bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of deep learning-based denoising methods in cardiac SPECT
Authors: Sohlberg Antti , Kangasmaa Tuija , Constable Chris , Tikkakoski Antti
Published: February 2023

Background

Myocardial perfusion SPECT (MPS) images often suffer from artefacts caused by low-count statistics. Poor-quality images can lead to misinterpretations of perfusion defects. Deep learning (DL)-based methods have been proposed to overcome the noise artefacts. The aim of this study was to investigate the differences among several DL denoising models.

Methods

Convolution neural network (CNN), residual neural network (RES), UNET and conditional generative adversarial neural network (cGAN) were generated and trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with full, half, three-eighths and quarter acquisition time. All DL methods were compared against each other and also against images without DL-based denoising. Comparisons were made using half and quarter time acquisition data. The methods were evaluated in terms of noise level (coefficient of variation of counts, CoV), structural similarity index measure (SSIM) in the myocardium of normal patients and receiver operating characteristic (ROC) analysis of realistic artificial perfusion defects inserted into normal MPS scans. Total perfusion deficit scores were used as observer rating for the presence of a perfusion defect.

Results

All the DL denoising methods tested provided statistically significantly lower noise level than OSEM without DL-based denoising with the same acquisition time. CoV of the myocardium counts with the different DL noising methods was on average 7% (CNN), 8% (RES), 7% (UNET) and 14% (cGAN) lower than with OSEM. All DL methods also outperformed full time OSEM without DL-based denoising in terms of noise level with both half and quarter acquisition time, but this difference was not statistically significant. cGAN had the lowest CoV of the DL methods at all noise levels. Image quality and polar map uniformity of DL-denoised images were also better than reduced acquisition time OSEM’s. SSIM of the reduced acquisition time OSEM was overall higher than with the DL methods. The defect detection performance of full time OSEM measured as area under the ROC curve (AUC) was on average 0.97. Half time OSEM, CNN, RES and UNET provided equal or nearly equal AUC. However, with quarter time data CNN, RES and UNET had an average AUC of 0.93, which was lower than full time OSEM’s AUC, but equal to quarter acquisition time OSEM. cGAN did not achieve the defect detection performance of the other DL methods. Its average AUC with half time data was 0.94 and 0.91 with quarter time data.

Conclusions

DL-based denoising effectively improved noise level with slightly lower perfusion defect detection performance than full time reconstruction. cGAN achieved the lowest noise level, but at the same time the poorest defect detection performance among the studied DL methods.
Quality and educator dispositions for indigenous families in the urban early learning and child care context: a scoping review
Authors: Freeborn Chelsea , Mardhani-Bayne Alvina , Soetaert Cheyanne
Published: February 2023

This scoping review focused on the experiences of Indigenous families and their children in accessing quality early learning and child care in a Canadian urban context. This scoping review was conducted to contribute to the field and frame a more extensive study involving focus groups and case studies. The analysis revealed a range of quality indicators that included the following: (1) families, educators, and community members must establish a definition of quality that best reflects their personal life experiences and cultural context; (2) many families express a desire for child care focused on developmental milestones, social skills, and Indigenous knowledge; (3) families value connections made between the home and the center that foster identity, encourage child and family autonomy, implement programming relevant to culture, and stimulate learning within the context of family; and (4) families desire child care that focuses on relationship building increased cultural safety. Results from the scoping review related to quality educator dispositions found the following: (1) families seek centers that are flexible, family-focused, and culturally relevant; (2) families value educators who value diversity and decolonization; and (3) some families favor a cultural match with educators from similar backgrounds. These findings point to several areas for further consideration that can improve the overall experiences of Indigenous children and families accessing quality early learning and child care in a Canadian urban setting.
Systemic vasculitis diagnosed during the post-partum period: case report and review of the literature
Authors: Demotier Sophie , Orquevaux Pauline , N’Guyen Yohan
Published: February 2023

Introduction

The vasculitis diagnosed specifically in the post-partum period are less well known. We report here such a case followed by a descriptive review of the literature.

Case report

A 25 year-old French nurse reported abrupt-onset musculoskeletal pain 15 days after delivery of her first infant. Her first pregnancy was uneventful. The physical examination yielded only bilateral conjunctivitis and purpuric eruption of lower limbs, and complementary investigations evidenced pulmonary renal syndrome in connection with the diagnosis of Granulomatosis with Polyangiitis.

Methods

We screened previous articles in Medline database using keywords (i) “post-partum” or “puerperium” (ii)”peripartum” (iii) “pregnancy” associated with “vasculitis”. Full texts were obtained from case reports or cases series whose title or abstract included keywords of interest (or synonyms). These references were secondarily excluded if the diagnosis of vasculitis was not confirmed or made before or more than 6 months after delivery and if vasculitis occurred only in the new born or affected only the cerebral vasculature or the retina.

