bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex and Estrous Cycle Are Not Mediators of S-Ketamine’s Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression
Authors: Arjmand Shokouh , Vadstrup Pedersen Marie , Silva Nicole R , Landau Anne M , Joca Sâmia , Wegener Gregers
Published: April 2023

Background

Recent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine’s antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach.

Methods

We evaluated the behavioral sensitivity to 20 mg/kg S-ketamine (i.p.) in male and female Flinders Sensitive Line rats (FSLs) and their counterpart Flinders Resistant Line rats (FRLs) subjected to the open field and forced swim tests. Female rats were disaggregated into different estrous phases, and the behavioral outcomes were compared.

Results

Acute administration of S-ketamine had robust antidepressant-like effects in FSLs. Within our study power, we could not detect sex– or estrous cycle–specific different antidepressant-like responses to S-ketamine in FSLs. Fluctuations in the levels of ovarian sex hormones across different estrous cycles did not behaviorally affect S-ketamine’s rapid-acting antidepressant mode of action. No sex-related or estrous cycle–related impact on behavioral despair was observed even among FRLs and saline-treated FSLs.

Conclusions

We conclude that physiological oscillations of estrogen and progesterone levels neither amplify nor diminish the behavioral antidepressant-like effect of S-ketamine. In addition, fluctuations of ovarian sex hormones do not predispose female animals to exhibit enhanced or reduced depressive-like and anxiety-like behaviors.
The Growth–Employment–Poverty Nexus in Africa
Authors: Fields Gary S
Published: April 2023

This paper focuses on employment and the labour market as a key mechanism leading from growth to poverty reduction in Africa. Given that the development goals are economy-wide outcomes—less poverty, shared prosperity, more and better job opportunities, etc.—the required analysis must be at the market level. Individual-level analysis is not enough. The paper brings together insights from labour economics and from development economics. It draws upon Fields’ work over decades at the intersection of these two fields. A concluding section presents suggestions for policy analysis.
The provenance of the forms of knowledge thesis
Authors: Standish Paul
Published: April 2023

This paper sets out to consider what is probably the most widely known of the writings of Paul Hirst, ‘Liberal Education and the Nature of Knowledge’. It examines the central concept of the ‘forms’ and goes on to explore the provenance of the ideas he develops in this paper, exposing diversity and some tension between these. At the end it offers some brief suggestions regarding the prospects for the idea of a liberal education today in the light of Hirst’s views.
Human metabolism and body composition: prospects for novel studies
Authors: Pontes-Silva André , Lopes André Luiz , Maciel Erika da Silva , Quaresma Fernando Rodrigues Peixoto , Dibai-Filho Almir Vieira
Published: April 2023

Context

Most articles on gut microbiota argue the importance of body composition assessment in patients; however, body composition assessments are fragile (ie, with methodological limitations) in the most recent studies.

Objective

To present two suggestions for further research using the human body composition assessment.

Methods

The methods used in this study are based on a Pinto et al article published in Nutrition Reviews.

Data extraction

On the basis of data

 

obtained from the PubMed, SCOPUS, LILACS, and Web of Science databases, Pinto et al provided a current survey of intermittent fasting protocols and an understanding of the outcomes to date in terms of the profile of the intestinal microbiota in obese organisms.

Data analysis

Of the 82 original articles identified from the databases, 35 were eliminated because of duplication and 32 were excluded for not meeting the inclusion criteria. Two additional articles found in a new search were added, yielding a total of 17 studies to be included in this review. Among the protocols, alternate-day fasting and time-restricted feeding were the most common, and they were shown to have different mechanisms of metabolic signaling. Time-restricted feeding influences body mass control and biochemical parameters by regulating the circadian system and improving satiety control systems by acting on leptin secretion. In contrast, alternate-day fasting leads to a reduction of ±75% of all energy consumption regardless of dietary composition, in addition to promoting hormonal adjustments that promote body mass control. Furthermore, both protocols could remodel the intestinal microbiota by changing the Firmicutes to Bacteroidetes ratio and increasing the abundance of strains such as Lactobacillus spp. and Akkermansia that have a protective effect on metabolism against the effects of body mass gain.

