bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non‐carriers with mild cognitive impairment due to Alzheimer's disease
Authors: Bakker Arnold , Rani Nisha , Mohs Richard , Gallagher Michela 
Published: October 2024

AbstractIntroductionHippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended‐release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78‐week trial to assess the progression of MCI due to AD. As reported in Mohs et al., the decline in the Clinical Dementia Rating Sum of Boxes score (CDR‐SB) was reduced by 40% in apolipoprotein E (APOE) ε4 non‐carriers over the 78‐week duration of the study with a negligible effect in carriers. Here we report an exploratory analysis of the effects of AGB101 on neuroimaging and biomarker measures in the 44 APOE ε4 non‐carriers who completed the 78‐week protocol.MethodsStructural magnetic resonance imaging scans obtained at baseline and after 78 weeks were analyzed using the Automated Segmentation of Hippocampal Subfields software providing volume measures of key structures of the medial temporal lobe relevant to AD progression. Blood samples collected at 78 weeks in the study were analyzed for plasma biomarkers.ResultsTreatment with AGB101 significantly reduced atrophy of the left entorhinal cortex (ERC) compared to placebo. This reduction in atrophy was correlated with less decline in the CDR‐SB score over 78 weeks and with lower neurofilament light chain (NfL), a marker of neurodegeneration.DiscussionThe HOPE4MCI study showed that APOE ε4 non‐carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers. Here we report that treatment with AGB101 in non‐carriers of APOE ε4 significantly reduced atrophy of the left ERC over 78 weeks. That reduction in atrophy was closely coupled with the change in CDR‐SB and with plasma NfL indicative of neurodegeneration in the brain. These exploratory analyses are consistent with a reduction in neurodegeneration in APOE ε4 non‐carriers treated with AGB101 before a clinical diagnosis of dementia.Highlights
AGB101 slows entorhinal cortex (ERC) atrophy in apolipoprotein E (APOE) ε4 non‐carriers with mild cognitive impairment (MCI) due to Alzheimer's disease (AD).
Slowing ERC atrophy by AGB101 is associated with less Clinical Dementia Rating Sum of Boxes decline.
Slowing ERC atrophy by AGB101 is associated with lower neurofilament light chain.
AGB101 treatment reduces neurodegeneration in APOE ε4 non‐carriers with MCI due to AD.
Enhancing efficiency and quality control: The impact of Digital Twins in drinking water networks
Authors: Baena‐Miret Sergi , Puig Marta Alet , Rodes Rafael Bardisa , Farran Laura Bonastre , Durán Santiago , Martí Marta Ganzer , Martínez‐Gomariz Eduardo , Valverde Antonio Carrasco 
Published: October 2024

AbstractThis paper showcases the successful development and implementation of two Digital Twin prototypes within the Lab Digital Twins project, designed to enhance the efficiency and quality control of Aigües de Barcelona's drinking water network. The first prototype focuses on asset management, using (near) real‐time data and statistical models, and achieving a 70% success rate in predicting pump station failures 137 days in advance. The second prototype addresses water quality monitoring, leveraging machine learning to accurately forecast trihalomethane levels at key points in the distribution system, and enabling proactive water quality management strategies, ensuring compliance with stringent safety standards and safeguarding public health. The paper details the methodology of both prototypes, highlighting their potential to revolutionize water network management.Practitioner Points
Digital representation of assets and processes in the drinking water treatment network
Early fault detection in assets, and predictions of trihalomethane formation in the drinking water distribution network
Reduction on monitoring time and incident response for target assets by means of Digital Twins
Improvement in visualization, prediction, and proactive measures for asset management and water quality control
Contribution to the growing knowledge on Digital Twins and their potential to revolutionize water network operations
Implementation and outcomes of an enhanced recovery after surgery pathway for laparoscopic cholecystectomy in East and Central Africa: A prospective non‐randomized controlled trial in Rwanda's Tertiary Teaching Hospital
Authors: Nyundo Martin , Kayondo King , Gasakure Miguel , Twagirumukiza Jean Damascene , Gashegu Julien , Detry Olivier 
Published: October 2024

