bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal GABAergic transmission primes vestibular gating of output for adult spatial navigation
Authors: Jiang Qiufen , Wu Kenneth Lap-Kei , Hu Xiao-Qian , Cheung Man-Him , Chen Wenqiang , Ma Chun-Wai , Shum Daisy Kwok-Yan , Chan Ying-Shing
Published: March 2024

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation.
The Effects of Layer-Induced Elastic Anisotropy on Microseismic Monitoring Records in Underground Coal Mines
Authors: Malovichko Liliya
Published: March 2024

Real-time microseismic observations are extensively used in underground hard rock mines. However, microseismic monitoring in coal mines is not common. In this study, the features of microseismic (MS) event waveforms were discussed under conditions of thin-layered sedimentary media. The possibility of source mechanism evaluation was considered for the MS event recorded in coal mine. Moment tensor (MT) inversion of the waveforms can be challenging due to influence of thin-layered medium structure. Splitting of shear SH- and SV-waves is one of the characteristic features that affect MS records in coal mines. The effect of splitting was demonstrated using real microseismic data collected by an underground seismic array installed in the Polosukhinskaya coal mine, Russia. Velocities of shear SH- and SV-waves were estimated from travel times. The results reveal significant variations in shear wave velocities composed of a radial anisotropy of 75%, thus confirming the importance of a thin-layered model for moment tensor inversion. The thin-layered model was built for geological conditions at the Polosukhinskaya coal mine and synthetic seismograms were generated using QSEIS (Pyrocko OS). A full moment tensor of a single typical event was found employing the layered 1D velocity model.
Asthma bronchiale und allergische Rhinitis – die Hautprobe offenbart eine schwerwiegende Systemerkrankung
Authors: Wölbing Priscila , Dugas-Breit Susanne , Hartschuh Wolfgang , Toberer Ferdinand
Published: March 2024

Vorgestellt wird eine 30-jährige Patientin, die seit Jahren an initial unspezifischen Symptomen, wie rezidivierenden, nicht allergischen und nicht infektiösen Sinusitiden, „late onset“ Asthma bronchiale und ausgeprägter Lymphadenopathie litt. Erst nach Auftreten erster Hauterscheinungen konnte durch die Entnahme einer Probebiopsie die Diagnose einer eosinophilen granulomatösen Polyangiitis (EGPA) gestellt werden. Die EGPA ist eine schwerwiegende Systemerkrankung, die unbehandelt multiple Organschäden verursachen und sogar einen tödlichen Verlauf nehmen kann. Mit der adäquaten Behandlung verläuft die Erkrankung in mehr als 90 % der Fälle milde und kann oft sogar vollständig in Remission gehen. Durch die richtige Diagnosestellung konnte die Patientin adäquat und erfolgreich behandelt und das Risiko für Spätmanifestationen und Folgeschäden mit potenziell tödlichem Verlauf vermindert werden.
No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts
Authors: Lund-Blix Nicolai A. , Bjerregaard Anne A. , Tapia German , Størdal Ketil , Brantsæter Anne Lise , Strøm Marin , Halldorsson Thorhallur I. , Granstrøm Charlotta , Svensson Jannet , Joner Geir , Skrivarhaug Torild , Njølstad Pål R. , Olsen Sjurdur F. , Stene Lars C.
Published: March 2024

Aims/hypothesis

The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children.

Methods

The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother–child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries.

Results

There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results.

Conclusions/interpretation

Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Graphical Abstract
Enhancing gadoxetic acid–enhanced liver MRI: a synergistic approach with deep learning CAIPIRINHA-VIBE and optimized fat suppression techniques
Authors: Wei Hong , Yoon Jeong Hee , Jeon Sun Kyung , Choi Jae Won , Lee Jihyuk , Kim Jae Hyun , Nickel Marcel Dominik , Song Bin , Duan Ting , Lee Jeong Min
Published: March 2024

Objective

To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid–enhanced liver MRI.

Methods

This retrospective single-center study included 168 patients who underwent gadoxetic acid–enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation.

Results

DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036).

Conclusion

DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid–enhanced liver MRI.

Clinical relevance statement

DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time.

Key Points

• DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time.

• DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE.

• HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.
The potential of posterior cruciate ligament buckling phenomenon as a sign for partial anterior cruciate ligament tears
Authors: Tokgoz Mehmet Ali , Oklaz Ethem Burak , Ak Oguzhan , Guler Oklaz Elif Banu , Ataoglu Muhammet Baybars , Kanatli Ulunay
Published: March 2024

Introduction

Diagnosis of a partial tear of the anterior cruciate ligament (ACL) can be challenging with physical examination and imaging techniques. Although magnetic resonance imaging (MRI) has high sensitivity and specificity for diagnosing complete ACL tears, its effectiveness may be limited when it is used to diagnose for partial tears. The hypothesis of the present study is that the posterior cruciate ligament (PCL) buckling phenomenon, which is a secondary sign of complete ACL tears on MRI, may be a useful method for diagnosing partial ACL tears.

Materials and methods

The data of 239 patients who underwent knee arthroscopy in a single institution between 2016 and 2022 were analyzed retrospectively. Patients were divided into three groups based on the condition of their ligaments: partial tears, complete tears and intact ligaments. To evaluate the buckling phenomenon on sagittal T2-weighted MRI, measurements of the posterior cruciate ligament angle (PCLA) and the posterior cruciate ligament-posterior cortex angle (PCL-PCA) were conducted in each group. Subsequently, the ability of these two measurement methods to distinguish partial tears from the other groups was assessed.

Results

Both methods provided significantly different results in all three groups. Partial tears could be distinguished from intact ligaments with 86.8% sensitivity, 89.9% specificity when PCLA < 123.13° and 94.5% sensitivity, 93.2% specificity when PCL-PCA < 23.77°. Partial tears could be distinguished from complete tears with 79.5% sensitivity, 78.4% specificity when PCLA > 113.88° and with 86.1% sensitivity, 85.3% specificity when PCL-PCA > 16.39°.

Conclusion

The main finding of the present study is that the PCLA and PCL-PCA methods are useful on MRI for diagnosing partial ACL tears. PCLA value between 113°-123° and PCL-PCA value between 16°-24° could indicate a partial ACL tear. With these methods, it is possible to distinguish partial tears from healthy knees and reduce missed diagnoses. In addition, the differentiation of partial and complete tears by these methods may prevent unnecessary surgical interventions.

Level of evidence

Level III.
Pregnancy in myasthenia gravis: a retrospective analysis of maternal and neonatal outcome from a large tertiary care centre in Germany
Authors: Draxler Jakob , Meisel Andreas , Stascheit Frauke , Stein Maike , Gerischer Lea , Mergenthaler Philipp , Herdick Meret , Doksani Paolo , Lehnerer Sophie , Verlohren Stefan , Hoffmann Sarah
Published: March 2024

Purpose

Myasthenia gravis (MG) is a rare, potentially life-threatening autoimmune disease with fluctuating muscle weakness frequently affecting women of childbearing age. MG can affect maternal as well as neonatal outcome with risk of worsening of myasthenic symptoms in the mothers and risk of transient neonatal myasthenia gravis (TNMG) and arthrogryposis multiplex congenita (AMC) or foetal acetylcholine receptor antibody-associated disorders (FARAD) in the neonates.

Methods

Retrospective analysis of maternal and neonatal outcome in a cohort of pregnant MG patients treated at a tertiary care centre in Germany.

Results

Overall, 66 pregnancies were analysed. During 40 (63%) pregnancies, women experienced a worsening of myasthenic symptoms, of whom 10 patients (15.7%) needed acute therapy with IVIg or plasma exchange. There was no case of myasthenic crisis. Rate of caesarean section was comparable to the overall C-section rate at our centre (38% vs. 40%). However, there was a slightly higher rate for operative vaginal delivery (15% vs. 10%) as potential indicator for fatiguing striated musculature in MG patients during the expulsion stage. Rate of TNMG as well as AMC was 3% (two cases each).

Conclusions

Maternal and neonatal outcome in our cohort was favourable with a low rate of myasthenic exacerbations requiring acute therapies and a low rate of TNMG and AMC/FARAD. Our data might help neurologists and obstetricians to advice MG patients with desire to have children.
Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics
Authors: Cantone Elena , D’Ascanio Luca , De Luca Pietro , Roccamatisi Dalila , La La Mantia Ignazio , Brenner Michael J. , Di Stadio Arianna
Published: March 2024

Purpose

Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.

Methods

After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin’ Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.

Results

The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.

