari , Yoshimura Hanako , Jo Tatsunori , Minami Jonsu , Takada Kohei , Yuan Bae , Kumasaka Toshio , Yamakawa Hideaki , Sato Shintaro , Tobino Kazunori , Matsushima Hidekazu , Takemura Tamiko , Izumo Takehiro
Published: June 2020

Transbronchial lung cryobiopsy (TBLC) has been increasingly utilised to diagnose diffuse parenchymal lung diseases (DPLDs) and lung cancers; however, TBLC protocols have not yet been standardised and the rate of complications associated with this procedure vary widely. Therefore, this prospective multicentre observational study investigated the safety and utility of the TBLC technique in patients with diffuse and localised respiratory diseases.

This study was conducted at multiple medical centres in Japan between July 2018 and April 2019. The study's primary end-point was the rate of severe or serious adverse events associated with TBLC. Adverse events included bronchial bleeding, pneumothorax, pneumonia, respiratory failure, and an acute exacerbation of interstitial pneumonia. Adverse events were graded according to severity. During the TBLC procedure, an endobronchial balloon catheter for bronchial blockade was used in all patients. Pathological confidence and quality of specimens were categorised into three groups.

A total of 112 patients were included. Neither severe nor serious adverse events were identified; therefore, the primary end-point was met. Nineteen patients (17%) experienced no bronchial bleeding. Mild or moderate bronchial bleeding was identified in 67% and 16% of patients, respectively. Mild pneumothoraces were identified in four patients (3.6%). The safety profile in patients aged ≥75 years was not significantly different from younger patients. Definite or probable pathological diagnoses were made in 84.9% of patients.

This TBLC protocol with routine use of an endobronchial balloon had an acceptable safety profile and diagnostic yield in patients, including elderly ones, with diffuse and localised respiratory diseases.
Klotho is regulated by transcription factor Sp1 in renal tubular epithelial cells
Authors: Li Yan , Liu Yong , Wang Kailong , Huang Yinghui , Han Wenhao , Xiong Jiachuan , Yang Ke , Liu Mingying , Xiao Tangli , Liu Chi , He Ting , Bi Xianjin , Zhang Jingbo , Zhang Bo , Zhao Jinghong
Published: June 2020

Background

Klotho is a multifunctional protein, which exists both in a membrane bound and a soluble form. In renal tubules, Klotho is involved in cell senescence, anti-oxidant response, and renal fibrosis, thus regulation of its expression is critical to understand its roles in renal diseases. Indeed, reduced expression was observed in various renal disease. However, the mechanisms underlying transcriptional regulation of the human klotho gene (KL) largely remain unknown.

Results

Here we demonstrated that the Klotho expression in human renal tubular epithelial cells (RTECs) was enhanced by overexpression of the transcription factor Sp1. On the contrary, Klotho expression was decreased by Sp1 knockdown. Besides, increased expression of Sp1 alleviated TGF-β1-induced fibrosis in HK-2 cells by inducing Klotho expression. Luciferase reporter assays and chromatin immunoprecipitation assays further identified the binding site of Sp1 was located in − 394 to − 289 nt of the KL promoter, which was further confirmed by mutation analysis.

Conclusions

These data demonstrate that KL is a transcriptional target of Sp1 and TGF-β1-induced fibrosis was alleviated by Sp1 in human RTECs by directly modulating Klotho expression, which help to further understand the transcriptional regulation of Klotho in renal disease models.
The effect of variant interference on de novo assembly for viral deep sequencing
Authors: Castro Christina J. , Marine Rachel L. , Ramos Edward , Ng Terry Fei Fan
Published: June 2020

Background

Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approaches have surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored.

Results

Our results from > 15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This “variant interference” (VI) is highly consistent and reproducible by ten commonly-used de novo assemblers, and occurs over a range of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the “rescue” of full viral genomes from fragmented contigs.

Conclusions

These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.
RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes
Authors: Onizuka Satoru , Yamazaki Yasuharu , Park Sung-Joon , Sugimoto Takayuki , Sone Yumiko , Sjöqvist Sebastian , Usui Michihiko , Takeda Akira , Nakai Kenta , Nakashima Keisuke , Iwata Takanori
Published: June 2020

Background

Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin.

Results

We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandible (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyzed the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1, an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs.

