bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analyses reveal cystatin c is a promising biomarker for evaluation of systemic lupus erythematosus
Authors: Huang He , Zhang Yukun , Gui Lan , Zhang Li , Cai Minglong , Sheng Yujun
Published: October 2023

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement, especially the kidneys. However, the underlying mechanism remains unclear, and accurate biomarkers are still lacking. This study aimed to identify biomarkers to assess organ damage and disease activity in patients with SLE using quantitative proteomics.

Methods

Proteomic analysis was performed using mass spectrometry in 15 patients with SLE and 15 age-matched healthy controls. Proteomic profiles were compared in four main subtypes: SLE with proteinuria (SLE-PN), SLE without proteinuria (SLE-non-PN), SLE with anti-dsDNA positivity (SLE-DP), and SLE with anti-dsDNA negativity (SLE-non-DP). Gene ontology biological process analysis revealed differentially expressed protein networks. Cystatin C (CysC) levels were measured in 200 patients with SLE using an immunoturbidimetric assay. Clinical and laboratory data were collected to assess their correlation with serum CysC levels.

Results

Proteomic analysis showed that upregulated proteins in both the SLE-PN and SLE-DP groups were mainly mapped to neutrophil activation networks. Moreover, CysC from neutrophil activation networks was upregulated in both the SLE-PN and SLE-DP groups. The associations of serum CysC level with proteinuria, anti-dsDNA positivity, lower complement C3 levels, and SLE disease activity index score in patients with SLE were further validated in a large independent cohort.

Conclusions

Neutrophil activation is more prominent in SLE with proteinuria and anti-dsDNA positivity, and CysC is a promising marker for monitoring organ damage and disease activity in SLE.
Advancements in predicting and modeling rare event outcomes for enhanced decision-making
Authors: Feng Cindy , Li Longhai , Xu Chang
Published: October 2023

Predicting rare events is a challenging task due to limited data and imbalanced datasets. This special issue explores methodological advancements in prediction and modeling for rare events. The research showcased in this issue aims to provide valuable insights and strategies to enhance the accuracy of rare event prediction and modeling.
Longitudinal plasmode algorithms to evaluate statistical methods in realistic scenarios: an illustration applied to occupational epidemiology
Authors: Souli Youssra , Trudel Xavier , Diop Awa , Brisson Chantal , Talbot Denis
Published: October 2023

Introduction

Plasmode simulations are a type of simulations that use real data to determine the synthetic data-generating equations. Such simulations thus allow evaluating statistical methods under realistic conditions. As far as we know, no plasmode algorithm has been proposed for simulating longitudinal data. In this paper, we propose a longitudinal plasmode framework to generate realistic data with both a time-varying exposure and time-varying covariates. This work was motivated by the objective of comparing different methods for estimating the causal effect of a cumulative exposure to psychosocial stressors at work over time.

Methods

We developed two longitudinal plasmode algorithms: a parametric and a nonparametric algorithms. Data from the PROspective Québec (PROQ) Study on Work and Health were used as an input to generate data with the proposed plasmode algorithms. We evaluated the performance of multiple estimators of the parameters of marginal structural models (MSMs): inverse probability of treatment weighting, g-computation and targeted maximum likelihood estimation. These estimators were also compared to standard regression approaches with either adjustment for baseline covariates only or with adjustment for both baseline and time-varying covariates.

Results

Standard regression methods were susceptible to yield biased estimates with confidence intervals having coverage probability lower than their nominal level. The bias was much lower and coverage of confidence intervals was much closer to the nominal level when considering MSMs. Among MSM estimators, g-computation overall produced the best results relative to bias, root mean squared error and coverage of confidence intervals. No method produced unbiased estimates with adequate coverage for all parameters in the more realistic nonparametric plasmode simulation.

