bluuebunny/crossref_metadata_2025 huggingface dataset:
Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels
Authors: Pardo Jèssica , Capdevila-Lacasa Clara , Segura Bàrbara , Pané Adriana , Montserrat Cristina , de Talló Forga-Visa Maria , Moreno Pedro J. , Garrabou Glòria , Grau-Junyent Josep M. , Junqué Carme ,   Consortium PKU.cat., Argudo-Ramírez Ana , Barrau-Martínez Blanca , Cantó Judith , Campistol Jaume , Cardellach Francesc , Casals-Pascual Climent , Chiva-Blanch Gemma , García-Arenas Dolores , García-García Francesc Josep , García-Villoria Judit , González de Aledo-Castillo José Manuel , González-Rodríguez Arnau , Guitart-Mampel Mariona , Isern Paula , Jiménez Amanda , Laudo Berta , Llorach Rafael , Andújar-Sánchez Félix , López-Galera Rosa , Meavilla Silvia Mª , Milisenda José Cesar , Morales Blai , Moreno-Lozano Pedro Juan , Moreno Julián , Nos Mònica , Ormazabal Aida , Ortega Ferrer Montserrat , Ortega Emilio , Padrosa Joan , Paredes Abraham José , Rubio Elisa , Tobías Ester , Torremade Josep , Urpi-Sarda Mireia , Valls Laura , Ventura Roser , Vergara-Gómez Andrea , Viaplana Judith , Viñals Clara
Published: June 2024

Background

Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce.

Objectives

This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU.

Methods

Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner.FreeSurfer(v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05).

Results

Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67;p = .010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000;p = .008), hippocampus (U = 243.000;p = .020), amygdala (U = 200.000;p = .002), and brainstem (t = 3.17;p = .006) as well as in total cerebral white matter volume (U = 175.000;p = .001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r = -0.417;p = .013) and brainstem (r = -0.455,p = .006) volumes.

Conclusions

Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity.
Water deficit response in nodulated soybean roots: a comprehensive transcriptome and translatome network analysis
Authors: Sainz María Martha , Filippi Carla V. , Eastman Guillermo , Sotelo-Silveira Mariana , Zardo Sofía , Martínez-Moré Mauro , Sotelo-Silveira José , Borsani Omar
Published: June 2024

Background

Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status—whether it is nodulated or not—can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit.

Results

Here, we analyzed soybean roots’ differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination.

Conclusions

Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.
Arabidopsis AGB1 participates in salinity response through bZIP17-mediated unfolded protein response
Authors: Cho Yueh
Published: June 2024

Background

Plant heterotrimeric G proteins respond to various environmental stresses, including high salinity. It is known that Gβ subunit AGB1 functions in maintaining local and systemic Na+/K+ homeostasis to accommodate ionic toxicity under salt stress. However, whether AGB1 contributes to regulating gene expression for seedling’s survival under high salinity remains unclear.

Results

We showed that AGB1-Venus localized to nuclei when facing excessive salt, and the induction of a set of bZIP17-dependent salt stress-responsive genes was reduced in the agb1 mutant. We confirmed both genetic and physical interactions of AGB1 and bZIP17 in plant salinity response by comparing salt responses in the single and double mutants of agb1 and bzip17 and by BiFC assay, respectively. In addition, we show that AGB1 depletion decreases nuclei-localization of transgenic mRFP-bZIP17 under salt stress, as shown in s1p s2p double mutant in the Agrobacteria-mediated transient mRFP-bZIP17 expression in young seedlings.

Conclusions

Our results indicate that AGB1 functions in S1P and/or S2P-mediated proteolytic processing of bZIP17 under salt stress to regulate the induction of salinity-responsive gene expression.
Trends in commonly used and potentially inappropriate medications in older Korean patients with polypharmacy
Authors: Shin Woo-young , Go Tae-Hwa , Kim Jung-ha
Published: June 2024

Background

Polypharmacy is a global public health concern. This study aimed to determine the prevalence of polypharmacy and trends in the use of commonly used and potentially inappropriate medications among older Korean patients.

