bluuebunny/crossref_metadata_2025 huggingface dataset:
Trust in healthcare before and during the COVID-19 pandemic
Authors: Skirbekk Helge , Magelssen Morten , Conradsen Stein
Published: May 2023

Background

Public trust is often advantageous for health authorities during crises such as the COVID-19 pandemic. Norwegian health authorities used the public´s high trust to control the pandemic, resulting in relatively few casualties.

Methods

We wanted to describe and compare the Norwegian public trust in GPs, public healthcare, information and treatment in hospitals before and during the early phases of the COVID-19 pandemic. Further, we wanted to investigate the relationship between somatic or mental illness, and trust in GPs and public health information, and to develop a theoretical understanding of the relationship between trust in healthcare institutions, generalised trust and the societal situation caused by the COVID-19 pandemic. We performed two surveys, the first in December 2019; the second in May 2020, thus providing two snapshots of the Norwegian public’s trust in healthcare and healthcare actors before and during the COVID-19 pandemic.

Results

There was statistically significant increased trust in public healthcare, in treatment at hospital and in information at hospital after the outbreak of the COVID-19 pandemic. There was a non-significant rise in trust in GPs. We found that trust in public health information was not related to mental health nor having a chronic, somatic disease.

Conclusion

The findings confirm that the Norwegian public’s trust in healthcare and healthcare actors is high. The trust levels are also relatively stable, and even show an increase during the early phases of the pandemic. We suggest that there is a dynamic relationship between trust in public health information, healthcare institutions, generalised trust and a societal crisis situation such as the COVID-19 pandemic. However, the GP-patient trust seems less affected by a crisis situation, than the public´s trust in healthcare institutions. This difference may be explained by the relative stability caused by mandates of trust obtained from the patient.
Messaging strategies for communicating health-related information in social media—a content and effectiveness analysis of organ donation posts on Instagram in Germany
Authors: Olsacher Alexandra , Bade Celina , Ehlers Jan , Freitag Bettina , Fehring Leonard
Published: May 2023

Background

Although organ transplantation is a very effective clinical solution to save the lives of patients suffering from organ failure, the supply of donated organs still cannot meet its growing demand. Educating the society about organ donation is a critical success factor in increasing donation rates, especially in countries that require potential donors to proactively register and opt-in (e.g., Germany). While social media has emerged as an effective tool for disseminating health information, recent evidence suggests that published organ donation content (both online and offline), aimed at raising awareness, still lacks effectiveness. To develop recommendations for optimizing organ donation messaging via social media, this study not only examines the current state of organ donation communication on Instagram, but also identifies factors that contribute to message effectiveness.

Methods

We conducted a retrospective content analysis to in-depth assess organ donation-related content published on Instagram in Germany between January and March 2022. Systematic coding allowed to identify common themes, sentiments, and communication strategies, which were analyzed for their effectiveness using linear regression analyses.

Results

Of the 500 organ donation posts, 57% were published by institutional authors while the remainder was shared by private accounts. Most content was aimed at the general population and shared neutral (80%) or positive sentiments (17%). Transformative messages, positive emotions, posts published by the transplant recipient and the image of a human served as predictors for post effectiveness measured in terms of likes (p < 0.001) and comments (p < 0.01). Sharing personal experiences (p < 0.01) and highlighting the meaning of organ donations (p < 0.05) resulted in significantly higher audience engagement than any other topic discussed.

Conclusion

Our findings highlight the need for health officials to work closely with organ transplant recipients to publicly advocate for organ donations by sharing personal and transformative messages. The high share of posts published by transplant recipients indicates a certain openness to share personal experiences with broad audiences. Different message characteristics served as predictors for message effectiveness (i.e., increased audience engagement) which can likely be extrapolated to other health-related use cases (e.g., cancer screening).
The association mental health of adolescents with economic impact during the COVID-19 pandemic: a 2020 Korean nationally representative survey
Authors: Park Hanul , Lee Kang-Sook
Published: May 2023

Background

COVID-19 has affected innumerable aspects of life, including education, economy, and religion. Economic problems and inequality are associated with poor mental health in adolescents. This study aimed to identify the relationship between economic damage to families due to COVID-19 and various mental health problems in Korean adolescents and to evaluate the risk factors of mental health.

Methods

In total, 54,948 Korean adolescent students from 398 middle and 395 high schools were surveyed between August and November 2020. Complex sample logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CI) for depression and suicidal ideation, respectively. A generalized linear model analysis was used to examine the association between mental health (unhappiness, loneliness, and stress) and the economic impact of COVID-19. Analyses were adjusted for age, gender, school grade, perceived academic achievement, perceived family economic status, and economic support.

