bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal Stromal Cell-Mediated Immune Regulation: A Promising Remedy in the Therapy of Type 2 Diabetes Mellitus
Authors: Chen Ji , Zheng Chen-Xi , Jin Yan , Hu Cheng-Hu 
Published: September 2021

Abstract
Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Among the multiple mechanisms involved in MSC-mediated immune regulation, the paracrine effects of MSCs have attracted much attention. Of note, extracellular vesicles (EVs), an important component of MSC secretome, have emerged as pivotal mediators of their immunoregulatory effects. Particularly, the necrobiology of MSCs, especially apoptosis, has recently been revealed to affect their immunomodulatory functions in vivo. In specific, a variety of preclinical studies have demonstrated the beneficial effects of MSCs on improving islet function and ameliorating insulin resistance. More importantly, clinical trials have further uncovered the therapeutic potential of MSCs for T2DM. In this review, we outline current knowledge regarding the plasticity and underlying mechanisms of MSC-mediated immune modulation, focusing on the paracrine effects. We also summarize the applications of MSC-based therapies for T2DM in both preclinical studies and clinical trials, with particular emphasis on the modulation of immune system.
A Synthetic mRNA Cell Reprogramming Method Using CYCLIN D1 Promotes DNA rEpair, Generating Improved Genetically Stable Human Induced Pluripotent Stem Cells
Authors: Alvarez-Palomo Ana Belén , Requena-Osete Jordi , Delgado-Morales Raul , Moreno-Manzano Victoria , Grau-Bove Carme , Tejera Agueda M. , Otero Manel Juan , Barrot Carme , Santos-Barriopedro Irene , Vaquero Alejandro , Mezquita-Pla Jovita , Moran Sebastian , Naya Carlos Hobeich , Garcia-Martínez Iris , Pérez Francisco Vidal , Blasco María A. , Esteller Manel , Edel Michael J. 
Published: September 2021

Abstract
A key challenge for clinical application of induced pluripotent stem cells (iPSC) to accurately model and treat human pathologies depends on developing a method to generate genetically stable cells to reduce long-term risks of cell transplant therapy. Here, we hypothesized that CYCLIN D1 repairs DNA by highly efficient homologous recombination (HR) during reprogramming to iPSC that reduces genetic instability and threat of neoplastic growth. We adopted a synthetic mRNA transfection method using clinically compatible conditions with CYCLIN D1 plus base factors (OCT3/4, SOX2, KLF4, LIN28) and compared with methods that use C-MYC. We demonstrate that CYCLIN D1 made iPSC have (a) lower multitelomeric signal, (b) reduced double-strand DNA breaks, (c) correct nuclear localization of RAD51 protein expression, and (d) reduced single-nucleotide polymorphism (SNP) changes per chromosome, compared with the classical reprogramming method using C-MYC. CYCLIN D1 iPSC have reduced teratoma Ki67 cell growth kinetics and derived neural stem cells successfully engraft in a hostile spinal cord injury (SCI) microenvironment with efficient survival, differentiation. We demonstrate that CYCLIN D1 promotes double-stranded DNA damage repair predominantly through HR during cell reprogramming to efficiently produce iPSC. CYCLIN D1 reduces general cell stress associated with significantly lower SIRT1 gene expression and can rescue Sirt1 null mouse cell reprogramming. In conclusion, we show synthetic mRNA transfection of CYCLIN D1 repairs DNA during reprogramming resulting in significantly improved genetically stable footprint in human iPSC, enabling a new cell reprogramming method for more accurate and reliable generation of human iPSC for disease modeling and future clinical applications.
Evolution of Impatiens (Balsaminaceae) in the Albertine Rift – The endemic Impatiens purpureoviolacea complex consists of ten species
Authors: Fischer Eberhard , Abrahamczyk Stefan , Holstein Norbert , Janssens Steven B. 
Published: September 2021

AbstractThe Albertine Rift harbours a highly diverse flora with numerous endemic species. An important component of the forest understorey is the herbaceous genus Impatiens. Fieldwork in Burundi, the Democratic Republic of the Congo and Rwanda as well as morphological studies indicated that the Albertine Rift endemic Impatiens purpureoviolacea represents a species complex. We analyzed the hidden diversity of the complex using morphological and molecular data supplemented by herbarium studies. We found that the Impatiens purpureoviolacea complex can be divided into morphologically and phylogenetically well characterized clades containing ten species and a natural hybrid. We describe all of these species, provide a species key and analyze their evolutionary history. Beside Impatiens purpureoviolacea and I. gesneroidea, the already described I. urundiensis is resurrected from synonymy. Two varieties, Impatiens purpureoviolacea var. longicalcarata and I. gesneroidea var. superglabra are raised to species status, and five new species (Impatiens elwiraurzulae, I. lotteri, I. ludewigii, I. lutzmannii, I. versicolor) and a new natural hybrid (I. ×troupinii) are described. Within the mostly insect‐pollinated species of the clade, two bird‐pollinated species (Impatiens gesneroidea, I. superglabra) evolved independently. The clade split from its sister taxon in the Pliocene and started diversifying during the Pliocene/Pleistocene transition in parallel to an increased mountain uplifting and volcanic activity in the Albertine Rift. It further diversified during the Pleistocene, likely due to the changes in forest cover and connectivity induced by climatic fluctuations.
The mechanism of N‐acetyl‐l‐cysteine in improving the secretion of porcine follicle‐stimulating hormone in Pichia pastoris
Authors: Luo Gang , Liu Jiying , Bian Ting , Zhang Zhendong , Li Muwang 
Published: September 2021

