bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and Treatment of Sciatica in the Netherlands: A Survey among Neurologists and Anesthesiologists
Authors: ter Meulen Bastiaan , Overweg Caroliene , Feenstra Thomas , Brouwer Brigitte , Terheggen Michel , van Dongen Hanneke , Kallewaard Jan Willem , Ostelo Raymond , Weinstein Henry
Published: April 2021

Background: This study aimed to assess how Dutch neurologists and anesthesiologists diagnose and treat people with sciatica in secondary care and to evaluate their adherence to the newest guidelines. Methods: We conducted a cross-sectional survey. Respondents were asked about their current clinical practice related to sciatica. Three authors rated the respondents’ adherence to the guidelines on a three-point Likert scale. Results: Eighty neurologists and 44 anesthesiologists completed the questionnaire. Neurologists diagnose their sciatica patients primarily using a magnetic resonance imaging (89%). Selective diagnostic nerve blocks are considered useful by 81% of the neurologists. Neurologists primarily treat patients with pain medication, and 40% of them think epidural steroid injections are effective in 40–60% of injected patients. Twenty-nine percent of neurologists refer patients to a neurosurgeon after 4 months. Anesthesiologists consider a selective diagnostic nerve root block to have a higher diagnostic value than mapping. The most reported side effect of epidural injections is exacerbation of pain (82%). Pulse radiofrequency is applied in 9–11% of acute cases. The results also indicate that Dutch neurologists and anesthesiologists follow an evidence-based approach that is strictly or broadly in line with the guideline. Conclusions: Neurologists treat sciatica patients initially with pain medication and physiotherapy, followed by epidural steroid injections and referral for surgery. Anesthesiologists treat sciatica patients with one or more steroid injections or may perform a selective nerve root block. Imaging, selective nerve root blocks, medication, physiotherapy, and pulse radiofrequency are topics of further research.
A Nomogram to Predict Individual Survival of Patients with Liver-Limited Metastases from Gastroenteropancreatic Neuroendocrine Neoplasms: A US Population-Based Cohort Analysis and Chinese Multicenter Cohort Validation Study
Authors: Xu Gang , Xiao Yao , Hu Hanjie , Jin Bao , Wu Xiang’an , Wan Xueshuai , Zheng Yongchang , Xu Haifeng , Lu Xin , Sang Xinting , Ge Penglei , Mao Yilei , Cai Jianqiang , Zhao Hong , Du Shunda
Published: April 2021

Introduction: Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. Methods: Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. Results: A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all p < 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. Conclusion: A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.
Quantitative Magnetic Resonance-Derived Biomarkers as Predictors of Function and Histotype in Adenohypophyseal Tumours
Authors: Lewis Daniel , Roncaroli Federico , Kearney Tara , Coope David John , Gnanalingham Kanna
Published: April 2021

Introduction: Magnetic resonance imaging (MRI) is the main modality to diagnose adenohypophyseal tumours, while biochemical assessment of pituitary hormones allows for their functional classification. In this retrospective exploratory cohort study, we investigated if quantitative differences in tumour MR signal intensity (SI) could be utilized to predict the function and histotype. Methods: Clinically acquired pretreatment MRI images were retrospectively analysed in 67 clinically non-functioning gonadotropinomas (NFG), 38 somatotropinomas, and 16 medically treated giant macroprolactinomas. Mean T1- and T2-weighted SI values were determined for each tumour and normalized against either centrum semiovale white matter or CSF to derive relative T1W and T2W SI values and the relative tumour T2/T1 SI ratio. Inter-group differences in quantitative MR parameters were compared, and the power of each parameter to discriminate tumour type and subtype was assessed using the area under the receiver operator characteristic curve (AUROC). In resected somatotropinomas, the relationship between tumour granulation status, relative MR SI values, and biochemical data was also compared. Results: Compared to somatotropinomas, NFG and macroprolactinomas displayed higher relative T2W SI (p < 0.001) and higher relative tumour T2/T1 SI ratio values (p < 0.001, ANOVA). Compared to intermediate/densely granulated tumours, sparsely granulated somatotropinomas were larger (p = 0.006, Mann-Whitney U test), had higher relative T2W SI (p ≤ 0.005), and higher relative tumour T2/T1 SI ratios (p ≤ 0.001, 2-tailed t test). Relative tumour T2W SI values and relative tumour T2/T1 ratio values demonstrated good discriminatory power in differentiating NFG from somatotropinoma (AUROC = 0.87–0.94) and predicting somatotropinoma subtypes (AUROC = 0.87–0.95). Conclusion: Quantitative SI-based MR parameters derived using clinical acquisition MRI protocols may help non-invasively discriminate the functional status of adenohypophyseal tumours and the histological subtype of somatotropinomas.
Spatiotemporal movement pattern of Asian Elephants Elephas maximus Linnaeus, 1758 in Sindhudurg District, Maharashtra, India
Authors: Patil Milind Digambar , Patil Vinayak Krishna , Mungi Ninad Avinash
Published: April 2021

