bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Spontaneous Movements in Infants With Torticollis
Authors: Kahraman Aysu , Büğüşan Oruç Sema , Erdoğan Derya , Mutlu Akmer
Published: December 2021

Purpose:

This study aimed to investigate whether the movements and postures of 3- to 5-month-old infants with torticollis differ from those of infants without torticollis and to determine the relationship between clinical characteristics and the Motor Optimality Score (MOS) in torticollis.

Methods:

Participants were 40 infants with torticollis and 40 infants developing typically without torticollis. The infants were evaluated with detailed general movement assessment.

Results:

There were significant differences in the MOS and subcategory scores for age-adequate movement repertoire and observed postural patterns between groups. Clinical characteristics were not related to the reduction in the MOS.

Conclusions:

Infants with torticollis have differences in movements and postures at 3 to 5 months of age compared with controls. Strategies supporting the movement repertoire of infants with torticollis can be added to rehabilitation programs for infants with the lower MOS to optimize their motor development.
Effects of Therapeutic Ultrasound on Growth Plates: A Systematic Review
Authors: Baghdadi Soroush , Harwood Kathleen , Greenberg Elliot , Baldwin Keith D. , Lawrence John Todd R.
Published: December 2021

Purpose:

The aim of this systematic review was to evaluate studies reporting on the effects of therapeutic ultrasound on the physis.

Summary of Key Points:

Eight studies were included in the final analysis, all of which were animal studies. At higher doses, studies found skin and bone necrosis and inhibition of growth, while in lower doses some studies found that ultrasound had a transient stimulatory effect on growth, increased thickness of the hypertrophic zone, and increased thickness of the whole growth plate. Overall, experimental evidence in animal models suggests that therapeutic ultrasound, even at low doses, might induce microscopic changes to the histology of the growth plate.

Conclusion:

While we found no reports of growth disturbance in humans, given the histological changes found in animal studies, the current limited literature seems to support the recommendation that the application of therapeutic ultrasound around the physis should be avoided.
Experiential Learning in Pediatric Physical Therapist Education: Challenges and Facilitators
Authors: Wynarczuk Kimberly D. , Gagnon Kendra , Schreiber Joseph , Rapport Mary Jane , Fiss Alyssa LaForme , Kendall Eydie
Published: December 2021

Purpose:

The purpose of this study was to conduct an in-depth investigation of physical therapist educators' challenges to and facilitators of the use of experiential learning (EL) with children. Although EL with children has been called an essential component of doctor of physical therapy (DPT) education, variability in the amount of EL used among DPT programs indicates that educators may experience different challenges and facilitators of the use of EL.

Methods:

Eighteen pediatric DPT educators participated in a semistructured interview. Researchers used thematic analysis to qualitatively analyze interview transcripts.

Results:

Three themes emerged: (1) stakeholder considerations, (2) pedagogical considerations, and (3) logistical considerations.

Conclusions:

This research illustrates challenges and facilitators to the use of EL with children. How these challenges and facilitators are perceived by DPT educators has implications for faculty and program directors, particularly as they consider the use of EL with children in DPT programs nationally.
Changing the Paradigm of School-Based Physical Therapist Service Delivery: Using Evidence to Support Intensive Intervention
Authors: Kinsey Erin , Curto Colleen , Glassman Dana , Sundberg Melissa , Rosemeyer Kathryn , Rapport Mary Jane
Published: December 2021

Purpose:

The purpose of this article is to highlight the paradigm shift away from the typical model of direct service delivery of consistent frequency and duration in the school setting to accommodate an intensive progressive resistive exercise intervention. School-based physical therapists describe how they applied an evidence-based intensive intervention with multiple students in an urban public school district.

Summary of Key Points:

The school-based physical therapists had to modify the typical service delivery model and overcome other challenges to implement this intensive intervention approach. Substantial improvements in strength and functional activities were observed in multiple students and measured across several months.

Conclusions and Recommendations for Clinical Practice:

An intensive intervention model appears effective and feasible in the school setting. Evidence-based intervention approaches should be considered when the student could benefit.

Video Abstract:

For more insights from the authors, see Supplemental Digital Content 1, available at: http://links.lww.com/PPT/A339.
Do partner services linked to molecular clusters yield people with viremia or new HIV?
Authors: Schneider John A. , Hayford Christina , Hotton Anna , Tabidze Irina , Wertheim Joel O. , Ramani Santhoshini , Hallmark Camden , Morgan Ethan , Janulis Patrick , Khanna Aditya , Ozik Jonathan , Fujimoto Kayo , Flores Rey , D’aquila Rich , Benbow Nanette
Published: December 2021

Objectives:

We examined whether molecular cluster membership was associated with public health identification of HIV transmission potential among named partners in Chicago.

Design:

Historical cohort study.

Methods:

We matched and analyzed HIV surveillance and partner services data from HIV diagnoses (2012–2016) prior to implementation of cluster detection and response interventions. We constructed molecular clusters using HIV-TRACE at a pairwise genetic distance threshold of 0.5% and identified clusters exhibiting recent and rapid growth according to the Centers for Disease Control and Prevention definition (three new cases diagnosed in past year). Factors associated with identification of partners with HIV transmission potential were examined using multivariable Poisson regression.

