bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Downstream Vortex Generators on Film Cooling a Flat Plate Fed by Crossflow
Authors: Straub Douglas , Weber Justin , Roy Arnab , Lee Chien-Shing , Shih Tom I-P. 
Published: December 2023

Abstract
Counter-rotating vortices, formed by the interaction of film-cooling jets and the hot gas flow, adversely affect the performance of conventional film-cooling designs. Downstream vortex generators have been shown to improve cooling effectiveness by mitigating the effects of the counter-rotating vortices and by deflecting the cooling jet laterally. In this study, computational and experimental methods were used to examine how cylindrical film-cooling holes (D = 3.2 mm, L/D = 6, p/D = 3, α = 30 deg) with and without downstream vortex generators perform when the coolant supply channel is perpendicular to the direction of the hot gas. For this study, the hot gas had a temperature of 650 K and an average Mach number of 0.23. The hot-gas-to-coolant temperature ratio was 1.9, and two blowing ratios (0.75 and 1.0) were studied. Results from the computational fluid dynamics study show how crossflow affects the interaction between the film-cooling jet and hot gas flow with and without downstream vortex generators. The experimental measurements were based on infrared thermography in a conjugate heat transfer environment. Results were obtained for film-cooling performance in terms of overall effectiveness, film effectiveness, and local heat transfer coefficients. The downstream vortex generators can increase the laterally averaged effectiveness by a factor of 1.5 relative to cylindrical holes, but this higher performance is restricted to low crossflow velocities and higher blowing ratios.
Rapid detection of
Mycobacterium tuberculosis
in sputum using CRISPR-Cas12b combined with cross-priming amplification in a single reaction
Authors: Peng Lijun , Fang Tingting , Cai Qingshan , Li Hao , Li Huanyu , Sun Haiqiong , Zhu Mingzhi , Dai Lingshan , Shao Yanqin , Cai Long 
Published: December 2023

ABSTRACT

The diagnosis of tuberculosis (TB) still lacks a rapid, user-friendly method. Recent research has revealed the significant diagnostic potential of the CRISPR system in TB detection. However, most current CRISPR-based diagnostic tests involve a two-step process, including nucleic acid amplification followed by CRISPR-guided sequence-specific detection, which raises concerns about cross-contamination and operational complexity. In this study, we introduced TB One-Pot, which combines CRISPR-Cas12b-mediated trans-cleavage with cross-priming amplification, enabling one-pot detection in a single reaction. TB One-Pot achieves a minimum detection limit of 0.8 copies/μL for H37Rv genomic DNA and a quantification limit of 50 CFU/mL. It exhibited no cross-reactivity with common nontuberculous mycobacteria and respiratory pathogens. TB One-Pot employs real-time fluorescence, enabling the process from nucleic acid extraction to result in reporting in just 80 minutes. It also includes a UV-based visual check, eliminating the need for specialized equipment. A retrospective cohort study evaluated the diagnostic performance of this method using a composite reference standard as the gold standard. TB One-Pot demonstrated a sensitivity of 67.2% and an area under the curve (AUC) of 0.820 in sputum samples, surpassing conventional methods such as culture and acid-fast bacilli (AFB) smear. Comparative analysis with Xpert (sensitivity:64.2%, AUC:0.821) showed no statistically significant difference (
P
> 0.05). TB One-Pot exhibited a specificity of 96.7%, similar to Xpert, culture, and AFB smear (
P
> 0.05). TB One-Pot excels in speed, sensitivity, specificity, and practical requirements. Ongoing refinements aim to improve sensitivity, making it a promising solution for overcoming limitations in molecular TB diagnosis, particularly in resource-constrained settings.

IMPORTANCE
In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.
Genome sequences of four colistin-resistant ESKAPE bacterial strains isolated from patients within the same hospital
Authors: Tunç Merve Nur , Guéneau Virgile , Loux Valentin , del Campo Rosa , Carballido Lopez Rut , Briandet Romain 
Published: December 2023

ABSTRACT
The genomes of four clinical Gram-negative ESKAPE bacterial strains highly resistant to the last-resort antibiotic colistin were sequenced and analyzed. The strains were found to carry multidrug-resistant genes besides colistin-resistant genes.
Introduction of allergenic food to infants and allergic and autoimmune conditions: a systematic review and meta-analysis
Authors: Tuballa Alana , Connell Danique , Smith Mary , Dowsett Caroline , O’Neill Hayley , Albarqouni Loai 
Published: December 2023

