bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel role for PGE2-EP4 in the developmental programming of the mouse ductus arteriosus: consequences for vessel maturation and function
Authors: Yarboro Michael T. , Boatwright Naoko , Sekulich Deanna C. , Hooper Christopher W. , Wong Ting , Poole Stanley D. , Berger Courtney D. , Brown Alexus J. , Jetter Christopher S. , Sucre Jennifer M. S. , Shelton Elaine L. , Reese Jeff
Published: August 2023

EP4 is the primary EP receptor in the ductus arteriosus (DA) and is critical during late gestation for its development and eventual closure. The “paradoxical” patent DA (PDA) phenotype of EP4-knockout mice arises from a combination of impaired contractile potential, altered signaling properties, and a failure to remodel associated with an underdeveloped immature vessel. These findings provide new mechanistic insights into women who receive NSAIDs to treat preterm labor, whose infants have unexplained PDA.
Lower hemoglobin levels associate with higher baroreflex sensitivity and heart rate variability
Authors: Tapio Joona , Kiviniemi Antti M. , Perkiömäki Juha , Junttila M. Juhani , Huikuri Heikki V. , Ukkola Olavi , Koivunen Peppi , Tulppo Mikko P.
Published: August 2023

Heart rate variability (HRV) and baroreflex sensitivity (BRS), which can be measured noninvasively, can predict cardiac and metabolic diseases. Our findings show that within normal variation subjects with lower hemoglobin (Hb) levels have an overall healthier HRV profile and increased cardiac parasympathetic activity in middle age, independent of age, sex, smoking status, and key metabolic covariates. These findings support our previous findings that Hb levels can be used in assessing long-term risks for cardiometabolic diseases.
Formulation of Fungal Media from Local Plant Materials
Authors: Oledibe Odira Johnson , Enweani-Nwokelo Ifeoma Bessie , Okigbo Raphael Nnajiofor , Achugbu Adaeze Nnedinma
Published: August 2023

A culture medium is a liquid or gelled substance that promotes microorganism growth in the laboratory. This study is aimed at exploring various local plant sources for fungal media formulation. The local plant materials used in this study were grains of Zea mays, seeds of Glycine max, and boiled and peeled Dioscorea dumetorum tubers. These plant materials were dried separately in the oven at 60°C, pulverized individually, measured in different proportions, and poured separately into conical flasks containing distilled water at various proportions to evaluate the potential of the fungal media formulation. The best formulation was derived from Z. mays (5 g), D. dumetorum (2.5 g), and G. max (2 g) in 50 ml of sterile distilled water (M5Y2.5S2). It was then autoclaved at 121°C for 15 mins at 15 psi and dispensed in various Petri dishes. Media characteristics such as gelling ability and consistency were compared with Sabouraud dextrose agar (SDA) as the standard media. Isolates of Aspergillus niger and Penicillium expansum were used; these were derived from deteriorating yam and bread and cultured on the media. The colony diameter, aerial growth, and sporulation of the test fungal isolates were ascertained. When compared to SDA (

8.92
±
0.10

), the colony diameter of A. niger on M5Y2.5S2 (

8.90
±
0.10

) did not differ significantly (

P
=
0.05

). This is also applicable in the case of P. expansum on M5Y2.5S2 (

8.93
±
0.06

) when compared with SDA (

8.92
±
0.07

). There was a significant difference (

P
=
0.05

) in the sporulation of A. niger (M5Y2.5S2

1.76
±
0.06

) when compared with SDA (

1.70
±
0.06

). This is also applicable in the case of P. expansum (M5Y2.5S2

2.73
±
0.06

) when compared with SDA (

2.70
±
0.0

). The fungal isolates showed luxuriant growth in both media. M5Y2.5S2 performed favorably in comparison to SDA in relation to all the parameters studied. M5Y2.5S2 is recommended for use in fungal culture and will save funds used for the importation of media.
Flavonoids from Peony Seed Meal by Nanofiltration Membrane Separation
Authors: Zou Ping , Chen Wentao , Xu Ying , Wang Yaohui , Zhang Yingyang , Xu Rong
Published: August 2023

Flavonoids are polyphenolic compounds with a wide range of biological activities (antioxidation, antitumor, and immunomodulatory). The membrane separation method of flavonoids has a high recovery and biological activity, overcoming the shortcomings of traditional methods for the separation of bioactive molecules. In this study, ethanol-water (

v
/
v

) solution was used to extract peony seed meal. The extraction rate of total flavonoids from peony seed meal was 35.28%. Five microfiltration membranes, polypropylene (PP), polyvinylidene fluoride (PVDF), cellulose acetate (CA), polyether sulfone (PES), and polyamide (PA), were selected to pretreat the extracts, and their separation performance was investigated. A new PA-supported silicone film was prepared by sol-gel method using 1,2-bis(TRIMETHOXYSILYL)ETHANE (BTESE) as a carrier. The synthesized BTESE/PA composite membrane was applied to the purification of organic silica PSMF solution by nanofiltration process. The optimal pressure of nanofiltration operation is 0.8 MPa, and the membrane flux can reach 2.06 kg·m-2·h-1. The mass concentration of flavonoids in the retention solution was decreased to 860.56 mg·L-1, and the permeable components of PSMF were effectively separated. The total flavonoid content of the purified lyophilized powder was 146.12 mg·g-1, which was 2.4 times that before purification. The results show that PSMF can be effectively separated by BTESE/PA membrane, and the membrane solution has good antioxidant activity.
The Deformation, Failure Mechanisms, and Stability Control of the Surrounding Rock of Deep Cross-Measure Roadway: A Case Study
Authors: Du Wenzheng , Pan Rui , Sun Hongjin
Published: August 2023