Results:

There were 5208 newly diagnosed index clients over this time period. Average age of index clients in clusters was 28; 47% were Black, 29% Latinx/Hispanic, 6% female and 89% MSM. Of the 537 named partners, 191 (35.6%) were linked to index cases in a cluster and of those 16% were either new diagnoses or viremic. There was no statistically significant difference in the probability of identifying partners with HIV transmission potential among index clients in a rapidly growing cluster versus those not in a cluster [adjusted relative risk 1.82, (0.81–4.06)].

Conclusion:

Partner services that were initiated from index clients in a molecular cluster yielded similar new HIV case finding or identification of those with viremia as did interviews with index clients not in clusters. It remains unclear whether these findings are due to temporal disconnects between diagnoses and cluster identification, unobserved cluster members, or challenges with partner services implementation.
Biomarkers to predict cardiovascular disease in people living with HIV
Authors: McGettrick Padraig , Mallon Patrick W.G.
Published: December 2021

Purpose of review

Cardiovascular diseases (CVD) is one of the leading cause of morbidity and mortality in antiretroviral treated people living with HIV (PWH) with risk score algorithms based on traditional risk factors being shown to be consistently unreliable in estimating risk in this population. This review aims to examine recent data published in last 18–24 months exploring biomarkers that may be useful in identifying PWH at risk of developing CVD.

Recent findings

Ongoing research explores the association of inflammatory biomarkers with subclinical CVD with few studies examining their clinical utility in improving CVD risk prediction. Further mechanistic studies explore the role of monocyte/macrophages in CVD pathogenesis with some studies examining functional assays as better predictors of CVD risk.

Although persistent associations with inflammatory markers and CVD are demonstrated, few biomarkers have emerged as being clinically useful. Large population studies are needed to assess their utility in improving CVD risk prediction in PWH.
Progress and challenges in human papillomavirus and cervical cancer in southern Africa
Authors: Ramogola-Masire Doreen , Luckett Rebecca , Dreyer Greta
Published: December 2021

Purpose of review

Although cervical cancer is preventable, it is the leading cancer among women in southern Africa. The association of high-risk human papillomavirus (HR-HPV) with almost all invasive cervical cancers has led to the development of effective primary and secondary prevention measures. This review focuses on updated and new evidence of the epidemiology of HPV and HPV-based secondary prevention in southern Africa.

Recent findings

HR-HPV prevalence in southern Africa differs between regions, and varies most by HIV prevalence and age. HR-HPV prevalence among women living with HIV (WLWH) is reported between 29 and 59.7%, and between 16.2 and 25.2% among women without HIV. HPV16 is the most common HR-HPV type present in invasive cervical cancers in the region; and vaccination may potentially prevent approximately 80% of these cancers. Concerning preliminary data suggests faster development of new cervical precancer within a short follow-up period.

We need tools that identify the small number of women with precancer from the many with transient HR-HPV infection in southern Africa. The high-volume of test-positive women leads to challenges in managing triage in a HR-HPV-based screening program. Longitudinal data from the entire region is urgently needed to guide effective implementation of HPV-based screening programs.
Uterine Uptake of 68Ga-FAPI-04 in Uterine Pathology and Physiology
Authors: Zhang Xiao , Song Wenyu , Qin Chunxia , Song Yangmeihui , Liu Fang , Hu Fan , Lan Xiaoli
Published: December 2021

Purpose

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) has been useful in the imaging of desmoplastic reaction in different tumors. As we have found that most female patients showed avid uterine uptake of 68Ga-FAPI-04, we sought to further investigate the pathological and physiological uptake of 68Ga-FAPI-04 characteristics in the uterus.

Patients and Methods

We reviewed the image data of female patients who had undergone 68Ga-FAPI-04 PET/MRI at our institute between May 22, 2020, and June 21, 2021. The characteristics of uterine uptake and clinical information were collected. The uterus with and without malignancy were compared. We further analyzed the relationship of age, uterus size, gynecological history, and 18F-FDG uptake (if performed) with 68Ga-FAPI-04 uptake.

Results

Seventy-seven patients were included in this study. Much higher cervical 68Ga-FAPI-04 accumulation was noticed in cervical cancer patients than in normal cases, and 37 more metastases were found in 68Ga-FAPI-04 PET than that in 18F-FDG. Uterine body malignancies displayed different uptake features. Two cases with the metastases to uterine body showed relative lower 68Ga-FAPI-04 activity compared with their normal uteri. Of 67 patients without malignancy, lower 68Ga-FAPI-04 uptake was noted in postmenopausal women than in reproductive and perimenopausal patients. The invasive operation or hysteromyoma may increase 68Ga-FAPI-04 uptake.

