bluuebunny/crossref_metadata_2025 huggingface dataset:
The Medicines Intelligence Data Platform: A Population‐Based Data Resource From New South Wales, Australia
Authors: Zoega Helga , Falster Michael O. , Gillies Malcolm B. , Litchfield Melisa , Camacho Ximena , Bruno Claudia , Daniels Benjamin , Donnolley Natasha , Havard Alys , Schaffer Andrea L. , Chambers Georgina , Degenhardt Louisa , Dobbins Timothy , Gisev Natasa , Ivers Rebecca , Jorm Louisa , Liu Bette , Vajdic Claire M. , Pearson Sallie‐Anne
Published: August 2024

Background

The Medicines Intelligence (MedIntel) Data Platform is an anonymised linked data resource designed to generate real‐world evidence on prescribed medicine use, effectiveness, safety, costs and cost‐effectiveness in Australia.

Results

The platform comprises Medicare‐eligible people who are ≥18 years and residing in New South Wales (NSW), Australia, any time during 2005–2020, with linked administrative data on dispensed prescription medicines (Pharmaceutical Benefits Scheme), health service use (Medicare Benefits Schedule), emergency department visits (NSW Emergency Department Data Collection), hospitalisations (NSW Admitted Patient Data Collection) plus death (National Death Index) and cancer registrations (NSW Cancer Registry). Data are currently available to 2022, with approval to update the cohort and data collections annually. The platform includes 7.4 million unique people across all years, covering 36.9% of the Australian adult population; the overall population increased from 4.8 M in 2005 to 6.0 M in 2020. As of 1 January 2019 (the last pre‐pandemic year), the cohort had a mean age of 48.7 years (51.1% female), with most people (4.4 M, 74.7%) residing in a major city. In 2019, 4.4 M people (73.3%) were dispensed a medicine, 1.2 M (20.5%) were hospitalised, 5.3 M (89.4%) had a GP or specialist appointment, and 54 003 people died. Anti‐infectives were the most prevalent medicines dispensed to the cohort in 2019 (43.1%), followed by nervous system (32.2%) and cardiovascular system medicines (30.2%).

Conclusion

The MedIntel Data Platform creates opportunities for national and international research collaborations and enables us to address contemporary clinically‐ and policy‐relevant research questions about quality use of medicines and health outcomes in Australia and globally.
ThermoLink: Bridging disulfide bonds and enzyme thermostability through database construction and machine learning prediction
Authors: Xu Ran , Pan Qican , Zhu Guoliang , Ye Yilin , Xin Minghui , Wang Zechen , Wang Sheng , Li Weifeng , Wei Yanjie , Guo Jingjing , Zheng Liangzhen
Published: August 2024

Disulfide bonds, covalently formed by sulfur atoms in cysteine residues, play a crucial role in protein folding and structure stability. Considering their significance, artificial disulfide bonds are often introduced to enhance protein thermostability. Although an increasing number of tools can assist with this task, significant amounts of time and resources are often wasted owing to inadequate consideration. To enhance the accuracy and efficiency of designing disulfide bonds for protein thermostability improvement, we initially collected disulfide bond and protein thermostability data from extensive literature sources. Thereafter, we extracted various sequence‐ and structure‐based features and constructed machine‐learning models to predict whether disulfide bonds can improve protein thermostability. Among all models, the neighborhood context model based on the Adaboost‐DT algorithm performed the best, yielding “area under the receiver operating characteristic curve” and accuracy scores of 0.773 and 0.714, respectively. Furthermore, we also found AlphaFold2 to exhibit high superiority in predicting disulfide bonds, and to some extent, the coevolutionary relationship between residue pairs potentially guided artificial disulfide bond design. Moreover, several mutants of imine reductase 89 (IR89) with artificially designed thermostable disulfide bonds were experimentally proven to be considerably efficient for substrate catalysis. The SS‐bond data have been integrated into an online server, namely, ThermoLink, available at guolab.mpu.edu.mo/thermoLink.
Biochemical characterization of naturally occurring mutations in SARS‐CoV‐2 RNA‐dependent RNA polymerase
Authors: Danda Matěj , Klimešová Anna , Kušková Klára , Dostálková Alžběta , Pagáčová Aneta , Prchal Jan , Kapisheva Marina , Ruml Tomáš , Rumlová Michaela
Published: August 2024

