bluuebunny/crossref_metadata_2025 huggingface dataset:
Validating the regional estimates of changes in soil organic carbon by using the data from paired-sites: the case study of Mediterranean arable lands
Authors: Schillaci Calogero , Saia Sergio , Lipani Aldo , Perego Alessia , Zaccone Claudio , Acutis Marco
Published: June 2021

Background

Legacy data are unique occasions for estimating soil organic carbon (SOC) concentration changes and spatial variability, but their use showed limitations due to the sampling schemes adopted and improvements may be needed in the analysis methodologies. When SOC changes is estimated with legacy data, the use of soil samples collected in different plots (i.e., non-paired data) may lead to biased results. In the present work, N = 302 georeferenced soil samples were selected from a regional (Sicily, south of Italy) soil database. An operational sampling approach was developed to spot SOC concentration changes from 1994 to 2017 in the same plots at the 0–30 cm soil depth and tested.

Results

The measurements were conducted after computing the minimum number of samples needed to have a reliable estimate of SOC variation after 23 years. By applying an effect size based methodology, 30 out of 302 sites were resampled in 2017 to achieve a power of 80%, and an α = 0.05.

A Wilcoxontestapplied to the variation of SOC from 1994 to 2017 suggested that there was not a statistical difference in SOC concentration after 23 years (Z = − 0.556; 2-tailed asymptotic significance = 0.578). In particular, only 40% of resampled sites showed a higher SOC concentration than in 2017.

Conclusions

This finding contrasts with a previous SOC concentration increase that was found in 2008 (75.8% increase when estimated as differences of 2 models built with non-paired data), when compared to 1994 observed data (Z = − 9.119; 2-tailed asymptotic significance < 0.001).

This suggests that the use of legacy data to estimate SOC concentration dynamics requires soil resampling in the same locations to overcome the stochastic model errors. Further experiment is needed to identify the percentage of the sites to resample in order to align two legacy datasets in the same area.
A HIF1α-GPD1 feedforward loop inhibits the progression of renal clear cell carcinoma via mitochondrial function and lipid metabolism
Authors: Liu Ren , Feng Yuanfa , Deng Yulin , Zou Zhihao , Ye Jianheng , Cai Zhiduan , Zhu Xuejin , Liang Yingke , Lu Jianming , Zhang Hui , Luo Yong , Han Zhaodong , Zhuo Yangjia , Xie Qingling , Hon Chi Tin , Liang Yuxiang , Wu Chin-Lee , Zhong Weide
Published: June 2021

Background

Hypoxia signaling, especially the hypoxia inducible factor (HIF) pathway, is a major player in clear cell renal cell carcinoma (ccRCC), which is characterized by disorders in lipid and glycogen metabolism. However, the interaction between hypoxia and lipid metabolism in ccRCC progression is still poorly understood.

Methods

We used bioinformatic analysis and discovered that glycerol-3-phosphate dehydrogenase 1 (GPD1) may play a key role in hypoxia and lipid metabolism pathways in ccRCC. Tissue microarray, IHC staining, and survival analysis were performed to evaluate clinical function. In vitro and in vivo assays showed the biological effects of GPD1 in ccRCC progression.

Results

We found that the expression of GPD1 was downregulated in ccRCC tissues, and overexpression of GPD1 inhibited the progression of ccRCC both in vivo and in vitro. Furthermore, we demonstrated that hypoxia inducible factor-1α (HIF1α) directly regulates GPD1 at the transcriptional level, which leads to the inhibition of mitochondrial function and lipid metabolism. Additionally, GPD1 was shown to inhibit prolyl hydroxylase 3 (PHD3), which blocks prolyl-hydroxylation of HIF1α and subsequent proteasomal degradation, and thus reinforces the inhibition of mitochondrial function and phosphorylation of AMPK via suppressing glycerol-3-phosphate dehydrogenase 2 (GPD2).

