bluuebunny/crossref_metadata_2025 huggingface dataset:
Techno–economic–environmental feasibility study of a photovoltaic system in northern part of Iran including a two-stage multi-string inverter with DC–DC ZETA converter and a modified P&O algorithm
Authors: Semeskandeh Sina , Hojjat Mehrdad , Hosseini Abardeh Mohamad
Published: January 2022

Inverters play a significant role in the configuration of grid-connected photovoltaic (PV) systems. The perturb-and-observe (P&O) algorithm is a common method to derive the maximum power from grid-connected inverters; however, the possibility of losing maximum power due to sudden changes in radiation is a significant drawback of this control strategy. To overcome this barrier, the two-stage multi-string inverter using the ZETA DC–DC converter and a novel P&O algorithm has been proposed to increase the efficiency of these systems. The proposed inverter has been simulated in MATLAB/SIMULINK software. To investigate the performance of the proposed inverter, technical, environmental and economic feasibility studies have been performed for the construction of a 5-kW PV power plant in a northern city of Iran (Sari) using the RETScreen software developed by Natural Resources Canada. On the other hand, most feasibility studies for power-plant construction are based on the concept of inverter peak efficiency, which leads to non-optimal system design due to the short operation duration of the inverter at this value. However, the weighted European efficiency has been used in the feasibility study for more accurate computations. Moreover, the performance of the proposed inverter is compared to that of a two-stage multi-string inverter using a conventional P&O algorithm and the single-stage (central) inverter. The simulation results indicated that the proposed inverter injects 7.6 MW of power into the grid per year. Moreover, it prevents the emission of 88 tons of CO2 (over 20 years), which is equivalent to saving 1883.5 litres of gasoline per year.
The life cycle-dependent transcriptional profile of the obligate intracellular amoeba symbiontAmoebophilus asiaticus
Authors: Selberherr E , Penz T , König L , Conrady B , Siegl A , Horn M , Schmitz-Esser S
Published: January 2022

Free-living amoebae often harbor obligate intracellular bacterial symbionts. Amoebophilus (A.) asiaticus is a representative of a lineage of amoeba symbionts in the phylum Bacteroidota. Here, we analyse the transcriptome of A. asiaticus strain 5a2 at four time points during its infection cycle and replication within the Acanthamoeba host using RNA sequencing. Our results reveal a dynamic transcriptional landscape throughout different A. asiaticus life cycle stages. Many intracellular bacteria and pathogens utilize eukaryotic-like proteins (ELPs) for host cell interaction and the A. asiaticus 5a2 genome shows a particularly high abundance of ELPs. We show the expression of all genes encoding ELPs and found many ELPs to be differentially expressed. At the replicative stage of A. asiaticus, ankyrin repeat proteins and tetratricopeptide/Sel1-like repeat proteins were upregulated. At the later time points, high expression levels of a type 6 secretion system that likely prepares for a new infection cycle after lysing its host, were found. This study reveals comprehensive insights into the intracellular lifestyle of A. asiaticus and highlights candidate genes for host cell interaction. The results from this study have implications for other intracellular bacteria such as other amoeba-associated bacteria and the arthropod symbionts Cardinium forming the sister lineage of A. asiaticus.
Close-kin mark–recapture abundance estimation: practical insights and lessons learned
Authors: Trenkel Verena M , Charrier Grégory , Lorance Pascal , Bravington Mark V
Published: January 2022

We present practical lessons learned from applying the recent close-kin mark–recapture (CKMR) abundance estimation method to thornback ray (Raja clavata). For CKMR, related individuals are identified from their genotypes and their number and pattern is used for abundance estimation. We genotyped over 7000 individuals collected in the Bay of Biscay using Single Nucleotide Polymorphism (SNP) markers finding 99 parent–offspring pairs. The estimated number of adult thornback rays in the central Bay of Biscay was around 135000 (CV 0.19) in 2013. In total, four lessons were drawn: (i) CKMR helps identifying metapopulation structure, which if ignored might affect abundance estimates and/or time trends. There was strong evidence for two distinct local populations of thornback ray with no demographic connectivity. (ii) Demographic sample composition can affect precision and needs to include a range of birth years, which turned out to be difficult for thornback ray. (iii) Reasonable age information for potential offspring is essential. (iv) The sex of potential parents is needed and might be identified from sex-related SNPs. Reliable abundance estimation by CKMR appears feasible for a wide range of species provided that: sampling adequately covers potential local population structure, has appropriate demographic composition, and the age of potential offspring is reasonably well-known.
Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study
Authors: Margot Nicolas , Vanderveen Laurie , Naik Vidula , Ram Renee , Parvangada PC , Martin Ross , Rhee Martin , Callebaut Christian
Published: January 2022

Background

Lenacapavir in vitro resistance selections identified seven mutations in HIV-1 capsid protein (CA) associated with reduced susceptibility.