Since the emergence of SARS‐CoV‐2, mutations in all subunits of the RNA‐dependent RNA polymerase (RdRp) of the virus have been repeatedly reported. Although RdRp represents a primary target for antiviral drugs, experimental studies exploring the phenotypic effect of these mutations have been limited. This study focuses on the phenotypic effects of substitutions in the three RdRp subunits: nsp7, nsp8, and nsp12, selected based on their occurrence rate and potential impact. We employed nano‐differential scanning fluorimetry and microscale thermophoresis to examine the impact of these mutations on protein stability and RdRp complex assembly. We observed diverse impacts; notably, a single mutation in nsp8 significantly increased its stability as evidenced by a 13°C increase in melting temperature, whereas certain mutations in nsp7 and nsp8 reduced their binding affinity to nsp12 during RdRp complex formation. Using a fluorometric enzymatic assay, we assessed the overall effect on RNA polymerase activity. We found that most of the examined mutations altered the polymerase activity, often as a direct result of changes in stability or affinity to the other components of the RdRp complex. Intriguingly, a combination of nsp8 A21V and nsp12 P323L mutations resulted in a 50% increase in polymerase activity. To our knowledge, this is the first biochemical study to demonstrate the impact of amino acid mutations across all components constituting the RdRp complex in emerging SARS‐CoV‐2 subvariants.
Integrating molecular dynamics simulation with small‐ and wide‐angle X‐ray scattering to unravel the flexibility, antigen‐blocking, and protease‐restoring functions in a hindrance‐based pro‐antibody
Authors: Liao Jun Min , Hong Shih‐Ting , Wang Yeng‐Tseng , Cheng Yi‐An , Ho Kai‐Wen , Toh Shu‐Ing , Shih Orion , Jeng U‐Ser , Lyu Ping‐Chiang , Hu I‐Chen , Huang Ming‐Yii , Chang Chin‐Yuan , Cheng Tian‐Lu
Published: August 2024

Spatial hindrance‐based pro‐antibodies (pro‐Abs) are engineered antibodies to reduce monoclonal antibodies' (mAbs) on‐target toxicity using universal designed blocking segments that mask mAb antigen‐binding sites through spatial hindrance. By linking through protease substrates and linkers, these blocking segments can be removed site‐specifically. Although many types of blocking segments have been developed, such as coiled‐coil and hinge‐based Ab locks, the molecular structure of the pro‐Ab, particularly the region showing how the blocking fragment blocks the mAb, has not been elucidated by X‐ray crystallography or cryo‐EM. To achieve maximal effect, a pro‐Ab must have high antigen‐blocking and protease‐restoring efficiencies, but the unclear structure limits its further optimization. Here, we utilized molecular dynamics (MD) simulations to study the dynamic structures of a hinge‐based Ab lock pro‐Ab, pro‐Nivolumab, and validated the simulated structures with small‐ and wide‐angle X‐ray scattering (SWAXS). The MD results were closely consistent with SWAXS data (χ2best‐fit = 1.845, χ2allMD = 3.080). The further analysis shows a pronounced flexibility of the Ab lock (root‐mean‐square deviation = 10.90 Å), yet it still masks the important antigen‐binding residues by 57.3%–88.4%, explaining its 250‐folded antigen‐blocking efficiency. The introduced protease accessible surface area method affirmed better protease efficiency for light chain (33.03 Å2) over heavy chain (5.06 Å2), which aligns with the experiments. Overall, we developed MD‐SWAXS validation method to study the dynamics of flexible blocking segments and introduced methodologies to estimate their antigen‐blocking and protease‐restoring efficiencies, which would potentially be advancing the clinical applications of any spatial hindrance‐based pro‐Ab.
Stable monomers in the ancestral sequence reconstruction of the last opisthokont common ancestor of dimeric triosephosphate isomerase
Authors: Pérez‐Niño Jorge Alejandro , Guerra Yasel , Díaz‐Salazar A. Jessica , Costas Miguel , Rodríguez‐Romero Adela , Fernández‐Velasco D. Alejandro
Published: August 2024

Function and structure are strongly coupled in obligated oligomers such as Triosephosphate isomerase (TIM). In animals and fungi, TIM monomers are inactive and unstable. Previously, we used ancestral sequence reconstruction to study TIM evolution and found that before these lineages diverged, the last opisthokonta common ancestor of TIM (LOCATIM) was an obligated oligomer that resembles those of extant TIMs. Notably, calorimetric evidence indicated that ancestral TIM monomers are more structured than extant ones. To further increase confidence about the function, structure, and stability of the LOCATIM, in this work, we applied two different inference methodologies and the worst plausible case scenario for both of them, to infer four sequences of this ancestor and test the robustness of their physicochemical properties. The extensive biophysical characterization of the four reconstructed sequences of LOCATIM showed very similar hydrodynamic and spectroscopic properties, as well as ligand‐binding energetics and catalytic parameters. Their 3D structures were also conserved. Although differences were observed in melting temperature, all LOCATIMs showed reversible urea‐induced unfolding transitions, and for those that reached equilibrium, high conformational stability was estimated (ΔGTot = 40.6–46.2 kcal/mol). The stability of the inactive monomeric intermediates was also high (ΔGunf = 12.6–18.4 kcal/mol), resembling some protozoan TIMs rather than the unstable monomer observed in extant opisthokonts. A comparative analysis of the 3D structure of ancestral and extant TIMs shows a correlation between the higher stability of the ancestral monomers with the presence of several hydrogen bonds located in the “bottom” part of the barrel.
Benralizumab‐resistant mucus plugs in severe asthma complicated by eosinophilic chronic rhinosinusitis
Authors: Hamakawa Masamitsu , Ishida Tadashi
Published: August 2024

Key message

It is an absolute necessity to achieve complete control of comorbidities to obtain optimal asthma control. Importantly, type 2 asthma and ECRS share the same inflammatory pathophysiology and are common co‐morbidities. If the initial biologic is insufficiently effective, it is worth considering an alternative biologic.
Implications of climate‐change‐induced stressors and water management for sterlet populations in the Middle and Upper River Danube
Authors: Šindler Martin , Kubala Maroš , Senko Dušan , Mišík Martin , Guti Gábor , Pekárik Ladislav , Drozd Bořek
Published: August 2024

