bluuebunny/crossref_metadata_2025 huggingface dataset:
Discriminating Inflammatory Radiation-Related Changes From Early Recurrence in Patients With Glioblastomas
Authors: Moreau Aurélie , Khayi Fouzi , Maureille Aurélien , Bonneville-Levard Alice , Larrouquere Louis , Ducray François , Kryza David
Published: June 2023

Purpose of the Report

Using morphological and functional imaging to discriminate recurrence from postradiation-related modifications in patients with glioblastomas remains challenging. This pilot study aimed to assess the feasibility of using 68Ga–prostate-specific membrane antigen (PSMA) 11 PET/CT compared with 18F-FDOPA PET/CT to detect early recurrence.

Methods

Nine patients followed up for glioblastomas who received MRI during 12 months of follow-up were referred for both 68Ga-PSMA-11 and 18F-FDOPA PET/CT. The SUVmax, lesion-to-striatum ratio, lesion-to-normal parenchyma ratio, and lesion-to-salivary gland ratio were calculated.

Results

Good correlation between 18F-FDOPA and 68Ga-PSMA PET/CT findings was seen in 5 patients. In 4 patients, the findings of both examinations were consistent with recurrence but were better visualized with the PSMA PET/CT. Examinations of the fifth patient were suggestive of postradiation-related changes and were better analyzed with the PSMA PET/CT, which displayed relatively low uptake compared with DOPA PET/CT. Conversely, 4 patients showed conflicting results: recurrence was not detected on the PSMA PET/CT because of previously introduced bevacizumab treatment; in another patient, both examinations were consistent with recurrence, but there was an uptake mismatch at the suspected lesion sites, and 2 patients presented with inconsistent findings.

Conclusions

Despite a few discrepancies, this study highlights the potential role of 68Ga-PSMA-11 PET/CT for discriminating postradiation inflammation from recurrence. 68Ga-PSMA-11 PET/CT has an excellent lesion-to-background ratio, and false-positive and false-negative results could be minimized through implementing certain protocols before performing the examination. More powerful prospective studies are required to validate our results.
Rapid Tumor Washout of 177Lu-PSMA Radioligand in Renal Cell Carcinoma
Authors: Zhang Jingjing , Schuchardt Christiane , Chen Xiaoyuan , Baum Richard P.
Published: June 2023

The role of prostate-specific membrane antigen (PSMA) targeted molecular imaging and radionuclide therapy in prostate cancer is well known. PSMA is also overexpressed in the neovasculature of a number of solid tumors, including renal cell carcinoma (RCC). Several studies have demonstrated the diagnostic utility of PSMA PET imaging in the setting of RCC. To date, no PSMA radioligand therapy of RCC patient has been reported according to literature. Here, we report our experience treating a patient with metastatic RCC with 177Lu-PSMA I&T radioligand therapy, but unexpected imaging findings with rapid washout of 177Lu-PSMA from the tumor.
68Ga-DOTATOC PET/CT in Pancreatic Metastasis From Clear Cell Renal Cell Carcinoma
Authors: Mansour Nabeel , Rangan Kasturi , Tiling Reinhold , Rübenthaler Johannes , Fabritius Matthias P.
Published: June 2023

We present a rare case of a 74-year-old woman who underwent 68Ga-DOTATOC PET/CT imaging for a suspected neuroendocrine tumor (NET) in the pancreatic head. PET/CT showed a solitary high somatostatis receptor (SSTR)-expressing lesion in the pancreatic head. Fine-needle aspiration of this lesion revealed a metastasis from a clear cell renal cell carcinoma (ccRCC). The patient had undergone nephrectomy 16 years prior due to ccRCC of the right kidney. Our case demonstrates that metastases originating from RCC can have high SSTR expression and therefore might mimic well-differentiated neuroendocrine tumors in 68Ga-DOTATOC PET/CT.
Clinical Characterization of Oral and Maxillofacial Tumors and Tumor-Like Lesions in Children and Adolescents
Authors: Zhang Jia-Li , Liu Ying , Shan Xiao-Feng , Xie Shang , Kang Yi-Fan , Cai Zhi-Gang
Published: June 2023

Purpose:

To investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents.

Methods:

This is a retrospective study of patients who had oral and maxillofacial tumors under the age of 18 years and were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January 1990 to July 2021 (31 y). Their general conditions, pathological diagnosis, gender, age, and anatomical location were counted to analyze their morbidity and composition characteristics.

Results:

This study contained 5405 cases, including 2903 male patients and 2502 female patients, with a median age of 9 years. Peak incidence was observed in the 14 to 18 years age group. The mandible (22.15%), maxilla (11.75%), and tongue (9.25%) were the most common sites of incidence. Malignant and intermediate type tumors accounted for 13.04%, benign tumors and tumor-like lesions for 55.67%, most often occurs in the maxillofacial bone, of which fibro-osseous lesions constitute an important part. Cysts accounted for 31.29%. Among the tumors occurring in the jaws, the most common malignant type was sarcoma, and ameloblastoma was the most common benign tumor. Malignant jaw tumors were mostly treated by resection, 10.64% by fibular flap reconstruction. While benign jaw tumors and tumor-like lesions were mostly treated by resection or curettage.

