bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal depression risk under the NSW SAFE START Strategic Policy: Who is missing out on universal screening?
Authors: Dong Vanessa , Montgomery Alicia , Adily Pejman , Eastwood John
Published: April 2023

Aim

To examine antenatal depression risk screening coverage under the NSW SAFE START Strategic Policy and to explore maternal and sociodemographic factors associated with under‐screening.

Methods

Completion rates for the Edinburgh Depression Scale (EDS) were examined in a retrospective dataset of routinely collected antenatal care data including all women who birthed at public health facilities in Sydney Local Health District from 1 October 2019 to 6 August 2020. Potential sociodemographic/clinical factors associated with under‐screening were identified using univariate and multivariate logistic regression. Free‐text responses regarding reasons for EDS non‐completion were examined using qualitative thematic analysis techniques.

Results

A total of 4810 women (96.6%) in our sample (N = 4980) completed antenatal EDS screening; only 170 (3.4%) were not screened or lacked data to indicate that screening had occurred. Multivariate logistic regression analyses showed that women under certain models of antenatal care (public hospital care, private midwife/obstetrician or no formal care), non‐English speaking women who required an interpreter, and women whose smoking status during pregnancy was unknown had a higher odds of missing screening. The reasons for EDS non‐completion indicated in the electronic medical record revealed language and time/practical constraints to be the most commonly‐reported barriers.

Conclusions

Antenatal EDS screening coverage was high in this sample. Refresher training for staff involved can emphasise the need to ensure appropriate screening for women who access shared care in external services (particularly private obstetric care). Additionally, at the service level, improved access to interpreter services and foreign language resources may help minimise EDS under‐screening for culturally and linguistically diverse families.
Sequential tariffs with increasing marginal costs
Authors: Choi Kangsik , Lim Seonyoung
Published: April 2023

This study examines the superiority of the discriminatory and uniform tariff regimes under both simultaneous and sequential arrangements in terms of social and global welfare by considering asymmetrically increasing marginal costs among exporters. Under Cournot competition, the importing country has an incentive to manipulate the tariff structure using a sequential tariff arrangement, which implies that it prefers to impose tariff on a low‐cost exporter first and a high‐cost exporter later. Sequential discriminatory (uniform) tariffs can achieve Pareto superiority from the perspective of consumer surplus, and social and global welfare if product differentiation is low (high). It is mainly because high‐cost (low‐cost) exporters are handicapped (subsidized) under alternative tariff regimes. In contrast to previous research, our analysis suggests the possibility that preferences for tariff regimes will change in the same direction for consumer surplus, social welfare, and global welfare.
Indirect maternal effects via nest microbiome composition drive gut colonization in altricial chicks
Authors: Diez‐Méndez David , Bodawatta Kasun H. , Freiberga Inga , Klečková Irena , Jønsson Knud A. , Poulsen Michael , Sam Katerina
Published: April 2023

Gut microbial communities are complex and heterogeneous and play critical roles for animal hosts. Early‐life disruptions to microbiome establishment can negatively impact host fitness and development. However, the consequences of such early‐life disruptions remain unknown in wild birds. To help fill this gap, we investigated the effect of continuous early‐life gut microbiome disruptions on the establishment and development of gut communities in wild Great tit (Parus major) and Blue tit (Cyanistes caeruleus) nestlings by applying antibiotics and probiotics. Treatment neither affected nestling growth nor their gut microbiome composition. Independent of treatment, nestling gut microbiomes of both species grouped by brood, which shared the highest numbers of bacterial taxa with both nest environment and their mother. Although fathers showed different gut communities than their nestlings and nests, they still contributed to structuring chick microbiomes. Lastly, we observed that the distance between nests increased inter‐brood microbiome dissimilarity, but only in Great tits, indicating that species‐specific foraging behaviour and/or microhabitat influence gut microbiomes. Overall, the strong maternal effect, driven by continuous recolonization from the nest environment and vertical transfer of microbes during feeding, appears to provide resilience towards early‐life disruptions in nestling gut microbiomes.
Ancient bears provide insights into Pleistocene ice age refugia in Southeast Alaska
Authors: da Silva Coelho Flavio Augusto , Gill Stephanie , Tomlin Crystal M. , Papavassiliou Marilena , Farley Sean D. , Cook Joseph A. , Sonsthagen Sarah A. , Sage George K. , Heaton Timothy H. , Talbot Sandra L. , Lindqvist Charlotte
Published: April 2023

