bluuebunny/crossref_metadata_2025 huggingface dataset:
Thalamic contributions to psychosis susceptibility: Evidence from co‐activation patterns accounting for intra‐seed spatial variability (μCAPs)
Authors: Delavari Farnaz , Sandini Corrado , Kojovic Nada , Saccaro Luigi F. , Eliez Stephan , Van De Ville Dimitri , Bolton Thomas A. W.
Published: March 2024

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro‐co‐activation patterns (μCAPs) and employed this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting‐state functional MRI and a data‐driven iterative process resulting in the identification of six whole‐brain μCAPs with specific activity patterns within the thalamus. Unlike conventional methods, μCAPs extract dynamic spatial patterns that reveal partially overlapping and non‐mutually exclusive functional subparts. Thus, the μCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a μCAP showing co‐activation of the mediodorsal thalamus with brain‐wide cortical regions was expressed significantly less frequently in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, activity within the auditory–visual cortex and their respective geniculate nuclei was expressed in two different μCAPs. One of these auditory–visual μCAPs co‐activated with salience areas, while the other co‐activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo‐auditory‐thalamus to the DMN + visuo‐auditory‐thalamus μCAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio‐visual cortex in 22q11.2DS in the context of dynamic functional connectivity, seen here as the specific hyper‐occurrence of these circuits with the task‐negative brain networks.
Higher‐order functional connectivity analysis of resting‐state functional magnetic resonance imaging data using multivariate cumulants
Authors: Hindriks Rikkert , Broeders Tommy A. A. , Schoonheim Menno M. , Douw Linda , Santos Fernando , van Wieringen Wessel , Tewarie Prejaas K. B.
Published: March 2024

Blood‐level oxygenation‐dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most common modality to study functional connectivity in the human brain. Most research to date has focused on connectivity between pairs of brain regions. However, attention has recently turned towards connectivity involving more than two regions, that is, higher‐order connectivity. It is not yet clear how higher‐order connectivity can best be quantified. The measures that are currently in use cannot distinguish between pairwise (i.e., second‐order) and higher‐order connectivity. We show that genuine higher‐order connectivity can be quantified by using multivariate cumulants. We explore the use of multivariate cumulants for quantifying higher‐order connectivity and the performance of block bootstrapping for statistical inference. In particular, we formulate a generative model for fMRI signals exhibiting higher‐order connectivity and use it to assess bias, standard errors, and detection probabilities. Application to resting‐state fMRI data from the Human Connectome Project demonstrates that spontaneous fMRI signals are organized into higher‐order networks that are distinct from second‐order resting‐state networks. Application to a clinical cohort of patients with multiple sclerosis further demonstrates that cumulants can be used to classify disease groups and explain behavioral variability. Hence, we present a novel framework to reliably estimate genuine higher‐order connectivity in fMRI data which can be used for constructing hyperedges, and finally, which can readily be applied to fMRI data from populations with neuropsychiatric disease or cognitive neuroscientific experiments.
Brain‐based sex differences in schizophrenia: A systematic review of fMRI studies
Authors: Salehi Mohammad Amin , Zafari Rasa , Mohammadi Soheil , Shahrabi Farahani Mohammad , Dolatshahi Mahsa , Harandi Hamid , Poopak Amirhossein , Dager Stephen R.
Published: March 2024

Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex‐based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex‐based symptom differences. This study aimed to summarize sex‐based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex‐based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level‐dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low‐frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low‐frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex‐based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex‐based differences in the clinical presentation and course of the disorder.
A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease
Authors: Candia‐Rivera Diego , Vidailhet Marie , Chavez Mario , De Vico Fallani Fabrizio
Published: March 2024

Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain–heart connection whose mechanisms remain unclear. Our study aimed to explore the large‐scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain–heart coupling in PD and their potential connection to motor symptoms. We developed a proof‐of‐concept method to quantify relationships between the co‐fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain–heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain–heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease.
Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population‐based study in Italy
Authors: Dal Maso Luigino , Toffolutti Federica , De Paoli Angela , Giudici Fabiola , Francisci Silvia , Bucchi Lauro , Zorzi Manuel , Fusco Mario , Caldarella Adele , Rossi Silvia , De Angelis Roberta , Botta Laura , Ravaioli Alessandra , Casella Claudia , Musolino Antonino , Vitale Maria Francesca , Mangone Lucia , Fanetti Anna Clara , Carpin Eva , Burgio Lo Monaco Maria Giovanna , Migliore Enrica , Gambino Maria Letizia , Ferrante Margherita , Stracci Fabrizio , Gasparotti Cinzia , Carrozzi Giuliano , Cavallo Rossella , Mazzucco Walter , Ballotari Paola , Ferretti Stefano , Sampietro Giuseppe , Rizzello Roberto Vito , Boschetti Lorenza , Cascone Giuseppe , Mian Michael , Pesce Maria Teresa , Piras Daniela , Galasso Rocco , Bella Francesca , Seghini Pietro , Pinna Pasquala , Crocetti Emanuele , Serraino Diego , Guzzinati Stefano ,   AIRTUM Working Group
Published: March 2024

