bluuebunny/crossref_metadata_2025 huggingface dataset:
Telehealth experiences of providers and patients who use augmentative and alternative communication
Authors: Beneteau Erin , Paradiso Ann , Pratt Wanda
Published: November 2021

Objective

We explore the telehealth experiences of adults who use augmentative and alternative communication (AAC) and clinicians who work with people using AAC.

Materials and Methods

We conducted semistructured, online interviews with 6 adults who use AAC and 8 clinicians who provide telehealth services to people who use AAC between July and September 2020. Participants were located in the United States and the United Kingdom. All participants had engaged in 2 or more telehealth visits in the past 6 months. We used an inductive, thematic approach to analyze the interview data.

Results

Our findings reveal that (1) telehealth is an essential service, (2) technology causes barriers, (3) policies meant to protect actually inhibit, and (4) remote monitoring devices have the potential to mitigate risks.

Discussion

Telehealth systems created for persons without disabilities do not provide equitable access to everyone. Telehealth should be flexible enough to allow patients to use the communication modality that best meets their needs. We suggest that healthcare systems think of the healthcare ecosystem as one which includes a variety of telehealth options in addition to traditional in-person clinical visits.

Conclusions

The benefits of telehealth for people who use AAC are substantial and should be an option for ongoing health care. However, the accessibility of telehealth technologies needs to be improved. Designers should view telehealth as part of a broad healthcare ecosystem, which includes in-person, telehealth, and remote health monitoring technologies. Designers should also include AAC users in the design and development process. Telehealth policies should encourage multimodality access to health care and address funding concerns.
Best Management Practices to Delay the Evolution of Bt Resistance in Lepidopteran Pests Without High Susceptibility to Bt Toxins in North America
Authors: Reisig Dominic D , DiFonzo Chris , Dively Galen , Farhan Yasmine , Gore Jeff , Smith Jocelyn
Published: November 2021

Canadian and United States (US) insect resistance management (IRM) programs for lepidopteran pests in Bacillus thuriengiensis (Bt)-expressing crops are optimally designed for Ostrinia nubilalis Hübner in corn (Zea mays L.) and Chloridea virescens Fabricius in cotton (Gossypium hirsutum L.). Both Bt corn and cotton express a high dose for these pests; however, there are many other target pests for which Bt crops do not express high doses (commonly referred to as nonhigh dose pests). Two important lepidopteran nonhigh dose (low susceptibility) pests are Helicoverpa zea Boddie (Lepidoptera: Noctuidae) and Striacosta albicosta Smith (Lepidoptera: Noctuidae). We highlight both pests as cautionary examples of exposure to nonhigh dose levels of Bt toxins when the IRM plan was not followed. Moreover, IRM practices to delay Bt resistance that are designed for these two ecologically challenging and important pests should apply to species that are more susceptible to Bt toxins. The purpose of this article is to propose five best management practices to delay the evolution of Bt resistance in lepidopteran pests with low susceptibility to Bt toxins in Canada and the US: 1) better understand resistance potential before commercialization, 2) strengthen IRM based on regional pest pressure by restricting Bt usage where it is of little benefit, 3) require and incentivize planting of structured corn refuge everywhere for single toxin cultivars and in the southern US for pyramids, 4) integrate field and laboratory resistance monitoring programs, and 5) effectively use unexpected injury thresholds.
The Narrative Shape of Orthopraxy: Storytelling,Dharma, and the Path to Liberation in Advaita Vedānta
Authors: Madaio James
Published: November 2021

This article analyses how Vidyāraṇya, a fourteenth-century Advaita Vedāntin, reads and re-tells life stories of exemplary sages to determine and establish duty, or dharma, on the Advaita Vedāntic path to liberation. Drawing on his Jīvanmuktiviveka, I show how Vidyāraṇya’s extrapolative, exegetical approach to life stories is shaped by hermeneutical concerns of the Dharmaśāstra tradition, which entails a narrative theology sensitive to the details of canonical life stories. In particular, the article closely examines Vidyāraṇya’s interpretation of episodes in the life of Yājñavalkya from the Bṛhadāraṇyaka Upaniṣad; Rāma, Śuka, Janaka, and Bhagīratha from the ‘Laghuyogavāsiṣṭha’; as well as the story of Nidāgha from the Viṣṇupurāṇa. I demonstrate how Vidyāraṇya’s reading of these narratives, including his diagnostic assessment of the soteriological status of the protagonists, engenders and authorises orthopraxy on the path to liberation. While setting out these issues, I pay particular attention to the way in which narrative accounts serve not only as theologically rich sources from which praxeological and theological positions are determined but also as examples in Vidyāraṇya’s argumentation.
3D mesoscopic architecture of a heterogeneous cellular network in the cementum–periodontal ligament–alveolar bone complex
Authors: Hirashima Shingo , Ohta Keisuke , Togo Akinobu , Nakamura Kei-ichiro
Published: November 2021