Methods

Individuals aged ≥ 65 years who were prescribed any medication between 2014 and 2018 were selected from the Korean National Health Information Database. Joinpoint regression analyses were used to determine trends in the age-adjusted polypharmacy rates by age group. The prescription rates of the most commonly used medications and the most commonly used potentially inappropriate medications were analysed by year or age group for patients with polypharmacy using the chi-square and proportion difference tests.

Results

This study included 1,849,968 patients, 661,206 (35.7%) of whom had polypharmacy. Age-adjusted polypharmacy rates increased significantly between 2014 and 2018 (P = 0.046). Among patients with polypharmacy, the most commonly prescribed medications were aspirin (100 mg), atorvastatin, metformin, glimepiride, and rosuvastatin. The most commonly prescribed and potentially inappropriate medications were alprazolam, diazepam, amitriptyline, zolpidem, and dimenhydrinate. There was a significant decrease in the prescription rates for each of these drugs in 2018 compared with 2014 among patients with polypharmacy (all P < 0.001), whereas there was a significant increase in alprazolam prescription among patients aged ≥ 85 years when analysed by age group (P < 0.001).

Conclusions

This study revealed an increasing prevalence of polypharmacy among older adults. Additionally, it highlighted that the utilisation of commonly prescribed potentially inappropriate medications, such as benzodiazepines and tricyclic antidepressants, has remained persistent, particularly among patients aged ≥ 85 years who practiced polypharmacy. These findings provide evidence-based guidance for the development of robust polypharmacy management strategies to ensure medication safety among older adults.
The relationship between traumatic childbirth and first-time mothers’ social identity and wellbeing: a cross-sectional observational study
Authors: El-Salahi Shama , Knowles Bevis Rebecca , Hogg Lorna
Published: June 2024

Background

Experiencing childbirth as traumatic is common and can have long-lasting negative consequences for women’s mental health. However, fostering a sense of social identity has been shown to protect psychological wellbeing and mental health during life transitions, such as entering parenthood. This study therefore investigated the relationship between traumatic childbirth and first-time mothers’ social identity and their psychological wellbeing, and more specifically whether strength of identity as a first-time mother protected psychological wellbeing following traumatic childbirth.

Method

Women over the age of 18 who were living in the UK and had given birth to their first child in the past nine months were recruited to the study from clinical and community settings. They completed digital self-report questionnaires about their birth experience, social identity, mental health, and psychological wellbeing. Women who perceived themselves to have had a traumatic birth (the trauma group;N = 84) were compared to women who did not perceive themselves to have had a traumatic birth (the control group,N = 39). T-tests and chi square tests assessed preliminary group differences before multivariate analyses of covariance controlled for covariates. Post-hoc tests identified the direction of differences. Multiple regression and moderation analyses analysed interaction effects.

Results

The trauma group had significantly lower psychological wellbeing (mean = 41.5, 95% CI [39.4–43.7],p = .008, partial η2 = 0.059), compared to the control group (mean = 48.4, 95% CI [45.3–51.5]), but the two groups did not differ in the strength of their first-time mother identity, which was high across both groups. Strength of identity did not moderate the relationship between traumatic childbirth and psychological wellbeing. Giving birth by caesarean section independently reduced the strength of the first-time mother identity (p = .017, partial η2 = 0.049). All analyses controlled for emotional and practical support, perceptions of healthcare staff, and mode of birth.