During the Late Pleistocene, major parts of North America were periodically covered by ice sheets. However, there are still questions about whether ice‐free refugia were present in the Alexander Archipelago along the Southeast (SE) Alaska coast during the last glacial maximum (LGM). Numerous subfossils have been recovered from caves in SE Alaska, including American black (Ursus americanus) and brown (U. arctos) bears, which today are found in the Alexander Archipelago but are genetically distinct from mainland bear populations. Hence, these bear species offer an ideal system to investigate long‐term occupation, potential refugial survival and lineage turnover. Here, we present genetic analyses based on 99 new complete mitochondrial genomes from ancient and modern brown and black bears spanning the last ~45,000 years. Black bears form two SE Alaskan subclades, one preglacial and another postglacial, that diverged >100,000 years ago. All postglacial ancient brown bears are closely related to modern brown bears in the archipelago, while a single preglacial brown bear is found in a distantly related clade. A hiatus in the bear subfossil record around the LGM and the deep split of their pre‐ and postglacial subclades fail to support a hypothesis of continuous occupancy in SE Alaska throughout the LGM for either species. Our results are consistent with an absence of refugia along the SE Alaska coast, but indicate that vegetation quickly expanded after deglaciation, allowing bears to recolonize the area after a short‐lived LGM peak.
Ruptured imaginings amid emerging nationhood: The unsettled narrative of “unity in resistance” in South Sudanese history textbooks
Authors: Bentrovato Denise , Skårås Merethe
Published: April 2023

This article explores the place of history education in state‐sponsored nation‐building in war‐torn South Sudan, the world's youngest country. It examines discourses around nationhood transmitted via the first history curricula, textbooks and teacher guides issued in the midst of civil war, after the country's secession from Sudan to its north. The analysis uncovers a central memory of violence and an ostensibly unifying narrative of the South's historical victimisation and struggle. An emerging emotionally charged discourse of “unity in resistance” illustrates the construction of a “usable past” through silencing and othering. Its offshoot is an unsettled narrative whose key focus on unity undergoes repeated rupture.
Protecting healthcare workers' mental health against COVID‐19‐related stress: The effects of stress mindset and psychological resilience
Authors: Emirza Sevgi , Yılmaz Kozcu Gizem
Published: April 2023

Healthcare workers have been on the frontline of the battle against COVID‐19 disease. However, this has taken a toll on them, resulting in elevated stress and poor mental health. We argue that healthcare workers' stress mindset and resilience could mitigate negative outcomes of COVID‐19‐related stress by helping them view this stressful situation in a more positive light and appraise it as a challenge rather than a threat. Accordingly, we hypothesized that both a stress‐is‐enhancing mindset about COVID‐19‐related stress and resilience would improve healthcare workers' appraisal of their personal resources and increase their challenge appraisals, positively contributing to their mental health. We collected data from 160 healthcare workers and performed structural equation modeling for hypothesis testing. The results indicate that both a stress‐is‐enhancing mindset about COVID‐19‐related stress and psychological resilience are indirectly related to better mental well‐being and lower health‐related anxiety through challenge appraisals. This study contributes to research in mental health by suggesting that protecting and promoting healthcare workers' mental health is possible by empowering them through increasing personal resources such as a positive mindset about stressful situations and resilience.
Night‐time detection and response in relation to deteriorating inpatients: A scoping review
Authors: Hotta Soichiro , Ashida Kaoru , Tanaka Makoto
Published: April 2023

Background

Although detection and response to clinical deterioration have been studied, the range and nature of studies focused on night‐time clinical setting remain unclear.

Aim

This study aimed to identify and map existing research and findings concerning night‐time detection and response to deteriorating inpatients in usual care or research settings.

Study Design

A scoping review method was used. PubMed, CINAHL, Web of Science, and Ichushi‐Web databases were systematically searched. We included studies focusing on night‐time detection and response to clinical deterioration.

Results

Twenty‐eight studies were included. These studies were organized into five categories: night‐time medical emergency team or rapid response team (MET/RRT) response, night‐time observation using the early warning score (EWS), available resources for physicians' practice, continuous monitoring of specific parameters, and screening for night‐time clinical deterioration. The first three categories were related to interventional measures in usual care settings, and relevant findings mainly demonstrated the actual situation and challenges of night‐time practice. The final two categories were related to the interventions in the research settings and included innovative interventions to identify at‐risk or deteriorating patients.

Conclusions

Systematic interventional measures, such as MET/RRT and EWS, could have been sub‐optimally performed at night. Innovations in monitoring technologies or implementation of predictive models could be helpful in improving the detection of night‐time deterioration.

Relevance to Clinical Practice

This review provides a compilation of current evidence regarding night‐time practice concerning patient deterioration. However, a lack of understanding exists on specific and effective practices regarding timely action for deteriorating patients at night.
Manipulation of plant immunity via an mRNA decapping pathogen effector
Authors: Banfield Mark J.
Published: April 2023

This article is a Commentary on McCombe et al. (2023), 239: 222–239.
Combined empirical techniques reveal key role for variation in plasticity in a novel environment
Authors: Cross Regan L. , Thompson Hana C.
Published: April 2023

This article is a Commentary on Walter et al. (2023), 239: 374–387.
Identifying behaviors that characterize emergence delirium: An observational study
Authors: O'Brien Jennifer M. , McKay William P. S. , McDonald Marguerite
Published: April 2023

Background

Diagnostic criteria for emergence agitation are sensitive but not specific; they misclassify patients who are angry or upset as having emergence delirium.

