bluuebunny/crossref_metadata_2025 huggingface dataset:
Drinking water quality in Cooch Behar Municipality, West Bengal, India: Assessment using WQI and public perception
Authors: Karmakar Dilip , Sarkar Bappa , Islam Nazrul
Published: April 2024

Effective assessment and management of groundwater quality are essential for safeguarding the integrity of freshwater resources. Cooch Behar Municipality of West Bengal has been chosen for the present study due to its reliance primarily on groundwater for drinking water. The study focuses on assessing groundwater quality in the study area, a planned city with a long history of urbanization. The primary objective is to analyze various parameters relevant to drinking water and compute the Water Quality Index (WQI) with the residents' perception. Forty water samples were collected from Cooch Behar Municipality's Public Health Engineering (PHE) department, encompassing all 20 wards. Each ward provided one sample from a Deep Tube Well (DTW) and a Shallow Tube Well (STW). EC, Fe, TH, Mn, pH, TDS, Turbidity, Ca, and Mg levels were determined using standard instruments and methods, and analyzed geospatial techniques and statistical methods were employed. Results revealed concerning levels of manganese (Mn) and total hardness (TH), exceeding permissible limits in 82.5% and 75% of samples, respectively. While some parameters remained within acceptable limits, computed WQI values ranged from 63.28 to 162.67, indicating significant overall water quality concerns. Alarmingly, 45% of samples were unsuitable for drinking, with an additional 40% classified as very poor. Notably, demographic factors such as household income and education level correlated with perceptions of poor water quality. Policy implications suggest the urgent need for a well‐structured management system to address these findings and ensure safe drinking water for residents.
Rhes, a striatal enriched protein, regulates post-translational small-ubiquitin-like-modifier (SUMO) modification of nuclear proteins and alters gene expression
Authors: Rivera Oscar , Sharma Manish , Dagar Sunayana , Shahani Neelam , Ramĺrez-Jarquĺn Uri Nimrod , Crynen Gogce , Karunadharma Pabalu , McManus Francis , Bonneil Eric , Pierre Thibault , Subramaniam Srinivasa
Published: April 2024

Rhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to cell via the formation of tunneling-like nanotubes (TNTs). However, the mechanisms by which Rhes mediates diverse functions remain unclear. Rhes is a small GTPase family member which contains a unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain that promotes SUMO post-translational modification of proteins (SUMOylation) by promoting “cross-SUMOylation” of the SUMO enzyme SUMO E1 (Aos1/Uba2) and SUMO E2 ligase (Ubc-9). Nevertheless, the identity of the SUMO substrates of Rhes remains largely unknown. Here, by combining high throughput interactome and SUMO proteomics, we report that Rhes regulates the SUMOylation of nuclear proteins that are involved in the regulation of gene expression. Rhes increased the SUMOylation of histone deacetylase 1 (HDAC1) and histone 2B, while decreasing SUMOylation of heterogeneous nuclear ribonucleoprotein M (HNRNPM), protein polybromo-1 (PBRM1) and E3 SUMO-protein ligase (PIASy). We also found that Rhes itself is SUMOylated at 6 different lysine residues (K32, K110, K114, K120, K124, and K245). Furthermore, Rhes regulated the expression of genes involved in cellular morphogenesis and differentiation in the striatum, in a SUMO-dependent manner. Our findings thus provide evidence for a previously undescribed role for Rhes in regulating the SUMOylation of nuclear targets and in orchestrating striatal gene expression via SUMOylation.
Resolvent model for aeroacoustics of trailing edge noise
Authors: Demange S. , Yuan Z. , Jekosch S. , Hanifi A. , Cavalieri A. V. G. , Sarradj E. , Kaiser T. L. , Oberleithner K.
Published: April 2024

This study presents a physics-based, low-order model for the trailing edge (TE) noise generated by an airfoil at low angle of attack. The approach employs incompressible resolvent analysis of the mean flow to extract relevant spanwise-coherent structures in the transitional boundary layer and near wake. These structures are integrated into Curle’s solution to Lighthill’s acoustic analogy to obtain the scattered acoustic field. The model has the advantage of predicting surface pressure fluctuations from first principles, avoiding reliance on empirical models, but with a free amplitude set by simulation data. The model is evaluated for the transitional flow ($$\text {Re} = 5e4$$

Re
=
5
e
4

) around a NACA0012 airfoil at 3 deg angle of attack, which features TE noise with multiple tones. The mean flow is obtained from a compressible large eddy simulation, and spectral proper orthogonal decomposition (SPOD) is employed to extract the main hydrodynamic and acoustic features of the flow. Comparisons between resolvent and SPOD demonstrate that the physics-based model accurately captures the leading coherent structures at the main tones’ frequencies, resulting in a good agreement of the reconstructed acoustic power with that of the SPOD (within 4 dB). Discrepancies are observed at high frequencies, likely linked to nonlinearities that are not considered in the resolvent analysis. The model’s directivity aligns well with the data at low Helmholtz numbers, but it fails at high frequencies where the back-scattered pressure plays a significant role in directivity. This modeling approach opens the way for efficient optimization of airfoil shapes in combination with low-fidelity mean flow solvers to reduce TE noise.