Conclusions:

The distribution of anatomical location and pathological types of oral and maxillofacial tumors in children has certain characteristics, so that the selection of their treatment options is different from that of adults due to the consideration of the growth and developmental characteristics of children.
Application of Surgery-First Approach in Treating Skeletal Dentofacial Asymmetry with Orthognathic Surgery
Authors: Chen Zhewei , Zhong Yehong , Li Binghang , Ma Hengyuan , Lei Bowen , Yang Bin
Published: June 2023

Background:

Skeletal dentofacial asymmetry decreases patient’s attractiveness by deteriorating symmetry of facial appearance which is of great significance to individuals. Surgery-first orthognathic approach manifests its advantages of shortening treatment time and improving patient’s quality of life. However, current literature on surgery-first approach mainly focuses on treating prognathism, overlooking its efficacy in improving facial symmetry of skeletal dentofacial asymmetry patients. This study aimed to assess SFA’s efficacy in improving facial appearance by analyzing morphological features of asymmetric bone and facial soft tissue in a three-dimensional manner.

Methods:

Thirty-four patients who received orthognathic surgery in a surgery-first fashion were included. Based on three-dimensional CT reconstruction, bilateral preoperative morphological features and postoperative symmetry of hard tissue were compared respectively. Efficacy of facial soft tissue symmetry restoration was evaluated using root mean square deviation (RMSD).

Results:

Asymmetric features mainly located in menton, mandibular body length, angulation between ramus and midsagittal plane (MSP), distance between gonion and MSP and so on, which were significantly restored after the whole treatment. RMSD of facial soft tissue surface were significantly declined after the treatment and prognathism was corrected simultaneously if existed.

Conclusions:

Surgery-first orthognathic approach is proved to be capable of treating skeletal dentofacial asymmetry effectively and efficiently.
Application of Adhesive Skin Electrode for Intraoperative Neuromonitoring During Enucleation of a Cervical Vagal Schwannoma
Authors: Kim Yeong Joon , Lee Kang Dae , Lee Hyoung Shin
Published: June 2023

Background:

No reports on applying adhesive skin electrodes for intraoperative nerve monitoring (IONM) of the vagus nerve during schwannoma enucleation have been reported in the literature.

Methods:

A 45-year-old patient was referred to our institution with a 2.2 cm mass in the left lateral neck, suspected to be a vagal nerve schwannoma. A pair of surface electrodes were attached to the lateral margin of the thyroid cartilage. After exposing the tumor, the authors selected the incision site avoiding the expected course of the vagus nerve fibers after mapping on the surface of the tumor.

Results:

Postoperative vocal cord function was intact, without aspiration or dysphagia.

Conclusions:

The authors report the successful use of skin electrodes for IONM of the vagus nerve during cervical vagal schwannoma removal, suggesting the feasibility of applying these electrodes for IONM of neck surgeries other than those associated with the thyroid or parathyroid glands.
Treatment of Oral Mucositis Using Platelet-Rich-Fibrin: A Retrospective Study on Oncological Patients
Authors: Miranda Michele , Gianfreda Francesco , Rosa Alessio , Fiorillo Luca , Cervino Gabriele , Cicciù Marco , Bollero Patrizio
Published: June 2023

Oral mucositis is an inflammatory mucosal demolition frequently observed during treatments for neoplastic diseases such as chemotherapy or radiation therapy. The side effects of these treatments often drastically reduce patients’ quality of life.

Oral mucositis is the result of the systemic consequences of chemotherapy and radiotherapy, which due to their cytotoxic and local effects, lead to pain and severe ulceration with a consequent decrease in the quality of life of affected subjects. Plasma rich in fibrin is often used to enhance soft tissue wound healing and fight bacterial sepsis through the presence of leukocytes within it.

The retrospective study aimed to evaluate the efficacy and safety of the topic use of platelet gel in the clinical management of oral mucositis to improve the life quality of patients. The results of the study were promising even though the topical application of platelet-rich-fibrin is like a skin-care treatment. Future studies with a larger sample of patients will be needed to understand the real benefits of platelet-rich-fibrin.
Outcomes of Kidney Transplantation in Patients That Underwent Bariatric Surgery: A Systematic Review and Meta-Analysis
Authors: Pencovich Niv , Long Jane J. , Smith Byron H. , Kinzelman-Vesely Elissa A. , Sudhindran Vineeth , Ryan Randi J. , Stegall Mark D. , Kukla Aleksandra , Diwan Tayyab S.
Published: June 2023

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes.
Microfungal Flora of Apis mellifera (Hymenoptera: Apidae)and Varroa destructor (Mesostigmata: Varroidae)from the Eastern Black Sea Region and Fungal Vector Capacity in Honey Bee Colonies
Authors: USTA MEHTAP
Published: June 2023

