bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Technology for Health-Related Tasks among Older Adults: Trend Analysis of Pre-&-during COVID
Authors: Choudhury Avishek , Asan Onur
Published: October 2022

The rapid digitization of health care during the Covid-19 pandemic has increased the concern of the ‘digital divide,’ particularly for older adults. This study captures the trend of technology use among older populations before and during the Covid-19 pandemic. The study also measures the impact of the pandemic, healthcare technologies, and health status on older adults’ likelihood of communicating with the doctors, making independent treatment decisions, and achieving health-related goals. According to the study, older adults during the Covid-19 pandemic were less likely to communicate with their doctors or achieve their health-related goals by a factor of 1.158 and 1.130, respectively. Older adults who had depression were more likely to make independent treatment-related decisions by a factor of 0.744. We noted an increased usage of mHealth appli- cations and the internet during the Covid-19 pandemic. However, fewer people had access to smartphones and tablet computers. We also reported a significant increase in the proportion of older adults who did not use or understand online medical records over the years. The study emphasizes that as more older adults adopt technology, it is imperative to consider human factors’ methodologies and considerations. Authorities should consider technology affordance and affordability for patients across various socio-economic gradients and with different physical and cognitive capabilities.
Risk Factors for Disability Upgrading Among Leprosy Patients During Treatment: Multilevel Modeling Analysis
Authors: Mulugeta Solomon Sisay , Maseresha Bezanesh Melese , Wassihun Selamawit Getachew , Moyehodie Yikeber Abebaw
Published: October 2022

Background

Leprosy not only brings about bodily incapacity but also creates a nasty image of affected individuals, triggering discrimination and social stigma. The purpose of this study was to evaluate the status of leprosy disability in patients registered at the All African TB and Leprosy Rehabilitation and Training Center.

Methods

The study consists of 205 leprosy patients who were undergoing treatment at the All African TB and Leprosy Rehabilitation and Training Center from January 2015 to December 2019. Regional states of the patients were used as a clustering effect in the multilevel logistic regression model.

Results

In total, 205 (66.3%) completed records revealed patients with leprosy were disabled. Among these, 64.88% of them were males. In multilevel binary logistic regression analysis, the individual-level variables, such as median age (AOR = 1.1; 95% CI: 1.043, 1.13) of patients, patients with duration of symptom [7–12 months (AOR = 2.26; 95% CI: 1.50, 3.39), 13–24 months (AOR = 2.13; 95% CI: 1.44, 3.15), and more than 24 months (AOR = 2.67; 95% CI: 1.8, 4.02)], the absence of sensory loss (AOR = 0.84; 95% CI: 0.72, 0.96), and patients with asymmetry lesion distribution (AOR = 0.74; 95% CI: 0.65, 0.85), were the most significant determinant factors of disability. The default leprosy patient (AOR = 15.53; 95% CI: 1.82, 134.96) and new leprosy patient (AOR = 0.51; 95% CI: 0.33, 1.68) were the significant determinant factors of disability due to leprosy patients.

Conclusion

An individual-level factor on the risk of disability was higher as age increased and for patients with a longer duration of symptoms. The risk of disability was lower for patients who do not lose their sensation and for patients whose lesion distribution is asymmetrical. The community-level factor, patient categories, was also a significant factor in disability due to leprosy. Furthermore, programs should emphasize raising community awareness, focusing on key messages and early case detection campaigns, such as active surveys, as well as the availability of leprosy care in a public health facility.
The drop in female homicide victimisation in Australia
Authors: Forrest Walter
Published: October 2022

Despite widespread community concern about the incidence of lethal violence against women in Australia, the numbers and rates of women murdered each year have been falling for almost 30 years. The risk of homicide victimisation among Australian women is now the lowest it has ever been since federation. Few studies have explored these patterns or sought to explain their development. One plausible explanation, anticipated by feminist theories of violence, is that homicide has declined as the status of women and gender equality have increased. In this paper, I analyse changes in the annual female homicide victimisation rate in Australia from 1962 to 2016. Using unobserved components models, I investigate the extent to which increases in either the status of women or gender equality can account for the decline in female homicide victimisation since the late 1980s. Despite absolute and relative advances in women's educational access and achievement, labour force participation, and earnings, those changes had little discernible impact on the aggregate-level risk of lethal violence against women. Instead, other social and economic conditions, such as falling unemployment, the shrinking of the young male population and ongoing urbanisation, seem better able to explain recent improvements in women's safety.
RUNX1 deficiency cooperates with SRSF2 mutation to induce multilineage hematopoietic defects characteristic of MDS
Authors: Huang Yi-Jou , Chen Jia-Yu , Yan Ming , Davis Amanda G. , Miyauchi Sayuri , Chen Liang , Hao Yajing , Katz Sigrid , Bejar Rafael , Abdel-Wahab Omar , Fu Xiang-Dong , Zhang Dong-Er
Published: October 2022

Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematologic malignancies with a propensity to progress to acute myeloid leukemia. Causal mutations in multiple classes of genes have been identified in patients with MDS with some patients harboring more than 1 mutation. Interestingly, double mutations tend to occur in different classes rather than the same class of genes, as exemplified by frequent cooccurring mutations in the transcription factor RUNX1 and the splicing factor SRSF2. This prototypic double mutant provides an opportunity to understand how their divergent functions in transcription and posttranscriptional regulation may be altered to jointly promote MDS. Here, we report a mouse model in which Runx1 knockout was combined with the Srsf2 P95H mutation to cause multilineage hematopoietic defects. Besides their additive and synergistic effects, we also unexpectedly noted a degree of antagonizing activity of single mutations in specific hematopoietic progenitors. To uncover the mechanism, we further developed a cellular model using human K562 cells and performed parallel gene expression and splicing analyses in both human and murine contexts. Strikingly, although RUNX1 deficiency was responsible for altered transcription in both single and double mutants, it also induced dramatic changes in global splicing, as seen with mutant SRSF2, and only their combination induced missplicing of genes selectively enriched in the DNA damage response and cell cycle checkpoint pathways. Collectively, these data reveal the convergent impact of a prototypic MDS-associated double mutant on RNA processing and suggest that aberrant DNA damage repair and cell cycle regulation critically contribute to MDS development.
Comparison of tracheal temperature and core temperature measurement in living donor liver transplant recipients: a clinical comparative study
Authors: Yang Seong-Mi , Cho Hye-Yeon , Kim Hee-Soo
Published: October 2022

Background

Body temperature is a vital sign, and temperature monitoring during liver transplantation is important. Tracheal temperature can be measured via an endotracheal tube with a temperature sensor on the cuff of the tube. This study aimed to investigate the accuracy and trending ability of tracheal temperature measurement compared to those of the core temperature measured at the esophagus and pulmonary artery (PA) in living donor liver transplant recipients.

Methods

Twenty-two patients who underwent living donor liver transplantation (LDLT) were enrolled. Patients were intubated using an endotracheal tube with a temperature sensor placed on the inner surface of the tube cuff. Tracheal, esophageal, and PA temperatures were recorded at five time points corresponding to the different phases of liver transplantation. The tracheal and esophageal, tracheal and PA, and esophageal and PA temperatures were compared using Bland–Altman analysis, four-quadrant plot/concordance analysis, and polar plot analysis.

Results

Bland–Altman analysis showed an overall mean bias (95% limits of agreement) between tracheal and esophageal temperatures of -0.10 °C (-0.37 °C to 0.18 °C), with a percentage error of 0.27%; between tracheal and PA temperatures, -0.05 °C (-0.91 °C to 0.20 °C), with a percentage error of -0.15%; and between esophageal and PA temperatures, 0.04 °C (-0.27 °C to 0.35 °C), with a percentage error of 0.12%. The concordance rates between tracheal and esophageal temperatures, tracheal and PA temperatures, and esophageal and PA temperatures were 96.2%, 96.2%, and 94.94%, respectively. The polar plot analysis showed a mean angular bias (radial limits of agreement) of 4° (26°), -3° (13°), and 2° (21°).

Conclusions

Monitoring core temperature at the inner surface of the endotracheal tube cuff is accurate in all phases of LDLT with good trending ability; thus, it can be an excellent alternative for monitoring during LDLTs.
Municipal community centers as healthy settings: evaluation of a real-world health promotion intervention in Jerusalem
Authors: Barasche-Berdah Deborah , Wetzler Sima , Greenshtein Iva , Greenberg Keren L. , Leiter Elisheva , Donchin Milka , Zwas Donna R.
Published: October 2022

Background

This study presents an intervention designed to foster the implementation of health promotion programs within District Municipality Community Centers (DMCCs) in Jerusalem, and the creation of a peer network of healthy settings with a shared aspiration of collaborating and implementing health-promoting policies at the community level. We also present the evaluation strategy, based on the EQUIHP and RE-AIM frameworks.

Methods

Twenty DMCCs completed our program. This evaluation research involved a comprehensive seminar during the first year for DMCCs coordinators, teaching them the principles of health promotion. An educational kit was distributed during the second year. The evaluation strategy included a process evaluation and annual evaluations based on the EQUIHP and RE-AIM frameworks. The EQUIHP tool was divided into four dimensions of evaluation: 1) Framework of health promotion principles, 2) Project development and implementation, 3) Project management, and 4) Sustainability; while the RE-AIM domains included: 1)Reach, 2)Effectiveness, 3)Adoption, 4)Implementation and 5)Maintenance.

Results

The program led to high responsiveness among DMCCs and to the implementation of diverse health promotion initiatives, with a participation of approximately 29,191 residents. The EQUIHP evaluation showed an improvement in program quality in Year 2. The final RE-AIM evaluation presented a total median score of 0.61 for all domains, where 0 was non-performance and 1.0 was full performance. The ‘Framework of health promotion principles’ and ‘Reach’ components received the highest median score (0.83, 1.0 and 0.87), while the ‘Sustainability and ‘Maintenance’ components received the lowest (0.5).