Conclusion

Changes in adipose tissue (eg, body mass loss, control, gain) should be interpreted via the sum of skinfolds in absolute values, waist perimeter, and patients' body proportionality, because fat is just a fraction of the adipocyte (lipid).
Language, Sexuality, History
Authors: Leap William L.
Published: April 2023

Discussions of language and sexuality within history typically aim to produce a chronology tracing how language use related to sexuality at some previous time became language use related to sexuality in more recent settings. But there are “far more possibilities for living than time as measurement would lead us to believe” (Dinshaw 2012: 137), and historical inquiry needs to capture those possibilities. This chapter proposes that a queer historical linguistics offers a useful framework for exploring those possibilities. Applying “scavenger methodology” to examples from an ongoing project (Leap 2020), the chapter explores relationships between language and sexuality in the years preceding the so-called Stonewall rebellion (late June 1969).
Indexicality of Grammar: The Case of Japanese Transgender Speakers
Authors: Abe Hideko
Published: April 2023

This article discusses how the intersection of grammatical gender and social gender, entwined in the core structure of language, can be analyzed to understand the dynamic status of selfhood. After reviewing a history of scholarship that demonstrates this claim, the discussion analyzes the language practices of transgender individuals in Japan, where transgender identity is currently understood in terms of sei-dōitsusei-shōgai (gender identity disorder). Based on fieldwork conducted between 2011 and 2019, the analysis reveals how individuals identifying with sei-dōitsusei-shōgai negotiate subject positions by manipulating the specific indexical meanings attached to grammatical structures.
Linguistic Landscapes of Language and Sexuality
Authors: Hiramoto Mie , Vitorio Raymund
Published: April 2023

This chapter outlines the benefits of a linguistic landscape studies approach for the broader study of language and sexuality. Chinese martial arts films, often described as highly masculine and dominated by male heroes and male characters, are a rich site for the analysis of the social construction of gender and sexuality, particularly in the way they portray an idealized male dominance through Confucian ideologies. These films are thus viewed as a legitimate space, albeit fictional and mediatized, for the application of a linguistic landscape perspective. Based on samples of over 200 films, the analysis argues that features in the linguistic landscapes of these films—among them referential names of landmarks and material constructions of settings and costumes—semiotically mark the gender and sexuality of the martial arts practitioner characters. Most notably, the linguistic landscapes in these films glorify celibacy—or controlled asexuality—as an ideal practice that goes along with ultimate masculinity, as seen in the homosocial rejection of romance and celebration of chastity.
Semiotics of Homonationalism
Authors: Lazar Michelle M.
Published: April 2023

This chapter discusses homonationalism as an analytical concept, which was developed originally to describe how queer identities get mobilized instrumentally to align with neoliberal agendas of nation-states. The chapter also discusses how this concept has been harnessed in newer ways to “do” a tactical politics of resistance by queer movements in illiberal contexts. Studies from the social sciences, broadly, and sociolinguistics, particularly, are presented, with a focus on how homonationalism as a discourse is semiotically construed in particular contexts. A detailed case study involving the Pink Dot movement in Singapore demonstrates the semiosis of homonationalism (in the sense of a resistive politics), through the multi- and inter-semiotic co-deployment of spoken and written language, color, visual images, photographic footages, symbols, music, and represented urban landscapes and embodiment cues. The chapter concludes by highlighting homonationalism as a complex analytical site at which queer politics can get done as well as undone.
A Deductive Solution to the Generalisation Problem for Horwich’s Minimalism about Truth
Authors: Busse Ralf
Published: April 2023

Minimalism is the view that our concept of truth is constituted by our disposition to accept instances of the truth schema ‘The proposition that p is true if and only if p’. The generalisation problem is the challenge to account for universal generalisations concerning logical truths such as ‘Every proposition of the form 〈if p, then p〉 is true’. This paper argues that such generalisations can be deduced using a single example of the logical truth in question and a single corresponding instance of the truth schema, employing the logical method of reasoning with arbitrary instances of universal and existential generalisations. Suggesting an inferentialist construal of Minimalism, the paper introduces conditional and general acceptance dispositions, distinguishes inferential meaning constitution from implicit definition, highlights the inferential nature of acceptance of instances of the truth schema, sketches a suitable account of structured propositions, compares higher-order with first-order means of quantification, and argues that the conception of truth Minimalism attributes to ordinary speakers is essentially inferential. It finally applies the deductive strategy to generalisations concerning logical validity as well as more complex logical truths.
Confluent and Reticulated Papillomatosis in Monozygotic Twins: A Case Series
Authors: Cascardo Camilla A. , Graham Shaveonté , Deirawan Hany , Daveluy Steven
Published: April 2023

Introduction:

Confluent and reticulated papillomatosis (CARP) is a non-inflammatory hyperkeratotic dermatosis that commonly affects teens and young adults. While the exact pathophysiology remains unknown, multiple theories exist including familial inheritance. The present literature on genetic predisposition remains limited to intergenerational relatives and siblings.