Conclusions

Having a traumatic birth was associated with lower psychological wellbeing, and the strength of first-time mother identity does not appear to moderate this relationship. Factors such as mode of birth may be more important. Further research, including longitudinal designs, is needed to understand the relationship between these constructs and identify more effective ways of protecting first-time mothers’ mental health.
Evaluating the causes of retinopathy of prematurity relapse following intravitreal bevacizumab injection
Authors: Milani Amir Eftekhari , Arasteh Amin , Saeedi-Maleki Zahra , Niyousha Mohamad Reza , Sahebazamani Mohamad Ali , Brumandpur Fariborz
Published: June 2024

Background

Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms of ROP, which does not restrict the visual field in comparison to laser therapy. The present study aimed to determine and evaluate the risk factors for ROP recurrence following IVB injection.

Materials and methods

In this retrospective study, 98 eyes of 49 infants with ROP who had received IVB injections as the primary treatment for type 1 ROP are included.

Results

Fifty-four eyes (55.1%) had aggressive retinopathy of prematurity (A-ROP), and forty-four (44.9%) had Stage III Plus ROP in Zone II. ROP recurred in 13 eyes (13.26%) of 8 infants. The mean period between IVB and the ROP recurrence was 8.08 (95% CI:5.32–10.83) weeks. The infants who had ROP recurrence had lower birth weight (P value = 0.002), lower postmenstrual age at IVB injection (P value = 0.001), lower IVB injection gap period from birth (P value = 0.044), higher oxygen therapy requirement rate after IVB injection (P value < 0.001, OR:19.0) and higher oxygen therapy duration (P value = 0.006). The ROP severity, gestational age at birth, and diet were not statistically different between the recurrence and complete regression groups. Out of 13 eyes treated with laser photocoagulation because of ROP relapse, macula dragging occurred in one eye, and all the cases met the complete regression.

Conclusion

Low birth weight and oxygen therapy are the most important risk factors for ROP relapse, which requires meticulous oxygen treatment guidelines for premature infants.
‘Before, we ended up in conflicts, now we can provide support’—Experiences of Community Reinforcement and Family Training (CRAFT) for parents of young adults with hazardous substance use
Authors: Siljeholm Ola , Eckerström Joachim , Molander Olof , Sundbye Jennie , Hammarberg Anders
Published: June 2024

Background

The prevalence of hazardous substance use is highest in the age between 18 and 25, but few young adults enter treatment. Community Reinforcement and Family Training (CRAFT) is a support program for concerned significant others (CSOs) of individuals with diverse substance use disorders and is proven efficacious in promoting treatment entry. The aim of the current study was to investigate the experiences of CRAFT among parents of substance using young adults.

Methods

We used a qualitative design conducting semi-structured interviews with 10 parents of young adults (18–24 years) with hazardous substance use. The participants were recruited from a randomized controlled trial of the CRAFT program. The transcribed interviews were analyzed using thematic analysis.

Results

We divided the results into three overall domains—Reasons for entering the CRAFT program, Strengths of the CRAFT program and Limitations of the CRAFT program – with three to four themes under each domain. The parents appreciated the accessible support at a time when they needed it due to feelings of shock and powerlessness, and they described communication strategies together with positive reinforcement as the two most helpful CRAFT-sessions. Regarding limitations of CRAFT in the current population, the parents wanted more accessible support for the young adults when they were ready to enter treatment, and described difficulties to practice CRAFT-components due to changing life-circumstances and fear of aggravated health for their young adults.

Conclusion

The results provide arguments for the health care system to implement support programs to parents of young adults with hazardous substance use. The results show that CRAFT is suitable for the current population, but with some possible additions due to changing circumstances that are common in the young adult developmental phase emerging adulthood.

Trial registration

The trial was pre-registered at isrctn.com, reference number ISRCTN12212515 date: November 7, 2018.
Specialized pro-resolution mediators in the bladder: effects of resolvin E1 on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model
Authors: Cervantes Anissa , Hughes Francis M. , Jin Huixia , Purves J. Todd
Published: June 2024

Background

One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction.

Methods

Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice.

Results

Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan’s blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks.