Conclusions

umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.
From source to surface: clues from garnet-bearing Carboniferous silicic volcanic rocks, Iberian Pyrite Belt, Portugal
Authors: Cravinho A. , Rosa D. , Relvas J. M. R. S. , Solá A. R. , Pereira I. , Paquette J.-L. , Borba M. L. , Tassinari C. C. G. , Chew D. , Drakou F. , Breiter K. , Araujo V.
Published: March 2024

This work investigates the relationships between partial melting, melt extraction, pluton growth and silicic volcanism in garnet-bearing felsic volcanic rocks that were extruded in the Iberian Pyrite Belt, at ca. 345 Ma. The garnets are of peritectic origin, displaying textural and chemical features of disequilibrium crystallization during partial melting reactions involving biotite at high temperatures (up to 870 °C) in the middle-lower crust. Major element composition suggests compositional equilibrium with the entrained and pinitized peritectic cordierite, but reveals some subsequent homogenization by diffusion. Trace element maps and spot analyses of garnet show, nonetheless, significant trace element variations, reflecting biotite and Y-REE-P-rich accessory phase breakdown during partial melting reactions. Peritectic garnet and cordierite growth resulted in the preservation of Th- and Y-rich prograde suprasolidus monazite, which constrains the timing of partial melting of the metapelitic protolith at ca. 356.8 ± 2.4 Ma. The zircon cargo further shows that a significant amount of zircon crystals from previously crystallized felsic melts were also remobilized and erupted. These were likely stored in an upper crustal pluton that grew episodically since ca. 390 Ma during voluminous melt generation periods within the middle to lower crust, which also resulted in voluminous volcanism. The geochemical trends of the felsic volcanic rocks reflect the entrainment of xenoliths of peritectic garnet, cordierite and feldspar, and as such, the garnet-bearing felsic volcanic rocks represent an erupted mixture of a lower-temperature (ca. 770 °C) silicic melt and autocrysts, and peritectic phases and zircon crystals from previously crystallized and stored felsic melts.
Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC
Authors: Melchior Linea , Hirschmann Astrid , Hofman Paul , Bontoux Christophe , Concha Angel , Mrabet-Dahbi Salima , Vannuffel Pascal , Watkin Emmanuel , Putzová Martina , Scarpino Stefania , Cayre Anne , Martin Paloma , Stoehr Robert , Hartmann Arndt
Published: March 2024

The current study assessed the performance of the fully automated RT-PCR-based Idylla™ GeneFusion Assay, which simultaneously covers the advanced non-small cell lung carcinoma (aNSCLC) actionable ALK, ROS1, RET, and MET exon 14 rearrangements, in a routine clinical setting involving 12 European clinical centers. The Idylla™ GeneFusion Assay detects fusions using fusion-specific as well as expression imbalance detection, the latter enabling detection of uncommon fusions not covered by fusion-specific assays. In total, 326 archival aNSCLC formalin-fixed paraffin-embedded (FFPE) samples were included of which 44% were resected specimen, 46% tissue biopsies, and 9% cytological specimen. With a total of 179 biomarker-positive cases (i.e., 85 ALK, 33 ROS1, 20 RET fusions and 41 MET exon 14 skipping), this is one of the largest fusion-positive datasets ever tested. The results of the Idylla™ GeneFusion Assay were compared with earlier results of routine reference technologies including fluorescence in situ hybridization, immunohistochemistry, reverse-transcription polymerase chain reaction, and next-generation sequencing, establishing a high sensitivity/specificity of 96.1%/99.6% for ALK, 96.7%/99.0% for ROS1, 100%/99.3% for RET fusion, and 92.5%/99.6% for MET exon 14 skipping, and a low failure rate (0.9%). The Idylla™ GeneFusion Assay was found to be a reliable, sensitive, and specific tool for routine detection of ALK, ROS1, RET fusions and MET exon 14 skipping. Given its short turnaround time of about 3 h, it is a time-efficient upfront screening tool in FFPE samples, supporting rapid clinical decision making. Moreover, expression-imbalance-based detection of potentially novel fusions may be easily verified with other routine technologies without delaying treatment initiation.
Improved survival over time with immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinomas
Authors: Schneider Sophie , Ferte Thomas , Ducharme Océane , Dousset Léa , Prey Sorilla , Dutriaux Caroline , Gerard Emilie , Beylot-Barry Marie , Pham-Ledard Anne
Published: March 2024

Purpose

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in white-skinned populations. There is little information on the epidemiology of cSCC, and even less on advanced cases (acSCC). Therefore, we analyzed acSCC patients to describe their characteristics, management, and outcomes over time.

