bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing symptoms of e-cigarette dependence: a qualitative study of young adults
Authors: Simpson Kelsey A. , Kechter Afton , Schiff Sara J. , Braymiller Jessica L. , Yamaguchi Naosuke , Ceasar Rachel Carmen , Bluthenthal Ricky N. , Barrington-Trimis Jessica L.
Published: May 2021

Background

While rates of e-cigarette use (‘vaping’) continue to potentiate concern, there is limited data on common symptoms of e-cigarette dependence among young adults who vape. This study sought to critically explore how young adults experience, manifest, and conceptualize vaping dependence symptoms in their everyday lives.

Methods

Between June 2018 and 2019, in-depth qualitative interviews were conducted with 62 young adults who use e-cigarettes (aged 18–25) and live in Southern California. We explored participants’ product preferences, daily e-cigarette use patterns, vaping history, withdrawal experiences, and quit attempts or periods of cessation. We used a thematic analysis approach to interpret the transcripts.

Results

Young adults discussed nine dimensions of vaping dependence that were organized into two categories: 1) general nicotine dependence symptoms, and 2) unique dependence symptoms related to vaping. Nicotine dependence symptoms included cravings and urgency to use, increased use to achieve desired effects, and unsuccessful quit attempts and withdrawal. Symptoms unique to vaping dependence included greater nicotine consumption due to accessibility and lack of restrictions, habitual vaping, inability to track vaping frequency, immediate gratification and comfort, social acceptability and norms, and awareness of vaping dependency.

Conclusions

In addition to nicotine dependence symptoms that have been characterized for other tobacco products, young adult e-cigarette users described unique symptoms of vaping dependence that necessitate the need for more refined measures. All dimensions of vaping dependence should be considered in discussions of policies as well as treatment and education efforts intended to protect young people from e-cigarette dependence.
Factors influencing nurses’ intention to work in the oncology specialty: multi-institutional cross-sectional study
Authors: Alrasheedi Omar , Schultz Timothy John , Harvey Gillian
Published: May 2021

Background

Nursing care for terminally ill cancer patients is routinely provided by oncology nurses in Saudi Arabia. Shortages and retention of oncology nurses is an important concern for healthcare leaders.

Objectives

To identify and describe predictors of nurses’ intention toward working in the oncology specialty amongst three groups: undergraduate nursing students, oncology registered nurses and postgraduate oncology nursing students. In particular, the study sought to analyse association between individual characteristics, job-related factors, palliative care knowledge, attitude toward caring for dying patients, general self-efficacy, job satisfaction and intention to work in oncology.

Methods

A cross-sectional study was conducted involving 477 participants in five major hospitals in Saudi Arabia. The Palliative Care Quiz for Nursing, Frommelt Attitudes Toward Care of the Dying Scale, General Self-Efficacy Scale and Minnesota Satisfaction Questionnaire short form were used for data collection. Multilevel logistic regression analysis was used to identify predictors associated with intention to work in oncology.

Results

43.9% (n = 208) of the sample reported an intention to work in oncology. Only one variable was a significant predictor of intention to work in oncology across all three groups studied: a more positive attitude toward caring for dying patients (Odds ratio (OR) = 1.09 [95% confidence interval (CI) 1.04–1.16]), (OR = 1.08 [95% CI 1.04–1.12]), (OR = 1.078 [95% CI 1.053–1.103] with P ≤ 0.001 for undergraduate, registered and postgraduate groups respectively. At post-graduate level, higher levels of palliative care knowledge and general self-efficacy were significantly associated with increased intention, whilst at undergraduate level, general self-efficacy was a significant predictor. Job satisfaction was a significant predictor of intention amongst registered nurses.

Conclusions

Attitude toward caring for dying patients and general self-efficacy appear to be the most important predictors of intention to work in the oncology nursing specialty. However, the significance of influencing factors varied between the different groups of nurses studied. Perhaps surprisingly, palliative care knowledge was an influential factor amongst the postgraduate group only. The study results provide important insights for nursing leaders and policymakers in Saudi Arabia to inform the future planning of nursing workforce strategies to address shortages and retention of oncology nurses.
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

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

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

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

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

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

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

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

Background

Though 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.

