bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual guidelines and tutoring in pediatric urological surgery
Authors: Kotcherov Stanislav , Rotem Shahar , Jaber Jawdat , Avraham Galit , Lev Gennady , Darmon Michal , Gabay Yudith , Chertin Boris
Published: December 2021

Background

The aim of this prospective randomized study was to evaluate the impact of visual guidelines (picture book) and parents tutoring on pediatric urological surgery on parent’s stress and anxiety, the number of postoperative contacts, and complications.

Materials and methods

Following institutional ethical committee approval, a special picture book reflecting different stages of the convalescent period following multiple types of pediatric urological surgery was developed. Parents were randomly divided into 2 groups in which 33 parents in Group 1 received the picture book in addition to routine instructions prior to the surgery and 31 in Group 2 received only routine postoperative instructions. The parents were asked to answer a questionnaire (Amsterdam Preoperative Anxiety and Information Scale) regarding the level of anxiety before surgery and immediately after surgery in the recovery room. The number of postoperative parent’s calls, nonplaned emergency room visits, and complications were recorded.

Results

No statistically significant difference in perioperative parental anxiety was found (p = 0.88). The visual tutoring group had a significantly lower rate of emergency room admissions (6.6% vs. 18.6%, p = 0.0433), however parents from this group made a higher number of postoperative calls (9.9% vs. 3.1%, p = 0.38). Two (6.6%) from the tutoring group expressed their desire to omit visual counseling in future surgical preparation and 4 (13.2%) did not have an opinion. Overall satisfaction with regards to the preoperative counseling and information and the number of postoperative complications was similar in both groups.

Conclusions

Visual tutoring does not add any value to parental anxiety but seems helpful in reducing postoperative emergency room visits. Some parents preferred to exclude visual information from future preoperative counseling.
Delivery of menopause care during a pandemic: an evaluation of patient satisfaction with telephone visits
Authors: Wright Emily , Shaltout Ola , Zokvic Mary Ann , Shirreff Lindsay
Published: December 2021

Objective:

We aimed to evaluate patient satisfaction with telephone appointments during the first wave of the COVID-19 pandemic, determine visit type preference (in-person vs telephone), and predictors of those preferences.

Methods:

In this cross-sectional study, patient visits during the first wave of COVID-19 (March 20 to July 15, 2020) were characterized (in-person vs telephone) in a single provider's weekly menopause clinic in Toronto, Canada. Patients attending telephone appointments were asked to complete a modified Telemedicine Satisfaction Questionnaire with 5-point Likert-scale responses. Demographic information was collected along with the patient-reported cost to attend an in-person appointment (monetary, travel time, and time away from work). Of those who experienced both visit types, preference was evaluated and bivariate analysis was performed identifying factors associated with visit type preference and included in a multivariable binary logistic regression model.

Results:

During the first wave of the COVID-19 pandemic, 214 women had 246 visits, attending mostly by telephone (221/246, 90%). Mean Telemedicine Satisfaction Questionnaire composite score was 4.23 ± 0.72. Of those who attended a prepandemic in-person appointment (118/139, 85%), a minority (24/118, 20%) preferred in-person visits. Those favoring in-person were more likely to commute less than 30 minutes (OR 3.78, 95% CI 1.16-12.29, P = 0.027), require less than 2 hours away from work (OR 4.05, 95% CI 1.07-15.4, P = 0.04), and spend less than $10 to attend (OR 3.67, 95% CI 1.1-12.26, P = 0.035).

Conclusions:

Menopause clinic telephone appointments had high patient satisfaction, with most preferring this visit type, although in-person visits are preferred among a minority of women.
Lipofibromatous Hamartoma of Digital Nerve: A Case Report
Authors: Soffar Mohammad M. , Fadali Geylan , Ghalab Mahmoud A. , Abouzaid Ahmed M.
Published: December 2021

A 9-year-old girl was investigated for a long-standing soft tissue swelling in her ring digit that recently developed tenderness and rapid growth within the last 3 months before presentation. Exploration of the swelling was done meticulously with total excision of the swelling from within its attachment to the digital nerve. The swelling was then sent for histopathological examination. The pathology report stated the presence of mature adipose tissue intersected by fiprocellular collagenic stroma infiltrating perineurium, epineurium, and nerve fascicles, which established the diagnosis of lipofipromatous hamartoma (LFH) of the nerve. LFH is a rare benign neoplasm that mainly affects the median nerve, but other nerves all over the body were also reported. Women are more affected than men.
Pyogenic Liver Abscess Caused by Staphylococcus hominis: A Case Report
Authors: Zhao Ze-Hua , Fan Yu-Chen , Wang Kai
Published: December 2021

Staphylococcus hominis is a component of the normal human microflora and is considered to be an opportunistic pathogen that may cause a variety of infections. It has been reported to cause bacteremia, endocarditis and endophthalmitis. However, abscesses caused by S. hominis are rarely documented. Here, we describe a case of pyogenic liver abscesses caused by S. hominis. Laboratory tests, imaging examinations, and abscess puncture fluid culture were used to identify the etiology and pathogenic bacterium. This case suggests that percutaneous drainage and targeted antibiotic treatment according to the results of antimicrobial susceptibility tests are effective therapeutic approaches for pyogenic liver abscesses caused by S. hominis.
Building Strong Clinician-Researcher Collaborations for Successful Hospice and Palliative Care Research
Authors: Hurley Susan Lysaght , DeSanto-Madeya Susan , Fortney Christine A. , Izumi Seiko , Phongtankuel Veerawat , Carpenter Joan G.
Published: December 2021

