bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos
Authors: Chen Jiasheng , Lin Yuxin , Gen Deyi , Chen Wanxian , Han Rui , Li Hao , Tang Shijie , Zheng Shukai , Zhong Xiaoping
Published: March 2024

Tobacco pollutants are prevalent in the environment, leading to inadvertent exposure of pregnant females. Studies of these pollutants' toxic effects on embryonic development have not fully elucidated the potential underlying mechanisms. Therefore, in this study, we aimed to investigate the developmental toxicity induced by cigarette smoke extract (CSE) at concentrations of 0.25, 1, and 2.5% using a zebrafish embryo toxicity test and integrated transcriptomic analysis of microRNA (miRNA) and messenger RNA (mRNA). The findings revealed that CSE caused developmental toxicity, including increased mortality and decreased incubation rate, in a dose-dependent manner. Moreover, CSE induced malformations and apoptosis, specifically in the head and heart of zebrafish larvae. We used mRNA and miRNA sequencing analyses to compare changes in the expression of genes and miRNAs in zebrafish larvae. The bioinformatics analysis indicates that the mechanism underlying CSE-induced developmental toxicity was associated with compromised genetic material damage repair, deregulated apoptosis, and disturbed lipid metabolism. The enrichment analysis and RT-qPCR show that the ctsba gene plays a crucial function in embryo developmental apoptosis, and the fads2 gene mainly regulates lipid metabolic toxicity. The results of this study improve the understanding of CSE-induced developmental toxicity in zebrafish embryos and contribute insights into the formulation of novel preventive strategies against tobacco pollutants during early embryonic development.
TYROBP/DAP12 knockout in Huntington’s disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration
Authors: Creus-Muncunill Jordi , Haure-Mirande Jean Vianney , Mattei Daniele , Bons Joanna , Ramirez Angie V. , Hamilton B. Wade , Corwin Chuhyon , Chowdhury Sarah , Schilling Birgit , Ellerby Lisa M. , Ehrlich Michelle E.
Published: March 2024

Introduction

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in the Huntingtin gene (HTT). Immune activation is abundant in the striatum of HD patients. Detection of active microglia at presymptomatic stages suggests that microgliosis is a key early driver of neuronal dysfunction and degeneration. Recent studies showed that deletion of Tyrobp, a microglial protein, ameliorates neuronal dysfunction in Alzheimer’s disease amyloidopathy and tauopathy mouse models while decreasing components of the complement subnetwork.

Objective

While TYROBP/DAP12-mediated microglial activation is detrimental for some diseases such as peripheral nerve injury, it is beneficial for other diseases. We sought to determine whether the TYROBP network is implicated in HD and whether Tyrobp deletion impacts HD striatal function and transcriptomics.

Methods

To test the hypothesis that Tyrobp deficiency would be beneficial in an HD model, we placed the Q175 HD mouse model on a Tyrobp-null background. We characterized these mice with a combination of behavioral testing, immunohistochemistry, transcriptomic and proteomic profiling. Further, we evaluated the gene signature in isolated Q175 striatal microglia, with and without Tyrobp.

Results

Comprehensive analysis of publicly available human HD transcriptomic data revealed that the TYROBP network is overactivated in the HD putamen. The Q175 mice showed morphologic microglial activation, reduced levels of post-synaptic density-95 protein and motor deficits at 6 and 9 months of age, all of which were ameliorated on the Tyrobp-null background. Gene expression analysis revealed that lack of Tyrobp in the Q175 model does not prevent the decrease in the expression of striatal neuronal genes but reduces pro-inflammatory pathways that are specifically active in HD human brain, including genes identified as detrimental in neurodegenerative diseases, e.g. C1q and members of the Ccr5 signaling pathway. Integration of transcriptomic and proteomic data revealed that astrogliosis and complement system pathway were reduced after Tyrobp deletion, which was further validated by immunofluorescence analysis.

Conclusions

Our data provide molecular and functional support demonstrating that Tyrobp deletion prevents many of the abnormalities in the HD Q175 mouse model, suggesting that the Tyrobp pathway is a potential therapeutic candidate for Huntington’s disease.
Birth by caesarean section and semen quality in adulthood: a Danish population-based cohort study
Authors: Huang Kun , Gaml-Sørensen Anne , Brix Nis , Ernst Andreas , Arendt Linn Håkonsen , Bonde Jens Peter Ellekilde , Hougaard Karin Sørig , Toft Gunnar , Tøttenborg Sandra Søgaard , Ramlau-Hansen Cecilia Høst
Published: March 2024

Background

The caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality.