The extension of the Asian Elephant’s Elephas maximus range in the northern Western Ghats (Sahyadri) was observed since 2002.  This colonization was marked by elephant crop raiding events in the newly colonized Sindhudurg District, where the local community had no experience of living with elephants.  The present study was conducted to understand the spatiotemporal patterns of crop depredation (raiding) and to prioritize areas to inform future interventions on managing this ecological phenomenon turned conflict.  Data on crop raiding between 2002 and 2015 was obtained from compensation records with the state forest department, and mapped at village scale.  Subsequently, we used three indices of crop raiding, viz., Crop Raiding Frequency (CRF), Relative Crop Raiding Intensity (RCRI), and Crop Raiding Vulnerability Index (CRVI).  Results show a gradual northern movement of elephants and of the crop raiding zone over the period of 2002–2015.  The rankings provided by CRVI, identified villages in a narrow strip of foothills of the Sahyadri mountains as severely vulnerable.  With sufficient long term data, CRVI would be a highly useful index for prioritization of villages for resolving human-elephant negative interactions; and other cases of human-wildlife interactions too.
The Malay Cardamom Meistera aculeata (Roxb.) Škorničk. & M.F. Newman (Zingiberaceae: Alpinioideae) from the Palghat gap: a new record to Kerala, India
Authors: Aswani Vadakkeveedu Jagadesh , Jabeena Manjakulam Khadhersha , Nair Maya Chandrashekaran
Published: April 2021

Meistera aculeata (Roxb.) Škorničk. & M.F.Newman (Zingiberaceae, subfamily - Alpinioideae) a lesser known species, has been located from the Palakkad (Palghat) Gap region in the Walayar Hill ranges of the southern Western Ghats and reported here as an addition to the flora of Kerala.  A detailed taxonomic description along with photographs are provided.
Two new species of Euphaea Selys, 1840 (Odonata: Zygoptera: Euphaeidae) from northern Western Ghats, India
Authors: Bhakare Shriram Dinkar , Nair Vinayan P. , Pawar Pratima Ashok , Bhoite Sunil Hanmant , Sadasivan Kalesh
Published: April 2021

Two new species of the damselfly genus Euphaea Selys, 1840 (Odonata: Euphaeidae) are described from the Western Ghats of Satara District, Maharashtra, distinguished by their distinct morphology and coloration. E. thosegharensis Sadasivan & Bhakare sp. nov. is similar to E. cardinalis (Fraser, 1924), but is distinguished by the extensor and flexor surface of all femora black while all femora bright red in E. cardinalis; apical fourth of Hw black while apical half of Hw black in E. cardinalis; genae reddish-orange, black in E. cardinalis; a tuft of sparse stub black hair on either side of tergite of S9 while both S8 and S9 with tufts of long ventral hairs in E. cardinalis.  Male genital vesicle matt black, with distal border rounded angles, while vesicle black and hexagonal in shape with rounded angles in E. cardinalis and S9 twice the length of S10, while S9 and S10 of equal length in E. cardinalis. E. pseudodispar Sadasivan & Bhakare sp. nov., is very close to E. dispar (Rambur, 1842), but is differentiated easily by the absence of yellow patch on legs as in E. dispar; only apical fifth of Hw black; genae being yellowish-white, while black in E. dispar; male genital vesicle brownish-black & rhomboid-shaped and with no transverse rugosities while black with distal border rounded and with fine transverse rugosities in E. dispar; penis with single seta on each side while E. dispar has three pairs; sternite of S9 very prominently extending ventrally like a beak in comparison with E. dispar.  We have identified additional morphological characters useful in taxonomy of Euphaea of the Western Ghats for example, tufts of ventral hairs on terminal abdominal segments genital vesicle, penile structure of males and sternite of S9 in the males, and vulvar scales of females.  A taxonomic key to all known species of genus Euphaea of the Western Ghats is also provided.
New records of six termite (Blattodea: Termitidae) species from Kerala, India
Authors: Amina Poovoli , Rajmohana K.
Published: April 2021

The present paper reports new records of six species of termites (Blattodea: Termitidae), viz.,  Angulitermes acutus Mathur & Sen-Sarma, Dicuspiditermes obtusus (Silvestri), Pericapritermes dunensis (Roonwal & Sen-Sarma), Pericapritermes topslipensis Thakur, Nasutitermes cherraensis Roonwal & Chhotani, and Nasutitermes kali Roonwal & Chhotani from Kerala.  Three species P. dunensis, N. cherraensis and N. kali are reported for the first time from the Western Ghats. The details of materials collected, diagnostic characters and distribution data in India are provided.
A checklist of fishes of Telangana State, India
Authors: Prasad Kante Krishna , Srinivasulu Chelmala
Published: April 2021

