bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B–induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling
Authors: Abdel-Rahman Doaa M. , Messiha Basim Anwar Shehata , Ali Fares E.M. , Azouz Amany A. 
Published: October 2023

AbstractAmphotericin B (AmB)–induced acute kidney injury (AKI) is a common health problem having an undesirable impact on its urgent therapeutic utility for fatal systemic fungal infections. Tadalafil (TAD), a phosphodiesterase-5 (PDE-5) inhibitor, has been observed to have a wide range of pharmacological actions, including nephroprotection. The study’s objective was to examine the possible underlying protective mechanism of TAD against AmB-induced nephrotoxicity. Experimentally, animals were divided randomly into four groups: control, TAD (5 mg/kg/day; p.o.), AmB (18.5 mg/kg/day; i.p.), and TAD+AmB groups. Sera and tissue samples were processed for biochemical, molecular, and histological analyses. The biochemical investigations showed that TAD significantly ameliorated the increase of kidney function biomarkers (creatinine, urea, CysC, KIM-1) in serum, renal nitric oxide (NO), lipid peroxidation (MDA), and inflammatory cytokines (TNF-α, IL-6) in AmB-treated rats. Meanwhile, TAD significantly retarded AmB-induced decrease in serum magnesium, sodium, potassium, and renal glutathione content. Molecular analysis revealed that TAD reduced AmB-induced imbalance in the protein expression of eNOS/iNOS, which explains its regulatory effect on renal NO content. These results were also supported by the down-regulation of nuclear NF-κB p65 and cleaved caspase-3 protein expressions, as well as the improvement of histological features by TAD in AmB-treated rats. Therefore, it can be suggested that TAD could be a promising candidate for renoprotection against AmB-induced AKI. That could be partly attributed to its regulatory effect on renal eNOS/iNOS balance and NO, the inhibition of NF-κB p65 nuclear translocation, its downstream inflammatory cytokines and iNOS, and ultimately the inhibition of caspase-3-induced renal apoptosis.
Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA)
Authors: Ebbers S. C. , Barentsz M. W. , de Vries-Huizing D. M. V. , Versleijen M. W. J. , Klompenhouwer E. G. , Tesselaar M. E. T. , Stokkel M. P. M. , Brabander T. , Hofland J. , Moelker A. , van Leeuwaarde R. S. , Smits M. L. J. , Braat A. J. A. T. , Lam M. G. E. H. 
Published: October 2023

Abstract
Purpose
Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1–2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity.

Methods
Twenty-seven patients with grade 1–2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a “second-pass” effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test.

Findings
After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle.

Conclusion
Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.
Impact of simulated reduced injected dose on the assessment of amyloid PET scans
Authors: Young Peter , Heeman Fiona , Axelsson Jan , Collij Lyduine E. , Hitzel Anne , Sanaat Amirhossein , Niñerola-Baizan Aida , Perissinotti Andrés , Lubberink Mark , Frisoni Giovanni B. , Zaidi Habib , Barkhof Frederik , Farrar Gill , Baker Suzanne , Gispert Juan Domingo , Garibotto Valentina , Rieckmann Anna , Schöll Michael ,   on behalf of the AMYPAD consortium
Published: October 2023

Abstract
Purpose
To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben.

Methods
Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90–110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated.

Results
At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aβ- from Aβ + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers.

Conclusion
This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.
Influence of deep gaps on laminar–turbulent transition in two-dimensional boundary layers at subsonic Mach numbers
Authors: Risius Steffen , Costantini Marco , Klein Christian 
Published: October 2023

AbstractSystematic experimental investigations on the influence of deep gaps on the location of laminar–turbulent transition are reported. The tests were conducted in the Cryogenic Ludwieg–Tube Göttingen, a blow-down wind tunnel with good flow quality, at eight different unit Reynolds numbers ranging from $$Re_1 = {17.5\,\,\times 10^{6}\,\mathrm{{m}^{-1}}}$$

R

e
1

=

17.5

×

10
6

m

-
1

to $$ 80\,\times\,10^{6}\,\mathrm{m}^{-1}$$

80

×

10
6

m

-
1

, three Mach numbers, $$M= 0.35$$

M
=
0.35

, 0.50 and 0.65, and various pressure gradients. A flat-plate configuration, the extended two-dimensional wind tunnel model PaLASTra was modified in order to allow the installation of gaps with nominal widths of $$30$$

