bluuebunny/crossref_metadata_2025 huggingface dataset:
Fortgeschrittenes Harnblasenkarzinom
Authors: Arnheim Katharina
Published: June 2022

Mit einer 5-Jahres-Überlebensrate von nur 15 % ist die Prognose von Patienten mit metastasiertem Blasenkarzinom weiterhin schlecht. Standard in der 1. Linie sind platinbasierte Regime sowie – bei nicht Platin-geeigneten Patienten – Checkpoint-Inhibitoren (CPI). Mit Sacituzumab Govitecan (SG) und Enfortumab Vedotin wurden mittlerweile Antikörper-Drug-Konjugate (ADC) in späteren Therapielinien erfolgreich geprüft.
Die Kraft der Selbstvermarktung – Beruflicher Erfolg
Authors: Tiebel Jakob
Published: June 2022

Um erfolgreich zu sein, braucht es – möchte man meinen – vor allem eine große Portion Kompetenz im eigenen Metier. Leider nein. Kompetenz ist zwar wichtig, reicht aber allein nicht aus. Zumindest dann nicht, wenn sie von anderen Personen oder auch der Politik kaum wahrgenommen wird. Und so gilt es zuerst einmal die Außendarstellung zu verbessern.
Bestens qualifiziert für die Behandlung – Ergotherapie bei Long Covid
Authors: Brinkmann Nicole
Published: June 2022

Von den vielen Millionen Deutschen, die seit Ausbruch der Corona-Pandemie an dem Virus erkrankten, leiden etwa 10 Prozent an Langzeitfolgen. Sie sind erschöpft und weniger leistungsfähig als zuvor. In der Rehabilitation der Betroffenen spielt die Ergotherapie zunehmend eine wichtige Rolle.
Überblick zur Supportivtherapie für Patienten mit Kopf-Hals-Tumoren
Authors: Büntzel Jens , Micke Oliver , Glatzel Michael , Kisters Klaus , Mücke Ralph
Published: June 2022

Fragestellung Es sollen die spezifischen Aspekte der Supportivtherapie bei Kopf-Hals-Karzinomen zusammengestellt werden.

Methode Darstellung der Symptome entsprechend des Zeitverlaufs der Behandlung. Supportive Therapieansätze entsprechend der S3-Leitlinie und Ansätze aus der Komplementärmedizin werden zugeordnet.

Ergebnisse Die Patienten erleben Funktionsverluste durch ihre Krankheit und die erfahrene Therapie. Im Vordergrund stehen dabei die Beeinträchtigungen der Stimme und Sprache sowie der Nahrungsaufnahme. Ästhetische Probleme, weitere Sinnesverluste (Riechen, Schmecken, Hören) und Komorbiditäten (insbesondere im psychiatrischen Bereich) prägen den Alltag unserer Patienten.

Schlussfolgerung Der multimodalen Behandlung eines fortgeschrittenen Kopf-Hals-Tumors muss eine multiprofessionelle Supportivmedizin entgegengesetzt werden, die für diese Patienten oft lebenslang notwendig ist.
Demnächst auch beim Pankreaskarzinom – vom Nischenprodukt zur breiten Anwendung
Authors: Kolac Corinna
Published: June 2022

Die CAR-T-Zell-Technologie feiert ihre Erfolge aktuell bei Patienten mit ausgewählten hämatologischen Tumoren, für die andere Therapieansätze scheiterten. Die Genialität dieser Technologie weckt weitere Begehrlichkeiten. Über funktionelle Hürden und Herausforderungen der Produktion und Logistik wurde beim diesjährigen Workshop der Paul-Martini-Stiftung, Berlin, intensiv diskutiert.
Triple-negatives Mammakarzinom
Authors: Krome Susanne
Published: June 2022

Etwa jede 4. Frau erleidet trotz aggressiver Chemotherapie eines triple-negativen Mammakarzinoms (TNBC) im Stadium II/III ein Rezidiv oder verstirbt daran. Kurzfristiges Ziel der neoadjuvanten Chemotherapie ist eine pathologisch komplette Remission, langfristig sollen Metastasierungen reduziert werden. In der randomisierten, doppelblinden Phase-III-Studie Keynote-522 erhielten die Teilnehmerinnen eine neoadjuvante Chemotherapie plus Pembrolizumab oder Placebo. Die Interimsanalyse bestätigte für den PD-1-Inhibitor nicht nur häufigere vollständige pathologische Remissionen, sondern ergab auch 37 % weniger Progressionen.
Nicht-kleinzellige Lungenkarzinome
Authors: Krome Susanne
Published: June 2022

Etwa 3 % der nicht-kleinzelligen Lungenkarzinome (NSCLC) weisen eine Mutation des HER2-Gens auf. Die Hoffnung, dass dessen Inhibition fortgeschrittene Tumoren effektiv ausbremsen kann, erfüllten sich nicht. Aber von der Kombination des HER2-Antikörpers Trastuzumab mit dem Topoisomerase-1-Inhibitor Deruxtecan profitierte mehr als jeder 2. Patient mit einem fortgeschrittenen, vorbehandelten NSCLC.
Immuncheckpoint-Inhibitoren
Authors: Krome Susanne
Published: June 2022

