bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of an expression platform for fungal secondary metabolite biosynthesis in Penicillium crustosum
Authors: Zhou Jenny , Chen Xiaoling , Li Shu-Ming
Published: July 2024

Filamentous fungi are prolific producers of bioactive natural products and play a vital role in drug discovery. Yet, their potential cannot be fully exploited since many biosynthetic genes are silent or cryptic under laboratory culture conditions. Several strategies have been applied to activate these genes, with heterologous expression as one of the most promising approaches. However, successful expression and identification of new products are often hindered by host-dependent factors, such as low gene targeting efficiencies, a high metabolite background, or a lack of selection markers. To overcome these challenges, we have constructed a Penicillium crustosum expression host in a pyrG deficient strain by combining the split-marker strategy and CRISPR-Cas9 technology. Deletion of ligD and pcribo improved gene targeting efficiencies and enabled the use of an additional selection marker in P. crustosum. Furthermore, we reduced the secondary metabolite background by inactivation of two highly expressed gene clusters and abolished the formation of the reactive ortho-quinone methide. Finally, we replaced the P. crustosum pigment gene pcr4401 with the commonly used Aspergillus nidulans wA expression site for convenient use of constructs originally designed for A. nidulans in our P. crustosum host strain. As proof of concept, we successfully expressed a single polyketide synthase gene and an entire gene cluster at the P. crustosum wA locus. Resulting transformants were easily detected by their albino phenotype. With this study, we provide a highly efficient platform for heterologous expression of fungal genes.

Key points

Construction of a highly efficient Penicillium crustosum heterologous expression host

Reduction of secondary metabolite background by genetic dereplication strategy

Integration of wA site to provide an alternative host besides Aspergillus nidulans

Graphical Abstract
Extrapulmonary hyalinizing granuloma: a rare case with intra-articular and tenosynovial involvement
Authors: Alhumayed Mohanad , Austin Ryan P. , Chang Eric Y.
Published: July 2024

Extrapulmonary hyalinizing granuloma (EPHG) is a notably rare condition, representing an exaggerated chronic immune response to antigenic stimuli. This report presents the first documented case of intra-articular and tenosynovial EPHG with radiological evaluation and pathological confirmation in a 60-year-old man presenting with wrist pain and swelling. Imaging findings were relatively symmetric with marked distension of the distal radioulnar joints and extensor tendon sheaths with masses and nodules of various sizes surrounded by synovitis and accompanied by bony erosions. On US, the masses were heterogeneous but mostly hypo- to iso-echoic compared to muscle and relatively hypovascular. On MRI, compared to muscle, the nodules exhibited iso-intense signal on T1-weighted images, iso- to mildly hyper-intense signal on T2-weighted fat-suppressed images, and minimal enhancement on post-contrast images. The diagnosis of EPHG was revealed through biopsy and pathologic examination with glucocorticoids being effective in treatment.
Comparison of the tolerability of 161Tb- and 177Lu-labeled somatostatin analogues in the preclinical setting
Authors: Busslinger Sarah D. , Mapanao Ana Katrina , Kegler Kristel , Bernhardt Peter , Flühmann Fabienne , Fricke Julia , Zeevaart Jan Rijn , Köster Ulli , van der Meulen Nicholas P. , Schibli Roger , Müller Cristina
Published: July 2024

Purpose

[177Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [177Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [161Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of 161Tb- and 177Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice.

Methods

Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the 177Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study.

Results

The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161Tb- and 177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40–50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30–50% and 6–12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities.

Conclusion

Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [161Tb]Tb-DOTA-LM3 and [161Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective 177Lu-based analogues.

Graphical Abstract
Anconeus and pronation: a palpatory and ultrasonographic study
Authors: Canoso Juan J. , Murillo-González Jorge , Mérida-Velasco José Ramón , Kalish Robert A. , Olivas-Vergara Otto , Gómez-Moreno Cristina , Blas Eva García-Carpintero , Fuensalida-Novo Gema , Naredo Esperanza
Published: July 2024

Purpose

Depending on its axis, pronation varies from the radius rotation around the steady ulna to the reciprocal adduction of the radius and abduction of the ulna. While there is no question that pronator teres is a central pronation agonist, anconeus’s role is not settled. The current investigation comparing palpation and ultrasonography in these two muscles during pronation along the axis capitulum-second digit evolved from a serendipitous finding in a clinical anatomy seminar.

Methods

Single-hand palpation and two-transducer ultrasonography over anconeus and pronator teres were used on ten normal subjects to investigate their contraction during pronation around the capitulum-second digit axis. These studies were done independently and blind to the results of the other. The statistical analysis between palpation and ultrasonography was performed with Cohen’s kappa coefficient and the χ2 test.