In view of the difficulty in controlling the surrounding rock stability of deep cross-measure roadways, a deep cross-measure roadway of the Wanfu coal mine, a typical high-stress mine, was monitored on site and analyzed under the original support scheme. The findings show that the degrees of deformation and failure of the cross-measure roadway varied under different working conditions and that the roadway deformation and failure were mainly characterized by a high fragmentation degree and a large failure range of the surrounding rock and the frequent failure of support components. Considering that the different parts of the cross-measure roadway are located in different lithostratigraphic units, establishing a numerical model of the cross-measure roadway under different working conditions; analyzing the deformation pattern of the surrounding rock of the roadway, the plastic range, and the morphological change pattern; and clarifying the deformation and failure mechanisms of the cross-measure roadway based on field monitoring results. On this basis, two types of evaluation indicators, that is, the deformations of the surrounding rock and the plastic ranges in the four typical parts (roof, shoulder, floor, and sidewalls) of the roadway, were selected to rate the stability of the roadway under different working conditions. Grouting reinforcement-based targeted control countermeasures are proposed to improve the surrounding rock stability. Subsequently, numerical analysis and field application of these control countermeasures were carried out to solve the problem of controlling the surrounding rock stability of deep cross-measure roadways.
Detection of Biomolecules and Glucose Concentration in Blood Using a Subwavelength Grating Optical Biosensor
Authors: Sahu Sourabh , Mudgal Nitesh , Agrawal Ankit , Singh Ghanshyam
Published: August 2023

The research paper describes the design and simulation of an optical biosensor based on a ring resonator with a strip waveguide and a subwavelength grating waveguide. The main goal of the device is to function in low‐loss regions and prevent bending losses in ring resonator configuration. The finite‐difference‐time‐domain analysis is performed to simulate the device and to observe the sensing parameters. The biosensor is intended to be used for sensing biological molecules. The working principle of the sensor is to detect changes in the resonant wavelength caused by changes in the refractive index of biomaterials. By observing the shift in the resonant wavelength, the sensor can provide sensitive and reliable detection of biomolecules in solution. The evaluated sensitivity of the device is 206.3 nm/RIU, with a limit of detection of the order of 10−5 RIU. The device is also tested for the detection of glucose concentration in blood and found to be well‐suited for on‐chip applications. This makes it a promising candidate for use in a wide range of biosensing applications, from medical diagnostics to food safety testing.
Trends in the Use of Probiotics in Aquaculture of Bangladesh—Present State, Problems, and Prospects
Authors: Hossain Md Kabir , Shahjahan Md , Kari Zulhisyam Abdul , Téllez-Isaías Guillermo
Published: August 2023

Aquaculture in Bangladesh has expanded, diversified, and intensified over the last decades. Control of infectious diseases is critical for a successful and sustainable aquaculture. In this study, we examined the extent of use of probiotics in aquaculture of Bangladesh, using a questionnaire. Data were collected from 200 individual respondents from commercial fish farms located at Mymensingh, Rajshahi, Jashore, and Cumilla (50 from each) regions. A total of 88 different probiotics products from 36 companies, mostly imported, are used in the aquaculture in Bangladesh. Although in most cases the purpose of the use of probiotics is not clear for the farm owners, several representatives of different companies suggested the use of their different probiotic products, for different situations. Most of the farm owners responded that they used probiotics to get higher production by promoting the growth of fish. A considerable number of farm owners responded that probiotics reduced mortality as well as reduced gas emissions from the aquaculture ponds. Although the use of commercial probiotics varies from region to region, Pondcare and Safegut, the product of SK + F, are mostly used in aquaculture based on the responses (32% and 21% of respondents, respectively). To safeguard and clarify the value and effectiveness of these goods, the fish feed manufacturers and regulatory authorities should monitor their production, collection, and marketing.
A Review on Recent Advances in Matrix Converter Technology: Topologies, Control, Applications, and Future Prospects
Authors: Ali Mohammad , Iqbal Atif , Khalid Muhammad
Published: August 2023

Matrix converters (MCs) are AC-AC power conversion topologies widely explored and applied in the industry for their attractive features of sinusoidal input and output currents, considerable size reduction, and reliable operation due to the omission of bulky passive components. Considerable research has made this technology a serious contender to the indirect AC-DC-AC topologies in industrial applications. This paper comprehensively reviews the state-of-the-art MC technology and its prospects. Furthermore, it presents the advancements in the topological structures of direct/indirect MCs and their modulation and control algorithms over the past decade. It also reports the recent progress in multiphase direct/indirect MC structural and control structures. This paper is aimed at providing comprehensive information to the researchers and engineers on MC technology’s current industrial applications and the research scope as the world moves towards AI and digitalization.
Solving Nonlinear Fractional Models in Superconductivity Using the q-Homotopy Analysis Transform Method
Authors: Ali Khalid K. , Maneea M. , Mohamed Mohamed S.
Published: August 2023

