bluuebunny/crossref_metadata_2025 huggingface dataset:
On triangle inequalities of correlation-based distances for gene expression profiles
Authors: Chen Jiaxing , Ng Yen Kaow , Lin Lu , Zhang Xianglilan , Li Shuaicheng
Published: February 2023

Background

Distance functions are fundamental for evaluating the differences between gene expression profiles. Such a function would output a low value if the profiles are strongly correlated—either negatively or positively—and vice versa. One popular distance function is the absolute correlation distance, $$d_a=1-|\rho |$$

d
a

=
1
-

|
ρ
|

, where $$\rho$$
ρ
is similarity measure, such as Pearson or Spearman correlation. However, the absolute correlation distance fails to fulfill the triangle inequality, which would have guaranteed better performance at vector quantization, allowed fast data localization, as well as accelerated data clustering.

Results

In this work, we propose $$d_r=\sqrt{1-|\rho |}$$

d
r

=

1
-
|
ρ
|

as an alternative. We prove that $$d_r$$

d
r

satisfies the triangle inequality when $$\rho$$
ρ
represents Pearson correlation, Spearman correlation, or Cosine similarity. We show $$d_r$$

d
r

to be better than $$d_s=\sqrt{1-\rho ^2}$$

d
s

=

1
-

ρ
2

, another variant of $$d_a$$

d
a

that satisfies the triangle inequality, both analytically as well as experimentally. We empirically compared $$d_r$$

d
r

with $$d_a$$

d
a

in gene clustering and sample clustering experiment by real-world biological data. The two distances performed similarly in both gene clustering and sample clustering in hierarchical clustering and PAM (partitioning around medoids) clustering. However, $$d_r$$

d
r

demonstrated more robust clustering. According to the bootstrap experiment, $$d_r$$

d
r

generated more robust sample pair partition more frequently (P-value $$<0.05$$

<
0.05

). The statistics on the time a class “dissolved” also support the advantage of $$d_r$$

d
r

in robustness.

Conclusion

$$d_r$$

d
r

, as a variant of absolute correlation distance, satisfies the triangle inequality and is capable for more robust clustering.
Association of circulating MtDNA with CVD in hemodialysis patients and in vitro effect of exogenous MtDNA on cardiac microvascular inflammation
Authors: Fan Zhen , Feng Ya , Zang Li , Guo Yi , Zhong Xiao-yi
Published: February 2023

Background

Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

Methods

Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were measured by standard assays. Ten-year CVD risk was calculated from the Framingham risk score (FRS) model. In vitro study, human cardiac microvascular endothelial cells (HCMECs) were incubated with normal or uremic serum, with or without exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 (ICAM-1), MCP-1 and tumor necrosis factor-α (TNF-α) and cytosolic MtDNA were detected by qPCR.

Results

Plasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 105 copies/mL; p = 0.000). Subsequently, the MHD patients were classified into two groups based on the MtDNA median (4.34 × 105 copies/mL). In stratified analyses, the levels of Hs-CRP (5.02 vs. 3.73 mg/L; p = 0.042) and MCP-l (99.97 vs. 64.72 pg/mL; p = 0.008) and FRS (21.80 vs. 16.52; p = 0.016) in the high plasma MtDNA group were higher than those in the low plasma MtDNA group. In vitro study, we found that exogenous MtDNA aggravated uremic serum-induced microvascular inflammation (ICAM-1 and TNF-α) in HCMECs (all p < 0.05). Besides, the addition of MtDNA to the medium resulted in a further increase in cytosolic MtDNA and TLR9 levels in uremic serum-treated cells (all p < 0.05). In patients with MHD, MtDNA levels in plasma were significantly reduced after a single routine hemodialysis (pre 4.47 vs. post 3.45 × 105 copies/mL; p = 0.001) or hemodiafiltration (pre 4.85 vs. post 4.09 × 105 copies/mL; p = 0.001). These two approaches seem similar in terms of MtDNA clearance rate (21.26% vs. 11.94%; p = 0.172).

Conclusions

Overall, the present study suggests that MtDNA released into the circulation under the uremic toxin environment may adversely affect the cardiovascular system by exacerbating microvascular inflammation, and that reducing circulating MtDNA might be a future therapeutic strategy for the prevention of MHD-related CVD.
Tofacitinib as a maintenance therapy in patients with ulcerative colitis stratified by OCTAVE Sustain baseline Mayo endoscopic subscore
Authors: Lee Scott D. , Allegretti Jessica R. , Steinwurz Flavio , Connelly Susan B. , Lawendy Nervin , Paulissen Jerome , Gecse Krisztina B.
Published: February 2023

Background

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We evaluated tofacitinib efficacy and safety in the 52-week maintenance study, OCTAVE Sustain, by baseline Mayo endoscopic subscore (MES) following 8-week induction.

Methods

The proportion of patients achieving efficacy endpoints at Week 24 or 52 of OCTAVE Sustain was evaluated by baseline MES following 8-week induction. Using logistic regression, the difference in treatment effect (tofacitinib vs. placebo) between baseline MES (0 vs. 1) for each endpoint was assessed. Adverse events were evaluated.