Conclusion

The proposed longitudinal plasmode algorithms can be important methodological tools for evaluating and comparing analytical methods in realistic simulation scenarios. To facilitate the use of these algorithms, we provide R functions on GitHub. We also recommend using MSMs when estimating the effect of cumulative exposure to psychosocial stressors at work.
Effectiveness of a person-centred eHealth intervention in reducing symptoms of burnout in patients with common mental disorders – secondary outcome analysis of a randomized controlled trial
Authors: Alsén Sara , Hadžibajramović Emina , Jonsdottir Ingibjörg H , Ali Lilas , Fors Andreas
Published: October 2023

Background

The number of people with common mental disorders (CMDs), especially stress-related disorders, has increased in several countries, including Sweden, during the past decade. Patients seeking care for long-term stress report severe symptoms. Although person-centred care (PCC) has shown several benefits, studies evaluating the effects of a PCC eHealth intervention on patients with CMDs are scarce.

Objective

The aim of this study was to compare levels of self-reported symptoms of burnout between a control group receiving treatment as usual (TAU) and an intervention group receiving TAU with the addition of a person-centred eHealth intervention, in patients on sick leave for CMDs.

Methods

This study reports analysis of a secondary outcome measure from a randomized controlled trial. Patients (n = 209) on sick leave for CMDs were recruited from nine primary health care centres and allocated to either a control group (n = 107) or an intervention group (n = 102). The intervention consisted of phone support and an interactive digital platform built on PCC principles. Self-reported symptoms of burnout were assessed using the Shirom-Melamed Burnout Questionnaire (SMBQ) at baseline and at 3 and 6 months.

Results

Our findings showed changes in SMBQ scores over time in both the control and the intervention group. There was no significant difference in SMBQ scores between the groups; however, a difference in change over time between the groups was observed. The SMBQ scores decreased significantly more in the intervention group than in the controls between 0 and 3 months and between 0 and 6 months. No differences in change between the two groups were seen between the 3- and 6-month follow-ups.

Conclusion

This person-centred eHealth intervention for patients on sick leave for CMDs showed a slight initial effect in reducing symptoms of burnout. Taking into account that both groups reported comparable SMBQ scores throughout the study period, the overall effect may be considered limited.

Trial registration

: The trial was registered in ClinicalTrials.gov (Identifier NCT03404583). Date of registration: 19/01/2018. https://clinicaltrials.gov/ct2/show/NCT03404583.
Impact of experiencing multiple vulnerabilities on fetal growth and complications in women with hyperglycemia in pregnancy
Authors: Bihan Helene , Nachtargeale Charlotte , Vicaud Eric , Sal Meriem , Berkane Narimane , Pinto Sara , Tatulashvili Sopio , Fermaut Marion , Carbillon Lionel , Cosson Emmanuel
Published: October 2023

Background

In women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators—food insecurity and poor language proficiency—on adherence to prenatal care and maternal and fetal outcomes.

Methods

In a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes.

Results

Among the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency.

Conclusion

We found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.
Cellular senescence-related genes: predicting prognosis in hepatocellular carcinoma
Authors: Yuan Weiwei , Xu Yuanmin , Wu Zhiheng , Huang Yang , Meng Lei , Dai Shiping , Ying Songcheng , Chen Zhangming , Xu Aman
Published: October 2023

Recent studies have shown that the high incidence and low cure rate of hepatocellular carcinoma (HCC) have not improved significantly. Surgery and liver transplantation are the mainstays of prolonging the survival of HCC patients. However, the surgical resection rate of HCC patients is very low, and even after radical surgical resection, the recurrence rate at 5 years postoperatively remains high and the prognosis is very poor, so more treatment options are urgently needed. Increasing evidence suggests that cellular senescence is not only related to cancer development but may also be one of its primary driving factors. We aimed to establish a prognostic signature of senescence-associated genes to predict the prognosis and therapeutic response of HCC patients. The aim of this study was to develop a risk model associated with cellular senescence and to search for potential strategies to treat HCC. We divided HCC patients into two clusters and identified differentially expressed genes (DEGs) between clusters. In this study, low-risk patients had a better prognosis, higher levels of immune cell infiltration, and better efficacy to fluorouracil, Paclitaxel and Cytarabine chemotherapy compared to high-risk patients. To further identify potential biomarkers for HCC, we further validated the expression levels of the four signature genes in HCC and neighbouring normal tissues by in vitro experiments. In conclusion, we identified and constructed a relevant prognostic signature, which performed well in predicting the survival and treatment response of HCC patients. This helps to differentiate between low-score and high-risk HCC, and the results may contribute to precise treatment protocols in clinical practice.
Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank
Authors: Hoang Tung , Cho Sooyoung , Choi Ji-Yeob , Kang Daehee , Shin Aesun
Published: October 2023

Background

This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk.

