bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of robotic‐assisted and manual techniques in restricted kinematically aligned total knee arthroplasty: coronal alignment improvement with no significant clinical differences
Authors: Turan Kayhan , Camurcu Yalkin , Kezer Murat , Uysal Yunus , Kizilay Yusuf Onur , Ucpunar Hanifi , Temiz Abdulaziz
Published: May 2023

Purpose

The purpose of this study was to compare radiographic and clinical outcomes of robotic‐assisted and conventional manual techniques in restricted kinematically aligned TKA.

Methods

Patients who underwent either manual or robotic‐assisted restricted kinematically aligned TKA between 2019 and 2020 were included in this retrospective comparative study. Radiographic outcomes comprised coronal plane measurements performed through standing full‐length anteroposterior radiographs. The Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford score, Visual Analog Scale pain and satisfaction score, and Forgotten Joint Score were used to determine the clinical outcome. The continuous data were compared by Student’s t test according to the Kolmogorov‒Smirnov normality test.

Results

The manual group consisted of 46 patients (38 females, eight males) with a mean age of 68.1 years, and the robotic group consisted of 70 patients (58 females, 12 males) with a mean age of 65.7 years (n.s.). Preoperatively, no significant difference was observed between groups concerning demographic characteristics, radiographic measurements, and clinical scores except for the symptom and pain domains of the KOOS score, which was significantly worse in the manual group (p = 0.011 and 0.035, respectively). At the postoperative 2‐year follow‐up, we observed significant differences between groups with respect to the mean HKA angle, mMPTA, and mLDFA (p = 0.034, 0.041, and 0.005, respectively). A comparison of clinical scores at the postoperative 2‐year follow‐up demonstrated no significant differences between groups.

Conclusion

The current study demonstrated that using robotic‐assisted technique for restricted kinematically aligned total knee arthroplasty (TKA) resulted in significantly better outcomes compared to the conventional manual technique in achieving normal ranges of lower extremity coronal alignment measurements. While the robotic‐assisted group demonstrated better clinical scores, there was no statistically significant difference in clinical outcomes between the robotic‐assisted group and the control group at the two‐year follow‐up. Concerning clinical relevance, the restoration of original anatomy and coronal alignment, a crucial concern in restricted kinematically aligned TKA, may be better achieved by the robotic‐assisted technique.

Level of evidence

Level III (Retrospective cohort study).
Information spillover in multiple zero-sum games
Authors: Pahl Lucas
Published: May 2023

This paper considers an infinitely repeated three-player zero-sum game with two-sided incomplete information, in which an informed player plays two zero-sum games simultaneously at each stage against two uninformed players. This is a generalization of the model in Aumann et al. (Repeated games with incomplete information. MIT Press, New York, 1995) of two-player zero-sum one-sided incomplete information games. Under a correlated prior, the informed player faces the problem of how to optimally disclose information among two uninformed players in order to maximize his long-term average payoffs (i.e., undiscounted payoffs). Our objective is to understand the adverse effects of “information spillover” from one game to the other in the equilibrium payoff set of the informed player. We provide conditions under which the informed player can fully overcome such adverse effects and characterize equilibrium payoffs. In a second result, we show how the effects of information spillover on the equilibrium payoff set of the informed player might be severe. Finally, we compare our findings on the equilibrium-payoff set of the informed player with those of Bayesian Persuasion models with multiple receivers.
Benefits and risks of using bacterial- and plant-produced nano-silver for Japanese quail hatching-egg sanitation
Authors: Hamouda Nagwa H. , Saleh W. D. , Nasr N. F. , El Sabry M. I.
Published: May 2023

This research compared how bacterial-, plant-produced silver nanoparticles (Ag-NPs) and TH4 affected the eggshells microbial load and quail chicks' liver structure, embryonic mortality, and features related to hatchability. Ag-NPs were sensitized by bacterial and plant methods, and then identified by UV–visible spectroscopy, TEM, and FTIR spectroscopy. B-Ag-NPs were found in spherical shapes in size ranging from 7.09 to 18.1 nm versus multi-shape with size range of 25.0–78.1 nm for P-Ag-NPs. A total number of 624 eggs (in three equal groups) of Japanese quail flock were sprayed with TH4 as control, B-Ag-NPs and P-Ag-NPs. Thereafter, three eggs were sampled randomly from each group for determining important microbial groups. The remaining eggs were incubated according to the recommended incubation conditions. On the day of hatching, the percentages of hatchability and embryonic mortality were measured. Besides, five chicks from each treatment were slaughtered and the livers were utilized for ICP and histological tests. The effects of all three treatments on the microbial count in eggshells were comparable, according to the results. In addition, there was no negative effect on either hatchability percentage or embryonic mortality rate. The liver structure from both B-Ag-NPs and P-Ag-NPs treatments exhibited severe and moderate degeneration of hepatocytes, which may indicate possible hazardous effects of using nanoparticles. Using TH4 did not cause liver structure abnormality. In conclusion, using Ag-NPs for sanitizing hatching eggs effectively reduces the eggshell microbial count without affecting the hatchability percentage. Nevertheless, histological changes are appropriate to be considered as a safety parameter in Ag-NPs applications.
Protein overproduction alters exosome secretion in Chinese hamster ovary cells
Authors: Steć Aleksandra , Targońska Monika , Karkosińska Edyta , Słowik Monika , Płoska Agata , Kalinowski Leszek , Wielgomas Bartosz , Waleron Krzysztof , Jasiecki Jacek , Dziomba Szymon
Published: May 2023