Conclusions

Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.
Histone deacetylase 3 is required for development and metamorphosis in the red flour beetle, Tribolium castaneum
Authors: George Smitha , Palli Subba Reddy
Published: June 2020

Background

Hormones are chemical communication signaling molecules released into the body fluids to stimulate target cells of multicellular organisms. We recently showed that histone deacetylase 1 (HDAC1) plays an important role in juvenile hormone (JH) suppression of metamorphosis in the red flour beetle,Tribolium castaneum. Here, we investigated the function of another class I HDAC member, HDAC3, and show that it is required for the normal development ofT. castaneum.

Results

RNA interference-mediated knockdown of theHDAC3gene affected development resulting in abnormally folded wings in pupae and adults. JH analog, hydroprene, suppressed the expression ofHDAC3inT. castaneumlarvae. The knockdown ofHDAC3during the final instar larval stage resulted in an increase in the expression of genes coding for proteins involved in JH action. Sequencing of RNA isolated from larvae injected with dsRNA targetingmalE(E. coligene, control) orHDAC3followed by differential gene expression analysis identified 148 and 741 differentially expressed genes based on theP-value< 0.01 and four-fold difference, and the P-value< 0.05 and two-fold difference, respectively. Several genes, including those coding for myosin-I heavy chain (Myosin 22), Shaven, and nuclear receptor corepressor 1 were identified as differentially expressed genes inHDAC3knockdown larvae. An increase in histone H3 acetylation, specifically H3K9, H3K18, and H3K27, was detected inHDAC3knockdown insects.

Conclusion

Overall, these data suggest that HDAC3 affects the acetylation levels of histones and influences the expression of genes coding for proteins involved in the regulation of growth, development, and metamorphosis.
A TaqMan-based multiplex real-time PCR assay for the rapid detection of tigecycline resistance genes from bacteria, faeces and environmental samples
Authors: Li Yiming , Shen Zhangqi , Ding Shuangyang , Wang Shaolin
Published: June 2020

Background

Tigecycline is a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant bacteria. Recently, novel tigecycline resistance genes tet(X3) and tet(X4) have been reported, which pose a great challenge to human health and food security. The current study aimed to establish a TaqMan-based real-time PCR assay for the rapid detection of the tigecycline-resistant genes tet(X3) and tet(X4).

Results

No false-positive result was found, and the results of the TaqMan-based real-time PCR assay showed 100% concordance with the results of the sequencing analyses. This proposed method can detect the two genes at the level of 1 × 102 copies/μL, and the whole process is completed within an hour, allowing rapid screening of tet(X3) and tet(X4) genes in cultured bacteria, faeces, and soil samples.

Conclusion

Taken together, the TaqMan-based real-time PCR method established in this study is rapid, sensitive, specific, and is capable of detecting the two genes not only in bacteria, but also in environmental samples.
Size-dependent activity of silver nanoparticles on the morphological switch and biofilm formation of opportunistic pathogenic yeasts
Authors: Szerencsés Bettina , Igaz Nóra , Tóbiás Ákos , Prucsi Zsombor , Rónavári Andrea , Bélteky Péter , Madarász Dániel , Papp Csaba , Makra Ildikó , Vágvölgyi Csaba , Kónya Zoltán , Pfeiffer Ilona , Kiricsi Mónika
Published: June 2020

Background

Dimorphism and biofilm formation are important virulence factors of some opportunistic human pathogenic yeasts. Such species commensally colonize skin or mucosal surfaces generally in yeast form, but under particular circumstances, convert into virulent hyphae and disseminate internal organs or cause mucocutaneous infections. The yeast-to-hypha shape-conversion promotes the development of a biofilm, a thick extracellular matrix with sessile cells within. The biofilm is capable to prevent the penetration of antifungal drugs, rendering the surviving biofilm-resident cells intrinsic sources of recurrent infections. The aim of this study was to evaluate the ability of silver nanoparticles (AgNPs) to attenuate the morphological switch and biofilm formation of several opportunistic pathogenic yeasts and to determine whether this feature depends on the nanoparticle size.

