bluuebunny/crossref_metadata_2025 huggingface dataset:
wrk-1 and rig-5 control pioneer and follower axon navigation in the ventral nerve cord of Caenorhabditis elegans in a nid-1 mutant background
Authors: Feresten Abigail H , Bhat Jaffar M , Yu Alex J , Zapf Richard , Rankin Catharine H , Hutter Harald
Published: December 2022

During nervous system development, neurons send out axons, which must navigate large distances to reach synaptic targets. Axons grow out sequentially. The early outgrowing axons, pioneers, must integrate information from various guidance cues in their environment to determine the correct direction of outgrowth. Later outgrowing follower axons can at least in part navigate by adhering to pioneer axons. In Caenorhabditis elegans, the right side of the largest longitudinal axon tract, the ventral nerve cord, is pioneered by the AVG axon. How the AVG axon navigates is only partially understood. In this study, we describe the role of two members of the IgCAM family, wrk-1 and rig-5, in AVG axon navigation. While wrk-1 and rig-5 single mutants do not show AVG navigation defects, both mutants have highly penetrant pioneer and follower navigation defects in a nid-1 mutant background. Both mutations increase the fraction of follower axons following the misguided pioneer axon. We found that wrk-1 and rig-5 act in different genetic pathways, suggesting that we identified two pioneer-independent guidance pathways used by follower axons. We assessed general locomotion, mechanosensory responsiveness, and habituation to determine whether axonal navigation defects impact nervous system function. In rig-5 nid-1 double mutants, we found no significant defects in free movement behavior; however, a subpopulation of animals shows minor changes in response duration habituation after mechanosensory stimulation. These results suggest that guidance defects of axons in the motor circuit do not necessarily lead to major movement or behavioral defects but impact more complex behavioral modulation.
Short-term consumption of the mycotoxin zearalenone by pubertal gilts causes persistent changes in the histoarchitecture of reproductive tissues
Authors: Soffa Dallas R , Stewart Jacob W , Pack Erica D , Arneson Alicia G , De Vita Raffaella , Knight James W , Fausnacht Dane W , Rhoads Robert P , Clark Sherrie G , Schmale David G , Rhoads Michelle L
Published: December 2022

Consumption of zearalenone (ZEN) detrimentally affects tissues and systems throughout the body, and these deleterious effects are especially pronounced in swine. The objectives of this project were to determine the effects of short-term consumption of ZEN (at concentrations that could be found on-farm) on growth, carcass weight, liver weight, and reproductive tissues of pubertal gilts, and to determine if the effects are transient or persistent. Cross-bred gilts (107.25 ± 2.69 kg) were randomly assigned to one of three feed treatments: 1) solvent only for 21 d (CON; n = 10), 2) ZEN for 7 d followed by 14 d of solvent (ZEN-7; 6 mg/d; n = 10), and 3) ZEN for 21 d (ZEN-21; 6 mg/d; n = 10). Body weights were collected at the beginning and end of the experiment (189.1 ± 0.8 and 211.1 ± 0.8 d of age, respectively). Carcass weights and tissues were collected at harvest. There were no treatment-based differences in growth, carcass, liver, or reproductive tissue weights. Histological analyses revealed differences based on treatment and the interaction between treatment and luteal status. The thickness of the ampullary muscularis declined with ZEN exposure (P < 0.05), while the isthmic epithelial cell height (P < 0.01) and uterine endometrial thickness (P < 0.02) increased. Interestingly, the thickness of the isthmic muscularis, uterine myometrium, and epithelial cell height only differed in the presence of a corpus luteum. Uterine epithelial cell height in the luteal phase was lowest in ZEN-7 pigs (P < 0.01). The isthmic muscularis in the luteal phase was thinner in pigs from both ZEN treatments (P < 0.01). Conversely, the luteal-stage myometrium was thicker in pigs from both ZEN treatments (P < 0.01). The discovery of these tissue-based differences during the luteal phase is particularly concerning since this corresponds with the time when embryos would be affected by the functional competency of the oviduct and uterus. The results of this work demonstrate that short-term consumption of ZEN produces microscopic, but not macroscopic alterations in reproductive organs which are likely to have negative effects on their subsequent function and that these differences persist even after ZEN consumption ceases. Taken together, these results indicate that it is insufficient to rely solely on outwardly visible symptoms as indicators of zearalenone exposure, as detrimental effects on reproductive tissues were found in the absence of phenotypic and morphologic changes.
Sunflower-Associated Reductions in Varroa Mite Infestation of Honey Bee Colonies
Authors: Palmer-Young Evan C , Malfi Rosemary , Zhou Yujun , Joyce Bryanna , Whitehead Hannah , Van Wyk Jennifer I , Baylis Kathy , Grubbs Kyle , Boncristiani Dawn L , Evans Jay D , Irwin Rebecca E , Adler Lynn S
Published: December 2022