Conclusions

Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.
The relationship between vaccine hesitancy and health literacy in pregnant women: a cross-sectional study *
Authors: Çetin Kübra , Sögüt Seda Cangöl
Published: June 2024

Background

Pregnancy; It is an important process that directly affects the mother and the fetus, where women benefit more from health services and the need for health-related decision-making and information increases. It is very important to determine and improve the health literacy level of these women. The study determined the relationship between vaccine hesitancy and health literacy in pregnant women.

Methods

It is a cross-sectional type of research. The research was carried out in a state hospital. The online form was sent to 230 pregnant women. Ethics committee, institution and scale permissions were obtained for the study. The data of the study were collected online by using the questionnaire prepared by scanning the literature, the Anti-Vaccination Scale and the Health Literacy Scale. Statistical analyzes of the data were performed using the SPSS version 25 program.

Results

The Vaccine Hesitancy Scale score of the pregnant women was 55.53 ± 10.15, whereas their Health Literacy Scale score was 98.57 ± 21.48. Health literacy was associated with the sociodemographic and obstetric characteristics of the pregnant women. Educational status, economic status, place of residence, and family structure were associated with vaccine hesitancy.

Conclusions

It was determined that there was a negative correlation between the anti-vaccination scale scores of the pregnant women and the health literacy scale scores. As a result, it was determined that the anti-vaccination level of the pregnant women was moderate and the health literacy level was sufficient. It can be recommended to provide appropriate trainings and counseling to target groups, which will increase the health literacy level of pregnant women.
Exploring hot topics and evolutionary paths in the Diagnosis-Related Groups (DRGs) field: a comparative study using LDA modeling
Authors: Chen Xinrui , Zhang Meng , Bu Qingqing , Tan Bo , Peng Peng , Zhou Yilin , Tang Yuqin , Tian Xiaoqin , Deng Dan
Published: June 2024

Background

This study reviews the research status of Diagnosis-related groups (DRGs) payment system in China and globally by analyzing topical issues in this field and exploring the evolutionary trends of DRGs in different developmental stages.

Methods

Abstracts of relevant literature in the field of DRGs were extracted from the China National Knowledge Infrastructure (CNKI) database and the Web of Science (WoS) core database and used as text data. A probabilistic distribution-based Latent Dirichlet Allocation (LDA) topic model was applied to mine the text topics. Topical issues were determined by topic intensity, and the cosine similarity of the topics in adjacent stages was calculated to analyze the topic evolution trend.

Results

A total of 6,758 English articles and 3,321 Chinese articles were included. Foreign research on DRGs focuses on grouping optimization, implementation effects, and influencing factors, whereas research topics in China focus on grouping and payment mechanism establishment, medical cost change evaluation, medical quality control, and performance management reform exploration.

Conclusions

Currently, the field of DRGs in China is developing rapidly and attracting deepening research. However, the implementation depth of research in China remains insufficient compared with the in-depth research conducted abroad.
Correlation between immune-related adverse events and efficacy of PD-(L)1 inhibitors in small cell lung cancer: a multi-center retrospective study
Authors: Zhang Jian , Gao Aiqin , Wang Shuyun , Sun Yanxin , Wu Jiake , Wang Dahai , Ge Yihui , Li Juan , Sun Haifeng , Cheng Qinglei , Sun Yuping
Published: June 2024

Background

Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown.

Method

This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated.

Results

140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P < 0.001) and DCR (97.9% vs. 79.8%, P < 0.001), as well as prolonged median PFS (8.8 vs. 4.5 months, P < 0.001) and OS (23.2 vs. 21.6 months, P < 0.05). Among the different spectra of irAEs, thyroid dysfunction, rash, and pneumonitis were the most powerful indicator for improved PFS. When analyzed as a time-dependent covariate, the occurrence of irAEs was associated with significant improvement in PFS rather than in OS. Furthermore, patients experiencing multisystem irAEs displayed a longer PFS and OS compared with single-system irAEs and the irAE-free ones. IrAEs grade and steroid use did not impact the predictive value of irAEs on PFS.