AbstractOur previous study revealed that N‐acetyl‐l‐cysteine (NAC) could enhance the secretion of recombinant proteins by Pichia pastoris, but the corresponding molecular mechanisms are still unclear. In the present study, we explored whether other thiols have a similar action on the secretion of recombinant human serum albumin and porcine follicle‐stimulating hormone fusion protein (HSA‐pFSHβ), to reveal the mechanism of NAC on HSA‐pFSHβ secretion. Transcriptome analysis showed that genes involved in oxidoreductase activity and oxidation–reduction process were upregulated in cells supplemented with NAC. The other three thiol‐reducing regents including dimercaptopropanol (DT), thioglycolic acid, and mercaptolactic acid could improve HSA‐pFSHβ production in the culture supernatant. Among them, only DT had similar effect as NAC on HSA‐pFSHβ secretion and the increase of GSH content. Moreover, 1–20 mM GSH, 1–10 mM cysteine, or 1–20 mM N‐acetyl‐d‐cysteine supplementation could improve the secretion of HSA‐pFSHβ. Furthermore, 0.4–3.2 mM ethacrynic acid, rather than 1–16 mM BSO could inhibit the effect of NAC on the production of HSA‐pFSHβ. These results indicated that NAC improved the secretion of HSA‐pFSHβ by increasing the intracellular GSH content through its thiol activity rather than as a precursor for GSH synthesis. In conclusion, our results demonstrate, for the first time, that the secretion of recombinant HSA‐pFSHβ in Pichia pastoris could be improved through thiol‐reducing agent supplementation, and the mechanism of the effect NAC has on HSA‐pFSHβ secretion is associated with improving the intracellular GSH content.
Higher-derivative supergravity, AdS4 holography, and black holes
Authors: Bobev Nikolay , Charles Anthony M. , Hristov Kiril , Reys Valentin 
Published: September 2021

Abstract
We use conformal supergravity techniques to study four-derivative corrections in four-dimensional gauged supergravity. We show that the four-derivative Lagrangian for the propagating degrees of freedom of the $$ \mathcal{N} $$
N
= 2 gravity multiplet is determined by two real dimensionless constants. We demonstrate that all solutions of the two-derivative equations of motion in the supergravity theory also solve the four-derivative equations of motion. These results are then applied to explicitly calculate the regularized on-shell action for any asymptotically locally AdS4 solution of the two-derivative equations of motion. The four-derivative terms in the supergravity Lagrangian modify the entropy and other thermodynamic observables for the black hole solutions of the theory. We calculate these corrections explicitly and demonstrate that the quantum statistical relation holds for general stationary black holes in the presence of the four-derivative corrections. Employing an embedding of this supergravity model in M-theory we show how to use supersymmetric localization results in the holographically dual three-dimensional SCFT to determine the unknown coefficients in the four-derivative supergravity action. This in turn leads to new detailed results for the first subleading $$ {N}^{\frac{1}{2}} $$

N

1
2

correction to the large N partition function of a class of three-dimensional SCFTs on compact Euclidean manifolds. In addition, we calculate explicitly the first subleading correction to the Bekenstein-Hawking entropy of asymptotically AdS4 black holes in M-theory. We also discuss how to add matter multiplets to the supergravity theory in the presence of four-derivative terms and to generalize some of these results to six- and higher-derivative supergravity.
Fracture fixation in extremity trauma with carbon fiber-reinforced polyetheretherketone (CFR-PEEK) plates: evidence today
Authors: Chloros George D. , Prodromidis Apostolos D. , Wilson Jo , Giannoudis Peter V. 
Published: September 2021

Abstract
Purpose
To compare the CFR-PEEK plates with conventional plates in fracture fixation with regards to clinical and radiological outcomes and complications.

Methods
A systematic literature search was conducted in four online databases independently by two reviewers using the Cochrane methodology for systematic reviews. The identified relevant studies were assessed against predetermined inclusion/exclusion criteria. Independent data extraction and assessment of risk of bias and study quality was carried out.

