bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental Acupuncture for Prevention of Recurrent Urinary Tract Infections. A Randomised Clinical Trial
Authors: Ots Thomas , Gold Daniela , Ziller Paul , Kuenzer Thomas , Dalpiaz Orietta , Pesto Lejla , Trutnovsky Gerda
Published: July 2024

Introduction and Hypothesis

Urinary tract infections (UTIs) are a common medical problem and prophylaxis of recurrent UTIs is an ongoing clinical challenge. In the present study we examined whether acupuncture is able to prevent recurrent UTIs in women.

Methods

This multicentre randomised controlled trial, based at a University clinic and private acupuncture clinics, recruited women suffering from recurrent uncomplicated UTIs. Participants were randomised to the acupuncture group or control group. Acupuncture therapy consisted of 12 treatments over a period of 18 weeks, using a set of predefined body and ear acupuncture points. Cranberry products were recommended to all participants as standard of care.

Results

A total of 137 women were randomised (68 acupuncture, 69 control group) and occurrence of UTIs at 6 and 12 months could be assessed in 123 and 120 women respectively. Acupuncture combined with cranberry slightly increased the proportion of UTI-free women compared with cranberry alone at 6 months (59% vs 46%, p = 0.2). Between 6 and 12 months the proportion of UTI-free women was significantly higher in the acupuncture group (66 vs 45%, p = 0.03). The number of UTIs decreased from baseline to 12 months in both study groups. The number of UTIs at 12 months was significantly lower in the acupuncture group (median difference 1, p = 0.01).

Conclusions

Segmental acupuncture may be an effective treatment option for women with recurrent UTIs over a longer follow-up period and may limit antibiotics use. Further studies are needed.
Nitrogen fixation rate and phosphorus enrichment effects on diazotrophic cyanobacteria in the Gulf of Riga
Authors: Liepina-Leimane Ineta , Barda Ieva , Jurgensone Iveta , Labucis Atis , Baraskova Lubova , Aigars Juris
Published: July 2024

In eutrophied marine systems such as the Baltic Sea, diazotrophic cyanobacteria have the potential to add additional bioavailable nitrogen (N) to the system through fixation of atmospheric dinitrogen (N2). However, their growth is regarded to be limited by phosphorus availability (P). This study investigates the response of two cyanobacteria species, Aphanizomenon flosaquae and Nodularia spumigena, collected from the Gulf of Riga under different environmental conditions to a short-period dissolved inorganic phosphorus (DIP) enrichment. The samples were collected during the summer cyanobacterial bloom of 2022 in the central region of the Gulf of Riga. Contrary to expectations, neither species demonstrated a significant increase in biomass. The study also established that N2-fixation rates did not correlate directly with the total diazotrophic cyanobacteria biomass, but showed a significant correlation with heterocyst presence in both species addressed during this study. The findings suggest the influence of additional factors beyond DIP availability on the N2-fixing cyanobacteria growth in the Gulf of Riga.
Drug administration via feeding tubes—a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients
Authors: Sommerfeldt Jana , Sartorius Hannes , von Sarnowski Bettina , Klein Sandra , Ritter Christoph A.
Published: July 2024

Purpose

Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients.

Methods

Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit. Physicochemical, pharmacokinetic, and stability properties of these drugs and data on drug-enteral nutrition interactions were systematically searched for in the European Pharmacopoeia, Hagers Handbook of Pharmaceutical Practice, Birchers clinical-pharmacological data compilation, and the Martindale Complete Drug Reference, as well as from databases including DrugBank, DrugDex, PubChem, Google Scholar, and PubMed.

Results

Of the drugs most commonly administered via feeding tubes in the present stroke patient cohort, bisoprolol, candesartan, and ramipril could be considered the least critical due to their overall favourable properties. Acetylsalicylic acid, amlodipine, hydrochlorothiazide, omeprazole and esomeprazole, simvastatin, and torasemide pose risks based on pH or light-dependent instability or proposed food effects. The most critical drugs to be administered via feeding tubes are considered to be furosemide, levodopa, and levothyroxine as they show relevant instabilities under administration conditions and substantial food effects; the latter two even possess a narrow therapeutic index. However, little information is available on drug-tube and drug-formula interactions.

Conclusion

Feeding tube administration of medications turned out to be a highly complex process with several unmet risks. Therefore, investigations that systematically assess these risk factors using clinically relevant model systems are urgently needed.
Targeting Fn14 as a therapeutic target for cachexia reprograms the glycolytic pathway in tumour and brain in mice
Authors: Burvenich Ingrid Julienne Georgette , Osellame Laura Danielle , Rigopoulos Angela , Huynh Nhi , Cao Zhipeng , Hoogenraad Nicholas Johannes , Scott Andrew Mark
Published: July 2024

Purpose

Cachexia is a complex syndrome characterized by unintentional weight loss, progressive muscle wasting and loss of appetite. Anti-Fn14 antibody (mAb 002) targets the TWEAK receptor (Fn14) in murine models of cancer cachexia and can extend the lifespan of mice by restoring the body weight of mice. Here, we investigated glucose metabolic changes in murine models of cachexia via [18F]FDG PET imaging, to explore whether Fn14 plays a role in the metabolic changes that occur during cancer cachexia.