The Ginzburg–Landau (GL) equation and the Ginzburg–Landau couple system are important models in the study of superconductivity and superfluidity. This study describes the q-homotopy analysis transform method (q-HATM) as a powerful technique for solving nonlinear problems, which has been successfully used with a set of mathematical models in physics, engineering, and biology. We apply the q-HATM to solve the Ginzburg–Landau equation and the Ginzburg–Landau coupled system and derive analytical solutions in terms of the q-series. Also, we investigate the convergence and accuracy of the obtained solutions. Our results show that q-HATM is a reliable and promising approach for solving nonlinear differential equations and provides a valuable tool for researchers in the field of superconductivity. Several graphs have been presented for the solutions obtained utilizing different levels of the fractional-order derivative and at various points in time.
Ursolic Acid Inhibits the Growth of Gastric Cancer by Targeting KLF4/YAP1
Authors: Xiang Fenfen , Zhang Mengzhe , Hao Wenbin , Liu Rongrong , Li Qian , Gu Qing , Zhu Zhaowei , Chen Zixi , Li Xiaoxiao , Kang Xiangdong , Wu Rong
Published: August 2023

Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor which has various mechanisms in different tumors. Ursolic acid (UA), a natural compound that exists in many herbs, is known to prevent tumor progression and has anticancer effects on many human cancers. The present study was to evaluate the antitumor effect of UA on gastric cancer (GC) through KLF4 and the Hippo pathway. Our data showed that UA inhibited the growth of GC in vivo and in vitro. UA treatment significantly increased the expression of KLF4 and decreased the expression of CTGF. The overexpression of KLF4 inhibited the proliferation and cell cycle of GC and decreased the expression of CTGF, whereas the knockdown of KLF4 attenuated the effects of UA. Furthermore, the inhibition of CTGF arrested tumor cells in G2/M which blocked proliferation progress. Confocal laser scanning and molecular simulation software MOE showed that KLF4 combined with YAP1 which may block the formation of the TEADs-YAP1 complex to interrupt the expression of CTGF and the downstream oncogenic process. In conclusion, UA can inhibit GC growth both in vivo and in vitro, and it activated KLF4 which may competitively bind with YAP1 against TEADs and block the oncogenic Hippo pathways.
A Novel Hybrid Approach for Power Quality Improvement in a Vehicle-to-Grid Setup Using Droop-ANN Model
Authors: Aurangzeb Muhammad , Xin Ai , Iqbal Sheeraz , Afzal Muhammad Zeshan , Kotb Hossam , AboRas Kareem M. , Ghadi Yazeed Yasin , Ngoussandou Bello-Pierre
Published: August 2023

The integration of electric vehicles (EVs) in the power grid has attracted considerable attention due to its potential benefits, such as demand response and power quality improvement. However, the intermittent and unpredictable nature of EVs’ charging and discharging behavior can cause significant challenges to the grid’s stability and power quality. This research study explores the use of a droop-ANN model to improve power quality in vehicle-to-grid (V2G) systems. The proposed approach integrates an artificial neural network (ANN) into the droop control technique to accurately predict the voltage and frequency of the charger. Through simulations, the model’s effectiveness in reducing power fluctuations and enhancing power quality was validated. The results indicate that the droop-ANN model significantly improves power quality across various battery state of charge (SoC) and charging/discharging scenarios. The findings highlight the potential of the droop-ANN model to enhance stability and reliability in V2G systems. Further research is needed to validate the model in real-world applications and explore its full potential. Overall, the droop-ANN model offers a promising solution for improving power quality in V2G systems.
Distinct Allelic Diversity of Plasmodium vivax Merozoite Surface Protein 3-Alpha (PvMSP-3α) Gene in Thailand Using PCR-RFLP
Authors: Kritsiriwuthinan Kanyanan , Ngrenngarmlert Warunee , Patrapuvich Rapatbhorn , Phuagthong Supaksajee , Choosang Kantima
Published: August 2023

Considering the importance of merozoite surface proteins (MSPs) as vaccine candidates, this study was conducted to investigate the polymorphism and genetic diversity of Plasmodium vivax merozoite surface protein 3-alpha (PvMSP-3α) in Thailand. To analyze genetic diversity, 118 blood samples containing P. vivax were collected from four malaria-endemic areas in western and southern Thailand. The DNA was extracted and amplified for the PvMSP-3α gene using nested PCR. The PCR products were genotyped by PCR-RFLP with Hha I and Alu I restriction enzymes. The combination patterns of Hha I and Alu I RFLP were used to identify allelic variants. Genetic evaluation and phylogenic analysis were performed on 13 sequences, including 10 sequences from our study and 3 sequences from GenBank. The results revealed three major types of PvMSP-3α, 91.5% allelic type A (∼1.8 kb), 5.1% allelic type B (∼1.5 kb), and 3.4% allelic type C (∼1.2 kb), were detected based on PCR product size with different frequencies. Among all PvMSP-3α, 19 allelic subtypes with Hha I RFLP patterns were distinguished and 6 allelic subtypes with Alu I RFLP patterns were identified. Of these samples, 73 (61%) and 42 (35.6%) samples were defined as monoallelic subtype infection by Hha I and Alu I PCR-RFLP, respectively, whereas 77 (65.3%) samples were determined to be mixed-allelic subtype infection by the combination patterns of Hha I and Alu I RFLP. These results strongly indicate that PvMSP-3α gene is highly polymorphic, particularly in blood samples collected from the Thai-Myanmar border area (the western part of Thailand). The combination patterns of Hha I and Alu I RFLP of the PvMSP-3α gene could be considered for use as molecular epidemiologic markers for genotyping P. vivax isolates in Thailand.
A Simple Ratiometric Electrochemical Aptasensor Based on Exonuclease III-Assisted Target Recycling for Ultrasensitive Detection of Prostate Specific Antigen
Authors: Wang Ping , Xie Yaoyao , Guan Zhimin , Ma Huikai , Xi Shoumin
Published: August 2023