Methods

This study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs).

Results

Among included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally.

Conclusions

This large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.
Monitoring redox stress in human airway epithelial cells exposed to woodsmoke at an air–liquid interface
Authors: Abzhanova Aiman , Berntsen Jon , Pennington Edward R. , Dailey Lisa , Masood Syed , George Ingrid , Warren Nina , Martin Joseph , Hays Michael D. , Ghio Andrew J. , Weinstein Jason P. , Kim Yong Ho , Puckett Earl , Samet James M.
Published: March 2024

Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air–liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures.
“sCT-Feasibility” - a feasibility study for deep learning-based MRI-only brain radiotherapy
Authors: Grigo Johanna , Szkitsak Juliane , Höfler Daniel , Fietkau Rainer , Putz Florian , Bert Christoph
Published: March 2024

Background

Radiotherapy (RT) is an important treatment modality for patients with brain malignancies. Traditionally, computed tomography (CT) images are used for RT treatment planning whereas magnetic resonance imaging (MRI) images are used for tumor delineation. Therefore, MRI and CT need to be registered, which is an error prone process. The purpose of this clinical study is to investigate the clinical feasibility of a deep learning-based MRI-only workflow for brain radiotherapy, that eliminates the registration uncertainty through calculation of a synthetic CT (sCT) from MRI data.

Methods

A total of 54 patients with an indication for radiation treatment of the brain and stereotactic mask immobilization will be recruited. All study patients will receive standard therapy and imaging including both CT and MRI. All patients will receive dedicated RT-MRI scans in treatment position. An sCT will be reconstructed from an acquired MRI DIXON-sequence using a commercially available deep learning solution on which subsequent radiotherapy planning will be performed. Through multiple quality assurance (QA) measures and reviews during the course of the study, the feasibility of an MRI-only workflow and comparative parameters between sCT and standard CT workflow will be investigated holistically. These QA measures include feasibility and quality of image guidance (IGRT) at the linear accelerator using sCT derived digitally reconstructed radiographs in addition to potential dosimetric deviations between the CT and sCT plan. The aim of this clinical study is to establish a brain MRI-only workflow as well as to identify risks and QA mechanisms to ensure a safe integration of deep learning-based sCT into radiotherapy planning and delivery.

Discussion

Compared to CT, MRI offers a superior soft tissue contrast without additional radiation dose to the patients. However, up to now, even though the dosimetrical equivalence of CT and sCT has been shown in several retrospective studies, MRI-only workflows have still not been widely adopted. The present study aims to determine feasibility and safety of deep learning-based MRI-only radiotherapy in a holistic manner incorporating the whole radiotherapy workflow.

Trial registration

NCT06106997.
Improving access to melarsomine therapy: treating canine heartworm infection in a high-volume, outpatient community clinic setting
Authors: Still Meghan B. , Tedesco Dana , Hawkins Christina , Putnam Holly
Published: March 2024

Background

Models that provide high-quality veterinary care for more affordable prices are emerging, but not well documented outside of wellness and preventative care. Effective treatment guidelines for heartworm disease have been developed by the American Heartworm Society; however, not all owners are able to access treatment due to the high costs associated with sick and emergency care services.

Methods

To increase access to high-quality adulticidal treatment of canine heartworm disease, we developed and implemented a technician-leveraged heartworm treatment protocol for high-volume, outpatient community clinic settings based on the American Heartworm Society guidelines. Modifications were few and included limited pre-treatment blood work, pre-injection sedation, post-injection pain medication, and a reduced exercise restriction period. We monitored retention rates for 556 dogs throughout treatment, evaluated treatment success (defined as no antigen detection 9 months post treatment) for patients that returned for post-treatment antigen testing, and reported on adverse reactions and therapy adherence throughout treatment.