Results

AgNPs in three different sizes were prepared by chemical reduction approach and characterized by transmission electron microscopy, ultraviolet–visible spectroscopy and dynamic light scattering. The antifungal activity was evaluated by the microdilution method, the inhibitory capacity on biofilm formation and the biofilm degradation ability of differently sized AgNPs was assessed by viability assay. The morphological state of opportunistic pathogenic yeast cells in monoculture and in co-culture with human keratinocytes in the presence of AgNPs was examined by flow cytometry and scanning electron microscopy. All the three AgNPs inhibited the growth of the examined opportunistic pathogenic yeasts, nevertheless, AgNPs with the smallest diameter exhibited the most prominent toxic activities. AgNPs attenuated the biofilm formation in a nanoparticle size-dependent manner; however, their biofilm destruction capacity was negligible. AgNPs with the smallest size exerted the most significant effect on suppressing the morphological change of pathogens in monoculture as well as in a co-culture with keratinocytes.

Conclusions

Our results confirm that AgNPs are capable to hinder yeast-to-hypha morphological conversion and biofilm formation of opportunistic pathogens and this biological effect of AgNPs is size-dependent.
Genome-wide identification and characterization of SnRK family genes in Brassica napus
Authors: Zhu Weizhuo , Wu Dezhi , Jiang Lixi , Ye Lingzhen
Published: June 2020

Background

Sucrose non-fermenting 1 related protein kinases (SnRK)play crucial roles in responding to biotic and abiotic stresses through activating protein phosphorylation pathways. However, little information ofSnRKgenes was available inBrassica napus, one of important oil crops. Recently, the released sequences of the reference genome ofB.napusprovide a good chance to perform genome-wide identification and characterization ofBnSnRKgene family in the rapeseed.

Results

Totally 114SnRKgenes distributed on 19 chromosomes were identified in the genome ofB.napusand classified into three subfamilies on the basis of phylogenetic analysis and the domain types. According to gene structure and motif composition analysis, theBnSnRKsequences showed obvious divergence among three subfamilies. Gene duplication and synteny between the genomes of the rapeseed andArabidopsiswere also analyzed to provide insights into the evolutionary characteristics ofBnSnRKfamily genes. Cis-element analysis revealed thatBnSnRKsmay response to diverse environmental stresses. Moreover, the expression patterns ofBnSnRKsin various tissues and under diverse abiotic stresses were distinct difference. Besides, Single Nucleotide Polymorphisms (SNP) distribution analysis suggests the function disparity ofBnSnRKfamily genes in different genotypes of the rapeseed.

Conclusion

We examined genomic structures, evolution features, expression patterns and SNP distribution of 114BnSnRKs. The results provide valuable information for functional characterization ofBnSnRKgenes in future studies.
Analysis of emergency department visits for all reasons by adults with depression in the United States
Authors: Hill Tyler , Jiang Yun , Friese Christopher R. , Darbes Lynae A. , Blazes Christopher K. , Zhang Xingyu
Published: June 2020

Background

We aimed to characterize Emergency Department (ED) utilization and outcomes of patients with depression seeking emergency care for all reasons.

Methods

Using 2014–2016 ED data from the National Hospital Ambulatory Medical Care Survey, we investigated demographics, ED resource utilization, clinical characteristics, and disposition of patients with depression versus those without depression.

Results

Approximately 10,626,184 (11.4%) out of 92,899,685 annual ED visits were by patients with depression. ED patients with depression were mostly non-Hispanic White (74.0%) and were less likely to be male than patients without depression (aOR: 0.62; [95%] CI: 0.57–0.68). ED patients with depression were more likely to be admitted to the hospital (aOR: 1.50; CI: 1.38–1.63) than patients without depression. Among ED patients with depression, males were more likely than females to be seeking emergency care for psychiatric reasons (OR: 2.45; 95% CI: 2.10–2.87)) and to present with overdose/poisoning (OR: 1.46; CI: 1.03–2.05).

Conclusions

We described the unique demographic, socioeconomic, and clinical characteristics of ED patients with depression, using the most comprehensive, nationally representative study to date. We revealed notable gender disparities in rates and reasons for admissions. The higher hospital and ICU admission rates of ED patients with depression suggests this population requires a higher level of emergency care, for reasons that remain poorly understood.
Clinical features of aseptic meningitis with varicella zoster virus infection diagnosed by next-generation sequencing: case reports
Authors: Chen Lanlan , Xu Yao , Liu Chunfeng , Huang Hong , Zhong Xingxing , Ma Cancan , Zhao Haina , Chen Yingzhu
Published: June 2020

Background

The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS).

Case presentation

Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22–52 years). The median symptoms onset to clinic time was 3.5 days (range 3–6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3–7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165–400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147–478 × 10^6/L; median 1.41 g/L, range 0.57–1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10–14 days. All patients recovered completely.