Conclusions

This innovative program adapts the Healthy Cities approach (initiated by the World Health Organization in 1986) to the development of community center health-promoting settings within the larger municipal framework, training local community center staff members to assess and address local health concerns and build community capacity. The local focus and efforts may help community actors to create health promotion programs more likely to be adopted, feasible in the ‘real-world’ and able to produce public health impact in the communities where people live. Moreover, collaboration and cooperation among DMCCs may lead to a broader community health vision, forging coalitions that can advocate more powerfully for health promotion.

Trial registration

NIH trial registration number: NCT04470960.

Retrospectively registered on: 14/07/2020.
The impact of entering poverty on the unmet medical needs of Korean adults: a 5-year cohort study
Authors: Jung Yun Hwa , Jeong Sung Hoon , Park Eun-Cheol , Jang Sung-In
Published: October 2022

Background

Studies on the effects of poverty on unmet medical needs are limited. Therefore, this study aimed to identify the impact of entering poverty on the unmet medical needs of South Korean adults.

Methods

This study used data from the Korea Health Panel Survey (2014–2018) and included 10,644 adults. Logistic regression was used to examine the impact of entering poverty on unmet medical needs (poverty status: no → no, yes → no, no → yes, yes → yes; unmet medical needs: no, yes). Poverty line was considered to be below 50% of the median income.

Results

When entering poverty, the proportion of unmet medical needs was 22.8% (adjusted odds ratio [AOR] 1.17, 95% confidence interval [CI] 1.01–1.36). Men (AOR 1.29, 95% CI 1.02–1.64), rural dwellers (AOR 1.24, 95% CI 1.01–1.50), and national health insurance (NHI) beneficiaries (AOR 1.21, 95% CI 1.04–1.42) were susceptible to unmet medical needs and entering poverty. Poverty line with below-median 40% had an AOR of 1.48 (95% CI 1.28–1.71). For the cause of unmet medical needs, the AORs were 1.50 for poverty (95% CI 1.16–1.94) and 1.08 for low accessibility to health care and information (95% CI 0.79–1.48).

Conclusions

Entering poverty had the potential to adversely affect unmet medical needs. Men, rural dwellers, and NHI beneficiaries were vulnerable to unmet medical needs after entering poverty. Rigid definitions of poverty and inaccessibility to health care and information increase the likelihood of unmet medical needs and poverty. Society must alleviate unmet medical needs due to the increase in the population entering poverty.
Psychometric evaluation of the Chinese version of advance care planning self-efficacy scale among clinical nurses
Authors: Yang Zhen , Wang Huan , Wang Aiping
Published: October 2022

Background

Nurses are one of the most critical members of advance care planning (ACP) discussion. The evaluation of ACP self-efficacy is of great significance for developing targeted ACP interventions among clinical nurses and update their professional roles. However, there are few instruments to evaluate their ACP self-efficacy in mainland China. The purpose of this study was to translate the ACP self-efficacy scale into Chinese and evaluate its psychometric properties among clinical nurses.

Methods

A methodological study of the translation and validation of the ACP self-efficacy scale was conducted from January to March 2022. It involved three phases: (1) the translation and revision of the scale; (2) the exploration and evaluation of the item (n = 436); (3) the psychometric evaluation of the scale (n = 674).

Results

After a rigorous translation and revision, the ACP self-efficacy scale with three dimensions and 16 items was finally formed. In this study, the critical ratios of the item ranged from 8.226 to 17.499, and the item-total correlation coefficients ranged from 0.437 to 0.732, and the factor loadings of the item ranged from 0.638 to 0.882. The content validity index of the scale was 0.946. Supported by the eigenvalues, the three-factor structure explained the cumulative 61.131% of the overall variance. As the results of confirmatory factor analysis, all the recommended fitting indexes were appropriate. The average variance extracted values ranged from 0.570 to 0.756, and the composite reliability values ranged from 0.858 to 0.925. The total Cronbach's α coefficient, split-half reliability coefficient and test–retest reliability coefficient of the scale were 0.896, 0.767 and 0.939, respectively.

Conclusion

The Chinese version of ACP self-efficacy scale was successfully introduced into China, showing good psychometric properties among clinical nurses, and can effectively assess the ACP self-efficacy. Also, the scale can provide nursing educators with a significant strategy to develop ACP educational procedure and post-intervention measures for clinical nurses to improve nurse-led ACP practice.
Central and effector memory T cells in peripheral blood of patients with interstitial pneumonia: preliminary clues from a COVID-19 study
Authors: Bekbossynova Makhabbat , Akhmaltdinova Lyudmila , Dossybayeva Kuanysh , Tauekelova Ainur , Smagulova Zauresh , Tsechoeva Tatyana , Turebayeva Gulsimzhan , Sailybayeva Aliya , Kalila Zhanar , Mirashirova Tahmina , Muratov Timur , Poddighe Dimitri
Published: October 2022

Background

SARS-CoV-2 pre-existing T-cell immune reactivity can be present in some people. A general perturbation of the main peripheral lymphocyte subsets has been described in severe COVID-19 patients, but very few studies assessed the general memory T-cell homeostasis in the acute phase of COVID-19. Here, we performed a general analysis of the main memory T cell populations in the peripheral blood of patients admitted to the hospital for a confirmed or probable COVID-19 diagnosis.