Case:

We describe a case of recurrent CARP with identical presentation and clinical course in two monozygotic 16-year-old female twins.

Discussion:

Though familial cases of CARP have been reported, the full pathogenesis of this dermatosis remains unknown. Metabolic conditions related to insulin resistance, thyroid and pituitary derangements, and pregnancy, have also been reported in patients with CARP. Thus, there may be a gene that links CARP to the development of other endocrinologic disorders. Furthermore, the simultaneous recurrence of CARP in our monozygotic twins supports an environmental trigger theory. Thus, we hypothesize that the pathophysiology of CARP is multifactorial.

Conclusion:

This case confirms a strong genetic predisposition, suggesting a greater inheritance component than previously considered.
Early COVID-19 Attitudes and Behaviors and Their Associations With Later Infection
Authors: Light Sophia W. , Opsasnick Lauren , Bailey Stacy C. , Yoshino Benavente Julia , Eifler Morgan , Lovett Rebecca M. , Russell Andrea , Yoon Esther , McCaffery Kirsten , Wolf Michael S.
Published: April 2023

Background:

At the onset of the pandemic, there was poor public awareness and inaction in response to COVID-19; it is less known whether this translated to subsequent infections.

Objectives:

To explore whether adults who perceived COVID-19 as less of a threat and who were not taking early actions were more likely to become infected over the following year.

Research Design:

Survey data from the ongoing (COVID-19 & Chronic Conditions (C3) anonymized for review) cohort study.

Participants:

Six hundred forty-two adults with a mean age of 63 and ≥1 chronic condition.

Measures:

Self-reported attitudes and behaviors regarding COVID-19 were assessed from March 13 to April 3, 2020, and COVID-19 infection status was captured between May 2020 and January 2021. Bivariate and multivariable analyses examined associations between early perceptions and behaviors with later infection.

Results:

Approximately 7% reported infection with COVID-19 (N = 46). Adults who perceived the threat of COVID-19 less seriously at the initial outbreak were more likely to test positive over the following year [odds ratio (OR): 0.81, CI: 0.70–0.94; P = 0.006]. Those who were less likely to believe their actions would affect whether they would become infected were more likely to test positive (OR: 0.87, CI: 0.77–0.99; P = 0.03), as were adults who reported not changing their routines (OR: 0.45; CI: 0.24–0.85; P = 0.01).

Conclusions:

Adults with delayed responses in acknowledging the threat of COVID-19 and in changing behaviors were more likely to contract the virus. This investigation provides insight into the consequences of inadequate public understanding and response to COVID-19, and it highlights the importance of promoting early awareness among high-risk groups during public health crises.
Assessment of PET/CT: National Electrical Manufacturers Association NU2-2018 Standards versus American Association of Physicists in Medicine Task Group 126
Authors: Akyol Sinem , Abuqbeitah Mohammad , Demir Mustafa
Published: April 2023

Objective

The aim of this study was to perform and evaluate PET/computed tomography acceptance tests separately using American Association of Physicists in Medicine (AAPM) Task Group 126 and National Electrical Manufacturers Association (NEMA) methods.

Materials and methods

Measurements of sensitivity, spatial resolution, count rate performance and scatter fraction, the accuracy of corrections for count losses and randoms, and image quality were obtained according to NEMA NU-2018. Likewise, the performance tests were made using the AAPM Task Group 126 method, and the results were compared with NEMA NU-2018.

Results

The sensitivity at the isocenter was 8.87 cps/kBq according to NEMA and 7.60 cps/kBq by using the AAPM Task Group 126. For the spatial resolution, the full width at half maximum (FWHM) and FWTM values were 4.34 mm and 6.78 mm at 1 cm radial offset by NEMA, while AAPM Task Group 126 yielded FWHM and FWTM values of 4.42 mm and 8.14 mm, respectively. In the image quality, NEMA exhibited hot lesions contrast of 40.8, 56.7, 69.9, and 77.3 for 10, 13, 17, and 22 mm spheres, respectively. As a ratio to 25 mm, the “Hot” max standard uptake values by AAPM Task Group 126 were found to be 1, 1.1, 1.37, and 1.68 for 8, 12, 16, and 25 mm lesions, respectively.