A checklist of freshwater fishes of Telangana State, India including accepted common name, vernacular name, IUCN status, and endemicity is presented.  Freshwater fish diversity of Telangana State is represented by 143 species belonging to 14 orders and 34 families.  Two species, Rita bakalu and Indoreonectes telanganaensis are endemic to Telangana State.
Stroke Care in the United Kingdom During the COVID-19 Pandemic
Authors: Douiri Abdel , Muruet Walter , Bhalla Ajay , James Martin , Paley Lizz , Stanley Kaili , Rudd Anthony G. , Wolfe Charles D.A. , Bray Benjamin D. ,   on behalf of the SSNAP Collaboration
Published: April 2021

Background and Purpose:

The coronavirus disease 2019 (COVID-19) pandemic has potentially caused indirect harm to patients with other conditions via reduced access to health care services. We aimed to describe the impact of the initial wave of the pandemic on admissions, care quality, and outcomes in patients with acute stroke in the United Kingdom.

Methods:

Registry-based cohort study of patients with acute stroke admitted to hospital in England, Wales, and Northern Ireland between October 1, 2019, and April 30, 2020, and equivalent periods in the 3 prior years.

Results:

One hundred fourteen hospitals provided data for a study cohort of 184 017 patients. During the lockdown period (March 23 to April 30), there was a 12% reduction (6923 versus 7902) in the number of admissions compared with the same period in the 3 previous years. Admissions fell more for ischemic than hemorrhagic stroke, for older patients, and for patients with less severe strokes. Quality of care was preserved for all measures and in some domains improved during lockdown (direct access to stroke unit care, 1-hour brain imaging, and swallow screening). Although there was no change in the proportion of patients discharged with good outcome (modified Rankin Scale score, ≤2; 48% versus 48%), 7-day inpatient case fatality increased from 6.9% to 9.4% (
P
<0.001) and was 22.0% in patients with confirmed or suspected COVID-19 (adjusted rate ratio, 1.41 [1.11–1.80]).

Conclusions:

Assuming that the true incidence of acute stroke did not change markedly during the pandemic, hospital avoidance may have created a cohort of untreated stroke patients at risk of poorer outcomes or recurrent events. Unanticipated improvements in stroke care quality should be used as an opportunity for quality improvement and to learn about how to develop resilient health care systems.
B-cell receptor signaling and genetic lesions in TP53 and CDKN2A/CDKN2B cooperate in Richter transformation
Authors: Chakraborty Supriya , Martines Claudio , Porro Fabiola , Fortunati Ilaria , Bonato Alice , Dimishkovska Marija , Piazza Silvano , Yadav Brijesh S. , Innocenti Idanna , Fazio Rosa , Vaisitti Tiziana , Deaglio Silvia , Zamò Alberto , Dimovski Aleksandar J. , Laurenti Luca , Efremov Dimitar G.
Published: April 2021

B-cell receptor (BCR) signals play a critical role in the pathogenesis of chronic lymphocytic leukemia (CLL), but their role in regulating CLL cell proliferation has still not been firmly established. Unlike normal B cells, CLL cells do not proliferate in vitro upon engagement of the BCR, suggesting that CLL cell proliferation is regulated by other signals from the microenvironment, such as those provided by Toll-like receptors or T cells. Here, we report that BCR engagement of human and murine CLL cells induces several positive regulators of the cell cycle, but simultaneously induces the negative regulators CDKN1A, CDKN2A, and CDKN2B, which block cell-cycle progression. We further show that introduction of genetic lesions that downregulate these cell-cycle inhibitors, such as inactivating lesions in CDKN2A, CDKN2B, and the CDKN1A regulator TP53, leads to more aggressive disease in a murine in vivo CLL model and spontaneous proliferation in vitro that is BCR dependent but independent of costimulatory signals. Importantly, inactivating lesions in CDKN2A, CDKN2B, and TP53 frequently co-occur in Richter syndrome (RS), and BCR stimulation of human RS cells with such lesions is sufficient to induce proliferation. We also show that tumor cells with combined TP53 and CDKN2A/2B abnormalities remain sensitive to BCR-inhibitor treatment and are synergistically sensitive to the combination of a BCR and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor both in vitro and in vivo. These data provide evidence that BCR signals are directly involved in driving CLL cell proliferation and reveal a novel mechanism of Richter transformation.
MADGAN: unsupervised medical anomaly detection GAN using multiple adjacent brain MRI slice reconstruction
Authors: Han Changhee , Rundo Leonardo , Murao Kohei , Noguchi Tomoyuki , Shimahara Yuki , Milacski Zoltán Ádám , Koshino Saori , Sala Evis , Nakayama Hideki , Satoh Shin’ichi
Published: April 2021

Background

Unsupervised learning can discover various unseen abnormalities, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer’s disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with either disease stages, various (i.e., more than two types of) diseases, or multi-sequence magnetic resonance imaging (MRI) scans.