Landscapes can affect parasite epidemiology in wild and agricultural animals. Honey bees are threatened by loss of floral resources and by parasites, principally the mite Varroa destructor and the viruses it vectors. Existing mite control relies heavily on chemical treatments that can adversely affect bees. Alternative, pesticide-free control methods are needed to mitigate infestation with these ectoparasites. Many flowering plants provide nectar and pollen that confer resistance to parasites. Enrichment of landscapes with antiparasitic floral resources could therefore provide a sustainable means of parasite control in pollinators. Floral rewards of Asteraceae plants can reduce parasitic infection in diverse bee species, including honey and bumble bees. Here, we tested the effects of sunflower (Helianthus annuus) cropland and pollen supplementation on honey bee resistance to macro- and microparasites. Although sunflower had nonsignificant effects on microparasites, We found that increased sunflower pollen availability correlated with reduced Varroa mite infestation in landscapes and pollen-supplemented colonies. At the landscape level, each doubling of sunflower crop area was associated with a 28% reduction in mite infestation. In field trials, late-summer supplementation of colonies with sunflower pollen reduced mite infestation by 2.75-fold relative to artificial pollen. United States sunflower crop acreage has declined by 2% per year since 1980, however, suggesting reduced availability of this floral resource. Although further research is needed to determine whether the observed effects represent direct inhibition of mite fecundity or mite-limiting reductions in honey bee brood-rearing, our findings suggest the potential for sunflower plantings or pollen supplements to counteract a major driver of honey bee losses worldwide.
Improvement of rimocidin production in Streptomyces rimosus M527 by reporter-guided mutation selection
Authors: Jiang Yujie , Zhang Jinyao , Huang Xinyi , Ma Zheng , Zhang Yongyong , Bechthold Andreas , Yu Xiaoping
Published: December 2022

In this study, we employed a reporter-guided mutation selection (RGMS) strategy to improve the rimocidin production of Streptomyces rimosus M527, which is based on a single-reporter plasmid pAN and atmospheric and room temperature plasma (ARTP). In plasmid pAN, PrimA, a native promoter of the loading module of rimocidin biosynthesis (RimA) was chosen as a target, and the kanamycin resistance gene (neo) under the control of PrimA was chosen as the reporter gene. The integrative plasmid pAN was introduced into the chromosome of S. rimosus M527 by conjugation to yield the initial strain S. rimosus M527-pAN. Subsequently, mutants of M527-pAN were generated by ARTP. 79 mutants were obtained in total, of which 67 mutants showed a higher level of kanamycin resistance (Kanr) than that of the initial strain M527-pAN. The majority of mutants exhibited a slight increase in rimocidin production compared with M527-pAN. Notably, 3 mutants, M527-pAN-S34, S38, and S52, which exhibited highest kanamycin resistance among all Kanr mutants, showed 34%, 52%, and 45% increase in rimocidin production compared with M527-pAN, respectively. Quantitative RT-PCR analysis revealed that the transcriptional levels of neo and rim genes were increased in mutants M527-pAN-S34, S38, and S52 compared with M527-pAN. These results confirmed that the RGMS approach was successful in improving the rimocidin production in S. rimosus M527.
Surgical Capability Utilization Time for Military Casualties at Role 2 and Role 3 Facilities
Authors: Hall Andrew , Graham Brock , Hanson Matthew , Stern Caryn
Published: December 2022

Introduction

Operative capability utilization time for casualties is an important metric for trauma planning in the military. Operative capabilities can be a choke point resulting in multiple patients waiting for the asset to become available during mass casualty events. The objective measurement of how long deployed operative capabilities are utilized for various categories of injury has not been described. This study provides the measurements for role 2 and role 3 facilities.

Materials and Methods

The Department of Defense Trauma Registry was sampled for each composite injury severity score (ISS) category in the registry (mild, moderate, severe, and critical). Thirty randomly selected samples for role 2 and role 3 facilities for each composite ISS category with an anesthesia record including a start and end time for the index surgical case were included.

Results

There were no statistical differences between role 2 and role 3 facility operative capability utilization times for any composite ISS category. The mean time (min) for mild, moderate, severe, and critical for role 2 and role 3 was 93.9 and 96.3, 142.2 and 144.3, 177.4 and 171.1, 182.9 and 205.6, respectively. The proportion of Department of Defense Trauma Registry surgical patients who were mild, moderate, severe, or critical were 57.5%, 18.2%, 13.6%, and 10.7%, respectively.

Conclusion

There is no statistical difference between roles of care in operative asset utilization time. The provided operative capability utilization times will be useful for casualty management planning and improvement initiatives.
Differences and synergies between local energy communities and microgrids
Authors: Hatziargyriou Nikos
Published: December 2022

This article reviews the basic definitions of microgrids and local energy communities in an attempt to clarify misconceptions, identify differences and find overlaps and similarities. It is shown that there are distinct differences between the two concepts; however, certain categories of microgrids, like the community microgrids, share common characteristics with local energy communities. In fact, the significant technical knowhow of the microgrids community and the advancements in decentralized techniques can critically support the operation and development of local energy communities. Microgrids can be regarded as valuable allies of local energy communities.
L’utilisation des probiotiques dans la population pédiatrique
Authors: Schneider Rilla , Sant’Anna Ana
Published: December 2022