Conclusion

Acceptance tests using NEMA are of high relevance and convenience for the reliability of the results. Alternatively, AAPM Task Group 126 seems convenient and more economical to apply with reliable outcomes for the equivalent tests.
Sex Difference in Primary Sjögren Syndrome
Authors: Zhang Yan , Chen Jia-Qi , Yang Jian-Ying , Liao Jia-He , Wu Tzu-Hua , Yu Xin-Bo , Huang Zi-Wei , He Qian , Wang Qin , Song Wei-Jiang , Luo Jing , Tao Qing-Wen
Published: April 2023

Objectives

The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS.

Methods

Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ2 test.

Results

This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries (p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels (p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 (p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity (p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease (p < 0.05).

Conclusions

Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.
Three-Dimensional Printed Titanium Prosthesis for Mandibular Condyle Reconstruction After Extensive Resection of Chondrosarcoma: A 6-year Follow-Up
Authors: Han Xiaodong , Song Baixuan , Chen Yuheng , Lin Xiaozhen
Published: April 2023

Chondrosarcomas (CHS) are malignant mesenchymal tumors arising from cartilage. Chondrosarcomas arising in the temporomandibular joint are especially rare. Herein, the authors report an unusual case of a 50-year-old female who presented with a progressive swelling in the left preauricular region. Computed tomography and magnetic resonance imaging revealed an osteolytic and expansive lesion in the left condyle. The diagnosis tended to be a malignant tumor. A resection guide and 3-dimensional printed titanium prosthesis for condyle reconstruction were designed. Extended resection of the left condyle and reconstruction were performed. The pathologic diagnosis was consistent with CHS (grade II). There was no tumor recurrence or distant metastasis at the 6-year follow-up, and good occlusion and satisfactory function of the temporomandibular joint were regained.
Penetration of a Wooden Foreign Body into the Zygomaticomaxillary Bone to the Nasal Cavity: Navigation-Guided Successful Treatment
Authors: Park Tae Hwan
Published: April 2023

Penetrations of the nasal cavity through the zygomaticomaxillary bone by wooden foreign bodies have not been reported yet. Wooden foreign bodies, characterized as hypodense signals resembling air bubbles on computed tomography scans, could increase the risk of infection and abscess formation if left untreated. Therefore, any possible attempts to remove it entirely should be made in a timely manner. Also, regarding removal surgery, the complications of the surgery, such as massive bleeding or iatrogenic injury to the adjacent structure, should be considered, especially in the paranasal area. At the construction site, a 67-year-old worker hit his right cheek with a wooden foreign body. A wooden foreign body penetrated the right cheek and extended into the right nasal cavity through the zygomaticomaxillary complex. Using a navigation system, the wooden foreign body was removed from the right zygomaticomaxillary bone to the unilateral nasal cavity, and we cauterized arterial bleeding. After bleeding control, we reconstructed the bony defect with an absorbable mesh with screws. Septal reconstruction was also done, along with debridement and irrigation of the nasal cavity. We conducted a follow-up computed tomography scan a week later and confirmed that the wooden foreign body was successfully removed without any residual ones. The fracture was also reduced successfully.
A classification scheme for mixed-species bird flocks
Authors: Mangini G. Giselle , Rutt Cameron L. , Sridhar Hari , Buitron Galo , Muñoz Jenny , Robinson Scott K. , Montaño-Centellas Flavia , Zarco Agustin , Fanjul M. Elisa , Fernández-Arellano Gilberto , Xing Shuang , Camerlenghi Ettore
Published: April 2023

The literature on mixed-species flocks references a wide variety of bird associations. These studies, however, have used an array of unstructured characteristics to describe flocks, ranging from the temporal occurrence of flocking to the identity and behavioural features of constituent members, with little consensus on which key traits define and characterize a mixed-species flock. Moreover, although most studies report species-specific roles, there is no clear consensus about what these roles signify nor how to define them. This lack of consistency limits our ability to compare flocks from different habitats, regions and species pools. To unify this sizable body of literature, we reviewed and synthesized 538 studies on mixed-species flocks. We propose 13 categories to classify mixed-species flocks using behavioural and physical traits at the flock and participant level, as well as the habitat where the flock occurs. Lastly, we discuss the historical terminology for different species roles and propose definitions to clarify and distinguish among nuclear, leader, sentinel, and flock-following species. We envision that these guidelines will provide a universal language for mixed-species flock research, paving the way for future comparisons and new insight between different regions and systems.

