bluuebunny/crossref_metadata_2025 huggingface dataset:
Geodetic deformation measurement and analysis of the ATLAS experimental cavern at CERN
Authors: Niewiem W. , Mergelkuhl D. , Gayde J.-C.
Published: November 2022

Caverns for large physics detectors, such as the one for the Large Hadron Collider experiments, sit nearly 100 m underground and measure several tens of meters in length, width and height. The deformation of the cavern base slab over decades has a direct influence on the relative alignment of detectors with respect to the accelerator. The expected long-term movements are larger than the fine adjustment of detectors and accelerators. In this paper, the measured deformations of the ATLAS experiment's main cavern floor and lateral walls over nearly 20 years have been analysed. The measurement series have been performed in various time intervals getting down to half a year. The used measurement techniques, such as the polar method (total station and laser tracker) and precise levelling, allow to obtain sub-millimetre precision. Even if the deformations are significantly (four times) lower compared to the predictions of the civil engineering consultants at the moment of the cavern construction, the measured ones reach values up to 5.0 mm for the base slab and up to 14.7 mm for the lateral walls.
Validation of transcriptome signature reversion for drug repurposing in oncology
Authors: Koudijs Karel K M , Böhringer Stefan , Guchelaar Henk-Jan
Published: November 2022

Transcriptome signature reversion (TSR) has been extensively proposed and used to discover new indications for existing drugs (i.e. drug repositioning, drug repurposing) for various cancer types. TSR relies on the assumption that a drug that can revert gene expression changes induced by a disease back to original, i.e. healthy, levels is likely to be therapeutically active in treating the disease. Here, we aimed to validate the concept of TSR using the PRISM repurposing data set, which is—as of writing—the largest pharmacogenomic data set. The predictive utility of the TSR approach as it has currently been used appears to be much lower than previously reported and is completely nullified after the drug gene expression signatures are adjusted for the general anti-proliferative downstream effects of drug-induced decreased cell viability. Therefore, TSR mainly relies on generic anti-proliferative drug effects rather than on targeting cancer pathways specifically upregulated in tumor types.
FUSTA: leveraging FUSE for manipulation of multiFASTA files at scale
Authors: Delehelle Franklin , Roest Crollius Hugues
Published: November 2022

Motivation

FASTA files are the de facto standard for sharing, manipulating and storing biological sequences, while concatenated in multiFASTA they tend to be unwieldy for two main reasons: (i) they can become big enough that their manipulation with standard text-editing tools is unpractical, either due to slowness or memory consumption; (ii) by mixing metadata (headers) and data (sequences), bulk operations using standard text streaming tools (such as sed or awk) are impossible without including a parsing step, which may be error-prone and introduce friction in the development process.

Results

Here, we present FUSTA (FUse for faSTA), a software utility which makes use of the FUSE technology to expose a multiFASTA file as a hierarchy of virtual files, letting users operate directly on the sequences as independent virtual files through classical file manipulation methods.

Availability and implementation

FUSTA is freely available under the CeCILL-C (LGPLv3-compatible) license at https://github.com/delehef/fusta.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Unbiased pangenome graphs
Authors: Garrison Erik , Guarracino Andrea
Published: November 2022

Motivation

Pangenome variation graphs model the mutual alignment of collections of DNA sequences. A set of pairwise alignments implies a variation graph, but there are no scalable methods to generate such a graph from these alignments. Existing related approaches depend on a single reference, a specific ordering of genomes or a de Bruijn model based on a fixed k-mer length. A scalable, self-contained method to build pangenome graphs without such limitations would be a key step in pangenome construction and manipulation pipelines.

Results

We design the seqwish algorithm, which builds a variation graph from a set of sequences and alignments between them. We first transform the alignment set into an implicit interval tree. To build up the variation graph, we query this tree-based representation of the alignments to reduce transitive matches into single DNA segments in a sequence graph. By recording the mapping from input sequence to output graph, we can trace the original paths through this graph, yielding a pangenome variation graph. We present an implementation that operates in external memory, using disk-backed data structures and lock-free parallel methods to drive the core graph induction step. We demonstrate that our method scales to very large graph induction problems by applying it to build pangenome graphs for several species.

Availability and implementation

seqwish is published as free software under the MIT open source license. Source code and documentation are available at https://github.com/ekg/seqwish. seqwish can be installed via Bioconda https://bioconda.github.io/recipes/seqwish/README.html or GNU Guix https://github.com/ekg/guix-genomics/blob/master/seqwish.scm.
Active learning for efficient analysis of high-throughput nanopore data
Authors: Guan Xiaoyu , Li Zhongnian , Zhou Yueying , Shao Wei , Zhang Daoqiang
Published: November 2022

