bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased genital mucosal cytokines in Canadian women associate with higher antigen-presenting cells, inflammatory metabolites, epithelial barrier disruption, and the depletion of L. crispatus
Authors: Farr Zuend Christina , Lamont Alana , Noel-Romas Laura , Knodel Samantha , Birse Kenzie , Kratzer Kateryna , McQueen Peter , Perner Michelle , Ayele Hossaena , Mutch Sarah , Berard Alicia R. , Schellenberg John J. , Senturk Faruk , McCorrister Stuart , Westmacott Garrett , Mulhall Fran , Sandberg Bonnie , Yu Adelicia , Burnett Margaret , Poliquin Vanessa , Burgener Adam D. 
Published: July 2023

Abstract
Background
Cervicovaginal inflammation has been linked to negative reproductive health outcomes including the acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health.

Results
In this study, we used a multi’-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome, and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and higher levels of cervical antigen-presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with lower levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions in carbohydrate metabolism and lactic acid, with increases in xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs.

Conclusions
This study identified key molecular and immunological relationships with cervicovaginal inflammation, including higher APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health.
Dynamic RNA profiles in the small intestinal epithelia of cats after Toxoplasma gondii infection
Authors: Zhai Bintao , Xie Shi-Chen , Zhang Jiyu , He Jun-Jun , Zhu Xing-Quan 
Published: July 2023

Abstract
Background
Felids are the only definitive hosts of Toxoplasma gondii. However, the biological features of the feline small intestine following T. gondii infection are poorly understood. We investigated the changes in the expression of RNAs (including mRNAs, long non-coding RNAs and circular RNAs) in the small intestinal epithelia of cats following T. gondii infection to improve our understanding of the life cycle of T. gondii and cat responses to T. gondii infection.

Methods
Fifteen cats were randomly assigned to five groups, and the infection groups were inoculated with 600 tissue cysts of the T. gondii Pru strain by gavage. The small intestinal epithelia of cats were collected at 6, 10, 14, and 30 days post infection (DPI). Using high-throughput RNA sequencing (RNA-seq), we investigated the changes in RNA expression. The expression levels of differentially expressed (DE) genes and non-coding RNAs (ncRNAs) identified by RNA-seq were validated by quantitative reverse transcription PCR (qRT-PCR). Differential expression was determined using the DESeq R package.

Results
In total, 207 annotated lncRNAs, 20,552 novel lncRNAs, 3342 novel circRNAs and 19,409 mRNAs were identified. Among these, 70 to 344 DE mRNAs, lncRNAs and circRNAs were detected, and the post-cleavage binding sites between 725 ncRNAs and 2082 miRNAs were predicted. Using the co-location method, we predicted that a total of 235 lncRNAs target 1044 protein-coding genes, while the results of co-expression analysis revealed that 174 lncRNAs target 2097 mRNAs. Pathway enrichment analyses of the genes targeted by ncRNAs suggested that most ncRNAs were significantly enriched in immune or diseases-related pathways. NcRNA regulatory networks revealed that a single ncRNA could be directly or indirectly regulated by multiple genes or ncRNAs that could influence the immune response of cats. Co-expression analysis showed that 242 circRNAs, mainly involved in immune responses, were significantly associated with T. gondii infection. In contrast, 1352 protein coding RNAs, mainly involved in nucleic acid process/repair pathways or oocyte development pathways, were negatively associated with T. gondii infection.

Conclusions
This study is the first to reveal the expression profiles of circRNAs, lncRNAs and mRNAs in the cat small intestine following T. gondii infection and will facilitate the elucidation of the role of ncRNAs in the pathogenesis of T. gondii infection in its definitive host, thereby facilitating the development of novel intervention strategies against T. gondii infection in humans and animals.