Methods

In this cross-sectional study, adult patients (aged ≥ 18 years) needing hospital admission for respiratory disease due to confirmed or probable COVID-19, were recruited before starting the therapeutic protocol for this disease. In addition to the assessment of the general lymphocyte subpopulations in the early phase of COVID-19, central memory T cells (Tmcentr cells: CD45RO+CCR7+) and effector memory T cells (Tmeff cells: CD45RO+CCR7−) were assessed by multi-color flow cytometry, in comparison to a control group.

Results

During the study period, 148 study participants were recruited. Among them, 58 patients turned out positive for SARS-CoV-2 PCR (including both patients with interstitial pneumonia [PCR+Pn+] and without this complication [PCR+Pn−]), whereas the remaining 90 patients resulted to be SARS-CoV-2 PCR negative, even though all were affected with interstitial pneumonia [PCR−Pn+]. Additionally, 28 control patients without any ongoing respiratory disease were recruited. A clear unbalance in the T memory compartment emerged from this analysis on the whole pool of T cells (CD3+ cells), showing a significant increase in Tmcentr cells and, conversely, a significant decrease in Tmeff cells in both pneumonia groups (PCR+Pn+ and PCR−Pn+) compared to the controls; PCR+Pn− group showed trends comprised between patients with pneumonia (from one side) and the control group (from the other side). This perturbation inside the memory T cell compartment was also observed in the individual analysis of the four main T cell subpopulations, based upon the differential expression of CD4 and/or CD8 markers.

Conclusion

Overall, we observed both absolute and relative increases of Tmcentr cells and decrease of Tmeff cells in patients affected with interstitial pneumonia (regardless of the positive or negative results of SARS-CoV-2 PCR), compared to controls. These results need confirmation from additional research, in order to consider this finding as a potential biological marker of interstitial lung involvement in patients affected with viral respiratory infections.
Sesquiterpenoid lactones as potential anti-cancer agents: an update on molecular mechanisms and recent studies
Authors: Dhyani Praveen , Sati Priyanka , Sharma Eshita , Attri Dharam Chand , Bahukhandi Amit , Tynybekov Bekzat , Szopa Agnieszka , Sharifi-Rad Javad , Calina Daniela , Suleria Hafiz A. R. , Cho William C.
Published: October 2022

Plants-based natural compounds are well-identified and recognized chemoprotective agents that can be used for primary and secondary cancer prevention, as they have proven efficacy and fewer side effects. In today's scenario, when cancer cases rapidly increase in developed and developing countries, the anti-cancerous plant-based compounds become highly imperative. Among others, the Asteraceae (Compositae) family's plants are rich in sesquiterpenoid lactones, a subclass of terpenoids with wide structural diversity, and offer unique anti-cancerous effects. These plants are utilized in folk medicine against numerous diseases worldwide. However, these plants are now a part of the modern medical system, with their sesquiterpenoid lactones researched extensively to find more effective and efficient cancer drug regimens. Given the evolving importance of sesquiterpenoid lactones for cancer research, this review comprehensively covers different domains in a spectrum of sesquiterpenoid lactones viz (i) Guaianolides (ii) Pseudoguaianolide (iii) Eudesmanolide (iv) Melampodinin A and (v) Germacrene, from important plants such as Cynara scolymus (globe artichoke), Arnica montana (wolf weeds), Spilanthes acmella, Taraxacum officinale, Melampodium, Solidago spp. The review, therefore, envisages being a helpful resource for the growth of plant-based anti-cancerous drug development.
As the virus evolves, so too must we: a drug developer’s perspective
Authors: Fang Fang Flora
Published: October 2022

The SARS-CoV-2 virus has been raging globally for over 2 years with no end in sight. It has become clear that this virus possesses enormous genetic plasticity, and it will not be eradicated. Under increasing selective pressure from population immunity, the evolution of SARS-CoV-2 has driven it towards greater infectivity, and evasion of humoral and cellular immunity. Omicron and its expanding army of subvariants and recombinants have impaired vaccine protection and made most antibody drugs obsolete. Antiviral drugs, though presently effective, may select for more resistant strains over time. It may be inevitable, then, that future SARS-CoV-2 variants will be immune to our current virus-directed countermeasures. Thus, to gain control over the virus, we need to adopt a new paradigm in searching for next-generation countermeasures and develop host-directed therapeutics (HDTx) and host-directed antivirals (HDA). Different from the virus-directed countermeasures, HDTx and HDA may offer variant agnostic treatment to reduce the risk and severity of infections. In addition, they may exert more uniform effects against the genetically diverse SARS-CoV-2 quasispecies, thereby diminishing the risk of selecting resistant variants. Some promising HDTx and HDA approaches are summarized here.
The effect of cardiopulmonary bypass on blood thiamine concentration and its association with post-operative lactate concentration
Authors: Odelli Andrea L. , Holyoak Adam , Yadav Sumit , Page Sarah M. , Lindsay Daniel
Published: October 2022

Objective

Cardiothoracic surgery is a large field in Australia, and evidence suggests post-cardiopulmonary bypass (CPB) hyperlactataemia is associated with higher morbidity and mortality. Low thiamine levels are a potentially common yet treatable cause of hyperlactataemia and may occur in the setting of exposure to CPB non-biological material. We hypothesized that cardiopulmonary bypass would result in decreased whole-blood thiamine levels, which may therefore result in increased whole-blood lactate levels in the post-operative period.