Results

Of the patients that began adulticide therapy, 539/556 (97%) successfully completed the three-injection series. No microfilariae were detected in 99% (428/433) of those who returned for post-injection microfilaria testing. Among those that returned for or reported the results of post-injection antigen testing, no antigen was detected for 99% (245/248) and no microfilariae were detected for 99.5% (200/201). During the course of treatment, 483/539 (90%) of patients experienced at least one adverse reaction, with the most frequently reported types being behavioral and injection site reactions. 25/539 (4.6%) of owners sought additional medical care for adverse reactions at some point during the treatment course. The overall mortality rate was 1.3% (7/556).

Conclusions

This study represents the first evaluation of a heartworm treatment protocol optimized for implementation in a high-volume, outpatient community clinic setting. Our findings align with those previously reported in private practice or tertiary referral centers, illustrating that through the inclusion of pre-treatment blood work, employing short-acting or reversible sedatives, ensuring proper analgesia, minimizing the use of ancillary diagnostics, reducing the duration of in-clinic monitoring while focusing on outpatient care, and maximizing technician involvement, we can deliver effective and safe melarsomine therapy at a more affordable cost to pet owners.

Graphical Abstract
Construction of luciferase-expressing Neospora caninum and drug screening
Authors: Wang Fei , Xue Yangfei , Pei Yanqun , Yin Meng , Sun Zhepeng , Zhou Zihui , Liu Jing , Liu Qun
Published: March 2024

Background

Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs.

Methods

Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies.

Results

The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 μM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain.

Conclusions

In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.

Graphical Abstract
Late cardiotoxicity related to HER2-targeted cancer therapy
Authors: Senechal Isabelle , Andres Maria Sol , Tong Jieli , Perone Ylenia , Ramalingam Sivatharshini , Nazir Muhummad Sohaib , Rosen Stuart D , Turner Nicholas , Ring Alistair , Lyon Alexander R
Published: March 2024

Long-term anti-HER2 therapy in metastatic HER2 + cancers is increasing, but data about the incidence and risk factors for developing late Cancer therapy-related cardiac dysfunction (CTRCD) are missing. We conducted a single-centre, retrospective analysis of a cohort of late anti-HER2 related cardiac dysfunction referred to our Cardio-Oncology service. We include seventeen patients with metastatic disease who developed CTRCD after at least five years of continuous anti-HER2 therapy. Events occurred after a median time of 6.5 years (IQR 5.3-9.0) on anti-HER2 therapy. The lowest (median) LVEF and GLS were 49% (IQR 45–55) and − 15.4% (IQR − 14.9 - -16.3) respectively. All our patients continued or restarted, after a brief interruption, their anti-HER2 therapy. Most (16/17) were started on heart failure medical therapy and normalized their left ventricular ejection fraction at a follow-up. Our study has demonstrated that CTRCD can occur after many years of stability on anti-HER2 therapy and reinforces the importance of continuing cardiovascular surveillance in this population.
The spectrum of TP53 mutations in Rwandan patients with gastric cancer
Authors: Nzitakera Augustin , Surwumwe Jean Bosco , Ndoricyimpaye Ella Larissa , Uwamungu Schifra , Uwamariya Delphine , Manirakiza Felix , Ndayisaba Marie Claire , Ntakirutimana Gervais , Seminega Benoit , Dusabejambo Vincent , Rutaganda Eric , Kamali Placide , Ngabonziza François , Ishikawa Rei , Rugwizangoga Belson , Iwashita Yuji , Yamada Hidetaka , Yoshimura Kimio , Sugimura Haruhiko , Shinmura Kazuya
Published: March 2024

Background

Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer.

Results

Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon–intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed.

Conclusions

Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.
A structured, journal-led peer-review mentoring program enhances peer review training
Authors: Lyons-Warren Ariel Maia , Aamodt Whitley W. , Pieper Kathleen M. , Strowd Roy E.
Published: March 2024

Background

Peer review is essential to the advancement of knowledge. However, training on how to conduct peer review is limited, unorganized, and not well studied. Thus, we sought to determine if a structured mentored peer-review program improved peer review training as measured by multiple quantitative and qualitative assessments.

Methods

This pre-post intervention study enrolled 55 mentees across 5 cohorts from 2020 to 2023. Each cohort completed pre-program evaluations, participated in 2 mentored reviews, and completed post-program evaluations over 6 months. Mentors and mentees completed pre-program demographic and review experience questionnaires. Outcome measures included (1) total and sub-scores on the modified Review Quality Index (mRQI) applied to the same pre-selected research manuscript reviewed by mentees both pre and post intervention, (2) mentee self-perceived comfort with and understanding of the review process using a custom questionnaire, and (3) mentor satisfaction surveys. Pre- and post-program measures were compared using the Wilcoxon signed-rank test.