Results

On palpation, on resisted full pronation, anconeus contracted in 8/10 subjects and pronator teres in 10/10 subjects. Without resistance, the corresponding ratios were 5/10 and 9/10. On two-transducer ultrasonography, the comparable ratios were 7/10 and 10/10, and 3/10 and 10/10. A fair concordance (Cohen’s kappa = 0.21) between palpation and ultrasonography in detecting the simultaneous status of anconeus and pronator teres during resisted full pronation. Anatomic dissection illustrated the elements involved.

Conclusions

Plain palpation confirmed by ultrasonography showed the simultaneous contraction of anconeus and pronator teres during resisted pronation in most of the studied subjects. The study suggests that palpation can be helpful in directly studying muscle activity during movement.
Superior detection of low-allele burden Janus kinase 2 V617F mutation and monitoring clonal evolution in myeloproliferative neoplasms using chip-based digital PCR
Authors: Lu Yiyi , Lin Lin , Lin Jiafei , Wu Beiying , Cai Gang , Wang Xuefeng , Ma Xuefei
Published: July 2024

The JAK2 V617F is a prevalent driver mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph−MPNs), significantly affecting disease progression, immunophenotype, and patient outcomes. The World Health Organization (WHO) guidelines highlight the JAK2 V617F mutation as one of the key diagnostic criterions for Ph−MPNs. In this study, we analyzed 283 MPN samples with the JAK2 V617F mutation to assess the effectiveness of three detection technologies: chip-based digital PCR (cdPCR), real-time quantitative PCR (qPCR), and next-generation sequencing (NGS). Additionally, we investigated the relationship between JAK2 V617F mutant allele burden (% JAK2 V617F) and various laboratory characteristics to elucidate potential implications in MPN diagnosis. Our findings demonstrated high conformance of cdPCR with qPCR/NGS for detecting % JAK2 V617F, but the mutant allele burdens detected by qPCR/NGS were lower than those detected by cdPCR. Moreover, the cdPCR exhibited high sensitivity with a limit of detection (LoD) of 0.08% and a limit of quantification (LoQ) of 0.2% for detecting % JAK2 V617F in MPNs. Clinical implications were explored by correlating % JAK2 V617F with various laboratory characteristics in MPN patients, revealing significant associations with white blood cell counts, lactate dehydrogenase levels, and particularly β2-microglobulin (β2-MG) levels. Finally, a case report illustrated the application of cdPCR in detecting low-allele burdens in a de novo chronic myeloid leukemia (CML) patient with a hidden JAK2 V617F subclone, which expanded during tyrosine kinase inhibitor (TKI) treatment. Our findings underscore the superior sensitivity and accuracy of cdPCR, making it a valuable tool for early diagnosis and monitoring clonal evolution.
Robustness of radiomics among photon-counting detector CT and dual-energy CT systems: a texture phantom study
Authors: Zhu Lan , Dong Haipeng , Sun Jing , Wang Lingyun , Xing Yue , Hu Yangfan , Lu Junjie , Yang Jiarui , Chu Jingshen , Yan Chao , Yuan Fei , Zhong Jingyu
Published: July 2024

Objectives

To evaluate the robustness of radiomics features among photon-counting detector CT (PCD-CT) and dual-energy CT (DECT) systems.

Methods

A texture phantom consisting of twenty-eight materials was scanned with one PCD-CT and four DECT systems (dual-source, rapid kV-switching, dual-layer, and sequential scanning) at three dose levels twice. Thirty sets of virtual monochromatic images at 70 keV were reconstructed. Regions of interest were delineated for each material with a rigid registration. Ninety-three radiomics were extracted per PyRadiomics. The test-retest repeatability between repeated scans was assessed by Bland-Altman analysis. The intra-system reproducibility between dose levels, and inter-system reproducibility within the same dose level, were evaluated by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-system variability among five scanners was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD).

Results

The test–retest repeatability analysis presented that 97.1% of features were repeatable between scan–rescans. The mean ± standard deviation ICC and CCC were 0.945 ± 0.079 and 0.945 ± 0.079 for intra-system reproducibility, respectively, and 86.0% and 85.7% of features were with ICC > 0.90 and CCC > 0.90, respectively, between different dose levels. The mean ± standard deviation ICC and CCC were 0.157 ± 0.174 and 0.157 ± 0.174 for inter-system reproducibility, respectively, and none of the features were with ICC > 0.90 or CCC > 0.90 within the same dose level. The inter-system variability suggested that 6.5% and 12.8% of features were with CV < 10% and QCD < 10%, respectively, among five CT systems.

Conclusion

The radiomics features were non-reproducible with significant variability in values among different CT techniques.

Clinical relevance statement

Radiomics features are non-reproducible with significant variability in values among photon-counting detector CT and dual-energy CT systems, necessitating careful attention to improve the cross-system generalizability of radiomic features before implementation of radiomics analysis in clinical routine.

Key Points

CT radiomics stability should be guaranteed before the implementation in the clinical routine.

Radiomics robustness was on a low level among photon-counting detectors and dual-energy CT techniques.

