bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of proteomic and metabolomic characterization in atrial fibrillation-induced heart failure
Authors: Zhang Haiyu , Wang Lu , Yin Dechun , Zhou Qi , Lv Lin , Dong Zengxiang , Shi Yuanqi
Published: December 2022

Background

The exact mechanism of atrial fibrillation (AF)-induced heart failure (HF) remains unclear. Proteomics and metabolomics were integrated to in this study, as to describe AF patients’ dysregulated proteins and metabolites, comparing patients without HF to patients with HF.

Methods

Plasma samples of 20 AF patients without HF and another 20 with HF were analyzed by multi-omics platforms. Proteomics was performed with data independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS), as metabolomics was performed with LC-MS/MS platform. Proteomic and metabolomic results were analyzed separately and integrated using univariate statistical methods, multivariate statistical methods or machine learning model.

Results

We found 35 up-regulated and 15 down-regulated differentially expressed proteins (DEPs) in AF patients with HF compared to AF patients without HF. Moreover, 121 up-regulated and 14 down-regulated differentially expressed metabolites (DEMs) were discovered in HF patients compared to AF patients without HF. An integrated analysis of proteomics and metabolomics revealed several significantly enriched pathways, including Glycolysis or Gluconeogenesis, Tyrosine metabolism and Pentose phosphate pathway. A total of 10 DEPs and DEMs selected as potential biomarkers provided excellent predictive performance, with an AUC of 0.94. In addition, subgroup analysis of HF classification was performed based on metabolomics, which yielded 9 DEMs that can distinguish between AF and HF for HF classification.

Conclusions

This study provides novel insights to understanding the mechanisms of AF-induced HF progression and identifying novel biomarkers for prognosis of AF with HF by using metabolomics and proteomics analyses.
The landscape of the long non-coding RNAs and circular RNAs of the abdominal fat tissues in the chicken lines divergently selected for fatness
Authors: Jing Yang , Cheng Bohan , Wang Haoyu , Bai Xue , Zhang Qi , Wang Ning , Li Hui , Wang Shouzhi
Published: December 2022

Background

Excessive deposition of abdominal fat poses serious problems in broilers owing to rapid growth. Recently, the evolution of the existing knowledge on long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have established their indispensable roles in multiple physiological metabolic processes, including adipogenesis and fat deposition. However, not much has been explored on their profiles in the abdominal fat tissues of broilers to date. In the study, we aimed to characterize the vital candidates of lncRNAs and circRNAs and their underlying regulations for abdominal fat deposition in broilers.

Results

The present study sequenced the lncRNAs and circRNAs expression profiles in the abdominal fat tissues isolated from 7-week-old broilers, who were divergently selected for their fatness. It identified a total of 3359 lncRNAs and 176 circRNAs, demonstrating differential expressed (DE) 30 lncRNAs and 17 circRNAs between the fat- and lean-line broilers (|log2FC| ≥ 1, P < 0.05). Subsequently, the 20 cis-targets and 48 trans-targets of the candidate DE lncRNAs were identified for depositing abdominal fat by adjacent gene analysis and co-expression analysis, respectively. In addition, the functional enrichment analysis showed the DE lncRNAs targets and DE circRNAs host genes to be mainly involved in the cellular processes, amino/fatty acid metabolism, and immune inflammation-related pathways and GO terms. Finally, the vital 16 DE lncRNAs located in cytoplasm and specifically expressed in fat/lean line and their targets were used to construct the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network, comprising 7 DE lncRNAs, 28 miRNAs, 11 DE mRNAs. Notably, three lncRNAs including XR_001468036.2, XR_003077610.1 and XR_001466431.2 with the most connected degrees might play hub regulatory roles in abdominal fat deposition of broilers.

Conclusions

This study characterized the whole expression difference of lncRNAs and circRNAs between the two lines broilers with divergently ability of abdominal fat. The vital candidate DE lncRNAs/circRNAs and ceRNA regulations were identified related to the deposition of abdominal fat in chicken. These results might further improve our understanding of regulating the non-coding RNAs in obesity.
Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
Authors: Lützhøft Ditte Olsen , Sinioja Tim , Christoffersen Berit Ø. , Jakobsen Rasmus Riemer , Geng Dawei , Ahmad Hajar Fauzan Bin , Straarup Ellen Marie , Pedersen Karen-Margrethe , Kot Witold , Pedersen Henrik Duelund , Cirera Susanna , Hyötyläinen Tuulia , Nielsen Dennis Sandris , Hansen Axel Kornerup
Published: December 2022

Background

Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.

Results

Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.

Conclusions

Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation
Authors: Liu Mengjie , Zhang Yaqiang , Yan Jie , Wang Yuelan
Published: December 2022

Background

Ventilator-induced lung injury (VILI) is caused by stretch stimulation and other factors related to mechanical ventilation (MV). NOD-like receptor protein 3 (NLRP3), an important innate immune component, is strongly associated with VILI. This study aimed to investigate the effect and mechanisms of aerobic exercise (EX) on VILI.