This article is part of the theme issue ‘Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes’.
Identifying the social context of single- and mixed-species group formation in large African herbivores
Authors: Saltz J. B. , Palmer M. S. , Beaudrot L.
Published: April 2023

Despite continued interest in mixed-species groups, we still lack a unified understanding of how ecological and social processes work across scales to influence group formation. Recent work has revealed ecological correlates of mixed-species group formation, but the mechanisms by which concomitant social dynamics produce these patterns, if at all, is unknown. Here, we use camera trap data for six mammalian grazer species in Serengeti National Park. Building on previous work, we found that ecological variables, and especially forage quality, influenced the chances of species overlap over small spatio-temporal scales (i.e. on the scales of several metres and hours). Migratory species (gazelle, wildebeest and zebra) were more likely to have heterospecific partners available in sites with higher forage quality, but the opposite was true for resident species (buffalo, hartebeest and topi). These findings illuminate the circumstances under which mixed-species group formation is even possible. Next, we found that greater heterospecific availability was associated with an increased probability of mixed-species group formation in gazelle, hartebeest, wildebeest and zebra, but ecological variables did not further shape these patterns. Overall, our results are consistent with a model whereby ecological and social drivers of group formation are species-specific and operate on different spatio-temporal scales.

This article is part of the theme issue ‘Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes’.
Relationship among vegetation structure and mixed-species flocks composition along the latitudinal gradient of the subtropical montane forest of the Yungas, Argentina
Authors: Fanjul María Elisa , Echevarria Ada Lilian , Martínez María Valeria
Published: April 2023

The structural and physiognomic characteristics of forests and mountain forest are fundamental aspects that influence the richness, abundance and composition in the bird community. The objective of the present work was to analyse how the vegetation structure could influence the species composition of mixed-species flocks (MSF), along the latitudinal gradient of the subtropical montane forest of the Yungas of Argentina. Eight sites were studied along the 700 km of distribution of the Argentine Yungas. Richness and abundance of MSF were determined. In addition, different variables of composition and structure of the vegetation were analysed. Multivariate analysis indicated that vertical strata coverage and litter depth were the main variables associated with changes in the species composition of MSF along the gradient. Variation in MSF composition within the Yungas was associated with the physiognomy of the subtropical montane forest, which could indicate that it is strongly linked to the condition of the local vegetation. Substantial changes in vegetation could drastically change the composition of the resident flocks.

This article is part of the theme issue ‘Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes’.
Revisiting the ‘nuclear species’ concept: do we really know what we think we know?
Authors: Bangal Priti , Sridhar Hari
Published: April 2023

The idea of ‘nuclear species’ has received a lot of attention in mixed-species flock research. Our impression of this literature is that referenced statements tend to cite the same papers in support of a small set of ideas, and often there is a mismatch between what papers contain and what they're cited for. Motivated by these impressions, we built and quantitatively examined a database of referenced statements about nuclearity in flocks. This confirmed our impression quantitatively, but more strikingly, a single paper stood out in its influence on ideas around nuclearity in flocks. Moynihan's 1962 monograph on mixed-species flocks in Panama, ‘The organization and probable evolution of some mixed-species flocks of neotropical birds’ published in Smithsonian Miscellaneous Collections, was cited twice as much as the next most-cited paper and was the most-cited paper for 10 out of 15 most-discussed ideas related to nuclearity. Further, a number of other highly cited papers are strongly influenced by Moynihan's ideas, i.e. its influence is much greater than what a count of citations conveys. We also found that Moynihan was mis-cited frequently. We juxtapose what we found from the citation analysis with what the paper actually contains to better understand the nature of support that Moynihan provides, and discuss the implications of our findings for what we know about and how we research nuclearity in flocks.

