bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies
Authors: Abdulmalek Shaymaa A. , Saleh Abdulrahman M. , Shahin Yasmin R. , El Azab Eman Fawzy
Published: April 2024

Oncogenic microRNA (miRNA), especially miRNA-21 upregulation in triple-negative breast cancer (TNBC), suggests a new class of therapeutic targets. In this study, we aimed to create GE11 peptide-conjugated small interfering RNA-loaded chitosan nanoparticles (GE11-siRNA-CSNPs) for the targeting of EGFR overexpressed TNBC and selectively inhibit miRNA-21 expression. A variety of in-silico and in vitro cellular and molecular studies were conducted to investigate the binding affinities of specific targets used as well as the anticancer efficacies and mechanisms of GE11-siRNA-CSNPs in TNBC cells. An in-silico assessment reveals a distinct binding affinity of miRNA-21 with siRNA as well as between the extracellular domain of EGFR and synthesized peptides. Notably, the in vitro results showed that GE11-siRNA-CSNPs were revealed to have better cytotoxicity against TNBC cells. It significantly inhibits miRNA-21 expression, cell migration, and colony formation. The results also indicated that GE11-siRNA-CSNPs impeded cell cycle progression. It induces cell death by reducing the expression of the antiapoptotic gene Bcl-2 and increasing the expression of the proapoptotic genes Bax, Caspase 3, and Caspase 9. Additionally, the docking analysis and immunoblot investigations verified that GE1-siRNA-CSNPs, which specifically target TNBC cells and suppress miRNA-21, can prevent the effects of miRNA-21 on the proliferation of TNBC cells via controlling EGFR and subsequently inhibiting the PI3K/AKT and ERK1/2 signaling axis. The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC.

Graphical Abstract
Multi-element analysis of unfiltered samples in river water monitoring—digestion and single-run analyses of 67 elements
Authors: Belkouteb Nadine , Schroeder Henning , Wiederhold Jan G. , Ternes Thomas A. , Duester Lars
Published: April 2024

Routine analysis of inorganic analytes in whole water samples from rivers (unfiltered river water) is rarely reported in scientific publications. However, this sample type is valuable and often used in long-term monitoring, regulation, and catchment element budgets, as it includes the dissolved, colloidal, and particulate fraction in one sample type. Preservation measures are not needed and solid–liquid partitioning can be disregarded, which simplifies automated sampling and storage procedures. In this study, we provide several digestion protocols for whole water samples from rivers and the subsequent multi-element analysis of 67 major, minor, and trace elements: Li, Be, B, Na, Mg, Al, Si, P, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, Ru, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Ir, Pt, Au, Hg, Tl, Pb, Bi, Th, U. In the absence of whole water reference materials for inorganic analytes, we introduce simulated whole water samples by suspending sediment reference materials as quality control measures. The applicability for improved routine water quality monitoring was successfully tested on samples from different rivers revealing variations of the element fingerprints over time.

Graphical abstract
Nearest-Neighbour Correlation Functions for the Supersymmetric XYZ Spin Chain and Painlevé VI
Authors: Hagendorf Christian , Rosengren Hjalmar
Published: April 2024

We study nearest-neighbour correlation functions for the ground state of the supersymmetric XYZ spin chain with odd length and periodic boundary conditions. Under a technical assumption related to the Q-operator of the corresponding eight-vertex model, we show that they can be expressed exactly in terms of the Painlevé VI tau functions $$s_n$$

s
n

and $${{\bar{s}}}_n$$

s

¯

n

introduced by Bazhanov and Mangazeev. Furthermore, we give an interpretation of the correlation functions in terms of the Painlevé VI Hamiltonian.
Early Post-operative ECG Changes as a Predictor of Post-pericardiotomy Syndrome Following Atrial Septal Defect Repair
Authors: Hyberg Kristen , El-Assaad Iqbal , Liu Wei , El-Assaad Iqbal , Baloglu Orkun , Heching Howard , Hanna William
Published: April 2024

