bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal variability is a major source of uncertainty in soil carbon measurements
Authors: Wuest Stewart B. , Durfee Nicole
Published: March 2024

Monitoring changes in soil organic carbon over time is important to many agricultural and environmental goals. Despite decades of measurements, temporal variability in soil carbon measurements has not been studied extensively. In this report, we examine five sets of monthly samples extending up to 3 years each that were collected from field experiments at four locations representative of dryland farming in the Pacific Northwest. The variance from month‐to‐month was 15%–32% of the random error, averaging 20%. This was often greater than the variance between replicate experimental units (2%–42%, averaging 17%). At certain sites, sequential samples were found to be temporally autocorrelated, but no consistent trend patterned on seasonal factors like precipitation was found. This suggests that a single point‐in‐time sample can deviate substantially from the long‐term average soil carbon at the site. We illustrate this problem with the results of repeated soil samples taken from 12 commercial farm fields. We recommend that confidence intervals for soil organic carbon estimates should include variance based on a large population of samples rather than from a single sample set at one timepoint.
Hydrazide‐Bridged Pyridazines for Cholinesterase Inhibitors: Synthesis, Characterizations, In Silico, and In Vitro Evaluation
Authors: Gursoy Sule , Taskor Onel Gulce , Turkmenoglu Burcin , Bozbey Merde Irem , Dilek Esra , Hepokur Ceylan , Algul Oztekin
Published: March 2024

In this study, we investigate the inhibitory potential of a series of hydrazide derivatives bearing different substituents with the pyridazine structure (5 a–i and 6 a–f) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using a modified Ellman's method. The inhibitory profiles of the synthesized compounds were assessed by comparing their IC50 and Ki values. Our results demonstrate that all the compounds exhibit significant inhibitory activity against both AChE and BChE when compared to the reference compound, tacrine. Particularly, compound 6 a exhibited the highest activity against Electrophorus electricus AChE (EeAChE) with a Ki value of 3.26 nM, while compound 5 a displayed the most potent inhibition against equine BChE (eqBChE) with a Ki value of 0.94 nM. The compounds did not possess significant cytotoxicity action using the MTT assay on the cancer cell lines. The DPPH assays revealed that all the compounds have moderate antioxidant activities. Furthermore, molecular docking studies provided valuable insights into the interaction mechanisms of these compounds within the active sites of AChE and BChE crystal structures (PDB ID: 4EY7 and 4BDS, respectively). The above results indicated that the pyridazine‐based compounds were a promising functional agent for the treatment of Alzheimer's disease.
Electrostatic Potential Design of Solid Additives for Enhanced Molecular Order of Polymer Donor in Efficient Organic Solar Cells
Authors: Chen Zhenghong , Guo Chuanhang , Wang Liang , Chen Chen , Cai Jinlong , Liu Chenhao , Gan Zirui , Sun Yuandong , Zhou Jinpeng , Zhou Jing , Liu Dan , Wang Tao , Li Wei
Published: March 2024

Polymeric semiconducting materials struggle to achieve fast charge mobility due to low structural order. In this work, five 1H‐indene‐1,3(2H)dione‐benzene structured halogenated solid additives namely INB‐5F, INB‐3F, INB‐1F, INB‐1Cl, and INB‐1Br with gradually varied electrostatic potential are designed and utilized to regulate the structural order of polymer donor PM6. Molecular dynamics simulations demonstrate that although the dione unit of these additives tends to adsorb on the backbone of PM6, the reduced electrostatic potential of the halogen‐substituted benzene can shift the benzene interacting site from alkyl side chains to the conjugated backbone of PM6, not only leading to enhanced π–π stacking in out‐of‐plane but also arising new π–π stacking in in‐plane together with the appearance of multiple backbone stacking in out‐of‐plane, consequent to the co‐existence of face‐on and edge‐on molecular orientations. This molecular packing transformation further translates to enhanced charge transport and suppressed carrier recombination in their photovoltaics, with a maximum power conversion efficiency of 19.4% received in PM6/L8‐BO layer‐by‐layer deposited organic solar cells.
A Versatile Microchannel Array Device for Portable and Parallel Droplet Generation
Authors: Tang Zhengmin , Reynolds David Eun , Lv Caishu , Zhang Dandan , Ko Jina , Wang Yongcheng
Published: March 2024

The efficient generation of monodispersed droplets holds great promise for micro‐/nanoparticle synthesis and biochemical analysis. However, it remains a challenge to achieve high‐throughput generation of monodispersed droplets in a portable and/or parallel manner in nonexpert biomedical laboratories. Herein, a versatile microchannel array (μCA) device is reported that is portable, multifaceted, reliable, and mass‐manufacturable, supporting the high‐throughput generation of monodispersed droplets in different ways. This device consists of a silicon‐based μCA chip based on the step emulsification principle, as well as two matching plastic containers, both of which can be mass‐manufactured by traditional microfabrication methods at low material costs. With the μCA device, aqueous solution can be dispersed into emulsion droplets by various modes, such as mechanical pump‐based large‐scale, handheld syringe‐based portable, and gas pump‐based highly parallel droplet generation. Furthermore, it is demonstrated that our cost‐effective device can be applied for digital polymerase chain reaction analysis, supporting the need for more accessible microfluidic systems. Thus, the present device is expected to have a significant impact on both benchside and bedside applications.
Arsenic exposure induced renal fibrosis via regulation of mitochondrial dynamics and the NLRP3‐TGF‐β1/SMAD signaling pathway
Authors: Ren Miaomiao , Li Jing , Xu Zehua , Nan Bingru , Gao Hongying , Wang Heng , Lin Yi , Shen Heqing
Published: March 2024