Conclusions

VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.
Towards accurate exclusion of neonatal bacterial meningitis: a feasibility study of a novel 16S rDNA PCR assay
Authors: Abelian Arthur , Mund Thomas , Curran Martin D. , Savill Stuart A. , Mitra Nipa , Charan Carol , Ogilvy-Stuart Amanda L. , Pelham Hugh R. B. , Dear Paul H.
Published: June 2020

Background

PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay’s potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the “field conditions” to attain a clinically useful level of specificity.

Methods

The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (Eppendorf™) replaced standard universal containers for collection of CSF to reduce environmental contamination.

Results

The assay’s specificity was 90.5% in CSF collected into the snap-top tubes – up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study.

Conclusions

A simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay’s sensitivity and its negative predictive value.
COVID-19 with acute cholecystitis: a case report
Authors: Ying Mingliang , Lu Bin , Pan Jiangfeng , Lu Guanghong , Zhou Shaobin , Wang Dingjun , Li Lu , Shen Junkang , Shu Jiner ,   From the COVID-19 Investigating and Research Team
Published: June 2020

Background

The 2019 novel coronavirus (COVID-19) presents a major threat to public health and has rapidly spread worldwide since the outbreak in Wuhan, Hubei Province, China in 2019. To date, there have been few reports of the varying degrees of illness caused by the COVID-19.

Case presentation

A case of 68-year-old female with COVID-19 pneumonia who had constant pain in the right upper quadrant of her abdomen during her hospitalization that was finally diagnosed as acute cholecystitis. Ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) was performed, and the real-time fluorescence polymerase chain reaction (RT-PCR) COVID-19 nucleic acid assay of the bile was found to be negative. PTGD, antibacterial and anti-virus combined with interferon inhalation treatment were successful.

Conclusion

The time course of chest CT findings is typical for COVID-19 pneumonia. PTGD is useful for acute cholecystitis in COVID-19 patients. Acute cholecystitis is likely to be caused by COVID-19 .
HIV patients retention and attrition in care and their determinants in Ethiopia: a systematic review and meta-analysis
Authors: Abebe Moges Nurilign , Olubukola Adesina , Micheal Okunlola , Berhane Yemane
Published: June 2020

Background

There is paucity of evidence on the magnitude of HIV patients’ retention and attrition in Ethiopia. Hence, the aim of this study was to determine the pooled magnitude of HIV patient clinical retention and attrition and to identify factors associated with retention and attrition in Ethiopia.

Methods

Systematic review and meta-analysis were done among studies conducted in Ethiopia using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Both published and unpublished studies conducted from January 1, 2005 to June 6th, 2019 were included. Major databases and search engines such as Google Scholar, PUBMED, African Journals Online (AJOL) and unpublished sources were searched to retrieve relevant articles. Data were assessed for quality, heterogeneity and publication bias. Analysis was conducted using STATA version 14 software.

Result

From a total of 45 studies 546,250 study participants were included in this review. The pooled magnitude of retention in care among HIV patients was 70.65% (95% CI, 68.19, 73.11). The overall magnitude of loss to follow up 15.17% (95% CI, 11.86, 18.47), transfer out 11.17% (95% CI, 7.12, 15.21) and death rate were 6.75% (95% CI, 6.22, 7.27). Major determinants of attrition were being unmarried patient (OR 1.52, 95% CI: 1.15–2.01), non-disclosed HIV status (OR 6.36, 95% CI: 3.58–11.29), poor drug adherence (OR 6.60, 95% CI: 1.41–30.97), poor functional status (OR 2.11, 95% CI: 1.33–3.34), being underweight (OR 2.21, 95% CI: 1.45–3.39) and advanced clinical stage (OR 1.85, 95% CI: 1.36–2.51). Whereas absence of opportunistic infections (OR 0.52, 95% CI: 0.30–0.9), normal hemoglobin status (OR 0.29, 95% CI: 0.20–0.42) and non-substance use (OR 95% CI: 0.41, 0.17–0.98) were facilitators of HIV patient retention in clinical care.