Results

The ORs of depression (OR = 1.77, 95% CI:1.57–2.00), suicidal ideation (OR = 2.14, 95% CI:1.84–2.50), unhappiness (OR = 1.51 95% CI 1.42–1.60) and lonely (OR = 1.38 95% CI 1.27–1.49) for the low level of perceived family economic status was higher compared to middle level. Adolescents who experienced economic deterioration in their households as COVID-19 showed a higher risk of depression (OR = 1.42, 95% CI:1.35–1.49), suicide ideation (OR = 1.36, 95% CI:1.28–1.44), unhappiness (OR = 2.23 95% CI 2.19–2.27), lonely (OR = 1.20 95% CI 1.17–1.22), and stress (OR = 1.14 95% CI 1.12–1.16) than those who did not.

Conclusions

The findings revealed an association between the decline in household economic status due to COVID-19 and mental health problems, such as stress, loneliness, suicidal ideation, depression, and unhappiness.
Sexual orientation knowledge and attitudes and its association with therapy satisfaction among lesbian, gay, and bisexual + Hispanic Puerto Ricans
Authors: Esteban Caleb , Francia-Martínez Margarita , Vázquez-Rivera Miguel , Crespo Frances , Bruno-Ortiz Taysha , Santiago-Ortiz Aquiria M. , Martínez-Taboas Alfonso
Published: May 2023

This study aimed to examine the difference in therapy satisfaction between lesbian, gay, and bisexual + (LGB +) individuals and heterosexual individuals, and to identify the association between therapy satisfaction and the perception of knowledge and attitudes of their last therapist among the LGB + participants. Through an exploratory design with a comparative group, 125 LGB + and 75 heterosexual participants were recruited online by availability. Results indicate that the participants’ sexual orientation has no significant relation on therapy satisfaction. However, there was a significant positive association between satisfaction with therapy and the LGB + participants’ perception that their therapist demonstrated knowledge and positive attitudes. This research highlights the importance for continuous education and curriculum efforts on LGB + issues.
Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia
Authors: Ferreira Rafael Short , Ribeiro Paulo Roberto , Silva Juliana Helena Castro e , Hoppe Juliana Bender , de Almeida Monique Marylin Alves , de Lima Ferreira Beatriz Correia , Andrade Gustavo Borges , de Souza Suzana Braga , Ferdandez Luzimar Gonzaga , de Fátima Dias Costa Maria , Salbego Christianne Gazzana , Rivera Andrea Domenico , Longoni Aline , de Assis Adriano Martimbianco , Pieropan Francesca , Moreira José Cláudio Fonseca , Costa Silvia Lima , Butt Arthur Morgan , da Silva Victor Diogenes Amaral
Published: May 2023

Background

Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensis has long been used in folk medicine and seed extract obtained with dichloromethane (EDAC) have previously been shown to exhibit cytoprotective activity in vitro. The aim of the present study was to analyse the activity of EDAC in hippocampal brain slices.

Methods

We prepared a dichloromethane extract (EDAC) from A. cearensis seeds and characterized the chemical constituents by 1H and 13C-NMR. Hippocampal slices from P6-8 or P90 Wistar rats were used for cell viability assay or glutamate uptake test. Hippocampal slices from P10-12 transgenic mice SOX10-EGFP and GFAP-EGFP and immunofluorescence for GS, GLAST and GLT1 were used to study oligodendrocytes and astrocytes.

Results

Astrocytes play a critical role in glutamate homeostasis and we provide immunohistochemical evidence that in excitotoxicity EDAC increased expression of glutamate transporters and glutamine synthetase, which is essential for detoxifying glutamate. Next, we directly examined astrocytes using transgenic mice in which glial fibrillary acidic protein (GFAP) drives expression of enhanced green fluorescence protein (EGFP) and show that glutamate excitotoxicity caused a decrease in GFAP-EGFP and that EDAC protected against this loss. This was examined further in the oxygen–glucose deprivation (OGD) model of ischemia, where EDAC caused an increase in astrocytic process branching, resulting in an increase in GFAP-EGFP. Using SOX10-EGFP reporter mice, we show that the acute response of oligodendrocytes to OGD in hippocampal slices is a marked loss of their processes and EDAC protected oligodendrocytes against this damage.