Results

Post-program total modified RQI score (median (IQR) = 31 (26.3–35.8)) was higher than pre-program total score (26.6 (19.7–29.7)) for the 42 mentees who completed both pre- and post-program reviews. Mentees reported improved perception of review (median (IQR) pre = 4 (3–4), post = 5 (4–5)) and editorial processes (pre = 3 (2–4), post = 4 (4–5)) as well as self-perceived confidence in completing an independent review of both scientific (median (IQR) pre = 2 (2–3), post = 4 (4–4)) and non-scientific (pre = 3 (2–4), post = 4 (4–5)) manuscripts following program participation. p < 0.0001 for all scores noted. Mentors reported high scores for enjoyment (median (range) 5/5 (3–5)) and interest in repeat participation (5/5 (2–5)).

Conclusions

A 6-month structured mentored-review program including 2 mentored reviews improves peer review training as measured by the modified RQI as well as participant self-perceived understanding of publication science with high mentor satisfaction.
Safe system for sustainable development
Authors: Lah Oliver
Published: March 2024

This paper presents a novel governance concept for sustainable development, introducing the 'Safe System Approach' as a transformative model that shifts focus from individual behavioural change to systemic transformation. This approach challenges traditional governance models that emphasize individual responsibility in achieving sustainable development and decarbonization. Instead, it advocates for creating an enabling environment that inherently guides individuals and communities towards sustainable actions. The Safe System Approach is centred on delivering low-carbon services across essential sectors, including electricity, mobility, industry, buildings, human settlements, and agriculture, thereby embedding sustainability as a default choice in societal systems. Drawing parallels with successful models in road safety, the paper explores the potential of this approach in urban development and climate action. It emphasizes the need for a broad coalition and integrated approaches in managing shared resources, highlighting the significance of systemic adjustments over individual behavioral change. By proposing a structure where sustainability is facilitated by the system's design, the paper builds on key concepts from seminal works by scholars like Garrett Hardin, Mancur Olson, Elinor Ostrom, and Ahrend Lijphart. It discusses the challenges and opportunities in creating safe operating spaces for sustainable development, emphasizing the need for multi-actor, multilevel governance systems that can manage shared resources sustainably and are resilient to political volatility. The paper aims to offer a robust, efficient, and inclusive pathway to sustainable development, contributing to the global discourse on environmental and social resilience.
Assessment of brain-derived neurotrophic factor levels in serum of children with autism spectrum disorders
Authors: Elhamid Salwa Amin Abd , Alkherkhisy Mohammad Mostafa , Kasem Rania Elsayed
Published: March 2024

Background

The autism spectrum disorder (ASD) has no identified biomarker for early detection or for its severity. As for the brain-derived neurotrophic factor (BDNF), it is a crucial neurotropic factor that regulates the plasticity and maturing of neuronal synapses. Accordingly, it might influence how children with autism develop.

Method

To evaluate the BDNF serum levels in autistic children and their relationship with the illness severity as well as with the common drugs received by autistic patients, 60 patients with autism along with another 60 normally developing children were involved in the study. Using the Childhood Autism Rating Scale (CARS), the severity of autism was then evaluated. The ELISA method was used to measure the BDNF level.

Results

It was seen that the BDNF concentrations were higher in autism patients (P < 0.001). There was also a highly strong positive association between the CARS score and the BDNF (P < 0.001). Using the cut-off value of > 2.8 of BDNF helped to distinguish between well-developing and autistic children, with the aspects of “sensitivity” and “specificity” being 88.3% and 80%, respectively. Moreover, children with autism who received omega-3 had statistically lower levels of BDNF than those who did not take any (P = 0.040).

Conclusion

The serum BDNF concentration is higher in autism; this proposes that the BDNF may contribute to the onset or progress of autism. Therefore, it may be used as a noninvasive biomarker for the illness severity because of its greater occurrence in autistic children who have severe social impairment.
PET-CT-based resection guide for treatment of auricular squamous cell carcinoma: an innovative clinical management of soft tissue tumors: a case report
Authors: Mekky Mohamed , Nawwar Muhammad A. , Nabawi Ayman Sameh , Aziz Mahmoud Yehya Abdul , Galal Ahmed , Sleem Heba
Published: March 2024

Purpose

To describe the successful use of a PET-CT-based resection guide for the treatment of auricular squamous cell carcinoma.