Results

Fifty-six cases of vasculitis diagnosed in the post-partum period were included, 50 (89.3%) were secondary to an immunological process and 44 corresponded to primary vasculitis, 4 were secondary to Systemic Lupus Erythematosus, 1 to cryoglobulinaemia and 1 to cryoglobulinaemia associated with inflammatory bowel disease. The main primary vasculitis diagnosed were Takayasu Arteritis (n = 10), Eosinophilic granulomatosis with polyangiitis (n = 9), Granulomatosis with Polyangiitis (n = 7), Periarteritis Nodosa (n = 5) and Behcet’s disease (n = 4). The first symptom occurred before delivery in 26 (59.1%) and maternal death occurred in 4 (9.1%) out of the 44 primary vasculitis cases.

Conclusion

The vasculitis diagnosed in the post-partum period were mainly primary vasculitis among patients in whom the diagnosis had not been made during pregnancy. In less than half of cases and as described in ours, there were no reported symptoms before delivery. Therefore, the physicians should pay attention to symptoms and keep a high degree of suspicion for vasculitis before as well as after delivery.
Surgical resection of a retroperitoneal liposarcoma producing insulin-like growth factor II: a case report
Authors: Nishiwaki Noriyuki , Mikuriya Yoshihiro , Takatsu Fumiaki , Ochiai Ryoji , Kakishita Tomokazu , Kobayashi Naruyuki , Kobatake Takaya , Hato Shinji , Teramoto Norihiro , Nagao Mototsugu , Fukuda Izumi , Ohta Koji
Published: February 2023

Background

Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II.

Case presentation

Here, we report the case of a 62-year-old woman who presented with an abdominal mass and hypoglycemia. Non-islet cell tumor hypoglycemia due to retroperitoneal liposarcoma was suspected. After complete resection of the tumor, the patient’s hypoglycemia improved and big insulin-like growth factor-II disappeared in the molecular weight analysis of serum insulin-like growth factor-II by western blotting. The patient had no tumor recurrence or reappearance of hypoglycemia 16 months after the operation without any adjuvant therapy.

Conclusions

Although insulin-like growth factor-II-producing tumors are generally large and difficult to operate on, surgical resection is currently the most effective and only treatment; thus, it is essential to attempt resection aggressively.
Influence of Resistance Training Proximity-to-Failure, Determined by Repetitions-in-Reserve, on Neuromuscular Fatigue in Resistance-Trained Males and Females
Authors: Refalo Martin C. , Helms Eric R. , Hamilton D. Lee , Fyfe Jackson J.
Published: February 2023

Background

This study examined the influence of proximity-to-failure in resistance training (RT), using subjective repetitions-in-reserve (RIR) prediction, on neuromuscular fatigue and perceptual responses.

Methods

Twenty-four resistance-trained males (n = 12) and females (n = 12) completed three experimental trials in a randomised order, each involving six RT sets (barbell bench press) with 75% 1-RM performed to either momentary muscular failure (FAIL), 1-RIR, or 3-RIR. Changes in lifting velocity with a fixed load were assessed from pre-exercise to post-exercise with the aim of quantifying acute neuromuscular fatigue (4 min post-exercise) and the associated time course of recovery (24 and 48 h post-exercise), and from the first to final set performed. Perceptual responses to RT were assessed at multiple time points during and following RT.

Results

Decreases in lifting velocity at 4 min post-exercise were greater for FAIL ( − 25%) versus 1-RIR ( − 13%) and 3-RIR ( − 8%), with greater decreases for male ( − 29%) versus female ( − 21%) participants following FAIL. At 24 h post-exercise, decreases in lifting velocity were greater for FAIL ( − 3%) and 1-RIR ( − 3%) versus 3-RIR (+ 2%), with all between-protocol differences diminishing at 48 h post-exercise. Loss of lifting velocity from the first to final set was greater for FAIL ( − 22%) versus 1-RIR ( − 9%) and 3-RIR ( − 6%), with a greater lifting velocity loss from the first to final set for males ( − 15%) versus females ( − 9%). As proximity-to-failure neared, ratings of perceived discomfort, exertion, and muscle soreness increased, general feelings worsened, and perceived recovery decreased.

Conclusion

These findings support a linear relationship between RT proximity-to-failure and both acute neuromuscular fatigue and negative perceptual responses, which may influence long-term physiological adaptations and adherence to RT.
Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson’s disease
Authors: Xu Junpeng , Chen Tsai-Yu , Tai Chun-Hwei , Hsu Shan-hui
Published: February 2023

Background

Parkinson’s disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel based on novel tannic acid crosslinker was developed to treat PD.