Conclusion

This study provides evidence that EDAC is cytoprotective against ischemia and glutamate excitotoxicity by modulating astrocyte responses and stimulating their glutamate homeostatic mechanisms.
Divergent expression of aristaless1 and aristaless2 during embryonic appendage and pupal wing development in butterflies
Authors: Bayala Erick X. , Cisneros Isabella , Massardo Darli , VanKuren Nicholas W. , Kronforst Marcus R.
Published: May 2023

Background

Gene duplication events are critical for the evolution of new gene functions. Aristaless is a major regulator of distinct developmental processes. It is most known for its role during appendage development across animals. However, more recently other distinct biological functions have been described for this gene and its duplicates. Butterflies and moths have two copies of aristaless, aristaless1 (al1) and aristaless2 (al2), as a result of a gene duplication event. Previous work in Heliconius has shown that both copies appear to have novel functions related to wing color patterning. Here we expand our knowledge of the expression profiles associated with both ancestral and novel functions of Al1 across embryogenesis and wing pigmentation. Furthermore, we characterize Al2 expression, providing a comparative framework between gene copies within the same species, allowing us to understand the origin of new functions following gene duplication.

Results

Our work shows that the expression of both Al1 and Al2 is associated with the ancestral function of sensory appendage (leg, mouth, spines, and eyes) development in embryos. Interestingly, Al1 exhibits higher expression earlier in embryogenesis while the highest levels of Al2 expression are shifted to later stages of embryonic development. Furthermore, Al1 localization appears extranuclear while Al2 co-localizes tightly with nuclei earlier, and then also expands outside the nucleus later in development. Cellular expression of Al1 and Al2 in pupal wings is broadly consistent with patterns observed during embryogenesis. We also describe, for the first time, how Al1 localization appears to correlate with zones of anterior/posterior elongation of the body during embryonic growth, showcasing a possible new function related to Aristaless’ previously described role in appendage extension.

Conclusions

Overall, our data suggest that while both gene copies play a role in embryogenesis and wing pigmentation, the duplicates have diverged temporally and mechanistically across those functions. Our study helps clarify principles behind sub-functionalization and gene expression evolution associated with developmental functions following gene duplication events.
Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium
Authors: Pouwels Simon D. , van den Berge Maarten , Vasse Gwenda F. , Timens Wim , Brandsma Corry-Anke , Aliee Hananeh , Hiemstra Pieter S. , Guryev Victor , Faiz Alen
Published: May 2023

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in various cell types in the lung but the expression is especially high in goblet and ciliated cells. Recently, it was shown that next to its full-length isoform, ACE2 also has a short isoform. The short isoform is unable to bind SARS-CoV-2 and does not facilitate viral entry. In the current study we investigated whether active cigarette smoking increases the expression of the long or the short ACE2 isoform. We showed that in active smokers the expression of the long, active isoform, but not the short isoform of ACE2 is higher compared to never smokers. Additionally, it was shown that the expression of especially the long, active isoform of ACE2 was associated with secretory, club and goblet epithelial cells. This study increases our understanding of why current smokers are more susceptible to SARS-CoV-2 infection, in addition to the already established increased risk to develop severe COVID-19.
Yeast extracts from different manufacturers and supplementation of amino acids and micro elements reveal a remarkable impact on alginate production by A. vinelandii ATCC9046
Authors: Sparviero Sarah , Dicke Max Daniel , Rosch Tobias M. , Castillo Tania , Salgado-Lugo Holjes , Galindo Enrique , Peña Carlos , Büchs Jochen
Published: May 2023

Background

In research and production, reproducibility is a key factor, to meet high quality and safety standards and maintain productivity. For microbial fermentations, complex substrates and media components are often used. The complex media components can vary in composition, depending on the lot and manufacturing process. These variations can have an immense impact on the results of biological cultivations. The aim of this work was to investigate and characterize the influence of the complex media component yeast extract on cultivations ofAzotobacter vinelandiiunder microaerobic conditions. Under these conditions, the organism produces the biopolymer alginate. The focus of the investigation was on the respiration activity, cell growth and alginate production.

Results

Yeast extracts from 6 different manufacturers and 2 different lots from one manufacturer were evaluated.Significant differences on respiratory activity, growth and production were observed. Concentration variations of three different yeast extracts showed that the performance of poorly performing yeast extracts can be improved by simply increasing their concentration. On the other hand, the results with well-performing yeast extracts seem to reach a saturation, when their concentration is increased. Cultivations with poorly performing yeast extract were supplemented with grouped amino acids, single amino acids and micro elements. Beneficial results were obtained with the supplementation of copper sulphate, cysteine or a combination of both. Furthermore, a correlation between the accumulated oxygen transfer and the final viscosity (as a key performance indicator), was established.