Despite the abundance of available cell lines, nearly 70% of all recombinant therapeutic proteins today are produced in Chinese hamster ovary (CHO) cells. The impact of protein overproduction on the secretion of exosomes by CHO cells has been investigated here. Increased secretion of extracellular vesicles (EVs) by protein overexpressing CHO cells was demonstrated with protein content assay, nanoparticle tracking analysis, and capillary electrophoresis. Our results revealed that a protein overproduction might induce EVs secretion, which might be accompanied by the sequestration and loading of overexpressed proteins into the exosomes. These findings are of vital importance for the manufacturing of therapeutics in CHO expression systems due to the risk of product loss during downstream processing of culture medium as well as the application of exosomes as nanocarriers of therapeutic proteins. The study indicates also the importance of culturing process control.
NMR-based comparison of the metabolome of beef from Simmental and black-and-white young bulls during wet- and dry-aging
Authors: Bischof Greta , Witte Franziska , Terjung Nino , Januschewski Edwin , Heinz Volker , Juadjur Andreas , Gibis Monika
Published: May 2023

Taste as an eating quality factor of beef can be influenced by the selection of the raw material and aging method. The metabolic changes of different breeds during aging were analyzed in wet-aged and dry-aged beef up to 28 days of aging using samples from the M. longissimus thoracis et lumborum of the Simmental and Black-and-White breeds by 1H NMR spectroscopy. Breed affected the metabolome of beef samples before and during the aging of beef. The concentration of 24 of the 30 metabolites differed significantly (P < 0.05) in unaged samples of both breeds. In addition, aging time and aging type of beef samples showed partially different effects on the metabolome caused by the breed. Aging time significantly affected (P < 0.05) 30 metabolites in beef of both breeds. Aspartate, betaine, creatinine, glycine, and niacinamide correlated with aging time only in samples of Black-and-White breed. Five metabolites (carnitine, creatine, inosine 5’ monophosphate, lactic acid and O-acetyl-l-carnitine) varied significantly (P < 0.05) between dry-aged and wet-aged beef of both breeds.
Prenatal ultrasound, magnetic resonance imaging and therapeutic options for fetal thoracic anomalies: a pictorial essay
Authors: Caro-Domínguez Pablo , Victoria Teresa , Ciet Pierluigi , de la Torre Estrella , Toscano Ángel Chimenea , Diaz Lutgardo García , Sainz-Bueno José Antonio
Published: May 2023

Congenital thoracic anomalies are uncommon malformations that require a precise diagnosis to guide parental counseling and possible prenatal treatment. Prenatal ultrasound (US) is the gold standard imaging modality to first detect and characterize these abnormalities and the best modality for follow-up. Fetal magnetic resonance imaging (MRI) is a complementary tool that provides multiplanar assessment and tissue characterization and can help estimate prognosis. Prenatal treatment is increasingly being used in fetuses with signs of distress and to potentially decrease morbidity and mortality. In this essay, the authors illustrate side-by-side US, MRI and therapeutic options for congenital thoracic anomalies in cases that presented to a tertiary pediatric hospital during the 7-year period 2014–2021. Entities included are congenital diaphragmatic hernia, congenital pulmonary airway malformation, bronchopulmonary sequestration, hybrid lesions, foregut duplications cysts and congenital lobar overinflation. Treatment options include maternal steroids, thoraco-amniotic shunt and fetal endotracheal occlusion. Recognition of typical findings in congenital thoracic anomalies is helpful to establish diagnosis, predict prognosis and plan perinatal treatment.