Graphical abstract
Interaction of the chemotherapeutic agent oxaliplatin and the tyrosine kinase inhibitor dasatinib with the organic cation transporter 2
Authors: Ahmed Eltayeb Sara , Dressler Julia M. , Schlatt Lukas , Pernecker Moritz , Neugebauer Ute , Karst Uwe , Ciarimboli Giuliano
Published: April 2024

Oxaliplatin (OHP) is effective in colorectal cancer treatment but induces peripheral neurotoxicity (OHP-induced peripheral neurotoxicity, OIPN), diminishing survivor quality of life. Organic cation transporter 2 (OCT2) is a key OHP uptake pathway in dorsal root ganglia. Competing for OCT2-mediated OHP uptake, such as with the tyrosine kinase inhibitor dasatinib, may mitigate OHP side effects. We investigated OHP and dasatinib interaction with OCT2 in human embryonic kidney 293 (HEK293) cells expressing OCT2 within a 10–3 to 10–7 M concentration range. Uptake competition experiments using fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP+, 1 µM) and mass spectrometry (MS) to determine cellular platinum content indicated that OHP (100 µM) is an OCT2 substrate, mediating OHP cellular toxicity. ASP+ and MS analysis revealed dasatinib as a non-transported inhibitor of hOCT2 (IC50 = 5.9 µM) and as a regulator of OCT2 activity. Dasatinib reduced transporter Vmax, potentially via Y544 phosphorylation suppression. MS analysis showed cellular dasatinib accumulation independent of hOCT2. Although 3 µM dasatinib reduced 100 µM OHP accumulation in hOCT2-HEK293 cells, co-incubation with dasatinib and OHP did not prevent OHP toxicity, possibly due to dasatinib-induced cell viability reduction. In summary, this study demonstrates OHP as an OCT2 substrate and dasatinib as a non-transported inhibitor and regulator of OCT2, offering potential for OIPN mitigation.
Spectrally separated dual-label upconversion luminescence lateral flow assay for cancer-specific STn-glycosylation in CA125 and CA15-3
Authors: Ekman Miikka , Salminen Teppo , Raiko Kirsti , Soukka Tero , Gidwani Kamlesh , Martiskainen Iida
Published: April 2024

Multiplexed lateral flow assays (LFAs) offer efficient on-site testing by simultaneously detecting multiple biomarkers from a single sample, reducing costs. In cancer diagnostics, where biomarkers can lack specificity, multiparameter detection provides more information at the point-of-care. Our research focuses on epithelial ovarian cancer (EOC), where STn-glycosylated forms of CA125 and CA15-3 antigens can better discriminate cancer from benign conditions. We have developed a dual-label LFA that detects both CA125-STn and CA15-3-STn within a single anti-STn antibody test line. This utilizes spectral separation of green (540 nm) and blue (450 nm) emitting erbium (NaYF4:Yb3+, Er3+)- and thulium (NaYF4: Yb3+, Tm3+)-doped upconverting nanoparticle (UCNP) reporters conjugated with antibodies against the protein epitopes in CA125 or CA15-3. This technology allows the simultaneous detection of different antigen variants from a single test line. The developed proof-of-concept dual-label LFA was able to distinguish between the ascites fluid samples from diagnosed ovarian cancer patients (n = 10) and liver cirrhosis ascites fluid samples (n = 3) used as a negative control. The analytical sensitivity of CA125-STn for the dual-label LFA was 1.8 U/ml in buffer and 3.6 U/ml in ascites fluid matrix. Here we demonstrate a novel approach of spectrally separated measurement of STn-glycosylated forms of two different cancer-associated protein biomarkers by using UCNP reporter technology.

Graphical Abstract
On the Existence of Global Weak Solutions to the 3D Electrically Conductive Rosensweig System and Their Convergence Towards Quasi-Equilibrium
Authors: Ndongmo Ngana A. , Razafimandimby P. A.
Published: April 2024

In this article, we study an electrically conductive Rosensweig model for ferrofluids, whose Bloch–Torrey regularization was studied by Hamdache and Hamroun (Appl Math Optim 81(2):479–509, 2020). We mainly prove the global existence of weak solutions to the non-regularized model under a certain smallness condition on the electric conductivity. Hence, our result not only solves a problem that was left open by Hamdache and Hamroun, but it can also serve as a confirmation that ferrofluids are naturally poor conductors of electric current. The proof, which is interesting in itself, is quite involved and relies on the Helmohltz–Leray decomposition of the magnetic fields and the use of renormalized solutions for the magnetization. We also give a rigorous and detailed description of the convergence of the global weak solutions towards the quasi-equilibrium in the relaxation time limit regime $$\tau \rightarrow 0$$

