bluuebunny/crossref_metadata_2025 huggingface dataset:
scSemiAAE: a semi-supervised clustering model for single-cell RNA-seq data
Authors: Wang Zile , Wang Haiyun , Zhao Jianping , Zheng Chunhou
Published: May 2023

Background

Single-cell RNA sequencing (scRNA-seq) strives to capture cellular diversity with higher resolution than bulk RNA sequencing. Clustering analysis is critical to transcriptome research as it allows for further identification and discovery of new cell types. Unsupervised clustering cannot integrate prior knowledge where relevant information is widely available. Purely unsupervised clustering algorithms may not yield biologically interpretable clusters when confronted with the high dimensionality of scRNA-seq data and frequent dropout events, which makes identification of cell types more challenging.

Results

We propose scSemiAAE, a semi-supervised clustering model for scRNA sequence analysis using deep generative neural networks. Specifically, scSemiAAE carefully designs a ZINB adversarial autoencoder-based architecture that inherently integrates adversarial training and semi-supervised modules in the latent space. In a series of experiments on scRNA-seq datasets spanning thousands to tens of thousands of cells, scSemiAAE can significantly improve clustering performance compared to dozens of unsupervised and semi-supervised algorithms, promoting clustering and interpretability of downstream analyses.

Conclusion

scSemiAAE is a Python-based algorithm implemented on the VSCode platform that provides efficient visualization, clustering, and cell type assignment for scRNA-seq data. The tool is available from https://github.com/WHang98/scSemiAAE.
Impact of a multidisciplinary approach involving clinical pharmacist on resolving drug related problems in chronic kidney patients: a prospective interventional study
Authors: Pehlivanli Aysel , Eyupoglu Sahin , Basgut Bilgen , Erturk Sehsuvar , Ozcelikay A. Tanju
Published: May 2023

Background

Chronic kidney disease (CKD) is a major public health concern due to its high mortality risk, high hospitalization rates and cost, and low life expectancy. Thus, CKD patients are among patient group that may benefit from clinical pharmacy services the most.

Methods

This was a prospective interventional study conducted between October 1, 2019, and March 18, 2020, in the nephrology ward of Ankara University School of the Medicine, Ibn-i Sina Hospital. DRPs were classified according to PCNE v8.03. The main outcomes were interventions proposed and the rate of acceptance by the physicians.

Results

269 pre-dialysis patients were included to determine DRPs during the treatment process of the patients. 205 DRPs were found in 131 (48.7%) patients. Treatment efficacy was found to be the main type of DRPs (56.2%) followed by treatment safety (39.6%). When patients with and without DRPs were compared, it was found that the number of female patients (55.0%) was higher in the group with DRPs (p < 0.05). The length of hospital stays (11.3 ± 7.7) and the mean number of drugs used (9.6 ± 3.6) in the group with DRPs were significantly higher than those without DRPs (9.3 ± 5.9; 8.1 ± 3.5, respectively) (p < 0.05). 91.7% of the interventions were accepted by the physicians, and patients and found clinically beneficial. 71.7% of DRPs were fully resolved, 1.9% partially resolved and 23.4% could not be resolved.

Conclusions

A high prevalence of DRPs in patients with chronic kidney disease was determined during therapy. Clinical pharmacist interventions were highly accepted by the physicians and patients. This may indicate implementation of clinical pharmacy services in the nephrology ward has a great impact on optimized therapy and prevention DRPs.
Effectiveness of midwifery-led care on pregnancy outcomes in low- and middle-income countries: a systematic review and meta-analysis
Authors: Fikre Rekiku , Gubbels Jessica , Teklesilasie Wondwosen , Gerards Sanne
Published: May 2023

Background

Midwifery-led care is an evidence-based practice in which a qualified midwife provides comprehensive care for low-risk pregnant women and new-borns throughout pregnancy, birth, and the postnatal period. Evidence indicates that midwifery-led care has positive impacts on various outcomes, which include preventing preterm births, reducing the need for interventions, and improving clinical outcomes. This is, however, mainly based on studies from high-income countries. Therefore, this systematic review and meta-analysis aimed to assess the effectiveness of midwifery-led care on pregnancy outcomes in low- and middle-income countries.

Methods

We used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Three electronic databases (PubMed, CINAHL, and EMBASE) were searched. The search results were systematically screened by two independent researchers. Two authors independently extracted all relevant data using a structured data extraction format. Data analysis for the meta-analysis was done using STATA Version 16 software. A weighted inverse variance random-effects model was used to estimate the effectiveness of midwifery-led care on pregnancy outcomes. Odds ratio with a 95% confidence interval (CI) was presented using a forest plot.

Results

Ten studies were eligible for inclusion in this systematic review, of which five studies were eligible for inclusion in the meta-analysis. Women receiving midwifery-led care had a significantly lower rate of postpartum haemorrhage and a reduced rate of birth asphyxia. The meta-analysis further showed a significantly reduced risk of emergency Caesarean section (OR = 0.49; 95% CI: 0.27–0.72), increased odds of vaginal birth (OR = 1.14; 95% CI: 1.04–1.23), decreased use of episiotomy (OR = 0.46; 95% CI: 0.10–0.82), and decreased average neonatal admission time in neonatal intensive care unit (OR = 0.59; 95% CI: 0.44–0.75).