Sturgeons are a group of iconic rheophilic fish whose populations worldwide are currently undergoing significant declines. The study investigates the impact of climate change and anthropogenic activities, particularly the Gabčíkovo barrage system, on the survival and distribution of the sterlet, the last surviving sturgeon species in the Middle and Upper Danube River, specifically in the river part rkm 1708–1920 divided into three river sections: PT1 (Danube river part 1: rkm 1708–Gabčíkovo impoundment), PT2 (Danube river part 2: rkm 1854–1920), and PT3 (Old Danube part 3: rkm 1850–1810). Between years 1996 and 2020, water temperatures in the Danube River (PT1, PT2) rose by over 1°C on average, with the Old Danube (PT3) experiencing an alarming average increase of 3.5°C (df = 2, F = 145.03, p = <2.2e‐16). Consequently, suitable sterlet habitat (depth ≥4 m) in the Old Danube (PT3) now covers only 11% of its total area compared with 67% in PT1 and 75% in PT2 (flow rate = 1924.27 m3 s−1) due to altered flow regimes, water levels, and siltation. Sterlets are increasingly caught in an artificial channel below to the Gabčíkovo Hydroelectric Power Plant (80%–90% of annual total catch), suggesting a shift in their distribution patterns. Conversely, there has been a notable decline in sterlet populations in other river sections, including a decrease in a section with moderate ecological status according to Water Frame Directive criteria. In light of these findings, the study proposes several mitigation measures to improve the status of the sterlet population in the area.
Information and communication technology, economic globalization, and environmental sustainability in APEC nations: Insights from LCC and EKC hypotheses testing
Authors: Ximei Kong , Javaid Muhammad Qasim , Shams Tanzeela , Sibt‐e‐Ali Muhammad
Published: August 2024

As the world grapples with pressing ecological issues, this study delves into the essential concept of environmental sustainability, following the sustainable development goal (SDG) 13, aiming to uncover pathways for a greener future. For this, the study examines the effects of information & communication technology (ICT) and economic globalization (ECG) on environmental sustainability (ENS) from a new angle, focusing on three ENS proxy variables; carbon dioxide emission (CO2e), ecological footprint (EFP), and load capacity factor (LCF), for better ecological assessment. Dissimilar to prior studies, the current study simultaneously tests the load capacity curve (LCC) and environmental Kuznets curve (EKC) hypotheses. The study employed advanced panel data estimation techniques along with causality tests, taking into account cross‐sectional dependence and slope heterogeneity for Asia‐Pacific Economic Cooperation (APEC) economies, for the period 1991–2020. The long‐run empirical outcomes reveal that information & communication technology, economic globalization, renewable energy consumption, and green financial development have the potential to enhance environmental sustainability; whereas industrialization has a detrimental influence over time. Further, the LCC and EKC hypotheses are supportable in APEC economies. Considering the overall findings there is a need for a favorable policy environment, that is APEC nations should bolster up the deployment of green ICT infrastructure; promote enhanced and collective efforts with global partners for ECG; expand the adoption of renewable energy; direct green financial development to areas of greatest benefit, and well‐managed industrialization as part of their environmental policies.
AI‐enabled information sharing mechanism and enterprise performance
Authors: Wang Fang , Zou Manting
Published: August 2024

In recent years, with the continuous application and popularization of Artificial intelligence, the influence of artificial intelligence technology applied in information‐sharing mechanisms on enterprise performance has attracted more and more attention. With the background of the extended application of artificial intelligence in information sharing, based on the data of 348 manufacturing enterprises in the eastern coastal areas of China, the theoretical model of “information sharing mechanism ‐ accounting information quality ‐ enterprise performance” is constructed, and the relationship between the three is analyzed empirically. The results show that the stronger the information sharing mechanism and accounting information quality, the higher the enterprise performance; the information sharing promotes the accounting information quality; the quality of accounting information disclosure plays an intermediary role between information sharing and enterprise performance. Therefore, enterprises should pay attention to the use of artificial intelligence technology in information sharing to improve the quality of enterprise financial reports, improve enterprise performance, and provide theoretical references for the growth of manufacturing enterprises.
Shear performance of basalt fiber composite RC beams with different laminated heights of basalt fiber
Authors: Xia Ting , Zhang Wei , Huang Min , Huang Hua
Published: August 2024

Basalt fiber (BF) is known for its high tensile strength, low elastic modulus, and environmental friendliness. To investigate the influence of basalt fiber reinforced concrete (BFRC) lamination heights on the beams' shear performance, four basalt fiber reinforced concrete and reinforced concrete (BFRC‐RC) beams featuring diverse laminated heights were fabricated and underwent bending tests. To further investigate the impact of stirrup and shear span ratios on the shear performance of BFRC‐RC beams, finite element models (FEMs) were established based on the experiments. The results indicated that four test beams experienced diagonal shear failure. Compared to RC beams, BFRC‐RC beams exhibited heightened ductility and stiffness. Additionally, as the BFRC laminated height rose, both cracking and peak loads increased. Compared to BFRC‐RC beams without stirrups, stirrups in those beams transitioned the diagonal shear failure to flexural failure. Stirrups in BFRC‐RC beams increased both the yield and peak loads, thereby enhancing their ductility. With a reduction in the shear span ratio, BFRC‐RC beams increased in both yield and peak loads, accompanied by a simultaneous decrease in yield and peak displacement. Finally, a model incorporating the influence of laminated height on BFRC‐RC beams' behavior was introduced to predict their bearing capacity. The theoretical values aligned well with the experimental results.
Optimised observables and new physics prospects in the penguin-mediated decays Bd(s) → K(∗)0ϕ
Authors: Biswas Aritra , Descotes-Genon Sébastien , Matias Joaquim , Tetlalmatzi-Xolocotzi Gilberto
Published: August 2024