Cell-to-cell communication orchestrates various cell and tissue functions. This communication enables cells to form cellular networks with each other through direct contact via intercellular junctions. Because these cellular networks are closely related to tissue and organ functions, elucidating the morphological characteristics of cellular networks could lead to the development of novel therapeutic approaches. The tooth, periodontal ligament (PDL) and alveolar bone form a complex via collagen fibres. Teeth depend on the co-ordinated activity of this complex to maintain their function, with cellular networks in each of its three components. Imaging methods for three-dimensional (3D) mesoscopic architectural analysis include focused ion beam/scanning electron microscopy (FIB/SEM), which is characterized by its ability to select observation points and acquire data from complex tissue after extensive block-face imaging, without the need to prepare numerous ultrathin sections. Previously, we employed FIB/SEM to analyse the 3D mesoscopic architecture of hard tissue including the PDL, which exists between the bone and tooth root. The imaging results showed that the cementum, PDL and alveolar bone networks are in contact and form a heterogeneous cellular network. This cellular network may orchestrate mechanical loading–induced remodelling of the cementum–PDL–alveolar bone complex as the remodelling of each complex component is coordinated, as exemplified by tooth movement due to orthodontic treatment and tooth dislocation due to occlusal loss. In this review, we summarize and discuss the 3D mesoscopic architecture of cellular networks in the cementum, PDL and alveolar bone as observed in our recent mesoscopic and morphological studies.
Parent and Well-Sibling Communication in Families With a Child Who Has a Life-Limiting Condition: Quantitative Survey Data
Authors: Jaaniste Tiina , Chin Wei Ling (Audrey) , Tan Sarah Caellainn , Cuganesan Anjali , Coombs Sandra , Heaton Maria , Cowan Sue , Potter Denise , Aouad Phillip , Smith Philippa Louise , Trethewie Susan
Published: November 2021

Objective

Living with a child with a life-limiting condition (LLC), for which there is no hope of cure and premature death is expected, places much stress on a family unit. Familial communication has the potential to serve as a buffer when children are faced with stressful situations. The overall aim of the study was to learn more about illness-related communication between parents and well-siblings, giving particular consideration to the amount of illness-related communication, and sibling satisfaction with familial communication.

Methods

Participants included 48 well-siblings (aged 6–21 years) of children with LLCs and their parents. Parents and well-siblings independently completed validated measures of familial communication and sibling functioning. Parents also provided demographic information and completed a questionnaire assessing amount of illness-related information provided to well-siblings.

Results

Parents reported that 47.8% of well-siblings never or rarely initiated conversations about their sibling's illness. Moreover, 52.2% of well-siblings never or rarely spoke about death. Amount of illness-related communication between parents and well-siblings was most strongly predicted by parental resilience and well-sibling age. Parents engaged in significantly more illness-related communication with girls than boys (t(44)=−2.28, p = .028). Well-siblings (p < .01) and parents (p < .05) rated satisfaction with familial communication significantly higher than published norms. The only significant predictor of well-sibling satisfaction with familial communication was greater familial cohesion. Family communication variables were not significantly correlated with measures of sibling functioning (all p’s>.05).

Conclusions

This study provides new information regarding parent and well-sibling communication in families who have a child with a LLC.
Concurrent granulomatous mastitis and invasive ductal cancer in contralateral breasts—a case report and review
Authors: Evans Jonathan , Sisk Louis , Chi Kee , Brown Shaun , To Henry
Published: November 2021

Idiopathic granulomatous mastitis (GM) is an uncommon chronic benign disease of the breast that is challenging to clinically distinguish from malignancy. However, it is unusual to diagnose GM concurrently with carcinoma in the same breast and rarer still to encounter GM and malignancy in contralateral breasts. We describe the case of a 39-year-old female who presented with right multifocal breast cancer and left granulomatous mastitis, discuss complexities in her management plan and review the literature on this unusual concurrent condition.
Delayed massive hemothorax after blunt thoracic trauma requiring thoracotomy by VATS: a case report
Authors: Park Chan Hee , Kim Kyeong Eui , Chae Min Cheol , Lee Jeong Woo
Published: November 2021

Delayed hemothorax after thoracic trauma is a rare type of thoracic injury that may require angioembolization and surgical treatment. We report a case of a 59-year-old man with a delayed massive hemothorax from a fall-induced blunt thoracic trauma, causing multiple right lower rib fractures. The patient fell from a chair while standing on and working from it. He was diagnosed with right 7th–11th rib fractures, scanty hemothorax and liver contusion. The patient was hospitalized and received conservative treatment, and a delayed massive hemothorax was present on the fourth day after the injury. Chest tube drainage and video-assisted thoracoscopic surgery were performed, and the patient was discharged 16 days after the surgery without bleeding or other complications. Delayed hemothorax should be considered when thoracic trauma patients complain of chest discomfort, dyspnea, cold sweating or fatigue. Early recognition, appropriate diagnosis and rapid intervention can improve prognosis and lead to successful patient treatment.
Pulmonary and aortic endarteritis revealing a patent ductus arteriosus in an adult
Authors: Bouhdadi H , Rhissassi J , Wazaren H , Idrissa M , Benlafqih C , Sayah R , Laaroussi M
Published: November 2021