Conclusions

This study not only demonstrated that HIF1α-GPD1 forms a positive feedforward loop inhibiting mitochondrial function and lipid metabolism in ccRCC, but also discovered a new mechanism for the molecular basis of HIF1α to inhibit tumor activity, thus providing novel insights into hypoxia-lipid-mediated ccRCC therapy.
Staphylococcus aureus ventilator-associated pneumonia in patients with COVID-19: clinical features and potential inference with lung dysbiosis
Authors: De Pascale Gennaro , De Maio Flavio , Carelli Simone , De Angelis Giulia , Cacaci Margherita , Montini Luca , Bello Giuseppe , Cutuli Salvatore Lucio , Pintaudi Gabriele , Tanzarella Eloisa Sofia , Xhemalaj Rikardo , Grieco Domenico Luca , Tumbarello Mario , Sanguinetti Maurizio , Posteraro Brunella , Antonelli Massimo
Published: June 2021

Background

Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.

Methods

We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.

Results

We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non–COVID-19 group of SA-VAP patients.

Conclusions

In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.
Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation
Authors: Albani Filippo , Pisani Luigi , Ciabatti Gianni , Fusina Federica , Buizza Barbara , Granato Anna , Lippolis Valeria , Aniballi Eros , Murgolo Francesco , Rosano Antonio , Latronico Nicola , Antonelli Massimo , Grasso Salvatore , Natalini Giuseppe
Published: June 2021

Background

The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation.

Methods

Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume.

Results

Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods.

Conclusions

Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions.
The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle
Authors: Furlan-Magaril Mayra , Ando-Kuri Masami , Arzate-Mejía Rodrigo G. , Morf Jörg , Cairns Jonathan , Román-Figueroa Abraham , Tenorio-Hernández Luis , Poot-Hernández A. César , Andrews Simon , Várnai Csilla , Virk Boo , Wingett Steven W. , Fraser Peter
Published: June 2021

Background

Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized.

Results

Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes.

Conclusion

Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations.
Global transcriptome landscape of the rabbit protozoan parasite Eimeria stiedae
Authors: Xie Yue , Xiao Jie , Zhou Xuan , Gu Xiaobin , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou
Published: June 2021

Background

Coccidiosis caused by Eimeria stiedae is a widespread and economically significant disease of rabbits. The lack of studies on the life-cycle development and host interactions of E. stiedae at the molecular level has hampered our understanding of its pathogenesis.

Methods

In this study, we present a comprehensive transcriptome landscape of E. stiedae to illustrate its dynamic development from unsporulated oocysts to sporulated oocysts, merozoites, and gametocytes, and to identify genes related to parasite-host interactions during parasitism using combined PacBio single-molecule real-time and Illumina RNA sequencing followed by bioinformatics analysis and qRT-PCR validation.

Results

In total, 12,582 non-redundant full-length transcripts were generated with an average length of 1808 bp from the life-cycle stages of E. stiedae. Pairwise comparisons between stages revealed 8775 differentially expressed genes (DEGs) showing highly significant description changes, which compiled a snapshot of the mechanisms underlining asexual and sexual biology of E. stiedae including oocyst sporulation between unsporulated and sporulated oocysts; merozoite replication between sporulated oocysts and merozoites; and gametophyte development and gamete generation between merozoites and gametocytes. Further, 248 DEGs were grouped into nine series clusters and five groups by expression patterns, and showed that parasite–host interaction-related genes predominated in merozoites and gametocytes and were mostly involved in steroid biosynthesis and lipid metabolism and carboxylic acid. Additionally, co-expression analyses identified genes associated with development and host invasion in unsporulated and sporulated oocysts and immune interactions during gametocyte parasitism.

Conclusions

This is the first study, to our knowledge, to use the global transcriptome profiles to decipher molecular changes across the E. stiedae life cycle, and these results not only provide important information for the molecular characterization of E. stiedae, but also offer valuable resources to study other apicomplexan parasites with veterinary and public significance.

Graphical Abstract
A case of lymphocytic esophagitis in a woman with multiple allergies
Authors: Wojas O. , Żalikowska-Gardocka M. , Krzych-Fałta E. , Szczepankiewicz B. , Samel-Kowalik P. , Samoliński B. , Przybyłkowski A.
Published: June 2021

Background

Lymphocytic esophagitis is a newly recognized entity of unknown origin. Dysphagia is defined as difficulty swallowing and represents a common symptom in the general population with a prevalence of approximately 20%. Chronic inflammation of the esophageal wall may manifest itself clinically and endoscopically, mimicking inflammation of another origin. However, little is known about the pathogenesis of the disease, as patients are seldom suspected and rarely diagnosed with lymphocytic esophagitis.