To identify risk factors associated with post-pericardiotomy syndrome (PPS) in patients undergoing surgical repair of atrial septal defects (ASD). A single-center retrospective study. Tertiary academic hospital. Included were patients of all ages who underwent surgical ASD repair, while exclusion criteria included the absence of post-operative electrocardiogram (ECG), lack of follow-up post-discharge and factors hindering ECG interpretation. Demographic and clinical data, including ECG changes indicative of pericardial inflammation, were collected. The primary outcome measure was the development of PPS, determined based on the standardized European Society of Cardiology (ESC) criteria. Among 190 patients who underwent surgical ASD repair, 154 (81%) met the inclusion criteria. Of these, 25 (16%)in total developed PPS, of which 60% were ≥ 18 years of age and 56% female. Significant associations relating both early ECG changes and pre-discharge pericardial effusion with subsequent occurrence of PPS were found in both univariate and multivariate analyses. The study establishes correlations of both early post-operative ECG changes indicative of inflammation and pre-discharge pericardial effusion with subsequent occurrence of PPS in patients undergoing surgical ASD repair. Both utilizing the standardized ESC definition of PPS and incorporating a physician-validated ECG evaluation strengthened the methodologic approach in establishing these relationships. The results also highlight the importance of considering age as a potential risk factor for PPS. Further research is needed to validate these findings and explore additional risk factors predicting early identification and management of patients at high risk for PPS following surgical ASD repairs.
Diagnostic accuracy of intrathecal fluorescein versus other radiological modalities in evaluating non-congenital skull base defects: a systematic review and meta-analysis
Authors: AlSharhan Salma S. , Aljubran Hussain J. , Alrusayyis Danah F. , AlGhuneem Aishah A. , AlMarzouq Wasan F. , Al Bar Mohammed H. , AlSaied Abdulmalik S. , Ashoor Mona M. , ALEnazi Abdulaziz S. , Alghamdi Amal A.
Published: April 2024

Purpose

The intraoperative detection of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery is critical to ensure watertight sealed defects. Intrathecal fluorescein (ITF) is a valuable adjunct to intraoperative investigation. Hence, our aim is to summarize the evidence of the efficacy of ITF as an accurate diagnostic modality and reconstruction guide for non-congenital skull base defects.

Methods

Using the Cochrane Central, MEDLINE, and Embase databases, we identified studies involving the use of ITF in non-congenital CSF leaks which were published until November 2023. The STATA 18 software was used for meta-analysis.

Results

Fourteen studies met the inclusion criteria, in which seven studies were included in the meta-analysis. ITF was used in 1898 (90.3%) of patients, with a detection rate of 88.1%. The overall detection rate of non-congenital CSF leaks among ITF concentrations of 5% and 10% had a statistically significant pooled effect size of 2.6 (95% CI = 2.25, 2.95), while when comparing the ITF to other alternative radiological tests, it was not statistically significant with a mean difference of 0.88 (95% CI = − 0.4, 2.16). Moreover, the pooled prevalence was statistically significant in regards of the complications associated with ITF with an effect size of 0.6 (95% CI = 0.39, 0.82), indicating that 60% of patients who underwent ITF would experience at least one of the measured complications.

Conclusion

ITF is considered as an efficient tool in localizing skull base defects. However, there was no significant results when comparing the ITF to other alternative radiological tests. Accordingly, if the ITF intervention is indicated, patients should be carefully selected based on their clinical need.
Comparison of classical, coblation, and combined adenoidectomy techniques in paediatric patients: a single-blind, prospective study
Authors: Alaskarov Elvin
Published: April 2024

Background and objectives

Adenoidectomy is one of the most commonly performed surgeries in pediatric otolaryngological practice. This prospective study compared three different adenoidectomy techniques' intra-operative and postoperative outcomes in pediatric patients. The techniques evaluated were classical (blind curettage), coblation, and a combined approach.

Materials and methods

Ninety pediatric patients undergoing adenoidectomy were enrolled in the study. The patients were divided into three groups based on the technique used: Group A, classical adenoidectomy (blind curettage); Group B, coblation adenoidectomy and Group C, combined (blind curettage + coblation) adenoidectomy. The intra-operative time, degree of bleeding, and complications during and after the operations were recorded.

Results

Group A had a significantly shorter operative time than the other groups. However, there was no significant difference in the mean operative time between Groups B and C. The mean amount of intra-operative bleeding differed significantly among the groups. Group B had significantly less bleeding than Group A or Group C. The amount of bleeding also differed significantly between Groups A and C. The postoperative pain scores did not differ significantly among the groups. While complications were infrequent in all groups, Group C did not exhibit a higher complication rate than Groups A and B. The absence of residual or recurrent adenoid tissue in any of the groups during long-term follow-up examinations highlights the effectiveness of all three adenoidectomy techniques in preventing adenoid regrowth.