30

$$\upmu $$
μ
m, $$100$$

100

$$\upmu $$
μ
m and $$200$$

200

$$\upmu $$
μ
m and a depth of $$d = {9\,\mathrm{mm}}$$

d
=

9

mm

. A maximum Reynolds number based on the gap width $$Re_{w} = Re_1 \cdot w \approx {16{,}000}$$

R

e
w

=
R

e
1

·
w
≈

16
,
000

was reached. Transition Reynolds numbers ranging from $$Re_{tr}\approx $$

R

e

tr

≈

1 × 106 to 11 × 106 were measured, as a function of gap width, pressure gradient and Mach and Reynolds number. This systematic investigation facilitates a linear approximation of $$Re_{tr}$$

R

e

tr

dependent on the boundary layer shape factor $$H_{12}$$

H
12

for various flow conditions and gap widths. It was therefore possible to conduct an investigation of $$Re_{tr}$$

R

e

tr

depending on $$Re_{1}$$

R

e
1

and the relative change of the transition location depending on the gap width w. Incompressible linear stability analysis was used to calculate amplification rates of Tollmien–Schlichting waves and determine critical N-factors by correlation with measured transition locations. The change in the critical N-factor $$\varDelta N$$

Δ
N

by installation of the gap is investigated as a function of w and $$Re_w$$

R

e
w

. It was found that a gap width of 30 $$\upmu $$
μ
m reduces the critical N-factors in the range of $$\varDelta N \approx 0.5 \pm 0.25$$

Δ
N
≈
0.5
±
0.25

, while gap widths of 100 $$\upmu $$
μ
m and 200 $$\upmu $$
μ
m reduce the critical N-factor in the range of $$\varDelta N \approx 1.5 \pm 1$$

Δ
N
≈
1.5
±
1

. Interestingly, an increase in gap width from 100 to 200 $$\upmu $$
μ
m was not found to induce smaller transition Reynolds numbers or reduced N-factors, which might be due to resonance effects.
High-precision interferometric measurement of slow and fast temperature changes in static fluid and convective flow
Authors: Ge Xinyang , Zielińska Joanna A. , Maldonado Sergio 
Published: October 2023

AbstractWe explore the strengths and limitations of using a standard Michelson interferometer to sample line-of-sight-averaged temperature in water via two experimental setups: slow-varying temperature in static fluid and fast temperature variations in convective flow. The high precision of our measurements (a few mK) is enabled by the fast response time and high sensitivity of the interferometer to minute changes in the refractive index of water caused by temperature variations. These features allow us to detect the signature of fine fluid dynamical patterns in convective flow in a fully non-intrusive manner. For example, we are able to observe an asymmetry in the rising thermal plume (i.e., an asynchronous arrival of two counter-rotating vortices at the measurement location), which is not possible to resolve with more traditional (and invasive) techniques, such as RTD (Resistance Temperature Detector) sensors. These findings, and the overall reliability of our method, are further corroborated by means of Particle Image Velocimetry and Large Eddy Simulations. While this method presents inherent limitations (mainly stemming from the line-of-sight-averaged nature of its results), its non-intrusiveness and robustness, along with the ability to readily yield real-time, highly accurate measurements, render this technique very attractive for a wide range of applications in experimental fluid dynamics.
The neuropathology of intimate partner violence
Authors: Dams-O’Connor Kristen , Seifert Alan C. , Crary John F. , Delman Bradley N. , Del Bigio Marc R. , Kovacs Gabor G. , Lee Edward B. , Nolan Amber L. , Pruyser Ariel , Selmanovic Enna , Stewart William , Woodoff-Leith Emma , Folkerth Rebecca D. 
Published: October 2023

AbstractLifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd–9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.
Agreement of cerebrospinal fluid biomarkers and amyloid-PET in a multicenter study
Authors: Guillén Núria , Contador José , Buongiorno Mariateresa , Álvarez Ignacio , Culell Natalia , Alcolea Daniel , Lleó Alberto , Fortea Juan , Piñol-Ripoll Gerard , Carnes-Vendrell Anna , Lourdes Ispierto María , Vilas Dolores , Puig-Pijoan Albert , Fernández-Lebrero Aida , Balasa Mircea , Sánchez-Valle Raquel , Lladó Albert 
Published: October 2023