Aims

The aim of this three‐phase study was to determine expert agreement on the behaviors that differentiate children with emergence delirium from those without.

Methods

In the first phase of this observational study, pediatric dental patients were video recorded while awakening from anesthesia. In the second phase, salient 10 s segments of the recordings showing patient activity were shown to an expert audience of pediatric dentists, anesthesiologists and Post Anesthetic Care nurses, who scored the recordings as showing or not showing “true emergence delirium.” In phase 3, the video segments were assessed by three research assistants using a behavior checklist for features that discriminate between those scored “true emergence delirium” and those scored “NOT true emergence delirium” by the experts.

Results

One hundred and fifty‐four pediatric dental patients were included. Subsequently, an expert audience consisting of 10 anesthesiologists, 12 anesthesiology residents, 3 pediatric dentists, and 4 experienced Post Anesthesia Care Unit nurses rated each 10‐second video segment. This resulted in three groups of patients: a group for whom all experts agreed was “True emergence delirium” (n = 33; CI 21 to 45), a group for whom all agreed was “Not True emergence delirium” (n = 120; CI 107 to 133), and a group where experts disagreed (n = 11; CI 4 to 18). Three research assistants then completed a behavior checklist for each of the 33 “True emergence delirium” video segments and matched “Not True” controls. Twenty‐four behaviors were identified as significantly different between videos scored True emergence delirium and those scored Not True emergence delirium. Research assistants reached almost perfect agreement (0.81–1.00) on one behavior, and substantial agreement (0.61–0.80) on seven behaviors that characterized “True emergence delirium.”

Conclusions

Eight behaviors that differentiate pediatric dental patients with emergence delirium from those without were found. These discriminators may be used to develop a scale that will lead to better diagnosis and treatment of emergence delirium.
Loneliness and social anxiety in young adults: The moderating and mediating roles of emotion dysregulation, depression and social isolation risk
Authors: Eres Robert , Lim Michelle H. , Bates Glen
Published: April 2023

Objectives

We aimed to investigate the mechanisms underlying loneliness, social anxiety, depression and emotion dysregulation, as well as how these relationships differ based on social isolation risk.

Design

We employed an online survey study to measure variables cross‐sectionally.

Methods

A total of 1239 (77.2% Female, Mage = 21.52, SD = 2.32) participants completed measures of loneliness, social isolation risk, social anxiety, depression and emotion dysregulation. A moderated serial mediation model was conducted to determine whether emotion dysregulation and depression jointly mediate the relationship between loneliness and social anxiety and to determine whether these relationships are moderated by risk of social isolation.

Results

Loneliness was found to predict social anxiety and was mediated by emotion dysregulation and depression both independently and combined. Participants with a low risk of social isolation were found to be protected against poor mental health.

Conclusions

Our studies replicate previous findings showing a relationship between loneliness and social anxiety. We also extend current knowledge to show the importance of social contact for protecting against elevated levels of social anxiety and depression. Overall, we provide empirical evidence for the role of social connection in managing mental health symptoms.
Morphology and molecular phylogeny of the marine diatom genus Nagumoea (Bacillariophyceae) from Japan
Authors: Sugawara Kazuki , Suzuki Hidekazu , Kamiya Mitsunobu , Osada Keigo , Witkowski Andrzej
Published: April 2023

The canal‐bearing diatom genus Nagumoea, described based on only morphological evidence, was tentatively assigned to the order Bacillariales, although its phylogenetic position remained unclear. Because three isolates of Nagumoea (SK002, SK024 and SK053) were successfully established from Japanese coasts, we performed their morphological observations and molecular phylogenetic analyses to discuss the phylogeny and taxonomic position of this genus. Strains SK002 and SK024 were identified as Nagumoea africana, whereas SK053 conformed with Nagumoea serrata. There was high interspecific divergence between N. africana and N. serrata in the rbcL sequences (8.03–8.17%), indicating their distinctness. Furthermore, intraspecific variations were detected within N. africana (2.35%) in the rbcL, implying its cryptic diversity. The maximum likelihood and Bayesian phylogenetic trees inferred from the plastid rbcL, psbC and nuclear 18S rDNA genes recovered Nagumoea as monophyletic with strong statistical support and embedded within an unresolved, poorly supported lineage containing Achnanthes, Craspedostauros, Staurotropis and Undatella in the canal‐bearing order Bacillariales (= the family Bacillariaceae). Although the constrained tree based on the monophyly of Nagumoea and the other canal‐bearing clade (Surirellales and Rhopalodiales) was statistically rejected by the topology tests, the phylogenetic position of Nagumoea with other Bacillarialean members remains equivocal. The possession of two plastids positioned fore and aft, observed in the present study, and lack of keel, typical of the Bacillariales, indicate the possibility of Nagumoea being part of the ingroup of the Bacillariales or its closely related outgroup.
Assessing late‐life anxiety in Japanese older adults: psychometric evaluation of the Japanese version of the Geriatric Anxiety Scale
Authors: Kashimura Masami , Ishizu Kenichiro , Kokubo Naomi , Segal Daniel L.
Published: April 2023