Conclusion

The presence of irAEs predicts superior clinical benefit in SCLC. Patients who develop multi-system irAEs may have an improved survival than those developed single-system irAEs and no-irAEs. This association persists even when systemic corticosteroids were used for irAEs management.
Which surrogate insulin resistance indices best predict coronary artery disease? A machine learning approach
Authors: Mirjalili Seyed Reza , Soltani Sepideh , Meybodi Zahra Heidari , Marques-Vidal Pedro , Firouzabadi Danial Dehghani , Eshraghi Reza , Restrepo David , Ghoshouni Hamed , Sarebanhassanabadi Mohammadtaghi
Published: June 2024

Background

Various surrogate markers of insulin resistance have been developed, capable of predicting coronary artery disease (CAD) without the need to detect serum insulin. For accurate prediction, they depend only on glucose and lipid profiles, as well as anthropometric features. However, there is still no agreement on the most suitable one for predicting CAD.

Methods

We followed a cohort of 2,000 individuals, ranging in age from 20 to 74, for a duration of 9.9 years. We utilized multivariate Cox proportional hazard models to investigate the association between TyG-index, TyG-BMI, TyG-WC, TG/HDL, plus METS-IR and the occurrence of CAD. The receiver operating curve (ROC) was employed to compare the predictive efficacy of these indices and their corresponding cutoff values for predicting CAD. We also used three distinct embedded feature selection methods: LASSO, Random Forest feature selection, and the Boruta algorithm, to evaluate and compare surrogate markers of insulin resistance in predicting CAD. In addition, we utilized the ceteris paribus profile on the Random Forest model to illustrate how the model’s predictive performance is affected by variations in individual surrogate markers, while keeping all other factors consistent in a diagram.

Results

The TyG-index was the only surrogate marker of insulin resistance that demonstrated an association with CAD in fully adjusted model (HR: 2.54, CI: 1.34–4.81). The association was more prominent in females. Moreover, it demonstrated the highest area under the ROC curve (0.67 [0.63–0.7]) in comparison to other surrogate indices for insulin resistance. All feature selection approaches concur that the TyG-index is the most reliable surrogate insulin resistance marker for predicting CAD. Based on the Ceteris paribus profile of Random Forest the predictive ability of the TyG-index increased steadily after 9 with a positive slope, without any decline or leveling off.

Conclusion

Due to the simplicity of assessing the TyG-index with routine biochemical assays and given that the TyG-index was the most effective surrogate insulin resistance index for predicting CAD based on our results, it seems suitable for inclusion in future CAD prevention strategies.
Association between atherogenic index of plasma and new-onset stroke in individuals with different glucose metabolism status: insights from CHARLS
Authors: Qu Longjie , Fang Shuang , Lan Zhen , Xu Shuai , Jiang Jialiu , Pan Yilin , Xu Yun , Zhu Xiaolei , Jin Jiali
Published: June 2024

Background

Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous.

Methods

A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan–Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states.

Results

During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan–Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05–1.71), 1.52 (1.19–1.93), and 1.84 (1.45–2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders.

Conclusions

An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual’s glucose metabolism status.
“We need to confirm at least from two or three”: Healthcare workers’ discretion as gatekeepers in the context of the Ethiopian abortion law
Authors: Jibat Nega , Tadele Getnet , Haukanes Haldis , Blystad Astrid
Published: June 2024

Introduction

Women’s access to legal and safe abortion is a vital means to reduce unsafe abortion, which in turn is known to reduce maternal morbidity and mortality. In 2005, Ethiopia enacted a relatively permissive abortion legislation. However, there is evidence that access to abortion care services may be challenging and controversial even if progressive abortion laws are in place. This article examines women’s access to abortion services from the perspective of healthcare workers in a rural setting in Ethiopia. Drawing on Lipsky’s theory of street-level bureaucrats, the article discusses healthcare workers’ discretion and the substantial authority they hold as gatekeepers to safe abortion services.