Honey bees have great economic importance both in our country and in the world with their products and their contribution to pollination. For this reason, many microflora studies have been carried out on bees. While these studies were only for the isolation of pathogens, today the ecological roles of non-pathogenic flora members and how they can be exploited are being investigated. This study was carried out to determine the microfungal flora of the body surfaces and digestive systems of honey bee (Apis mellifera) and Varroa destructor dead bee samples taken from different apiaries in the Eastern Black Sea Region (Gümüşhane, Trabzon, Artvin, and Ordu) in 2022. As a result of the research; A total of 11 different fungi species belonging to Penicillium, Alternaria, Mucor, Trichoderma, Fusarium, Aspergillus and Verticillium genera were identified and the relationships of these fungi with bees were discussed based on the literature.
Selection, optimization, and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse populations
Authors: Lennon Niall J , Kottyan Leah C , Kachulis Christopher , Abul-Husn Noura , Arias Josh , Belbin Gillian , Below Jennifer E , Berndt Sonja , Chung Wendy , Cimino James J. , Clayton Ellen Wright , Connolly John J. , Crosslin David , Dikilitas Ozan , Velez Edwards Digna R. , Feng QiPing , Fisher Marissa , Freimuth Robert , Ge Tian ,   The GIANT Consortium,   The All of Us Research Program, Glessner Joseph T. , Gordon Adam , Guiducci Candace , Hakonarson Hakon , Harden Maegan , Harr Margaret , Hirschhorn Joel , Hoggart Clive , Hsu Li , Irvin Ryan , Jarvik Gail P. , Karlson Elizabeth W. , Khan Atlas , Khera Amit , Kiryluk Krzysztof , Kullo Iftikhar , Larkin Katie , Limdi Nita , Linder Jodell E. , Loos Ruth , Luo Yuan , Malolepsza Edyta , Manolio Teri , Martin Lisa J. , McCarthy Li , Meigs James B , Mersha Tesfaye B. , Mosley Jonathan , Namjou Bahram , Pai Nihal , Pesce Lorenzo L. , Peters Ulrike , Peterson Josh , Prows Cynthia A. , Puckelwartz Megan J. , Rehm Heidi , Roden Dan , Rosenthal Elisabeth A. , Rowley Robb , Sawicki Konrad Teodor , Schaid Dan , Schmidlen Tara , Smit Roelof , Smith Johanna , Smoller Jordan W. , Thomas Minta , Tiwari Hemant , Toledo Diana , Vaitinadin Nataraja Sarma , Veenstra David , Walunas Theresa , Wang Zhe , Wei Wei-Qi , Weng Chunhua , Wiesner Georgia , Xianyong Yin , Kenny Eimear
Published: June 2023

Polygenic risk scores (PRS) have improved in predictive performance supporting their use in clinical practice. Reduced predictive performance of PRS in diverse populations can exacerbate existing health disparities. The NHGRI-funded eMERGE Network is returning a PRS-based genome-informed risk assessment to 25,000 diverse adults and children. We assessed PRS performance, medical actionability, and potential clinical utility for 23 conditions. Standardized metrics were considered in the selection process with additional consideration given to strength of evidence in African and Hispanic populations. Ten conditions were selected with a range of high-risk thresholds: atrial fibrillation, breast cancer, chronic kidney disease, coronary heart disease, hypercholesterolemia, prostate cancer, asthma, type 1 diabetes, obesity, and type 2 diabetes. We developed a pipeline for clinical PRS implementation, used genetic ancestry to calibrate PRS mean and variance, created a framework for regulatory compliance, and developed a PRS clinical report. eMERGE’s experience informs the infrastructure needed to implement PRS-based implementation in diverse clinical settings.
Comparison of the Multivariate Genetic Architecture of Eight Major Psychiatric Disorders Across Sex
Authors: Schwaba Ted , Mallard Travis T. , Maihofer Adam X. , Rhemtulla Mijke , Lee Phil H. , Smoller Jordan W. , Davis Lea K. , Nivard Michel G. , Grotzinger Andrew D. , Tucker-Drob Elliot M.
Published: June 2023