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5‐year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III–IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III–IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow‐up in the years after diagnosis, thus avoiding patients' discrimination.
Novel serum protein biomarker panel for early diagnosis of pancreatic cancer
Authors: Byeon Sooin , McKay Matthew J. , Molloy Mark P. , Gill Anthony J. , Samra Jaswinder S. , Mittal Anubhav , Sahni Sumit
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, which can be used to diagnose PDAC patients at an early resectable stage. This study performed proteomic mass spectrometry to identify novel blood‐based biomarkers for early diagnosis of PDAC. Serum specimens from 88 PDAC patients and 88 healthy controls (60 discovery cohort and 28 validation cohort) were analyzed using data independent acquisition high resolution mass spectrometry to identify candidate biomarker proteins. A total of 249 proteins were identified and quantified by the mass spectrometric analysis. Six proteins were markedly (>1.5 fold) and significantly (p < .05; q < 0.1) increased in PDAC patients compared to healthy controls in discovery cohort. Notably, four of these six proteins were significantly upregulated in an independent validation cohort. The top three upregulated proteins (i.e., Polymeric Immunoglobulin Receptor [PIGR], von Willebrand Factor [vWF], and Fibrinogen) were validated using enzyme linked immunosorbent assay, which led to selection of PIGR and vWF as a diagnostic biomarker panel for PDAC. The panel showed high ability to diagnose early stage (stage I and II) PDAC patients (area under the curve [AUC]: 0.8926), which was further improved after the addition of clinically used prognostic biomarker (Ca 19‐9) to the panel (AUC: 0.9798). In conclusion, a novel serum protein biomarker panel for early diagnosis of PDAC was identified.
Direct inkjet writing of polylactic acid/β‐tricalcium phosphate composites for bone tissue regeneration: A proof‐of‐concept study
Authors: Nayak Vasudev Vivekanand , Sanjairaj Vijayavenkataraman , Behera Rakesh Kumar , Smay James E. , Gupta Nikhil , Coelho Paulo G. , Witek Lukasz
Published: March 2024

There is an ever‐evolving need of customized, anatomic‐specific grafting materials for bone regeneration. More specifically, biocompatible and osteoconductive materials, that may be configured dynamically to fit and fill defects, through the application of an external stimulus. The objective of this study was to establish a basis for the development of direct inkjet writing (DIW)‐based shape memory polymer‐ceramic composites for bone tissue regeneration applications and to establish material behavior under thermomechanical loading. Polymer‐ceramic (polylactic acid [PLA]/β‐tricalcium phosphate [β‐TCP]) colloidal gels were prepared of different w/w ratios (90/10, 80/20, 70/30, 60/40, and 50/50) through polymer dissolution in acetone (15% w/v). Cytocompatibility was analyzed through Presto Blue assays. Rheological properties of the colloidal gels were measured to determine shear‐thinning capabilities. Gels were then extruded through a custom‐built DIW printer. Space filling constructs of the gels were printed and subjected to thermomechanical characterization to measure shape fixity (Rf) and shape recovery (Rr) ratios through five successive shape memory cycles. The polymer‐ceramic composite gels exhibited shear‐thinning capabilities for extrusion through a nozzle for DIW. A significant increase in cellular viability was observed with the addition of β‐TCP particles within the polymer matrix relative to pure PLA. Shape memory effect in the printed constructs was repeatable up to 4 cycles followed by permanent deformation. While further research on scaffold macro‐/micro‐geometries, and engineered porosities are warranted, this proof‐of‐concept study suggested suitability of this polymer‐ceramic material and the DIW 3D printing workflow for the production of customized, patient specific constructs for bone tissue engineering.
A theoretical investigation of benzothiadiazole derivatives for high efficiency OLEDs
Authors: Zhu Zhiye , Wei Xiaoqing , Liang Wanzhen
Published: March 2024