Conclusions

This systematic review indicated that midwifery-led care has a significant positive impact on improving various maternal and neonatal outcomes in low- and middle-income countries. We therefore advise widespread implementation of midwifery-led care in low- and middle-income countries.
The association of healthy lifestyle score and risk of non-alcoholic fatty liver disease
Authors: Jahromi Mitra Kazemi , Daftari Ghazal , Farhadnejad Hossein , Tehrani Asal Neshatbini , Teymoori Farshad , Salehi-Sahlabadi Ammar , Mirmiran Parvin
Published: May 2023

Background

The combined role of important environmental factors as a single lifestyle index in predicting non-alcoholic fatty liver disease (NAFLD) risk is not fully assessed. Therefore, we aimed to investigate the association of healthy lifestyle factor score (HLS) with the odds of NAFLD in Iranian adults.

Methods

This case-control study was conducted on 675 participants, aged ≥ 20–60 years, including 225 new NAFLD cases and 450 controls. We measured dietary intake information using a validated food frequency questionnaire and determined diet quality based on the alternate healthy eating index-2010(AHEI-2010). The score of HLS was calculated based on four lifestyle factors, including a healthy diet, normal body weight, non-smoking, and high physical activity. An ultrasound scan of the liver was used to detect NAFLD in participants of the case group. Logistic regression models were used to determine the odds ratios(ORs) and 95% confidence interval(CI) of NAFLD across tertiles of HLS and AHEI.

Results

Mean ± SD age of the participants were 38.13 ± 8.85 years. The Mean ± SD HLS in the case and control groups was 1.55 ± 0.67 and 2.53 ± 0.87, respectively. Also, the Mean ± SD AHEI in the case and control groups was 48.8 ± 7.7 and 54.1 ± 8.1, respectively. Based on the age and sex-adjusted model, the odds of NAFLD were decreased across tertiles of AHEI (OR:0.18;95%CI:0.16–0.29,Ptrend<0.001) and HLS(OR:0.03;95%CI:0.01–0.05,Ptrend<0.001). Also, in the multivariable model, the odds of NAFLD were decreased across tertiles AHEI (OR:0.12;95%CI:0.06–0.24,Ptrend<0.001) and HLS(OR:0.02;95%CI:0.01–0.04,Ptrend<0.001).

Conclusions

Our findings reported that higher adherence to lifestyle with a higher score of HLS was associated with decreased odds of NAFLD. Also, a diet with a high AHEI score can reduce the risk of NAFLD in the adult population.
Community dialogue meetings among district leaders improved their willingness to receive COVID-19 vaccines in Western Uganda, May 2021
Authors: Nsubuga Edirisa Juniour , Fitzmaurice Arthur G. , Komakech Allan , Odoi Tom Dias , Kadobera Daniel , Bulage Lilian , Kwesiga Benon , Elyanu Peter James , Ario Alex Riolexus , Harris Julie R.
Published: May 2023

Background

Widespread COVID-19 vaccine uptake can facilitate epidemic control. A February 2021 study in Uganda suggested that public vaccine uptake would follow uptake among leaders. In May 2021, Baylor Uganda led community dialogue meetings with district leaders from Western Uganda to promote vaccine uptake. We assessed the effect of these meetings on the leaders’ COVID-19 risk perception, vaccine concerns, perception of vaccine benefits and access, and willingness to receive COVID-19 vaccine.

Methods

All departmental district leaders in the 17 districts in Western Uganda, were invited to the meetings, which lasted approximately four hours. Printed reference materials about COVID-19 and COVID-19 vaccines were provided to attendees at the start of the meetings. The same topics were discussed in all meetings. Before and after the meetings, leaders completed self-administered questionnaires with questions on a five-point Likert Scale about risk perception, vaccine concerns, perceived vaccine benefits, vaccine access, and willingness to receive the vaccine. We analyzed the findings using Wilcoxon’s signed-rank test.

Results

Among 268 attendees, 164 (61%) completed the pre- and post-meeting questionnaires, 56 (21%) declined to complete the questionnaires due to time constraints and 48 (18%) were already vaccinated. Among the 164, the median COVID-19 risk perception scores changed from 3 (neutral) pre-meeting to 5 (strong agreement with being at high risk) post-meeting (p < 0.001). Vaccine concern scores reduced, with medians changing from 4 (worried about vaccine side effects) pre-meeting to 2 (not worried) post-meeting (p < 0.001). Median scores regarding perceived COVID-19 vaccine benefits changed from 3 (neutral) pre-meeting to 5 (very beneficial) post-meeting (p < 0.001). The median scores for perceived vaccine access increased from 3 (neutral) pre-meeting to 5 (very accessible) post-meeting (p < 0.001). The median scores for willingness to receive the vaccine changed from 3 (neutral) pre-meeting to 5 (strong willingness) post-meeting (p < 0.001).