Methods

The oxidized tannic acid modified gold nano-crosslinker was synthesized and used to effectively crosslink chitosan for preparation of the bioactive self-healing hydrogel. The crosslinking density, conductivity, self-healing ability, and injectability of the hydrogel were characterized. Abilities of the hydrogel to promote the proliferation and differentiation of neural stem cells (NSCs) were assessed in vitro. Anti-inflammatory property was analyzed on J774A.1 macrophages. The hydrogel was injected in the PD rat model for evaluation of the motor function recovery, electrophysiological performance improvement, and histological repair.

Results

The hydrogel exhibited self-healing property and 34G (~ 80 μm) needle injectability. NSCs grown in the hydrogel displayed long-term proliferation and differentiation toward neurons in vitro. Besides, the hydrogel owned strong anti-inflammatory and antioxidative capabilities to rescue inflamed NSCs (~ 90%). Brain injection of the bioactive hydrogel recovered the motor function of PD rats. Electrophysiological measurements showed evident alleviation of irregular discharge of nerve cells in the subthalamic nucleus of PD rats administered with the hydrogel. Histological examination confirmed that the hydrogel alone significantly increased the density of tyrosine hydroxylase positive neurons and fibers as well as reduced inflammation, with a high efficacy similar to drug-loaded hydrogel.

Conclusion

The new bioactive hydrogel serves as an effective brain injectable implant to treat PD and a promising biomaterial for developing novel strategies to treat brain diseases.

Graphical Abstract
Arthrogryposis multiplex congenita with maxillofacial involvement: a case report
Authors: Cirillo Stefano , Regge Daniele , Garagiola Umberto , Tortarolo Alessandro , Iorio Giuseppe Carlo , Spahiu Orges , Piancino Maria Grazia
Published: February 2023

Background

Arthrogryposis multiplex congenita is a rare condition that mainly involves the lower limbs, characterized by severe joint deformity and contracture, muscular atrophy, and functional impairment. Its clinical manifestations are heterogenous and may involve the maxillofacial district as well.

Case presentation

This case report describes a 20-year-old patient with arthrogryposis multiplex congenita with skeletal crossbite, facial asymmetry, reduced mouth opening and absence of lateral mandibular movement on the left side. After clinical evaluation, the following exams were required: postero-anterior cephalometric tracing, head and neck electromyography, computerized axiography, computed tomography scan, and maxillofacial magnetic resonance imaging. Orthognathodontic evaluation indicated skeletal asymmetry, reduced condylar movements on the left side and abnormally low electromyography activity of the masticatory muscles on the left side. Computed tomography and magnetic resonance imaging revealed unilateral left mandibular hypoplasia, hypotrophy, and fatty infiltration of masticatory muscles on the left side, as well as immobility of the left condyle during mouth opening, and hypoplasia of the left articular disk, which was however not displaced. Surgery was not indicated and conservative orthognathodontic treatment with function generating bite was suggested to balance the occlusal plane, as well as stretching exercises.

Conclusions

A rare case of arthrogryposis multiplex congenita with maxillofacial involvement illustrates that a patient-centred, multidisciplinary approach with accurate diagnosis is required to formulate the best treatment plan. Because of the considerable damage to the masticatory muscles, conservative orthognathodontic therapy may be the best treatment option.
Visual and quantitative assessment of hip implant-related metal artifacts at low field MRI: a phantom study comparing a 0.55-T system with 1.5-T and 3-T systems
Authors: Breit Hanns-Christian , Vosshenrich Jan , Clauss Martin , Weikert Thomas J. , Stieltjes Bram , Kovacs Balázs K. , Bach Michael , Harder Dorothee
Published: February 2023

Background

To investigate hip implant-related metal artifacts on a 0.55-T system compared with 1.5-T and 3-T systems.

Methods

Total hip arthroplasty made of three different alloys were evaluated in a water phantom at 0.55, 1.5, and 3 T using routine protocols. Visually assessment (VA) was performed by three readers using a Likert scale from 0 (no artifacts) to 6 (extremely severe artifacts). Quantitative assessment (QA) was performed using the coefficient of variation (CoV) and the fraction of voxels within a threshold of the mean signal intensity compared to an automatically defined region of interest (FVwT). Agreement was evaluated using intra/inter-class correlation coefficient (ICC).

Results

Interreader agreement of VA was strong-to-moderate (ICC 0.74−0.82). At all field strengths (0.55-T/1.5-T/3-T), artifacts were assigned a lower score for titanium (Ti) alloys (2.44/2.9/2.7) than for stainless steel (Fe-Cr) (4.1/3.9/5.1) and cobalt-chromium (Co-Cr) alloys (4.1/4.1/5.2) (p < 0.001 for both). Artifacts were lower for 0.55-T and 1.5-T than for 3-T systems, for all implants (p ≤ 0.049). A strong VA-to-QA correlation was found (r = 0.81; p < 0.001); CoV was lower for Ti alloys than for Fe-Cr and Co-Cr alloys at all field strengths. The FVwT showed a negative correlation with VA (-0.68 < r < -0.84; p < 0.001).