Results

At Week 52 of OCTAVE Sustain, a numerically higher proportion of tofacitinib-treated patients achieved remission with OCTAVE Sustain baseline MES of 0 versus 1 (61.9% vs. 36.5% for tofacitinib 5 mg twice daily [BID] and 75.0% vs. 54.2% for tofacitinib 10 mg BID). Similar trends were observed for endoscopic remission and endoscopic improvement. Logistic regression analyses showed a larger treatment effect at Week 52 in patients with baseline MES of 0 versus 1 for clinical response (p = 0.0306) in the tofacitinib 5 mg BID group (other endpoints all p > 0.05); differences were not significant for any endpoint in the 10 mg BID group (all p > 0.05). Infection adverse events were less frequent among patients with baseline MES 0 versus 1.

Conclusions

MES may be important in predicting long-term efficacy outcomes for tofacitinib maintenance treatment. Aiming for endoscopic remission during induction with tofacitinib 10 mg BID may allow successful maintenance with tofacitinib 5 mg BID. Safety was consistent with the known tofacitinib safety profile.

Trial registration NCT01458574.
The psychometric properties of the Chinese version of the Parkinson Anxiety Scale (C-PAS) among Parkinson’s disease
Authors: Jiang Yuanyuan , Jiang Yelin , Peng Tiantian , Wang Mengyue , Li Manman , Zhang Min , Li Li , Zhang Qi
Published: February 2023

Background

Anxiety disorder is a common non-motor symptom among individuals with Parkinson’s disease (PD). At present, there are no specific tools in China for assessing the anxiety level of patients with PD. This study aimed to test the reliability and validity of the Chinese version of the Parkinson Anxiety Scale (C-PAS) in Chinese patients with PD.

Methods

A total of 158 patients with PD at one hospital in Nanjing were recruited through convenience sampling. The C-PAS was translated into Chinese using a classic ‘forward-backward’ translation method. Reliability tests included internal consistency and test-reliability. And in addition to content, structure and criterion-related validity were performed for the validity tests. Criterion-related validity was evaluated with the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A).

Results

Results confirmed the three-factor structure of the original C-PAS with 12 items, including persistent anxiety (5 items), episodic anxiety (4 items) and avoidance behavior (3 items). Significant and positive correlations were obtained between C-PAS and HADS-A (r = 0.82, P<0.01). The Cronbach’s α and test-retest reliability of the total scale were 0.89 and 0.84, respectively.

Conclusion

The C-PAS has demonstrated good psychometric properties. Therefore, it can be employed in patients with PD to evaluate the condition of anxiety.
LncRNA ANRIL promotes HR repair through regulating PARP1 expression by sponging miR-7-5p in lung cancer
Authors: Du Zhipeng , Zhang Fangxiao , Liu Lei , Shen Hui , Liu Tingting , Jin Jing , Yu Nanxi , Wan Zhijie , Wang Hang , Hu Xuguang , Chen Yuanyuan , Cai Jianming
Published: February 2023

Background

Radiotherapy is an important treatment for lung cancer, mainly by triggering DNA double-strand breaks to induce cell death. Blocking DNA damage repair can increase the radiosensitivity of tumor cells. Recent studies have identified long noncoding RNAs as key regulators in DNA damage repair. The lncRNA ANRIL was previously shown to be involved in homologous recombination (HR) repair, but its specific mechanism has not been fully elucidated.

Methods

The downstream interacting miRNAs of ANRIL were predicted according to miRanda software. Fluorescence quantitative PCR was used to detect the expression levels of ANRIL and candidate miRNAs. Clone formation experiment and cell viability assays detect cell viability after ionizing radiation. Apoptosis assay was used to detect the apoptosis of cells after 8 h of ionizing radiation. Western blot analysis and immunofluorescence assays verified the protein expression levels of the downstream target molecule PARP1 of miR-7-5p and key molecules in the HR pathway. Fluorescent reporter gene experiments were used to verify the interaction between ANRIL and miR-7-5p and between miR-7-5p and PARP1.

Results

Bioinformatics analysis and qPCR validation suggested that miR-7-5p might be a downstream molecule of ANRIL. The expression of miR-7-5p was up-regulated after knockdown of ANRIL, and the expression of miR-7-5p was down-regulated after overexpression of ANRIL. Meanwhile, there was a negative correlation between ANRIL and miR-7-5p expression changes before and after ionizing radiation. The luciferase reporter gene assay confirmed the existence of ANRIL binding site with miR-7-5p, and found that transfection of miR-7-5p inhibitor can reduce the radiation sensitivity of ANRIL-KD cells. A downstream target molecule of miR-7-5p related to HR repair, PARP1, was screened through website prediction. Subsequently, it was confirmed by Western blot and luciferase reporter assays that miR-7-5p could down-regulate the expression of PARP1, and there was a miR-7-5p binding site on the 3'UTR of PARP1 mRNA. This suggests that ANRIL may act as a competitive endogenous RNA to bind miR-7-5p and upregulate the expression of PARP1. Western blot and immunofluorescence staining were used to detect the expression changes of HR repair factors in ANRIL-KD cells after ionizing radiation, and it was found that knockdown of ANRIL can inhibit the expression of PARP1, BRCA1 and Rad51, hinder radiation-induced HR repair, and eventually result in resensitizing ANRIL-KD cells to ionizing radiation.