Results

We propose unsupervised medical anomaly detection generative adversarial network (MADGAN), a novel two-step method using GAN-based multiple adjacent brain MRI slice reconstruction to detect brain anomalies at different stages on multi-sequence structural MRI: (Reconstruction) Wasserstein loss with Gradient Penalty + 100$$\ell _1$$ℓ1loss—trained on 3 healthy brain axial MRI slices to reconstruct the next 3 ones—reconstructs unseen healthy/abnormal scans; (Diagnosis) Average$$\ell _2$$ℓ2loss per scan discriminates them, comparing the ground truth/reconstructed slices. For training, we use two different datasets composed of 1133 healthy T1-weighted (T1) and 135 healthy contrast-enhanced T1 (T1c) brain MRI scans for detecting AD and brain metastases/various diseases, respectively. Our self-attention MADGAN can detect AD on T1 scans at a very early stage, mild cognitive impairment (MCI), with area under the curve (AUC) 0.727, and AD at a late stage with AUC 0.894, while detecting brain metastases on T1c scans with AUC 0.921.

Conclusions

Similar to physicians’ way of performing a diagnosis, using massive healthy training data, our first multiple MRI slice reconstruction approach, MADGAN, can reliably predict the next 3 slices from the previous 3 ones only for unseen healthy images. As the first unsupervised various disease diagnosis, MADGAN can reliably detect the accumulation of subtle anatomical anomalies and hyper-intense enhancing lesions, such as (especially late-stage) AD and brain metastases on multi-sequence MRI scans.
Paired-end small RNA sequencing reveals a possible overestimation in the isomiR sequence repertoire previously reported from conventional single read data analysis
Authors: Sanchez Herrero Jose Francisco , Pluvinet Raquel , Luna de Haro Antonio , Sumoy Lauro
Published: April 2021

Background

Next generation sequencing has allowed the discovery of miRNA isoforms, termed isomiRs. Some isomiRs are derived from imprecise processing of pre-miRNA precursors, leading to length variants. Additional variability is introduced by non-templated addition of bases at the ends or editing of internal bases, resulting in base differences relative to the template DNA sequence. We hypothesized that some component of the isomiR variation reported so far could be due to systematic technical noise and not real.

Results

We have developed the XICRA pipeline to analyze small RNA sequencing data at the isomiR level. We exploited its ability to use single or merged reads to compare isomiR results derived from paired-end (PE) reads with those from single reads (SR) to address whether detectable sequence differences relative to canonical miRNAs found in isomiRs are true biological variations or the result of errors in sequencing. We have detected non-negligible systematic differences between SR and PE data which primarily affect putative internally edited isomiRs, and at a much smaller frequency terminal length changing isomiRs. This is relevant for the identification of true isomiRs in small RNA sequencing datasets.

Conclusions

We conclude that potential artifacts derived from sequencing errors and/or data processing could result in an overestimation of abundance and diversity of miRNA isoforms. Efforts in annotating the isomiRnome should take this into account.
CarSite-II: an integrated classification algorithm for identifying carbonylated sites based on K-means similarity-based undersampling and synthetic minority oversampling techniques
Authors: Zuo Yun , Lin Jianyuan , Zeng Xiangxiang , Zou Quan , Liu Xiangrong
Published: April 2021

Background

Carbonylation is a non-enzymatic irreversible protein post-translational modification, and refers to the side chain of amino acid residues being attacked by reactive oxygen species and finally converted into carbonyl products. Studies have shown that protein carbonylation caused by reactive oxygen species is involved in the etiology and pathophysiological processes of aging, neurodegenerative diseases, inflammation, diabetes, amyotrophic lateral sclerosis, Huntington’s disease, and tumor. Current experimental approaches used to predict carbonylation sites are expensive, time-consuming, and limited in protein processing abilities. Computational prediction of the carbonylation residue location in protein post-translational modifications enhances the functional characterization of proteins.

Results

In this study, an integrated classifier algorithm, CarSite-II, was developed to identify K, P, R, and T carbonylated sites. The resampling method K-means similarity-based undersampling and the synthetic minority oversampling technique (SMOTE-KSU) were incorporated to balance the proportions of K, P, R, and T carbonylated training samples. Next, the integrated classifier system Rotation Forest uses “support vector machine” subclassifications to divide three types of feature spaces into several subsets. CarSite-II gained Matthew’s correlation coefficient (MCC) values of 0.2287/0.3125/0.2787/0.2814, False Positive rate values of 0.2628/0.1084/0.1383/0.1313, False Negative rate values of 0.2252/0.0205/0.0976/0.0608 for K/P/R/T carbonylation sites by tenfold cross-validation, respectively. On our independent test dataset, CarSite-II yield MCC values of 0.6358/0.2910/0.4629/0.3685, False Positive rate values of 0.0165/0.0203/0.0188/0.0094, False Negative rate values of 0.1026/0.1875/0.2037/0.3333 for K/P/R/T carbonylation sites. The results show that CarSite-II achieves remarkably better performance than all currently available prediction tools.