Case presentation

A 69-year-old male presented with a painless growing mass in his left ear helix that had been unsuccessfully treated conservatively by another surgeon. An incisional biopsy revealed moderately differentiated squamous cell carcinoma, and the patient was referred to the department for further management. A PET/CT was performed, which showed uptake of FDG in the ear with a SUV max value and T3N0M0 status. The treatment plan was based on a multidisciplinary team discussion and a thorough evaluation of the PET/CT imaging findings. A decision was made to proceed with excision of the mass with a wide safety margin, using a PET/CT-based resection guide for ear resection. Additionally, partial temporal bone resection, selective neck dissection, and superficial parotidectomy were planned. The patient opted for reconstruction with a scalp rotational flap. The patient’s treatment plan was successful, and at follow-up visits, he remained disease-free. This case report highlights the importance of using a PET-CT-based resection guide for the treatment of soft tissue tumors, specifically auricular squamous cell carcinoma. It also demonstrates the importance of a multidisciplinary team approach and thorough evaluation of imaging findings in determining an effective treatment plan for patients.

Conclusions

The use of PET-CT-based resection guide can be an effective tool in the treatment of auricular squamous cell carcinoma. It can provide more precise and accurate information about the extent of the tumor, leading to a more effective treatment plan. Multidisciplinary team approach and thorough evaluation of imaging findings are crucial in determining the best course of treatment for patients.
Multichannel deconvolution with a high-frequency structural regularization
Authors: Wang Pengfei , Zhao Dongfeng , Niu Yue , Li Guofa , Gu Weiwei
Published: March 2024

The resolution of seismic data determines the ability to characterize stratigraphic features from observed seismic records. Sparse spike inversion, as an important processing method, can effectively improve the band-limited property of the seismic data. However, this approach ignores the spatial information along seismic traces, which causes the unreliability of the reconstructed high-resolution data. In this paper, we develop a high-frequency structure-constrained multichannel deconvolution (HFSC-MD) to alleviate this issue. This method allows the cost function to incorporate high-frequency spatial information in the form of a prediction-error filter (PEF) to regularize the components of the result beyond the original frequency. The PEF, also called a high-frequency reflection structural characterization operator, is estimated from the mapping relationship of low- and high-frequency components. We adopt the alternating direction method of multipliers to solve the cost function in HFSC-MD. Synthetic and field data demonstrate that our method recovers more reliable high-resolution data and enriches reflective structures.
Stress-dependent reflection and transmission of elastic waves under confining, uniaxial, and pure shear prestresses
Authors: Yang Haidi , Fu Li-Yun , Müller Tobias M. , Fu Bo-Ye
Published: March 2024

Insights into the reflection and transmission (R/T) of waves at a prestressed interface are important in geophysical applications, such as evaluating the angle-dependent elastic properties for monitoring geopressure and tectonic stress using sonic logging data or seismic data. Although many studies deal with wave propagation in prestressed media, the angle-dependent R/T of waves at an interface subject to different prestress loading modes remains largely unaddressed. We address this issue by applying the theory of acoustoelasticity with third-order acoustoelastic constants to study the R/T coefficients at the interface between two prestressed media. Stress-induced elastic deformations are assumed to be locally homogeneous without boundary dislocations caused by stress concentration so that the static boundary conditions can be applied. We consider three typical prestress modes (confining, uniaxial, and pure shear), each of which takes into account the incidence of upgoing and downgoing P and S waves. The Knott equations under different types of prestresses are derived, followed by the estimation of angle-dependent R/T coefficients. The energy conservation at the interface and the acoustoelastic finite-difference simulation of predicted P and S modes verify the correctness of the angle-dependent R/T coefficients under confining prestress. Comparisons with the elastic case (prestress [Formula: see text]) indicate the important influence of prestresses on the energy distribution of reflected and transmitted waves, including stress-dependent critical angles, converted waves, and R/T energy ratios. Such acoustoelastic effects mainly occur around/after the critical angle. For small-angle incidence, prestresses mainly affect the gradient of R/T coefficients. The type and magnitude of prestress are closely related to the angle-dependent R/T coefficients and must be considered for amplitude-variation-with-offset analysis in prestressed media.
Shell game with a quantum pea
Authors: Yi Juyeon
Published: March 2024