Conclusions

Our findings provide evidence that ANRIL targets the miR-7-5p/PARP1 axis to exert its regulatory effect on HR repair, suggesting that altering ANRIL expression may be a promising strategy to overcome radiation resistance.
Home environment and nutritional status mitigate the wealth gap in child development: a longitudinal study in Vietnam
Authors: Tran Lan Mai , Nguyen Phuong Hong , Young Melissa F. , Ramakrishnan Usha , Alderman Harold
Published: February 2023

Background

Inequity in child development is found at early age, but limited evidence exists on whether these gaps change over time and what are the mediators.

Objective

We aim to (1) quantify wealth related gaps in cognitive and socio-emotional development in early and middle childhood; (2) examine how these gaps were mitigated by maternal, child factors and home environment.

Methods

We assessed the offspring of women who participated in a randomized controlled trial of preconception micronutrient supplementation in Vietnam (n = 1599). Child development was measured by the Bayley Scales of Infant Development-III (at 1-2y) and the Wechsler Intelligence Scale for Children®—IV (at 6-7y). We used multivariable regression to estimate the changes in wealth gaps for child development over time, adjusting for potential factors that potentially influence cognitive development.

Results

We found significant wealth gaps in cognitive development during early childhood (gaps between top and bottom quintiles: 0.5 SD); these gaps increased substantially in middle childhood (0.9 SD). Wealth disparity in social emotion did not change over time (0.26–0.28 SD). Maternal factors, quality of home environment, and child nutritional status mitigated the wealth gap in cognitive development (7-42%) in early childhood. The contribution of these mitigating factors was smaller in middle childhood (2- 15%). Wealth gap in social emotion reduced by 13% and 43% among children with better nutritional status at 2y and higher quality of home environment at 6-7y, respectively.

Conclusion

Interventions focusing on improving quality of home environment, maternal education, wellbeing, and child nutrition status may help reduce developmental deficits associated with poverty.
Comparative study of lumbar bone mineral content using DXA and CT Hounsfield unit values in chest CT
Authors: Lee Dong-Ha , Kim MinWoo
Published: February 2023

Background

Bone mineral content (BMC) values in certain bones and changes in BMC over time are key features for diagnosing osteoporosis. This study examined those features using morphometric texture analysis in chest computational tomography (CT) by comparing a dual-energy X-ray absorptiometry (DXA)-based BMC. An accessible approach for screening osteoporosis was suggested by accessing BMC using only Hounsfield units (HU).

Methodology

The study included a total of
510 cases (255 patients) acquired between May 6, 2012, and June 30, 2020, at a
single institution. Two cases were associated with two chest CT scans from one
patient with a scan interval of over two years, and each scan was followed soon
after by a DXA scan. Axial cuts of the first lumbar vertebra in CT and
DXA-based L1 BMC values were corrected for each case. The maximum trabecular
area was selected from the L1 spine body, and 45 texture features were
extracted from the region using gray-level co-occurrence matrices. A regression
model was employed to estimate the absolute BMC value in each case using 45
features. Also, an additional regression model was used to estimate the change
in BMC between two scans for each patient using 90 features from the
corresponding cases.

Results

The correlation coefficient (CC) and mean absolute
error (MAE) between estimates and DXA references were obtained for the
evaluation of regressors. In the case of the BMC estimation, CC and MAE were
0.754 and 1.641 (g). In the case of the estimation of change in BMC, CC and MAE
were 0.680 and 0.528 (g).

Conclusion

The modality using morphometric texture analysis
with CT HUs can indirectly help screening osteoporosis because it provides
estimates of BMC and BMC change that show moderate positive correlations with
DXA measures.
Explaining sexual self-care status and its predictor factors in women referring to healthcare centers of Sari, Iran, 2021
Authors: Yazdani Fereshteh , Simbar Masoumeh , Hamzehgardeshi Zeinab , Zare Elham , Nasiri Malihe
Published: February 2023

Introduction

With the increase in the prevalence of non-communicable diseases and chronic health problems along with population growth, one of the definitions that is expanding is the ability to adapt and self-manage against diseases and self-care. Although there are several studies to examine self-care in medical conditions, there are not enough concepts and data related to sexual self-care. Therefore, the present study was conducted with the aim of explaining the status of sexual self-care and its predictor factors in women of reproductive age referring to healthcare centers.