It is of great importance and worthy of efforts to give a clear structure–property relationship and microscopic mechanism of fluorescence emitters with high quantum yield. In this work, we perform a detailed computational investigation to give an explanation to the high efficiency of a fluorescence emitter XBTD‐NPh based TADF sensitized fluorescence (TSF) OLEDs, and construct a symmetry structure DSBNA‐BTD. Theoretical calculations show that XBTD‐NPh is a long‐time phosphorescent material at 77 K and TADF is attributed to the RISC of T1 to S1 state. For DSBNA‐BTD, excitons arrived at T1 state comes to a large rate of nonradiatively path to the ground state, meaning it is may not be an efficient TADF molecule. For both molecules, the fast IC between T2 and T1 state results in that the hot exciton channel T1‐Tn‐S1 makes no contribution to the TADF.
Incidence and outcomes of postoperative fluid collections after minimally invasive distal pancreatectomy without placement of surgical drain. A prospective observational cohort study
Authors: Lluís Núria , Kunzler Filipe , Asbun Domenech , Jimenez Ramon E. , Asbun Horacio J.
Published: March 2024

Background/Purpose

There is uncertainty about the role of prophylactic intra‐abdominal drains after distal pancreatectomy. In the present study, we aimed to describe the long‐term outcomes of postoperative pancreatic collections in patients who underwent a minimally invasive distal pancreatectomy (MIDP) without surgical drain placement.

Methods

From 2018 to 2022, consecutive patients who underwent a MIDP were recorded. Patients were followed at 90 days, 6 months, and in the long term. The use of interventional procedures and antibiotic therapy were documented, and the overall evolution of the collections was assessed.

Results

A total of 91 patients underwent MIDP; 11 were excluded; 80 were analyzed. Median age was 63 (51–73) years; 61.3% were women. Most lesions (71.3%) were malignant; 15 patients received neoadjuvant therapy. Procedures were laparoscopic (87.5%) or robotic (12.5%). Incidence of postoperative pancreatic collections was 33%; 10 patients were symptomatic. Interventional endoscopic (n = 3) or percutaneous (n = 3) procedures were required. At a follow‐up of 24 (17.5–33.1) months, 18 collections resolved completely, eight partially, and one increased.

Conclusions

Patients who undergo MIDP without surgical drain placement develop well‐tolerated pancreatic collections. Although a minority may require endoscopic or percutaneous drainage, the majority can be managed conservatively and resolve spontaneously in the long term.
Synthesis, characterization, and antibacterial activity studies of β‐lactam capped silver nanoparticles
Authors: Thakur Aarti , Pandey Suvidha , Mittal Mona , Thapar Renu
Published: March 2024

A highly efficient, novel, two‐phase liquid method using phase transfer catalyst is reported to prepare β‐lactam‐conjugated silver nanoparticles as an approach to improve antibacterial activity of β‐lactams. In the method assisted by cetyltrimethylammonium bromide, NaBH4 reduced AgNO3 producing silver NPs that are coated with β‐lactams. The studies conducted provide a generalized method applicable to all types of β‐lactam substrates for capping on silver NPs. The NPs have been characterized by UV–Visible, Fourier transform infrared spectroscopy, x‐ray diffraction, transmission electron microscopy, and dynamic light scattering methods.
What can pediatricians learn from adult inherited metabolic diseases?
Authors: Mochel Fanny
Published: March 2024

The field of inherited metabolic diseases (IMD) has initially emerged and developed over decades in pediatric departments. Still, today, about 50% of patients with IMD are adults, and adult metabolic medicine (AMM) is getting more structured at national and international levels. There are several domains in which pediatricians can learn from AMM. First, long‐term evolution of IMD patients, especially those treated since childhood, is critical to determine nutritional and neuropsychiatric outcomes in adults so that these outcomes can be better monitored, and patient care adjusted as much as possible from childhood. Conversely, the observation of attenuated phenotypes in adults of IMD known to present with severe phenotypes in children calls for caution in the development of newborn screening programs and, more largely, in the interpretation of next‐generation sequencing data. Third, it is important for pediatricians to be familiar with adult‐onset IMD as they expand our understanding of metabolism, including in children, such as oxysterols and glycogen metabolism. Last, the identification of common molecular and cellular mechanisms in neurodevelopment and neurodegeneration opens the way to synergistic therapeutic developments that will benefit both fields of pediatric and adult medicine. Overall, these observations underline the need of strong interdisciplinarity between pediatricians and adult specialists for the diagnosis and the treatment of IMD well beyond the issues of patient transition from pediatric to adult medicine.
Evolution of wind speed observed in Brazil between 1961 and 2020
Authors: Lima Gizelly Cardoso , Rodrigues Daniele Tôrres , Santos E Silva Cláudio Moisés , de Sousa Costa Patrícia Catarine
Published: March 2024