Background

This study developed a Japanese version of the Geriatric Anxiety Scale (GAS‐J) and its short form (GAS‐10‐J) to evaluate anxiety in Japanese older adults and assess its psychometric properties using a cross‐sectional design.

Methods

A total of 331 community‐dwelling older adult participants (208 men, 116 women, seven unknowns; mean age = 73.47 ± 5.17 years, range = 60–88 years) recruited from two Silver Human Resources Centres in the Kanto region, Japan, answered a set of self‐report questionnaires. Of these respondents, 120 participated in a follow‐up survey to evaluate test–retest reliability.

Results

Confirmatory factor analysis suggested that, as with the original GAS, the GAS‐J had a three‐factor structure and the GAS‐10‐J had a unifactor structure with high standardised factor loadings. Test–retest correlations and internal consistency analyses indicated that these scales were reliable. Correlations between the GAS‐J/GAS‐10‐J with the Geriatric Anxiety Inventory, Generalised Anxiety Disorder‐7, Geriatric Depression Scale‐15, World Health Organization‐Five Well‐Being Index, and Kihon Checklist were mostly consistent with our hypotheses, thereby supporting the construct validity of the GAS‐J/GAS‐10‐J.

Conclusions

The findings indicate that the GAS‐J and GAS‐10‐J have robust psychometric properties for assessing late‐life anxiety in Japanese older adults. Further GAS‐J studies are required for clinical groups.
The influence of risk awareness and government trust on risk perception and preparedness for natural hazards
Authors: Cisternas Pamela C. , Cifuentes Luis A. , Bronfman Nicolás C. , Repetto Paula B.
Published: April 2023

Risk perception is considered the primary motivator for taking preparedness actions. But people with prior experience and a high‐risk perception are not necessarily more prepared. This relationship is even more complex when assessing preparedness levels for hazards with different characteristics. These inconsistent findings can be explained by how preparedness has been measured and the influence of other factors, such as trust and risk awareness. Thus, the main goal of this study was to analyze the role of risk awareness and trust in authorities on risk perception and intention to prepare for natural hazards in a coastal city in Chile. A representative sample of the city of Concepción, located in the center‐south zone of Chile (n = 585), completed a survey. We measured risk awareness, risk perception, trust in authorities, and intention to prepare for two hazards: earthquakes/tsunamis and floods. Through structural equation models, we tested five hypotheses. We found that the perception of risk maintained a direct and positive influence on the intention to prepare for both hazards. The results showed that awareness and risk perception influence the intention to prepare and should be considered different concepts. Finally, trust did not significantly influence risk perception when faced with known hazards for the population. Implications for understanding the relationship between risk perception and direct experience are discussed.
An extremely rare case of Oro‐facial digital syndrome: A case report
Authors: Dwivedi Shilpy , Thakur Arpita
Published: April 2023

Background

Oro‐facial digital(OFD) syndrome is a rare anomaly which is often missed out as just cleft lip and palate.It is an X‐linked dominant condition with lethality in males. It however results from the pleotropic effect of a morphogenetic impairment affecting almost invariably the mouth, face and digits and it also includes lower IQ and mental retardation. 14 different variations of these syndrome can be seen with the majority of cases of type 1 and 2 based on characteristic clinical manifestations.

Case report

Present case report describes a 9 year old girl patient who was mis‐diagnosed with partial cleft palate and was later diagnosed as orofacial digital syndrome based on the clinical and oral features.