This article is part of the theme issue ‘Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes’.
Haematological malignancies as disorders negatively impacting specificities of the direct agglutination and rapid rK39 strip tests as reference diagnostics for visceral leishmanisis
Authors: Nail Abd Elsalam , Ahmed Ikram , Ali Osman Hussam , el Harith Abdallah
Published: April 2023

Introduction. During several years of work in Sudan, we occasionally had been confronted with patients who presented clinical features highly suggestive of visceral leishmaniasis (VL) however direct agglutination test (DAT) readings that were either at the high negative or low positive titre range. Inquiries on the fate of those particular patients revealed mortality, undetermined diagnosis or that in some of them leukaemia was finally diagnosed.

Gap statement. Investigate as to what extent haematological malignancies (HMs) interfere with VL diagnosis.

Aim. Evaluate specificity of DAT version newly developed in this study wherein sodium dodecyle sulphate (SDS) was incorporated as a test sample denaturant in comparison with a standard reference wherein β-mercaptoethanol (β-ME) was used in test execution.

Methodology. Seventy plasma samples from patients with HMs were collected and tested in a primary DAT version (P-DAT). The results obtained were compared with those of the rK39 strip test as VL reference diagnostic. HM samples revealing titres higher than the start dilution (1 : 100) in P-DAT were further tested in a β-ME- and urea-modified DAT versions. The specificity of the newly developed SDS-DAT was assessed against that of β-ME-DAT and rK39 strip tests as current reference diagnostics for VL.

Results. Seven out of 70 patients with HMs scored positive outcomes (titre ≥1 : 3200) in P-DAT and four in the reference rK39 strip test. Of the seven that tested positive in P-DAT or four in the reference rK39, none reacted at titre >1 : 100 in the SDS-DAT. Significant reduction in non-specific agglutination reactions was achieved as a result in respect to the HM plasma samples (P value <0.05).

Conclusion. To establish desired specificity for VL diagnosis in respect to HMs and subsequently minimize or avoid serious side effects due to unjustified anti-leishmanials prescription the combined application of the SDS-DAT here described and an improved version of the rK39 for confirmation is recommended.
Halobacterium salinarum: Life with more than a grain of salt
Authors: Eichler Jerry
Published: April 2023

Halobacterium salinarum

is a halophilic (salt-loving) archaeon that grows in salt concentrations near or at saturation. Although isolated from salted fish a century ago, it was the 1971 discovery of bacteriorhodopsin, the light-driven proton pump, that raised interest in Hbt. salinarum across a range of disciplines, including biophysics, chemistry, molecular evolution and biotechnology. Hbt. salinarum have since contributed to numerous discoveries, such as advances in membrane protein structure determination and the first example of a non-eukaryal glycoprotein. Work on Hbt. salinarum, one of the species used to define Archaea, has also elucidated molecular workings in the third domain. Finally, Hbt. salinarum presents creative solutions to the challenges of life in high salt.
Upsurge in Hospitalization of Pediatric Patients with Severe Acute Respiratory Infections in Kolkata and Surrounding Districts Caused by Recombinant Human Respiratory Adenovirus Type B 7/3
Authors: Majumdar Agniva , Saha Ritubrita , Chatterjee Ananya , Gupta Rudrak , Chaudhuri Ratul Datta , Chakrabarti Alok Kumar , Chawla-Sarkar Mamta , Dutta Shanta
Published: April 2023

Globally, different genotypes of human adenoviruses are associated with outbreaks of acute respiratory infection though such evidence is lacking from India. In the present study, we report a sudden increase in the positivity of respiratory adenovirus among hospitalized children with acute respiratory infection from Kolkata and the surrounding districts of West Bengal, India, from December 2022 till date. A sharp rise in the positivity rate of respiratory adenovirus was found which ranged from 22.1% in early December 2022 to 52.6% in mid-March 2023. The overall positivity was 40.4% during the period and children in the 2 to <5 years (51.0%) age group were mostly affected. Single infection with adenovirus was found in 72.4% of cases while co-infection with Rhinovirus was the maximum (9.4%). Around 97.5% of positive cases required hospitalization. Cough, breathlessness, and wheeze were the most common clinical features among positive patients. Phylogenetic analysis of the hexon and fiber gene of all the sequenced strains revealed HAdV-B 7/3 recombination with more than 99% homology within themselves. This report of a respiratory adenovirus outbreak in West Bengal, India causing severe illness in the pediatric population underscores the need for regular monitoring of the circulating strains.
Prevalence and Associated Factors of Hearing impairment among Children attending Birhanzare Primary School, Addis Ababa, Ethiopia
Authors: Haile Bitseat W. , Feyissa Yibeltal M. , Kassa Betelehem B , Etissa Eyob Kebede , Asrat Haregewoin , Tadesse Michael A. , Mekasha Amha
Published: April 2023

Background

Hearing impairment is the most prevalent sensory disability globally and a condition of growing concern with around 5.3% of the population having disabling hearing loss. It has significant impacts on the individual and society. The problem is even greater for children as hearing is the main source for language, speech, and cognitive developments.