AbstractBackgroundEnhanced recovery after surgery (ERAS) programs have demonstrated efficacy in optimizing perioperative care and improving patient outcomes in various surgeries. However, their implementation and outcomes in resource‐limited settings remain underexplored. This study aimed to assess the implementation of an ERAS protocol for laparoscopic cholecystectomy in such a setting.MethodsThis prospective non‐randomized controlled trial involved 100 patients undergoing laparoscopic cholecystectomy at the University Teaching Hospital of Kigali, Rwanda. The first 50 patients on the ERAS pathway were prospectively evaluated and retrospectively compared to the last 50 patients operated on before ERAS implementation. Data on demographics, preoperative information, intraoperative compliance, postoperative events, and patient feedback were collected and analyzed.ResultsERAS implementation resulted in a significant reduction in hospital length of stay (LOS) (p < 0.001) without increase in complications. Compliance with ERAS principles, including preoperative education and perioperative management, was more than 90%. ERAS also reduced costs due to quicker recovery and shorter hospital LOS.ConclusionThe implementation of ERAS for laparoscopic cholecystectomy in a limited‐resource setting is feasible and safe, suggesting the possibility of its potential adoption in other abdominal procedures. A high level of adherence to the ERAS pathway can be achieved with effective patient education and the dedication of healthcare providers.
Note on higher-group structure in 6d self-dual gauge theory
Authors: Nakajima Tatsuki , Nakamura Kikyo , Sakai Tadakatsu 
Published: October 2024

Abstract
We analyze higher-group structure of a 6d model coupled with a self-dual 2-form gauge field. This model is defined from 6d axion-electrodynamics with a 1-form Chern-Weil(CW) symmetry gauged dynamically. The gauging leads to a Green-Schwarz-West-Sagnotti(GSWS) term, which gives rise to an anomaly through a GSWS transformation acting on the 2-form gauge field. We cancel this anomaly by gauging a 3-form CW symmetry in 6d axion-electrodynamics. We find out the global symmetries in the resultant model and derive the gauge invariant action in the presence of the background gauge fields. It is argued that a discrete 1-form symmetry is anomalous because turning on the associated background gauge field causes quantum inconsistency due to an operator-valued ambiguity. Higher-group structure in this model that is manifested as a Green-Schwarz-like transformation for CW background gauge fields is discussed.
Time-reversal anomalies of QCD3 and QED3
Authors: Hsin Po-Shen 
Published: October 2024

Abstract
Anomalies of global symmetry provide powerful tool to constrain the dynamics of quantum systems, such as anomaly matching in the renormalization group flow and obstruction to symmetric mass generation. In this note we compute the anomalies in 2+1d time-reversal symmetric gauge theories with massless fermions in the fundamental and rank-two tensor representations, where the gauge groups are SU(N), SO(N), Sp(N), U(1). The fermion parity is part of the gauge group and the theories are bosonic. The time-reversal symmetry satisfies T2 = 1 or T2 = $$ \mathcal{M} $$
M
where $$ \mathcal{M} $$
M
is an internal magnetic symmetry. We show that some of the bosonic gauge theories have time-reversal anomaly with c− ≠ 0 mod 8 that is absent in fermionic systems. The anomalies of the gauge theories can be nontrivial even when the number of Majorana fermions is a multiple of 16 and ν = 0.
Elliptic fourth-order operators with Wentzell boundary conditions on Lipschitz domains
Authors: Ploß David 
Published: October 2024

AbstractFor bounded domains $$\Omega $$
Ω
with Lipschitz boundary $$\Gamma $$
Γ
, we investigate boundary value problems for elliptic operators with variable coefficients of fourth-order subject to Wentzell (or dynamic) boundary conditions. Using form methods, we begin by showing general results for an even wider class of operators of type $$\begin{aligned} {\mathcal {A}}=\begin{pmatrix} B^*B & 0 \\ -{\mathscr {N}}^{\mathfrak {b}}B & \gamma \end{pmatrix}, \end{aligned}$$

A
=

B
∗

B

0

-

N

b

B

γ

,

where B is associated to a quadratic form $${\mathfrak {b}}$$
b
and $${\mathscr {N}}^{{\mathfrak {b}}}$$

N

b

an abstractly defined co-normal Neumann trace. Even in this general setting, we prove generation of an analytic semigroup on the product space $${\mathcal {H}}:=L^2(\Omega ) \times L^2(\Gamma )$$

H
:
=

L
2

(
Ω
)

×

L
2

(
Γ
)

. Using recent results concerning weak co-normal traces, we apply our abstract theory to the elliptic fourth-order case and are able to fully characterize the domain in terms of Sobolev regularity for operators in divergence form $$B=-\mathop {{div} }Q \nabla $$

B
=
-

div

Q
∇

with $$Q \in C^{1,1}({\overline{\Omega }},{\mathbb {R}}^{d\times d}),$$

Q
∈

C

1
,
1

(

Ω
¯

,

R

d
×
d

)