Conclusions

The combined approach, which was one of the techniques studied, demonstrated an intermediate profile in terms of operative time and intra-operative bleeding compared to the classical and coblation techniques. These findings suggest that this combined approach may be a feasible option for adenoidectomy in pediatric patients, considering its similar low incidence of postoperative complications.
NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease
Authors: Wilms Annelise E. , de Boer I. , Pelzer N. , in’t Veld S. G. J. G. , Middelkoop H. A. M. , Teunissen C. E. , Terwindt G. M.
Published: April 2024

Background

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).

Methods

NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning.

Results

Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (β[95%CI] = − 2.86 [− 5.58 to − 0.13], p = 0.04 and β[95%CI] =  − 6.85 [− 11.54 to − 2.15], p = 0.01, respectively) and prolonged psychomotor test times (β[95%CI] = 6.71 [0.78–12.65], p = 0.03 and β[95%CI] = 13.84 [3.09–24.60], p = 0.01).

Discussion

Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.
Wernicke’s functional neuroanatomy model of language turns 150: what became of its psychological reflex arcs?
Authors: Roelofs Ardi
Published: April 2024

Wernicke (Der aphasische Symptomencomplex: Eine psychologische Studie auf anatomischer Basis. Cohn und Weigert, Breslau. https://wellcomecollection.org/works/dwv5w9rw, 1874) proposed a model of the functional neuroanatomy of spoken word repetition, production, and comprehension. At the heart of this epoch-making model are psychological reflex arcs underpinned by fiber tracts connecting sensory to motor areas. Here, I evaluate the central assumption of psychological reflex arcs in light of what we have learned about language in the brain during the past 150 years. I first describe Wernicke’s 1874 model and the evidence he presented for it. Next, I discuss his updates of the model published in 1886 and posthumously in 1906. Although the model had an enormous immediate impact, it lost influence after the First World War. Unresolved issues included the anatomical underpinnings of the psychological reflex arcs, the role of auditory images in word production, and the sufficiency of psychological reflex arcs, which was questioned by Wundt (Grundzüge der physiologischen Psychologie. Engelmann, Leipzig. http://vlp.mpiwg-berlin.mpg.de/references?id=lit46, 1874; Grundzüge der physiologischen Psychologie (Vol. 1, 5th ed.). Engelmann, Leipzig. http://vlp.mpiwg-berlin.mpg.de/references?id=lit806, 1902). After a long dormant period, Wernicke’s model was revived by Geschwind (Science 170:940–944. https://doi.org/10.1126/science.170.3961.940, 1970; Selected papers on language and the brain. Reidel, Dordrecht, 1974), who proposed a version of it that differed in several important respects from Wernicke’s original. Finally, I describe how new evidence from modern research has led to a novel view on language in the brain, supplementing contemporary equivalents of psychological reflex arcs by other mechanisms such as attentional control and assuming different neuroanatomical underpinnings. In support of this novel view, I report new analyses of patient data and computer simulations using the WEAVER++/ARC model (Roelofs 2014, 2022) that incorporates attentional control and integrates the new evidence.
Arterial hypertension in infants with congenital diaphragmatic hernia following surgical repair
Authors: Engel Clara , Leyens Judith , Bo Bartolomeo , Hale Lennart , Lagos Kalhoff Hannah , Lemloh Lotte , Mueller Andreas , Kipfmueller Florian
Published: April 2024

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension.

  Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up.

What is Known:• Due to decreasing mortality, morbidity is increasing in surviving CDH patients.• Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH.

What is New:• There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication.• A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension.
Probabilistic sigma taxonomy of Darwin’s finches (Galápagos)
Authors: Thackeray Francis
Published: April 2024