Prostate specific antigen (PSA) is considered as an important biomarker in prostate cancer diagnosis. Herein, an ultrasensitive ratiometric electrochemical aptasensor was constructed for analyzing PSA. The ferrocene (Fc)-labeled thiolated hairpin probe 2 (Fc-HP2) was conjugated to the gold nanoparticles (AuNPs)-modified gold electrode (AuE) surface by Au-S bonds. With the introduction of PSA, the aptamer region of hairpin probe 1 (HP1) preferred to bind with PSA, and the rest of HP1 could hybridize with Fc-HP2 to form Fc-HP2/HP1/PSA complex with a blunt 3′ terminus, which triggered the exonuclease III (Exo III) cleavage process accompanied by Fc leaving from the electrode and recycling of HP1/PSA. The remaining Fc-HP2 fragments left on the electrode surface were then hybridized with methylene blue-labeled DNA (MB-DNA). This resulted in an enhancement of MB signal (IMB) and a decrement of Fc signal (IFc). Under the optimal conditions, the proposed aptasensor showed good analytical performance for sensitive detection of PSA with a linear range from 100 fg·mL−1 to 10 ng·mL−1 and a detection limit of 34.7 fg·mL−1. The fabricated aptasensor had been applied to detect PSA in diluted human serum samples and obtained satisfied results, suggesting it had great potential in clinical diagnosis.
Clinical Significance of Carnitine in the Treatment of Cancer: From Traffic to the Regulation
Authors: Farahzadi Raheleh , Hejazi Mohammad Saeid , Molavi Ommoleila , Pishgahzadeh Elahe , Montazersaheb Soheila , Jafari Sevda
Published: August 2023

Metabolic reprogramming is a common hallmark of cancer cells. Cancer cells exhibit metabolic flexibility to maintain high proliferation and survival rates. In other words, adaptation of cellular demand is essential for tumorigenesis, since a diverse supply of nutrients is required to accommodate tumor growth and progression. Diversity of carbon substrates fueling cancer cells indicate metabolic heterogeneity, even in tumors sharing the same clinical diagnosis. In addition to the alteration of glucose and amino acid metabolism in cancer cells, there is evidence that cancer cells can alter lipid metabolism. Some tumors rely on fatty acid oxidation (FAO) as the primary energy source; hence, cancer cells overexpress the enzymes involved in FAO. Carnitine is an essential cofactor in the lipid metabolic pathways. It is crucial in facilitating the transport of long-chain fatty acids into the mitochondria for β-oxidation. This role and others played by carnitine, especially its antioxidant function in cellular processes, emphasize the fine regulation of carnitine traffic within tissues and subcellular compartments. The biological activity of carnitine is orchestrated by specific membrane transporters that mediate the transfer of carnitine and its derivatives across the cell membrane. The concerted function of carnitine transporters creates a collaborative network that is relevant to metabolic reprogramming in cancer cells. Here, the molecular mechanisms relevant to the role and expression of carnitine transporters are discussed, providing insights into cancer treatment.
Autologous Plasma Gel as an Effective Method of Facial Volume Restoration and Skin Rejuvenation
Authors: Majewska Lidia
Published: August 2023

The primary aim of this retrospective study was to investigate the potential effectiveness of autologous platelet gel as a method for facial volume restoration and skin rejuvenation. High‐frequency ultrasonography was utilized to assess the outcomes of the treatment. The study included a cohort of ten female patients aged between 40 and 50 who actively participated in the research. They reported moderate‐to‐severe static and dynamic wrinkles, volume loss, thinning, and roughness of the skin. Each patient received one session of autologous platelet gel injections. The gel was prepared accordingly with the manufacturer’s (INNMEDIS, ATR™) instructions. Medium viscosity gel was injected into the superficial subdermal fat pads in the temples, as well as in the middle and lower face areas, to improve facial volume. A high‐frequency ultrasound (US) device was employed to quantify skin density, skin thickness, and the depth of nasolabial folds. The US images were captured at three time points: before gel administration, one month after the procedure, and three months after the procedure. The imaging focused on the nasolabial folds area to monitor changes and assess the effectiveness of the treatment over time. Based on the analyses, the use of autologous platelet gel is beneficial towards improving skin density and decreasing nasolabial fold depth. However, further research should be conducted into the gel’s effects on dermis thickness to achieve a stronger, more statistically significant conclusion. The level of satisfaction of the enrolled patients regarding their facial appearance was evaluated using the visual analogue scale (VAS). The VAS assessment revealed an average score of 4.1 before the commencement of the treatment, an average score of 7.9 one month after the treatment, and an average score of 7.5 three months following the treatment. The results indicate a significant increase in patient satisfaction following treatment completion. Autologous platelet gel appears to hold promise as a treatment option for volume replacement and skin rejuvenation, making it an attractive choice for individuals seeking natural skin treatments. Despite the encouraging findings from this observation, further validation is required through a larger controlled study to definitively confirm whether autologous platelet gel is indeed an effective method for volume replacement and skin rejuvenation.
Effectiveness and Cost of an Enhanced Mailed Fecal Test Outreach Colorectal Cancer Screening Program: Findings from the PROMPT Stepped-Wedge Trial
Authors: Coronado Gloria D. , Nyongesa Denis B. , Escaron Anne L. , Petrik Amanda F. , Thompson Jamie H. , Smith Dave , Davis Melinda M. , Schneider Jennifer L. , Rivelli Jennifer S. , Laguna Tanya , Leo Michael C.
Published: August 2023

Background:

Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening rates, yet little is known about how to optimize these programs for effectiveness and cost.

