bluuebunny/crossref_metadata_2025 huggingface dataset:
Deconvolution at the single-cell level reveals ovarian cell-type-specific transcriptomic changes in PCOS
Authors: Li Shumin , Li Yimeng , Sun Yu , Feng Gengchen , Yang Ziyi , Yan Xueqi , Gao Xueying , Jiang Yonghui , Du Yanzhi , Zhao Shigang , Zhao Han , Chen Zi-Jiang
Published: February 2024

Background

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood. Transcriptomic characterization of cells isolated from PCOS cases have been assessed using bulk RNA-seq but cells isolated contain a mixture of many ovarian cell types.

Methods

Here we utilized the reference scRNA-seq data from human adult ovaries to deconvolute and estimate cell proportions and dysfunction of ovarian cells in PCOS, by integrating various granulosa cells(GCs) transcriptomic data.

Results

We successfully defined 22 distinct cell clusters of human ovarian cells. Then after transcriptome integration, we obtained a gene expression matrix with 13,904 genes within 30 samples (15 control vs. 15 PCOS). Subsequent deconvolution analysis revealed decreased proportion of small antral GCs and increased proportion of KRT8high mural GCs, HTRA1high cumulus cells in PCOS, especially increased differentiation from small antral GCs to KRT8high mural GCs. For theca cells, the abundance of internal theca cells (TCs) and external TCs was both increased. Less TCF21high stroma cells (SCs) and more STARhigh SCs were observed. The proportions of NK cells and monocytes were decreased, and T cells occupied more in PCOS and communicated stronger with inTCs and exTCs. In the end, we predicted the candidate drugs which could be used to correct the proportion of ovarian cells in patients with PCOS.

Conclusions

Taken together, this study provides insights into the molecular alterations and cellular compositions in PCOS ovarian tissue. The findings might contribute to our understanding of PCOS pathophysiology and offer resource for PCOS basic research.
Out-of-pocket pharmaceutical expenditure and its determinants among Iranian households with elderly members: a double-hurdle model
Authors: Faraji Mehran , Sharifi Tahereh , Mohammad-pour Saeed , Javan-Noughabi Javad , Aboutorabi Ali , yousefi Shaghayegh , Jakovljevic Mihajlo
Published: February 2024

Objectives

The population of older adults continues to grow in Iran, with pharmaceutical costs as a leading driver of household health-related costs. The present study was conducted to estimate the out-of-pocket pharmaceutical expenditure and its socioeconomic predictors among households with the elderly in Iran.

Method

This study is a secondary analysis using 2019 national household expenditure and income survey data in Iran. The sample size was 9381 households with at least one member older than 65. The double-hurdle model in STATA 16 was used to examine the association between independent variables and households’ out-of-pocket pharmaceutical expenditures.

Results

The mean out-of-pocket pharmaceutical expenditures for each household with elderly member was $8065 per year. There was a positive association between the (female) gender of the household head, urban residence, employment status, insurance expenditure and a higher level of education of the head of the household with the out-of-pocket pharmaceutical expenditures (P < 0.05). The income of elderly households did not affect these expenditures (P > 0.05).

Conclusions

This study showed that the socioeconomic characteristics of elderly families not only influenced their decision to enter the medicine market, but also the rate of medicine purchase. It is helpful to manage and control the pharmaceutical costs among the elderly.
Dopamine enhances recovery after traumatic brain injury through ubiquitylation and autophagic degradation of RIPK1
Authors: Luo Hui , Liu Ning , Lin Chao
Published: February 2024

Background

Although the neurotransmitter dopamine (DA) plays a crucial pathophysiologic role after traumatic brain injury (TBI), its function and specific underlying mechanisms of action remain unclear.

Methods

Adult male mice underwent controlled cortical impact (CCI). We administered DA intraperitoneally to mice for 14 consecutive days, starting 8 h before CCI. On day 3 after brain injury, cortical lesion volume and brain water content were measured. On days 7–13, behavioral tests were performed.

Results

Herein we report that DA inhibits neural death after injury, which is mediated via the dopamine D1 receptor (DRD1). Our results also showed that DRD1 signaling promotes RIPK1 ubiquitination via the E3 ubiquitin ligase Chip and then degradation through autophagy. Importantly, in vivo data revealed that DRD1 signaling prevented neural death, suppressed neuroinflammation, and restored many TBI-related functional sequelae.