,

also obtaining Hölder-regularity of solutions. Finally, we also discuss asymptotic behavior and (eventual) positivity.
Well-posedness for the NLS hierarchy
Authors: Adams Joseph 
Published: October 2024

AbstractWe prove well-posedness for higher-order equations in the so-called NLS hierarchy (also known as part of the AKNS hierarchy) in almost critical Fourier–Lebesgue spaces and in modulation spaces. We show the jth equation in the hierarchy is locally well-posed for initial data in $${{\hat{H}}}^s_r({\mathbb {R}})$$

H
^

r
s

(
R
)

for $$s \ge \frac{j-1}{r'}$$

s
≥

j
-
1

r
′

and $$1 < r \le 2$$

1
<
r
≤
2

and also in $$M^s_{2, p}({\mathbb {R}})$$

M

2
,
p

s

(
R
)

for $$s = \frac{j-1}{2}$$

s
=

j
-
1

2

and $$2 \le p < \infty $$

2
≤
p
<
∞

. Supplementing our results with corresponding ill-posedness results in Fourier–Lebesgue and modulation spaces shows optimality. Using the conserved quantities derived in Koch and Tataru (Duke Math J 167(17), 3207–3313, 2018), we argue that the hierarchy equations are globally well-posed for data in $$H^s({\mathbb {R}})$$

H
s

(
R
)

for $$s \ge \frac{j-1}{2}$$

s
≥

j
-
1

2

. Our arguments are based on the Fourier restriction norm method in Bourgain spaces adapted to our data spaces and bi- and trilinear refinements of Strichartz estimates.
Digitale Tools in der Fort- und Weiterbildung im Rahmen eines Digital-Media-Konzepts
Authors: Schlüter Ulrike , Sowa Ralf , Finkenzeller Ingmar , Mencke Thomas , Reuter Daniel A. 
Published: October 2024

ZusammenfassungHeutzutage gibt es viele Online-Angebote zu Aus- und Weiterbildung in der Anästhesiologie, Intensivtherapie, Schmerz‑, Notfall- und Palliativmedizin. Von traditionellen Lehrbüchern und Präsenzveranstaltungen über Lernplattformen, Applikationen und Podcasts bis zum Training im Simulationszentrum und Virtual-Reality-Szenarien; es gibt viele Wege, sich fort- und weiterzubilden. Insbesondere durch die Coronapandemie gab es große Fortschritte, medizinische Lerninhalte besser zugänglich zu gestalten, um u. a. auch die Übertragung von Wissen zu beschleunigen.Um Kollegen auf das Ziel des Life-long Learning mitzunehmen und alle modernen Tools miteinzubeziehen, empfehlen wir die Entwicklung eines Digital-Media-Konzepts, welches auf jede anästhesiologische Abteilung zugeschnitten ist. Zunächst gilt es, die Ziele einer Abteilung zu erfassen, z. B. ob vorhandene Lehr- und Lernmaterialien digital zugänglicher gemacht werden können, im Sinne des asynchronen Lernens. Danach sollten die Ressourcen dieser Abteilung erfasst werden, z. B. welche Lernplattform schon genutzt wird, oder ob/wie Social Media eine Rolle spielen soll. Eine oder mehrere verantwortliche Personen sollten dann für die Erhaltung des Konzepts bestimmt werden. In diesem Zuge empfiehlt es sich, einheitliche Qualitätskriterien, mit denen digitale Inhalte überprüft werden, zu entwickeln.Durch die Unterstützung der eigenen Abteilung kann konventionelle Fort- und Weiterbildung mit neuen digitalen Möglichkeiten gut kombiniert werden. Hiermit können speziell individuelle Dienstmodelle, wechselnde Beteiligung an Präsenzveranstaltungen und verschiedene Lerntypen berücksichtigt werden. Digitale Tools sind vielfältig, stellen eine großartige Bereicherung für die Aus- und Weiterbildung jedes Teammitgliedes einer anästhesiologischen Abteilung dar und werden uns in die Zukunft begleiten.
Empfehlung zur Versorgung von Frühgeborenen an der Grenze der Lebensfähigkeit
Authors: Berger Angelika , Simma Burkhard , Kiechl-Kohlendorfer Ursula , Urlesberger Berndt , Wald Martin , Wald Martin , Csillag Bernhard , Badinger-Sobotka Barbara , Kletecka-Pulker Maria , Salzer Hans 
Published: October 2024