Hospice and palliative care research aim to build a knowledge base to guide high-quality care for people with serious illness and improve their quality of life. Considering its focus on patient and family caregiver's experiences, hospice and palliative care research activities primarily take place in real-world clinical settings where seriously ill patients and their family caregivers receive care (eg, nursing homes, clinics, inpatient units). Conducting research in these settings poses many challenges because researchers, clinicians, and administrators may have different priorities—and scientific control is difficult. Therefore, clinician-researcher-administrator collaboration in planning and conducting studies is critical for successful hospice and palliative care research. For an effective collaboration, clinicians, researchers, and site administrators must be considered equal partners. Each collaborator brings their unique expertise, knowledge, and skills that when combined can strengthen scientific rigor, feasibility, and success of the project, as well as have study outcomes that are more translatable to real-world practice. However, little guidance exists to give actionable steps to build collaborative partnerships for hospice and palliative care researchers. The purpose of this article is to describe the process of forming successful clinician-researcher-administrator collaborations through five phases of the research life cycle: idea generation, partnership, proposal writing, research process, and dissemination. Exemplars are drawn from the authors' experiences conducting collaborative research and highlight strategies and resources for successful hospice and palliative care collaborations.
Effect of a Palliative Care Screening Tool for Oncology Patients
Authors: Schierenbeck Sara J. , Elertson Kathleen
Published: December 2021

This pilot quality improvement project implemented an adapted screening tool within an outpatient oncology center for patients with advanced cancer to identify unmet patient needs, aid decision making, and increase the number of patients referred to palliative care. Baseline data were collected via retrospective convenience sampling to track the number of palliative care referrals generated from the oncology center. Over a 6-week period, screening was implemented during patient evaluations with their oncologist to identify needs for palliative care intervention and as a decision aid to support referring patients to a specialized palliative care service. During the pilot, key nursing staff were affected by COVID-19, and the ideal sample size was not met. Despite a small sample size, the number of palliative care referrals increased. The increased number of referrals affirms the use of a screening tool to identify palliative care needs and as a formal decision-making process to improve patient access to palliative care.
Anatomic Asymmetry of Transverse Sinus May Be Irrelevant to the Prognosis of Intracerebral Hemorrhage
Authors: Chen Zhiying , Ding Jiayue , Wu Xiaoqin , Cao Xianming , Liu Hao , Yin Xiaoping , Ding Yuchuan , Ji Xunming , Meng Ran
Published: December 2021

Background:

We investigate the probable effect of anatomic asymmetry of transverse sinus (TS) on the outcomes of acute intracerebral hemorrhage (ICH), to provide reference for customized treatment.

Methods:

Consecutive patients with imaging-confirmed acute ICH were enrolled from October 2015 through October 2019, and divided into 2 groups: symmetrical and unilateral (left or right) slender TS groups, based on the status of TS in imaging maps. Brain computed tomography (CT) maps of all patients at baseline and half-month post-ICH were obtained, and the volumes of hematoma and the perihematomal edemas (PHE), as well as the modified Rankin Scale (mRS) scores at the month-3 post-ICH between the 2 groups were assessed and analyzed.

Results:

A total of 46 eligible patients entered into final analysis, including 18 cases in the slender TS group (14 cases involved the left side while 4 cases involved the right side), and 28 cases in the symmetrical TS group. The mRS scores, hematoma absorption rates, and the residual volumes of PHE of all patients in the 2 groups at half-month post-ICH showed no statistical significance (all P>0.05), and all of the items mentioned above were related to the hematoma volume at baseline (all P<0.001). At the month-3 follow-up post-ICH, the mRS scores between the 2 groups showed no statistical significance as well (P=0.551).

Conclusions:

Anatomic asymmetry of TS may not affect the prognosis of PHE and clinical outcome after ICH.
Application Value of Flexible Endoscopic Examination of Swallowing in Acute Stoke Patients With Dysphagia
Authors: Zhang Xinran , Lin Fangzhu , Ma Fumei , Cui Shulin , OuYang Gaoxiang
Published: December 2021

Background:

The aim was to study the application value of flexible endoscopic examination of swallowing (FEES) for the aspiration screening, the diagnosis of dysphagia and evaluation of the therapeutic effect in acute stoke patients with dysphagia.

Methods:

A total of 525 patients with acute stoke who were hospitalized from October 2015 to January 2021 in the Rehabilitation Medicine Department of our hospital underwent FEES for analyzing the characteristic performance. Twenty-one cases of them were examined by video fluoroscopic swallow study and compared with the results of FEES for evaluating the reliability of the FEES, the reliability of diagnosis of dysphagia, and the consistency of the 2 methods. The effect of rehabilitation was evaluated by comparing the FEES test results before and after treatment.