Material and methods

This research was a cross-sectional study that was conducted on 400 women of reproductive age that referring to healthcare centers affiliated to Mazandaran University of Medical Sciences, Sari in 2021. Data were collected using personal-obstetric characteristics and sexual self-care questionnaires in women of reproductive age. Pearson correlation coefficients, independent t-test, one-way analysis of variance and multiple linear regression model were used to analyze the data.

Results

The average total score of sexual self-care in reproductive age women participating in the research was 70.66% ± 12.52%. In addition, the prevention of women's cancers and the prevention of unintended pregnancies obtained the lowest and highest scores, respectively. Factors such as age, education, education related to medical sciences, history of HIV testing, history of HPV vaccination, source of sexual information, method of contraception and infection-related action in a person can affect the level of sexual self-care in women. Based on the final regression model, education related to medical sciences (B = 5.46, P = 0.035), family income (B = 5.58, P = 0.025), prevention method (B = 10.127, P = 0.000) and action related to infection in the person (B = 12.27, P = 0.047) were the final predictors of sexual self-care score in reproductive age women.

Conclusion

Based on the findings of the study, development of self-care promotion programs for reproductive aged women are necessary in all areas of reproductive health, with a priority for women’s cancer prevention, and focusing on promoting education and related economic assistance. The results of this study can be available to experts and policy makers to design programs to promote sexual self-care in women.
Co-design and implementation of a mHealth intervention targeting fathers and mothers to improve breastfeeding
Authors: Gebremariam Kidane Tadesse , Mulugeta Afework , Gallegos Danielle
Published: February 2023

Background

Evidence has shown that SMS text message-based health education is effective in improving exclusive breastfeeding. However, there is limited evidence on the development and design of SMS messaging intervention targeting fathers and mothers.

Method

This is the formative assessment and intervention design for a larger trial targeting both fathers and mothers for breastfeeding support in Tigray, Ethiopia. A total of 42 parents of children less than 2 years of age were involved in the design process that also included nutrition experts. We recruited 128 expectant couples to the intervention (1-month antenatally) who continued for 3 months postnatally.

Results

Sixteen messages were developed specific to feeding in the antenatal and postnatal periods. These messages were revised with parents and experts and pretested with parents. Over 4 months 87% of fathers and mothers received 3 or more SMS text messages. All fathers and 97% of mothers read the weekly SMS text messages. Almost 90% of mothers and fathers indicated their willingness to continue to receive SMS text messages related to infant feeding.

Conclusion

Development of SMS based breastfeeding interventions should involve the target population in content design. The role of experts and target population in the co-design process is also crucial.
Deep time extinction of largest insular ant predators and the first fossil Neoponera (Formicidae: Ponerinae) from Miocene age Dominican amber
Authors: Fiorentino Gianpiero , Lattke John , Troya Adrian , Sosiak Christine , Dong Minsoo , Barden Phillip
Published: February 2023

Background

Ponerine ants are almost exclusively predatory and comprise many of the largest known ant species. Within this clade, the genus Neoponera is among the most conspicuous Neotropical predators. We describe the first fossil member of this lineage: a worker preserved in Miocene-age Dominican amber from Hispaniola.

Results

Neoponera vejestoria sp. nov. demonstrates a clear case of local extinction—there are no known extant Neoponera species in the Greater Antilles. The species is attributable to an extant and well-defined species group in the genus, which suggests the group is older than previously estimated. Through CT scan reconstruction and linear morphometrics, we reconstruct the morphospace of extant and fossil ants to evaluate the history and evolution of predatory taxa in this island system.

Conclusions

The fossil attests to a shift in insular ecological community structure since the Miocene. The largest predatory taxa have undergone extinction on the island, but their extant relatives persist throughout the Neotropics. Neoponera vejestoria sp. nov. is larger than all other predatory ant workers known from Hispaniola, extant or extinct. Our results empirically demonstrate the loss of a functional niche associated with body size, which is a trait long hypothesized to be related to extinction risk.
The impact of COVID-19 on the mental health and substance use health (MHSUH) workforce in Canada: a mixed methods study
Authors: Tulk Christine , Bartram Mary , Leslie Kathleen , Atanackovic Jelena , Chamberland-Rowe Caroline , Bourgeault Ivy Lynn
Published: February 2023

Background

The increased need for mental health and substance use health (MHSUH) services during the COVID-19 pandemic underscores the need to better understand workforce capacity. This study aimed to examine the pandemic’s impact on the capacity of MHSUH service providers and to understand reasons contributing to changes in availability or ability to provide services.

Methods

We conducted a mixed method study including a pan-Canadian survey of 2177 providers of MHSUH services and semi-structured interviews with 13 key informants. Survey participants answered questions about how the pandemic had changed their capacity to provide services, reasons for changes in capacity, and how their practice had during the pandemic. Thematic analysis of key informant interviews was conducted to gain a deeper understanding of the impact of the pandemic on the MHSUH workforce.