Methods

A school based cross-sectional study at an elementary school in Addis Ababa, Ethiopia was conducted in May 2018. One hundred and ten students from grades 1-5 were enrolled in the study. A structured questionnaire filled by parents/caregivers. Audiometric testing and otoscopic examinations were used to determine hearing impairment and abnormal otoscopic findings respectively. Data was analyzed using SPSS version 25. Descriptive and basic statistical analysis was applied. Logistic regression was used to identify risk factors for hearing impairment. Statistical significance was declared at p values < 0.05.

Results

A total of 106 students (27.4% male and 72.6% female) were enrolled in the study. Abnormal otoscopic findings were observed among 30.2% of the participants, with wax being the commonest abnormality observed in twenty-two point eight (22.8%), pus discharge and dull tympanic membrane in 4%, foreign bodies were found in 3 of the participating students (2.8%). The prevalence of disabling hearing impairment in this study (>25db on the better hearing ear), was 34% where the majority (32.1%) had mild hearing impairment. Abnormal otoscopic finding showed significant association with hearing impairment.

Conclusion

The prevalence of hearing impairment in our study is higher than WHO and other regional estimates. Given the high prevalence of HI, availability of management options for mild HI, and its underlying causes, early hearing screening programs in children should be integrated into existing systems such as the Ethiopian school health program as well as early childhood growth and development monitoring entry points.
A CRISPR-drug perturbational map for identifying new compounds to combine with commonly used chemotherapeutics
Authors: Lee Hyeong-Min , Wright William C. , Pan Min , Low Jonathan , Currier Duane , Fang Jie , Singh Shivendra , Nance Stephanie , Delahunty Ian , Kim Yuna , Chapple Richard H. , Zhang Yinwen , Liu Xueying , Steele Jacob A. , Qi Jun , Pruett-Miller Shondra M. , Easton John , Chen Taosheng , Yang Jun , Durbin Adam D. , Geeleher Paul
Published: April 2023

Combination chemotherapy is crucial for achieving durable cancer cures, however, developing safe and effective drug combinations has been a significant challenge. To improve this process, we conducted large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritized neuroblastoma, the most common pediatric solid tumor, where 50% of high-risk patients do not survive. Our screen examined all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest drug combination screens ever reported. Remarkably, using dense drug-drug rescreening, we found that the top CRISPR-nominated drug combinations were far more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discovered that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicinin vitroandin vivousing PDX models. Our findings provide a valuable resource for the development of improved chemotherapeutic strategies and demonstrate the feasibility of using targeted CRISPR knockout to discover new combinations with common chemotherapeutics, a methodology with application across all cancers.
Base Editor Scanning Reveals Activating Mutations of DNMT3A
Authors: Garcia Emma M. , Lue Nicholas Z. , Liang Jessica K. , Lieberman Whitney K. , Hwang Derek D. , Woods James , Liau Brian B.
Published: April 2023

DNA methyltransferase 3A (DNMT3A) is ade novocytosine methyltransferase responsible for establishing proper DNA methylation during mammalian development. Loss-of-function (LOF) mutations to DNMT3A, including the hotspot mutation R882H, frequently occur in developmental growth disorders and hematological diseases, including clonal hematopoiesis (CH) and acute myeloid leukemia (AML). Accordingly, identifying mechanisms that activate DNMT3A is of both fundamental and therapeutic interest. Here, we applied a base editor mutational scanning strategy with an improved DNA methylation reporter to systematically identify DNMT3A activating mutations in cells. By integrating an optimized cellular recruitment strategy with paired isogenic cell lines with or without the LOF hotspot R882H mutation, we identify and validate three distinct hyperactivating mutations within or interacting with the regulatory ADD domain of DNMT3A, nominating these regions as potential functional target sites for pharmacological intervention. Notably, these mutations are still activating in the context of a heterozygous R882H mutation. Altogether, we showcase the utility of base editor scanning for discovering functional regions of target proteins.