Methods

[18F]FDG PET/MRI imaging was performed in cachexia-inducing tumour models versus models that do not induce cachexia. SUVaverage was calculated for all tumours via volume of interest (VOI) analysis of PET/MRI overlay images using PMOD software.

Results

[18F]FDG PET imaging demonstrated increased tumour and brain uptake in cachectic versus non-cachectic tumour-bearing mice. Therapy with mAb 002 was able to reduce [18F]FDG uptake in tumours (P < 0.05, n = 3). Fn14 KO tumours did not induce body weight loss and did not show an increase in [18F]FDG tumour and brain uptake over time. In non-cachectic mice bearing Fn14 KO tumours, [18F]FDG tumour uptake was significantly lower (P < 0.01) than in cachectic mice bearing Fn14 WT counterparts. As a by-product of glucose metabolism, l-lactate production was also increased in cachexia-inducing tumours expressing Fn14.

Conclusion

Our results demonstrate that Fn14 receptor activation is linked to glucose metabolism of cachexia-inducing tumours.

Graphical Abstract
FDG-PET/MRI in colorectal cancer care: an updated systematic review
Authors: Lo Hui Zhen , Choy Kay Tai , Kong Joseph Cherng Huei
Published: July 2024

Purpose

Since its introduction in 2011, FDG-PET/MRI has been advocated as a useful adjunct in colorectal cancer care. However, gaps and limitations in current research remain. This systematic review aims to review the current literature to quantify the utility of FDG-PET/MRI in colorectal cancer care.

Methods

An up-to-date review was performed on the available literature between 2000 and 2023 on PubMed, EMBASE, Medline, databases. All studies reporting on the use of FDG-PET/MRI in colorectal cancer care were analyzed. The main outcome measures were accuracy in initial staging, restaging, and detection of metastatic disease in both rectal as well as colon cancers. The secondary outcome was comparing the performance of FDG-PET/MRI versus Standard of Care Imaging (SCI). Finally, the clinical significance of FDG-PET/MRI was measured in the change in management resulting from imaging findings.

Results

A total of 22 observational studies were included, accounting for 988 patients. When individually compared to current Standard of Care Imaging (SCI)—MRI pelvis for rectal cancer and thoraco-abdominal contrast CT, PET/MRI proved superior in terms of distant metastatic disease detection. This led to as much as 21.0% change in management. However, the technological limitations of PET/MRI were once again highlighted, suggesting SCI should retain its place as first-line imaging.

Conclusion

FDG-PET/MRI appears to be a promising adjunct in staging and restaging of colorectal cancer in carefully selected patients.

Graphical Abstract
Shallow storage of the explosive Earthquake Flat Pyroclastics magma body, Okataina Volcanic Center, Taupo Volcanic Zone, New Zealand: evidence from phase-equilibria experiments
Authors: Grant Elizabeth R. G. , Blatter Dawnika L. , Sisson Thomas W. , Cooper Kari M.
Published: July 2024

Rhyolitic tuffs range widely in their crystal contents from nearly aphyric to crystal-rich, and their crystal cargoes inform concepts of upper crustal magma reservoirs. The Earthquake Flat pyroclastics (Okataina Volcanic Center, Taupo Volcanic Zone, New Zealand) are 10 km3 of rhyolitic tuffs with abundant (~ 40 vol.%) plagioclase and quartz, minor biotite, hornblende, and orthopyroxene, and accessory Fe-Ti oxides, apatite, and zircon, set in high-silica rhyolitic glass. Major minerals form large, euhedral phenocrysts and abundant glomerocrysts with few disequilibrium textures excepting some faintly resorbed quartz. Plagioclase phenocrysts have thick rims of nearly constant composition near An30, and hornblende is weakly zoned or unzoned. The abundant and texturally complex mineral assemblage contrasts with the nearby (~ 25 km), nearly synchronous, but more voluminous and crystal-moderate rhyolite tuffs from Rotoiti caldera. New H2O-saturated phase-equilibria results on the erupted Earthquake Flat melt (glass) determine its co-saturation with the partial phenocryst assemblage of plagioclase, quartz, biotite, and Fe-Ti oxides at: 140 MPa, 755 ºC. These closely approximate the conditions of the pre-eruptive magma body assuming it was saturated with nearly pure H2O and at an fO2 of ~ Ni–NiO. Absence of hornblende and orthopyroxene from the synthesized assemblages may result from those minerals being in a peritectic reaction relation with melt to produce biotite, so they would not grow from the liquid used as starting material. Experimental results on Rotoiti rhyolite (Nicholls et al. 1992) show that the two bodies resided at similar pressures, temperatures, and fO2s. Lower crystal abundance of the Rotoiti tuffs may result from slight compositional differences. We interpret that the Earthquake Flat pyroclastics were sourced from the crystal-rich periphery of a mushy reservoir system with the Rotoiti occupying a more melt-rich central location. Uncertain is whether this was a single intrusion zoned continuously in crystallinity, or discrete adjacent intrusions, but our results illustrate and quantify complexities of magma storage across relatively short distances.
Limitations of the Impagliazzo–Nisan–Wigderson Pseudorandom Generator Against Permutation Branching Programs
Authors: Hoza William M. , Pyne Edward , Vadhan Salil
Published: July 2024