Objectives

To analyse lenacapavir activity against lenacapavir-associated resistance mutations in multiple assays. We also report Day 10 resistance analyses conducted in a Phase 1b study of lenacapavir (Study 4072) in people with HIV (PWH).

Methods

Mutations were inserted in a proviral DNA clone by site-directed mutagenesis, and viruses (n = 12) were generated by transfection. Sequences were used to generate single-cycle (SC) test vectors that were evaluated in a Gag-Pro assay, and replicative viruses were tested in a multicycle (MC) MT-2 assay to determine lenacapavir susceptibility. Study 4072 was a Phase 1b, double-blinded, placebo-controlled, dose-ranging, randomized study of lenacapavir in untreated PWH. Participants received a single dose of lenacapavir (up to 750 mg) or placebo (10 day monotherapy). CA resistance was characterized using genotypic and/or phenotypic assays.

Results

Lenacapavir susceptibility in the SC assay showed an inverse relationship between replication capacity and resistance. In Study 4072, all 29 participants receiving lenacapavir showed a robust virological response with no rebound. At baseline, no participant had resistance mutations to lenacapavir, and all had WT susceptibility to lenacapavir. Post-monotherapy analyses revealed the emergence of CA mutation Q67H at Day 10 in two participants.

Conclusions

In vitro assays confirmed that increased resistance to lenacapavir was associated with decreased replication capacity of mutant viruses. In the clinical study no pre-existing lenacapavir resistance was detected. Emergence of Q67H occurred at exposures below the dose used in current Phase 2/3 studies. These results support development of lenacapavir as an antiretroviral agent.
Comparative Greenness Metric Estimates for Content Uniformity Testing of Anti-Cov-2, GS-5734 in Commercial Vials: Validated Micellar Electrokinetic Chromatographic Assay
Authors: Elonsy Sohila M , Kamal Miranda F , Hamdy Mohamed M A , Abdel Moneim Mona M
Published: January 2022

Background

The antiviral drug GS-5734 remdesivir is a new phosphoramidate prodrug developed initially as a treatment for Ebola virus which then proved to have antiviral properties against other viruses. After clinical trials, it was the first antiviral to be approved by the U.S. Food and Drug Administration in 2020 to treat severe coronavirus (COVID-19) cases. The widespread current pandemic gave an urge to its fast production and marketing. Thus, new analytical methods must be available for its analysis in a fast and easy manner with low cost to be applicable in all laboratories.

Objective

In the current study, a green and economic micellar electrokinetic chromatographic (MEKC) method is proposed for remdesivir analysis.

Methods

A fused-silica capillary (58.5 cm × 50 μm id, 50 cm effective length) with 20 mM borate buffer (pH 9) and 25 mM sodium dodecyl sulfate was used under a positive potential of 30 kV at 25°C with detection at 245 nm.

Results

Remdesivir analysis was achieved in approximately 5 min. The method proved to be linear in range of 1–50 μg/mL with correlation coefficient, r > 0.999.

Conclusion

The MEKC method proposed was applied to the analysis of remdesivir in its commercial vials. The method was validated per International Conference on Harmonization guidelines.

Highlights

Green chemistry has been the focus of the analytical community in the past few years. This method is considered green due to its low energy and solvent consumption without sacrificing the method’s sensitivity or selectivity. The method’s green profile has been assessed by different greenness assessment scales to ensure the method is eco-friendly and can be used in the pharmaceutical industry.
Context-Dependent Viral Transgenerational Immune Priming in Honey Bees (Hymenoptera: Apidae)
Authors: Lang Sarah , Simone-Finstrom Michael , Healy Kristen
Published: January 2022

Transgenerational immune priming is the process of increased resistance to infection in offspring due to parental pathogen exposure. Honey bees (Apis mellifera L. (Hymenoptera: Apidae)) are hosts to multiple pathogens, and this complex immune function could help protect against overwhelming infection. Honey bees have demonstrated transgenerational immune priming for the bacterial pathogen Paenibacillus larvae; however, evidence for viral transgenerational immune priming is lacking across insects in general. Here we test for the presence of transgenerational immune priming in honey bees with Deformed wing virus (DWV) by injecting pupae from DWV-exposed queens and measuring virus titer and immune gene expression. Our data suggest that there is evidence for viral transgenerational immune priming in honey bees, but it is highly context-dependent based on route of maternal exposure and potentially host genetics or epigenetic factors.
Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis
Authors: Machitori Yumiko , Ito Kei , Kito Satoshi , Nakajima Yujiro , Saito Makoto , Karasawa Katsuyuki
Published: January 2022

Background

Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors.

Methods

Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013–18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique.

Results

Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed.