Motivation

As the third-generation sequencing technology, nanopore sequencing has been used for high-throughput sequencing of DNA, RNA, and even proteins. Recently, many studies have begun to use machine learning technology to analyze the enormous data generated by nanopores. Unfortunately, the success of this technology is due to the extensive labeled data, which often suffer from enormous labor costs. Therefore, there is an urgent need for a novel technology that can not only rapidly analyze nanopore data with high-throughput, but also significantly reduce the cost of labeling. To achieve the above goals, we introduce active learning to alleviate the enormous labor costs by selecting the samples that need to be labeled. This work applies several advanced active learning technologies to the nanopore data, including the RNA classification dataset (RNA-CD) and the Oxford Nanopore Technologies barcode dataset (ONT-BD). Due to the complexity of the nanopore data (with noise sequence), the bias constraint is introduced to improve the sample selection strategy in active learning. Results: The experimental results show that for the same performance metric, 50% labeling amount can achieve the best baseline performance for ONT-BD, while only 15% labeling amount can achieve the best baseline performance for RNA-CD. Crucially, the experiments show that active learning technology can assist experts in labeling samples, and significantly reduce the labeling cost. Active learning can greatly reduce the dilemma of difficult labeling of high-capacity nanopore data. We hope active learning can be applied to other problems in nanopore sequence analysis.

Availability and implementation

The main program is available at https://github.com/guanxiaoyu11/AL-for-nanopore.

Supplementary information

Supplementary data are available at Bioinformatics online.
PoDCall: positive droplet calling and normalization of droplet digital PCR DNA methylation data
Authors: Jeanmougin Marine , Brodal Hans Petter , Dietrichson Pharo Heidi , Vedeld Hege Marie , Lind Guro Elisabeth
Published: November 2022

Motivation

Droplet digital PCR (ddPCR) holds great promises for investigating DNA methylation with high sensitivity. Yet, the lack of methods for analyzing ddPCR DNA methylation data has resulted in users processing the data manually at the expense of standardization.

Results

PoDCall is an R package performing automated calling of positive droplets, quantification and normalization of methylation levels in ddPCR experiments. A Shiny application provides users with an intuitive and interactive interface to access PoDCall functionalities.

Availability and implementation

The PoDCall R package is freely available on Bioconductor at https://bioconductor.org/packages/PoDCall/. The Shiny application can be executed from the R console using the wrapper function PoDCall::podcallShiny().

Supplementary information

Supplementary data are available at Bioinformatics online.
Systematic identification of biochemical networks in cancer cells by functional pathway inference analysis
Authors: Badshah Irbaz I , Cutillas Pedro R
Published: November 2022

Motivation

Pathway inference methods are important for annotating the genome, for providing insights into the mechanisms of biochemical processes and allow the discovery of signalling members and potential new drug targets. Here, we tested the hypothesis that genes with similar impact on cell viability across multiple cell lines belong to a common pathway, thus providing a conceptual basis for a pathway inference method based on correlated anti-proliferative gene properties.

Methods

To test this concept, we used recently available large-scale RNAi screens to develop a method, termed functional pathway inference analysis (FPIA), to systemically identify correlated gene dependencies.

Results

To assess FPIA, we initially focused on PI3K/AKT/MTOR signalling, a prototypic oncogenic pathway for which we have a good sense of ground truth. Dependencies for AKT1, MTOR and PDPK1 were among the most correlated with those for PIK3CA (encoding PI3Kα), as returned by FPIA, whereas negative regulators of PI3K/AKT/MTOR signalling, such as PTEN were anti-correlated. Following FPIA, MTOR, PIK3CA and PIK3CB produced significantly greater correlations for genes in the PI3K-Akt pathway versus other pathways. Application of FPIA to two additional pathways (p53 and MAPK) returned expected associations (e.g. MDM2 and TP53BP1 for p53 and MAPK1 and BRAF for MEK1). Over-representation analysis of FPIA-returned genes enriched the respective pathway, and FPIA restricted to specific tumour lineages uncovered cell type-specific networks. Overall, our study demonstrates the ability of FPIA to identify members of pro-survival biochemical pathways in cancer cells.

Availability and implementation

FPIA is implemented in a new R package named ‘cordial’ freely available from https://github.com/CutillasLab/cordial.

Supplementary information

Supplementary data are available at Bioinformatics online.
On the statistical role of inexact matching in observational studies
Authors: Guo Kevin , Rothenhäusler Dominik
Published: November 2022

In observational causal inference, exact covariate matching plays two statistical roles: (i) it effectively controls for bias due to measured confounding; (ii) it justifies assumption-free inference based on randomization tests. In this paper we show that inexact covariate matching does not always play these same roles. We find that inexact matching often leaves behind statistically meaningful bias, and that this bias renders standard randomization tests asymptotically invalid. We therefore recommend additional model-based covariate adjustment after inexact matching. In the framework of local misspecification, we prove that matching makes subsequent parametric analyses less sensitive to model selection or misspecification. We argue that gaining such robustness is the primary statistical role of inexact matching.
Patient-Centered Access to IBD Care: A Qualitative Study
Authors: Heisler Courtney , Rohatinsky Noelle , Mirza Raza M , Kits Olga , Zelinsky Sandra , Veldhuyzen van Zanten Sander , Nguyen Geoffrey , McCurdy Jeffrey , MacMillan Mark , Lakatos Peter L , Targownik Laura , Fowler Sharyle , Rioux Kevin , Jones Jennifer
Published: November 2022

Background

Canada has the highest global age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Due to IBD patient volumes and limited resources, challenges to timely access to specialty care have emerged. To address this gap, the aim of this paper was to understand the experiences and perspectives of persons living with IBD with a focus on accessing health care.