Le présent document de principes définit les probiotiques et fournit une analyse des publications scientifiques les plus récentes sur leur utilisation en pédiatrie. De nombreuses études ont évalué les avantages potentiels des probiotiques, mais en raison des variations importantes dans les souches et les doses utilisées, des populations de patients étudiées et des méthodologies privilégiées, les résultats sont hétérogènes. Selon les données probantes à jour, les probiotiques peuvent réduire le taux de mortalité et l’incidence d’entérocolite nécrosante chez les nouveau-nés prématurés et de petit poids à la naissance. Ils peuvent également être bénéfiques pour réduire l’intolérance alimentaire. Chez les nourrissons, on peut envisager de les utiliser pour limiter les symptômes de coliques, et chez les enfants plus âgés, pour prévenir la diarrhée associée aux antibiotiques ou au Clostridium difficile. Les suppléments de probiotiques utilisés conjointement avec un traitement standard peuvent contribuer à éradiquer l’Helicobacter pylori et à atténuer les effets secondaires du traitement. On peut envisager d’utiliser des espèces de Lactobacillus pour traiter le syndrome du côlon irritable ou de recourir à des probiotiques pour contribuer à prévenir la dermatite atopique et l’eczéma. Afin d’optimiser les politiques et les pratiques en pédiatrie, de vastes études de qualité devront être réalisées pour déterminer les types et les combinaisons de probiotiques les plus efficaces.
Beyond a platform protein for the degradosome assembly: The Apoptosis-Inducing Factor as an efficient nuclease involved in chromatinolysis
Authors: Novo Nerea , Romero-Tamayo Silvia , Marcuello Carlos , Boneta Sergio , Blasco-Machin Irene , Velázquez-Campoy Adrián , Villanueva Raquel , Moreno-Loshuertos Raquel , Lostao Anabel , Medina Milagros , Ferreira Patricia
Published: December 2022

The Apoptosis-Inducing Factor (AIF) is a moonlighting flavoenzyme involved in the assembly of mitochondrial respiratory complexes in healthy cells, but also able to trigger DNA cleavage and parthanatos. Upon apoptotic-stimuli, AIF redistributes from the mitochondria to the nucleus, where upon association with other proteins such as endonuclease CypA and histone H2AX, it is proposed to organize a DNA–degradosome complex. In this work, we provide evidence for the molecular assembly of this complex as well as for the cooperative effects among its protein components to degrade genomic DNA into large fragments. We have also uncovered that AIF has nuclease activity that is stimulated in the presence of either Mg2+ or Ca2+. Such activity allows AIF by itself and in cooperation with CypA to efficiently degrade genomic DNA. Finally, we have identified TopIB and DEK motifs in AIF as responsible for its nuclease activity. These new findings point, for the first time, to AIF as a nuclease able to digest nuclear dsDNA in dying cells, improving our understanding of its role in promoting apoptosis and opening paths for the development of new therapeutic strategies.
Pathogen-Derived Extracellular Vesicles: Emerging Mediators of Plant-Microbe Interactions
Authors: Wang Zhangying , Zeng Jiayue , Deng Jiliang , Hou Xiangjie , Zhang Jiefu , Yan Wei , Cai Qiang
Published: December 2022

Extracellular vesicles (EVs) are lipid bilayer–enclosed nanoparticles that deliver bioactive proteins, nucleic acids, lipids, and other small molecules from donor to recipient cells. They have attracted significant interest recently due to their important roles in regulating plant-microbe interaction. During microbial infection, plant EVs play a prominent role in defense by delivering small regulatory RNA into pathogens, resulting in the silencing of pathogen virulence genes. Pathogens also deliver small RNAs into plant cells to silence host immunity genes. Recent evidence indicates that microbial EVs may be involved in pathogenesis and host immunity modulation by transporting RNAs and other biomolecules. However, the biogenesis and function of microbial EVs in plant-microbe interaction remain ill-defined. In this review, we discuss various aspects of microbial EVs, with a particular focus on current methods for EV isolation, composition, biogenesis, and their roles in plant-microbe interaction. We also discussed the potential role of microbial EVs in cross-kingdom RNA trafficking from pathogens to plants, as it is a highly likely possibility to explore in the future.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Rubber Tree (Heveae brasiliensis) MLO Protein HbMLO12 Promotes Plant Susceptibility to Sustain Infection by a Powdery Mildew Fungus
Authors: Li Xiao , Zhao Wenyuan , Zhang Zhongming , Fang Yuxiao , Dong Linpeng , Yin Jinyao , Liu Yuhan , Chen Daipeng , Li Zhigang , Liu Wenbo , Lin Chunhua , Miao Weiguo
Published: December 2022

Powdery mildew severely affects several important crops and cash plants. Disruption of mildew resistance locus O ( MLO) genes elevates resistance against powdery mildew in several plants. However, whether rubber tree ( Heveae brasiliensis) MLO proteins are linked to susceptibility remains unknown, owing to technical limitations in the genetic manipulation of this woody plant. A previous study showed that the H. brasiliensis MLO-like protein HbMLO12 demonstrates high amino acid sequence similarity with the known Arabidopsis MLO protein AtMLO12. In this study, we investigated whether HbMLO12 regulates susceptibility to powdery mildew. H. brasiliensis leaves take up exogenously synthesized double-stranded RNAs (dsRNAs), and foliar application of dsRNA homologous to HbMLO12 gene specifically induces HbMLO12 silencing in H. brasiliensis leaf tissues. Notably, HbMLO12 silencing inhibited fungal infection and elevated the immune response during interaction with the rubber tree powdery mildew fungus. Furthermore, the heterologous expression of HbMLO12 suppressed bacterial flg22– and fungal chitin–induced immune responses and enhanced bacterial infection in Arabidopsis. Our study provides evidence that HbMLO12 contributes to susceptibility to powdery mildew.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Papaya Sticky Disease Caused by Virus “Couples”: A Challenge for Disease Detection and Management
Authors: Quito-Avila Diego F. , Reyes-Proaño Edison , Cañada Gabriela , Cornejo-Franco Juan F. , Alvarez-Quinto Robert , Moreira Lisela , Grinstead Sam , Mollov Dimitre , Karasev Alexander V.
Published: December 2022