Methods

Interactive 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.

Results

HEI-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.

Conclusions

Our 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

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.
Relationship between admission coagulopathy and prognosis in children with traumatic brain injury: a retrospective study
Authors: You Cheng-yan , Lu Si-wei , Fu Yue-qiang , Xu Feng
Published: May 2021

Background

Coagulopathy in adult patients with traumatic brain injury (TBI) is strongly associated with unfavorable outcomes. However, few reports focus on pediatric TBI-associated coagulopathy.

Methods

We retrospectively identified children with Glasgow Coma Scale ≤ 13 in a tertiary pediatric hospital from April 2012 to December 2019 to evaluate the impact of admission coagulopathy on their prognosis. A classification and regression tree (CART) analysis using coagulation parameters was performed to stratify the death risk among patients. The importance of these parameters was examined by multivariate logistic regression analysis.

Results

A total of 281 children with moderate to severe TBI were enrolled. A receiver operating characteristic curve showed that activated partial thromboplastin time (APTT) and fibrinogen were effective predictors of in-hospital mortality. According to the CART analysis, APTT of 39.2 s was identified as the best discriminator, while 120 mg/dL fibrinogen was the second split in the subgroup of APTT ≤ 39.2 s. Patients were stratified into three groups, in which mortality was as follows: 4.5 % (APTT ≤ 39.2 s, fibrinogen > 120 mg/dL), 20.5 % (APTT ≤ 39.2 s and fibrinogen ≤ 120 mg/dL) and 60.8 % (APTT > 39.2 s). Furthermore, length-of-stay in the ICU and duration of mechanical ventilation were significantly prolonged in patients with deteriorated APTT or fibrinogen values. Multiple logistic regression analysis showed that APTT > 39.2 s and fibrinogen ≤ 120 mg/dL was independently associated with mortality in children with moderate to severe TBI.

Conclusions

We concluded that admission APTT > 39.2 s and fibrinogen ≤ 120 mg/dL were independently associated with mortality in children with moderate to severe TBI. Early identification and intervention of abnormal APTT and fibrinogen in pediatric TBI patients may be beneficial to their prognosis.
Semi-field evaluation of the exposure-free mosquito electrocuting trap and BG-Sentinel trap as an alternative to the human landing catch for measuring the efficacy of transfluthrin emanators against Aedes aegypti
Authors: Tambwe Mgeni M. , Saddler Adam , Kibondo Ummi Abdul , Mashauri Rajabu , Kreppel Katharina S. , Govella Nicodem J. , Moore Sarah J.
Published: May 2021

Background

The human landing catch (HLC) measures human exposure to mosquito bites and evaluates the efficacy of vector control tools. However, it may expose volunteers to potentially infected mosquitoes. The mosquito electrocuting trap (MET) and BG-Sentinel traps (BGS) represent alternative, exposure-free methods for sampling host-seeking mosquitoes. This study investigates whether these methods can be effectively used as alternatives to HLC for measuring the efficacy of transfluthrin emanator against Aedes aegypti.

Methods

The protective efficacy (PE) of freestanding passive transfluthrin emanators (FTPEs), measured by HLC, MET and BGS, was compared in no-choice and choice tests. The collection methods were conducted 2 m from an experimental hut with FTPEs positioned at 3 m on either side of them. For the choice experiment, a competitor HLC was included 10 m from the first collection point. One hundred laboratory-reared Ae. aegypti mosquitoes were released and collected for 3 consecutive h.

Results

In the no-choice test, each method measured similar PE: HLC: 66% (95% confidence interval [CI]: 50–82), MET: 55% (95% CI: 48–63) and BGS: 64% (95% CI: 54–73). The proportion of mosquitoes recaptured was consistent between methods (20–24%) in treatment and varied (47–71%) in the control. However, in choice tests, the PE measured by each method varied: HLC: 37% (95% CI: 25–50%), MET: 76% (95% CI: 61–92) and BGS trap: 0% (95% CI: 0–100). Recaptured mosquitoes were no longer consistent between methods in treatment (2–26%) and remained variable in the control (7–42%). FTPE provided 50% PE to the second HLC 10 m away. In the control, the MET and the BGS were less efficacious in collecting mosquitoes in the presence of a second HLC.