Methods

To test the effects of the PKC inhibitor bisindolylmaleimide I on PKC and NLRP3, male C57BL/6 mice (7 weeks old, 19 ~ 23 g) were randomly divided into four groups: control group(C), bisindolylmaleimide I-pretreated group(B), MV group, and bisindolylmaleimide I-pretreated + MV (B + MV) group. The mice were pretreated with bisindolylmaleimide I through intraperitoneal injection (0.02 mg/kg) 1 h before MV. MV was performed at a high tidal volume (30 ml/kg). To explore the ameliorative effect of EX on VILI, the mice were randomly divided into C group, MV group, EX group and EX + MV group and subjected to either MV or 5 weeks of EX training. After ventilation, haematoxylin-eosin (HE) staining and wet/dry weight ratio was used to assess lung pathophysiological changes. PKCɑ, P-PKCɑ, ASC, procaspase-1, caspase-1, pro-IL-1β, IL-1β, NLRP3 and occludin (tight junction protein) expression in lung tissues was determined by Western blotting. The level of IL-6 in alveolar lavage fluid was determined by ELISA.

Results

NLRP3, P-PKCɑ, and PKCɑ levels were inceased in MV group, but bisindolylmaleimide I treatment reversed these changes. Inhibition of PKC production prevented NLRP3 activation. Moreover, MV increased ASC, procaspase-1, caspase-1, pro-IL-1β, and IL1β levels and decreased occludin levels, but EX alleviated these changes. HE staining and lung injury scoring confirmed an absence of obvious lung injury in C group and EX group. Lung injury was most severe in MV group but was improved in EX + MV group. Overall, these findings suggest that MV activates the NLRP3 inflammasome by activating PKCɑ and inducing occludin degradation, while Exercise attenuates NLRP3 inflammasome and PKCɑ activation. Besides, exercise improves cyclic stretch-induced degradation of occludin.

Conclusion

PKC activation can increase the level of NLRP3, which can lead to lung injury. Exercise can reduce lung injury by inhibiting PKCɑ and NLRP3 activation. Exercise maybe a potential measure for clinical prevention of VILI.
The bidirectional relationship between homebound status and falls among older adults: a longitudinal study
Authors: Liu Minhui , Peng Wenting , Miyawaki Christina E. , Mo Cen , Luo Yuqian , Gong Ni
Published: December 2022

Background

Previous research has shown an association between homebound status and falls among older adults. However, this association was primarily drawn from cross-sectional studies. This study aimed to determine the bidirectional relationship between homebound status and falls among older adults in the community.

Methods

We used data of the community-dwelling older adults from 2011 to 2015 of the National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the United States (Sample 1 [No falls at baseline]: N = 2,512; Sample 2 [Non-homebound at baseline]: N = 2,916). Homebound status was determined by the frequency, difficulty, and needing help for outdoor mobility. Falls were ascertained by asking participants whether they had a fall in the last year. Generalized estimation equation models were used to examine the bidirectional association between homebound status and falls longitudinally.

Results

Participants with no falls at baseline (n = 2,512) were on average, 76.8 years old, non-Hispanic whites (70.1%), and female (57.1%). After adjusting for demographics and health-related variables, prior year homebound status significantly contributed to falls in the following year (Odds ratio [OR], 1.28, 95% CI: 1.09–1.51). Participants who were non-homebound at baseline (n = 2,916) were on average, 75.7 years old, non-Hispanic white (74.8%), and female (55.8%). Previous falls significantly predicted later homebound status (OR, 1.26, 95% CI: 1.10–1.45) in the full adjusted model.

Conclusion

This is the first longitudinal study to determine the bidirectional association between homebound status and falls. Homebound status and falls form a vicious circle and mutually reinforce each other over time. Our findings suggest the importance of developing programs and community activities that reduce falls and improve homebound status among older adults.
Buccal mucosal membrane graft for correction of cicatricial lower eyelid retraction
Authors: Rafizadeh Seyed Mohsen , Daryabari Seyed-Hashem , Hassanpour Seyed Rahim
Published: December 2022

Background

To evaluate the outcomes of a surgical technique using buccal mucosal membrane graft for correction of cicatricial lower eyelid retraction.

Methods

Twelve patients with unilateral cicatricial lower eyelid retraction were enrolled in the study. All patients underwent a four-step surgical technique consisted of release of scars, midface lift, transfer of buccal mucosal membrane to posterior lamella as spacer graft, and canthal tightening. All patients were followed for at least 12 months.

Results

Mean preoperative Margin-to-Reflex-Distance 2 (MRD2) was 7.73 ± 1.10 mm, compared to mean postoperative MRD2 of 5.04 ± 0.49 mm (P < 0.0001). The mean improvement in retraction was 2.69 mm. Postoperative scleral show was present in only one case and no major complications were observed.

