bluuebunny/crossref_metadata_2025_split huggingface dataset:
New robust subtilisins from halotolerant and halophilic Bacillaceae
Authors: Falkenberg Fabian , Voß Leonie , Bott Michael , Bongaerts Johannes , Siegert Petra 
Published: May 2023

Abstract
The aim of the present study was the characterisation of three true subtilisins and one phylogenetically intermediate subtilisin from halotolerant and halophilic microorganisms. Considering the currently growing enzyme market for efficient and novel biocatalysts, data mining is a promising source for novel, as yet uncharacterised enzymes, especially from halophilic or halotolerant Bacillaceae, which offer great potential to meet industrial needs. Both halophilic bacteria Pontibacillus marinus DSM 16465T and Alkalibacillus haloalkaliphilus DSM 5271T and both halotolerant bacteria Metabacillus indicus DSM 16189 and Litchfieldia alkalitelluris DSM 16976T served as a source for the four new subtilisins SPPM, SPAH, SPMI and SPLA. The protease genes were cloned and expressed in Bacillus subtilis DB104. Purification to apparent homogeneity was achieved by ethanol precipitation, desalting and ion-exchange chromatography. Enzyme activity could be observed between pH 5.0–12.0 with an optimum for SPPM, SPMI and SPLA around pH 9.0 and for SPAH at pH 10.0. The optimal temperature for SPMI and SPLA was 70 °C and for SPPM and SPAH 55 °C and 50 °C, respectively. All proteases showed high stability towards 5% (w/v) SDS and were active even at NaCl concentrations of 5 M. The four proteases demonstrate potential for future biotechnological applications.

Key points
• Halophilic and halotolerant Bacillaceae are a valuable source of new subtilisins.
• Four new subtilisins were biochemically characterised in detail.
• The four proteases show potential for future biotechnological applications.
Transoropharyngeal closed reduction for traumatic atlantoaxial dislocation: a novel technique for fast and precise reduction
Authors: Zhong Yanlong , Xin Yu , Liu Xuqiang , Xiao Xinmao , Guo Fengfen , Yao Haoqun 
Published: May 2023

Abstract
Purpose
The aim of this study is to introduce a new technique for the rapid and accurate reduction of traumatic atlantoaxial dislocation (TAAD) and to investigate its radiological and clinical outcomes.

Methods
The clinical outcomes of 18 patients who were diagnosed with acute TAAD and underwent rapid transoropharyngeal closed reduction in our hospital were retrospectively analyzed from January 2015 to December 2020. Following general anaesthesia, all patients were immediately treated with oropharyngeal reduction under somatosensory evoked potential monitoring. The Japanese Orthopedic Association score, neck disability index and visual analog scale score for neck pain were used to evaluate clinical efficacy. Atlantodental distance, posterior atlantodental interval, and the clivus-canal angle were used to assess reduction and spinal cord compression.

Results
The mean follow-up time was 23.3 months, with a range of 13–38 months. No neurovascular injury occurred during the operations. For all patients, the closed reduction method through the oropharynx under general anaesthesia was successful, and the success rate of reduction was 100%. All patients recovered uneventfully with marked improvement in clinical outcomes and imaging parameters (P < 0.01). Two patients developed mild postoperative dysphagia. One patient developed postoperative fever and pulmonary infection.

Conclusion
Rapid trans-oropharyngeal closed reduction can safely, effectively, and rapidly reduce acute TAAD. This method provides a new strategy for treatment of the condition.
An anthropogenic landscape reduces the influence of climate conditions and moonlight on carnivore activity
Authors: Wereszczuk Anna , Zalewski Andrzej 
Published: May 2023

Abstract
Abiotic factors are limitations that can affect animal activity and distribution, whether directly or indirectly. The objective of this study was to evaluate how abiotic factors influence the activity of two mustelid species inhabiting the same region but different habitats in NE Poland—pine marten inhabits forests and stone marten occupy built-up areas. From 1991 to 2016, we obtained 23,639 year-round observations of 15 pine martens and 8524 observations of 47 stone martens. We explore the influence of ambient temperature, snow cover depth and moonlight reaching the ground and interactions between these variables on the probability of martens’ activity. The activity of pine martens living in natural habitats is more affected by climate conditions and moonlight than that of stone martens living in anthropogenic areas. Pine martens inhabiting forests increased activity when the ambient temperature was above 0 °C and snow cover was absent, as well as when the ambient temperature dropped to − 15 °C and snow cover depth was about 10 cm. Stone marten occupying anthropogenic areas did not reduce their activity if the temperature dropped. Variation of activity in relation to ambient conditions is probably related to pine martens’ behavioural thermoregulation. The pine marten was active more frequently on bright nights, while moonlight intensity did not affect the activity of the stone marten. Our study concludes that complex interactions among abiotic factors concerning different habitats play a synergetic role in shaping carnivore activity and suggest that climate warming may affect the behaviour of both martens.