Methods

A single-center retrospective study was conducted over a period of 5 years, including all patients who started systemic therapy for acSCC. The patient characteristics, cSCC management, response to therapy, and survival were recorded. Patients were stratified into equal chronological periods (periods 1 and 2). A subgroup analysis was performed to compare patients who received immunotherapy (group 1) with those who did not (group 2).

Results

The study included 127 patients, and patient numbers increased by an average of 19.7% per year. Most patients were male (88/127), elderly (mean 81.6 years), with comorbidities, and 27.6% were immunocompromised. The median overall survival (OS) was higher in period 2 (20 months) than in period 1 (10 months) (hazard ratio [95% confidence interval] = 0.62 [0.39; 0.98], p = 0.04). The risk of progression increased with age and immunosuppression. Of the 64 patients who received second-line therapy, 38 had immunotherapy (group 1) and 26 received other therapies (group 2). Immunotherapy reduced mortality and progression by 71% (p = 0.004) and 67% (p = 0.002), respectively.

Conclusions

Patients with acSCC are usually very frail and elderly. OS increased over time, with a twofold improvement between periods 1 and 2, whereas progression-free survival (PFS) did not increase. Access to immunotherapy reduced mortality in a majority of patients in period 2. Immunosuppression and advanced age were associated with lower PFS.
Diffusion-weighted imaging-based radiomics model using automatic machine learning to differentiate cerebral cystic metastases from brain abscesses
Authors: Cui Linyang , Qin Zheng , Sun Siyuan , Feng Weihua , Hou Mingyuan , Yu Dexin
Published: March 2024

Objectives

To develop a radiomics model based on diffusion-weighted imaging (DWI) utilizing automated machine learning method to differentiate cerebral cystic metastases from brain abscesses.

Materials and methods

A total of 186 patients with cerebral cystic metastases (n = 98) and brain abscesses (n = 88) from two clinical institutions were retrospectively included. The datasets (129 from institution A) were randomly portioned into separate 75% training and 25% internal testing sets. Radiomics features were extracted from DWI images using two subregions of the lesion (cystic core and solid wall). A thorough image preprocessing method was applied to DWI images to ensure the robustness of radiomics features before feature extraction. Then the Tree-based Pipeline Optimization Tool (TPOT) was utilized to search for the best optimized machine learning pipeline, using a fivefold cross-validation in the training set. The external test set (57 from institution B) was used to evaluate the model’s performance.

Results

Seven distinct TPOT models were optimized to distinguish between cerebral cystic metastases and abscesses either based on different features combination or using wavelet transform. The optimal model demonstrated an AUC of 1.00, an accuracy of 0.97, sensitivity of 1.00, and specificity of 0.93 in the internal test set, based on the combination of cystic core and solid wall radiomics signature using wavelet transform. In the external test set, this model reached 1.00 AUC, 0.96 accuracy, 1.00 sensitivity, and 0.93 specificity.

Conclusion

The DWI-based radiomics model established by TPOT exhibits a promising predictive capacity in distinguishing cerebral cystic metastases from abscesses.
CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model
Authors: Fikry Heba , Saleh Lobna A. , Mahmoud Faten A. , Gawad Sara Abdel , Abd-Alkhalek Hadwa Ali
Published: March 2024

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.
Characteristics of A-type voltage-gated K+ currents expressed on sour-sensing type III taste receptor cells in mice
Authors: Moribayashi Takeru , Nakao Yoshiki , Ohtubo Yoshitaka
Published: March 2024

Sour taste is detected by type III taste receptor cells that generate membrane depolarization with action potentials in response to HCl applied to the apical membranes. The shape of action potentials in type III cells exhibits larger afterhyperpolarization due to activation of transient A-type voltage-gated K+ currents. Although action potentials play an important role in neurotransmitter release, the electrophysiological features of A-type K+ currents in taste buds remain unclear. Here, we examined the electrophysiological properties of A-type K+ currents in mouse fungiform taste bud cells using in-situ whole-cell patch clamping. Type III cells were identified with SNAP-25 immunoreactivity and/or electrophysiological features of voltage-gated currents. Type III cells expressed A-type K+ currents which were completely inhibited by 10 mM TEA, whereas IP3R3-immunoreactive type II cells did not. The half-maximal activation and steady-state inactivation of A-type K+ currents were 17.9 ± 4.5 (n = 17) and − 11.0 ± 5.7 (n = 17) mV, respectively, which are similar to the features of Kv3.3 and Kv3.4 channels (transient and high voltage-activated K+ channels). The recovery from inactivation was well fitted with a double exponential equation; the fast and slow time constants were 6.4 ± 0.6 ms and 0.76 ± 0.26 s (n = 6), respectively. RT-PCR experiments suggest that Kv3.3 and Kv3.4 mRNAs were detected at the taste bud level, but not at single-cell levels. As the phosphorylation of Kv3.3 and Kv3.4 channels generally leads to the modulation of cell excitability, neuromodulator-mediated A-type K+ channel phosphorylation likely affects the signal transduction of taste.
The Near Exact Bin Covering Problem
Authors: Levin Asaf
Published: March 2024