Conclusions

68Ga-FAPI-04 PET might be a promising method in cervical cancers. However, physiological uptake may limit its diagnostic value in uterine body malignancy. It should be noticed that the metastatic lesion in the uterus may show relative lower uptake of 68Ga-FAPI-04 compared with the rest of the uterus. Age, fibroids, and uterine volume may influence 68Ga-FAPI-04 uptake in the uterus. More patients with various uterine diseases could be involved to provide more differential diagnostic information.
Supernumerary Nostril: Formation of a Large Additional Nasal Cavity in an Adult Patient
Authors: Kong Tae Hyun , Kim Yong Ha
Published: December 2021

The supernumerary nostril is one of the rarest congenital nasal deformities. Most of the reported cases published were in young patients, and surgery was performed according to the surgeon's preference. The authors report a case of supernumerary nostril in an adult with a large additional nasal cavity and describe an effective surgical method. The operation was performed with the following steps: alar base and open rhinoplasty incisions were performed to widen the surgical field of view. An incision was made around the additional nostril in the nasal vestibule. The tract of the additional nostril was circumferentially excised, and the raw areas were approximated. The remnant portion was completely removed to combine the two nasal cavities into one. Weir excision, augmentation rhinoplasty, and tip-plasty were performed. The authors were able to obtain satisfactory aesthetic and functional effects by performing separate surgical methods for a supernumerary nostril with large additional nasal cavities in an adult.
Altererythrobacter lutimaris sp. nov., a marine bacterium isolated from a tidal flat and reclassification of Altererythrobacter deserti, Altererythrobacter estronivorus and Altererythrobacter muriae as Tsuneonella deserti comb. nov., Croceicoccus estronivorus comb. nov. and Alteripontixanthobacter muriae comb. nov.
Authors: Kim Dongjun , Yoo Yeonjae , Khim Jong Seong , Yang Dongmin , Pathiraja Duleepa , Park Byeonghyeok , Choi In-Geol , Kim Jae-Jin
Published: December 2021

A yellow-coloured bacterium, designated strain JGD-16T, was isolated from a tidal flat in Janggu-do, Garorim Bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and short ovoid to coccoid-shaped. Growth was observed at 10–37 °C (optimum, 30 °C), pH 6.0–9.0 (pH 8.0) and with 1–5% (w/v) NaCl (2%). Results of 16S rRNA gene sequence analysis indicated that strain JGD-16T was closely related to

Altererythrobacter xiamenensis

LY02T (97.1 %),

Altererythrobacter aurantiacus

O30T (96.3 %),

Altererythrobacter ishigakiensis

JPCCMB0017T (95.8 %),

Altererythrobacter epoxidivorans

JCS350T (95.7 %) and

Altererythrobacter insulae

BPTF-M16T (95.3%). Phylogenomic analysis using the maximum-likelihood algorithm showed that strain JGD-16T formed a clade with the genus

Altererythrobacter

. The genomic DNA G+C content was 57.8 mol%. The predominant respiratory quinone was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, a sphingoglycolipid, an unidentified glycolipid and an unidentified lipid. The major fatty acids were C18:1
ω7c (31.5 %) and C18:3
ω6c (19.6 %). On the basis of its phylogenomic, physiological and chemotaxonomical characteristics, strain JGD-16T represents a novel species within the genus

Altererythrobacter

, for which the name Altererythrobacter lutimaris JGD-16Tsp. nov. is proposed. The type strain is JGD-16T (=KCTC 72632T=KACC 21405T=JCM 33750T). We also propose the reclassification of

Altererythrobacter deserti

as Tsuneonella deserti comb. nov.,

Altererythrobacter estronivorus

as Croceicoccus estronivorus comb. nov. and

Altererythrobacter muriae

as Alteripontixanthobacter muriae comb. nov.
Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides
Authors: Lai Alex L. , Freed Jack H.
Published: December 2021

Coronaviruses are a major infectious disease threat, and include the human pathogens of zoonotic origin SARS-CoV (“SARS-1”), SARS-CoV-2 (“SARS-2”) and MERS-CoV (“MERS”). Entry of coronaviruses into host cells is mediated by the viral spike (S) protein. Previously, we identified that the domain immediately downstream of the S2’ cleavage site is the bona fide FP (amino acids 798-835) for SARS-1 using ESR spectroscopy technology. We also found that the SARS-1 FP induces membrane ordering in a Ca2+ dependent fashion. In this study, we want to know which residues are involved in this Ca2+ binding, to build a topological model and to understand the role of the Ca2+. We performed a systematic mutation study on the negatively charged residues on the SARS-1 FP. While all six negatively charged residues contributes to the membrane ordering activity of the FP to some extent, D812 is the most important residue. We provided a topological model of how the FP binds Ca2+ ions: both FP1 and FP2 bind one Ca2+ ion, and there are two binding sites in FP1 and three in FP2. We also found that the corresponding residue D830 in the SARS-2 FP plays a similar critical role. ITC experiments show that the binding energies between the FP and Ca2+ as well as between the FP and membranes also decreases for all mutants. The binding of Ca2+, the folding of FP and the ordering activity correlated very well across the mutants, suggesting that the function of the Ca2+ is to help to folding of FP in membranes to enhance its activity. Using a novel pseudotyped virus particle (PP)-liposome methodology, we monitored the membrane ordering induced by the FPs in the whole S proteins in its trimer form in real time. We found that the SARS-1 and SARS-2 PPs also induce membrane ordering as the separate FPs do, and the mutations of the negatively charged residues also greatly reduce the membrane ordering activity. However, the difference in kinetic between the PP and FP indicates a possible role of FP trimerization. This finding could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel to combat the ongoing COVID-19 pandemic.
Pandemic-scale phylogenetics
Authors: Ye Cheng , Thornlow Bryan , Kramer Alexander , McBroome Jakob , Hinrichs Angie , Corbett-Detig Russell , Turakhia Yatish
Published: December 2021

1.