A study is undertaken using anatomical measurements of specimens attributed to six species of Geospiza, the ground finches from the Galápagos archipelago. In a demonstration of method, a probabilistic approach associated with “sigma taxonomy” is adopted to assess the probability that pairs of specimens are or are not conspecific. We use a definition of a species based on morphometric analyses of the kind previously undertaken on extant vertebrate taxa (including mammals, birds and reptiles), using pairwise comparisons of anatomical measurements in regression analyses of the form y = mx + c from which the log-transformed standard error of the m-coefficient is calculated (“log sem”). The latter statistic is a reflection of variability in morphology. There is a high probability that at a species level, specimens attributed to G. magnirostris are different from those attributed to G. fulginosa, G. difficilis or G. scandens. Results of this study, using probabilistic sigma taxonomy, confirm the refutation of a single species hypothesis. In addition, we apply the log sem method to demonstrate that in case of comparisons between G. fortis and G. scandens (which are known to hybridise), there is a high probability that they are not different at a species level.
Loss-of-function variants affecting the STAGA complex component SUPT7L cause a developmental disorder with generalized lipodystrophy
Authors: Kopp Johannes , Koch Leonard A. , Lyubenova Hristiana , Küchler Oliver , Holtgrewe Manuel , Ivanov Andranik , Dubourg Christele , Launay Erika , Brachs Sebastian , Mundlos Stefan , Ehmke Nadja , Seelow Dominik , Fradin Mélanie , Kornak Uwe , Fischer-Zirnsak Björn
Published: April 2024

Generalized lipodystrophy is a feature of various hereditary disorders, often leading to a progeroid appearance. In the present study we identified a missense and a frameshift variant in a compound heterozygous state in SUPT7L in a boy with intrauterine growth retardation, generalized lipodystrophy, and additional progeroid features. SUPT7L encodes a component of the transcriptional coactivator complex STAGA. By transcriptome sequencing, we showed the predicted missense variant to cause aberrant splicing, leading to exon truncation and thereby to a complete absence of SUPT7L in dermal fibroblasts. In addition, we found altered expression of genes encoding DNA repair pathway components. This pathway was further investigated and an increased rate of DNA damage was detected in proband-derived fibroblasts and genome-edited HeLa cells. Finally, we performed transient overexpression of wildtype SUPT7L in both cellular systems, which normalizes the number of DNA damage events. Our findings suggest SUPT7L as a novel disease gene and underline the link between genome instability and progeroid phenotypes.
Outcome 10 years after Shiga toxin-producing E. coli (STEC)-associated hemolytic uremic syndrome: importance of long-term follow-up
Authors: Rosales Alejandra , Kuppelwieser Sarah , Giner Thomas , Hofer Johannes , Riedl Khursigara Magdalena , Orth-Höller Dorothea , Borena Wegene , Cortina Gerard , Jungraithmayr Therese , Würzner Reinhard ,   for the German-Austrian H. U. S.-Study Group
Published: April 2024

Background

Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae.

Methods

Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis.

Results

A total of 66% (n = 91, 95% CI 0.57–0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27–0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05).

Conclusions

Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.

Graphical abstract
Does glenoid inclination affect the anterior stability of reverse total shoulder arthroplasty? A biomechanical study
Authors: Pastor Marc-Frederic , Nebel Dennis , Becker Lennart Mathis , Hurschler Christof , Karrer Alba Aurora , Smith Tomas
Published: April 2024

Purpose

The anterior stability of reverse total shoulder arthroplasty is affected by multiple factors. However, the effect of glenosphere inclination on stability has rarely been investigated, which is what this study aims to look into.

Methods

Reverse shoulder arthroplasty was performed on 15 cadaveric human shoulders. The anterior dislocation forces and range of motion in internal rotation in the glenohumeral joint (primary measured parameters) were tested in a shoulder simulator in different arm positions and implant configurations, as well as with a custom-made 10° inferiorly inclined glenosphere. The inclination and retroversion of the baseplate as well as the distance between the glenoid and coracoid tip in two planes (secondary measured parameters) were evaluated on CT scans.

Results

In biomechanical testing, the custom-made inclined glenosphere showed no significant influence on anterior stability other than glenoid lateralisation over all arm positions as well as the neck-shaft angle in two arm positions. The 6 mm lateralised glenosphere reduced internal rotation at 30° and 60° of glenohumeral abduction. In 30° of glenohumeral abduction, joint stability was increased using the 155° epiphysis compared with the 145° epiphysis. The mean inclination was 16.1°. The inclination was positively, and the distance between the glenoid and coracoid tip in the anterior-to-posterior direction was negatively correlated with anterior dislocation forces.