Graphical Abstract
New robust subtilisins from halotolerant and halophilic Bacillaceae
Authors: Falkenberg Fabian , Voß Leonie , Bott Michael , Bongaerts Johannes , Siegert Petra
Published: May 2023

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

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

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

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

Rare 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

We 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

Honeybee 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

This 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

Pontine 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

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

Ulotaront 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

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.
Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy
Authors: Jenkinson Allan , Bednarczuk Nadja , Kaltsogianni Ourania , Williams Emma E. , Lee Rebecca , Bhat Ravindra , Dassios Theodore , Milner Anthony D. , Greenough Anne
Published: May 2023

Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised “tube-breathing” circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37–41] weeks, birthweight of 3.1 [2.2–4.0] kg, and postnatal age of 33 (21–62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112).

    Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response.

What is Known:• Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control.• The potential impact of maternal second-hand smoke exposure, however, has not yet been
determined.

What is New:• We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in
newborns with second-hand smoke exposure during pregnancy, in infants whose mothers
smoked, and in controls (non-smoke exposed).• Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was
associated with a delayed newborn ventilatory response.
Management of children with febrile seizures: a Greek nationwide survey
Authors: Kopsidas Ioannis , Dasoula Foteini Eleni , Kourkouni Eleni , Krepi Adamantia , Mystakelis Harry Α. , Spyridis Nikos , Vartzelis George
Published: May 2023

The purpose of this study was to investigate knowledge, principles, and practices concerning the management of children with febrile seizures among pediatricians in Greece. A cross-sectional study was performed across Greece. Pediatricians completed an anonymous and voluntary 11-item questionnaire about their knowledge, attitudes, and practices with respect to the management of febrile seizures; the survey also collected demographic data. It was first administered in paper form in October 2017. This was followed by an online survey performed between June and August of 2018 and publicized by medical boards across Greece. Descriptive statistics and comparisons between groups were conducted with the significance level set at p ≤ 0.05. We recorded 457 responses. Pediatricians admitted to modifying their advice to the parents of children with febrile seizures by suggesting more “aggressive” fever management at low temperatures or systematically (63%), referral to a specialist after any episode of febrile seizures (63%), or hospitalization in a subsequent episode (67%), even though 72% admitted these practices were of no efficacy. Almost one in three pediatricians (28%) believed aggressive management of fever could delay the onset of febrile seizures; increasing age was associated with this perception. A minority (28%) would make parents aware of febrile seizures before a first episode regardless of family history; 38% would do so in the event of family history.

Conclusions: Several pediatricians in Greece use outdated and ineffective practices for the management of febrile seizures, despite the availability of updated evidence-based guidelines. Further training of practitioners is needed to bridge this gap.

What is Known:•Aggressive management of fever at low temperatures with antipyretics, referral to a neurologist, and hospitalization are not supported by evidence or recent guidelines on childhood febrile seizures.•Febrile seizures are especially disturbing to uninformed parents, who may be inclined to pursue aggressive but ineffective treatments as a result.

What is New:•Pediatricians in Greece use non-evidence-based practices for the management of febrile seizures, even when they are aware that these practices are not effective.•Older age increases the likelihood that a pediatrician will pursue guideline non-compliant practices in Greece. At the same time, physicians with over 20 years of experience are more likely to inform parents in advance about febrile seizures.
Prognostic value of preoperative circulating tumor cells for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis
Authors: Yu Jing-jing , Li Ya-ni , Shu Chang , Yang Hui-yuan , Huang Zhao , Tao Ran , Chen Yue-yue , Chen Xiao-ping , Xiao Wei
Published: May 2023

Purpose

The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood.

Methods

In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS).

Results

Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC ≥ 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC ≥ 2 remained an independent predictor in all groups’ multivariate analysis.

Conclusion

We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.
Efficient multi-task learning with adaptive temporal structure for progression prediction
Authors: Zhou Menghui , Zhang Yu , Liu Tong , Yang Yun , Yang Po
Published: May 2023