Die Immunantworten von Frauen und Männern unterscheiden sich. In der Beobachtungsstudie mit 1369 Senioren, die wegen eines malignen Melanoms Immuncheckpoint-Inhibitoren (ICI) bekamen, schlug sich dies mit einem ungünstigeren Gesamtüberleben (OS) bei den Patientinnen nieder. Der ICI-Typ spielte dabei eine besondere Rolle.
Psychische Gesundheit nach einem Mammakarzinom
Authors: Krome Susanne
Published: June 2022

Mehr als 90 % der betroffenen Frauen überleben ihre Brustkrebserkrankung. Damit rücken die negativen Therapiefolgen und die psychischen Auswirkungen der Krankheit in den Fokus. Neben Depressionen und Angstsymptomatik kommen nach Mammakarzinomen Anpassungsstörungen (AD) vor, die bislang weniger erforscht sind. Eine aktuelle niedeländische Studie zeigt hierzu unterschiedliche AD-Verläufe und Prädiktoren, die damit verbunden waren.
A Technical Guide to Palliative Ablation of Recurrent Cancers in the Deep Spaces of the Suprahyoid Neck
Authors: Hui Terrence Chi Hong , Lim Ming Yann , Karandikar Amit Anand , Loke Siu Cheng , Pua Uei
Published: June 2022

Treatment options for patients with recurrent head and neck cancer, whether locoregional recurrence of previously treated head and neck cancer or secondary primary malignancy, are limited. Percutaneous ablation is a minimally invasive procedure that can be used with palliative intent in the head and neck to achieve symptomatic relief and local tumor control, potentially fulfilling treatment gaps of current standard of care options. Image guidance is key when navigating the deep spaces of the neck with special attention paid to critical structures within the carotid sheath. This review article provides an overview and highlights the important nuances of performing percutaneous ablations in the head and neck. It covers general principles, ablative modalities, image guidance, procedural technique, expected outcomes, and possible complications.
Genicular Artery Embolization for Primary Knee Osteoarthritis
Authors: Tyagi Ravi , Ahmed S. Samaduddin , Koethe Yilun , Raskind Aleksandr , Ahmed Osman
Published: June 2022

Genicular artery embolization (GAE) is a novel treatment for knee osteoarthritis (OA) with increasing interest and utilization worldwide. The genicular arteries are selectively embolized using microspheres with subsequent cessation of abnormal synovial hyperemia, a process believed to arrest the inflammatory changes and pain associated with OA. Current data indicate that GAE offers sustained, 6-month improvement in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and visual analog scale scores in 80 to 85% of patients with mild to moderate OA. As GAE gains traction, future studies are needed to establish its safety and efficacy relative to placebo and other standard-of-care therapies while also characterizing populations for which it is most effective.
Transient liquid phase bonding of graphite to Ti6Al4V alloy
Authors: Jiang Qianyao , Wang Yujin , Xu Huimin , Ma Xinjian , Wang Shenggao , Mao Yangwu
Published: June 2022

Transient liquid phase bonding of graphite to Ti6Al4V alloy has been conducted with Cu foil, Ti/Cu and Cu/Ti/Cu foils, respectively. A diffusion zone containing Ti-based solid solution and Ti2Cu develops between the bonding zone and Ti6Al4V substrate for all the joints. The bonding zones of joints with Cu foil and Cu/Ti/Cu foils are both composed of TiCu and Ti2Cu. However, the bonding zone of joint with Ti/Cu foils consists of zones I, II and III. Both zones I and III are mainly comprised of TiCu and Ti2Cu, while zone II is a Ti residual zone. The joints with Cu/Ti/Cu foils exhibit the highest shear strength of 17.5 ± 1.7 MPa due to the most favourable interfacial bonding.
The impact of laser energy on the photoresponsive characteristics of CdO/Si visible light photodetector
Authors: Bashir Mohamed Bashir Ali , Salih Ethar Yahya , Rajpar Altaf Hussain , Bahmanrokh Ghazaleh , Mohd Sabri Mohd Faizul
Published: June 2022

In this article, cadmium oxide (CdO) was deposited using pulsed laser deposition approach on porous silicon (Si) wafer for visible light photodetector application, through which a series of devices were proposed as a function of the deposition energy. The microstructural as well as optical characteristics of the prepared film/s were demonstrated, respectively, using x-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and ultraviolet visible light spectroscopy (UV–Vis) analysis. In details, the UV–Vis analysis revealed the occurrence of optical band gaps within the range of 2.38–2.42eV, while an average nanoparticle diameter was found to be 45nmusing FE-SEM technique. This in turn demonstrated a sound relation with the photoresponsive behavior of the attained photodetectors. A photoresponsivity and specific detectivity of 1.9μAmW−1and1.21×109Jones were attained using 700mJlaser energy. In the meanwhile, the estimated response/recover time of the addressed laser energy was found to be 300sand 340s, respectively. The photo-responsive characteristics of the fabricated devices were found to be in positive linear correlation with the applied laser energy.
Kinetics of charged species in non-equilibrium plasma in water vapor- and hydrocarbon-containing gaseous mixtures
Authors: Aleksandrov N L , Bazelyan E M , Ponomarev A A , Starikovsky A Yu
Published: June 2022