Methods

Using a qualitative descriptive approach, patients diagnosed with IBD (≥18 years of age) were purposively sampled from rural and urban gastroenterology clinics and communities across Canada. Co-facilitated by a researcher and patient research partner, 14 focus groups were recorded, transcribed, and coded for themes. Thematic analysis was used to ascertain the congruence or discordance of IBD specialty care access experiences.

Results

A total of 63 individuals participated in the study. The majority of participants were female (41/63, 65%) and from urban/suburban regions (33/63, 52%), with a mean age of 48.39 (range 16–77 years). The analysis generated three main themes: (1) need for patient to be partner, (2) adapting IBD care access to individual context, and (3) patient-defined care priorities should guide access to IBD care.

Conclusions

The complexity of specialty care access for IBD patients cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the impact of these factors on accessing care. Using a patient-centered exploration of barriers and facilitators, IBD specialty care access in Canada can be better understood and improved on provincial and national levels.
Phenomapping in heart failure with preserved ejection fraction: insights, limitations, and future directions
Authors: Peters Anthony E , Tromp Jasper , Shah Sanjiv J , Lam Carolyn S P , Lewis Gregory D , Borlaug Barry A , Sharma Kavita , Pandey Ambarish , Sweitzer Nancy K , Kitzman Dalane W , Mentz Robert J
Published: November 2022

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity with complex pathophysiology and manifestations. Phenomapping is the process of applying statistical learning techniques to patient data to identify distinct subgroups based on patterns in the data. Phenomapping has emerged as a technique with potential to improve the understanding of different HFpEF phenotypes. Phenomapping efforts have been increasing in HFpEF over the past several years using a variety of data sources, clinical variables, and statistical techniques. This review summarizes methodologies and key takeaways from these studies, including consistent discriminating factors and conserved HFpEF phenotypes. We argue that phenomapping results to date have had limited implications for clinical care and clinical trials, given that the phenotypes, as currently described, are not reliably identified in each study population and may have significant overlap. We review the inherent limitations of aggregating and utilizing phenomapping results. Lastly, we discuss potential future directions, including using phenomapping to optimize the likelihood of clinical trial success or to drive discovery in mechanisms of the disease process of HFpEF.
Pericardial effusion and tamponade in the context of herpes zoster: a novel occurrence
Authors: Easton Aleisha , Joret Maximilian , Xian Susan , Ternouth Ian
Published: November 2022

Background

Pericarditis and pericardial effusion are relatively common hospital presentations, which rarely result in cardiac tamponade. The aetiology is often undetermined and presumed idiopathic or viral. This article reviews varicella zoster virus (VZV)–associated pericardial effusion and peri/myopericarditis and constitutes the first report of VZV-associated cardiac tamponade in the adult population.

Case summary

We report the case of a 59-year-old woman who presented to hospital with pleuritic chest pain, haemodynamic instability, and a recent herpes zoster rash in the left T1 distribution. Computed tomography revealed a large pericardial effusion, and echocardiography showed features of cardiac tamponade. The patient was treated with pericardial drainage. Aspirate analysis revealed abundant polynuclear cells and histocytes with no organism. Polymerase chain reaction did not determine a cause.

Discussion

There are 13 reported cases of VZV-associated peri/myopericarditis in adults in the literature published in the English language. Of these, only three patients had a pericardial effusion. Aetiological diagnosis of an effusion is challenging and rarely made on virological grounds but rather on clinical features. Varicella zoster virus–associated pericardial effusion should be considered in patients presenting with haemodynamic instability and a dermatomal rash affecting the C3–C5 and T1–T4 distributions.
Foliar Residual Toxicity of Insecticides to Brassica Pests and Their Natural Enemies
Authors: Anjum Farida , Wright Denis J
Published: November 2022

Overuse of pesticides can result in the development of resistance, secondary pest outbreaks, and pest resurgence due to a reduction in natural enemies. The present study compares the residual toxicity of lambda-cyhalothrin, a relatively nonselective insecticide, with abamectin, indoxacarb, and spinosad, compounds which have been reported to be less harmful to arthropod natural enemies. Two key cosmopolitan pests of crucifer crops, (Plutella xylostella) and (Myzus persicae), and two of their respective hymenopteran parasitoids, (Cotesia vestalis) and (Aphidius colemani) were used as representative pests and natural enemies. The pyrethroid lambda-cyhalothrin was found to be the most persistent toxicant against both pest and both parasitoid species tested, while the lactones abamectin and spinosad were the least persistent toxicants. A leaf wax stripping technique was used to compare the contact toxicity of insecticide residues against adult C. vestalis and A. colemani in the epicuticular wax layer. For each compound, removal of epicuticular wax reduced the 24 h residual toxicity (LC50) of fresh deposits (day 0) by about an order of magnitude against C. vestalis. A second residual toxicity experiment showed that removal of epicuticular wax significantly reduced the residual toxicity of each compound against A. colemani at 0, 7, and 14 d after application, with little or no detectable residual activity for the oxadiazine indoxacarb or abamectin/spinosad respectively after 14 d. The present data supports the view that in addition to the intrinsic toxicity of insecticides to natural enemies, differences in their persistence as foliar residues should also be considered in IPM systems.
AVA inversion for novel fluid indicator considering consolidation parameter
Authors: Yang Wenqiang , Yang Zhifang , Zong Zhaoyun , Sun Qianhao , Yan Xinfei
Published: November 2022