Methods

We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term.

Results

During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05–1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18–1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97–2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08–1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00–1.19 for low vs. high WCRF dietary scores).

Conclusion

Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.
Association between NDRG1 protein expression and aggressive features of breast cancer: a systematic review and meta-analysis
Authors: Kotepui Kwuntida , Kotepui Manas , Majima Hideyuki J. , Tangpong Jitbanjong
Published: October 2023

Background

N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.

Methods

The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.

Results

A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13–1.05, I2: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32–(-0.20), I2: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).

Conclusion

The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Carpal tunnel syndrome and its associated factors among computer user bankers in South Gondar Zone, Northwest Ethiopia, 2021: a cross sectional study
Authors: Demissie Biruk , Yenew Chalachew , Alemu Alelign , Bantie Berihun , Sume Bickes Wube , Deml Yikeber Argachew , Tegegne Eniyew
Published: October 2023

Introduction

The use of information devices like computers is skyrocketed in recent years, leading injuries. Carpal Tunnel Syndrome is a leading cause of upper extremity MSDs specially to banking workers. Hence, this paper was intended to highlight its magnitude associated factors in the study area.

Methods and materials

Institutional based cross-sectional study was conducted from September 13, 2021 to October 09, 2021. A total of 422 private and government owned computer user bankers were participated. Simple random sampling technique was used to select the study participants. Data were collected using Durkan’s compression test, flexion and compression test, Phalen’s test, and Tinel’s test. Multivariable logistic regression model was used to investigate the relationship between predictors and Carpal Tunnel Syndrome. P-value less than 0.05 was considered to declare as a significant and Adjusted Odds Ration for strength association between risk factors and Carpal Tunnel Syndrome.

Result

Among 422 participants, the annual prevalence of CTS was 11.7%. Being smoker [AOR: 4.2; 95% CI: 1.76–10.26], having > 5-year work experience [AOR: 7.98; 95% CI: 3.7-17.33], movement repetition [AOR: 3.9; 95% CI: 1.66–9.4] and lack of ergonomics training [AOR: 5.2; 95% CI: 2.8–9.5] were independently associated risk factors to Carpal Tunnel Syndrome.

Conclusion

Carpal Tunnel Syndrome was high (11.7%) among bankers in this study area. Carpal Tunnel Syndrome was predicted by smoking, length of employment, movement repetition, and not received ergonomics training. Therefore, fore the banking industry, it would be better to maintain strict follow-up and provision of ergonomics training.
An evaluation of subtalar titanium screw arthroereisis for the treatment of symptomatic paediatric flatfeet - early results
Authors: Szesz Anna , Małecki Krzysztof , Sibiński Marcin , Niedzielski Kryspin R.
Published: October 2023

Background

Idiopathic flexible flatfoot is a common condition in children which typically improves with age and remains asymptomatic. However, the condition can sometimes be more severe, and cause mechanical impairment or pain. The aim of the study was to perform a prospective clinical, radiological, podoscopic and pedobarographic assessment (static and dynamic) of subtalar titanium screw arthroereisis for the treatment of symptomatic, idiopathic, flexible flatfeet.

Methods

A prospective, consecutive, non-controlled, cohort, clinical follow-up study was performed. In total, 30 patients (41 feet), mean age 10 (6 to 16 years), were evaluated. Clinical and standing radiological assessments, static and dynamic pedobarography, as well as podoscopy, were performed before surgery and at final follow-up.

Results

Treatment was associated with significant improvements in heel valgus angle, radiographic parameters (lateral and dorso-planar talo-first metatarsal angle, calcaneal inclination angle, talar declination angle, longitudinal arch angle) and podoscopic parameters (Clark’s angle, Staheli’s arch index and Chippaux-Smirak index). Significant increases were noted for lateral loading, forefoot contact phase and double support / swing phase, and reduced medial loading (dynamic pedobarography), as well as lateral midfoot area and loading, but decreased were observed for medial forefoot loading (static pedobarography). Four patients reported persistent pain in the sinus tarsi region (six feet), and in one case, the implant was replaced for a larger one due to undercorrection. No overcorrections or infection complications were noted in the study group.