Graphical Abstract
Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel
Authors: Lang Jessica D. , Nguyen Tuong Vi V. , Levin Maren K. , Blas Page E. , Williams Heather L. , Rodriguez Esther San Roman , Briones Natalia , Mueller Claudius , Selleck William , Moore Sarah , Zismann Victoria L. , Hendricks William P.D. , Espina Virginia , O’Shaughnessy Joyce 
Published: July 2023

Abstract
Background
A subset of triple-negative breast cancers (TNBCs) have homologous recombination deficiency with upregulation of compensatory DNA repair pathways. PIKTOR, a combination of TAK-228 (TORC1/2 inhibitor) and TAK-117 (PI3Kα inhibitor), is hypothesized to increase genomic instability and increase DNA damage repair (DDR) deficiency, leading to increased sensitivity to DNA-damaging chemotherapy and to immune checkpoint blockade inhibitors.

Methods
10 metastatic TNBC patients received 4 mg TAK-228 and 200 mg TAK-117 (PIKTOR) orally each day for 3 days followed by 4 days off, weekly, until disease progression (PD), followed by intravenous cisplatin 75 mg/m2 plus nab paclitaxel 220 mg/m2 every 3 weeks for up to 6 cycles. Patients received subsequent treatment with pembrolizumab and/or chemotherapy. Primary endpoints were objective response rate with cisplatin/nab paclitaxel and safety. Biopsies of a metastatic lesion were collected prior to and at PD on PIKTOR. Whole exome and RNA-sequencing and reverse phase protein arrays (RPPA) were used to phenotype tumors pre- and post-PIKTOR for alterations in DDR, proliferation, and immune response.

Results
With cisplatin/nab paclitaxel (cis/nab pac) therapy post PIKTOR, 3 patients had clinical benefit (1 partial response (PR) and 2 stable disease (SD) ≥ 6 months) and continued to have durable benefit in progression-free survival with pembrolizumab post-cis/nab pac for 1.2, 2, and 3.6 years. Their post-PIKTOR metastatic tissue displayed decreased mismatch repair (MMR), increased tumor mutation burden, and significantly lower levels of 53BP1, DAG Lipase β, GCN2, AKT Ser473, and PKCzeta Thr410/403 compared to pre-PIKTOR tumor tissue.

Conclusions
Priming patients’ chemotherapy-pretreated metastatic TNBC with PIKTOR led to very prolonged response/disease control with subsequent cis/nab pac, followed by pembrolizumab, in 3 of 10 treated patients. Our multi-omics approach revealed a higher number of genomic alterations, reductions in MMR, and alterations in immune and stress response pathways post-PIKTOR in patients who had durable responses.

Trial Registration
This clinical trial was registered on June 21, 2017, at ClinicalTrials.gov using identifier NCT03193853.
Impact of H3K27 trimethylation loss in meningiomas: a meta-analysis
Authors: Cello Gregory , Patel Ruchit V. , McMahon James Tanner , Santagata Sandro , Bi Wenya Linda 
Published: July 2023

AbstractTrimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in measuring H3K27me3 loss, quantifying its impact, and interpreting its clinical utility. We conducted a systematic review across Pubmed, Embase, and Web of Science to identify studies examining H3K27me3 loss in meningioma. Clinical, histopathological, and immunohistochemistry (IHC) characteristics were aggregated. A meta-analysis was performed using a random-effects model to assess prevalence of H3K27me3 loss and meningioma recurrence risk. Study bias was characterized using the NIH Quality Assessment Tool and funnel plots. Nine publications met inclusion criteria with a total of 2376 meningioma cases. The prevalence of H3K27me3 loss was 16% (95% CI 0.09–0.27), with higher grade tumors associated with a significantly greater proportion of loss. H3K27me3 loss was more common in patients who were male, had recurrent meningiomas, or required adjuvant radiation therapy. Patients were 1.70 times more likely to have tumor recurrence with H3K27me3 loss (95% CI 1.35–2.15). The prevalence of H3K27me3 loss in WHO grade 2 and 3 meningiomas was found to be significantly greater in tissue samples less than five years old versus tissue of all ages and when a broader definition of IHC staining loss was applied. This analysis demonstrates that H3K27me3 loss significantly associates with more aggressive meningiomas. While differences in IHC and tumor tissue age have led to heterogeneity in studying H3K27me3 loss, a robust prognostic signal is present. Our findings suggest an opportunity to improve study design and standardize tissue processing to optimize clinical viability of this epigenetic marker.
RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer
Authors: Li Yi-Qun , Sun Fang-Zhou , Li Chun-Xiao , Mo Hong-Nan , Zhou Yan-Tong , Lv Dan , Zhai Jing-Tong , Qian Hai-Li , Ma Fei 
Published: July 2023