Abstract
Core Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers have shown incomplete agreement with amyloid-positron emission tomography (PET). Our goal was to analyze the agreement between AD CSF biomarkers and amyloid-PET in a multicenter study. Retrospective multicenter study (5 centers). Participants who underwent both CSF biomarkers and amyloid-PET scan within 18 months were included. Clinical diagnoses were made according to latest diagnostic criteria by the attending clinicians. CSF Amyloid Beta1-42 (Aβ1-42, A), phosphorliated tau 181 (pTau181, T) and total tau (tTau, N) biomarkers were considered normal (−) or abnormal ( +) according to cutoffs of each center. Amyloid-PET was visually classified as positive/negative. Agreement between CSF biomarkers and amyloid-PET was analyzed by overall percent agreement (OPA). 236 participants were included (mean age 67.9 years (SD 9.1), MMSE score 24.5 (SD 4.1)). Diagnoses were mild cognitive impairment or dementia due to AD (49%), Lewy body dementia (22%), frontotemporal dementia (10%) and others (19%). Mean time between tests was 5.1 months (SD 4.1). OPA between single CSF biomarkers and amyloid-PET was 74% for Aβ1-42, 75% for pTau181, 73% for tTau. The use of biomarker ratios improved OPA: 87% for Aβ1-42/Aβ1-40 (n = 155), 88% for pTau181/Aβ1-42 (n = 94) and 82% for tTau/Aβ1-42 (n = 160). A + T + N + cases showed the highest agreement between CSF biomarkers and amyloid-PET (96%), followed by A-T-N- cases (89%). Aβ1-42/Aβ1-40 was a better marker of cerebral amyloid deposition, as identified by amyloid tracers, than Aβ1-42 alone. Combined biomarkers in CSF predicted amyloid-PET result better than single biomarkers.
A lighthouse to enhance the quality of life in the Nile River basin
Authors: Batisha Ayman 
Published: October 2023

AbstractThe future of large rivers is related to regional cooperation programs for the sustainable development of water and related resources in great river basins. The objective of this article is to present how roadmaps can be utilized for both building up sustainable development for the Nile River, and supporting the integration of national and regional development strategies in Egypt and other Nile basin countries. The strategic objective is to highlight a wide range of sustainable freshwater pathways for an inclusive, peaceful, and sustainable future for all. In particular, it focuses on generating innovative water solutions, actions, and practices that enhance water exploitation in large river basins, transboundary shared rivers, and other transboundary shared water resources. The roadmapping approach is adopted and developed widely in the science, technology, and innovation community. The paper concentrates on roadmapping as an important tool that promotes sound planning of sustainability of large rivers, and in particular, transboundary shared rivers. The roadmap analyzes the benefits of planning shared water cooperation that extends to ecological, economic, and political features, and also beyond the river for the benefit of all, and identifies at an early stage the actions needed to manage the associated technology and environmental risk. The roadmap includes the key water resources governance characteristics, geographical scope, climate change (CC), and its impact, member states, organizational structure, decision-making, data information sharing, monitoring, the role of multiple stakeholders, financing, legal basis, dispute resolution, and benefit sharing. Therefore, a roadmap for the Nile River can help raise productivity and support faster growth, if considered as a lighthouse for national development strategies. Roadmap for the Nile River proposes windows of opportunity and is a vital milestone for cooperation, peace, stability, joint investment, and prosperity. With possible benefits exceeding those derived from the river itself, a roadmap for the Nile River can catalyze strengthened cooperation and greater regional ecological, economic, social, and political integration. The paper concludes that the roadmap for the Nile River sustainability (NRS) is a promising model for assuring the sustainability of transboundary shared large rivers.
N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation
Authors: Xie Rongjun , Liu Longfei , Lu Xianzhou , He Chengjian , Yao Hongyi , Li Guoxin 
Published: October 2023

Abstract
Background
Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC.

Methods
OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays.

Results
In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway.

Conclusions
In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.
Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients
Authors: De Novellis Danilo , Folliero Veronica , Giudice Valentina , Pezzullo Luca , Sanna Giuseppina , Fontana Raffaele , Guariglia Roberto , Zannella Carla , Mettivier Laura , Ferrara Idalucia , Boccia Giovanni , Buonanno Maria Teresa , Martorelli Maria Carmen , Luponio Serena , Crudele Andrea , Pagliano Pasquale , Sessa Anna Maria , Velino Francesca , Langella Maddalena , Manzin Aldo , Galdiero Massimiliano , Selleri Carmine , Franci Gianluigi , Serio Bianca 
Published: October 2023

AbstractSARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production.