Abstract

We study the penguin-mediated $$ {\overline{B}}_{d(s)}\to {\overline{K}}^{\ast 0}\left({K}^{\ast 0}\right)\phi $$

B
¯

d

s

→

K
¯

∗
0

K

∗
0

ϕ
transitions, proposing a new optimised observable LK*ϕ from the ratio of longitudinal branching ratios of these decays, with limited hadronic uncertainties and enhanced sensitivity to New Physics. This observable exhibits a deviation at the 1.48 σ level between its experimental value and its SM determination within QCD factorisation. This result can be accommodated together with the significant deviations found for the $$ {K}^{\left(\ast \right)}{\overline{K}}^{\left(\ast \right)} $$

K

∗

K
¯

∗

modes in our earlier works if New Physics affects either the QCD penguin operator Q4 or the chromomagnetic dipole operator Q8g for both b → d and b → s transitions. The allowed range for the Wilson coefficients C4s,8gs is narrower compared to C4d,8gd since the b → s transition channel $$ {\overline{B}}_d\to {\overline{K}}^{\ast 0}\phi $$

B
¯

d

→

K
¯

∗
0

ϕ
is in better agreement with the SM. However, if we add the measured branching ratio for the $$ {\overline{B}}_d\to {\overline{K}}^0\phi $$

B
¯

d

→

K
¯

0

ϕ
to our analysis, the simultaneous explanation of all the experimental data for the $$ {K}^{\left(\ast \right)}{\overline{K}}^{\left(\ast \right)} $$

K

∗

K
¯

∗

and the $$ {K}^{\ast}\left({\overline{K}}^{\left(\ast \right)}\right)\phi $$

K
∗

K
¯

∗

ϕ
channels in terms of New Physics in the Wilson coefficients C4d,s or C8gd,s only, is not possible. This set of observables can be explained more easily if we assume New Physics in both f = d, s sectors, either in (C4f , C6f ) or (C6f , C8gf ). The addition of the branching ratios of the charged modes B− → K(∗)−ϕ to the above mix of observables results in a reduction of the parameter space for the (C4f , C6f ) scenario, while discarding the (C6f , C8gf ) scenario completely. This can be traced to the discrepancy of more than 1 σ between the experimental measurements of the branching ratios of the $$ {\overline{B}}_d\left({B}^{-}\right)\to {\overline{K}}^0\left({K}^{-}\right)\phi $$

B
¯

d

B
−

→

K
¯

0

K
−

ϕ
transitions. This should provide a strong incentive for the LHCb/Belle II experiments to measure the branching ratios of $$ {\overline{B}}_d\to {\overline{K}}^{\left(\ast \right)0}\phi $$

B
¯

d

→

K
¯

∗

0

ϕ
, $$ {\overline{B}}_s\to {K}^{\ast 0}\phi $$

B
¯

s

→

K

∗
0

ϕ
and particularly B− → K−ϕ to confirm or dismiss the conclusions hinted at by present data.
SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses
Authors: Vu Manh Thien-Phong , Gouin Carla , De Wolf Julien , Jouneau Luc , Pascale Florentina , Bevilacqua Claudia , Ar Gouilh Meriadeg , Da Costa Bruno , Chevalier Christophe , Glorion Matthieu , Hannouche Laurent , Urien Céline , Estephan Jérôme , Magnan Antoine , Le Guen Morgan , Marquant Quentin , Descamps Delphyne , Dalod Marc , Schwartz-Cornil Isabelle , Sage Edouard
Published: August 2024

Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.
Repeated exposure to novelty promotes resilience against the amyloid-beta effect through dopaminergic stimulation
Authors: Velázquez-Delgado Cintia , Hernández-Ortiz Eduardo , Landa-Navarro Lucia , Tapia-Rodríguez Miguel , Moreno-Castilla Perla , Bermúdez-Rattoni Federico
Published: August 2024

Rationale

The accumulation of beta-amyloid peptide (Aβ) in the forebrain leads to cognitive dysfunction and neurodegeneration in Alzheimer's disease. Studies have shown that individuals with a consistently cognitively active lifestyle are less vulnerable to Aβ toxicity. Recent research has demonstrated that intrahippocampal Aβ can impact catecholaminergic release and spatial memory. Interestingly, exposure to novelty stimuli has been found to stimulate the release of catecholamines in the hippocampus. However, it remains uncertain whether repeated enhancing catecholamine activity can effectively alleviate cognitive impairment in individuals with Alzheimer's disease.