Conclusion

The level of retention to the care among HIV patients was low in Ethiopia. Socio-economic, clinical, nutritional and behavioral, intervention is necessary to achieve adequate patient retention in clinical care.
Utility of FDG PET/CT for assessment of lung nodules identified during low dose computed tomography screening
Authors: Hadique Sarah , Jain Pranav , Hadi Yousaf , Baig Aneeqah , Parker John E.
Published: June 2020

Background

Many clinical guidelines recommend FDG PET/CT for the evaluation of pulmonary nodules ≥8 mm detected during low dose computed tomography (LDCT) lung cancer screening. However, its added value in this setting requires confirmation. We evaluated the clinical utility of FDG PET/CT, including incidental findings, during the evaluation of lung nodules detected on LDCT screening.

Methods

A retrospective cohort study was performed among 75 patients who completed FDG PET/CT between January 2010 and December 2017, after lung nodules > 8 mm had been detected on LDCT lung cancer screening. We report demographic variables, characteristics of the initial nodules on LDCT and FDG PET/CT, incidental findings on FDG PET/CT, as well as further work up performed and the influence of FDG PET/CT findings on management.

Results

Nodules were reported to be benign on FDG PET/CT in 38/75 (50.6%) patients. Physicians chose either radiological follow-up or no further work up in all 38. FDG PET/CT was indeterminate or suggested malignancy in 37 (49.3%) patients. Biopsy was performed in 32 (86%) of these patients. Incidental findings on FDG PET/CT were reported in 37/75 (49%) patients. Further work-up of incidental findings was performed in 21/75 (28%) of patients.

Conclusions

In this study, for majority of individuals with lung nodules identified during LDCT lung cancer screening, FDG PET/CT results were able to guide physicians in choosing between routine follow up or invasive biopsies. Conversely, 28% of these patients required additional investigations to address incidental findings.
Prevalence of renal dysfunction among HIV infected patients receiving Tenofovir at Mulago: a cross-sectional study
Authors: Nyende Louis , Kalyesubula Robert , Sekasanvu Emmanuel , Byakika-Kibwika Pauline
Published: June 2020

Background

There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly.

Method

This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented.

Results

We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29–45) years; median duration on ART was 36 (IQR 24–60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%).

Conclusions

The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.
Diagnosis of triple negative breast cancer based on radiomics signatures extracted from preoperative contrast-enhanced chest computed tomography
Authors: Feng Qingliang , Hu Qiang , Liu Yan , Yang Tao , Yin Ziyi
Published: June 2020

Background

To explore the diagnostic value of radiomics features of preoperative computed tomography (CT) for triple negative breast cancer (TNBC) for better treatment of patients with breast cancer.

Methods

A total of 890 patients with breast cancer admitted to our hospital from June 2016 to January 2018 were analyzed. They were diagnosed by surgery and pathology to have mass and invasive breast cancer and had contrast-enhanced chest CT examination before operation. 300 patients were randomly selected for the study, including 100 TNBC and 200 non-TNBC (NTNBC) patients. Among them 180 were used in discovery group and 120 were used in validation group. The molecular subtypes of breast cancer in the patients were determined immunohistochemistrially. Radiomics features were extracted from three dimensional CT-images. The LASSO logistic method was used to select image features and calculate radiomics scores. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of radiomics scores for TNBC.

Results

Five image features were found to be related to TNBC subtype (P < 0.001). These image features based-radiomic signatures had good predictive values for TNBC with the areas under ROC curve (AUC) of 0.881 (95% CI: 0.781–0.921) in the discovery group and 0.851 (95% CI: 0.761–0.961) in the validation group, respectively. The sensitivities and specificities were 0.767, and 0.873 in the discovery group and 0.785 and 0.915 in the validation group.

Conclusions

Radiomic signature based on preoperative CT is capable of distinguishing patients with TNBC and NTNBC. It adds additional value for conventional chest contrast-enhanced CT and helps plan the strategy for clinical treatment of the patients.
The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer
Authors: Ma Fang , Xie Yangchun , Lei Yiyu , Kuang Zengshuyu , Liu Xianling
Published: June 2020

Background

Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells along with metastasis in vivo, and to explore the underlying mechanism.

Methods

RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual-luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-5p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays.

Results

miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interact with STK32A to promote its expression. Following the validation of the supporting role of STK32A in NSCLC cells and NF-κB p65 phosphorylation, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo.