Conclusion

COVID-19 dialogue meetings led to district leaders’ increased risk perception, reduced concerns, and improvement in perceived vaccine benefits, vaccine access, and willingness to receive the COVID-19 vaccine. These could potentially influence public vaccine uptake if leaders are vaccinated publicly as a result. Broader use of such meetings with leaders could increase vaccine uptake among themselves and the community.
LGBTQ College student health and wellbeing at the onset of the pandemic: additional evidence and lessons learned from COVID-19
Authors: Gonzales Gilbert , de Mola Emilio Loret , Robertson Lee , Gavulic Kyle A. , McKay Tara
Published: May 2023

Background

The coronavirus (COVID-19) pandemic has killed more than six million people and disrupted health care systems globally. In the United States alone, more than one million people have died from COVID-19 infections. At the start of the pandemic, nearly all aspects of our lives paused to prevent the spread of the novel coronavirus. Many institutions of higher education transitioned to remote learning and enacted social distancing measures. This study examined the health needs and vulnerabilities of lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) college students at the start of the COVID-19 pandemic in the United States.

Methods

We fielded a rapid-response online survey between April and June of 2020. We recruited 578 LGBTQ-identifying college students aged 18 years and older by reaching out to LGBTQ-serving organizations on 254 college campuses and via targeted social media advertising.

Results

Approximately 40% of LGBTQ college students surveyed were dissatisfied with life at the start of the COVID-19 pandemic, and almost all (90%) were concerned that COVID-19 would threaten their mental health. Moreover, about 40% of LGBTQ college students reported unmet mental health needs, and 28% were worried about seeking care during the pandemic because of their LGBTQ identity. One out of four LGBTQ college students had to go back in the closet because of the pandemic, and approximately 40% were concerned about their finances or personal safety during the COVID-19 pandemic. Some of these adverse outcomes were prominent among younger students, Hispanic/Latinx students, and students with unsupportive families or colleges.

Conclusions

Our study adds novel findings to the large body of research demonstrating that LGBTQ college students experienced distress and elevated mental health needs early in the pandemic. Future research should examine the long-term consequences of the pandemic among LGBTQ and other minoritized college students. Public health policymakers, health care providers, and college and university officials should provide LGBTQ students affirming emotional supports and services to ensure their success as the COVID-19 pandemic transitions to endemic.
Association between sleep problems and multimorbidity patterns in older adults
Authors: Idalino Stefany Cristina Claudino , Canever Jaquelini Betta , Cândido Letícia Martins , Wagner Katia Jakovljevic Pudla , de Souza Moreira Bruno , Danielewicz Ana Lúcia , de Avelar Núbia Carelli Pereira
Published: May 2023

Background

Sleep problems are frequent in older adults and are associated with chronic diseases. However, the association with multimorbidity patterns is still unknown. Considering the negative impacts that multimorbidity patterns can have on older adults’ life, knowledge of this association can help in the screening and early identification of older adults with sleep problems. The objective was to verify the association between sleep problems and multimorbidity patterns in older Brazilian adults.

Methods

This was a cross-sectional study conducted with data from 22,728 community-dwelling older adults from the 2019 National Health Survey. The exposure variable was self-reported sleep problems (yes/no). The study outcomes were: multimorbidity patterns, analyzed by self-report of the coexistence of two or more chronic diseases with similar clinical characteristics: (1) cardiopulmonary; (2) vascular-metabolic; (3) musculoskeletal; (4) coexisting patterns.

Results

Older adults with sleep problems had 1.34 (95%CI: 1.21; 1.48), 1.62 (95%CI: 1.15; 2.28), 1.64 (95%CI: 1.39; 1.93), and 1.88 (95%CI: 1.52; 2.33) greater odds of presenting vascular-metabolic, cardiopulmonary, musculoskeletal, and coexisting patterns, respectively.

Conclusions

These results suggest that public health programs aimed at preventing sleep problems in older adults are essential to reduce possible adverse health outcomes, including multimorbidity patterns and their negative consequences for older adults’ health.
Association of depressive symptoms with retirement in Chinese employees: evidence from national longitudinal surveys from 2011 to 2018
Authors: Xu Fenglin , Yuan Jingmin , Wu Hongxia
Published: May 2023

Background

The relationship between depressive symptoms and retirement remains controversial. Thus, we aimed to explore the effect of retirement on individuals' depressive symptoms in Chinese employees.

Methods

In this panel data analysis, a data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013, 2015 and 2018 was adopted with a total of 1390 employees aged ≥ 45-years-old who had complete follow-up for the four waves. Random-effects logistic regression was used to examine the associations between retirement and depressive symptoms.

Results

After adjusting several socio-demographic variables, retirement still increases the risk of depressive symptoms in the retirees (odds ratio 1.5, 95% CI 1.14–1.97). Through subgroup analysis, we found that people who are male, with lower education level, married, living in rural areas, suffering from chronic diseases, and those who do not participate in social activities are more likely to experience depression after retirement.