The classic Impagliazzo–Nisan–Wigderson (INW) pseudorandom generator (PRG) (STOC ‘94) for space-bounded computation uses a seed of length $$O(\log n \cdot \log (nw/\varepsilon )+\log d)$$

O
(
log
n
·
log
(
n
w
/
ε
)
+
log
d
)

to fool ordered branching programs of length n, width w, and alphabet size d to within error $$\varepsilon $$
ε
. A series of works have shown that the analysis of the INW generator can be improved for the class of permutation branching programs or the more general regular branching programs, improving the $$O(\log ^2 n)$$

O
(

log
2

n
)

dependence on the length n to $$O(\log n)$$

O
(
log
n
)

or $${\tilde{O}}(\log n)$$

O
~

(
log
n
)

. However, when also considering the dependence on the other parameters, these analyses still fall short of the optimal PRG seed length $$O(\log (nwd/\varepsilon ))$$

O
(
log
(
n
w
d
/
ε
)
)

. In this paper, we prove that any “spectral analysis” of the INW generator requires seed length $$\begin{aligned} \Omega \left( \log n\cdot \log \log \left( \min \{n,d\}\right) +\log n\cdot \log \left( w/\varepsilon \right) +\log d\right) \end{aligned}$$

Ω

log
n
·
log
log

min
{
n
,
d
}

+
log
n
·
log

w
/
ε

+
log
d

to fool ordered permutation branching programs of length n, width w, and alphabet size d to within error $$\varepsilon $$
ε
. By “spectral analysis” we mean an analysis of the INW generator that relies only on the spectral expansion of the graphs used to construct the generator; this encompasses all prior analyses of the INW generator. Our lower bound matches the upper bound of Braverman–Rao–Raz–Yehudayoff (FOCS 2010, SICOMP 2014) for regular branching programs of alphabet size $$d=2$$

d
=
2

except for a gap between their $$O\left( \log n \cdot \log \log n\right) $$

O

log
n
·
log
log
n

term and our $$\Omega \left( \log n \cdot \log \log \min \{n,d\}\right) $$

Ω

log
n
·
log
log
min
{
n
,
d
}

term. It also matches the upper bounds of Koucký–Nimbhorkar–Pudlák (STOC 2011), De (CCC 2011), and Steinke (ECCC 2012) for constant-width ($$w=O(1)$$

w
=
O
(
1
)

) permutation branching programs of alphabet size $$d=2$$

d
=
2

to within a constant factor. To fool permutation branching programs in the measure of spectral norm, we prove that any spectral analysis of the INW generator requires a seed of length $$\Omega \left( \log n\cdot \log \log n+\log n\cdot \log (1/\varepsilon )\right) $$

Ω

log
n
·
log
log
n
+
log
n
·
log
(
1
/
ε
)

when the width is at least polynomial in n ($$w=n^{\Omega (1)}$$

w
=

n

Ω
(
1
)

), matching the recent upper bound of Hoza–Pyne–Vadhan (ITCS 2021) to within a constant factor.
A higher-order job crafting mediation model with PLS-SEM: relationship between organizational identification and communication satisfaction
Authors: Ciavolino Enrico , Angelelli Mario , Sternativo Giovanna Alessia , De carlo Elisa , Catalano Alessia Anna , Ingusci Emanuela
Published: July 2024

In recent years, global events have redefined working life, stimulating new organizational models. This work focuses on job crafting, which is considered the way to improve the relationship between some organizational variables and other individual variables such as organizational identification and satisfaction with communication, both of which are crucial to achieving sustainable levels of well-being. The study examines the role of latent constructs that can promote adaptive responses as well as their relations. In particular, we focus on organizational identification in promoting adaptive responses, including the increase in structural resources, the increase in challenging demands, and the increase in social resources as adaptive strategies to improve satisfaction with communication. The analysis is carried out using robust statistical techniques that are suited to the study of causal relations between abstract constructs. Specifically, after Confirmatory Composite Analysis (CCA-PLS) to evaluate the quality of the data collected, a higher order mediation model, based on partial least squares structural equation modeling (PLS-SEM), was performed to test the mediation role of the job crafting. In addition, we prioritize such latent constructs using importance–performance map analysis (IPMA) to evaluate the relevance and performance of each construct of this model. The results show a relationship between organizational identification, corresponding to a high sense of belonging, and communication satisfaction at all levels through the mediation of job crafting.
Analysis of strategies for scalable transaction creation in blockchains
Authors: Delzer Ole , Hobeck Richard , Weber Ingo , Kaaser Dominik , Sober Michael , Schulte Stefan
Published: July 2024

The growing popularity of blockchains highlights the need to improve their scalability. While previous research has focused on scaling transaction processing, the scalability of transaction creation remains unexplored. This issue is particularly important for organizations needing to send large volumes of transactions quickly or continuously. Scaling transaction creation is challenging, especially for blockchain platforms like Ethereum, which require transactions to include a sequence number. This paper proposes four different methods to scale transaction creation. Our experimental evaluation assesses the scalability and latency of these methods, identifying two as feasible for scaling transaction creation. Additionally, we provide an in-depth theoretical analysis of these two methods.
Agricultural low-cost waste adsorption of methylene blue and modelling linear isotherm method versus nonlinear prediction
Authors: Yetgin Senem , Amlani Merilyn
Published: July 2024

