bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term barriers to global fertility convergence
Authors: Papagni Erasmo
Published: March 2022

After WWII, the demographic transition exhibited features of convergence between developing countries and the forerunner countries with low fertility. Although today fertility is low in the majority of countries, significant differences persist. In this article, I study club convergence of fertility in 190 countries over the period 1950 to 2018. First, I apply a novel econometric method for convergence analysis and club clustering. I find no evidence of global fertility convergence, and I classify the 190 countries into four clubs. I further classify countries into two clubs at the beginning of the period and identify a club of countries transitioning from high to low fertility. Second, I interpret fertility convergence clubs as a feature of the long-term process of economic development and estimate an ordered probit model of the probability that a country enters one of three clubs characterized by high, medium, and low barriers to global fertility convergence. Here, the focus is on ancestral fundamental factors of diversity in economic development. Estimates show a statistically significant inverted U-shaped relationship between interpersonal population diversity and the probability of lower barriers, consistent with the literature on diversity and development. Estimates also highlight that genetic distance to the USA and years since the Neolithic transition to agriculture cause higher barriers to fertility decline.
Long-term outcome after routine surgery for pelvic organ prolapse—A national register-based cohort study
Authors: Nüssler Emil , Granåsen Gabriel , Bixo Marie , Löfgren Mats
Published: March 2022

Introduction and hypothesis

Pelvic organ prolapse (POP) is common, and women have an estimated 12–19% lifetime risk for needing POP surgery. Aims were to measure re-operation rates up to 10 years after POP surgery and patient-reported outcomes (PROMs) 5 years after a first-time operation for POP.

Methods

This is a cohort study using the Swedish National Quality Register for Gynaecological Surgery (GynOp). We retrieved information from 32,086 POP-operated women up to 10 years later. After validation, a web-based PROM questionnaire was sent to 4380 women who 5 years previously had standard POP surgery. Main outcome measures were reoperations due to a relapse of prolapse and PROMs 5 years after the primary operation.

Results

Among women operated for all types of POP, 11% had re-operations 5 years later and an additional 4% 10 years later, with similar frequencies for various compartments/types of surgery. PROMs yielded a 75% response rate after 5 years. Cure rate was 68% for anterior, 70% for posterior, and 74% for combined anterior-posterior native repairs. Patient satisfaction exceeded 70%, and symptom reduction was still significant after 5 years (p < 0.0001).

Conclusions

Following primary prolapse surgery, re-operation rates are low, even after 10 years. A web-based survey for follow-up of PROMs after POP surgery is feasible and yields a high response rate after 5 years. The subjective cure rate after primary POP operations is high, with reduced symptoms and satisfied patients regardless of compartment. Standard prolapse surgery with native tissue repair produces satisfactory long-term results.
Development and in vitro investigation of a biodegradable mesh for the treatment of stress urinary incontinence
Authors: MacCraith E. , Joyce M. , do Amaral R. J. F. C. , O’Brien F. J. , Davis N. F.
Published: March 2022

Introduction and hypothesis

The use of polypropylene (PP) mesh for stress urinary incontinence (SUI) surgery has declined because of safety concerns. The aim of this study is to evaluate a biodegradable polycaprolactone (PCL) mesh and a PCL composite mesh tissue engineered with human uterine fibroblasts (HUFs) for SUI surgery by comparing mechanical properties and in vitro biocompatibility to commercially available PP and porcine dermis (PD).

Methods

The mechanical properties of four scaffold materials were evaluated: PCL, PCL-collagen-hyaluronic acid composite, acellular porcine dermal collagen (PD) (Pelvicol™) and polypropylene (Gynecare TVT™ Exact®). HUFs were seeded on separate scaffolds. After 7 and 14 days scaffolds were assessed for metabolic activity and cell proliferation using Alamar Blue, Live/Dead and PicoGreen assays. Soluble collagen production was evaluated using a Sircol assay.

Results

PCL and the composite scaffold reached ultimate tensile strength (UTS) values closest to healthy pelvic floor tissue (PCL = 1.19 MPa; composite = 1.13 MPa; pelvic floor = 0.79 MPa; Lei et al. Int Urogynecol J Pelvic Floor Dysfunct. 18(6):603-7, 2007). Cells on PCL showed significantly greater cell viability than PP at day 7 (p < 0.0001). At D14 the composite scaffold showed significantly greater cell viability than PP (p = 0.0006). PCL was the best performing scaffold for soluble collagen production at day 14 (106.1 μg versus 13.04 μg for PP, p = 0.0173).