Conclusion

The related results revealed that CarSite-II achieved better performance than the currently available five programs, and revealed the usefulness of the SMOTE-KSU resampling approach and integration algorithm. For the convenience of experimental scientists, the web tool of CarSite-II is available in http://47.100.136.41:8081/
Genetic diversity structure of western-type carrots
Authors: Stelmach Katarzyna , Macko-Podgórni Alicja , Allender Charlotte , Grzebelus Dariusz
Published: April 2021

Background

Carrot is a crop with a wide range of phenotypic and molecular diversity. Within cultivated carrots, the western gene pool comprises types characterized by different storage root morphology. First western carrot cultivars originated from broad-based populations. It was followed by intercrosses among plants representing early open-pollinated cultivars, combined with mass phenotypic selection for traits of interest. Selective breeding improved root uniformity and led to the development of a range of cultivars differing in root shape and size. Based on the root shape and the market use of cultivars, a dozen of market types have been distinguished. Despite their apparent phenotypic variability, several studies have suggested that western cultivated carrot germplasm was genetically non-structured.

Results

Ninety-threeDcS-ILP markers and 2354 SNP markers were used to evaluate the structure of genetic diversity in the collection of 78 western type open-pollinated carrot cultivars, each represented by five plants. The mean percentage of polymorphic loci segregating within a cultivar varied from 31.18 to 89.25% forDcS-ILP markers and from 45.11 to 91.29% for SNP markers, revealing high levels of intra-cultivar heterogeneity, in contrast to its apparent phenotypic stability. Average inbreeding coefficient for all cultivars was negative for bothDcS-ILP and SNP, whereas the overall genetic differentiation across all market classes, as measured by FST, was comparable for both marker systems. ForDcS-ILPs 90–92% of total genetic variation could be attributed to the differences within the inferred clusters, whereas for SNPs the values ranged between 91 to 93%. Discriminant Analysis of Principal Components enabled the separation of eight groups cultivars depending mostly on their market type affiliation. Three groups of cultivars, i.e. Amsterdam, Chantenay and Imperator, were characterized by high homogeneity regardless of the marker system used for genotyping.

Conclusions

Both marker systems used in the study enabled detection of substantial variation among carrot plants of different market types, therefore can be used in germplasm characterization and analysis of genome relationships. The presented results likely reveal the actual genetic diversity structure within the western carrot gene pool and point at possible discrepancies within the cultivars’ passport data.
Using logic regression to characterize extreme heat exposures and their health associations: a time-series study of emergency department visits in Atlanta
Authors: Jiang Shan , Warren Joshua L. , Scovronick Noah , Moss Shannon E. , Darrow Lyndsey A. , Strickland Matthew J. , Newman Andrew J. , Chen Yong , Ebelt Stefanie T. , Chang Howard H.
Published: April 2021

Background

Short-term associations between extreme heat events and adverse health outcomes are well-established in epidemiologic studies. However, the use of different exposure definitions across studies has limited our understanding of extreme heat characteristics that are most important for specific health outcomes or subpopulations.

Methods

Logic regression is a statistical learning method for constructing decision trees based on Boolean combinations of binary predictors. We describe how logic regression can be utilized as a data-driven approach to identify extreme heat exposure definitions using health outcome data. We evaluated the performance of the proposed algorithm in a simulation study, as well as in a 20-year time-series analysis of extreme heat and emergency department visits for 12 outcomes in the Atlanta metropolitan area.

Results

For the Atlanta case study, our novel application of logic regression identified extreme heat exposure definitions that were associated with several heat-sensitive disease outcomes (e.g., fluid and electrolyte imbalance, renal diseases, ischemic stroke, and hypertension). Exposures were often characterized by extreme apparent minimum temperature or maximum temperature over multiple days. The simulation study also demonstrated that logic regression can successfully identify exposures of different lags and duration structures when statistical power is sufficient.

Conclusion

Logic regression is a useful tool for identifying important characteristics of extreme heat exposures for adverse health outcomes, which may help improve future heat warning systems and response plans.
Epidemiology, clinical characteristics, and treatment outcomes of patients with COVID-19 at Thailand’s university-based referral hospital
Authors: Sirijatuphat Rujipas , Suputtamongkol Yupin , Angkasekwinai Nasikarn , Horthongkham Navin , Chayakulkeeree Methee , Rattanaumpawan Pinyo , Koomanachai Pornpan , Assanasen Susan , Rongrungruang Yong , Chierakul Nitipatana , Ratanarat Ranistha , Jitmuang Anupop , Wangchinda Walaiporn , Kantakamalakul Wannee
Published: April 2021

Background

The epidemiology and outcomes of COVID-19 patients in Thailand are scarce.

Methods

This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020.

Results

The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive.