Conclusions

These data reveal a novel mechanism involving dopamine, and suggest that DRD1 activation positively regulates Chip-mediated ubiquitylation of RIPK1—leading to its autophagic degradation.
High estrogen during ovarian stimulation induced loss of maternal imprinted methylation that is essential for placental development via overexpression of TET2 in mouse oocytes
Authors: Lu Xueyan , Mao Jiaqin , Qian Chenxi , Lei Hui , Mu Fei , Sun Huijun , Yan Song , Fang Zheng , Lu Jie , Xu Qian , Dong Jie , Su Danjie , Wang Jingjing , Jin Ni , Chen Shuqiang , Wang Xiaohong
Published: February 2024

Background

Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear.

Methods

Mouse oocytes and mouse parthenogenetic embryonic stem cells (pESCs) were used to investigate the roles of OS in oocyte DNA methylation. Global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels were evaluated using immunofluorescence or colorimetry. Genome-wide DNA methylation was quantified using an Agilent SureSelectXT mouse Methyl-Seq. The DNA methylation status of mesoderm-specific transcript homologue (Mest) promoter region was analyzed using bisulfite sequencing polymerase chain reaction (BSP). The regulatory network between estrogen receptor alpha (ERα, ESR1) and DNA methylation status of Mest promoter region was further detected following the knockdown of ERα or ten-eleven translocation 2 (Tet2).

Results

OS resulted in a significant decrease in global 5mC levels and an increase in global 5hmC levels in oocytes. Further investigation revealed that supraphysiological β-estradiol (E2) during OS induced a notable decrease in DNA 5mC and an increase in 5hmC in both oocytes and pESCs of mice, whereas inhibition of estrogen signaling abolished such induction. Moreover, Tet2 may be a direct transcriptional target gene of ERα, and through the ERα-TET2 axis, supraphysiological E2 resulted in the reduced global levels of DNA 5mC. Furthermore, we identified that MEST, a maternal imprinted gene essential for placental development, lost its imprinted methylation in parthenogenetic placentas originating from OS, and ERα and TET2 combined together to form a protein complex that may promote Mest demethylation.

Conclusions

In this study, a possible mechanism of loss of DNA methylation in oocyte caused by OS was revealed, which may help increase safety and reduce epigenetic abnormalities in ART procedures.
Food environment research in Canada: a rapid review of methodologies and measures deployed between 2010 and 2021
Authors: Vaillancourt Caroline , Ahmed Mavra , Kirk Sara , Labonté Marie-Ève , Laar Amos , Mah Catherine L. , Minaker Leia , Olstad Dana Lee , Potvin Kent Monique , Provencher Véronique , Prowse Rachel , Raine Kim D. , Schram Ashley , Zavala-Mora Daniela , Rancourt-Bouchard Maryka , Vanderlee Lana
Published: February 2024

Numerous research methodologies have been used to examine food environments. Existing reviews synthesizing food environment measures have examined a limited number of domains or settings and none have specifically targeted Canada. This rapid review aimed to 1) map research methodologies and measures that have been used to assess food environments; 2) examine what food environment dimensions and equity related-factors have been assessed; and 3) identify research gaps and priorities to guide future research. A systematic search of primary articles evaluating the Canadian food environment in a real-world setting was conducted. Publications in English or French published in peer-reviewed journals between January 1 2010 and June 17 2021 and indexed in Web of Science, CAB Abstracts and Ovid MEDLINE were considered. The search strategy adapted an internationally-adopted food environment monitoring framework covering 7 domains (Food Marketing; Labelling; Prices; Provision; Composition; Retail; and Trade and Investment). The final sample included 220 articles. Overall, Trade and Investment (1%, n = 2), Labelling (7%, n = 15) and, to a lesser extent, Prices (14%, n = 30) were the least studied domains in Canada. Among Provision articles, healthcare (2%, n = 1) settings were underrepresented compared to school (67%, n = 28) and recreation and sport (24%, n = 10) settings, as was the food service industry (14%, n = 6) compared to grocery stores (86%, n = 36) in the Composition domain. The study identified a vast selection of measures employed in Canada overall and within single domains. Equity-related factors were only examined in half of articles (n = 108), mostly related to Retail (n = 81). A number of gaps remain that prevent a holistic and systems-level analysis of food environments in Canada. As Canada continues to implement policies to improve the quality of food environments in order to improve dietary patterns, targeted research to address identified gaps and harmonize methods across studies will help evaluate policy impact over time.
The psychosocial impact of male infertility on men undergoing ICSI treatment: a qualitative study
Authors: de Vries Carmen E. J. , Veerman-Verweij Esther M. , van den Hoogen Agnes , de Man-van Ginkel Janneke M. , Ockhuijsen Henriëtta D. L.
Published: February 2024