Case presentation

Here, we present a rare case of lymphocytic esophagitis in a patient with multiple allergies and suspected eosinophilic esophagitis. A 28-year-old woman with polyvalent sensitization to food and inhalant allergens presented with intermittent dysphagia, a sensation of a foreign body in the throat, itchiness of the oral cavity after ingesting certain foods, heartburn, and prolonged chewing time. A skin prick test showed positive results for birch-tree, alder, hazel, and rye pollen, as well as house dust mites. Apart from obesity (BMI 30 kg/m2), multiple pustules and excoriations on the skin, her physical examination was insignificant. Esophagogastroduodenoscopy (EGD) was performed revealing full-length but discrete trachealization of the esophagus. A barium swallow test showed slowing of esophageal peristalsis in the recumbent position. No esophageal pathology was observed. A histopathological analysis of mucosal samples revealed slight hyperplasia of the basal layer of the esophagus, and the stomach showed changes typical of chronic gastritis.

Conclusions

In summary, this clinical case illustrates that lymphocytic esophagitis, as a newly recognized entity, should be considered in the differential diagnosis of chronic dysphagia. Additionally, when treating allergic patients, clinicians should be aware that lymphocytic esophagitis, distinct from eosinophilic esophagitis, should be considered in the diagnosis of patients with atopy and upper gastrointestinal symptoms.
Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum
Authors: Suzman Evan , Williams Zachary J. , Feldman Jacob I. , Failla Michelle , Cascio Carissa J. , Wallace Mark T. , Niarchou Maria , Sutcliffe James S. , Wodka Ericka , Woynaroski Tiffany G.
Published: June 2021

Background

Individuals on the autism spectrum are reported to display alterations in interoception, the sense of the internal state of the body. The Interoception Sensory Questionnaire (ISQ) is a 20-item self-report measure of interoception specifically intended to measure this construct in autistic people. The psychometrics of the ISQ, however, have not previously been evaluated in a large sample of autistic individuals.

Methods

Using confirmatory factor analysis, we evaluated the latent structure of the ISQ in a large online sample of adults on the autism spectrum and found that the unidimensional model fit the data poorly. Using misspecification analysis to identify areas of local misfit and item response theory to investigate the appropriateness of the seven-point response scale, we removed redundant items and collapsed the response options to put forth a novel eight-item, five-response choice ISQ.

Results

The revised, five-response choice ISQ (ISQ-8) showed much improved fit while maintaining high internal reliability. Differential item functioning (DIF) analyses indicated that the items of the ISQ-8 were answered in comparable ways by autistic adolescents and adults and across multiple other sociodemographic groups.

Limitations

Our results were limited by the fact that we did not collect data for typically developing controls, preventing the analysis of DIF by diagnostic status. Additionally, while this study proposes a new 5-response scale for the ISQ-8, our data were not collected using this method; thus, the psychometric properties for the revised version of this instrument require further investigation.

Conclusion

The ISQ-8 shows promise as a reliable and valid measure of interoception in adolescents and adults on the autism spectrum, but additional work is needed to examine its psychometrics in this population. A free online score calculator has been created to facilitate the use of ISQ-8 latent trait scores for further studies of autistic adolescents and adults (available athttps://asdmeasures.shinyapps.io/ISQ_score/).
From hypotonic maintenance fluid to severe hyponatremia: a case report
Authors: Denis M. , Di Giacomo A. , Lacotte E. , Porcheret F. , Letouzé N. , Lauzier B. , Goyer I. , Brossier D.
Published: June 2021

Background

The principles for maintenance intravenous fluid prescription in children were developed in the 1950s. These guidelines based on the use of hypotonic solutions have been challenged regularly for they seem to be associated with an increased risk of hospital-acquired hyponatremia.

Case presentation

We report the case of a 4-week-old Caucasian child admitted for acute bronchiolitis who received hypotonic maintenance fluids and developed severe hyponatremia (94 mmol/L) with hyponatremic encephalopathy.

Conclusion

This clinical situation can serve as a reminder of the latest recommendations from the American Academy of Pediatrics regarding the use of intravenous fluids that promote the use of isotonic fluids in children.
Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state
Authors: Shan Ti-Dong , Yue Han , Sun Xue-Guo , Jiang Yue-Ping , Chen Li
Published: June 2021

Background

The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism.

Methods

Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM.