Abstract
Background
Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated.

Methods
Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.

Results
We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.

Conclusions
Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.
Modern contraceptive method utilization and determinant factors among women in Ethiopia: Multinomial logistic regression mini- EDHS-2019 analysis
Authors: Negash Berhan Tsegaye , Chekol Aklile Tsega , Wale Mastewal Aschale 
Published: July 2023

AbstractBackgroundGlobally, approximately 290,000 women between the ages of 15 and 49 died from pregnancy-related problems in 2014 alone, with these sub-Saharan Africa accounts for 65% (179,000) of the deaths. Although studies are conducted on modern contraceptives, information is scarce on multinomial regression analysis at the national level data. Therefore, this study aimed to assess modern contraceptive method utilization and determinant factors among women in Ethiopia.MethodsData for this study were extracted from the national representative 2019 Ethiopian Mini Demographic and Health Survey. Data was collected using a 2-stage cluster design, in which enumeration areas formed the first stage and households made the second stage. The survey was conducted from March 21, 2019, to June 28, 2019. The analysis was done using multinomial logistic regression using STATA software version 14. The overall categorical variables with a P value of < 0.25 at the binomial analysis were included in the final model of the multinomial logistic regression model in which odds ratios with 95% CIs were estimated to identify the independent variables of women’s modern contraceptive utilization. P values less than 0.05 were used to declare statistical significance. All analysis was done on weighted data.ResultsA total of 8885 (weighted) participants were included in the current study from these,. The current study revealed that the prevalence of modern contraceptive utilization was 28.1% (95%CI: 27.6.7-28.6%). Factors like: women 25 to 34 years (aRRR = 1.5;95% CI:1.2–1.9), 35 to 44 years (aRRR = 2.4; 95% CI: 3.3–5.4), and greater than 45 years (aRRR = 2.9; 95% CI: 2.2–3.7); place of residence (rural; aRRR = 0.89; 95% CI 0.81–0.99), higher educational status (aRRR = 0.035;95%CI:0.61–0.98), grandmultipara (aRRR = 1.73;95%CI:1.6–1.9), and wealth index (poorer aRRR = 0.541;95%CI:0.46–0.631.9) were the factors significantly associated with the outcome variable.ConclusionsIn this, modern contraceptive utilization is low as compared to other countries. It was influenced by age, place of residence, education, the number of children, and wealth index. This suggests that creating awareness of contraceptive utilization is paramount for rural residence women by policymakers and health managers to empower women for family planning services. Moreover, all stakeholders, including governmental and nongovernmental organizations, better to emphasize on modern contraceptive use.
Design of canonical signed digit multiplier using spurious power suppression technique adder
Authors: K. P. Jayalakshmi , Miranda Priya Seema , Shri K. Aarya 
Published: July 2023