In this review we describe the kinetics of non-equilibrium discharge plasma when the ion composition is dominated by water or hydrocarbon ions. Plasmas with water ions are formed in atmospheric discharges and discharges in the presence of liquid water or water vapor, including plasma applications for air purification, medicine and combustion. Reactions with hydrocarbon ions play an important role in interstellar chemistry, plasma enhanced chemical vapor deposition, synthetic diamond film deposition and plasma assisted combustion. The modeling of water ion chemistry and chemistry of hydrocarbon-containing plasmas requires large amount of data on the rates of ion formation and loss. This review provides the core database for the rate coefficients describing the kinetics of charged particles in plasmas with water and hydrocarbon ions as a function of temperature, pressure, and local electric field. Particular attention is given to cluster ions, which are important at not-too-low gas pressures, whereas the majority of studies of ion–molecule reactions have been performed at low pressures in the absence of cluster ions. To illustrate importance of the described processes, the development of streamer discharges in long humid air gaps is discussed and the influence of water ions on the streamer properties is demonstrated. In addition, the decay of non-equilibrium plasma with water and hydrocarbon ions is analyzed in combustible gaseous mixtures excited by a repetitively pulsed nanosecond discharge.
Constant frequency reconfigurable terahertz metasurface based on tunable electromagnetically induced transparency-like approach
Authors: Cao Pengfei , Li Yuan , Deng Yubo , Wu Yuyao
Published: June 2022

A terahertz constant frequency reconfigurable metasurface based on tunable electromagnetically induced transparency (EIT)-like property was designed, whose transparency window frequency did not vary with Fermi energy. This structure was composed of two single-layer graphene resonators, namely, left double big rings and right double small rings. An evident transparency window (EIT-like phenomenon) was caused by the near-field coupling between bright modes of the two resonators in the transmission spectrum, in which amplitude over 80% was acquired at 1.98 THz. By individually reconfiguring the Fermi energy of each resonator, the EIT-like effects, transparency window amplitude, modulation speed and group delay could be actively controlled while the frequency of EIT-like window remained constant. Significantly, the transparency window was fully modulated without changing the frequency, and the maximum modulation depth reached 78%. Furthermore, the modulation speed also increased because the total graphene areaAwas effectively reduced in the proposed structure. Compared with other metasurface structures, the modulation properties of the proposed structure showed higher performance while the EIT-like window frequency remained static. This research provides an alternative method for developing constant frequency reconfigurable modulation terahertz devices (such as optical switches and modulators), as well as a potential approach for miniaturization of terahertz devices.
Tuning curved DNA origami structures through mechanical design and chemical adducts
Authors: Xie Chun , Hu Yingxin , Chen Zhekun , Chen Kuiting , Pan Linqiang
Published: June 2022

The bending and twisting of DNA origami structures are important features for controlling the physical properties of DNA nanodevices. It has not been fully explored yet how to finely tune the bending and twisting of curved DNA structures. Traditional tuning of the curved DNA structures was limited to controlling the in-plane-bending angle through varying the numbers of base pairs of deletions and insertions. Here, we developed two tuning strategies of curved DNA origami structures from in silico and in vitro aspects. In silico, the out-of-plane bending and twisting angles of curved structures were introduced, and were tuned through varying the patterns of base pair deletions and insertions. In vitro, a chemical adduct (ethidium bromide) was applied to dynamically tune a curved spiral. The 3D structural conformations, like chirality, of the curved DNA structures were finely tuned through these two strategies. The simulation and TEM results demonstrated that the patterns of base pair insertions and deletions and chemical adducts could effectively tune the bending and twisting of curved DNA origami structures. These strategies expand the programmable accuracy of curved DNA origami structures and have potential in building efficient dynamic functional nanodevices.
Physical mechanisms of the influence of γ-ray surface treatment on the characteristics of close AuNi/n–n+-GaN Schottky contacts
Authors: Torkhov Nikolay A , Gradoboev Alexandr V , Budnyaev Vadim A , Ivonin Ivan V , Novikov Vadim A
Published: June 2022

The results obtained here suggest that low-dose 60Co γ-irradiation (Dγ
∼ 140 Gy) has a complex effect on close AuNi/n–n+-GaN{0001} Schottky contacts. This manifests in the disappearance of current steps in the initial section of the forward current–voltage curve, improvement in the average values of the ideality factor n, a decrease in the average values of the true Schottky barrier height ϕ
bn in the middle section and an increase in series resistance R
S and enhancement of the inhomogeneous metal–semiconductor contact series resistance effect in the final section. In all cases, the observed changes are sustainable. A combination of the Zur–McGill–Smith close Schottky contact defect model, the inhomogeneous contact model and the radiation-induced defect formation model provides an explanation for the physical mechanisms of changes observed in electrophysical and instrumental characteristics after γ-irradiation. Such mechanisms are associated with changes in the electrophysical nature of GaN structural defects (dislocations and interface states) and degradation of the homogeneity of contact conductivity. This paper shows that the low-temperature anomaly also manifests itself in close AuNi/n–n+-GaN Schottky contacts subjected to γ-irradiation.
Driven superconducting vortex dynamics in systems with twofold anisotropy in the presence of pinning
Authors: Roe E J , Eskildsen M R , Reichhardt C , Reichhardt C J O
Published: June 2022