Results

Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression.

Conclusions

Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.
Crucial mutation in the exoribonuclease domain of nsp14 of PEDV leads to high genetic instability during viral replication
Authors: Niu Xiaoyu , Kong Fanzhi , Hou Yixuan J. , Wang Qiuhong
Published: June 2021

Background

Coronavirus (CoV) nonstructural protein 14 (nsp14) has exoribonuclease (ExoN) activity, responsible for proofreading and contributing to replication fidelity. It has been reported that CoVs exhibit variable sensitivity to nsp14-ExoN deficiency. Betacoronavirus murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV were viable upon nsp14-ExoN deficiency. While betacoronavirus Middle East respiratory syndrome (MERS)-CoV and SARS-CoV-2 were non-viable with disabled nsp14-ExoN. In this study, we investigated the nsp14-ExoN deficiency of alphacoronavirus porcine epidemic diarrhea virus (PEDV) in viral pathogenesis using reverse genetics.

Results

Eight nsp14-ExoN deficient mutants, targeting the predicted active sites and the Zinc finger or mental-coordinating sites, of PEDV were designed. Only one mutant E191A with a mutation in the Mg2+-binding site was rescued using the infectious clone of PEDV PC22A strain (icPC22A). The passage no.1–3 (P1-3) of E191A grew to very low titers in Vero cells. To evaluate the pathogenesis of the E191A, 4 or 5-day-old gnotobiotic pigs were inoculated orally with 100 TCID50/pig of the E191A-P1, icPC22A, or mock. All mock pigs did not shed virus in feces or show clinical signs. All pigs inoculated with icPC22A shed high viral RNA levels, had severe diarrhea, and died by 6 days post-inoculation (dpi). In contrast, only 3 pigs (3/4, 75%) in the E191A-P1 group shed low levels of viral RNA and 2 pigs had moderate diarrhea at acute infection phase. At 22 dpi, each pig was challenged orally with 106 plaque forming unit of virulent icPC22A. All pigs in the mock group developed severe diarrhea and 2 of the 5 pigs died. Pigs in the E191A-P1 group had less severe diarrhea and no pigs died. Sanger sequencing analysis revealed that the viral genome in the fecal sample of one E191A-P1-inoculated pig and the P4 virus passaged in vitro lost the E191A mutation, suggesting the genetic instability of the E191A mutant.

Conclusion

The recombinant PEDV variants carrying mutations at the essential functional sites within nsp14-ExoN were either lethal or genetically unstable. Our finding further confirmed the critical role of nsp14-ExoN in CoV life cycle, suggesting that it may be a target for the design of universal anti-CoV drugs.
Latency optimization for D2D-enabled parallel mobile edge computing in cellular networks
Authors: Cai Yan , Ran Liang , Zhang Jun , Zhu Hongbo
Published: June 2021

Edge offloading, including offloading to edge base stations (BS) via cellular links and to idle mobile users (MUs) via device-to-device (D2D) links, has played a vital role in achieving ultra-low latency characteristics in 5G wireless networks. This paper studies an offloading method of parallel communication and computation to minimize the delay in multi-user systems. Three different scenarios are explored, i.e., full offloading, partial offloading, and D2D-enabled partial offloading. In the full offloading scenario, we find a serving order for the MUs. Then, we jointly optimize the serving order and task segment in the partial offloading scenario. For the D2D-enabled partial offloading scenario, we decompose the problem into two subproblems and then find the sub-optimal solution based on the results of the two subproblems. Finally, the simulation results demonstrate that the offloading method of parallel communication and computing can significantly reduce the system delay, and the D2D-enabled partial offloading can further reduce the latency.
A global perspective on macroprudential policy interaction with systemic risk, real economic activity, and monetary intervention
Authors: Stolbov Mikhail I. , Shchepeleva Maria A. , Karminsky Alexander M.
Published: June 2021