Conclusions

Subtalar arthroereisis is a minimally-invasive and effective surgical method for treating symptomatic, idiopathic, flexible flatfeet; it has an acceptable complication rate with good early clinical results.

Level of evidence

II b.
Utilization of traditional herbal medicine formulas for unexplained female infertility in Korea: a retrospective study
Authors: Choi Su-Ji , Kim Dong-Il
Published: October 2023

Background

This study aimed to investigate the prescription of traditional herbal medicines for the treatment of unexplained female infertility in Korea. By analyzing the relationships among the prescriptions and between the prescriptions and treatment outcomes, we aimed to confirm the utilization of standardized prescriptions and the effectiveness of this standardization.

Methods

The data were derived from the “support projects” of the local government for infertile women to receive Korean medical treatments. The presciption data of 453 participants from 2017 to 2018 were analyzed. Data preprocessing, frequency analysis, and network analysis were conducted. For network analysis, the characteristics of the herbal medicine prescriptions were used to calculate the degree centrality, closeness centrality and eigenvector centrality. Modularity clustering was also performed for cluster analysis.

Results

Fifty different prescriptions were used, among which only 22 were used for participants who became pregnant. The recommended standard prescriptions for support projects were used frequently. “BaeranChacksangBang” showed the highest level of in-degree centrality. Among the prescriptions for participants who became pregnant, “JogyeongJongokTang” and “BaeranChacksangBang” were the most influential nodes. “BaeranChacksangBang”, “AnjeonYicheonTang”, “YukLinZu” and “JogyeongJongokTang” had high closeness centrality among the prescriptions for participants who became pregnant. Clustering analysis of the prescriptions for participants who became pregnant revealed that the prescriptions showed the best modularity when divided into five groups.

Conclusions

These findings depict the utilization of Korean herbal medicine in the real world and the dynamics underlying the herbal medicine prescription patterns for infertile women.
Expectations of Polish undergraduate medical students for medical humanities classes: a survey-based pilot study
Authors: Makowska Marta , Dec-Pietrowska Joanna , Szczepek Agnieszka J.
Published: October 2023

Background

Medical schools teach Medical Humanities (MH) to provide students with knowledge about the human experience related to health, illness, disease, medicine, and healthcare. Due to the previously observed negative opinions about MH courses, we examined the expectations of medical students in Poland toward humanities subjects.

Methods

We conducted a voluntary, anonymous electronic survey in one medical school (single-center study) and collected data from 166 medical students. The results were analyzed by comparing continuous and categorical variables between groups (gender, year of study, previous participation in MH classes).

Results

The students expected to learn how to communicate with patients and their families, especially about difficult topics. They also expected the classes to be active, stress-free, and without passing grades. The preferred MH teacher was a physician, although choosing a psychologist or other qualified person as an MH teacher was also popular. Previous participants in MH courses were more likely to expect such a course to be compulsory than those who had yet to attend it.

Conclusion

Considering the students’ expectations when designing MH classes could increase students’ satisfaction with MH courses.
Disease and social factors associated with healthcare utilization for the treatment of SARS-CoV-2 infections in a longitudinal cohort of essential workers in Arizona
Authors: Rivers Patrick , Jovel Krystal , Ramadan Ferris , Barnett Jared Joshua Anucha , Ellingson Katherine D. , Burgess Jefferey L. , Lutrick Karen
Published: October 2023

Background

Demands on health systems due to COVID-19 are substantial, but drivers of healthcare utilization are not well defined in non-severe SARS-CoV-2 infections. Among a prospective cohort of frontline workers from July 2020 to February 2023, we assessed predictors of healthcare utilization during SARS-CoV-2 infection.

Methods

Weekly specimens tested via real-time reverse transcriptase polymerase chain reaction analysis. Participants reported sociodemographic, health status information, and illness experience information. Primary outcome was healthcare utilization during SARS-CoV-2 infection. Predictors included sociodemographic characteristics, baseline health status, and measures of illness severity. Multivariable logistic regression was utilized to generate odds ratios for predictors of healthcare utilization.