Conclusions

Retirement can increase the depression risk of Chinese employees. It is necessary to formulate relevant supporting policies to reduce the risk of depression.
Impacts of COVID-19 on career choices in health professionals and medical students
Authors: Doan Linh Phuong , Dam Vu Anh Trong , Boyer Laurent , Auquier Pascal , Fond Guillaume , Tran Bach , Vu Thuc Minh Thi , Do Hoa Thi , Latkin Carl A. , Zhang Melvyn W.B. , Ho Roger C.M. , Ho Cyrus S.H.
Published: May 2023

Backgrounds

The COVID-19 pandemic has resulted in not only significant mortalities in Vietnam but has had an impact on its economy. Previous studies have highlighted how the pandemic has had a marginal impact on Vietnamese healthcare workers working at the frontlines. To date, there have been several other studies examining the impact of COVID-19 on intentions to transition between jobs among healthcare professionals, but this has yet to be explored amongst Vietnamese healthcare workers.

Methods

To achieve the study’s objectives an online cross-sectional study was conducted between September to November 2021. Snowball sampling methodology was adopted for the recruitment of participants. The questionnaire that was used for this study comprised of the following sections: (a) socio-demographic information; (b) impact of COVID-19 on work; (c) risk of exposure to COVID-19; (d) career choices/intentions to change job, and (e) motivation at work.

Results

There were 5727 completed the entire survey. 17.2% of the respondents have had increased job satisfaction, 26.4% reported increased motivation to work, and 40.9% reported decreased motivation to work. Whilst there were changes in the daily work intensity and the level of work-related stress, more than 60% of respondents we sampled did not intend to switch careers. Demographic variables like gender, whether one was a student or an existing healthcare worker, and income related to work motivation. The community’s stigma was a negative factor that declined intrinsic motivation as well as decreased work retention.

Conclusions

Our study is instrumental in identifying the impact of COVID-19 on career choices amongst Vietnamese healthcare workers. The factors identified have clear implications for policymaking.
Spatial differentiation and driving factors of the high-quality development of undertakings for the aged of China
Authors: Peng Rong , Huang Jianhang , Deng Xueqin , Wang Yingying
Published: May 2023

Background

Promoting the high-quality development (HQD) of undertakings for the aged is an important action to proactively respond to the rapid population aging in China. This study analyzes spatial differentiation and driving factors of the HQD of China’s undertakings for the aged.

Methods

Based on a quantitative indicator system consisting of old-age social security, elder care services, health care service and older adults’ social participation, the HQD levels of 31 Chinese provincial administrative regions during 2013–2019 are measured by using the entropy weight method. Spatial panel regression models are used to analyze the impact of population aging, economic development and digital technology on the HQD of undertakings for the aged.

Results

The comprehensive level of the HQD slightly increased from 0.212 to 2013 to 0.220 in 2019, and the overall level was low. The HQD of the eastern region was the highest (0.292), followed by the western region (0.215), and the central region was the lowest (0.151). The high-high cluster type was mainly distributed in the eastern region; the low-low cluster type was mainly distributed in the western and central regions. Economic development and digital technology have significant positive effects while population aging has significant negative effects on the HQD of undertakings for the aged.

Conclusion

There is a significantly spatial differentiation in the HQD of China’s undertakings for the aged. In order to promote the HQD of undertakings for the aged, it is necessary to identify development gaps through making HQD evaluation and to focus on the indicators that are critical in maintaining sustainable economic development and to develop digital technology in order to get rid of those gaps.
Tumor microenvironment-responsive spherical nucleic acid nanoparticles for enhanced chemo-immunotherapy
Authors: Ma Bing , Ma Yingying , Deng Bo , Xiao Pengjun , Huang Pengyu , Wang Dali , Liu Lanxia
Published: May 2023

Certain chemotherapeutics can induce tumor cells’ immunogenic cell death (ICD), release tumor antigens, and thereby trigger personalized antitumor immune responses. Co-delivery of adjuvants using nanocarriers could amplify the ICD-induced tumor-specific immunity achieving a synergistic chemo-immunotherapeutic effect. However, complicated preparation, low drug loading efficiency, and potential carrier-associated toxicity are the major challenges that limited its clinical applications. Herein, a carrier-free core–shell nanoparticle (MPLA-CpG-sMMP9-DOX, MCMD NPs) was constructed by facile self-assembly of spherical nucleic acids (SNA) with two adjuvants of CpG ODN and monophosphoryl lipid A (MPLA) as a core and doxorubicin (DOX) radially around the dual-adjuvants SNA as a shell. The results demonstrated that MCMD NPs could enhance drugs accumulation in tumors, and release DOX upon enzymatic degradation of matrix metalloproteinase-9 (MMP-9) peptide in the tumor microenvironment (TME), which enhanced the direct-killing effect of DOX on tumor cells. The core of MPLA-CpG SNA efficiently boosted the ICD-induced antitumor immune response to further attack tumor cells. Thus, MCMD NPs achieved a synergistic therapeutic effect of chemo-immunotherapy with reduced off-target toxicity. This study provided an efficient strategy for the development of a carrier-free nano-delivery system for enhanced cancer chemo-immunotherapy.
Meaningful coproduction with clinicians: establishing a practice-based research network with physiotherapists in regional Australia
Authors: Gleadhill Connor , Williams Christopher M. , Kamper Steven J. , Bolsewicz Katarzyna , Delbridge Andrew , Mahon Benjamin , Donald Bruce , Delore Caitlin , Boettcher Craig , Renfrew David , Manvell Joshua , Dooley Katherine , Byrne Michael , Watson Toby , Makaroff Andrew , Gibbs Benedicta , Barnett Christopher , Corrigan Michael , Leyland Murray , Mullen Nicholas , Gallagher Ryan , Zelinski Samuel , Lamond Steven , Maude Travis , Davidson Simon R. E. , Robson Emma , Da Silva Priscilla Viana , Manvell Nicole
Published: May 2023