Conclusions

We have designed a biodegradable PCL mesh and a composite mesh which demonstrate better biocompatibility than PP and mechanical properties closer to that of healthy pelvic floor tissue. This in vitro study provides promising evidence that these two implants should be evaluated in animal and human trials.
Candidate master microRNA regulator of arsenic-induced pancreatic beta cell impairment revealed by multi-omics analysis
Authors: Todero Jenna E. , Koch-Laskowski Kieran , Shi Qing , Kanke Matt , Hung Yu-Han , Beck Rowan , Styblo Miroslav , Sethupathy Praveen
Published: March 2022

Arsenic is a pervasive environmental toxin that is listed as the top priority for investigation by the Agency for Toxic Substance and Disease Registry. While chronic exposure to arsenic is associated with type 2 diabetes (T2D), the underlying mechanisms are largely unknown. We have recently demonstrated that arsenic treatment of INS-1 832/13 pancreatic beta cells impairs glucose-stimulated insulin secretion (GSIS), a T2D hallmark. We have also shown that arsenic alters the microRNA profile of beta cells. MicroRNAs have a well-established post-transcriptional regulatory role in both normal beta cell function and T2D pathogenesis. We hypothesized that there are microRNA master regulators that shape beta cell gene expression in pathways pertinent to GSIS after exposure to arsenicals. To test this hypothesis, we first treated INS-1 832/13 beta cells with either inorganic arsenic (iAsIII) or monomethylarsenite (MAsIII) and confirmed GSIS impairment. We then performed multi-omic analysis using chromatin run-on sequencing, RNA-sequencing, and small RNA-sequencing to define profiles of transcription, gene expression, and microRNAs, respectively. Integrating across these data sets, we first showed that genes downregulated by iAsIII treatment are enriched in insulin secretion and T2D pathways, whereas genes downregulated by MAsIII treatment are enriched in cell cycle and critical beta cell maintenance factors. We also defined the genes that are subject primarily to post-transcriptional control in response to arsenicals and demonstrated that miR-29a is the top candidate master regulator of these genes. Our results highlight the importance of microRNAs in arsenical-induced beta cell dysfunction and reveal both shared and unique mechanisms between iAsIII and MAsIII.
Liver Venous Deprivation (LVD) Versus Portal Vein Embolization (PVE) Alone Prior to Extended Hepatectomy: A Matched Pair Analysis
Authors: Böning Georg , Fehrenbach Uli , Auer Timo Alexander , Neumann Konrad , Jonczyk Martin , Pratschke Johann , Schöning Wenzel , Schmelzle Moritz , Gebauer Bernhard
Published: March 2022

Background

To investigate whether liver venous deprivation (LVD) as simultaneous, portal vein (PVE) and right hepatic vein embolization offers advantages in terms of hypertrophy induction before extended hepatectomy in non-cirrhotic liver.

Materials and Methods

Between June 2018 and August 2019, 20 patients were recruited for a prospective, non-randomized study to investigate the efficacy of LVD. After screening of 134 patients treated using PVE alone from January 2015 to August 2019, 14 directly matched pairs regarding tumor entity (cholangiocarcinoma, CC and colorectal carcinoma, CRC) and hypertrophy time (defined as time from embolization to follow-up imaging) were identified. In both treatment groups, the same experienced reader (> 5 years experience) performed imaging-based measurement of the volumes of liver segments of the future liver remnant (FLR) prior to embolization and after the standard clinical hypertrophy interval (~ 30 days), before surgery. Percentage growth of segments was calculated and compared.

Results

After matched follow-up periods (mean of 30.5 days), there were no statistically significant differences in relative hypertrophy of FLRs. Mean ± standard deviation relative hypertrophy rates for LVD/PVE were 59 ± 29.6%/54.1 ± 27.6% (p = 0.637) for segments II + III and 48.2 ± 22.2%/44.9 ± 28.9% (p = 0.719) for segments II–IV, respectively.

Conclusions

LVD had no significant advantages over the standard method (PVE alone) in terms of hypertrophy induction of the FLR before extended hepatectomy in this study population.
Robotic versus open pancreatic surgery: a propensity score-matched cost-effectiveness analysis
Authors: Benzing Christian , Timmermann Lea , Winklmann Thomas , Haiden Lena Marie , Hillebrandt Karl Herbert , Winter Axel , Maurer Max Magnus , Felsenstein Matthäus , Krenzien Felix , Schmelzle Moritz , Pratschke Johann , Malinka Thomas
Published: March 2022

Background

Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis.

Methods

Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2.

Results

In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334€ vs. 5115€, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit—RPS: 57€ vs. OPS: − 2894€, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue).