Differences in the patterning of genetic sharing and differentiation between groups may arise from differences in biological pathways, social mechanisms, phenotyping and ascertainment. We expand the Genomic Structural Equation Modeling framework to allow for testing Genomic Structural Invariance (GSI): the formal comparison of multivariate genetic architecture across groups of individuals. We apply GSI to systematically compare the autosomal multivariate genetic architecture of eight psychiatric disorders spanning three broad factors (psychotic, neurodevelopmental, and internalizing) between cisgender males and females. We find that the genetic factor structure is largely similar between males and females, permitting meaningful comparisons of associations at the level of broad factors. However, problematic alcohol use loads on psychotic disorders in males but not in females, and both problematic alcohol use and post-traumatic stress disorder load more strongly on internalizing disorders in females than in males. Despite a high between-sex genetic correlation, the neurodevelopmental disorders factor exhibited weaker genetic correlations with psychotic and internalizing factors in females compared to males. Four biobehavioral phenotypes (educational attainment, insomnia, smoking ever, and Townsend Deprivation Index) had significant albeit small sex-differentiated associations with the psychotic factor. As GWAS samples continue to grow and diversify, GSI will become increasingly valuable for studying multivariate genetic architecture across groups.
Leveraging multi-source to resolve inconsistency across pharmacogenomic datasets in drug sensitivity prediction
Authors: Das Trisha , Bhattarai Kritib , Rajaganapathy Sivaraman , Wang Liewei , Cerhan James R. , Zong Nansu
Published: June 2023

Pharmacogenomics datasets have been generated for various purposes, such as investigating different biomarkers. However, when studying the same cell line with the same drugs, differences in drug responses exist between studies. These variations arise from factors such as inter-tumoral heterogeneity, experimental standardization, and the complexity of cell subtypes. Consequently, drug response prediction suffers from limited generalizability. To address these challenges, we propose a computational model based on Federated Learning (FL) for drug response prediction. By leveraging three pharmacogenomics datasets (CCLE, GDSC2, and gCSI), we evaluate the performance of our model across diverse cell line-based databases. Our results demonstrate superior predictive performance compared to baseline methods and traditional FL approaches through various experimental tests. This study underscores the potential of employing FL to leverage multiple data sources, enabling the development of generalized models that account for inconsistencies among pharmacogenomics datasets. By addressing the limitations of low generalizability, our approach contributes to advancing drug response prediction in precision oncology.
Explainable drug side effect prediction via biologically informed graph neural network
Authors: Huang Tongtong , Lin Ko-Hong , Machado-Vieira Rodrigo , Soares Jair C , Jiang Xiaoqian , Kim Yejin
Published: June 2023

Early detection of potential side effects (SE) is a critical and challenging task for drug discovery and patient care. In-vitro or in-vivo approach to detect potential SEs is not scalable for many drug candidates during the preclinical stage. Recent advances in explainable machine learning may facilitate detecting potential SEs of new drugs before market release and elucidating the critical mechanism of biological actions. Here, we leverage multi-modal interactions among molecules to develop a biologically informed graph-based SE prediction model, called HHAN-DSI. HHAN-DSI predicted frequent and even uncommon SEs of the unseen drug with higher or comparable accuracy against benchmark methods. When applying HHAN-DSI to the central nervous system, the organs with the largest number of SEs, the model revealed diverse psychiatric medications’ previously unknown but probable SEs, together with the potential mechanisms of actions through a network of genes, biological functions, drugs, and SEs.
Psychological outcomes of 12-15-year-olds with gender dysphoria receiving pubertal suppression in the UK: assessing reliable and clinically significant change
Authors: McPherson Susan , Freedman David E.P.
Published: June 2023

The evidence base for psychological benefits of GnRHA for adolescents with gender dysphoria (GD) was deemed “low quality” by the UK National Institute of Health and Care Excellence. Limitations identified include inattention to clinical importance of findings. This secondary analysis of UK clinical study data uses Reliable and Clinically Significant Change approaches to address this gap. The original uncontrolled study collected data within a specialist GD service. Participants were 44 12-15-year-olds with GD. Puberty was suppressed using “triptorelin”; participants were followed-up for 36 months. Secondary analysis used data from parent-report Child Behaviour Checklists and Youth Self-Report forms. Reliable change results: 15-34 percent of participants reliably deteriorated depending on the subscale, time point and parent versus child report. Clinically significant change results: 27-58 percent were in the borderline (subclinical) or clinical range at baseline (depending on subscale and parent or child report). Rates of clinically significant change ranged from 0-35%, decreasing over time towards zero on both self-report and parent-report. The approach offers an established complementary method to analyse individual level change and to examine who might benefit or otherwise from treatment in a field where research designs have been challenged by lack of control groups and low sample sizes.
The timecourse of inter-object contextual facilitation
Authors: Quek Genevieve L. , Theodorou Alexandra , Peelen Marius V.
Published: June 2023

High-level vision is frequently studied at the level of either individual objects or whole scenes. An intermediate level of visual organisation that has received less attention is the “object constellation” – a familiar configuration of contextually-associated objects (e.g., plate + spoon). Recent behavioural studies have shown that information from multiple objects can be integrated to support observers’ high-level understanding of a “scene” and its constituent objects. Here we used EEG in human participants (both sexes) to test when the visual system integrates information across objects to support recognition. We briefly presented masked object constellations consisting of object silhouettes of either large (e.g., chair + table) or small (e.g., plate + spoon) real-world size, while independently varying retinal size. As a control, observers also viewed each silhouette in isolation. If object context facilitates object recognition, real-world size should be inferred more effectively when the objects appear in their contextually-associated pairs than in isolation, leading to the emergence of real-world size information in multivariate EEG patterns. Representational similarity analysis revealed that neural activity patterns captured information about the real-world size of object constellations from ∼200 ms after stimulus onset. This representation was stronger for, and specific to, object pairs as compared to single objects, and remained significant after regressing out visual similarity models derived from computational models. These results provide evidence for inter-object facilitation of visual processing, leading to a qualitatively different high-level representation of object pairs than single objects.