Significance statement
The survival and reproduction of animals depends on their activity, which is subject to various constraints. We studied the influence of climate conditions and moonlight intensity on the ground on the activity of pine and stone marten. We found that pine martens in natural habitat were greatly impacted by ambient conditions, whereas stone martens in built-up areas were less so. Natural habitats involve limitations related to harsh winters but may mitigate the effects of high temperatures. In contrast, animals living in built-up areas are exposed to higher temperatures in summer, which is of particular importance in the face of climate change. Our results show that the combination of several environmental factors affects animal behaviour and these factors have varying effects in various habitats.
An unusual combination of a bilateral aberrant suprascapular artery with neurovascular structures variants
Authors: Piagkou Maria , Tsakotos George , Chytas Dimitrios , Totlis Trifon , Triantafyllou George , Panagiotopoulos Nikitas-Apollon , Tousia Athina , Natsis Konstantinos 
Published: May 2023

Abstract
Purpose
The report describes a bilateral suprascapular artery (SPSA) of atypical origin in coexistence with neurovascular aberrant structures.

Methods
The variants were identified in a 91-year-old formalin-embalmed male cadaver, derived from a body donation program after a signed informed consent.

Results
The left-sided SPSA emanated from the 1st part of the axillary artery, coursed between the brachial plexus lateral and medial cords, accompanied by the suprascapular nerve, and passed below the superior transverse scapular ligament. Ipsilateral coexisted variants were the lateral thoracic artery multiplication, the subscapular trunk formation, and the musculocutaneous nerve duplication. In the right supraclavicular area, a SPSA duplication was identified. The main artery emanated from the thyrocervical trunk in common with the transverse cervical artery and the accessory SPSA emanated from the dorsal scapular artery. Both SPSAs coursed over the superior transverse scapular ligament, while the suprascapular nerve ran below the ligament.

Conclusions
The current study reported a bilateral aberrant SPSA, originating from the AA 1st part (left side) and from the dorsal scapular artery (right side), which coexisted with adjacent neurovascular structures’ variants. The left SPSA atypically coursed below the superior transverse scapular ligament. Such an unusual combination of variations, present bilaterally in the current study, may be challenging for radiologists and surgeons.
Knockout mouse models as a resource for the study of rare diseases
Authors: da Silva-Buttkus Patricia , Spielmann Nadine , Klein-Rodewald Tanja , Schütt Christine , Aguilar-Pimentel Antonio , Amarie Oana V. , Becker Lore , Calzada-Wack Julia , Garrett Lillian , Gerlini Raffaele , Kraiger Markus , Leuchtenberger Stefanie , Östereicher Manuela A. , Rathkolb Birgit , Sanz-Moreno Adrián , Stöger Claudia , Hölter Sabine M. , Seisenberger Claudia , Marschall Susan , Fuchs Helmut , Gailus-Durner Valerie , Hrabě de Angelis Martin 
Published: May 2023

AbstractRare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium (IMPC) and INFRAFRONTIER, the pan-European consortium for modeling human diseases, the GMC expands these preclinical data toward global collaborative approaches with researchers, clinicians, and patient groups.Here, we highlight proprietary genes that when deleted mimic clinical phenotypes associated with known RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) which highlight novel phenotypes capable of optimizing clinical diagnosis. In addition, we present genes with intriguing phenotypic data (Zdhhc5, Wsb2) that are not presently associated with known human RDs.This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to further explore the underlying physiological mechanisms and their overall therapeutic potential.
Surface-electrode ion trap design for near-field microwave quantum gates
Authors: Tarlton James E. , Thompson Richard C. , Lucas David M. 
Published: May 2023