Conclusions

The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.
Correction to: Predictors of willingness to get a COVID-19 vaccine in the U.S
Authors: Kelly Bridget J. , Southwell Brian G. , McCormack Lauren A. , Bann Carla M. , MacDonald Pia D. M. , Frasier Alicia M. , Bevc Christine A. , Brewer Noel T. , Squiers Linda B.
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Identification of novel prognostic biomarkers by integrating multi-omics data in gastric cancer
Authors: Liu Nannan , Wu Yun , Cheng Weipeng , Wu Yuxuan , Wang Liguo , Zhuang Liwei
Published: April 2021

Background

Gastric cancer is a fatal gastrointestinal cancer with high morbidity and poor prognosis. The dismal 5-year survival rate warrants reliable biomarkers to assess and improve the prognosis of gastric cancer. Distinguishing driver mutations that are required for the cancer phenotype from passenger mutations poses a formidable challenge for cancer genomics.

Methods

We integrated the multi-omics data of 293 primary gastric cancer patients from The Cancer Genome Atlas (TCGA) to identify key driver genes by establishing a prognostic model of the patients. Analyzing both copy number alteration and somatic mutation data helped us to comprehensively reveal molecular markers of genomic variation. Integrating the transcription level of genes provided a unique perspective for us to discover dysregulated factors in transcriptional regulation.

Results

We comprehensively identified 31 molecular markers of genomic variation. For instance, the copy number alteration ofWASHC5(also known asKIAA0196) frequently occurred in gastric cancer patients, which cannot be discovered using traditional methods based on significant mutations. Furthermore, we revealed that several dysregulation factors played a hub regulatory role in the process of biological metabolism based on dysregulation networks. Cancer hallmark and functional enrichment analysis showed that these key driver (KD) genes played a vital role in regulating programmed cell death. The drug response patterns and transcriptional signatures of KD genes reflected their clinical application value.

Conclusions

These findings indicated that KD genes could serve as novel prognostic biomarkers for further research on the pathogenesis of gastric cancers. Our study elucidated a multidimensional and comprehensive genomic landscape and highlighted the molecular complexity of GC.
Trajectories of child cognitive development during ages 0–3 in rural Western China: prevalence, risk factors and links to preschool-age cognition
Authors: Wang Lei , Chen Yifei , Sylvia Sean , Dill Sarah-Eve , Rozelle Scott
Published: April 2021

Background

Cognitive development after age three tends to be stable and can therefore predict cognitive skills in later childhood. However, there is evidence that cognitive development is less stable before age three. In rural China, research has found large shares of children under age three are developmentally delayed, yet little is known about the trajectories of cognitive development between 0 and 3 years of age or how developmental trajectories predict later cognitive skills. This study seeks to describe the trajectories of child cognitive development between the ages of 0–3 years and examine how different trajectories predict cognitive development at preschool age.

Methods

We collected three waves of longitudinal panel data from 1245 children in rural Western China. Child cognitive development was measured by the Bayley Scales of Infant Development when the child was 6–12 months and 22–30 months, and by the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition when the child was 49–65 months. We used the two measures of cognitive development before age three to determine the trajectories of child cognitive development.

Results

Of the children, 39% were never cognitively delayed; 13% were persistently delayed; 7% experienced improving cognitive development; and 41% experienced deteriorating development before age 3. Compared to children who had never experienced cognitive delay, children with persistent cognitive delay and those with deteriorating development before age 3 had significantly lower cognitive scores at preschool age. Children with improving development before age 3 showed similar levels of cognition at preschool age as children who had never experienced cognitive delay.

Conclusions

Large shares of children under age 3 in rural Western China show deteriorating cognitive development from infancy to toddlerhood, which predict lower levels of cognition at preschool age. Policymakers should invest in improving cognitive development before age 3 to prevent long-term poor cognition among China’s rural children.
Spinal pain in pre-adolescence and the relation with screen time and physical activity behavior
Authors: Joergensen Anne Cathrine , Strandberg-Larsen Katrine , Andersen Per Kragh , Hestbaek Lise , Andersen Anne-Marie Nybo
Published: April 2021

Background

To investigate how screen time and physical activity behavior were associated with spinal pain in pre-adolescence.

Methods

This study included 45,555 pre-adolescents who participated in the 11-year follow-up of the Danish National Birth Cohort. The 11-year follow-up included self-reported information on computer and TV behavior, aspects of physical activity, as well as frequency and intensity of spinal pain (neck-, mid back- and low back pain). Data were linked with parental socioeconomic data from Statistics Denmark registers. Associations were estimated using multinomial logistic regression models. To account for sample selection, we applied inverse probability weighting.

Results

Duration of screen time was stepwise associated with the degree of spinal pain. Compared with those spending < 2 h/day in front of a screen, screen time of ≥6 h/day was associated with a substantially increased relative risk ratio (RRR) of severe pain for both girls (RRR: 2.49, 95% CI: 2.13–2.92) and boys (RRR: 1.95, 95% CI: 1.65–2.32). Being physical inactive was likewise associated with higher likelihood of severe spinal pain (RRR: 1.22, 95% CI: 1.10–1.34) relative to those being moderately active. We observed that being physically active was seemingly associated with lower risk of spinal pain among boys with high frequency of screen time.