The study empirically assesses how macroprudential policy interacts with systemic risk, industrial production, and monetary intervention on a global level from January 2006 to December 2018. We adopt the aggregate proxies of these variables, capturing their global effects, and use a novel econometric technique, namely, smooth local projections. The study finds that global macroprudential policy leads the monetary policy, exhibiting a countercyclical pattern concerning industrial production. The latter has an inverse bidirectional linkage with systemic risk. Thus, an ex-ante tight macroprudential policy can indirectly mitigate global systemic risk through its pro-growth effect on industrial production, although no convincing evidence exists for the direct impact of a macroprudential intervention on systemic risk. The study results endure several extensions and a robustness check, which builds on alternative measures of global systemic stress and real economic activity, thereby legitimizing the increased importance attached to the macroprudential policy since the 2007–2009 global financial crisis.
A community-based, cross-sectional study to assess interactions between income, nutritional status and enteric parasitism in two Brazilian cities: are we moving positively towards 2030?
Authors: Calegar Deiviane A. , Bacelar Polyanna A. , Monteiro Kerla J. L. , dos Santos Jessica P. , Gonçalves Andressa B. , Boia Márcio N. , Jaeger Lauren H. , Coronato-Nunes Beatriz , Carvalho-Costa Filipe A.
Published: June 2021

Background

This study assessed the interactions between income, nutritional status and intestinal parasitism in children in Brazil.

Methods

A cross-sectional study (n = 421 children aged 1 to 14 years living in the states of Piauí (rural communities in the city of Teresina) and Rio de Janeiro (rural and periurban communities in the city of Cachoeiras de Macacu) was performed in order to obtain income and anthropometric data, as well as fecal samples for parasitological analyses through the Ritchie technique.

Results

Children infected with Ascaris lumbricoides had significantly lower means of height-for-age z scores (− 1.36 ± 0.75 vs. − 0.11 ± 1.02; p < 0.001), weight-for-age z scores (− 1.23 ± 0.74 vs. 0.09 ± 1.15; p = 0.001), and weight-for-height z scores (− 0.68 ± 0.44 vs. 0.23 ± 1.25; p = 0.006) when compared with uninfected children. Infection with hookworm was also associated with lower means of height-for-age z scores (− 1.08 ± 1.17 vs. − 0.12 ± 1.02; p = 0.015) and weight-for-age z scores (− 1.03 ± 1.13 vs. 0.08 ± 1.15; p = 0.012). Children infected with Entamoeba coli presented significantly lower means of height-for-age z scores (− 0.54 ± 1.02 vs. − 0.09 ± 1.02; p = 0.005) and weight-for-age z scores (− 0.44 ± 1.15 vs. 0.12 ± 1.15; p = 0.002). The multivariate multiple linear regression analysis showed that height-for-age z scores are independently influenced by monthly per capita family income (β = 0.145; p = 0.003), female gender (β = 0.117; p = 0.015), and infections with A. lumbricoides (β = − 0.141; p = 0.006) and Entamoeba coli (β = − 0.100; p = 0.043). Weight-for-age z scores are influenced by monthly per capita family income (β = 0.175; p < 0.001), female gender (β = 0.123; p = 0.010), and infections with A. lumbricoides (β = − 0.127; p = 0.012), and Entamoeba coli (β = − 0.101; p = 0.039). Monthly per capita family income (β = 0.102; p = 0.039) and female gender (β = 0.134; p = 0.007) positively influences mid upper arm circumpherence.

Conclusions

Intestinal parasitism and low family income negatively influence the physical development of children in low-income communities in different Brazilian regions.
Patient-reported anxiety and depression measures for use in Indian head and neck cancer populations: a psychometric evaluation
Authors: Shunmugasundaram Chindhu , Dhillon Haryana M. , Butow Phyllis N. , Sundaresan Puma , Chittem Mahati , Akula Niveditha , Veeraiah Surendran , Rutherford Claudia
Published: June 2021

Background

Head and neck cancers (HNC) are one of the most traumatic forms of cancer because they affect essential aspects of life such as speech, swallowing, eating and disfigurement. HNCs are common in India, with over 100,000 cases being registered each year. HNC and treatment are both associated with considerable anxiety and depression. With increasing multinational research, no suitable measures in Indian languages are available to assess anxiety and depression in Indian HNC patients. This study evaluated the psychometric properties of cross-culturally adapted versions of Zung’s self-rating Anxiety Scale (SAS) and the Patient health questionnaire – 9 (PHQ-9) in Tamil, Telugu and Hindi speaking Indian HNC populations.

Methods

HNC patients were recruited from three tertiary cancer centres in India. Patients completed the cross-culturally adapted versions of SAS and PHQ-9. We assessed targeting, scaling assumptions, construct validity (exploratory and confirmatory factor analyses), convergent validity, and internal consistency reliability.