Results:

In 525 patients, the FEES revealed 378 cases of aspiration (139 cases were silent aspiration), showing a higher detection rate than water swallow test. Patients with potential cricopharyngeus achalasia got the same results through both of examinations. FEES can provide more positive indicators, guide clinical rehabilitation treatment and objectively assess the effect of rehabilitation.

Conclusions:

Acute stoke patients with dysphagia have characteristic pharyngeal and laryngeal performance. FEES is simple to operate and has high application value in the diagnosis and treatment of dysphagia.
Evaluation of Weight Shift and X-Factor During Golf Swing of Veterans With Lower Limb Loss
Authors: Sidiropoulos Alexis N. , Nelson Leif M. , Pruziner Alison L. , Glasberg Jonathan J. , Maikos Jason T.
Published: December 2021

Objective

The purpose of this study was to assess the weight shift and X-Factor values of golfers with lower limb loss.

Design

Veterans with above or below knee limb loss participated in a 3-day adaptive golf event hosted by the Department of Veterans Affairs. Professional golf instructors educated participants on proper golf swing mechanics, after which kinematic analysis of trunk rotation and kinetic analysis of weight transfer between the legs during the golf swing were evaluated using three-dimensional motion capture and force platforms.

Results

Golfers with a trail leg amputation, regardless of level of limb loss, demonstrated superior weight shift, whereas golfers with lead limb amputation showed greater X-Factor values (all P < 0.05). Golfers with below knee limb loss demonstrated better weight shift strategies compared to those with above knee limb loss, regardless of which leg was amputated (i.e., lead or trail limb, all P < 0.05).

Conclusions

Sports rehabilitation programs should focus on increased weight bearing on the prosthetic limb to achieve appropriate weight shift and increased flexibility to increase X-Factor values. Participation in such programs can offer both physical and psychosocial benefits and may be a valid tool to increase the overall quality of life of veterans with lower limb loss.
Improving same-day antiretroviral therapy in Botswana: effects of a multifaceted national intervention
Authors: Montebatsi Milton , Lavoie Marie-Claude C. , Blanco Natalia , Marima Reson , Sebina Kagiso , Mangope Justin , Ntwayagae Ookeditse , Whittington Anna , Letebele Mpho , Lekone Phenyo , Hess Kristen L. , Thomas Vasavi , Ramaabya Dinah , Ramotsababa Mareko , Stafford Kristen A. , Ndwapi Ndwapi
Published: December 2021

Background:

In 2019, the Botswana Ministry of Health and Wellness (MOHW) implemented an HIV national Reboot program, which was needed for refocusing and intensifying efforts for achieving epidemic control. The strategies deployed as part of Reboot were reviewed and evaluated for their effect on same-day and within-seven-days (fast-track initiation) antiretroviral therapy (ART) initiation among adults newly identified with HIV.

Methods:

We conducted a retrospective cohort analysis of patients aged 18 years or older who were newly diagnosed with HIV from October 2018 to September 2019 across 41 health facilities. We used generalized linear mixed models, adjusting for clustering by facility, to assess the association of the Reboot with same-day or within-seven-days ART initiation (fast-track initiation).

Results:

From October 2018 to January 2019, 28% (636/2269) of newly diagnosed HIV patients were initiated the same day of diagnosis, and 56% (1260/2269) were initiated within seven days. Following the launch of Reboot (February to September 2019), 59% (2092/3553) were initiated the same day of diagnosis, and 77% (2752/3553) were initiated within seven days. Clients were 2.08 (adjusted risk ratio 95% confidence interval 1.79–2.43) times more likely to be initiated the same day of diagnosis and 1.39 (adjusted risk ratio 95% confidence interval 1.28–1.52) times more likely to be initiated within seven days than before Reboot after adjusting for sex and age.

Conclusion:

In Botswana, a multifaceted national intervention improved timely ART initiation. Identifying and implementing different client-centered strategies to facilitate ART initiation is critical to preventing AIDS-related complications and prevent ongoing transmission.
Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes
Authors: Girometti Nicolò , McCormack Sheena , Tittle Victoria , McOwan Alan , Whitlock Gary
Published: December 2021

Introduction:

Preexposure prophylaxis (PrEP) is contributing to achieve a reduction in HIV diagnoses in men having sex with men (MSM). Albeit infrequent, HIV infections in the context of recent PrEP exposure represent a clinical challenge.

Methods:

Data on recent PrEP use and possible reasons leading to HIV infection were analysed in individuals newly diagnosed with HIV at 56 Dean Street clinic in 2016–2020. Demographics, immune-virological parameters, genotypic resistance test results and treatment management in this group were compared with those not reporting recent PrEP exposure using Mann–Whitney U test and Fisher's exact test.

Results:

Fifty-two of 1030 (5%) individuals reported recent PrEP exposure at HIV diagnosis; 98% were MSM, median age 34 years (interquartile range [IQR] 28–42), 65% of white ethnicity, 65% non-UK-born. 35% reported PrEP intake the day before testing HIV positive, 46% reported sub-optimal PrEP adherence since their last negative HIV test result. Thirty-three of 52 (63%) were self-sourcing PrEP and 9/52 (17%) reported issues with its supply. Recent PrEP use was associated to lower HIV viral load and higher CD4+ cell count at baseline than in counterparts non-recently exposed to PrEP (P < 0.01). M184V mutation was harboured more commonly in the recent PrEP use group (30% vs. 1%, P < 0.01). The proportion of individuals recently exposed to PrEP among those diagnosed with HIV rose sharply, reaching 21% in the first semester of 2020. Viral suppression was achieved by all patients intensified from PrEP to antiretroviral treatment (ART) who remained in care at week 24.

