bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-427 Do endometrial leucocytes and angiogenesis in the peri-implantation period predict hypertensive disorders in the subsequent pregnancy?
Authors: Chen X 
Published: July 2024

Abstract

Study question
Do endometrial leucocytes and angiogenesis in the peri-implantation period from women with a history of recurrent reproductive failure predict hypertensive disorders in the subsequent pregnancy?

Summary answer
uNK cells, T cells, B cells and macrophages in the peri-implantation endometrium did not correlate with hypertensive disease of pregnancy in the subsequent pregnancy.

What is known already
Women with a history of recurrent reproductive failure are thought to have a higher risk of hypertensive disorders of pregnancy (HDP) subsequently. Immunological interactions and vascular factors in the placental bed are considered to be two important pathways for the initiation and development of HDP. However, the prognostic value of endometrial leucocytes and angiogenesis around the time of implantation in a cycle prior to conception and HDP in the subsequent pregnancy is still unclear.

Study design, size, duration
This is a prospective cohort study. A total of 694 women were included in this study from Jan 2019 to Jun 2023.

Participants/materials, setting, methods
Immunohistochemistry for vWF and multiplex immunofluorescence for endometrial leukocytes, including CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages, were performed in the precisely timed LH + 7 endometrium. The subsequent pregnancy outcomes of the subjects were followed up as well.

Main results and the role of chance
Endometrial leukocytes including CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages were found in the peri-implantation endometrium. There was no significant difference in the CD56+ uNK cells, CD3+ T cells, CD20+ B cells and CD68+ macrophages numbers percentage between women with and without gestational hypertension in the subsequent pregnancy. The median micro vessel density in women who developed gestational hypertension in the subsequent pregnancy (9.4 ± 3.1 /mm2 ) was significantly (P=0.038) lower than the MVD in those who did not (13.5 ± 4.9/mm2 ).

Limitations, reasons for caution
1. It is not clear whether the uNK cell number during the peri-implantation period is reflective of those in the first trimester when spiral artery remodelling occurs. 2. This study was carried out in women with reproductive failure and the results may not apply to the general populations.

Wider implications of the findings
Vascularization features in the endometrium may provide prognostic value of subsequent hypertensive disease of pregnancy.

Trial registration number
not applicable
P-571 Mutations in FOXO3 mutation cause human premature ovarian insufficiency
Authors: Sun L , Tong K , Huang G , Li J 
Published: July 2024

Abstract

Study question
Do variants in front fork transcription factor 3 (FOXO3) account for premature ovarian insufficiency (POI) in humans? Is there is a potential treatment for POI caused by FOXO3 mutations?

Summary answer
Heterozygous variants in FOXO3 cause human female infertility owing to POI by inducing oocyte apoptosis.

What is known already
Front fork transcription factor 3 (FOXO3) is a member of the forkhead box family of transcription factors. Previous study had reported that FOXO3 encodes an evolutionarily conserved primary regulator and an effective inhibitor of primordial follicle activation. The null mutants of Foxo3 or its ortholog in multiple organisms displayed POI owing to deficiencies in maintaining the ovarian reserve. However, whether FOXO3 variants can underline POI phenotype in humans were unclear, and the causal relationship has not yet been established with functional evidence.

Study design, size, duration
107 primary infertility families with POI were recruited for pathogenic variants screening. The proband with and her parents were verified for FOXO3 variants.

Participants/materials, setting, methods
All the patients were diagnosed with POI were confirmed by clinical analyses. Exome sequencing and subsequent bioinformatic analyses were performed to screen for candidate pathogenic variants. The pathogenicity of identified variants was assessed and studied in vivo in mice carrying the equivalent mutations.

Main results and the role of chance
Novel heterozygous variant in FOXO3 was identified in the patient with POI. Mice modeling the Foxo3 variant identified in patients recapitulated the ovarian reserve defects of patients, confirming the pathogenicity of the identified variants. The mutation caused constitutive activation of FOXO3 lead to POI by inducing oocyte apoptosis, which will facilitate the genetic diagnosis of POI in patients and provide a potential therapeutic target for female fertility.

Limitations, reasons for caution
A limitation of the current study is the small sample size. More primary infertility patients with POI should be screened to enrich the pathogenetic mutations of FOXO3.

Wider implications of the findings
FOXO3 was detected as a novel gene underlie human POI, thus providing new targets for the molecular diagnosis and treatment.

Trial registration number
the National Natural Science Foundation of China (NSFC) (Grant number:82302083)
P-598 Novel inactivating homozygous mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) and first live birth after in vitro maturation (IVM): a breakthrough
Authors: Labrosse J , Sifer C , Cedrin I , Peigne M , Grynberg M 
Published: July 2024

Abstract

Study question
How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation?