Methods

Adult patients undergoing non-emergent CPB were recruited in a single centre, prospective, analytic observational study at Townsville University Hospital, Australia. The primary outcome was a comparison of pre- and post-CPB thiamine diphosphate level, secondarily aiming to assess any relationship between lactate and thiamine levels. Prospective pre- and post-CPB blood samples were taken and analysed at a central reference laboratory.

Results

Data was available for analysis on 78 patients. There was a statistically significant increase in thiamine diphosphate level from pre-CPB: 1.36 nmol/g Hb, standard deviation (SD) 0.31, 95% confidence intervals (CI) 1.29–1.43, to post-CPB: 1.77 nmol/g Hb, SD 0.53, 95% CI 1.43–1.88,pvalue < 0.001. There was a non-statistically significant (p > 0.05) trend in rising whole-blood lactate levels with increasing time. Analysis of lactate levels at varying time periods found a significant difference between baseline measurements and increased levels at 13–16 h (p < 0.05). There was no significant relationship observed between whole-blood thiamine levels and post-operative lactate levels.

Conclusion

Whole-blood thiamine levels were found to increase immediately post-CPB in those undergoing elective cardiac surgery. There was no correlation between whole-blood thiamine levels and post-operative arterial lactate levels.
Community-based referral transportation system for accessing emergency obstetric services in the Rohingya refugee camp during the COVID-19 pandemic in Bangladesh: facilitators and barriers through beneficiaries’ and providers’ lens using a mixed-method design
Authors: Barua Mrittika , Chowdhury Sayantan , Saha Avijit , Mia Chand , Sajow Stenly Hely , Sarker Malabika
Published: October 2022

Background

Delays in seeking timely maternity care from health care professionals are crucial to address among the Rohingya population where many preventable pregnancy-related deaths occur within the camps when care is not sought. To address the challenges related to the referral of emergency and routine Sexual and Reproductive Health and Rights (SRHR) cases, United Nations Population Fund, through its partners, implemented a community-based referral transportation project called Referral hub. This paper presents the barriers and facilitators to the implementation of this referral transportation system from the perspectives of the beneficiaries and providers.

Methods

The research adopted a sequential explanatory mixed-method design. The quantitative phase consisted of a survey among 100 women while the qualitative phase comprised of in-depth interviews with a total of 12 mothers who used the services and key informant interviews with 21 providers.

Results

The barriers identified for referral hub are discordant understanding of emergency, strict gender norms and practices, distrust in providers, poor roads and mobile phone networks. The facilitators are partnership with the community, within and other organizations.

Conclusion

The study observed that the referral hub has a high potential to increase the utilization of SRHR services. Despite the barriers, the facilitating factors show a scope of improvement for these services.
Interpretation of TSH and T4 for diagnosing minor alterations in thyroid function: a comparative analysis of two separate longitudinal cohorts
Authors: Andersen Stig , Karmisholt Jesper , Bruun Niels Henrik , Riis Johannes , Noahsen Paneeraq , Westergaard Louise , Andersen Stine Linding
Published: October 2022

Background

Minor alterations in thyroid function are frequent, and interpretation of thyroid function tests in the individual patient can be challenging. Furthermore, the choice of thyroid function test is debatable. To inform the debate, we performed a comparative evaluation of the variation in thyrotropin (TSH) and thyroxine (T4) in two different cohorts to illustrate the precision of TSH and T4 in the diagnosis and monitoring of thyroid dysfunction.

Methods

A comparative analysis of two separate longitudinal studies previously surveyed with monthly blood sampling for one year among 35 subjects. Participants were included based on T4 within the reference range and TSH either within (euthyroid; n = 15) or above (subclinical hypothyroidism; n = 20) the laboratory reference range on two independent blood samplings before inclusion. Exclusion criteria were known thyroid disease or use of thyroid interfering medication. TSH and T4 in individual samples were measured in a single batch to prevent between-batch variation. The distributions TSH and T4 were compared among euthyroid and subclinical hypothyroid individuals, and bootstrap estimates were used to calculate area under the curve (AUC).

Results

Collection of twelve, monthly blood samples in the 35 participants provided 420 samples, and data completeness was 100%. The mean TSH was 1.27/7.19 mIU/L and the mean total T4 was 106/85 nmol/L in euthyroid/subclinical hypothyroid participants. The subclinical hypothyroidism state deviated from the euthyroid by 20% for total T4 and by 466% for TSH. The overlap between the euthyroid and subclinical hypothyroid groups was 92.6% (389/420) for total T4 and 9.0% (38/420) of test results for TSH. The estimated AUC was 0.999 (95%-CI: 0.995; 1.00) for TSH and 0.853 (0.736; 0.935) for total T4. There was no confidence interval overlap between participant groups for TSH while there was a considerable overlap for total T4 (p < 0.001).