Environmental arsenic exposure is one of the major global public health problems. Studies have shown that arsenic exposure can cause renal fibrosis, but the underlying mechanism is still unclear. Integrating the in vivo and in vitro models, this study investigated the potential molecular pathways for arsenic‐induced renal fibrosis. In this study, SD rats were treated with 0, 5, 25, 50, and 100 mg/L NaAsO2 for 8 weeks via drinking water, and HK2 cells were treated with different doses of NaAsO2 for 48 h. The in vivo results showed that arsenic content in the rats' kidneys increased as the dose increased. Body weight decreased and kidney coefficient increased at 100 mg/L. As a response to the elevated NaAsO2 dose, inflammatory cell infiltration, renal tubular injury, glomerular atrophy, tubulointerstitial hemorrhage, and fibrosis became more obvious indicated by HE and Masson staining. The kidney transcriptome profiles further supported the protein–protein interactions involved in NaAsO2‐induced renal fibrosis. The in vivo results, in together with the in vitro experiments, have revealed that exposure to NaAsO2 disturbed mitochondrial dynamics, promoted mitophagy, activated inflammation and the TGF‐β1/SMAD signaling pathway, and finally resulted in fibrosis. In summary, arsenic exposure contributed to renal fibrosis via regulating the mitochondrial dynamics and the NLRP3‐TGF‐β1/SMAD signaling axis. This study presented an adverse outcome pathway for the development of renal fibrosis due to arsenic exposure through drinking water.
Discovery of the tryptanthrin‐derived indoloquinazoline as an anti‐breast cancer agent via ERK/JNK activation
Authors: Chang Chih‐Shiang , Bai Li‐Yuan , Chiu Chang‐Fang , Hu Jing‐Lan , Weng Jing‐Ru
Published: March 2024

Tryptanthrin, an alkaloid applied in traditional Chinese medicine, exhibits a variety of pharmacological activities. This study aimed to investigate the anti‐tumor activity of the tryptanthrin derivative (8‐cyanoindolo[2,1‐b]quinazoline‐6,12‐dione [CIQ]) in breast cancer cells. In both MDA‐MB‐231 and MCF‐7 breast cancer cells, CIQ inhibited cell viability and promoted caspase‐dependent apoptosis. At the concentration‐ and time‐dependent ways, CIQ increased the levels of p‐ERK, p‐JNK, and p‐p38 in breast cancer cells. We found that exposure to the JNK inhibitor or the ERK inhibitor partially reversed CIQ's viability. We also observed that CIQ increased reactive oxygen species (ROS) generation, and upregulated the phosphorylation and expression of H2AX. However, the pretreatment of the antioxidants did not protect the cells against CIQ's effects on cell viability and apoptosis, which suggested that ROS does not play a major role in the mechanism of action of CIQ. In addition, CIQ inhibited the invasion of MDA‐MB‐231 cells and decreased the expression of the prometastatic factors (MMP‐2 and Snail). These findings demonstrated that the possibility of this compound to show promise in playing an important role against breast cancer.
Synthesis and antibacterial activity of metallic copper‐chitosan nanomaterial using environmentally friendly Cleistocalyx operculatus leaf extract as a reducing agent
Authors: Pham Phuong Anh , Doan Thi Hai , Nguyen Thi Nhiem , Nguyen Minh Viet , Ngo Quoc Anh , Kulikouskaya Viktoryia , Tran Quang Vinh
Published: March 2024

The copper‐chitosan nanomaterial (CuNPs‐CTS) was effectively produced through a chemical reduction process employing Cleistocalyx operculatus leaf extract (COLE) as a reduction agent and chitosan as a stabilization agent. Both COLE and chitosan were derived from natural sources and are environmentally friendly. Various techniques including XRD, SEM, TEM, and DLS were used to characterize the samples. The findings revealed the exclusive presence of CuNPs metal when COLE was used as the reducing agent, while the presence of both metallic Cu and Cu2O was the result of using NaBH4. The CuNPs‐CTS material synthesized with COLE displayed CuNPs particles with diameters varying from 10 to 30 nm. CuNPs‐CTS materials were tested for their antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria. CuNPs‐CTS materials effectively inhibited the growth of these bacteria, significantly expanding the bacterial inhibition zone compared to the control sample (distilled water). The CuNPs‐CTS material using COLE exhibited a bacterial inhibition zone diameter of around 20 and 18 mm against S. aureus and E. coli, respectively. This surpassed the antibacterial performance of the CuNPs‐CTS material employing NaBH4 against S. aureus (18 mm).
The colourful antenna subtraction method
Authors: Gehrmann T. , Glover E. W. N. , Marcoli M.
Published: March 2024