Methods

The study draws upon a qualitative, interpretative methodological approach, with in-depth semi-structured interviews with healthcare workers as the key method of data generation. The data was analyzed and interpreted thematically. Healthcare workers’ perspectives were examined with reference to the national abortion legislation and guidelines.

Results

The findings reveal that healthcare workers make decisions on behalf of the women who seek abortion, and they involve parents and partners in abortion-related decision-making processes. Moreover, they assess the social context of the pregnancy such as the marital and economic statuses of the abortion-seeking women in ways that restrict women’s access to legally-endorsed abortion services.

Conclusions

Healthcare workers’ practices in this rural area were found to challenge the basic provisions laid out in Ethiopia’s abortion legislation. Their negative discretion of the legislation contributes to the substantial barriers Ethiopian abortion-seeking women face in gaining access to legal abortion services, despite the presence of a progressive legal framework and guidelines.
The impact of the expanded health insurance coverage policy on healthcare spending: evidence from Korea
Authors: Ji Seokmin , Lee Munjae , Choi Mankyu , Park Sewon
Published: June 2024

Background

South Korea’s National Health Insurance (NHI) system pursues universal health coverage, but it has not been able to alleviate patients’ financial burden owing to limited coverage and a high proportion of out-of-pocket expenses. In 2017, the government announced a plan to strengthen universality by providing coverage for all unincluded services, expanding coverage, and alleviating household financial burden. We aimed to evaluate the effect of “Moon Care” with a focus on changes in health expenditures following policy implementation, and to provide empirical evidence for future policies to strengthen the NHI system’s universality.

Methods

Using data from the 2016 and 2018 Korea Health Panel (KHP), we established a treatment group affected by the policy and an unaffected control group; we ensured homogeneity between the groups using propensity score matching (PSM). Subsequently, we examined changes in NHI payments, non-payments, and out-of-pocket payments (OOP); we performed difference-in-differences (DID) analysis to evaluate the policy’s effect.

Results

Following policy implementation, the control group had a higher increase than the treatment group in all categories of health expenditures, including NHI payments, non-payments, and OOP. We noted significant decreases in all three categories of health expenditures when comparing the differences before and after policy implementation, as well as between the treatment and control groups. However, we witnessed a significant decrease in the interaction term, which confirms the policy’s effect, but only for non-payments.

Conclusions

We observed the policy’s intervention effect over time as a decrease in non-payments, on the effectivity of remunerating covered medical services. However, the policy did not work for NHI payments and OOP, suggesting that it failed to control the creation of new non-covered services as noncovered services were converted into covered ones. Thus, it is crucial to discuss the financial spending of health insurance regarding the inclusion of non-covered services in the NHI benefits package.
A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy
Authors: Peng Shumin , Fu Haojie , Li Rui , Li Hui , Wang Shuyuan , Li Bingyan , Sun Jingjing
Published: June 2024

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

Graphical Abstract
Treatment of chronic mini-thoracotomy wound pain and lung herniation with intercostal cryoablation and surgical mesh repair: a case report
Authors: Jung Eun Yeung , Lee Seok Soo
Published: June 2024

Background

The incidence of minimally invasive heart surgery via mini-thoracotomy (MT; right anterior thoracotomy) is on the rise, accompanied by an increase in post-MT intercostal nerve neuralgia and the risk of lung herniation through the incision site. While various methods have been proposed to address these issues, none have been commonly effective. In this case report, we attempted to simultaneously address these problems by performing intercostal cryoablation (IC) and mesh repair.