Geofluid identification from seismic data are crucial for understanding reservoir characteristics. However, fluid indicators based on elastic parameter combinations show strong ambiguity in terms of geofluid identification. Although the effective pore-fluid bulk modulus proves to be the superior fluid indicator in geofluid discrimination, it is limited to empirical models such as the critical porosity model. The consolidation parameter model can evaluate the consolidation and compaction of sediments and is widely used due to its better applicability. Therefore, a novel fluid indicator considering consolidation parameter is proposed and a boundary-constrained inversion strategy for geofluid identification is developed. First, the novel fluid indicator is defined based on the poroelasticity theory. Then, the linearized AVA (amplitude variation with angle) approximation equation related to the new fluid indicator is derived to directly link seismic data and properties of pore-filling materials. The model analysis verifies the accuracy of the derived approximation equation at moderate incident angles, which can be used for parameter prediction by pre-stack seismic inversion. Furthermore, the contribution of each attribute of the novel equation to the reflectivity is analyzed to validate the feasibility of new fluid indicator inversion. Finally, a boundary-constrained AVA pre-stack inversion method is presented to enhance the robustness of the inversion results of the model parameter. The reliability of the improved method is proved by accurate inversion results of synthetic seismic records. After determining the consolidation parameter using well-log data combined with BGT (Biot–Gassmann Theory), the field data further demonstrated that the proposed approach is accurate and effective.
Transmission of SARS-CoV-2 Delta variant from an infected aircrew member on a short-haul domestic flight, Australia 2021
Authors: Williamson Kirsten M , Butler Michelle , Elton Benjamin , Taylor Joanne , Islam Fakhrul , Douglas Michael P , Kirk Martyn D , Durrheim David N
Published: November 2022

In June 2021, when COVID-19 incidence in Australia was low, a COVID-19 (Delta variant) cluster occurred on an 81-minute domestic flight, with an aircrew member as the likely source. Outbreak investigation demonstrated that SARS-CoV-2 may be transmitted during short-haul flights and that mask use protected against infection.
Outliers in the Ep,z – Eγ relation of Fermi-GBM long-duration gamma-ray bursts
Authors: Jiang Lu-Yao , Wang Yun , Wei Da-Ming , Ren Jia , Xie Lang , Li Jing
Published: November 2022

Long gamma-ray bursts (GRBs) are typically associated with massive star core collapse, while the short GRBs are associated with compact binary mergers. However, recent evidence indicates that some peculiar long-duration bursts may correspond to compact binary mergers origins. In this paper, we use the data of the Fermi Gamma-ray Burst Monitor to search for peculiar long-duration bursts which may be from compact binary mergers based on outlier events in the $E_{p,z}\!-\!E_{\gamma ,\rm iso}$ relation. We obtained 10 outlier events by systematically analysing bursts with $T_{90}\gt 4.2 \rm \ s$ from 2008 August to 2021 July. In order to determine whether these outlier events were from compact binary mergers, we analysed their properties, including spectral lag, hardness ratio, and energy-hardness parameter. Based on the distributions of T90 − HR and T90 − Ep, we calculated the probability of outlier events belonging to the short GRBs. Our analysis indicates that GRB 120304B is likely to arise from the merger of a neutron star and a massive white dwarf. GRB 150210A is likely to arise from massive star core collapse. The other eight GRBs are fuzzy bursts that have both long and short GRBs properties. Additionally, we find that outlier samples have relatively high Ep and low fluences.
Investigating RNA–protein recognition mechanisms through supervised molecular dynamics (SuMD) simulations
Authors: Pavan Matteo , Bassani Davide , Sturlese Mattia , Moro Stefano
Published: November 2022