Conclusions

Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.
Individual differences in mental imagery modulate effective connectivity of scene-selective regions during resting state
Authors: Tullo Maria Giulia , Almgren Hannes , Van de Steen Frederik , Sulpizio Valentina , Marinazzo Daniele , Galati Gaspare
Published: March 2022

Successful navigation relies on the ability to identify, perceive, and correctly process the spatial structure of a scene. It is well known that visual mental imagery plays a crucial role in navigation. Indeed, cortical regions encoding navigationally relevant information are also active during mental imagery of navigational scenes. However, it remains unknown whether their intrinsic activity and connectivity reflect the individuals’ ability to imagine a scene. Here, we primarily investigated the intrinsic causal interactions among scene-selective brain regions such as Parahipoccampal Place Area (PPA), Retrosplenial Complex, and Occipital Place Area (OPA) using Dynamic Causal Modelling for resting-state functional magnetic resonance data. Second, we tested whether resting-state effective connectivity parameters among scene-selective regions could reflect individual differences in mental imagery in our sample, as assessed by the self-reported Vividness of Visual Imagery Questionnaire. We found an inhibitory influence of occipito-medial on temporal regions, and an excitatory influence of more anterior on more medial and posterior brain regions. Moreover, we found that a key role in imagery is played by the connection strength from OPA to PPA, especially in the left hemisphere, since the influence of the signal between these scene-selective regions positively correlated with good mental imagery ability. Our investigation contributes to the understanding of the complexity of the causal interaction among brain regions involved in navigation and provides new insight in understanding how an essential ability, such as mental imagery, can be explained by the intrinsic fluctuation of brain signal.
Establishment of a virtual transborder tumor board for cancer patients in Central and Southeastern Europe
Authors: Thallinger Christiane , Berzinec Peter , Bicakcic Emina , Dan Adelina , Fabian Gabriella , Gales Laurentia Nicoletta , Kuhar Cvetka Grasic , Janzic Urska , Kahan Zsusanna , Mencinger Marina , Penthedourakis George , Sgouros Joseph , Simetic Luka , Sirbu Daniela , Vosmik Milan , Wrona Anna , Zielinski Christoph
Published: March 2022

Purpose

To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE).

Methods

We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment.

Results

A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%).

Conclusion

When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV‑2 (severe acute respiratory syndrome coronavirus type 2) pandemic.
Fluctuation estimates for the multi-cell formula in stochastic homogenization of partitions
Authors: Bach Annika , Ruf Matthias
Published: March 2022

In this paper we derive quantitative estimates in the context of stochastic homogenization for integral functionals defined on finite partitions, where the random surface integrand is assumed to be stationary. Requiring the integrand to satisfy in addition a multiscale functional inequality, we control quantitatively the fluctuations of the asymptotic cell formulas defining the homogenized surface integrand. As a byproduct we obtain a simplified cell formula where we replace cubes by almost flat hyperrectangles.
The nodal set of solutions to some nonlocal sublinear problems
Authors: Tortone Giorgio
Published: March 2022

We study the nodal set of stationary solutions to equations of the form $$(-\Delta )^s u = \lambda _+ (u_+)^{q-1} - \lambda _- (u_-)^{q-1}\quad \text {in }B_1,$$

(
-
Δ
)

s

u
=

λ
+

(

u
+

)

q
-
1

-

λ
-

(

u
-

)

q
-
1

in

B
1

,

where $$\lambda _+,\lambda _->0, q \in [1,2)$$

λ
+

,

λ
-

>
0
,
q
∈

[
1
,
2
)

, and $$u_+$$

u
+

and $$u_-$$

u
-

are respectively the positive and negative part of u. This collection of nonlinearities includes the unstable two-phase membrane problem $$q=1$$

q
=
1

as well as sublinear equations for $$1<q<2$$

1
<
q
<
2

. We initially prove the validity of the strong unique continuation property and the finiteness of the vanishing order, in order to implement a blow-up analysis of the nodal set. As in the local case $$s=1$$

s
=
1

, we prove that the admissible vanishing orders can not exceed the critical value $$k_q= 2s/(2- q)$$

k
q

=
2
s
/

(
2
-
q
)

. Moreover, we study the regularity of the nodal set and we prove a stratification result. Ultimately, for those parameters such that $$k_q< 1$$

k
q

<
1

, we prove a remarkable difference with the local case: solutions can only vanish with order $$k_q$$

k
q

and the problem admits one dimensional solutions. Our approach is based on the validity of either a family of Almgren-type or a 2-parameter family of Weiss-type monotonicity formulas, according to the vanishing order of the solution.
Patterns of free amino acids in tundra soils reflect mycorrhizal type, shrubification, and warming
Authors: Andresen Louise C. , Bodé Samuel , Björk Robert G. , Michelsen Anders , Aerts Rien , Boeckx Pascal , Cornelissen J. Hans C. , Klanderud Kari , van Logtestijn Richard S. P. , Rütting Tobias
Published: March 2022