Significance Statement

This study used electroencephalography decoding to reveal the neural timecourse of inter-object facilitation present for contextually-associated groups of objects (e.g., chair + table). Although ubiquitous in daily life, the ’object constellation’ level of representation has rarely been examined compared to isolated objects or entire scenes. By shedding new light on facilitatory interactions between objects, arising before 200ms of visual processing, our results provide insight into the continuum along which objects and scenes exist. At the same time, this work advances the current understanding of the neural basis of real-world size, using strict visual controls to show that inferred real-world size representations emerge around 200 ms after stimulus onset.
Deep learning from harmonized peptide libraries enables retention time prediction of diverse post translational modifications
Authors: Wilburn Damien Beau , Shannon Ariana E. , Spicer Vic , Richards Alicia L. , Yeung Darien , Swaney Danielle L. , Krokhin Oleg V. , Searle Brian C.
Published: June 2023

In proteomics experiments, peptide retention time (RT) is an orthogonal property to fragmentation when assessing detection confidence. Advances in deep learning enable accurate RT prediction for any peptide from sequence alone, including those yet to be experimentally observed. Here we present Chronologer, an open-source software tool for rapid and accurate peptide RT prediction. Using new approaches to harmonize and false-discovery correct across independently collected datasets, Chronologer is built on a massive database with >2.2 million peptides including 10 common post-translational modification (PTM) types. By linking knowledge learned across diverse peptide chemistries, Chronologer predicts RTs with less than two-thirds the error of other deep learning tools. We show how RT for rare PTMs, such as OGlcNAc, can be learned with high accuracy using as few as 10-100 example peptides in newly harmonized datasets. This iteratively updatable workflow enables Chronologer to comprehensively predict RTs for PTM-marked peptides across entire proteomes.
POST-COVID ORTHOPAEDIC ELECTIVE RESOURCE PLANNING USING SIMULATION MODELLING
Authors: Harper Alison , Monks Thomas , Wilson Rebecca , Redaniel Maria Theresa , Eyles Emily , Jones Tim , Penfold Chris , Elliott Andrew , Keen Tim , Pitt Martin , Blom Ashley , Whitehouse Michael , Judge Andrew
Published: June 2023

Objectives

To develop a simulation model to support orthopaedic elective capacity planning.

Methods

An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016-2019 of elective orthopaedic procedures from an NHS Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths-of-stay, delayed discharges, theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.

Results

A higher number of beds (65-70) than the proposed number (40 beds) will be required if lengths-of-stay and delayed discharge rates remain unchanged. Reducing lengths-of-stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.

Conclusions

The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.

Strengths and Limitations of this study

The simulation model provides rapid quantitative estimates to support post-COVID elective services recovery toward medium-term elective targets.

Parameter combinations include changes to both resourcing and productivity.

The interactive web app enables intuitive parameter changes by users while underlying source code can be adapted or re-used for similar applications.

Patient attributes such as complexity are not included in the model but are reflected in variables such as length-of-stay and delayed discharge rates.

Theatre schedules are simplified, incorporating the five key orthopaedic elective surgical procedures.
Principles for Optimal Window Size Selection for Infant and Adult EEG Connectivity Analysis
Authors: Santamaria Lorena , Canales-Johnson Andres , Noreika Valdas , Leong Victorial
Published: June 2023

Neural connectivity analysis is often performed on continuous data that has been discretized into temporal windows of a fixed length. However, the selection of an optimal window length is non-trivial, and depends on the properties of the connectivity metric being used as well as the effects of interest within the data (e.g. developmental or inter-brain effects). A systematic investigation of these factors, and objective criteria for window size selection are currently missing in the literature, particularly in regard to pediatric datasets. Here, we provide a principled examination of the effect of window size on optimization of signal to noise ratio for linear and non-linear EEG connectivity, as applied to infant, adult and dyadic (infant-adult) datasets. We employed a linear weighted phase lag index (wPLI), and a nonlinear weighted symbolic mutual information (wSMI) metric to assess brain connectivity for each dataset. Our results showed a clear polar dissociation between linear and non-linear metrics, as well as between infant and adult datasets in optimal window size. Further, optimal dyadic (infant-adult) window size settings defaulted to one or the partner rather than reflecting an intermediate compromise. Given the specificity of these results (i.e. there was no single window size that was optimal for all contrasts), we conclude that a formal analysis of optimal window size may be useful prior to conducting any new connectivity analysis. Here, we recommend guiding principles, performance metrics and decision criteria for optimal and unbiased window size selection.
Metabuli: sensitive and specific metagenomic classification via joint analysis of amino-acid and DNA
Authors: Kim Jaebeom , Steinegger Martin
Published: June 2023