Abstract

We present a general subtraction scheme for NNLO calculations in massless QCD: the colourful antenna subtraction method. It is a reformulation of the antenna subtraction approach designed to address some of the limitations of the traditional framework, especially aiming at high-multiplicity processes. In the context of the new formalism, structures needed to locally subtract the infrared-divergent behaviour of real emission corrections are systematically inferred from virtual subtraction terms, relying on the cancellation of infrared singularities and on the correspondence between integrated and unintegrated antenna functions. We illustrate in detail how the colourful antenna subtraction method works up to NNLO. The algorithm is particularly suited to be fully automated for the generation of NNLO subtraction terms for generic processes. We employ the new formalism to assemble the subtraction terms required for the calculation of the NNLO correction to hadronic three-jet production and describe their validation procedure.
Boosting likelihood learning with event reweighting
Authors: Chen Siyu , Glioti Alfredo , Panico Giuliano , Wulzer Andrea
Published: March 2024

Abstract

Extracting maximal information from experimental data requires access to the likelihood function, which however is never directly available for complex experiments like those performed at high energy colliders. Theoretical predictions are obtained in this context by Monte Carlo events, which do furnish an accurate but abstract and implicit representation of the likelihood. Strategies based on statistical learning are currently being developed to infer the likelihood function explicitly by training a continuous-output classifier on Monte Carlo events. In this paper, we investigate the usage of Monte Carlo events that incorporate the dependence on the parameters of interest by reweighting. This enables more accurate likelihood learning with less training data and a more robust learning scheme that is more suited for automation and extensive deployment. We illustrate these advantages in the context of LHC precision probes of new Effective Field Theory interactions.
Fully nonlinear transformations of the Weyl-Bondi-Metzner-Sachs asymptotic symmetry group
Authors: Flanagan Éanna É. , Nichols David A.
Published: March 2024

Abstract

The asymptotic symmetry group of general relativity in asymptotically flat spacetimes can be extended from the Bondi-Metzner-Sachs (BMS) group to the generalized BMS (GMBS) group suggested by Campiglia and Laddha, which includes arbitrary diffeomorphisms of the celestial two-sphere. It can be further extended to the Weyl BMS (BMSW) group suggested by Freidel, Oliveri, Pranzetti and Speziale, which includes general conformal transformations. We compute the action of fully nonlinear BMSW transformations on the leading order Bondi-gauge metric functions: specifically, the induced metric, Bondi mass aspect, angular momentum aspect, and shear. These results generalize previous linearized results in the BMSW context by Freidel et al., and also nonlinear results in the BMS context by Chen, Wang, Wang and Yau. The transformation laws will be useful for exploring implications of the BMSW group.
The exon junction complex is required for DMD gene splicing fidelity and myogenic differentiation
Authors: Da Cunha Dylan , Miro Julie , Van Goethem Charles , Notarnicola Cécile , Hugon Gérald , Carnac Gilles , Cossée Mireille , Koenig Michel , Tuffery-Giraud Sylvie
Published: March 2024

Deposition of the exon junction complex (EJC) upstream of exon-exon junctions helps maintain transcriptome integrity by preventing spurious re-splicing events in already spliced mRNAs. Here we investigate the importance of EJC for the correct splicing of the 2.2-megabase-long human DMD pre-mRNA, which encodes dystrophin, an essential protein involved in cytoskeletal organization and cell signaling. Using targeted RNA-seq, we show that knock-down of the eIF4A3 and Y14 core components of EJC in a human muscle cell line causes an accumulation of mis-splicing events clustered towards the 3′ end of the DMD transcript (Dp427m). This deregulation is conserved in the short Dp71 isoform expressed ubiquitously except in adult skeletal muscle and is rescued with wild-type eIF4A3 and Y14 proteins but not with an EJC assembly-defective mutant eIF4A3. MLN51 protein and EJC-associated ASAP/PSAP complexes independently modulate the inclusion of the regulated exons 71 and 78. Our data confirm the protective role of EJC in maintaining splicing fidelity, which in the DMD gene is necessary to preserve the function of the critical C-terminal protein–protein interaction domain of dystrophin present in all tissue-specific isoforms. Given the role of the EJC in maintaining the integrity of dystrophin, we asked whether the EJC could also be involved in the regulation of a mechanism as complex as skeletal muscle differentiation. We found that eIF4A3 knockdown impairs myogenic differentiation by blocking myotube formation. Collectively, our data provide new insights into the functional roles of EJC in human skeletal muscle.
Contests on networks
Authors: Matros Alexander , Rietzke David
Published: March 2024

We develop a model of contests on networks. Each player is connected to a set of contests and exerts a single effort to increase the probability of winning each contest to which she is connected. We explore how behavior is shaped by the pattern of interactions and characterize the networks that tend to induce greater effort; in particular, we show that the complete bipartite network is the unique structure that maximizes aggregate player effort. We also obtain a new exclusion result—akin to the Exclusion Principle of Baye et al. (Am Econ Rev 83(1):289-294, 1993)—which holds under the lottery CSF, and contrasts prior work in contests. Finally, new insight into uniqueness of equilibrium for network contest games is provided. Our framework has a broad range of applications, including research and development, advertising, and research funding.
End-time regularity theorem for Brakke flows
Authors: Stuvard Salvatore , Tonegawa Yoshihiro
Published: March 2024