Background

Male infertility is in 20–70% of cases the cause of a couple’s infertility. Severe forms of male infertility are best treated with Intracytoplasmic Sperm Injection (ICSI). The psychosocial impact of infertility and ICSI on men is unclear because the focus is socially, clinically, and scientifically on women. However, there is evidence that it can affect the psychological well-being of men, but these studies are mainly quantitative. Qualitative research needed to explore the experiences of infertile men in-depth is limited. Therefore, the objective of this study was to clarify the psychosocial consequences of male infertility on men undergoing ICSI to understand their experiences with reproduction problems more comprehensively.

Methods

In this generic qualitative study, men who were undergoing or had undergone ICSI after a male factor infertility diagnosis were included. A purposive sample with maximum variation was sought in a fertility clinic of one university medical centre in the Netherlands. Data were collected through individual face-to-face semi-structured interviews. Thematic analysis was used to identify themes from the data.

Results

Nineteen Dutch men were interviewed. The mean duration of the interviews was 90 min. An everyday contributing backpack was identified as the main theme, as men indicated that they always carried the psychosocial consequences of infertility and ICSI with them. Different world perspective, Turbulence of emotions, Changing relation, and Selective sharing were the psychosocial consequences that men were most affected by. Moreover, men indicated that they were Searching for contribution during ICSI because the focus was entirely on the woman.

Conclusion

Men with male infertility experience psychosocial problems due to infertility and ICSI treatment. Healthcare professionals need to recognize the impact of infertility on men and create room for a role for them during ICSI.
To what extent did implementing a community-embedded intervention align with the goals and roles of stakeholders in adolescent sexual and reproductive health?
Authors: Ekwueme Chinazom N. , Okeke Chinyere , Eze Irene Ifeyinwa , Mbachu Chinyere Ojiugo , Onwujekwe Obinna
Published: February 2024

Background

Adolescents’ sexual and reproductive health (SRH) needs are largely unmet due to poor access to SRH information and services. A multicomponent community-embedded intervention, comprising advocacy to policymakers and community leaders, training of health workers on the provision of youth-friendly SRH services, and establishment of school health clubs, was implemented in Ebonyi State, Nigeria, to improve access to SRH information and services for adolescents aged 13–18 years in selected communities and secondary schools. This study explored the extent to which the intervention aligned with goals and roles of stakeholders in the State.

Methods

Qualitative in-depth interviews (30) were conducted with key stakeholders in adolescent health programming in the State, and community gatekeepers (traditional and religious leaders) in the intervention communities. Sex-disaggregated focus group discussions (10) were conducted with health service providers, parents/guardians of adolescents. Data was analyzed deductively based on fit of strategy and two constructs of the Theoretical Framework for Acceptability – burden, and opportunity cost. The transcripts were coded in NVivo 12, and the subthemes that emerged from each construct were identified.

Results

Stakeholders perceived the ASRH intervention activities to align with their individual goals of sense of purpose from serving the community and organizational goals of improving the visibility of adolescent reproductive health programs and aligned with their routine work. Hence, implementing or participating in the interventions was not considered a burden by many. Although the delivery of the interventions constituted additional workload and time commitment for the implementers, the benefits of partaking in the intervention were perceived to outweigh the inputs that they were required to make. Some of the community health workers in the intervention felt that provision of financial incentive will help with making the intervention less burdensome. To participate in the intervention, opportunity cost included forgoing work and business activities as well as family commitments.