Current metagenomic classifiers analyze either DNA or amino-acid (AA) sequences. DNA-based methods have better specificity in distinguishing well-studied clades, but they have limited sensitivity in detecting under-studied clades. AA-based methods suffer the opposite problem. To tackle this trade-off, we developed Metabuli for a joint analysis of DNA and AA using a novel k-mer,metamer. In benchmarks, Metabuli was simultaneously as specific as DNA-based methods and as sensitive as AA-based methods. In the CAMI2 plant-associated dataset, Metabuli covers 99% and 98% of classifications of state-of-the-art DNA-based and AA-based classifiers, respectively. Metabuli is available as free and open-source software for Linux and macOS atmetabuli.steineggerlab.com.
Rewiring protein binding specificity in paralogous DRG/DFRP complexes
Authors: Westrip Christian A. E. , Smerdon Stephen J , Coleman Mathew L.
Published: June 2023

The Developmentally Regulated GTP-binding (DRG) proteins are an ancient subfamily of GTPases implicated in the regulation of translation and cell growth. In eukaryotes, there are two paralogs: DRG1 and DRG2, both of which have a conserved binding partner called DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively. These binding partners are required for the function of DRGs, including their stabilisation at the protein level. Moreover, DFRPs interact with their respective DRG via a conserved region called the DFRP domain. Despite being highly similar, DRG1 and DRG2 have strict binding specificity for their respective DFRP. Using AlphaFold generated structure models of the human DRG/DFRP complexes, we have biochemically characterised their interactions and identified interface residues involved in determining specificity. This analysis revealed that as few as five mutations in DRG1 are able to switch its binding from DFRP1 to DFRP2. We show how two DRG1 residues in the core of the interface are most important for specifying the interaction with DFRP1 over DFRP2. We also demonstrate that whilst DFRP1 can stimulate the GTPase activity of DRG1, DFRP2 binding cannot. Overall, this work provides new insight into the structural determinants responsible for the binding specificities of the DRG:DFRP translation factor complexes, which are known to be essential for normal development in mice and humans.
Unraveling the Efficiency of Non-Navigated 2D Intraoperative Ultrasound in Glioma Surgery: Challenging the Demand for Increased Technological Sophistication in Intraoperative Imaging
Authors: Cepeda Santiago , García-García Sergio , Arrese Ignacio , Sarabia Rosario
Published: June 2023

Background

In an era characterized by rapid progression in neurosurgical technologies, traditional tools such as the non-navigated two-dimensional intraoperative ultrasound (nn-2D-IOUS) risk being overshadowed. Against this backdrop, this study endeavors to provide a comprehensive and rigorous assessment of the clinical efficacy and surgical relevance of nn-2D-IOUS, specifically in the context of glioma resections.

Methods

This retrospective study undertaken at a single center evaluated 99 consecutive, non-selected patients diagnosed with both high-grade and low-grade gliomas. The primary objective was to assess the proficiency of nn-2D-IOUS in generating satisfactory image quality, identifying residual tumor tissue, and its influence on the extent of resection. To validate these results, early postoperative MRI data served as the reference standard.

Results

The nn-2D-IOUS exhibited a high level of effectiveness, successfully generating good quality images in 79% of the cases evaluated. With a sensitivity rate of 68% and a perfect specificity of 100%, nn-2D-IOUS unequivocally demonstrated its utility in intraoperative tumor detection. Notably, in cases where total tumor removal was the surgical objective, a resection exceeding 95% of the initial tumor volume was achieved in 86% of patients. Additionally, in cases where residual tumor was not detected by nn-2D-IOUS, the mean volume of undetected tumor tissue was remarkably minimal, averaging at 0.29 cm3.

Conclusion

Our study provides compelling evidence supporting the invaluable role and efficacy of nn-2D-IOUS in glioma surgery. The results underscore the potential of harnessing traditional, cost-effective technologies such as nn-2D-IOUS to achieve enhanced surgical outcomes, even in the face of more advanced alternatives. These insights carry significant implications, particularly for resource-constrained settings, emphasizing the importance of optimizing the use of existing tools to improve patient care in a practical and efficient manner.
Phylodynamics Uncovers the Transmission of Antibiotic-ResistantEscherichia colibetween Canines and Humans in an Urban Environment
Authors: Walas Nikolina , Müller Nicola F. , Parker Emily , Henderson Abigail , Capone Drew , Brown Joe , Barker Troy , Graham Jay P.
Published: June 2023