Conclusions

Measuring the PE in isolation was fairly consistent for HLC, MET and BGS. Because HLC is not advisable, it is reasonable to use either MET or BGS as a proxy for HLC for testing volatile pyrethroid (VP) in areas of active arbovirus-endemic areas. The presence of a human host in close proximity invalidated the PE estimates from BGS and METs. Findings also indicated that transfluthrin can protect multiple people in the peridomestic area and that at short range mosquitoes select humans over the BGS.

Graphical Abstract
Opioid use, motivation to quit, and treatment status related to COVID-19: a cross-sectional study
Authors: Parker Maria A. , Agley Jon , Adams Zachary W. , Villanti Andrea C.
Published: May 2021

Objective

Persons who use opioids may be at elevated risk of harm from the coronavirus disease 2019 (COVID-19) pandemic, yet few data currently exist that can be used to examine this risk. As part of a rapid response survey, this study measured opioid users’ perceptions of risk or harm from COVID-19, as well as potential changes in motivation to quit, frequency of use, and engagement with treatment. Data collected from Amazon’s Mechanical Turk (n = 562) were analyzed.

Results

Participants perceived modest risk elevation from COVID-19 due to their opioid use, and perceived moderate risk to themselves or their community from COVID-19. Since learning about COVID-19, 31.2% reported decreasing their opioid use, and 26.0% reported increased motivation to quit. Thirty-seven percent of participants reported both their use and motivation to quit stayed the same; 16.6% reported decreased use and increased motivation to quit. Participants who reported that their opioid use increased after learning about COVID-19, or whose motivation to quit opioids decreased, were more likely to also be engaged in treatment than those whose use or motivation stayed the same. These preliminary findings suggest that there likely is an association between COVID-19, opioid use, and treatment engagement that merits further in-depth investigation.
Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells
Authors: Yao Yunqi , Xia Zhemin , Cheng Fuyi , Jang Qingyuan , He Jiao , Pan Cheng , Zhang Lin , Ye Yixin , Wang Yuan , Chen Shuang , Su Dongsheng , Su Xiaolan , Cheng Lin , Shi Gang , Dai Lei , Deng Hongxin
Published: May 2021

Background

Liver fibrosis (LF) is a common pathological process characterized by the activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix. Severe LF causes cirrhosis and even liver failure, a major cause of morbidity and mortality worldwide. Transplantation of human placental mesenchymal stem cells (hPMSCs) has been considered as an alternative therapy. However, the underlying mechanisms and the appropriate time window for hPMSC transplantation are not well understood.

Methods

We established mouse models of CCl4-injured LF and administered hPMSCs at different stages of LF once a week for 2 weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses. In vitro, the effect of hPMSCs and the secretomes of hPMSCs on the inhibition of activated HSCs was assessed. RNA sequencing (RNA-seq) analysis, real-time PCR array, and western blot were performed to explore possible signaling pathways involved in treatment of LF with hPMSCs.

Results

hPMSC treatment notably alleviates experimental hepatic fibrosis, restores liver function, and inhibits inflammation. Furthermore, the therapeutic effect of hPMSCs against mild-to-moderate LF was significantly greater than against severe LF. In vitro, we observed that the hPMSCs as well as the secretomes of hPMSCs were able to decrease the activation of HSCs. Mechanistic dissection studies showed that hPMSC treatment downregulated the expression of fibrosis-related genes, and this was accompanied by the upregulation of Caveolin-1 (Cav1) (p < 0.001). This suggested that the amelioration of LF occurred partly due to the restoration of Cav1 expression in activated HSCs. Upregulation of Cav1 can inhibit the TGF-β/Smad signaling pathway, mainly by reducing Smad2 phosphorylation, resulting in the inhibition of activated HSCs, whereas this effect could be abated if Cav1 was silenced in advance by siRNAs.