For a general k-dimensional Brakke flow in $${\mathbb {R}}^n$$

R

n

locally close to a k-dimensional plane in the sense of measure, it is proved that the flow is represented locally as a smooth graph over the plane with estimates on all the derivatives up to the end-time. Moreover, at any point in space-time where the Gaussian density is close to 1, the flow can be extended smoothly as a mean curvature flow up to that time in a neighborhood: this extends White’s local regularity theorem to general Brakke flows. The regularity result is in fact obtained for more general Brakke-like flows, driven by the mean curvature plus an additional forcing term in a dimensionally sharp integrability class or in a Hölder class.
Predicting Peri-Operative Cardiorespiratory Adverse Events in Children with Idiopathic Pulmonary Arterial Hypertension Undergoing Cardiac Catheterization Using Echocardiography: A Cohort Study
Authors: Dawes Timothy J. W. , Woodham Valentine , Sharkey Emma , McEwan Angus , Derrick Graham , Muthurangu Vivek , Moledina Shahin , Hepburn Lucy
Published: March 2024

General anesthesia in children with idiopathic pulmonary arterial hypertension (PAH) carries an increased risk of peri-operative cardiorespiratory complications though risk stratifying individual children pre-operatively remains difficult. We report the incidence and echocardiographic risk factors for adverse events in children with PAH undergoing general anesthesia for cardiac catheterization. Echocardiographic, hemodynamic, and adverse event data from consecutive PAH patients are reported. A multivariable predictive model was developed from echocardiographic variables identified by Bayesian univariable logistic regression. Model performance was reported by area under the curve for receiver operating characteristics (AUCroc) and precision/recall (AUCpr) and a pre-operative scoring system derived (0–100). Ninety-three children underwent 158 cardiac catheterizations with mean age 8.8 ± 4.6 years. Adverse events (n = 42) occurred in 15 patients (16%) during 16 catheterizations (10%) including cardiopulmonary resuscitation (n = 5, 3%), electrocardiographic changes (n = 3, 2%), significant hypotension (n = 2, 1%), stridor (n = 1, 1%), and death (n = 2, 1%). A multivariable model (age, right ventricular dysfunction, and dilatation, pulmonary and tricuspid regurgitation severity, and maximal velocity) was highly predictive of adverse events (AUCroc 0.86, 95% CI 0.75 to 1.00; AUCpr 0.68, 95% CI 0.50 to 0.91; baseline AUCpr 0.10). Pre-operative risk scores were higher in those who had a subsequent adverse event (median 47, IQR 43 to 53) than in those who did not (median 23, IQR 15 to 33). Pre-operative echocardiography informs the risk of peri-operative adverse events and may therefore be useful both for consent and multi-disciplinary care planning.
Long-term CT follow-up of patients with lumbar spondylolysis reveals low rate of spontaneous bone fusion
Authors: Staudenmann Anita , Marth Adrian Alexander , Stern Christoph , Fröhlich Stefan , Sutter Reto
Published: March 2024

Objectives

Knowledge about the long-term outcome of patients with lumbar spondylolysis (LS) is limited. This study assessed the frequency of bone fusion in conservatively treated lumbar spondylolysis with photon counting detector computed tomography.

Methods

Patients with lumbar spondylolysis diagnosed with CT or MRI were prospectively enrolled and underwent CT 5–10 years after initial imaging. Image assessment included evaluation of Meyerding grade, listhesis size, measurement of the lysis gap, and disc integrity on the lysis level. Comparisons were made between bone fusion as the primary endpoint and sex, body mass index, age at diagnosis, follow-up interval, size of listhesis, Meyerding grade, size of the lysis gap, sports activity, and presence of pain.

Results

A total of 39 patients (26.0 ± 3.1 years, 15 female) with lumbar spondylolysis on 41 levels were included after a mean follow-up period of 9.1 ± 2.2 years. Nine patients (22.0%, four female) showed complete fusion of the lysis gap. Patients with bone fusion of the lysis gap had a significantly lower Meyerding grade (p = 0.01), smaller size of the listhesis (p = 0.019), and smaller anterior and posterior lysis gap size (p = 0.046 and p = 0.011, respectively). Unilateral lyses showed significantly higher fusion rates than bilateral lyses (40.0% vs. 16.1%, p = 0.01). No statistically significant difference was found for pain at follow-up between patients with and without bone fusion (p = 0.253).

Conclusion

Bone fusion occurred in about a fifth of conservatively treated lumbar spondylolysis after a follow-up period of 9 years. Factors associated with a successful fusion were a lower Meyerding grade, minimal listhesis, and a small lysis gap.
Background contrast affects detection and recognition of courting wolf spiders by intended and unintended receivers
Authors: Uetz George W. , Gilbert Rachel , Wilson Rebecca , Mann Jacqueline , Macedonia Joseph , Clark David L.
Published: March 2024