We present a new generalization of the bin covering problem that is known to be a strongly NP-hard problem. In our generalization there is a positive constant $$\varDelta $$
Δ
, and we are given a set of items each of which has a positive size. We would like to find a partition of the items into bins. We say that a bin is near exact covered if the total size of items packed into the bin is between 1 and $$1+\varDelta $$

1
+
Δ

. Our goal is to maximize the number of near exact covered bins. If $$\varDelta =0$$

Δ
=
0

or $$\varDelta >0$$

Δ
>
0

is given as part of the input, our problem is shown here to have no approximation algorithm with a bounded asymptotic approximation ratio (assuming that $$P\ne NP$$

P
≠
N
P

). However, for the case where $$\varDelta >0$$

Δ
>
0

is seen as a constant, we present an asymptotic fully polynomial time approximation scheme (AFPTAS) that is our main contribution.
Cortical microtubule dynamics during reaction wood formation ensures context-appropriate cellulose microfibril angle in woody trees
Authors: Tobias Larissa Machado , McFarlane Heather E. , Bossinger Gerd , Spokevicius Antanas V.
Published: March 2024

Key message

Cortical microtubule arrays are the primary mechanism for guiding the re-orientation of cellulose microfibrils and determining MFA in secondary cell wall of wood fibre and tracheid cells in reaction wood.

Microtubules are directly and indirectly involved in guiding cellulose synthase complexes (CSCs) through the plasma membrane. The angle of cellulose deposition is a critical response to environmental signals and/or stress conditions, and particularly crucial during reaction wood formation, a process in which woody plants deposit additional cell wall material to counteract gravitational forces. Tubulin genes are upregulated in response to gravitational stimulus during reaction wood formation, which can result in changes to microtubule assembly. In this study, microtubules were visualised in three woody tree species (two angiosperms: Eucalyptus globulus Labill., Populus alba L., and one gymnosperm: Pinus radiata D. Don.) using immunofluorescence to quantitatively evaluate microtubule organisation during reaction wood formation. Our results suggest that reorientation of the cortical microtubule array affects secondary cell wall deposition, even across different types of reaction wood, by ensuring context-appropriate orientation of cellulose microfibrils and determining MFA in wood cells. Pharmacological studies conducted on in vitro cultured stem segments or in vivo during reaction wood formation corroborated these important roles for microtubules during wood development. This study starts to unveil the role of tubulins during wood formation by exploring cortical microtubule array organisation in trees subjected to gravitational stimulus and it sheds light on cellular and molecular mechanisms behind cellulose deposition in tree species.
Effects of root-colonizing fungi on pioneer Pinus thunbergii seedlings in primary successional volcanic mudflow on Kuchinoerabu Island, Japan
Authors: Ishikawa Akira , Hayasaka Daisuke , Nara Kazuhide
Published: March 2024

Root-colonizing fungi, such as mycorrhizal fungi and dark septate endophyte fungi, are often found on pioneer plant species during early primary succession. However, little is known about which fungal species are responsible for the establishment of pioneer plants when these symbionts colonize simultaneously. We investigated the root-colonizing fungal communities of Pinus thunbergii that established prior to lichens, bryophytes, and short-lived herbaceous plants in a primary successional volcanic mudflow site on Kuchinoerabu Island, Japan. We collected a total of 54 current-year and 1- to 2-year-old seedlings. The colonization of root fungi was evaluated by direct observation of key structures (e.g., mantle, arbuscule, microsclerotia, and hyphae) and molecular analysis. Of the 34 current-year seedlings collected, only 12 individuals were colonized by ectomycorrhizal (ECM) fungi. By contrast, all 1- to 2-year-old seedlings were colonized by ECM fungi. Seedlings colonized by pine-specific ECM fungi, specifically Rhizopogon roseolus and Suillus granulatus, showed higher nitrogen and phosphorus contents in their needles compared to non-ECM seedlings. Arbuscular mycorrhizal fungi and dark septate endophyte fungi were found in only two and three individuals, respectively. The high density of mycophagous deer on Kuchinoerabu-jima may contribute to the favored dispersal of ECM fungi over other root-colonizing fungi. In conclusion, the seedling establishment of P. thunbergii at the volcanic mudflow may be largely supported by ECM fungi, with negligible effects of arbuscular mycorrhizal fungi and dark septate endophytes.
The role of the Flb protein family in the life cycle of Aspergillus niger
Authors: Chen Xiaoyi , Moran Torres Juan P. , Wösten Han A. B.
Published: March 2024