Conclusions

DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.
Advances in Deep Neuropathological Phenotyping of Alzheimer Disease: Past, Present, and Future
Authors: Shakir Mustafa N , Dugger Brittany N
Published: January 2022

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the presence of neurofibrillary tangles and amyloid beta (Aβ) plaques in the brain. The disease was first described in 1906 by Alois Alzheimer, and since then, there have been many advancements in technologies that have aided in unlocking the secrets of this devastating disease. Such advancements include improving microscopy and staining techniques, refining diagnostic criteria for the disease, and increased appreciation for disease heterogeneity both in neuroanatomic location of abnormalities as well as overlap with other brain diseases; for example, Lewy body disease and vascular dementia. Despite numerous advancements, there is still much to achieve as there is not a cure for AD and postmortem histological analyses is still the gold standard for appreciating AD neuropathologic changes. Recent technological advances such as in-vivo biomarkers and machine learning algorithms permit great strides in disease understanding, and pave the way for potential new therapies and precision medicine approaches. Here, we review the history of human AD neuropathology research to include the notable advancements in understanding common co-pathologies in the setting of AD, and microscopy and staining methods. We also discuss future approaches with a specific focus on deep phenotyping using machine learning.
The Impact of COVID-19 Among Black Girls: A Social-Ecological Perspective
Authors: Crooks Natasha , Sosina Wuraola , Debra Alyssa , Donenberg Geri
Published: January 2022

Objective

To explore the impact of the COVID-19 pandemic on Black adolescent girls’ physical, psychological, and sexual development.

Methods

Semistructured interviews were conducted with 25 girls (9–18 years old) primarily across the Midwestern United States. Interviews were conducted until theoretical saturation was reached. We conducted a conventional content analysis by reviewing transcripts, coding data, and developing themes.

Results

Utilizing the social-ecological model findings revealed themes related to the individual-, interpersonal-, institutional-, and community-level changes that Black girls experienced during the COVID-19 pandemic.

Conclusions

Black adolescent girls need opportunities to discuss the changes, receive relevant resources, and have spaces to support their physical, psychological, and sexual development. Systems such as families, schools, and clinics should implement programming to facilitate discussions around the impact of COVID-19 on Black girls.
Supernova siblings and their parent galaxies in the Zwicky Transient Facility Bright Transient Survey
Authors: Graham Melissa L , Fremling Christoffer , Perley Daniel A , Biswas Rahul , Phillips Christopher A , Sollerman Jesper , Nugent Peter E , Nance Sarafina , Dhawan Suhail , Nordin Jakob , Goobar Ariel , Miller Adam , Neill James D , Hall Xander J , Hankins Matthew J , Duev Dmitry A , Kasliwal Mansi M , Rigault Mickael , Bellm Eric C , Hale David , Mróz Przemek , Kulkarni S R
Published: January 2022

Supernova (SN) siblings – two or more SNe in the same parent galaxy – are useful tools for exploring progenitor stellar populations as well as properties of the host galaxies such as distance, star-formation rate, dust extinction, and metallicity. Since the average SN rate for a Milky Way-type galaxy is just one per century, a large imaging survey is required to discover an appreciable sample of SN siblings. From the wide-field Zwicky Transient Facility (ZTF) Bright Transient Survey (which aims for spectroscopic completeness for all transients which peak brighter than r < 18.5 mag) we present 10 SN siblings in five parent galaxies. For each of these families, we analyse the SN’s location within the host and its underlying stellar population, finding agreement with expectations that SNe from more massive progenitors are found nearer to their host core and in regions of more active star formation. We also present an analysis of the relative rates of core collapse and thermonuclear SN siblings, finding a significantly lower ratio than past SN sibling samples due to the unbiased nature of the ZTF.
Placental Mammals Acquired Functional Sequences in NRK for Regulating the CK2–PTEN–AKT Pathway and Placental Cell Proliferation
Authors: Lestari Beni , Naito Satomi , Endo Akinori , Nishihara Hidenori , Kato Akira , Watanabe Erika , Denda Kimitoshi , Komada Masayuki , Fukushima Toshiaki
Published: January 2022

The molecular evolution processes underlying the acquisition of the placenta in eutherian ancestors are not fully understood. Mouse NCK-interacting kinase (NIK)-related kinase (NRK) is expressed highly in the placenta and plays a role in preventing placental hyperplasia. Here, we show the molecular evolution of NRK, which confers its function for inhibiting placental cell proliferation. Comparative genome analysis identified NRK orthologs across vertebrates, which share the kinase and citron homology (CNH) domains. Evolutionary analysis revealed that NRK underwent extensive amino acid substitutions in the ancestor of placental mammals and has been since conserved. Biochemical analysis of mouse NRK revealed that the CNH domain binds to phospholipids, and a region in NRK binds to and inhibits casein kinase-2 (CK2), which we named the CK2-inhibitory region (CIR). Cell culture experiments suggest the following: 1) Mouse NRK is localized at the plasma membrane via the CNH domain, where the CIR inhibits CK2. 2) This mitigates CK2-dependent phosphorylation and inhibition of PTEN and 3) leads to the inhibition of AKT signaling and cell proliferation. Nrk deficiency increased phosphorylation levels of PTEN and AKT in mouse placenta, supporting our hypothesis. Unlike mouse NRK, chicken NRK did not bind to phospholipids and CK2, decrease phosphorylation of AKT, or inhibit cell proliferation. Both the CNH domain and CIR have evolved under purifying selection in placental mammals. Taken together, our study suggests that placental mammals acquired the phospholipid-binding CNH domain and CIR in NRK for regulating the CK2–PTEN–AKT pathway and placental cell proliferation.
The scaffolding protein DLG5 promotes glioblastoma growth by controlling Sonic Hedgehog signaling in tumor stem cells
Authors: Kundu Somanath , Nandhu Mohan S , Longo Sharon L , Longo John A , Rai Shawn , Chin Lawrence S , Richardson Timothy E , Viapiano Mariano S
Published: January 2022