Papaya sticky disease (PSD) is a major virus disorder of papaya (Carica papaya). The disease is characterized by fruit damage caused by the oxidation of spontaneously exuded latex. In Brazil, PSD is caused by the coinfection of two viruses, papaya meleira virus (PMeV), a toti-like virus, and papaya meleira virus-2 (PMeV-2), an umbra-like virus. The disorder has also been reported in Mexico and, more recently, in Australia, but the presence of both PMeV and PMeV-2 in symptomatic plants has been documented only in Brazil. In 2021, 2-year-old papaya plants (cultivar Passion Red) exhibiting PSD-like symptoms were observed in Santa Elena Province, Ecuador. Molecular tests of leaf tissue and fruit latex from symptomatic plants failed to detect PMeV. However, papaya virus Q (PpVQ), an umbra-like virus related to but distinct from PMeV-2, and a novel virus, tentatively named papaya sticky fruit-associated virus (PSFaV), were found in the symptomatic samples. PSFaV shares 56% nucleotide identity with the genome of PMeV, suggesting that PSD symptoms can be caused by “couples” of viruses related to but distinct from PMeV (a toti-like virus) and PMeV-2 (an umbra-like virus). This review discusses the history and epidemiology of PSD and the genomic features of newly discovered virus couples involved in this syndrome. Given the unusual etiology of PSD, which involves distinct virus species, the importance of implementing proper diagnostic approaches for PSD is highlighted.
Addressing nurses' prolonged grief due to the COVID-19 pandemic
Authors: Wilson-Mooney Catherine , Smith Erin Murphy , Browne-Bradwisch Sarah A.
Published: December 2022

The COVID-19 pandemic resulted in physical and emotional tolls on healthcare workers and caregivers, which have caused prolonged grief disorder and persistent complex bereavement disorder. Highlighting key learnings from healthcare workers' experiences during the pandemic, this article outlines self-care strategies to help nurses better prepare for future healthcare emergencies.
Yellowknife: Canada’s First Circumpolar Family Medicine Residency Site
Authors: Horvey Samantha , Babenko Oksana , Szafran Olga , D’Hont Thomsen , Heyes Kajsa , Pontin David
Published: December 2022

Problem

Canada’s Northwest Territories (NWT), like other regions in the circumpolar north primarily inhabited by Indigenous peoples, faces challenges in recruiting and retaining physicians. Communities in this vast, diverse region depend largely on external medical professionals for health care. Consequently, these communities receive discontinuous medical care from physicians who lack local knowledge and are available only temporarily. The shortage of physicians for people residing in northern Canada requires a sustainable, long-term solution.

Approach

The authors describe establishing Canada’s first circumpolar family medicine residency training site in Yellowknife, NWT. The site was launched in 2020 as a partnership between the University of Alberta, Alberta Health Services, and 3 local health authorities in the NWT. The residency site, which bases residents in the local community, is expected to positively impact family physician recruitment and retention by allowing residents to build connections with local communities and identify as a northern physician.

Outcomes

As of fall 2022, 4 residents had trained with the Yellowknife family medicine residency site. Two of these 4 residents graduated in 2022, both of whom plan to continue practicing medicine in the NWT. Residents have positively influenced medical care in the NWT, providing care in close to 20 small and remote communities. The presence of residents decreased appointment wait-times for some teams by as much as 60%, improved primary care screening, and enabled the provision of medical services at critical times. Furthermore, their presence has fostered academic spirit in the medical communities and had a positive impact on the communities as a whole.

Next Steps

The authors provide key insights and lessons learned from the establishment of the remote residency site. To develop and improve the site, continuous program evaluation is planned.
Postmastectomy breast reconstruction for women with hereditary gastric and breast cancer syndrome
Authors: De Lorenzi Francesca , Borelli Francesco , Catapano Simone , Alessandri-Bonetti Mario , Sala Pietro , Veronesi Paolo
Published: December 2022

Post mastectomy reconstruction is nowadays an integral part of breast cancer treatment, usually performed in the immediate setting. Among women with hereditary gastric and breast cancer syndromes, three different scenarios can be identified. First, healthy women seeking for prophylactic mastectomies. Second, cancer patients requiring mastectomy at the tumor site and simultaneous risk reducing mastectomy of the healthy breast. Third, cancer patients who have been treated for primary cancer requiring risk reducing mastectomies in a further stage. In this paper, we present a schematic guide for reconstruction for each subpopulation of subjects and their peculiarities.
Comparing acupoint catgut embedding and acupuncture therapies for simple obesity: A systematic review and meta-analysis
Authors: Zhao Hui Yan , Kim Sungha , Son Mi Ju
Published: December 2022

Background:

This systematic review aimed to assess the effectiveness and safety of acupoint catgut embedding (ACE), which is widely used in simple obese patients.

Methods:

Nine electronic databases and 2 trial registries were searched from inception to September 2021 without language limitations. All randomized controlled trials involving ACE therapies for simple obesity were included. Assessment of Cochrane’s risk of bias and meta-analysis, as well as GRADE evaluation, were also performed.