Conclusion

The four-step procedure (scar release, midface lift, buccal mucosal graft and canthal tightening) was an effective procedure to correct cicatricial lower eyelid retractions with acceptable outcomes and a low morbidity rate.
Multidisciplinary peer-led sexual and reproductive health education programme in France, a prospective controlled-study
Authors: Nuttall Anaïs , Mancini Julien , Lizin Camille , Hamzaoui Sabrina , Mariotti Sophie , Louesdon Héloïse , Tardieu Sophie , Viton Jean-Michel , Delotte Jérôme , Bretelle Florence
Published: December 2022

Background

Sexual education is an international priority to promote sexual and reproductive health (SRH) and to reduce risky sexual behaviour. Experts recommend holistic and comprehensive SRH peer-led education.

In 2018, the French government launched a new public peer-led health prevention programme called the “Service Sanitaire” (SeSa), consisting of health education provided by healthcare students (peer educators) to teenagers. For the first time in France, the impact of the programme was prospectively evaluated during its first year to examine whether the programme improved the SRH knowledge of healthcare students and teenagers. Risk perception and risky sexual behaviour among these populations were also evaluated.

Method

A prospective multicentre controlled study was conducted from November 2018 to May 2019. SRH knowledge was compared before and after the SeSa programme, and the evolution of this knowledge was compared, with linear regression, between healthcare students part of the SRH SeSa programme and those who were part of another programme. The same analysis of knowledge was performed with respect to teenagers who received SRH interventions as part of the SeSa compared to teenagers who did not participate in a specific SRH education programme. Risk perception and risky behaviour were studied before and after the programme among healthcare students and teenagers.

Results

More than 70% of the targeted population participated in the study, with 747 healthcare students and 292 teenagers. SRH peer educators increased their knowledge score significantly more than other peer educators (a difference of 2.1 points/30 [95% CI 1.4–2.9] (p [between group] <  0.001)). Teenagers participating in the SeSa interventions also had a greater increase in their knowledge score than the other teenagers (+ 5.2/30 [95% CI 3.2–7.4] p [between group] < 0.001). There was no evidence of change in sexual risk behaviours for the healthcare student population.

Conclusion

The “Service Sanitaire” programme significantly improved the sexual and reproductive health knowledge of peer-educator healthcare students and teenagers compared to a classic education programme. Longer and/or qualitative studies are needed to evaluate changes in sexual behaviour as well as positive impacts on sexuality.
Dynamics of Hepatitis B infection prevention practices among pregnant women attending antenatal care at Lubaga Hospital Kampala, Uganda using the constructs of information-motivation-behavioural skills model
Authors: Afolabi Ismail Bamidele , Aremu Abdulmujeeb Babatunde , Maidoki Lawal Abdurraheem , Atulomah Nnodimele Onuigbo
Published: December 2022

Background

Hepatitis B virus (HBV) infection is considered a significant global public health challenge with infectivity as well as estimated potential for transmission more than 50 to 100 times that of HIV. Over time, numerous empirical studies have shown that majority of HBV-related yearly global deaths are secondary to carcinoma of the liver. It is also known that HBV infected Women have the potential to transmit the infection vertically to their infants during pregnancy. This accounts for the WHO reported 3.16% prevalence among children less than 5 years of age in Uganda. This study assessed the predictors of HBV infection prevention practices among eligible consenting pregnant women using Lubaga health facility for antenatal care (ANC).

Methods

A cross-sectional descriptive study employing quantitative data collection based on the constructs of IMB model was used to capture data on the study variables among 385 randomly selected eligible pregnant women attending antenatal care at Lubaga hospital between September 2020 and October 2020. Data derived from the quantitative instrument was analysed by data reduction and transformation to summaries of descriptive statistics using (SPSS version 26) and regression analysis was performed to establish characteristics of the association between the variables with significance level set as (p < 0.05). Chi-square goodness-of-fit test was employed for significant differences in the proportion of dichotomous responses.

Results

The findings showed that more than half of the respondents (59%) were between the ages of 18 and 28 and majority of them (42.3%) had secondary education. Furthermore, an average but inadequate knowledge ($$\overline{X }=$$

X
¯

=

5.97 ± 6.61; B = 0.57; p < .001), positive perception ($$\overline{X }=$$

X
¯

=

17.10 ± 18.31; B = 0.97; p = .014) and good behavioural skills ($$\overline{X }=$$

X
¯

=

12.39 ± 13.37; B = 0.56; p < .001) for adopting prevention practices all statistically predicted the averagely acceptable level of prevention practices ($$\overline{X }=$$

X
¯

=

15.03 ± 16.20) among the study respondents as measured on rating scales of 12, 33, 21 and 30 respectively.