Summary answer
We report the first live birth after IVM in a patient with a novel homozygous inactivating LHCGR mutation (exon 6,c.470A&gt;G).

What is known already
LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells.
Inactivating mutations of the LHCG receptor lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purpose.
Until now, egg donation represented the only option to treat their infertility.

Study design, size, duration
A case report.

Participants/materials, setting, methods
A 35 year-old nulliparous patient was referred to our university hospital for primary infertility.

Main results and the role of chance
The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia.
Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger.
We identified by genetic analysis a novel homozygous inactivating LHCGR mutation (exon 6, c.470A&gt;G) that had never been described previously.
IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen.
Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy.
The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain.

Limitations, reasons for caution
By definition, a case-report requires further studies to confirm our findings.

Wider implications of the findings
We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this live birth successfully obtained places IVM as the only reliable option for these patients to conceive with their own eggs.

Trial registration number
not applicable
P-617 The investigation of the shared genetic architecture between hypothyroidism and age at menopause
Authors: Long P , Ruping Q , Hongmei X 
Published: July 2024

Abstract

Study question
Is there a shared genetic architecture and a putative causal association between hypothyroidism and age at menopause (AM)?

Summary answer
There is a genetic correlation and a causal relationship between Hypothyroidism and AM.

What is known already
Thyroid disease is more common in women. The interplay between thyroid function and the gonadal axes remains interconnected throughout a woman’s reproductive cycle. Notably, the menopausal phase represents a critical period for metabolic alterations, wherein thyroid hormones and metabolic status are intricately intertwined.

Study design, size, duration
Data from publicly available genome-wide association study (GWAS) summary statistics of hypothyroidism (European-based: 51,194 hypothyroidism cases and 443,383 controls) and AM (European-based: N = 141,926) were used to investigate shared genetic assosiation.

Participants/materials, setting, methods
Shared genetics between hypothyroidism and AM were explored using linkage disequilibrium score regression, ρ-HESS, cross-trait meta-analysis, colocalization analysis and summary data-based Mendelian randomization, and investigated causal associations using Mendelian randomization.

Main results and the role of chance
The estimated liability scale of the single nucleotide polymorphisms (SNPs) heritability for AM and hypothyroidism was 13.0% and 5.1%, respectively. A substantial negative genetic association (rg = -0.081, P = 0.0055) was found by bivariate LDSC between hypothyroidism and AM. Local Genetic Correlations identified a strong local signal at 6p21.32-21.33 (chromosome 6: 31571218-32682664) (P = 1.39E-5). Ten important common SNPs were found. Hypothyroidism had a causal effect on AM, but not vice versa. Genetic association between hypothyroidism and AM in blood were enriched in Genotype-Tissue Expression (GTEx) data. In addition, two potentially functional genes, PPM1F and RPL23AP1, were identified to be associated with both hypothyroidism and AM.

Limitations, reasons for caution
Hypothyroidism encompasses primary and secondary forms, and due to limited data availability, our study could not perform phenotype-specific analyses. Second, even though our research identified genes associated with hypothyroidism and AM, more experimental research and long-term studies are required to fully understand the biological mechanisms underlying the observed genetic relationships.

Wider implications of the findings
Our study, thorough genome-wide cross-trait analysis, reveals a shared genetic architecture and causal relationship between hypothyroidism and AM. These may open up a new avenue for future research between hypothyroidism and AM.

Trial registration number
Not applicable
Correlation between kinetic parameters, reactor performance, and biogas and methane potential of co-digestion and mono-digestion of active sludge and olive mill wastewater
Authors: Al bkoor Alrawashdeh Khalideh , Al-Sameraie La’aly , Al Bsoul Abeer , Khasawneh Ayat , Al-Tabbal Jalal 
Published: July 2024