We examine the dynamics of superconducting vortices with twofold anisotropic interaction potentials driven over random pinning, and compare the behavior under drives applied along the hard and the soft anisotropy directions. As the driving force increases, the number of topological defects reaches a maximum near the depinning threshold, and then decreases as the vortices form one-dimensional (1D) chains. This coincides with a transition from a pinned nematic to a moving smectic aligned with the soft anisotropy direction. The system is generally more ordered when the drive is applied along the soft direction of the anisotropy. For driving along the hard direction, there is a critical value of the twofold anisotropy above which the system remains aligned with the soft direction. Hysteretic behavior appears upon cycling the driving force, with 1D vortex chains persisting during the decreasing leg below the threshold for chain formation for increasing drive. More anisotropic systems have a greater amount of structural disorder in the moving state. For lower anisotropy, the system forms a moving smectic-A state, while at higher anisotropy, a moving nematic state appears instead.
Multi-messenger detection prospects of gamma-ray burst afterglows with optical jumps
Authors: Guarini Ersilia , Tamborra Irene , Bégué Damien , Pitik Tetyana , Greiner Jochen
Published: June 2022

Some afterglow light curves of gamma-ray bursts (GRBs) exhibit very complex temporal and
spectral features, such as a sudden intensity jump about one hour after the prompt emission in the
optical band. We assume that this feature is due to the late collision of two relativistic shells
and investigate the corresponding high-energy neutrino emission within a multi-messenger
framework, while contrasting our findings with the ones from the classic afterglow model. For a
constant density circumburst medium, the total number of emitted neutrinos can increase by about
an order of magnitude when an optical jump occurs with respect to the self-similar afterglow
scenario. By exploring the detection prospects with the IceCube Neutrino Observatory and future
radio arrays such as IceCube-Gen2 radio, RNO-G and GRAND200k, as well as the POEMMA spacecraft, we
conclude that the detection of neutrinos with IceCube-Gen2 radio could enable us to constrain the
fraction of GRB afterglows with a jump as well as the properties of the circumburst medium. We
also investigate the neutrino signal expected for the afterglows of GRB 100621A and a GRB
130427A-like burst with an optical jump. The detection of neutrinos from GRB afterglows could be
crucial to explore the yet-to-be unveiled mechanism powering the optical jumps.
A strategy to optimize the complexity of Chudnovsky-type algorithms over the projective line
Authors: Ballet Stéphane , Bonnecaze Alexis , Pacifico Bastien
Published: June 2022

Chudnovsky-type algorithms of multiplication in finite fields are well known for their good bilinear complexity. Recently, two advances have been obtained in the study of these algorithms: a strategy to optimize the scalar complexity of the original algorithm and the development of a generic recursive construction over the projective line. The construction of recursive Chudnodvsky-type algorithms over the projective line makes possible an efficient generic strategy to optimize their complexity (number of scalar and bilinear multiplications and additions in the base field). Then, several examples are given. In particular, considering Baum-Shokrollahi’s experiment (1992), this constructive method provides a Chudnovsky-type algorithm of multiplication in

F

256

/

F

4

\mathbb {F}_{256}/\mathbb {F}_4

with the best known complexity, while being much more efficient than existing optimization methods.
How big is the image of the Galois representations attached to CM elliptic curves?
Authors: Campagna Francesco , Pengo Riccardo
Published: June 2022

Using an analogue of Serre’s open image theorem for elliptic curves with complex multiplication, one can associate to each CM elliptic curve

E
E

defined over a number field

F
F

a natural number

I

(
E

/

F
)

\mathcal {I}(E/F)

which describes how big the image of the Galois representation associated to

E
E

is. We show how one can compute

I

(
E

/

F
)

\mathcal {I}(E/F)

, using a closed formula that we obtain from the classical theory of complex multiplication.
Introduction to Drinfeld modules
Authors: Poonen Bjorn
Published: June 2022

Our goal is to introduce Drinfeld modules and to explain their application to explicit class field theory.
A note on an overdetermined problem for minimal surface equation
Authors: Cui Qing
Published: June 2022

We show in this short note an overdetermined problem for minimal surface equation, which is defined over a domain with connected boundary, has a solution if and only if the domain is either the complement of a round disk or a half plane. Equivalently, we show that a minimal graph with connected zero boundary and makes a constant angle at all boundary points with a plane is a part of a catenoid or a half-plane.
Obstructions to countable saturation in corona algebras
Authors: Farah Ilijas , Vignati Alessandro
Published: June 2022

We study the extent of countable saturation for coronas of abelian

C

∗

\mathrm {C}^{*}

-algebras. In particular, we show that the corona algebra of

C
0

(

R

n

)

C_0(\mathbb {R}^n)

is countably saturated if and only if

n
=
1

n=1

.
Enumeration of algebraic and tropical singular hypersurfaces
Authors: Sinichkin Uriel
Published: June 2022

We develop a version of Mikhalkin’s lattice path algorithm for projective hypersurfaces of arbitrary degree and dimension, which enumerates singular tropical hypersurfaces passing through appropriate configuration of points. By proving a correspondence theorem combined with the lattice path algorithm, we construct a

δ
\delta

dimensional linear space of degree

d
d

real hypersurfaces containing
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartFraction 1 Over delta factorial EndFraction left-parenthesis gamma Subscript n Baseline d Superscript n Baseline right-parenthesis Superscript delta plus upper O left-parenthesis d Superscript n delta minus 1 Baseline right-parenthesis">

1

δ
!