Ribonucleic acid (RNA) plays a key regulatory role within the cell, cooperating with proteins to control the genome expression and several biological processes. Due to its characteristic structural features, this polymer can mold itself into different three-dimensional structures able to recognize target biomolecules with high affinity and specificity, thereby attracting the interest of drug developers and medicinal chemists. One successful example of the exploitation of RNA’s structural and functional peculiarities is represented by aptamers, a class of therapeutic and diagnostic tools that can recognize and tightly bind several pharmaceutically relevant targets, ranging from small molecules to proteins, making use of the available structural and conformational freedom to maximize the complementarity with their interacting counterparts. In this scientific work, we present the first application of Supervised Molecular Dynamics (SuMD), an enhanced sampling Molecular Dynamics-based method for the study of receptor–ligand association processes in the nanoseconds timescale, to the study of recognition pathways between RNA aptamers and proteins, elucidating the main advantages and limitations of the technique while discussing its possible role in the rational design of RNA-based therapeutics.
The Impatiens Downy Mildew Epidemic in the United States Is Caused by New, Introgressed Lineages of Plasmopara destructor with Prominent Genotypic Diversity and High Evolutionary Potential
Authors: Salgado-Salazar Catalina , Castroagudín Vanina L. , LeBlanc Nicholas R. , Daughtrey Margery L. , Hausbeck Mary K. , Palmer Cristi L. , Shishkoff Nina , Warfield Colleen , Crouch Jo Anne
Published: November 2022

Impatiens downy mildew (IDM) caused by Plasmopara destructor is currently the primary constraint on the production and use of impatiens (Impatiens walleriana) as bedding plants worldwide. Downy mildew has been documented since the 1880s from wild-grown Impatiens spp. but epidemic outbreaks of the disease affecting the commercially grown, ornamental I. walleriana were only reported for the first time in 2003 in the United Kingdom and in 2004 in the United States. Here, we assess the genetic diversity, level of differentiation, and population structure from 623 samples associated with current and preepidemic IDM outbreaks, by genotyping the samples with simple sequence repeat markers. P. destructor population structure following the emergence of IDM in the United States is subdivided into four genetic lineages characterized by high genetic diversity, mixed reproduction mode, inbreeding, and an excess of heterozygosity. P. destructor genotypes are significantly differentiated from preepidemic IDM samples from hosts other than I. walleriana but no geographical or temporal subdivision is evident. P. destructor samples from different Impatiens spp. show significant but very low levels of differentiation in the analysis of molecular variance test that did not hold in discriminant analysis of principal components analyses. The same was observed between samples of P. destructor and P. velutina recovered from I. walleriana. The finding of shared genotypes in samples from different countries and lack of differentiation among U.S. and Costa Rican samples indicate the occurrence of international movement of the pathogen. Our study provides the first high-resolution analysis of the diversity of P. destructor populations and the IDM epidemic that may be instrumental for disease management and breeding efforts.
Perthes disease: comparison of two surgical options
Authors: Grothaus Olivia , Desperes Matias , Vanderhorst Anna , Wu Chaorong , Presson Angela , Stevens Peter
Published: November 2022

Varus intertrochanteric osteotomy (ITO) remains the most popular method to contain the fragmenting femoral head in Perthes disease. However, resultant compromise of hip abductors may result in coxa brevis and acetabular dysplasia, increasing the risk of requiring future surgery. A minimally invasive strategy of tension plating the greater trochanter was developed in effort to avoid these consequences. The objective is to compare greater trochanter-guided growth to ITO for treatment of Perthes disease. This IRB approved, retrospective review compares two series of children with Perthes, one treated with ITO and one with greater trochanter-guided growth (GG). Clinical examination findings and clinical course were recorded via chart review. Weight-bearing pelvic X-rays were analyzed preoperatively and at the last known follow-up prior to other procedures. There were 58 patients: 18 underwent ITO versus 40 GG. The groups matched in age, sex, examination, and radiographic parameters. Average follow-up was 5 years. The change in the center head-trochanteric distance (CTD) was statistically significant (P < 0.05), −0.3 cm in GG versus −1.09 cm in ITO patients. At final follow-up, the ITO group was more likely to have LLD ≥ 2 cm (16.67% vs. 0%; P = 0.03) and 52.5% of GG patients were classified as Stulberg III or greater, versus 72.2% of the ITO group (P < 0.001). Ninety-four percent of ITO patients versus 40% of GG required additional surgery. Containment by ITO reflects exclusive focus upon the femoral head, without considering long-term sequelae. GG addresses the femoral neck issues potentially providing better outcomes. Level of Evidence. This is a level III study providing further understanding of the properties of the proximal femoral physes and an alternative for surgical management of perthes disease.
Evaluating safe time to discharge after closed reduction and percutaneous pinning of uncomplicated type III supracondylar humerus fractures: a single-center retrospective review
Authors: Cole Austin A. , Parker Wesley , Tanner Stephanie L. , Bray Christopher C. , Lazarus David E. , Beckish Michael L.
Published: November 2022