Conclusions

Our findings suggest that hPMSCs could provide multifaceted therapeutic benefits for the treatment of LF, and the TGF-β/Cav1 pathway might act as a therapeutic target for hPMSCs in the treatment of LF.
CpG oligodeoxynucleotides attenuate RORγt-mediated Th17 response by restoring histone deacetylase-2 in cigarette smoke-exposure asthma
Authors: Li Hongtao , Ye Qimei , Lin Yusen , Yang Xuena , Zou Xiaoling , Yang Hailing , Wu Wenbin , Meng Ping , Zhang Tiantuo
Published: May 2021

Background

Cigarette smoke (CS) exposure increases corticosteroid insensitive asthma related to increased Th17 phenotype, and new treatment strategies are needed for CS-associated asthma. Histone deacetylase 2 (HDAC2), found in the airway epithelium, is critical for ameliorating glucocorticoids insensitivity. We recently demonstrated the anti-inflammatory effects of CpG oligodeoxynucleotides (CpG-ODNs) on CS-exposure asthma. However, the effects of CpG-ODNs on HDAC2 expression and enzymatic activity remain unclear. This study aimed to assess whether CpG-ODNs protect against excessive Th17 immune responses in CS-induced asthma through HDAC2-dependent mechanisms and compared their effects with those of corticosteroids.

Methods

The effects of CpG-ODNs alone and in combination with budesonide (BUD) on airway inflammation and Th2/Th17-related airway immune responses were determined using an in vivo model of CS-induced asthma and in cultured bronchial epithelial (HBE) cells administered ovalbumin (OVA) and/or cigarette smoke extract (CSE). HDAC2 and retinoid-related orphan nuclear receptor γt (RORγt) expression were also assessed in mouse lung specimens and HBE cells.

Results

CpG-ODNs and BUD synergistically attenuated CS exposure asthmatic responses in vivo by modulating the influx of eosinophils and neutrophils, airway remodeling, Th2/Th17 associated cytokine and chemokine production, and airway hyperresponsiveness and blocking RORγt-mediated Th17 inflammation through induced HDAC2 expression/activity. In vitro, CpG-ODNs synergized with BUD to inhibit Th17 cytokine production in OVA- and CSE-challenged HBE cells while suppressing RORγt and increasing epithelial HDAC2 expression/activity.

Conclusions

CpG-ODNs reversed CS-induced HDAC2 downregulation and enhanced the sensitivity of CS-exposed asthmatic mice and CSE-induced HBE cells to glucocorticoid treatment. This effect may be associated with HDAC2 restoration via RORγt/IL-17 pathway regulation, suggesting that CpG-ODNs are potential corticosteroid-sparing agents for use in CS-induced asthma with Th17-biased immune conditions.
Effectiveness of matching human leukocyte antigens (HLA) in corneal transplantation: a systematic review protocol
Authors: Sachdeva Gagandeep Singh , Cabada Joshua Piollo , Karim Syed Saad , Kahandawa Dmitry Lakvin , Thomas Kevin Anil , Kumar Anusha , Barry Robert J. , Butt Gibran Farook
Published: May 2021

Background

Corneal transplantation is the most frequently performed transplantation in the UK. Despite this, the therapeutic value of matching human leukocyte antigen (HLA) subtypes for transplanted corneas remains controversial. Ocular immune privilege was originally deemed to render matching unnecessary; however, more recently, matching has demonstrated improved outcomes including graft success, amongst others. This systematic review aims to evaluate the effectiveness of major and minor antigen matching on graft outcomes in corneal transplantation.

