bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequelae, persistent symptomatology and outcomes after COVID-19 hospitalization: the ANCOHVID multicentre 6-month follow-up study
Authors: Romero-Duarte Álvaro , Rivera-Izquierdo Mario , Guerrero-Fernández de Alba Inmaculada , Pérez-Contreras Marina , Fernández-Martínez Nicolás Francisco , Ruiz-Montero Rafael , Serrano-Ortiz Álvaro , González-Serna Rocío Ortiz , Salcedo-Leal Inmaculada , Jiménez-Mejías Eladio , Cárdenas-Cruz Antonio 
Published: May 2021

Abstract
Background
Long-term effects of COVID-19, also called Long COVID, affect more than 10% of patients. The most severe cases (i.e. those requiring hospitalization) present a higher frequency of sequelae, but detailed information on these effects is still lacking. The objective of this study is to identify and quantify the frequency and outcomes associated with the presence of sequelae or persistent symptomatology (SPS) during the 6 months after discharge for COVID-19.

Methods
Retrospective observational 6-month follow-up study conducted in four hospitals of Spain. A cohort of all 969 patients who were hospitalized with PCR-confirmed SARS-CoV-2 from March 1 to April 15, 2020, was included. We collected all the SPS during the 6 months after discharge reported by patients during follow-up from primary care records. Cluster analyses were performed to validate the measures. The main outcome measures were return to the Emergency Services, hospital readmission and post-discharge death. Surviving patients’ outcomes were collected through clinical histories and primary care reports. Multiple logistic regression models were applied.

Results
The 797 (82.2%) patients who survived constituted the sample followed, while the rest died from COVID-19. The mean age was 63.0 years, 53.7% of them were men and 509 (63.9%) reported some sequelae during the first 6 months after discharge. These sequelae were very diverse, but the most frequent were respiratory (42.0%), systemic (36.1%), neurological (20.8%), mental health (12.2%) and infectious (7.9%) SPS, with some differences by sex. Women presented higher frequencies of headache and mental health SPS, among others. A total of 160 (20.1%) patients returned to the Emergency Services, 35 (4.4%) required hospital readmission and 8 (1.0%) died during follow-up. The main factors independently associated with the return to Emergency Services were persistent fever, dermatological SPS, arrythmia or palpitations, thoracic pain and pneumonia.

Conclusions
COVID-19 cases requiring hospitalization during the first wave of the pandemic developed a significant range of mid- to long-term SPS. A detailed list of symptoms and outcomes is provided in this multicentre study. Identification of possible factors associated with these SPS could be useful to optimize preventive follow-up strategies in primary care for the coming months of the pandemic.
Metabolic syndrome and the plasma proteome: from association to causation
Authors: Elhadad Mohamed A. , Wilson Rory , Zaghlool Shaza B. , Huth Cornelia , Gieger Christian , Grallert Harald , Graumann Johannes , Rathmann Wolfgang , Koenig Wolfgang , Sinner Moritz F. , Hveem Kristian , Suhre Karsten , Thorand Barbara , Jonasson Christian , Waldenberger Melanie , Peters Annette 
Published: May 2021

Abstract
Background
The metabolic syndrome (MetS), defined by the simultaneous clustering of cardio-metabolic risk factors, is a significant worldwide public health burden with an estimated 25% prevalence worldwide. The pathogenesis of MetS is not entirely clear and the use of molecular level data could help uncover common pathogenic pathways behind the observed clustering.

Methods
Using a highly multiplexed aptamer-based affinity proteomics platform, we examined associations between plasma proteins and prevalent and incident MetS in the KORA cohort (n = 998) and replicated our results for prevalent MetS in the HUNT3 study (n = 923). We applied logistic regression models adjusted for age, sex, smoking status, and physical activity.
We used the bootstrap ranking algorithm of least absolute shrinkage and selection operator (LASSO) to select a predictive model from the incident MetS associated proteins and used area under the curve (AUC) to assess its performance. Finally, we investigated the causal effect of the replicated proteins on MetS using two-sample Mendelian randomization.