ObjectivesTo evaluate the effects of early introduction to allergenic foods compared with late introduction and its impact on food allergy, food sensitisation and autoimmune disease risk.Design and settingThe systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Four electronic databases (MEDLINE, CENTRAL, EMBASE and CINAHL) were searched from inception till 24 October 2022 using keywords and MeSH without limitations on publication’s language or date. A forward and backwards citation analysis was also conducted. Risk of bias was assessed by three authors independently, in pairs using the Cochrane Risk of Bias Tool 2. Findings were narratively and quantitatively synthesised. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.ParticipantsRandomised controlled trials (RCTs) on allergenic food introduction prior to 12 months of age that evaluated its effect on the development of allergic and autoimmune conditions.InterventionEarly introduction to allergenic foods to infants diet.Main outcome measures(1) Food allergy and sensitisation with main measures including oral food challenge, specific-IgE, skin prick testing, physician assessment and parental reporting. (2) Allergic and autoimmune conditions such as asthma and eczema.ResultsOf the 9060 identified records, we included 12 RCTs. We found high to moderate certainty evidence suggested that early introduction of allergen-containing foods reduces the risk of multiple food allergies (4 RCTs, 3854 participants, RR 0.49, 95% CI 0.33 to 0.74), egg (8 RCTs, 5193 participants, RR 0.58, 95% CI 0.44 to 0.78), peanut (3 RCTs, 4183 participants, RR 0.31, 95% CI 0.17 to 0.54) and atopic dermatitis or eczema (4 RCTs, 3579 participants, RR 0.88, 95% CI 0.78 to 1.00). Effects on other food allergies including milk, wheat, fish; autoimmune conditions, and food sensitisation are very uncertain and informed by low and very-low certainty evidence. No important subgroup differences were observed related to baseline risk of allergy and age at introduction. Sensitivity analyses limited to low risk of bias RCTs showed similar results.ConclusionsThis systematic review and meta-analysis shows that early introduction of allergen-containing food from 4 to 12 months of age, was associated with lower risk of multiple food allergy and eczema. Further research on other allergenic foods, and their long-term impact on food allergy and autoimmune risk is essential for enhancing our understanding on development of these conditions and guiding future clinical recommendations.PROSPERO registration numberCRD42022375679.
Gender disparities in clinical outcomes of urothelial carcinoma linked to X chromosome geneKDM6Amutation
Authors: Liu Zhaopei , Jin Kaifeng , Xu Ziyue , Xu Jingtong , Su Xiaohe , Li Bingyu , Liu Ge , Liu Hailong , Chang Yuan , Wang Yiwei , Xu Le , Zhang Weijuan , Wang Zewei , Zhu Yu , Xu Jiejie 
Published: December 2023

ObjectiveKDM6A, a representative tumour suppressor gene with sex bias, is frequently altered in urothelial carcinoma (UC). The specific impacts ofKDM6Amutations on gender-based clinical outcomes in UC remain poorly understood.Methods and analysisWe enrolled 2438 patients with UC from seven independent real-world cohorts possessing comprehensive clinical and genomic data. Point mutations and homozygous deletions ofKDM6Aare categorised asKDM6AMut. We assessed the correlation between gender disparities in relation toKDM6Astatus and clinical outcomes, as well as genomic and immunological profiles.ResultsKDM6Amutations were identified in 679 of the 2306 patients with UC (29.4%), with 505 of 1768 (28.6%) in men and 174 of 538 (32.3%) in women.KDM6Amutations correlated with enhanced overall survival exclusively in male patients but were linked to improved outcomes following adjuvant chemotherapy only in female patients. Concerning immunotherapeutic responses,KDM6AMutmale patients displayed the most favourable clinical outcomes, whereasKDM6AMutfemale patients demonstrated the least favourable outcomes. Independent of gender variations,KDM6AMutpatients exhibited heightened androgen receptor and diminished oestrogen receptor 1 filtered regulon activity. Additionally,KDM6AMutmale patients showed increased infiltration of T cells, cytotoxic T cells and NK cells with enriched neoantigens, in contrast toKDM6AMutfemale patients who manifested a more pronounced angiogenesis signature.ConclusionOur findings offer preliminary clinical evidence accentuatingKDM6Aalterations as a promising prognostic and predictive biomarker while elucidating the gender disparities observed in patients with UC.
Impact of cellular morphology and three-tiered nuclear grade on progression of conventional renal cell carcinoma
Authors: Domonkos Lilla , Yusenko Maria , Kovacs Gyula , Peterfi Lehel 
Published: December 2023