Results

Analyses of the survey data indicated that the pandemic has had diverse effects on the capacity of MHSUH workers to provide services: 43% indicated decreased, 24% indicated no change, and 33% indicated increased capacity. Logistic regression analyses showed that privately funded participants had 3.2 times greater odds of increased capacity (B = 1.17, p < 0.001), and participants receiving funding from a mix of public and private sources had 2.4 times greater odds of increased capacity (B = 0.88, p < 0.001) compared to publicly funded participants. Top reasons for decreases included lockdown measures and clients lacking access or comfort with virtual care. Top reasons for increases included using virtual care and more people having problems relevant to the participant's skills. Three themes were constructed from thematic analysis of key informant interviews: the differential impact of public health measures, long-term effects of pandemic work conditions, and critical gaps in MHSUH workforce data.

Conclusions

The COVID-19 pandemic has had a substantial impact on the capacity of the MHSUH workforce to provide services. Findings indicate the importance of increasing and harmonizing funding for MHSUH services across the public and private sectors, developing standardized datasets describing the MHSUH workforce, and prioritizing equity across the spectrum of MHSUH services.
Alterations in the human oral microbiota in systemic lupus erythematosus
Authors: Guo Jinyan , Cui Guangying , Huang Wei , Zheng Zhaohui , Li Tianfang , Gao Guanmin , Huang Zhen , Zhan Yuwei , Ding Suying , Liu Shengyun , Yu Zujiang , Ren Zhigang
Published: February 2023

Background

Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota.

Methods

We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized.

Results

The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848–0.9483, p < 0.0001), 0.8422 (95% CI 0.7687–0.9157, p < 0.0001), and 0.8406 (95% CI 0.7677–0.9135, p < 0.0001) in the derivation, validation, and cross-regional validation groups, respectively. Moreover, as disease activity increased, Abiotrophia and Lactobacillales increased, while Phyllobacterium and unclassified Micrococcusaceae decreased. Finally, nine OTUs were selected to construct a classifier distinguishing posttreatment SLE patients from healthy controls, which achieved a diagnostic efficacy of 0.9942 (95% CI 0.9884–1, p < 0.0001).

Conclusions

Our study comprehensively characterizes the oral microbiome of SLE and shows the potential of the oral microbiota as a non-invasive diagnostic biomarker in SLE.
Women’s reflections on timing of motherhood: a meta-synthesis of qualitative evidence
Authors: Temmesen Camilla Gry , Faber Frandsen Tove , Svarre-Nielsen Henriette , Petersen Kathrine Birch , Clemensen Jane , Andersen Heidi Lene Myglegaard
Published: February 2023

Introduction

Fertility declines with increasing age, especially in women. In recent decades women’s age at the birth of their first child has risen markedly in many countries, and an increasing number of women do not establish a family until their late-twenties to mid-thirties. Although there can be various reasons that couples experience fertility problems, advanced maternal age is the most frequent cause for difficulties with achieving pregnancy.

Objective

In this meta-synthesis, we investigated reflections on timing of motherhood in women who have not yet had children.

Methods

A systematic literature search of six electronic databases and manual searches of reference lists identified eight qualitative studies published between 2011 and 2018 that focused on women’s reflections on timing of motherhood. The studies were assessed with the Critical Assessment Skills Programme (CASP) quality appraisal tool. The results were synthesized using Noblit and Hare’s meta-ethnographic approach as described by Malterud.

Findings

An overall theme of ‘Timing of motherhood’ and four overlapping subthemes were identified: Making a life-changing decision, The right time, Fear of regret, and Plan B. The dilemmas associated with timing of motherhood leave women of reproductive age balancing their priorities and values against a biological deadline for having children naturally or through assisted reproductive technology.

Conclusions

Women of reproductive age are aware that they must make a life-changing decision as to if or when to have children, but they consider having children at ‘the right time’ to be important. Simultaneously, while some women are reluctant to have children for various reasons, they express fear that waiting too long could result in their regretting not having children later in life. Although women of reproductive age express concern about their ability to achieve pregnancy, they have limited focus on the medical risks associated with postponing motherhood. There is a need to establish preventive health initiatives to support women of reproductive age in their considerations regarding timing of motherhood.

Trial registration number: PROSPERO: CRD42020175151.
Charged particle therapy for high-grade gliomas in adults: a systematic review
Authors: Wang Yuhang , Liu Ruifeng , Zhang Qiuning , Dong Meng , Wang Dandan , Chen Junru , Ou Yuhong , Luo Hongtao , Yang Kehu , Wang Xiaohu
Published: February 2023

High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1–2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity‐modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.
Dosimetric comparison of two dose expansion methods in intensity modulated radiotherapy for breast cancer
Authors: Tang Ran , Li Aimin , Li Yingjing , Deng Guanhua , Wang Yufeng , Xiao Qing , Zhang Luosheng , Luo Yue
Published: February 2023

Background

To explore the dosimetric difference between IMRT-VB plan based on the establishment of external expansion structure and virtual bolus (VB) and IMRT-SF based on the skin flash (SF) tool of the Eclipse treatment planning system in postoperative chest wall target intensity modulation radiotherapy plan of breast cancer.