The study's main objective was to analyse daily wind speed data in Brazil collected on‐site from 1961 to 2020 and assess changes in two 30‐year climatological normals, denoted as P1 and P2. Data were sourced from 54 INMET‐managed meteorological stations, with missing data filled using the bootstrap expectation maximization algorithm. Imputation performance was evaluated, and results suggested that the 10% imputed level was most reliable, showing low RMSE values (below 0.5), SD values near 1, and r values exceeding 0.93. This method proved suitable for reconstructing historical wind speed data in Brazil. The analysis included the application of the Mann–Kendall test to detect linear trends and Sen's slope test to quantify trend intensity, both at a 5% significance level. Positive trends during P2 were observed in the Amazon basin and Brazil's semiarid region, while negative trends increased along the coast and in the Southeast region. Average wind speeds during P1 were higher than in P2. Comparing the two climatological normals revealed significant positive trends in some regions during P2, with an increase in average monthly variation of up to 0.85 m·s−1. The average slopes of significant trends were −1 and 1 m·s−1·decade−1 for all periods. The results indicated high wind magnitudes, with maximum power density of 778.08 W·m−2 for the NEB region, 170.90 W·m−2 for the SEB region and 401.67 W·m−2 for the SUB, making these regions promising for future wind power projects. These findings have the potential to enhance the optimization of renewable wind energy generation in Brazil.
Use of the dummy approach for the synthesis of ion imprinted polymers with Ni(II) or Zn(II) as template ion for the solid‐phase extraction of Cu(II)
Authors: Cao Pengchao , Pichon Valérie , Dreanno Catherine , Boukerma Kada , Delaunay Nathalie
Published: March 2024

There is a strong interest in monitoring copper in environmental waters, but its direct analysis suffers from strong matrix interferences. This is why, a sample pretreatment based on solid‐phase extraction (SPE) is often used but conventional sorbents usually lack specificity. It is overcome with ion‐imprinted polymers (IIPs). This work evaluates for the first time the use of the dummy approach for the synthesis of Cu(II)‐targeting IIPs. Two analog ions Ni(II) and Zn(II) were tested as templates and the resulting IIPs were packed in SPE cartridges. The SPE procedure was designed by optimizing a washing step following the sample percolation, to eliminate the interfering ions retained on the IIP by non‐specific interactions. To optimize the washing step, solutions at different pH or containing tris(hydroxymethyl)aminomethane as a complexing agent at different concentrations were tested and combined. Zn‐IIP appeared more promising than Ni‐IIP, showing excellent specificity and a high selectivity. Its retention capacity was determined to be 100 µg/g, and different isotherm models were evaluated to fit with the adsorption data. Finally, applications to mineral and sea waters were successfully completed and led to high and repeatable extraction recoveries for Cu(II) (88 ± 1% and 83 ± 3%, respectively).
Hypoxia‐inducible factor‐1α contributes to the proliferation of cholesteatoma keratinocytes through regulating endothelin converting enzyme 1 expression
Authors: Chen Nie , Xu Lei , Bi Zhi , Wu Jian
Published: March 2024

Objective

Cholesteatoma is a hyperproliferative, pseudoneoplastic lesion of the middle ear characterized by aggressive growth and bone destruction. Hypoxia‐inducible factor‐1α (HIF‐1α, also known as HIF1A) is a key transcription factor that enters the nucleus and upregulates many genes involved in cancer progression in the oxygen‐free environment. This study is designed to explore the role and mechanism of HIF1A in the progression of cholesteatoma.

Methods

HIF1A and endothelin converting enzyme 1 (ECE1) levels were determined using real‐time quantitative polymerase chain reaction. The protein levels of HIF1A, Cyclin D1, proliferating cell nuclear antigen, and ECE1 were measured using western blot. Cell viability, proliferation, and cell cycle progression were analyzed using cell counting kit‐8, Colony formation, 5‐ethynyl‐2′‐deoxyuridine, and flow cytometry assays. Binding between HIF‐1α and ECE1 promoter was predicted by Jaspar and verified using Chromatin immunoprecipitation and dual‐luciferase reporter assays.

Results

HIF1A and ECE1 were highly expressed in cholesteatoma patients and keratinocytes. Moreover, HIF1A knockdown might suppress the cell viability, proliferation, and cycle progression of cholesteatoma keratinocytes. Furthermore, HIF1A upregulated the transcription of ECE1 through binding to its promoter region.

Conclusion

HIF1A might expedite cholesteatoma keratinocyte proliferation partly by increasing ECE1 expression, providing a possible therapeutic target for the cholesteatoma treatment.
The relationship between cleft palate repair technique and audiological outcomes: A retrospective cohort study
Authors: Kazemi Tayebeh , Nabavizadeh Sara S. , Nadjmi Nasser , Ahmadkhani Alireza , Ghaemmaghami Parvin , Kafaei Ardavan , Faramarzi Ali
Published: March 2024

Objective

Otitis media with effusion is common in children with cleft palates. This study aimed to investigate the link between palatal closure techniques and audiological outcomes.