Objectives

Our primary aim was to investigate whether repeated exposure to novelty could enable cognitive resilience against Aβ. This protection could be achieved by modulating catecholaminergic activity within the hippocampus.

Methods

To investigate this hypothesis, we subjected mice to three different conditions—standard housing (SH), repeated novelty (Nov), or daily social interaction (Soc) for one month. We then infused saline solution (SS) or Aβ (Aβ1-42) oligomers intrahippocampally and measured spatial memory retrieval in a Morris Water Maze (MWM). Stereological analysis and extracellular baseline dopamine levels using in vivo microdialysis were assessed in independent groups of mice.

Results

The mice that received Aβ1-42 intrahippocampal infusions and remained in SH or Soc conditions showed impaired spatial memory retrieval. In contrast, animals subjected to the Nov protocol demonstrated remarkable resilience, showing strong spatial memory expression even after Aβ1-42 intrahippocampal infusion. The stereological analysis indicated that the Aβ1-42 infusion reduced the tyrosine hydroxylase axonal length in SH or Soc mice compared to the Nov group. Accordingly, the hippocampal extracellular dopamine levels increased significantly in the Nov groups.

Conclusions

These compelling results demonstrate the potential for repeated novelty exposure to strengthen the dopaminergic system and mitigate the toxic effects of Aβ1-42. They also highlight new and promising therapeutic avenues for treating and preventing AD, especially in its early stages.
Investigating the quality of extraction and quantification of bioactive compounds in berries through liquid chromatography and multivariate curve resolution
Authors: Gondo Thamani Freedom , Huang Fang , Marungruang Nittaya , Heyman-Lindén Lovisa , Turner Charlotta
Published: August 2024

Berries are a rich source of natural antioxidant compounds, which are essential to profile, as they add to their nutritional value. However, the complexity of the matrix and the structural diversity of these compounds pose challenges in extraction and chromatographic separation. By relying on multivariate curve resolution alternating least squares (MCR-ALS) ability to extract components from complex spectral mixtures, our study evaluates the contributions of various extraction techniques to interference, extractability, and quantifying different groups of overlapping compounds using liquid chromatography diode array detection (LC-DAD) data. Additionally, the combination of these methods extends its applicability to evaluate polyphenol degradation in stored berry smoothies, where evolving factor analysis (EFA) is also used to elucidate degradation products. Results indicate that among the extraction techniques, ultrasonication-assisted extraction employing 1% formic acid in methanol demonstrated superior extractability and selectivity for the different phenolic compound groups, compared with both pressurized liquid extraction and centrifugation of the fresh berry smoothie. Employing MCR-ALS on the LC-DAD data enabled reliable estimation of total amounts of compound classes with high spectral overlaps. Degradation studies revealed significant temperature-dependent effects on anthocyanins, with at least 50% degradation after 7 months of storage at room temperature, while refrigeration and freezing maintained fair stability for at least 12 months. The EFA model estimated phenolic derivatives as the main possible degradation products. These findings enhance the reliability of quantifying polyphenolic compounds and understanding their stability during the storage of berry products.

Graphical abstract
Implantierbare intravitreale Kortikosteroide bei chronischer nichtinfektiöser Uveitis
Authors: Kessler L. J. , Albrecht M. , Naujokaitis T. , Auffarth G. , Khoramnia Ramin
Published: August 2024

Hintergrund

Die Uveitis führt in Industrienationen in 10–15 % der Fälle zur Erblindung. Die Prävalenz variiert je nach Literatur von 9 bis 730 Fällen pro 100.000 Einwohner. Lokale und systemische Steroidanwendungen stellen neben Therapien mit Immunmodulatoren die Hauptbehandlungsoptionen dar. Bei chronischer und refraktärer Uveitis, aber insbesondere auch bei Manifestation eines uveitischen Makulaödems können intravitreale Kortikosteroide dazu beitragen, dass die systemische immunmodulative Therapie mit krankheitsmodifizierenden antirheumatischen Medikamenten („disease modifying anti-rheumatic drugs“ [DMARDS]), Biologika oder Kortikosteroiden reduziert oder ersetzt wird.

Ziel der Arbeit

In diesem Übersichtsartikel werden die 3 gängigen, injizierbaren, intravitrealen Kortikosteroidimplantate, die zur Behandlung der nichtinfektiösen Uveitis eingesetzt werden, vorgestellt. Die Indikation, Effektivität und das Nebenwirkungsprofil werden im Rahmen einer Darstellung der aktuellen Literatur erörtert. Es wurden 6 randomisierte, kontrollierte Studien zu FAc- und DEX-Implantaten mit > 100 Studienpatienten sowie eine Subgruppenanalyse aus einer multizentrischen, randomisierten kontrollierten Studie mit 315 Patienten gefunden und ihre Ergebnisse dargestellt.