Conclusion

Findings from the study show that the intervention aligned with individual/organizational goals of stakeholders. To improve acceptability of the ASRH interventions, interventions should leverage on existing programs and routine work of people who will deliver the interventions.
‘It depends’: what 86 systematic reviews tell us about what strategies to use to support the use of research in clinical practice
Authors: Boaz Annette , Baeza Juan , Fraser Alec , Persson Erik
Published: February 2024

Background

The gap between research findings and clinical practice is well documented and a range of strategies have been developed to support the implementation of research into clinical practice. The objective of this study was to update and extend two previous reviews of systematic reviews of strategies designed to implement research evidence into clinical practice.

Methods

We developed a comprehensive systematic literature search strategy based on the terms used in the previous reviews to identify studies that looked explicitly at interventions designed to turn research evidence into practice. The search was performed in June 2022 in four electronic databases: Medline, Embase, Cochrane and Epistemonikos. We searched from January 2010 up to June 2022 and applied no language restrictions. Two independent reviewers appraised the quality of included studies using a quality assessment checklist. To reduce the risk of bias, papers were excluded following discussion between all members of the team. Data were synthesised using descriptive and narrative techniques to identify themes and patterns linked to intervention strategies, targeted behaviours, study settings and study outcomes.

Results

We identified 32 reviews conducted between 2010 and 2022. The reviews are mainly of multi-faceted interventions (n = 20) although there are reviews focusing on single strategies (ICT, educational, reminders, local opinion leaders, audit and feedback, social media and toolkits). The majority of reviews report strategies achieving small impacts (normally on processes of care). There is much less evidence that these strategies have shifted patient outcomes. Furthermore, a lot of nuance lies behind these headline findings, and this is increasingly commented upon in the reviews themselves.

Discussion

Combined with the two previous reviews, 86 systematic reviews of strategies to increase the implementation of research into clinical practice have been identified. We need to shift the emphasis away from isolating individual and multi-faceted interventions to better understanding and building more situated, relational and organisational capability to support the use of research in clinical practice. This will involve drawing on a wider range of research perspectives (including social science) in primary studies and diversifying the types of synthesis undertaken to include approaches such as realist synthesis which facilitate exploration of the context in which strategies are employed.
Successful tricuspid valve repair and right atrial mass excision for calcified thrombus causing severe tricuspid regurgitation and near-occlusion of inferior vena cava
Authors: Pennacchio Caroline , Rosinski Brad , Grimm Richard , Unai Shinya
Published: February 2024

Background

Calcified right atrial thrombus is rare and commonly occurs secondary to atrial fibrillation and long-term central venous catheterization which present risk for embolization. Treatment typically involves anticoagulation and antiplatelet therapy but rarely surgical excision can be performed, especially in patients with venous obstruction or concomitant valvular dysfunction.

Case presentation

We present the case of a 69 year old symptomatic female with a history of atrial fibrillation and long-term venous catheterization found to have a large calcified right atrial thrombus causing inferior vena cava obstruction and severe tricuspid regurgitation. Patient underwent full median sternotomy with ascending arterial cannulation with superior vena cava and femoral venous cannulation. Intraoperatively, extensive right atrial calcified thrombus was found extending into the inferior vena cava and involving the septal portion of the tricuspid valve annulus causing regurgitation. The calcified thrombus was removed which resolved the inferior vena cava obstruction and the tricuspid valve was repaired by transecting septal leaflet chordae, commissuroplasty, and ring annuloplasty. Postoperative course was uncomplicated and pathology confirmed a calcified right atrial thrombus. At 6 month follow up, the patient was asymptomatic with echocardiogram showing no inferior vena cava stenosis and trivial tricuspid regurgitation.

Conclusions

Surgical excision of calcified right atrial thrombus is rare and is often indicated for symptomatic patients with extensive involvement causing venous inflow obstruction or valvular dysfunction. Sufficient preoperative imaging and a multi-disciplinary approach are essential for accurate diagnosis to guide targeted treatment. When the tricuspid valve is involved, repair is preferred over replacement in this patient population given their propensity for calcification and thrombus formation which may result in an increased risk of early bioprosthetic valve degeneration or mechanical valve thrombosis.
The anatomy of safe surgical teams: an interview-based qualitative study among members of surgical teams at tertiary referral hospitals in Norway
Authors: Vikan Magnhild , Deilkås Ellen CT. , Valeberg Berit T. , Bjørnnes Ann K. , Husby Vigdis S. , Haugen Arvid S. , Danielsen Stein O.
Published: February 2024

Background

In spite of the global implementation of surgical safety checklists to improve patient safety, patients undergoing surgical procedures remain vulnerable to a high risk of potentially preventable complications and adverse outcomes. The present study was designed to explore the surgical teams’ perceptions of patient safety culture, capture their perceptions of the risk for adverse events, and identify themes of interest for quality improvement within the surgical department.