Discussion:

Rapid PrEP intensification to ART allowed to achieve high rates of HIV viral suppression despite significant rates of M184V mutation harboured in those newly diagnosed with HIV and reporting recent PrEP exposure.
Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy
Authors: Dalla-Pozza Paul , Hentzien Maxime , Allavena Clotilde , Doe de Maindreville Anne , Bouiller Kévin , Valantin Marc-Antoine , Lafont Emmanuel , Zaegel-Faucher Olivia , Cheret Antoine , Martin-Blondel Guillaume , Cotte Laurent , Bani-Sadr Firouzé
Published: December 2021

Objectives and methods

: Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4+ cell count more than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat’AIDS cohort.

Results

: Among 571 diagnoses of PML reported in the Dat’AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4+ cell count greater than 200 cells/μl and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4+ cell count at PML diagnosis was 395 cells/μl (IQR 310–477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2–67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1).

Conclusion

: This study highlights that factors other than low CD4+ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.
Effect of HIV suppression on the cytokine network in blood and seminal plasma
Authors: Rawlings Stephen A. , Torres Felix , Wells Alan , Lisco Andrea , Fitzgerald Wendy , Margolis Leonid , Gianella Sara , Vanpouille Christophe
Published: December 2021

Objective:

HIV infection disrupts the cytokine network and this disruption is not completely reversed by antiretroviral therapy (ART). Characterization of cytokine changes in blood and genital secretions is important for understanding HIV pathogenesis and the mechanisms of HIV sexual transmission. Here, we characterized the cytokine network in individuals longitudinally sampled before they began ART and after achieving suppression of HIV RNA.

Methods:

We measured concentrations of 34 cytokine/chemokines using multiplex bead-based assay in blood and seminal plasma of 19 men with HIV-1 prior to and after viral suppression. We used Partial Least Squares Discriminant Analysis (PLS-DA) to visualize the difference in cytokine pattern between the time points. Any cytokines with VIP scores exceeding 1 were deemed important in predicting suppression status and were subsequently tested using Wilcoxon Signed Rank Tests.

Results:

PLS-DA projections in blood were fairly similar before and after viral suppression. In contrast, the difference in PLS-DA projection observed in semen emphasizes that the immunological landscape and immunological needs are very different before and after ART in the male genital compartment. When tested individually, four cytokines were significantly different across time points in semen (MIG, IL-15, IL-7, I-TAC), and two in blood (MIG and IP-10).

Conclusion:

Viral suppression with ART impacts the inflammatory milieu in seminal plasma. In contrast, the overall effect on the network of cytokines in blood was modest but consistent with prior analyses. These results identify specific changes in the cytokine networks in semen and blood as the immune system acclimates to chronic, suppressed HIV infection.
Pneumococcal serotypes causing non-invasive pneumonia in adults from a South Indian tertiary care hospital and the impact of the newer conjugate vaccines
Authors: Varghese Rosemol , Yesudhason Binesh Lal , Vimala Leena Robinson , Neeravi Ayyanraj , Anandhan Kavipriya , Baskar Pavithra , Elangovan Divyaa , Manesh Abi , James Prince , Gupta Richa , Veeraraghavan Balaji
Published: December 2021

Background.

Streptococcus pneumoniae

is the leading cause of community-acquired pneumonia (CAP) in adults. Ageing, chronic conditions and comorbidities are important risk factors for pneumococcal pneumonia.

Purpose. There is lack of data on the pneumococcal serotypes causing non-invasive pneumonia in India. This study aims to determine the prevalent pneumococcal serotypes causing non-invasive pneumonia, the associated comorbidities, and the coverage of both the available pneumococcal vaccines in India and conjugate vaccines that are currently undergoing clinical trials.

Methods. A total of 280 subjects (aged >16 years) who had clinical symptoms correlating with radiological findings for non-invasive bacteremic pneumonia and microbiological evidence of

S. pneumoniae

between 2018 and 2020 were included. The clinical, demographic, radiological and microbiological findings were retrieved from the Hospital Information System (HIS).

Results. The common serotypes in order of prevalence were 19F, 9V, 23F, 6B, 11A, 13, 34, 10A, 19A and 6A. The predominant non-vaccine serotypes were 13, 34, 35B, 31 and 16F. The associated radiological findings were pneumonic consolidation and multi-lobar involvement. Other coinfected bacterial pathogens included H. influenzae, S. aureus, K. pneumoniae and P. aeruginosa.