Results

The study sample included 205 Tamil, 216 Telugu and 200 Hindi speaking HNC patients. Exploratory and confirmatory factor analyses indicated a two-factor solution for PHQ-9 and four-factor solution for SAS in all three languages. Cronbach’s alpha coefficients ranged between 0.717 and 0.890 for PHQ-9 and between 0.803 and 0.868 for SAS, indicating good reliability. Correlations between hypothesized scales were as expected providing evidence towards convergent validity.

Conclusions

This first psychometric evaluation of the measurement properties of Tamil, Telugu and Hindi versions of the SAS and PHQ-9 in large, Indian HNC populations supported their use as severity and outcome measures across the disease and treatment continuum.
Percutaneous transhepatic treatment of a unique portal vein malformation with portal hypertension in a pediatric patient
Authors: Marra Paolo , Dulcetta Ludovico , Pellegrinelli Claudia , D’Antiga Lorenzo , Sironi Sandro
Published: June 2021

Background

Anomalies of the portal venous system can be congenital or acquired, the latter being related to spontaneous thrombosis or iatrogenic alterations such as complications of perinatal catheterization of the umbilical vein. These conditions can be clinically silent for years and then manifest abruptly causing severe clinical emergencies.

Case presentation

This case report describes the diagnosis and interventional management of a singular abnormality in the portal venous system of an 8-year-old female that led to severe portal hypertension and acute variceal bleeding. Peculiar imaging findings were not pathognomonic for any of the known congenital and acquired portal vein anomalies: absence of a normal extrahepatic portal vein; splenic and mesenteric veins merging into a dilated left gastric vein; presence of an aberrant mesenteric venous collateral with a stenotic connection with the intrahepatic right portal branch; and absence of porto-systemic shunt. The case was successfully managed with percutaneous transhepatic portography and angioplasty.

Conclusions

Prompt non-invasive imaging characterization allowed to understand the singular vascular abnormality and mini-invasive interventional radiology management resolved portal hypertension and variceal bleeding.
Letter to the Editor: Analysis of stroke patient migration for mechanical thrombectomy and changes in neurointerventional center size in Germany
Authors: Weber Ralph , Bartig Dirk , Krogias Christos , Richter Daniel , Hacke Werner , Eyding Jens
Published: June 2021

Aim and methods

To analyse nationwide changes in neurointerventional center size of all German hospitals performing mechanical thrombectomy (MT) in stroke patients from 2016 to 2019. Furthermore, we assessed cross-district patient migration for MT for the first time using hospitals’ structured quality reports and German Diagnosis-Related Groups data in 2019.

Findings

Number of hospitals performing more than 100 MT procedures/year doubled in Germany from 2016 (n = 36) to 2019 (n = 71), and these neurointerventional centers performed 71% of all MT procedures in 2019. The overall increase in MT procedures was largely driven by these high-volume neurointerventional centers with ability to perform MT 24/7 (121% increase as compared with 8% increase in hospitals performing less than 100 MT procedures/year). The highest cross-district patient mobility/transfer of stroke patients for MT was observed in districts adjacent to these high-volume neurointerventional centers with existing neurovascular networks.

Conclusion

The substantial increase in MT procedures observed in Germany between 2016 and 2019 was almost exclusively delivered by high-volume stroke centers performing more than 100 MT procedures per year in established neurovascular networks. As there is still a reasonable number of districts with low MT rates, further structural improvement including implementation of new or expansion of existing neurovascular networks and regional tailored MT triage concepts is needed.
The global challenge of providing mental health services in poverty: the situation of Northern Haiti
Authors: Cénat Jude Mary , Harerimana Boniface , Michel Guesly , McIntee Sara-Emilie , Mukunzi Joana N. , Hajizadeh Saba , Dalexis Rose Darly
Published: June 2021