Methods

This qualitative study had an explorative design with an abductive approach. Individual semi-structured in-depth interviews were conducted between 10/01/23 and 11/05/23. The participants were members of surgical teams (n = 17), general and orthopedic surgeons (n = 5), anesthesiologists (n = 4), nurse anesthetists (n = 4) and operating room nurses (n = 4). Middle managers recruited purposively from general and orthopedic surgical teams in two tertiary hospitals in Norway, aiming for a maximum variation due to gender, age, and years within the specialty. The data material was analyzed following Braun and Clarke’s method for reflexive thematic analysis to generate patterns of meaning and develop themes and subthemes.

Results

The analysis process resulted in three themes describing the participants’ perceptions of patient safety culture in the surgical context: (1) individual accountability as a safety net, (2) psychological safety as a catalyst for well-being and safe performance in the operating room, and (3) the importance of proactive structures and participation in organizational learning.

Conclusions

This study provided an empirical insight into the culture of patient safety in the surgical context. The study highlighted the importance of supporting the individuals’ competence, building psychological safety in the surgical team, and creating structures and culture promoting a learning organization. Quality improvement projects, including interventions based on these results, may increase patient safety culture and reduce the frequency of adverse events in the surgical context.
Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade
Authors: Zhang Baoyuan , Li Ning , Gao Jiaming , Zhao Yuxi , Jiang Jun , Xie Shuang , Zhang Cuiping , Zhang Qingyu , Liu Leo , Wang Zaiqi , Ji Dongmei , Wu Lingying , Ren Ruibao
Published: February 2024

Backgrounds

Immune checkpoint blockade (ICB) is widely considered to exert long-term treatment benefits by activating antitumor immunity. However, many cancer patients show poor clinical responses to ICB due in part to the lack of an immunogenic niche. Focal adhesion kinase (FAK) is frequently amplified and acts as an immune modulator across cancer types. However, evidence illustrates that targeting FAK is most effective in combination therapy rather than in monotherapy.

Methods

Here, we used drug screening, in vitro and in vivo assays to filter out that doxorubicin and its liposomal form pegylated liposome doxorubicin (PLD) showed synergistic anti-tumor effects in combination with FAK inhibitor IN10018. We hypothesized that anti-tumor immunity and immunogenic cell death (ICD) may be involved in the treatment outcomes through the data analysis of our clinical trial testing the combination of IN10018 and PLD. We then performed cell-based assays and animal studies to detect whether FAK inhibition by IN10018 can boost the ICD of PLD/doxorubicin and further established syngeneic models to test the antitumor effect of triplet combination of PLD, IN10018, and ICB.

Results

We demonstrated that the combination of FAK inhibitor IN10018, and PLD/doxorubicin exerted effective antitumor activity. Notably, the doublet combination regimen exhibited response latency and long-lasting treatment effects clinically, outcomes frequently observed in immunotherapy. Our preclinical study confirmed that the 2-drug combination can maximize the ICD of cancer cells. This approach primed the tumor microenvironment, supplementing it with sufficient tumor-infiltrating lymphocytes (TILs) to activate antitumor immunity. Finally, different animal studies confirmed that the antitumor effects of ICB can be significantly enhanced by this doublet regimen.

Conclusions

We confirmed that targeting FAK by IN10018 can enhance the ICD of PLD/doxorubicin, further benefiting the anti-tumor effect of ICB. The animal tests of the triplet regimen warrant further discovery in the real world.
High levels of fatty acid-binding protein 5 excessively enhances fatty acid synthesis and proliferation of granulosa cells in polycystic ovary syndrome
Authors: Liu Jingyu , Li Jie , Wu Xin , Zhang Mei , Yan Guijun , Sun Haixiang , Li Dong
Published: February 2024

Background

Polycystic ovary syndrome (PCOS) is one of the most complex endocrine disorders in women of reproductive age. Abnormal proliferation of granulosa cells (GCs) is an important cause of PCOS. This study aimed to explore the role of fatty acid-binding protein 5 (FABP5) in granulosa cell (GC) proliferation in polycystic ovary syndrome (PCOS) patients.