Phylogenetics has been central to the genomic surveillance, epidemiology and contact tracing efforts during the COVD-19 pandemic. But the massive scale of genomic sequencing has rendered the pre-pandemic tools inadequate for comprehensive phylogenetic analyses. Here, we discuss the phylogenetic package that we developed to address the needs imposed by this pandemic. The package incorporates several pandemic-specific optimization and parallelization techniques and comprises four programs: UShER, matOptimize, RIPPLES and matUtils. Using high-performance computing, UShER and matOptimize maintain and refine daily a massive mutation-annotated phylogenetic tree consisting of all SARS-CoV-2 sequences available in online repositories. With UShER and RIPPLES, individual labs – even with modest compute resources – incorporate newly-sequenced SARS-CoV-2 genomes on this phylogeny and discover evidence for recombination in real-time. With matUtils, they rapidly query and visualize massive SARS-CoV-2 phylogenies. These tools have empowered scientists worldwide to study the SARS-CoV-2 evolution and transmission at an unprecedented scale, resolution and speed.
Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Authors: Dejnirattisai Wanwisa , Huo Jiandong , Zhou Daming , Zahradník Jiří , Supasa Piyada , Liu Chang , Duyvesteyn Helen M.E. , Ginn Helen M. , Mentzer Alexander J. , Tuekprakhon Aekkachai , Nutalai Rungtiwa , Wang Beibei , Dijokaite Aiste , Khan Suman , Avinoam Ori , Bahar Mohammad , Skelly Donal , Adele Sandra , Johnson Sile Ann , Amini Ali , Ritter Thomas , Mason Chris , Dold Christina , Pan Daniel , Assadi Sara , Bellass Adam , Omo-Dare Nikki , Koeckerling David , Flaxman Amy , Jenkin Daniel , Aley Parvinder K , Voysey Merryn , Costa Clemens Sue Ann , Naveca Felipe Gomes , Nascimento Valdinete , Nascimento Fernanda , Fernandes da Costa Cristiano , Resende Paola Cristina , Pauvolid-Correa Alex , Siqueira Marilda M. , Baillie Vicky , Serafin Natali , Ditse Zanele , Silva Kelly Da , Madhi Shabir , Nunes Marta C , Malik Tariq , Openshaw Peter JM , Baillie J Kenneth , Semple Malcolm G , Townsend Alain R , Huang Kuan-Ying A. , Tan Tiong Kit , Carroll Miles W. , Klenerman Paul , Barnes Eleanor , Dunachie Susanna J. , Constantinides Bede , Webster Hermione , Crook Derrick , Pollard Andrew J , Lambe Teresa ,   OPTIC consortium,   ISARIC4C consortium, Paterson Neil G. , Williams Mark A. , Hall David R. , Fry Elizabeth E. , Mongkolsapaya Juthathip , Ren Jingshan , Schreiber Gideon , Stuart David I. , Screaton Gavin R
Published: December 2021

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.
Investigation of Vaccine Breakthrough Infections by Vaccine strategy during the Delta Variant Wave in France
Authors: Bal Antonin , Destras Grégory , Simon Bruno , Giannoli Jean-Marc , Morfin Florence , Lina Bruno , Josset Laurence ,   IVAC study group
Published: December 2021

Herein, we describe the characteristics of vaccine breakthrough infections (VBI) in fully vaccinated individuals according to five vaccine strategies during the Delta wave in France. Inclusion criterion was a positive test at least 2 weeks after a full vaccine schedule: homologous vaccination with Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273); heterologous vaccination with Astrazeneca and Pfizer-BioNTech (ChadOx1/BNT162b2); single-dose vaccines Johnson & Johnson (Ad26.COV2.S) or Astrazeneca (ChadOx1). A total of 1630 VBI from patients fully vaccinated between February and July were included in this study. SARS-CoV-2 sequencing performed for 1366 samples showed that the delta variant represented 94.1% (1286/1366). Delta-VBI were mainly symptomatic (mild symptoms) with no difference according to the vaccine strategy (p=0.362). The median RT-PCR Ct values at diagnosis were significantly different between symptomatic and asymptomatic cases only for BNT162b2 group (17.7 (15.07, 20.51) vs 19.00 (16.00, 23.00), p=0.004). Up to 50% of VBI was classified as early-VBI (infected less than one month after full immunization) for BNT162b2, mRNA-1273, ChadOx1, and J Ad26.COV2.S. People aged 14-49 yo were overrepresented in early VBI compared to non-early VBI for BNT162b2 and mRNA-1273 (73.92% vs 37.87% for BNT162b2 and 77.78% vs 46.67 % for mRNA-1273, p<0.05). Our data emphasize a high prevalence of Delta-VBI occurring only one month after full immunization in young patients that might be related to relaxation of barrier gestures.
The Effect of Spatial Frequency on the Visual Category Representation in the Macaque Inferior Temporal Cortex
Authors: Farhang Esmaeil , Toosi Ramin , Karami Behnam , Koushki Roxana , Rezayat Ehsan , Shakerian Farideh , Noroozi Jalaledin , Dehaqani Mohammad-Reza A.
Published: December 2021