Genes flbA-E are involved in sporulation and vegetative growth in Aspergillus nidulans. Inactivation of either of these genes results in a fluffy phenotype with delayed or even abolished sporulation. Previously, a non-sporulating phenotype was obtained by inactivating flbA in Aspergillus niger, which was accompanied by lysis, thinner cell walls, and an increased secretome complexity. Here, we further studied the role of the flb genes of A. niger. Strains ΔflbA, ΔflbB and ΔflbE showed increased biomass formation, while inactivation of flbA-D reduced, or even abolished, formation of conidia. Strain ΔflbA was more sensitive to H2O2, DTT, and the cell wall integrity stress compounds SDS and Congo Red (CR). Also, ΔflbC was more sensitive to SDS, while ΔflbB, ΔflbD, and ΔflbE were more sensitive to CR. On the other hand, inactivation of flbE increased resistance to H2O2. Enzyme secretion was impacted when the Δflb strains were grown on xylose. Strain ΔflbE showed reduced xylanase, cellulase and amylase secretion. On the other hand, amylase secretion at the periphery of the ΔflbA colony was reduced but not in its center, while secretion of this enzyme was increased in the center of the ΔflbB colony but not at its periphery. Inactivation of flbC and flbD also impacted zonal cellulase and amylase activity. Together, the Flb protein family of A. niger function in biomass formation, sporulation, stress response, and protein secretion.
A self-amplifying loop of TP53INP1 and P53 drives oxidative stress-induced apoptosis of bone marrow mesenchymal stem cells
Authors: Li Fanchao , Zhang Fei , Wang Tao , Xie Zhihong , Luo Hong , Dong Wentao , Zhang Jian , Ren Chao , Peng Wuxun
Published: March 2024

Bone marrow mesenchymal stem cell (BMSC) transplantation is a promising regenerative therapy; however, the survival rate of BMSCs after transplantation is low. Oxidative stress is one of the main reasons for the high apoptosis rate of BMSCs after transplantation, so there is an urgent need to explore the mechanism of oxidative stress-induced apoptosis of BMSCs. Our previous transcriptome sequencing results suggested that the expression of P53-induced nuclear protein 1 (TP53INP1) and the tumor suppressor P53 (P53) was significantly upregulated during the process of oxidative stress-induced apoptosis of BMSCs. The present study further revealed the role and mechanism of TP53INP1 and P53 in oxidative stress-induced apoptosis in BMSCs. Overexpression of TP53INP1 induced apoptosis of BMSCs, knockdown of TP53INP1 alleviated oxidative stress apoptosis of BMSCs. Under oxidative stress conditions, P53 is regulated by TP53INP1, while P53 can positively regulate the expression of TP53INP1, so the two form a positive feedback loop. To clarify the mechanism of feedback loop formation. We found that TP53INP1 inhibited the ubiquitination and degradation of P53 by increasing the phosphorylation level of P53, leading to the accumulation of P53 protein. P53 can act on the promoter of the TP53INP1 gene and increase the expression of TP53INP1 through transcriptional activation. This is the first report on a positive feedback loop formed by TP53INP1 and P53 under oxidative stress. The present study clarified the formation mechanism of the positive feedback loop. The TP53INP1–P53 positive feedback loop may serve as a potential target for inhibiting oxidative stress-induced apoptosis in BMSCs.
Unchanged water stress induces growth retardation, histopathological alterations, and antioxidant-immune disruptions in Oreochromis niloticus: the promising role of dietary organic acids
Authors: Abdel-Aziz Mohamed F. A. , El Basuini Mohammed F. , Sadek Mohamed F. , Elokaby Mohamed A. , El-Dakar Ashraf Y. , Metwally Mohamed M. M. , Shehab Ahmed , Mabrok Mahmoud , Abdel Rahman Afaf N.
Published: March 2024