Background

The disconnect between research and clinical practice leads to research evidence that is often not useful for clinical practice. Practice-based research networks are collaborations between researchers and clinicians aimed at coproducing more useful research. Such networks are rare in the physiotherapy field. We aimed to describe (i) clinicians’ motivations behind, and enablers to, participating in a network, (ii) the process of network establishment and (iii) research priorities for a practice-based network of physiotherapists in the Hunter Region of New South Wales (NSW), Australia that supports research coproduction.

Methods

We describe the methods and outcomes of the three steps we used to establish the network. Step 1 involved consultation with local opinion leaders and a formative evaluation to understand clinicians’ motivations behind, and enablers to, participating in a network. Step 2 involved establishment activities to generate a founding membership group and codesign a governance model. Step 3 involved mapping clinical problems through a workshop guided by systems thinking theory with local stakeholders and prioritizing research areas.

Results

Through formative evaluation focus groups, we generated five key motivating themes and three key enablers for physiotherapists’ involvement in the network. Establishment activities led to a founding membership group (n = 29, 67% from private practice clinics), a network vision and mission statement, and a joint governance group (9/13 [70%] are private practice clinicians). Our problem-mapping and prioritization process led to three clinically relevant priority research areas with the potential for significant change in practice and patient outcomes.

Conclusions

Clinicians are motivated to break down traditional siloed research generation and collaborate with researchers to solve a wide array of issues with the delivery of care. Practice-based research networks have promise for both researchers and clinicians in the common goal of improving patient outcomes.
Utilization obstacles to hypertension services provided at comprehensive health centers: a content analysis study
Authors: Faraji-Khiavi Farzad , Ghorbani Kalkhajeh Sasan , Gholizadeh Behnam , Dindamal Behnaz
Published: May 2023

Introduction

Hypertensive patients' failure to refer to health centers for the management of their disease is the most fundamental public health challenge in most societies. The aim of this study was to identify the utilization obstacles to hypertension services provided at comprehensive health centers (CHCs) from the perspective of patients and the staff of health centers.

Methods

This was a qualitative study using conventional content analysis which was conducted in 2022. Participants included 15 hypertensive patients referring to CHCs and 10 staff (including personnel of CHCs and expert staff) of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, southwest of Iran. Data were collected using semi-structured interviews. Interviews were analyzed using content analysis method, and coding was done manually.

Results

In total, 15 codes and 8 categories were extracted from the interviews which were organized in two main themes of "individual problems" and "systemic problems". More particularly, the main theme of “individual problems” involved attitudinal obstacles, occupational obstacles, and economic obstacles. The main theme of "systemic problems" included educational obstacles, motivational obstacles, procedural obstacles, structural obstacles, and managerial obstacles.

Conclusion

In order to address individual problems associated with the patients' failure to refer to CHCs, we need to take appropriate measures. These include using motivational interviewing techniques and utilizing the effective activity of healthcare liaisons and volunteers in CHCs to increase patients' awareness and change their negative attitudes and misconceptions. To solve systemic problems, it is imperative that effective training courses be held for health center staff.
Phylogenetic analysis of HA and NA genes of influenza A viruses in immunosuppressed inpatients in Beijing during the 2018–2020 influenza seasons
Authors: Liu Yafen , Wang Yue , Wang Yanxin , Mai Huan , Chen YuanYuan , Zhang Yifan , Ji Ying , Cong Xu , Gao Yan
Published: May 2023

Background

Influenza A viruses have undergone rapid evolution with virulent; however, complete and comprehensive data on gene evolution and amino acid variation of HA and NA in immunosuppressed patients was few. In this study, we analysed molecular epidemiology and evolution of influenza A viruses in immunosuppressed population, and immunocompetent population were used as controls.

Methods

Full sequences of HA and NA of A(H1N1)pdm09 and A(H3N2) were acquired through reverse transcription-polymerase chain reaction (RT-PCR). HA and NA genes were sequenced using the Sanger method and phylogenetically analysed using ClustalW 2.10 and MEGA software version 11.0.

Results

During the 2018–2020 influenza seasons, 54 immunosuppressed and 46 immunocompetent inpatients screened positive for influenza A viruses by using the quantitative real-time PCR (qRT-PCR) were enrolled. 27 immunosuppressed and 23 immunocompetent nasal swab or bronchoalveolar lavage fluid samples were randomly selected and sequenced using the Sanger method. A(H1N1)pdm09 were detected in 15 samples and the remaining 35 samples were A(H3N2) positive. By analyzing the HA and NA gene sequences of these virus strains, we found that all A(H1N1)pdm09 viruses shared high similarities to each other and the HA and NA genes of these viruses exclusively belonged to subclade 6B.1A.1. Some NA genes of A(H3N2) viruses were not in the same clade as those of A/Singapore/INFIMH-16-0019/2016 and A/Kansas/14/2017, which may have led to A(H3N2) being the dominant strain in the 2019–2020 influenza season. Both A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Compared with the vaccine strains, there were no statistically significant of HA and NA genes and amino acid sequences of influenza A viruses in immunosuppressed and immunocompetent patients. However, the oseltamivir resistance substitution of NA-H275Y and R292K have been observed in immunosuppressed patients.

Conclusions

A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Both immunocompetent and immunosuppressed patients have some key substitutions, which should be of note monitored, especially those with potential to affect the viral antigen.
Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing
Authors: Zhang Chuan , Yan Yousheng , Zhou Bingbo , Wang Yupei , Tian Xinyuan , Hao Shengju , Ma Panpan , Zheng Lei , Zhang Qinghua , Hui Ling , Wang Yan , Cao Zongfu , Ma Xu
Published: May 2023

Background

Phenylketonuria (PKU) is an autosomal recessive congenital metabolic disorder caused by PAH variants. Previously, approximately 5% of PKU patients remained undiagnosed after Sanger sequencing and multiplex ligation-dependent probe amplification. To date, increasing numbers of pathogenic deep intronic variants have been reported in more than 100 disease-associated genes.

Methods

In this study, we performed full-length sequencing of PAH to investigate the deep intronic variants in PAH of PKU patients without definite genetic diagnosis.

Results

We identified five deep intronic variants (c.1199+502A>T, c.1065+241C>A, c.706+368T>C, c.706+531>C, and c.706+608A>C). Of these, the c.1199+502A>T variant was found at high frequency and may be a hotspot PAH variant in Chinese PKU. c.706+531T>C and c.706+608A>C are two novel variants that extend the deep intronic variant spectrum of PAH.

Conclusion

Deep intronic variant pathogenicity analysis can further improve the genetic diagnosis of PKU patients. In silico prediction and minigene analysis are powerful approaches for studying the functions and effects of deep intronic variants. Targeted sequencing after full-length gene amplification is an economical and effective tool for the detection of deep intron variation in genes with small fragments.
Comparing angiotensin receptor–neprilysin inhibitors with sodium–glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus
Authors: Tsai Ming-Lung , Lin Yuan , Lin Ming-Shyan , Tsai Tzu-Hsien , Yang Ning-I , Wang Chao-Yung , Hsieh I-Chang , Hung Ming-Jui , Chen Tien-Hsing
Published: May 2023

Background and aims

Clinical comparisons of angiotensin receptor–neprilysin inhibitors (ARNI) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set.

Methods

We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes.

Results

The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06–1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05–1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02–1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62–5.23). The improvements in echocardiographic parameters were comparable between the groups.

Conclusions

Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.
Abnormal glycosylation in glioma: related changes in biology, biomarkers and targeted therapy
Authors: Yue Juan , Huang Roujie , Lan Zehao , Xiao Bo , Luo Zhaohui
Published: May 2023

Glioma is a rapidly growing and aggressive primary malignant tumor of the central nervous system that can diffusely invade the brain tissue around, and the prognosis of patients is not significantly improved by traditional treatments. One of the most general posttranslational modifications of proteins is glycosylation, and the abnormal distribution of this modification in gliomas may shed light on how it affects biological behaviors of glioma cells, including proliferation, migration, and invasion, which may be produced by regulating protein function, cell—matrix and cell‒cell interactions, and affecting receptor downstream pathways. In this paper, from the perspective of regulating protein glycosylation changes and abnormal expression of glycosylation-related proteins (such as glycosyltransferases in gliomas), we summarize how glycosylation may play a crucial role in the discovery of novel biomarkers and new targeted treatment options for gliomas. Overall, the mechanistic basis of abnormal glycosylation affecting glioma progression remains to be more widely and deeply explored, which not only helps to inspire researchers to further explore related diagnostic and prognostic markers but also provides ideas for discovering effective treatment strategies and improving glioma patient survival and prognosis.
Effects of cellulase and xylanase on fermentative profile, bacterial diversity, and in vitro degradation of mixed silage of agro-residue and alfalfa
Authors: Mu Lin , Wang Qinglan , Wang Yating , Zhang Zhifei
Published: May 2023