Conclusion

Not much literature is present regarding this topic and with no relevent family history makes this case a one in a million case of OFD. Therefore, this case report is a complete insight on Oro‐facial digital syndrome.
Revisiting the vulnerable dark triad hypothesis using a bifactor model
Authors: Gamache Dominick , Maheux‐Caron Véronique , Théberge David , Côté Alexandre , Rancourt Marie‐Anne , Hétu Sébastien , Savard Claudia
Published: April 2023

Miller et al. (2010) previously suggested that borderline pathology, vulnerable narcissism, and Factor 2 psychopathy share a common “Vulnerable Dark Triad” (VDT) core. The present study (N = 1,023 community participants) aims to test that hypothesis using exploratory and confirmatory bifactor analyses. We found support for a bifactor model that obtained satisfactory fits and other adequate validity indices, which included a general VDT factor and three group factors (Reckless, Entitled, Hiding). The general VDT factor was mostly saturated with borderline symptoms items reflecting self‐hatred and worthlessness, which did not form a group factor; these results add to previous research suggesting that features of borderline pathology may represent the core of personality pathology. The three group factors had distinctive relationships with Dark Triad traits, pathological trait domains, and aggression. In contrast with the three group factors, the general VDT factor more strongly incremented the prediction of negative affectivity and hostility; the group factors more strongly incremented the prediction of grandiosity, egocentrism, callousness, Machiavellianism, and direct (physical/verbal) aggression. Alignment of the retained bifactor model with influent models of personality pathology and conceptual/methodological implications of the present results for research on the hypothesized VDT are discussed, as well as some clinical implications of the findings.
The multilateral spatial integer‐valued process of order 1
Authors: Karlis Dimitris , Chutoo Azmi , Mamode Khan Naushad , Jowaheer Vandna
Published: April 2023

In spatial count data analysis, modeling with a multilateral lattice structure presents some important challenges. They include both the model construction and the estimation of the model parameters, since the structure accommodates the left, right, top, bottom, and diagonal site effects. Thus, the multilateral spatial process unifies all the popular spatial subclasses that include the unilateral, Rook, Bishop, and Queen models and, hence, makes it suitable for a wide variety of applications. This paper introduces a first‐order multilateral integer‐valued spatial process, based on a binomial thinning mechanism and some innovation term, under both stationary and nonstationary conditions. The estimation of parameters is handled by the conditional maximum likelihood estimation (CML) approach. Simulation experiments are implemented to assess the consistency of the CML estimators in the stationary and nonstationary multilateral spatial model and its subclasses, based on different grid sizes and under both covariate and noncovariate designs. The proposed model, along with its subclasses are applied to real datasets.
RSI1/FLD and its epigenetic target RRTF1 are essential for the retention of infection memory in Arabidopsis thaliana
Authors: Singh Deepjyoti , Patil Vishal , Kumar Ranjan , Gautam Janesh Kumar , Singh Vijayata , Nandi Ashis Kumar
Published: April 2023

Plants can retain a memory of previous pathogen infections to mount a more robust defense response during subsequent infections by developing systemic acquired resistance (SAR). However, the mechanism through which plants develop and retain infection memory is not known. Experiments have shown the association of epigenetic modifications of specific defense‐related genes with SAR. RSI1/FLD codes for a histone demethylase and is required for the activation of SAR in Arabidopsis. Here we report the identification of RRTF1 as an epigenetic target of RSI1. RRTF1 expression is higher in pathogen‐free distal tissues of the rsi1 mutant. Experiments with loss‐of‐function and overexpression lines suggest RRTF1 is a negative regulator of basal defense against virulent and avirulent pathogens as well as SAR. Enhanced expression of RRTF1 in a wild‐type (WT) background specifically impairs SAR without impacting local resistance. RSI1 is recruited at the RRTF1 locus in a SAR‐inducible manner and contributes to H3K4me2 and H3K4me3 demethylation. Introduction of the rrtf1 mutation rescues the loss‐of‐SAR phenotype of rsi1 plants. However, these plants fail to retain infection memory beyond 7 days post‐primary inoculation, whereas WT plants retain memory for at least 11 days. Our results demonstrate that RSI1 and RRTF1 form a functional module for retaining infection memory in Arabidopsis.
Modelo productivo, desarrollo territorial y ODS en localidades de Córdoba, Argentina
Authors: Aloranti Vanesa Crissi , Valinotti María Florencia
Published: April 2023

Esta investigación ofrece algunas líneas de reflexión en relación con el modelo productivo de la región de la pampa húmeda (llanura) como componente del desarrollo territorial, con el objetivo de analizar el vínculo entre modelo productivo territorial y el cumplimiento de los Objetivos de Desarrollo Sostenible (ODS) en el municipio de General Deheza y en la comuna de General Fotheringham. Metodológicamente, la investigación es abordada a partir de una triangulación cuali-cuantitativa. Cualitativamente, desde una revisión de antecedentes y perspectivas teóricas y epistemológicas en la temática. Cuantitativamente, se utilizan datos estadísticos para analizar los escenarios locales en relación con el modelo productivo, su impacto en el desarrollo territorial y en los ODS 11 y 8, específicamente. Los resultados expuestos permiten evidenciar la relevancia del modelo productivo hegemónico y las limitaciones de los gobiernos locales en la implementación de los ODS.
Differences in Neurocognitive Functions Between Healthy Controls and Anterior Cruciate Ligament-Reconstructed Male Athletes Who Passed or Failed Return to Sport Criteria: A Preliminary Study
Authors: Kiani Haft Lang Maryam , Mofateh Razieh , Orakifar Neda , Goharpey Shahin
Published: April 2023