Schlussfolgerung

Die Effektivität und das Sicherheitsprofil von intravitrealen Kortikosteroiden bei uveitischem Makulaödem wurden in den vergangenen Jahren in mehreren Studien untersucht und mit bestehenden Therapieformen, wie z. B. systemischer Therapie, verglichen. Durch lang wirksame Kortikosteroidimplantate lässt sich das rezidivfreie Intervall verlängern, und die Anzahl der Rezidive wird reduziert. Kurz wirksame Kortikosteroid(KS)-Implantate können auch während eines Schubes eingesetzt werden. Das KS-typische Nebenwirkungsprofil ist in der Regel beherrschbar, sollte jedoch v. a. bei phaken und/oder jungen Patienten berücksichtigt und ausführlich besprochen werden (z. B. die vorzeitige Entwicklung einer Linsentrübung), da in der Regel eine längerfristige Therapie nötig ist.
Rapid complete blood count and C-reactive protein determination with the Horiba Microsemi analyzer: the experience in neonatal intensive care unit of Careggi University Hospital
Authors: Nencini Francesca , Bonari Alessandro , Romano Francesca , Ciullini Mannurita Sara , Mongia Alessandra , Garieri Maria , Dani Carlo , Manzo Orazio , Pontieri Maria , Fanelli Alessandra
Published: August 2024

Microsystems represent an alternative but proficient approach of analysis outside the laboratory, and their use could help in reducing the impact of pre-analytical errors, in particular in challenging newborn samples. The study purpose is to compare the Horiba Microsemi CRP LC-767G system for rapid 3-part complete blood count (CBC) and C-reactive protein (CRP) determination with the laboratory reference systems (respectively Sysmex XN-9100™ and Roche Cobas® c702) in samples of adult patients and newborns hospitalized in the neonatal intensive care unit (NICU) samples. The comparison between the analyzers was performed through Passing-Bablok regression analysis and Bland–Altman plot. One hundred eighty-three blood samples were analyzed. The regression analysis results, performed in the newborn (n = 70) and in adult (n = 113) populations, showed a good agreement between the instruments. The evaluation of the Bland–Altman plots showed comparable values of bias < 10% for most of the parameters, but not for MPV, lymphocyte, and monocyte count. Conclusion: The comparison between the Microsemi CRP LC-767G system and the laboratory instrumentations demonstrated comparable results. The Microsemi CRP LC-767G system provides reliable analytical data and faster turnaround time, particularly useful in NICU.

What is Known:• Microsystems for point-of-care testing (POCT) represent an alternative but proficient approach of analysis outside the laboratory, in order to perform a rapid, safe, and exhaustive evaluation for critical patients’ management, acting as a valid support for treatment in acute care.

What is New:• The Microsemi CRP LC-767G system can represent an alternative but effective testing approach outside the laboratory, particularly in NICU, to reduce the impact of pre-analytical errors on newborn samples.
Barriers to the adoption of routine surgical video recording: a mixed-methods qualitative study of a real-world implementation of a video recording platform
Authors: Lam Kyle , Simister Catherine , Yiu Andrew , Kinross James M.
Published: August 2024

Background

Routine surgical video recording has multiple benefits. Video acts as an objective record of the operative record, allows video-based coaching and is integral to the development of digital technologies. Despite these benefits, adoption is not widespread. To date, only questionnaire studies have explored this failure in adoption. This study aims to determine the barriers and provide recommendations for the implementation of routine surgical video recording.

Materials and methods

A pre- and post-pilot questionnaire surrounding a real-world implementation of a C-SATS©, an educational recording and surgical analytics platform, was conducted in a university teaching hospital trust. Usage metrics from the pilot study and descriptive analyses of questionnaire responses were used with the non-adoption, abandonment, scale-up, spread, sustainability (NASSS) framework to create topic guides for semi-structured interviews. Transcripts of interviews were evaluated in an inductive thematic analysis.

Results

Engagement with the C-SATS© platform failed to reach consistent levels with only 57 videos uploaded. Three attending surgeons, four surgical residents, one scrub nurse, three patients, one lawyer, and one industry representative were interviewed, all of which perceived value in recording. Barriers of ‘change,’ ‘resource,’ and ‘governance,’ were identified as the main themes. Resistance was centred on patient misinterpretation of videos. Participants believed availability of infrastructure would facilitate adoption but integration into surgical workflow is required. Regulatory uncertainty was centred around anonymity and data ownership.

Conclusion

Barriers to the adoption of routine surgical video recording exist beyond technological barriers alone. Priorities for implementation include integration recording into the patient record, engaging all stakeholders to ensure buy-in, and formalising consent processes to establish patient trust.
Deep dive into RNA: a systematic literature review on RNA structure prediction using machine learning methods
Authors: Budnik Michał , Wawrzyniak Jakub , Grala Łukasz , Kadziński Miłosz , Szóstak Natalia
Published: August 2024

The discovery of non-coding RNAs (ncRNAs) has expanded our comprehension of RNAs’ inherent nature and capabilities. The intricate three-dimensional structures assumed by RNAs dictate their specific functions and molecular interactions. However, the limited number of mapped structures, partly due to experimental constraints of methods such as nuclear magnetic resonance (NMR), highlights the importance of in silico prediction solutions. This is particularly crucial in potential applications in therapeutic drug discovery. In this context, machine learning (ML) methods have emerged as prominent candidates, having previously demonstrated prowess in solving complex challenges across various domains. This review focuses on analyzing the development of ML-based solutions for RNA structure prediction, specifically oriented toward recent advancements in the deep learning (DL) domain. A systematic analysis of 33 works reveals insights into the representation of RNA structures, secondary structure motifs, and tertiary interactions. The review highlights current trends in ML methods used for RNA structure prediction, demonstrates the growing research involvement in this field, and summarizes the most valuable findings.
Enhanced capacity of thiol-functionalized sugarcane bagasse and rice husk biochars for arsenite sorption in aqueous solutions
Authors: Masood ul Hasan Israr , Niazi Nabeel Khan , Bibi Irshad , Younas Fazila , Al-Misned Fahad , Shakoor Muhammad Bilal , Ali Fawad , Ilyas Shazia , Hussain Muhammad Mahroz , Qiao Jinli , Lüttge Andreas
Published: August 2024

