bluuebunny/crossref_metadata_2025_split huggingface dataset:
Between-sex variability of resting state functional brain networks in amyotrophic lateral sclerosis (ALS)
Authors: Trojsi Francesca , Di Nardo Federica , Caiazzo Giuseppina , Siciliano Mattia , D’Alvano Giulia , Passaniti Carla , Russo Antonio , Bonavita Simona , Cirillo Mario , Esposito Fabrizio , Tedeschi Gioacchino 
Published: September 2021

AbstractThe organization of brain functional connectivity (FC) has been shown to differ between sexes. Amyotrophic lateral sclerosis (ALS) is characterized by sexual dimorphism, showing sex-specific trends in site of onset, phenotypes, and prognosis. Here, we explored resting state (RS) FC differences within major large-scale functional networks between women and men in a sample of ALS patients, in comparison to healthy controls (HCs). A group-level independent component analysis (ICA) was performed on RS-fMRI time-series enabling spatial and spectral analyses of large-scale RS FC networks in 45 patients with ALS (20 F; 25 M) and 31 HCs (15 F; 16 M) with a focus on sex-related differences. A whole-brain voxel-based morphometry (VBM) was also performed to highlight atrophy differences. Between-sex comparisons showed: decreased FC in the right middle frontal gyrus and in the precuneus within the default mode network (DMN), in affected men compared to affected women; decreased FC in the right post-central gyrus (sensorimotor network), in the right inferior parietal gyrus (right fronto-parietal network) and increased FC in the anterior cingulate cortex and right insula (salience network), in both affected and non-affected men compared to women. When comparing affected men to affected women, VBM analysis revealed atrophy in men in the right lateral occipital cortex. Our results suggest that in ALS sex-related trends of brain functional and structural changes are more heavily represented in DMN and in the occipital cortex, suggesting that sex is an additional dimension of functional and structural heterogeneity in ALS.
Levetiracetam, lamotrigine and carbamazepine: which monotherapy during pregnancy?
Authors: Mari Luisa , Placidi Fabio , Romigi Andrea , Tombini Mario , Del Bianco Chiara , Ulivi Martina , Liguori Claudio , Manfredi Natalia , Castelli Alessandro , Mercuri Nicola Biagio , Izzi Francesca 
Published: September 2021

Abstract
Objective
Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy.

Methods
A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV.

Results
Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p < 0.001) and in women on LEV (p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found.

Conclusions
A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.
Single source unsplittable flows with arc-wise lower and upper bounds
Authors: Morell Sarah , Skutella Martin 
Published: September 2021

AbstractIn a digraph with a source and several destination nodes with associated demands, an unsplittable flow routes each demand along a single path from the common source to its destination. Given some flow x that is not necessarily unsplittable but satisfies all demands, it is a natural question to ask for an unsplittable flow y that does not deviate from x by too much, i.e., $$y_a\approx x_a$$

y
a

≈

x
a

for all arcs a. Twenty years ago, in a landmark paper, Dinitz et al. (Combinatorica 19:17–41, 1999) proved that there exists an unsplittable flow y such that $$y_a\le x_a+d_{\max }$$

y
a

≤

x
a

+

d
max

for all arcs a, where $$d_{\max }$$

d
max

denotes the maximum demand value. Our first contribution is a considerably simpler one-page proof for this classical result, based upon an entirely new approach. Secondly, using a subtle variant of this approach, we obtain a new result: There is an unsplittable flow y such that $$y_a\ge x_a-d_{\max }$$

y
a

≥

x
a

-

d
max

for all arcs a. Finally, building upon an iterative rounding technique previously introduced by Kolliopoulos and Stein (SIAM J Comput 31:919–946, 2002) and Skutella (Math Program 91:493–514, 2002), we prove existence of an unsplittable flow that simultaneously satisfies the upper and lower bounds for the special case when demands are integer multiples of each other. For arbitrary demand values, we prove the weaker simultaneous bounds $$x_a/2-d_{\max }\le y_a\le 2x_a+d_{\max }$$

x
a

/
2
-

d
max

≤

y
a

≤
2

x
a

+

d
max

for all arcs a.
Land in Central America will become less suitable for coffee cultivation under climate change
Authors: Lara-Estrada Leonel , Rasche Livia , Schneider Uwe A. 
Published: September 2021