When people living in poverty are asked to describe their living conditions, mental health issues quickly come to mind (grief, sadness, anger, fear, bitterness, frustration, discontent, anxiety, and emotional damage consisting of low mood and depression, fatigue, hypersensitivity, sleep difficulties and physical pain). Although the association between poverty and mental health have been widely demonstrated in the literature, care must be taken to avoid the psychiatrization of poverty. However, how can healthcare be provided to people living in poverty when basic needs are not met? This article explores the global challenge of providing mental health services in impoverished populations, using the example of the poorest country in America: Haiti. It examines the availability of services offered through the Mental Health Centre at Morne Pelé, and the necessity for innovative and comprehensive approaches to provide culturally appropriate care that meets the real needs of populations. It highlights effective measures that policy makers should implement to develop an efficient mental healthcare system based on the lessons of the Mental Health Centre at Morne Pelé.
Implementing Electronic Patient-Reported Outcomes for Patients With New Oral Chemotherapy Prescriptions at an Academic Site and a Community Site
Authors: Doolin Jim W. , Berry Jonathan L. , Forbath Natalia S. , Tocci Noah X. , Dechen Tenzin , Li Stephanie , Hartwell Rebekah A. , Espiritu Jennifer K. , Roberts Daniel A. , Zerillo Jessica A. , Shea Meghan
Published: June 2021

PURPOSE

Oral chemotherapy challenges providers' abilities to safely monitor patients' symptoms, adherence, and financial toxicity. COVID-19 has increased the urgency of caring for patients remotely. Collection of electronic patient-reported outcomes (ePROs) has demonstrated efficacy for patients on intravenous chemotherapy, but limited data support their use in oral chemotherapy. We undertook a pilot project to assess the feasibility of implementing an ePRO system for patients starting oral chemotherapy at our cancer center, which includes both an academic site and a community site.

METHODS

Patients initiating oral chemotherapy were asked to participate. A five-question tool was built in REDCap. Concerning responses triggered outreach within one business day. The primary outcome was time to first symptom assessment. For comparison, we used a historical cohort of patients who had been prescribed oral chemotherapies by providers in the same disease groups at the cancer center.

RESULTS

Twenty-five of 62 (40%) patients completed ePRO assessments. Fifty historical charts were reviewed. Time to first symptom assessment was 7 days (IQR, 4-14 days) in the historical group compared with 3 days (IQR, 2-4 days) in the ePRO group. Time to clinical action was 14 days (7-35 days) in the historical group compared with 8 days (4-19 days) in the ePRO group. No statistically significant differences were detected in 30-day emergency department visit or hospitalization (12% for both groups) or 90-day emergency department visit or hospitalization rates (historical 28% and ePRO 20%).

CONCLUSION

An ePRO tool monitoring patient concerns about adherence, cost, and toxicities for patients with new oral chemotherapy regimens is feasible and improves time to symptom assessment. Further investigation is needed to improve patient engagement with ePROs and evaluate the long-term impacts for patients on oral chemotherapy.
Clinicopathologic Features and Response to Therapy ofNRG1Fusion–Driven Lung Cancers: The eNRGy1 Global Multicenter Registry
Authors: Drilon Alexander , Duruisseaux Michael , Han Ji-Youn , Ito Masaoki , Falcon Christina , Yang Soo-Ryum , Murciano-Goroff Yonina R. , Chen Haiquan , Okada Morihito , Molina Miguel Angel , Wislez Marie , Brun Philippe , Dupont Clarisse , Branden Eva , Rossi Giulio , Schrock Alexa , Ali Siraj , Gounant Valérie , Magne Fanny , Blum Torsten Gerriet , Schram Alison M. , Monnet Isabelle , Shih Jin-Yuan , Sabari Joshua , Pérol Maurice , Zhu Viola W. , Nagasaka Misako , Doebele Robert , Camidge D. Ross , Arcila Maria , Ou Sai-Hong Ignatius , Moro-Sibilot Denis , Rosell Rafael , Muscarella Lucia Anna , Liu Stephen V. , Cadranel Jacques
Published: June 2021

PURPOSE

Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion–positive lung cancers in the largest and most diverse series to date.

METHODS

From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion–positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed.

RESULTS

Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion–positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5′ partners, 20 unique epidermal growth factor domain–inclusive chimeric events, and heterogeneous 5′/3′ breakpoints were found. Platinum-doublet and taxane-based (post–platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS.