Background

Tumor invasion, a hallmark of malignant gliomas, involves reorganization of cell polarity and changes in the expression and distribution of scaffolding proteins associated with polarity complexes. The scaffolding proteins of the DLG family are usually downregulated in invasive tumors and regarded as tumor suppressors. Despite their important role in regulating neurodevelopmental signaling, the expression and functions of DLG proteins have remained almost entirely unexplored in malignant gliomas.

Methods

Western blot, immunohistochemistry, and analysis of gene expression were used to quantify DLG members in glioma specimens and cancer datasets. Over-expression and knockdown of DLG5, the highest-expressed DLG member in glioblastoma, were used to investigate its effects on tumor stem cells and tumor growth. qRT-PCR, Western blotting, and co-precipitation assays were used to investigate DLG5 signaling mechanisms.

Results

DLG5 was upregulated in malignant gliomas compared to other solid tumors, being the predominant DLG member in all glioblastoma molecular subtypes. DLG5 promoted glioblastoma stem cell invasion, viability, and self-renewal. Knockdown of this protein in vivo disrupted tumor formation and extended survival. At the molecular level, DLG5 regulated Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand. Loss of DLG5 increased the proteasomal degradation of Gli1, underlying the loss of Shh signaling and tumor stem cell sensitization.

Conclusions

The high expression and pro-tumoral functions of DLG5 in glioblastoma, including its dominant regulation of Shh signaling in tumor stem cells, reveal a novel role for this protein that is strikingly different from its proposed tumor-suppressor role in other solid tumors.
A Phase II Study of Pembrolizumab in Combination with Capecitabine and Oxaliplatin with Molecular Profiling in Patients with Advanced Biliary Tract Carcinoma
Authors: Monge Cecilia , Pehrsson Erica C , Xie Changqing , Duffy Austin G , Mabry Donna , Wood Bradford J , Kleiner David E , Steinberg Seth M , Figg William D , Redd Bernadette , Budhu Anuradha , Wang Sophie , Tandon Mayank , Ma Lichun , Wei Wang Xin , Greten Tim F
Published: January 2022

Background

We conducted a phase II study of the combination of pembrolizumab with capecitabine and oxaliplatin (CAPOX) in patients with advanced biliary tract carcinoma (BTC) to assess response rate and clinical efficacy. Exploratory objectives included correlative studies of immune marker expression, tumor evolution, and immune infiltration in response to treatment.

Patients and Methods

Adult patients with histologically confirmed BTC were enrolled and received oxaliplatin and pembrolizumab on day 1 of cycles 1-6. Capecitabine was administered orally twice daily as intermittent treatment, with the first dose on day 1 and the last dose on day 14 of cycles 1-6. Starting on cycle 7, pembrolizumab monotherapy was continued until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, tolerability, feasibility, and response rate. Immunohistochemistry (IHC) for PD-L1 and immune infiltrates was analyzed in paired tumor biopsies, as well as bulk transcriptome and exome profiling for five patients and single-cell RNA sequencing for one partial responder.

Results

Eleven patients enrolled, three of whom had received no prior systemic therapy. Treatment was well tolerated, and the most common treatment-related grade 3 or 4 adverse events were lymphocytopenia, anemia, and decreased platelet count. Three patients (27.3%) achieved a partial response, and six (54%) had stable disease. The disease control rate was 81.8%. The median PFS was 4.1 months with a 6-month PFS rate of 45.5%. Molecular profiling suggests qualitative differences in immune infiltration and clonal evolution based on response.

Conclusion

Capecitabine and oxaliplatin in combination with pembrolizumab is tolerable and a potentially effective treatment for refractory advanced BTC. This study highlights a design framework for the precise characterization of individual BTC tumors.