τ
→
0

.
A physics-informed deep learning approach for solving strongly degenerate parabolic problems
Authors: Ambrosio Pasquale , Cuomo Salvatore , De Rosa Mariapia
Published: April 2024

In recent years, Scientific Machine Learning (SciML) methods for solving Partial Differential Equations (PDEs) have gained increasing popularity. Within such a paradigm, Physics-Informed Neural Networks (PINNs) are novel deep learning frameworks for solving initial-boundary value problems involving nonlinear PDEs. Recently, PINNs have shown promising results in several application fields. Motivated by applications to gas filtration problems, here we present and evaluate a PINN-based approach to predict solutions to strongly degenerate parabolic problems with asymptotic structure of Laplacian type. To the best of our knowledge, this is one of the first papers demonstrating the efficacy of the PINN framework for solving such kind of problems. In particular, we estimate an appropriate approximation error for some test problems whose analytical solutions are fortunately known. The numerical experiments discussed include two and three-dimensional spatial domains, emphasizing the effectiveness of this approach in predicting accurate solutions.
Stable fixation using absorbable sutures in craniofacial surgery in patients over 24 months of age—a retrospective study
Authors: Faber Julian , Linz Christian , Böhm Hartmut , Kunz Felix , Schweitzer Tilmann
Published: April 2024

Purpose

In craniofacial surgery, the stable fixation of transposed bone segments is crucial in order to ensure good long-term results. The use of absorbable material in fixation avoids the need for a second surgery, which would otherwise be required to remove osteosynthesis material. The authors of the present manuscript have already demonstrated that absorbable sutures ensure the stable fixation of bone segments in patients up to 24 months of age. However, it has thus far remained unclear whether stable fixation is possible in older patients by using only absorbable sutures due to the slower bone remodelling and prolonged healing time in this cohort.

Method

For the present study, osteosynthesis was performed in 50 patients ranging from 25.7 to 192.1 months of age (mean, 61.4 ± 21.7 months) using solely absorbable sutures (PDS II®, Ethicon, Germany). Post-operative stability and possible restrictions—such as foreign body reactions—were evaluated within clinical and radiological routine follow-ups.

Results

All children demonstrated clinically and radiologically stable osteosynthesis both directly post-operatively and in follow-ups. No significant foreign body reaction could be seen.

Conclusion

The present study demonstrates—for the first time—that absorbable sutures with a longer absorption period are also very well suited for the fixation of bone segments in patients over 24 months of age. The sole use of absorbable sutures in children over 24 months of age is a safe procedure with nearly no foreign body reactions. The procedure enables stable and highly cost-effective osteosynthesis without altering the osteotomy design.
Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer
Authors: Fröhlich Ann-Kathrin , Porthun Jan , Talha Khawaja M. , Lena Alessia , Hadzibegovic Sara , Wilkenshoff Ursula , Sonntag Frederike , Nikolski Anja , Ramer Luisa Valentina , Zeller Tanja , Keller Ulrich , Bullinger Lars , Anker Stefan D. , Haverkamp Wilhelm , von Haehling Stephan , Doehner Wolfram , Rauch Ursula , Skurk Carsten , Cleland John G. F. , Butler Javed , Coats Andrew J. S. , Landmesser Ulf , Karakas Mahir , Anker Markus S.
Published: April 2024

Background

Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia.

Objectives

We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer.

Methods

We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50–61, > 61 g/m2; men, < 60, 60–74, > 74 g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24 kg/m2 and weight loss ≥ 5% in the prior 12 months). Repeat echocardiograms were obtained usually within 3–6 months for 85 patients.

Results

Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9–4.2), 0.8 (0.2–2.2), 0.5 (0.3–1.6) ng/mL, p = 0.029; men, 2.1 (0.8–3.2), 0.6 (0.1–1.7), 0.7 (0.2–1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48–116), 72 (48–95), 49 (35–76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r =  − 0.591, p < 0.001; men, r =  − 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r =  − 0.318, p = 0.003).

Conclusion

In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associated with a decrease in relative LVmass during follow-up.

Graphical abstract
Detection sensitivity of fluorescence lifetime imaging ophthalmoscopy for laser-induced selective damage of retinal pigment epithelium
Authors: Sonntag Svenja Rebecca , Hamann Maximilian , Seifert Eric , Grisanti Salvatore , Brinkmann Ralf , Miura Yoko
Published: April 2024

Purpose

To investigate the sensitivity of fluorescence lifetime imaging ophthalmoscopy (FLIO) to detect retinal laser spots by comparative analysis with other imaging modalities.