Conclusion. The pneumococcal vaccines: PCV10/GSK, PCV10/SII, PCV13, PCV15, PCV20 and PPSV23 provide an overall serotype coverage of 36, 41, 47, 48, 61 and 69 %, respectively of

S. pneumoniae

causing non-invasive pneumonia in South India. Increasing catch-up vaccination using PCV10(SII) in pre-school children could have a more significant impact on reducing pneumococcal pneumonia in adults (>50 years) in terms of increased herd immunity at an affordable cost.
Mariniplasma anaerobium gen. nov., sp. nov., a novel anaerobic marine mollicute, and proposal of three novel genera to reclassify members of Acholeplasma clusters II–IV
Authors: Watanabe Miho , Kojima Hisaya , Okano Kunihiro , Fukui Manabu
Published: December 2021

A novel strictly anaerobic chemoorganotrophic bacterium, designated Mahy22T, was isolated from sulfidic bottom water of a shallow brackish meromictic lake in Japan. Cells of the strain were Gram-stain-negative, non-motile and coccoid in shape with diameters of about 600–800 nm. The temperature range for growth was 15–37 °C, with optimum growth at 30–32 °C. The pH range for growth was pH 6.2–8.9, with optimum growth at pH 7.2–7.4. The strain grew with NaCl concentrations of 5% or below (optimum, 2–3%). Growth of the strain was enhanced by the addition of thiosulfate. The major cellular fatty acids were C16:0 and anteiso-C15:0. Respiratory quinones were not detected. The complete genome sequence of strain Mahy22T possessed a 1 885 846 bp circular chromosome and a 12 782 bp circular genetic element. The G+C content of the genome sequence was 30.1 mol%. Phylogenetic analysis based on the 16S rRNA gene revealed that the novel strain belonged to the family

Acholeplasmataceae

, class

Mollicutes

. The closest relative of strain Mahy22T with a validly published name was

Acholeplasma palmae

J233T with a 16S rRNA gene sequence similarity of 90.5%. Based on the results of polyphasic analysis, the name Mariniplasma anaerobium gen. nov., sp. nov. is proposed to accommodate strain Mahy22T, along with reclassification of some

Acholeplasma

species into Alteracholeplasma gen. nov., Haploplasma gen. nov. and Paracholeplasma gen. nov.
Machine learning prediction of novel pectinolytic enzymes in Aspergillus niger through integrating heterogeneous (post-) genomics data
Authors: Peng Mao , de Vries Ronald P.
Published: December 2021

Pectinolytic enzymes are a variety of enzymes involved in breaking down pectin, a complex and abundant plant cell-wall polysaccharide. In nature, pectinolytic enzymes play an essential role in allowing bacteria and fungi to depolymerize and utilize pectin. In addition, pectinases have been widely applied in various industries, such as the food, wine, textile, paper and pulp industries. Due to their important biological function and increasing industrial potential, discovery of novel pectinolytic enzymes has received global interest. However, traditional enzyme characterization relies heavily on biochemical experiments, which are time consuming, laborious and expensive. To accelerate identification of novel pectinolytic enzymes, an automatic approach is needed. We developed a machine learning (ML) approach for predicting pectinases in the industrial workhorse fungus, Aspergillus niger. The prediction integrated a diverse range of features, including evolutionary profile, gene expression, transcriptional regulation and biochemical characteristics. Results on both the training and the independent testing dataset showed that our method achieved over 90 % accuracy, and recalled over 60 % of pectinolytic genes. Application of the ML model on the A. niger genome led to the identification of 83 pectinases, covering both previously described pectinases and novel pectinases that do not belong to any known pectinolytic enzyme family. Our study demonstrated the tremendous potential of ML in discovery of new industrial enzymes through integrating heterogeneous (post-) genomimcs data.
SNPPar: identifying convergent evolution and other homoplasies from microbial whole-genome alignments
Authors: Edwards David J. , Duchene Sebastián , Pope Bernard , Holt Kathryn E.
Published: December 2021

Homoplasic SNPs are considered important signatures of strong (positive) selective pressure, and hence of adaptive evolution for clinically relevant traits such as antibiotic resistance and virulence. Here we present a new tool, SNPPar, for efficient detection and analysis of homoplasic SNPs from large whole genome sequencing datasets (>1000 isolates and/or >100 000 SNPs). SNPPar takes as input an SNP alignment, tree and annotated reference genome, and uses a combination of simple monophyly tests and ancestral state reconstruction (ASR, via TreeTime) to assign mutation events to branches and identify homoplasies. Mutations are annotated at the level of codon and gene, to facilitate analysis of convergent evolution. Testing on simulated data (120

Mycobacterium tuberculosis

alignments representing local and global samples) showed SNPPar can detect homoplasic SNPs with very high specificity (zero false-positives in all tests) and high sensitivity (zero false-negatives in 89 % of tests). SNPPar analysis of three empirically sampled datasets (

Elizabethkingia anophelis

,

Burkholderia dolosa

and

M. tuberculosis

) produced results that were in concordance with previous studies, in terms of both individual homoplasies and evidence of convergence at the codon and gene levels. SNPPar analysis of a simulated alignment of ~64 000 genome-wide SNPs from 2000

M. tuberculosis

genomes took ~23 min and ~2.6 GB of RAM to generate complete annotated results on a laptop. This analysis required ASR be conducted for only 1.25 % of SNPs, and the ASR step took ~23 s and 0.4 GB of RAM. SNPPar automates the detection and annotation of homoplasic SNPs efficiently and accurately from large SNP alignments. As demonstrated by the examples included here, this information can be readily used to explore the role of homoplasy in parallel and/or convergent evolution at the level of nucleotide, codon and/or gene.
Interplay between stress and reproduction: Novel epigenetic markers in response to shearing patterns in Australian Merino sheep (Ovis aries)
Authors: Narayan Edward , Sawyer Gregory , Fox Dylan , Smith Ryan , Tilbrook Alan
Published: December 2021