The purpose of this retrospective study was to review complications following closed reduction, percutaneous pinning of isolated, type III supracondylar fractures without associated injuries to evaluate if patients may be discharged safely on the day of surgery. We performed a retrospective chart and radiographic review of patients with isolated Gartland type III supracondylar humerus fractures who underwent closed reduction and percutaneous pinning over a 4-year period. We reviewed admission time to the emergency department, time and length of surgery, time to discharge, postoperative complications, readmission rate and office visits. Of the 110 patients included, 19 patients were discharged in less than 6 h, 45 patients between 6 and 12 h and 46 patients greater than 12 h. A total of 61 patients were discharged on the same day as surgery and 49 were discharged the next day. There were 11 postoperative complications. No postoperative complications were found in patients discharged less than 6 hours from surgery. For patients discharged between 6 and 12 hours postoperatively, one patient returned to the office earlier than scheduled. The result of our review suggests that patients can be safely discharged within the 12-h postoperative period with no increased risk of complications. This is contingent upon the patient having a stable neurovascular examination, pain control and caregiver’s comfort level. This can decrease medical cost, family stress and burden to the hospital system. Time to discharge should still be evaluated on a case-by-case basis after evaluating medical and social barriers.
Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study
Authors: Yao Chi-Yuan , Agathangelidis Andreas , Chuang Shih-Sung , Tsou Hsiao-Hui , Feng Wei-Lien , Liu Ta-Chih , Chen Tsai-Yun , Yu Yuan-Bin , Yeh Su-Peng , Yao Ming , Wang Chuan-Cheng , Lin Johnson , Hwang Wen-Li , Gau Jyh-Pyng , Chou Wen-Chien , Chao Tsu-Yi , Lin Liang-In , Tien Hwei-Fang , Ghia Paolo , Wu Shang-Ju
Published: November 2022

Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.
Changing landscape of living kidney donation and the role of telemedicine
Authors: Al Ammary Fawaz , Muzaale Abimereki D. , Tantisattamoa Ekamol , Hanna Ramy M. , Reddy Uttam G. , Bunnapradist Suphamai , Kalantar-Zadeh Kamyar
Published: November 2022

Purpose of review

There has been a decline in living kidney donation over the last two decades. Donors from low-income families or racial/ethnic minorities face greater disproportionate geographic, financial, and logistical barriers to completing lengthy and complex evaluations. This has contributed to the decreased proportion of these subgroups. The authors view telemedicine as a potential solution to this problem.

Recent findings

Since the initial decline of donors in 2005, biologically related donors have experienced a lack of growth across race/ethnicity. Conversely, unrelated donors have emerged as the majority of donors in recent years across race/ethnicity, except for unrelated black donors. Disparities in access to living kidney donation persist. Telemedicine using live-video visits can overcome barriers to access transplant centers and facilitate care coordination. In a U.S. survey, nephrologists, surgeons, coordinators, social workers, and psychologists/psychologists across transplant centers are favorably disposed to use telemedicine for donor evaluation/follow-up beyond the coronavirus disease 2019 pandemic. However, with the waning of relaxed telemedicine regulations under the Public Health Emergency, providers perceive payor policy and out-of-state licensing as major factors hindering telemedicine growth prospects.

Permanent federal and state policies that support telemedicine services for living kidney donation can enhance access to transplant centers and help overcome barriers to donor evaluation.
Practicing health equity in involuntary discharges to overcome disparities in dialysis and kidney patient care
Authors: Edwards Dawn P. , Kalantar-Zadeh Kamyar , Streja Elani , Ahdoot Rebecca S. , Norris Keith C. , Molony Donald
Published: November 2022

Purpose of review

Potential causes and consequences of involuntary discharge (IVD) of patients from dialysis facilities are widely unknown. So, also are the extent of racial disparities in IVDs and their impact on health equity.

Recent findings

Under the current End-Stage Renal Disease (ESRD) program

Conditions for Coverage (CFC), there are limited justifications for IVDs. The ESRD Networks oversee dialysis quality and safety including IVDs in US dialysis facilities, with support from the Agency for Healthcare Quality and Research (AHRQ) and other stakeholders. Whereas black Americans constitute a third of US dialysis patients, they are even more overrepresented in the planned and executed IVDs. Cultural gaps between patients and dialysis staff, psychosocial and regional factors, structural racism in kidney care, antiquated ESRD policies, unintended consequences of quality incentive programs, other perverse incentives, and failed patient–provider communications are among potential contributors to IVDs.

Practicing health equity in kidney care may be negatively impacted by IVDs. Accurate analyses of patterns and trends of involuntary discharges, along with insights from well designed AHRQ surveys and qualitative research with mixed method approaches are urgently needed. Pilot and feasibility programs should be designed and tested, to address the root causes of IVDs and related racial disparities.
The contemporary role of varicocele repair: why operate when in-vitro fertilization results are so good?
Authors: Gal Jonathan , Goldstein Marc
Published: November 2022

Purpose of review

A male factor is either the primary cause or is contributory in at least half of all couples with infertility. Currently, many male factor problems may be disregarded, as reproductive technology has advanced so much that in-vitro fertilization (IVF)/Intracytoplasmic sperm injection (ICSI) allows the use of even a single sperm to achieve pregnancy.

Recent findings

Varicocele is the most commonly diagnosed correctable cause. Microsurgical repair is considered the gold standard for repair. Research has shown that varicocele repair can impact the outcome of reproductive management and upgrade male infertility from adoption or donor sperm only to IVF/ICSI and microTESE, or IVF/ICSI with ejaculated sperm, or from IVF/ICSI to intrauterine insemination (IUI) or often naturally conceived.