AbstractCoffee cultivation in Central America provides goods and services at local, national, and international levels. Climate change is likely to affect the magnitude and continuity of these benefits by reducing the land suitability for coffee cultivation. To quantify the impacts of climate change on land suitability, we use the Bayesian network model Agroecological Land Evaluation for Coffea arabica L. (ALECA) and estimate the land suitability for coffee production in 2000, 2050, and 2080 under three climate change scenarios based on relative concentration pathways (RCPs) 2.6, 4.5, and 8.5. Results indicate that even under the less severe climate scenarios, over half of the current coffee area in Central America will experience a decline in its land suitability for coffee production, from excellent or good to moderate and marginal, and that the change will not happen in the more distant future of 2080, but by 2050. Under RCP 8.5, most coffee areas become of marginal and moderate suitability. The findings show that the continuity of coffee cultivation in a large portion of coffee areas in Central America is under threat and that farmers and policy-makers should develop adaptation portfolios for their farms and regions in a timely manner.
Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial
Authors: Fuchs Charles S. , Özgüroğlu Mustafa , Bang Yung-Jue , Di Bartolomeo Maria , Mandala Mario , Ryu Min-Hee , Fornaro Lorenzo , Olesinski Tomasz , Caglevic Christian , Chung Hyun C. , Muro Kei , Van Cutsem Eric , Elme Anneli , Thuss-Patience Peter , Chau Ian , Ohtsu Atsushi , Bhagia Pooja , Wang Anran , Shih Chie-Schin , Shitara Kohei 
Published: September 2021

Abstract
Background
In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019).

Methods
Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models.

Results
366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%).

Conclusion
In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel.

Trial registration
ClinicalTrials.gov, NCT02370498
Valuing informal carers’ quality of life using best-worst scaling—Finnish preference weights for the Adult ﻿Social Care Outcomes Toolkit for carers (ASCOT-Carer)
Authors: Nguyen Lien , Jokimäki Hanna , Linnosmaa Ismo , Saloniki Eirini-Christina , Batchelder Laurie , Malley Juliette , Lu Hui , Burge Peter , Trukeschitz Birgit , Forder Julien 
Published: September 2021

AbstractThis study developed Finnish preference weights for the seven-attribute Adult Social Care Outcomes Toolkit for carers (ASCOT-Carer) and investigated survey fatigue and learning in best-worst scaling (BWS) experiments. An online survey that included a BWS experiment using the ASCOT-Carer was completed by a sample from the general population in Finland. A block of eight BWS profiles describing different states from the ASCOT-Carer were randomly assigned to each respondent, who consecutively made four choices (best, worst, second best and second worst) per profile. The analysis panel data had 32,160 choices made by 1005 respondents. A scale multinomial logit (S-MNL) model was used to estimate preference weights for 28 ASCOT-Carer attribute levels. Fatigue and learning effects were examined as scale heterogeneity. Several specifications of the generalised MNL model were employed to ensure the stability of the preference estimates. The most and least-valued states were the top and bottom levels of the control over daily life attribute. The preference weights were not on a cardinal scale. We observed the position effect of the attributes on preferences associated with the best or second-best choices. A learning effect was found. The established preference weights can be used in evaluations of the effects of long-term care services and interventions on the quality of life of service users and caregivers. The learning effect implies a need to develop study designs that ensure equal consideration to all profiles (choice tasks) in a sequential choice experiment.
Which factors influence the density of birch (Betula pendula Roth) seeds in soil seed banks in temperate woodlands?
Authors: Tiebel Katharina 
Published: September 2021

AbstractThe natural regeneration of disturbed forest sites is becoming increasingly important due to climate change. Following disturbance events affecting large areas seed trees are often absent from the site, and regeneration solely by means of seed rain may not be successful. In these situations, soil seed banks are an important driver of the regeneration and reforestation of forest sites. The aim of the study was to determine the birch seed density in the soil of birch stands, spruce–birch stands and spruce stands dependent upon the number of seed trees (stands) and upon varying degrees of ground cover using the ‘seedling emergence method.’ The study revealed a significant link between the quantity of germinated birch seedlings in soil samples and the presence of seed sources. Seedling densities of birch in the different stand categories reached 2644–6414 seedlings per m2 [n m−2] in birch stands, 392–759 n m−2in spruce–birch stands and 25–122 n m−2in pure spruce stands. The density of germinated birch seedlings was also negatively affected by the soil layer. In all stand types, the factors humus thickness, litter cover, moss cover and herb cover had no significant influence on the amount of birch seedlings. Successful rapid regeneration of disturbed sites by means of the birch soil seed bank is guaranteed in cases where birch stands, or at least birch seed trees, were present before the event. The influence of ground cover on the regeneration potential of birch from the soil is negligible.
Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague–Dawley rats
Authors: Jung Jae In , Lee Hyun Sook , Jeon Young Eun , Kim So Mi , Hong Su Hee , Moon Joo Myung , Lim Cho Young , Kim Yoon Hee , Kim Eun Ji 
Published: September 2021