Methods

In this retrospective‐prospective cohort study, we examined the relationship between palate repair techniques and hearing outcomes in children with cleft palates. From 2017 to 2022, 190 ears of 95 cleft patients were studied at the Cleft Lip and Palate Department of Shiraz University of Medical Sciences. Variables assessed included the surgical technique, cleft severity, auditory brainstem response (ABR) threshold, and tympanometry configuration.

Results

The mean ABR improved from a prepalatoplasty value of 39.51(11.62) decibels (dB) to a postpalatoplasty mean of 26.61(11.60) dB (Cohen's d: 1.12 [95% CI; 0.90–1.34]). Initially, 87.9% of the studied ears exhibited abnormal tympanometry, but this significantly decreased to 47% postsurgery (risk ratio: 4.43 [95% CI; 1.20–16.43]). When compared with Sommerlad intravelar veloplasty, the Nadjmi modified Furlow palatoplasty was associated with a notably lower mean ABR (β: −6.58 [95% CI: −10.43 to −2.73], p‐value = .001) and a reduced frequency of abnormal tympanometry (odds ratio [OR]: −1.10; 95% CI: −1.85 to −0.36, p‐value = .004). Factors like prepalatoplasty ABR, cleft palate severity, gender, and syndromic did not confound these findings.

Conclusions

Although the Nadjmi modified Furlow palatoplasty showed better results, our findings indicate a significant improvement in ABR and tympanometry outcomes for both techniques. Future randomized controlled trials are suggested to confirm the influence of palatal closure techniques on audiological outcomes.

Level of Evidence

3b.
Double Cross‐Linked Polyisobutylene‐Based Polyurethane (xPIB‐PU) I: Synthesis, Processing, and Properties
Authors: Nugay Turgut , Kurnaz Elif , Naficy Sina , Kennedy Joseph P.
Published: March 2024

This publication concerns the synthesis of a novel class of hybrid thermoset/thermoplastic elastomers, i.e., double cross‐linked polyisobutylene‐based polyurethanes (xPIB‐PUs), together with their processing and some key properties. These materials are designed to exhibit a combination of properties for indwelling medical applications, specifically for heart valve prostheses. The chemical cross‐links are introduced by well‐defined 3‐arm PIB stars fitted with HO‐end groups of molecular weights (MWs) of Mn = 3081 and 9000 g mole−1 and narrow MW dispersities (<1.3). Processibility of xPIB‐PU containing 70 wt% PIB (for biocompatibility and calcification resistance) is achieved by driving the syntheses to high conversions (>97%) close to but still below the gel point and completing the cross‐linking in heated molds. The processibility period (minutes) is controlled by controlling the MW of the cross‐linking agent in the 3081 to 9000 g mole−1 range. Blends of 3‐arm stars and linear bifunctional PIBs can also control the processibility period. The creep resistance of xPIB‐PU is significantly improved (from 13.2% to 5.5%) relative to physically cross‐linked PIB‐PU. xPIB‐PUs exhibit negligible permanent set (1–2%), and high Young's modulus (41 MPa). The stress/strain properties of xPIB‐PUs are also investigated. The data clearly show the contribution of two modes of cross‐linking.
Second‐order trace formulas
Authors: Chattopadhyay Arup , Das Soma , Pradhan Chandan
Published: March 2024

Koplienko [Sib. Mat. Zh. 25 (1984), 62–71; English transl. in Siberian Math. J. 25 (1984), 735–743] found a trace formula for perturbations of self‐adjoint operators by operators of Hilbert–Schmidt class . Later, Neidhardt introduced a similar formula in the case of pairs of unitaries via multiplicative path in [Math. Nachr. 138 (1988), 7–25]. In 2012, Potapov and Sukochev [Comm. Math. Phys. 309 (2012), no. 3, 693–702] obtained a trace formula like the Koplienko trace formula for pairs of contractions by answering an open question posed by Gesztesy, Pushnitski, and Simon [Zh. Mat. Fiz. Anal. Geom. 4 (2008), no. 1, 63–107, 202; Open Question 11.2]. In this paper, we supply a new proof of the Koplienko trace formula in the case of pairs of contractions , where the initial operator is normal, via linear path by reducing the problem to a finite‐dimensional one as in the proof of Krein's trace formula by Voiculescu [Oper. Theory Adv. Appl. 24 (1987) 329–332] and Sinha and Mohapatra [Proc. Indian Acad. Sci. Math. Sci. 104 (1994), no. 4, 819–853] and [Integral Equations Operator Theory 24 (1996), no. 3, 285–297]. Consequently, we obtain the Koplienko trace formula for a class of pairs of contractions using the Schäffer matrix unitary dilation. Moreover, we also obtain the Koplienko trace formula for a pair of self‐adjoint operators and maximal dissipative operators using the Cayley transform. At the end, we extend the Koplienko–Neidhardt trace formula for a class of pairs of contractions via multiplicative path using the finite‐dimensional approximation method.
On rank 3 instanton bundles on P3$\mathbb {P}^3$
Authors: Andrade A. V. , Santiago D. R. , Silva D. D. , Sobral L. C. S.
Published: March 2024