Conclusions

Artifact intensity was lowest for Ti alloys at 0.55 T. For other alloys, it was similar at 0.55 T and 1.5 T, higher at 3 T. Despite an inferior gradient system and a larger bore width, the 0.55-T system showed the same artifact intensity of the 1.5-T system.
Determinants of the quality of life in Egyptian patients with cerebrovascular stroke by using the stroke specific QoL questionnaire
Authors: Aziz Arjuman Mohamed , Rizian Alice Edwar , Tawfik Fayza Mohamed , Mekky Jaidaa Farouk
Published: February 2023

Background

Stroke is a neurological disorder resulting from a sudden decline in blood flow to a localized area of the brain. It is the second most common cause of death and the third most common cause of disability worldwide. Quality of life (QOL) is increasingly being used as an outcome measure designed to evaluate the quality of care for patients with stroke.

Objective

The study aims to assess the quality of life of cerebrovascular stroke patients in Alexandria, Egypt.

Methods

A descriptive crossover study was held on 80 adult cerebrovascular stroke patients admitted to the stroke unit at (Elhadra) University Hospital, Neuropsychiatry Department, and the outpatient clinics at the Main University Hospital.

Result

The main result of study revealed that there was a highly significant relation between socio-demographic characteristics and the patient’s quality of life (QOL), especially age, employment status, and the monthly income, the overall QOL (P < 0.05).

Recommendation

The study recommended that design health education program to raise stroke patient QOL, design program to improve care giver attitude toward stroke patient, collaborative efforts among the governmental agencies to improve the educational level of the citizens, further studies to examine QOL on larger group of patients to generalize the results.
Systematic combinations of major cannabinoid and terpene contents in Cannabis flower and patient outcomes: a proof-of-concept assessment of the Vigil Index of Cannabis Chemovars
Authors: Vigil Jacob Miguel , Stith Sarah See , Brockelman Franco , Keeling Keenan , Hall Branden
Published: February 2023

Background

Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects.

Methods

Between 09/10/2016 and 03/11/2021, 204 people used the freely available, educational mobile software application, Releaf App, to record 6309 real-time consumption sessions using 633 distinct Cannabis flower products, unique at the user level, with terpene and cannabinoid potency information. The indexing system is based on retrospective data analysis of the products’ primary and secondary terpene contents and tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies and yielded a total of 478 distinct chemovars. Analyses of covariances (ANCOVAs) were used to compare symptom levels and side effects experienced across the five most common chemovars before and after cannabis consumption for app users overall and for those treating chronic pain and depression or anxiety.

Results

Examination of the five most frequently consumed chemovars showed significant differences in symptom treatment effectiveness for chronic pain and for depression and anxiety (ps < .001). While the effects varied in magnitude, the five chemovars were effective across conditions except for MC61 (mercene .01–0.49%/beta-caryophyllene .01 to 0.49%/THC 20–25%/CBD 0.01–1.0%), which exacerbated feelings of anxiety or depression. The chemovars also differed in their association with experiencing positive, negative, and context-specific side effects, with two chemovars, MC61 and MC62 (mercene .01–0.49%/beta-caryophyllene .01–0.49%/THC 20–25%/CBD 1–5%), generating two to three fewer positive side effects and as much as one more negative and two more context-specific side effects than the other three chemovars.

Conclusions

The findings provide “proof-of-concept” that a simple, yet comprehensive chemovar indexing system can be used to identify systematic differences in clinically relevant patient health outcomes and other common experiences across Cannabis flower products, irrespective of the product’s commercial or strain name. This study was limited by self-selection into cannabis and app use and a lack of user-specific information. Further research using this chemovar indexing system should assess how distinct combinations of phytochemicals interact with user-level characteristics to produce general and individualized Cannabis consumption experiences and health outcomes, ideally using randomized methods to assess differences in effects across chemovars.
Impact of chronic war trauma exposure on PTSD diagnosis from 2006 -2021: a longitudinal study in Palestine
Authors: Altawil Mohamed A. S. , El-Asam Aiman , Khadaroo Ameerah
Published: February 2023

Background

Trauma and Post-Traumatic Stress Disorders (PTSD) are a common result of the occurrence of natural and man-made disasters, the refugees are one of these traumas in which some resulted from political conflicts. Today, Palestinians are the largest refugee population in the world after the Nakba in 1948. This study aims to discover the impact of chronic war traumas on PTSD diagnosis and symptoms from 2006 to 2021. The current study is a follow-up of 607 adolescents and adults, aged between 10–30 years of which are also those children who participated in the 2006 study. This research used an adapted PTSD scale (PTSD-SRII, 33 items) from a validated original questionnaire developed by Altawil in 2008 to measure PTSD based on symptoms reported in DSM-IV and ICD-10.