We examine the role of quantum measurement and coherence, considering the shell game with a quantum particle. The game consists of three sites arranged to form a ring geometry and a particle visiting the sites through a unitary evolution. A player selects one of the sites as a target site and wins if the target site contains the particle at a preassigned time. The player has two options for determining win or loss: local and global measurements, which perform projective measurements on the occupancy of the target site and the particle's position, respectively. The game can be played over multiple rounds, and each round begins with the state reached at the end of the previous round. We calculate the probability of winning at each round and the probability of consecutive losses and find that those probabilities have characteristic asymptotes. We obtain the analytic expressions of the asymptote and scrutinize their essential dependence on the measurement options and coherence in the initial ensemble.
One-for-all: Support-free optimized Fourier random phase for real-time multiple kinoforms generation
Authors: Zhang Cheng , Zhou Hao , Wu Feng , Han Peng , Shi Jisen , Yang Hairong , Hong Cheng , Shen Chuan , Wei Sui
Published: March 2024

Existing optimized random phase (ORAP) approach mainly faces the limitations of fixed supports. Different ORAPs need to be generated for different target images with different support sizes, thus lacking flexibility and severely limiting applicability. This paper proposes a support-free optimized Fourier random phase (SF-OFRAP) approach for non-iterative kinoform generation, which greatly improves the speed and flexibility of generating kinoforms, and can achieve comparable performance to the ORAP approach. The proposed SF-OFRAP approach not only breaks the fixed support constraint of a target image, but can generate kinoforms of target images with different shapes, different positions, etc. with arbitrary supports. Our proposed SF-OFRAP approach can achieve real-time generation of kinoforms for multi-view holographic display using only a single generated SF-OFRAP without the need for additional phase compensation. The SF-OFRAP approach is suitable for real-time holographic display. Experiments verified the superiority of the produced SF-OFRAP over the ORAP method in terms of flexibility and adaptability to multiple different objects in different positions and different shapes using only one kind of these. The experimental results verify the effectiveness and excellent flexibility of SF-OFRAP for video holographic display and multi-view holographic display.
The Search for the Causes of Common Hyperandrogenism, 1965 to Circa 2015
Authors: Rosenfield Robert L
Published: March 2024

From 1965 to 2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology, insulin resistance, hyperinsulinism, type 2 diabetes mellitus, folliculogenesis, androgen secretion, obesity, phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large-scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicate that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and proinflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in 40 percent of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.
Survey of Lactating Anesthesiologists Using Wearable Breast Milk Pumps While Working in Operating Rooms and Other Clinical Settings
Authors: Titler Sarah S. , Dexter Franklin
Published: March 2024

We performed a prospective Internet survey study of anesthesiologists lactating in 2022 or 2023. Approximately half (48%, 75 of 156) lacked convenient dedicated lactation space and approximately half (55%, 86 of 155) used a wearable breast pump. The vast majority using a wearable pump did so in clinical settings, including operating rooms (88%, 76 of 86). When using during cases, approximately half reported that milk production was sufficient to substitute for lactation pumping sessions (52%, 39 of 75). Based on probability distributions of surgical times, future research can evaluate the usefulness of wearable pumps based on the objective of reducing anesthesiologists’ durations of lactation sessions to <15 minutes.
Cadherin-dependent adhesion is required for muscle stem cell niche anchorage and maintenance
Authors: Hung Margaret , Lo Hsiao-Fan , Beckmann Aviva G. , Demircioglu Deniz , Damle Gargi , Hasson Dan , Radice Glenn L. , Krauss Robert S.
Published: March 2024