Results:

A total of 73 randomized clinical trials involving 5872 participants were included. The overall risk of bias was high or unclear. ACE showed higher efficacy in total effective rate, body mass index, and body weight than manual acupuncture. In addition, ACE is more beneficial in total effective rate than electroacupuncture (EA). Moreover, combination therapy of ACE with EA is more effective in total body mass index and body weight than EA alone.

Conclusions:

Despite some potential improvement, the evidence regarding the effectiveness and efficacy of ACE for simple obesity is inconclusive due to the poor quality of evidence. Further well-designed randomized controlled trials are needed to confirm the effectiveness of ACE for simple obesity.
A prognostic risk prediction model based on ferroptosis-related long non-coding RNAs in bladder cancer: A bulk RNA-seq research and scRNA-seq validation
Authors: Xiang Xuebao , Guo Yi , Chen Zhongyuan , Zhang Fangxin , Huang Jiefu , Qin Yan
Published: December 2022

Background:

To construct a prognostic risk model of bladder cancer (BC) from the perspective of long non-coding RNAs (lncRNAs) and ferroptosis, in order to guide clinical prognosis and identify potential therapeutic targets.

Methods:

In-hours BC samples were collected from 4 patients diagnosed with BC, who underwent radical cystectomy. Single cell transcriptome sequencing was performed and Seurat package were used for quality control and secondary analysis. LncRNAs expression profiles of BC samples were extracted from The Cancer Genome Atlas database. And sex, age, tumor, node, metastasis stage and other clinical data was downloaded at the same time. Ferroptosis-related lncRNAs were identified by co-expression analysis. We constructed a risk model by Cox regression and least absolute shrinkage and selection operator regression analyses. The predictive strength of the risk model for overall survival (OS) of patients with BC was evaluated by the log-rank test and Kaplan–Meier method. Finally, the enrichment analysis was performed and visualized.

Results:

We identified and included 15 prognostic ferroptosis-related lncRNAs (AL356740.1, FOXC2AS1, ZNF528AS1, LINC02535, PSMB8AS1, AL590428.1, AP000347.2, OCIAD1-AS1, AP001347.1, AC104986.2, AC018926.2, LINC00867, AC099518.4, USP30-AS1, and ARHGAP5-AS1), to build our ferroptosis-related lncRNAs risk model. Using this risk model, BC patients were divided into high and low-risk groups, and their respective survival lengths were calculated. The results showed that the OS of the low-risk group was significantly longer than that of the high-risk group. A nomogram was utilized to predict the survival rate of BC patients. As indicated in the nomogram, risk score was the most important indicator of OS in patients with BC. The ferroptosis-related lncRNAs risk model is an independent tool for prognostic risk assessment in patients with BC. Single cell transcriptome sequencing suggests that ferroptosis-related lncRNAs express specifically in BC tumor microenvironment. AL356740.1, LINC02535 and LINC00867 were mainly expressed in tumor cells.

Conclusion:

The risk model based on the ferroptosis-related lncRNAs and the genomic clinico-pathological nomogram could be used to accurately predict the prognosis of patients with BC. The lncRNAs used to build this model might become potential therapeutic targets in the future.
Pediatric acute liver failure in Saudi Arabia: prognostic indicators, outcomes and the role of genetic testing
Authors: Alhadab Abdulhamid , AlShihabi Hadeel , Mohamed Fatema , AlDuhilib Zahra , Arain Zahid , Bader Razan
Published: December 2022

Objective

The objective of this study was to determine the etiologies, outcomes, prognostic indicators and the role of genetic testing in children with acute liver failure (ALF).

Methods

This retrospective study included 46 patients with pediatric acute liver failure (PALF) according to the PALF study group definition, admitted to King Fahad Specialist Hospital-Dammam, Saudi Arabia, between January 2014 and December 2021. Patients who survived with supportive therapy were designated as the recovery group, whereas those who died or underwent liver transplantation were designated as the death/transplant group.

Results

There were 26 (56.5%) patients in the recovery group and 20 (43.5%) patients in the death/transplant group. Four patients (8.7%) underwent liver transplantation. After indeterminate causes (45.6%), genetic-metabolic diseases and drug-induced liver injury (DILI) were the most common cause with 15.2 and 13%, respectively. Genetic testing had a high yield of (6/31) in identifying monogenic disease associated with ALF. Younger age, lower Glasgow Coma Scale and higher international normalized ratio (INR) on admission were predictors for poor prognosis. The death/transplant group had longer intensive care unit stay (P < 0.001), and on admission they had more advanced hepatic encephalopathy (P < 0.005), more prolonged prothrombin time (P < 0.001), higher lactate (P < 0.006), higher total and direct bilirubin (P < 0.008) and (P < 0.001), respectively.

Conclusion

Genetic, metabolic and DILI causes constituted the most common cause of PALF after indeterminate causes. The use of genetic testing can improve diagnostic rates in special cases, but we could not assess the effect of genetic testing on prognosis. The overall survival rate in our study was 65.2%. Younger age, higher admission INR and lower Glasgow coma scale were indicators of poor prognosis.
Nursing staff communication with pediatric patients and families in a pediatric transitional care unit: a best practice implementation project
Authors: Sandridge Shanda , Palokas Michelle , Odom Anna
Published: December 2022

Objectives:

The objective of this project was to promote evidence-based practices regarding nursing communication with pediatric patients/families.