Limited inter-system robustness of radiomic features may impact the generalizability of models.
Gas detection using cavity-enhanced Raman spectroscopy with a bidirectional multi-pass cell and polarization beam-splitting optical path
Authors: Zheng Yuhao , Zou Xiaer , He Sailing
Published: July 2024

We demonstrate a substantial enhancement of gas Raman scattering using a bidirectional multi-pass cavity CERS system, which incorporates a polarization beam-splitting optical path. The system design allows the laser light to traverse the multi-pass cavity for four specific trips, satisfying the need for quick detection of various gas components. Our gas detection experiments using multi-pass cavities with different times of reflection indicate that the addition of polarization beam-splitting optical path gives 1.5 to 1.68 times enhancement of Raman signal compared with that of the system without polarization beam-splitting. For the detection of CH4, a limit of detection of 1.66 ppm was achieved with our system using a multi-pass cell with 41 times of reflection and an integration time of 30s. Our proposed design, which integrates a bidirectional multi-pass cavity with polarization beam-splitting optical path, gives an economical multicomponent gas detection system and a valuable tool for guiding the design and precise alignment of these cavities. This system shows significant promise for applications in e.g. human breath and environmental monitoring.
The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH: a retrospective cohort study
Authors: Chen Congcong , Pan Ningrui , Chen Zongping , Gou Chengren , He Xu , Wang Min , Chen Bo , Zhou Zidong , Ren Qixu , Zhong Youzhuang , Xiang You , Zhao Sicong , Yan Yong , Song Tao
Published: July 2024

Purpose

To confirm if the CYP17A1 gene regulates the ratio of T/E leading to MetS-BPH.

Methods

824 men, aged 47–88 years, were recruited into this study through consecutive routine physical examination programs and long-term outpatient screening. Several parameters, including SNPs of CYP17A1 gene, total testosterone, estradiol, and the ratio of total testosterone to estradiol (T/E) were obtained for each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and non-BPH groups, MetS and non-MetS groups, and MetS-BPH and non-MetS-BPH groups. Values of the obtained parameters were evaluated using one-way analysis of variance, Student’s t-test, Chi-squared test, and logistic regression analysis.

Results

SNPs of the CYP17A1 gene, including the rs743572 genotypes (GG, GA, and AA), rs3781287 genotypes (GG, GT, TT), and rs4919686 genotypes (CC, CA, and AA), were present in every group. Only the GG genotype of rs743572 was independently associated with BPH (OR = 5.868, 95% CI: 3.363–7.974, P < 0.001), MetS (OR = 7.228, 95% CI: 3.925–11.331, P < 0.001), and MetS-BPH (OR = 3.417, 95% CI: 1.783–5.266, P < 0.001) after adjusting for age. In the population of genotype GG of rs743572, the decrease in T/E ratio was an independent risk factor for BPH (OR = 839.756, 95% CI: 36.978-1334.263, P = 0.001), MetS (OR = 376.988, 95% CI: 12.980-488.976, P < 0.003), and MetS-BPH (OR = 388.236, 95% CI: 24.869-495.363, P = 0.003).

Conclusion

The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH populations.

Trial registration number

ChiCTR2200057632 “retrospectively registered”.

Date of registration

March 15, 2022 “retrospectively registered”.
Stereotactic Body Radiotherapy: is less fractionation more effective in adrenal and renal malignant lesions?
Authors: Rivas Daniel , de la Torre-Luque Alejandro , Moreno-Olmedo Elena , Moreno Paloma , Suárez Vladimir , Serradilla Ana , Arregui Gregorio , Álvarez David , Sallabanda Morena , Lazo Antonio , Núñez María Isabel , López Escarlata
Published: July 2024

Purpose

Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery.

Methods

This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study.

Results

Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months).

Conclusions

This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment.
Declining utilization of urodynamic studies in urological care in Germany: time to say goodbye?
Authors: Baunacke Martin , Kontschak Livia , Menzel Viktoria , Grabbert Markus , Borkowetz Angelika , Mehralivand Sherif , Eisenmenger Nicole , Huber Johannes , Thomas Christian , Schultz-Lampel Daniela
Published: July 2024

Introduction

The number of urodynamic studies (UDS) has been declining steadily in recent decades, yet the reasons behind this trend remain poorly understood. This study aims to investigate the structural aspects of UDS in urology and explore the factors contributing to this decline.

Material & methods

We surveyed all urological departments performing UDS as well as a representative sample of private practices in Germany in 2023. We examined structural situation, waiting times, capacities and limitations of UDS. All invasive urodynamic examinations were defined as UDS.

Results

In 2019, 259/474 (55%) urological departments in Germany performed UDS. 206/259 (80%) urological departments responded to the survey. 163/200 (82%) urological departments stated that their capacities were exhausted, a main reason being lack of medical and nursing staff. 54.8% urological departments performed more than 50% of their UDS for referring physicians. Urological departments with a low number of UDS/year (≤ 100) showed a shorter waiting time (up to 4 weeks: 49% vs. 30%; p = 0.01), reduced UDS capacities (55% vs. 12%; p < 0.001) and these capacities were often not fully utilized (25% vs. 9%; p = 0.007). 122/280 (44%) office urologists responded to the survey. 18/122 (15%) office urologists performed UDS. Main reasons for not offering UDS were lack of personnel and low reimbursement.