We investigate rank 3 instanton vector bundles on of charge and its correspondence with rational curves of degree . For , we present a correspondence between stable rank 3 instanton bundles and stable rank 2 reflexive linear sheaves of Chern classes and we use this correspondence to compute the dimension of the family of stable rank 3 instanton bundles of charge 2. Finally, we use the results above to prove that the moduli space of rank 3 instanton bundles on of charge 2 coincides with the moduli space of rank 3 stable locally free sheaves on of Chern classes . This moduli space is irreducible, has dimension 16 and its generic point corresponds to a generalized't Hooft instanton bundle.
Uniform bounds of families of analytic semigroups and Lyapunov Linear Stability of planar fronts
Authors: Latushkin Yuri , Pogan Alin
Published: March 2024

We study families of analytic semigroups, acting on a Banach space, and depending on a parameter, and give sufficient conditions for existence of uniform with respect to the parameter norm bounds using spectral properties of the respective semigroup generators. In particular, we use estimates of the resolvent operators of the generators along vertical segments to estimate the growth/decay rate of the norm for the family of analytic semigroups. These results are applied to prove the Lyapunov linear stability of planar traveling waves of systems of reaction–diffusion equations, and the bidomain equation, important in electrophysiology.
The W(E6)$W(E_6)$‐invariant birational geometry of the moduli space of marked cubic surfaces
Authors: Schock Nolan
Published: March 2024

The moduli space of marked cubic surfaces is one of the most classical moduli spaces in algebraic geometry, dating back to the nineteenth‐century work of Cayley and Salmon. Modern interest in was restored in the 1980s by Naruki's explicit construction of a ‐equivariant smooth projective compactification of , and in the 2000s by Hacking, Keel, and Tevelev's construction of the Kollár–Shepherd‐Barron–Alexeev (KSBA) stable pair compactification of as a natural sequence of blowups of . We describe generators for the cones of ‐invariant effective divisors and curves of both and . For Naruki's compactification , we further obtain a complete stable base locus decomposition of the ‐invariant effective cone, and as a consequence find several new ‐equivariant birational models of . Furthermore, we fully describe the log minimal model program for the KSBA compactification , with respect to the divisor , where is the boundary and is the sum of the divisors parameterizing marked cubic surfaces with Eckardt points.
Signatures of microstructure in gradient‐echo and spin‐echo signals
Authors: Storey Pippa , Novikov Dmitry S.
Published: March 2024

Purpose

To determine whether the spatial scale and magnetic susceptibility of microstructure can be evaluated robustly from the decay of gradient‐echo and spin‐echo signals.

Theory and Methods

Gradient‐echo and spin‐echo images were acquired from suspensions of spherical polystyrene microbeads of 10, 20, and 40 μm nominal diameter. The sizes of the beads and their magnetic susceptibility relative to the medium were estimated from the signal decay curves, using a lookup table generated from Monte Carlo simulations and an analytic model based on the Gaussian phase approximation.

Results

Fitting Monte Carlo predictions to spin‐echo data yielded acceptable estimates of microstructural parameters for the 20 and 40 μm microbeads. Using gradient‐echo data, the Monte Carlo lookup table provided satisfactory parameter estimates for the 20 μm beads but unstable results for the diameter of the largest beads. Neither spin‐echo nor gradient‐echo data allowed accurate parameter estimation for the smallest beads. The analytic model performed poorly over all bead sizes.

Conclusions

Microstructural sources of magnetic susceptibility produce distinctive non‐exponential signatures in the decay of gradient‐echo and spin‐echo signals. However, inverting the problem to extract microstructural parameters from the signals is nontrivial and, in certain regimes, ill‐conditioned. For microstructure with small characteristic length scales, parameter estimation is hampered by the difficulty of acquiring accurate data at very short echo times. For microstructure with large characteristic lengths, the gradient‐echo signal approaches the static‐dephasing regime, where it becomes insensitive to size. Applicability of the analytic model was further limited by failure of the Gaussian phase approximation for all but the smallest beads.
An exploration of low back pain beliefs held by health care professionals in Northern America
Authors: Ray B. Michael , Washington Leah , Thompson Bronwyn Lennox , Kelleran Kyle
Published: March 2024

Background

Prior research demonstrated that people in the United States and Canada (Northern America) hold predominantly biomedical beliefs about Low back pain (LBP); such beliefs were attributed to healthcare professionals (HCP). Further investigation is needed to understand HCP' LBP beliefs, preferred management strategies, and sources of beliefs.