Results
Prevalent MetS was associated with 116 proteins, of which 53 replicated in HUNT. These included previously reported proteins like leptin, and new proteins like NTR domain-containing protein 2 and endoplasmic reticulum protein 29. Incident MetS was associated with 14 proteins in KORA, of which 13 overlap the prevalent MetS associated proteins with soluble advanced glycosylation end product-specific receptor (sRAGE) being unique to incident MetS. The LASSO selected an eight-protein predictive model with an (AUC = 0.75; 95% CI = 0.71–0.79) in KORA.
Mendelian randomization suggested causal effects of three proteins on MetS, namely apolipoprotein E2 (APOE2) (Wald-Ratio = − 0.12, Wald-p = 3.63e−13), apolipoprotein B (APOB) (Wald-Ratio = − 0.09, Wald-p = 2.54e−04) and proto-oncogene tyrosine-protein kinase receptor (RET) (Wald-Ratio = 0.10, Wald-p = 5.40e−04).

Conclusions
Our findings offer new insights into the plasma proteome underlying MetS and identify new protein associations. We reveal possible casual effects of APOE2, APOB and RET on MetS. Our results highlight protein candidates that could potentially serve as targets for prevention and therapy.
Anaerobic biosynthesis of rhamnolipids by Pseudomonas aeruginosa: performance, mechanism and its application potential for enhanced oil recovery
Authors: Zhao Feng , Wang Qingzhi , Zhang Ying , Lei Liying 
Published: May 2021

Abstract
Background
Pseudomonas aeruginosa, the rhamnolipids-producer, is one of dominant bacteria in oil reservoirs. Although P. aeruginosa strains are facultative bacteria, the anaerobic biosynthesis mechanism of rhamnolipids is unclear. Considering the oxygen scarcity within oil reservoirs, revealing the anaerobic biosynthesis mechanism of rhamnolipids are significant for improving the in-situ production of rhamnolipids in oil reservoirs to enhance oil recovery.

Results
Pseudomonasaeruginosa SG anaerobically produced rhamnolipids using glycerol rather than glucose as carbon sources. Two possible hypotheses on anaerobic biosynthesis of rhamnolipids were proposed, the new anaerobic biosynthetic pathway (hypothesis 1) and the highly anaerobic expression of key genes (hypothesis 2). Knockout strain SGΔrmlB failed to anaerobically produce rhamnolipids using glycerol. Comparative transcriptomics analysis results revealed that glucose inhibited the anaerobic expression of genes rmlBDAC, fabABG, rhlABRI, rhlC and lasI. Using glycerol as carbon source, the anaerobic expression of key genes in P. aeruginosa SG was significantly up-regulated. The anaerobic biosynthetic pathway of rhamnolipids in P. aeruginosa SG were confirmed, involving the gluconeogenesis from glycerol, the biosynthesis of dTDP-l-rhamnose and β-hydroxy fatty acids, and the rhamnosyl transfer process. The engineered strain P. aeruginosa PrhlAB constructed in previous work enhanced 9.67% of oil recovery higher than the wild-type strain P. aeruginosa SG enhancing 8.33% of oil recovery.

Conclusion
The highly anaerobic expression of key genes enables P. aeruginosa SG to anaerobically biosynthesize rhamnolipids. The genes, rmlBDAC, fabABG, rhlABRI, rhlC and lasI, are key genes for anaerobic biosynthesis of rhamnolipid by P. aeruginosa. Improving the anaerobic production of rhamnolipids better enhanced oil recovery in core flooding test. This study fills the gaps in the anaerobic biosynthesis mechanism of rhamnolipids. Results are significant for the metabolic engineering of P. aeruginosa to enhance anaerobic production of rhamnolipids.
Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer
Authors: Zhao Tianyi , Zhang Yifang , Ma Xiaohong , Wei Lina , Hou Yixin , Sun Rui , Jiang Jie 
Published: May 2021

Abstract
Background
Endometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women’s lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets.

Methods
Differentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates.

Results
Twenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression.