Aims and methodsThe aims of this study were to evaluate the prognostic impact of cytomorphology and three-tiered grading on tumour-free survival of patients with conventional renal cell carcinoma (cRCC). Formalin-fixed, paraffin-embedded samples from 710 patients were assessed and the results were evaluated according to the clinical data.ResultsKaplan-Meier regression model showed that 90.9% of patients with clear cell, and 50.9% with pure eosinophilic cRCC were free of metastasis during follow-up. The three-triered grading showed a good correlation with progression as 95.2% of patients with of G1 tumours, 66.1% with G2 tumours and only 25.3% with G3 tumours were tumour free (p<0.001). The grading was correlated with cytomorphology and coagulation necrosis. In multivariate analysis, tumour grade and stage were independent prognostic markers (p<0.001).ConclusionsThe three-tiered grading predicts the progression of cRCC irrespectively of cytomorphology. However, the cytomorphology and necrosis show a good correlation with three-tiered grading in estimate disease progression.
Recontact to return new or updatedPALB2genetic results in the clinical laboratory setting
Authors: Panchal Seema , Mahajan Radhika , Aujla Navneet , McKay Paul , Casalino Selina , Di Gioacchino Vanessa , Charames George S , Lefebvre Maude , Metcalfe Kelly A , Akbari Mohammad Reza , McCuaig Jeanna Marie , Lerner-Ellis Jordan 
Published: December 2023

ObjectiveThe purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients.MethodsGenetic testing was conducted on 2977 individuals originally referred forBRCA1andBRCA2hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted toPALB2for the purposes of this study. A patient recontact decision tree was developed to assist in the returning of updated genetic test results to clinics and patients.ResultsNovel clinically actionable pathogenic variants were identified in thePALB2gene in 18 participants (0.6%), the majority of whom were recontacted with their new or updated genetic test results. Eight individuals were unable to be recontacted; five individuals had already learnt about their new or updated findings from genetic testing outside the context of this study; three individuals prompted cascade testing in family members; two individuals were deceased.ConclusionNovel pathogenic variants inPALB2were identified in 18 individuals through retrospective gene panel testing. Recontacting these individuals regarding these new or updated findings had a range of outcomes. The process of conveying genomic results within this framework can be effectively accomplished while upholding patient autonomy, potentially leading to advantageous outcomes for patients and their families.
Protective Effects of Sanyar Prebiotic on Immunity and Tissue Changes of Common Carp (Cyprinus carpio) Exposed to CuSO4 Stress
Authors: Rajani Ramezan , Farhangi Mohammad , Jafaryan Hojjatallah , Adineh Hossein , Alizadeh Maryam 
Published: December 2023

Prebiotics, as feed additives, can activate the antioxidant and immune systems of fish and significantly improve the survival of aquaculture animals in stressful conditions. The exposure of fish to copper sulfate leads to oxidative stress, suppression of the immune system, and destruction of vital body tissues. This study aimed to investigate the protective effects of Sanyar prebiotic on the immunity and tissue changes of common carp (Cyprinus carpio) exposed to CuSO4 stress. Two hundred common carp fish with an average weight of 12.33 ± 0.93 g were stocked in four treatments (triplicates) for 60 days. The experimental treatments contained Sanyar commercial prebiotics in 100 g of food, which included P1 (1 ml prebiotic liquid), P2 (0.1 g prebiotic powder), P3 (0.5 ml liquid and 0.05 g powder), and treatment C (control treatment without any additives). At the end of the experimental period, the fish were exposed to acute toxicity of Cu (0.1 m/l) for 96 hours. Gill, kidney, and liver tissue samples were collected and evaluated after 96 hours. According to the results obtained, there were significant differences in specific growth rate (SGR) and final weight (

p

< 0.05). The lowest feed conversion ratio (FCR) was observed in the Sanyar treatments (1.56 ± 0.37), which had a significant difference from the control treatment (1.85 ± 0.35) (

p

< 0.05). The results showed that immunity indices such as lysozyme, cortisol, and ACH50 increased in the experimental treatments compared to the control treatment (

p

< 0.05). The highest and lowest lysozyme activities were observed in P2 (16.35 ± 0.57) and control treatments (13.15 ± 1.00), respectively (

p

< 0.05). Generally, no significant difference was observed between growth and nutrition indices in Sanyar treatments (

p

< 0.05). Symptoms of kidney, liver, and gill tissue damage were reported from mild (hyperemia and infiltration of inflammatory cells) to severe (hemorrhage and necrosis). The lowest severity of tissue damage was observed in the treatments fed with Sanyar food supplement. In general, the results of this study showed that the addition of Sanyar prebiotic to the diet of common carp improves the growth indicators and immune response and can also be beneficial in increasing fish resistance to copper toxicity.
Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven 
Published: December 2023