Results
Nine studies (patient n = 361) out of 6594 records were included for analysis: 2 RCTs (n = 63), 3 prospective cohort studies (n = 151), and 4 retrospective cohort studies (n = 147). Studies were grouped per anatomic area of fixation. Four studies (n = 200) examined fixation of proximal humerus fractures. Two studies (n = 74) examined fixation of distal radius fractures. Two studies (n = 53) assessed outcomes of fixation of distal femur fractures. One study (n = 87) assessed the outcomes of fixation of ankle fractures. All nine studies reported very high union rates (from 91% in distal femur to 100% in upper limb) for the CFR-PEEK plate groups and low complication rates. There was no significant difference in clinical outcomes, and rate of complications as compared to the conventional plate groups.

Conclusion
CFR-PEEK plates have high union rates in extremity fracture fixation similar to conventional plates with comparable good clinical outcomes and a very low and comparable rate of complications. Considering their advantages, CFR-PEEK plates seem to be valid alternative to conventional plating.
Enter the metrics: critical theory and organizational operationalization of AI ethics
Authors: Krijger Joris 
Published: September 2021

AbstractAs artificial intelligence (AI) deployment is growing exponentially, questions have been raised whether the developed AI ethics discourse is apt to address the currently pressing questions in the field. Building on critical theory, this article aims to expand the scope of AI ethics by arguing that in addition to ethical principles and design, the organizational dimension (i.e. the background assumptions and values influencing design processes) plays a pivotal role in the operationalization of ethics in AI development and deployment contexts. Through the prism of critical theory, and the notions of underdetermination and technical code as developed by Feenberg in particular, the organizational dimension is related to two general challenges in operationalizing ethical principles in AI: (a) the challenge of ethical principles placing conflicting demands on an AI design that cannot be satisfied simultaneously, for which the term ‘inter-principle tension’ is coined, and (b) the challenge of translating an ethical principle to a technological form, constraint or demand, for which the term ‘intra-principle tension’ is coined. Rather than discussing principles, methods or metrics, the notion of technical code precipitates a discussion on the subsequent questions of value decisions, governance and procedural checks and balances. It is held that including and interrogating the organizational context in AI ethics approaches allows for a more in depth understanding of the current challenges concerning the formalization and implementation of ethical principles as well as of the ways in which these challenges could be met.
Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial
Authors: Voss Martin , Wenger Katharina J. , von Mettenheim Nina , Bojunga Jörg , Vetter Manuela , Diehl Bianca , Franz Kea , Gerlach Ruediger , Ronellenfitsch Michael W. , Harter Patrick N. , Hattingen Elke , Steinbach Joachim P. , Rödel Claus , Rieger Johannes 
Published: September 2021

Abstract
Purpose
The prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries.

Methods
50 patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21–23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples.

Results
The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. Substantial decreases in leptin and insulin and an increase in uric acid were observed. The SD group, of note, had a lower calorie intake than expected (21 kcal/kg/d instead of 30 kcal/kg/d). Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis.

Conclusion
The strict caloric goals of the ERGO2 trial were tolerated well by patients with recurrent brain cancer. The short diet schedule led to significant metabolic changes with low glucose emerging as a candidate marker of better prognosis. The unexpected lower calorie intake of the control group complicates the interpretation of the results.
Clinicaltrials.gov number: NCT01754350; Registration: 21.12.2012.
High-sensitivity FEES® with the professional image enhancement technology “PIET”
Authors: Kraus Fabian , Hackenberg Stephan , Shehata-Dieler Wafaa , Hagen Rudolf 
Published: September 2021

Abstract
Purpose
Flexible endoscopic evaluation of swallowing (FEES®) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the “professional image enhancement technique” (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES® procedure.

Methods
Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES® was performed and recorded with the two systems during daily routine.

Results
Performing an image enhancement during FEES® is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected.

Conclusions
PIET proved to be non-inferior to NBI during image enhancement FEES®. So far, image enhancement FEES® was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.
Multiorgan tropism of SARS-CoV-2 lineage B.1.1.7
Authors: Ondruschka Benjamin , Heinrich Fabian , Lindenmeyer Maja , Edler Carolin , Möbius Dustin , Czogalla Jan , Heinemann Axel , Braun Fabian , Aepfelbacher Martin , Lütgehetmann Marc , Huber Tobias B. 
Published: September 2021

AbstractDue to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein’s affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.
Endovascular versus surgical treatment of cranial dural arteriovenous fistulas: a single-center 8-year experience
Authors: Sorteberg Wilhelm , Sorteberg Angelika , Jacobsen Eva Astrid , Rønning Pål , Nome Terje , Eide Per Kristian 
Published: September 2021

Abstract
Background
Cranial dural arteriovenous fistulas (dAVFs) are rare lesions managed mainly with endovascular treatment (EVT) and/or surgery. We hypothesize that there may be subtypes of dAVFs responding better to a specific treatment modality in terms of successful obliteration and cessation of symptoms and/or risks.