Adhesion between stem cells and their niche provides stable anchorage and signaling cues to sustain properties such as quiescence. Skeletal muscle stem cells (MuSCs) adhere to an adjacent myofiber via cadherin-catenin complexes. Previous studies on N- and M-cadherin in MuSCs revealed that although N-cadherin is required for quiescence, they are collectively dispensable for MuSC niche localization and regenerative activity. Although additional cadherins are expressed at low levels, these findings raise the possibility that cadherins are unnecessary for MuSC anchorage to the niche. To address this question, we conditionally removed from MuSCs β- and γ-catenin, and, separately, αE- and αT-catenin, factors that are essential for cadherin-dependent adhesion. Catenin-deficient MuSCs break quiescence similarly to N-/M-cadherin-deficient MuSCs, but exit the niche and are depleted. Combined in vivo, ex vivo and single cell RNA-sequencing approaches reveal that MuSC attrition occurs via precocious differentiation, re-entry to the niche and fusion to myofibers. These findings indicate that cadherin-catenin-dependent adhesion is required for anchorage of MuSCs to their niche and for preservation of the stem cell compartment. Furthermore, separable cadherin-regulated functions govern niche localization, quiescence and MuSC maintenance.
Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial
Authors: Goetze Thorsten O. , Reichart Alexander , Bankstahl Ulli S. , Pauligk Claudia , Loose Maria , Kraus Thomas W. , Elshafei Moustafa , Bechstein Wolf O. , Trojan Jörg , Behrend Matthias , Homann Nils , Venerito Marino , Bohle Wolfram , Varvenne Michael , Bolling Claus , Behringer Dirk M. , Kratz-Albers Karsten , Siegler Gabriele M. , Hozaeel Wael , Al-Batran Salah-Eddin
Published: March 2024

Background

Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer.

Patients and Methods

This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS).

Results

Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms.

Conclusions

Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.
A EPISTEMOLOGIA ESPECISTA E O AVANÇO MITIGADO NA PROTEÇÃO DOS ANIMAIS NO BRASIL
Authors: Oliveira Amanda Muniz , Drescher Sophia Wilhelm
Published: March 2024

Contextualização: Em 2019, foi apresentado na Câmara o Projeto de Lei nº 1.095 que objetivava tornar mais severa a legislação relativa aos maus-tratos dos animais como um todo. Após modificações, o Projeto foi sancionado como a Lei nº 14.064 de 2020, que alterou a Lei de Crimes Ambientais (Lei nº 9.605 de 1998) criando o §1º- A do artigo 32, no intuito de promover um aumento de pena para a prática do crime de maus-tratos a animais, restringindo seu alcance, entretanto, a cães e a gatos, apenas.
Objetivo: O trabalho visa a compreender as motivações pelas quais a Lei nº 14.064 de 2020 restringiu o aumento da pena do crime de maus-tratos a animais apenas a cães e a gatos.
Método: Neste trabalho, foi utilizado o método indutivo, realizado por meio de revisão bibliográfica e análise empírica documental, a partir de uma abordagem qualitativa. Especificamente, procedeu-se à análise do processo legislativo percorrido pelo Projeto de Lei nº 1.095 de 2019, que deu origem à Lei nº 14.064/2020, e, além da leitura e da análise de bibliografia sobre o Direito Animal e os documentos oficiais que compõem o processo legislativo na Câmara dos Deputados e no Senado Federal, foram analisados os conteúdos das reuniões e das audiências públicas realizadas durante o trâmite.
Conclusão: Foi possível concluir que o aumento de pena no crime de maus-tratos foi restrito a cães e a gatos em virtude de uma epistemologia especista, embasada em uma visão de mundo antropocêntrica, que permeia o discurso do legislativo brasileiro.
Μελέτη και καθορισμός των παραμέτρων ειδικών χαρακτηριστικών της εφαρμογής του μοριακού καρυοτύπου από τη χαμηλή στη στοχευμένη και υψηλή ευκρίνεια στον προγεννητικό έλεγχο
Authors: Παπαγεωργίου Ελένη
Published: March 2024