Trial Registration

This study was registered in ClinicalTrials.gov (NCT03111732).
Writing the History of Endemic Viral Disease: The Case of Bovine Viral Diarrhoea, c.1945–1980
Authors: Woods Abigail
Published: January 2022

In Western countries during the post-World War II decades, endemic viral diseases were increasingly important to health. Such diseases have attracted limited historical attention. Due to changing methods of livestock production, they were particularly prevalent on the farm. This article uses a case study of the cattle disease, bovine viral diarrhoea (BVD), to demonstrate their historical significance. Spanning North America, the UK and Australia, it reveals the complex nature of BVD, and how and why its clinical, aetiological, epidemiological and host species identities evolved over time. This analysis sheds new light on how endemic viral diseases of livestock were experienced, understood and distributed in this period, and the influence exerted by changing agricultural practices, concerns about biological warfare and the development of virology as applied to veterinary medicine.
Leaving the Pervasive Barrio: Gang Disengagement under Criminal Governance
Authors: Cruz José Miguel , Rosen Jonathan D
Published: January 2022

Is it possible to disengage from street gangs in communities and districts where gang organizations rule? We argue that disengagement is possible when this process does not alter the social order that allows street gangs to continue controlling and establishing the rules that govern economic activities and relationships in the barrios they control. We explore the process of gang disengagement under criminal governance in El Salvador, a country plagued by the powerful MS-13 and Barrio 18 gangs. We conducted a survey with nearly 1,200 people with a history of gang membership and 25 in-depth interviews with former gang members. We find that disengagement through religious conversion allows the gang to continue exerting power over the deserters, while at the same time enforcing religious commitment to the congregation. The religious community provides the normative framework that reassures the gang that its former associates will not act against it, consolidating its local authority.
The protective impacts of Spirulina platensis against cisplatin-induced renal injury through the regulation of oxidative stress, pro-inflammatory cytokines and Bax/Bcl2
Authors: Abouzed Tarek Kamal , Soliman Mohamed Mohamed , Khatab Shymaa A , Gouda Wael M , Eldomany Ehab B , Dorghamm Doaa Abdullah
Published: January 2022

One of the main antineoplastic chemotherapy medications is cisplatin, of which nephropathy is a major side effect. In this current study, we aim to investigate the molecular protective effect of Spirulina platensis (SP) on cisplatin-induced nephrotoxicity. In total, 48 healthy male albino rats were allocated into 4 groups. Group 1 received saline intraperitoneally (IP) twice per week (normal rats). Group 2 received SP (100 mg/kg BW orally). Group 3 were injected with cisplatin (1.5 mg/kg IP) twice per week. Group 4 received SP and on the 4th day received cisplatin (1.5 mg/kg IP) for 21 days. After 3 weeks of experiment, blood and renal tissues were taken for serum analysis, gene expression using qRT-polymerase chain reaction, and renal histopathology. As per our findings, it was found that SP significantly ameliorated the alterations in body weight, relative kidney weight, and the disturbance in examined renal markers. Furthermore, SP recovered and restored cisplatin-induced oxidative stress biomarkers (MDA and NO) and antioxidant activity (SOD and GSH) and cisplatin-induced upregulation in the gene expression of TNF-α, inducible nitric oxide synthase, TGF1-β, IL-1β, and IL-6. Interestingly, these gene expressions were ameliorated by the SP pre-administration. Furthermore, cisplatin upregulated pro-apoptotic gene Bax, whereas it downregulated anti-apoptotic gene Bcl2. Interestingly, SP mitigated this alteration in apoptosis and anti-apoptotic associated genes. Renal histopathology revealed the protective impacts of SP against cisplatin-induced severe glomerular congestion, hemorrhage, inflammatory cell infiltration, degeneration, and severe necrosis in renal glomeruli and tubules. In conclusion, SP has a protective effect against cisplatin-induced renal damage through modulating oxidative stress and anti-inflammatory, anti-necrotic, and anti-apoptotic-associated genes.
Mapping of Crown Rust (Puccinia coronataf. sp.avenae) Resistance GenePc54and a Novel Quantitative Trait Locus Effective Against Powdery Mildew (Blumeria graminisf. sp.avenae) in the Oat (Avena sativa) Line Pc54
Authors: Admassu-Yimer Belayneh , Klos Kathy Esvelt , Griffiths Irene , Cowan Alexander , Howarth Catherine
Published: January 2022