This study shows that geographically marked wheat hull, named Siyez, rice hull Sarı Kılçık, and Taşköprü Garlic stalk were used as agricultural waste to potential adsorbent materials for removing methylene blue from aqueous solution. Experimental data were evaluated in both equilibrium batch process and kinetic studies. In addition, the factors that affect the adsorption capacities, such as pH solutions, methylene blue concentration, contact time, and temperatures, were also investigated. Obtained data were subject to two constant adsorption models of Langmuir, Freundlich, Temkin, and Dubinin−Radushkevich. The kinetic models (pseudo-first-order, pseudo-second-order, intra-particle diffusion and film diffusion) and thermodynamic parameters were evaluated. The adsorption isotherms, characterized by an excellent fit with the Langmuir model (R2 = 0.99) across all adsorbents, underscore the prevalence of monolayer adsorption of methylene blue, in contrast to the Freundlich equation. Adsorption kinetics of the methylene blue onto the adsorbents followed pseudo-second-order kinetic model. According to high regression coefficient (R2) and minimal values of nonlinear error functions like RMSE; the maximum monolayer adsorption capacities of wheat hull, rice hull and garlic stalk were found to be 62.50 (mg/g), 54.94 (mg/g), and 370.37 (mg/g), respectively. The results indicated that these proposed adsorbents could be low-cost and effective adsorbents for water purification and have adsorption capacity as much as comparable with the literature. In batch equilibrium studies, the adsorption of methylene blue dye onto the wheat hull, rice hull, and garlic stalk exhibited a significant correlation with temperature, contact time, and initial concentration of methylene blue dye and Adaptive Neuro-Fuzzy Inference System algorithm for forecasting overall the system parameter well fitted with these findings with the accuracy of outputs (R2 about 0.99 for each). Consequently, the thermodynamic analysis revealed that the adsorption process takes place in bulk diffusion by liquid phase mass transfer and occurred spontaneously with endothermically except garlic stalk. Adsorption thermodynamic studies show that the adsorption of methylene blue onto the garlic stalk was spontaneous and exothermic.

Graphical Abstract
Anterior interhemispheric vs. pterional approach in the microsurgical management of anterior communicating artery aneurysms: a comparative analysis employing a novel multidimensional matching-tool
Authors: Swiatek Vanessa M. , Amini Amir , Spitz Lena , Rashidi Ali , Dumitru Claudia A. , Stein Klaus-Peter , Saalfeld Sylvia , Sandalcioglu I. Erol , Neyazi Belal
Published: July 2024

The surgical management of anterior communicating artery aneurysms (AcomA) is challenging due to their deep midline position and proximity to complex skull base anatomy. This study compares the pterional craniotomy with the interhemispheric approach based on the specific aneurysm angulation. A total of 129 AcomA cases were analyzed, with 50 undergoing microsurgical clipping via either the pterional or interhemispheric approach. All selected cases had computed tomography-angiography with sagittal imaging slices and 2D-angiography. Using an interactive tool, 14 cases treated via the interhemispheric approach were matched with 14 cases approached pterionally based on clinical and morphological parameters, emphasizing intracranial aneurysm (IA) dome angulation relative to the frontal skull base. Outcomes included IA occlusion, temporary clipping incidence, intraoperative rupture, postoperative strokes, hemorrhages, hydrocephalus, vasospasm, and patient functionality. Matched cohorts had consistent demographics. Both approaches resulted in similar IA occlusion rates, but the interhemispheric approach led to improved clinical outcomes, measured by the modified Rankin Scale. It also had a lower incidence of hydrocephalus and reduced need for permanent ventriculoperitoneal shunt placement. Vasospasms and postoperative infarction rates were comparable between the groups. Our findings suggest potential advantages of the interhemispheric approach in managing AcomA, depending on aneurysm angulation. Despite a small sample size, the results highlight the importance of customized surgical decision-making based on the unique traits of each aneurysm and the surgeon's expertise.
Some counterexamples to Alt–Caffarelli–Friedman monotonicity formulas in Carnot groups
Authors: Ferrari Fausto , Giovagnoli Davide
Published: July 2024

In this paper we continue the analysis of an Alt–Caffarelli–Friedman (ACF) monotonicity formula in Carnot groups of step $$s >1$$

s
>
1

confirming the existence of counterexamples to the monotone increasing behavior. In particular, we provide a sufficient condition that implies the existence of some counterexamples to the monotone increasing behavior of the ACF formula in Carnot groups. The main tool is based on the lack of orthogonality of harmonic polynomials in Carnot groups. This paper generalizes the results proved in Ferrari and Forcillo (Atti Accad Naz Lincei Rend Lincei Mat Appl 34(2):295–306, 2023).
Efficient uncertainty quantification in a spatially multiscale model of pulmonary arterial and venous hemodynamics
Authors: Colebank M. J. , Chesler N. C.
Published: July 2024