(

γ
n

d
n

)

δ

+
O
(

d

n
δ
−
1

)

\frac {1}{\delta !}(\gamma _nd^n)^{\delta }+O(d^{n\delta -1})

hypersurfaces with

δ
\delta

real nodes, where

γ
n

\gamma _n

are positive and given by a recursive formula. This is asymptotically comparable to the number
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartFraction 1 Over delta factorial EndFraction left-parenthesis left-parenthesis n plus 1 right-parenthesis left-parenthesis d minus 1 right-parenthesis Superscript n Baseline right-parenthesis Superscript delta plus upper O left-parenthesis d Superscript n left-parenthesis delta minus 1 right-parenthesis Baseline right-parenthesis">

1

δ
!

(
(
n
+
1
)
(
d
−
1

)
n

)

δ

+
O

(

d

n
(
δ
−
1
)

)

\frac {1}{\delta !} \left ( (n+1)(d-1)^n \right )^{\delta }+O\left (d^{n(\delta -1)} \right )

of complex hypersurfaces having

δ
\delta

nodes in a

δ
\delta

dimensional linear space. In the case

δ
=
1

\delta =1

we give a slightly better leading term.
A Buchsbaum theory for tight closure
Authors: Ma Linquan , Quy Pham
Published: June 2022

A Noetherian local ring

(
R
,

m

)

(R,\frak {m})

is called Buchsbaum if the difference

ℓ
(
R

/

q

)
−
e
(

q

,
R
)

\ell (R/\mathfrak {q})-e(\mathfrak {q}, R)

, where

q

\mathfrak {q}

is an ideal generated by a system of parameters, is a constant independent of

q

\mathfrak {q}

. In this article, we study the tight closure analog of this condition. We prove that in an unmixed excellent local ring

(
R
,

m

)

(R,\frak {m})

of prime characteristic

p
>
0

p>0

and dimension at least one, the difference

e
(

q

,
R
)
−
ℓ
(
R

/

q

∗

)

e(\mathfrak {q}, R)-\ell (R/\mathfrak {q}^*)

is independent of

q

\mathfrak {q}

if and only if the parameter test ideal

τ

p
a
r

(
R
)

\tau _{\mathrm {par}}(R)

contains

m

\frak {m}

. We also provide a characterization of this condition via derived category which is analogous to Schenzel’s criterion for Buchsbaum rings.
A probabilistic gene expression barcode for annotation of cell types from single-cell RNA-seq data
Authors: Grabski Isabella N , Irizarry Rafael A
Published: June 2022

Single-cell RNA sequencing (scRNA-seq) quantifies gene expression for individual cells in a sample, which allows distinct cell-type populations to be identified and characterized. An important step in many scRNA-seq analysis pipelines is the annotation of cells into known cell types. While this can be achieved using experimental techniques, such as fluorescence-activated cell sorting, these approaches are impractical for large numbers of cells. This motivates the development of data-driven cell-type annotation methods. We find limitations with current approaches due to the reliance on known marker genes or from overfitting because of systematic differences, or batch effects, between studies. Here, we present a statistical approach that leverages public data sets to combine information across thousands of genes, uses a latent variable model to define cell-type-specific barcodes and account for batch effect variation, and probabilistically annotates cell-type identity from a reference of known cell types. The barcoding approach also provides a new way to discover marker genes. Using a range of data sets, including those generated to represent imperfect real-world reference data, we demonstrate that our approach substantially outperforms current reference-based methods, particularly when predicting across studies.
A hierarchical prior for generalized linear models based on predictions for the mean response
Authors: Alt Ethan M , Psioda Matthew A , Ibrahim Joseph G
Published: June 2022

There has been increased interest in using prior information in statistical analyses. For example, in rare diseases, it can be difficult to establish treatment efficacy based solely on data from a prospective study due to low sample sizes. To overcome this issue, an informative prior to the treatment effect may be elicited. We develop a novel extension of the conjugate prior of Chen and Ibrahim (2003) that enables practitioners to elicit a prior prediction for the mean response for generalized linear models, treating the prediction as random. We refer to the hierarchical prior as the hierarchical prediction prior (HPP). For independent and identically distributed settings and the normal linear model, we derive cases for which the hyperprior is a conjugate prior. We also develop an extension of the HPP in situations where summary statistics from a previous study are available. The HPP allows for discounting based on the quality of individual level predictions, and simulation results suggest that, compared to the conjugate prior and the power prior, the HPP efficiency gains (e.g., lower mean squared error) where predictions are incompatible with the data. An efficient Monte Carlo Markov chain algorithm is developed. Applications illustrate that inferences under the HPP are more robust to prior-data conflict compared to selected nonhierarchical priors.
Towards network-guided neuromodulation for epilepsy
Authors: Piper Rory J , Richardson R Mark , Worrell Gregory , Carmichael David W , Baldeweg Torsten , Litt Brian , Denison Timothy , Tisdall Martin M
Published: June 2022

Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of ‘network-guided neuromodulation’ for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key ‘propagation points’ in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points — including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients’ individual epileptogenic networks.
Ageing meets kidney disease
Authors: Ortiz Alberto , Mattace-Raso Francesco , Soler María José , Fouque Denis
Published: June 2022

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for ˃3 months, with implications for health. The most used diagnostic criteria are a urinary albumin: creatinine ratio ≥30 mg/g or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Either of these diagnostic thresholds is associated with adverse health outcomes. GFR decreases with age and the prevalence of CKD is highest in older adults; moreover, the presence of CKD is associated with an increased risk of all-cause and cardiovascular death related to accelerated ageing in all age ranges, and the absolute increase in risk is highest for those aged ˃75 years. Indeed, premature death is a more common outcome than CKD progression to kidney failure requiring kidney replacement therapy. The progressive ageing of the world population contributes to the projection that CKD will become the second most common cause of death before the end of the century in countries with long life expectancy. The current collection of selected studies on kidney disease and ageing published in Age&Ageing, NDT and CKJ provides an overview of key topics, including cognitive decline, sarcopaenia, wasting and cardiovascular and non-cardiovascular morbidity and mortality, the management of kidney failure and gender differences in CKD progression.
Electrical modulation properties of DNA drug molecules
Authors: He Lijun , Xie Zhiyang , Long Xing , Zhang Chaopeng , Qi Fei , Zhang Nan
Published: June 2022

DNA drug molecules are not only widely used in gene therapy, but also play an important role in controlling the electrical properties of molecular electronics. Covalent binding, groove binding and intercalation are all important forms of drug–DNA interaction. But its applications are limited due to a lack of understanding of the electron transport mechanisms after different drug–DNA interaction modes. Here, we used a combination of density functional theory calculations and nonequilibrium Green’s function formulation with decoherence to study the effect of drug molecules on the charge transport property of DNA under three different binding modes. Conductance of DNA is found to decrease from 2.35E-5 G0 to 1.95E-6 G0 upon doxorubicin intercalation due to modifications of the density of states in the near-highest occupied molecular orbital region, δG = 1105.13%. Additionally, the conductance of DNA after cis-[Pt(NH3)2(py)Cl]+ covalent binding increases from 1.02E-6 G0 to 5.25E-5 G0, δG = 5047.06%. However, in the case of pentamidine groove binding, because there is no direct change in DNA molecular structure during drug binding, the conductance changes before and after drug binding is much smaller than in the two above cases, δG = 90.43%. Our theoretical calculations suggest that the conductance of DNA can be regulated by different drug molecules or switching the interaction modes between small molecules and DNA. This regulation opens new possibilities for their potential applications in controllable modulation of the electron transport property of DNA.
Highly efficient CRISPR systems for loss-of-function and gain-of-function research in pear calli
Authors: Ming Meiling , Long Hongjun , Ye Zhicheng , Pan Changtian , Chen Jiali , Tian Rong , Sun Congrui , Xue Yongsong , Zhang Yingxiao , Li Jiaming , Qi Yiping , Wu Jun
Published: June 2022

CRISPR/Cas systems have been widely used for genome engineering in many plant species. However, their potentials have remained largely untapped in fruit crops, particularly in pear, due to the high levels of genomic heterozygosity and difficulties in tissue culture and stable transformation. To date, only a few reports on the application of the CRISPR/Cas9 system in pear have been documented, and have shown very low editing efficiency. Here we report a highly efficient CRISPR toolbox for loss-of-function and gain-of-function research in pear. We compared four different CRISPR/Cas9 expression systems for loss-of-function analysis and identified a potent system that showed nearly 100% editing efficiency for multi-site mutagenesis. To expand the targeting scope, we further tested different CRISPR/Cas12a and Cas12b systems in pear for the first time, albeit with low editing efficiency. In addition, we established a CRISPR activation (CRISPRa) system for multiplexed gene activation in pear calli for gain-of-function analysis. Furthermore, we successfully engineered the anthocyanin and lignin biosynthesis pathways using both CRISPR/Cas9 and CRISPRa systems in pear calli. Taking these results together, we have built a highly efficient CRISPR toolbox for genome editing and gene regulation, paving the way for functional genomics studies as well as molecular breeding in pear.
O-018 Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomised controlled trial
Authors: Andersen E , Juhl C R , Kjøller E T , Lundgren J R , Janus C , Saupstad M , Ingerslev L R , Jensen S B K , Holst J J , Stallknecht B M , Madsbad S , Torekov S S , Barrès R
Published: June 2022

Study question

Does diet-induced weight loss improve semen parameters, and are these possible improvements maintained with sustained weight loss?