The Pc54 oat line carries the crown rust resistance gene Pc54 and an unknown gene effective against powdery mildew. In this study, two recombinant inbred line (RIL) populations were developed to identify the genomic locations of the two genes and produce lists of molecular markers with a potential for marker-assisted selection. The RILs and parents were phenotyped for crown rust and powdery mildew in a controlled environment. They were also genotyped using the 6K Illumina Infinium iSelect oat single nucleotide polymorphism (SNP) chip. Multiple interval mapping placed Pc54 on the linkage group Mrg02 (chromosome 7D) and the novel powdery mildew quantitative trait locus (QTL) QPm.18 on Mrg18 (chromosome 1A) both in mapping and in the validating populations. A total of 9 and 31 significant molecular markers were identified linked with the Pc54 gene and QPm.18, respectively. Reactions to crown rust inoculations have justified separate identities of Pc54 from other genes and QTLs that have previously been reported on Mrg02 except for qPCRFd. Pm3 is the only powdery mildew resistance gene previously mapped on Mrg18. However, the pm3 differential line, Mostyn, was susceptible to the powdery mildew race used in this study, suggesting that Pm3 and QPm.18 are different genes. Determining the chromosomal locations of Pc54 and QPm.18 is helpful for better understanding of the molecular mechanism of resistance to crown rust and powdery mildew in oats. Furthermore, SNPs and single sequence repeats that are closely linked with the genes could be valuable for developing PCR-based molecular markers and facilitating the utilization of these genes in oat breeding programs.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Sodium Valproate Is Effective Against Botrytis cinerea Infection of Tomato by Enhancing Histone H3 Acetylation-Directed Gene Transcription and Triggering Tomato Fruit Immune Response
Authors: Xu Yang , Wang Yameng , Wang Lulu , Liang Wenxing , Yang Qianqian
Published: January 2022

Botrytis cinerea causes gray mold resulting in enormous financial loss. Fungicide resistance of B. cinerea has become a serious issue in food safety and agricultural environmental protection. Sodium valproate (SV) has been used in clinical trials; thus, it is an excellent candidate for fungicide development, considering its safety. However, the antifungal activity remains unclear. SV was effective against B. cinerea by enhancing acetylation of histone H3, including H3K9ac, H3K14ac, and H3K56ac. A transcriptomics analysis revealed that the expression of 1,557 genes changed significantly in response to SV. A pathway enrichment analysis identified 16 significant GO terms, in which molecular functions were mainly involved. In addition, the expression levels of 13 genes involved in B. cinerea virulence and five genes involved in tomato immune response were altered by the SV treatment. These results indicate that SV inhibits B. cinerea by enhancing acetylation of histone H3 and modifying gene transcription. Thus, SV is an effective, safe, potential antifungal agent for control of both pre- and postharvest losses caused by B. cinerea.
Professional Roles of Oncologic Specialty Physical Therapists in the United States
Authors: Stout Nicole L. , Pfalzer Lucinda , Drouin Jacqueline S , Litterini Amy , Tible Amy , Demarse Elizabeth
Published: January 2022

Background:

Oncologic specialty physical therapists (OncPTs) are a growing discipline in the cancer workforce. The complexities of cancer care delivery and the multidimensional nature of cancer care teams require oncology providers to serve in professional roles beyond clinical care. This project aims to assess the professional roles that OncPTs play in cancer care delivery.

Methods:

A 27-item survey was developed by the Oncologic Specialty Council of the American Board of Physical Therapy Specialties and sent electronically to board-certified oncologic clinical specialists in the United States. The survey was open for 45 days. Demographics of the population and frequency data were analyzed in Qualtrics.

Results:

Fifty-seven complete surveys were received out of 106 eligible specialists (response rate 53%). Respondents were predominantly female (91%) and White (78%). Fifty-six percent (n = 32) had greater than 15 years of practice experience and 68% (n = 39) held DPTs. Seventy-three percent reported greater than 50% of their work week dedicated to oncology practice and 52.6% reported providing consultations or treatment in the physical space of a cancer center. All respondents have been board-certified OncPTs for at least 1 year. Providing clinical care accounted for 71% of the cohorts' work time and 14% was spent in program development (outside of clinical care). Specialists reported oncology-specific program development responsibilities across 3 themes: workforce development (mentoring and teaching peers and staff), establishing clinical practice standards (standardizing assessment tools and clinical pathways), and program assessment (quality improvement and research). The OncPT professional roles included leadership responsibilities within their health system (n = 24) and leadership or committee roles in rehabilitation-specific professional organizations (n = 55). No respondents reported serving in roles regarding research mentorship or advising on state policy or payer issues, and 1 respondent identified a role in advising on federal policy issues.

Conclusion:

Oncologic specialty physical therapists primarily serve clinical patient care roles. Aside from clinical practice, program development roles focus on rehabilitation-centric staff and student education and clinical pathways for rehabilitation care delivery. However, at the cancer care delivery system level, participation in professional roles beyond the rehabilitation clinic is less frequent. Gaps in participation are identified at the societal level with no representation from this cohort in payment and policy initiatives at the state and federal levels. We provide a roadmap to action that describes multilevel interventions to improve the integration of OncPTs into cancer care delivery. These findings may inform competencies for clinical specialists and guide residency program development.
Interprofessional Collaborative Practice and Education in Oncology: Practical Applications and Experiences, From Physical Therapy Classroom to Clinic
Authors: Yoon Lisa , Brough Colleen , Fu Wing , Johnson Michael
Published: January 2022