Conclusions

The custom-made inferiorly inclined glenosphere did not influence anterior stability, but baseplate inclination itself had a significant effect on stability.
Confinement of N-Body Systems and Non-integer Dimensions
Authors: Garrido E. , Jensen A. S.
Published: April 2024

The squeezing process of a three-dimensional quantum system by use of an external deformed one-body oscillator potential can also be described by the d-method, without external field and where the dimension can take non-integer values. In this work we first generalize both methods to N particles and any transition between dimensions below 3. Once this is done, the use of harmonic oscillator interactions between the particles allows complete analytic solutions of both methods, and a direct comparison between them is possible. Assuming that both methods describe the same process, leading to the same ground state energy and wave function, an analytic equivalence between the methods arises. The equivalence between both methods and the validity of the derived analytic relation between them is first tested for two identical bosons and for squeezing transitions from 3 to 2 and 1 dimensions, as well as from 2 to 1 dimension. We also investigate the symmetric squeezing from 3 to 1 dimensions of a system made of three identical bosons. We have in all the cases found that the derived analytic relations between the two methods work very well. This fact permits to relate both methods also for large squeezing scenarios, where the brute force numerical calculation with the external field is too much demanding from the numerical point of view, especially for systems with more than two particles.
Minimal extensions in smooth dynamics
Authors: Dirbák Matúš
Published: April 2024

A classical result of Fathi and Herman from 1977 states that a smooth compact connected manifold without boundary admitting a locally free action of a 1-torus, respectively, an almost free action of a 2-torus, admits a minimal diffeomorphism, respectively, a minimal flow. In the first part of our paper we study the existence of locally free and almost free actions of tori on homogeneous spaces of compact connected Lie groups, thus providing new examples of spaces admitting minimal diffeomorphisms or flows. In the second part we combine the ideas of Fathi and Herman with our recent ideas to study the existence of minimal skew products over certain minimal flows with general connected Lie groups as acting groups. Our results apply to so called flows with free cycles. In the last part of our work we study the existence of free cycles in homogeneous flows.
Silver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy
Authors: Banti Christina N. , Kalousi Foteini D. , Psarra Anna-Maria G. , Moushi Eleni E. , Leonidas Demetres D. , Hadjikakou Sotiris K.
Published: April 2024

The anti-proliferative activity of the known metalloantibiotic {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) (CIPH = ciprofloxacin) against the human breast adenocarcinoma cancer cells MCF-7 (hormone dependent (HD)) and MDA-MB-231 (hormone independent (HI)) is evaluated. The in vitro toxicity and genotoxicity of the metalloantibiotic were estimated toward fetal lung fibroblast (MRC-5) cells. The molecular mechanism of the CIPAG activity against MCF-7 cells was clarified by the (i) cell morphology, (ii) cell cycle arrest, (iii) mitochondrial membrane permeabilization, and (iv) by the assessment of the possible differential effect of CIPAG on estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) transcriptional activation, applying luciferase reporter gene assay. Moreover, the ex vivo mechanism of CIPAG was clarified by its binding affinity toward calf thymus (CT-DNA).

Graphical abstract
Virtual reality games for cognitive rehabilitation of older adults: a review of adaptive games, domains and techniques
Authors: Guzmán D. E. , Rengifo C. F. , Guzmán J. D. , Garcia Cena C. E.
Published: April 2024

In recent decades, the senior adults population worldwide has increased, as well as the medical conditions related to aging, such as cognitive decline. Virtual reality (VR) games are a valuable addition to conventional cognitive rehabilitation as they increase engagement to the therapy through customization, socialization, immersion, and feedback. This review, performed according to PRISMA protocol, addresses the following questions: How VR games have been used for cognitive rehabilitation?, What cognitive domains have been addressed by VR games and in which populations have these games been used?, Which features have been considered to improve engagement in VR games for cognitive rehabilitation?, How is the difficulty adjustment of exercises carried out in VR games for cognitive rehabilitation?. We found 25 scientific works related to these questions, 92% of them treating one cognitive domain at a time, despite the fact that the related literature recognizes the value of training multiple domains simultaneously. Our review indicates that, despite the existence of serious VR games for working memory training, such as those described in Flak et al. (Front Psychol 10:807, 2019. https://doi.org/10.3389/fpsyg.2019.00807), to our knowledge, there are no applications that simultaneously address multiple cognitive domains and incorporate dynamic difficulty adjustment, which are important to ensure ecological validity of therapy and therapy adherence, respectively. In addition, we found that games themselves could be used to monitor the user’s progression. It is also important to determine the impact of multiplayer interactions in the game, test difficulty adjustment approaches that use physiological variables, and define difficulty-skill relationships aligned with the user’s preferences. This paper concludes that the main barriers to implement dynamic difficulty adjustment in VR games for cognitive rehabilitation are: (i) the absence of metrics to estimate when the game offers to the players a challenge adapted their skills, and (ii) the lack of a conceptual framework that integrates relevant theories such as state of flow, cognitive load, cognitive rehabilitation, and feedback systems.
Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis
Authors: Matsukawa Akihiro , Rajwa Pawel , Kawada Tatsushi , Bekku Kensuke , Laukhtina Ekaterina , Klemm Jakob , Pradere Benjamin , Mori Keiichiro , Karakiewicz Pierre I. , Kimura Takahiro , Chlosta Piotr , Shariat Shahrokh F. , Yanagisawa Takafumi
Published: April 2024

Background

Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear.