Introduction:

Effective communication between healthcare providers and patients/families is an essential component of patient care and plays a vital role in patient outcomes. Ineffective communication among the healthcare team and patient families has been described as a significant factor contributing to adverse events and poor health outcomes.

Methods:

The project used JBI's Practical Application of Clinical Evidence System and Getting Research into Practice audit tool for encouraging evidence-based practices. A baseline audit was conducted, followed by the implementation of targeted strategies. The project was completed with a follow-up audit to determine change in practice.

Results:

Three evidence-based practices were utilized as audit criteria for the project. The baseline audit on the three audit criteria revealed an average compliance of 30%. After providing communication skills training to nursing staff and education and visual aids to patients/families and nursing staff regarding the use of white boards, follow-up audits revealed an average compliance of 62%, an increase of 32%.

Conclusions:

These implementation strategies will continue to be utilized on the unit and will be implemented in other areas of the hospital to further improve communication between patients/families and their healthcare team.
The St. Vincent’s Free Congestive Heart Failure Comprehensive Care Clinic: A Community-Based Intervention and Analysis
Authors: Davis John W , Ditmars Frederick S. , Manno Gabrielle , Moran Jacob , Reisler Jenna , Davis Elizabeth , Chatila Khaled , Farr Norman M , Khalife Wissam , Thomas Robert D
Published: December 2022

Introduction

Heart Failure disease management clinics have been historically successful in reducing complications, but little has been done in uninsured settings.

Methods

This is a pilot program for uninsured HF patients following a recent hospitalization. Uninsured patients were offered enrollment in the disease management clinic during or immediately following hospitalization for a primary HF diagnosis at our institution during 2021. The program included twice-weekly visits with interprofessional support. Patients were scheduled 16 visits (2 months of follow-up) post-hospitalization. Patients who attended two visits were considered enrolled.

Results

Of 59 patients referred, 47(80%) were enrolled. Just four patients (8.5%,95%CI:2.5%,20.5%) were readmitted at 30 days, while four of twelve (33%,95%CI:13.6%,61.2%) were readmitted at 30 days in those who did not enroll. Program participants were readmitted significantly less frequently than national readmission rate estimates (23%,p=0.02).

Conclusion

The CHFC3 program is feasible and holds promise for materially reducing 30-day readmissions for HF complications in the uninsured.
Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic
Authors: Bose-Brill Seuli , Hirabayashi Kathryn , Pajor Nathan M , Rao Suchitra , Mejias Asuncion , Jhaveri Ravi , Forrest Christopher B. , Bailey Charles , Christakis Dimitri A. , Thacker Deepika , Hanley Patrick C. , Patel Payal B. , Cogen Jonathan D. , Block Jason P. , Prahalad Priya , Lorman Vitaly , Lee Grace M.
Published: December 2022

Objective

This study was conducted to identify rates of pediatric nirmatrelvir/ritonavir (Paxlovid) prescriptions overall and by patient characteristics.

Methods

Patients up to 23 years old with a clinical encounter and a nirmatrelvir/ritonavir (Paxlovid, n/r) prescription in a PEDSnet-affiliated institution between December 1, 2021 and September 14, 2022 were identified using electronic health record (EHR) data.

Results

Of the 1,496,621 patients with clinical encounters during the study period, 920 received a nirmatrelvir/ritonavir prescription (mean age 17.2 years; SD 2.76 years). 40% (367/920) of prescriptions were provided to individuals aged 18-23, and 91% (838/920) of prescriptions occurred after April 1, 2022. The majority of patients (70%; 648/920) had received at least one COVID-19 vaccine dose at least 28 days before nirmatrelvir/ritonavir prescription. Only 40% (371/920) of individuals had documented COVID-19 within the 0 to 6 days prior to receiving a nirmatrelvir/ritonavir prescription. 53% (485/920) had no documented COVID-19 infection in the EHR. Among nirmatrelvir/ritonavir prescription recipients, 64% (586/920) had chronic or complex chronic disease and 9% (80/920) had malignant disease. 38/920 (4.5%) were hospitalized within 30 days of receiving nirmatrelvir/ritonavir.

Conclusion

Clinicians prescribe nirmatrelvir/ritonavir infrequently to children. While individuals receiving nirmatrelvir/ritonavir generally have significant chronic disease burden, a majority are receiving nirmatrelvir/ritonavir prescriptions without an EHR-recorded COVID-19 positive test or diagnosis. Development and implementation of concerted pediatric nirmatrelvir/ritonavir prescribing workflows can help better capture COVID-19 presentation, response, and adverse events at the population level.
Changes in depression and anxiety among people with cognitive impairment and dementia during the COVID-19 pandemic: Analysis of the English Longitudinal Study of Ageing
Authors: Beach Brian , Steptoe Andrew , Zaninotto Paola
Published: December 2022

Background

Some studies have identified declines in mental health over the course of the COVID-19 pandemic across the world and in different age groups, including older people. As anxiety and depression are common neuropsychiatric symptoms among people with dementia or mild cognitive impairment, the mental health experiences of older people during the pandemic should therefore take cognitive function into consideration. This should also be examined using quantitative measures that were assessed prior to the pandemic. This study addresses such gaps in the evidence base on depression and anxiety among older people with cognitive impairment before and throughout the COVID-19 pandemic.