Conclusion

In German urological departments, UDS capacities are consistently fully utilized, primarily due to staffing shortages. This trend towards centralization prompts questions about the role of UDS in urologists’ training.
A systematic review comparing the efficacy of 980 nm vs. 1470 nm wavelengths in laser hemorrhoidoplasty
Authors: Li Zhicheng , Wu Jiong , Brown Nana Kwame Domme , Kumassah Philemon Kwame , Agbedinu Kwabena , Ambe Peter C.
Published: July 2024

Background

Laser Hemorrhoidoplasty (LHP) is a minimally invasive surgical option for the management of hemorrhoidal disease that has been increasingly adopted by surgeons over the last decade. Two wavelengths; 980 nm and 1470 nm have been employed in LHP. However, no data exist comparing the effects of these two wavelengths for this indication. This systematic review investigates both wavelengths for the management of hemorrhoids via the LHP procedure.

Methods

This systematic analysis and meta-analysis was performed following the PICOS and PRISMA guidelines. A systematic research of MEDLINE, Scopus, Clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials, CENTRAL and Google Scholar databases from inception until March 2024 was performed.

Results

Overall, 19 studies including seven randomized control trials (RCT) and 12 non-randomized control trials with a total of 2492 patients were included in this systematic review and meta-analysis. The duration of LHP with both wavelengths was significantly shorter compared to open hemorrhoidectomy, postoperative pain and the rate of postoperative complications were significantly lower following LHP. There was no statistically significant difference in the rate of recurrence between LHP with the 980-nm wavelength and open hemorrhoidectomy. However, LHP with 1470-nm wavelength resulted in significantly higher recurrence rate compared to hemorrhoidectomy.

Conclusion

Although no direct studies have compared the two wavelengths used in LHP, the outcomes of LHP seem to be independent of the wavelength used. Both wavelengths, when correctly used provide similar results, which are mostly better compared to open hemorrhoidectomy in terms of postoperative complications and postoperative pain, but not in terms of recurrence, where at least for the 1470-nm wavelength, LHP seems to show a higher recurrence rate when compared to open hemorrhoidectomy. Although a direct comparison of both wavelengths was not possible, technical issues regarding number of shots and energy per pile represent relevant parameters for recurrence after LHP.
A novel polyp retrieval bag reduces the polyp fragmentation rate in colon polypectomy: a single-blind randomized controlled study
Authors: Chu Jindong , Ma Cuiyun , Min Min , Bi Qian , Shen Wei , Zhang Xueting , Zhang Hanqing , Li Aitong , Liu Yan , Lu Zheng
Published: July 2024

Purpose

The fragmentation of polyps affects complete resection confirmation. The primary aim of this study was to assess the feasibility of a novel polyp retrieval bag for reducing the fragmentation rate of colon polyps.

Methods

Patients with a 5–15 mm colon polyp were recruited and randomized into two groups at a 1:1 ratio. After polyp resection, polyps obtained from patients in the treatment group were extracted via a novel polyp retrieval bag without traversing the instrument channel, whereas polyps obtained from patients in the control group were collected through the instrument channel, attaching the polyp trap to the instrument channel port, and applying suction.

Results

From January to July 2022, 225 patients were assessed for eligibility. The study participants included 204 patients, and seven patients whose samples were not retrieved were excluded. Polyp fragmentation was significantly lower in the treatment group than in the control group (3.0% [3/100] vs. 17.5% [17/97], P = 0.001). The retrieval failure rates in the treatment group and control group were not significantly different (2.0% [2/102] vs. 4.9% [5/102], P = 0.442). There were fewer colonoscope insertions in the treatment group than in the control group (102 vs. 110), but a significant difference was not present (P = 0.065). No significant adverse events were observed during the follow-up.

Conclusions

This study demonstrated that the polyp retrieval bag was safe and feasible for reducing the fragmentation rate of retrieved polyps.