Methods

We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist.

Results

Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64–0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52–0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease.

Conclusions

Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
Higher integrability for singular doubly nonlinear systems
Authors: Moring Kristian , Schätzler Leah , Scheven Christoph
Published: April 2024

We prove a local higher integrability result for the spatial gradient of weak solutions to doubly nonlinear parabolic systems whose prototype is $$\begin{aligned} \partial _t \left( |u|^{q-1}u \right) -{{\,\textrm{div}\,}}\left( |Du|^{p-2} Du \right) = {{\,\textrm{div}\,}}\left( |F|^{p-2} F \right) \quad \text { in } \Omega _T:= \Omega \times (0,T) \end{aligned}$$

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0
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with parameters $$p>1$$

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and $$q>0$$

q
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and $$\Omega \subset {\mathbb {R}}^n$$

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⊂

R

n

. In this paper, we are concerned with the ranges $$q>1$$

q
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and $$p>\frac{n(q+1)}{n+q+1}$$

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+
1

. A key ingredient in the proof is an intrinsic geometry that takes both the solution u and its spatial gradient Du into account.
Satellite laser ranging to BeiDou-3 satellites: initial performance and contribution to orbit model improvement
Authors: Zajdel Radosław , Nowak Adrian , Sośnica Krzysztof
Published: April 2024

Abstract

In January 2023, the International Laser Ranging Service (ILRS) approved the tracking of 20 additional BeiDou-3 Medium Earth Orbit (BDS-3 MEO) satellites, integrating them into the ILRS tracking network. Before that, only 4 BDS-3 MEO satellites had been tracked. BDS satellites employ highly advanced GNSS components and technological solutions; however, microwave-based orbits still contain systematic errors. Satellite Laser Ranging (SLR) tracking is thus crucial for better identification and understanding of orbit modeling issues. Orbit improvements are necessary to consider BDS in future realizations of terrestrial reference frames, supporting the determination of global geodetic parameters and utilizing them for the co-location of GNSS and SLR in space. In this study, we summarize the first 6 months of SLR tracking 24 BDS-3 MEO satellites. The study indicates that the ILRS network effectively executed the request to track the entire BDS-3 MEO constellation. The number of observations is approximately 1300 and 450 for high- and low-priority BDS-3 satellites, respectively, over the 6 months. More than half of the SLR observations to BDS-3 MEO satellites were provided by 5 out of the 24 laser stations, which actively measured GNSS targets. For 14 out of 24 BDS-3 MEO satellites, the standard deviation of SLR residuals is at the level of 19–20 mm, which is comparable with the quality of the state-of-the-art Galileo orbit solutions. However, the SLR validation of the individual satellites revealed that the BDS-3 MEO constellation consists of more ambiguous groups of satellites than originally reported in the official metadata files distributed by the BDS operators. For 8 BDS-3 satellites, the quality of the orbits is noticeably inferior with a standard deviation of SLR residuals above 100 mm. Therefore, improving orbit modeling for BDS-3 MEO satellites remains an urgent challenge for the GNSS community.
Allocating operating room time in orthopaedic trauma: a survey in medical ethics
Authors: Lynch Mary-Katherine , Rivas Gabriella , Gregoski Mathew J. , Hartsock Langdon , Reid Kristoff
Published: April 2024

Introduction

Allocation of operating room time is a challenging dilemma that surgeons frequently confront. When deciding upon a daily caseload, the surgeon may consider clinical, logistical, and social factors. Although previous studies have outlined guiding principles, there is no universal algorithm for prioritizing surgical patients. Our study aims to learn which factors orthopaedic trauma surgeons use when determining case priority.

Methods

A survey regarding the allocation of operating room time was administered to orthopaedic trauma surgeons from the community and members of the Southeastern Fracture Consortium. Questions included a list of characteristics and a series of theoretical case scenarios to be ranked according to perceived priority.