Αυτή η μελέτη πραγματοποιήθηκε για την αξιολόγηση της βέλτιστης ανάλυσης για προγεννητικό έλεγχο με την χρήση συστοιχίας συγκριτικού γονιδιωματικού υβριδισμού (aCGH), προκειμένου να εντοπιστεί το επίπεδο ανάλυσης που συνεπάγεται τη μέγιστη διαγνωστική απόδοση με ταυτόχρονη ελάχιστη ανίχνευση παραλλαγών αβέβαιης κλινικής σημασίας (VUS).Πρόκειται για προοπτική μελέτη στην οποία χρησιμοποιήθηκαν δεδομένα 2.336 εμβρύων που υποβλήθηκαν σε προγεννητικό έλεγχο μέσω επεμβατικής διαδικασίας, και τα δείγματα αναλύθηκαν με aCGH. Συνολικά, μελετήθηκαν έξι διαφορετικές πλατφόρμες aCGH, εφαρμόζοντας τέσσερα διαφορετικά επίπεδα ανάλυσης (0,18 Mb, 0,5 Mb, 1 Mb και 2 Mb) και δύο σχεδιασμούς πλατφόρμας (κάλυψη ολόκληρου του γονιδιώματος [WG] και στοχευμένη κάλυψη). Τα αποτελέσματα αυτών συγκρίθηκαν με βάση τη διαγνωστική τους απόδοση και το ποσοστό ανίχνευσης VUS. Η απόδοση των διαφορετικών πλατφορμών αναλύθηκε περαιτέρω σύμφωνα με την υπερηχογραφική ένδειξη για επεμβατική διαδικασία. Η διαγνωστική απόδοση με βάση τη συχνότητα των παραλλαγών του αριθμού αντιγράφων αυξήθηκε με το αυξανόμενο επίπεδο ανάλυσης. Τα ποσοστά ανίχνευσης των κλινικά σημαντικών χρωμοσωμικών ανωμαλιών ήταν σχεδόν τα ίδια στις πλατφόρμες στοχευμένων συστοιχιών, 7,2% με 0,18 Mb backbone/0,05 Mb έναντι 7,1% με 0,5 Mb backbone/0,05 Mb (p >0,05). Ωστόσο, παρατηρήθηκε σημαντική διαφορά στο ποσοστό ανίχνευσης VOUS. 9,4% με 0,18 Mb backbone/0,05 Mb έναντι 6% με 0,5 Mb backbone/0,05 Mb (p <0,001). Παράλληλα, αφού αναλύσαμε τα αποτελέσματα ανάλογα με τις διαφορετικές ενδείξεις για προγεννητικό έλεγχο, διαπιστώσαμε ότι η εφαρμογή μη στοχευμένων πλατφορμών και χαμηλότερων επιπέδων ανάλυσης (όπως 1 Mb WG ή 0,5 MbL/1 MbG WG) προσφέρει παρόμοια διαγνωστική απόδοση στις περισσότερες περιπτώσεις με μείζονες συγγενείς ανωμαλίες, και παράλληλα χαμηλότερα ποσοστά VUS. Παρ’ όλο τα στατιστικά σημαντικά αποτελέσματα, το μέγεθος του δείγματος για αρκετές ομάδες ενδείξεων ήταν μικρό για την εξαγωγή ισχυρών συσχετισμών. H πλατφόρμα στοχευμένης ανάλυσης μεγέθους 0,5 Mb σε ολόκληρο το γονιδίωμα και 0,05 Mb σε στοχευμένες πλούσιες σε γονίδια περιοχές φαίνεται να είναι η βέλτιστη για εφαρμογή σε επίπεδο ρουτίνας στην προγεννητική διάγνωση, με τα λιγότερα αγνώστου σημασίας ευρήματα. Πιθανά, θα ήταν διαγνωστικά ωφέλιμο, να υπάρξουν κατευθυντήριες οδηγίες εξατομίκευσης της ανάλυσης της μεθόδου, ανάλογα με την ένδειξη παραπομπής.
Policy Brief 12: De-risking of Russian clients: best intentions, unintended consequences
Authors: Boguslavska Kateryna
Published: March 2024

After the Russian invasion of Ukraine and the wide-reaching sanctions which ensued, many Western financial institutions began to de-risk Russian clients. Dealing with Russian clients, in many cases, has become expensive from a compliance point of view and toxic from the reputational side.

However, the de-risking of unsanctioned Russian individuals may have a significant impact on the fight against financial crime by potentially causing:

an increase in the use of shadow/unregulated channels of moving money;

a withdrawal of funds away from the European zone to sanctioned countries or non-cooperative jurisdictions;

severe burdens on the investigation of financial crimes (especially in relation to Russian assets and investments) and on international cooperation in criminal matters;

increased opportunities for enablers, such as unscrupulous lawyers and accountants, to take advantage of the situation.

This Policy Brief outlines the current situation and suggests how to better manage risk without having a negative impact on the fight against financial crime.