Conclusion and recommendation

There were observed gaps in their knowledge about some basic features of the infection like transmission and risk factors as well as some misperceptions about vaccination despite the relatively average score level for both, which is likely to influence their prevention behaviours and predispose them to the risk of the infection if actions are not taken. Therefore, personalized health education is needed during antenatal visits and subsequent health campaign in order to inform better prevention practices among this vulnerable population group.
Cemented vs. uncemented reverse total shoulder arthroplasty for the primary treatment of proximal humerus fractures in the elderly—a retrospective case–control study
Authors: Kramer Manuel , Olach Martin , Zdravkovic Vilijam , Manser Melanie , Jost Bernhard , Spross Christian
Published: December 2022

Background

Uncemented reverse total shoulder arthroplasty (RTSA) for the primary treatment of proximal humerus fractures (PHF) in elderly patients was introduced at our institution in 2017. Recent reports have raised concerns about increased rates of early bone resorption at the proximal humerus with uncemented fracture stems. The aim of this study was to find out whether there was any difference in functional or radiographic outcomes between cemented and uncemented RTSA for PHF.

Methods

Seventeen consecutive patients who underwent uncemented RTSA (group nC) in 2017 and 2018 were age and sex matched (propensity score matching 1:2) to 34 patients with cemented RTSA implanted between 2011 and 2016 (group C) for the primary treatment of PHF. These two groups were compared in terms of clinical and radiographic outcomes at 2 years after the index surgery.

Results

The mean bone quality was low in both groups: in group nC the deltoid tuberosity index (DTI) was 1.43 (1.22–1.72) and in group C 1.42 (1.22–1.67). At the final 2 year follow-up, the relative CS was 98.3% (71–118) in group nC and 97.9% (36–125) in group C (p = 0.927); the absolute CS was 70.2 (49–89) in group nC and 68.0 (30–94) in group C (p = 0.509). Lucent lines at the humeral site were seen in 8 cases (47%) in group nC and in 13 cases (38%) in group C (p = 0.056). Compared to 3% in group C, all patients in group nC showed at least grade 1 and 65% showed grade 3 bone resorption at the proximal humerus (p < 0.001).

Conclusion

Compared to cemented RTSA bone resorption at the proximal humerus was significantly more frequent in patients with uncemented RTSA for PHF. So far, this is rather a radiographic than a clinical finding, because both groups showed very satisfying functional outcomes and low revision rates at the 2 year follow-up.

Level of Evidence III.

A retrospective case–control study.
Altered expression of SOCS genes periodontitis
Authors: Ghafouri-Fard Soudeh , Gholami Leila , Sadeghpour Saba , Nazer Naghme , Hussen Bashdar Mahmud , Sayad Arezou , Taheri Mohammad
Published: December 2022

Suppressor of cytokine signalling (SOCS) family comprises a group of proteins that impede JAK/STAT signalling, thus being involved in the pathogenesis of immune-related conditions. In the present work, we aimed at identification of the role of SOCS genes in the pathogenesis of periodontitis through evaluation of their expression levels both in the circulation and in the affected tissues of patients. Thus, we measured expression levels of SOCS1-3 and SOCS5 transcripts in the blood and gingival samples of patients with periodontitis in comparison with control samples obtained during dental crown lengthening. Expressions of SOCS1, SOCS2, SOCS3 and SOCS5 genes were similar between gingival tissues of patients and controls. However, our results demonstrated under-expression of SOCS1 in blood samples of patients compared with controls (Ratio of mean expression (RME) = 0.47, P value = 0.04). The same pattern was observed among female subjects (RME = 0.38, P value = 0.04). SOCS2 was down-regulated in blood samples of female patients compared with female controls (RME = 0.22, P value = 0.04). SOCS3 was also under-expressed in the circulation of total cases versus total controls (RME = 0.29, P value = 0.02) and in female patients compared with female controls (RME = 0.19, P value = 0.04). Expression of SOCS5 was not different between blood samples two study groups. SOCS2 had the best function in separation of affected tissues from unaffected ones (AUC = 0.66, sensitivity = 0.39, specificity = 0.83). SOCS3 was superior to other transcripts in differentiation of blood samples of patients from normal blood samples (AUC = 0.69, sensitivity = 0.81, specificity = 0.68). Combination of transcript levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes enhanced the AUC values to 0.64 and 0.67 in tissue and blood specimens, respectively. Taken together, certain SOCS genes have been found to be dysregulated in the circulation of patients with periodontitis.
eHealth, teledentistry and health workforce challenges: results of a pilot project
Authors: Németh Orsolya , Simon Fanni , Benhamida Abdallah , Kivovics Márton , Gaál Péter
Published: December 2022

Background

In the twenty-first century, health systems have to cope with the challenges posed by their rapidly changing environment. Among these changes, the emergence of digital health solutions is an opportunity to make health systems better, but also a compelling force to change. Community dentistry is one area of health care, where the rapid technological development has the potential for substantial performance improvement benefitting dental patients in terms of access to care and conveniance.

Methods

This study is based on a survey of the dental care provided by three units (Oral Medicine, Periodontology, Orthodontics) of the Department of Community Dentistry, Semmelweis University, Budapest. During a period of 12 weeks, we have collected time balance data on 1131 patients, 539 in the traditional and 592 in a pilot teledentistry setting, in order to estimate how much time could be spared by monitoring patients through videoconferencing instead of face-to-face visits.