Methods

Twenty patients with breast cancer were randomly selected as subjects to develop IMRT-VB plan based on virtual bolus and IMRT-SF plan based on skin flash tool of Eclipse treatment planning system. The planning target volume, monitor unit (MU) of every single treatment and the dosimetric parameters of organ at risk (OARs) were recorded. Paired t-test was used for normal distribution data while nonparametric paired Wilcoxon rank sum test was used for non-normal distribution data.

Results

Both IMRT-VB and IMRT-SF plan can expand outward to the chest wall skin and meet the dose requirements of clinical prescription. The conformal index, the homogeneity index, D2%, D98% and D50% were significantly better in IMRT-SF plan than those in IMRT-VB plan (P < 0.05). The average MU of the IMRT-SF plan was much higher than that of the IMRT-VB plan (866.0 ± 68.1 MU vs. 760.9 ± 50.4 MU, P < 0.05). In terms of organ at risk protection, IMRT-SF plan had more advantages in the protection of ipsilateral lung and spinal cord than IMRT-VB plan (P < 0.05).

Conclusion

Our study indicated that IMRT-SF plan displayed clinical application superiority compared to IMRT-VB plan, and the operation steps of which are simpler and faster. Besides, IMRT-SF plan took advantages in achieve effective external expansion of skin dose intensity and OARs protection.
Reciprocal relationships between self-esteem, coping styles and anxiety symptoms among adolescents: between-person and within-person effects
Authors: Li Wenyan , Guo Yangfeng , Lai Wenjian , Wang Wanxin , Li Xiuwen , Zhu Liwan , Shi Jingman , Guo Lan , Lu Ciyong
Published: February 2023

Background

Previous researches have not distinguished the between-person effects from the within-person effects when exploring the relationship between self-esteem, coping styles, and anxiety symptoms among adolescents. To address this gap, this study investigated reciprocal associations among self-esteem, coping styles, and anxiety symptoms in a three-wave longitudinal panel survey, using an analytical strategy that disaggregates the within-person and the between-person variance.

Methods

Data was drawn from the Longitudinal Study of Adolescents’ Mental and Behavioral Well-being Research study conducted in 10 public schools in the Guangdong province of China. All participants had a baseline visit (N = 1957, mean age 13.6, grades 7 and 10) and follow-up interviews at 1-year intervals for 3 years. A random intercept cross-lagged panel model combined with mediation analysis was performed.

Results

At the within-person level, the following results were observed. (1) Low self-esteem and anxiety symptoms bidirectionally predicted each other. (2) Low self-esteem and negative coping style bidirectionally predicted each other. (3) Anxiety symptoms predicted subsequent negative coping style but not vice versa. At the between-person level, we obtained the following main results. (1) Significant predictive effects on the random intercept were found among all three study constructs. (2) There were sex differences regarding the association between self-esteem and anxiety symptoms and the correlation of females was stronger than that of males. (3) Self-esteem mediated the reciprocal relations between coping styles and anxiety symptoms.

Conclusions

Overall, findings revealed a reciprocal relationship between low self-esteem and anxiety symptoms for both females and males. Besides, anxiety symptoms predict subsequent negative coping style but not vice versa. We also highlighted the mediating role of self-esteem in the reciprocal relations between coping styles and anxiety symptoms. Thus, interventions targeted at promoting self-esteem and cultivating positive coping style may help reduce adolescent anxiety.
Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1
Authors: Ludwig Carolin Lisa Michaela , Bohleber Simon , Lapp Rebecca , Rebl Alexander , Wirth Eva Katrin , Langhammer Martina , Schweizer Ulrich , Weitzel Joachim M. , Michaelis Marten
Published: February 2023

The development and maturation of ovarian follicles is a complex and highly regulated process, which is essential for successful ovulation. During recent decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 (FL1) is a worldwide unique selection experiment for increased female reproductive performance and extraordinary high fertility. Interactions of cycle-related alterations of parameters of the hypothalamic pituitary gonadal axis and molecular factors in the ovary lead to improved follicular development and therefore increased ovulation rates in FL1 mice. FL1 females almost doubled the number of ovulated oocytes compared to the unselected control mouse line. To gain insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing. Based on the results of the transcriptome analysis we additionally measured hormones and growth factors associated with follicular development to complement the picture of how the signaling pathways are regulated. While IGF1 levels are decreased in FL1 mice in estrus, we found no differences in insulin, prolactin and oxytocin levels in FL1 mice compared to the control line. The results of the mRNA sequencing approach revealed that the actions of insulin, prolactin and oxytocin are restricted local to the granulosa cells, since hormonal receptor expression is differentially regulated in FL1 mice. Additionally, numerous genes, which are involved in important gonadotropin, apoptotic and metabolic signaling pathways in granulosa cells, are differentially regulated in granulosa cells of FL1 mice.