AbstractWe present a design study into an ion trap electrode geometry for applying near-field microwave two-qubit gates. This design features an ‘S’-shaped meander electrode to passively null the microwave field. It has ground planes separating the meander electrode from all of the DC and single-qubit microwave electrodes, which should reduce the sensitivity of the microwave field distribution to the boundary conditions of these electrodes. We show that it is possible to design a single-layer trap with this geometry such that the simulated microwave field null overlaps with the RF field null, and that the positions of these nulls can be simulated to a precision of 100 nm with moderate computing resources. We also show that such a trap can be designed such that ion chains can be trapped, transported and split with feasible DC and RF voltages. While this particular design is optimized for$$^{43}$$43Ca$$^{+}$$+ions, our approach could be applied to other ions by changing the microwave frequency to match the corresponding qubit transition frequency.
Sub-cell scale features govern the placement of new cells by honeybees during comb construction
Authors: Gallo Vincent , Bridges Alice D. , Woodgate Joseph L. , Chittka Lars 
Published: May 2023

AbstractHoneybee comb architecture and the manner of its construction have long been the subject of scientific curiosity. Comb is characterised by an even hexagonal layout and the sharing of cell bases and side walls, which provides maximised storage volume while requiring minimal wax. The efficiency of this structure relies on a regular layout and the correct positioning of cells relative to each other, with each new cell placed at the junction of two previously constructed cells. This task is complicated by the incomplete nature of cells at the edge of comb, where new cells are to be built. We presented bees with wax stimuli comprising shallow depressions and protuberances in simulation of features found within partially formed comb, and demonstrated that construction work by honeybee builders was influenced by these stimuli. The building of new cells was aligned to concave stimuli that simulated the clefts that naturally appear between two partially formed cells, revealing how new cells may be aligned to ensure proper tessellation within comb. We also found that bees built cell walls in response to edges formed by our stimuli, suggesting that cell and wall construction was specifically directed towards the locations necessary for continuation of hexagonal comb.
Adaptive density-based robust topology optimization under uncertain loads using parallel computing
Authors: Herrero-Pérez David , Picó-Vicente Sebastián Ginés , Martínez-Barberá Humberto 
Published: May 2023

AbstractThis work presents an efficient parallel implementation of density-based robust topology optimization (RTO) using adaptive mesh refinement (AMR) schemes permitting us to address the problem with modest computational resources. We use sparse grid stochastic collocation methods (SCMs) for transforming the RTO problem into a weighted multiple-loading deterministic problem at the collocation points. The calculation of these deterministic problems and the functional sensitivity is computationally expensive. We combine distributed-memory parallel computing and AMR techniques to address the problem efficiently. The former allows us to exploit the computational resources available, whereas the latter permits us to increase performance significantly. We propose the parallel incremental calculation of the deterministic problems and the contribution to the functional sensitivity maintaining a similar memory allocation to the one used in the deterministic counterpart. The cumulative computing uses buffers to adapt the evaluation at the collocation points to the parallel computing resources permitting the exploitation of the embarrassing parallelism of SCMs. We evaluate the deterministic problems in a coarse mesh generated for each topology optimization iteration to increase the performance. We perform the regularization and design variable update in a fine mesh to obtain an equivalent design to the one generated in such a mesh. We evaluate the proposal in two- and three-dimensional problems to test its feasibility and scalability. We also check the performance improvement using computational buffers in parallel computing nodes. Finally, we compare the proposal to the same approach using different preconditioners without AMR schemes showing significant performance improvements.
DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy
Authors: Trkova Katerina , Sumerauer David , Krskova Lenka , Vicha Ales , Koblizek Miroslav , Votava Tomas , Priban Vladimir , Zapotocky Michal 
Published: May 2023

AbstractPontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG. Due to the low age of the patient, the MRI appearance of DIPG, and anaplastic astrocytoma histology, intensive chemotherapy based on the HIT-SKK protocol with vinblastine maintenance chemotherapy was administered. Rapid clinical improvement and radiological regression of the tumor were observed with nearly complete remission with durable effect and excellent clinical condition more than 6.5 years after diagnosis. Based on this unexpected therapeutic outcome, genome-wide DNA methylation array was employed and the sample was classified into the methylation class “Low-grade glioma, MYB(L1) altered.” Additionally, RT-PCR revealed the presence of MYB::QKI fusion. Taken together, the histopathological classification, molecular-genetic and epigenetic features, clinical behavior, and pontine location have led us to reclassify the tumor as a pontine MYB-altered glioma. Our case demonstrates that more intensive chemotherapy can achieve long-term clinical effect in the treatment of MYB-altered pontine gliomas compared to previously used LGG-based regimens or radiotherapy. It also emphasizes the importance of a biopsy and a thorough molecular investigation of pontine lesions.
Prophylactic effect of angiotensin receptor blockers in children with genetic aortopathies: the early bird catches the worm
Authors: Olfe J. , Kanitz J. J. , Stark V. C. , Stute F. , von Kodolitsch Y. , Biermann D. , Huebler M. , Kozlik-Feldmann R. , Mir T. S. 
Published: May 2023