Methods

Participants were recruited via social media to complete a qualitative cross‐sectional online survey. The survey was distributed to assess LBP beliefs in a U.S. and Canadian‐based clinician population. Participants answered questions about the cause of LBP, reasons for recurrence or persistence, use of imaging, management strategies, and sources of beliefs. Responses were analysed using an inductive thematic analysis.

Results

One hundred and sixty three participants were included, reporting multiple causes for LBP. However, many references were anchored to biological problems. When psychological variables were mentioned, it typically involved patient blaming. Like prior research studies, minimal attention was given to societal and environmental influences. Management strategies often aligned with guideline care except for the recommendation of inappropriate imaging and a reliance on passive interventions.

Conclusions

These findings align with prior research studies on general population beliefs, demonstrating a preference for biological causes of LBP. Further updates are needed for clinical education, while future studies should seek to assess the translation of clinician beliefs into clinical practice and health system constraints.
Recurrent neural network‐based simultaneous cardiac T1, T2, and T1ρ mapping
Authors: Tao Yiming , Lv Zhenfeng , Liu Wenjian , Qi Haikun , Hu Peng
Published: March 2024

The purpose of the current study was to explore the feasibility of training a deep neural network to accelerate the process of generating T1, T2, and T1ρ maps for a recently proposed free‐breathing cardiac multiparametric mapping technique, where a recurrent neural network (RNN) was utilized to exploit the temporal correlation among the multicontrast images. The RNN‐based model was developed for rapid and accurate T1, T2, and T1ρ estimation. Bloch simulation was performed to simulate a dataset of more than 10 million signals and time correspondences with different noise levels for network training. The proposed RNN‐based method was compared with a dictionary‐matching method and a conventional mapping method to evaluate the model's effectiveness in phantom and in vivo studies at 3 T, respectively. In phantom studies, the RNN‐based method and the dictionary‐matching method achieved similar accuracy and precision in T1, T2, and T1ρ estimations. In in vivo studies, the estimated T1, T2, and T1ρ values obtained by the two methods achieved similar accuracy and precision for 10 healthy volunteers (T1: 1228.70 ± 53.80 vs. 1228.34 ± 52.91 ms, p > 0.1; T2: 40.70 ± 2.89 vs. 41.19 ± 2.91 ms, p > 0.1; T1ρ: 45.09 ± 4.47 vs. 45.23 ± 4.65 ms, p > 0.1). The RNN‐based method can generate cardiac multiparameter quantitative maps simultaneously in just 2 s, achieving 60‐fold acceleration compared with the dictionary‐matching method. The RNN‐accelerated method offers an almost instantaneous approach for reconstructing accurate T1, T2, and T1ρ maps, being much more efficient than the dictionary‐matching method for the free‐breathing multiparametric cardiac mapping technique, which may pave the way for inline mapping in clinical applications.
An a posteriori error analysis for an augmented discontinuous Galerkin method applied to Stokes problem
Authors: Barrios Tomás P. , Bustinza Rommel
Published: March 2024

This paper deals with the a posteriori error analysis for an augmented mixed discontinuous formulation for the stationary Stokes problem. By considering an appropriate auxiliary problem, we derive an a posteriori error estimator. We prove that this estimator is reliable and locally efficient, and consists of just five residual terms. Numerical experiments confirm the theoretical properties of the augmented discontinuous scheme as well as of the estimator. They also show the capability of the corresponding adaptive algorithm to localize the singularities and the large stress regions of the solution.
Environmental Risk Factors, Protective Factors, and Biomarkers for Hearing Loss: An Umbrella Review
Authors: Xu Xianpeng , Liao Yiru , Zhang Lihong , He Yu , Zhang Ying , Xiong Dajing , Xie Hui
Published: March 2024

Objective

We aimed to investigate the potential environmental risk factors, protective factors, and biomarkers of hearing loss (HL), and establish a hierarchy of evidence.

Data Sources

Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to June 1, 2023.

Review Methods

We included meta‐analyses of observational studies of associations between HL and environmental risk factors, protective factors, or biomarkers. We calculated summary effect estimates, 95% confidence interval, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases.