Results

According to our findings, teledentistry has the potential to shorten the visit with an average of 5–10 min per patient, which adds up to 58–116 work hours in a year. If the pilot was rolled out to all the 13 chairs of the surveyed 3 specialties (orthodontics, periodontology and oral medicine) the time saving would sum up to 186 workdays in one shift alone, which would translate to close to 4500 additional patients per year, considering remote patient monitoring cases alone. Further, if inactive doctors and highly qualified dental hygienists were involved in delivering telecare, 2.67 times as many workdays could be spared, which would allow about 12,000 more patients treated per year.

Conclusions

The rapid development of digital health technologies coupled with the evolving task distribution between health professionals have a great potential to improve health system performance in pursuit of population health. Unfortunately, the adaptation to these technological changes is uneven, and without a national strategy, the poor will unlikely benefit from these opportunities in public dental care.
Knowledge, perceptions, attitudes, and clinical experiences on molar incisor hypomineralization among Syrian pediatric dentists and general dental practitioners: a cross-sectional study
Authors: Karkoutly Mawia , Hamza Blend , Al Batal Sami , Al Barazi Amat , Bshara Nada
Published: December 2022

Background

Molar incisor hypomineralization (MIH) is a widespread oral health problem. Dentists encounter several challenges regarding MIH management worldwide. The aim of this study was to evaluate and compare the knowledge, perceptions, attitudes, and clinical experiences on MIH among general dental practitioners and pediatric dentists in Syria.

Methods

All general dental practitioners and pediatric dentists belonging to the Syrian Dental Syndicate of Damascus were invited to complete a cross-sectional structured questionnaire (n = 1936). The questionnaire consisted of four sections and required responses regarding demographic data, knowledge, perceptions, attitudes, and experiences on MIH. Data were analyzed with Pearson’s chi-square test and multivariate regression models using SPSS Ver. 23.0.

Results

The overall response rate was 36.31% (703/1936). Pediatric dentists were significantly more familiar with MIH (p < 0.001) and more confident when diagnosing it (p < 0.001). Most participants (43.95%) perceived an increase in MIH prevalence in Syria. Stainless steel crowns were the most favorable restorative material for molars with post-eruptive breakdown (51.38%). As for molars and incisors with opacities, composite resin was preferred with (41.82%), and (67.51%) respectively. General dental practitioners requested further training regarding MIH treatment (p < 0.001).

Conclusions

Pediatric dentists were equipped with further knowledge regarding MIH, and were more confident when diagnosing it. There is a need for additional training and education for general dental practitioners. Most respondents perceived an increase in the prevalence of MIH. There is a dearth of data regarding MIH prevalence in Syria. The materials of choice for restoring teeth with MIH were stainless steel crowns and composite resin.
Named entity recognition of Chinese electronic medical records based on a hybrid neural network and medical MC-BERT
Authors: Chen Peng , Zhang Meng , Yu Xiaosheng , Li Songpu
Published: December 2022

Background

Named entity recognition (NER) of electronic medical records is an important task in clinical medical research. Although deep learning combined with pretraining models performs well in recognizing entities in clinical texts, because Chinese electronic medical records have a special text structure and vocabulary distribution, general pretraining models cannot effectively incorporate entities and medical domain knowledge into representation learning; separate deep network models lack the ability to fully extract rich features in complex texts, which negatively affects the named entity recognition of electronic medical records.

Methods

To better represent electronic medical record text, we extract the text’s local features and multilevel sequence interaction information to improve the effectiveness of electronic medical record named entity recognition. This paper proposes a hybrid neural network model based on medical MC-BERT, namely, the MC-BERT + BiLSTM + CNN + MHA + CRF model. First, MC-BERT is used as the word embedding model of the text to obtain the word vector, and then BiLSTM and CNN obtain the feature information of the forward and backward directions of the word vector and the local context to obtain the corresponding feature vector. After merging the two feature vectors, they are sent to multihead self-attention (MHA) to obtain multilevel semantic features, and finally, CRF is used to decode the features and predict the label sequence.

Results

The experiments show that the F1 values of our proposed hybrid neural network model based on MC-BERT reach 94.22%, 86.47%, and 92.28% on the CCKS-2017, CCKS-2019 and cEHRNER datasets, respectively. Compared with the general-domain BERT-based BiLSTM + CRF, our F1 values increased by 0.89%, 1.65% and 2.63%. Finally, we analyzed the effect of an unbalanced number of entities in the electronic medical records on the results of the NER experiment.
Use of the knowledge to action model improved physical therapist adherence to a common clinical practice guideline across multiple settings: a multisite case series
Authors: Tilson Julie K. , Martinez Clarisa A. , MacDowell Sara , D’Silva Linda J. , Howard Robbin , Roth Heidi R. , Skop Karen M. , Dannenbaum Elizabeth , Farrell Lisa
Published: December 2022

Background

When a new guideline is published  there is a need to understand how its recommendations can best be implemented in real-world practice. Yet, guidelines are often published with little to no roadmap for organizations to follow to promote adherence to their recommendations. The purpose of this study was to evaluate the impact of using a common process model to implement a single clinical practice guideline across multiple physical therapy clinical settings.