The ductus arteriosus, an essential fetal structure, normally closes spontaneously soon after birth. Its persistence into late adulthood is considered to be rare; infective endarteritis (IE) complicating a patent ductus arteriosus (PDA) is an even rarer event. The clinical picture of an infected PDA could be subtle, and the diagnosis is frequently delayed. We present the case of a young woman who presented with prolonged fever for whom we made the diagnosis of a PDA complicated by IE, with vegetations in both pulmonary and aortic walls with mycotic aneurysms of the descending aorta. She underwent surgery and the post-operative course was uneventful. To our knowledge, this is the first reported case of a PDA complicated with both pulmonary and aortic endarteritis.
ABA-INSENSITIVE 3 with or without FUSCA3 highly up-regulates lipid droplet proteins and activates oil accumulation
Authors: Yang Zheng , Liu Xiangling , Wang Kai , Li Zhuowei , Jia Qingli , Zhao Cuizhu , Zhang Meng
Published: November 2021

ABA-INSENSITIVE 3 (ABI3) has long been known for activation of storage protein accumulation. A role of ABI3 on oil accumulation was previously suggested based on a decrease of oil content in seeds of abi3 mutant. However, this conclusion could not exclude possibilities of indirect or pleiotropic effects, such as through mutual regulatory interactions with FUSCA3 (FUS3), an activator of oil accumulation. To identify that ABI3 functions independent of the effects of related seed transcription factors, we expressed ABI3 under the control of an inducible promoter in tobacco BY2 cells and Arabidopsis rosette leaves. Inducible expression of ABI3 activated oil accumulation in these non-seed cells, demonstrating a general role of ABI3 in regulation of oil biosynthesis. Further expressing ABI3 in rosette leaves of fus3 knockout mutant still caused up to 3-fold greater triacylglycerol accumulation, indicating ABI3 can activate lipid accumulation independently of FUS3. Transcriptome analysis revealed that LIPID DROPLET PROTEIN (LDP) genes, including OLEOSINs and CALEOSINs, were up-regulated up to 1000-fold by ABI3 in the absence of FUS3, while the expression of WRINKLED1 was doubled. Taken together, our results provide genetic evidence that ABI3 activates oil accumulation with or without FUS3, most likely through up-regulating LDPs and WRINKLED1.
High-energy neutrinos from X-rays flares of blazars frequently observed by the Swift X-ray Telescope
Authors: Stathopoulos S I , Petropoulou M , Giommi P , Vasilopoulos G , Padovani P , Mastichiadis A
Published: November 2021

Blazar flares have been suggested as ideal candidates for enhanced neutrino production. While the neutrino signal of γ-ray flares has been widely discussed, the neutrino yield of X-ray flares has received less attention. Here, we compute the predicted neutrino signal from X-ray flares detected in 66 blazars observed more than 50 times with the X-ray Telescope (XRT) on board the Neil Gehrels Swift  Observatory. We consider a scenario where X-ray flares are powered by synchrotron radiation of relativistic protons, and neutrinos are produced through photomeson interactions between protons with their own synchrotron X-ray photons. Using the 1 keV X-ray light curves for flare identification, the 0.5–10 keV fluence of each flare as a proxy for the all-flavour neutrino fluence, and the IceCube point-source effective area for different detector configurations, we calculate the number of muon and antimuon neutrinos above 100 TeV expected for IceCube from each flaring source. The bulk of the neutrino events from the sample originates from flares with durations ∼1–10 d. Accounting for the X-ray flare duty cycle of the sources in the sample, which ranges between ∼2 and 24 per cent, we compute an average yearly neutrino rate for each source. The median of the distribution (in logarithm) is ∼0.03 yr−1, with Mkn 421 having the highest predicted rate 1.2 ± 0.3 yr−1, followed by 3C 273 (0.33 ± 0.03 yr−1) and PG 1553+113 (0.25 ± 0.02 yr−1). Next-generation neutrino detectors together with regular X-ray monitoring of blazars could constrain the duty cycle of hadronic X-ray flares.
Constraints on star formation in NGC 2264
Authors: Parker Richard J , Schoettler Christina
Published: November 2021

We quantify the spatial distribution of stars for two subclusters centred around the massive/intermediate-mass stars S Mon and IRS 1/2 in the NGC 2264 star-forming region. We find that both subclusters have neither a substructured nor a centrally concentrated distribution according to the $\mathcal {Q}$-parameter. Neither subcluster displays mass segregation according to the ΛMSR ratio, but the most massive stars in IRS 1/2 have higher relative surface densities according to the ΣLDR ratio. We then compare these quantities to the results of N-body simulations to constrain the initial conditions of NGC 2264, which are consistent with having been dense ($\tilde{\rho } \sim 10^4$ M⊙ pc−3), highly substructured and subvirial. These initial conditions were also derived from a separate analysis of the runaway and walkaway stars in the region, and indicate that star-forming regions within 1 kpc of the Sun likely have a broad range of initial stellar densities. In the case of NGC 2264, its initial stellar density could have been high enough to cause the destruction or truncation of protoplanetary discs and fledgling planetary systems due to dynamical encounters between stars in the early stages of its evolution.
Phase II trial of response-based radiation therapy for patients with localized germinoma: a Children’s Oncology Group study
Authors: Bartels Ute , Onar-Thomas Arzu , Patel Sunita K , Shaw Dennis , Fangusaro Jason , Dhall Girish , Souweidane Mark , Bhatia Aashim , Embry Leanne , Trask Christine L , Murphy Erin S , MacDonald Shannon , Wu Shengjie , Boyett James M , Leary Sarah , Fouladi Maryam , Gajjar Amar , Khatua Soumen
Published: November 2021

Background

The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3–21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate.