Trial registration

The study was registered at ClinicalTrials.gov (NCT05189912, 1/12/2021).
Galectin-3 protects distal convoluted tubules in rhabdomyolysis-induced kidney injury
Authors: Kulow Vera A. , Labes Robert , Czopek Claudia S. , Rosenberger Christian , Fähling Michael
Published: July 2024

Advanced glycation endproducts (AGEs) contribute to cellular damage of various pathologies, including kidney diseases. Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we observed elevated levels of AGEs and the AGE receptor galectin-3 (LGALS3) in the kidney. Immunofluorescence localized LGALS3 to distal nephron segments. According to transcriptomic profiling via next-generation sequencing, RIAKI led to profound changes in kidney metabolism, oxidative stress, and inflammation. Cellular stress was evident in both proximal and distal tubules, as shown by kidney injury markers KIM-1 and NGAL. However, only proximal tubules exhibited overt damage and apoptosis, as detected by routine morphology, active Caspase-3, and TUNEL assay, respectively. In vitro, distal convoluted tubule (DCT) cells challenged with AGEs underwent apoptosis, which was markedly enhanced by Lgals3 siRNA treatment. Thus, in RIAKI, the upregulation of LGALS3 may protect the distal nephron from AGE-mediated damage, while proximal tubules lacking LGALS3 stay at risk. Thus, stimulating LGALS3 in the proximal nephron, if achievable, may attenuate RIAKI.
Impact of lengthening velocity on the generation of eccentric force by slow-twitch muscle fibers in long stretches
Authors: Weidner Sven , Tomalka André , Rode Christian , Siebert Tobias
Published: July 2024

After an initial increase, isovelocity elongation of a muscle fiber can lead to diminishing (referred to as Give in the literature) and subsequently increasing force. How the stretch velocity affects this behavior in slow-twitch fibers remains largely unexplored. Here, we stretched fully activated individual rat soleus muscle fibers from 0.85 to 1.3 optimal fiber length at stretch velocities of 0.01, 0.1, and 1 maximum shortening velocity, vmax, and compared the results with those of rat EDL fast-twitch fibers obtained in similar experimental conditions. In soleus muscle fibers, Give was 7%, 18%, and 44% of maximum isometric force for 0.01, 0.1, and 1 vmax, respectively. As in EDL fibers, the force increased nearly linearly in the second half of the stretch, although the number of crossbridges decreased, and its slope increased with stretch velocity. Our findings are consistent with the concept of a forceful detachment and subsequent crossbridge reattachment in the stretch’s first phase and a strong viscoelastic titin contribution to fiber force in the second phase of the stretch. Interestingly, we found interaction effects of stretch velocity and fiber type on force parameters in both stretch phases, hinting at fiber type-specific differences in crossbridge and titin contributions to eccentric force. Whether fiber type-specific combined XB and non-XB models can explain these effects or if they hint at some not fully understood properties of muscle contraction remains to be shown. These results may stimulate new optimization perspectives in sports training and provide a better understanding of structure–function relations of muscle proteins.
Scabies vaccines: where we stand and challenges ahead
Authors: Sharaf Mahmoud S.
Published: July 2024

Scabies is an itchy skin disease caused by the burrowing mite,Sarcoptes scabiei. During their lifespan, female mites invade the stratum corneum and create tunnels in which they reside, move, feed, deposit fecal pellets, and lay eggs. Globally, more than 200 million people are estimated to be affected by scabies annually. Currently, using scabicidal agents is the only approved method for treating scabies. However, resistance to commonly used agents such as permethrin and ivermectin has been observed in scabies mites. Therefore, the development of vaccines for scabies, either as a preventative measure or for treatment, is crucial to control such neglected diseases. Since the host could evolve a protective immune response that could prevent re-infestation by scabies mites, vaccine development is theoretically possible. This review aims to provide a comprehensive overview of the ongoing challenges regarding the currently available control measures for scabies. It also explores the promising path of scabies vaccine development, highlighting the current state of research and challenges that need to be addressed to develop new and innovative measures for both treating and preventing scabies infections.
Plasticity in biomass allocation underlies tolerance to leaf damage in native and non-native populations of Datura stramonium
Authors: Liñán-Vigo Franco , Núñez-Farfán Juan
Published: July 2024

An introduction to a novel habitat represents a challenge to plants because they likely would face new interactions and possibly different physical context. When plant populations arrive to a new region free from herbivores, we can expect an evolutionary change in their defense level, although this may be contingent on the type of defense, resistance or tolerance, and cost of defense. Here, we addressed questions on the evolution of tolerance to damage in non-native Spanish populations of Datura stramonium by means of two comparative greenhouse experiments. We found differences in seed production, specific leaf area, and biomass allocation to stems and roots between ranges. Compared to the Mexican native populations of this species, non-native populations produced less seeds despite damage and allocate more biomass to roots and less to stems, and had higher specific leaf area values. Plasticity to leaf damage was similar between populations and no difference in tolerance to damage between native and non-native populations was detected. Costs for tolerance were detected in both regions. Two plasticity traits of leaves were associated with tolerance and were similar between regions. These results suggest that tolerance remains beneficial to plants in the non-native region despite it incurs in fitness costs and that damage by herbivores is low in the non-native region. The study of the underlying traits of tolerance can improve our understanding on the evolution of tolerance in novel environments, free from plants’ specialist herbivores.
Investigating the interactive effects of habitat type and light intensity on rocky shores
Authors: Schaefer Nina , Dafforn Katherine A. , Johnston Emma L. , Clark Graeme F. , Mayer-Pinto Mariana
Published: July 2024