Conclusion

The distributions of thyroid function tests illustrated how TSH outperforms T4 for detecting delicate differences in thyroid function in an individual. Thus, TSH was markedly better than T4 to discriminate between the subtle differences in thyroid function corroborating that TSH is the more sensitive and accurate index of thyroid function status in the individual patient.
Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis
Authors: Qiu Shengkui , Xie Li , Lu Chen , Gu Chao , Xia Yiwen , Lv Jialun , Xuan Zhe , Fang Lang , Yang Jing , Zhang Lu , Li Zheng , Wang Weizhi , Xu Hao , Li Bowen , Xu Zekuan
Published: October 2022

Background

Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM.

Methods

Sequential differential centrifugation, transmission electron microscopy and NanoSight analysis were used to extract and characterize exosomes. MicroRNA sequencing in GC-derived exosomes and mRNA sequencing in PMA-treated THP-1 cells were used to identify differentially expressed miRNAs in exosomes and the functional targets of exosomal miR-519a-3p (exo-miR-519a-3p) in macrophages, respectively. Tracing and internalization of exosomes and transfer of exo-miR-519a-3p were observed by immunofluorescence. Tubule formation assays, aortic ring assays, and exosome-educated GC-LM model were used to investigate the roles of GC-derived exosomes and exo-miR-519a-3p in angiogenesis and GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry and immunofluorescence were used to investigate the regulatory mechanism of exo-miR-519a-3p at GC-LM.

Results

The expression level of miR-519a-3p in serum exosomes was significantly higher in GC-LM patients than in patients without LM, and high expression of exo-miR-519a-3p indicates a worse prognosis. GC-derived exosomes are mainly accumulated in the liver and internalized by intrahepatic macrophages. Mechanistically, exo-miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, thereby causing M2-like polarization of macrophages. M2-like polarized macrophages accelerate GC-LM by inducing angiogenesis and promoting intrahepatic premetastatic niche formation.

Conclusions

Our results indicate that exo-miR-519a-3p plays a critical role in mediating crosstalk between primary GC cells and intrahepatic macrophages and is a potential therapeutic target for GC-LM.
In silico optimization of RNA–protein interactions for CRISPR-Cas13-based antimicrobials
Authors: Park Ho-min , Park Yunseol , Berani Urta , Bang Eunkyu , Vankerschaver Joris , Van Messem Arnout , De Neve Wesley , Shim Hyunjin
Published: October 2022

RNA–protein interactions are crucial for diverse biological processes. In prokaryotes, RNA–protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA–protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA–protein interactions in the current tools. Here, we investigate the RNA–protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA–protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA–protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.
Identification of target genes regulated by encystation-induced transcription factor Myb2 using knockout mutagenesis in Giardia lamblia
Authors: Kim Juri , Park Eun-Ah , Shin Mee Young , Park Soon-Jung
Published: October 2022

Background

Encystation is one of the two processes comprising the life cycle of Giardia lamblia, a protozoan pathogen with tetraploid genome. Giardia lamblia Myb2 (GlMyb2) is a distinct encystation-induced transcription factor whose binding sites are found in the promoter regions of many encystation-induced genes, including its own.

Methods

Two sequential CRISPR/Cas9 experiments were performed to remove four glmyb2 alleles. The expression level of G. lamblia cyst wall protein 1 (GlCWP1), a well-known target gene of GlMyb2, was measured via western blotting and immunofluorescence assays. Chromatin immunoprecipitation experiments using anti-GlMyb2 antibodies were performed on the encysting G. lamblia cells. Quantitative real-time PCR was performed to confirm an expression of candidate GlMyb2-regulated genes by comparing the transcript level for each target candidate in wild-type and knockout mutant Giardia. The promoter region of glcwp1 was analyzed via deletion and point mutagenesis of the putative GlMyb2 binding sites in luciferase reporters.

Results

Characterization of the null glmyb2 mutant indicated loss of functions related to encystation, i.e. cyst formation, and expression of GlCWP1. The addition of the wild-type glmyb2 gene to the null mutant restored the defects in encystation. Chromatin immunoprecipitation experiments revealed dozens of target genes. Nineteen genes were confirmed as GlMyb2 regulons, which include the glmyb2 gene, six for cyst wall proteins, five for signal transduction, two for transporter, two for metabolic enzymes, and three with unknown functions. Detailed analysis on the promoter region of glcwp1 defined three GlMyb2 binding sites important in its encystation-induced expression.

Conclusions

Our data confirm that GlMyb2 acts as a transcription activator especially during encystation by comparing the glmyb2 knockout mutant with the wild type. Further investigation using glmyb2 null mutant will provide knowledge regarding transcriptional apparatus required for the encystation process of G. lamblia.

Graphical Abstract
The influence of physical performance on technical and tactical outcomes in the UEFA Champions League
Authors: Modric Toni , Malone James J. , Versic Sime , Andrzejewski Marcin , Chmura Paweł , Konefał Marek , Drid Patrik , Sekulic Damir
Published: October 2022

Background

To clarify does physical performance affect success in highest-level soccer, the purpose of the present study was to identify differences in technical-tactical performance (TP) between teams covering high and low running performance (RP) during the UEFA Champions League (UCL) matches.