Methods

The FABP5 gene, which is related to lipid metabolism, was identified through data analysis of the gene expression profiles of GSE138518 from the Gene Expression Omnibus (GEO) database. The expression levels of FABP5 were measured by quantitative real-time PCR (qRT‒PCR) and western blotting. Cell proliferation was evaluated with a cell counting kit-8 (CCK-8) assay. Western blotting was used to assess the expression of the proliferation marker PCNA, and immunofluorescence microscopy was used to detect Ki67 expression. Moreover, lipid droplet formation was detected with Nile red staining, and qRT‒PCR was used to analyze fatty acid storage-related gene expression.

Results

We found that FABP5 was upregulated in ovarian GCs obtained from PCOS patients and PCOS mice. FABP5 knockdown suppressed lipid droplet formation and proliferation in a human granulosa-like tumor cell line (KGN), whereas FABP5 overexpression significantly enhanced lipid droplet formation and KGN cell proliferation. Moreover, we determined that FABP5 knockdown inhibited PI3K-AKT signaling by suppressing AKT phosphorylation and that FABP5 overexpression activated PI3K-AKT signaling by facilitating AKT phosphorylation. Finally, we used the PI3K-AKT signaling pathway inhibitor LY294002 and found that the facilitation of KGN cell proliferation and lipid droplet formation induced by FABP5 overexpression was inhibited. In contrast, the PI3K-AKT signaling pathway agonist SC79 significantly rescued the suppression of KGN cell proliferation and lipid droplet formation caused by FABP5 knockdown.

Conclusions

FABP5 promotes active fatty acid synthesis and excessive proliferation of GCs by activating PI3K-AKT signaling, suggesting that abnormally high expression of FABP5 in GCs may be a novel biomarker or a research target for PCOS treatment.
Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer’s disease
Authors: Qiu Che , Zhou Wei , Shen Hui , Wang Jintao , Tang Ran , Wang Tao , Xie Xinyi , Hong Bo , Ren Rujing , Wang Gang , Song Zhongchen
Published: February 2024

Background

The relationship between periodontitis and Alzheimer’s disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time.

Methods

This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) analysis, respectively.

Results

Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC–MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression.

Conclusions

This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.
Polyhydramnios associated with rare genetic syndromes: two case reports
Authors: Lim C. W. C. , Lustestica I. E. , Poon W. B. , Tan W. C.
Published: February 2024

Background

We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester.

Case presentation

Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks’ gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith–Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks’ gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami–Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks’ gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome.

Conclusion

These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.
Willingness to pay for an mRNA-based anti-cancer treatment: results from a contingent valuation study in Israel
Authors: Ben-Aharon Omer , Sergienko Ruslan , Iskrov Georgi , Greenberg Dan
Published: February 2024

Background

mRNA technology is currently being investigated for a range of oncology indications. We assessed the willingness to pay (WTP) of the general population in Israel for a hypothetical novel mRNA-based treatment for oncology indications.

Methods

We used a contingent valuation methodology to elicit WTP using a web-based questionnaire. A sample of adult participants were presented with a hypothetical scenario in which an mRNA-based intervention increased the likelihood of a cure for various cancer types from 20% to 40% (half of the sample), or 60% (the other half of the sample).

Results

531 respondents completed the questionnaire. The mean, median and mode WTP for the proposed hypothetical treatment in both scenarios were ILS65,000 (± ILS114,000), ILS20,000 and ILS50,000, respectively (1USD = 3.4ILS). The WTP was skewed towards zero, and 9.6% of the respondents were not willing to pay any amount. WTP higher amounts was significantly associated with higher income (p < 0.01), self-reported good health (p < 0.05), supplementary health insurance (p < 0.05), Jews compared to other populations (p < 0.01), interest in technology (p < 0.001) and a tendency to adopt medical innovations (p < 0.001). No statistical difference between the 40% vs. the 60% potential cure scenarios was found. Logistic and OLS regressions indicated that age, religion, income, and interest in adopting medical innovations were the best predictors of respondents' WTP.