CONCLUSION

NRG1 fusion–positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.
Mobile Health Application for Patients Undergoing Breast Cancer Surgery: Feasibility Study
Authors: Ponder Madison , Venkatraman Vishal , Charalambous Lefko , Ansah-Yeboah Abena A. , Adil Syed M. , Antezana Luis A. , Dharmapurikar Rajeev , Gellad Ziad F. , Lad Shivanand P. , Hwang E. Shelley , Plichta Jennifer K.
Published: June 2021

PURPOSE:

Contemporary breast cancer surgery often requires hospital stays of 1 day or less, presenting challenges to delivery of high-quality care. Without sufficient time for proper education and guidance, patients may delay seeking care, experience anxiety, or seek unnecessary care, leading to poorer outcomes and increased costs. To address this, we evaluated the feasibility of a planning-, outcomes-, and analytics-based mobile health application called Manage My Surgery (MMS) for patients undergoing elective breast cancer surgery.

METHODS:

Patients undergoing breast cancer surgery at an academic health center were invited to use MMS. Those who used the application received pre- and postoperative surveys, which recorded and reported patient satisfaction and outcomes related to the application.

RESULTS:

Thirty-three female patients undergoing elective breast cancer surgery used MMS. The median age was 58 years. Nineteen patients underwent lumpectomy, and 14 underwent mastectomy. Users logged on to the application an average of 3.5 times. The median number of questions viewed was 12 (range 2-35). Of 17 patients who completed the feedback survey, 100% said that MMS was helpful during preparation for surgery, 82.3% said that MMS was helpful postoperatively, and 94.1% would recommend MMS to others. Preliminary data on patient-reported outcomes collected by MMS suggest improvements in anxiety and depression over time.

CONCLUSION:

Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs.
Calcifediol Treatment and COVID-19–Related Outcomes
Authors: Nogues Xavier , Ovejero Diana , Pineda-Moncusí Marta , Bouillon Roger , Arenas Dolors , Pascual Julio , Ribes Anna , Guerri-Fernandez Robert , Villar-Garcia Judit , Rial Abora , Gimenez-Argente Carme , Cos Maria Lourdes , Rodriguez-Morera Jaime , Campodarve Isabel , Quesada-Gomez José Manuel , Garcia-Giralt Natalia
Published: June 2021

Context

COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity.

Objective

This work aims to elucidate the effect of 25(OH)D3 (calcifediol) treatment on COVID-19–related outcomes.

Methods

This observational cohort study was conducted from March to May 2020, among patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 patients with COVID-19 were included; 92 were excluded because of previous calcifediol intake. Of the remaining 838, a total of 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), whereas 391 were not treated at the time of hospital admission (intention-to-treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy individuals, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main outcome measures were ICU admission and mortality.

Results

ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required the ICU, compared to 82 (21%) out of 391 nontreated (P < .001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25-hydroxyvitamin D levels at baseline, and comorbidities showed that treated patients had a reduced risk of requiring the ICU (odds ratio [OR] 0.13; 95% CI 0.07-0.23). Overall mortality was 10%. In the intention-to-treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 nontreated (P = .001). Adjusted results showed a reduced mortality risk with an OR of 0.21 (95% CI, 0.10-0.43). In the second analysis, the obtained OR was 0.52 (95% CI, 0.27-0.99).

Conclusion

In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality.
Piecemeal regulation of convergent neuronal lineages by bHLH transcription factors inCaenorhabditis elegans
Authors: Masoudi Neda , Yemini Eviatar , Schnabel Ralf , Hobert Oliver
Published: June 2021

Cells of the same type can be generated by distinct cellular lineages that originate in different parts of the developing embryo (‘lineage convergence’). Several Caenorhabditis elegans neuron classes composed of left/right or radially symmetric class members display such lineage convergence. We show here that the C. elegans Atonal homolog lin-32 is differentially expressed in neuronal lineages that give rise to left/right or radially symmetric class members. Loss of lin-32 results in the selective loss of the expression of pan-neuronal markers and terminal selector-type transcription factors that confer neuron class-specific features. Another basic helix-loop-helix (bHLH) gene, the Achaete-Scute homolog hlh-14, is expressed in a mirror image pattern relative to lin-32 and is required to induce neuronal identity and terminal selector expression on the contralateral side of the animal. These findings demonstrate that distinct lineage histories converge via different bHLH factors at the level of induction of terminal selector identity determinants, which thus serve as integrators of distinct lineage histories. We also describe neuron-to-neuron identity transformations in lin-32 mutants, which we propose to also be the result of misregulation of terminal selector gene expression.