Methods

Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim.

Results

One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment.

Conclusions

While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
An analog of Friedel oscillations in nanoconfined water
Authors: Xue Minmin , Hu Zhili , Qiu Hu , Shen Chun , Guo Wanlin , Zhang Zhuhua
Published: November 2021

Water confined in nanometer-scale crevices and cavities underpins a wide range of fundamental processes, such as capillary flow, ion transport and protein folding. However, how water responds within these confined spaces, with prevalent inhomogeneity built in or caused by impurities, is not well understood. Here, we show theoretically that water confined in one-dimensional nanochannels with localized perturbation exhibits pronounced density oscillations. The oscillations occur vividly like the Friedel oscillations in electron density resulting from defects in metals. A model analysis reveals that the density oscillations result from the perturbation-induced molecular scattering that is augmented by the confinement-enhanced correlation of water dipoles. This renders the oscillations a general behavior independent of the channel geometries and specific forms of the perturbation. Under confinements comparable to biological ion channels, such oscillations can strikingly extend over 10 nm, resulting in non-trivial effects at large distances that, for example, repel all ions from the channels with their long-range force. These results deepen the understanding of biological functions and inspire new applications in a variety of domains, such as ionic sensing and seawater desalination.
Resolving Frege’s Other Puzzle
Authors: Snyder Eric , Samuels Richard , Shapiro Stewart
Published: November 2021

Number words seemingly function both as adjectives attributing cardinality properties to collections, as in Frege’s ‘Jupiter has four moons’, and as names referring to numbers, as in Frege’s ‘The number of Jupiter’s moons is four’. This leads to what Thomas Hofweber calls Frege’s Other Puzzle: How can number words function as modifiers and as singular terms if neither adjectives nor names can serve multiple semantic functions? Whereas most philosophers deny that one of these uses is genuine, we instead argue that number words, like many related expressions, are polymorphic, having multiple uses whose meanings are systematically related via type shifting.
Fully automated opportunistic screening of vertebral fractures and osteoporosis on more than 150 000 routine computed tomography scans
Authors: Roux Christian , Rozes Antoine , Reizine Daniel , Hajage David , Daniel Christel , Maire Aurélien , Bréant Stéphane , Taright Namik , Gordon Ronen , Fechtenbaum Jacques  , Kolta Sami , Feydy Antoine , Briot Karine , Tubach Florence
Published: November 2021

Objective

Osteoporosis is underdiagnosed and undertreated, although severe complications of osteoporotic fractures, including vertebral fractures, are well known. This study sought to assess the feasibility and results of an opportunistic screening of vertebral fractures and osteoporosis in a large database of lumbar or abdominal CT scans.

Material and methods

Data were analysed from CT scans obtained in 35 hospitals from patients aged 60 years or older and stored in a Picture Archiving and Communication System in Assistance-Publique-Hôpitaux de Paris, from 2007 to 2013. Dedicated software was used to analyse the presence or absence of at least 1 vertebral fracture (VF), and the radiodensity of the lumbar vertebrae was measured Hounsfield Units (HUs). A simulated T-score was calculated.

Results

Data were analysed from 152 268 patients [mean age (S.D.) = 73.2 (9.07) years]. Success rates for VF assessment and HUs measurements were 82 and 87%, respectively. The prevalence of VFs was 24.5% and increased with age. Areas under the receiver operating characteristic curves for the detection of VFs were 0.61 and 0.62 for the mean HUs of the lumbar vertebrae and the L1 HUs, respectively. In patients without VFs, HUs decreased with age, similarly in males and females. The prevalence of osteoporosis (sT-score ≤ –2.5) was 23.8% and 36.5% in patients without and with VFs, respectively.