We used video playback of courting male Schizocosa ocreata wolf spiders to examine responses of intended receivers (conspecific females) and eavesdroppers (competitor males, predatory spiders, toads) to manipulations of spider color (natural color, monochromatic gray, monochromatic RBG average) displayed against complex leaf litter backgrounds (color, grayscale). Models of chromatic and achromatic contrast between spider stimuli and backgrounds were used to predict receiver responses. The results support the hypothesis that interactions between spider and background coloration affect detection and recognition, although responses varied with receiver type. Detection responses of intended receivers (female S. ocreata) did not fit predictions of the chromatic contrast model in some cases, but showed a fair fit to the achromatic model. Detection responses of social eavesdroppers (male S. ocreata) fit the chromatic and achromatic contrast models slightly better than did female responses (poor fit and very good fit, respectively). Eavesdropping wolf spider predators (Rabidosa) exhibited detection responses that significantly matched predictions of the chromatic (very good fit) and achromatic (excellent fit) models. Whereas jumping spiders (Phidippus) showed a good fit to the chromatic and achromatic contrast models, toad predators had a good fit only to the chromatic model. Recognition responses revealed a different pattern of fit to the chromatic and achromatic models across receiver types, although Rabidosa again indicated a significant fit to both models. Taken together, the results of this study identify both chromatic and achromatic features of spider appearance as likely explanations for differences in behavioral responses of intended and unintended receivers. This outcome suggests the possibility that both sexual and natural selection likely target different features of male appearance during courtship.
A systematic review of indicators and methods used to assess coastal to offshore marine ecosystems in the western Canadian Arctic
Authors: Bilous Miranda , Wight Kevin , Galappaththi Eranga K. , Dunmall Karen M.
Published: March 2024

Integration and coordination among monitoring programs are needed to better assess the impacts of climate change on Arctic marine ecosystems. The use of common indicators and methods could facilitate this comprehensive understanding. We completed a systematic review of published marine research in the western Canadian Arctic from 1962 to 2021 to identify the commonalities in methods and indicators present in assessments of coastal and offshore ecosystems. Most abundant in our sample were indicators addressing the environmental context, followed by indicators concerning trophic webs and biological organisms, and finally indicators associated with anthropogenic stressors and threats. Ship-based studies located far offshore were by far the most common and focused on indicators that characterized the physical environment and lower trophic levels. Commonalities in data collection methods suggest possibilities for standardization among programs for some parameters. Differences and data gaps highlighted areas for future coordination and the potential to integrate among indicators, especially as some indicators may span coastal to offshore ecosystems whereas individual monitoring programs may not. The results of this review could be used to identify and gather data into broad-spanning datasets. Overall, this systematic review highlights opportunities to link indicators and methods among coastal to offshore programs and will therefore facilitate connectivity and coordination of ecological research and monitoring in the western Canadian Arctic.
The diagnostic performance of ultrafast MRI to differentiate benign from malignant breast lesions: a systematic review and meta-analysis
Authors: Amitai Yoav , Freitas Vivianne A. R. , Golan Orit , Kessner Rivka , Shalmon Tamar , Neeman Rina , Mauda-Havakuk Michal , Mercer Diego , Sklair-Levy Miri , Menes Tehillah S.
Published: March 2024

Objectives

To assess the diagnostic performance of ultrafast magnetic resonance imaging (UF-DCE MRI) in differentiating benign from malignant breast lesions.

Materials and methods

A comprehensive search was conducted until September 1, 2023, in Medline, Embase, and Cochrane databases. Clinical studies evaluating the diagnostic performance of UF-DCE MRI in breast lesion stratification were screened and included in the meta-analysis. Pooled summary estimates for sensitivity, specificity, diagnostic odds ratio (DOR), and hierarchic summary operating characteristics (SROC) curves were pooled under the random-effects model. Publication bias and heterogeneity between studies were calculated.

Results

A final set of 16 studies analyzing 2090 lesions met the inclusion criteria and were incorporated into the meta-analysis. Using UF-DCE MRI kinetic parameters, the pooled sensitivity, specificity, DOR, and area under the curve (AUC) for differentiating benign from malignant breast lesions were 83% (95% CI 79–88%), 77% (95% CI 72–83%), 18.9 (95% CI 13.7–26.2), and 0.876 (95% CI 0.83–0.887), respectively. We found no significant difference in diagnostic accuracy between the two main UF-DCE MRI kinetic parameters, maximum slope (MS) and time to enhancement (TTE). DOR and SROC exhibited low heterogeneity across the included studies. No evidence of publication bias was identified (p = 0.585).

Conclusions

UF-DCE MRI as a stand-alone technique has high accuracy in discriminating benign from malignant breast lesions.

Clinical relevance statement

UF-DCE MRI has the potential to obtain kinetic information and stratify breast lesions accurately while decreasing scan times, which may offer significant benefit to patients.

Key Points

• Ultrafast breast MRI is a novel technique which captures kinetic information with very high temporal resolution.

• The kinetic parameters of ultrafast breast MRI demonstrate a high level of accuracy in distinguishing between benign and malignant breast lesions.

• There is no significant difference in accuracy between maximum slope and time to enhancement kinetic parameters.
Update DVO-Leitlinie 2023 „Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern ab dem 50. Lebensjahr“ – Was ist neu für die Rheumatologie?
Authors: Pfeil Alexander , Lange Uwe
Published: March 2024

Im Oktober 2023 veröffentlichte der Dachverband der deutschsprachigen wissenschaftlichen osteologischen Gesellschaften e. V. (DVO) die überarbeitete Leitlinie zur „Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern ab dem 50. Lebensjahr“. Dieser Übersichtsartikel geht auf die Neuerungen der Leitlinie und deren Relevanz in der Betreuung von Betroffenen mit entzündlich-rheumatischen Erkrankungen ein.