Pulmonary hypertension (PH) is a debilitating disease that alters the structure and function of both the proximal and distal pulmonary vasculature. This alters pressure-flow relationships in the pulmonary arterial and venous trees, though there is a critical knowledge gap in the relationships between proximal and distal hemodynamics in disease. Multiscale computational models enable simulations in both the proximal and distal vasculature. However, model inputs and measured data are inherently uncertain, requiring a full analysis of the sensitivity and uncertainty of the model. Thus, this study quantifies model sensitivity and output uncertainty in a spatially multiscale, pulse-wave propagation model of pulmonary hemodynamics. The model includes fifteen proximal arteries and twelve proximal veins, connected by a two-sided, structured tree model of the distal vasculature. We use polynomial chaos expansions to expedite sensitivity and uncertainty quantification analyses and provide results for both the proximal and distal vasculature. We quantify uncertainty in blood pressure, blood flow rate, wave intensity, wall shear stress, and cyclic stretch. The latter two are important stimuli for endothelial cell mechanotransduction. We conclude that, while nearly all the parameters in our system have some influence on model predictions, the parameters describing the density of the microvascular beds have the largest effects on all simulated quantities in both the proximal and distal arterial and venous circulations.
Are aortic biomechanical properties early markers of dilatation in patients with Marfan syndrome? A systematic review and meta-analysis
Authors: Rosnel Claire , Sivera Raphael , Cervi Elena , Danton Mark , Schievano Silvia , Capelli Claudio , Aggarwal Ankush
Published: July 2024

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), $$\beta $$
β
-stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. $$\beta $$
β
-SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and $$\beta $$
β
-stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, $$\beta $$
β
-SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery.
3D Features Fusion for Automated Segmentation of Fluid Regions in CSCR Patients: An OCT-based Photodynamic Therapy Response Analysis
Authors: Goyanes Elena , de Moura Joaquim , Fernández-Vigo José I. , García-Feijóo Julián , Novo Jorge , Ortega Marcos
Published: July 2024

Central Serous Chorioretinopathy (CSCR) is a significant cause of vision impairment worldwide, with Photodynamic Therapy (PDT) emerging as a promising treatment strategy. The capability to precisely segment fluid regions in Optical Coherence Tomography (OCT) scans and predict the response to PDT treatment can substantially augment patient outcomes. This paper introduces a novel deep learning (DL) methodology for automated 3D segmentation of fluid regions in OCT scans, followed by a subsequent PDT response analysis for CSCR patients. Our approach utilizes the rich 3D contextual information from OCT scans to train a model that accurately delineates fluid regions. This model not only substantially reduces the time and effort required for segmentation but also offers a standardized technique, fostering further large-scale research studies. Additionally, by incorporating pre- and post-treatment OCT scans, our model is capable of predicting PDT response, hence enabling the formulation of personalized treatment strategies and optimized patient management. To validate our approach, we employed a robust dataset comprising 2,769 OCT scans (124 3D volumes), and the results obtained were significantly satisfactory, outperforming the current state-of-the-art methods. This research signifies an important milestone in the integration of DL advancements with practical clinical applications, propelling us a step closer towards improved management of CSCR. Furthermore, the methodologies and systems developed can be adapted and extrapolated to tackle similar challenges in the diagnosis and treatment of other retinal pathologies, favoring more comprehensive and personalized patient care.
Amplitude and duration hazard-consistent ground-motion selection for seismic risk assessment in Mexico City
Authors: López-Castañeda Alhelí S. , Martín del Campo Osvaldo , Reinoso Eduardo
Published: July 2024

The emphasis of seismic design regulations on applying nonlinear dynamic analyses (NDAs) promotes using accelerograms that characterize site-specific ground motions. Commonly, amplitude levels of such accelerograms are defined by a target spectrum that could be based on a uniform hazard spectrum (UHS), which is determined by a probabilistic seismic hazard analysis (PSHA) and represents a response spectrum with ordinates having an equal probability of being exceeded within a given return period, $${T}_{r}$$

T
r

. Conversely, the definition of ground-motion duration levels is not yet properly defined in current regulations to select accelerograms. Thus, adhering to data handling as that for amplitude ground-motion parameters, this study motivates executing PSHAs to define hazard-consistent levels for the ground-motion duration. That is, accelerograms can be selected to match both amplitude and duration ground-motion levels associated with $${T}_{r}$$

T
r

. Further, fragility functions conditional on $${T}_{r}$$

T
r

that cover typical performance objectives can be developed using sets of hazard-consistent accelerograms to implement, e.g., multiple stripe analyses (MSAs). To demonstrate the importance of choosing fully hazard-consistent accelerograms to perform NDAs, this study includes the displacement- and energy-based seismic-response evaluation of a steel frame building located at different soil-profile sites in Mexico City. Sets of fully hazard-consistent accelerograms and solely amplitude-based hazard-consistent accelerograms were artificially generated per site for values of $${T}_{r}$$