Conclusion

It is feasible on a large scale to screen for VFs and osteoporosis during opportunistic screening in patients 60 years or older having lumbar or abdominal CT.
The Long-Term Consequences of Imprisoning Our Youth: The Lasting Impact of Time Spent in Adult Jails and Prisons
Authors: Kurlychek Megan C , Kijowski Matthew C , Gagnon Alysha M
Published: November 2021

We explore the possible deleterious lifelong impacts for youth who serve stints of incarceration in adult jails or prisons. Our study uses a sample of all youth ages 16 and 17 arrested in New York State in 1987 and follows their criminal careers for 24 years. New York was selected as the state processed, not just some, but all youth of this age as adults, allowing us to overcome issues of selection bias and to use natural variation to create a propensity score matched sample to compare similar youth who either were, or who were not, subject to this punishment. Findings reveal that youth who spent time in an adult jail or prison recidivate more often, more quickly, and commit more total offenses. We also find that being offered youthful offender status, a status that removes the public stigma of a criminal record, reduces recidivism, regardless of the incarceration experience. Our study is situated in theories of deterrence, social learning, and labeling, and we apply our findings to greater societal implications of subjecting youth to punishments traditionally reserved for mature adults.
Interaction sites of the Epstein–Barr virus Zta transcription factor with the host genome in epithelial cells
Authors: Godfrey Anja , Osborn Kay , Sinclair Alison J.
Published: November 2021

Epstein–Barr virus (EBV) is present in a state of latency in infected memory B-cells and EBV-associated lymphoid and epithelial cancers. Cell stimulation or differentiation of infected B-cells and epithelial cells induces reactivation to the lytic replication cycle. In each cell type, the EBV transcription and replication factor Zta (BZLF1, EB1) plays a role in mediating the lytic cycle of EBV. Zta is a transcription factor that interacts directly with Zta response elements (ZREs) within viral and cellular genomes. Here we undertake chromatin-precipitation coupled to DNA-sequencing (ChIP-Seq) of Zta-associated DNA from cancer-derived epithelial cells. The analysis identified over 14 000 Zta-binding sites in the cellular genome. We assessed the impact of lytic cycle reactivation on changes in gene expression for a panel of Zta-associated cellular genes. Finally, we compared the Zta-binding sites identified in this study with those previously identified in B-cells and reveal substantial conservation in genes associated with Zta-binding sites.
Aliarcobacter, Halarcobacter, Malaciobacter, Pseudarcobacter and Poseidonibacter are later synonyms of Arcobacter: transfer of Poseidonibacter parvus, Poseidonibacter antarcticus, ‘Halarcobacter arenosus’, and ‘Aliarcobacter vitoriensis’ to Arcobacter as Arcobacter parvus comb. nov., Arcobacter antarcticus comb. nov., Arcobacter arenosus comb. nov. and Arcobacter vitoriensis comb. nov.
Authors: On Stephen L. W. , Miller William G. , Biggs Patrick J. , Cornelius Angela J. , Vandamme Peter
Published: November 2021

This paper re-examines the taxonomic positions of recently described

Poseidonibacter

(P. parvum and

P. antarcticus

),

Aliarcobacter

(‘Al. vitoriensis’),

Halarcobacter

(‘H. arenosus’) and

Arcobacter

(

A. caeni

,

A. lacus

) species, and other species proposed to represent novel genera highly related to the genus

Arcobacter

. Phylogenomic and several overall genome relatedness indices (OGRIs) were applied to a total of 118 representative genomes for this purpose. Phylogenomic analyses demonstrated the

Arcobacter

clade to be distinct from other

Epsilonproteobacteria

, clearly defined and containing closely related species.

Aliarcobacter butzleri

and

Malaciobacter pacificus

did not cluster with other members of these proposed genera, indicating incoherence of these genera. Every OGRI measure applied indicated a high level of relatedness among all

Arcobacter

clade species, including the recently described taxa studied here, and substantially lower between type species representatives for other Epsilonproteobacteria. Where published guidelines were available, OGRI values for

Arcobacter

clade species were either unsupportive of division into other genera or were at the lowest boundary range (for average amino acid identity). We propose that

Aliarcobacter

,

Halarcobacter

,

Malaciobacter

,

Pseudarcobacter

,

Poseidonibacter

and Arcobacter sensu stricto be considered members of a single genus,

Arcobacter

, and subsequently transfer P. parvum,

P. antarcticus

, ‘

Al. vitoriensis

’ and ‘H. arenosus’ to

Arcobacter

as Arcobacter parvum comb. nov., Arcobacter antarcticus comb. nov., Arcobacter vitoriensis comb. nov. and Arcobacter arenosus comb. nov.
Genome evolution drives transcriptomic and phenotypic adaptation in Pseudomonas aeruginosa during 20 years of infection
Authors: Wardell Samuel J.T. , Gauthier Jeff , Martin Lois W. , Potvin Marianne , Brockway Ben , Levesque Roger C. , Lamont Iain L.
Published: November 2021

The opportunistic pathogen

Pseudomonas aeruginosa

chronically infects the lungs of patients with cystic fibrosis (CF). During infection the bacteria evolve and adapt to the lung environment. Here we use genomic, transcriptomic and phenotypic approaches to compare multiple isolates of