Results

Of the participating surgeons, 92% practiced at an academic center and 89.7% at a level 1 trauma center. Of the case characteristics, “severity of orthopaedic problem” was most frequently ranked as most important versus “social pressure from family members,” which was most frequently ranked as least important in case priority. The coefficient of concordance among respondents was 0.427 for individual case characteristics versus 0.287 for the theoretical scenarios. The average rate of agreement among respondents was 31.9 ± 19% for individual factors versus 36.3 ± 8.9% in the clinical vignettes.

Conclusions

A consensus exists regarding severity of the presenting orthopaedic problem being the most important factor when considering case priority. The lower agreement in the clinical vignettes indicates a strong interplay between the multiple factors in a case. Survey commentary suggests that outside factors – training, experience, politics, the team available – also play a role in a surgeon’s decision on case priority.

Level of evidence: IV.
Telomeres and aging: on and off the planet!
Authors: Mason Christopher E. , Sierra Maria A. , Feng Henry J. , Bailey Susan M.
Published: April 2024

Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective “caps” at the ends of linear chromosomes, are essential for maintaining genome stability of eukaryotic genomes. Due to their physical location and the “end-replication problem” first envisioned by Dr. Alexey Olovnikov, telomeres shorten with cell division, the implications of which are remarkably profound. Telomeres are hallmarks and molecular drivers of aging, as well as fundamental integrating components of the cumulative effects of genetic, lifestyle, and environmental factors that erode telomere length over time. Ongoing telomere attrition and the resulting limit to replicative potential imposed by cellular senescence serves a powerful tumor suppressor function, and also underlies aging and a spectrum of age-related degenerative pathologies, including reduced fertility, dementias, cardiovascular disease and cancer. However, very little data exists regarding the extraordinary stressors and exposures associated with long-duration space exploration and eventual habitation of other planets, nor how such missions will influence telomeres, reproduction, health, disease risk, and aging. Here, we briefly review our current understanding, which has advanced significantly in recent years as a result of the NASA Twins Study, the most comprehensive evaluation of human health effects associated with spaceflight ever conducted. Thus, the Twins Study is at the forefront of personalized space medicine approaches for astronauts and sets the stage for subsequent missions. We also extrapolate from current understanding to future missions, highlighting potential biological and biochemical strategies that may enable human survival, and consider the prospect of longevity in the extreme environment of space.
Anonymous attribute-based broadcast encryption with hidden multiple access structures
Authors: Phuong Tran Viet Xuan
Published: April 2024

Due to the high demands of data communication, the broadcasting system streams the data daily. This service not only sends out the message to the correct participant but also respects the security of the identity user. In addition, when delivered, all the information must be protected for the party who employs the broadcasting service. Currently, Attribute-Based Broadcast Encryption (ABBE) is useful to apply for the broadcasting service. (ABBE) is a combination of Attribute-Based Encryption (ABE) and Broadcast Encryption (BE), which allows a broadcaster (or encrypter) to broadcast an encrypted message, including a predefined user set and specified access policy to install the authorization mechanism. It is desirable to hide all the information when producing in the ciphertext, which has not been considered in the previous works of ABBE. Motivated by the above issue, we devise a solution to achieve anonymity for the ABBE scheme, which not only hides the access structures but also anonymizes the user’s identity. In this work, we propose two schemes as Anonymous Key Policy (AKP)-ABBE and Anonymous Ciphertext Policy (ACP)-ABBE with supporting multiple access structures by using $$\textsf {OR}/\textsf {AND}$$

OR
/
AND

gates. Specifically, we present the generic constructions of AKP/ACP-ABBE on the building block of the Inner Product Encryption ($$\textsf {IPE}$$
IPE
), which enables the hidden user’s identity and complex $$\textsf {OR}/\textsf {AND}$$

OR
/
AND

-Gate access structure. We show that our proposed schemes are secured under the standard models.
Unveiling the microstructure evolution and mechanical properties in a gas tungsten arc-welded Fe–Mn–Si–Cr–Ni shape memory alloy
Authors: Lopes J. G. , Martins D. , Zhang K. , Li B. , Wang B. , Wang X. , Schell N. , Ghafoori E. , Baptista A. C. , Oliveira J. P.
Published: April 2024