Methods

A diode laser with a wavelength of 514 nm was applied with pulse durations of 5.2, 12, 20, and 50 µs. The laser pulse energy was increased so that the visibility of the laser spot by slit-lamp fundus examination (SL) under the irradiator’s observation covers from the subvisible to visible range immediately after irradiation. The irradiated areas were then examined by fundus color photography (FC), optical coherence tomography (OCT), fundus autofluorescence (AF), FLIO, and fluorescein angiography (FA). The visibility of a total of over 2200 laser spots was evaluated by two independent researchers, and effective dose (ED) 50 laser pulse energy values were calculated for each imaging modality and compared.

Results

Among examined modalities, FA showed the lowest mean of ED50 energy value and SL the highest, that is, they had the highest and lowest sensitivity to detect retinal pigment epithalium (RPE)-selective laser spots, respectively. FLIO also detected spots significantly more sensitively than SL at most laser pulse durations and was not significantly inferior to FA. AF was also often more sensitive than SL, but the difference was slightly less significant than FLIO.

Conclusion

Considering its high sensitivity in detecting laser spots and previously reported potential of indicating local wound healing and metabolic changes around laser spots, FLIO may be useful as a non-invasive monitoring tool during and after minimally invasive retinal laser treatment.
The time course of spontaneous closure of idiopathic full-thickness macular holes
Authors: Neubauer Jonas , Gelisken Faik , Ozturk Taylan , Bartz-Schmidt Karl-Ulrich , Dimopoulos Spyridon
Published: April 2024

Purpose

Spontaneous closure of idiopathic full-thickness macular holes (iFTMH) has been reported regularly. However, little is known about its probability and timeline.

Methods

In this retrospective study all consecutive patients who presented between August 2008 and August 2019 were screened for the presence of a macular hole and only iFTMHs were included. The primary outcome measure was the spontaneous closure of the iFTMH.

Results

Of 1256 eyes with macular holes, 338 fulfilled the inclusion criteria. Spontaneous closure of the iFTMH was detected in 31 eyes (9.2%) with a median time of 44 days after diagnosis. Eyes exhibiting spontaneous closure demonstrated a higher baseline best-corrected visual-acuity (BCVA) and smaller iFTMH diameter (p < 0.0001 and p < 0.0001, respectively). The mean BCVA improved from 0.4 logMAR (SD ± 0.21) to 0.29 logMAR (SD ± 0.20) after spontaneous closure (p = 0.031). The iFTMH diameter was positively correlated with the time to spontaneous closure (Pearson-r = 0.37, p = 0.0377). Spontaneously closed iFTMHs reopened in 16% (n = 5) of cases, with a median of 136 days after closure. A logistic regression model showed the hole diameter was associated with spontaneous closure (odds-Ratio 0.97, 95%CI [0.96, 0.98]). The Kaplan–Meier-Curve revealed that approximately 25% of small-iFTMH (n = 124) and 55% of iFTMH with a diameter < 150µm (n = 48) closed spontaneously within two months.

Conclusion

The established gold-standard for the treatment of iFTMHs is macular surgery. However, the potential for spontaneous closure of small iFTMHs must be acknowledged. Therefore, if surgical treatment is delayed in individual cases, close observation is recommended.
Flooding, season and habitat interact to drive changes in vertebrate scavenging and carcass persistence rates
Authors: Krige Zyna , Spencer Emma E. , Crowther Mathew S. , Dickman Christopher R. , Newsome Thomas M.
Published: April 2024

Scavenging dynamics are influenced by many abiotic and biotic factors, but there is little knowledge of how scavengers respond to extreme weather events. As carrion is a major driver of the organisation and structure of food webs within ecological communities, understanding the response of scavengers to extreme weather events is critical in a world that is increasingly subject to climate change. In this study, vertebrate scavenging and carcass persistence rates were quantified in the Simpson Desert of central Australia; a system that experiences major fluctuations and extremes in weather conditions. Specifically, a total of 80 adult red kangaroo (Osphranter rufus) carcasses were placed on the landscape and monitored using remote sensor cameras. This included 40 carcasses monitored before and then 40 carcasses monitored after a major flooding event. The carcasses were monitored equally before and after the flood across different seasons (warm and cool) and in dune and interdune habitats. Overall, a total of 8124 scavenging events for 97,976 visitation minutes were recorded for 11 vertebrate species within 30 days of carcass placement pre- and post-flood. Vertebrate scavenging increased post-flood in the warm season, especially by corvids which quadrupled their scavenging events during this time. There was little difference in carcass persistence between habitats, but carcasses persisted 5.3-fold longer post-flood in warm seasons despite increased vertebrate scavenging. The results demonstrate that a flood event can influence scavenging dynamics and suggest a need to further understand how seasons, habitats and extreme weather events can drive changes in carrion-based food webs.
Globally Linked Pairs of Vertices in Generic Frameworks
Authors: Jordán Tibor , Villányi Soma
Published: April 2024