Eine zentrale Änderung der Leitlinie stellt die Umstellung des 10-Jahres-Frakturrisikos auf das 3‑Jahres-Frakturrisiko dar. Die Basisdiagnostik wird aktuell ohne definierte Frakturschwelle durchgeführt. Als weitere Schlüsselneuerung sind die Therapieschwellen für die spezifisch osteologische Therapie mit 3 % bis < 5 %, 5 % bis < 10 % und ab 10 % für Wirbelkörper- sowie Schenkelhalsfrakturen zu nennen. Bei einem 3‑Jahres-Frakturrisiko > 10 % ist primär eine osteoanabole Therapie durchzuführen und eine antiresorptive Therapie wird an die osteoanabole Therapie angeschlossen. Weiterführend sollten Patientinnen und Patienten mit einer Osteoporose sowie einer länger andauernden Glukokortikoidtherapie primär osteoanabol mittels Teriparatid behandelt werden. Zusammenfassend reflektieren die Änderungen der DVO-Leitlinie die aktuellen wissenschaftlichen Studienerkenntnisse in der Osteologie und führen zu einer detaillierten Differentialtherapie der Osteoporose.
Optical coherence tomography angiography suggests choriocapillaris perfusion deficit as etiology of acute macular neuroretinopathy
Authors: von der Burchard Claus , Gruben Arved , Roider Johann
Published: March 2024

Purpose

Acute macular neuroretinopathy (AMN) can cause sudden-onset and permanent scotoma in healthy young patients. Analysis of optical coherence tomography (OCT) and OCT angiography (OCTA) of AMN patients may provide insights into disease mechanism.

Methods

We conducted a retrospective study of consecutive SARS-Cov-2-related AMN patients that presented in our clinic between Jan 1st, 2022, and April 30th, 2023, within 30 days of symptom onset. Retinal vessel area density (VAD) of AMN lesions in OCTA was quantified and compared to an adjacent tissue control (ATC). This quantification was performed for the superficial vascular plexus (SVP), the intermediate capillary plexus (ICP), the deep capillary plexus (DCP), the choriocapillaris (CC), and choroid. Furthermore, en face OCT images were analyzed.

Results

Nine AMN patients were identified, 6 of these (4 female, 2 male, average age 25 years) fulfilled the inclusion criteria and were included into this study. Average time from symptom onset to OCTA was 14.3 days. No VAD differences between AMN and adjacent tissue were found in either retinal layer (SVP, ICP, DCP). In contrast, VAD in CC was reduced by 27% against the ATC (p = 0.007) and choroidal VAD was reduced by 41% (p = 0.017). Further analysis of en face OCT could show that the pathognomonic infrared hyporeflectivity in AMN is caused by photoreceptor alterations rather than changes in the inner retinal layers.

Conclusions

Our data suggests that a perfusion deficit in the choroidal layers is responsible for AMN rather than in the DCP, which is the predominant hypothesis in current literature.
The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer
Authors: Osakabe Mitsumasa , Yamada Noriyuki , Sugimoto Ryo , Uesugi Noriyuki , Nakao Eiichi , Honda Michitaka , Yanagawa Naoki , Sugai Tamotsu
Published: March 2024

Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.
Longitudinal analysis of carotenoid content in preterm human milk
Authors: Uretzky Adi , Mandel Dror , Schwartz Anat , Kaganov Kira , Mezad-Koursh Daphna , Mangel Laurence , Lubetzky Ronit
Published: March 2024

To describe the variability in carotenoid content of human milk (HM) in mothers of very to extremely low birth weight preterm infants throughout lactation and to explore the relationship between lutein in HM and the occurrence of retinopathy of prematurity (ROP) in preterm infants. We recruited healthy mothers along with their preterm infants that were born at gestational age 24 + 2 to 29 + 6 weeks or with a birth weight under 1500 g and were exclusively breastfed HM. Each participant provided up to 7 HM samples (2–10 ml) on day 0–3 and once a week until 6 weeks. Additionally, when possible, a blood sample was collected from the infant at week 6. Concentrations of the major carotenoids (lutein, zeaxanthin, beta-carotene, and lycopene) in all HM and blood samples were assessed and compared. Thirty-nine mother-infant dyads were included and 184 HM samples and 21 plasma samples were provided. Mean lutein, zeaxanthin, beta-carotene, and lycopene concentration decreased as lactation progressed, being at their highest in colostrum samples (156.9 vs. 66.9 vs. 363.9 vs. 426.8 ng/ml, respectively). Lycopene (41%) and beta-carotene (36%) were the predominant carotenoids in colostrum and up to 2 weeks post-delivery. Inversely, the proportion of lutein and zeaxanthin increased with lactation duration to account for 45% of the carotenoids in mature HM. Lutein accounted for 58% of the carotenoids in infant plasma and only 28% in HM. Lutein content of transition and mature HM did not differ between mothers of ROP and non-ROP infants.

Conclusion Carotenoid content of HM was dynamic and varied between mothers and as lactation progressed. Infant plasma displayed a distinct distribution of carotenoids from HM.
Integrative analysis with machine learning identifies diagnostic and prognostic signatures in neuroblastoma based on differentially DNA methylated enhancers between INSS stage 4 and 4S neuroblastoma
Authors: Li Shan , Mi Tao , Jin Liming , Liu Yimeng , Zhang Zhaoxia , Wang Jinkui , Wu Xin , Ren Chunnian , Wang Zhaoying , Kong Xiangpan , Liu Jiayan , Luo Junyi , He Dawei
Published: March 2024

Introduction

Accumulating evidence demonstrates that aberrant methylation of enhancers is crucial in gene expression profiles across several cancers. However, the latent effect of differently expressed enhancers between INSS stage 4S and 4 neuroblastoma (NB) remains elusive.