In this paper, we propose a novel efficient multi-task learning formulation for the class of progression problems in which its state will continuously change over time. To use the shared knowledge information between multiple tasks to improve performance, existing multi-task learning methods mainly focus on feature selection or optimizing the task relation structure. The feature selection methods usually fail to explore the complex relationship between tasks and thus have limited performance. The methods centring on optimizing the relation structure of tasks are not capable of selecting meaningful features and have a bi-convex objective function which results in high computation complexity of the associated optimization algorithm. Unlike these multi-task learning methods, motivated by a simple and direct idea that the state of a system at the current time point should be related to all previous time points, we first propose a novel relation structure, termed adaptive global temporal relation structure (AGTS). Then we integrate the widely used sparse group Lasso, fused Lasso with AGTS to propose a novel convex multi-task learning formulation that not only performs feature selection but also adaptively captures the global temporal task relatedness. Since the existence of three non-smooth penalties, the objective function is challenging to solve. We first design an optimization algorithm based on the alternating direction method of multipliers (ADMM). Considering that the worst-case convergence rate of ADMM is only sub-linear, we then devise an efficient algorithm based on the accelerated gradient method which has the optimal convergence rate among first-order methods. We show the proximal operator of several non-smooth penalties can be solved efficiently due to the special structure of our formulation. Experimental results on four real-world datasets demonstrate that our approach not only outperforms multiple baseline MTL methods in terms of effectiveness but also has high efficiency.
New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics
Authors: Dothel Giovanni , Barbaro Maria Raffaella , Di Vito Aldo , Ravegnini Gloria , Gorini Francesca , Monesmith Sarah , Coschina Emma , Benuzzi Eva , Fuschi Daniele , Palombo Marta , Bonomini Francesca , Morroni Fabiana , Hrelia Patrizia , Barbara Giovanni , Angelini Sabrina
Published: May 2023

Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut–brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators of several mechanisms involved in IBS pathophysiology. These epigenetic factors include biomolecular mechanisms inducing chromosome-related and heritable changes in gene expression regardless of DNA coding sequence. Accordingly, altered gut microbiota may increase the production of metabolites such as sodium butyrate, a prominent inhibitor of histone deacetylases. Patients with IBS showed an increased amount of butyrate-producing microbial phila as well as an altered profile of methylated genes and micro-RNAs (miRNAs). Importantly, gene acetylation as well as specific miRNA profiles are involved in different IBS mechanisms and may be applied for future diagnostic purposes, especially to detect increased gut permeability and visceromotor dysfunctions. In this review, we summarize current knowledge of the role of epigenetics in IBS pathophysiology.
Integrated microfluidic systems for fluorescence monitoring rapid kinetic reactions in bioanalysis
Authors: Écija-Arenas Ángela , Zafra-Poyato Antonio , Fernández-Romero Juan Manuel
Published: May 2023

A stopped-flow microfluidic fluorimetric biosensor to monitor alkaline phosphatase (ALP) activity and evaluate the potential inhibitors has been developed, integrating a magnetically retained enzyme microreactor (MREµR) in the reaction/detection zone of the microfluidic chip. The integration supposed the alignment of the MREµR at the sample compartment of a conventional spectrofluorometer using a 3D-printed device. The analytical signal is based on the fluorescence decrease in the signal obtained in the dephosphorylation reaction of the substrate 4-methylumbelliferone phosphate (4-MUP) by the retained ALP-MNPs in an alkaline medium caused by sulfonamides. The excitation and emission wavelengths to monitor the reaction were 363 and 444 nm, respectively. Three sulfonamides, acetazolamide, furosemide, and sulfasalazine, have been used as model analytes. The front-face operating mode of the spectrofluorometer was used to acquire the instrumental signals. The influence of the rotation angle of the microfluidic device on the efficiency of the signal collection has also been studied, obtaining the signals with greater intensity at 75° from the excitation beam. The dynamic range of the calibration graph was 16.81–1111.22 µg mL−1, expressed as sulfonamide concentration, with a limit of detection of 5.04 µg mL−1 (R2 = 0.9989, n = 10, r = 3) for acetazolamide. The method was applied to determine sulfonamide residues in tap water and milk samples, with 88.9–98.7% recovery values. The results have been compared with those obtained using a commercial device connected to the spectrofluorometer, getting faster reaction kinetics.

Graphical abstract
Artificial intelligence to automate the systematic review of scientific literature
Authors: de la Torre-López José , Ramírez Aurora , Romero José Raúl
Published: May 2023

Artificial intelligence (AI) has acquired notorious relevance in modern computing as it effectively solves complex tasks traditionally done by humans. AI provides methods to represent and infer knowledge, efficiently manipulate texts and learn from vast amount of data. These characteristics are applicable in many activities that human find laborious or repetitive, as is the case of the analysis of scientific literature. Manually preparing and writing a systematic literature review (SLR) takes considerable time and effort, since it requires planning a strategy, conducting the literature search and analysis, and reporting the findings. Depending on the area under study, the number of papers retrieved can be of hundreds or thousands, meaning that filtering those relevant ones and extracting the key information becomes a costly and error-prone process. However, some of the involved tasks are repetitive and, therefore, subject to automation by means of AI. In this paper, we present a survey of AI techniques proposed in the last 15 years to help researchers conduct systematic analyses of scientific literature. We describe the tasks currently supported, the types of algorithms applied, and available tools proposed in 34 primary studies. This survey also provides a historical perspective of the evolution of the field and the role that humans can play in an increasingly automated SLR process.