The soil nitrogen (N) cycle in cold terrestrial ecosystems is slow and organically bound N is an important source of N for plants in these ecosystems. Many plant species can take up free amino acids from these infertile soils, either directly or indirectly via their mycorrhizal fungi. We hypothesized that plant community changes and local plant community differences will alter the soil free amino acid pool and composition; and that long-term warming could enhance this effect. To test this, we studied the composition of extractable free amino acids at five separate heath, meadow, and bog locations in subarctic and alpine Scandinavia, with long-term (13 to 24 years) warming manipulations. The plant communities all included a mixture of ecto-, ericoid-, and arbuscular mycorrhizal plant species. Vegetation dominated by grasses and forbs with arbuscular and non-mycorrhizal associations showed highest soil free amino acid content, distinguishing them from the sites dominated by shrubs with ecto- and ericoid-mycorrhizal associations. Warming increased shrub and decreased moss cover at two sites, and by using redundancy analysis, we found that altered soil free amino acid composition was related to this plant cover change. From this, we conclude that the mycorrhizal type is important in controlling soil N cycling and that expansion of shrubs with ectomycorrhiza (and to some extent ericoid mycorrhiza) can help retain N within the ecosystems by tightening the N cycle.
Total positivity of some polynomial matrices that enumerate labeled trees and forests I: forests of rooted labeled trees
Authors: Sokal Alan D.
Published: March 2022

We consider the lower-triangular matrix of generating polynomials that enumeratek-component forests of rooted trees on the vertex set [n] according to the number of improper edges (generalizations of the Ramanujan polynomials). We show that this matrix is coefficientwise totally positive and that the sequence of its row-generating polynomials is coefficientwise Hankel-totally positive. More generally, we define the generic rooted-forest polynomials by introducing also a weight$$m! \, \phi _m$$m!ϕmfor each vertex withm proper children. We show that if the weight sequence $$\varvec{\phi }$$ϕis Toeplitz-totally positive, then the two foregoing total-positivity results continue to hold. Our proofs use production matrices and exponential Riordan arrays.
Körpermessdaten bei Kindern
Authors: Haeusler Gabriele , Wrba Thomas , Riedl Stefan , Karall Daniela
Published: March 2022

Die Verwendung von geeigneten Referenzen zur Beurteilung von Körpermessdaten bei Kindern ist zentraler Bestandteil der kinderfachärztlichen Praxis. Es stehen seit Mai 2019 von der Fachgesellschaft empfohlene, großteils neu erstellte, österreichische Daten zur digitalen Anwendung zur Verfügung (www.wachstum.at).

In diesem Beitrag werden die während der Implementierung häufig diskutierten Aspekte erläutert und der Zugang zur Software für verschiedene Anwender beschrieben. Die österreichweite Implementierung wird durch die Österreichische Gesellschaft für Kinder-und Jugendheilkunde unterstützt, getragen durch deren Arbeitsgruppe Pädiatrische Endokrinologie und Kooperationspartner an der Medizinischen Universität Wien. Eine flächendeckende Nutzung setzt Impulse interessierter Abteilungsleitungen, Krankenhausbetreiber und deren IT-Abteilungen sowie Aufgeschlossenheit und Kundenfreundlichkeit der Softwareanbieter voraus.
How do I update my model? On the resilience of Predictive Process Monitoring models to change
Authors: Rizzi Williams , Di Francescomarino Chiara , Ghidini Chiara , Maggi Fabrizio Maria
Published: March 2022

Existing well-investigated Predictive Process Monitoring techniques typically construct a predictive model based on past process executions and then use this model to predict the future of new ongoing cases, without the possibility of updating it with new cases when they complete their execution. This can make Predictive Process Monitoring too rigid to deal with the variability of processes working in real environments that continuously evolve and/or exhibit new variant behaviours over time. As a solution to this problem, we evaluate the use of three different strategies that allow the periodic rediscovery or incremental construction of the predictive model so as to exploit new available data. The evaluation focuses on the performance of the new learned predictive models, in terms of accuracy and time, against the original one, and uses a number of real and synthetic datasets with and without explicit Concept Drift. The results provide an evidence of the potential of incremental learning algorithms for predicting process monitoring in real environments.
A complex slope deformation case—history
Authors: Picarelli L. , Santo A. , Di Crescenzo G. , Vassallo R. , Urciuoli G. , Silvestri F. , Olivares L.
Published: March 2022

Slope movements represent a class of phenomena, which can display a great variety of styles, sizes and displacement rates. Some are extremely rapid, short-lived and highly destructive; others are extremely slow and apparently endless. This paper describes an extremely slow soil slope deformation process that is probably active since thousands of years and will certainly go on for many years to come. The results of in-depth investigations carried out after the 1980 Irpinia-Basilicata earthquake integrated by satellite images covering the time interval 1992–2013 have provided a global and consistent framework that allows to draw a reliable scenario about the effects of the geological processes that are active in the area on slope deformation mechanisms.
Evaluation of flexibility in adaptation projects for climate change
Authors: Kim Myung-Jin , Nicholls Robert J. , Preston John M. , De Almeida Gustavo A.
Published: March 2022