Results

The main findings show at least 97.2% of participants had experienced at least 6 traumatic experiences up to the year 2006 and 100% of the participants were exposed to traumas in 2021. This study found four categories of responses to chronic war trauma: (a) Acute group (n = 321, 52.9%) shows high PTSD symptoms in 2006 and in 2021; (b) Remitters group (n = 54, 8.9%) shows high PTSD symptoms in 2006 but did not show significant PTSD symptoms in 2021; (c) Delayed group (n = 204, 33.6%) shows no PTSD symptoms in 2006 but showed significant PTSD symptoms in 2021; (d) Resilient group (n = 28, 4.6%) had no PTSD symptoms in 2006 and did not show PTSD symptoms in 2021.

Conclusions

The authors conclude that Palestinian children, youth, adults and their families in the Gaza Strip are continually at a huge risk of developing PTSD and other psychological problems.

This means that Palestinians will suffer for a long time from PTSD, which should be called Chronic Traumatic Stress Disorder (CTSD) rather than PTSD. This PTSD or CTSD cannot be changed unless the root of the problem is solved by ending the 74 years of living under occupation.
Assessment of pharmacovigilance activities among pharmacist interns in Nigeria: a cross-sectional study
Authors: Eze Shadrach Chinecherem , Odoh Evaristus Chinonso , Eze Kingsley Chinemerem , Arugo Wisdom Enyinnaya , Ozota Gerald Obinna , Anyaji Ugomma Loveth , Mbakamma Chidimma Elizabeth , Magbo Collins Chukwuemeka , Ofili Samuel Chijioke , Amaechi Victor Chikaodiri , Nwiyi Chimaobi Jude , Onyesoro Joy Chekwube , Etukudo Uwakmfon Bassey , Odoh Cornelius Chinedum , Kalu Loveth Onyinyechi , Eze Caleb Febechukwu
Published: February 2023

Background

Pharmacovigilance (PV) and adverse drug reaction (ADR) reporting is at the core of the services and functions of a pharmacist. Pharmacist interns undergoing their one-year mandatory internship program are expected to be armed with this tool kit in order to provide adequate pharmaceutical services in all areas of pharmacy practice.

Objectives

This study sought to assess the knowledge and perception of pharmacovigilance and adverse drug reaction reporting among pharmacist interns in Nigeria.

Methods

This study was a cross-sectional study among pharmacist interns in their one-year mandatory internship program across Nigeria. The 32-item semi-structured questionnaires were administered online using simple random sampling with the snowballing technique to recruit the participants in the study. The results were analyzed with IBM SPSS version 25. Descriptive statistics were used to summarize the data. The Chi-square test and contingency coefficient were used to determine the association between knowledge of PV and the demographics of the participants.

Results

A total of 450 pharmacist interns participated in this study. The participants' knowledge of pharmacovigilance and ADR is 92.5%. About 96.2% of respondents feel that responses to newly released pharmaceuticals must be recorded, compared to 79.1% for older drugs already on the market. There is a high correlation between the duration of the internship program and understanding of PV and ADR reporting among participants. More than fifty percent of respondents concur that ADR reporting is critical, while more than eighty percent concur that ADR reporting is required for pharmacists, the most significant health professionals in ADR reporting. The participants' length of participation in an internship program and their internship location significantly impact their opinion of ADR reporting. Seventy-four percent (74%) of respondents from tertiary hospitals say their internship center encourages ADR reporting.

Conclusion

Most participants have a solid understanding of PV and ADR reporting, but perceptions of PV and ADR reporting are substantially correlated with internship location and program length. Active measures should be implemented to ensure that all pharmacy interns comprehend and embrace PV and ADR reporting as their exclusive duty.
Seismic acquisition design based on full-wavefield migration
Authors: Revelo-Obando Billy , Blacquière Gerrit
Published: February 2023

The ultimate goal in survey design is to obtain the acquisition parameters that enable acquiring the most affordable data that fulfill certain image quality requirements. A method that allows optimization of the receiver geometry for a fixed source distribution is proposed. The former is parameterized with a receiver density function that determines the number of receivers per unit area. We optimize this receiver density function through an iterative gradient descent scheme that minimizes the difference between the image obtained with the current acquisition geometry and a reference image. The reference image is obtained from prior subsurface information that is assumed to be available. We tested the method with different subsurface models. The results indicate that the acquisition geometry is optimized according to the complexity of each subsurface model. The receivers are moved toward the areas where more data are needed for obtaining better imaging.
Using a synthetic data trained convolutional neural network for predicting subresolution thin layers from seismic data
Authors: Qu Dongfang , Mosegaard Klaus , Feng Runhai , Nielsen Lars
Published: February 2023