A d-dimensional framework is a pair (G, p), where $$G=(V,E)$$

G
=
(
V
,
E
)

is a graph and p is a map from V to $${\mathbb {R}}^d$$

R

d

. The length of an edge $$xy\in E$$

x
y
∈
E

in (G, p) is the distance between p(x) and p(y). A vertex pair $$\{u,v\}$$

{
u
,
v
}

of G is said to be globally linked in (G, p) if the distance between p(u) and p(v) is equal to the distance between q(u) and q(v) for every d-dimensional framework (G, q) in which the corresponding edge lengths are the same as in (G, p). We call (G, p) globally rigid in $${\mathbb {R}}^d$$

R

d

when each vertex pair of G is globally linked in (G, p). A pair $$\{u,v\}$$

{
u
,
v
}

of vertices of G is said to be weakly globally linked in G in $${\mathbb {R}}^d$$

R

d

if there exists a generic framework (G, p) in which $$\{u,v\}$$

{
u
,
v
}

is globally linked. In this paper we first give a sufficient condition for the weak global linkedness of a vertex pair of a $$(d+1)$$

(
d
+
1
)

-connected graph G in $${\mathbb {R}}^d$$

R

d

and then show that for $$d=2$$

d
=
2

it is also necessary. We use this result to obtain a complete characterization of weakly globally linked pairs in graphs in $${\mathbb {R}}^2$$

R

2

, which gives rise to an algorithm for testing weak global linkedness in the plane in $$O(|V|^2)$$

O
(
|
V

|
2

)

time. Our methods lead to a new short proof for the characterization of globally rigid graphs in $${\mathbb {R}}^2$$

R

2

, and further results on weakly globally linked pairs and globally rigid graphs in the plane and in higher dimensions.
Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study
Authors: Makuuchi Motoki , Kakuta Yoichi , Umeno Junji , Fujii Toshimitsu , Takagawa Tetsuya , Ibuka Takashi , Miura Miki , Sasaki Yu , Takahashi Sakuma , Nakase Hiroshi , Kiyohara Hiroki , Tominaga Keiichi , Shimodaira Yosuke , Hiraoka Sakiko , Ueno Nobuhiro , Yanai Shunichi , Yoshihara Takeo , Kakimoto Kazuki , Matsuoka Katsuyoshi , Hayashi Ryohei , Nanjo Sohachi , Iwama Itaru , Ishiguro Yoh , Chiba Hirofumi , Endo Katsuya , Kagaya Takashi , Fukuda Tomohiro , Sakata Yasuhisa , Kudo Takahiro , Takagi Tomohisa , Takahashi Kenichi , Naganuma Makoto , Shinozaki Masaru , Ogata Noriyuki , Tanaka Hiroki , Narimatsu Kazuyuki , Miyazaki Haruka , Ishige Takashi , Onodera Motoyuki , Hashimoto Yu , Nagai Hiroshi , Shimoyama Yusuke , Naito Takeo , Moroi Rintaro , Shiga Hisashi ,   Post-MENDEL study group, Kinouchi Yoshitaka , Andoh Akira , Hisamatsu Tadakazu , Masamune Atsushi
Published: April 2024

Background

This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.

Methods

A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.

Results

Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.

Conclusions

NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Uncovering Failure and Cracking Behaviors of Double-Flawed Sandstone Under Compressive-Shear Loading Using Digital Image Correlation (DIC) Technique
Authors: Zhou Tao , Chen Jiarong , Wang Fei , Zhou Changtai
Published: April 2024

The coalescence of flaws provides valuable insights into the failure behaviors of rock masses, which is a critical issue in rock engineering. In this study, a series of compressive-shear tests were conducted on sandstone specimens containing double flaws. The failure and cracking behaviors of specimens with different geometric configurations under various loading conditions were analyzed using the digital image correlation (DIC) technique. The strain and displacement fields effectively demonstrate crack propagation and coalescence, accompanied by the axial load–displacement curve. The results revealed the effect of eccentric and overlapping distance of double flaws on the compressive-shear bearing capacity. The relative displacement method (RDM) was applied to analyze the crack characteristics in this study. Based on the relative displacement behaviors of the cracks, five typical types of crack modes were identified, including tensile mode, shear mode, mixed-I mode, mixed-II mode, and mixed-III mode. Both wing cracks initiated from flaw outer tips and anti-wing cracks generated from flaw inner tips were classified as a tensile mode or mode-I, dominated by normal relative displacement. In contrast, the secondary cracks were categorized as either shear mode or mode-III, which are dominated by tangential relative displacement. The geometry configurations of flaws affected both the coalescent mode and cracking path, which in turn influenced the failure mode of specimens. This study identified and summarized eight types of coalescent modes between double flaws. The findings presented in this paper contribute to a better understanding of the failure behavior of rock masses containing flaws subjected to compressive-shear loads.
An externally validated clinical-laboratory nomogram for myocardial involvement in adult idiopathic-inflammatory-myopathy patients
Authors: Liang Junyu , Wan Liyan , Yao Yake , Cui Xiao , He Ye , Li Shuangshuang , Jiang Mengdi , Sun Yiduo , Cao Heng , Lin Jin
Published: April 2024