Methods:

PROMPT was a pragmatic, stepped-wedge, cluster-randomized effectiveness trial of mailed FIT outreach. Participants in the standard condition were mailed a FIT and received live telephone reminders to return it. Participants in the enhanced condition also received a tailored advance notification (text message or live phone call) and two automated phone call reminders. The primary outcome was 6-month FIT completion; secondary outcomes were any colorectal cancer screening completion at 6 months, implementation, and program costs.

Results:

The study included 27,585 participants (80% ages 50–64, 82% Hispanic/Latino; 68% preferred Spanish). A higher proportion of enhanced participants completed FIT at 6 months than standard participants, both in intention-to-treat [+2.8%, 95% confidence interval (CI; 0.4–5.2)] and per-protocol [limited to individuals who were reached; +16.9%, 95% CI (12.3–20.3)] analyses. Text messages and automated calls were successfully delivered to 91% to 100% of participants. The per-patient cost for standard mailed FIT was $10.84. The enhanced program's text message plus automated call reminder cost an additional $0.66; live phone calls plus an automated call reminder cost an additional $10.82 per patient.

Conclusions:

Adding advance notifications and automated calls to a standard mailed FIT program boosted 6-month FIT completion rates at a small additional per-patient cost.

Impact:

Enhancements to mailed FIT outreach can improve colorectal cancer screening participation. Future research might test the addition of educational video messaging for screening-naïve adults.
Data from Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial
Authors: Mellinghoff Ingo K. , Penas-Prado Marta , Peters Katherine B. , Burris Howard A. , Maher Elizabeth A. , Janku Filip , Cote Gregory M. , de la Fuente Macarena I. , Clarke Jennifer L. , Ellingson Benjamin M. , Chun Saewon , Young Robert J. , Liu Hua , Choe Sung , Lu Min , Le Kha , Hassan Islam , Steelman Lori , Pandya Shuchi S. , Cloughesy Timothy F. , Wen Patrick Y.
Published: August 2023

AbstractPurpose:
Lower grade gliomas (LGGs) are malignant brain tumors. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor grade is associated with contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.
Patients and Methods:
We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154.
Results:
Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG in patients with nonenhancing glioma was 18% (one partial response, three minor responses). The median progression-free survival was 36.8 months [95% confidence interval (CI), 11.2–40.8] for patients with nonenhancing glioma and 3.6 months (95% CI, 1.8–6.5) for patients with enhancing glioma. Exploratory evaluation of tumor volumes in patients with nonenhancing glioma showed sustained tumor shrinkage in multiple patients.
Conclusions:
Vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing mIDH LGG.
Immune Marker Spatial Distribution and Clinical Outcome after PD-1 Blockade in Mismatch Repair–deficient, Advanced Colorectal Carcinomas
Authors: Saberzadeh-Ardestani Bahar , Graham Rondell P. , McMahon Sara , Ahanonu Eze , Shi Qian , Williams Crystal , Hubbard Antony , Zhang Wenjun , Muranyi Andrea , Yan Dongyao , Jin Zhaohui , Shanmugam Kandavel , Sinicrope Frank A.
Published: August 2023

Purpose:

Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) interaction has led to durable responses in fewer than half of patients with mismatch repair–deficient (MMR-d) advanced colorectal cancers. Immune contexture, including spatial distribution of immune cells in the tumor microenvironment (TME), may predict immunotherapy outcome.

Experimental Design:

Immune contexture and spatial distribution, including cell-to-cell distance measurements, were analyzed by multiplex immunofluorescence (mIF) in primary colorectal cancers with d-MMR (N = 33) from patients treated with anti–PD-1 antibodies. By digital image analysis, density, ratio, intensity, and spatial distribution of PD-L1, PD-1, CD8, CD3, CD68, LAG3, TGFβR2, MHC-I, CD14, B2M, and pan-cytokeratin were computed. Feature selection was performed by regularized Cox regression with LASSO, and a proportional hazards model was fitted to predict progression-free survival (PFS).

Results:

For predicting survival among patients with MMR-d advanced colorectal cancer receiving PD-1 blockade, cell-to-cell distance measurements, but not cell densities or ratios, achieved statistical significance univariately. By multivariable feature selection, only mean number of PD-1+ cells within 10 μm of a PD-L1+ cell was significantly predictive of PFS. Dichotomization of this variable revealed that those with high versus low values had significantly prolonged PFS [median not reached (>83 months) vs. 8.5 months (95% confidence interval (95% CI), 4.7–NR)] with a median PFS of 28.4 months for all patients [adjusted HR (HRadj) = 0.14; 95% CI, 0.04–0.56; P = 0.005]. Expression of PD-1 was observed on CD8+ T cells; PD-L1 on CD3+ and CD8+ T lymphocytes, macrophages (CD68+), and tumor cells.