Climate change adaptation inherently entails investment decision-making under the high levels of uncertainty. To address this issue, a single fixed large investment can be divided into two or more sequential investments. This reduces the initial investment cost and adds flexibility about the size and timing of subsequent investment decisions. This flexibility enables future investment decisions to be made when further information about the magnitude of climate change becomes available. This paper presents a real option analysis framework to evaluate adaptations including flexibility to reduce both the risk and uncertainty of climate change, against increasing coastal flooding due to sea-level rise as an example. The paper considers (i) how to design the sequence of adaptation options under growing risk of sea-level rise, and (ii) how to make the efficient use of flexibility included in adaptations for addressing uncertainty. A set of flexibilities (i.e. wait or future growth) are incorporated into single-stage investments (i.e. raising coastal defence from 2.5 mAOD to 3.5mAOD or 4.0 mAOD) in stages so that multiple-stage adaptations with different heights are created. The proposed method compares these sequentially growing adaptations in economic terms, including optimisation, providing additional information on the efficiency of flexible adaptation strategies given the uncertainty of climate change. The results from the evaluation enable decision-makers to identify long-lasting robust adaptation against the uncertainty of climate change.
Explaining Free Will by Rational Abilities
Authors: Hofmann Frank
Published: March 2022

In this paper I present an account of the rational abilities that make our decisions free. Following the lead of new dispositionalists, a leeway account of free decisions is developed, and the rational abilities that ground our abilities to decide otherwise are described in detail. A main result will be that the best account of the relevant rational abilities makes themtwo-wayabilities: abilities to decide to do or not to do x in accordance with one’s apparent reasons. Dispositionalism about rational abilities will be vindicated, since it helps to see why and how these two-way abilities entail an ability to decide otherwise and, thus, free will.
A comprehensive Benchmark for fake news detection
Authors: Galli Antonio , Masciari Elio , Moscato Vincenzo , Sperlí Giancarlo
Published: March 2022

Nowadays, really huge volumes of fake news are continuously posted by malicious users with fraudulent goals thus leading to very negative social effects on individuals and society and causing continuous threats to democracy, justice, and public trust. This is particularly relevant in social media platforms (e.g., Facebook, Twitter, Snapchat), due to their intrinsic uncontrolled publishing mechanisms. This problem has significantly driven the effort of both academia and industries for developing more accurate fake news detection strategies: early detection of fake news is crucial. Unfortunately, the availability of information about news propagation is limited. In this paper, we provided a benchmark framework in order to analyze and discuss the most widely used and promising machine/deep learning techniques for fake news detection, also exploiting different features combinations w.r.t. the ones proposed in the literature. Experiments conducted on well-known and widely used real-world datasets show advantages and drawbacks in terms of accuracy and efficiency for the considered approaches, even in the case of limited content information.
Effects of acute ischemia and hypoxia in young and adult calsequestrin (CSQ2) knock-out and wild-type mice
Authors: Neumann Joachim , Bödicker Konrad , Buchwalow Igor B. , Schmidbaur Constanze , Ramos Gustavo , Frantz Stefan , Hofmann Ulrich , Gergs Ulrich
Published: March 2022

Calsequestrin (CSQ2) is the main Ca2+-binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4–5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(−/−)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiography, in adult mice, the basal left ventricular ejection fraction and the spontaneous beating rate were lower in CSQ2(−/−) compared to CSQ2(+/+). The increase in ejection fraction by β-adrenergic stimulation (intraperitoneal injection of isoproterenol) was lower in adult CSQ2(−/−) versus adult CSQ2(+/+). After hypoxia in vitro (isolated atrial preparations) by gassing the organ bath buffer with 95% N2, force of contraction in electrically driven left atria increased to lower values in young CSQ2(−/−) than in young CSQ2(+/+). In addition, after global ischemia and reperfusion (buffer-perfused hearts according to Langendorff; 20-min ischemia and 15-min reperfusion), the rate of tension development was higher in young CSQ2(−/−) compared to young CSQ2(+/+). Finally, we evaluated signs of inflammation (immune cells, autoantibodies, and fibrosis). However, whereas no immunological alterations were found between all investigated groups, pronounced fibrosis was found in the ventricles of adult CSQ2(−/−) compared to all other groups. We suggest that in young mice, CSQ2 is important for cardiac performance especially in isolated cardiac preparations under conditions of impaired oxygen supply, but with differences between atrium and ventricle. Lack of CSQ2 leads age dependently to fibrosis and depressed cardiac performance in echocardiographic studies.
Single brain metastasis versus glioblastoma multiforme: a VOI-based multiparametric analysis for differential diagnosis
Authors: Romano Andrea , Moltoni Giulia , Guarnera Alessia , Pasquini Luca , Di Napoli Alberto , Napolitano Antonio , Espagnet Maria Camilla Rossi , Bozzao Alessandro
Published: March 2022

Purpose

The authors’ purpose was to create a valid multiparametric MRI model for the differential diagnosis between glioblastoma and solitary brain metastasis.