We showed that an overlap of different signaling pathways reflects the crosstalk between gonadotropin and growth factor signaling pathways, follicular atresia in FL1 mice is decreased due to improved granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate. Therefore, this worldwide unique high fertility model can provide new insights into different factors leading to improved follicular development and has the potential to improve our understanding of high fertility.
The dynamics of plasma biomarkers across the Alzheimer’s continuum
Authors: Guo Yu , Shen Xue-Ning , Wang Hui-Fu , Chen Shi-Dong , Zhang Ya-Ru , Chen Shu-Fen , Cui Mei , Cheng Wei , Dong Qiang , Ma Tao , Yu Jin-Tai
Published: February 2023

Background

Failures in drug trials strengthen the necessity to further determine the neuropathological events during the development of Alzheimer’s disease (AD). We sought to investigate the dynamic changes and performance of plasma biomarkers across the entire Alzheimer’s continuum in the Chinese population.

Methods

Plasma amyloid-β (Αβ)42, Aβ40, Aβ42/Aβ40, phosphorylated tau (p-tau)181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured utilizing the ultrasensitive single-molecule array technology across the AD continuum (n=206), wherein Aβ status was defined by the values of cerebrospinal fluid (CSF) Aβ42 or Aβ positron emission tomography (PET). Their trajectories were compared with those of putative CSF biomarkers.

Results

Plasma GFAP and p-tau181 increased only in Aβ-positive individuals throughout aging, whereas NfL increased with aging regardless of Aβ status. Among the plasma biomarkers studied, GFAP was the one that changed first. It had a prominent elevation early in the cognitively unimpaired (CU) A+T− phase (CU A+T− phase: 97.10±41.29 pg/ml; CU A−T− phase: 49.18±14.39 pg/ml; p<0.001). From preclinical to symptomatic stages of AD, plasma GFAP started to rise sharply as soon as CSF Aβ became abnormal and continued to increase until reaching its highest level during the AD dementia phase. The greatest slope of change was seen in plasma GFAP. This is followed by CSF p-tau181 and total-tau, and, to a lesser extent, then plasma p-tau181. In contrast, the changes in plasma NfL, Aβ42/Aβ40, Aβ42, and Aβ40 were less pronounced. Of note, these plasma biomarkers exhibited smaller dynamic ranges than their CSF counterparts, except for GFAP which was the opposite. Plasma GFAP and p-tau181 were tightly associated with AD pathologies and amyloid tracer uptake in widespread brain areas. Plasma GFAP could accurately identify CSF Aβ42 (area under the curve (AUC)=0.911) and Aβ PET (AUC=0.971) positivity. Plasma p-tau181 also performed well in discriminating Aβ PET status (AUC=0.916), whereas the discriminative accuracy was relatively low for other plasma biomarkers.

Conclusions

This study is the first to delineate the trajectories of plasma biomarkers throughout the Alzheimer’s continuum in the Chinese population, providing important implications for future trials targeting plasma GFAP to facilitate AD prevention and treatment.
Anatomical variation of the sacroiliac joints: an MRI study with synthetic CT images
Authors: Vereecke Elke , Morbée Lieve , Laloo Frederiek , Chen Min , Jaremko Jacob L. , Herregods Nele , Jans Lennart
Published: February 2023

Background

Synthetic computed tomography (sCT) images are magnetic resonance imaging (MRI)-based images, generated using artificial intelligence. This study aimed to determine the prevalence of anatomical variants of sacroiliac joints (SIJ) on sCT images and the correlation with age, sex and body weight.

Methods

MRI of the SIJ including sCT images of 215 patients clinically suspected for sacroiliitis were retrospectively analyzed. The presence of anatomical variants of the SIJ was assessed. Age, sex and body mass index at the time of the MRI were recorded.

Results

SIJ variants were found in 82.8% (356/430) of the evaluated joints. The most frequent variants were iliosacral complex (27.7%), bipartite iliac bony plate (27.2%) and crescent iliac bony plate (27%). One new variant was identified, consisting of an accessory facet of the SIJ on the superior side. Overall, SIJ variants were slightly more frequent in women (85.8% vs. 77.8%), but iliosacral complex was significantly more frequent in men. Isolated synostosis was more prevalent with advancing age, in contrast to semicircular defect and unfused ossification center. The occurrence of iliosacral complex was associated with higher BMI, while crescent iliac bony plate occurred more in patients with lower BMI.

Conclusion

Over 80% of patients in this study, who were all suspected of sacroiliitis, had at least one SIJ variant. These variants may actually represent subtypes of the normal SIJ. sCT enables detection of very small or subtle findings including SIJ variants.
Reproducibility of 2D versus 3D radiomics for quantitative assessment of fetal lung development: a retrospective fetal MRI study
Authors: Watzenboeck Martin L. , Heidinger Benedikt H. , Rainer Julian , Schmidbauer Victor , Ulm Barbara , Rubesova Erika , Prayer Daniela , Kasprian Gregor , Prayer Florian
Published: February 2023

Purpose

To investigate the reproducibility of radiomics features extracted from two-dimensional regions of interest (2D ROIs) versus whole lung (3D) ROIs in repeated in-vivo fetal magnetic resonance imaging (MRI) acquisitions.