Objectives

This study aimed at identifying clinical and laboratory risk factors for myocardial involvement (MI) in idiopathic inflammatory myopathies (IIMs) patients as well as constructing a risk-predicted nomogram for prediction and early identification of MI.

Methods

An IIMs cohort in southeastern China was constructed, including 504 adult IIMs patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine from January 1st 2018 to April 30st 2022. After dividing patients into the training cohort and the validation cohort, risk factors for MI were identified through least absolute shrinkage and selection operator regression and multivariate logistic regression. A risk-predicted nomogram was established and validated internally and externally for discrimination, calibration and practicability.

Results

In this cohort, 17.7% of patients developed MI and the survival was significantly inferior to that of IIMs patients without MI (P < 0.001). In the training cohort, age > 55 years old (P < 0.001), disease activity > 10 points (P < 0.001), interleukin-17A (IL-17A) > 7.5 pg/ml (P < 0.001), lactic dehydrogenase (LDH) > 425 U/L (P < 0.001), anti-mitochondrial antibodies (AMAs, P = 0.017), and anti-MDA5 antibody (P = 0.037) were significantly correlated with development of MI. A nomogram was established by including the above values to predict MI and was found efficient in discrimination, calibration, and practicability through internal and external validation.

Conclusion

This study developed and validated a nomogram model to predict the risk of MI in adult IIMs patients, which can benefit the prediction and early identification of MI as well as timely intervention in these patients.
From enterprise models to low-code applications: mapping DEMO to Mendix; illustrated in the social housing domain
Authors: Krouwel Marien R. , Op ’t Land Martin , Proper Henderik A.
Published: April 2024

Due to hyper-competition, technological advancements, regulatory changes, etc, the conditions under which enterprises need to thrive become increasingly turbulent. Consequently, enterprise agility increasingly determines an enterprise’s chances for success. As software development often is a limiting factor in achieving enterprise agility, enterprise agility and software adaptability become increasingly intertwined. As a consequence, decisions that regard flexibility should not be left to software developers alone. By taking a Model-driven Software Development (MDSD) approach, starting from DEMO ontological enterprise models and explicit (enterprise) implementation design decisions, the aim of this research is to bridge the gap from enterprise agility to software adaptability, in such a way that software development is no longer a limiting factor in achieving enterprise agility. Low-code technology is a growing market trend that builds on MDSD concepts and claims to offer a high degree of software adaptability. Therefore, as a first step to show the potential benefits to use DEMO ontological enterprise models as a base for MDSD, this research shows the design of a mapping from DEMO models to Mendix for the (automated) creation of a low-code application that also intrinsically accommodates run-time implementation design decisions.
Computational Investigation of Vessel Injury Due to Catheter Tracking During Transcatheter Aortic Valve Replacement
Authors: Symes David G. , McNamara Laoise M. , Conway Claire
Published: April 2024

Catheter reaction forces during transcatheter valve replacement (TAVR) may result in injury to the vessel or plaque rupture, triggering distal embolization or thrombosis. In vitro test methods represent the arterial wall using synthetic proxies to determine catheter reaction forces during tracking, but whether they can account for reaction forces within the compliant aortic wall tissue in vivo is unknown. Moreover, the role of plaque inclusions is not well understood. Computational approaches have predicted the impact of TAVR positioning, migration, and leaflet distortion, but have not yet been applied to investigate aortic wall reaction forces and stresses during catheter tracking. In this study, we investigate the role that catheter design and aorta and plaque mechanical properties have on the risk of plaque rupture during TAVR catheter delivery. We report that, for trackability testing, a rigid test model provides a reasonable estimation of the peak reaction forces experienced during catheter tracking within compliant vessels. We investigated the risk of rupture of both the aortic tissue and calcified plaques. We report that there was no risk of diseased aortic tissue rupture based on an accepted aortic tissue stress threshold (4.2 MPa). However, we report that both the aortic and plaque tissue exceed a rupture stress threshold (300 kPa) with and without the presence of stiff and soft plaque inclusions. We also highlight the potential risks associated with shorter catheter tips during catheter tracking and demonstrate that increasing the contact surface will reduce peak contact pressures experienced in the tissue.
Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness
Authors: Kaneko Hiroki , Ozono Yoshinori , Iwakiri Hisayoshi , Hatada Hiroshi , Uchiyama Naomi , Komaki Yuri , Nakamura Kenichi , Hasuike Satoru , Nagata Kenji , Kawakami Hiroshi
Published: April 2024

Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6 days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24 weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.
Combining shape-adaptive blades and active flow control in a multi-stage axial compressor: a numerical study
Authors: Seidler M. , Montano Z. , Mimic D. , Meinicke N. , Friedrichs J. , Riemenschneider J. , Seume J. R.
Published: April 2024

Shape adaption (SA) via piezo-ceramic actuation, and active flow control (AFC) by means of fluid injection and aspiration, are investigated within the Cluster of Excellence for Sustainable and Energy-Efficient Aviation (SE2A) with the goal of increasing the efficiency of multi-stage compressors—particularly at part-load, and of extending their operating range. Although both technologies have shown to be beneficial for the compressor off-design operation, drawbacks are still apparent at the aerodynamic design point when a single rotor or stator is equipped with SA or AFC, because of wake disturbances, which increase the incidence angle of the following row. Especially matching an improved component with its respective stage counterpart poses a major challenge in both research areas and is, therefore, addressed within this investigation. This work focuses on the first two stages of a high-pressure compressor, to compare and evaluate different combinations of shape adaption and active flow control. By considering structural requirements, such as a minimum blade thickness for the actuator application, and aerodynamic sensitivities, such as flow incidence and deviation due to off-design operation, a suitable configuration is derived and investigated in further detail.
Evolution of transplant oncology indications: a single-institution experience over 40 years
Authors: Lai Quirino , Parisse Simona , Ginanni Corradini Stefano , Ferri Flaminia , Kolovou Konstantina , Campagna Pasquale , Melandro Fabio , Mennini Gianluca , Merli Manuela , Rossi Massimo
Published: April 2024

Liver transplantation (LT) for uncommon tumoral indications has changed across the decades, with impaired results reported in the first historical series mainly for non-tumoral-related causes. Recently, renewed interest in liver transplant oncology has been reported. The study aims to analyze a mono-center experience exploring the evolution and the impact on patient survival of LT in uncommon tumoral indications. A retrospective analysis of 851 LT performed during 1982–2023 was investigated. 33/851 (3.9%) uncommon tumoral indications were reported: hepatocellular carcinoma (HCC) on non-cirrhotic liver (n = 14), peri-hilar (phCCA) (n = 8) and intrahepatic cholangiocarcinoma (i-CCA) (n = 3), metastatic disease (n = 4), hepatic hemangioendothelioma (n = 2), and benign tumor (n = 2). Uncommon tumoral indications were mainly transplanted during the period 1982–1989, with a complete disappearance after the year 2000 and a slight rise in the last years. Poor outcomes were reported: 5-year survival rates were 28.6%, 25.0%, 0%, and 0% in the case of HCC on non-cirrhotic liver, phCCA, i-CCA, and metastases, respectively. However, the cause of patient death was often related to non-tumoral conditions. LT for uncommon oncological diseases has increased worldwide in recent decades. Historical series report poor survival outcomes despite more recent data showing promising results. Hence, the decision to transplant these patients should be under the risk and overall benefit of the patient. The results of the ongoing protocol studies are expected to confirm the validity of the unconventional tumor indications.
Incipient tuberculosis: a comprehensive overview
Authors: Rotundo Salvatore , Tassone Maria Teresa , Serapide Francesca , Russo Alessandro , Trecarichi Enrico Maria
Published: April 2024

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies.
Fully accurate approximation of piecewise smooth functions using corrected B-spline quasi-interpolants
Authors: Li Zhilin , Pan Kejia , Ruiz Juan , Yáñez Dionisio F.
Published: April 2024

This article is devoted to introducing new spline quasi-interpolants for the sharp approximation of data in one and several dimensions. The new construction aims to obtain accurate approximations close to singularities of the function from which the data are obtained. The technique relies in an accurate knowledge of the position of the singularity, which can be known or approximated, and that allows for the obtention of accurate approximations of the jumps of the function and its derivatives at this point. With this information, it is possible to compute correction terms for the B-spline bases of the spline that are affected by the presence of singularities. The result is a piecewise smooth reconstruction with full accuracy (meaning by full accuracy, the accuracy of the spline at smooth zones). The numerical experiments presented support the theoretical results obtained.
A European survey of older peoples’ preferences, and perceived barriers and facilitators to inform development of a medication-related fall-prevention patient portal
Authors: Ploegmakers Kim J. , Linn A. J. , Medlock S. , Seppälä L. J. , Bahat G. , Caballero-Mora M. A. , Ilhan B. , Landi F. , Masud T. , Morrissey Y. , Ryg J. , Topinkova E. , van der Velde N. , van Weert J. C. M. ,   European Geriatric Medicine Society (EuGMS) Task and Finish group on Fall-Risk Increasing Drugs (FRIDs)
Published: April 2024

Purpose

Falls are a major and growing health care problem in older adults. A patient portal has the potential to provide older adults with fall-prevention advice to reduce fall-risk. However, to date, the needs and preferences regarding a patient portal in older people who have experienced falls have not been explored. This study assesses content preferences, potential barriers and facilitators with regard to using a patient portal, as perceived by older people who have experienced falls, and explores regional differences between European participants.