Conclusion

Despite the scientific breakthroughs in oncology treatment over the last few decades, many types of cancer are still incurable. Given the expected development of innovative mRNA-based treatments for cancer, these results should inform policymakers, the pharmaceutical industry and other stakeholders on the future coverage and reimbursement of these technologies incorporating patients’ and societal views. To date, WTP considerations have not been given much weight in prioritization of drug reimbursement processes, neither in Israel nor in other countries. As a pioneer in adoption of the mRNA technology, Israel can also lead the incorporation of WTP considerations in this field.
Sustainability reporting in focus: analysing Spanish transposition of the Non-Financial Reporting European Directive in the agri-food sector
Authors: Anguiano-Santos Carlos , Rodríguez-Entrena Macario
Published: February 2024

In recent decades, the business world has undergone a paradigm shift, prioritizing social and environmental considerations over the exclusive pursuit of economic profits. Corporate social responsibility has become an essential practice, and Sustainability reports (SRs) play a crucial role in facilitating the disclosure of these practices. In the European Union (EU), Directive 2014/95/EU (Non-Financial Reporting Directive—NFRD) was enacted to compel companies to disclose information on matters addressing social, environmental, ethical, and corporate governance aspects. Spain transposed this directive through Law 11/2018, considered one of the strictest in the EU. This study aims to explore and analyse its impact on the agri-food sector. For this purpose, the SRs of 16 agri-food companies that used the Global reporting initiative standard before and after the enforcement of Law 11/2018 were evaluated applying content analysis along with repeated measures ANOVA. The results show a low level of disclosure for both periods and that Law 11/2018 does not succeed in improving the level of disclosure. This suggests that legislators should develop regulations that ensure the usefulness of the disclosed information and that companies should be more involved in the preparation of SRs.
Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins
Authors: Chen Tian-Qi , Huang Heng-Jing , Zhu Shun-Xin , Chen Xiao-Tong , Pu Ke-Jia , Wang Dan , An Yan , Lian Jun-Yi , Sun Yu-Meng , Chen Yue-Qin , Wang Wen-Tao
Published: February 2024

Background

Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements.

Methods

qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux.

Results

The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation.

Conclusions

The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.
Association between body composition standards and eating disorder medical claims among active-duty service women
Authors: Korona-Bailey Jessica , Banaag Amanda , Walker Jasmine , Fortin Stephanie , Eyeler Megan , Koehlmoos Tracey Pérez
Published: February 2024

Introduction

Eating disorders are a worldwide public health concern with the United States having a particularly high prevalence. Eating disorders are of particular concern to the Department of Defense and Military Health System (MHS) because body composition standards are in place for active-duty service members.

Methods

We conducted a cross-sectional study of active-duty service women (ADSW) ages 18 and older in the U.S. Army, Air Force, Navy, and Marine Corps during fiscal years (FY) 2018–2019. Utilizing claims data from the MHS Data Repository (MDR), we identified ADSW with a Body Mass Index (BMI) measure during the study period and compared their BMI to Service-specific requirements and diagnosis of an eating disorder.

Results

We identified a total of 161,209 ADSW from the MDR in FYs 2018–2019 with a recorded BMI, of whom 61,711 (38.3%) had a BMI exceeding the maximum BMI Service-specific standards during the study period and 0.5% had an eating disorder diagnosis. Increased risk of an eating disorder was found in ADSW with an Underweight BMI. Further, we found that there was no association of disordered eating diagnoses among ADSW who were near the maximum height/weight standard set by their Service.