Numerous studies have demonstrated the capability of supervised deep learning techniques for predicting geological features of interest from seismic sections, including features that are difficult to identify using traditional interpretation methods. However, the successful application of these techniques in practice has been limited by the difficulty of obtaining a large training data set where the seismic data and corresponding ground truth labels are well-defined. Manually creating large amounts of labels requires a heavy workload, and the uncertainty of the interpretation and labeling process decreases the model’s ability for making accurate predictions. Using the chalk-flint sequence scenario onshore Denmark as an example, we have developed a novel workflow for predicting subresolution thin layers from seismic sections. It entails generating large quantities of synthetic training data with high-quality labels using stochastic geological modeling, training a convolutional neural network based on the synthetic data set, and applying it to real seismic data. This is, to our knowledge, the first example of using deep learning to predict subresolution thin layers from seismic data based on geostatistically generated training images. It is shown that a neural network trained on synthetic data can predict a realistic number of subresolution flint layers from the real seismic data that have been collected from the Stevns region in Denmark, which has value for the understanding of the overall geological characteristics of succession and engineering applications such as construction site evaluation.
DRAGON-Data: a platform and protocol for integrating genomic and phenotypic data across large psychiatric cohorts
Authors: Lynham Amy J. , Knott Sarah , Underwood Jack F. G. , Hubbard Leon , Agha Sharifah S. , Bisson Jonathan I. , van den Bree Marianne B. M. , Chawner Samuel J. R. A. , Craddock Nicholas , O'Donovan Michael , Jones Ian R. , Kirov George , Langley Kate , Martin Joanna , Rice Frances , Roberts Neil P. , Thapar Anita , Anney Richard , Owen Michael J. , Hall Jeremy , Pardiñas Antonio F. , Walters James T. R.
Published: February 2023

Background

Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.

Aims

Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.

Method

As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.

Results

We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.

Conclusions

DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium
Authors: Wang Yucai , Jain Preetesh , Locke Frederick L. , Maurer Matthew J. , Frank Matthew J. , Munoz Javier L. , Dahiya Saurabh , Beitinjaneh Amer M. , Jacobs Miriam T. , Mcguirk Joseph P. , Vose Julie M. , Goy Andre , Andreadis Charalambos , Hill Brian T. , Dorritie Kathleen A. , Oluwole Olalekan O. , Deol Abhinav , Paludo Jonas , Shah Bijal , Wang Trent , Banerjee Rahul , Miklos David B. , Rapoport Aaron P. , Lekakis Lazaros , Ghobadi Armin , Neelapu Sattva S. , Lin Yi , Wang Michael L. , Jain Michael D.
Published: February 2023

PURPOSE

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.

PATIENTS AND METHODS

Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines.

RESULTS

Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis.

CONCLUSION

In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
Mutation Spectrum in Liquid Versus Solid Biopsies From Patients With Advanced Gastroenteropancreatic Neuroendocrine Carcinoma
Authors: Knappskog Stian , Grob Tobias , Venizelos Andreas , Amstutz Ursula , Hjortland Geir O. , Lothe Inger M. , Kersten Christian , Hofsli Eva , Sundlöv Anna , Elvebakken Hege , Garresori Herish , Couvelard Anne , Svensson Johanna , Sorbye Halfdan , Perren Aurel
Published: February 2023

PURPOSE

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and have a poor prognosis. Most GEP-NEC are diagnosed with metastatic disease, with only minor biopsies available for molecular diagnostics. We assessed the applicability of liquid biopsies for molecular profiling of GEP-NEC.

MATERIALS AND METHODS

We performed massive parallel sequencing of 76 cancer-related genes in circulating tumor DNA from 50 patients with advanced GEP-NEC and compared findings to previous analyses of solid tumor biopsies from the same patients. Plasma samples were collected before therapy, and the median time span between blood and tissue sampling was 25 days.

RESULTS

We detected 178 somatic mutations in the liquid biopsies, 127 (71%) were also detected in the solid biopsies, whereas 51 (29%) were unique to the liquid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (single nucleotide variants) in solid biopsies, of which 127 (64%) were also now detected in liquid biopsies. In exploratory subgroup assessments, concordance was higher in patients with liver metastases ( P = 1.5 × 10–5) and increasing with level of liver involvement ( P = 1.2 × 10–4). The concordance was similar between GEP-NEC with different primary sites, except being lower in esophageal cases ( P = .001). Concordance was not associated with tumor mutation burden. Tumor tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumors (70%; P = 7.8 × 10–4). We identified potentially targetable mutations in plasma of 26 (52%) of patients with GEP-NEC; nine patients (18%) had potentially targetable mutation detected only in liquid biopsies.