T
r

up to 5000 years. Results indicate that the probability of failure can be underestimated if the ground-motion duration is unvaried in MSAs, e.g., structural damage caused by 50-year return-period or higher events can be more noticeable when fully hazard-consistent accelerograms take place.
Copper doped hydroxyapatite nanocomposite thin films: synthesis, physico–chemical and biological evaluation
Authors: Ciobanu Carmen Steluta , Predoi Daniela , Iconaru Simona Liliana , Predoi Mihai Valentin , Ghegoiu Liliana , Buton Nicolas , Motelica-Heino Mikael
Published: July 2024

Cu-doped hydroxyapatite (CuHAp) thin films were obtained using spin coating method. To make these thin films, CuHAp suspensions obtained by sol–gel method were used. The coatings obtained were thermally treated at 500 °C. After the thermal treatment, the thin films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM). Moreover, the stability of the suspensions before being used to obtain the thin films was certified by dynamic light scattering (DLS), zeta potential methods and ultrasound measurements. In the XRD patterns, the peaks associated with hexagonal hydroxyapatite were identified in accordance with JCPDS no. 09-0432. EDS and XPS results confirmed the presence of Cu ions in the samples. Data about the morphological features and chemical composition of CuHAp thin films were obtained by performing scanning electron microscopy (SEM) measurements. Our results suggest that the CuHAp thin films surface is continuous and homogenous. The presence of the functional groups in the CuHAp thin films was confirmed by Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy studies. Information about the surface topography of the CuHAp thin films has been obtained using atomic force microscopy (AFM). The AFM images determined that the surface topography of the CuHAp thin layer is homogenous and continuous without presenting any unevenness or fissures. The cytotoxicity of CuHAp thin films was assessed using human gingival fibroblasts (HGF-1) cells. The results of the cell viability assays demonstrated that the thin films presented good biocompatible properties towards the HGF-1 cells. Additionally, the adherence and development of HGF-1 cells on the surface of CuHAp thin films were determined using AFM. The AFM surface topographies highlighted that the CuHAp thin film’s surface favored the attachment and proliferation of HGF-1 cells on their surface.
Proteasome activity inhibition mediates endoplasmic reticulum stress-apoptosis in triptolide/lipopolysaccharide-induced hepatotoxicity
Authors: Cheng Ruohan , Jiang Yihan , Zhang Yue , Ismail Mohammed , Zhang Luyong , Jiang Zhenzhou , Yu Qinwei
Published: July 2024

Triptolide (TP) is a major active and toxic composition of the Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), exhibiting various therapeutic bioactivities. Among the toxic effects, the hepatotoxicity of TP deserves serious attention. Previously, our research group proposed a new view of TP-related hepatotoxicity: hepatic hypersensitivity under lipopolysaccharide (LPS) stimulation. However, the mechanism of TP/LPS-induced hepatic hypersensitivity remains unclear. In this study, we investigated the mechanism underlying TP/LPS-induced hypersensitivity from the perspective of the inhibition of proteasome activity, activated endoplasmic reticulum stress (ERS)-related apoptosis, and the accumulation of reactive oxygen species (ROS). Our results showed that N-acetylcysteine (NAC), a common ROS inhibitor, decreased the expression of cleaved caspase-3 and cleaved PARP, which are associated with FLIP enhancement. Moreover, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was able to alleviate TP/LPS-induced hepatotoxicity by reducing ERS-related apoptosis protein expression (GRP78, p-eIF2α/eIF2α, ATF4, CHOP, cleaved caspase-3 and cleaved PARP) and ROS levels, with ATF4 being an indispensable mediator. In addition, the proteasome activity inhibitor MG-132 further aggravated ERS-related apoptosis, which indicated that the inhibition of proteasome activity also plays an important role in TP/LPS-related liver injuries. In summary, we propose that TP/LPS may upregulate the activation of ERS-associated apoptosis by inhibiting proteasome activity and enhancing ROS production through ATF4.

Graphical Abstract
U.S. Housing Outcomes by Race, Ethnicity, and Sexual Orientation, 2005–2021
Authors: Jepsen Christopher , Jepsen Lisa
Published: July 2024

Using American Community Survey data from 2005 to 2021, we document differences in housing outcomes by race, ethnicity, and sexual orientation. Relative to White couples, Black couples have substantially lower homeownership probabilities and home values. The Hispanic-White gap in housing outcomes is smaller than the Black-White gap. With respect to sexual orientation, same-sex couples have lower ownership probabilities than married, different-sex couples. By revealing where inequities in housing exist, our results can inform policies to close the gaps in housing outcomes.
Unraveling bacterial stress responses: implications for next-generation antimicrobial solutions
Authors: Avci Fatma Gizem
Published: July 2024