Abstract
Aims

In genetic aortopathies (GA) particular attention is paid to aortic root dilatation which has an impact on morbidity and mortality. This study focuses on the effects of therapy with angiotensin-II-receptor-blockers (ARB) or beta-blockers (BB) on aortic root growth and the question which therapy should be initiated at which dosage and at what age.

Methods

Since 1998 we diagnosed 208 patients with GA (170 FBN-1). 81 patients between 5 months and 18 years receiving either ARB or BB therapy were included. We retrospectively analyzed the progression of the dilatation of Sinus Valsalva aortae (SV) using calculated z-scores before and after therapy initiation and compared BB and ARB treatment.

Results
Both ARB and BB (p < 0.05) therapy showed significant improvement in aortic root growth, while the effect is significantly more pronounced in ARB (p < 0.01) independent of age and genetic cause. A detailed comparison of the two drug groups showed a more sustained effect in limiting the progression of the dilatation of the aortic root in patients treated with ARB. Progression of dilatation of the SV was significantly lower in children treated with ARBs compared to BB (delta z-score, p < 0.05). In addition, ARBs were better tolerated and had a significantly lower discontinuation rate (3%) compared to BB (50%) (p < 0.01). Independently of age at initiation all children and adolescents were able to reach the target dose under ARB.

Conclusion

We demonstrated a significant change in both treatment options, with the effect of ARB being more pronounced while being better tolerated throughout the treatment period.
Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia
Authors: Achtyes Eric D. , Hopkins Seth C. , Dedic Nina , Dworak Heather , Zeni Courtney , Koblan Kenneth 
Published: May 2023

AbstractUlotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and 5-HT2A receptor antagonism, while demonstrating an antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 26-week open-label extension) which led to Breakthrough Therapy Designation from the US Food and Drug Administration for the treatment of schizophrenia. In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative Syndrome Scale (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also observed across secondary endpoints. Post-hoc analyses of the acute trial revealed additional evidence to support the effect of ulotaront on negative symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with a number needed to harm [NNH] for individual ulotaront AEs all > 40). The open-label extension demonstrated further improvement across schizophrenia symptoms and confirmed the tolerability of ulotaront, with a 6-month completion rate of 67%. Based on current data, ulotaront shows potential to be a first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and efficacy profile distinct from current antipsychotics.
Pathological study of sternal osteomyelitis after median thoracotomy—a prospective cohort study
Authors: Bota Olimpiu , Pablik Jessica , Taqatqeh Feras , Mülhausen Maxime , Matschke Klaus , Dragu Adrian , Rasche Stefan , Bienger Kevin 
Published: May 2023

Abstract
Purpose
Osteomyelitis of the sternum may arise either as a primary condition or secondary to median thoracotomy after cardiac surgery, with the latter being decidedly more frequent. Deep sternal wound infections appear as a complication of median thoracotomy in 0.2 to 4.4% of cases and may encompass the infection of the sternal bone. To date, there are no exhaustive histopathological studies of the sternal osteomyelitis.

Methods
Our work group developed a surgical technique to remove the complete infected sternal bone in deep sternal wound infections. We therefore prospectively examined the en bloc resected sternal specimens. Seven standard histological sections were made from the two hemisternums.

Results
Forty-seven sternums could be investigated. The median age of the patients in the cohort was 66 (45–81) years and there were 10 females and 37 males. Two methods were developed to examine the histological findings, with one model dividing the results in inflammatory and non-inflammatory, while the second method using a score from 0 to 5 to describe more precisely the intensity of the bone inflammation. The results showed the presence of inflammation in 76.6 to 93.6% of the specimens, depending on the section. The left manubrial sections were more prone to inflammation, especially when the left mammary artery was harvested. No further risk factors proved to have a statistical significance.

Conclusion
Our study proved that the deep sternal wound infection may cause a ubiquitous inflammation of the sternal bone. The harvest of the left mammary artery may worsen the extent and intensity of infection.