Methods

Five organizationally distinct sites with physical therapy services for patients with peripheral vestibular hypofunction participated. The Knowledge to Action model served as the foundation for implementation of a newly published guideline. Site leaders conducted preliminary gap surveys and face-to-face meetings to guide physical therapist stakeholders’ identification of target-behaviors for improved guideline adherence. A 6-month multimodal implementation intervention included local opinion leaders, audit and feedback, fatigue-resistant reminders, and communities of practice. Therapist adherence to target-behaviors for the 6 months before and after the intervention was the primary outcome for behavior change.

Results

Therapist participants at all sites indicated readiness for change and commitment to the project. Four sites with more experienced therapists selected similar target behaviors while the fifth, with more inexperienced therapists, identified different goals. Adherence to target behaviors was mixed. Among four sites with similar target behaviors, three had multiple areas of statistically significantly improved adherence and one site had limited improvement. Success was most common with behaviors related to documentation and offering patients low technology resources to support home exercise. A fifth site showed a trend toward improved therapist self-efficacy and therapist behavior change in one provider location.

Conclusions

The Knowledge to Action model provided a common process model for sites with diverse structures and needs to implement a guideline in practice. Multimodal, active interventions, with a focus on auditing adherence to therapist-selected target behaviors, feedback in collaborative monthly meetings, fatigue-resistant reminders, and developing communities of practice was associated with long-term improvement in adherence. Local rather than external opinion leaders, therapist availability for community building meetings, and rate of provider turnover likely impacted success in this model.

Trial registration

This study does not report the results of a health care intervention on human participants.
Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data
Authors: Chen Hongmin , Shi Xiaoxiao , Ren Li , Zhuo Hongyu , Zeng Li , Qin Qing , Wan Yuming , Sangdan Wangmu , Zhou Lin
Published: December 2022

Background

The current study set out to identify the miRNA-mRNA regulatory networks that influence the radiosensitivity in esophageal cancer based on the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases.

Methods

Firstly, esophageal cancer-related miRNA-seq and mRNA-seq data were retrieved from the TCGA database, and the mRNA dataset of esophageal cancer radiotherapy was downloaded from the GEO database to analyze the differential expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in radiosensitive and radioresistant samples, followed by the construction of the miRNA-mRNA regulatory network and Gene Ontology and KEGG enrichment analysis. Additionally, a prognostic risk model was constructed, and its accuracy was evaluated by means of receiver operating characteristic analysis.

Results

A total of 125 DEmiRNAs and 42 DEmRNAs were closely related to the radiosensitivity in patients with esophageal cancer. Based on 47 miRNA-mRNA interactions, including 21 miRNAs and 21 mRNAs, the miRNA-mRNA regulatory network was constructed. The prognostic risk model based on 2 miRNAs (miR-132-3p and miR-576-5p) and 4 mRNAs (CAND1, ZDHHC23, AHR, and MTMR4) could accurately predict the prognosis of esophageal cancer patients. Finally, it was verified that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR could affect the radiosensitivity in esophageal cancer.

Conclusion

Our study demonstrated that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR were critical molecular pathways related to the radiosensitivity of esophageal cancer.
Effects of colonization-associated gene yqiC on global transcriptome, cellular respiration, and oxidative stress in Salmonella Typhimurium
Authors: Fan Hung-Hao , Fang Shiuh-Bin , Chang Yu-Chu , Huang Sheng-Tung , Huang Chih-Hung , Chang Pei-Ru , Chang Wei-Chiao , Yang Lauderdale Tsai-Ling , Lin Pei-Chun , Cheng Hung-Yen
Published: December 2022

Background

yqiC is required for colonizing the Salmonella enterica serovar Typhimurium (S. Typhimurium) in human cells; however, how yqiC regulates nontyphoidal Salmonella (NTS) genes to influence bacteria–host interactions remains unclear.

Methods

The global transcriptomes of S. Typhimurium yqiC-deleted mutant (ΔyqiC) and its wild-type strain SL1344 after 2 h of in vitro infection with Caco-2 cells were obtained through RNA sequencing to conduct comparisons and identify major yqiC-regulated genes, particularly those involved in Salmonella pathogenicity islands (SPIs), ubiquinone and menaquinone biosynthesis, electron transportation chains (ETCs), and carbohydrate/energy metabolism. A Seahorse XFp Analyzer and assays of NADH/NAD+ and H2O2 were used to compare oxygen consumption and extracellular acidification, glycolysis parameters, adenosine triphosphate (ATP) generation, NADH/NAD+ ratios, and H2O2 production between ΔyqiC and SL1344.