The accelerated spread of antimicrobial-resistant bacteria has caused a serious health problem and rendered antimicrobial treatments ineffective. Innovative approaches are crucial to overcome the health threat posed by resistant pathogens and prevent the emergence of untreatable infections. Triggering stress responses in bacteria can diminish susceptibility to various antimicrobials by inducing resistance mechanisms. Therefore, a thorough understanding of stress response control, especially in relation to antimicrobial resistance, offers valuable perspectives for innovative and efficient therapeutic approaches to combat antimicrobial resistance. The aim of this study was to evaluate the stress responses of 8 different bacteria by analyzing reporter metabolites, around which significant alterations were observed, using a pathway-driven computational approach. For this purpose, the transcriptomic data that the bacterial pathogens were grown under 11 different stress conditions mimicking the human host environments were integrated with the genome-scale metabolic models of 8 pathogenic species (Enterococcus faecalis OG1R, Escherichia coli EPEC O127:H6 E2348/69, Escherichia coli ETEC H10407, Escherichia coli UPEC 536, Klebsiella pneumoniae MGH 78578, Pseudomonas aeruginosa PAO1, Staphylococcus aureus MRSA252, and Staphylococcus aureus MSSA476). The resulting reporter metabolites were enriched in multiple metabolic pathways, with cofactor biosynthesis being the most important. The results of this study will serve as a guide for the development of antimicrobial agents as they provide a first insight into potential drug targets.
Multilevel Modelling in Economics: A Way to Test the Natural-Partner Hypothesis
Authors: Martínez-Martínez Alejandra , Esteve-Pérez Silviano , Gil-Pareja Salvador , Llorca-Vivero Rafael
Published: July 2024

This study applies multilevel modelling to the analysis of trade flows. This methodology can complement the use of the standard gravity equation in addressing the influence of geographical distance on the impact of trade agreements on bilateral trade (the natural-partner hypothesis). The analysis suggests that the simplest, most obvious, and best way to nest country pairs with international trade data is by distance. To this end, a sample of 69 countries with data on domestic flows over the period 1986–2016 was used. This sample accounts for around 85% of world trade data. The estimations suggest that the pro-trade effects of preferential trade agreements decrease with distance to trade partners, while this does not occur with the multilateral trading system. What is more interesting is that the former result only holds for the preferential trade agreements involving goods, which supports the natural-trading partner hypothesis, but not for those that include services. In the latter case, the impact increases with distance. This suggests that deeper preferential trade agreements reduce the cost of distance as a barrier to trade, which probably reflects cultural (regulation) distance.
Novel Program Connects Medical Students with Startups Focused on Social Determinants of Health
Authors: Brown Danielle E. , Malinovitch Angela , Posner Hannah , Indrakanti Deepak , Sharma Medha , Karamardian Michael , Dine C. Jessica
Published: July 2024

Background

Understanding health equity is critical for the development of patient-centered physicians, but few avenues exist for medical students to participate in experiential learning related to social determinants of health (SDOH).

Aim

To create and evaluate the PennHealthX SDOH Accelerator Program, which pairs students with health equity startups.

Setting

The program matches medical students at our institution with startups focused on SDOH for voluntary, part-time internships.

Participants

Medical students of all years are eligible to apply. Startups are typically early-stage (≤ 10 employees).

Program Description

Two pre-clinical students lead the program. Startups are sourced via alumni networking, partnerships with venture capital firms, and cold outreach. Startups and students apply and are matched based on project goals and student backgrounds/skills. Upon completion, feedback is gathered through open-ended interviews with all students.

Program Evaluation

Twenty medical students were matched with 11 startups. In post-program interviews, students expressed high satisfaction. Students specifically valued the opportunity to learn about SDOH in a hands-on and solution-oriented way.

Discussion

This program gives students the opportunity to impact their communities and learn about addressing SDOH with innovative solutions. We are continuing to build the program at our institution and expand its impact to other medical schools.
Protection from oxygen–glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes
Authors: Moloney Roisin , Pavy Carlton L. , Kahl Richard G. S. , Palliser Hannah K. , Hirst Jon J. , Shaw Julia C.
Published: July 2024

Preterm birth results in an increased risk of neonatal brain injury and neurobehavioural disorders. Despite the seriousness of these adverse outcomes, there are currently no effective therapies to protect the vulnerable developing brain. We propose that neurosteroid replacement therapy may be a novel approach in reducing detrimental neurological outcomes following preterm birth. The use of guinea pig primary neuronal and oligodendrocyte cultures with relevance to late gestation allows insight into the mechanisms behind the effectiveness of these treatments. Primary neuronal and oligodendrocyte cultures were derived from fetal guinea pig frontal cortex brain tissue at gestational age 62 (GA62). Cell cultures were pre-treated with either etifoxine (5 µM) or zuranolone (1 µm) for 24 h prior to insult. Cells were then exposed to either oxygen–glucose deprivation (OGD; 0% O2 and no glucose DMEM; preterm birth insult) or sham (standard cell culture conditions; 25 mM DMEM) for 2 h. Lactate dehydrogenase assay (LDH) was performed following OGD as a measure of cytotoxicity. Relative mRNA expression of key neuronal and oligodendrocyte markers, as well as neuronal receptors and transporters, were quantified using high throughput (Fluidigm) RT-PCR. OGD significantly increased cellular cytotoxicity in both neurons and oligodendrocytes. Additionally, key neuronal marker mRNA expression was reduced following OGD, and oligodendrocytes displayed arrested mRNA expression of key markers of lineage progression. Treatment with etifoxine restored a number of parameters back to control levels, whereas treatment with zuranolone provided a robust improvement in all parameters examined. This study has demonstrated the neuroprotective potential of neurosteroid replacement therapy in a model of hypoxia related to preterm birth. Neuroprotection appears to be mediated through glutamate reduction and increased brain derived neurotrophic factor (BDNF). Future work is warranted in examining these treatments in vivo, with the overall aim to suppress preterm associated brain damage and reduce long term outcomes for affected offspring.
State of the Art of Coupled Thermo–hydro-Mechanical–Chemical Modelling for Frozen Soils
Authors: Li Kai-Qi , Yin Zhen-Yu
Published: July 2024