The utilization of biowastes for producing biochar to remove potentially toxic elements from water represents an important pathway for aquatic ecosystem decontamination. Here we explored the significance of thiol-functionalization on sugarcane bagasse biochar (Th/SCB–BC) and rice husk biochar (Th/RH–BC) to enhance arsenite (As(III)) removal capacity from water and compared their efficiency with both pristine biochars (SCB–BC and RH–BC). The maximum As(III) sorption was found on Th/SCB–BC and Th/RH–BC (2.88 and 2.51 mg g−1, respectively) compared to the SCB–BC and RH–BC (1.51 and 1.40 mg g−1). Relatively, a greater percentage of As(III) removal was obtained with Th/SCB–BC and Th/RH–BC (92% and 83%, respectively) at a pH 7 compared to pristine SCB–BC and RH–BC (65% and 55%) at 6 mg L−1 initial As(III) concentration, 2 h contact time and 1 g L−1 sorbent dose. Langmuir (R2 = 0.99) isotherm and pseudo-second-order kinetic (R2 = 0.99) models provided the best fits to As(III) sorption data. Desorption experiments indicated that the regeneration ability of biochars decreased and it was in the order of Th/SCB–BC (88%) > Th/RH–BC (82%) > SCB–BC (77%) > RH–BC (69%) up to three sorption–desorption cycles. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy results demonstrated that the thiol (-S–H) functional groups were successfully grafted on the surface of two biochars and as such contributed to enhance As(III) removal from water. Spectroscopic data indicated that the surface functional moieties, such as -S–H, − OH, − COOH, and C = O were involved to increase As(III) sorption on thiol-functionalized biochars. This study highlights that thiol-grafting on both biochars, notably on SCB–BC, enhanced their ability to remove As(III) from water, which can be used as an effective technique for the treatment of As from drinking water.

Graphical Abstract
Maternal exposure to bioclimatic stress and hypertensive disorders of pregnancy in Western Australia: identifying potential critical windows of susceptibility
Authors: Gebremedhin Amanuel T. , Nyadanu Sylvester Dodzi , Hanigan Ivan C. , Pereira Gavin
Published: August 2024

The anthropogenic climate change may impact pregnancy outcomes. Rather than ambient temperature, we aimed to use a composite bioclimatic metric (Universal Thermal Climate Index, UTCI) to identify critical susceptible windows for the associations between bioclimatic exposure and hypertensive disorders of pregnancy (HDPs) risk. Daily UTCI exposure from 12 weeks of preconception through pregnancy was linked to 415,091 singleton pregnancies between 1st January 2000 and 31st December 2015 in Western Australia. Adjusted weekly-specific and cumulative odds ratios (ORs) and 95% confidence intervals (CIs) of gestational hypertension and preeclampsia were estimated with distributed lag non-linear and standard non-linear logistic regressions. Exposures from early pregnancy to week 30 were associated with greater odds of HDPs with critical susceptible windows, particularly elevated at the 1st (10.2 °C) and 99th (26.0 °C) exposure centiles as compared to the median (14.2 °C). The most elevated ORs were 1.07 (95% CI 1.06, 1.08) in weeks 8–18 for gestational hypertension and 1.10 (95% CI 1.08, 1.11) in weeks 11–16 for preeclampsia for the 99th exposure centile. Cumulative exposures associated with HDPs with relatively higher but less precise ORs. The effects of high exposure to HDPs indicated sociodemographic inequalities. The identified critical periods and subpopulations could benefit from climate-related interventions.
Single-Cell Cortical Transcriptomics Reveals Common and Distinct Changes in Cell-Cell Communication in Alzheimer’s and Parkinson’s Disease
Authors: Le Bars Sophie , Glaab Enrico
Published: August 2024

Alzheimer's disease (AD) and Parkinson's disease (PD) cause significant neuronal loss and severely impair daily living. Despite different clinical manifestations, these disorders share common pathological molecular hallmarks, including mitochondrial dysfunction and synaptic degeneration. A detailed comparison of molecular changes at single-cell resolution in the cortex, as one of the main brain regions affected in both disorders, may reveal common susceptibility factors and disease mechanisms. We performed single-cell transcriptomic analyses of post-mortem cortical tissue from AD and PD subjects and controls to identify common and distinct disease-associated changes in individual genes, cellular pathways, molecular networks, and cell-cell communication events, and to investigate common mechanisms. The results revealed significant disease-specific, shared, and opposing gene expression changes, including cell type-specific signatures for both diseases. Hypoxia signaling and lipid metabolism emerged as significantly modulated cellular processes in both AD and PD, with contrasting expression alterations between the two diseases. Furthermore, both pathway and cell-cell communication analyses highlighted shared significant alterations involving the JAK-STAT signaling pathway, which has been implicated in the inflammatory response in several neurodegenerative disorders. Overall, the analyses revealed common and distinct alterations in gene signatures, pathway activities, and gene regulatory subnetworks in AD and PD. The results provide insights into coordinated changes in pathway activity and cell-cell communication that may guide future diagnostics and therapeutics.
Diet and Physical Activity Interventions for People from Minority Ethnic Backgrounds in the UK: A Scoping Review Exploring Barriers, Enablers and Cultural Adaptations
Authors: Katangwe-Chigamba Thando , Kantilal Kumud , Hartley-Palmer Joseph , Salisu-Olatunji Shukrat O. , Seeley Carys , Naughton Felix , Chester Rachel
Published: August 2024