Conclusion

The choice of yeast extract is crucial forA. vinelandiicultivations, to maintain reproducibility and comparability between cultivations. The proper use of specific yeast extracts allows the cultivation results to be specifically optimised. In addition, supplements can be applied to modify and improve the properties of the alginate. The results only scratch the surface of the underlying mechanisms, as they are not providing explanations on a molecular level. However, the findings show the potential of optimising media containing yeast extract for alginate production withA. vinelandii,as well as the potential of targeted supplementation of the media.
A novel aptamer-G-quadruplex/hemin self-assembling color system: rapid visual diagnosis of invasive fungal infections
Authors: Hua Ying , Hu Feng , Ren Xia , Xiong Yueling , Hu Jian , Su Fan , Tang Xiaolei , Wen Yufeng
Published: May 2023

Background

The clinical symptoms of invasive fungal infections (IFI) are nonspecific, and early clinical diagnosis is challenging, resulting in high mortality rates. This study reports the development of a novel aptamer-G-quadruplex/hemin self-assembling color system (AGSCS) based on (1 → 3)-β-D-glucans’ detection for rapid, specific and visual diagnosis of IFI.

Methods

We screened high affinity and specificity ssDNA aptamers binding to (1 → 3)-β-D-glucans, the main components of cell wall from Candida albicans via Systematic Evolution of Ligands by EXponential enrichment. Next, a comparison of diagnostic efficiency of AGSCS and the (1 → 3)-β-D-glucans assay (“G test”) with regard to predicting IFI in 198 clinical serum samples was done.

Results

Water-soluble (1 → 3)-β-D-glucans were successfully isolated from C. albicans ATCC 10,231 strain, and these low degree of polymerization glucans (< 1.7 kD) were targeted for aptamer screening with the complementary sequences of G-quadruplex. Six high affinity single stranded DNA aptamers (A1, A2, A3, A4, A5 and A6) were found. The linear detection range for (1 → 3)-β-D-glucans stretched from 1.6 pg/mL to 400 pg/mL on a microplate reader, and the detection limit was 3.125 pg/mL using naked eye observation. Using a microplate reader, the sensitivity and specificity of AGSCS for the diagnosis of IFI were 92.68% and 89.65%, respectively, which was higher than that of the G test.

Conclusion

This newly developed visual diagnostic method for detecting IFI showed promising results and is expected to be developed as a point-of-care testing kit to enable quick and cost effective diagnosis of IFI in the future.
Safety evaluation of curative gastrectomy for gastric cancer patients who underwent liver transplantation: a comparative study with conventional gastrectomy for gastric cancer patients
Authors: Ko Chang Seok , Jheong Jin Ho , Jeong Seong-A. , Kim Byung Sik , Yook Jeong Hwan , Kim Beom Su , Lee In-Seob , Gong Chung Sik , Kim Na Young , Yoo Moon-Won
Published: May 2023

Background

We aimed to examine the technical and oncological safety of curative gastrectomy for gastric cancer patients who underwent liver transplantation.

Methods

In this study, we compared the surgical and oncological outcomes of two groups. The first group consisted of 32 consecutive patients who underwent curative gastrectomy for gastric cancer after liver transplantation (LT), while the other group consisted of 127 patients who underwent conventional gastrectomy (CG). In addition, a subgroup analysis was performed to evaluate the impact of the background differences and the surgical outcomes on the involvement of a specialized liver transplant surgery team.

Results

The mean operative time was significantly longer in the LT group (p < 0.05). Furthermore, there were more frequent cases of postoperative transfusion in the LT group compared to the CG group (p < 0.05). However, there were no significant differences in the overall complications between the groups (25.00 vs 23.62%, p = 0.874). The 5-year overall survival rates of the LT and CG groups were 76.7% and 90.1%, respectively (p < 0.05). The results of the subgroup analysis demonstrated no statistically significant difference in various early surgical outcomes, such as time to transfusion during surgery, first flatus, time to first soft diet, postoperative complications, hospital stay after surgery, and the number of harvested lymph nodes except for operation time.

Conclusions

Despite one’s medical history of undergoing LT, our study demonstrated that curative gastrectomy could be a surgically safe treatment for gastric cancer. However, further study should be conducted to identify the reason gastric cancer patients who underwent liver transplant surgery have lower overall survival rate.
The abiding, hidden, and pervasive centrality of the health research workforce
Authors: Ferrinho Paulo , Makanga Michael , Sarfraz Shabnum , Poz Mario Dal
Published: May 2023

Research for health and development (R4HD) acknowledges that many of the determinants of health lie outside the boundaries of the health system. The size and quality of the health and care workforce (HCWF) are key drivers towards the future trajectory of many of these factors. We consider researchers for health and development an abiding, pervasive but neglected constituent part of this HCWF. This workforce straddles many professional groups and sectors. The diversity of occupations, lack of standardization in occupational cadres, the complexity and gendered aspects of the labour market, and the variable demographic, epidemiological, socio-economic and health systems’ contexts in the global south and the global north, led to a kaleidoscopic perception of the health research workforce that have kept it hidden from public opinion. This led to neglect by science as well as health policymakers and created an orphan sub-set of the HCWF. Understanding the health researchers’ labour market will help to identify means to develop, retain and utilize the health research workforce, addressing size, composition, role, skills transferability, careers and social impact through building, enabling or sustaining its research functions, capacity, employment opportunities and career tracks, among other issues. This thematic series of the Human Resources for Health Journal, calls for papers that go beyond narrow conceptual approaches and professional understandings of health care workers and the health research workforce, and requests that contributors examine important workforce issues through the broad lens of R4HD within a sustainable development goals framework.
Cancer-associated fibroblasts in radiotherapy: Bystanders or protagonists?
Authors: Martinez-Zubiaurre Inigo , Hellevik Turid
Published: May 2023