Abstract
Anaerobic co-digestion(AcoD) of active sludge (AS) and olive mill wastewater (OMW) is becoming an increasingly recognized alternative to manage waste and generate renewable energy. A kinetic study of the performance of biochemical methane potential (BMP) and continuous stirred tank reactors (CSTR) bioreactors was conducted to identify critical parameters influencing. Substrates of 100%OMW, 100%AS, 25:75%, 75:25%, and 50:50 were utilized in the BMP and CSTR digesters. To identify the optimum mixing, BMP tests were conducted under three different operating conditions: no mixing (NM), low-continuous mixing intensity (LM) of 25 rpm, and high continuous mixing intensity (HM) of 60 rpm. CSTR with an optimum mixing regime is utilized to identify the optimum substrate. In particular, the removal efficiency of volatile solids (VSs), total chemical oxygen demand (TCOD), and the production of biogas and methane (CH4) were investigated to specify the performance of the anaerobic digestion (AD) process. The results revealed that the optimum mixing regime is LM with BMP tests. Also, the maximum performance in CSTR-ML was achieved by 75:25 AS:OMW, 0.339 Nm3/kg VS of biogas, 69.89% of CH4, and a removal efficiency of 87.12% of VS and 79.23% of TCOD. For BMP tests, the biogas and CH4 yield production kinetics were best fitted by the modified Gompertz models: mono-digestion and co-digestion 75:25 and 50:50 of AS:OMW, while the best-fit model for co-digestion 25:75 was achieved by the transfer model. The production kinetics were well described by modified Gompertz models in CSTR tests. These results point to the possibility of optimizing digester systems on a wide scale using the outputs that have been observed.
Novelty statement.
This research work provides novel insights into the performance of the digester under diverse mixing conditions and varying co-substrate concentrations of AS:OMW and presents the best model to predicate the biogas and CH4 at various operation conditions.
Type IV secretion system effector sabotages multiple defense systems in a competing bacterium
Authors: Wang Bingxin , Xu Fugui , Zhang Zeyu , Shen Danyu , Wang Limin , Wu Huijun , Yan Qing , Cui Chuanbin , Wang Pingping , Wei Qi , Shao Xiaolong , Wang Mengcen , Qian Guoliang 
Published: July 2024

Abstract
Effector proteins secreted by bacteria that infect mammalian and plant cells often subdue eukaryotic host cell defenses by simultaneously affecting multiple targets. However, instances when a bacterial effector injected in the competing bacteria sabotage more than a single target have not been reported. Here, we demonstrate that the effector protein, LtaE, translocated by the type IV secretion system from the soil bacterium Lysobacter enzymogenes into the competing bacterium, Pseudomonas protegens, affects several targets, thus disabling the antibacterial defenses of the competitor. One LtaE target is the transcription factor, LuxR1, that regulates biosynthesis of the antimicrobial compound, orfamide A. Another target is the sigma factor, PvdS, required for biosynthesis of another antimicrobial compound, pyoverdine. Deletion of the genes involved in orfamide A and pyoverdine biosynthesis disabled the antibacterial activity of P. protegens, whereas expression of LtaE in P. protegens resulted in the near-complete loss of the antibacterial activity against L. enzymogenes. Mechanistically, LtaE inhibits the assembly of the RNA polymerase complexes with each of these proteins. The ability of LtaE to bind to LuxR1 and PvdS homologs from several Pseudomonas species suggests that it can sabotage defenses of various competitors present in the soil or on plant matter. Our study thus reveals that the multi-target effectors have evolved to subdue cell defenses not only in eukaryotic hosts but also in bacterial competitors.
A Comparison of Racial and Ethnic Disparities in Complications Following Burn Injury in Adult Patients
Authors: Ragan Mecklin V , Yemele Kitio Sibelle Aurelie , Bergus Katherine C , Wala Samantha J , Patterson Kelli N , Nafiu Olubukola O , Thakkar Rajan K , Schwartz Dana M 
Published: July 2024

Abstract
Burn injury contributes to significant morbidity and mortality in the United States. Despite an increased focus on racial and ethnic disparities in healthcare, there remains a critical knowledge gap in our understanding of the effect of these disparities on complications experienced by burn patients. The American Burn Association’s National Burn Repository data were reviewed from 2010 to 2018. Information regarding demographics, burn mechanism and severity, complications, and clinical outcomes were recorded. Data analysis was performed using 1:1 propensity score matching and logistic regression modeling. A separate analysis of Hispanic and non-Hispanic patients was performed using Chi-squared tests. Among 215,071 patients, racial distribution was 65.16% White, 19.13% Black, 2.18% Asian, 0.74% American Indian/Alaskan Native, and 12.78% other. Flame injuries were the most common cause (35.2%), followed by scald burns (23.3%). All comparisons were made in reference to the White population. Black patients were more likely to die (OR: 1.28; 95% CI, 1.17-1.40), experience all (OR: 1.08; 95% CI, 1.03-1.14), cardiovascular (OR: 1.24; 95% CI, 1.08-1.43), or infectious (OR: 1.64; 95% CI, 1.40-1.91) complications, and less likely to experience airway complications (OR: 0.83; 95% CI, 0.74-0.94). American Indian/Alaskan Native patients were more likely to experience any complication (OR: 1.33; 95% CI, 1.05-1.70). All minority groups had increased length of hospital stay. Black, Asian, and other patients had longer length of ICU stay. Black patients had longer ventilator duration. Among 82 775 patients, 24 075 patients were identified as Hispanic and 58 700 as non-Hispanic. Statistically significant differences were noted between groups in age, total body surface area, proportion of 2nd-degree burn, and proportion of 3rd-degree burn (P &lt; .01). These findings highlight the need for further work to determine the etiology of these disparities to improve burn care for all patients.
How Do Consumers React to Ads That Meddle in Out-Party Primaries?
Authors: Hussein Mohamed A , Lee Courtney , Wheeler S Christian 
Published: July 2024