The role of canines in transmitting antibiotic resistant bacteria to humans in the urban environment is poorly understood. To elucidate this role, we utilized genomic sequencing and phylogenetics to characterize the burden and transmission dynamics of antibiotic resistantEscherichia coli(ABR-Ec) cultured from canine and human feces present on urban sidewalks in San Francisco, California. We collected a total of fifty-nine ABR-Ec from human (n=12) and canine (n=47) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antibiotic resistance (ABR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and canines from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Overall, we found human and canine samples to carry similar amounts and profiles of ABR genes. Our results provide evidence for multiple transmission events of ABR-Ec between humans and canines. In particular, we found one instance of likely transmission from canines to humans as well as an additional local outbreak cluster consisting of one canine and one human sample. Based on this analysis, it appears that canine feces act as an important reservoir of clinically relevant ABR-Ec within the urban environment. Our findings support that public health measures should continue to emphasize proper canine feces disposal practices, access to public toilets and sidewalk and street cleaning.Importance:Antibiotic resistance inE. coliis a growing public health concern with global attributable deaths projected to reach millions annually. Current research has focused heavily on clinical routes of antibiotic resistance transmission to design interventions while the role of alternative reservoirs such as domesticated animals remain less well understood. Our results suggest canines are part of the transmission network that disseminates high-risk multidrug resistance inE. coliwithin the urban San Francisco community. As such, this study highlights the need to consider canines, and potentially domesticated animals more broadly, when designing interventions to reduce the prevalence of antibiotic resistance in the community. Additionally, it showcases the utility of genomic epidemiology to reconstruct the pathways by which antimicrobial resistance spreads.
The effect of linker conformation on performance and stability of a two-domain lytic polysaccharide monooxygenase
Authors: Forsberg Zarah , Stepnov Anton A. , Tesei Giulio , Wang Yong , Buchinger Edith , Kristiansen Sandra K. , Aachmann Finn L. , Arleth Lise , Eijsink Vincent G. H. , Lindorff-Larsen Kresten , Courtade Gaston
Published: June 2023

A considerable number of lytic polysaccharide monooxygenases (LPMOs) and other carbohydrate-active enzymes are modular, with catalytic domains being tethered to additional domains, such as carbohydrate-binding modules, by flexible linkers. While such linkers may affect the structure, function, and stability of the enzyme, their roles remain largely enigmatic, as do the reasons for natural variation in length and sequence. Here, we have explored linker functionality using the two-domain cellulose-activeScLPMO10C fromStreptomyces coelicoloras a model system. In addition to investigating the wild-type enzyme, we engineered three linker variants to address the impact of both length and sequence and characterized these using SAXS, NMR, MD simulations, and functional assays. The resulting data revealed that, in the case ofScLPMO10C, linker length is the main determinant of linker conformation and enzyme performance. Both the wild-type and a serine-rich variant, which have the same linker length, demonstrated better performance compared to those with either a shorter or longer linker. A highlight of our findings was the substantial thermostability observed in the serine-rich variant. Importantly, the linker affects thermal unfolding behavior and enzyme stability. In particular, unfolding studies show that the two domains unfold independently when mixed, while the full-length enzyme shows one cooperative unfolding transition, meaning that the impact of linkers in biomass processing enzymes is more complex than mere structural tethering.
Demonstration that sublinear dendrites enable linearly non-separable computations
Authors: Cazé Romain D. , Tran-Van-Minh Alexandra , Gutkin Boris S. , DiGregorio David A.
Published: June 2023

Theory predicts that nonlinear summation of synaptic potentials within dendrites allows neurons to perform linearly non-separable computations (LNSCs). Using Boolean analysis approaches, we predicted that both supralinear and sublinear synaptic summation could allow single neurons to implement a type of LNSC, the feature binding problem (FBP), which does not require inhibition contrary to the XOR. Notably, sublinear dendritic operations enable LNSCs when scattered synaptic activation generates increased somatic spike output. However, experimental demonstrations of scatter-sensitive neuronal computations have not yet been described. Using glutamate uncaging onto cerebellar molecular layer interneurons, we show that scattered synaptic-like activation of dendrites evoked larger compound EPSPs than clustered synaptic activation, generating a higher output spiking probability. Moreover, we also demonstrate that single interneurons can indeed implement the FBP. We use a biophysical model to predict under what conditions a neuron can implement the FBP and what leads to failures. Experimental results agree with the model-determined conditions and hence validate our protocol as a solid benchmark for a neuron to implement linearly non-separable computations. Since sublinear synaptic summation is a property of passive dendrites we expect that many different neuron types can implement LNSCs.
In vitro modelling of anterior primitive streak patterning with human pluripotent stem cells identifies the path to notochord progenitors
Authors: Robles-Garcia M. , Thimonier C. , Angoura K. , Ozga E. , MacPherson H. , Blin G.
Published: June 2023

Notochord progenitors (NotoPs) represent a scarce yet crucial embryonic cell population, playing important roles in embryo patterning and eventually giving rise to the cells that form and maintain intervertebral discs. The mechanisms regulating NotoPs emergence are unclear. This knowledge gap persists due to the inherent complexity of cell fate patterning during gastrulation, particularly within the anterior primitive streak (APS), where NotoPs first arise alongside other important progenitors including neuro-mesodermal and endodermal progenitors.

To gain insights into this process, we use micropatterning together with FGF and the WNT pathway activator CHIR9901, to guide the development of human embryonic stem cells into reproducible patterns of APS cell fates. We show that small variations in CHIR9901 dosage dictate the downstream dynamics of endogenous TGFbeta signalling which in turn controls cell fate decisions. We show that sustained NODAL signalling induces endoderm while NODAL inhibition is needed for NMP specification. Furthermore, we unveil a crosstalk between TGFbeta and WNT signaling pathways, wherein TGFbeta inhibition enhances WNT activity. Finally, we demonstrate that the timely inhibition of TGFbeta signalling is imperative for the emergence of NotoPs.

Our work elucidates the signalling regimes underpinning NotoPs emergence and provides novel insights into the regulatory mechanisms controlling the balance of APS cell fates during gastrulation.
A prospective two-year longitudinal follow-up study depicting humoral and cell-mediated immune responses in Covaxin vaccinated individuals
Authors: Tripathy Archana , Podder Sreeparna , Sradhanjali Swatishree , Bhattacharya Debdutta , Pati Sanghamitra , Raghav Sunil K.
Published: June 2023

There are majorly two variants of SARS-CoV-2 vaccine that were employed worldwide on emergency basis to contain the COVID-19 pandemic i.e., RNA based or adenovirus construct based Spike protein expression system which was broadly used and the inactivated virus particle composition. Due to emergency usage starting from the onset of 2021, the immunogenicity data pertaining to long term effects of these vaccines is unexplored. Therefore, in this study we assessed the immunogenicity analysis of Covaxin (BBV152), an inactivated virus-based vaccine for a longitudinal time-span of two years. We investigated the humoral and cell-mediated immune responses in 250 subjects for two years by estimating the RBD specific IgG titres and CD4+/CD8+ T-cell responses. We found that anti-RBD IgG titres that were almost reaching at the basal levels within a year of 2nd dose of vaccination, went significantly high immediately after Omicron infection wave in January 2022. Moreover, the pseudo-virus neutralization by the serum of these subjects showed concordant and drastic increase in virus neutralization activity. At the same time, mild or no symptoms were observed in individuals infected with Omicron variant of SARS-CoV-2. These observations strongly suggested that Omicron variant could have been the best SARS-CoV-2 variant for effective vaccine formulations to generate robust protective immune response along with lesser side effects. Interestingly, the CD4+ and CD8+T-cell activity in Covaxin vaccinees depicted mild to moderate but sustained responses. The spike peptivator pool activated PBMCs of vaccinees depicted an enhancement of CD4+ and CD8+ antigenic responses after 2ndand 3rddose of vaccine administration. In comparison to Covishield, the antibody and T-cell responses were found to be milder in BBV152 vaccinees. This milder antibody and T-cell response could be the reason behind no or less side effects with BBV152 administration than other RNA based vaccines. Overall, our study is one of the first studies profiling the longitudinal humoral and T-cell responses of inactivated virus-based vaccines like COVAXIN, which was predominantly used in India and neighbouring Southeast Asian countries.
Spirometry performance quality and lung function pattern during pregnancy; should testing conditions and interpretation criteria be re-evaluated?
Authors: Ruhighira Jacktan J , Mashili Fredirick L , Tungu Alexander M , Kibusi Stephen
Published: June 2023

Introduction

Despite the prevalence of respiratory disorders in the gravid state, and the crucial role of spirometry in respiratory medicine, its utility for assessing lung function during pregnancy remains infrequent. Putative reasons for this include reservations regarding spirometry performance and its potential influence on test outcomes, although the literature documenting such concerns is insufficient. This study sought to evaluate whether variations in spirometry test performance could impact the diagnosis of pulmonary function patterns throughout gestation.

Methods

We used spirometry data from a cross-sectional study of 120 pregnant and 114 non-pregnant women who underwent spirometry with uniform instructions given to all subjects. Data were subjected to chi-square testing and subsequently evaluated through logistic regression analysis.

Results

The acceptable performance rate among pregnant participants was 77.3%, with the most common quality grade being C (37.5%). Pregnant individuals exhibited 2.1 times the odds of achieving a B grade (p=0.037, 95% CI=1.0-4.2) and 4.1 times the odds of achieving an F grade (p=0.02, 95% CI=1.6-9.9) instead of an A grade. Additionally, they manifested 2.9 times the odds of generating unsatisfactory performance (p=0.007, 95% CI=1.3-6.1) compared to non-pregnant participants. Also, pregnant participants displayed 2.5 times the odds of exhibiting a restrictive pattern (p=0.021, 95% CI=1.1-5.7); but pattern classification was not associated with quality grades.

Conclusion

Despite the higher likelihood of suboptimal spirometry quality, the observed pattern classification remains as expected physiologically, suggesting that spirometry is still a valid tool for assessing lung function in pregnancy.