Methods
All dAVFs treated during 2011–2018 at our hospital were analyzed retrospectively. Presenting symptoms, radiological variables, treatment modality, complications, and residual symptoms were related to dAVF type using the original Djindjian classification.

Results
We treated 112 dAVFs in 107 patients (71, 66% males). They presented with hemorrhage (n = 23; 21%), non-hemorrhagic symptoms (n = 75; 70%), or were discovered incidentally (n = 9; 8%). There were 25 (22%) type I, 29 (26%) type II, 26 (23%) type III, and 32 (29%) type IV fistulas. EVT was the primary treatment modality in 72/112 (64%) dAVFs whereas 40/112 (36%) underwent primary surgery with angiographic obliteration rates of 60% and 90%, respectively. Using a secondary treatment modality in 23 dAVFs, we obtained a final obliteration rate of 93%, including all type III/IV and 26/27 (96%) type II dAVFs. Except for headache, residual symptoms were rare and minor. Permanent neurological complications consisted of five cranial nerve deficits.

Conclusions
We recommend EVT as first treatment modality in types I, II, and in non-hemorrhagic type III/IV dAVFs. We recommend surgery as first treatment choice in acute hemorrhagic dAVFs and as secondary choice in type III/IV dAVFs not successfully occluded by EVT. Combining the two modalities provides obliteration in 9/10 dAVF cases at a low procedural risk.
Frank–Wolfe and friends: a journey into projection-free first-order optimization methods
Authors: Bomze Immanuel M. , Rinaldi Francesco , Zeffiro Damiano 
Published: September 2021

AbstractInvented some 65 years ago in a seminal paper by Marguerite Straus-Frank and Philip Wolfe, the Frank–Wolfe method recently enjoys a remarkable revival, fuelled by the need of fast and reliable first-order optimization methods in Data Science and other relevant application areas. This review tries to explain the success of this approach by illustrating versatility and applicability in a wide range of contexts, combined with an account on recent progress in variants, improving on both the speed and efficiency of this surprisingly simple principle of first-order optimization.
Understanding indirect requests for information in high-functioning autism
Authors: Marocchini Eleonora , Di Paola Simona , Mazzaggio Greta , Domaneschi Filippo 
Published: September 2021

AbstractFew works have addressed the processing of indirect requests in High-Functioning Autism (HFA), and results are conflicting. Some studies report HFA individuals’ difficulties in indirect requests comprehension; others suggest that it might be preserved in HFA. Furthermore, the role of Theory of Mind in understanding indirect requests is an open issue. The goal of this work is twofold: first, assessing whether comprehension of indirect requests for information is preserved in HFA; second, exploring whether mind-reading skills predict this ability. We tested a group of (n = 14; 9–12 years) HFA children and two groups of younger (n = 19; 5–6 years) and older (n = 28; 9–12 years) typically developing (TD) children in a semi-structured task involving direct, indirect and highly indirect requests for information. Results suggested that HFA can understand indirect and highly indirect requests, as well as TD children. Yet, while Theory of Mind skills seem to enhance older TD children understanding, this is not the case for HFA children. Therefore, interestingly, they could rely on different interpretative strategies.
Upper bounds for Steklov eigenvalues of subgraphs of polynomial growth Cayley graphs
Authors: Tschanz Léonard 
Published: September 2021

AbstractWe study the Steklov problem on a subgraph with boundary $$(\Omega ,B)$$

(
Ω
,
B
)

of a polynomial growth Cayley graph $$\Gamma$$
Γ
. For $$(\Omega _l, B_l)_{l=1}^\infty$$

(

Ω
l

,

B
l

)

l
=
1

∞

a sequence of subgraphs of $$\Gamma$$
Γ
such that $$|\Omega _l| \longrightarrow \infty$$

|

Ω
l

|
⟶
∞

, we prove that for each $$k \in {\mathbb {N}}$$

k
∈
N

, the kth eigenvalue tends to 0 proportionally to $$1/|B|^{\frac{1}{d-1}}$$

1
/

|
B
|

1

d
-
1

, where d represents the growth rate of $$\Gamma$$
Γ
. The method consists in associating a manifold M to $$\Gamma$$
Γ
and a bounded domain $$N \subset M$$

N
⊂
M

to a subgraph $$(\Omega , B)$$

(
Ω
,
B
)

of $$\Gamma$$
Γ
. We find upper bounds for the Steklov spectrum of N and transfer these bounds to $$(\Omega , B)$$

(
Ω
,
B
)

by discretizing N and using comparison theorems.