Results

1,923 SARS-CoV-2 infections (1,276 first infections and 647 reinfections from 4,208 participants): 1221 (63.5%) individuals were between 40 and 65 years old; 1115 (58.0%) were female; 449 (23.3%) were Hispanic and 1305 (67.9%) non-Hispanic White. 294 (15.3%) individuals sought medical care during first infection, 106 (5.5%) during reinfection. Sociodemographic and baseline health characteristics were not associated with healthcare utilization during infections from any variant for first infections, while age (OR 1.04, 95%CI 1.01–1.07) was during Omicron reinfection. In first infection, number of symptoms (OR 1.16, 95%CI 1.00-1.36 in Origin/Alpha, OR 1.12, 95%CI 1.00-1.49 in Delta, OR 1.09, 95%CI 1.01–1.16 in Omicron), number of days spent in bed (OR 1.13, 95%CI 1.02–1.33 in Origin/Alpha, OR 1.23, 95%CI 1.00-1.59 in Delta, OR 1.12, 95%CI 1.03–1.22 in Omicron), and illness duration (OR 1.01, 95%CI 1.00-1.04 in Origin/Alpha, OR 1.01, 95%CI 1.00-1.03 in Delta, OR 1.01, 95%CI 1.00-1.02 in Omicron) were related to healthcare utilization for all variants. Number of days in bed (OR 1.12, 95%CI 1.01–1.27), illness duration (OR 1.01, 95%CI 1.00-1.02), and hours of work missed (OR 2.24, 95%CI 1.11–4.74) were positively associated with healthcare utilization during Omicron reinfection.

Conclusion

The main factors associated with healthcare utilization for SARS-CoV-2 infection were symptom severity and duration. Practices and therapeutics aimed at decreasing these factors would be most helpful in easing the burden on health systems.
Spatiotemporal evolution and influencing factors of the allocation of social care resources for the older adults in China
Authors: Peng Rong , Huang Jianhang , Deng Xueqin
Published: October 2023

Background

The reasonable allocation of social care resources for the older adults is a key measure to actively respond to population aging. This study aims to evaluate the evolutionary trend, spatial differences and influencing factors of the social elderly care resources (SECR) allocation in China.

Methods

This study constructed a comprehensive index system consisting of three dimensions: material resources, human resources and financial resources, to measure the level of SECR in mainland China. The Kernel density estimation was used to reveal the dynamic evolution trend, and Dagum Gini Coefficient and its decomposition method were used to investigate the equity of SECR allocation. Spatial panel regression models were used to analyze the influencing factors of the allocation of SECR.

Results

The level of SECR is rising from 0.197 in 2013 to 0.208 in 2019. The middle-high- and high-level areas of SECR were mainly distributed in the eastern and western China. The Gini coefficient of SECR decreased from 0.262 in 2013 to 0.249 in 2019. Per capita GDP, the proportion of social welfare expenditure in GDP and the proportion of the tertiary industry in GDP have significant positive effects on the allocation of SECR. Population aging and the development of service industry exhibit significant negative spatial spillover effects on the allocation of SECR.

Conclusions

The fairness of the allocation of SECR in China has been improved, while the spatial distribution is imbalanced. Economic development, fiscal input and the development of service industry have significant positive effects while population aging has significant negative effects on the SECR allocation.
Engineering siRNA therapeutics: challenges and strategies
Authors: Ali Zaidi Syed Saqib , Fatima Faria , Ali Zaidi Syed Aqib , Zhou Dezhong , Deng Wuquan , Liu Shuai
Published: October 2023

Small interfering RNA (siRNA) is a potential method of gene silencing to target specific genes. Although the U.S. Food and Drug Administration (FDA) has approved multiple siRNA-based therapeutics, many biological barriers limit their use for treating diseases. Such limitations include challenges concerning systemic or local administration, short half-life, rapid clearance rates, nonspecific binding, cell membrane penetration inability, ineffective endosomal escape, pH sensitivity, endonuclease degradation, immunological responses, and intracellular trafficking. To overcome these barriers, various strategies have been developed to stabilize siRNA, ensuring their delivery to the target site. Chemical modifications implemented with nucleotides or the phosphate backbone can reduce off-target binding and immune stimulation. Encapsulation or formulation can protect siRNA from endonuclease degradation and enhance cellular uptake while promoting endosomal escape. Additionally, various techniques such as viral vectors, aptamers, cell-penetrating peptides, liposomes, and polymers have been developed for delivering siRNA, greatly improving their bioavailability and therapeutic potential.
The association between reallocations of time and health using compositional data analysis: a systematic scoping review with an interactive data exploration interface
Authors: Miatke Aaron , Olds Tim , Maher Carol , Fraysse Francois , Mellow Maddison L , Smith Ashleigh E , Pedisic Zeljko , Grgic Jozo , Dumuid Dorothea
Published: October 2023