P. aeruginosa

collected more than 20 years apart during a chronic infection in a CF patient. Complete genome sequencing of the isolates, using short- and long-read technologies, showed that a genetic bottleneck occurred during infection and was followed by diversification of the bacteria. A 125 kb deletion, an 0.9 Mb inversion and hundreds of smaller mutations occurred during evolution of the bacteria in the lung, with an average rate of 17 mutations per year. Many of the mutated genes are associated with infection or antibiotic resistance. RNA sequencing was used to compare the transcriptomes of an earlier and a later isolate. Substantial reprogramming of the transcriptional network had occurred, affecting multiple genes that contribute to continuing infection. Changes included greatly reduced expression of flagellar machinery and increased expression of genes for nutrient acquisition and biofilm formation, as well as altered expression of a large number of genes of unknown function. Phenotypic studies showed that most later isolates had increased cell adherence and antibiotic resistance, reduced motility, and reduced production of pyoverdine (an iron-scavenging siderophore), consistent with genomic and transcriptomic data. The approach of integrating genomic, transcriptomic and phenotypic analyses reveals, and helps to explain, the plethora of changes that

P. aeruginosa

undergoes to enable it to adapt to the environment of the CF lung during a chronic infection.
A functional menadione biosynthesis pathway is required for capsule production by Staphylococcus aureus
Authors: Altwiley Dina , Brignoli Tarcisio , Edwards Andrew , Recker Mario , Lee Jean C. , Massey Ruth C.
Published: November 2021

Staphylococcus aureus

is a major human pathogen that utilises a wide array of pathogenic and immune evasion strategies to cause disease. One immune evasion strategy, common to many bacterial pathogens, is the ability of

S. aureus

to produce a capsule that protects the bacteria from several aspects of the human immune system. To identify novel regulators of capsule production by S. aureus, we applied a genome wide association study (GWAS) to a collection of 300 bacteraemia isolates that represent the two major MRSA clones in UK and Irish hospitals: CC22 and CC30. One of the loci associated with capsule production, the menD gene, encodes an enzyme critical to the biosynthesis of menadione. Mutations in this gene that result in menadione auxotrophy induce the slow growing small-colony variant (SCV) form of

S. aureus

often associated with chronic infections due to their increased resistance to antibiotics and ability to survive inside phagocytes. Utilising such an SCV, we functionally verified this association between menD and capsule production. Although the clinical isolates with polymorphisms in the menD gene in our collections had no apparent growth defects, they were more resistant to gentamicin when compared to those with the wild-type menD gene. Our work suggests that menadione is involved in the production of the

S. aureus

capsule, and that amongst clinical isolates polymorphisms exist in the menD gene that confer the characteristic increased gentamicin resistance, but not the major growth defect associated with SCV phenotype.
Exploring the Temporal Dynamics of County-Level Vulnerability Factors on COVID-19 Outcomes
Authors: Zhang Jing , Choi Daesung , Patel Shivani A , Ho Joyce C.
Published: November 2021

As the outbreak of COVID-19 has become a severe worldwide pandemic, every country fights against the spread of this deadly disease with incredible efforts. There are numerous researches along with every conceivable dimension for COVID-19. Among these researches, different demographic and contextual factors of populations and communities also play an essential role in providing more information for decision-makers. This paper mainly utilizes existing data on county contextual factors at the United States county-level to develop a model that can capture the dynamic trajectory of COVID-19 (i.e., cases) and its impacts across the United States. Moreover, our methods applied to contextual data achieves better results compared with existing measures of vulnerability.
A Comprehensive HPV-STI NGS Assay for Detection of 29 HPV Types and 14 non-HPV Sexually Transmitted Infections
Authors: Ma Zhihai , Gharizadeh Baback , Cai Xingsheng , Li Mengzhen , Fellner María Dolores , Basiletti Jorge Alejandro , Correa Rita Mariel , Colucci María Celeste , Baldoni Gabriela , Vacchino Martín , Galarza Patricia , Picconi María Alejandra , Wang Chunlin
Published: November 2021

Sexually transmitted infections (STIs) are prevalent throughout the world and impose a significant burden on individual health and public health systems. Missed diagnosis and late treatment of STIs can lead to serious complications such as infertility and cervical cancer. Although sexually transmitted co-infections are common, most commercial assays target one or a few STIs. The HPV-STI ChapterDx Next Generation Sequencing (NGS) assay detects and quantifies 29 HPVs and 14 other STIs in a single-tube and single-step PCR reaction and can be applied to tens to thousands of samples in a single sequencing run. The assay was evaluated in this study, and the limit of detection was 100% at 50 copies for all targets, and 100%, 96%, 88% at 20 copies for 34, 8, and 1 target, respectively. The performance of this assay has been compared to Roche cobas HPV test, showing an overall agreement of 97.5% for hr-HPV, and 98.5% for both, HPV16 and HPV18. The assay also detected all HPV-infected CIN2/3 with 100% agreement with Roche cobas HPV results. Moreover, several co-infections with non-HPV STIs, such as C. trachomatis, T. vaginalis, M. genitalium, and HSV2 were identified. The ChapterDx HPV-STI NGS assay is a user-friendly, easy to automate and cost-efficient assay, which provides accurate and comprehensive results for a wide spectrum of HPVs and STIs.
SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates Against Symptomatic Infection
Authors: Schuh Amy J. , Satheshkumar Panayampalli S. , Dietz Stephanie , Bull-Otterson Lara , Charles Myrna , Edens Chris , Jones Jefferson M. , Bajema Kristina L. , Clarke Kristie E.N. , McDonald L. Clifford , Patel Sadhna , Cuffe Kendra , Thornburg Natalie J. , Schiffer Jarad , Chun Kelly , Bastidas Monique , Fernando Manory , Petropoulos Christos J. , Wrin Terri , Cai Suqin , Adcock Dot , Sesok-Pizzini Deborah , Letovsky Stanley , Fry Alicia M. , Hall Aron J. , Gundlapalli Adi V.
Published: November 2021