Methods and Findings

Using data from the English Longitudinal Study of Ageing (ELSA) collected from 2018/19 to Nov/Dec 2020, we estimated changes in depression and anxiety for people aged 50+ in England across three cognitive function groups: no impairment, mild cognitive impairment, and dementia.

We found that depression (measured with CES-D score) worsened from 2018/19 to Nov/Dec 2020 for people with mild cognitive impairment (1.39 (95%CI: 1.29-1.49) to 2.16 (2.02-2.30)) or no impairment (1.17 (95%CI: 1.12-1.22) to 2.03 (1.96-2.10)). Anxiety, using a single-item rating of 0-10 also worsened among those with mild cognitive impairment (2.48 (2.30-2.66) to 3.14 (2.95-3.33)) or no impairment (2.20 (2.11-2.28) to 2.85 (2.77-2.95)). No statistically significant increases were found for those with dementia. Using a clinical cutoff for likely depression (CES-D≥4), we found statistically significant increases in the probability of likely clinical depression between 2018/19 and Nov/Dec 2020 for those with no impairment (0.110 (0.099-0.120) to 0.206 (0.191-0.222)) and those with mild impairment (0.139 (0.120-0.159) to 0.234 (0.204-0.263)).

We also found that differences according to cognitive function that existed before the pandemic were no longer present by June/July 2020, and there were no statistically significant differences in depression or anxiety among cognitive groups in Nov/Dec 2020.

Conclusions

Our findings on measures collected before and during the pandemic suggest a convergence in mental health across cognitive function groups during the pandemic. This suggests mental health services will need to meet an increased demand that will come from older adults, especially those not living with cognitive impairment or dementia. We also found little significant change in mental health outcomes among those with dementia; as their existing need for support will remain, policymakers and care practitioners will need to ensure this group continues to have equitable access to support for their mental health.
Striatal Dopaminergic Asymmetry as a marker of Brain-First and Body-First Subtypes in de novo Parkinson’s Disease
Authors: Boertien Jeffrey M , Nazmuddin Muhammad , Kłos Justyna , Slomp Anne C , van der Zee Sygrid , Borra Ronald JH , van Laar Teus
Published: December 2022

Recently, the α-Synuclein Origin and Connectome (SOC) model of Parkinson’s disease (PD) has been proposed, which predicts a more malignant clinical subtype and symmetrical neurodegeneration in body-first compared to brain-first PD.

Here, motor symptoms (MDS-UPDRS III), non-motor symptoms (NMSQ) and T1 MRI data of an incidentde novoPD cohort, were compared between PD subjects with levels of putaminal dopaminergic asymmetry in the lowest tertile (PD-sym, n=41) and highest tertile (PD-asym, n=41), as measured by FDOPA-PET.

PD-sym was associated with a higher burden of motor symptoms and non-motor symptoms with a probable neurological substrate caudally from the substantia nigra. Though overall brain volume was lower in PD-sym, no differences in the volumes and asymmetricity of specific brain regions could be found between PD-sym and PD-asym after adjusting for multiple testing.

The more malignant clinical picture suggests an overrepresentation of body-first PD subjects in PD-sym according to the SOC-model. Also, lower overall brain volumes were found in PD-sym. However, structural MRI data might not be sufficient to assess regional differential degeneration between PD-sym and PD-asym inde novoPD. Additional imaging modalities and longitudinal follow-up could be required to support or reject the SOC-model.
Impact of BA.1, BA.2, and BA.4/BA.5 Omicron Mutations on Therapeutic Monoclonal Antibodies
Authors: Jawad Bahaa , Adhikari Puja , Podgornik Rudolf , Ching Wai-Yim
Published: December 2022

The emergence of Omicron SARS-CoV-2 subvariants (BA.1, BA.2, BA.4, and BA.5) with an unprecedented number of mutations in their receptor-binding domain (RBD) of the spike-protein has fueled a new surge of COVID-19 infections, posing a major challenge to the efficacy of existing vaccines and monoclonal antibody (mAb) therapeutics. Here, a thorough and systematic molecular dynamics (MD) simulation study is conducted to investigate how the RBD mutations on these subvariants affect the interactions with broad mAbs including AstraZeneca (COV2-2196 and COV2-2130), Brii Biosciences (BRII-196), Celltrion (CT-P59), Eli Lilly (LY-CoV555 and LY-CoV016), Regeneron (REGN10933 and REGN10987), Vir Biotechnology (S309), and S2X259. Our results show a complete loss of binding for COV2-2196, BRII-196, CT-P59, and LY-CoV555 with all Omicron RBDs. REGN10987 also loses its binding against BA.1 but partially retains against BA.2 and BA.4/5. The reduction in binding is either significant for LY-CoV016 and REGN10933 or moderate for COV2-2130. S309 and S2X259 retain their binding strength against BA.1 but decrease against others. We introduce a mutational escape map for each mAb to identify the key RBD sites and critical mutation. Overall, our findings suggest that majority of therapeutic mAbs have diminished or lost their activity against Omicron subvariants, indicating the urgent need for a new therapeutic mAb, modifying current ones with a better mAb design, or seeking an alternative approach.
“Quasigenus” amongPhycodnaviridae: A diversity of chlorophyte-infecting viruses in response to a dense algal culture in a high-rate algal pond
Authors: Chase Emily E. , Pitot Thomas M. , Monteil-Bouchard Sonia , Desnues Christelle , Blanc Guillaume
Published: December 2022