Results

Of the 9211 articles retrieved, 60 eligible articles were included. The 60 eligible articles identified 47 potential environmental risk and protective factors (N = 4,123,803) and 46 potential biomarkers (N = 173,701). Evidence of association was convincing (class I) for rheumatoid arthritis (RA) and every 1 cm increase in height. Evidence of association was highly suggestive (class II) for human immunodeficiency virus (HIV), diabetes, cumulative noise exposure (CNE), smoking, congenital cytomegalovirus (CMV) infection, combined exposure to organic solvents and noise, non‐Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and alopecia areata (AA).

Conclusion

In this umbrella review, RA, every 1 cm increase in height, HIV, diabetes, CNE, smoking, congenital CMV infection, combined exposure to organic solvents and noise, non‐Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and AA were strongly associated with HL.
The effect of academic freedom on electoral democracy in the Asian region
Authors: Kumara Ajantha Sisira , Samaratunge Ramanie
Published: March 2024

This paper examines how academic freedom influences electoral democracy in 44 Asian nations drawing on country‐wide panel data (2000–2019) obtained from the Varieties of Democracy (V‐Dem)‐2022. For its analytical framework, this study employs dynamic panel regression models. The Asian region, which represents the world's largest and most economically dynamic democracies, is an interesting research site to investigate this nexus due to the region's long‐term struggle to achieve its democratic aspirations. The study finds that the current‐level of electoral democracy in Asian countries is significantly associated with their antecedent level of academic freedom. Moreover, the results reveal that it takes approximately 7 years for academic freedom to yield a significant impact on electoral democracy. These results are robust across different sets of model specifications, sub‐samples, and definitions of academic freedom.
A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614)
Authors: Greengard Emily , Williams Robin , Moriarity Branden , Liu Xiaowei , Minard Charles G. , Reid Joel M. , Fisher Terrence , Evans Elizabeth , Pastore Desa Rae , Zauderer Maurice , Voss Stephan , Fox Elizabeth , Weigel Brenda J
Published: March 2024

Purpose

Pepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high‐affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low‐affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T‐cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto‐oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma.

Experimental design

Pepinemab was administered intravenously on Days 1 and 15 of a 28‐day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2‐stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood.

Results

Pepinemab (20 mg/kg) was well tolerated and no dose‐limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults.

Conclusions

Pepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response.

Clinical trial registry

This trial is registered as NCT03320330 at Clinicaltrials.gov.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Intraoperative radiation therapy for pediatric sarcomas and other solid tumors
Authors: Conte Brianna , Casey Dana L. , Tringale Kathryn R. , LaQuaglia Michael P. , Gerstle J. Ted , Wexler Leonard , Ortiz Michael V. , Wolden Suzanne L.
Published: March 2024

Purpose

To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST).

Methods

A single‐institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan–Meier method, both from the day of surgery.

Results

Median age at time of IORT was 8 years (range: 0.8–20.9 years). Median follow‐up for all patients and surviving patients was 16 months and 3 years, respectively. The most common histologies included rhabdomyosarcoma (n = 42), Ewing sarcoma (n = 10), and Wilms tumor (n = 9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12 Gy (range: 4–18 Gy), and median area treated was 24 cm2 (range: 2–198 cm2). The cumulative incidence of LF was 17% at 2 years and 23% at 5 years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients.

Conclusion

Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances.
Study on the mechanical properties of ramie fiber/polypropylene composites prepared by hot pressing after the carding machine mixing
Authors: Jin Yangxi , Huang Weizhi , Guo Yi , Deng Jiaqi , Yu Haoyang , He Bobing
Published: March 2024

A growing variety of composites utilize natural plant fibers with naturally occurring veins structured hierarchically in an effort to reduce dependence on petroleum‐based materials. In this article, ramie fibers were extracted by alkaline delignification. Then, ramie fibers and PP matrix, were prepared in filament form and an amino‐silane coupling agent KH550, and maleic anhydride grafted polypropylene were added to improve interfacial compatibility. Ramie fiber/polypropylene fiber‐reinforced polymer composites (FRC) were prepared by hot pressing after using a carding machine. This method preserves the structure and length of ramie fibers to a large extent, thus greatly improving the mechanical properties of the material. After optimization, the FRC prepared from plant fibers of 2 cm length and 60% content had a density of 0.95 g/cm3, showed an increase in tensile and flexural strength of 276% and 339%, respectively, compared to the pure PP matrix. The specific strength of the FRC in the work was higher than galore FRC prepared from talc, carbon fiber, other plant fibers, and so forth. The FRC has a wide range of potential applications due to its own low‐cost, lightweight, and high‐performance, and is highly feasible in replacing the current polymers in the preparation of numerous everyday items.

Highlights

The preparation method of FRC resulted in a more complete fiber length and structure.

The mechanism to improve the interfacial compatibility of RF and PP is discussed.

The effect of varying fiber length on the FRC mechanical properties was investigated.