Background: Only 55% of anterior cruciate ligament-reconstructed (ACLR) athletes return to competitive sports. This brings into question the usefulness of current return to sport (RTS) criteria. High cognitive demand of sport environment clarifies the value of incorporating neurocognitive tests when making decisions regarding the time of RTS. This preliminary study aimed to compare the neurocognitive functions between healthy controls and ACLR male athletes who passed or failed RTS criteria. Methods: A total of 45 male football players, including 15 ACLR who passed RTS criteria, 15 ACLR who did not pass, and 15 healthy controls participated in this cross-sectional study. The Cambridge Neuropsychological Test Automated Battery was used to measure a battery of neurocognitive tasks, including speed of response, sustained attention, working memory, cognitive flexibility, and response inhibition. Results: The results revealed that compared with both the ACLR-passed and healthy groups, the ACLR-failed group showed greater values of 5-choice movement time (P = .02, P = .01, respectively) but lower values of stop signal reaction time (P = .03, P = .001, respectively) and proportion of successful stops variables (P = .02). In addition, compared with the healthy group, both the ACLR-failed and ACLR-passed groups indicated greater values in between errors (P < .001, P = .008, respectively) and reaction latency variables (P = .002, P = .01, respectively) but lower values of A′ (P < .001, P = .007, respectively), probability of hit (P < .001, P = .03, respectively), and percent correct trials variables (P = .006, P = .02, respectively). Conclusions: Our findings indicated deficits in neurocognitive functions in ACLR male athletes. In addition, poor performance in sustained attention, working memory, and cognitive flexibility measures observed in the ACLR-passed group highlighted the necessity for using a multimodal approach via implementation of neurocognitive measures in conjunction with the functional and muscular assessments when making RTS decisions.
Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release
Authors: Labzin Larisa I. , Chew Keng Yih , Eschke Kathrin , Wang Xiaohui , Esposito Tyron , Stocks Claudia J. , Rae James , Patrick Ralph , Mostafavi Helen , Hill Brittany , Yordanov Teodor E. , Holley Caroline L. , Emming Stefan , Fritzlar Svenja , Mordant Francesca L. , Steinfort Daniel P. , Subbarao Kanta , Nefzger Christian M. , Lagendijk Anne K. , Gordon Emma J. , Parton Robert G. , Short Kirsty R. , Londrigan Sarah L. , Schroder Kate
Published: April 2023

Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1–derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection.
Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus
Authors: Stone Madeleine C. , Mychack Aaron , Coe Kathryn A. , Walker Suzanne
Published: April 2023

Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out the terminal step in protein secretion.
Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge
Authors: Jakielaszek Charles , Hilliard Jamese J. , Mannino Frank , Hossain Mohammad , Qian Lian , Fishman Cindy , Chou Ying-Liang , Henning Lisa , Novak Joseph , Demons Samandra , Hershfield Jeremy , O’Dwyer Karen
Published: April 2023

Francisella tularensis
(
F. tularensis
) is a Centers for Disease Control (CDC) category “A” Gram-negative biothreat pathogen. Inhalation of
F. tularensis
can cause pneumonia and respiratory failure and is associated with high mortality rates without early treatment.
Studies of Streptococcus anginosus Virulence in Dictyostelium discoideum and Galleria mellonella Models
Authors: Budziaszek Joanna , Pilarczyk-Zurek Magdalena , Dobosz Ewelina , Kozinska Aleksandra , Nowicki Dariusz , Obszanska Katarzyna , Szalewska-Pałasz Agnieszka , Kern-Zdanowicz Izabela , Sitkiewicz Izabela , Koziel Joanna
Published: April 2023

For many years,
Streptococcus anginosus
has been considered a commensal colonizing the oral cavity, as well as the gastrointestinal and genitourinary tracts. However, recent epidemiological and clinical data designate this bacterium as an emerging opportunistic pathogen.
Role of Bacterial Extracellular Vesicles in Manipulating Infection
Authors: Zhao Guanqi , Jones Melissa K.
Published: April 2023

Mammalian-cell-derived extracellular vesicles, such as exosomes, have been a key focal point for investigating host-pathogen interactions and are major facilitators in modulating both bacterial and viral infection. However, in recent years, increasing attention has been given to extracellular vesicles produced by bacteria and the role they play in regulating infection and disease.
Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
Authors: Bellomo Carla M. , Alonso Daniel O. , Pérez-Sautu Unai , Prieto Karla , Kehl Sebastian , Coelho Rocio M. , Periolo Natalia , Di Paola Nicholas , Ferressini-Gerpe Natalia , Kuhn Jens H. , Sanchez-Lockhart Mariano , Palacios Gustavo , Martínez Valeria P.
Published: April 2023

Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%).
Dual spinal accessory nerve: an anatomical anomaly during neck dissection
Authors: Shah Faizan , Qamar Sabih Nadeem , Jaffer Mehaab , Crosbie Robin
Published: April 2023

The spinal accessory nerve (SAN) is an important cranial nerve encountered during neck dissection. Preservation of this nerve from iatrogenic damage is crucial to avoid debilitating sequalae, which can be made challenging due to variation of its anatomical course. In this case report, we present a patient who underwent supraomohyoid neck dissection, where a rare variation of a dual SAN, traversing the internal jugular vein midway, was encountered. In this case report, we study this anatomical finding, which is undoubtedly a valuable addition to the existing knowledge of the SAN. Ultimately, allowing surgeons to develop further awareness of the variations of the SAN and contributing to favourable postoperative outcomes.
GiantKlebsiella pneumoniaepyogenic liver abscess in the left liver lobe presenting with dyspepsia and vaginal discharge
Authors: Tran Melanie , Tran Patrick
Published: April 2023

Pyogenic liver abscess (PLA) commonly occurs in the right liver lobe, causing the typical symptoms of fever and right upper quadrant pain. Less than one-third of cases occur in the left lobe. We describe an unusual presentation of a giant left-sided PLA that was compressing the stomach and surrounding venous vasculature, causing the respective symptoms of gastro-oesophageal reflux and vaginal discharge from secondary pelvic congestion syndrome. CT revealed a solitary 14 cm×10 cm×10 cm multiloculated lesion, replacing most of the left liver lobe. It was successfully treated with intravenous antibiotics and percutaneous drainage, resulting in complete resolution at 1-year follow-up. This case explores the predisposing risk factor of diabetes in PLA and its association withKlebsiella pneumoniae,which was the offending pathogen in our patient. We also discuss the phenomenon of secondary pelvic venous congestion syndrome and compare similar cases of left-sided PLA, highlighting the different modes of presentation and treatment options.
Association between minimal decrease in platelet counts and outcomes in septic patients: a retrospective observational study
Authors: Liu Xing , Yin Wanhong , Li Yi , Qin Yiwei , Zou Tongjuan
Published: April 2023

Objectives

Although platelets have been linked to inflammatory development in sepsis, knowledge on their role as an indicator in sepsis treatment is scarce. Here, we investigated the association between time-dependent changes in platelet counts with mortality rates to reveal the role of platelets in sepsis therapy.

Design

A retrospective cohort study.

Setting

We screened the Medical Information Mart for Intensive Care (MIMIC-IV), a public database comprising data from critical care subjects at the Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, USA.

Participants

A total of 7981 patients, who were admitted to the BIDMC between 2008 and 2019, were analysed based on Sepsis-3 criteria from MIMIC-IV.

Primary and secondary outcome measures

Primary and secondary outcomes included 30-day mortality after admission and length of intensive care unit (ICU) stay and hospitalisation, respectively.

Results

Patients with ≤10% reduction in proportion of platelet counts were associated with significantly lower 30-day mortality (14.1% vs 23.5%, p<0.001, Kaplan-Meier analysis, p<0.0001). Multivariable analysis revealed that decreased platelet-count percentage ≤10% on day 4 after ICU admission was associated with lower probability of 30-day non-survival (OR=0.73, 95% CI 0.64 to 0.82, p＜0.001). Patients in the ≤10% group had significantly shorter ICU stays than those in the >10% group (6.8 vs 7.5, p＜0.001). Restricted cubic spline curves revealed that mortality rates decreased with increase in proportion of platelet counts.

Conclusions

A ≤10% decrease in platelet-count percentage among sepsis patients after treatments is independently associated with decreased 30-day mortality, suggesting that changes in proportion of platelet counts after treatments could be an indicator for assessing the therapeutic effects of sepsis.
Effects of discontinuation of levothyroxine treatment in older adults: protocol for a self-controlled trial
Authors: Ravensberg A Janneke , Poortvliet Rosalinde K E , Du Puy Robert S , Dekkers Olaf M , Mooijaart Simon P , Gussekloo Jacobijn
Published: April 2023

Background

Many older persons use the thyroid hormone levothyroxine which is often continued for life. Scientifically, there is much uncertainty whether simple continuation is the optimal approach. First, the physical need for levothyroxine can decrease with age thereby posing a higher risk of overtreatment and adverse effects. Second, large trials in subclinical hypothyroidism have shown no benefit for the use of levothyroxine. Interestingly, guidelines do not address re-evaluation of the indication. This self-controlled trial aims to determine the effects of discontinuation of levothyroxine treatment in older adults.