Materials and methods

Forty-one patients (twenty glioblastomas and twenty-one brain metastases) were retrospectively evaluated. MRIs were analyzed with Olea Sphere® 3.0. Lesions’ volumes of interest (VOIs) were drawn on enhanced 3D T1 MP-RAGE and projected on ADC and rCBV co-registered maps. Another two VOIs were drawn in the region of hyperintense cerebral edema, surrounding the lesion, respectively, within 5 mm around the enhancing tumor and into residual edema. Perfusion curves were obtained, and the value of signal recovery (SR) was reported. A two-sample T test was obtained to compare all parameters of GB and BM groups. Receiver operating characteristics (ROC) analysis was performed.

Results

According to ROC analysis, the area under the curve was 88%, 78% and 74%, respectively, for mean ADC VOI values of the solid component, the mean and max rCBV values in the perilesional edema and the PSR. The cumulative ROC curve of these parameters reached an area under the curve of 95%. Using perilesional max rCBV > 1.37, PSR > 75% and mean lesional ADC < 1 × 10−3 mm2 s−1 GB could be differentiated from solitary BM (sensitivity and specificity of 95% and 86%).

Conclusion

Lower values of ADC in the enhancing tumor, a higher percentage of SR in perfusion curves and higher values of rCBV in the peritumoral edema closed to the lesion are strongly indicative of GB than solitary BM.
Scanning the solutions for the sustainable supply of forest ecosystem services in Europe
Authors: Hernández-Morcillo M. , Torralba M. , Baiges T. , Bernasconi A. , Bottaro G. , Brogaard S. , Bussola F. , Díaz-Varela E. , Geneletti D. , Grossmann C. M. , Kister J. , Klingler M. , Loft L. , Lovric M. , Mann C. , Pipart N. , Roces-Díaz J. V. , Sorge S. , Tiebel M. , Tyrväinen L. , Varela E. , Winkel G. , Plieninger T.
Published: March 2022

Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES.

Graphical abstract
Fish-Inspired Heuristics: A Survey of the State-of-the-Art Methods
Authors: Alhaqbani Amjaad , Kurdi Heba A. , Hosny Manar
Published: March 2022

The collective behaviour of fish schools, shoals and other swarms in nature has long inspired researchers to develop solutions for optimization problems. Instinct influences the behaviour of fish to group into schools to increase safety, enhance foraging success, and promote breeding. According to these instinctive behaviours, several fish-inspired algorithms have been introduced to solve hard problems. This paper presents a comprehensive survey of fish-inspired heuristics, exploring their evolution within the context of general optimization problems. To our knowledge, this survey is the first to cover both main fish-inspired heuristics in the literature, namely, the artificial fish swarm algorithm (AFSA) and Fish school search (FSS), in addition to other algorithms inspired by specific fish species. The review covers more than 50 papers published in the Web of Science and IEEE databases since 2000. We first review the basic fish heuristics, highlighting their advantages and drawbacks, and then detail attempts in the literature to improve their behaviour to solve complex, multi-objective and high-dimensional problems in several domains. Our work is intended to provide guidance for researchers and practitioners for the purpose of further advancing research in the area of fish-inspired heuristics. We aspire to encourage their utilization in various fields for global optimization and in real-life applications. The survey findings indicate that fish-inspired heuristics are very alive in recent literature and still have great potential. Several challenges and future research directions are also identified among the findings of this survey, which can help to enhance this vibrant line of research.
Optimal Strategies for Colorectal Cancer Screening
Authors: Jain Shailavi , Maque Jetrina , Galoosian Artin , Osuna-Garcia Antonia , May Folasade P.
Published: March 2022