Summary answer

An 8-week low-calorie diet-induced weight loss was associated with improved sperm count, which was maintained after one year in men who maintained weight loss.

What is known already

Obesity is associated with impaired semen parameters. Weight loss improves metabolic health in obesity, but there is a lack of knowledge on the acute and long-term effects of weight loss on semen parameters.

Study design, size, duration

This is a substudy of men with obesity enrolled in a randomised, controlled, double-blinded trial (the S-LITE trial). The trial was conducted between August 2016 and November 2019. A total of 56 men was included in the study and assigned to an initial 8-week low-calorie diet (800 kcal/day) followed by randomisation to 52 weeks of either: placebo, exercise training, and placebo (exercise), the GLP-1 analogue liraglutide (liraglutide) or liraglutide in combination with exercise training (combination).

Participants/materials, setting, methods

Inclusion criteria were men who delivered semen samples, 18 to 65 years of age and a body mass index between 32 to 43 kg/m2, but otherwise healthy. The study was carried out at Hvidovre Hospital and at the University of Copenhagen, and the participants were from the Greater Copenhagen Area. We assessed semen parameters, anthropometrics and collected blood samples before (T0) and after the 8-week low-calorie dietary intervention (T1) and after 52 weeks (T2).

Main results and the role of chance

The men lost on average 16.5 kg (95% CI: 15.2-17.8) bodyweight during the low-calorie diet, which increased sperm concentration 1.49 fold (95% CI: 1.18-1.88, P<0.01) and sperm count 1.41 fold (95% CI: 1.07-1.87, P<0.01). These improvements were maintained for 52 weeks in men who maintained the weight loss but not in men who regained weight. Semen volume, sperm motility and motile sperm count did not change.

Limitations, reasons for caution

The S-LITE trial was a randomised controlled trial of weight loss maintenance. Analysis of semen was preregistered to explore the effects of weight loss and weight loss maintenance on semen parameters. Due to the small sample size, definite inferences cannot be made.

Wider implications of the findings

This study shows that sperm concentration and sperm count were improved after a diet-induced weight loss in men with obesity. Our findings indicate that both liraglutide and exercise as weight maintenance strategies may be used to maintain the improvements in sperm concentration and count.

Trial registration number

H-16027082
O-022 A randomised controlled trial on Recurrent Implantation Failure treatment in a study model performed on women who failed egg donation cycles using GM-CSF (MOLGRAMOSTIM)
Authors: Sbracia M , Scarpellini F
Published: June 2022

Study question

Is the use of GM-CSF (molgramostim) effective in the treatment of recurrent implantation failure in egg donation cycles?

Summary answer

The clinical use of GM-CSF in women experienced implantation failure in egge donation cycles may be useful,

What is known already

The GM-CSF is a cytokine promoting leukocyte growth as well as trophoblast development. Recurrent implantation failure (RIF) is a clinical entity referring when implantation repeatedly failed to reach a stage recognizable by pelvic ultrasound in IVF cycles. There is no universally accepted definition for RIF. Several factors may determine implantation failure, such as maternal age, embyo aneuploidy, uterine anomalies. The efficacy of a specific treatment is difficult to test in this affection since embryos in general cases show an implantation rate of less than 50%.

Study design, size, duration

The study was conducted to the CERM-Hungaria, Rome, Italy, from the January 2020 to May 2021 on women with recurrent implantation failure after egg donation cycles. Inclusion criteria were: women, aged in between 35-49 years old underwent egg donation cycles with at least three previous transfers with good quality blastocysts that failed to reach pregnancy with no uterine defects (included adenomyosis), no systemic diseases.

Participants/materials, setting, methods

50 women with recurrent implantation failure after egg donation cycles. Patients were randomly subdivided in two groups: one (25 women) treated with subcutaneous GM-CSF (Molgramostim) 0.3mg/kg/daily from the day before embryo transfer to the b-hcg day. The treatment was continued until the 8th week of gestation: the control group (25 women) was treated with subcutaneous saline solution infusion in the same way of the study group. Primary outcome was the ongoing pregnancy rate.

Main results and the role of chance

Epidemiological data of the two groups did not show statistically significant differences. The ongoing pregnancy rate in the group treated with GM-CSF was 84.0% (21/25) whereas in the control group was 44.0% (11/25), P < 0.0072. The absolute risk reduction was 40.0% (95%CI: 15.8%-64.2%). The NNT was 3.0 (95%CI: 1.6-6.3).

Limitations, reasons for caution

This study has a limited number of patients and more studies are needed to confirm these findings. Furthermore, recurrent implantation failure is a clinical entity difficult to classify and define, consequently to extrapolate a common indication for all patients with this should be carefully done.

Wider implications of the findings

The clinical use of GM-CSF in women experienced implantation failure may be an interesting treatment, if these data will confirmed, this treatment can be extended to all patients with recurrent implantation failure. Furthermore, the study model used may ba an interesting way to study recurrent implantation failure.