Varicocele diagnosis and repair is an essential part of infertility evaluation. Not only does it potentially impact antiretroviral therapy choices, but it can also increase testosterone levels benefiting long-term male health.
T-cell receptor specific protein language model for prediction and interpretation of epitope binding (ProtLM.TCR)
Authors: Essaghir Ahmed , Sathiyamoorthy Nanda Kumar , Smyth Paul , Postelnicu Adrian , Ghiviriga Stefan , Ghita Alexandru , Singh Anjana , Kapil Shruti , Phogat Sanjay , Singh Gurpreet
Published: November 2022

The cellular adaptive immune response relies on epitope recognition by T-cell receptors (TCRs). We used a language model for TCRs (ProtLM.TCR) to predict TCR-epitope binding. This model was pre-trained on a large set of TCR sequences (~62.106) before being fine-tuned to predict TCR-epitope bindings across multiple human leukocyte antigen (HLA) of class-I types. We then tested ProtLM.TCR on a balanced set of binders and non-binders for each epitope, avoiding model shortcuts like HLA categories. We compared pan-HLA versus HLA-specific models, and our results show that while computational prediction of novel TCR-epitope binding probability is feasible, more epitopes and diverse training datasets are required to achieve a better generalized performances inde novoepitope binding prediction tasks. We also show that ProtLM.TCR embeddings outperform BLOSUM scores and hand-crafted embeddings. Finally, we have used the LIME framework to examine the interpretability of these predictions.
Can blood at adult age predict epigenetic changes of the brain during fetal stages?
Authors: Strawn Monica , Safranski Timothy J. , Behura Susanta K
Published: November 2022

Correspondence in DNA methylation between blood and brain is known in humans. If this pattern is present in pig has not been examined. In this study, we profiled DNA methylation of blood from pigs at adult ages, and compared those with the methylation profiles of fetal brain. Neural network regression modeling showed specific methylations in the adult blood that can reliably predict methylation of the fetal brain. Genes associated with these predictive methylations included markers of specific cell types of blood and brain, in particular, markers of bone marrow hematopoietic progenitors, and glial cells primarily the ependymal and Schwann cells of brain. The results of this study show that developmental methylation changes of the brain during fetal stages are maintained as an epigenetic memory in the blood in adult life. Thus, pig models may be harnessed to uncover potential roles of epigenetic memory in brain health and diseases.
SELECTIVE INHIBITION OF SOLUBLE TNF ATTENUATES HIPPOCAMPAL NEUROINFLAMMATION AND PSD-95 EXPRESSION TO IMPROVE NEUROLOGICAL FUNCTIONS IN A RAT MODEL OF GULF WAR ILLNESS
Authors: Janakiraman Udaiyappan , Larson Katelyn , Nixon-Lee Nancy , Damon Melissa , Biscardi Andrew , Hawkins Elisa , Deshpande Laxmikant S. , Dixon Kirsty J.
Published: November 2022

BACKGROUND

Systemic inflammation is a major contributor to poor brain pathology across many disease conditions. Specifically, the upregulation of the pro-inflammatory cytokine TNF in the hippocampus activates its receptor TNFR1, reducing AMPA receptor trafficking to impair LTP and associated behavioral outcomes. Studies using animal models of GWI have shown both a chronic upregulation of TNF and impaired neurological function. Therefore, this study aimed to investigate whether selectively inhibiting only the soluble form of TNF (solTNF) that preferentially activates TNFR1 can reverse neuroinflammation to improve neuroplasticity and neurological function.

METHODS

GWI was induced in rats by treating with DFP (or vehicle) for 5 consecutive days. Six months later, the rats were treated with XPro1595 (or vehicle) for 2 weeks to selectively inhibit solTNF, after which they were subjected to a battery of behavioral tests (cognition, anxiety-related, depressive-like behavior, and neuropathic pain). MRI brain scans were performed, and the animals were euthanized for brain pathological analysis.

RESULTS

The hippocampus of the GWI rats had significantly increased neuroinflammatory levels, resulting in edema and reduced AMPA receptor trafficking to the post-synaptic membrane that collectively promoted impairments in memory, anxiety, depressive-like behavior, and neuropathic pain. However, treating the rats with XPro1595 in the chronic environment attenuated the neuroinflammatory response, that reduced edema and impaired AMPA receptor trafficking, allowing for improvements in all areas of neurological function.