Legal restrictions and consumer trends are contributing to the growing movement for fish welfare. Therefore, the aquaculture sector is a means of reducing animal stress and enhancing physiological state, which raises financial profits. Feed additives have therefore been suggested as possible dietary stress alleviation. In this trend, a 75-day feeding trial was conducted to evaluate the effects of three organic acids (formic acid (FA), lactic acid (LA), and commercial organic acids mix (COM)) as dietary additives in Nile tilapia (Oreochromis niloticus) reared under a stressful condition (unchanged water). Fish (weighing 3.95 ± 0.05 g) were randomly housed into eight groups (n = 210 fish/group; 70 fish/replicate; 3 replicates/group). The first (negative control) and second (positive control) groups were fed a basal diet without additives and with water exchange at 20% of the water volume every 2 days for the first group and without water exchange for the second. The other six groups (FA1, FA2, LA1, LA2, COM1, and COM2) were fed basal diets supplemented with OAs at two doses (1 and 2%) without water exchange during the trial. The results revealed that fish kept without water exchange (positive control) had the highest level of water-unionized ammonia and nitrite and a marked decline in growth performance (weight gain and specific growth rate). The unchanged water induced substantial decreases in the hematological profile (white and red blood cell count, hemoglobin value, and hematocrit %), protein profile indices (total protein, albumin, and globulin), and antioxidant-immune response (superoxide dismutase, catalase, lysozyme, and total immunoglobulin M). In addition, the biochemical indices (glucose, creatinine, urea, alanine aminotransferase, and aspartate aminotransferase) and lipid peroxide (malondialdehyde) were substantially increased in the positive control group. In addition to that, marked and severe histopathological alteration in the gills, liver, and intestine including hyperplasia, hemorrhage, and degenerative and necrotic changes that were associated with desquamation and sloughing were obvious in the PC group. Dietary LA1 significantly enhanced (P < 0.05) the overall measured indices; meanwhile, the dietary FA and COM recorded the worst results. Overall, our findings demonstrate that the unchanged water negatively affected the growth and physiological functions of Nile tilapia. Dietary incorporation of organic acids did not protect the fish from these hazards except the LA (1%). The latter can reduce nitrogenous compounds, enhance immune response, and alleviate these alterations for the sustainable aquaculture industry.
Composition as Identity and the Logical Roots of Leibniz’s Nominalism
Authors: Costantini Filippo
Published: March 2024

The paper deals with Leibniz’s ontology and the metaphysics of the aggregate. Concerning the ontology of aggregates, the main aim is to provide a new argument in favor of the claim that an aggregate and its constituents have the same ontological import. This argument takes the form of a weakening of a principle known in the contemporary literature of mereology as ‘composition as identity’ (CAI). The paper shows that Leibniz’s nominalism toward aggregates is a direct consequence of two elements: the way in which he considers the relationship between aggregates and their constituents in his logical calculus; and his theory of identity (and more generally, equivalence relations) as providing us with the ground for substitution salva veritate. It is concluded that Leibniz is committed to a principle that the author dubs Ontological-CAI: the aggregate/whole is ontologically identical (i.e. it has the same ontological import) as its constituents/parts. Concerning the metaphysics of aggregates, the paper outlines in what sense aggregates are grounded on their constituents: arguing that Leibniz is committed to a further principle that the author calls Metaphysical-CAI: the aggregate/whole is metaphysically grounded on its constituents/parts. From this it can be understood in which sense Leibniz could be considered a mereological nihilist, and in which sense not. The paper also sets out two different and competing readings of Metaphysical-CAI, and argues that Leibniz accepted both of them by interpreting them as different levels of explanation of the nature of aggregates.
Domain Restrictions in the Aggregation of Classifications
Authors: Craven John
Published: March 2024

The possibility of domain restrictions that allow the consistent use of majority-based aggregators for rankings of objects has been widely explored. This paper extends this exploration to structures in which equivalence relations or classifications are aggregated, and shows that there is very limited scope for such restrictions in the binary structure of Mirkin and in the unary structure of Maniquet and Mongin. We develop a hybrid structure that combines binary and unary conditions on the aggregator, and that allows the use of a majority-based aggregator if and only if each object is eligible for inclusion in no more than two categories out of some greater number. We also show that in many circumstances, the surjectivity requirement of Maniquet and Mongin implicitly introduces binary conditions on the aggregator, and that their structure is entailed by the hybrid structure introduced here.
Should Type Theory Replace Set Theory as the Foundation of Mathematics?
Authors: Altenkirch Thorsten
Published: March 2024