Abstract
In 2022, Democrats spent $53 million on ads helping far-right candidates win Republican primaries. Paying for ads that support far-right candidates, the reasoning went, could help Democrats win in the general elections because it is easier to beat extreme than moderate candidates. In the current research, we ask: how do consumers react to the use of “meddle ads”? On the one hand, because of rising levels of polarization, consumers might be accepting, or even supportive, of meddle ads. On the other hand, because meddle ads might come across as unethical and risky, consumers might be averse to their use. Across 7 main studies and 10 supplemental studies (N = 7,740) using multiple empirical approaches—including conjoint analysis, vignette studies, incentive-compatible donation studies, and analysis of online comments using human coders and NLP tools—we find that consumers are averse to the use of meddle ads. This aversion is driven by three factors: concerns about the character of the candidate, outcome-related risk (losing elections), and system-related risk (losing trust in democracy). These findings contribute to research on political marketing, provide practical guidance for marketers around meddle ads, and identify a novel type of risk perceptions with implications for consumer behavior research.
Cloning and functional analysis of the juvenile hormone receptor gene CsMet in Coccinella septempunctata
Authors: Cheng Ying , Zhou Yuhang , Li Cao , Jin Jianxue 
Published: July 2024

Abstract
The potential role of the juvenile hormone receptor gene (methoprene-tolerant, Met) in reproduction of Coccinella septempunctata L. (Coleoptera: Coccinellidae)(Coleoptera: Coccinellidae), was investigated by cloning, analyzing expression profiles by quantitative real-time PCR, and via RNA interference (RNAi). CsMet encoded a 1518-bp open reading frames with a predicted protein product of 505 amino acids; the latter contained 2 Per-Arnt-Sim repeat profile at amino acid residues 30–83 and 102–175. CsMet was expressed in different C. septempunctata larvae developmental stages and was most highly expressed in third instar. CsMet expression in female adults gradually increased from 20 to 30 d, and expression levels at 25 and 30 d were significantly higher than levels at 1–15 d. CsMet expression in 20-d-old male adults was significantly higher than in males aged 1–15 d. CsMet expression levels in fat body tissues of male and female adults were significantly higher than expression in the head, thorax, and reproductive system. At 5 and 10 d after CsMet-dsRNA injection, CsMet expression was significantly lower than the controls by 75.05% and 58.38%, respectively. Ovary development and vitellogenesis in C. septempunctata injected with CsMet-dsRNA were significantly delayed and fewer mature eggs were produced. This study provides valuable information for the large-scale rearing of C. septempunctata.
Experience with chemotherapy for postoperative metastases of adenosquamous carcinoma of the esophagogastric junction and pathological study of its development
Authors: Mita Kazuhito , Oda Hideaki , Shimaguchi Mayu , Kouno Michitaka , Toyota Naoyuki , Hatano Minoru , Toyota Tsuyoshi , Sasaki Junichi 
Published: July 2024

Abstract
We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors.
Inner dusty regions of protoplanetary discs – III. The role of non-radial radiation pressure in dust dynamics
Authors: Vinković Dejan , Čemeljić Miljenko 
Published: July 2024

ABSTRACT
We explore the dynamical behaviour of dust particles that populate the surface of inner optically thick protoplanetary discs. This is a disc region with the hottest dust and is of a great importance for planet formation and dust evolution, but we still struggle to understand all the forces that shape this environment. In our approach, we combine results from two separate numerical studies, one is the wind velocity and density distributions obtained from magnetohydrodynamical simulations of accretion discs, and the other is a high-resolution multigrain dust radiation transfer. In our previous paper in the series, we described the methodology for utilizing these results as an environmental input for the integration of dust trajectories driven by gravity, gas drag, and radiation pressure. Now we have two improvements, we incorporate time changes in the wind density and velocity, and we implement the non-radial radiation pressure force. We applied our analysis on the Herbig Ae and T Tau stars. We confirm that the radiation pressure force can lead to dust outflow, especially in the case of more luminous stars. Additionally, it opposes dust accretion at the inner disc edge and reduces dust settling. These effects are enhanced by the disc wind, especially in the zone where the stellar and the disc magnetic fields meet. Our results suggest that dust grains can stay in the hottest disc region for an extended period and then end up ejected into the outer disc regions.