Methods

The RP and TP data were collected from UCL group stage matches in the 2020/21 season. RP variables included total distance covered (TD), high intensity running (HIR), total distance when in ball possession (TDB), and high intensity running when in ball possession (HIRB). TP variables included goal chances, shots, shots on target, passes, accurate passes, key passes, key passes accurate, crosses, crosses accurate, counter attacks, counter attacks with a shot, high pressing, high pressing successful, low pressing, low pressing successful, tackles, tackles successful, entrances to the opponent’s box, total actions, and successful actions. K-means cluster analysis method was used to classify teams covering (i) low and high TD, (ii) low and high HIR, (iii) low and high TDB, (iv) low and high and HIRB. Linear mixed models were used to identify differences in teams’ TP according to their RP. Pearson’s correlations were used to establish direct association between team TP and RP.

Results

Similar TP were observed whether teams covering high or low TD/HIR. Teams covering greater TDB/HIRB had more goal chances, shots, shots on target, passes, accurate passes, key passes, accurate key passes, crosses, successful high pressing, entrances to the opponent’s box, total actions, and successful actions were observed (all moderate to very large effect sizes. Significant association between specific TP variables and TDB/HIRB were evidenced (Pearson’s r = 0.35–0.96, allp < 0.05).

Conclusion

Covering greater TDB and HIRB may allow more frequent execution of fundamental TP which are considered essential for match success, indicating that RP when team has ball in possession is important determinant of success in highest-level soccer. This study shows that physical performance affect success in highest-level soccer.
Altered basal forebrain function during whole-brain network activity at pre- and early-plaque stages of Alzheimer’s disease in TgF344-AD rats
Authors: van den Berg Monica , Adhikari Mohit H. , Verschuuren Marlies , Pintelon Isabel , Vasilkovska Tamara , Van Audekerke Johan , Missault Stephan , Heymans Loran , Ponsaerts Peter , De Vos Winnok H. , Van der Linden Annemie , Keliris Georgios A. , Verhoye Marleen
Published: October 2022

Background

Imbalanced synaptic transmission appears to be an early driver in Alzheimer’s disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks are influenced at pre- and early-plague stages of AD and if these manifestations are associated with concomitant cellular and synaptic deficits. 

Methods

To this end, we used an established AD rat model (TgF344-AD) and employed resting state functional MRI and quasi-periodic pattern (QPP) analysis, a method to detect recurrent spatiotemporal motifs of brain activity, in parallel with state-of-the-art immunohistochemistry in selected brain regions.

Results

At the pre-plaque stage, QPPs in TgF344-AD rats showed decreased activity of the basal forebrain (BFB) and the default mode-like network. Histological analyses revealed increased astrocyte abundance restricted to the BFB, in the absence of amyloid plaques, tauopathy, and alterations in a number of cholinergic, gaba-ergic, and glutamatergic synapses. During the early-plaque stage, when mild amyloid-beta (Aβ) accumulation was observed in the cortex and hippocampus, QPPs in the TgF344-AD rats normalized suggesting the activation of compensatory mechanisms during this early disease progression period. Interestingly, astrogliosis observed in the BFB at the pre-plaque stage was absent at the early-plaque stage. Moreover, altered excitatory/inhibitory balance was observed in cortical regions belonging to the default mode-like network. In wild-type rats, at both time points, peak activity in the BFB preceded peak activity in other brain regions—indicating its modulatory role during QPPs. However, this pattern was eliminated in TgF344-AD suggesting that alterations in BFB-directed neuromodulation have a pronounced impact in network function in AD.

Conclusions

This study demonstrates the value of rsfMRI and advanced network analysis methods to detect early alterations in BFB function in AD, which could aid early diagnosis and intervention in AD. Restoring the global synaptic transmission, possibly by modulating astrogliosis in the BFB, might be a promising therapeutic strategy to restore brain network function and delay the onset of symptoms in AD.
Severe hyponatremia in an infant with epidermolysis bullosa: a case report
Authors: Dehghani Soheil , Akbarzadeh Pasha Boshra , Karimi Amirali , Afshin Azadeh
Published: October 2022

Background

Epidermolysis bullosa is a rare inherited connective tissue disorder compromising cellular junctions. Blister formation is the first manifestation of epidermolysis bullosa. As cellular adhesion is affected, it can affect many organs. Due to compromised skin integrity, water loss and electrolyte imbalances are prevalent in these patients. However, hypernatremia is the usual observed sodium imbalance rather than hyponatremia.