In this study, we determined the effect(s) of shearing on Australian Merino ewes (Ovis aries). To test this research question, we used a suite of field and laboratory methods including GPS collars, wool cortisol and novel epigenetic markers identified using Illumina NovaSeq RRBS. Single shorn ewes (n =24) kept on their full fleece throughout the entire gestation period while twice shorn ewes (n =24) had their wool shorn early in gestation. We have discovered one locus (Chr20:50404014) which was significantly associated with different shearing treatments (twice or single shorn ewes), (FDR = 0.005). This locus is upstream of a protein coding gene (ENSOARG00000002778.1), which shows similarities to the forkhead box C1 (FOXC1) mRNA using BLAST searches. We discovered that 36 gene loci were significantly modulated either between different shearing treatments or late vs early pregnancy ewes. Similarly, in lambs we identified 16 annotated gene loci that were significant between late vs early pregnancy. Early shorn ewes grazed 10% higher and maintained stronger body condition. Wool cortisol levels were significantly lower in the early shorn ewes during mid- and late gestation. Lambs bred from twice shorn ewes had on average better visual wool quality parameters in terms of micron, spin finesses and curvature. Collectively, this research provides a new dataset combining physiological, molecular epigenetics and digital tracking indices that advances our understanding of how Merino ewes respond to shearing frequency and this information could guide further research on sheep breeding and welfare.

Significance Statement

This study provides novel data on the molecular epigenetic signatures in Merino sheep under exposure to natural environmental and management factors. We have discovered DNA methylation profiles from ewes and lambs that are directly associated with whole- animal physiology, development and growth. The baseline data can provide a useful resource for future research in many key areas such as animal welfare, diseases and climatic resilience that will benefit sheep and wool production.
The impact of the COVID-19 pandemic on children with medical complexity
Authors: Diskin Catherine , Buchanan Francine , Cohen Eyal , Dewan Tammie , Diaczun Tessa , Gordon Michelle , Lee Esther , Moore-Hepburn Charlotte , Major Nathalie , Orkin Julia , Patel Hema , Gill Peter J.
Published: December 2021

Background

Descriptions of the COVID-19 pandemic’s indirect consequences on children are emerging. We aimed to describe the impacts of the pandemic on children with medical complexity (CMC) and their families.

Methods

A one-time survey of Canadian paediatricians using the Canadian Paediatric Surveillance Program (CPSP) was conducted in Spring 2021.

Results

A total of 784 paediatricians responded to the survey, with 70% (n=540) providing care to CMC. Sixty-seven (12.4%) reported an adverse health outcome due to a COVID-19 pandemic-related disruption in healthcare delivery. Disruption of the supply of medication and equipment was reported by 11.9% of respondents (n=64). Respondents reported an interruption in family caregiving (47.5%, n=252) and homecare delivery (40.8%, n=218). Almost 47% of respondents (n=253) observed a benefit to CMC due to COVID-19 related changes in healthcare delivery, including increased availability of virtual care and reduction in respiratory illness. Some (14.4%) reported that CMC were excluded from in-person learning when their peers without medical complexity were not.

Conclusion

Canadian paediatricians reported that CMC experienced adverse health outcomes during the COVID-19 pandemic, including disruptions to family caregiving and community supports. These results highlight the need for healthcare, community and education policymakers to collaborate with families to optimize their health.

“What This Study Adds”

Children with medical complexity experienced adverse health outcomes related to the direct and indirect effects of the COVID-19 pandemic.

The COVID-19 pandemic has interrupted family caregiving, homecare support, access to education, and key supports for CMC and their families.

Canadian paediatricians observed benefits associated with structural changes relating to the COVID-19 pandemic, including the expansion of virtual care and the reduced incidence of respiratory illness
Worldwide routine immunisation coverage regressed during the first year of the COVID-19 pandemic
Authors: Evans Beth , Jombart Thibaut
Published: December 2021

We modelled historical, country-specific routine immunisation trends using publicly available vaccination coverage data for diphtheria, tetanus and pertussis-containing vaccine first-dose (DTP1) and third-dose (DTP3) from 2000 to 2019. We evaluate changes in coverage in 2020 by comparing model predictions to WUENIC-reported coverage. We report a 2.9% (95%CI: [2.2%; 3.6%]) global decline in DTP3 coverage, and important increases in missed immunisations in some countries with middle-income countries, and the Americas, being most affected.
Computed Tomography Radiomics Signatures: Sensitive biomarkers for clinical decision support in pancreatic cancer- a pilot study
Authors: Habibalahi Abbas , Moses Daniel , Campbell Jared , Mahbub Saabah , Barbour Andrew P , Samra Jaswinder S , Haghighi Koroush S , Gebski Val J , Goldstein David , Goldys Ewa
Published: December 2021

Aim

To evaluate if suitably designed computed tomography (CT) radiomic signatures are sensitive to tumour transformation, and able to predict disease free survival (DFS) and overall survival (OS) time in patients with pancreatic cancer.