Oncology is a complex clinical domain that requires physical therapists (PTs) to engage in multidisciplinary collaboration to achieve optimal patient outcomes. The emerging role of PT in oncology highlights the need to include interprofessional education (IPE) and interprofessional collaborative practice (IPCP) during entry-level training, yet few curricular models, which integrate IPE and IPCP, exist. New clinical opportunities in oncology within our Doctor of Physical Therapist (DPT) program create a multidimensional platform for students to engage with the entire health care team to address the complex needs of this population, and to demonstrate the value of the PT as a member. Such opportunities not only meet the standards and required elements of DPT education, but are initiatives supported by the World Health Organization, and the American Physical Therapy Association. The purpose of this article is to highlight opportunities and practical strategies employed by one academic institution to integrate IPE and IPCP into their entry-level program, share lessons learned, and ideas for future development of this important topic. In our integrated curricular model, physical therapist students learn about the roles and responsibilities of each interprofessional team member, learn to share information, and collaborate during a dynamic and practical clinical environment under the supervision of faculty. Knowledge from previous didactic coursework is applied to pediatric and adult oncology survivors participating in a wellness program or group exercise class. All activities and exercises are modified based on the patients' needs and responses.
Concise Definitive Review for Reinitiation of Antidepressants, Antipsychotics, and Gabapentinoids in ICU Patients
Authors: Cucci Michaelia D. , Chester Katleen W. , Hamilton Leslie A.
Published: January 2022

OBJECTIVE:

Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients.

DATA SOURCES:

Available literature on PubMed and MEDLINE databases.

STUDY SELECTION:

Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included.

DATA EXTRACTION:

Eligible studies were identified by authors, and recommendations were summarized.

DATA SYNTHESIS:

Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay.

CONCLUSIONS:

Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.
Noninvasive prenatal diagnosis of congenital factor XIII deficiency in Iran
Authors: Motlagh Hoda , Dorgalaleh Akbar , Tabibian Shadi , Naderi Majid , Zaker Farhad
Published: January 2022

Congenital factor (F) XIII deficiency is a rare coagulation factor deficiency that is inherited in an autosomal recessive manner. FXIII deficiency presents various clinical manifestations, such as intracranial hemorrhage (ICH), which is the most common cause of morbidity and mortality. As ICH can occur in the neonatal period, prenatal diagnosis (PND) is an effective way to reduce neonatal ICH and its associated fatal consequences. In this study, we investigated a noninvasive prenatal diagnosis (NIPD) method, cell-free fetal DNA (cffDNA), for PND in FXIII deficiency. This study was conducted on seven pregnant women in the first trimester. After extraction of cffDNA from maternal plasma, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to find the underlying F13A gene mutations previously identified in the family members. PCR-RFLP was also performed on postnatal DNA samples. Sanger sequencing was performed to confirm the results. Four cases were heterozygous for F13A gene mutations, whereas three were unaffected. PCR- RFLP results for cffDNA and postnatal DNA samples were identical, and Sanger sequencing confirmed the results. cffDNA is a noninvasive and effective method for PND in congenital FXIII deficiency.
Hidden Telltale Signs in Hyperacute Ischemic Stroke Caused by Aortic Dissection
Authors: Ge Beihai , Wei Ninglin , Mo Yun , Qin Guangping , Li Huiyue , Xu Guolong
Published: January 2022

Introduction:

Rapid identification of hidden telltale signs in hyperacute ischemic stroke caused by aortic dissection (AD) is challenging, mainly owing to the narrow time window for bridging therapy.

Case Report:

A 63-year-old man was referred for sudden right-side weakness accompanied by a decreased level of consciousness for almost 1 hour and 37 minutes. He had a history of hypertension. His skin was clammy, and on physical examination, there was involuntary chest thumping in the left upper limb. Hyperacute cerebral infarction was considered after no bleeding was observed on emergency head computed tomography, and intravenous thrombolysis with alteplase was administered immediately after. The patient was then taken to the catheter room, ready for endovascular thrombectomy. Stanford type A AD was found by cerebral angiography before endovascular thrombectomy. The infusion of alteplase was stopped immediately during cerebral angiography, but the patient’s blood pressure, heart rate, and blood oxygen were still declining progressively, and the degree of consciousness disturbance deepened. The patient died after the combined but failed rescue attempts of multiple departments.

Conclusion:

Hyperacute ischemic stroke caused by AD often hides some telltale signs. Clinicians should master basic clinical skills to exclude AD by looking for these telltale signs hidden in hyperacute ischemic stroke to avoid the fatal consequences of intravenous thrombolysis and/or cerebral angiography within the narrow window of time.
Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls
Authors: Yokota Rumi , Kwiatkowski David M. , Journel Chloe , Adamson Greg T. , Zucker Evan , Suarez Geovanna , Lechich Kirstie M. , Chaudhuri Abanti , Collins R. Thomas
Published: January 2022

OBJECTIVES:

Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery–related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI.

DESIGN:

This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure.

SETTING:

Patients underwent cardiac surgery and postoperative care at Lucile Packard Children’s Hospital Stanford.