Opinion statement

Colorectal cancer (CRC) imposes significant morbidity and mortality, yet it is also largely preventable with evidence-based screening strategies. In May 2021, the US Preventive Services Task Force updated guidance, recommending screening begin at age 45 for average-risk individuals to reduce CRC incidence and mortality in the United States (US). The Task Force recommends screening with one of several screening strategies: high-sensitivity guaiac fecal occult blood test (HSgFOBT), fecal immunochemical test (FIT), multi-target stool DNA (mt-sDNA) test, computed tomographic (CT) colonography (virtual colonoscopy), flexible sigmoidoscopy, flexible sigmoidoscopy with FIT, or traditional colonoscopy. In addition to these recommended options, there are several emerging and novel CRC screening modalities that are not yet approved for first-line screening in average-risk individuals. These include blood-based screening or “liquid biopsy,” colon capsule endoscopy, urinary metabolomics, and stool-based microbiome testing for the detection of colorectal polyps and/or CRC. In order to maximize CRC screening uptake in the US, patients and providers should engage in informed decision-making about the benefits and limitations of recommended screening options to determine the most appropriate screening test. Factors to consider include the invasiveness of the test, test performance, screening interval, accessibility, and cost. In addition, health systems should have a programmatic approach to CRC screening, which may include evidence-based strategies such as patient education, provider education, mailed screening outreach, and/or patient navigation, to maximize screening participation.
Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study
Authors: Endepols Heike , Anglada-Huguet Marta , Mandelkow Eckhard , Schmidt Yannick , Krapf Philipp , Zlatopolskiy Boris D. , Neumaier Bernd , Mandelkow Eva-Maria , Drzezga Alexander
Published: March 2022

Cerebral glucose hypometabolism is a typical hallmark of Alzheimer’s disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [18F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [18F]PI-2620 for tau deposition, [18F]DPA-714 for TSPO expression associated with neuroinflammation, and [18F]UCB-H for synaptic density in a transgenic tauopathy mouse model. Seven-month-old rTg4510 mice (n = 8) and non-transgenic littermates (n = 8) were examined in a small animal PET scanner with the tracers listed above. Hypometabolism was observed throughout the forebrain of rTg4510 mice. Tau pathology, increased TSPO expression, and synaptic loss were co-localized in the cortex and hippocampus and correlated with hypometabolism. In the thalamus, however, hypometabolism occurred in the absence of tau-related pathology. Thus, cerebral hypometabolism was associated with two regionally distinct forms of molecular pathology: (1) characteristic neuropathology of the Alzheimer-type including synaptic degeneration and neuroinflammation co-localized with tau deposition in the cerebral cortex, and (2) pathological changes in the thalamus in the absence of other markers of AD pathophysiology, possibly reflecting downstream or remote adaptive processes which may affect functional connectivity. Our study demonstrates the feasibility of a multitracer approach to explore complex interactions of distinct AD-pathomechanisms in vivo in a small animal model. The observations demonstrate that multiple, spatially heterogeneous pathomechanisms can contribute to hypometabolism observed in AD mouse models and they motivate future longitudinal studies as well as the investigation of possibly comparable pathomechanisms in human patients.
Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Hypopharynx, Larynx, Trachea and Parapharyngeal Space
Authors: Zidar Nina , Gale Nina
Published: March 2022

In this article, we review the chapter on tumors of the larynx, hypopharynx, trachea and parapharyngeal space in the new edition of the WHO book, focusing on the new developments in comparison to the previous edition. Squamous cell carcinoma (SCC) and its variants are by far the most common malignancies at these locations, with very limited new insights. The most important is the introduction of new targeted treatment—checkpoint inhibitors, with a new task for pathologists, who may help to predict the response to treatment by analyzing the expression of targeted proteins in biopsy samples. Precancerous lesions remain a controversial topic and, similarly to other organs, it is acceptable to use the terms “dysplasia” or “squamous intraepithelial lesion” (SIL), but there is a slight difference between low-grade dysplasia and low-grade SIL: in the former, mild atypia must be present, while the latter also includes hyperplastic epithelium without atypia. Two approaches have been proposed: a two-tiered system with low- and high-grade dysplasia/SIL and a three-tiered system with an additional category, carcinoma in situ. We are still searching for reliable diagnostic markers to surpass the subjectivity in biopsy diagnosis, with a few potential candidate markers on the horizon, e.g., stem cell markers. Other tumors are rare at these locations, e.g., hematolymphoid, neuroendocrine and salivary gland neoplasms, and are no longer included in Chapter 3. They must be diagnosed according to criteria described in specific chapters. The same holds true for soft tissue tumors, with the exception of cartilaginous neoplasms, which are still included in Chapter 3.
Stable Carbon and Nitrogen Isotope Composition in Suspended Particulate Matter Reflects Seasonal Dynamics of Phytoplankton Assemblages in the Gulf of Riga, Baltic Sea
Authors: Tunēns Juris , Aigars Juris , Poikāne Rita , Jurgensone Iveta , Labucis Atis , Labuce Astra , Liepiņa-Leimane Ineta , Buša Lauma , Vīksna Arturs
Published: March 2022