Case presentation

The patient was a 48-day-old Iranian male infant born near term. He was diagnosed with epidermolysis bullosa at 1 month of age. The patient was brought to the pediatrics center with apnea and respiratory distress, and was intubated and admitted to the pediatric intensive care unit. His symptoms started 4 days before the admission with vomiting and poor feeding, and the patient later developed loss of consciousness. Vital signs revealed a pulse rate of 154 beats per minute, respiratory rate of 70 per minute, a temporal temperature of 36.5 °C, nondetectable blood pressure, and oxygen saturation of 96%. The patient was anuric at presentation and was rehydrated. Physical examination showed bolus eruptions all over the body but not in mucosal membranes. Important laboratory findings were white blood cell count of 41,000/mm3 with 68% neutrophils, hemoglobin of 10.8 g/dL, platelet count of 856,000/mm2, negative C-reactive protein (CRP), blood sugar of 514 mg/dL, urea of 129 mg/dL, sodium of 98 mg/dL, corrected sodium of 105 mg/dL, potassium of 5.5 mg/dL, serum creatinine of 1.7 mg/dL, and serum procalcitonin of more than 75 ng/mL. Urine analysis revealed many red blood cells. Brain computed tomography demonstrated loss of differentiation between gray and white matter and effacement of cortical sulci suggesting severe cytotoxic edema.

We administered 3% hypertonic saline and corrected the plasma sodium levels, and provided the patient with multiple doses of mannitol as well as antibiotics due to the leukocytosis. Subsequently, after 3 days in pediatric intensive care unit, the symptoms of brain edema resolved, and after 4 days, he was weaned from the ventilator and extubated. Later he was discharged from the pediatric intensive care unit.

Conclusion

This study illustrates the possibility of severe hyponatremia in patients with epidermolysis bullosa to clinicians. Although uncommon, knowledge on such possibilities is vital due to the possible detrimental outcomes for patients.
Pre-cooling with ingesting a high-carbohydrate ice slurry on thermoregulatory responses and subcutaneous interstitial fluid glucose during heat exposure
Authors: Naito Takashi , Saito Tatsuya , Morito Akihisa , Yamada Satoshi , Shimomasuda Masatsugu , Nakamura Mariko
Published: October 2022

The purpose of this study was to compare the effects of ingesting ice slurries with two different carbohydrate contents on body temperatures and the subcutaneous interstitial fluid glucose level during heat exposure. Seven physically active men underwent one of three interventions: the ingestion of 7.5 g/kg of a control beverage (CON: 26°C), a normal-carbohydrate ice slurry (NCIS: −1°C), or a high-carbohydrate ice slurry (HCIS: −5°C). The participants were monitored for a 120-min period that included 10 min of rest, 25 min of exposure to the experimental cooling intervention (during which the beverage was ingested), and 85 min of seated rest in a climate chamber (36°C, 50% relative humidity). The rectal temperature in the HCIS and NCIS trials was lower than that in the CON trial from 40 to 75 min. The infrared tympanic temperature was also lower in the HCIS and NCIS trials than in the CON trial from 20 to 50 min, whereas the deep thigh or mean skin temperatures were not significantly different among the three groups. From 90 to 120 min, the subcutaneous interstitial fluid glucose level in the NCIS trial was lower than that at 65 min; however, reductions were not seen in the HCIS and CON trials. These findings suggest that both HCIS ingestion and conventional NCIS ingestion were effective cooling strategies for reducing thermal strain, while HCIS ingestion may also enable a higher subcutaneous interstitial fluid glucose level to be maintained, ensuring an adequate supply of required muscle substrates.
Biomimetic anti-inflammatory and osteogenic nanoparticles self-assembled with mineral ions and tannic acid for tissue engineering
Authors: Byun Hayeon , Jang Gyu Nam , Hong Min-Ho , Yeo Jiwon , Shin Hyunjung , Kim Won Jong , Shin Heungsoo
Published: October 2022

Bone healing involves complex processes including inflammation, induction, and remodeling. In this context, anti-inflammatory and osteoconductive multi-functional nanoparticles have attracted considerable attention for application in improved bone tissue regeneration. In particular, nanoparticles that promote suppression of inflammatory response after injury and direction of desirable tissue regeneration events are of immense interest to researchers. We herein report a one-step method to prepare multi-functional nanoparticles using tannic acid (TA) and simulated body fluid (SBF) containing multiple mineral ions. Mineral-tannic acid nanoparticles (mTNs) were rapidly fabricated in 10 min, and their size (around 250–350 nm) and chemical composition were controlled through the TA concentration. In vitro analysis using human adipose derived stem cells (hADSCs) showed that mTNs effectively scavenged reactive oxygen species (ROS) and enhanced osteogenesis of hADSCs by inducing secretion of alkaline phosphatase. mTNs also increased osteogenic marker gene expression even in the presence of ROS, which can generally arrest osteogenesis (OPN: 1.74, RUNX2: 1.90, OCN: 1.47-fold changes relative to cells not treated with mTNs). In vivo analysis using a mouse peritonitis model revealed that mTNs showed anti-inflammatory effects by decreasing levels of pro-inflammatory cytokines in blood (IL-6: 73 ± 4, TNF-α: 42 ± 2%) and peritoneal fluid (IL-6: 78 ± 2, TNF-α: 21 ± 6%). We believe that this one-step method for fabrication of multi-functional nanoparticles has considerable potential in tissue engineering approaches that require control of complex microenvironments, as required for tissue regeneration.