AbstractReducing power consumption is a major challenge in developing integrated processors for smart portable devices. This is particularly important for extending battery life and ensuring extended usage of the device. However, some DSP processing applications involve complex algorithms that consume more power, which poses a significant challenge in designing DSP applications for VLSI circuits. To address this issue, low-power consumption methodologies are required. Although various strategies have been developed to reduce power consumption, they have not demonstrated a significant decrease in dynamic power consumption, which is the primary factor determining the total amount of power dissipation.The focus of this research is to develop a low-power multiplier using the spurious power suppression technique (SPST), a method that divides the arithmetic unit into the most significant part (MSP) and least significant part (LSP) and turns off the MSP when it is not required for computation. This approach reduces dynamic power and overall power consumption of the VLSI combinational circuit. The proposed system also utilizes canonical signed digit (CSD) representation to further reduce power usage.The system was designed using Cadence design suite, and the results showed a significant reduction of 35.8% in power consumption for a 32-bit SPST-enabled CSD multiplier. The proposed system’s total power consumption is 0.561 mW. Additionally, the proposed system was used in a power and area-efficient 256-point FFT architecture, resulting in an 86.6% reduction in power consumption. This system is suitable for real-time applications such as systems that use orthogonal frequency division multiplexing.
Feasibility study of pore-pressure prediction in carbonate rocks
Authors: Sharifi Javad , Hafezi Moghaddas Naser , Khoshdel Hossein , Khanehbad Mohammad 
Published: July 2023

In the recent past, the applicability and uncertainty of pore-pressure prediction methods that work based on seismic signals have been serious challenges in carbonate reservoirs. In this context, enormous research has been conducted on the prediction of pore pressure in these rocks, some of which have ended with failure due to the complexity of carbonates. To address the main cause of such failures, we experimentally simulate the pore fluid in carbonates under reservoir conditions to interpret and classify the factors contributing to the pore pressure. The results are then built into a novel hybrid experimental model for evaluating the feasibility of pore pressure prediction — one that could bridge the gap between laboratory and empirical approaches. For this purpose, 34 core samples are collected from different geologic formations at different wells penetrating reservoir intervals. The mechanical properties of the samples are investigated by conducting experiments in a triaxial cell where pore pressure is applied under different regimes while simultaneously acquiring the ultrasonic response of the sample. Sensitivity analyses of pore pressure are carried out under drained and undrained conditions and the results are used to evaluate our methodology. Pore pressure coefficients of P- and S-wave velocities are introduced in two different conditions, namely constant differential stress and constant pore pressure, with the same dimension as compressibility. Results are interpreted statistically and effective parameters are identified from a pool of many variables; these include the static bulk modulus, Young’s modulus, Biot’s coefficients, porosity, permeability, and sedimentary textures (e.g., micritization, neomorphism, cementation, fracture, blocky calcite, and dissolution). A feasibility study template is further introduced for investigating pore pressure detectability based on commonly available data in carbonate reservoirs by incorporating the main controlling factors. Our template and findings of this research are important for pore pressure prediction before performing further research and implementing operation programs. They also can decrease the risk of underestimating the pore pressure, thereby improving the well planning performance and mitigating the drilling hazards.
Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial
Authors: Husain Muhammad Ishrat , Blumberger Daniel M. , Castle David J. , Ledwos Nicole , Fellows Elise , Jones Brett D. M. , Ortiz Abigail , Kloiber Stefan , Wang Wei , Rosenblat Joshua D. , Mulsant Benoit H. 
Published: July 2023

Background
Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.

Aims
To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).

Method
In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.

Results
This trial will advance the understanding of psilocybin's mechanism of antidepressant action.

Conclusions
This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis
Authors: Sattari Shahab Aldin , Rincon-Torroella Jordina , Sattari Ali Reza , Feghali James , Yang Wuyang , Kim Jennifer E. , Xu Risheng , Jackson Christopher M. , Mukherjee Debraj , Lin Shih-Chun , Gallia Gary L. , Comair Youssef G. , Weingart Jon , Huang Judy , Bettegowda Chetan 
Published: July 2023

BACKGROUND AND OBJECTIVES:
Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions.

METHODS:
MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day).

RESULTS:
Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = −2.99 days [−5.09, −0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [−34.09, 109.86], P = .30).

CONCLUSION:
Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.