Background

The primary goal of radiotherapy (RT) is to induce cellular damage on malignant cells; however, it is becoming increasingly recognized the important role played by the tumor microenvironment (TME) in therapy outcomes. Therapeutic irradiation of tumor lesions provokes profound cellular and biological reconfigurations within the TME that ultimately may influence the fate of the therapy.

Main content

Cancer-associated fibroblasts (CAFs) are known to participate in all stages of cancer progression and are increasingly acknowledged to contribute to therapy resistance. Accumulated evidence suggests that, upon radiation, fibroblasts/CAFs avoid cell death but instead enter a permanent senescent state, which in turn may influence the behavior of tumor cells and other components of the TME. Despite the proposed participation of senescent fibroblasts on tumor radioprotection, it is still incompletely understood the impact that RT has on CAFs and the ultimate role that irradiated CAFs have on therapy outcomes. Some of the current controversies may emerge from generalizing observations obtained using normal fibroblasts and CAFs, which are different cell entities that may respond differently to radiation exposure.

Conclusion

In this review we present current knowledge on the field of CAFs role in radiotherapy; we discuss the potential tumorigenic functions of radiation-induced senescent fibroblasts and CAFs and we make an effort to integrate the knowledge emerging from preclinical experimentation with observations from the clinics.
Trend of clinical trials of new drugs for rare diseases in China in recent 10 years
Authors: Peng Ai , Fan Xue , Zou Linling , Chen Huan , Xiang Jin
Published: May 2023

Background

Rare disease is a general term for a disease that affects a small number of people but recognized as a global public health priority. Governments worldwide are paying more and more attention to the academical research and drug investment of rare diseases. The conduct of rare disease clinical trials is still difficult, despite the promotion of government policies and the awakening of social consciousness. In this article, we outlined the characteristics and obstacles of clinical trials of rare diseases in China and expected to provide reference for subsequent clinical trials in this field.

Results

In recent years, China has made some progress in clinical trials of rare diseases in the past 10 years. There were 481 clinical trials on rare diseases in total, covering more than 10 rare diseases with high incidence. Clinical trial applications on rare diseases for a total of 481 were submitted and with an average annual growth rate of 28.2% from 2013 to 2022. The number of clinical trial application for rare diseases in 2016 dramatically increased by 80% compared to 2015 due to the policy document issued by China for clinical research in rare diseases in 2015. Besides, about 70% of applications registering for clinical trials could recruit subjects as expected. Despite this, the number of clinical trials of rare diseases in China was less compared with the United States, Europe and Japan, and the types of infant drugs were limited to biological products and chemical drugs lacking other new treatments.

Conclusions

Efforts have been made in recent years to develop clinical research on rare diseases in China. The number of clinical trials for rare diseases in China was growing steadily every year, which was inseparable from the support of the country, society and rare disease patients. Still, there was a large gap between China and other developed countries in this field and this merit further investigation.
A new paradigm of learned cooperation reveals extensive social coordination and specific cortical activation in mice
Authors: Zhang Ke-Ming , Shen Yan , Jia Chun-Hui , Wang Hao , Bi Guo-Qiang , Lau Pak-Ming
Published: May 2023

Cooperation is a social behavior crucial for the survival of many species, including humans. Several experimental paradigms have been established to study cooperative behavior and related neural activity in different animal species. Although mice exhibit limited cooperative capacity in some behavioral paradigms, it is still interesting to explore their cooperative behavior and the underlying neural mechanisms. Here, we developed a new paradigm for training and testing cooperative behavior in mice based on coordinated lever-pressing and analyzed social interactions between the animals during cooperation. We observed extensive social contact and waiting behavior in cooperating animals, with the number of such events positively correlated with the success of cooperation. Using c-Fos immunostaining and a high-speed volumetric imaging with synchronized on-the-fly scan and readout (VISoR) system, we further mapped whole-brain neuronal activity trace following cooperation. Significantly higher levels of c-Fos expression were observed in cortical areas including the frontal pole, motor cortex, anterior cingulate area, and prelimbic area. These observations highlight social interaction and coordination in cooperative behavior and provide clues for further study of the underlying neural circuitry mechanisms.
Effects of programmed flexor–extensor alternating electrical acupoint stimulation on upper limb motor functional reconstruction after stroke: study protocol for a double-blind, randomized controlled trial
Authors: Liu Yang , Dong Xu , Huo Hong , Feng Liyuan , Tong Dan , Liu Jiahui , Zhang Hongyan , Zheng Yingkang , Wang Shuai , Wang Dongyan
Published: May 2023