Background

How time is allocated influences health. However, any increase in time allocated to one behaviour must be offset by a decrease in others. Recently, studies have used compositional data analysis (CoDA) to estimate the associations with health when reallocating time between different behaviours. The aim of this scoping review was to provide an overview of studies that have used CoDA to model how reallocating time between different time-use components is associated with health.

Methods

A systematic search of four electronic databases (MEDLINE, Embase, Scopus, SPORTDiscus) was conducted in October 2022. Studies were eligible if they used CoDA to examine the associations of time reallocations and health. Reallocations were considered between movement behaviours (sedentary behaviour (SB), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA)) or various activities of daily living (screen time, work, household chores etc.). The review considered all populations, including clinical populations, as well as all health-related outcomes.

Results

One hundred and three studies were included. Adiposity was the most commonly studied health outcome (n = 41). Most studies (n = 75) reported reallocations amongst daily sleep, SB, LPA and MVPA. While other studies reported reallocations amongst sub-compositions of these (work MVPA vs. leisure MVPA), activity types determined by recall (screen time, household chores, passive transport etc.) or bouted behaviours (short vs. long bouts of SB). In general, when considering cross-sectional results, reallocating time to MVPA from any behaviour(s) was favourably associated with health and reallocating time away from MVPA to any behaviour(s) was unfavourably associated with health. Some beneficial associations were seen when reallocating time from SB to both LPA and sleep; however, the strength of the association was much lower than for any reallocations involving MVPA. However, there were many null findings. Notably, most of the longitudinal studies found no associations between reallocations of time and health. Some evidence also suggested the context of behaviours was important, with reallocations of leisure time toward MVPA having a stronger favourable association for health than reallocating work time towards MVPA.

Conclusions

Evidence suggests that reallocating time towards MVPA from any behaviour(s) has the strongest favourable association with health, and reallocating time away from MVPA toward any behaviour(s) has the strongest unfavourable association with health. Future studies should use longitudinal and experimental study designs, and for a wider range of outcomes.
The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer
Authors: Duan Sai-li , Wu Min , Zhang Zhe-Jia , Chang Shi
Published: October 2023

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize “metabolic reprogramming” to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.
NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration
Authors: Droho Steven , Voigt Andrew P. , Sterling Jacob K. , Rajesh Amrita , Chan Kyle S. , Cuda Carla M. , Perlman Harris , Lavine Jeremy A.
Published: October 2023

Background

Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1−/− mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes. While Nr4a1−/− mice are deficient in non-classical monocytes, results are confounded by macrophage hyper-activation. Nr4a1se2/se2 mice lack a transcriptional activator, resulting in non-classical monocyte loss without macrophage hyper-activation.

Main body

We subjected Nr4a1−/− and Nr4a1se2/se2 mice to the laser-induced CNV model and performed multi-parameter flow cytometry. We found that both models lack non-classical monocytes, but only Nr4a1−/− mice displayed increased CNV area. Additionally, CD11c+ macrophages were increased in Nr4a1−/− mice. Single-cell transcriptomic analysis uncovered that CD11c+ macrophages were enriched from Nr4a1−/− mice and expressed a pro-angiogenic transcriptomic profile that was disparate from prior reports of macrophage hyper-activation.