To expand our knowledge about the object recognition, it is critical to understand the role of spatial frequency (SF) in an object representation that occurs in the inferior temporal (IT) cortex at the final stage of processing the visual information across the ventral visual pathway. Object categories are being recognized hierarchically in at least three levels of abstraction: superordinate (e.g., animal), mid-level (e.g., human face), and subordinate (e.g., face identity). Psychophysical studies have shown rapid access to mid-level category information and low SF (LSF) contents. Although the hierarchical representation of categories has been shown to exist inside the IT cortex, the impact of SF on the multi-level category processing is poorly understood. To gain a deeper understanding of the neural basis of the interaction between SF and category representations at multiple levels, we examined the neural responses within the IT cortex of macaque monkeys viewing several SF-filtered objects. Each stimulus could be either intact or bandpass filtered into either the LSF (coarse shape information) or high SF (HSF) (fine shape information) bands. We found that in both High- and Low-SF contents, the advantage of mid-level representation has not been violated. This evidence suggests that mid-level category boundary maps are strongly represented in the IT cortex and remain unaffected with respect to any changes in the frequency content of stimuli. Our observations indicate the necessity of the HSF content for the superordinate category representation inside the IT cortex. In addition, our findings reveal that the representation of global category information is more dependent on the HSF than the LSF content. Furthermore, the lack of subordinate representation in both LSF and HSF filtered stimuli compared to the intact stimuli provide strong evidence that all SF contents are necessary for fine category visual processing.
Improving replicability using interaction with laboratories: a multi-lab experimental assessment
Authors: Jaljuli Iman , Kafkafi Neri , Giladi Eliezer , Golani Ilan , Gozes Illana , Chesler Elissa J. , Bogue Molly A. , Benjamini Yoav
Published: December 2021

Experimentation with mouse and rat models has become a central strategy for discovering mammalian gene function, and for preclinical testing of pharmacological treatments, yet the utility of any findings critically depends on their replicability in other laboratories. In previous publications we proposed a statistical approach for estimating the inter-laboratory replicability of novel discoveries made in a single laboratory. We demonstrated that previous phenotyping results from multi-lab databases can be used to derive a Genotype-by-Lab (GxL) adjustment factor to greatly enhance the replicability of the single-lab findings, for similarly measured phenotypes, even before making the effort of replicating these finding in additional laboratories.

This demonstration, however, still raised several important questions that could only be answered by an additional large-scale prospective experiment: 1) Does GxL-adjustment work in single-lab experiments that were not intended to be standardized across laboratories, and with genotypes that were not included in the previous experiments? And 2) Can it be used to adjust the results of pharmacological experiments? We investigated these questions by attempting to replicate, across three laboratories, results from five single-lab studies in the Mouse Phenome Database (MPD), offering 212 comparisons, including 60 involving a pharmacological treatment: 18 mg/kg/day fluoxetine. In addition, we define and use a dimensionless GxL factor, by dividing the GxL variance by the standard deviation between animals within groups, as a more robust vehicle to transfer the adjustment from the multi-lab analysis to very different labs and genotypes.

For genotype comparisons, GxL-adjustment reduced the rate of non-replicable discoveries from 60% to 12%, for the price of reducing the power to make replicable discoveries from 87% to 66%. In absolute numbers, the adjustment prevented 23 non-replicable discoveries for the price of missing only three replicated ones. Tools and data needed for deployment of this method across other mouse experiments are publicly available in MPD. Our results further point at some phenotypes as more prone to produce non-replicable results, while others, known to be more difficult to measure, are as likely to produce replicable results (once adjusted) such as the physiological measure, body weight.
Genetic conversion of a split-drive into a full-drive element
Authors: Terradas Gerard , Bennett Jared B. , Li Zhiqian , Marshall John M. , Bier Ethan
Published: December 2021

Gene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an independent static source of Cas9. We previously designed a system engineered to turn split into full gene drives. Here, we provide experimental proof-of-principle for such a convertible system inserted at the spo11 locus, which is recoded to restore gene function. In multigenerational cage studies, the reconstituted spo11 fGD cassette initially drives with slower kinetics than the unlinked sGD element (using the same Mendelian vasa-Cas9 source), but eventually reaches a similar level of final introgression. Different kinetic behaviors may result from transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.
Tissue remodeling and cell signaling underpin changes in tumor microenvironment heterogeneity in glioma oncogenesis
Authors: Dinevska Marija , Widodo Samuel S. , Furst Liam , Cuzcano Lucero , Fang Yitong , Mangiola Stefano , Neeson Paul J. , Darcy Phillip K. , Ramsay Robert G. , MacKay Fabienne , Stylli Stanley S. , Mantamadiotis Theo
Published: December 2021