Background

Type 2 diabetes (T2D) and cardiovascular disease (CVD) are a global pandemic, driven by obesity, poor diet and physical inactivity. In the UK, the prevalence of T2D and CVD is higher in minority ethnic groups. Lifestyle prevention interventions can be effective but uptake amongst minority ethnic groups in the UK is low and the extent of cultural adaptations to increase engagement unknown.

Aim

To explore barriers, enablers and culturally adapted lifestyle interventions in UK minority ethnic groups.

Methods

Four electronic databases were searched from to January 2013–2023. Two independent reviewers carried out manuscript selection and data extraction. Barriers and enablers were mapped to the Capability + Opportunity + Motivation = Behaviour (COM-B) theoretical model. Intervention adaptations were linked to behaviour change strategies and reported within a Cultural Adaptation framework.

Results

Twenty-three studies were included, reporting barriers/enablers, culturally adapted interventions or both. Barriers and enablers mostly mapped to social and physical opportunity, and reflective motivation. Common adaptation strategies considered behavioural influences related to culture, values, religious beliefs and/or traditions. Most impactful strategies were associated with using credible sources of information and reorganising social and environmental contexts.

Discussion and conclusions

The current umbrella approach to preventative intervention delivery is unlikely to promote sustained participation in behaviour change amongst UK ethnic minorities. Engagement strategies for this population should consider key determinants such as social contexts, beliefs and cultural norms. Important research gaps include interventions investigating tailored interventions for Black populations, and the impact of negative social experiences (e.g., racism) on engagement.
Modeling interactions in a dynamic heuristic business network
Authors: Kostelić Katarina , Turk Marko
Published: August 2024

This article presents a novel model for understanding the structure and dynamics of business networks, emphasizing the role of propensities to connect and cooperate as key drivers. The model incorporates behavioral elements and imperfect information updates, departing from traditional rational actor approaches. Starting from the theoretical background, several propositions are outlined, such as dynamism, connection choices, costs, strategy selection, information update, and the update based on experiences. Through simulations, the study successfully demonstrates that the proposed model effectively captures essential characteristics of business networks, including reciprocity, complexity, adaptation, and cooperation. The findings highlight the significance of propensities to connect and cooperate in shaping network structure, evolution, and stability. Particularly, higher propensities to cooperate and connect lead to denser and more cohesive networks, fostering reciprocity, stability, and network performance. The increase only in connection propensities does not have the same result. The lower cooperation propensities result in scale-free networks and asymmetrical distribution of cumulative payoffs. This highlights a crucial insight: different levels of cooperation lead to distinct network properties. Practical implications, increasingly relevant with the rise of digital platforms and metaverse, suggest targeted interventions to enhance network effectiveness, such as incentivizing cooperation, reducing relationship costs, and promoting a culture of trust and collaboration. While providing valuable insights, certain limitations exist, such as not considering the influence of preexisting economic or social structures, equalizing costs and payoffs among actors, and overlooking specific reasons for network connections. Future research should address these refinements and explore their effects on network structure and process characteristics.
A Workflow for Building Computationally Rational Models of Human Behavior
Authors: Chandramouli Suyog , Shi Danqing , Putkonen Aini , De Peuter Sebastiaan , Zhang Shanshan , Jokinen Jussi , Howes Andrew , Oulasvirta Antti
Published: August 2024

Computational rationality explains human behavior as arising due to the maximization of expected utility under the constraints imposed by the environment and limited cognitive resources. This simple assumption, when instantiated via partially observable Markov decision processes (POMDPs), gives rise to a powerful approach for modeling human adaptive behavior, within which a variety of internal models of cognition can be embedded. In particular, such an instantiation enables the use of methods from reinforcement learning (RL) to approximate the optimal policy solution to the sequential decision-making problems posed to the cognitive system in any given setting; this stands in contrast to requiring ad hoc hand-crafted rules for capturing adaptive behavior in more traditional cognitive architectures. However, despite their successes and promise for modeling human adaptive behavior across everyday tasks, computationally rational models that use RL are not easy to build. Being a hybrid of theoretical cognitive models and machine learning (ML) necessitates that model building take into account appropriate practices from both cognitive science and ML. The design of psychological assumptions and machine learning decisions concerning reward specification, policy optimization, parameter inference, and model selection are all tangled processes rife with pitfalls that can hinder the development of valid and effective models. Drawing from a decade of work on this approach, a workflow is outlined for tackling this challenge and is accompanied by a detailed discussion of the pros and cons at key decision points.