Numerous studies have investigated the coupled multi-field processes in frozen soils, focusing on the variation in frozen soils and addressing the influences of climate change, hydrological processes, and ecosystems in cold regions. The investigation of coupled multi-physics field processes in frozen soils has emerged as a prominent research area, leading to significant advancements in coupling models and simulation solvers. However, substantial differences remain among various coupled models due to the insufficient observations and in-depth understanding of multi-field coupling processes. Therefore, this study comprehensively reviews the latest research process on multi-field models and numerical simulation methods, including thermo-hydraulic (TH) coupling, thermo-mechanical (TM) coupling, hydro-mechanical (HM) coupling, thermo–hydro-mechanical (THM) coupling, thermo–hydro-chemical (THC) coupling and thermo–hydro-mechanical–chemical (THMC) coupling. Furthermore, the primary simulation methods are summarised, including the continuum mechanics method, discrete or discontinuous mechanics method, and simulators specifically designed for heat and mass transfer modelling. Finally, this study outlines critical findings and proposes future research directions on multi-physical field modelling of frozen soils. This study provides the theoretical basis for in-depth mechanism analyses and practical engineering applications, contributing to the advancement of understanding and management of frozen soils.
Racial and Ethnic Disparities in Peri-and Post-operative Cardiac Surgery
Authors: Scott Shane S. , Gouchoe Doug A. , Azap Lovette , Henn Matthew C. , Choi Kukbin , Mokadam Nahush A. , Whitson Bryan A. , Pawlik Timothy M. , Ganapathi Asvin M.
Published: July 2024

Purpose of Review

Despite efforts to curtail its impact on medical care, race remains a powerful risk factor for morbidity and mortality following cardiac surgery. While patients from racial and ethnic minority groups are underrepresented in cardiac surgery, they experience a disproportionally elevated number of adverse outcomes following various cardiac surgical procedures. This review provides a summary of existing literature highlighting disparities in coronary artery bypass surgery, valvular surgery, cardiac transplantation, and mechanical circulatory support.

Recent Findings

Unfortunately, specific causes of these disparities can be difficult to identify, even in large, multicenter studies, due to the complex relationship between race and post-operative outcomes. Current data suggest that these racial/ethnic disparities can be attributed to a combination of patient, socioeconomic, and hospital setting characteristics.

Proposed solutions to combat the mechanisms underlying the observed disparate outcomes require deployment of a multidisciplinary team of cardiologists, anesthesiologists, cardiac surgeons, and experts in health care equity and medical ethics. Successful identification of at-risk populations and the implementation of preventive measures are necessary first steps towards dismantling racial/ethnic differences in cardiac surgery outcomes.
Identifying managed aquifer recharge and rain water harvesting sites and structures for storing non-conventional water using GIS-based multi-criteria decision analysis approach
Authors: Seif Ahmed Khaled , Masria Ali , Ghareeb Mohamed , Saleh Ahmed Adel , Soliman Karim , Ammar A. I.
Published: July 2024

In arid climates, conventional water resources are severely limited and stressed in the face of rapid population growth and future climate change. So, it is necessary to find alternative non-conventional water resources for use in drought situations. Additionally, the non-conventional water resources in these areas are not sufficient to meet future water demand. Therefore, non-conventional water resources can be adopted as a strategic reserve to bridge the gap between water supply and demand in case of emergency and drought events. These resources might include rainwater harvesting, treated wastewater, and desalinated seawater. Managed aquifer recharge (MAR) can be applied to store these resources in the hydrogeological system using Geo information System—Multi Criteria Decision Analysis (GIS-MCDA) approach for determining the suitable MAR location for storage. North-west Kingdom of Saudi Arabia area was chosen for this study because it is extremely arid, has high potential for social and economic development, and it has newly constructed non-conventional water infrastructures distributed throughout the area including water desalination plants, Tertiary Sewage Effluent (TSE) waste water plants, and flash-flood storage dams. To identify the suitable MAR site location and structure, different data related to aquifer hydrogeology, surface hydrology, hydrometeorology, and water quality were applied. Then, GIS-MCDA holistic approach was applied with aid of ordered weighting average (OWA) technique. Finally, two maps were created to show the MAR location and structure type. Potential map indicates that ~ 18.85% of the area is suitable for MAR installations. About 0.17% of the total area exhibited very high potential, where infiltration ponds can be applied, 1.86% had high potential for construction of check dams with diversion channels, and 16.82% had moderate potential for installation of recharge wells. Additionally, 56 MAR structures were proposed and a map showing their locations has been created. Thus, results indicated that the study area is promising for MAR installation. These maps could aid the decision makers to propose a sustainable development plan for the future water resources of the area.