Fe–Mn–Si–Cr–Ni shape memory alloys (SMAs) are unique low-cost materials with shape memory properties that grant them the ability to be used in both functional and structural applications. Such SMAs are especially sought in the construction sector for the creation of new components and/or the reinforcement of damaged ones. In this study, a Fe–17Mn–5Si–10Cr–4Ni–1(V, C) wt% SMA was gas tungsten arc welded, with the objective to investigate the microstructure and mechanical performance changes occurring after welding. A comprehensive assessment of processing, microstructure and properties relationships was established combining microscopy (optical and electron), synchrotron X-ray diffraction, microhardness mapping and tensile testing including cycling assessment of the joint’s functional performance. It is shown that the present SMA has good weldability, with the joints reaching nearly 883 MPa at fracture strain of 23.6 ± 2.1%. Alongside this, several microstructure differences were encountered between the as-received and as-welded condition, including the formation of ferrite and Fe5Ni3Si2 P213 cubic precipitates amidst the fusion zone in the latter region.

Graphical abstract
Spanish Adaptation of the Social Worries Questionnaire (SWQ): A Tool to Assess Social Anxiety in Preadolescent Children
Authors: Amorós-Reche Víctor , Pineda David , Orgilés Mireia , Espada Jose P.
Published: April 2024

Social anxiety may appear during preadolescence, causing children to worry and avoid situations where they may be evaluated by others. Previous studies have shown that about 4% of preadolescents present clinically elevated levels of social anxiety, which is related to the later onset of other problems. Therefore, it becomes necessary to have available screening measures, with few items, that assess the different social situations that elicit anxiety, as is the case of the Social Worries Questionnaire (SWQ). The objective of this study was to adapt and assess the psychometric properties of the SWQ in Spanish preadolescent children. The sample was composed of 218 children aged 8 to 12 years (54.1% boys). The SWQ, along with other measures of depression, anxiety and self-concept, were online administered to children. An item addressing videoconference anxiety was added to the SWQ. Using Confirmatory Factor Analysis, a one-factor structure composed of 14 items demonstrated favorable fit indices. The results indicate evidence of concurrent and discriminant validity, good internal consistency (Cronbach’s α = 0.81; ordinal α = 0.87) and moderate-to-good test-retest stability. Despite some limitations, the Spanish adaptation of the SWQ shows good psychometric properties and enables the assessment of social anxiety generalization to several situations. The questionnaire can be a valuable self-reported tool for detecting risk cases and guiding the treatment in clinical settings.
Solving the medical student scheduling problem using simulated annealing
Authors: Zanazzo Eugenia , Ceschia Sara , Dovier Agostino , Schaerf Andrea
Published: April 2024

We consider the medical student scheduling (MSS) problem, which consists of assigning medical students to internships of different disciplines in various hospitals during the academic year to fulfill their educational and clinical training. The MSS problem takes into account, among other constraints and objectives, precedences between disciplines, student preferences, waiting periods, and hospital changes. We developed a local search technique, based on a combination of two different neighborhood relations and guided by a simulated annealing procedure. Our search method has been able to find the optimal solution for all instances of the dataset proposed by Akbarzadeh and Maenhout (Comput Oper Res 129: 105209, 2021b), in a much shorter runtime than their technique. In addition, we propose a novel dataset in order to test our technique on a more challenging ground. For this new dataset, which is publicly available along with our source code for inspection and future comparisons, we report the experimental results and a sensitivity analysis.
Breaking the left-right symmetry in fluttering artificial cilia that perform nonreciprocal oscillations
Authors: Boiardi Ariel Surya , Marchello Roberto
Published: April 2024

Recent investigations on active materials have introduced a new paradigm for soft robotics by showing that a complex response can be obtained from simple stimuli by harnessing dynamic instabilities. In particular, polyelectrolyte hydrogel filaments actuated by a constant electric field have been shown to exhibit self-sustained oscillations as a consequence of flutter instability. Owing to the nonreciprocal nature of the emerging oscillations, these artificial cilia are able to generate flows along the stimulus. Building upon these findings, in this paper we propose a design strategy to break the left-right symmetry in the generated flows, by endowing the filament with a natural curvature at the fabrication stage. We develop a mathematical model based on morphoelastic rod theory to characterize the stability of the equilibrium configurations of the filament, proving the persistence of flutter instability. We show that the emerging oscillations are nonreciprocal and generate thrust at an angle with the stimulus. The results we find at the level of the single cilium open new perspectives on the possible applications of artificial ciliary arrays in soft robotics and microfluidics.