Results

After S. Typhimurium interacts with Caco-2 cells, yqiC represses gene upregulation in aspartate carbamoyl transferase, type 1 fimbriae, and iron–sulfur assembly, and it is required for expressing ilvB operon, flagellin, tdcABCD, and dmsAB. Furthermore, yqiC is required for expressing mainly SPI-1 genes and specific SPI-4, SPI-5, and SPI-6 genes; however, it diversely regulates SPI-2 and SPI-3 gene expression. yqiC significantly contributes to menD expression in menaquinone biosynthesis. A Kyoto Encyclopedia of Genes and Genomes analysis revealed the extensive association of yqiC with carbohydrate and energy metabolism. yqiC contributes to ATP generation, and the analyzer results demonstrate that yqiC is required for maintaining cellular respiration and metabolic potential under energy stress and for achieving glycolysis, glycolytic capacity, and glycolytic reserve. yqiC is also required for expressing ndh, cydA, nuoE, and sdhB but suppresses cyoC upregulation in the ETC of aerobically and anaerobically grown S. Typhimurium; priming with Caco-2 cells caused a reversed regulation of yiqC toward upregulation in these ETC complex genes. Furthermore, yqiC is required for maintaining NADH/NAD+ redox status and H2O2 production.

Conclusions

Specific unreported genes that were considerably regulated by the colonization-associated gene yqiC in NTS were identified, and the key role and tentative mechanisms of yqiC in the extensive modulation of virulence factors, SPIs, ubiquinone and menaquinone biosynthesis, ETCs, glycolysis, and oxidative stress were discovered.
Multidrug resistance genes screening of pancreatic ductal adenocarcinoma based on sensitivity profile to chemotherapeutic drugs
Authors: Zhao Bangbo , Qin Cheng , Li Zeru , Wang Yuanyang , Li Tianhao , Cao Hongtao , Yang Xiaoying , Li Tianyu , Wang Weibin
Published: December 2022

Backgrounds

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types and chemotherapeutic drug resistance is a stumbling block in improving the overall survival of PDAC patients. The nature of specific drug resistant subpopulation within pancreatic ductal adenocarcinoma is believed to be partly attributed to epithelial-mesenchymal transition (EMT) and cell stemness. Various PDAC cell lines show various degrees of resistance to chemotherapeutic agents including gemcitabine (GEM) and 5-fluorouracil (5-FU). In-depth understanding of drug resistance mechanisms and profile heterogeneities could lead to the development of novel and precise therapeutic strategies for addressing the chemo-resistant dilemma in PDAC patients.

Methods

Cytotoxicity assays were performed by CCK8 in ten common PDAC cell lines including AsPC-1, BxPC-3, CAPAN-1, CFPAC, HPAFII, MIA PaCa-2, PANC-1, Patu-8988, SW1990 and T3M4. RNA-seq data of the ten cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE) database and subsequently analyzed for differentially expressed genes (DEGs). Based on first-line chemotherapy regimens of PDAC, DEGs between resistant and sensitive cell lines were validated by qRT-PCR. Enriched pathways of differentially expressed genes between the resistant and sensitive cell lines were acquired by Metascape database.

Results

We found that the top two toxic drugs for PDAC cell lines were paclitaxel (PTX) and GEM. Among the ten PDAC cell lines, SW1990 was the most resistant PDAC cell line with the highest IC50 levels for three drugs, while MIA PaCa-2 and BxPC-3 were the most sensitive PDAC cell lines. Differential expression analysis revealed the highest number of DEGs associated with cisplatin (CIS) sensitivity up to 642 genes, of which 181 genes were upregulated and 461 genes were downregulated in CIS-resistant cell lines. The least number of DEGs are associated with GEM sensitivity, of which 37 genes were highly expressed in GEM-resistant PDAC cell lines and 25 genes were lowly expressed. Enrichment analysis of the DEGs revealed that pathways associated with drug resistance were mainly extracellular matrix and cell–cell junction related pathways.

Conclusions

PDAC cell lines showed diverse sensitivities to commonly used chemotherapeutic agents, which was caused by differential gene expression between the resistant and sensitive cell lines. The heterogeneity and its associated genes were enriched in extracellular matrix and cell–cell junction related pathways. Our study first portrayed the sensitivity profile to chemotherapeutic drugs of PDAC, which would benefit the chemoresistance mechanism study by reemphasizing the vital role of extracellular matrix and cell–cell junction related pathways and helping the selection of suitable PDAC cell lines.
Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia
Authors: Assefa Ashenafi , Mohammed Hussein , Anand Anjoli , Abera Adugna , Sime Heven , Minta Anna A. , Tadesse Mekonnen , Tadesse Yehualashet , Girma Samuel , Bekele Worku , Etana Kebede , Alemayehu Bereket Hailegiorgis , Teka Hiwot , Dilu Dereje , Haile Mebrahtom , Solomon Hiwot , Moriarty Leah F. , Zhou Zhiyong , Svigel Samaly Souza , Ezema Bryan , Tasew Geremew , Woyessa Adugna , Hwang Jimee , Murphy Matthew
Published: December 2022

Background

Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax.

Methods

The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods.

Results

A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96–100), 98% in CQ-P. vivax (95% CI: 95–100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported.

Conclusion

This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option.
Low dimensional nanomaterials for treating acute kidney injury
Authors: Nie Yuanpeng , Wang Liying , You Xinru , Wang Xiaohua , Wu Jun , Zheng Zhihua
Published: December 2022

Acute kidney injury (AKI) is one of the most common severe complications among hospitalized patients. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. AKI treatment has received significant attention recently due to the excellent drug delivery capabilities of low-dimensional nanomaterials (LDNs) and their unique therapeutic effects. Diverse LDNs have been proposed to treat AKI, with promising results and the potential for future clinical application. This article aims to provide an overview of the pathogenesis of AKI and the recent advances in the treatment of AKI using different types of LDNs. In addition, it is intended to provide theoretical support for the design of LDNs and implications for AKI treatment.

Graphical Abstract
Cost-effectiveness analysis of dapagliflozin in the management of heart failure with reduced ejection fraction (HFrEF): a systematic review
Authors: Mohammadnezhad Ghader , Azadmehr Behniya , Mirheidari Mehdi , Yousefi Nazila
Published: December 2022

Objectives

This study was aimed to systematically review published economic studies to determine whether dapagliflozin, a sodium-glucose co-transporter inhibitor, plus standard care therapy (SCT) is cost-effective in heart failure with reduced ejection fraction (HFrEF).

Method

We searched relevant keywords in PubMed, Scopus, Web of science, and Google Scholar to find related articles. Costs, QALYs, ICERs were extracted from eligible studies.

Results

Ten studies finally included in the systematic review. The results of quality assessment of the study showed that a reasonable quality of all studies. Incremental QALYs were in favor of dapagliflozin plus SCT treatment regimen. In all the studies, the incremental costs per QALY was below the willingness-to-pay (WTP) threshold with the exception of one study in United Kingdom which the ICER and WTP were $83,650 and $50,000. All the studies determined the National Health Care perspective. The highest and lowest ICERs were $83,650 and $1991 per QALY in United Kingdom and Thailand, respectively.

Conclusion

Results of cost-effectiveness analyses showed that adjunct dapagliflozin plus SCT is cost-effective compared to SCT alone despite the additional costs of the drug. Finally it can be concluded that dapagliflozin is a worldwide cost-effective as an adjunct medicine in HFrEF management.
“I am not shy anymore”: A qualitative study of the role of an interactive mHealth intervention on sexual health knowledge, attitudes, and behaviors of South African adolescents with perinatal HIV
Authors: Bergam Scarlett , Sibaya Thobekile , Ndlela Nompumelelo , Kuzwayo Mpume , Fomo Messaline , Goldstein Madeleine H. , Marconi Vincent C. , Haberer Jessica E. , Archary Moherndran , Zanoni Brian C.
Published: December 2022

Background

South Africa has one of the highest burdens of adolescents with perinatally-acquired HIV (APHIV) in the world. APHIV in South Africa have limited access to sexual and reproductive health (SRH) education and services specific to their HIV status. When lacking comprehensive SRH education, APHIV are prone to sexual risk behaviors that can lead to unintended pregnancy, sexually transmitted infections, and HIV transmission. The use of mHealth interventions has been shown to deliver information, foster social support, and improve decision-making skills. In this study, we evaluate how an mHealth intervention influences sexual health knowledge and behaviors in APHIV.

Methods

We purposively enrolled adolescents from the intervention arm of a randomized clinical trial assessing a multi-module, moderated WhatsApp-based intervention—Interactive Transition Support for Adolescents Living with HIV (InTSHA)—within a government supported clinic in KwaMashu, an urban township of KwaZulu-Natal, South Africa. We conducted in-depth interviews based on World Health Organization guidelines for asking adolescents about SRH. We thematically analyzed data through an iterative, team-based coding approach combining deductive and inductive elements to contextualize SRH attitudes, knowledge, and behaviors before and after receiving the InTSHA intervention.

Results

Of the 21 participants, 13 (61.9%) were female and the mean age was 16.6 years. Most participants reported first learning about SRH as young teenagers in school through non-targeted and negative ways, seeking clarification through peers and the internet rather than clinicians or caregivers. Participants reported that InTSHA provided a holistic perspective on relationships, gender, and sexuality specific to growing up with HIV in South Africa. They praised the ability to give and receive information from peers in a moderated setting through the mHealth intervention, building their confidence, decision-making skills, and communication with partners and caregivers throughout their everyday lives. Despite reporting some technological challenges, adolescents agreed that InTSHA was convenient, confidential, and user-friendly.

Conclusions

South African APHIV receive incomplete and conflicting sexual education from peers, caregivers, teachers, and technology that can be supplemented by mHealth curricula targeted for the unique needs of APHIV. Future, scaled-up mHealth interventions can lower SRH stigma by expanding access to sexual education and peer support, supplementing adolescents’ existing SRH education.