This study approaches a high rate algal pond (HRAP) culture by metagenomic sequencing of the viral DNA fraction, this includes the so-called giant virus fraction (phylumNucleocytoviricota), with the goal of revealing viruses coexisting within an intensified algal culture. A wealth of interesting novel viruses is revealed, including members ofNucleocytoviricota, Lavidaviridae, and polinton-like viruses, which are taxa containing previously characterized algal viruses. Our sequencing results are coupled with a virus targeted qPCR study and 18S rDNA metabarcoding to elucidate potential virus-host interactions. Several species of green algae are identified (Chlorophyta), likely representing the alternating dominant populations during the year of study. Finally, we observe a bloom of viral diversity within the familyPhycodnaviridae(Nucleocytoviricota), including highly related but non-identical genotypes, appearing in the HRAP in September and October 2018. This bloom is most likely the cause of a mass mortality event of the cultured algae that occurred during these same months. We hypothesize that these relatedPhycodnaviridaelineages selectively infect different strains of the same algal species of the GenusPicochlorumthat have been identified in the HRAP by metabarcoding and coined this phenomenon a “quasigenus” by analogy to the RNA virus quasispecies concept.
Hybotidae (Diptera) of the Botanic Garden Jean Massart (Brussels-Capital Region, Belgium) with description of two newPlatypalpusspecies and comments on the Red Data List
Authors: Grootaert Patrick
Published: December 2022

Ninety hybotid species are recognized in the Botanic Garden Jean Massart (Brussels), representing 52 % of the hybotids ever recorded in Belgium. Two species new to science are described:Platypalpus massartisp. nov. andP. pictitarsoidessp. nov. Following species are reported for the first time in Belgium:Drapetis infitialis(Collin, 1961),Platypalpus negroboviGrootaert, Kustov & Shamshev, 2012 andTrichina opacaLoew, 1864. In addition, comments are given on a selected number of species:Bicellaria intermediaLundbeck, 1910,Platypalpus aurantiacus(Collin, 1926),Platypalpus longimanus(Corti, 1907),Platypalpus nanus(Oldenberg, 1924),Platypalpus rapidoidesChvála, 1975,Platypalpus subtilis(Collin, 1926),Stilpon subnubilusChvála, 1988 and on the genusHybosMeigen, 1803. The holotype ofP. cryptospina(Frey, 1909) is revised.

Only 30 species or 33% of the species present are in a ‘Safe/Low risk’ Red Data Book category meaning that the other 66% are in a more or less ‘Threatened’ category.
An alpaca-derived nanobody recognizes a unique conserved epitope and retains potent activity against the SARS-CoV-2 omicron variant
Authors: Modhiran Naphak , Lauer Simon Malte , Amarilla Alberto A , Hewins Peter , van den Broek Sara Irene Lopes , Low Yu Shang , Thakur Nazia , Liang Benjamin , Nieto Guillermo Valenzuela , Jung James , Paramitha Devina , Isaacs Ariel , de Sng Julian , Song David , Jørgensen Jesper Tranekjær , Cheuquemilla Yorka , Bürger Jörg , Andersen Ida Vang , Himelreichs Johanna , Jara Ronald , MacLoughlin Ronan , Miranda-Chacon Zaray , Chana-Cuevas Pedro , Kramer Vasko , Spahn Christian M.T. , Mielke Thorsten , Khromykh Alexander A , Munro Trent , Jones Martina , Young Paul R , Chappell Keith , Bailey Dalan , Kjaer Andreas , Herth Matthias Manfred , Jurado Kellie Ann , Schwefel David , Rojas-Fernandez Alejandro , Watterson Daniel
Published: December 2022

The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity.In vivoevaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.
Returns on library investment: seeking causative relationship between the library investment and the institutional research output
Authors: Singh Shivendra , Pandita Ramesh , Baidwan Kiran
Published: December 2022

Purpose

This study aims to seek the causative relationship between the library budget and research output with the ranking of 20 leading medial institutes in India. More so, the study also attempts to find out whether the libraries associated with academic and research institutes in general and medical institutes in particular have turned redundant or irrelevant, or have become more relevant in the changing times by embracing technology in its every new form.

Design/methodology/approach

The study is based on the secondary data retrieved from the official website of the Ministry of Education, Government of India and research output against each institution under study has been retrieved from Scopus. The study is limited to Indian medical institutions that participated in the 2019 National Institutional Ranking Framework (NIRF), conducted by the Ministry of Education, India each year. The findings of the study can be generalized to all the medical institutions of the country.

Findings

On average, INR 160.90m were spent by each medical institute on the procurement of library resources at an average of INR 0.104m on procurement of resources against each individual published research article. Of the total research articles published by medical institutes under study, 26.39% of research articles were published by researchers from AIIMS, New Delhi, alone.

Research limitations/implications

Financial aid or funding is very vital for the survival, sustenance and excellence of research institutions, and this funding becomes more important when the investigation is aimed toward the furtherance of medical advances. Any medical advancement is hell-bent to influence the overall welfare and betterment of society at large, whereby the benefit of any investment made in medical science is bound to be reaped by one and all alike.

Originality/value

In India, a good number of studies have been undertaken on the NIRF data to dive deeper to assess the role and importance of libraries in the overall ranking of institutions like universities, management institutes, engineering and technology institutes, but no major study has been so far conducted covering leading medical institutes in India. The study is the original and first of its kind undertaken in India.