The objective was to determine effects of cellulase, xylanase, and commercial fibrolytic enzymes on fermentation quality, aerobic stability, bacterial community, and in vitro degradation of mixed silages. Mixtures of alfalfa, wheat bran, and rice straw [80:15:5 on a fresh matter (FM) basis] were ensiled for 1, 3, 5, 7, 15, 30, and 45 d after treatment with: distilled water (control, C); cellulase (E); xylanase (X); or commercial fibrolytic enzymes (EX), with all enzyme preparations applied at 100 U/g FM. The 45-day silages were subjected to an in vitro degradation test. Each of the three enzyme-treated groups enriched relative abundance (RA) of Lactobacillus, Weissella, and Stenotrophomonas maltophilia, increased water soluble carbohydrate (WSC) concentrations, and extended aerobic stability over 384 h, but concurrently inhibited growth of undesirable microbes (i.e., Acinetobacter sp, Lelliottia amnigena, and Sphingomonas sp), reducing pH and concentrations of ammonia nitrogen (AN), butyric acid (BA) and propionic acid (PA). Compared to C, adding X or EX increased the RA of L. paralimentarius and L. parabrevis, enhanced accumulation of acetic acid (AA) and crude protein (CP), and reduced hemicellulose content. Furthermore, E group silage had the highest abundance of W. cibaria. In addition, EX enriched RA of Bacillus velezensis, reduced AN concentration, increased DM degradability, total VFA production, and gas production during in vitro incubation. In conclusion, addition of X or EX enhanced ensiling by enhancing concentrations of AA; however, EX was the most promising enzyme, based on reducing AN concentration and increasing DM content and DM degradability.

Graphical Abstract
Deep subduction of the Philippine Sea slab and formation of slab window beneath central Japan
Authors: Miyazaki Kazuki , Nakajima Junichi , Suenaga Nobuaki , Yoshioka Shoichi
Published: May 2023

The geometry of the Philippine Sea slab (PHS) subducting beneath the Japanese islands has been imaged to 400 km depth beneath the Kyushu and Chugoku regions, whereas the PHS slab geometry beneath the Hokuriku region has only been determined to ~ 140 km depth, thereby indicating a large east–west asymmetry in the slab subduction. However, geologic evidence suggests that there was symmetrical east–west seafloor spreading along the axis of the Kinan seamount chain when the Shikoku basin was an active spreading center in the PHS plate. This inconsistency suggests that the PHS slab should be present beneath the Hokuriku region. Here we perform P-wave travel-time tomography across central Japan and conduct a two-dimensional plate subduction numerical simulation that reproduces the dual subduction of the PHS and Pacific (PAC) plates to elucidate the PHS slab geometry beneath central Japan. The tomography results reveal a high-velocity anomaly at ~ 150–250 km depth that extends from Wakasa bay to Noto peninsula and a slab window beneath the Hokuriku region. The numerical simulation results suggest that the PHS slab may have torn when it collided with the PAC slab, with the once leading edge of the PHS slab now present along the upper surface of the PAC slab beneath Noto peninsula. These results indicate that the PHS slab exists at ~ 250 km depth beneath the Hokuriku region, although it has been torn owing to its collision with the PAC slab, with this tear propagating westward to form a triangular slab window beneath the Hokuriku region.

Graphical Abstract
The diabetes insulin self-management education (DIME) intervention for people with type 2 diabetes starting insulin: a pilot feasibility randomised controlled trial
Authors: Winkley Kirsty , Sorsa Taru , Tian Qingxiu , Reece Ilse , Fitzgerald Christina , Chamley Mark , Ismail Khalida , Forbes Angus , Upsher Rebecca
Published: May 2023

Objective

To determine the feasibility and acceptability of a diabetes insulin self-management education (DIME) group intervention for people with type 2 diabetes starting insulin.

Design

Single-centre parallel randomised pilot trial.

Setting

Primary care, South London, UK.

Subjects

Adults with type 2 diabetes, requiring insulin treatment, on maximum tolerated dose of 2 or more oral antidiabetic drugs with HbA1c > / = 7.5% (58 mmol/mol) on 2 occasions. We excluded people who were non-fluent in English; morbid obesity (BMI > / = 35 kg/m2); in employment that contraindicates insulin treatment; and those with severe depression, anxiety disorders, psychotic disorders, personality disorders, or cognitive impairment.

Methods

Participants were randomised using blocks of 2 or 4 to 3, 2-h group, face-to-face, DIME sessions or standard insulin group education sessions (control). We assessed feasibility according to consent to randomisation and attendance at intervention (DIME) and standard group insulin education sessions. Acceptability of the interventions was determined using exit interviews. We additionally measured change in self-reported insulin beliefs, diabetes distress and depressive symptoms between baseline and 6-month post-randomisation.

Results

There were 28 potentially eligible participants, of which 17 consented to randomisation, 9 were allocated to the DIME group intervention and 8 were allocated to the standard group insulin education. Three people withdrew from the study (1 from DIME and 2 from standard insulin education) before the start of the first session and did not complete baseline questionnaires. Of the remaining participants (n = 14), all DIME participants (n = 8) completed all 3 sessions, and all standard insulin education participants (n = 6) completed at least 1 standard insulin education session. The median group size was 2, the mean age of participants was 57.57 (SD 6.45) years, and 64% were female (n = 9). Exit interviews demonstrated that all participants (n = 7) found the group sessions acceptable, and thematic analysis of interview transcripts indicated social support, the content of group sessions and post-group experiences were positive, especially amongst DIME participants. There was improvement on self-report questionnaires.