Conclusion

Findings indicate that both duration of screen time and physical inactivity are correlated with spinal pain in pre-adolescents with the strongest associations for screen time. Reducing screen time or increasing physical activity might help preventing spinal pain in pre-adolescents, particularly among high frequent screen users. Future prospective studies investigating the causal relationship are necessary.
Etiology and surgical management of pediatric acute colon perforation beyond the neonatal stage
Authors: Tan Sarah Siyin , Wang Kai , Pang Wenbo , Wu Dongyang , Peng Chunhui , Wang Zengmeng , Zhang Dan , Chen Yajun
Published: April 2021

Purpose

Acute colon perforation is a pediatric surgical emergency. We aimed to analyze the different etiologies and clinical characteristics of acute non-traumatic colon perforation beyond the neonatal period and to identify surgical management and outcomes.

Methods

This retrospective study included 18 patients admitted with acute colon perforation and who received surgical treatment.

Results

Age of patients ranged between 1 month and 15 years. Five patients swallowed foreign objects (two swallowed magnets), two had colon perforation secondary to a malignant tumor (both colorectal adenocarcinoma) and two were iatrogenic (one prior colonoscopy, one air enema for intussusception). There was one perforation due to chemotherapy and Amyand’s hernia respectively. The remaining seven patients had unknown etiologies; five of them were diagnosed with colitis. Fifteen (83.3 %) patients underwent open laparotomy, among which four attempted laparoscopy first. Three (16.7 %) patients underwent laparoscopic surgery. Fourteen (77.8 %) patients received simple suture repairs and four (22.2 %) received colonic resections and anastomosis. Four (22.2 %) patients received a protective diverting colostomy and three (16.7 %) received an ileostomy.

Conclusions

There is a wide range of etiology besides necrotizing enterocolitis and trauma, but a significant portion of children present with unknown etiology. Type of surgery elected should be dependent on the patient’s etiology, disease severity and experience of surgeons.
Correction to: Chemopreventive effect of Betulinic acid via mTOR -Caspases/Bcl2/Bax apoptotic signaling in pancreatic cancer
Authors: Guo Yangyang , Zhu Hengyue , Weng Min , Wang Cheng , Sun Linxiao
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Exploring factors associated with research involvement of undergraduate students at the College of Medicine and Health Sciences, University of Rwanda
Authors: Mugabo Eric , Velin Lotta , Nduwayezu Richard
Published: April 2021

Background

Early involvement of students in research processes is an important step in professional development and can increase the academic output of the university. Previous studies indicate low research involvement amongst undergraduate students, however limited research has been done in sub-Saharan Africa. This study aimed to describe the level of research involvement amongst undergraduate students at the College of Medicine and Health Sciences (CMHS) at University of Rwanda (UR) and to assess factors associated with research involvement.

Methods

This cross-sectional study covered the three CMHS campuses. A survey was shared in class WhatsApp groups from July to September 2020. Data were analyzed using Stata IC 16.0 with descriptive statistics and Fisher’s exact test. P-values < 0.05 were considered statistically significant.

Results

In total, 324 students participated with the mean age being 23.3 (standard deviation 2.27). Males constituted 65.1% of respondents vs. 33.3% females. The largest portion of respondents were from the School of Medicine and Pharmacy (46.6%), and Medicine was the most frequent department (33.3%). On a Likert scale from 1 to 10, 60.0% of the respondents thought that research was 10/10 important for undergraduate students, with the mean value being 8.8. Rating their interest in taking part in research during undergraduate studies, 48.2% scored it 10/10, with the mean value being 8.57. 80.3% of respondents had attended a research module, course, or workshop; however, only 48.8% had participated in a research project and 72.0% of them had been involved in data collection. Inadequate knowledge about research processes and lack of mentors were the main barriers to research participation in 48.0 and 40.2% of respondents respectively. Establishment of a UR-Undergraduate research support center (77.2%), and involving students in ongoing UR projects (69.4%) were the most frequent suggestions to improve students’ research participation.

Conclusion

Undergraduate students at the CMHS in the UR have a large research interest, yet their involvement is currently low. Limited knowledge about research processes and shortage of mentors remains potent barriers to participation. Inviting undergraduate students to partake in ongoing projects and establishing a UR undergraduate research support center are recommended to strengthen undergraduate research experience at the UR-CMHS.
Key components influencing the sustainability of a multi-professional obstetric emergencies training programme in a middle-income setting: a qualitative study
Authors: Ghag Kiren , Bahl Rachna , Winter Cathy , Lynch Mary , Bautista Nayda , Ilagan Rogelio , Ellis Matthew , de Salis Isabel , Draycott Timothy J.
Published: April 2021

Background

Multi-professional obstetric emergencies training is one promising strategy to improve maternity care. Sustaining training programmes following successful implementation remains a challenge. Understanding, and incorporating, key components within the implementation process can embed interventions within healthcare systems, thereby enhancing sustainability. This study aimed to identify key components influencing sustainability of PRactical Obstetric Multi-Professional Training (PROMPT) in the Philippines, a middle-income setting.