Methods

We conducted a survey of older adults attending an outpatient clinic due to a fall or fall-related injury, to explore their content preferences, perceived barriers, and facilitators with respect to a fall-prevention patient portal. Older adults (N = 121, 69.4% female, mean age: 77.9) were recruited from seven European countries.

Results

Almost two-thirds of respondents indicated they would use a fall-prevention patient portal. The portal would preferably include information on Fall-Risk-Increasing Drugs (FRIDs), and ways to manage other related/relevant medical conditions. Facilitators included a user-friendly portal, with easily accessible information and physician recommendations to use the portal. The most-commonly-selected barriers were privacy issues and usage fees. A family member’s recommendation to use the portal was seemingly more important for Southern and Eastern European participants compared to the other regions.

Conclusion

The majority of older people with lived falls experience expressed an interest in a fall-prevention patient portal providing personalized treatment advice to prevent further falls. The results will be used to inform the development of a fall-prevention patient portal. The fall-prevention patient portal is intended to be used in addition to a consultation with a physician. Future research is needed to explore how to prevent falls in older patients who are not interested in a fall-prevention patient portal.
An Underwater Biomimetic Robot that can Swim, Bipedal Walk and Grasp
Authors: Wu Qiuxuan , Pan Liwei , Du FuLin , Wu ZhaoSheng , Chi XiaoNi , Gao FaRong , Wang Jian , Zhilenkov Anton A.
Published: April 2024

In developing and exploring extreme and harsh underwater environments, underwater robots can effectively replace humans to complete tasks. To meet the requirements of underwater flexible motion and comprehensive subsea operation, a novel octopus-inspired robot with eight soft limbs was designed and developed. This robot possesses the capabilities of underwater bipedal walking, multi-arm swimming, and grasping objects. To closely interact with the underwater seabed environment and minimize disturbance, the robot employs a cable-driven flexible arm for its walking in underwater floor through a bipedal walking mode. The multi-arm swimming offers a means of three-dimensional spatial movement, allowing the robot to swiftly explore and navigate over large areas, thereby enhancing its flexibility. Furthermore, the robot’s walking arm enables it to grasp and transport objects underwater, thereby enhancing its practicality in underwater environments. A simplified motion models and gait generation strategies were proposed for two modes of robot locomotion: swimming and walking, inspired by the movement characteristics of octopus-inspired multi-arm swimming and bipedal walking. Through experimental verification, the robot’s average speed of underwater bipedal walking reaches 7.26 cm/s, while the horizontal movement speed for multi-arm swimming is 8.6 cm/s.
In silico analysis on binding action of beta-lactam drugs against TEM and SHV class A beta-lactamases from Klebsiella pneumoniae
Authors: Akinola Omowumi Temitayo , Oyebamiji Abel Kolawole , Oke David Gbenga , Adekunle David O. , Olanrewaju Adesoji Alani , Akintelu Sunday Adewale
Published: April 2024

One of the leading Gram-negative bacteria that causes nosocomial illnesses such as pneumonia, urinary tract infections, meningitis, etc. is Klebsiella pneumoniae. Conventionally, K. pneumoniae infections are treated with beta-lactam (β-lactam) based antibiotics like penicillin; however, these treatments are becoming less and less successful as the bacterium generates various kinds of beta-lactamases (β-lactamases) to inactivate the medicines. In the present study, whole genome sequencing was used to obtain class A β-lactamase from an isolate that showed antibiotic resistance using the disk diffusion method. Class A β-lactamase, TEM and SHV obtained from the isolate were used for docking. We downloaded the structure of two enzymes (amino acids) (TEM and SHV background) from Protein DataBank (PDB) with PDB IDs: 1n9b and 2zd8. The structures of the β-lactams antibiotics (ceftazidime, cefepime, Amoxicillin clavulanic acid, and meropenem) were drawn using Chemsketch. The interactions of the inhibitors with several β-lactams antibiotics were studied after docking using Autodock software. The docking results showed that of all the five drugs docked with the enzymes (inhibitors), cefepime excelled in terms of ability to bind well against both the TEM and SHV enzymes. This was shown with the binding affinity against 1n9b and 2zd8 being − 8.23996162 and − 8.5358305 respectively, as such making it the best β-lactam antibiotic against TEM and SHV of all the five drugs.