Conclusions

The DIME intervention was acceptable and feasible to deliver to participants with type 2 diabetes starting insulin in South London, UK.

Trial registration

International Study Registration Clinical Trial Network (ISRCTN registration number 13339678).
Feasibility study of using mobile phone-based experience sampling to assess drug checking by opioid street drug users
Authors: Swartz James A. , Mackesy-Amiti Mary Ellen , Jimenez A. David , Robison-Taylor Lisa , Prete Elizabeth
Published: May 2023

Background

To date, evaluations of take-home fentanyl (and/or benzodiazepine) test strip use — the most common form of drug checking services — and potential effects on overdose risk have relied on retrospective accounts for some preceding time period, usually a week to several months. Such accounts, however, are subject to recall and memory biases. This pilot study assessed the feasibility of using experiential sampling to collect daily information in situ on drug checking and associated overdose risk reduction — the primary outcomes — among a sample of street opioid users and compared the results to retrospective reports.

Methods

We recruited 12 participants from a Chicago-based syringe services program. Participants were 18 years of age or older, reported using opioids purchased on the street 3 + times per week in the past month, and had an available Android mobile phone. A phone-based app was programmed to collect daily drug checking information and provided to each participant along with a supply of fentanyl and benzodiazepine test strips and instructions for use over 21 days. Comparable retrospective data were collected via follow-up in-person surveys at the conclusion of daily report collection.

Results

We found a reasonably high rate of daily reporting (63.5%) with participants submitting reports on 160 “person-days” out of 252 possible days. Participants submitted daily reports an average of 13 of 21 days. Reports of test strip use frequency varied between the retrospective and daily reports with a relatively higher percentage of days/time using test strips obtained from the daily reports. We also found higher proportions reporting overdose risk reduction behaviors on the daily reports compared with the retrospective reviews.

Conclusions

We believe the results support using daily experience sampling to collect information on drug checking behaviors among street drug users. Although resource intensive in comparison to retrospective reports, daily reporting potentially provides more detailed information on test strip use and its association with overdose risk reduction and, ultimately, fewer overdoses. Needed are larger trials and validation studies of daily experience sampling to identify the optimum protocol for collecting accurate information on drug checking and overdose risk reduction behavior.
Non-traditional cognitive brain network involvement in insulo-Sylvian gliomas: a case series study and clinical experience using Quicktome
Authors: Wu Zhiqiang , Hu Guanjie , Cao Bowen , Liu Xingdong , Zhang Zifeng , Dadario Nicholas B. , Shi Qinyu , Fan Xiao , Tang Yao , Cheng Zhangchun , Wang Xiefeng , Zhang Xia , Hu Xiaorong , Zhang Junxia , You Yongping
Published: May 2023

Background

Patients with insulo-Sylvian gliomas continue to present with severe morbidity in cognitive functions primarily due to neurosurgeons’ lack of familiarity with non-traditional brain networks. We sought to identify the frequency of invasion and proximity of gliomas to portions of these networks.

Methods

We retrospectively analyzed data from 45 patients undergoing glioma surgery centered in the insular lobe. Tumors were categorized based on their proximity and invasiveness of non-traditional cognitive networks and traditionally eloquent structures. Diffusion tensor imaging tractography was completed by creating a personalized brain atlas using Quicktome to determine eloquent and non-eloquent networks in each patient. Additionally, we prospectively collected neuropsychological data on 7 patients to compare tumor-network involvement with change in cognition. Lastly, 2 prospective patients had their surgical plan influenced by network mapping determined by Quicktome.

Results

Forty-four of 45 patients demonstrated tumor involvement (< 1 cm proximity or invasion) with components of non-traditional brain networks involved in cognition such as the salience network (SN, 60%) and the central executive network (CEN, 56%). Of the seven prospective patients, all had tumors involved with the SN, CEN (5/7, 71%), and language network (5/7, 71%). The mean scores of MMSE and MOCA before surgery were 18.71 ± 6.94 and 17.29 ± 6.26, respectively. The two cases who received preoperative planning with Quicktome had a postoperative performance that was anticipated.

Conclusions

Non-traditional brain networks involved in cognition are encountered during surgical resection of insulo-Sylvian gliomas. Quicktome can improve the understanding of the presence of these networks and allow for more informed surgical decisions based on patient functional goals.
Association of maternal exposure to Superstorm Sandy and maternal cannabis use with development of psychopathology among offspring: the Stress in Pregnancy Study
Authors: Nomura Yoko , Ham Jacob , Pehme Patricia M. , Wong Waiman , Pritchett Lexi , Rabinowitz Sima , Foldi Nancy S. , Hinton Veronica J. , Wickramaratne Priya J. , Hurd Yasmin L.
Published: May 2023

Background

Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied.

Aims

To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology.

Method

The study included 163 children (53.4% girls), longitudinally tracked (ages 2–5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed.

Results

A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n= 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06,P= 0.03) and anxiety disorders (synergy index, 2.60,P= 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support.

Conclusions

Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.