Conclusions:

In d-MMR colorectal cancers, PD-1+ to PD-L1+ receptor to ligand proximity is a potential predictive biomarker for the effectiveness of PD-1 blockade.
Supplementary table 1 from FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: August 2023

Supplementary table 1
ANXA1 Promotes Tumor Immune Evasion by Binding PARP1 and Upregulating Stat3-Induced Expression of PD-L1 in Multiple Cancers
Authors: Xiao Ding , Zeng Ting , Zhu Wei , Yu Zheng-Zheng , Huang Wei , Yi Hong , Lu Shan-Shan , Feng Juan , Feng Xue-Ping , Wu Di , Wen Qi , Zhou Jian-Hua , Yuan Li , Zhuang Wei , Xiao Zhi-Qiang
Published: August 2023

The deregulation of Annexin A1 (ANXA1), a regulator of inflammation and immunity, leads to cancer growth and metastasis. However, whether ANXA1 is involved in cancer immunosuppression is still unclear. Here, we report that ANXA1 knockdown (i) dramatically downregulates programmed cell death-ligand 1 (PD-L1) expression in breast cancer, lung cancer, and melanoma cells; (ii) promotes T cell–mediated killing of cancer cells in vitro; and (iii) inhibits cancer immune escape in immune-competent mice via downregulating PD-L1 expression and increasing the number and killing activity of CD8+ T cells. Mechanistically, ANXA1 functioned as a sponge molecule for interaction of PARP1 and Stat3. Specifically, binding of ANXA1 to PARP1 decreased PARP1’s binding to Stat3, which reduced poly(ADP-ribosyl)ation and dephosphorylation of Stat3 and thus, increased Stat3’s transcriptional activity, leading to transcriptionally upregulated expression of PD-L1 in multiple cancer cells. In clinical samples, expression of ANXA1 and PD-L1 was significantly higher in breast cancer, non–small cell lung cancer, and skin cutaneous melanoma compared with corresponding normal tissues and positively correlated in cancer tissues. Moreover, using both ANXA1 and PD-L1 proteins for predicting efficacy of anti–PD-1 immunotherapy and patient prognosis was superior to using individual proteins. Our data suggest that ANXA1 promotes cancer immune escape via binding PARP1 and upregulating Stat3-induced expression of PD-L1, that ANXA1 is a potential new target for cancer immunotherapy, and combination of ANXA1 and PD-L1 expression is a potential marker for predicting efficacy of anti–PD-1 immunotherapy in multiple cancers.
Supplementary Video 1B from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Video 1B shows representative images of a naltrindole-treated spheroid. Scale bar: 200 µm, number at top left: days post-implantation.
Supplementary Table 6 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Table 6 shows Sorting events for each cell included in the final data set
Supplementary Figure 2 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Figure 2 shows clustering of 44 single cells and their gene expression heat map based on 230 differentially expressed genes
The Ghent Psychotherapy Study: A Pragmatic, Stratified, Randomized Parallel Trial into the Differential Efficacy of Psychodynamic and Cognitive-Behavioral Interventions in Dependent and Self-Critical Depressive Patients
Authors: Meganck Reitske , Desmet Mattias , Van Nieuwenhove Kimberly , De Smet Melissa , Hennissen Vicky , Truijens Femke , De Geest Rosa , Hermans Goedele , Bockting Claudi , Norman Ufuoma Angelica , Loeys Tom , Inslegers Ruth , Van den Abeele Tim , Baeken Chris , Vanheule Stijn
Published: August 2023

Introduction: Different types of psychotherapy are effective for treating major depressive disorder across groups yet show large within-group differences. Patient personality style is considered a potentially useful variable for treatment matching. Objective: This study is the first experimental test of the interaction between therapeutic approach and patients’ dependent versus self-critical personality styles. Methods: A pragmatic stratified parallel trial was carried out with 100 adult patients diagnosed with DSM-IV-TR major depressive disorder. They were randomly assigned to short-term (16–20 sessions) cognitive behavioral therapy (CBT) or short-term psychodynamic psychotherapy (STPP). Patients were assessed at baseline, during therapy, post-therapy, and at 3- and 6-month follow-up. Primary outcome is depression severity measured by the Hamilton Rating Scale for Depression posttreatment. Primary analysis was by intention to treat. This trial is registered with the ISRCTN registry (www.isrctn.com), number ISRCTN17130982. Results: The intention-to-treat sample consisted of 100 participants; 40 with self-critical and 60 with dependent personality styles were randomized to either CBT (n = 50) or STPP (n = 50). We observed no interaction effect (−0.34 [−6.14, 5.46]) between therapy and personality style and found no evidence for a difference in effectiveness between the treatments in general in terms of symptom reduction and maintained benefits at 6-month follow-up. Conclusion: We found no evidence that dependent versus self-critical personality styles moderate the relation between treatment and outcome in depression. Research using individual patient data could gain further insight into why specific therapeutic approaches work better for specific patients.
Safety and Efficacy of Autologous Melanocyte/Keratinocyte Transplantation in Patients with Refractory Stable Vitiligo
Authors: Shahbazi Atefeh , Abedi Valugerdi Manuchehr , Kazemi Sepide , Samadi Kochaksaraei Sarvenaz , Naseh Mohammad Hassan , Aghdami Nasser , Sadeghi Behnam
Published: August 2023