Brain tumor cells thrive by adapting to the signals in their microenvironment. Understanding how the tumor microenvironment evolves during disease progression is crucial to deciphering the mechanisms underlying the functional behavior of cancer cells. To adapt, cancer cells activate signaling and transcriptional programs and migrate to establish micro-niches, in response to signals from neighboring cells and non-cellular stromal factors. Using multiple tissue analysis approaches to identify and measure immune cell infiltration and extracellular matrix deposition in brain tumors, we show that low-grade glioma is largely devoid of infiltrating immune cells and extracellular matrix proteins, while high-grade glioma exhibits abundant immune cell infiltration and activation, as well as extensive collagen deposition. Spatial analysis shows that most T-cells are sequestered in perivascular nests, but macrophages penetrate deep into tumor cell rich regions. High-grade gliomas exhibit heterogeneous PI3K and MAPK signaling, which correlates with distinct pathological hallmarks, including tumor angiogenesis, tumor cell density and extracellular matrix deposition. Our results also provide compelling evidence that tissue remodeling is an important element in glioma progression, and that targeting the extracellular matrix will be critical to improving GBM therapy.
An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines
Authors: Seifert Stephanie N. , Bai Shuangyi , Fawcett Stephen , Norton Elizabeth B. , Zwezdaryk Kevin J. , Robinson James , Gunn Bronwyn , Letko Michael C.
Published: December 2021

Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and −2 has resulted in the discovery of numerous animal sarbecoviruses – the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and −2, one virus, Khosta-2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2

ONE SENTENCE SUMMARY

European bat coronaviruses that are only distantly related to SARS-CoV-2 but use the same cell entry route, escape the immune response against SARS-CoV-2 vaccines, driving the need for broader vaccines.
Efemp1 modulates elastic fiber formation and mechanics of the extrahepatic bile duct
Authors: Llewellyn Jessica , Roberts Emilia , Liu Chengyang , Naji Ali , Assoian Richard K. , Wells Rebecca G.
Published: December 2021

EGF-Containing Fibulin Extracellular Matrix Protein 1 (EFEMP1, also called fibulin 3) is an extracellular matrix protein linked in a genome-wide association study to biliary atresia, a fibro-inflammatory disease of the neonatal extrahepatic bile duct. EFEMP1 is expressed in most tissues and Efemp1 null mice have decreased elastic fibers in visceral fascia; however, in contrast to other short fibulins (fibulins 4 and 5), EFEMP1 does not have a role in the development of large elastic fibers, and its overall function remains unclear. We demonstrated that EFEMP1 is expressed in the submucosa of both neonatal and adult mouse and human extrahepatic bile ducts and that, in adult Efemp1+/- mice, elastin organization into fibers is decreased. We used pressure myography, a technique developed to study the mechanics of the vasculature, to show that Efemp1+/- extrahepatic bile ducts are more compliant to luminal pressure, leading to increased circumferential stretch. We conclude that EFEMP1 has an important role in the formation of elastic fibers and mechanical properties of the extrahepatic bile duct. These data suggest that altered expression of EFEMP1 in the extrahepatic bile duct leads to an abnormal response to mechanical stress such as obstruction, potentially explaining the role of EFEMP1 in biliary atresia.
Functional Anatomy of the TDP-43 Redox Sensor
Authors: Zhou Xiaoming , Sumrow Lily , Sutherland Lillian , Liu Daifei , Qin Tian , McKnight Steven L. , Liszczak Glen
Published: December 2021

TAR binding protein 43 (TDP-43) is an RNA binding protein that assists in the maturation, export and sub-cellular localization of mRNA. The carboxyl terminal 153 residues of TDP-43 are of low sequence complexity and allow for self-association of the protein in a manner leading to its phase separation from an aqueous environment. These interactions assist TDP-43 in forming cytoplasmic RNA granules involved in the transport of mRNA for localized translation. Self-association of the TDP-43 low complexity (LC) domain is facilitated by a region of twenty five residues that are of extreme evolutionary conservation. The molecular basis for self-adherence of the protein through this region has been illuminated by a combination of structural and biochemical studies, allowing definition of a morphologically specific cross-β structure predicted to be weakly assembled by main chain hydrogen bonds. In this study we have investigated the importance of individual, Pauling hydrogen bonds hypothesized to facilitate self-adherence of the TDP-43 LC domain.
Work-related musculoskeletal disorders and associated factors among cleaners of health institutions in Gondar town, Northwest Ethiopia: an institution based cross-sectional study
Authors: Suleyman Jemal , Gelaw Asmare Yitayeh
Published: December 2021

Background

Musculoskeletal disorders are growing public health problems both in developed and developing countries including Ethiopia. However, its prevention and control has not yet received due attention. This study aimed to determine.

the prevalence and associated factors of musculoskeletal disorders musculoskeletal disorders among cleaners of health institutions in Gondar town, Northwest Ethiopia

Method

An institutional based cross-sectional study was conducted, from April to May 2016 in all health institutions of Gondar town. All the available cleaners of health institutions were taken as study participants. Data were collected by face-to-face interview technique after verbal informed consent. Additionally, weight and height of participants were measured following standard procedures. Data were collected by trained physiotherapists and then entered into a computer using Epi Info version 3.5.3 and exported to SPSS version 20 for analysis. Descriptive statistics was performed to describe the data in percentage and mean. Multiple logistic regressions were fitted and Odds ratios with 95% confidence intervals were calculated to identify associated factors.