Conclusions

miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A/NF-κB p65 axis, offering possible targets for the treatment for NSCLC.
Immune-related genes in tumor-specific CD4+ and CD8+ T cells in colon cancer
Authors: Yang Xi , Wu Wei , Pan Yuefen , Zhou Qing , Xu Jiamin , Han Shuwen
Published: June 2020

Background

Immune escape is an immunological mechanism underlying tumorigenesis, and T cells play an important role in this process. In this study, immune-related genes were evaluated in tumor-infiltrating CD4+and CD8+T cells in colon cancer.

Methods

ESTIMATE was used to calculate stromal and immune scores for tumor datasets downloaded from The Cancer Genome Atlas–Colon Cancer (COAD). Differentially expressed genes (DEGs) between samples with high and low stromal and immune scores were screened, followed by a functional enrichment analysis of the overlapping DEGs. The DEGs related to CD4+and the CD8+T cells were then screened. Predicted miRNA–mRNA and lncRNA–miRNA pairs were used to construct a competing endogenous RNA (ceRNA) network. Furthermore, chemical–gene interactions were predicted for genes in the ceRNA network. Kaplan–Meier survival curves were also plotted.

Results

In total, 83 stromal-related DEGs (5 up-regulated and 78 down-regulated) and 1270 immune-related DEGs (807 up-regulated and 293 down-regulated genes) were detected. The 79 overlapping DEGs were enriched for 39 biological process terms. Furthermore, 79 CD4+T cell-related genes and 8 CD8+T cell-related genes, such as ELK3, were screened. Additionally, ADAD1 and DLG3, related to CD4+T cells, were significantly associated with the prognosis of patients with colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes obtained from CD4+and CD8+T cell-related ceRNAs were identified as candidates for further studies.

Conclusion

ELK3 is a candidate immune-related gene in colon cancer. The chr22-38_28785274–29,006,793.1–miR-106a-5p-DDHD1 and chr22-38_28785274–29,006,793.1–miR-4319-GRHL1 axes may be related to CD4+and CD8+T cell infiltration in colon cancer.
Acute retinal necrosis following dexamethasone intravitreal implant (Ozurdex®) administration in an immunocompetent adult with a history of HSV encephalitis: a case report
Authors: Zhang Zhi-Yong , Liu Xiu-Yun , Jiang Tao
Published: June 2020

Background

Dexamethasone intravitreal implants (0.7 mg) (Ozurdex®, Allergan Inc., Madison, NJ) are FDA approved for managing macular oedema (ME) of retinal vein occlusion (RVO). The major complications associated with intravitreal Ozurdex® implant include increased intraocular pressure and cataract progression. In regard to the occurrence of retinal complications, we report an unusual intravitreal Ozurdex® implantation-related acute retinal necrosis (ARN).

Case presentation

A 45-year-old immunocompetent woman with a history of encephalitis presented with photophobia, redness, floaters, and rapidly decreased vision in her left eye. Three and six months ago, she received two doses of intravitreal Ozurdex® implant for ME of RVO. Clinical evaluation, including slit-lamp biomicroscopy, retinal photography, and fluorescein angiography, revealed anterior chamber cells, granulomatous keratic precipitates, cells in the vitreous, optic disc oedema, occlusive retinal vasculitis, scattered retinal haemorrhages, one quadrant of peripheral white areas with retinal necrosis, optic disc and vessels fluorescein staining, and retinal nonperfusion zones. All the above clinical manifestations showed an ARN. Herpes simplex virus was detected in the aqueous and vitreous humour by quantitative polymerase chain reaction testing. Intravenous acyclovir 500 mg tid for 7 days followed by oral valcyclovir was immediately performed for ARN. At 4 months, the patient’s condition improved without retinal detachment, and the best-corrected visual acuity remained stable at 0.3.

Conclusions

ARN might represent a risk of Ozurdex® administration.
Comparison of fundus changes following silicone oil and sterilized air tamponade for macular-on retinal detachment patients
Authors: Zhou Yifan , Zhang Siqi , Zhou Hao , Gao Min , Liu Haiyun , Sun Xiaodong
Published: June 2020

Background

To investigate different tamponade effects of intravitreal silicone oil (SO) and sterilized air on macular vasculature and structure after successful retinal repair for macular-on rhegmatogenous retinal detachment (RRD) patients.