CONCLUSION

Liquid biopsy analyses may be an applicable alternative to solid biopsies in GEP-NEC. Liquid biopsies may add additional mutations compared with tumor biopsies alone and could be useful for biomarker assessment in clinical trials for these patients.
FCH-PET/CT in Primary Hyperparathyroidism With Discordant/Negative MIBI Scintigraphy and Ultrasonography
Authors: Koumakis Eugenie , Gauthé Mathieu , Martinino Alessandro , Sindayigaya Rémy , Delbot Thierry , Wartski Myriam , Clerc Jérôme , Roux Christian , Borderie Didier , Cochand-Priollet Beatrix , Cormier Catherine , Gaujoux Sébastien
Published: February 2023

Context

The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown.

Objective

To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX).

Design

Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism.

Setting

Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism.

Patients

Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX.

Main outcome measures

To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT.

Results

The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients.

Conclusion

This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.
Phosphate NIMA-Related Kinase 2-Dependent Epigenetic Pathways in Dorsal Root Ganglion Neurons Mediates Paclitaxel-Induced Neuropathic Pain
Authors: Hsieh Ming-Chun , Lai Cheng-Yuan , Cho Wen-Long , Lin Li-Ting , Yeh Chou-Ming , Yang Po-Sheng , Cheng Jen-Kun , Wang Hsueh-Hsiao , Lin Kuan-Hung , Nie Siao-Tong , Lin Tzer-Bin , Peng Hsien-Yu
Published: February 2023

BACKGROUND:

The microtubule-stabilizing drug paclitaxel (PTX) is an important chemotherapeutic agent for cancer treatment and causes peripheral neuropathy as a common side effect that substantially impacts the functional status and quality of life of patients. The mechanistic role for NIMA-related kinase 2 (NEK2) in the progression of PTX-induced neuropathic pain has not been established.

METHODS:

Adult male Sprague-Dawley rats intraperitoneally received PTX to induce neuropathic pain. The protein expression levels in the dorsal root ganglion (DRG) of animals were measured by biochemical analyses. Nociceptive behaviors were evaluated by von Frey tests and hot plate tests

RESULTS:

PTX increased phosphorylation of the important microtubule dynamics regulator NEK2 in DRG neurons and induced profound neuropathic allodynia. PTX-activated phosphorylated NEK2 (pNEK2) increased jumonji domain–containing 3 (JMJD3) protein, a histone demethylase protein, to specifically catalyze the demethylation of the repressive histone mark H3 lysine 27 trimethylation (H3K27me3) at the Trpv1 gene, thereby enhancing transient receptor potential vanilloid subtype-1 (TRPV1) expression in DRG neurons. Moreover, the pNEK2-dependent PTX response program is regulated by enhancing p90 ribosomal S6 kinase 2 (RSK2) phosphorylation. Conversely, intrathecal injections of kaempferol (a selective RSK2 activation antagonist), NCL 00017509 (a selective NEK2 inhibitor), NEK2-targeted siRNA, GSK-J4 (a selective JMJD3 inhibitor), or capsazepine (an antagonist of TRPV1 receptor) into PTX-treated rats reversed neuropathic allodynia and restored silencing of the Trpv1 gene, suggesting the hierarchy and interaction among phosphorylated RSK2 (pRSK2), pNEK2, JMJD3, H3K27me3, and TRPV1 in the DRG neurons in PTX-induced neuropathic pain.

CONCLUSIONS:

pRSK2/JMJD3/H3K27me3/TRPV1 signaling in the DRG neurons plays as a key regulator for PTX therapeutic approaches.
The Media Swirl
Authors: Vernallis Carol
Published: February 2023

From fan-generated content on TikTok to music videos, the contemporary media landscape is becoming ever more vast, spectacular, and intense. In The Media Swirl Carol Vernallis examines short-form audiovisual media—Beyoncé’s Lemonade, brief sequences from Baz Luhrmann’s The Great Gatsby, TikTok challenges, YouTube mashups, commercials, and many other examples—to offer ways of understanding digital media. She analyzes music videos by Beyoncé, Lady Gaga, Janelle Monáe, Kendrick Lamar, Anderson .Paak, and others to outline how sound and image enhance each other and shape a viewer’s mood. Responding to today’s political-media landscape through discussions of Fox News and Presidential inaugurations, Vernallis shows how a media literacy that exceeds newscasts and campaign advertising is central to engaging with the democratic commons. Forays into industry studies, neuroscience, and ethics also inform her readings. By creating our own content and knowing what corporations, the wealthy, and the government do through media, Vernallis contends, we can create a more just world.
Mendings
Authors: Sweeney Megan
Published: February 2023