Method

Ethical approval by UNSW review board was obtained for this retrospective analysis. This study consisted of 27 patients with pancreatic cancer. Unsupervised principal component analysis was employed to evaluate the sensitivity of radiomic signatures to cancer presence and treatment. Further, optimised radiomic signatures were discovered using swarm intelligence and assessed for their capability to predict DFS and OS based on Kaplan-Meier analysis and receiver-operator characteristics (ROC) curves.

Results

We found that appropriate two radiomic signature are sensitive to cancer presence (area under the curve, AUC=0.95) and cancer treatment, respectively. Two other optimized radiomics signatures showed significant correlations with DFS and OS, respectively (p<0.05).

Conclusion

The CT radiomics signatures are an independent biomarkers which are modified when cancer is present and can help to estimate DFS and OS in patients. These signatures have the potential to be used to support clinical decision-making in pancreatic cancer treatment.
Evaluation of intron-1 of odorant-binding protein-1 of Anopheles stephensi as a marker for the identification of biological forms or putative sibling species
Authors: Singh Om P. , Mishra Shobhna , Sharma Gunjan , Sindhania Ankita , Kaur Taranjeet , Sreehari U. , Das Manoj K. , Kapoor Neera , Gupta Bhavna
Published: December 2021

Background

Anopheles stephensi, an invasive malaria vector, has been reported to have three biological forms identifiable mainly based on the number of ridges present on the egg’s floats. Recently, the first intron of the odorant-binding protein-1 (AsteObp1) has been introduced as a molecular marker for the identification of these forms, and based on this marker, the presence of three putative sibling species (designated as species A, B and C) has been proposed. However, there is no data on the association of proposed markers with biological form or putative species on field populations.

Methods

Field collected and laboratory-reared An. stephensi were characterized for biological forms based on the number of ridges on the egg’ s float. DNA sequencing of the partial AsteObp1 gene of An. stephensi individuals were performed by Sanger’s method, either directly or after cloning with a plasmid vector. Additionally, AsteObp1 sequences of various laboratory lines of An. stephensi were retrieved from a public sequence database.

Results

AsteObp1 intron-1 in Indian An. stephensi populations are highly polymorphic with the presence of more than 13 haplotypes exhibiting nucleotides as well as length-polymorphism (90-to-121 bp). No specific haplotype or a group of closely related haplotypes of intron-1 was found associated with any biological form identified morphologically. High heterozygosity for this marker with a low inbreeding coefficient in field and laboratory populations indicates that this marker is not suitable for the delimitation of putative sibling species, at least in Indian populations.

Conclusions

AsteObp1 cannot serve as a marker for identifying biological forms of An. stephensi or putative sibling species in Indian populations.
CRISPR Cas13-based tools to track and manipulate endogenous telomeric repeat-containing RNAs in living cells
Authors: Xu Meng , Chigumira Tafadzwa , Chen Ziheng , Tones Jason , Zhao Rongwei , Dahl Kris Noel , Chenoweth David M. , Zhang Huaiying
Published: December 2021

TERRA, TElomeric Repeat-containing RNA, is a long non-coding RNA transcribed from telomeres. Emerging evidence indicates that TERRA regulates telomere maintenance and chromosome end protection in normal and cancerous cells. However, the mechanism of how TERRA contributes to telomere functions is still unclear, partially owing to the shortage of approaches to track and manipulate endogenous TERRA molecules in live cells. Here, we developed a method to visualize TERRA in live cells via a combination of CRISPR Cas13 RNA labeling and Suntag technology. Single-particle tracking reveals that TERRA foci undergo anomalous diffusion in a manner that depends on the timescale and telomeric localization. Furthermore, we used a chemically-induced protein dimerization system to manipulate TERRA subcellular localization in live cells. Overall, our approaches to monitor and control TERRA locations in live cells provide powerful tools to better understand its roles in telomere maintenance and genomic integrity.
Disrupted controlling mechanism of salience network on default-mode network and central-executive network in schizophrenia
Authors: Chand Ganesh B. , Thakuri Deepa S. , Soni Bhavin
Published: December 2021

Neuroimaging studies suggest that the human brain consists of intrinsically organized large-scale neural networks. Among those networks, the interplay among default-mode network (DMN), salience network (SN), and central-executive network (CEN)has been widely employed to understand the functional interaction patterns in health and diseases. This triple network model suggests that SN causally controls DMN and CEN in healthy individuals. This interaction is often referred to as the dynamic controlling mechanism of SN. However, such interactions are not well understood in individuals with schizophrenia. In this study, we leveraged resting state functional magnetic resonance imaging (fMRI) data of schizophrenia (n = 67) and healthy controls (n = 81) to evaluate the functional interactions among DMN, SN, and CEN using dynamical causal modeling. In healthy controls, our analyses replicated previous findings that SN regulates DMN and CEN activities (Mann-Whitney U test; p < 10−8). In schizophrenia, however, our analyses revealed the disrupted SN-based controlling mechanism on DMN and CEN (Mann-Whitney U test; p < 10−16). These results indicate that the disrupted controlling mechanism of SN on two other neural networks may be a candidate neuroimaging phenotype in schizophrenia.
Genomic map of blood group alleles in Malaysian indigenous Orang Asli population from whole genome sequences
Authors: Rophina Mercy , Teh Lay Kek , Sivasubbu Sridhar , Scaria Vinod , Salleh Mohd Zaki
Published: December 2021

Purpose

Differences in the distribution of RBC antigens defining the blood group types among different populations have been well established. However, very few studies exist that have explored the blood group profiles of indigenous populations worldwide. With the rapid advent of next generation sequencing techniques and availability of population scale genomic datasets, we have successfully explored the blood group profiles of the Orang Aslis, who are the indigenous population of Malaysia and provide a systematic comparison of the same with major global population datasets.