Zusammenfassung
Die österreichische Empfehlung zum Vorgehen bei extrem unreifen Frühgeborenen an der Grenze der Lebensfähigkeit wurde zuletzt 2017 aktualisiert und empfahl unter anderem in SSW 220–6 aufgrund extrem niedriger Überlebensraten einen primär palliativen Behandlungsansatz.
Zwischenzeitlich wurden aus verschiedenen Ländern und Institutionen Daten veröffentlicht, die ein deutlich verbessertes, über 50 %iges Überleben in SSW 220–6 in spezialisierten Zentren zeigten. Die aktualisierte Empfehlung berücksichtigt diese neuen Erkenntnisse und trägt den Fortschritten in der neonatologischen Intensivmedizin Rechnung.
Als wichtigste Änderung zur Vorversion wird eine Erweiterung der Grauzone von SSW 230–6 auf SSW 22+0–23+6 auf Basis rezenter Literatur empfohlen. Die Bedeutung des Antenataltransfers in wenige, darauf spezialisierte Zentren und die Praxis des „shared decision-making“, bei der Eltern in den Entscheidungsprozess eingebunden werden, wird betont.
In dem Beitrag werden ethische, rechtliche und medizinische Aspekte abgehandelt. Es wird eine individuelle Empfehlung für das postnatale Management von extrem unreifen Frühgeborenen in den Schwangerschaftswochen 220–6, 230–6 und 240–6 ausgesprochen, mit dem Ziel, den Entscheidungsprozess im individuellen Fall zu unterstützen.
Preclinical evaluation of 225Ac-labeled minigastrin analog DOTA-CCK-66 for Targeted Alpha Therapy
Authors: Holzleitner Nadine , Vilangattil Meryl , Swaidan Abir , Garcia-Prada Clara Diaz , Taddio Marco F. , Jeanjean Pauline , Mona Christine E. , Lapa Constantin , Casini Angela , Günther Thomas , Carlucci Giuseppe 
Published: October 2024

Abstract
The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.

Methods
Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.

Results
Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.

Conclusion
We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.

Graphical abstract
Vocal-visual combinations in wild chimpanzees
Authors: Mine Joseph G. , Wilke Claudia , Zulberti Chiara , Behjati Melika , Bosshard Alexandra B. , Stoll Sabine , Machanda Zarin P. , Manser Andri , Slocombe Katie E. , Townsend Simon W. 
Published: October 2024

AbstractLiving organisms throughout the animal kingdom habitually communicate with multi-modal signals that use multiple sensory channels. Such composite signals vary in their communicative function, as well as the extent to which they are recombined freely. Humans typically display complex forms of multi-modal communication, yet the evolution of this capacity remains unknown. One of our two closest living relatives, chimpanzees, also produce multi-modal combinations and therefore may offer a valuable window into the evolutionary roots of human communication. However, a currently neglected step in describing multi-modal systems is to disentangle non-random combinations from those that occur simply by chance. Here we aimed to provide a systematic quantification of communicative behaviour in our closest living relatives, describing non-random combinations produced across auditory and visual modalities. Through recording the behaviour of wild chimpanzees from the Kibale forest, Uganda we generated the first repertoire of non-random combined vocal and visual components. Using collocation analysis, we identified more than 100 vocal-visual combinations which occurred more frequently than expected by chance. We also probed how multi-modal production varied in the population, finding no differences in the number of visual components produced with vocalisations as a function of age, sex or rank. As expected, chimpanzees produced more visual components alongside vocalizations during longer vocalization bouts, however, this was only the case for some vocalization types, not others. We demonstrate that chimpanzees produce a vast array of combined vocal and visual components, exhibiting a hitherto underappreciated level of multi-modal complexity.
A role for plasma membrane Ca2+ ATPases in regulation of cellular Ca2+ homeostasis by sphingosine kinase-1
Authors: Volk Luisa Michelle , Bruun Jan-Erik , Trautmann Sandra , Thomas Dominique , Schwalm Stephanie , Pfeilschifter Josef , zu Heringdorf Dagmar Meyer 
Published: October 2024