Conclusions

These results suggest that non-classical monocytes are dispensable during CNV, and NR4A1 deficiency results in increased recruitment of pro-angiogenic macrophages.
Comparing DNA isolation methods for forest trees: quality, plastic footprint, and time-efficiency
Authors: Guillardín Laura , MacKay John J.
Published: October 2023

Background

Genetic and genomic studies are seeing an increase in sample sizes together with a wider range of species investigated in response to environmental change concerns. In turn, these changes may come with challenges including the time and difficulty to isolate nucleic acids (DNA or RNA), the sequencing cost and environmental impacts of the growing amount of plastic waste generated in the process. Pseudotsuga menziesii var. menziesii (Mirbel) Franco (PM), Tsuga heterophylla (Raf.) Sarg. (TH) and Thuja plicata Donn ex D.Don (TP) are conifer species found in diverse woodlands both as natives and naturalized exotics. Our study was carried out whilst investigating their genetics to understand their population structure and potential for adaptation.

Results

In the present study, we compared two different DNA isolation methods, i.e., spin-column DNeasy plant mini kit (QIAGEN), and temperature-driven enzymatic cocktail Plant DNA Extraction (MicroGEM). The quantity of recovered DNA and the quality of DNA were assessed along with the plastic footprint and time needed for three tree species. Both methods were optimised and proven to provide enough DNA for each studied species. The yield of DNA for each method depended on the species: QIAGEN showed higher yield in P. menziesii and T. heterophylla, while T. plicata recovered similar amount of DNA for both methods. The DNA quality was investigated using DNA barcoding techniques by confirming species identity and species discrimination. No difference was detected in the PCR amplification of the two barcoding loci, (rbcL and trnH-psbA), and the recovered sequences between DNA isolation methods. Measurement of the plastic use and the processing time per sample indicated that MicroGEM had a 52.64% lower plastic footprint and was 51.8% faster than QIAGEN.

Conclusions

QIAGEN gave higher yields in two of the species although both methods showed similar quality results across all species. However, MicroGEM was clearly advantageous to decrease the plastic footprint and improve the time efficiency. Overall, MicroGEM recovers sufficient and reliable DNA to perform common downstream analyses such as PCR and sequencing. Our findings illustrate the benefits of research and efforts towards developing more sustainable methods and techniques to reduce the environmental footprint of molecular analyses.
The predictive factors of moral courage among hospital nurses
Authors: Hakimi Hamideh , Mousazadeh Noushin , Sharif-Nia Hamid , Nazari Roghieh , Dehghani Maryam
Published: October 2023

Background

Having moral courage is a crucial characteristic for nurses to handle ethical quandaries, stay true to their professional obligations towards patients, and uphold ethical principles. This concept can be influenced by various factors including personal, professional, organizational, and leadership considerations. The purpose of this study was to explore the predictors of moral courage among nurses working in hospitals.

Methods

In 2018, an observational cross-sectional study was carried out on 267 nurses employed in six hospitals located in the northern region of Iran. The participants were selected through a simple random sampling technique. To collect data, a demographic information form was used along with two questionnaires. The first questionnaire was a standard survey on moral courage, while the second questionnaire was designed to assess the ethical climate. Linear regression was used to assess the predictors of moral courage.

Results

Nurses had an average moral courage score of 87.07 ± 15.52 and an average moral climate score of 96.12 ± 17.17. The study showed that 16% of the variation in moral courage scores among nurses was explained by ethical climate and monthly overtime hours.

Conclusion

This study underscores the significance of establishing an ethical work environment and minimizing overtime hours in order to enhance moral courage among nurses. These findings carry weight for both nursing practice and organizational policies focused on fostering ethical conduct within healthcare settings.
Does the registry speak your language? A case study of the Global Angelman Syndrome Registry
Authors: Tones Megan , Zeps Nikolajs , Wyborn Yvette , Smith Adam , Barrero Roberto A. , Heussler Helen , Cross Meagan , McGree James , Bellgard Matthew
Published: October 2023