Light availability and habitat complexity are two key drivers of community assembly. Urbanisation has been shown to affect both, with important consequences to ecological communities. On the intertidal, for instance, studies have shown that light intensity is greater on natural rocky shores than on less complex artificial habitats (seawalls), though different habitats can also experience similar light intensities, for example when shaded by urban structures. Understanding therefore how these factors individually, and combined, affect communities is important to understand the mechanisms driving changes in community structure, and consequently provide solutions to tackle the increasing homogenisation of habitats and lightscapes in urbanised spaces through smart infrastructure designs. Here, we assessed how different light levels affect the recruitment of communities in rock pools and on emergent rock on an intertidal rocky shore. We cleared 30 patches of emergent rock and 30 rock pools and manipulated light using shades with different light transmissions (full light, procedural control, 75%, 35%, and 15% light transmission, full shade) and assessed mobile and sessile communities monthly for 6 months. Effects of reducing light levels were generally stronger on rock than in pools. Fully shaded plots supported double the amount of mobile organisms than plots in full sunlight, in both habitats. Algal cover was higher in pools compared to rock, and at intermediate light levels, but effects varied with site. This study highlights the importance of variable light conditions and different habitats for rocky shore communities, which should be considered in future coastal developments to retain natural biodiversity.
Validity and Reliability of Dysphagia Outcome Severity Scale (DOSS) When Used to Rate Flexible Endoscopic Evaluations of Swallowing (FEES)
Authors: Fransson Johanna , Thorén Sofia , Selg Jenny , Bergström Liza , Hägglund Patricia
Published: July 2024

The Dysphagia Outcome and Severity Scale is used both clinically and within dysphagia research, internationally. Although it was developed using videofluoroscopic swallowing studies, it is frequently used to rate Flexible Endoscopic Evaluations of Swallowing. The validity and reliability of DOSS-use with FEES, however, has not previously been evaluated. This study investigated the validity and rater reliability of clinicians using DOSS to rate FEES. Eleven Speech-Language Pathologists (SLPs) with varied dysphagia experience were recruited to review and DOSS-rate 17 soundless FEES (198 bolus swallows) recorded from 11 heterogenic dysphagic patients (2 cases with repeat FEES) and 4 healthy adults. The SLPs DOSS-ratings were compared against the initial comprehensive dysphagia evaluation (including patient diagnosis, interview, cranial nerve and complete FEES assessment) with Functional Oral Intake Scale (FOIS) and DOSS outcome measures. The SLPs were blinded to patient details and comprehensive dysphagia examination. Re-randomised rating of FEES cases occurred two weeks later (intra rater reliability). Criterion validity for DOSS-ratings (compared against comprehensive dysphagia evaluation with FOIS and DOSS) were strong–very strong (rs = 0.858 and 0.936 respectively; p < 0.001). Inter rater reliability demonstrated high agreement (α = 0.891), also intra rater reliability demonstrated almost perfect agreement (Kw = 0.945). This study’s results, with strong–very strong criterion validity and high rater reliability by SLPs, adds to the evidence for DOSS-use with FEES. Future validity research comparing DOSS with both FEES and VFSS simultaneously is recommended.
Multi-objective optimization of virtual machine migration among cloud data centers
Authors: Maldonado Carrascosa Francisco Javier , Seddiki Doraid , Jiménez Sánchez Antonio , García Galán Sebastián , Valverde Ibáñez Manuel , Marchewka Adam
Published: July 2024

Workload migration among cloud data centers is currently an evolving task that requires substantial advancements. The incorporation of fuzzy systems holds potential for enhancing performance and efficiency within cloud computing. This study addresses a multi-objective problem wherein the goal is to maximize the interpretability and the percentage of renewable energy consumed by a fuzzy meta-scheduler system in cloud scenarios. To accomplish this objective, the present research proposes a novel approach utilizing a multi-objective Knowledge Acquisition with a Swarm Intelligence Approach algorithm. Additionally, it takes advantage of a framework built on CloudSim, which includes virtual machine migration capabilities based on an expert system. Furthermore, a hierarchical fuzzy system is employed to assess rule base interpretability, along with another multi-objective algorithm, named Non-dominated Sorting Genetic Algorithm II. The framework and hierarchical system are employed to perform various simulation results concerning renewable energy and interpretability, while the algorithms aim to enhance the system’s performance and interpretability. Empirical results demonstrate that it is possible to improve the performance of cloud data centers while improving the interpretability of the corresponding fuzzy rule-based system. The proposed multi-objective algorithm shows comparable or superior performance to the genetic algorithm across diverse scenarios. The simulation results indicate that improvements in cloud data center performance can be achieved while enhancing system interpretability. The average improvement in the interpretability index ranges from 0.6 to 6%, with a corresponding increase in renewable energy utilization ranging from 5 to 6%.
Time series data mining for railway wheel and track monitoring: a survey
Authors: Lourenço Afonso , Ribeiro Diogo , Fernandes Marta , Marreiros Goreti
Published: July 2024