AbstractSphingosine-1-phosphate (S1P) is a ubiquitous lipid mediator, acting via specific G-protein-coupled receptors (GPCR) and intracellularly. Previous work has shown that deletion of S1P lyase caused a chronic elevation of cytosolic [Ca2+]i and enhanced Ca2+ storage in mouse embryonic fibroblasts. Here, we studied the role of sphingosine kinase (SphK)-1 in Ca2+ signaling, using two independently generated EA.hy926 cell lines with stable knockdown of SphK1 (SphK1-KD1/2). Resting [Ca2+]i and thapsigargin-induced [Ca2+]i increases were reduced in both SphK1-KD1 and -KD2 cells. Agonist-induced [Ca2+]i increases, measured in SphK1-KD1, were blunted. In the absence of extracellular Ca2+, thapsigargin-induced [Ca2+]i increases declined rapidly, indicating enhanced removal of Ca2+ from the cytosol. In agreement, plasma membrane Ca2+ ATPase (PMCA)-1 and -4 and their auxiliary subunit, basigin, were strongly upregulated. Activation of S1P-GPCR by specific agonists or extracellular S1P did not rescue the effects of SphK1 knockdown, indicating that S1P-GPCR were not involved. Lipid measurements indicated that not only S1P but also dihydro-sphingosine, ceramides, and lactosylceramides were markedly depleted in SphK1-KD2 cells. SphK2 and S1P lyase were upregulated, suggesting enhanced flux via the sphingolipid degradation pathway. Finally, histone acetylation was enhanced in SphK1-KD2 cells, and the histone deacetylase inhibitor, vorinostat, induced upregulation of PMCA1 and basigin on mRNA and protein levels in EA.hy926 cells. These data show for the first time a transcriptional regulation of PMCA1 and basigin by S1P metabolism. It is concluded that SphK1 knockdown in EA.hy926 cells caused long-term alterations in cellular Ca2+ homeostasis by upregulating PMCA via increased histone acetylation.
Sohlstabilisierung, Gewässerökologie und Wasserkraft: Die Sanierungsvariante E1+ „Mehr Fluss“ an der Unteren Salzach
Authors: Jähnel Christian , Zöschg Hannes , Wesemann Johannes , Aufleger Markus 
Published: October 2024

ZusammenfassungDie fortschreitende globale Erwärmung erfordert eine Reduktion der Treibhausgasemissionen. In diesem Zusammenhang kommt der Wasserkraft eine zentrale Rolle in der regenerativen Energieerzeugung zu, insbesondere in Österreich. Wasserkraftanlagen zeichnen sich durch zahlreiche Vorteile wie hohe Energieeffizienz, niedrige CO2-Äquivalentemissionen und hohe Erntefaktoren aus. Gleichzeitig sind jedoch große Teile der heimischen Fließgewässer durch anthropogene Einflüsse wie Wasserkraftanlagen sowohl in ihrer gewässerökologischen als auch morphologischen Beschaffenheit beeinträchtigt.Ein Beispiel hierfür ist die Untere Salzach an der Grenze zwischen Österreich und Deutschland. Durch Begradigungen und Befestigungen der Ufer weist der Fluss hier kaum Strukturvielfalt auf und befindet sich, auch bedingt durch Geschieberückhalt im Einzugsgebiet und Oberlauf, in einem Eintiefungsprozess. Der Fokus der flussbaulichen Sanierung liegt hier in der langfristigen Stabilisierung der Sohle und ökologischen Verbesserung nach dem Leitbild eines eigendynamischen voralpinen Kiesflusses. An einem derart stark anthropogen beeinflussten Gewässerabschnitt, an dem ohnehin flussbauliche Anpassungen erforderlich sind, erweist sich ein integratives Konzept zur Verbindung von Renaturierungsmaßnahmen mit klimaneutraler Energiegewinnung als besonders vielversprechend. Die Sanierungsvariante E1+ „Mehr Fluss“ an der Unteren Salzach stellt ein solches integratives Konzept dar, welches die Aspekte der notwendigen Sohlstabilisierung und Verbesserung der Gewässerökologie mit erneuerbarer Energienutzung kombiniert. Neben der Sohlstabilisierung durch eine aufgelöste asymmetrische Rampe sind Initialmaßnahmen zur eigendynamischen Aufweitung im Unterwasser geplant. Die durch die Rampe entstehende Fallhöhe soll durch ein Fließgewässerkraftwerk energetisch genutzt werden. Dieses ist so konzipiert, dass potenziell negative Auswirkungen herkömmlicher Flusskraftwerke, wie Störungen in der biologischen Durchgängigkeit, Sedimentrückhalt oder Verlust des Fließgewässercharakters, weitestgehend vermieden werden können.Das Konzept kann so einen Beitrag zum Klimaschutz leisten und gleichzeitig zu einer Verbesserung der Gewässer- und Gesamtökologie beitragen, während die Sohle der Unteren Salzach sofort nachhaltig stabilisiert und angehoben wird.