Global disease registries are critical to capturing common patient related information on rare illnesses, allowing patients and their families to provide information about their condition in a safe, accessible, and engaging manner that enables researchers to undertake critical research aimed at improving outcomes. Typically, English is the default language of choice for these global digital health platforms. Unfortunately, language barriers can significantly inhibit participation from non-English speaking participants. In addition, there is potential for compromises in data quality and completeness. In contrast, multinational commercial entities provide access to their websites in the local language of the country they are operating in, and often provide multiple options reflecting ethnic diversity. This paper presents a case study of how the Global Angelman Syndrome Registry (GASR) has used a novel approach to enable multiple language translations for its website. Using a “semi-automated language translation” approach, the GASR, which was originally launched in English in September 2016, is now available in several other languages. In 2020, the GASR adopted a novel approach using crowd-sourcing and machine translation tools leading to the availability of the GASR in Spanish, Traditional Chinese, Italian, and Hindi. As a result, enrolments increased by 124% percent for Spain, 67% percent for Latin America, 46% percent for Asia, 24% for Italy, and 43% for India. We describe our approach here, which we believe presents an opportunity for cost-effective and timely translations responsive to changes to the registry and helps build and maintain engagement with global disease communities.
Forms of sexual violence perpetrated in conflict and post-conflict settings against South Sudanese men resettled in two communities in Uganda: an exploratory qualitative study
Authors: Olaluwoye Tosin , Hoban Elizabeth , Williams Joanne
Published: October 2023

Background

Consideration for men as survivors of sexual violence in conflict and post-conflict settings has gained some prominence in the last decade. There remains a paucity of empirical data on forms of sexual violence from the survivors’ perspective, and no study has considered the context of the 2013 South Sudan conflict specifically.

Methods

This paper reports the findings of an exploratory qualitative study on the forms of sexual violence perpetrated against men in conflict and post-conflict settings, with the survivors as the main participants. A purposive sampling technique was used to recruit 26 South Sudanese male sexual violence survivors who have resettled in two refugee resettlement communities in Uganda since the onset of the 2013 South Sudan conflict. In-depth semi-structured interviews were used to collect the data from the male survivors. Six humanitarian aid workers who support sexual violence survivors also participated as key informants. Thematic data analysis was performed on the qualitative data.

Results

The 26 survivors reported experiencing eight direct and two indirect forms of sexual violence in conflict and post-conflict settings. The direct forms include (1) striping men naked; (2) male rape; (3) exchange of sex for favours; (4) forcing men to rape other people; (5) genital mutilation; (6) genital beating; (7) insertion of objects into men’s anus, and (8) taking men as wives. The indirect forms were forcing men to witness the rape of a female relative and forcing men to cheer or assist during the rape of other people.

Conclusion

To maximize positive health outcomes for survivors, stakeholders must consider both direct and indirect forms of male-directed conflict-related sexual violence in policy and practice.
Green synthesis of highly functionalized heterocyclic bearing pyrazole moiety for cancer-targeted chemo/radioisotope therapy
Authors: Anwer Kurls E. , Sayed Galal H. , Essa Basma M. , Selim Adli A.
Published: October 2023

New derivatives of heterocyclic bearing pyrazole moiety were synthesized (eight new compounds from 2 to 9) via green synthesis methods (microwave-assisted and grinding techniques). 4,6-Diamino-1,3-diphenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (2) shows high anti-cancer activity against both HepG2 and HCT-116 with IC50of 9.2 ± 2.8 and 7.7 ± 1.8 µM, respectively, which referenced to 5-Fu which is showing activity of 7.86 ± 0.5 and 5.35 ± 0.3 against both HepG2 and HCT-116, respectively. The cytotoxic activity against HCT-116 and HepG2 was slightly decreased and slightly increased, respectively, by a different pyrazole moiety (compound 5). Pharmacokinetics of compound 2 was carried out using the radioiodination technique in tumour-bearing Albino mice which shows good uptake at the tumour site. The biodistribution showed high accumulation in tumour tissues with a ratio of 13.7% ID/g organ after one hour in comparison with 2.97% ID/g organ at normal muscle at the same time point. As I-131 has maximum beta and gamma energies of 606.3 and 364.5 keV, respectively, therefore the newly synthesized compound 2 may be used for chemotherapy and TRT.
Janus kinase inhibitor, tofacitinib, in refractory juvenile dermatomyositis: a retrospective multi-central study in China
Authors: Zhang Junmei , Sun Li , Shi XinWei , Li Shipeng , Liu Cuihua , Li Xiaoqing , Lu Meiping , Deng Jianghong , Tan Xiaohua , Guan Wanzhen , Li Guomin , Wen Xinran , Liu Ping , Li Caifeng
Published: October 2023

Objectives

Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients.

Methods

A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann–Whitney U test, and chi-square test.

Results

Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis.

Conclusion

In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.