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ∼88% of neutralizing and ∼63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ∼30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.
Germany’s current COVID-19 crisis is mainly driven by the unvaccinated
Authors: Maier Benjamin F. , Wiedermann Marc , Burdinski Angelique , Klamser Pascal , Jenny Mirjam A. , Betsch Cornelia , Brockmann Dirk
Published: November 2021

Vaccines are the most powerful pharmaceutical tool to combat the COVID-19 pandemic. While the majority (about 65%) of the German population were fully vaccinated, incidence started growing exponentially in October 2021 with about 41% of recorded new cases aged twelve or above being symptomatic breakthrough infections, presumably also contributing to the dynamics. At the time, it (i) remains elusive how significant this contribution is and (ii) whether targeted non-pharmaceutical interventions (NPIs) may stop the amplification of the ongoing crisis. Here, we estimate that about 67%–76% of all new infections are caused by unvaccinated individuals, implying that only 24%–33% are caused by the vaccinated. Furthermore, we estimate 38%–51% of new infections to be caused by unvaccinated individuals infecting other unvaccinated individuals. In total, unvaccinated individuals are expected to be involved in 8–9 of 10 new infections. We further show that decreasing the transmissibility of the unvaccinated by, e. g. targeted NPIs, causes a steeper decrease in the effective reproduction number ℛ than decreasing the transmissibility of vaccinated individuals, potentially leading to temporary epidemic control. Furthermore, reducing contacts between vaccinated and unvaccinated individuals serves to decrease ℛ in a similar manner as increasing vaccine uptake. Taken together, our results contribute to the public discourse regarding policy changes in pandemic response and highlight the importance of combined measures, such as vaccination campaigns and contact reduction, to achieve epidemic control and preventing an overload of public health systems.
Large-scale seroepidemiology uncovers nephrological pathologies in people with tau autoimmunity
Authors: Magalhães Andreia D. , Emmenegger Marc , De Cecco Elena , Carta Manfredi , Frontzek Karl , Chincisan Andra , Guo Jingjing , Hornemann Simone , Aguzzi Adriano
Published: November 2021

Importance

Intraneuronal aggregates of the microtubule-associated protein tau play a pivotal role in Alzheimer’s disease and several other neurodegenerative syndromes. Anti-tau antibodies can reduce pathology in mouse models of neurodegeneration and are currently being tested in humans.

Objective

To evaluate the seroprevalence of natural anti-tau autoantibodies and their potential association with diseases.

Design

In a cross-sectional study, plasma samples from a randomized university hospital cohort and healthy blood donors, collected from 2017 to 2020, were screened for anti-MTBD-tau plasma IgG autoantibodies (ατ) in a miniaturized, high-throughput ELISA. Samples were included if basic demographic data was available and age was ≥18 years. Data analysis was performed from De-cember 2017 to August 2024. Titers were defined as −log10(EC50) values. Titers of ≥1.8 were clas-sified as ατ+.

Participants

Blood was obtained during routine clinical care from 32,291 patients admitted as inpatients or outpatients to any department of a university hospital, or from 8,206 healthy blood donors.

Results

High-titer ατ+samples were surprisingly prevalent, with hospital patients being three times more likely to be ατ+than healthy blood donors (4.8% vs 1.6%). ατ autoantibodies ligated selectively tau, inhibited tau aggregation in vitro, and interfered with tau detection in plasma sam-ples. No association was found between ατ autoantibodies and neurologic disorders. Instead, tau autoreactivity showed a significant association with kidney and urinary disorders (adjusted risk ratio (RR) 1.27, 95% CI 1.10-1.45, P=0.001 and 1.40, 95% CI 1.20-1.63, P<0.001 respectively).

Conclusions and Relevance

While ατ autoimmunity was not associated with neurologic dis-eases, its association with extraneural pathologies will require scrutiny in the context of anti-tau therapies. Moreover, immunochemical plasma tau assays were confounded by ατ antibodies, whose high prevalence may limit their usefulness as biomarker.
Examining the intersection of child protection and public housing: development, health and justice outcomes using linked administrative data
Authors: Malvaso Catia , Montgomerie Alicia , Pilkington Rhiannon , Baker Emma , Lynch John
Published: November 2021

Objective

We described development, health and justice system outcomes for children in contact with child protection and public housing.

Design

Descriptive analysis of outcomes for children known to child protection who also had contact with public housing drawn from the South Australian (SA) Better Evidence Better Outcomes Linked Data (BEBOLD) platform.

Setting

The BEBOLD platform holds linked administrative records collected by government agencies for whole-population successive birth cohorts in South Australia beginning in 1999.