Case presentation

A 43-year-old male was referred to our hospital for chronic post-thoracotomy neuralgia following heart surgery via MT, involving patch closure of an atrial septal defect and tricuspid annuloplasty. He presented with intercostal nerve neuralgia and lung herniation accompanied by severe pain. Despite medication and lidocaine injections, there was no relief. Consequently, he underwent surgical treatment with IC for chronic MT wound pain and simultaneously underwent mesh repair for a lung hernia. He was discharged from hospital free of complications. Subsequently, he no longer required further pain medication and experienced a favorable recovery.

Conclusion

Our findings suggest that concurrent IC and mesh repair can effectively relieve chronic post-MT intercostal nerve neuralgia and severe lung herniation pain in patients who underwent MT surgery, leading to a decrease in opioid medication usage.
Massive hemothorax induced by pulmonary arteriovenous malformation rupture: a case report and literature review
Authors: Li Xiang , Duan Lijun , Mu Shengnan , Dong Xin , Lu Xiaoqian , Cao Dianbo
Published: June 2024

Background

Pulmonary arteriovenous malformation (PAVM), also known as pulmonary arteriovenous fistula, is a rare vascular developmental anomaly. Most cases of PAVM are associated with hereditary hemorrhagic telangiectasia (HHT). Hemothorax associated with PAVM is even rarer, and management concerning this complication still challenges.

Case presentation

A 55-year-old man with sudden onset of dyspnea and chest pain was admitted to our hospital. He had a medical history of epistaxis, intraperitoneal germ cell tumor and PAVM. Chest unenhanced CT revealed the left-sided pleural effusion together with partial passive atelectasis and gradual increase at the interval of six days. Diagnostic thoracocentesis further revealed hemorrhagic effusion. CT angiography (CTA) showed tortuously dilated lumen of the left lower pulmonary artery and PAVM with the formation of aneurysm. Due to his family's refusal of surgery, the patient underwent transcatheter embolization therapy. However, the left pleural effusion did not significantly reduce and there was a slow drop in hemoglobin value even after interventional treatment, indicating the possibility of ongoing active bleeding. Eventually, the patient received lobectomy of the left lower lobe with a satisfactory outcome.

Conclusions

Massive hemothorax resulting from PAVM rupture into the pleural space can lead to fatal outcomes. CTA can accurately diagnose this pathologic condition. Transcatheter embolization is frequently used in the treatment of PAVM, but it may be challenging to achieve the desirable effect in patients with hemothorax. Combined with our case and literature review, direct radical surgery can lead to a successful outcome when PAVM complicated with hemothorax and a large diameter of the draining vein.
The Acoel nervous system: morphology and development
Authors: Martinez Pedro , Bailly Xavier , Sprecher Simon G. , Hartenstein Volker
Published: June 2024

Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.

In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.
Radiomics models of contrast-enhanced computed tomography for predicting the activity and prognosis of acute pancreatitis
Authors: Yu Ning Jun , Li Xing Hui , Liu Chao , Chen Chao , Xu Wen Han , Chen Chao , Chen Yong , Liu Ting Ting , Chen Tian Wu , Zhang Xiao Ming
Published: June 2024

Background

The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn’t include indicators that directly reflect pathophysiology processes and imaging characteristics.

Objectives

To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP.

Methods

AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model.

Results

There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74.

Conclusions

The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS.

Critical relevance statement

This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management.

Key Points

Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis.

The combined model provides a new method to predict the activity and prognosis of AP.

The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System.

Graphical Abstract
Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes
Authors: Zhang Hengliang , Sen Payel , Hamers Jules , Sittig Theresa , Woestenburg Brent , Moretti Allessandra , Dendorfer Andreas , Merkus Daphne
Published: June 2024

Background

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart.

Methods

CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel.

Results

In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA.

Conclusion

By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.
Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation
Authors: Zhou Zhengli , Wu Xiaomei , Chen Tingwei , Zhang Bo , Li Wenxin , Zhou Min , Zhao Jingxue , Dong E. , Li Tianqing
Published: June 2024

Background

Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA.

Methods

Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis.

Results

We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor.

Conclusions

Due to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA.