bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructive Approaches Following Sphenoorbital Meningioma Resection
Authors: Rochlin Danielle H. , Mittermiller Paul A. , DeMitchell-Rodriguez Evellyn , Weiss Hannah , Dastagirzada Yosef , Patel Vishal , Hagiwara Mari , Flores Roberto , Sen Chandra , Staffenberg David A.
Published: December 2022

Sphenoorbital meningiomas are a challenge to access and reconstruct. Although there is much neurosurgical literature on resection of such tumors, there is little discussion on the best methods for the reconstruction of consequent defects, which are often extensive due to large areas of hyperostosis requiring resection. We performed a retrospective analysis of patients who underwent resection and reconstruction of a sphenoorbital meningioma by the senior authors (C.S. and D.A.S.) between 2010 and 2020. Surgical access in all cases included an orbitozygomatic osteotomy. The study cohort consisted of 23 patients (20 female, 3 male) with an average age of 50 (range: 37–72) years at the time of surgery. Most patients had progressive proptosis before the ablative operation. Orbital reconstruction was with a combined titanium-Medpor implant in 18 patients, split calvarial bone graft in 3 patients, and a Medpor implant in 2 patients. Calvarial reconstruction was performed with titanium mesh in 21 patients, split calvarial bone graft and titanium mesh in 1 patient, and craniotomy bone and titanium plate in 1 patient. Reoperation was required in 7 patients due to hypoglobus or enophthalmos (N=2), orbital implant malposition (N=1), abscess (N=1), pain (N=1), intracranial fat graft modification (N=1), and soft tissue deformities (N=2). Our experience demonstrates that sphenoorbital meningiomas can require broad areas of resection of the skull base and calvarium and necessitate comprehensive reconstruction of the anterior cranial fossa, orbital walls, and cranium. Collaboration between craniofacial surgeons and neurosurgeons can achieve optimal results.
Effects of the Orthognathic Surgery on the Voice Characteristics of Skeletal Class III Patients
Authors: Sahin Serife , Sen Yilmaz Berza
Published: December 2022

Objectives:

To analyze the effects of the bimaxillary orthognathic surgery on the voice characteristics of skeletal Class III cases, and to evaluate correlations between acoustic and skeletal changes.

Method:

Skeletal Class III adult patients (7 male, 18 female) were asked to pronounce the sounds “[a], [ɛ], [ɯ], [i], [ɔ], [œ], [u], [y]” for 3 seconds. Voice records and lateral cephalometric x-rays were taken before the surgery (T0) and 6 months after (T1). Voice records were taken for the control group with 6 months of interval (n=20). The formant frequencies (F0, F1, F2, and F3), Shimmer, Jitter and Noise to Harmonic Ratio (NHR) parameters were considered with Praat version 6.0.43.

Results:

In the surgery group, significant differences were observed in the F1 of [e], F2 and Shimmer of [ɯ] and F1 and F2 of [œ] and F1 of [y] sound, the post-surgery values were lower. F3 of [u] sound was higher. In comparison with the control group, ΔF3 of the [ɔ], ΔF3 of the [u] and ΔF1 of the [y] sound, ΔShimmer of [ɛ], [ɯ], [i], [ɔ], [u] and [y], and the ΔNHR of [ɔ] sound significantly changed. The Pearson correlation analysis proved some correlations; ΔF2 between ΔSNA for [ɯ] and [œ] sounds, ΔF1 between ΔHBV for [y] sound.

Conclusion:

Bimaxillary orthognathic surgery changed some voice parameters in skeletal Class III patients. Some correlations were found between skeletal and acoustic parameters. We advise clinicians to consider these findings and inform their patients.
Large Vertex Encephaloceles: Management and Outcomes
Authors: Schneider Hoa , Cappitelli Alex , Langa Olivia C. , Goobie Susan M. , Meara John G. , Proctor Mark , Ganske Ingrid M.
Published: December 2022

Background:

Complex vertex and posterior encephaloceles containing brain tissue have uncertain prognosis and high operative risk. Patients may not be offered operative intervention depending on local and regional specialist expertise. The authors present their experience treating 5 such pediatric patients.

Methods:

This is a retrospective review of the surgical assessment, planning, and technique of cranial repairs, as well as surgical outcomes and developmental follow-up regarding adaptive functioning for patients presenting for second opinion for encephalocele of the cranial vertex after having been deemed too high risk at another institution.

Results:

Five consecutive patients presented between January 2014 and June 2016. One patient was not offered repair. Of 4 patients who underwent reconstruction, average age at time of repair was 2.7 months (range, 0.9–6.7). One presented with ruptured encephalocele, whereas the remaining 3 underwent drainage of the encephalocele (average volume of 1200 mL) at time of surgical resection. Operative time averaged 3.7 hours (range, 2.2–5.3). There were no deaths. One patient had a single seizure postoperatively. Two patients required placement of permanent shunt for hydrocephalus. Two patients completed developmental evaluations, both of whom exhibited delays in adaptive functioning relative to same-aged peers.

Conclusions:

Patients with large, complex encephalocele warrant evaluation by an experienced high-volume tertiary care pediatric craniofacial center. The decision to proceed with surgical management should include an interdisciplinary team of surgeons, anesthesiologists, neurologists, and social work. Further study of developmental outcomes in both operated and unoperated patients is necessary to better understand risks and benefits of reconstruction.
Nasal Anthropometric Analysis in Turkish Rhinoplasty Patients
Authors: Altinkaya Altug
Published: December 2022

This study aimed to determine the mean values of the nasal anthropometric measurements through 2-dimensional photogrammetry in for rhinoplasty patients. The study group included 72 healthy individuals, 36 men, and 36 women. The patients were aged 18 to 42 years. All patients had undergone primary rhinoplasty in our clinic between 2013 and 2020. Seven landmarks were identified from the preoperative photographs taken with the patient’s head in neutral position in the frontal and lateral planes. Five distances (total nasal length, nasal bridge length, morphological nose width, alar length, and nasal tip protrusion) and 2 angles (nasofrontal and nasolabial) measurements were calculated. We noted a statistically significant difference between the male and female sexes in terms of total nasal length and morphological nose width (P<0.05). The results were compared with the nasal anthropometric measurements reported in the literature for the Turkish population as well as other ethnic groups. We believe results of this study may facilitate preoperative planning in Turkish patients who request rhinoplasty and improve the success rate of the surgery.
Single Surgeon’s Experience in Repair of Median Cleft Lip: A Case Series of 5 Median Craniofacial Dysplasia Patients
Authors: Yoo Hyokyung , Ha Jeong Hyun , Chung Jee Hyeok , Kim Sukwha
Published: December 2022

Median craniofacial dysplasia is a rare congenital anomaly with a broad spectrum of severity, which can be classified as hypoplasia, dysraphia, and hyperplasia, depending on the involved tissue amount. A retrospective chart review was performed of patients with median craniofacial dysplasia who underwent repair of the upper lip median cleft between January 2013 and February 2020. The median cleft of the upper lip was present in 5 cases. The average age at operation was 11 months. Two patients had a median notch in the vermilion, 2 patients had an incomplete median cleft lip, and 1 patient had a complete median cleft lip with the absence of columella, prolabium, and premaxilla. A variety of surgical correction was performed for each case, including simple rhombus-shaped excision, modified version of straight-line repair, and columella reconstruction using an intranasal dorsal flap and bilateral cleft margin flaps. Each case needs to be carefully assessed with individualization for appropriate surgical treatment.
Altmetric Analysis of the Most Mentioned Articles Online in the Contemporary Craniofacial Surgery Literature
Authors: Patel Parth A. , Boyd Carter J.
Published: December 2022

As online media acquires increased utilization as a means of disseminating scientific research, Altmetric analyses are useful to identify socially impactful publications and their characteristics. Accordingly, the objective of this investigation was to determine the most mentioned articles online regarding craniofacial surgery and compare these articles with their most cited counterparts. Using the Web of Science database, 7097 craniofacial surgery publications were identified. Altmetric Attention Score (AAS) and average citations per year (ACpY) were extracted, and articles were ranked by their social and scientific impact. Descriptive, comparative, and correlational analyses were performed to examine characteristics including AAS, ACpY, country of origin, journal, open access (OA) status, publication year, study design, and topic. The average AAS of the 50 most mentioned articles was 83.68 (SD±107.40), and the average citation count of the 50 most cited articles was 76.38 (SD±35.15). OA status was significantly more prevalent among the most mentioned articles (24.0%) relative to all articles (10.72%) and the most cited articles (4.0%). The most mentioned and the most cited articles primarily originated from the United States (64.0% and 38.0%, respectively), discussed topics related to the medical and surgical management of patients (48.0% and 58.0%, respectively), and were systematic reviews (16.0% and 28.0%, respectively). However, there was significantly more geographic diversity in the latter cohort. In summary, this comparative examination reveals important differences between the most mentioned and most cited articles, highlighting the distinct utility of AAS and citation count when evaluating research impact.
Simulation-Based Education in US Undergraduate Medical Education
Authors: Campbell Krystle K. , Wong Kristen E. , Kerchberger Anne Marie , Lysikowski Jerzy , Scott Daniel J. , Sulistio Melanie S.
Published: December 2022

Purpose

Simulation-based education (SBE) provides experiential learning, improvement in quality of care, and reduction in errors. In 2011, the Association of American Medical Colleges described adoption of SBE in 68.0% of medical schools and 25.0% of teaching hospitals. We sought to examine current trends of SBE integration in American undergraduate medical education since previous publications.

Methods

From 2016 to 2019, University of Texas Southwestern Medical Center postgraduate year 1 residents were invited to participate in a survey assessing medical school simulation experience with 26 clinical tasks from three categories: procedural, communication, and other. Deidentified results were analyzed to assess demographics including sex, specialty, residency program type, allopathic versus osteopathic medical school, and medical school region.

Results

Nine hundred sixty-seven of 1047 (92.3%) responses were obtained, representing 139 US medical schools, 91% from allopathic training. Of procedural tasks, most simulated was suturing (n = 848, 89.6%) and least simulated was thoracentesis (n = 737, 80.9%). Of communication tasks, most simulated was taking a history (n = 475, 51.1% reporting simulation >30) and least simulated (never or ≤1) were obtaining a consent (n = 669, 73.2%) and disclosing a medical error (n = 666, 72.4%). Of other tasks, most simulated was chest compressions (n = 898, 96.0%) and least simulated was operating a defibrillator (n = 206, 22.1%). Results were similar regardless of procedural or nonprocedural program. There was no significant difference in SBE exposure between allopathic and osteopathic students (P = 0.89). Two participants (0.002%) reported no simulation exposure.

Conclusions

Our study is the first to describe a high prevalence of SBE adoption in medical schools nationwide since the Association of American Medical Colleges' 2011 publication, with overall equal exposure for students regardless of residency type and allopathic or osteopathic medical school. Despite widespread adoption of simulation, opportunities remain to expand SBE use to teach critically important communication skills.
The Histological Spectrum and Clinical Significance of T Cell–mediated Rejection of Kidney Allografts
Authors: Filippone Edward J. , Farber John L.
Published: December 2022

T cell–mediated rejection (TCMR) remains a significant cause of long-term kidney allograft loss, either indirectly through induction of donor-specific anti-HLA alloantibodies or directly through chronic active TCMR. Whether found by indication or protocol biopsy, Banff defined acute TCMR should be treated with antirejection therapy and maximized maintenance immunosuppression. Neither isolated interstitial inflammation in the absence of tubulitis nor isolated tubulitis in the absence of interstitial inflammation results in adverse outcomes, and neither requires antirejection treatment. RNA gene expression analysis of biopsy material may supplement conventional histology, especially in ambiguous cases. Lesser degrees of tubular and interstitial inflammation (Banff borderline) may portend adverse outcomes and should be treated when found on an indication biopsy. Borderline lesions on protocol biopsies may resolve spontaneously but require close follow-up if untreated. Following antirejection therapy of acute TCMR, surveillance protocol biopsies should be considered. Minimally invasive blood-borne assays (donor-derived cell-free DNA and gene expression profiling) are being increasingly studied as a means of following stable patients in lieu of biopsy. The clinical benefit and cost-effectiveness require confirmation in randomized controlled trials. Treatment of acute TCMR is not standardized but involves bolus corticosteroids with lymphocyte depleting antibodies for severe, refractory, or relapsing cases. Arteritis may be found with acute TCMR, active antibody-mediated rejection, or mixed rejections and should be treated accordingly. The optimal treatment ofchronic active TCMR is uncertain. Randomized controlled trials are necessary to optimally define therapy.
The Utility of Spatial Transcriptomics for Solid Organ Transplantation
Authors: Li Jennifer S.Y. , Raghubar Arti M. , Matigian Nicholas A. , Ng Monica S.Y. , Rogers Natasha M. , Mallett Andrew J.
Published: December 2022

Spatial transcriptomics (ST) measures and maps transcripts within intact tissue sections, allowing the visualization of gene activity within the spatial organization of complex biological systems. This review outlines advances in genomic sequencing technologies focusing on in situ sequencing–based ST, including applications in transplant and relevant nontransplant settings. We describe the experimental and analytical pipelines that underpin the current generation of spatial technologies. This context is important for understanding the potential role ST may play in expanding our knowledge, including in organ transplantation, and the important caveats/limitations when interpreting the vast data output generated by such methodological platforms.
CD40-CD40L Blockade: Update on Novel Investigational Therapeutics for Transplantation
Authors: Singh Avneesh K. , Goerlich Corbin E. , Zhang Tianshu , Lewis Billeta G.T. , Hershfeld Alena , Mohiuddin Muhammad M.
Published: December 2022

Effective immune responses require antigen presentation by major histocompatibility complexes with cognate T-cell receptor and antigen-independent costimulatory signaling for T-cell activation, proliferation, and differentiation. Among several costimulatory signals, CD40-CD40L is of special interest to the transplantation community because it plays a vital role in controlling or regulating humoral and cellular immunity. Blockade of this pathway has demonstrated inhibition of donor-reactive T-cell responses and prolonged the survival of transplanted organs. Several anti-CD154 and anti-CD40 antibodies have been used in the transplantation model and demonstrated the potential of extending allograft and xenograft rejection-free survival. The wide use of anti-CD154 antibodies was hampered because of thromboembolic complications in transplant recipients. These antibodies have been modified to overcome the thromboembolic complications by altering the antibody binding fragment (Fab) and Fc (fragment, crystallizable) receptor region for therapeutic purposes. Here, we review recent preclinical advances to target the CD40-CD40L pair in transplantation.
Caregiver Burden in Adult Solid Organ Transplantation
Authors: Deng Lisa X. , Sharma Arjun , Gedallovich Seren M. , Tandon Puneeta , Hansen Lissi , Lai Jennifer C.
Published: December 2022

The informal caregiver plays a critical role in supporting patients with various end-stage diseases throughout the solid organ transplantation journey. Caregiver responsibilities include assistance with activities of daily living, medication management, implementation of highly specialized treatments, transportation to appointments and treatments, and health care coordination and navigation. The demanding nature of these tasks has profound impacts across multiple domains of the caregiver’s life: physical, psychological, financial, logistical, and social. Few interventions targeting caregiver burden have been empirically evaluated, with the majority focused on education or mindfulness-based stress reduction techniques. Further research is urgently needed to develop and evaluate interventions to improve caregiver burden and outcomes for the patient–caregiver dyad.
Expanding Donor Options for Lung Transplant: Extended Criteria, Donation After Circulatory Death, ABO Incompatibility, and Evolution of Ex Vivo Lung Perfusion
Authors: Noda Kentaro , Furukawa Masashi , Chan Ernest G. , Sanchez Pablo G.
Published: December 2022

Only using brain-dead donors with standard criteria, the existing donor shortage has never improved in lung transplantation. Currently, clinical efforts have sought the means to use cohorts of untapped donors, such as extended criteria donors, donation after circulatory death, and donors that are ABO blood group incompatible, and establish the evidence for their potential contribution to the lung transplant needs. Also, technical maturation for using those lungs may eliminate immediate concerns about the early posttransplant course, such as primary graft dysfunction or hyperacute rejection. In addition, recent clinical and preclinical advances in ex vivo lung perfusion techniques have allowed the safer use of lungs from high-risk donors and graft modification to match grafts to recipients and may improve posttransplant outcomes. This review summarizes recent trends and accomplishments and future applications for expanding the donor pool in lung transplantation.
A First in Human Trial to Evaluate the Safety and Immunogenicity of a G Protein Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18-45 Years
Authors: Cheng Xin , Zhao Gan , Dong Aihua , He Zhonghuai , Wang Jiarong , Jiang Brian , Wang Bo , Wang Miaomiao , Huai Xuefen , Zhang Shijie , Feng Shuangshuang , Qin Hong , Wang Bin
Published: December 2022

Background

With enormous morbidity and mortality induced by respiratory syncytial virus (RSV) infection among infants and the elderly, vaccines against RSV infection are in huge market demand.

Methods

We conducted a First-in-human (FIH), randomized, double-blind, placebo-controlled dose escalation study to evaluate the safety and immunogenicity response of the rRSV vaccine (BARS13) in healthy adults aged 18-45. A total of 60 eligible participants were randomized in a 4:1 ratio to receive one of four dose levels or vaccination regimens of BARS13 or placebo.

Results

No serious adverse event (SAE) was experienced by any study participant. The geometric mean fold increase (GMFI) from baseline in all participants post-administration indicated that compared with single dose regimens, the IgG antibody level from baseline in participants received repeat dose regimens at Day 60 has increased over a 3-fold.

Conclusions

BARS13 has a generally good safety and tolerability profile, and no significant difference in terms of adverse reaction severity or frequency has been observed between different dose groups. The immune response in repeat dose recipients shows more potential in further study and has guiding significance for the dose selection of subsequent studies.
Clinical Validation of Optical Genome Mapping for the Detection of Structural Variations in Hematological Malignancies
Authors: Pang Andy Wing Chun , Kosco Karena , Sahajpal Nikhil , Sridhar Arthi , Hauenstein Jen , Clifford Benjamin , Estabrook Joey , Chitsazan Alex , Sahoo Trilochan , Iqbal Anwar , Kolhe Ravindra , Raca Gordana , Hastie Alex R. , Chaubey Alka
Published: December 2022

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescencein situhybridization (FISH), employed globally for the past three decades have significant limitations in the resolution or the number of recurrent aberrations that can be simultaneously assessed, respectively. Next-generation sequencing (NGS) based technologies are now widely used to detect clinically significant sequence variants but are limited in their ability to accurately detect SVs. Optical genome mapping (OGM) is an emerging technology enabling the genome-wide detection of all classes of SVs at a significantly higher resolution than karyotyping and FISH. OGM neither requires cultured cells nor amplification of DNA and hence addresses the limitations of culture and amplification biases. This study reports the clinical validation of OGM as a laboratory developed test (LDT), according to CLIA guidelines, for genome-wide SV detection in different hematological malignancies. In total, 68 cases with hematological malignancies (of various subtypes), 27 controls and two cancer cell lines were used for this study. Ultra-high molecular weight DNA was extracted from the samples, fluorescently labeled, and run on the Bionano Genomics Saphyr system. A total of 207 datasets, including replicates, were generated and 100% could be analyzed successfully. Sample data were then analyzed using either disease specific or pan-cancer specific BED files to prioritize calls that are known to be diagnostically or prognostically relevant. Accuracy, precision, PPV and NPV were all 100% against standard of care results. Sensitivity, specificity, and reproducibility were 100%, 100% and 96%, respectively. Following the validation, 11 cases were run and analyzed using OGM at three additional sites. OGM found more clinically relevant SVs compared to SOC testing due to its ability to detect all classes of SVs at much higher resolution. The results of this validation study demonstrate OGM’s superiority over traditional SOC methods for the detection of SVs for the accurate diagnosis of various hematological malignancies.
Putting on academic armor: How Black physicians and trainees take stances to make racism visible amidst publishing constraints
Authors: Johnson M. , Maggio L.A. , Konopasky A.
Published: December 2022

Introduction

While there are a growing number of empirical studies of Black physicians’ and trainees’ experiences of racism, there are still few accounts from a first-person perspective. These personal commentaries or editorials require taking a delicate stance, balancing the professional, social, and individual. Black authors in the medical publishing space, who already experience microaggressions and racial trauma in their work spaces, must put on their academic armor to further experience them in publishing spaces. Medicine and medical education interpellate each of us, including the authors and readers of this piece, as a particular kind of subject. Beginning with a narrative grounding in the authors’ personal stances, this study seeks to understand the stances Black physicians and trainees take as they share their personal experiences of racism while protecting the institution of medicine from racism’s irreparable harms.

Methods

The authors searched four databases identifying 29 articles authored by Black physicians and trainees describing their experiences. During initial analysis, the authors identified three sets of discursive strategies:identification(introducing and tracking themselves throughout the article);intertextuality(dialoguing and drawing on other “texts” beyond the focus of the articles); andspace-time(social constructions of space and time linked to a network of social practices). The authors used a Google form to capture these strategies and direct quotes from the articles. Throughout the study, the authors reflected on theirownstances in relation to the experience of conducting the study and its findings.

Results

Authors engaged in stance taking, which aligned with the concept of donning academic armor, by evaluating and positioning themselves with respect to racism and the norms of academic discourse in response to ongoing conversations both within medicine and in the broader US culture. They did this by (a) positioning themselves as being Black and, therefore, qualified to notice and name personal racist experiences while also aligning themselves with the reader through shared professional experiences and goals, (b) intertextual connections to other related events, people, and institutions that they–and their readers–value and (c) aligning themselves with a hoped-for future rather than a racist present.

Discussion

Because the discourses of medicine and medical publishing interpellate Black authors as Others they must carefully consider the stances they take, particularly when naming racism. The academic armor they put on must not only be able to defend them from attack, but help them slip unseen through institutional bodies replete with mechanisms to eject them. In addition to analyzing their own personal stance, authors leave readers with thought provoking questions regarding this armor as they return to narrative grounding.
Alternative Polyadenylation alters UBASH3B-ZNF652 competition to involve in Triple-Negative Breast Cancer
Authors: Wu Sijia , Hu Changbao , Wu Xiaoming , Zhou Xiaobo , Huang Liyu
Published: December 2022

Alternative polyadenylation (APA) is an RNA-processing mechanism which may affect gene expression. Its involvements in cancers including the triple-negative breast cancer (TNBC) have been demonstrated in previous studies. Given the lack of biomarkers for TNBC, in this study, we were committed to finding novel biomarkers related to TNBC prognosis from the perspective of APA-mediated microRNA regulation. For this goal, raw bulk RNA sequencing data was collected for the identification of nine survival-related APA events by multivariate Cox regression analysis and forward-selected Likelihood Ratio Test. They showed good prognosis ability on TNBC risk. Of them, the APA event inUBASH3Bwas proposed as a novel potential biomarker. This event disturbed microRNA regulation on its host gene and other competing tumor genes to possibly involve in the pathogenesis of TNBC.
A new framework for metabolic connectivity mapping using bolus [18F]FDG PET and kinetic modelling
Authors: Volpi Tommaso , Vallini Giulia , Silvestri Erica , De Francisci Mattia , Durbin Tony , Corbetta Maurizio , Lee John J. , Vlassenko Andrei G. , Goyal Manu S. , Bertoldo Alessandra
Published: December 2022

Purpose

Metabolic connectivity (MC) has been previously proposed as the covariation of static [18F]FDG PET images across participants, which we callacross-individualMC (ai-MC). In few cases, MC has also been inferred from dynamic [18F]FDG signals, similarly to fMRI functional connectivity (FC), which we termwithin-individualMC (wi-MC). The validity and interpretability of both MC approaches is an important open issue.

Here we reassess this topic, aiming to 1) develop a novel methodology for wi-MC estimation; 2) compare ai-MC maps obtained using different [18F]FDG parameters (K1, i.e. tracer transport rate,k3, i.e. phosphorylation rate,Ki, i.e. tracer uptake rate, and the standardized uptake value ratio,SUVR); 3) assess the interpretability of ai-MC and wi-MC in comparison to structural and functional connectivity (FC) measures.

Methods

We analyzed dynamic [18F]FDG data from 54 healthy adults using kinetic modelling to quantify the macro- and microparameters describing the tracer behavior (i.e.Ki,K1, k3). We also calculatedSUVR. From the across-individual correlation ofSUVR, Ki, K1, k3, we obtained four different ai-MC matrices. A new approach based on Euclidean distance was developed to calculate wi-MC from PET time-activity curves.

Results

We identified Euclidean similarity as the most appropriate metric to calculate wi-MC. ai-MC networks changed with different [18F]FDG parameters (k3MC vs.SUVRMC, r = 0.44). We found that wi-MC and ai-MC matrices are dissimilar (maximum r = 0.37), and that the match with FC is higher for wi-MC (Dice similarity: 0.47-0.63) than for ai-MC (0.24-0.39).

Conclusion

Our data demonstrate that individual-level MC from dynamic [18F]FDG data using Euclidean similarity is feasible and yields interpretable matrices that bear similarity to resting-state fMRI FC measures.
Prop3D: A Flexible, Python-based Platform for Machine Learning with Protein Structural Properties and Biophysical Data
Authors: Draizen Eli J. , Readey John , Mura Cameron , Bourne Philip E.
Published: December 2022

Background

Machine learning (ML) has a rich history in structural bioinformatics, and modern approaches, such as deep learning, are revolutionizing our knowledge of the subtle relationships between biomolecular sequence, structure, function, dynamics and evolution. As with any advance that rests upon statistical learning approaches, the recent progress in biomolecular sciences is enabled by the availability of vast volumes of sufficiently-variable data. To be useful, such data must be well-structured, machine-readable, intelligible and manipulable. These and related requirements pose challenges that become especially acute at the computational scales typical in ML. Furthermore, in structural bioinformatics such data generally relate to protein three-dimensional (3D) structures, which are inherently more complex than sequence-based data. A significant and recurring challenge concerns the creation of large, high-quality, openly-accessible datasets that can be used for specific training and benchmarking tasks in ML pipelines for predictive modeling projects, along with reproducible splits for training and testing.

Results

Here, we report ‘Prop3D’, a platform that allows for the creation, sharing and extensible reuse of libraries of protein domains, featurized with biophysical and evolutionary properties that can range from detailed, atomically-resolved physicochemical quantities (e.g., electrostatics) to coarser, residue-level features (e.g., phylogenetic conservation). As a community resource, we also supply a ‘Prop3D-20sf’ protein dataset, obtained by applying our approach to CATH. We have developed and deployed the Prop3D framework, both in the cloud and on local HPC resources, to systematically and reproducibly create comprehensive datasets via the Highly Scalable Data Service (HSDS). Our datasets are freely accessible via a public HSDS instance, or they can be used with accompanying Python wrappers for popular ML frameworks.

Conclusion

Prop3D and its associated Prop3D-20sf dataset can be of broad utility in at least three ways. Firstly, the Prop3D workflow code can be customized and deployed on various cloud-based compute platforms, with scalability achieved largely by saving the results to distributed HDF5 files via HSDS. Secondly, the linked Prop3D-20sf dataset provides a hand-crafted, already-featurized dataset of protein domains for 20 highly-populated CATH families; importantly, provision of this pre-computed resource can aid the more efficient development (and reproducible deployment) of ML pipelines. Thirdly, Prop3D-20sf’s construction explicitly takes into account (in creating datasets and data-splits) the enigma of ‘data leakage’, stemming from the evolutionary relationships between proteins.
Mathematical modeling of mpox: a scoping review
Authors: Molla Jeta , Sekkak Idriss , Mundo Ortiz Ariel , Moyles Iain , Nasri Bouchra
Published: December 2022

Background

Mpox (monkeypox), a disease historically endemic to Africa, has seen its largest outbreak in 2022 by spreading to many regions of the world and has become a public health threat. Informed policies aimed at controlling and managing the spread of this disease necessitate the use of adequate mathematical modelling strategies.

Objective

In this scoping review, we sought to identify the mathematical models that have been used to study mpox transmission in the literature in order to determine what are the model classes most frequently used, their assumptions, and the modelling gaps that need to be addressed in the context of the epidemiological characteristics of the ongoing mpox outbreak.

Methods

This study employed the methodology of the PRISMA guidelines for scoping reviews to identify the mathematical models available to study mpox transmission dynamics. Three databases (PubMed, Web of Science and MathSciNet) were systematically searched to identify relevant studies.

Results

A total of 5827 papers were screened from the database queries. After screening, 35 studies that met the inclusion criteria were analyzed, and 19 were finally included in the scoping review. Our results show that compartmental, branching process, Monte Carlo (stochastic), agent-based, and network models have been used to study mpox transmission dynamics between humans as well as between humans and animals. Furthermore, compartmental and branching models have been the most commonly used classes.

Conclusions

There is a need to develop modelling strategies for mpox transmission that take into account the conditions of the current outbreak, which has been largely driven by human-to-human transmission in urban settings. In the current scenario, the assumptions and parameters used by most of the studies included in this review (which are largely based on a limited number of studies carried in Africa in the early 80s) may not be applicable, and therefore, can complicate any public health policies that are derived from their estimates. The current mpox outbreak is also an example of how more research into neglected zoonoses is needed in an era where new and re-emerging diseases have become global public health threats.
Whole-Brain Three-Dimensional Imaging of RNAs at Single-Cell Resolution
Authors: Kanatani Shigeaki , Kreutzmann Judith C. , Li Yue , West Zoe , Vougesi Nikou Danai , Lercke Skytte Jacob , Lydolph Larsen Lea , Tanaka Daisuke H. , Kaczynska Dagmara , Fukumoto Keishiro , Uesaka Naofumi , Tanabe Tsutomu , Miyakawa Ayako , Roostalu Urmas , Hecksher-Sørensen Jacob , Uhlén Per
Published: December 2022

Whole-brain three-dimensional (3D) imaging is desirable to obtain a comprehensive and unbiased view of architecture and neural circuitry. However, current spatial analytic methods for brain RNAs are limited to thin sections or small samples. Here, we combined multiple new techniques to develop TRIC-DISCO, a new pipeline that allows imaging of RNA spatial distributions in whole adult mouse brains. First, we developed Tris-mediated retention ofin situhybridization signal during clearing (TRIC), which produces highly transparent tissue while maintaining the RNA signal intensities. We then combined TRIC with DISCO clearing (TRIC-DISCO) by controlling temperature during thein situhybridization chain reaction (isHCR) to ensure uniform whole-brain staining. This pipeline eliminates the requirements for both strict RNase-free environments and workflow-compatible RNase inhibitors. Our TRIC-DISCO pipeline enables simple and robust, single-cell, whole-brain, 3D imaging of transcriptional signatures, cell-identity markers, and noncoding RNAs across the entire brain.
To remain modern, the coexistence program requires modern statistical rigor
Authors: Armitage David W.
Published: December 2022

A recent study by Van Dyke et al.1paired experimental drought manipulations with demographic models and trait measurements to project major shifts in coexistence among a number of annual plant taxa. However, re-analysis of the data under alternative, more predictive competition models reveals that the authors’ original conclusions are very sensitive to slight variations in model form. Furthermore, propagating model parameter error into coexistence predictions results in relatively weak support for the majority of coexistence shifts predicted by the authors’ original model. These results highlight the need for increased statistical rigor when treating binary predictions of species coexistence as observed experimental outcomes, as is commonly practiced in empirical coexistence studies.
BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA
Authors: Bell Jason C. , Dombrowski Christopher C. , Plank Jody L. , Jensen Ryan B. , Kowalczykowski Stephen C.
Published: December 2022

Mutations in the breast cancer susceptibility gene, BRCA2, greatly increase an individual’s lifetime risk of developing breast and ovarian cancers. BRCA2 suppresses tumor formation by potentiating DNA repair via homologous recombination. Central to recombination is the assembly of a RAD51 nucleoprotein filament, which forms on single-stranded DNA (ssDNA) generated at or near the site of chromosomal damage. However, Replication Protein-A (RPA) rapidly binds to and continuously sequesters this ssDNA, imposing a kinetic barrier to RAD51 filament assembly that suppresses unregulated recombination. Recombination mediator proteins––of which BRCA2 is the defining member in humans ––alleviate this kinetic barrier to catalyze RAD51 filament formation. We combined microfluidics, microscopy, and micromanipulation to directly measure both the binding of full-length BRCA2 to––and the assembly of RAD51 filaments on––a region of RPA-coated ssDNA within individual DNA molecules designed to mimic a resected DNA lesion common in replication-coupled recombinational repair. We demonstrate that a dimer of RAD51 is minimally required for spontaneous nucleation; however, growth self-terminates below the diffraction limit. BRCA2 accelerates nucleation of RAD51 to a rate that approaches the rapid association of RAD51 to naked ssDNA, thereby overcoming the kinetic block imposed by RPA. Furthermore, BRCA2 eliminates the need for the rate-limiting nucleation of RAD51 by chaperoning a short pre-assembled RAD51 filament onto the ssDNA complexed with RPA. Therefore, BRCA2 regulates recombination by initiating RAD51 filament formation.

Significance

Despite decades of genetic and cell biological studies, mechanistic biochemical analyses of human BRCA2 function in recombinational DNA repair have only been possible since the purification of full-length BRCA2. These mechanistic studies crucially inform with respect to the molecular function of BRCA2 in genome maintenance. Here, we use single-molecule methods to visualize the assembly of RAD51 on individual RPA-coated ssDNA molecules and to see how this process is regulated by the tumor suppressor protein, BRCA2. We show that BRCA2 serves as a chaperone to nucleate RAD51 and deliver it to RPA-coated ssDNA. This work advances understanding of the molecular functions of BRCA2 and, consequently, the molecular etiology of breast cancer in an important way.
On-line reoptimization of mammalian fed-batch culture using a nonlinear model predictive controller
Authors: Ohkubo Tomoki , Sakumura Yuichi , Kunida Katsuyuki
Published: December 2022

Fed-batch culture enables high productivity by maintaining low substrate concentrations in the early stage of the culture to suppress the accumulation of by-products that are harmful to cell growth. Therefore, they are widely used in the production of biopharmaceuticals by mammalian cells. However, there exists a trade-off in the design of the fed-batch process: early feeding results in the accumulation of harmful by-products, whereas late feeding results in a shortage of substrates needed for cell growth and synthesis of the desired product. To manage this trade-off and maximize the product yield, model-based optimization of the feeding trajectory has been reported in several studies. A significant drawback of this off-line optimization approach is the mismatch between the predictions made using the model and the actual process states, called the process-model mismatch (PMM). If the PMM is large, the off-line optimized feeding trajectory is no longer optimal for the actual process, resulting in lower product yields. Mammalian cell culture models typically contain dozens of unknown parameters that must be estimated prior to optimization. Sufficient parameter estimation is often unachievable owing to the nonlinear nature of these models. We believe that reoptimizing the feeding trajectory in real time using a nonlinear model predictive controller (NLMPC) is an effective solution to this PMM. Although NLMPC is a model-based feedback controller widely utilised in mammalian fed-batch culture, only a few studies have applied it to on-line reoptimization, and it remains unclear whether NLMPC with a standard kinetic model can effectively compensate for a large PMM. In this study, we demonstrated the reoptimization of the feeding trajectory with a NLMPC using two previously reported standard monoclonal antibody (mAb) production models. In both models, NLMPC successfully suppressed the reduction in mAb yield caused by the intentional introduction of PMM.
Temperature moderates eDNA-biomass relationships in northern pike
Authors: Ogonowski M. , Karlsson E. , Vasemägi A. , Sundin J. , Bohman P. , Sundblad G.
Published: December 2022

Support for eDNA as a quantitative monitoring tool is growing worldwide. Despite advances there are still uncertainties regarding the representability of the eDNA signal over varying spatiotemporal scales, influence of abiotic forcing and phenological changes affecting behavior of the study organism, particularly in open environments. To assess the spatiotemporal variability and predictive power of quantitative eDNA analysis, we applied species-specific real-time quantitative PCR on water filtrates during two visits to 22 coastal bays in the Baltic Sea. Within bays, we collected water along four transects across each bay and compared the pooled eDNA concentration to temporally matched catches from standardized angling targeting the northern pike (Esox lucius) a species for which reliable monitoring data is lacking. We found the variability in eDNA concentrations between transects to be moderate (21%) but still considerably lower than across bays and visits (52%), suggesting small scale spatial differences are of less importance during spring when pike spawn. Standardized angling catches, bay area, and water temperature together explained 48% of the variance in eDNA concentrations. DNA concentrations decreased with increasing bay area, likely indicating a dilution effect. Notably, the relationship between eDNA and standardized catches was positive but varied with temperature and the eDNA-abundance relationship was only significant at higher temperatures, which also coincided with a higher proportion of spawning/spent fish. We conclude that temperature is a key moderating factor driving changes in pike behaviour and spring DNA-dynamics. We recommend that future surveys focus on larger spatiotemporal scales during times when the influence of changing temperatures is minimized.
Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and MPROof SARS-CoV-2
Authors: Bello Shaibu Oricha , Imam Mustapha Umar , Bello Muhammad Bashir , Yunusa Abdulmajeed , Adamu Adamu Ahmed , Shuaibu Abdulmalik , Igumbor Ehimario Uche , Habib Zaiyad Garba , Popoola Mustapha Ayodele , Ochu Chinwe Lucia , Bello Aishatu Yahaya , Deeni Yusuf Yahaya , Okoye Ifeoma
Published: December 2022

We previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 μM, 4.23 μM, 9.29 μM, 3.19 μM and 84.31 μM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50of 0.94 μM, 0.88 μM, 1.14 μM, 1.07 μM, 1.51 μM respectively and the main protease(MPRO) with IC50of 1.35 μM, 1.25 μM, 7.36 μM, 1.15 μM and 2.44 μM respectively. The IC50for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
Selective transduction and photoinhibition of pre-Botzinger neurons that project to the facial nucleus in rats affect the nasofacial activity
Authors: Melo MR , Wykes A , Connelly AA , Bassi JK , Cheung SD , McDougall S , Menuet C , Bathgate RAD , Allen AM
Published: December 2022

The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.
Fraction of copy-number alterations significantly predicts survival following immunotherapy in a few cancers
Authors: Chang Tiangen , Cao Yingying , Shulman Eldad D. , Schäffer Alejandro A. , Ruppin Eytan
Published: December 2022

Various studies have shown that high tumor mutation burden (TMB) may predict response to immune checkpoint therapy, at least in some cancer types1,2. However, identifying patients with low TMB that are still likely to respond to cancer immunotherapy is an important open challenge. Recently, Spurr et al.3reported that the tumoraneuploidy score(AS), defined as the fraction of chromosome arms with arm-level copy number alterations in a sample, is predictive of survival following immunotherapy in low-TMB patients across multiple cancers. By re-analyzing the same data set by performing survival analysis in individual cancer types separately, we find that AS only significantly predicts survival in one single cancer indication. We further find that another metric conceptually related to the AS,the fraction of genome encompassed by copy number alterations (FGA), if called with a conventional copy number calling cutoff, has stronger predictive power than the AS proposed in3, and that this observation holds even if the FGA and AS thresholds for presence/absence of copy number events are set comparably. However, with the current available data, even FGA can predict survival following immunotherapy in only a few cancer indications.