Methods

Thirty fetal MRI scans including two axial T2-weighted acquisitions of the lungs were analysed. 2D (lung at the level of the carina) and 3D (whole lung) ROIs were manually segmented using ITK-Snap. Ninety-five radiomics features were extracted from 2 and 3D ROIs in initial and repeat acquisitions using Pyradiomics. Radiomics feature intra-class correlation coefficients (ICC) were calculated between 2 and 3D ROIs in the initial acquisition, and between 2 and 3D ROIs in repeated acquisitions, respectively.

Results

MRI data of 11 (36.7%) female and 19 (63.3%) male fetuses acquired at a median 25 + 0 gestational weeks plus days (GW) (interquartile range [IQR] 23 + 4 − 27 + 0 GW) were assessed. Median radiomics feature ICC between 2 and 3D ROIs in the initial MRI acquisition was 0.733 (IQR 0.313–0.814, range 0.018–0.970). ICCs between radiomics features extracted using 3D ROIs in initial and repeat acquisitions (median 0.908 [IQR 0.824–0.929, range 0.335–0.996]) were significantly higher compared to 2D ROIs (0.771 [0.699–0.835, 0.048–0.965]) (p < 0.001).

Conclusion

Fetal MRI radiomics features extracted from 3D whole lung segmentation masks showed significantly higher reproducibility across repeat acquisitions compared to 2D ROIs. Therefore, fetal MRI whole lung radiomics features are robust diagnostic and potentially prognostic tools in the image-based in-vivo quantitative assessment of lung development.
Shining the light on mesenchymal stem cell-derived exosomes in breast cancer
Authors: Al-Awsi Ghaidaa Raheem Lateef , Alsaikhan Fahad , Margiana Ria , Ahmad Irfan , Patra Indrajit , Najm Mazin A. A. , Yasin Ghulam , Rasulova Iroda , Hammid Ali Thaeer , Kzar Hamzah H. , Al-Gazally Moaed E. , Siahmansouri Homayoon
Published: February 2023

In women, breast cancer (BC) is the second most frequently diagnosed cancer and the leading cause of cancer death. Mesenchymal stem cells (MSCs) are a subgroup of heterogeneous non-hematopoietic fibroblast-like cells that have the ability to differentiate into multiple cell types. Recent studies stated that MSCs can migrate into the tumor sites and exert various effect on tumor growth and development. Multiple researches have demonstrated that MSCs can favor tumor growth, while other groups have indicated that MSCs inhibit tumor development. Emerging evidences showed exosomes (Exo) as a new mechanism of cell communication which are essential for the crosstalk between MSCs and BC cells. MSC-derived Exo (MSCs-Exo) could mimic the numerous effects on the proliferation, metastasis, and drug response through carrying a wide scale of molecules, such as proteins, lipids, messenger RNAs, and microRNAs to BC cells. Consequently, in the present literature, we summarized the biogenesis and cargo of Exo and reviewed the role of MSCs-Exo in development of BC.
The potential application of MR-derived ADCmin values from 68Ga-DOTATATE and 18F-FDG dual tracer PET/MR as replacements for FDG PET in assessment of grade and stage of pancreatic neuroendocrine tumors
Authors: Gao Jing , Xu Si , Ju Huijun , Pan Yu , Zhang Yifan
Published: February 2023

Background

To evaluate the utility of 68Ga-DOTATATE and 18F-FDG PET/MR for prediction of grade and stage of pancreatic neuroendocrine tumors (PNETs), and to examine the correlation between parameters obtained from FDG PET and diffusion-weighted imaging (DWI) MR parameters.

Methods

A retrospective study using 68Ga-DOTATATE and 18F-FDG PET/MR imaging was performed between April 2020 and May 2022 on 46 individuals with histologically confirmed PNETs. Metabolic tumor volume (MTV), maximum standardized uptake value (FSUVmax), and tumor lesion glycolysis (TLG) for FDG; somatostatin receptor density (SRD), maximum standardized uptake value (GSUVmax), and total lesion somatostatin receptor density (TLSRD) for DOTATATE; and minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) values for MRI, respectively. We performed Spearman’s correlation analysis to examine the links between these variables and primary tumor stage and grading.

Results

Higher PNET grading was associated with higher FSUVmax, MTV, and TLG values (P < 0.05). TLG, SRD, ADCmin, and ADCmean values were correlated with N staging, while SRD, MTV, ADCmin, TLG, and ADCmean were associated with M staging. Notably, ADCmin was a negative correlation between FSUVmax (r =  − 0.52; P < 0.001), MTV (r =  − 0.50; P < 0.001), and TLG (r =  − 0.56; P < 0.001).

Conclusions

This study highlights significant correlative relationships between FDG PET-derived parameters and ADCmin. ADCmin may offer utility as a tool for PNET staging and grading in lieu of FDG PET. 68Ga-DOTATATE PET/MR alone may be a sufficient alternative to dual tracer PET/MR when conducting grading and staging of primary PNETs.