The ratio of stable carbon and nitrogen isotopes in the suspended particulate matter has been widely used to study processes occurring in the marine ecosystem. At the same time, the signals provided by isotope ratios in coastal ecosystems can be difficult to interpret, due to several, often contradictory processes taking place simultaneously. In this study, we hypothesized that the carbon and nitrogen isotopic variation is predominantly affected by seasonally occurring phytoplankton species succession in the Gulf of Riga, Baltic Sea. Cyclical seasonal patterns were observed for carbon and nitrogen isotopic compositions of both SPM and phytoplankton data. Enrichment of heavy isotopes in the Gulf of Riga took place during spring phytoplankton bloom (from on average between + 7.1 and + 8.8 ‰, and between − 23.7 and − 21.9 ‰ for δ15N and δ13C, respectively) and pooled at significantly lower values (from + 3.1 to + 5.1 ‰ and from − 28.7 to − 25.1 ‰ for δ15N and δ13C, respectively) for the rest of the year. At the same time, the spatial gradient of isotope ratios was sporadic and inconclusive. The results showed that terrestrial and anthropogenic input to particulate matter is negligible from spring to autumn. Multivariate analysis revealed that the observed seasonal variability was indeed driven by variation in phytoplankton species composition. The diatoms, dinoflagellates, and the ciliate Mesodinium rubrum facilitated enrichment of 15N and 13C in spring. In contrast, atmospheric nitrogen fixation by cyanobacteria and the assimilation of their released nutrients by other organisms resulted in lower δ15N values during summer. This variability requires careful considerations for conducting food web studies in temperate coastal and estuarine environments during high phytoplankton biomass periods.
Thrive during a crisis: the role of digital technologies in fostering antifragility in small and medium-sized enterprises
Authors: Corvello Vincenzo , Verteramo Saverino , Nocella Isabella , Ammirato Salvatore
Published: March 2022

The crisis triggered by the COVID-19 emergency is changing the competitive landscape by pushing companies to adapt to sudden change. Small and medium-sized enterprises (SMEs) that want to survive must innovate their business. Antifragility represents the capability of a system to absorb shocks and get better, allowing it to overcome a crisis and improve its performance. The use of digital technologies by enterprises is expected to play an important role in building antifragility. The aim of this paper is to study how digital technologies can contribute to the development of antifragility in SMEs. This study analyzed the responses to the COVID-19 pandemic crisis of six small and medium-sized enterprises located in Calabria, South of Italy. All the six enterprises have turned the crisis into a business opportunity developing new products, investing in marketing and communication, or starting new collaborations. The research identifies the factors leveraged by the investigated organizations that enabled this anti fragile behavior. They include slack financial resources, strategic agility, and relations with research institutions. The study highlights the positive impact of digital technologies in developing antifragility. Results were summarized into research propositions to be tested in future confirmatory studies. The findings of the study are useful for researchers interested in antifragility and digital technologies in SMEs. The results are also important for entrepreneurs and managers of SMEs, since they can support their decisions in terms of survival and transformation of their companies.
The Effects of Mindfulness-Based Stress Reduction on Trauma in Victims of Gun Violence: a Pilot Study
Authors: Khatib Lora , Riegner Gabriel , Dean Jon G. , Oliva Valeria , Cruanes Gael , Mulligan Beth A. , Zeidan Fadel
Published: March 2022

Objectives

Gun violence is a significant problem in the United States of America. Gun violence produces lifelong psychological adversity, trauma, and grief. In the face of this epidemic, efficacious therapies that assuage gun violence-based trauma and negative health are lacking.

Methods

The proposed, longitudinal pilot experiment examined the effects of an 8-week mindfulness-based stress reduction (MBSR) program on traumatized individuals as a direct consequence of gun violence. Twenty-four victims of gun violence (median age = 53 years; 21 female) completed measures of the primary outcome: trauma. Secondary outcomes were characterized as grief, depression, sleep quality, life satisfaction, and mindfulness. All assessments were administered before, after 5, and 8 weeks of MBSR training. It was hypothesized that trauma and other comorbidities would improve following MBSR. It was also predicted that outcomes would be significantly stronger from baseline to 5 weeks of MBSR training than from 5 to 8 weeks of training.

Results

Before MBSR, volunteers exhibited high levels of trauma, depression, sleep difficulty, and grief. Participation in MBSR was associated with improved trauma, depression, sleep difficulty, and life satisfaction. The most pronounced improvements in psychological disposition were exhibited within the first 5 weeks of MBSR. However, these benefits were largely preserved after completion of the course. Importantly, increases in dispositional mindfulness predicted lower trauma, complicated grief, and sleep difficulties.

Conclusions

The present findings should be interpreted with caution because they were derived from an uncontrolled, non-randomized trial. However, said findings suggest that MBSR may reduce trauma and improve overall well-being in gun violence victims.