Mathematicians often consider Zermelo-Fraenkel Set Theory with Choice (ZFC) as the only foundation of Mathematics, and frequently don’t actually want to think much about foundations. We argue here that modern Type Theory, i.e. Homotopy Type Theory (HoTT), is a preferable and should be considered as an alternative.
Davidsonian Metasemantics and Radical Interpretation
Authors: Tarnowski Maciej
Published: March 2024

In the current debate on the metaphysical grounding of semantic properties Donald Davidson is usually taken to represent interpretationism, a stance according to which the meaning of expressions is metaphysically grounded by the process of assigning them semantic values which maximize certain parameters such as truth or rationality of the speaker. This stance is often contrasted with productivism, which takes circumstances of expression’s production, not interpretation, to ground its meaning. In this article, I argue that this widespread understanding of Davidson’s thought is false and that given such demarcation Davidson should be regarded as a productivist. To support my claim, I begin by briefly outlining the state of debate on metasemantics and main theses of Davidson’s program, and then I present three exegetical arguments against interpretationist reading of Davidson’s work. I conclude by reconstructing what I take to be the actual metaphysical picture of semantic properties emerging from Davidson’s work.
Near-infrared spectroscopy and multivariate analysis as real-time monitoring strategy of TEMPO-mediated oxidation of cellulose fibers from different feedstocks
Authors: Mazega André , Fortuny Montserrat , Signori-Iamin Giovana , Aguado Roberto J. , Tarrés Quim , Santos Alexandre F. , Delgado-Aguilar Marc
Published: March 2024

The regioselective oxidation of the primary hydroxyl groups of cellulose, usually mediated by the (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO), is highly popular in the scientific literature. However, the lack of efficient monitoring techniques imposes a severe limitation to its upscaling. This work involves a portable, user-friendly near-infrared spectroscopy device, optimized preprocessing techniques, and multivariate calibration to quickly estimate the carboxyl group content of modified cellulose (i.e., the extent of the oxidation). For that, bleached pulps from eucalyptus, pine, hemp, and sisal were submitted to TEMPO-mediated oxidation, varying the dosage of spent oxidizer (NaClO) and thus attaining samples of different values of carboxyl group content. These values were related to near-infrared spectra (908–1676 nm) by Partial Least Squares regression, yielding cross-validation coefficients (RCV2) above 0.97 for wood pulps, 0.95 for sisal pulp, and 0.91 for hemp pulp. Based on the residual prediction deviation, the model for each pulp was found to show good predictability. Nonetheless, the overall regression model, comprising the four different materials, was unreliable. In light of this, spectra were submitted to principal components analysis (PCA), hinting that pulps could be classified in terms of their hemicellulose to cellulose ratio. Considering all the statistical parameters, the overall proposal presented here begins with a PCA—Linear Discriminant Analysis model to classify the sample by its fiber type, subsequently selecting a specific regression model for that class. Overall, the presented models in this work allow the determination of the extent of oxidation of different cellulosic feedstocks, expressed as carboxyl content, in a fast and simple approach using a benchtop near-infrared equipment.
Debt Stabilisation and Dynamic Interaction Between Monetary Authority and National Fiscal Authorities
Authors: Gori Luca , Purificato Francesco , Sodini Mauro
Published: March 2024

The main aim of the present research is to consider a monetary union’s economy consisting of N countries, N fiscal authorities (one for each country) and a single monetary authority. The fiscal authorities want to stabilise output and public debt through the primary government balance, and they can exhibit heterogeneous preferences about the trade-off between output and debt stability. Unlike these, the monetary authority has the aim of price and output stability. They play a non-cooperative policy game, in which they independently and simultaneously choose monetary and fiscal instruments to pursue their goals. In a dynamic setting, each authority must choose its policy instrument prevailing in the next period without knowing—at the end of each period—the choice of other authorities. By assuming static expectations, the present work shows the possibility of several dynamic outcomes. First, there exists one Nash equilibrium representing the optimal level for the macro economy; this equilibrium is stable if the average weight that fiscal authorities assign to output stability is not excessively high; therefore, this result holds even if some authorities are less willing to promote debt stabilisation. Second, in addition to this equilibrium, there exist other Nash equilibria representing steady-state values for macroeconomic variables that differ from the targets adopted by the authorities; these equilibria emerge and are stable if the authorities’ preference for output stability is even greater and with a higher degree of heterogeneity compared to the previous case. Third, the parameters of the model matter to determine the stability properties of the equilibria, and the analysis shows the possibility of nonlinear dynamics.