Background

Stroke’s prevalence and morbidity are increasing (Guano, et al. Neuro 89:53–61, 2017), and limb motor dysfunction is left in most patients (Gittler, et al. JAMA 319:820–821, 2018). Particularly, the rehabilitation of upper limbs is more difficult and time-consuming (Borges, et al. The Cochrane database of systematic reviews 10:CD011887, 2018).

Methods

A double-blind randomized controlled trial (RCT) will be conducted to investigate whether a new functional electrical stimulation (FES) combined with acupoint therapy is more effective in the rehabilitation of upper limb motor dysfunction after stroke. Patients who meet the inclusion criteria will be randomly divided into two groups: programmed flexor–extensor alternating electrical acupoint stimulation group (PES group) and conventional flexor–extensor alternating electrical acupoint stimulation group (CES group), which will be treated for 3 weeks. The primary outcome measures are electroencephalogram (EEG) and surface electromyogram (sEMG). The secondary outcome variables include MBI (modified Barthel index), China Stroke Scale (CSS), FMA-U (Fugl-Meyer assessment upper limb), MMT (manual muscle testing), and Brunnstrom.

Discussion

The results of this study are expected to verify the efficacy of PES therapy in the rehabilitation of upper limb motor function after stroke. This may promote the widespread use of the therapy in hospitals, communities, and homes for early and continuous treatment.

Trial registration

ClinicalTrials.gov NCT05333497. Registered on April 11, 2022.
A health-system-embedded deprescribing intervention targeting patients and providers to prevent falls in older adults (STOP-FALLS trial): study protocol for a pragmatic cluster-randomized controlled trial
Authors: Balderson Benjamin H. , Gray Shelly L. , Fujii Monica M. , Nakata Kanichi G. , Williamson Brian D. , Cook Andrea J. , Wellman Robert , Theis Mary Kay , Lewis Cara C. , Key Dustin , Phelan Elizabeth A.
Published: May 2023

Background

Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults.

Methods

We will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18–26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention.

Discussion

The STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention.

Trial registration

ClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered.
Sustainable and high-level microbial production of plant hemoglobin in Corynebacterium glutamicum
Authors: Wang Mengmeng , Shi Zhong , Gao Ning , Zhou Yingyu , Ni Xiaomeng , Chen Jiuzhou , Liu Jiao , Zhou Wenjuan , Guo Xuan , Xin Bo , Shen Yanbing , Wang Yu , Zheng Ping , Sun Jibin
Published: May 2023

Background

Plant hemoglobin shows great potential as a food additive to circumvent the controversy of using animal materials. Microbial fermentation with engineered microorganisms is considered as a promising strategy for sustainable production of hemoglobin. As an endotoxin-free and GRAS (generally regarded as safe) bacterium, Corynebacterium glutamicum is an attractive host for hemoglobin biosynthesis.

Results

Herein, C. glutamicum was engineered to efficiently produce plant hemoglobin. Hemoglobin genes from different sources including soybean and maize were selected and subjected to codon optimization. Interestingly, some candidates optimized for the codon usage bias of Escherichia coli outperformed those for C. glutamicum regarding the heterologous expression in C. glutamicum. Then, saturated synonymous mutation of the N-terminal coding sequences of hemoglobin genes and fluorescence-based high-throughput screening produced variants with 1.66- to 3.45-fold increase in hemoglobin expression level. To avoid the use of toxic inducers, such as isopropyl-β-d-thiogalactopyranoside, two native inducible expression systems based on food additives propionate and gluconate were developed. Promoter engineering improved the hemoglobin expression level by 2.2- to 12.2-fold. Combination of these strategies and plasmid copy number modification allowed intracellular production of hemoglobin up to approximately 20% of total protein. Transcriptome and proteome analyses of the hemoglobin-producing strain revealed the cellular response to excess hemoglobin accumulation. Several genes were identified as potential targets for further enhancing hemoglobin production.