Background: Vitiligo is a common depigmentation skin disease associated with significant psychosocial morbidity and profound effect on the quality of life. The treatment of vitiligo is still a major challenge in the field of dermatology. Currently, topical steroids, calcineurin inhibitors, ultraviolet phototherapy, surgery, and cultured and non-cultured epidermal melanocyte transplantation are used for the treatment of vitiligo. However, the effectiveness of these treatment modalities is limited by the lack of response, long-term treatment periods, high cost, and inevitable adverse effects. Objectives: In this study, we aimed to evaluate the efficacy of intraepidermal injection of autologous non-cultured melanocytes and keratinocytes as an alternative therapy for the refractory and stable (RS) vitiligo. Methods: The treatment procedure was performed on thirty-nine RS vitiligo patients. The autologous skin grafts obtained from the buttock area and epidermis were separated from dermis using dispase. Single-cell autologous melanocytes and keratinocytes were prepared from the epidermis by trypsin/ethylene diamine tetra acetic acid and injected at the concentration of 100–400 × 103 cells/cm2, intra-epidermally to the selected vitiligo lesions. Vitiligo re-pigmentation was monitored employing photography. Photographs were taken prior to and 2, 4, and 6 months after the cell transplantation. Improvement of the skin depigmentation was classified as follows: <25% as minimal response, 26–50% as moderate response, 51–75% as good response, and finally 76–100% as excellent response. Results: Cell infusion appeared to be safe as none of the patients exhibited any adverse effects. At the end of the sixth month follow-up period, of the treated patients, 12.8% demonstrated an excellent response, 36% exhibited a good response, and 51.2% showed a moderate to minimal response to the administered therapy. Obtained significant p value for Wilcoxon test over the checkpoints at 2nd, 4th, and 6th month (p = 0.03, 0.04, and 0.039, respectively) post-cell transplantation confirmed notable growing trend in the re-pigmentation. Conclusion: Our findings provide a strong support for the therapeutic efficacy of autologous non-cultured melanocytes and keratinocytes in patients with RS vitiligo.
The Impact of Pregnancy on Diabetic Retinopathy: A Single-Site Study of Clinical Risk Factors
Authors: Rathinavelu Jay , Sarvepalli Swara M. , Bailey Beth , D'Alessio David , Hadziahmetovic Majda
Published: August 2023

Introduction: This study aimed to provide information on modifiable and non-modifiable risk factors for the progression and development of diabetic retinopathy (DR) and diabetic macular edema (DME). This retrospective chart review case-control study was designed to provide perspective on clinical variables. Methods: Single-center study analysis was completed with chart review, identifying 50 patients (100 eyes) ultimately included in the final analysis. Included patients were women with type 1 or 2 diabetes that entered prenatal care and had a delivery from January 2010 to December 2022. The primary outcome measure was clinical variables between progression and no progression groups. Data were analyzed via χ2 analysis and independent samples t test when appropriate. Significantly different variables were further analyzed by binary logistic regression. Results: The DR progression group had significantly higher prepregnancy HbA1c levels (9.9) when compared to the no progression group (8.5, p value 0.028). DR progression group also had higher rates (51.9%) of full-term births. The DME progression group had significantly higher rates of type 2 diabetics (100%) compared to the no progression group (30.9%, p value 0.029). Hypertension treatment before (81.8%; p value 0.008) pregnancy was also more common in the DME progression group. Intravitreal injections were more common in patients with visual acuity deterioration (26.7%, p value 0.046). The average number of fetal complications was significantly higher in the visual acuity non-worsening group (1.1) compared to the progression group (0.5, p value 0.04). These variables were not statistically significant after entry into multivariate analysis. Discussion: Severity and treatment of retinopathy before pregnancy, type of diabetes, and blood pressure control are all significant factors affecting the progression and development of severe ocular complications in pregnancy.
СИНДРОМ ВЗАЄМНОГО ОБТЯЖЕННЯ ПРИ ХВОРОБІ ЖИЛЬБЕРА
Authors: Процайло М. Д. , Процайло О. М.
Published: August 2023

Мета дослідження – загострити увагу на комплексному обстеженні дітей з хворобою Жильбера. Ця «доброякісна» хронічна недуга поєднується з низкою розладів розвитку дітей – синдром взаємного обтяження, що необхідно враховувати при плануванні профілактичних та лікувальних заходів.

Матеріали та методи. Досліджено два сімейні випадки хвороби Жильбера. Вивчали сімейний анамнез шляхом співбесіди з дітьми, батьками, аналізували виписки амбулаторних та стаціонарних документів, результати клінічних обстежень, даних біохімічних лабораторних, рентгенологічних, ультрасонографічних, медико-генетичних результатів. Особливу увагу надавали скаргам, погрішностям дієти, рухливого способу життя.

Результати дослідження та їх обговорення. Описано сімейні випадки із практики хвороби Жильбера. Головною ознакою хвороби Жильбера є жовтизна шкіри, долонь, стоп, носо-губного трикутника, пахових ділянок, іктеричність склер, яка мала перемінний характер. Хворобу діагностували в хлопчиків (вік 13–14 років) випадково з приводу інших обстежень – хронічного гастриту, дисфункції жовчного міхура, підшлункової залози, головного мозку. Точний діагноз був встановлений після молекулярного обстеження – (гомозиготне носійство) Т1, А1. При загостренні ХЖ спостерігалися нудота, блювання, печія, метеоризм, біль у правому підребер’ї, загальне нездужання, головний біль, підвищене потовиділення, серцебиття, розлади сну, астенодепресивний синдром, м’язовий біль, безпричинний страх, напади паніки. Головними причинами загострення хвороби Жильбера були порушення дієти, фізичні навантаження на тлі статевого дозрівання. В обох клінічних випадках хвороба Жильбера поєднувалася з низкою природжених захворювань лицевого черепа, грудної клітки, стоп, хребетного стовпа, гіпереластичністю зв’язкового апарату скелета, ретинопатією очей, високорослістю (фенотип хвороби Марфана), множинними невусами шкірних покровів.