Abstract

Purpose:
This phase Ib open-label, multicenter, platform study (NCT02646748) explored safety, tolerability, and preliminary activity of itacitinib (Janus kinase 1 inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ inhibitor) in combination with pembrolizumab [programmed death-1 (PD-1) inhibitor].

Experimental Design:
Patients with advanced or metastatic solid tumors with disease progression following all available therapies were enrolled and received itacitinib (Part 1 initially 300 mg once daily) or parsaclisib (Part 1 initially 10 mg once daily; Part 2 all patients 0.3 mg once daily) plus pembrolizumab (200 mg every 3 weeks).

Results:
A total of 159 patients were enrolled in the study and treated with itacitinib (Part 1, n = 49) or parsaclisib (Part 1, n = 83; Part 2, n = 27) plus pembrolizumab. The maximum tolerated/pharmacologically active doses were itacitinib 300 mg once daily and parsaclisib 30 mg once daily. Most common itacitinib treatment-related adverse events (TRAE) were fatigue, nausea, and anemia. Most common parsaclisib TRAEs were fatigue, nausea, diarrhea, and pyrexia in Part 1, and fatigue, maculopapular rash, diarrhea, nausea, and pruritus in Part 2. In patients receiving itacitinib plus pembrolizumab, four (8.2%) achieved a partial response (PR) in Part 1. Among patients receiving parsaclisib plus pembrolizumab, 5 (6.0%) achieved a complete response and 9 (10.8%) a PR in Part 1; 5 of 27 (18.5%) patients in Part 2 achieved a PR.

Conclusions:
Although combination of itacitinib or parsaclisib with pembrolizumab showed modest clinical activity in this study, the overall response rates observed did not support continued development in patients with solid tumors.

Significance:
PD-1 blockade combined with targeted therapies have demonstrated encouraging preclinical activity. In this phase I study, patients with advanced solid tumors treated with pembrolizumab (PD-1 inhibitor) and either itacitinib (JAK1 inhibitor) or parsaclisib (PI3Kδ inhibitor) experienced limited clinical activity beyond that expected with checkpoint inhibition alone and showed little effect on T-cell infiltration in the tumor. These results do not support continued development of these combinations.
FASN Gene Methylation is Associated with Fatty Acid Synthase Expression and Clinical-genomic Features of Prostate Cancer
Authors: Dairo Oluwademilade , DePaula Oliveira Lia , Schaffer Ethan , Vidotto Thiago , Mendes Adrianna A. , Lu Jiayun , Huynh Sophie Vo , Hicks Jessica , Sowalsky Adam G. , De Marzo Angelo M. , Joshu Corrine E. , Hanratty Brian , Sfanos Karen S. , Isaacs William B. , Haffner Michael C. , Lotan Tamara L. 
Published: December 2023

Abstract

Fatty acid synthase (FASN) catalyzes the synthesis of long-chain saturated fatty acids and is overexpressed during prostatic tumorigenesis, where it is the therapeutic target in several ongoing trials. However, the mechanism of FASN upregulation in prostate cancer remains unclear. Here, we examine FASN gene CpG methylation pattern by InfiniumEPIC profiling and whole-genome bisulfite sequencing across multiple racially diverse primary and metastatic prostate cancer cohorts, comparing with FASN protein expression as measured by digitally quantified IHC assay and reverse phase protein array analysis or FASN gene expression. We demonstrate that the FASN gene body is hypomethylated and overexpressed in primary prostate tumors compared with benign tissue, and FASN gene methylation is significantly inversely correlated with FASN protein or gene expression in both primary and metastatic prostate cancer. Primary prostate tumors with ERG gene rearrangement have increased FASN expression and we find evidence of FASN hypomethylation in this context. FASN expression is also significantly increased in prostate tumors from carriers of the germline HOXB13 G84E mutation compared with matched controls, consistent with a report that HOXB13 may contribute to epigenetic regulation of FASN in vitro. However, in contrast to previous studies, we find no significant association of FASN expression or methylation with self-identified race in models that include ERG status across two independent primary tumor cohorts. Taken together, these data support a potential epigenetic mechanism for FASN regulation in the prostate which may be relevant for selecting patients responsive to FASN inhibitors.