Results

A total of 242 participants were included in this study. The majority of the study participants were females (79.3%) and between 25-44 age group (65.3%). Two hundred 0ne (83.1%) of the respondents reported that they had pain in at least one of the body parts in the previous 12 months. Of the nine body parts examined, neck (76%), upper back (40.5%) and lower back (45%) were the most frequently body parts reported to exhibit pain. Job status (AOR = 2.71, 95%CI; 1.37-5.36), and static work habit (AOR = 2.71, 95%CI; 1.37-5.36), were factors associated with musculoskeletal disorders.

Conclusion

There is a high prevalence of musculoskeletal disorders among cleaners in the health institutions of Gondar Town. Job status and static work habit were the significant associated factors. Hence, we recommend the design and implementation of institution based screening programs for musculoskeletal disorders
Proactive vs. reactive country responses to the COVID19 pandemic shock
Authors: Sacco Pier Luigi , Valle Francesco , De Domenico Manlio
Published: December 2021

The infection caused by SARS-CoV-2, responsible for the COVID-19 pandemic, is characterized by an infectious period with either asymptomatic or pre-symptomatic phases, leading to a rapid surge of mild and severe cases putting national health systems under serious stress. To avoid their collapse, and in the absence of pharmacological treatments, during the early pandemic phase countries worldwide were forced to adopt strategies, from elimination to mitigation, based on non-pharmacological interventions which, in turn, overloaded social, educational and economic systems. To date, the heterogeneity and incompleteness of data sources does not allow to quantify the multifaceted impact of the pandemic at country level and, consequently, to compare the effectiveness of country responses. Here, we tackle this challenge from a complex systems perspective, proposing a model to evaluate the impact of systemic failures in response to the pandemic shock. We use health, behavioral and economic indicators for 44 countries to build a shock index quantifying responses in terms of robustness and resilience, highlighting the crucial advantage of proactive policy and decision making styles over reactive ones.
EpyNN: Educational python for Neural Networks
Authors: Malard Florian , Danner Laura , Rouzies Emilie , Meyer Jesse G , Lescop Ewen , Olivier-Van Stichelen Stéphanie
Published: December 2021

Artificial Neural Networks (ANNs) have achieved unequaled performance for numerous problems in many areas of Science, Business, Public Policy, and more. While experts are familiar with performance-oriented software and underlying theory, ANNs are difficult to comprehend for non-experts because it requires skills in programming, background in mathematics and knowledge of terminology and concepts. In this work, we release EpyNN, an educational python resource meant for a public willing to understand key concepts and practical implementation of scalable ANN architectures from concise, homogeneous and idiomatic source code. EpyNN contains an educational Application Programming Interface (API), educational workflows from data preparation to ANN training and a documentation website setting side-by-side code, mathematics, graphical representation and text to facilitate learning and provide teaching material. Overall, EpyNN provides basics for python-fluent individuals who wish to learn, teach or develop from scratch.

Availability

EpyNN documentation is available at https://epynn.net and repository can be retrieved from https://github.com/synthaze/epynn.

Contact

Stéphanie Olivier-Van-Stichelen, solivier@mcw.edu.

Supplementary Information

Supplementary files and listings.
Patterned mechanical feedback establishes a global myosin gradient
Authors: Gustafson Hannah J. , Claussen Nikolas , De Renzis Stefano , Streichan Sebastian J.
Published: December 2021

Morphogenesis, the coordinated execution of developmental programs that shape embryos, raises many fundamental questions at the interface between physics and biology. In particular, how the dynamics of active cytoskeletal processes are coordinated across the surface of entire embryos to generate global cell flows is poorly understood. Two distinct regulatory principles have been identified: genetic programs and dynamic response to mechanical stimuli. Despite progress, disentangling these two contributions remains challenging. Here, we combine in toto light sheet microscopy with genetic and optogenetic perturbations of tissue mechanics to examine theoretically predicted dynamic recruitment of non-muscle myosin II to cell junctions during Drosophila embryogenesis. We find dynamic recruitment has a long-range impact on global myosin configuration, and the rate of junction deformation sets the rate of myosin recruitment. Mathematical modeling and high frequency analysis reveal myosin fluctuations on junctions around a mean value set by mechanical feedback. Our model accounts for the early establishment of the global myosin pattern at 80% fidelity. Taken together our results indicate spatially modulated mechanical feedback as a key regulatory input in the establishment of long-range gradients of cytoskeletal configurations and global tissue flow patterns.
IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing early targeting of plasma cells
Authors: Alomari Nedaa , Aalam Farizeh , Nabiee Romina , Castano Jesus Ramirez , Totonchy Jennifer
Published: December 2021