Conclusion

There appears to be no association between body composition standards of the Services and eating disorder diagnoses in ADSW. We were not able to investigate unhealthy habits around diet or exercise directly related to body composition standards.
Glass eel migration in an urbanized catchment: an integral bottleneck assessment using mark-recapture
Authors: Griffioen A. B. , Wilkes T. , van Keeken O. A. , van der Hammen T. , Buijse A. D. , Winter H. V.
Published: February 2024

Diadromous fish such as the European eel (Anguilla anguilla L.) are hampered by a high density of barriers in estuaries and freshwater systems. Modified and fragmented waterbodies lack tidal flows, and habitat may be less accessible and underutilized compared to free-flowing rivers and estuaries. With rising sea levels and increased occurrence of droughts, the number of barriers may further increase, implying that the need to study migration in such areas may even become more urgent worldwide. To study glass eel migration and behaviour in such highly modified water systems, a mark-recapture study was carried out in the North Sea Canal (NSC) basin, which drains into the North Sea via a large sluice complex. In total, eight uniquely tagged groups (3,797 glass eels) were released near the sluice complex, and 11 groups (2,663 glass eels) were released at inland barriers upstream over a 28 km long stretch in the NSC in spring 2018. The sluice complex attracted 10.3 million glass eel and did not block or delay their immigration. The large and diurnally intensively used coastal ship locks and allowings some saltwater intrusion, efficiently facilitated glass eel migration. Once in the NSC, water outlets from adjacent polders attracted glass eels relative proportional to the discharge of pumping stations. In the NSC, average migration speeds of 0.7 km/day (max. 1.8 km/day) were measured, and this increased with higher temperatures. Redistribution of glass eel from accumulations at inland barriers to other outlet locations was observed in both upstream and downstream directions in the NSC. Passage success and residence time (‘delays’ of 4.1–13.7 days) varied between the different inland barriers. Most of the glass eel, however, appears to settle in the easily accessible habitats within the brackish NSC catchment. This study combined an integral assessment of successive bottlenecks in a modified inland water system.
Correlation study on firing temperature and color of plain pottery excavated from the Tang Dynasty tomb of Liu Jing in Shaanxi, China
Authors: Zhang Biao , Wang Hang , He Xuanliang , Zhu Jianfeng , Luo Hongjie , Liu Daiyun , Wang Fen , Zhao Xichen , Fei Guiqiang , Shi Pei
Published: February 2024

Plain pottery excavated from the Tang Dynasty tomb of Liu Jing was taken as the research object. The color, chemical composition, microstructure, and phase were tested to investigate the influencing factors of color for plain pottery fragments. The results indicated that the contents of Fe2O3 and TiO2 in all fragments varied little, and the influence of humic acids in clay as well as the firing atmosphere on the appearance color of plain pottery was excluded. Therefore, the main factor affecting color saturation (C*) was identified as the firing temperature (T). More importantly, the correlation between C* and firing temperature was established by replicas fired at different temperatures. Before the appearance of the glass phase, iron-containing minerals played a major role in coloring, and after that, iron ions in the glass phase and iron crystallization rose the important function of coloring. Consequently, with the increase of firing temperature, C* value increased firstly and then decreased. The inflection point of the fitted C* − T curve corresponded to the glass phase formation temperature. By comparing the estimated firing temperatures obtained by the fitted C* − T correlation curve with the known firing temperature of replicas, it was demonstrated that the color measurement is an ideal method for deducing the firing temperatures of ancient plain pottery.
Disaggregation of humanitarian data by disability: a realist evaluation of the use of the Washington Group Questions to support more inclusive practices
Authors: O’Reilly Claire F. , Jagoe Caroline
Published: February 2024

People with disabilities make up approximately 16% of the world’s population and disproportionately experience the risks and negative impacts of humanitarian emergencies. In humanitarian contexts, understanding who has a disability, where they are located, and what their needs are is crucial to delivering the right assistance at the right place and time. In recent years, global attention to disability inclusion in the humanitarian sector has focused on the generation of disaggregated data, most commonly using one of the Washington Group Sets of Questions. The implicit assumption behind the collection of more and more data disaggregated by disability, that it will lead to more inclusive action and outcomes, is incorrect. Our findings nuance the current push for disability disaggregated data in all settings and advocate a shift away from the blanket application of disaggregation to a more bespoke approach. Humanitarian and development contexts present multiple challenges to disaggregating data sets by demographic factors such as disability, including the use of households rather than individuals as the unit of analysis, small and non-representative samples, and minority languages with limited translation capacity. Through evaluation of the use of the Washington Group set across the world’s largest humanitarian organization, and its cooperating partners, we present five decision-making criteria that can be flexibly but consistently applied across operating contexts. This enables contextualized decision-making that uses consistent logic to predict the likelihood of data disaggregation by disability leading to more inclusive action and outcomes.