The railway sector has witnessed a significant surge in condition-based maintenance, thanks to the proliferation of sensing technologies and data-driven methodologies, such as machine learning. However, despite the plethora of algorithms designed to detect and classify track irregularities and wheel out-of-roundness, they often fall short when put to the test in real-world scenarios. These shortcomings typically stem from their inability to meet all four critical requirements for constructing an effective maintenance plan: (R1) suitability of the condition-based maintenance strategy, (R2) availability of relevant data, (R3) proper problem formulation, and (R4) accurate evaluation of data mining methods. In response to the absence of a unified framework and standardized guidelines, this survey delves into the realm of time series sensor data and wheel-track interface components for railway structural health monitoring. This survey aims to bridge this gap by offering an extensive categorization, pinpointing existing challenges, and outlining potential directions for future research. Through these efforts, this survey provides a more thorough and targeted exploration of the subject matter, contributing to the advancement of this field.
ETSVF-COVID19: efficient two-stage voting framework for COVID-19 detection
Authors: Akyol Kemal
Published: July 2024

COVID-19 disease, an outbreak in the spring of 2020, reached very alarming dimensions for humankind due to many infected patients during the pandemic and the heavy workload of healthcare workers. Even though we have been saved from the darkness of COVID-19 after about three years, the importance of computer-aided automated systems that support field experts in the fight against with global threat has emerged once again. This study proposes a two-stage voting framework called ETSVF-COVID19 that includes transformer-based deep features and a machine learning approach for detecting COVID-19 disease. ETSVF-COVID19, which offers 99.2% and 98.56% accuracies on computed tomography scan and X-radiation images, respectively, could compete with the related works in the literature. The findings demonstrate that this framework could assist field experts in making informed decisions while diagnosing COVID-19 with its fast and accurate classification role. Moreover, ETSVF-COVID19 could screen for chest infections and help physicians, particularly in areas where test kits and specialist doctors are inadequate.
Tips and tricks in tremor treatment
Authors: Hopfner Franziska , Buhmann Carsten , Classen Joseph , Holtbernd Florian , Klebe Stephan , Koschel Jiri , Kohl Zacharias , Paus Sebastian , Pedrosa David J.
Published: July 2024

Tremor, whether arising from neurological diseases, other conditions, or medication side effects, significantly impacts patients' lives. Treatment complexities necessitate clear algorithms and strategies. Levodopa remains pivotal for Parkinson's tremor, though response variability exists. Some dopamine agonists offer notable tremor reduction targeting D2 receptors. Propranolol effectively manages essential tremor and essential tremor plus (ET/ET +), sometimes with primidone for added benefits, albeit dose-dependent side effects. As reserve medications anticholinergics and clozapine are used for treatment of parkinsonian tremor, 1-Octanol and certain anticonvulsant drugs for tremor of other orign, especially ET. Therapies such as invasive deep brain stimulation and lesional focused ultrasound serve for resistant cases. A medication review is crucial for all forms of tremor, but it is particularly important if medication may have triggered the tremor. Sensor-based detection and non-drug interventions like wristbands and physical therapy broaden diagnostic and therapeutic horizons, promising future tremor care enhancements. Understanding treatment nuances is a key for tailored tremor management respecting patient needs and tolerability. Successful strategies integrate pharmacological, non-invasive, and technological modalities, aiming for optimal symptom control and improved quality of life.
Effects of proanthocyanidin-functionalized hydroxyapatite nanoparticles on dentin bonding
Authors: Enrich-Essvein Tattiana , González-López Santiago , Rodríguez-Navarro Alejandro B. , Cifuentes-Jiménez Carolina , Maravic Tatjana , Mazzitelli Claudia , Checchi Vittorio , Josic Uros , Mazzoni Annalisa , Breschi Lorenzo
Published: July 2024

Objectives

To evaluate the effect of proanthocyanidin-functionalized hydroxyapatite nanoparticles (nHAp_PA) used as pretreatment at different concentrations on the microtensile bond strength (µTBS) and endogenous enzymatic activity (MMPs) on pH-cycled dentin after 24 h and 6 months of artificial aging.

Materials and methods

Fifty human sound dentin blocks were randomly assigned to 5 groups (n = 10): (i) negative control (no treatment); (ii) positive control (pH-cycling); (iii) pH-cycling + 2% nHAp_PA for 60s; (iv) pH-cycling + 6.5% nHAp_PA for 60s; (v) pH-cycling + 15% nHAp_PA for 60s. A self-etch adhesive was used for bonding procedures before resin composite build-ups. Specimens were tested with the µTBS test after 24 h and 6 months of laboratory storage. The proteolytic activity in each group was evaluated with gelatin zymography and in situ zymography. Data were statistically analyzed (p < 0.05).