Significance:
Here, we leverage multiple independent primary and metastatic prostate cancer cohorts to demonstrate that FASN gene body methylation is highly inversely correlated with FASN gene and protein expression. This finding may shed light on epigenetic mechanisms of FASN regulation in prostate cancer and provides a potentially useful biomarker for selecting patients in future trials of FASN inhibitors.
СУЧАСНІ УЯВЛЕННЯ ПРО ЕТІОЛОГІЮ ТА ПАТОГЕНЕЗ ДЕРМАТОМІКОЗІВ
Authors: Москалюк В. Д. , Кравчук І. І. 
Published: December 2023

Представлено узагальнену інформацію про грибкові ураження (дерматомікози) шкіри, її додатків, слизових оболонок порожнини рота та статевих органів.
За спектром збудників і глибиною ураження дерматомікози поділяються на кератомікози; дерматоміцети; кандидоз і глибокі мікози. Грибкові захворювання шкіри переважно зумовлені трьома групами збудників: дерматоміцетами, дріжджоподібними грибами та пліснявою. Висвітлено патогенез захворювань, які спричиняють усі зазначені збудники, їх антигени, фактори вірулентності та патогенності, продуковані антибіотикоподібні речовини, а також здатність модулювати імунну відповідь організму хазяїна.
АНАЛІЗ ЗАХВОРЮВАНОСТІ НА РАК ШКІРИ ТА ОРГАНІЗАЦІЇ НАДАННЯ МЕДИЧНОЇ ДОПОМОГИ ХВОРИМ З ОНКОПАТОЛОГІЄЮ ШКІРИ В ЖИТОМИРСЬКІЙ ОБЛАСТІ
Authors: Парій В. Д. 
Published: December 2023

Мета: визначити віково-статеві особливості онкопатології шкіри та стану надання медичної допомоги хворим на рак шкіри в Житомирській області протягом 2012–2022 рр.
Матеріали і методи. Матеріалами дослідження стали офіційні статистичні дані звітів Центру медичної статистики ЦГЗ МОЗ України «Показники захворюваності на злоякісні новоутворення та діяльність онкологічної служби в Україні» за 2012–2022 р.р.
Результати. Значна увага до поширення онкопатології шкіри в Житомирській області (яка значно постраждала в результаті аварії на ЧАЕС) спричинена тим, що у 2022 р. в ній зафіксовано найвищий рівень захворюваності на меланому серед усіх областей України – 8,56 випадку на 100 тис. нас. За рівнем захворюваності на немеланомні новоутворення шкіри Житомирська область посідає 7 місце в рейтингу областей. Встановлено, що за досліджуваний період захворюваність на меланому в Україні знизилася на 21,3 %, а в області зросла на 52,8 %. Загальна і регіональна динаміка захворюваності на інші новоутворення шкіри позитивна, але обласний рівень захворюваності перевищує середньоукраїнський на 49 %. Смертність населення від злоякісних новоутворень при позитивній динаміці щодо зниження в Житомирській області перевищує рівні смертності в Україні від усіх новоутворень на 24,7 %, від меланоми – на 26,6 %, від інших новоутворень шкіри – на 8,5 %. Основні показники надання медичної допомоги онкохворим характеризуються відносною стабільністю. Забезпеченість населення області онкологами збільшилася на 14,3 %, щоправда, кваліфікаційну категорію мають лише 42 % онкологів області.
Висновки. Захворюваність на немеланомні новоутворення шкіри населення Житомирської області протягом останнього десятиріччя знизилась, а на меланому – зросла, рівні захворюваності перевищують відповідні в Україні. Захворюваність на меланому та немеланомні новоутворення шкіри мають певні віково-статеві особливості, найвищі її рівні притаманні чоловікам старшого віку. Актуальною залишається первинна профілактика онкозахворювань з огляду на радіаційне забруднення окремих населених пунктів області. Удосконалення потребує організація медичної допомоги онкохворим, особливо в частині раннього виявлення онкозахворювань, підвищення кваліфікації медичного персоналу.