Conclusion
These findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.
Spatial–temporal clustering of malaria using routinely collected health facility data on the Kenyan Coast
Authors: Kamau Alice , Mtanje Grace , Mataza Christine , Bejon Philip , Snow Robert W. 
Published: May 2021

Abstract
Background
The over-distributed pattern of malaria transmission has led to attempts to define malaria “hotspots” that could be targeted for purposes of malaria control in Africa. However, few studies have investigated the use of routine health facility data in the more stable, endemic areas of Africa as a low-cost strategy to identify hotspots. Here the objective was to explore the spatial and temporal dynamics of fever positive rapid diagnostic test (RDT) malaria cases routinely collected along the Kenyan Coast.

Methods
Data on fever positive RDT cases between March 2018 and February 2019 were obtained from patients presenting to six out-patients health-facilities in a rural area of Kilifi County on the Kenyan Coast. To quantify spatial clustering, homestead level geocoded addresses were used as well as aggregated homesteads level data at enumeration zone. Data were sub-divided into quarterly intervals. Kulldorff’s spatial scan statistics using Bernoulli probability model was used to detect hotspots of fever positive RDTs across all ages, where cases were febrile individuals with a positive test and controls were individuals with a negative test.

Results
Across 12 months of surveillance, there were nine significant clusters that were identified using the spatial scan statistics among RDT positive fevers. These clusters included 52% of all fever positive RDT cases detected in 29% of the geocoded homesteads in the study area. When the resolution of the data was aggregated at enumeration zone (village) level the hotspots identified were located in the same areas. Only two of the nine hotspots were temporally stable accounting for 2.7% of the homesteads and included 10.8% of all fever positive RDT cases detected.

Conclusion
Taking together the temporal instability of spatial hotspots and the relatively modest fraction of the malaria cases that they account for; it would seem inadvisable to re-design the sub-county control strategies around targeting hotspots.
Relationship between benzodiazepine prescription, aggressive behavior, and behavioral disinhibition: a retrospective study in a Swiss prison
Authors: Baggio Stéphanie , Starcevic Vladan , Heller Patrick , Brändle Karen , Franke Irina , Schneeberger Andreas , Buadze Anna , Gamma Alex , Schleifer Roman , Gétaz Laurent , Wolff Hans , Liebrenz Michael 
Published: May 2021

Abstract
Background
Benzodiazepines are commonly prescribed in prisons amidst the controversies surrounding their potential role in causing behavioral disinhibition and aggressive behavior and their association with use and trafficking of illicit and addictive substances. The present study aimed to (1) ascertain the relationship between benzodiazepine prescription (including their dosage and duration of use) and aggressive behavior and behavioral disinhibition in prison and (2) investigate whether there was an association between benzodiazepine prescription, (including their dosage and duration of use) and using and trafficking illicit and addictive substances during imprisonment.

Methods
Data were extracted from the electronic database of an “open” Swiss prison (n = 1206, 1379 measures) over a 5-year period (2010–2015). Measures included benzodiazepine prescription, duration of benzodiazepine use and mean dosage, and punishable behaviors (physical and verbal aggression, disinhibited but not directly aggressive behaviors, property damage or theft, substance-related offenses, and rule transgression). We assessed the relationship between benzodiazepine prescription and punishable behaviors after propensity score matching. Logistic regressions were also used to test the relationship of benzodiazepine use duration and dosage with punishable behaviors among participants who received benzodiazepines.

Results
After propensity score matching, benzodiazepine prescription was not significantly associated with any punishable behavior. Among detained persons who took benzodiazepines, there was no significant association of dosage and duration of use with offenses involving illicit or addictive substance use or trafficking.

Conclusions
Our study did not empirically support the occurrence of increased aggressive or disinhibited behaviors or increased risk of substance abuse in detained persons who received benzodiazepines in prison. This suggests a need to reconsider restrictions in prescribing benzodiazepines in the prison setting.
TMT-based proteomic and bioinformatic analyses of human granulosa cells from obese and normal-weight female subjects
Authors: Si Chenchen , Wang Nan , Wang Mingjie , Liu Yue , Niu Zhihong , Ding Zhide 
Published: May 2021

Abstract
Background
Increasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart.

Methods
GC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups.

Results
A total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects.