Висновки. Генетичний дефект довгого плеча 37 смужки 2 хромосоми, що відповідає за обмін білірубіну, очевидно, опосередковано або напряму негативно впливає на морфогенез усього організму дитини і проявляється різними клінічними захворюваннями – синдром взаємного обтяження. Надлишковий непрямий, токсичний білірубін, внаслідок притаманної йому жиророзчинності потрапляє до центральної нервової системи, підшлункової залози, кісткового мозку, де спричиняє функціональні розлади з відповідними клінічними проявами.
ПРОФІЛАКТИКА ПРЕЕКЛАМПСІЇ: СУЧАСНИЙ СТАН ПРОБЛЕМИ
Authors: Гусєва А. Є. , Кирильчук М. Є. , Медведь В. І.
Published: August 2023

Прееклампсія – це класичне вагітність-асоційоване захворювання, що має негативний вплив як на вагітну жінку, так і на плід. Важливо запобігати захворюванню заради покращення перинатальних результатів. Зазвичай жінкам групи ризику призначають ацетилсаліцилову кислоту, а тим, хто у раціоні харчування отримують недостатньо кальцію, додають препарати кальцію. Проте через їх недостатню ефективність пошуки нових альтернативних методів активно продовжуються. Найбільшої уваги серед них заслуговують застосування низькомолекулярних гепаринів, метформіну, правастатину, вітамінів D, C та E, фолієвої кислоти, магнію, омега-3 поліненасичених жирних кислот, фізичної активності або, навпаки, фізичного відпочинку. Низькомолекулярний гепарин має сприятливий вплив на судини, вірогідно, він може принести користь жінкам із найвищим ризиком ранньої прееклампсії. Клінічні дослідження показали, що метформін може зменшити ризик гестаційної гіпертензії у жінок з гестаційним діабетом і може запобігти прееклампсії. Правастатин знижує секрецію ендотеліну-1 та розчинної fms-подібної тирозинкінази-1 в ендотеліальних клітинах пупкової вени людини та мікросудинних клітинах матки. Вітамін D може бути потужним ендокринним супресором та регулювати ренін-ангіотензинову систему, яка відіграє важливу роль в урегулюванні артеріального тиску. Оскільки одним із потенційних механізмів розвитку прееклампсії є окислювальний стрес – додавання антиоксидантів може зменшити тяжкість захворювання або запобігти його появі. Вітаміни-антиоксиданти сприяють стабілізації реактивних вільних радикалів, які поводяться як перша лінія захисту від вільних радикалів і перекисного окислення ліпідів. Підвищений рівень гомоцистеїну в крові є причиною гестаційної гіпертензії та прееклампсії, фолієва кислота здатна знизити його рівень. Приймання пероральних добавок магнію може знизити ризик прееклампсії, проте цей ефект ймовірно помітніший у вагітних жінок із групи високого ризику. У мета-аналізі було показано, що приймання добавок омега-3 знижує ризик прееклампсії на 16 %.  Фізичні вправи можуть зменшити ризик гестаційної гіпертензії та прееклампсії на ≈30 і 40 % відповідно. Вважається, що відпочинок є корисним для жінок із підвищеним ризиком прееклампсії, у тому числі з нормальним артеріальним тиском. Усі альтернативні профілактичні методи за диференційованого підходу можуть знайти місце у стратегії профілактики прееклампсії.
РАК МОЛОЧНОЇ ЗАЛОЗИ, АСОЦІЙОВАНИЙ З МУТАЦІЄЮ 5382INSC У ГЕНІ BRCA1
Authors: Лисенко С. А. , Березовський А. М. , Некращук О. П. , Стойка Я. В. , Людкевич Г. П. , Дністріянська А. П.
Published: August 2023

Мета дослідження – висвітлити клінічний випадок пацієнтки, яка хворіла на рак молочної залози, асоційований з мутацією 5382insC у гені BRCA1.

Матеріали та методи. Проведено динамічне обстеження пацієнтки, яка хворіла на рак молочної залози. Пошук актуальної інформації щодо механізмів розвитку захворювання, асоційованого з мутаціями в гені BRCA, проводили в наукометричних базах, зокрема PubMed, Google Scholar, Web of Science, Scopus.

Результати дослідження та їх обговорення. Після діагностики раку молочної залози пацієнтці було проведено чотири курси хіміотерапії та органозберігальну операцію. Після лікування п’ять років спостерігалася ремісія, але згодом у пацієнтки було діагностовано рак яєчників. З приводу цього їй було рекомендовано провести діагностику на наявність мутації в гені BRCA. В результаті було виявлено наявність поліморфізму 5382insC вищезгаданого гену. Відомо, що для пацієнтів з даною мутацією рекомендовано інші схеми лікування, зокрема призначення інгібіторів полі (ADP-рибозо) полімерази, які є більш ефективними в пацієнток із раком молочної залози, асоційованим з мутаціями в гені BRCA. Також даним пацієнтам рекомендуються радикальні операції з мастектомією і видаленням придатків. Дане лікування могло би бути більш ефективним та запобігти розвитку раку яєчників через п’ять років. Пацієнтка мала двох доньок, яким був проведений такий самий аналіз і в результаті було виявлено, що старша дочка є носієм поліморфізму 5382insC. Їй було рекомендовано проводити щорічні планові обстеження для раннього виявлення патології у разі маніфестації захворювання та дотримуватися заходів задля запобігання розвитку раку молочної залози.

Висновки. Визначення поліморфізмів у груп ризику розвитку раку молочної залози, зокрема наявність в сімейному анамнезі хворих на дане захворювання, є доцільним задля запобігання розвитку даної патології, а також для призначення відповідної терапії, задля запобігання рецидивам.