Methods

Standard systematic review methodology will be used to identify, select and extract data from observational studies and clinical trials assessing the effects of HLA matching on corneal graft outcomes. Bibliographic databases (Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus), clinical trial registers, abstract and conference proceedings, in addition to dissertation, thesis and grey literature will be searched. Neither date of publication nor language will be restricted, and non-English articles will be translated where necessary. The primary outcome will be to assess corneal graft success for different degrees of HLA matching/mismatching. The precise end outcome measure varies amongst studies and includes graft rejection, immunoreaction, failure and survival. Therefore, data will be extracted across all relevant outcome parameters and grouped for subsequent statistical tests. Risk of bias assessment will be completed, appropriate to each study design. Study selection, data extraction and risk of bias assessment will be independently completed by two reviewers. Data will be tabulated, and a narrative synthesis presented. Meta-analysis will be performed where there is sufficient homogeneity between studies to warrant its effective completion. Subgroup and sensitivity analysis will be undertaken if appropriate.

Discussion

Many studies have investigated the effectiveness of HLA matching for corneal transplantation. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review may form the basis of evidence-based recommendations on pre-operative HLA typing and matching of corneal grafts for transplantation.

Systematic review registration

PROSPERO reference CRD42020198882
Hermite–Hadamard integral inequalities on coordinated convex functions in quantum calculus
Authors: Alqudah Manar A. , Kashuri Artion , Mohammed Pshtiwan Othman , Abdeljawad Thabet , Raees Muhammad , Anwar Matloob , Hamed Y. S.
Published: May 2021

At first, we recall the q-operators in the context of q-calculus and by examining these operators we will introduce new definitions of the partial q-operators. Then, we investigate some new refinements inequalities of Hermite–Hadamard ($H-H$
H
−
H
) type on the coordinated convex functions involving the new defined partial q-operators. From our main results, we establish several specific inequalities and we point out the existing results which had already been obtained in the literature.
The effect of a hand hygiene intervention on infections in residents of nursing homes: a cluster randomized controlled trial
Authors: Teesing G. R. , Richardus J. H. , Nieboer D. , Petrignani M. , Erasmus V. , Verduijn-Leenman A. , Schols J. M. G. A. , Koopmans M. P. G. , Vos M. C. , Voeten H. A. C. M.
Published: May 2021

Background

The primary goal of hand hygiene is to reduce infectious disease rates. We examined if a nursing home’s participation in a hand hygiene intervention resulted in residents having fewer healthcare associated infections (HAIs) when compared to nursing homes without the hand hygiene intervention.

Methods

This study is a part of a cluster randomized controlled trial (RCT) in 33 nursing homes to improve hand hygiene (HANDSOME). The incidence of five illnesses was followed over 13 months: gastroenteritis, influenza-like illness, pneumonia, urinary tract infections and infections from methicillin-resistant Staphylococcus aureus (MRSA). Incidence rates per study arm were reported for baseline (October–December 2016) and two follow-up periods (January–April 2017, May–October 2017). HAI rates were compared in a Poisson multilevel analysis, correcting for baseline differences (the baseline infection incidence and the size of the nursing home), clustering of observations within nursing homes, and period in the study.

Results

There was statistically significantly more gastroenteritis (p < 0.001) and statistically significantly less influenza-like illness (p < 0.01) in the intervention arm when compared to the control arm. There were no statistically significant differences or pneumonia, urinary tract infections, and MRSA infections in the intervention arm when compared to the control arm. In a sensitivity analysis, gastroenteritis was no longer statistically significantly higher in the intervention arm (p = 0.92).

Conclusions

As in comparable studies, we could not conclusively demonstrate the effectiveness of an HH intervention in reducing HAIs among residents of nursing homes, despite the use of clearly defined outcome measures, a standardized reporting instrument, and directly observed HH in a multicenter cluster RCT.

Trial registration Netherlands Trial Register, trial NL6049 (NTR6188). Registered October 25, 2016, https://www.trialregister.nl/trial/6049.
Neurodegenerative diseases: a hotbed for splicing defects and the potential therapies
Authors: Li Dunhui , McIntosh Craig Stewart , Mastaglia Frank Louis , Wilton Steve Donald , Aung-Htut May Thandar
Published: May 2021

Precursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function. The continuous changes in splicing patterns and a high demand on manycis-andtrans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect(s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy. Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics. Here we review our current understanding of the effects alternative splicing has on neuronal differentiation, neuronal migration, synaptic maturation and regulation, as well as the impact on neurodegenerative diseases. We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.