Methods

Three hospitals were purposively sampled to represent private, public and teaching hospital settings. Two focus groups, one comprising local trainers and one comprising training participants, were conducted in each hospital using a semi-structured topic guide. Focus groups were audio recorded. Data were analysed using thematic analysis. Three researchers independently coded transcripts to ensure interpretation consistency.

Results

Three themes influencing sustainability were identified; attributes of local champions, multi-level organisational involvement and addressing organisational challenges.

Conclusions

These themes, including potential barriers to sustainability, should be considered when designing and implementing training programmes in middle-income settings. When ‘scaling-up’, local clinicians should be actively involved in selecting influential implementation champions to identify challenges and strategies specific to their organisation. Network meetings could enable shared learning and sustain enthusiasm amongst local training teams. Policy makers should be engaged early, to support funding and align training with national priorities.
Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities
Authors: Glaspole Ian , Bonella Francesco , Bargagli Elena , Glassberg Marilyn K. , Caro Fabian , Stansen Wibke , Quaresma Manuel , Orsatti Leticia , Bendstrup Elisabeth
Published: April 2021

Background

Idiopathic pulmonary fibrosis (IPF) predominantly affects individuals aged > 60 years who have several comorbidities. Nintedanib is an approved treatment for IPF, which reduces the rate of decline in forced vital capacity (FVC). We assessed the efficacy and safety of nintedanib in patients with IPF who were elderly and who had multiple comorbidities.

Methods

Data were pooled from five clinical trials in which patients were randomised to receive nintedanib 150 mg twice daily or placebo. We assessed outcomes in subgroups by age < 75 versus ≥ 75 years, by < 5 and ≥ 5 comorbidities, and by Charlson Comorbidity Index (CCI) ≤ 3 and > 3 at baseline.

Results

The data set comprised 1690 patients. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks versus placebo in patients aged ≥ 75 years (difference: 105.3 [95% CI 39.3, 171.2]) (n = 326) and < 75 years (difference 125.2 [90.1, 160.4]) (n = 1364) (p = 0.60 for treatment-by-time-by-subgroup interaction), in patients with < 5 comorbidities (difference: 107.9 [95% CI 65.0, 150.9]) (n = 843) and ≥ 5 comorbidities (difference 139.3 [93.8, 184.8]) (n = 847) (p = 0.41 for treatment-by-time-by-subgroup interaction) and in patients with CCI score ≤ 3 (difference: 106.4 [95% CI 70.4, 142.4]) (n = 1330) and CCI score > 3 (difference: 129.5 [57.6, 201.4]) (n = 360) (p = 0.57 for treatment-by-time-by-subgroup interaction). The adverse event profile of nintedanib was generally similar across subgroups. The proportion of patients with adverse events leading to treatment discontinuation was greater in patients aged ≥ 75 years than < 75 years in both the nintedanib (26.4% versus 16.0%) and placebo (12.2% versus 10.8%) groups. Similarly the proportion of patients with adverse events leading to treatment discontinuation was greater in patients with ≥ 5 than < 5 comorbidities (nintedanib: 20.5% versus 15.7%; placebo: 12.1% versus 10.0%).

Conclusions

Our findings suggest that the effect of nintedanib on reducing the rate of FVC decline is consistent across subgroups based on age and comorbidity burden. Proactive management of adverse events is important to reduce the impact of adverse events and help patients remain on therapy.

Trial registration: ClinicalTrials.gov NCT00514683, NCT01335464, NCT01335477, NCT02788474, NCT01979952.
Codon usage bias regulates gene expression and protein conformation in yeast expression system P. pastoris
Authors: Xu Yichun , Liu Kunshan , Han Yu , Xing Yanzi , Zhang Yuanxing , Yang Qiuying , Zhou Mian
Published: April 2021

Background

Protein synthesis is one of the extremely important anabolic pathways in the yeast expression system Pichia pastoris. Codon optimization is a commonly adopted strategy for improved protein expression, although unexpected failures did appear sometimes waiting for further exploration. Recently codon bias has been studied to regulate protein folding and activity in many other organisms.

Results

Here the codon bias profile of P. pastoris genome was examined first and a direct correlation between codon translation efficiency and usage frequency was identified. By manipulating the codon choices of both endogenous and heterologous signal peptides, secretion abilities of N-terminal signal peptides were shown to be tolerant towards codon changes. Then two gene candidates with different levels of structural disorder were studied, and full-length codon optimization was found to affect their expression profiles differentially. Finally, more evidences were provided to support possible protein conformation change brought by codon optimization in structurally disordered proteins.

Conclusion

Our results suggest that codon bias regulates gene expression by modulating several factors including transcription and translation efficiency, protein folding and activity. Because of sequences difference, the extent of affection may be gene specific. For some genes, special codon optimization strategy should be adopted to ensure appropriate expression and conformation.