Methods

We utilized the transcriptome and methylation data of stage 4S and 4 NB patients to perform Enhancer Linking by Methylation/Expression Relationships (ELMER) analysis, discovering a differently expressed motif within 67 enhancers between stage 4S and 4 NB. Harnessing the 67 motif genes, we established the INSS stage related signature (ISRS) by amalgamating 12 and 10 distinct machine learning (ML) algorithms across 113 and 101 ML combinations to precisely diagnose stage 4 NB among all NB patients and to predict the prognosis of NB patients. Based on risk scores calculated by prognostic ISRS, patients were categorized into high and low-risk groups according to median risk score. We conducted comprehensive comparisons between two risk groups, in terms of clinical applications, immune microenvironment, somatic mutations, immunotherapy, chemotherapy and single-cell analysis. Ultimately, we empirically validated the differential expressions of two ISRS model genes, CAMTA2 and FOXD1, through immunochemistry staining.

Results

Through leave-one-out cross-validation, in both feature selection and model construction, we selected the random forest algorithm to diagnose stage 4 NB, and Enet algorithm to develop prognostic ISRS, due to their highest average C-index across five NB cohorts. After validations, the ISRS demonstrated a stable predictive capability, outperforming the previously published NB signatures and several clinic variables. We stratified NB patients into high and low-risk group based on median risk score, which showed the low-risk group with a superior survival outcome, an abundant immune infiltration, a decreased mutation landscape, and an enhanced sensitivity to immunotherapy. Single-cell analysis between two risk groups reveals biologically cellular variations underlying ISRS. Finally, we verified the significantly higher protein levels of CAMTA2 and FOXD1 in stage 4S NB, as well as their protective prognosis value in NB.

Conclusion

Based on multi-omics data and ML algorithms, we successfully developed the ISRS to enable accurate diagnosis and prognostic stratification in NB, which shed light on molecular mechanisms of spontaneous regression and clinical utilization of ISRS.
The long-term outcome of revision microdiscectomy for recurrent sciatica
Authors: Lequin M. B. , Verbaan D. , Schuurman P. R. , Tasche Saskia , Peul W. C. , Vandertop W. P. , Bouma G. J.
Published: March 2024

Purpose

To study the long-term outcome of revision microdiscectomy after classic microdiscectomy for lumbosacral radicular syndrome (LSRS).

Methods

Eighty-eight of 216 patients (41%) who underwent a revision microdiscectomy between 2007 and 2010 for MRI disc-related LSRS participated in this study. Questionnaires included visual analogue scores (VAS) for leg pain, RDQ, OLBD, RAND-36, and seven-point Likert scores for recovery, leg pain, and back pain. Any further lumbar re-revision operation(s) were recorded.

Results

Mean (SD) age was 59.8 (12.8), and median [IQR] time of follow-up was 10.0 years [9.0–11.0]. A favourable general perceived recovery was reported by 35 patients (40%). A favourable outcome with respect to perceived leg pain was present in 39 patients (45%), and 35 patients (41%) reported a favourable outcome concerning back pain. The median VAS for leg and back pain was worse in the unfavourable group (48.0/100 mm (IQR 16.0–71.0) vs. 3.0/100 mm (IQR 2.0–5.0) and 56.0/100 mm (IQR 27.0–74.0) vs. 4.0/100 mm (IQR 2.0–17.0), respectively; both p < 0.001). Re-revision operation occurred in 31 (35%) patients (24% same level same side); there was no significant difference in the rate of favourable outcome between patients with or without a re-revision operation.

Conclusion

The long-term results after revision microdiscectomy for LSRS show an unfavourable outcome in the majority of patients and a high risk of re-revision microdiscectomy, with similar results. Based on also the disappointing results of alternative treatments, revision microdiscectomy for recurrent LSRS seems to still be a valid treatment. The results of our study may be useful to counsel patients in making appropriate treatment choices.
An empirical investigation of challenges of specifying training data and runtime monitors for critical software with machine learning and their relation to architectural decisions
Authors: Heyn Hans-Martin , Knauss Eric , Malleswaran Iswarya , Dinakaran Shruthi
Published: March 2024

The development and operation of critical software that contains machine learning (ML) models requires diligence and established processes. Especially the training data used during the development of ML models have major influences on the later behaviour of the system. Runtime monitors are used to provide guarantees for that behaviour. Runtime monitors for example check that the data at runtime is compatible with the data used to train the model. In a first step towards identifying challenges when specifying requirements for training data and runtime monitors, we conducted and thematically analysed ten interviews with practitioners who develop ML models for critical applications in the automotive industry. We identified 17 themes describing the challenges and classified them in six challenge groups. In a second step, we found interconnection between the challenge themes through an additional semantic analysis of the interviews. We explored how the identified challenge themes and their interconnections can be mapped to different architecture views. This step involved identifying relevant architecture views such as data, context, hardware, AI model, and functional safety views that can address the identified challenges. The article presents a list of the identified underlying challenges, identified relations between the challenges and a mapping to architecture views. The intention of this work is to highlight once more that requirement specifications and system architecture are interlinked, even for AI-specific specification challenges such as specifying requirements for training data and runtime monitoring.
Voluntary E-Learning Exercises Support Students in Mastering Statistics
Authors: Schwerter Jakob , Brahm Taiga
Published: March 2024