Methods and analysis

Participants are community-dwelling subjects aged ≥60 years using levothyroxine continuously at a stable dosage of ≤150 µg and a level of thyroid-stimulating hormone (TSH) <10 mU/L. After a control period of 12 weeks, levothyroxine treatment is discontinued gradually using a stepwise approach with regular monitoring of thyroid function guided by their GP. The primary outcome is the proportion of participants withdrawn from levothyroxine while maintaining a free T4 level within the reference range and a TSH level <10 mU/L, 52 weeks after the start of discontinuation. Secondary outcomes are compared with the control period (self-controlled) and include among others, the effects on thyroid-specific and general health-related quality of life. Furthermore, patients’ attitudes towards deprescribing and regret regarding discontinuing levothyroxine treatment will be recorded. A total of 513 participants will be recruited to estimate the expected proportion of 50% with a 95% CI ranging from 45% to 55%.

Ethics and dissemination

Approval was obtained from the institutional Medical Ethics Committee. The Older People Advisory Board Health and Well-being has reviewed the research proposal and their comments were used for improvement. In line with the funding policies of the grant organisation funding this study, the study results will be proactively disseminated to the general public and key public health stakeholders.

Trial registration number

NL7978;NCT05821881.
Critical disease related to SARS-CoV-2 infection in children from the Amazon region: an observational study
Authors: Farias Emmerson Carlos Franco de , Pavão Júnior Manoel Jaime Castro , de Sales Susan C D , do Nascimento Luciana M P P , de Mello Mary , Carvalho Patricia , Terreri Maria Teresa , Clemente Gleice
Published: April 2023

This is a multicentre prospective cohort including critically ill children and adolescents, with confirmed critical disease related to SARS-CoV-2, admitted to three tertiary paediatric intensive care units in the Brazilian Amazon, between April 2020 and July 2022. 208 patients were included (median age was 3.5 years). The majority had malnutrition (62%) and comorbidities (60.6%). Mechanical ventilation support, cardiogenic shock and acute respiratory distress syndrome occurred in 47%, 30% and 34.1% of patients, respectively. There were 37 (18%) deaths. A poor outcome of severe COVID-19 and multisystem inflammatory syndrome in children was observed in children and adolescents from the Brazilian Amazon.
Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma
Authors: Chakiryan Nicholas H , Kim Youngchul , Berglund Anders , Chang Andrew , Kimmel Gregory J , Hajiran Ali , Nguyen Jonathan , Moran-Segura Carlos , Saeed-Vafa Daryoush , Katende Esther N , Lopez-Blanco Neale , Chahoud Jad , Rappold Phillip , Spiess Philippe E , Fournier Michelle , Jeong Daniel , Wang Liang , Teer Jamie K , Dhillon Jasreman , Kuo Fengshen , Hakimi Abraham Ari , Altrock Philipp M , Mulé James J , Manley Brandon J
Published: April 2023

Introduction

In clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.

Methods

Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley’s K analysis, a methodology adapted from ecology.

Results

Clustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stroma interface was associated with worse clinical stage (tumor/CD163+nK(75): stage I/II: 4.4 (IQR −0.5 to 5.1); stage III: 1.4 (IQR −0.3 to 3.5); stage IV: 0.6 (IQR −2.1 to 2.1); p=0.04 between stage I/II and stage IV), and worse overall survival (OS) and cancer-specific survival (CSS) (tumor/CD163+nK(75): median OS–hi=149 months, lo=86 months, false-discovery rate (FDR)-adj. Cox p<0.001; median CSS–hi=174 months, lo=85 months; FDR-adj. Cox p<0.001). An RNA-seq differential gene expression score was developed using this geospatial metric, and was externally validated in multiple independent cohorts of patients with ccRCC including: TCGA KIRC, and the IMmotion151, IMmotion150, and JAVELIN Renal 101 clinical trials. In addition, this CD163+ geospatial pattern was found to be associated with a higher TIM-3+ proportion of CD8+T cells, indicative of terminal exhaustion (tumor-core: 0.07 (IQR 0.04–0.14) vs 0.40 (IQR 0.15–0.66), p=0.05).

Conclusions

Geospatial clustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stromal interface was associated with poor clinical outcomes and CD8+T cell terminal exhaustion.
Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression
Authors: Xu Jiuhui , Shi Qianyu , Lou Jingbing , Wang Boyang , Wang Wei , Niu Jianfang , Guo Lei , Chen Chenglong , Yu Yiyang , Huang Yi , Guo Wei , Lan Jianqiang , Zhu Yu , Ren Tingting , Tang Xiaodong
Published: April 2023

Background

Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets.

Methods

Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC).

Results

The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo.

Conclusions

Our study implicates that the CCL5–CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5–CCR5 axis is a potential therapeutic target in chordoma.