Factors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Here, using our unique model of KSHV infection in tonsil lymphocytes, we investigate the influence of host cytokines on the establishment of KSHV infection in human B cells. Our data demonstrate that KSHV manipulates the host cytokine microenvironment during early infection and susceptibility is generally associated with downregulation of multiple cytokines. However, we show that IL-21 signaling promotes KSHV infection by promoting both plasma cell numbers and increasing KSHV infection in plasma cells as early as 3 days post-infection. Our data reveal that this phenotype is dependent upon a specific milieu of T cells, that includes IL-21 producing Th17, Tc17 and CD8+ central memory T cells. These results suggest that IL-21 plays a significant role in the early stages of KSHV infection in the human immune system and that specific immunological states favor the initial establishment of KSHV infection by increasing infection in plasma cells.
panModule: detecting conserved modules in the variable regions of a pangenome graph
Authors: Bazin Adelme , Medigue Claudine , Vallenet David , Calteau Alexandra
Published: December 2021

The recent years have seen the rise of pangenomes as comparative genomic tools to better understand the evolution of gene content among microbial genomes in close phylogenetic groups such as species. While the core or persistent genome is often well-known as it includes essential or ubiquitous genes, the variable genome is usually less characterized and includes many genes with unknown functions even among the most studied organisms. It gathers important genes for strain adaptation that are acquired by horizontal gene transfer. Here, we introduce panModule, an original method to identify conserved modules in pangenome graphs built from thousands of microbial genomes. These modules correspond to synteny blocks composed of consecutive genes that are conserved in a subset of the compared strains. Identifying conserved modules can provide insights on genes involved in the same functional processes, and as such is a very helpful tool to facilitate the understanding of genomic regions with complex evolutionary histories. The panModule method was benchmarked on a curated dataset of conserved modules in Escherichia coli genomes. Its use was illustrated through a study of a high pathogenicity island in Klebsiella pneumoniae that allowed a better understanding of this region. panModule is freely available and accessible through the PPanGGOLiN software suite (https://github.com/labgem/PPanGGOLiN).
Among-individual variation of risk-taking behaviour in group and solitary context is uncorrelated but independently repeatable in a juvenile Arctic charr (Salvelinus alpinus) aquaculture strain
Authors: Philip Joris , Dellinger Marion , Benhaïm David
Published: December 2021

Behavioural traits have been shown to have implications in fish welfare and growth performances in aquaculture. If several studies have demonstrated the existence of repeatable and heritable behavioural traits (i.e., animal personality), the methodology to assess personality in fishes is often carried out in solitary context, which appears to somewhat limit their use from a selective breeding perspective because these tests are too time consuming. To address this drawback, group-based tests have been developed. In Nordic country, Arctic charr (Salvelinus alpinus) is widely used in aquaculture, but no selection effort on behavioural traits has yet been carried out. Specifically, in this study we examined if risk-taking behaviour was repeatable and correlated in group and solitary context and if the early influences of physical environment affect the among-individual variation of behavioural trait across time in order to verify whether a group risk-taking test could be used as a selective breeding tool. Here, we found that in both contexts and treatments, the risk-taking behaviour was repeatable across a short period of 6 days. However, no cross-context consistency was found between group and solitary, which indicates that Arctic charr express different behavioural trait in group and solitary.
Mutational cascade of SARS-CoV-2 leading to evolution and emergence of omicron variant
Authors: Bansal Kanika , Kumar Sanjeet
Published: December 2021

Background

Emergence of new variant of SARS-CoV-2, namely omicron, has posed a global concern because of its high rate of transmissibility and mutations in its genome. Researchers worldwide are trying to understand the evolution and emergence of such variants to understand the mutational cascade events.

Methods

We have considered all omicron genomes (n = 302 genomes) available till 2nd December 2021 in the public repository of GISAID along with representatives of variants of concern (VOC), i.e., alpha, beta, gamma, delta, and omicron; variant of interest (VOI) mu and lambda; and variant under monitoring (VUM). Whole genome-based phylogeny and mutational analysis were performed to understand the evolution of SARS CoV-2 leading to emergence of omicron variant.

Results

Whole genome-based phylogeny depicted two phylogroups (PG-I and PG-II) forming variant specific clades except for gamma and VUM GH. Mutational analysis detected 18,261 mutations in the omicron variant, majority of which were non-synonymous mutations in spike (A67, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H), followed by RNA dependent RNA polymerase (rdrp) (A1892T, I189V, P314L, K38R, T492I, V57V), ORF6 (M19M) and nucleocapsid protein (RG203KR).

Conclusion

Delta and omicron have evolutionary diverged into distinct phylogroups and do not share a common ancestry. While, omicron shares common ancestry with VOI lambda and its evolution is mainly derived by the non-synonymous mutations.