Conclusions

In this study, production of plant hemoglobin in C. glutamicum was systematically engineered by combining codon optimization, promoter engineering, plasmid copy number modification, and multi-omics-guided novel target discovery. This study offers useful design principles to genetically engineer C. glutamicum for the production of hemoglobin and other recombinant proteins.
Outcomes of surgical treatment with patterns of bacterial culture and antimicrobial susceptibility testing in cases of cervical abscessation in dogs: 82 cases (2018–2021)
Authors: Walker Alexandra , Amato Nicole , Brisson Jennifer , Stewart Samuel
Published: May 2023

Objective:The objective of this study was to summarize the presentation, diagnosis, and outcome for dogs surgically treated for chronic cervical abscessation following suspected or reported cervical or oropharyngeal trauma, as well as to report on culture results and antimicrobial susceptibility patterns.

Results:Eighty-two dogs were identified by retrospective review. Successful surgical outcome was achieved in 92.7% of dogs. Abscess recurrence was confirmed or suspected in 6/82 (7.3%) cases, and surgical intervention for abscess recurrence was performed in 4/82 (4.9%) cases. Foreign material was identified at surgery in 5/82 (6%) cases. Incisional healing complications were noted in 9/82 (10.9%) cases and required additional surgery in 5/82 (6%) cases. Twenty-three (28%) dogs had negative culture results. The results of antimicrobial sensitivity testing led to a change in antimicrobial treatment in only 9% of cases.

Surgically treated cervical abscessation carries a good prognosis with a low incidence of recurrence in this cohort (in contrast to previous reports), despite low frequency of foreign body removal or identification of the underlying cause of the abscess. Excision of chronic inflammatory tissue may not be necessary for a successful outcome, contrary to previous recommendations. Multi-pathogen infections and anaerobic infections are commonly encountered.
Competitive PCR with dual fluorescent primers enhances the specificity and reproducibility of genotyping animals generated from genome editing
Authors: Fu Liezhen , Ma Emily , Okada Morihiro , Shibata Yuki , Shi Yun-Bo
Published: May 2023

Targeted genome editing is a powerful tool for studying gene function in almost every aspect of biological and pathological processes. The most widely used genome editing approach is to introduce engineered endonucleases or CRISPR/Cas system into cells or fertilized eggs to generate double-strand DNA breaks within the targeted region, leading to DNA repair through homologous recombination or non-homologous end joining (NHEJ). DNA repair through NHEJ mechanism is an error-prone process that often results in point mutations or stretches of indels (insertions and deletions) within the targeted region. Such mutations in embryos are germline transmissible, thus providing an easy means to generate organisms with gene mutations. However, point mutations and short indels present difficulty for genotyping, often requiring labor intensive sequencing to obtain reliable results. Here, we developed a single-tube competitive PCR assay with dual fluorescent primers that allowed simple and reliable genotyping. While we used Xenopus tropicalis as a model organism, the approach should be applicable to genotyping of any organisms.
Time-domain adaptive attention network for single-channel speech separation
Authors: Wang Kunpeng , Zhou Hao , Cai Jingxiang , Li Wenna , Yao Juan
Published: May 2023

Recent years have witnessed a great progress in single-channel speech separation by applying self-attention based networks. Despite the excellent performance in mining relevant long-sequence contextual information, self-attention networks cannot perfectly focus on subtle details in speech signals, such as temporal or spectral continuity, spectral structure, and timbre. To tackle this problem, we proposed a time-domain adaptive attention network (TAANet) with local and global attention network. Channel and spatial attention are introduced in local attention networks to focus on subtle details of the speech signals (frame-level features). In the global attention networks, a self-attention mechanism is used to explore the global associations of the speech contexts (utterance-level features). Moreover, we model the speech signal serially using multiple local and global attention blocks. This cascade structure enables our model to focus on local and global features adaptively, compared with other speech separation feature extraction methods, further boosting the separation performance. Versus other end-to-end speech separation methods, extensive experiments on benchmark datasets demonstrate that our approach obtains a superior result. (20.7 dB of SI-SNRi and 20.9 dB of SDRi on WSJ0-2mix).
A randomised controlled, feasibility study to establish the acceptability of early outpatient review and early cardiac rehabilitation compared to standard practice after cardiac surgery and viability of a future large-scale trial (FARSTER)
Authors: Ngaage Dumbor L. , Mitchell Natasha , Dean Alexandra , Mitchell Alex , Hinde Sebastian , Akowuah Enoch , Doherty Patrick , Nichols Simon , Fairhurst Caroline , Flemming Kate , Hewitt Catherine , Ingle Lee , Watson Judith
Published: May 2023

Objective

To determine the acceptability and feasibility of delivering early outpatient review following cardiac surgery and early cardiac rehabilitation (CR), compared to standard practice to establish if a future large-scale trial is achievable.