Trial registration number

NCT01718210
O-039 Novel sperm centrosome function, structure, and composition during fertilization
Authors: Avidor-Reiss T
Published: June 2022

Sperm centrioles play a critical role in sperm differentiation and embryo development, and they are implicated in infertility and miscarriages. However, the precise way centrioles function and are inherited during fertilization in mammals remains unresolved. A key reason for this lack of understanding is that many proteins are only transiently present in the sperm centriole because of a process known as Centrosome Reduction and that sperm centrioles exhibit dramatic species-specific adaptions. It was long widely accepted that structural degeneration and functional inactivation occur at one or two of the centrioles in mammals, resulting in a vestigial remnant. This led to the belief that human spermatozoa have only one functional centriole (the Proximal Centriole, PC). While Centrosome Reduction happens in mice, our studies suggest that two centrioles are present, and both are essential in non-murine mammals. However, the Distal Centriole (DC) has a highly atypical structure and composition, while the PC is only modestly modified. These findings led us to a new model: Centriole Remodeling, which states that preexisting spermatid centrioles, along with their pericentriolar material (PCM), go through a structural and compositional transformation during differentiation resulting in remodeled centrioles and PCM that functions as a dynamic basal complex (DBC) in the spermatozoon and as a precursor for the embryonic centrioles. A crucial mystery remaining is: what are the centrioles' essential functions? To answer this question, we study the sperm centrioles' function and remodeling process in infertile men and rabbit mutants with partially disabled sperm centrioles.

Trial registration number

-
O-040 Investigating why early embryonic mitoses are highly error prone by real time imaging
Authors: Ellenberg J
Published: June 2022

Maintenance of genomic integrity during early embryogenesis is essential for faithful embryonic development. However, mitotic errors during preimplantation development are surprisingly common and despite the fundamental importance of the cell divisions at the beginning of life, the mechanisms that control the correct progression through mitosis during pre-implantation development are not well characterized. The sensitivity of mammalian embryos to light and its demanding in vitro culture requirements have limited real-time imaging during the first embryonic divisions in the past. Today, advances in light-sheet microscopy allow in toto imaging of preimplantation mouse development from zygote to blastocyst at single chromosome resolution and enable us to study spindle assembly, chromosome restructuring and segregation. This presentation will discuss the insights we have gained by real-time imaging of the first cell divisions in mammalian life, and the role of the key molecular mechanisms that regulate mitosis during the critical first stages of embryo development.
O-042 ESHRE good practice recommendations on chromosomal mosaicism
Authors: De Rycke M , Capalbo A , Coonen E , Coticchio G , Fiorentino F , Goossens V , MCheik S , Rubio C , Sermon K , Sfontouris I , Spits C , Vermeesch J , Vermeulen N , Wells D , Zambelli F , Kakourou G
Published: June 2022

The implementation of high-resolution genome-wide methods, usually next-generation sequencing-based, in preimplantation genetic testing (PGT), has led to the frequent detection of embryos with chromosomal mosaicism (whole chromosome and/or segmental aberrations). Despite a growing series of papers showing the birth of healthy babies following the transfer of embryos indicating mosaicism on PGT-A analysis - albeit with lower implantation rates and higher miscarriage rates in comparison with euploid embryo transfer - many questions remain, making it difficult to decide on how to handle chromosomally mosaic embryos in the clinic.

A dedicated ESHRE working group developed good practice recommendations on how to manage chromosomal mosaicism in clinical practice. The recommendations were formulated based on the expert opinion of the working group while taking into consideration the published data and outcomes of a survey on current practices in 239 PGT laboratories and ART clinics, mostly within Europe, Asia and America. The recommendations with regards to detection and management of chromosomal mosaicism were developed following the manual for development of ESHRE good practice recommendations with a stakeholder review of the paper on the ESHRE website. In addition to the recommendations, the working group identified missing information and scientific questions, which should guide further research in PGT, with relevance to the occurrence, detection and impact of chromosomal mosaicism.

Trial registration number:
O-051 The male reproductive health initiative - global collaboration and progress update
Authors: De Jonge C
Published: June 2022

The Male Reproductive Health Initiative (MRHI) was launched in 2018 and is a global collaboration of more than a dozen key opinion leaders in research, medicine, and patient support groups, from the Americas, Australia, the United Kingdom, and Europe.

The mission of the Male Reproductive Health Initiative (MRHI) is to advance the science and practice of male reproductive medicine. The MRHI accomplishes its mission by promoting and contributing to high quality research in both basic and clinical science, forging collaborative relationships with professional societies to contribute to a mission of education, and through advocacy of male reproductive health to all stakeholders including patient support groups, funding agencies, non-for-profit organizations, industry, and the public.

Since its inception, interest in MRHI is expanding, as evidenced by invitations from a dozen or more professional societies from around the world requesting presentations to educate their memberships about the initiative. Helping to spread the scientific, medical, and social importance of male reproductive health are six publications and an additional three manuscripts in press, submitted and or being finalized for submission. These papers, each building on the next, highlight gaps in knowledge that exist regarding diagnosis and treatment of male infertility, how lifestyle and the environment impacts the father and his offspring, and the connection between male reproductive health and somatic health. These gaps collectively raise a present and growing global alarm for the man, his partner and family, and society.