CONCLUSION

Overall findings suggest that selectively inhibiting solTNF using XPro1595 reduces neuroinflammation, synaptic plasticity, and overall function when administered in the chronic setting of a rat model of GWI. This data supports the use of XPro1595 in Veterans with GWI.
The simulation of functional heterogeneity in procedurally generated fibrotic atrial tissue
Authors: Kalinin A.I. , Kovalenko S.G. , Berezhnoy A.K. , Slotvitsky M.M. , Shcherbina S.A. , Syrovnev V.A. , Tsvelaya V.A.
Published: November 2022

The occurrence of atrial fibrillation (AF), one of the most common and socially significant arrhythmias, is associated with the presence of fibrosis sites. Fibrosis is the presence of non-conductive fibroblast cells, separating cardiomyocytes and introducing heterogeneity into the conducting atrial tissue. Thus fibrosis may be a substrate of spiral-wave reentry, provoking the occurrence of AF and is often associated with its persistent form. In this work, we propose for the first time a fundamentally new approach to modeling the fibrotic heart that takes into account the cellular structure of the tissue: a realistic texture of atrial tissue remodeled by fibroblasts is generated by the Potts model, and the local membrane potential of individual cells is calculated by the Courtemanche model. We have shown the occurrence of conductive pathways in such a system with a low proportion of fibroblasts (up to 10%) and revealed the connection of the form of the action potential (AP) of cells with their location in the tissue and the direction of the propagating wave front. The combination of these effects creates dynamic heterogeneity of the conducting tissue and affects the migration and pinning of spiral waves, which makes the model a potential tool for prognostic modeling of AP and search for ablation targets. The computer prediction of ablation targets (reentry nodes) will help to increase the efficiency of treatment of patients with persistent form of AF.
Addiction recovery stories: Lauren Wearing in conversation with Lisa Ogilvie
Authors: Wearing Lauren , Ogilvie Lisa
Published: November 2022

Purpose

This purpose of this paper is to contribute to a series of recovery stories that examine candid accounts of addiction and recovery. Shared components in the recovery process are considered, along with the change and growth needed to support the transition from addiction to recovery.

Design/methodology/approach

The connectedness, hope, identity, meaning in life and empowerment (CHIME) framework comprises five elements important to recovery. CHIME provides a standard to qualitatively study recovery. As a model, it has been extended to include growth (G-CHIME), an element that is important for sustained addiction recovery. In this paper a first-hand account of addiction recovery is presented, followed by a semi-structured e-interview with the author of the account that is based on the G-CHIME model.

Findings

This paper shows that addiction recovery is a remarkable process that can be effectually explained using the G-CHIME model. The significance of each element in the model is apparent from the biography and e-interview presented.

Originality/value

Each account of recovery in this series is unique, and as yet, untold.
Acuver: social media strategy for visibility
Authors: Sringeswara Sharada , Singh Jang Bahadur , Sharma Sujeet K.
Published: November 2022

Learning outcomes

■ Understand the functionalities of various social media platforms. ■ Choose social media platforms to align various business goals. ■Consider how to develop strategies for monitoring, understanding and responding to different social media activities.

Case overview/synopsis

Acuver Consulting Private Limited (Acuver) is a niche, self-funded IT consulting services start-up. Founded in 2013 with the aim of providing IT consulting services in the supply chain domain, Acuver delivers IT solutions to the world’s leading IT conglomerates, Fortune 500 companies and emerging players across multiple geographies and industries. Changing consumer buying patterns in recent years has forced retailers and supply-chain businesses to invest in digital transformation projects, providing ample growth opportunities for Acuver. To meet increased demand, Acuver needs to acquire direct engagements with clients and hire the right talent to help it ride this growth wave. This case described challenges faced by the start-up in building visibility to expand its reach. The case provided an overview of the IT consulting services industry and Acuver’s vision. It then detailed the reasons for the company’s lack of visibility, which was curtailing its growth opportunities. It described the dilemma and possible strategies to overcome the problem statement. It also discussed the limitations associated with the potential strategies, which needed to be contemplated by the reader.

Complexity academic level

This case is appropriate for MBA and Executive MBA courses on Management of Information System, Digital Governance, Strategic Management of IT and Managing Digital Transformation.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy.
A machine learning approach on analysing the sentiments in the adoption of telemedicine application during COVID-19
Authors: M. Dhanya , S. Sanjana
Published: November 2022

Purpose

The purpose of this paper is to understand the customer sentiment towards telemedicine apps and also to apply machine learning algorithms to analyse the sentiments in the adoption during the COVID-19 pandemic.

Design/methodology/approach

Text mining that uses natural language processing to extract insights from unstructured text is used to find out the customer sentiment towards the telemedicine apps during the COVID-19 pandemic. Machine learning algorithms like support vector machine (SVM) and Naïve Bayes classifier are used for classification, and their sensitivity and specificity are found using a confusion matrix.

Findings

The paper explores the customer sentiment towards telemedicine apps and their adoption during the COVID-19 pandemic. Text mining that uses natural language processing to extract insights from unstructured text is used to find out the customer sentiment towards the telemedicine apps during the COVID-19 pandemic. Machine learning algorithms like SVM and Naïve Bayes classifier are used for classification, and their sensitivity and specificity are found using a confusion matrix. The customers who used telemedicine apps have positive sentiment as well as negative sentiment towards the telemedicine apps. Some of the customers have concerns about the medicines delivered, their delivery time, the quality of service and other technical difficulties. Even a small percentage of doctors feel uncomfortable in online consultation through the application.

Originality/value

The primary value of this paper lies in providing an overview of the customers’ approach towards the telemedicine apps, especially during the COVID-19 pandemic.