Conclusions
In GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.
Examining the association between meal context and diet quality: an observational study of meal context in older adults
Authors: Shams-White Marissa M. , Korycinski Robert W. , Dodd Kevin W. , Barrett Brian , Jacobs Stephanie , Subar Amy F. , Park Yikyung , Bowles Heather R. 
Published: May 2021

AbstractBackgroundThough a healthy diet is widely associated with reduced risks for chronic disease and mortality, older adults in the U.S. on average do not meet dietary recommendations. Given that few studies have examined the association between meal context on older adult diet quality, the aims of this study were (1) to compare the dietary quality of foods consumed in different meal contexts, as measured by the Healthy Eating Index 2015 (HEI-2015): meal location, the presence of others, and the use of electronic screens; and (2) to examine which components of the HEI-2015 drove differences in HEI-2015 total scores by meal context.MethodsInteractive Diet and Activity Tracking in AARP study participants (50–74 years) completed the Automated Self-Administered 24-h Dietary Assessment tool (ASA24, version 2011) that included foods and beverages consumed and three meal contexts: “at home” versus “away from home,” “alone” versus “with company,” and “with screen time” versus “without screen time.” A population ratio approach was used to estimate HEI-2015 total and component scores for all food items consumed by meal context. Mean HEI-2015 scores (range: 0–100) for the three meal context variables were compared using t-tests. Where there were significant differences in total scores, additional t-tests were used to explore which HEI-2015 components were the primary drivers. All tests were stratified by sex and adjusted for multiple comparisons.ResultsHEI-2015 scores were lower for meals consumed away vs. at home (mean difference (SE), males: − 8.23 (1.02); females: − 7.29 (0.93); bothp < 0.0001) and for meals eaten with vs. without company (mean difference (SE), males: − 6.61 (1.06); females: − 7.34 (1.18); bothp < 0.0001). There was no difference comparing with vs. without screen time. When HEI-2015 component scores were examined, fewer total fruits, whole grains, and dairy were consumed away from home or with company; more total vegetables and greens and beans, and less added sugars were consumed with company.ConclusionsOur findings suggest an association between the behavior cues of meal location and companions and dietary choices among older adults. Future studies can explore the individual and interactive effects of meal context on diet quality and subsequent health outcomes.
Effects of thymectomy on late-onset non-thymomatous myasthenia gravis: systematic review and meta-analysis
Authors: Zhang Jinwei , Chen Yuan , Zhang Hui , Yang Zhaoyu , Zhang Peng 
Published: May 2021

Abstract
Background
The effects of thymectomy on late-onset non-thymomatous myasthenia gravis (NTMG) remain controversial. The objective of this study was to conduct a systematic review in order to answer two questions pertinent to late-onset NTMG: (1) do patients with late-onset NTMG experience the same effects from thymectomy as their early-onset counterparts? (2) Compared with conservative treatment, does thymectomy have any benefits for late-onset NTMG patients?

Methods
We searched the PubMed, EMBASE, and Cochrane Library databases for studies published from January 1, 1950 to March 10, 2021. Outcomes were measured via clinical stable remission/pharmacological remission (CSR/PR) and improvement rates. We used Stata software to analyze the data.

Results
We ultimately included a total of 12 observational articles representing the best evidence answering the questions of our study objective. Of these, nine studies, which included 896 patients overall (766 early-onset and 230 late-onset), compared postoperative outcomes between early- and late-onset NTMG. The remaining three articles, which included 216 patients (75 in the thymectomy group and 141 in the conservative-treatment group), compared thymectomy with conservative treatment for late-onset NTMG. The early- versus late-onset NTMG studies demonstrated that patients in the former category were 1.95× likelier than their late-onset counterparts to achieve clinical remission (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.39–2.73; I2 = 0%). No difference was seen in improvement or remission + improvement rates between these two groups. When comparing thymectomy with conservative treatments in late-onset NTMG patients, neither did we observe any difference in CSR/PR.

Conclusion
We found that late-onset NTMG patients had a lower chance of achieving CSR after thymectomy than early-onset patients. Thymectomy in late-onset NTMG also yielded no benefit to CSR or PR compared with conservative treatments. In late-onset NTMG patients, thymectomy should therefore be performed with caution, and the appropriate cutoff between early- and late-onset MG should be further explored in order to tailor and execute the proper therapeutic strategies.