AbstractNovel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague–Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.
Erziehung zur Moralität in einer komplexen Welt
Authors: Rucker Thomas 
Published: September 2021

ZusammenfassungIn diesem Beitrag wird das Problem behandelt, wie eine Erziehung zur Moralität in einer komplexen Welt sinnvoll konzipiert werden kann. Um eine Antwort auf diese Frage zu finden, wird zunächst ein von Michael Hand entwickelter Lösungsvorschlag für die Problemstellung rekonstruiert. Daraufhin wird der Vorschlag auf den Prüfstand gestellt und gezeigt, dass dieser ein in der Pädagogik bereits erreichtes Problemniveau in spezifischer Hinsicht unterschreitet. Im Mittelpunkt stehen zwei Einwände, die als das Kombinationsdefizit erzieherischer Grundformen und als der Vorwurf aus der Imperfektheit der Ethik bezeichnet werden. Schließlich wird argumentiert, dass die Theorie nichtaffirmativer Moralerziehung die Möglichkeit eröffnet, die Problemkonstellation zu umgehen, in die Hands Theorieentwurf hineinführt. Umgekehrt wird die Position vertreten, dass dieser Entwurf Anlass dazu gibt, die Theorie nichtaffirmativer Moralerziehung selbst nicht unbefragt zu affirmieren, sondern an deren Weiterentwicklung zu arbeiten, um moralische Erziehung in einer komplexen Welt zukünftig differenzierter zu konzipieren.
The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Improves Ex Vivo and In Vivo Amyloid Beta (1–42)-Induced Neuroinflammation in Mouse Models of Alzheimer’s Disease
Authors: Trojan Ewa , Tylek Kinga , Schröder Nicole , Kahl Iris , Brandenburg Lars-Ove , Mastromarino Margherita , Leopoldo Marcello , Basta-Kaim Agnieszka , Lacivita Enza 
Published: September 2021

Abstract
The major histopathological hallmarks of Alzheimer’s disease (AD) include β-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Aβ 1–42 (Aβ1-42) has been shown to induce neurotoxicity and secretion of proinflammatory mediators that potentiate neurotoxicity. Proinflammatory and neurotoxic activities of Aβ1-42 were shown to be mediated by interactions with several cell surface receptors, including the chemotactic G protein-coupled N-formyl peptide receptor 2 (FPR2). The present study investigated the impact of a new FPR2 agonist, MR-39, on the neuroinflammatory response in ex vivo and in vivo models of AD. To address this question, organotypic hippocampal cultures from wild-type (WT) and FPR2-deficient mice (knockout, KO, FPR2−/−) were treated with fibrillary Aβ1-42, and the effect of the new FPR2 agonist MR-39 on the release of pro- and anti-inflammatory cytokines was assessed. Similarly, APP/PS1 double-transgenic AD mice were treated for 20 weeks with MR-39, and immunohistological staining was performed to assess neuronal loss, gliosis, and Aβ load in the hippocampus and cortex. The data indicated that MR-39 was able to reduce the Aβ1-42-induced release of proinflammatory cytokines and to improve the release of anti-inflammatory cytokines in mouse hippocampal organotypic cultures. The observed effect was apparently related to the inhibition of the MyD88/TRAF6/NFкB signaling pathway and a decrease in NLRP3 inflammasome activation. Administration of MR-39 to APP/PS1 mice improved neuronal survival and decreased microglial cell density and plaque load.These results suggest that FPR2 may be a promising target for alleviating the inflammatory process associated with AD and that MR-39 may be a useful therapeutic agent for AD.
Role of ultrasound in the diagnosis of cervical tuberculous lymphadenitis in children
Authors: Yu Tian-Zhuo , Zhang Ying , Zhang Wen-Zhi , Yang Gao‑Yi 
Published: September 2021

Abstract
Background
To describe sonographic characteristics of cervical tuberculous lymphadenitis (CTBL) in children, clinical information, and sonograms of 348 lymph nodes (LNs) from 57 children with CTBL were retrospectively analyzed in this study.