Mendings tells an intimate story about family, selfhood, and the love and loss lodged in garments. In this narrative about making meaning of brokenness and grief, Megan Sweeney reflects on her childhood entanglement with her mother, her loss-filled relationship with her alcoholic father, and her attachment to the clothes that have mended her as she has mended them. Sweeney explores how clothing fosters communication and enables us to cultivate relationships with ourselves and with others, both living and deceased. In dialogue with other clothing lovers, writers, fiber artists, evolutionary biologists, historians, and environmentalists, Sweeney also foregrounds the entwinement of clothing, race, and gender as she considers the ethics and environmental effects of clothing consumption, the history of clothing in the US prison system, and the roles that textiles play as sources of creativity, artistry, and self-fashioning, even within conditions of constraint. For Sweeney, the act of mending is a way of living. Unlike fixing, which leaves no trace of damage or loss, mending allows Sweeney to embrace holes, rips, and threadbare patches as part of her life’s design.
Association of Postoperative Drift in Hemoglobin With Mortality After Brain Tumor Craniotomy
Authors: Zhang Yu , Jia Lu , Tian Yixin , He Jialing , He Miao , Chen Lvlin , Hao Pengfei , Li Tiangui , Peng Liyuan , Chong Weelic , Hai Yang , You Chao , Fang Fang
Published: February 2023

BACKGROUND:

Postoperative downward drift in hemoglobin (Hb) concentration may be associated with complications and death, even if nadir Hb remains more than the red blood cell transfusion threshold of 7 g/dL.

OBJECTIVE:

To assess whether postoperative Hb drift in patients undergoing brain tumor craniotomy influences mortality in the immediate perioperative period.

METHODS:

This retrospective cohort study included patients undergoing craniotomy for brain tumors. We defined no postoperative Hb decrease, mild decrease, moderate decrease, and severe decrease as postoperative Hb drift of ≤25%, 26% to 50%, 51% to 75%, and >75%, respectively. The primary outcome was 30-day mortality after craniotomy.

RESULTS:

This study included 8159 patients who underwent a craniotomy for brain tumors. Compared with patients with no postoperative Hb drift, the odds of postoperative mortality at 30 days increased in patients with mild postoperative Hb drift (adjusted odds ratio [OR] 2.47, 95% CI 1.72-3.56), moderate drift (adjusted OR 6.56, 95% CI 3.42-12.59), and severe drift (adjusted OR 12.33, 95% CI 3.48-43.62). When postoperative Hb drift was analyzed as a continuous variable, for each 10% increase in Hb drift, the adjusted OR of postoperative mortality at 30 days was 1.46 (95% CI 1.31-1.63).

CONCLUSION:

In patients undergoing brain tumor craniotomy, a small postoperative Hb drift was associated with increased odds of postoperative mortality at 30 days, even if the nadir Hb level remained greater than the red blood cell transfusion threshold of 7 g/dL. Future randomized clinical trials of perioperative transfusion practices may examine the effect of both nadir Hb and Hb drift.
Energetic costs of bill heat exchange demonstrate contributions to thermoregulation at high temperatures in toco toucans (Ramphastos toco)
Authors: Chaves Jussara N. , Tattersall Glenn J. , Andrade Denis V.
Published: February 2023

Body temperature regulation under changes in ambient temperature involves adjustments in heat production and heat exchange rates between the animal and the environment. One mechanism involves the modulation of the surface temperature of specific areas of the body through vasomotor adjustment. In homeotherms, this thermoregulatory adjustment is essential for the maintenance of body temperature over a moderate temperature range, known as the thermal neutral zone (TNZ). The bill of the toco toucan (Ramphastos toco) has been described as a highly efficient thermal window and hypothesized to assist in the thermal homeostasis of this bird. Herein, we directly evaluated the contribution of heat exchange through the bill of the toco toucan and role of the bill in the delimitation of the TNZ. To do this, we measured metabolic rate (MR), via oxygen consumption, over a range of ambient temperatures from 0 to 35°C. MR measurements were made in birds with the bill intact and with the bill insulated. The limits of the TNZ did not differ between treatments, ranging from 10.8 to 25.0°C. The MR differed among treatments only at elevated temperatures (30 and 35°C), reaching 0.92±0.11 ml O2 g−1 h−1 (mean±s.d.) for the intact group and 1.13±0.13 ml O2 g−1 h−1 for the insulated group. These results indicate that although heat dissipation through the bill does not contribute significantly to widening of the TNZ, it may well be critically important in assisting body temperature regulation at higher temperatures extending above the upper limit of the TNZ.