PATIENTS:

There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7–3.8 yr) for WS and 1.7 years (IQR, 0.8–3.1 yr) for controls.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.

Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1–16; p = 0.034). Higher RPP at postoperative hours 9–16 was associated with decreased OR of CS-AKI (0.88 [0.8–0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14–1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13–3.17]; p = 0.015).

CONCLUSIONS:

The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.
Comparison of infectious SARS-CoV-2 from the nasopharynx of vaccinated and unvaccinated individuals
Authors: Peña-Hernández Mario A. , Klein Jon , Malik Amyn A. , Coppi Andreas , Kalinich Chaney , Vogels Chantal B. F. , Silva Julio ,   Yale SARS-CoV-2 Genomic Surveillance Initiative, Peaper David R. , Landry Marie-Louise , Wilen Craig , Grubaugh Nathan D. , Schulz Wade , Omer Saad B. , Iwasaki Akiko
Published: January 2022

The frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinated and 53 unvaccinated individuals, to assess the levels of infectious virus in vaccinated and unvaccinated individuals. Quantitative plaque assays showed no significant differences in the titers of virus between these cohorts. However, the proportion of nasopharyngeal samples with culturable virus was lower in the vaccinated patients relative to unvaccinated patients (21% vs. 40%). Finally, time-to-event analysis with Kaplan-Myer curves revealed that protection from culturable infectious virus waned significantly starting at 5 months after completing a 2-dose regimen of mRNA vaccines. These results have important implications in timing of booster dose to prevent onward transmission from breakthrough cases.
Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveal the potential role of ketogenesis to slow tumor growth: A secondary analysis of the CAPS2 diet trial
Authors: Chi Jen-Tsan , Lin Pao-Hwa , Tolstikov Vladimir , Howard Lauren , Chen Emily Y. , Bussberg Valerie , Greenwood Bennett , Narain Niven R. , Kiebish Michael A. , Freedland Stephen J.
Published: January 2022

Background

Systemic treatments for prostate cancer (PC) have significant side effects. Thus, newer alternatives with fewer side effects are urgently needed. Animal and human studies suggest the therapeutic potential of low carbohydrate diet (LCD) for PC. To test this possibility, Carbohydrate and Prostate Study 2 (CAPS2) trial was conducted in PC patients with biochemical recurrence (BCR) after local treatment to determine the effect of a 6-month LCD intervention vs. usual care control on PC growth as measured by PSA doubling time (PSADT). We previously reported the LCD intervention led to significant weight loss, higher HDL, and lower triglycerides and HbA1c with a suggested longer PSADT. However, the metabolic basis of these effects are unknown.

Methods

To identify the potential metabolic basis of effects of LCD on PSADT, serum metabolomic analysis was performed using baseline, month 3, and month 6 banked sera to identify the metabolites significantly altered by LCD and that correlated with varying PSADT.

Results

LCD increased the serum levels of ketone bodies, glycine and hydroxyisocaproic acid. Reciprocally, LCD reduced the serum levels of alanine, cytidine, asymmetric dimethylarginine (ADMA) and 2-oxobutanoate. As high ADMA level is shown to inhibit nitric oxide (NO) signaling and contribute to various cardiovascular diseases, the ADMA repression under LCD may contribute to the LCD-associated health benefit. Regression analysis of the PSADT revealed a correlation between longer PSADT with higher level of 2-hydroxybutyric acids, ketone bodies, citrate and malate. Longer PSADT was also associated with LCD reduced nicotinamide, fructose-1, 6-biphosphate (FBP) and 2-oxobutanoate.

Conclusion

These results suggest a potential association of ketogenesis and TCA metabolites with slower PC growth and conversely glycolysis with faster PC growth. The link of high ketone bodies with longer PSADT supports future studies of ketogenic diets to slow PC growth.
Robust expansion of phylogeny for fast-growing genome sequence data
Authors: Ye Yongtao , Shum Marcus H. , Tsui Joseph L. , Yu Guangchuang , Smith David K. , Zhu Huachen , Wu Joseph T. , Guan Yi , Lam Tommy T.
Published: January 2022

Massive sequencing of SARS-CoV-2 genomes has led to a great demand for adding new samples to a reference phylogeny instead of building the tree from scratch. To address such challenge, we proposed an algorithm ‘TIPars’ by integrating parsimony analysis with pre-computed ancestral sequences. Compared to four state-of-the-art methods on four benchmark datasets (SARS-CoV-2, Influenza virus, Newcastle disease virus and 16S rRNA genes), TIPars achieved the best performance in most tests. It took only 21 seconds to insert 100 SARS-CoV-2 genomes to a 100k-taxa reference tree using near 1.4 gigabytes of memory. Its efficient and accurate phylogenetic placements and incrementation for phylogenies with highly similar and divergent sequences suggest that it will be useful in a wide range of studies including pathogen molecular epidemiology, microbiome diversity and systematics.