Methods

Variant call files from whole genome sequence data (hg19) of 114 Orang Asli were retrieved from The Orang Asli Genome Project (OAGP). Systematic variant annotations were performed using ANNOVAR and only those variants spanning genes of 43 blood group systems and transcription factors KLF1 and GATA1 were filtered. Blood group associated allele and phenotype frequencies were determined and were duly compared with other datasets including Singapore Sequencing Malay Project (SSMP), aboriginal western desert Australians and global population datasets including The 1000 Genomes Project and gnomAD.

Results

This study reports 4 alleles(rs12075, rs7683365, rs586178 and rs2298720) ofDUFFY, MNS, RH and KIDD blood group systems which were significantly distinct between indigenous Orang Asli and cosmopolitan Malaysians. Eighteen (18) alleles which belong to 14 blood group systems were found distinct in comparison to global population datasets. Although not much significant differences were observed in phenotypes of most blood group systems, major insights were observed on comparing Orang Asli with aboriginal Australians and cosmopolitan Malaysians.

Conclusion

This study serves as the first of its kind to utilize genomic data to interpret blood group antigen profiles of the Orang Asli population. In addition, systematic comparison of blood group profiles with related populations were also analysed and documented.
Omicron: A heavily mutated SARS-CoV-2 variant exhibits stronger binding to ACE2 and potently escape approved COVID-19 therapeutic antibodies
Authors: Shah Masaud , Woo Hyun Goo
Published: December 2021

The new SARS-CoV-2 variant of concern “Omicron” was recently (Nov. 24th. 2021) spotted in South Africa and already spread around the world due to its enhanced transmissibility. The variant became conspicuous as it harbors more than thirty mutations in the spike protein with 15 mutations in the RBD region alone, potentially dampening the potency of therapeutic antibodies and enhancing the ACE2 binding. More worrying, Omicron infections have been reported in individuals who have received vaccines jabs in South Africa and Hong Kong. Here, we investigated the binding strength of Omicron with ACE2 and seven monoclonal antibodies that are either approved by FDA for COVID-19 therapy or undergoing phase III clinical trials. Computational mutagenesis and binding free energies could confirm that Omicron Spike binds ACE2 stronger than prototype SARS-CoV-2. Notably, three substitutions, i.e., T478K, Q493K, and Q498R, significantly contribute to the binding energies and doubled electrostatic potential of the RBDOmic-ACE2 complex. Instead of E484K substitution that helped neutralization escape of Beta, Gamma, and Mu variants, Omicron harbors E484A substitution. Together, T478K, Q493K, Q498R, and E484A substitutions contribute to a significant drop in the electrostatic potential energies between RBDOmic-mAbs, particularly in Etesevimab, Bamlanivimab, and CT-p59. CDR diversification could help regain the neutralization strength of these antibodies; however, we could not conduct this analysis to this end. Conclusively, our findings suggest that Omicron binds ACE2 with greater affinity, enhancing its infectivity and transmissibility. Mutations in the Spike are prudently devised by the virus that enhances the receptor binding and weakens the mAbs binding to escape the immune response.
Design principles to assemble drug combinations for effective tuberculosis therapy using interpretable pairwise drug response measurements
Authors: Larkins-Ford Jonah , Degefu Yonatan N. , Van Nhi , Sokolov Artem , Aldridge Bree B.
Published: December 2021

A challenge in designing treatment regimens for tuberculosis is the necessity to use three or more antibiotics in combination. The combination space is too large to be comprehensively assayed; therefore, only a small number of possible combinations are tested. We narrowed the prohibitively large search space of combination drug responses by breaking down high-order combinations into units of drug pairs. Using pairwise drug potency and drug interaction metrics from in vitro experiments across multiple growth environments, we trained machine learning models to predict outcomes associated with higher-order combinations in the BALB/c relapsing mouse model, an important preclinical model for drug development. We systematically predicted treatment outcomes of >500 combinations among twelve antibiotics. Our classifiers performed well on test data and predicted many novel combinations to be improved over bedaquiline + pretomanid + linezolid, an effective regimen for multidrug-resistant tuberculosis that also shortens treatment in BALB/c mice compared to the standard of care. To understand the design features of effective drug combinations, we reformulated classifiers as simple rulesets to reveal guiding principles of constructing combination therapies for both preclinical and clinical outcomes. One example ruleset is to include a drug pair that is synergistic in dormancy and another pair that is potent in a cholesterol-rich growth environment. These rulesets are predictive, intuitive, and practical, thus enabling rational construction of effective drug combinations based on in vitro pairwise drug synergies and potencies. As more preclinical and clinical drug combination data become available, we expect to improve predictions and combination design rules.