Results

At 24 h, the µTBS of the experimental groups were significantly higher than the controls (p ≤ 0.001), and no differences were observed between different concentrations (p > 0.05). Artificial aging significantly decreased bond strength in all groups (p ≤ 0.008); however, nHAp_PA 2% still yielded higher bonding values than controls (p ≤ 0.007). The groups pretreated with nHAp_PA exhibited lower MMP-9 and MMP-2 activities compared to the positive control group and almost the same enzymatic activity as the negative control group. In situ zymography showed that after 6 months of aging, nHAp_PA 2% and nHAp_PA 6,5% decreased enzymatic activity as well as the negative control.

Conclusions

Dentin pretreatment with nHAp_PA increased the bonding performance of a self-etch adhesive and decreased MMP-2 and MMP-9 activities after 6 months.
Effects of temperature, chloride and perchlorate salt concentration on the metabolic activity of Deinococcus radiodurans
Authors: Symeonidou Eftychia , Jørgensen Uffe Gråe , Madsen Morten Bo , Priemé Anders
Published: July 2024

The extremophile bacterium Deinococcus radiodurans is characterized by its ability to survive and sustain its activity at high levels of radiation and is considered an organism that might survive in extraterrestrial environments. In the present work, we studied the combined effects of temperature and chlorine-containing salts, with focus on perchlorate salts which have been detected at high concentrations in Martian regolith, on D. radiodurans activity (CO2 production rates) and viability after incubation in liquid cultures for up to 30 days. Reduced CO2 production capacity and viability was observed at high perchlorate concentrations (up to 10% w/v) during incubation at 0 or 25 °C. Both the metabolic activity and viability were reduced as the perchlorate and chloride salt concentration increased and temperature decreased, and an interactive effect of temperature and salt concentration on the metabolic activity was found. These results indicate the ability of D. radiodurans to remain metabolically active and survive in low temperature environments rich in perchlorate.
The role of the environment within a constellation of interacting causal factors shaping mobility—the example of three oases in Northern Africa
Authors: Sobczak-Szelc Karolina
Published: July 2024

Northern Africa’s oases are fragile agroecosystems that, through environmental limitations on agricultural development, such as insufficient amounts of water for irrigation, have had to face a profound transformation of the environment on which livelihoods depend. A common strategy in such a situation is mobility. Though mobility responds to similar environmental limitations, the varying economic, social, demographic, and political contexts lead to divergent forms of it. Based on the mixed-method research conducted in the three oases located on the edge of the Sahara Desert (Mhamid in Morocco, El Faouar, and El Ferch in Tunisia), this paper explores the complex interplay of environmental and non-environmental factors shaping mobility. It highlights the need for a contextualization analysis of the mobility-environment nexus, illustrating how different factors’ constellations make mobility part of adaptation, coping, or escape strategies. The results reveal the dynamics of intertwined factors influencing mobility in the oases, sometimes dominated by environmental factors, other times by economic ones, and so forth. This makes their residents subject to fluid categorisation as environmental migrants, and the mobility-environmental nexus itself is highly complex.
Effects of night-float shifts on cognitive function among radiology residents
Authors: Flink Carl C. , Hobohm Robert E. , Zhang Bin , Jacobson Deborah L. , England Eric B.
Published: July 2024

Background

Many radiology programs utilize a night-float system to mitigate the effects of fatigue, improve patient care, and provide faster report turnaround times. Prior studies have demonstrated an increase in discrepancy rates during night-float shifts.

Objectives

This study was performed to examine the effects of night-float shift work on radiology resident cognition. We hypothesized that there would be diminished cognitive function on testing following night-float shifts when compared to testing following day shifts.

Methods

Diagnostic radiology residents in their second to fifth years of residency at a single institution were recruited to participate in this pilot study. Cognitive function was evaluated using the Lumosity Neurocognitive Performance Tests (NCPT), standardized performance tests that provide real-time, objective measurements of cognitive function. Study participants completed the NCPT in 5 sessions following 5 consecutive day shifts to evaluate their baseline cognitive function. The tests were re-administered at the end of consecutive night-float shifts to assess for any changes. Sleep was objectively monitored using actigraphy devices worn around the wrist during all study weeks. Descriptive and summary statistics were performed.

Results

23 prospectively recruited diagnostic radiology residents working night-float shifts took a mean 13.6 (± 5.1) neurocognitive performance tests during the study period. There was a statistically significant decline in 2 of the 6 cognitive tests administered, signifying a decrease in attention, speed, and complex reasoning ability. Night-float shifts were significantly longer than the day shifts and associated with a significantly higher study volume and cross-sectional study volume. Fitbit data demonstrated that there were no significant differences in level of activity while awake. However, participants slept significantly longer during day shifts.

Conclusions

A sample of 23 radiology residents working night-float shifts demonstrated declines in attention, speed, and complex reasoning ability following sequential administration of standardized neurocognitive performance tests. While the sample size is small, these findings demonstrate the potential deleterious effects of night-float shift work and provide evidence to support further inquiry into this phenomenon.