University students often learn statistics in large classes, and in such learning environments, students face an exceptionally high risk of failure. One reason for this is students’ frequent statistics anxiety. This study shows how students can be supported using e-learning exercises with automated knowledge of correct response feedback, supplementing a face-to-face lecture. To this end, we surveyed 67 undergraduate social science students at a German university and observed their weekly e-learning exercises. We aggregated students’ exercise behavior throughout the semester to explain their exam performance. To control for participation bias, we included essential predictors of educational success, such as prior achievement, motivation, personality traits, time preferences, and goals. We applied a double selection procedure based on the machine learning method Elastic Net to include an optimal but sparse set of control variables. The e-learning exercises indirectly promoted the self-regulated learning techniques of retrieval practice and spacing and provided corrective feedback. Working on the e-learning exercises increased students’ performance on the final exam, even after controlling for the rich set of control variables. Two-thirds of students used our designed e-learning exercises; however, only a fraction of students spaced out the exercises, although students who completed the exercises during the semester and were not cramming at the end benefited additionally. Finally, we discuss how the results of our study inform the literature on retrieval practice, spacing, feedback, and e-learning in higher education.
Mapping ethical, legal, and social implications (ELSI) of preimplantation genetic testing (PGT)
Authors: Alon Ido , Bussod Ilona , Ravitsky Vardit
Published: March 2024

Purpose

Preimplantation Genetic Testing (PGT) has attracted considerable ethical, legal, and social scrutiny, but academic debate often fails to reflect clinical realities.

Methods

Addressing this disconnect, a review of 506 articles from 1999 to 2019 across humanities and social sciences was conducted to synthesize the Ethical, Legal, and Social Implications (ELSI) of PGT. This review mined PubMed, WoS, and Scopus databases, using both MeSH terms and keywords to map out the research terrain.

Results

The findings reveal a tenfold increase in global research output on PGT’s ELSI from 1999 to 2019, signifying rising interest and concern. Despite heightened theoretical discourse on selecting “optimal” offspring, such practices were scarcely reported in clinical environments. Conversely, critical issues like PGT funding and familial impacts remain underexplored. Notably, 86% of the ELSI literature originates from just 12 countries, pointing to a research concentration.

Conclusion

This review underscores an urgent need for ELSI research to align more closely with clinical practice, promoting collaborations among ethicists, clinicians, policymakers, and economists. Such efforts are essential for grounding debates in practical relevance, ultimately steering PGT towards ethical integrity, societal acceptance, and equitable access, aiming to harmonize PGT research with real-world clinical concerns, enhancing the relevance and impact of future ethical discussions.
Causality-Driven Intra-class Non-equilibrium Label-Specific Features Learning
Authors: Ge Wenxin , Wang Yibin , Xu Yuting , Cheng Yusheng
Published: March 2024

In multi-label learning, label-specific feature learning can effectively avoid some ineffectual features that interfere with the classification performance of the model. However, most of the existing label-specific feature learning algorithms improve the performance of the model for classification by constraining the solution space through label correlation. The non-equilibrium of the label distribution not only leads to some spurious correlations mixed in with the calculated label correlations but also diminishes the performance of the classification model. Causal learning can improve the classification performance and robustness of the model by capturing real causal relationships from limited data. Based on this, this paper proposes a causality-driven intra-class non-equilibrium label-specific features learning, named CNSF. Firstly, the causal relationship between the labels is learned by the Peter-Clark algorithm. Secondly, the label density of all instances is calculated by the intra-class non-equilibrium method, which is used to relieve the non-equilibrium distribution of original labels. Then, the correlation of the density matrix is calculated using cosine similarity and combined with causality to construct the causal density correlation matrix, to solve the problem of spurious correlation mixed in the label correlation obtained by traditional methods. Finally, the causal density correlation matrix is used to induce label-specific feature learning. Compared with eight state-of-the-art multi-label algorithms on thirteen datasets, the experimental results prove the reasonability and effectiveness of the algorithms in this paper.
Die Verschiebung des Sagbaren in organisationalen Schweigepraktiken
Authors: Lorenz-Sinai Friederike
Published: March 2024

Im Beitrag wird der Frage nachgegangen, wie sich das Sagbare in organisationalen Schweigepraktiken im Kontext von Machtmissbrauch und Gewalt gegen Kinder und Jugendliche durch Mitarbeiter:innen verschiebt. Anhand einer Fallstudie im Bereich der stationären Eingliederungshilfe wird diskutiert, wie Übergriffe im professionellen Sprechen und Schreiben umgedeutet und ausgelassen werden können. Deutlich wird, wie in solchen Praktiken ein Schweigen über Gewalt in organisationalen Routinen und Praktiken über Jahre unaufwändig vollzogen werden kann. Der Artikel endet mit einem Resümee der Befunde und Überlegungen zu den Herausforderungen von Supervision in Bezug auf verschwiegene Gewaltkonstellationen in Organisationen.