Method

21 eyes (21 patients) with macular-on RRD underwent single pars plana vitrectomy following intravitreal SO or sterilized air (Gas) tamponade. Optical Coherence Tomography (OCT) and angiography were used to evaluate retinal layer thickness and flow density (FD) changes throughout the observation period of 12 weeks. Retinal layers were segmented into 7 sets: NFL, GCL + IPL, INL, OPL, ONL + IS, OS+RPE and BRM. Macular perfusion system was segmented into superficial and deep capillary plexus flow density (SCPFD, DCPFD), and choriocapillaries plexus flow density (CCPFD).

Result

Compared to Gas tamponade, SO tamponade led to more decrease in both superficial and deep retinal blood flow during observation. NFL thickness was found to decrease in both Gas tamponade and SO tamponade eyes. SO tamponade resulted in more pronounced decrease which led to significant intergroup difference. Opposite changing trends were found in GCL + IPL and ONL + IS thicknesses due to different means of tamponade. SO tamponade caused thicknesses of these two segmented layers to decrease, which led to significant intergroup differences. SO tamponade also led to more decrease in INL, OPL thicknesses. No significant intergroup difference of choroidal thickness was observed.

Conclusion

Compared to gas, silicone oil could have more negative tamponade effects on both fundus vasculature and structure.
Mental health stigma and mental health knowledge in Chinese population: a cross-sectional study
Authors: Yin Huifang , Wardenaar Klaas J. , Xu Guangming , Tian Hongjun , Schoevers Robert A.
Published: June 2020

Background

Little is known about the public stigma on mental illness and mental health knowledge (MHK) in China, public stigma and low MHK can negatively affect patients’ health and increase the burden of mental disorders on society. This study aimed at investigating the rates of stigma and MHK, the correlates of stigma and MHK, and the association between MHK and stigma among a Chinese population.

Methods

The data is from the Tianjin Mental Health Survey (TJMHS), which involved a large and a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). In a 12% random subsample (n = 1775) the Perceived Discrimination and Devaluation scale (PDD) and a Mental Health Knowledge Questionnaire (MHKQ) were administered. First, percentages of the responses to the individual items of the PDD and MHKQ were investigated. Second, sociodemographic correlates of PDD and MHK, and the association between stigma and MHK were investigated.

Results

We found that a sizable proportion of participants responded that others would hold a negative attitude towards (former) mental patients, especially with regard to engaging in closer personal relationships. Most people were not familiar about the causes, treatments and prevention of mental illness. Resident area, age, education level, Per capita family income and employment status were related to devaluation score and MHKQ score. MHK was negatively associated with public stigma.

Conclusions

There is room for improvement with regard to levels of public stigma and MHK in China. Providing psychoeducation to improve public MHK could also contribute to reduction of public stigma.
Building towards common psychosocial measures in U.S. cohort studies: principal investigators’ views regarding the role of religiosity and spirituality in human health
Authors: Shields Alexandra E. , Balboni Tracy A.
Published: June 2020

Background

The goal of this study was to understand prospective cohort study Principal Investigators’ (PIs’) attitudes regarding the importance of religion and spirituality (R/S) on disease etiology in order to identify barriers and opportunities for greater inclusion of these domains in high-quality epidemiological research.

Methods

One-hour, semi-structured qualitative interviews were conducted with 20 PIs, who represent 24 different National Institutes of Health (NIH)-funded prospective cohort studies in the U.S. Collectively, these PIs collect detailed health data on approximately 1.25 of every 100 adult Americans. Sample size was calculated to achieve thematic saturation.

Results

The majority of PIs we interviewed viewed R/S as potentially important factors influencing disease etiology, particularly among minority communities that report higher levels of religiosity. Yet nearly all PIs interviewed felt there was not yet a compelling body of evidence elucidating R/S influences on health, and the potential mechanisms through which R/S may be operating to affect health outcomes. PIs identified 5 key areas that would need to be addressed before they would be persuaded to collect more R/S measures in their cohorts: (1) high-quality, prospective studies that include all appropriate covariates for the outcome under study; (2) studies that posit a plausible biological mechanism of effect; (3) well-validated R/S measures, collected in common across multiple cohorts; (4) the need to address bias against R/S research among investigators; and (5) NIH funding for R/S research.

Conclusions

Results of this study provide a roadmap for future R/S research investigating the impact of R/S influences on disease etiology within the context of U.S. prospective cohort studies. Identifying significant R/S influences on health could inform novel interventions to improve population health. Given the higher levels of religiosity/spirituality among minority communities, R/S research may also provide new leverage points for reducing health disparities.