Methods

A randomised controlled, feasibility trial with embedded health economic evaluation and qualitative interviews, recruited patients aged 18–80 years from two UK cardiac centres who had undergone elective or urgent cardiac surgery via a median sternotomy. Eligible, consenting participants were randomised 1:1 by a remote, centralised randomisation service to postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control), or postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention). The primary outcome measures related to trial feasibility including recruitment, retention, CR adherence, and acceptability to participants/staff. Secondary outcome measures included health-rated quality of life using EQ-5D-5L, NHS resource-use, Incremental Shuttle Walk Test (ISWT) distance, 30- and 90-day mortality, surgical site complications and hospital readmission rates.

Results

Fifty participants were randomised (25 per group) and 92% declared fit for CR. Participant retention at final follow-up was 74%; completion rates for outcome data time points ranged from 28 to 92% for ISWT and 68 to 94% for follow-up questionnaires. At each time point, the mean ISWT distance walked was greater in the intervention group compared to the control. Mean utility scores increased from baseline to final follow-up by 0.202 for the intervention (0.188 control). Total costs were £1519 for the intervention (£2043 control). Fifteen participants and a research nurse were interviewed. Many control participants felt their outpatient review and CR could have happened sooner; intervention participants felt the timing was right. The research nurse found obtaining consent for willing patients challenging due to discharge timings.

Conclusion

Recruitment and retention rates showed that it would be feasible to undertake a full-scale trial subject to some modifications to maximise recruitment. Lower than expected recruitment and issues with one of the clinical tests were limitations of the study. Most study procedures proved feasible and acceptable to participants, and professionals delivering early CR.

Trial registration

ISRCTN80441309 (prospectively registered on 24/01/2019).
Diphtheria in Pakistan post-COVID-19, a potential public health threat: an update
Authors: Saeed Mahnoor , Shahid Muhammad Bilal , Naeem Aroma , Tabassum Shehroze , Dave Tirth
Published: May 2023

Diphtheria, a vaccine-preventable disease, remains a concern in Pakistan as cases have risen post-COVID-19 pandemic causing more than 45 deaths in Pakistan in the year 2022. The respiratory variant of the disease is more common and can lead to serious complications, such as myocarditis and respiratory insufficiency. Diphtheria has caused havoc in the past killing millions of people worldwide before the development of its vaccine. Although the diphtheria toxoid vaccine is effective against toxigenic strains, there have been cases of treatment-resistant strains, particularly the non-toxigenic strains of C. diphtheriae. Pakistan's economic and health systems have suffered setbacks, which have been exacerbated by the COVID-19 pandemic. The pandemic has disrupted routine vaccination programs, and recent floods have contributed to an increase in diphtheria cases and rendered millions homeless. Poor immunization services, inadequate training of vaccination teams, and wealth inequality have all contributed to unequal vaccination coverage in Pakistan. The rising cases of diphtheria call for prompt action, including booster shots, updating vaccination records and administering immediate doses of the toxoid to close contacts.
Effect of Waiting Time for Radioactive Iodine Therapy on Outcome in N1 Stage Papillary Thyroid Cancer
Authors: Sun Yungang , Sun Qiaoling , Tian Jinyu , He Xiaochuan
Published: May 2023

Context

The waiting time for radioactive iodine therapy (WRAIT) after total thyroidectomy (TT) in patients with papillary thyroid cancer (PTC) and lymph node metastases (N1) has not been sufficiently investigated for risk of adverse outcomes.

Objective

This work aimed to estimate the effect of WRAIT on the outcomes of disease persistence and recurrence among patients with N1 PTC and investigate factors predictive of delayed radioactive iodine therapy (RAIT).

Methods

This retrospective cohort study was conducted in a university hospital. A total of 909 patients with N1 PTC were referred for RAIT between 2014 and 2018. WRAIT is the duration between TT and initial RAIT. The optimal WRAIT threshold determined using recursive partitioning analysis was used to define early and delayed RAIT. The primary end point was tumor persistence/recurrence. We compared the outcomes of patients with early and delayed RAIT using inverse probability weighting based on the propensity score.

Results

The WRAIT threshold that optimally differentiated worse long-term remission/excellent response outcomes was greater than 88 days (51% of our cohort; n = 464). WRAIT exceeding 88 days was associated with an augmented risk of disease persistence/recurrence (odds ratio, 2.47; 95% CI, 1.60-3.82) after adjustment. Predictors of delayed RAIT included residence in lower-income areas, reoperation before the initial RAIT, TT at a nonuniversity-affiliated hospital, multifocality, extrathyroidal extension, N1b disease, and pre–RAIT-stimulated thyroglobulin level less than 1 ng/mL.

Conclusion

Delayed RAIT beyond 88 days after TT in patients with N1 PTC independently increased the risk of disease persistence/recurrence. Evaluation of the predictive determinants of prolonged WRAIT may help target at-risk patients and facilitate interventions.