Participants

This study included data from birth registrations, perinatal, child protection, public housing, hospital, emergency department, early education, and youth justice for all SA children born 1999-2013 and followed until 2016. The base population notified at least once to child protection was n=67,454.

Primary outcome measure

Contact with the public housing system.

Secondary outcome measures

hospitalisations and emergency department presentations before age 5, and early education at age 5, and youth justice contact before age 17.

Results

More than 60% of children with at least one notification to child protection had contact with public housing, and 60.2% of those known to both systems were known to housing first. Children known to both systems experienced more emergency department and hospitalisation contacts, greater developmental vulnerability and were about 6 times more likely to have youth justice system contact.

Conclusions

There is substantial overlap between involvement with child protection and public housing in SA. Those children are more likely to face a life trajectory characterised by greater contact with the health system, greater early life developmental vulnerability, and greater contact with the criminal justice system. Ensuring the highest quality of supportive early life infrastructure for families in public housing may contribute to prevention of contact with child protection and better life trajectories for children.

Strengths and limitations of this study

This descriptive study provides epidemiological insight into the largely unexplored intersection between child protection and housing systems using whole-of-population linked administrative data

The findings of this study are based on data drawn from South Australia and may not be directly generalizable to other locations because of different administrative systems

Despite data being drawn from one Australian jurisdiction, the qualitative relationship between child protection and housing is likely to be similar
Cryo-EM structure of hexameric yeast Lon (PIM1) highlights importance of conserved structural elements
Authors: Yang Jie , Song Albert S. , Wiseman R. Luke , Lander Gabriel C.
Published: November 2021

Lon protease is a conserved ATP-dependent serine protease composed of an AAA+ domain that mechanically unfolds substrates and a serine protease domain that degrades unfolded substrates. In yeast, dysregulation of Lon protease (PIM1) attenuates lifespan and leads to gross mitochondrial morphologic perturbations. Although structures of bacterial and human Lon protease reveal a hexameric assembly, PIM1 was speculated to form a heptameric assembly, and is uniquely characterized by a ~50 residue insertion between the ATPase and protease domains. To understand the yeast-specific properties of PIM1, we determined a high-resolution cryo-EM structure of PIM1 in a substrate-translocating state. Here, we reveal that PIM1 forms a hexamer, conserved with that of bacterial and human Lon proteases, wherein the ATPase domains form a canonical closed spiral that enables pore loop residues to translocate substrate to the protease chamber. In the substrate-translocating state, PIM1 protease domains form a planar protease chamber in an active conformation and are uniquely characterized by a ~15 residue C-terminal extension. These additional C-terminal residues form an alpha-helix that is located along the base of the protease domain. Finally, we did not observe density for the yeast-specific insertion between the ATPase and protease domains, likely due to high conformational flexibility. Biochemical studies to investigate the insertion using constructs that truncated or replaced the insertion with a glycine-serine linker suggest that the yeast-specific insertion is dispensable for PIM1’s enzymatic function. Altogether, our structural and biochemical studies highlight unique components of PIM1 machinery and demonstrate evolutionary conservation of Lon protease function.
The DOMINO web-server for active module identification analysis
Authors: Levi Hagai , Rahmanian Nima , Elkon Ran , Shamir Ron
Published: November 2021

Active module identification (AMI) is an essential step in many omics analyses. Such algorithms receive a gene network and a gene activity profile as input and report subnetworks that show significant over-representation of accrued activity signal (“active modules”). Such modules can point out key molecular processes in the analyzed biological conditions.

Results

We recently introduced a novel AMI algorithm called DOMINO, and demonstrated that it detects active modules that capture biological signals with markedly improved rate of empirical validation. Here, we provide an online server that executes DOMINO, making it more accessible and user-friendly. To help the interpretation of solutions, the server provides GO enrichment analysis, module visualizations, and accessible output formats for customized downstream analysis. It also enables running DOMINO with various gene identifiers of different organisms.

Availability and implementation

The server is available athttp://domino.cs.tau.ac.il. Its codebase is available athttps://github.com/Shamir-Lab.
Possible Regulation of Toll-Like Receptor 4 By Lysine Acetylation Through LPCAT2 Activity in RAW264.7 Cells
Authors: Poloamina Victory Ibigo , Abate Wondwossen , Fejer Gyorgy , Jackson Simon K.
Published: November 2021

1

Inflammation is central to several diseases. TLR4 mediates inflammatory signals, however, there are gaps in the understanding of its mechanisms. Recently, TLR4 was found to co-localise with LPCAT2, a lysophospholipid acetyltransferase. This interaction influenced TLR4 subcellular localisation through an unknown mechanism.

In this study, we have combined computational analysis, RNA interference technology, and biochemical analysis to investigate the possibility of TLR4 lysine acetylation and the influence of LPCAT2 on the detected lysine acetylation.

The results suggest for the first time that TLR4 can undergo lysine acetylation and LPCAT2 can influence TLR4 lysine acetylation. This lays a foundation for further research on the role of lysine acetylation on TLR4 and characterisation of LPCAT2 as a protein acetyltransferase.