Methods
We retrospectively reviewed the clinical data and sonograms of 348 LNs from 31 boys and 26 girls with CTBL, who were confirmed by pathology or laboratory examination, at the Hangzhou Red Cross Hospital between June 2014 and December 2020. The age of the children ranged from 1 to 14 years (average 7.1 ± 2.9 years).

Results
Night sweats, fatigue and loss of appetite were the most common clinical symptoms observed in children with CTBL. Unilateral LN involvements were common. Occasionally, CTBL was found in healthy children with no symptoms. On sonography, the hilus was absent or unclear in all LNs. The short-to-long axis (S/L) ratio was ≥ 0.5, and the edges were unclear in most LNs. Other accompanying findings included necrosis (47.4%), an echogenic thin layer (36.8%), surrounding soft-tissue edema (38.5%), multiple intra-nodal strong echo (28.2%), sinus (22.7%) and abscess formation (6.9%). The Doppler ultrasound showed that the majority of vascularity patterns of CTBL were capsular or peripheral (33.3%).

Conclusions
Ultrasound is a recommended examination method for children from different age groups with cervical lymphadenitis. The ultrasonic signs of hilus absence, S/L ratio ≥ 0.5, unclear edge, necrosis, echogenic thin layer, strong echoes and capsular or peripheral vascularity may aid in the diagnosis of cervical tuberculous lymphadenitis.
Visualizing dynamic data with heat triangles
Authors: Hu Ya Ting , Burch Michael , Wetering Huub van de 
Published: September 2021

AbstractIn this paper, an overview-based interactive visualization for temporally long dynamic data sequences is described. To reach this goal, each data object at a certain time point can be mapped to a number value based on a given property. Among others, a property is application-dependent and can be number of vertices, number of edges, average degree, density, number of self-loops, degree (maximum and total), or edge weight (minimum, maximum, and total) for dynamic graph data, but it can as well be the number of ball contacts in a football match, or the time-dependent visual attention paid to a stimulus in an eye tracking study. To achieve an overview over time, an aggregation strategy based on either the mean, minimum, or maximum of two values is applied. This temporal value aggregation generates a triangular shape with an overview of the entire data sequence as the peak. The color coding can be adjusted, forming visual patterns that can be rapidly explored for certain data features over time, supporting comparison tasks between the properties. The usefulness of the approach is illustrated by means of applying it to dynamic graphs generated from US domestic flight data as well as to dynamic Covid-19 infections on country levels.

Graphic abstract
Gray matter heterotopia: clinical and neuroimaging report on 22 children
Authors: Di Nora A. , Costanza G. , Pizzo F. , Oliva C. F. , Di Mari A. , Greco F. , Pavone P. 
Published: September 2021

Abstract
Objective
To investigate the clinical characteristics and neuroimaging features of childhood presenting with gray matter heterotopia observed in a single tertiary Pediatric Department in Catania and compare the data with those reported in the literature.

Methods
A retrospectively review of the history, clinical findings, electrophysiological features and magnetic resonance images of 22 children presenting with gray matter heterotopia observed from January 2010 to January 2020.

Results
Among the 22 children included in the study, 17 presented with periventricular heterotopia (PVNH), two with Subcortical Band Heterotopia (SBH), and three with other subcortical heterotopia (SUBH). In the affected children, the ages at first diagnosis ranged from 3 months to 16 years with a mean age of 8.2 years (± 5.4); twelve (54.5%) suffered by developmental delay and intellectual deficit; eleven children (50%) complained of epileptic seizures, mostly focal to bilateral tonic–clonic seizure. In addition, in the periventricular heterotopia group (PVNH), cerebral and systemic malformations were reported in twelve (70%) and in ten (58%) children, respectively, out of seventeen. In the SBH plus SUBH group, epileptic seizures were recorded in 3 (60%) out of 5 children, cerebral malformations in one child and systemic malformations in two children.

Conclusions
Heterotopic gray matter malformations include a group of disorders that manifest with a variety of neurological implications, such as cognitive impairment and epilepsy, and often related with epilepsy, other cerebral malformations and systemic anomalies.