Synopsis

Using base editor mutagenesis and a DNA methylation reporter optimized to find activating mutations, we identify novel hyperactivating mutations in DNMT3A that suggest new mechanisms of allosteric control.
Novel lytic and lysogenic cyanophages predicted to infectMicrocoleusassociated with anatoxin-producing benthic mats
Authors: Valadez-Cano Cecilio , Reyes-Prieto Adrian , Lawrence Janice
Published: April 2023

Proliferations of toxic benthic cyanobacteria are increasingly being reported around the world. Of particular concern areMicrocoleus-dominated mats associated with anatoxin production that have resulted in dog fatalities. Although the impact of cyanophages has been demonstrated in planktonic systems, their role in the population dynamics of benthic cyanobacteria has received little attention. Here we use metagenomics to explore phage presence in benthic mats from the Wolastoq|Saint John River (WR; New Brunswick, Canada) and Eel River (ER; California, US). Our survey recovered multiple viral-like sequences associated with different putative bacterial hosts, including two cyanophage genomes with apparently different replication strategies. A lysogenic cyanophage (predicted as a prophage) was found integrated in the genomes ofMicrocoleussp. 3 recovered from five ER mat samples. This Microcoleus phage is related to previously described Phormidium phage counterparts. Also, we recovered lytic cyanophages from WR and ER mats dominated by anatoxin-producingMicrocoleus, which was predicted as the putative host. Despite the geographical distance between WR and ER, the lytic Microcoleus phage genomes recovered from each river have similar sizes (circa 239 Kbp) and share similar gene content with high sequence identity. Phylogenetic analysis suggests that these lytic Microcoleus phages are distant from any other cyanophage previously described. Our results constitute the first report of cyanophages predicted to infect and therefore influence the population dynamics of mat-formingMicrocoleusspp. associated with anatoxin production.
Effect of Intermittent Pneumatic Compression on Preventing Deep Vein Thrombosis Using Microfluidic Vein Chip
Authors: Dai Hongtao , Chai Senlin , Xu Wei , Yao Yao , Tang Wenlai , Shi Jianping , Yang Ji quan , Jiang Qing , Zhu Liya
Published: April 2023

Deep vein thrombosis (DVT) is a common disease often occurring in the lower limb veins of bedridden patients. Intermittent pneumatic compression (IPC) has been considered an effective approach to solve this problem. In our previous research, 264 patients were randomly treated either with IPC for one or eight hours per day. The incidence of severe venous thrombosis was significantly lowered in the IPC group than in the control group. However, it is still a chanllenge to real-time monitoring the blood flow and thrombus formation process during IPC operation periods. Here we made a microfluidic vein chip with valves embedded in a flexible channel that can mimic the compression of vessels by IPC contractrion. Driven by inlet blood velocity obtained clinally, numerical simulation were conducted to identify the shear stress and laminar pressure distribution in the vein. The obtained results showed that the thrombus formation can be reduced with Higher compressive pressure and smaller time interval. 24s interval time and 40mmHg maximum contractive pressure was considered to be the most appropriate parameters for DVT prevention. This vein chip offers a new approachin vitroto observe the working mechanism of IPC device, offering important data for its further clinical standard regulation.
Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study
Authors: Bosworth Matthew L. , Shenhuy Boran , Walker A. Sarah , Nafilyan Vahé , Alwan Nisreen A. , O’Hara Margaret E. , Ayoubkhani Daniel
Published: April 2023

Background

Little is known about the risk of Long Covid following reinfection with SARS-CoV-2. We estimated the likelihood of new-onset, self-reported Long Covid after a second SARS-CoV-2 infection, and compared to a first infection.

Methods

We included UK COVID-19 Infection Survey participants who tested positive for SARS-CoV-2 between 1 November 2021 and 8 October 2022. The primary outcome was self-reported Long Covid 12 to 20 weeks after each infection. Separate analyses were performed for those <16 years and ≥16 years. We estimated adjusted odds ratios (aORs) for new-onset Long Covid using logistic regression, comparing second to first infections, controlling for socio-demographic characteristics and calendar date of infection, plus vaccination status in those ≥16 years.

Results

Overall, Long Covid was reported by those ≥16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those <16 years were 1.0% and 0.6%. The aOR for Long Covid after second compared to first infections was 0.72 (95% confidence interval: 0.63–0.81) for those ≥16 years and 0.93 (0.57–1.53) for those <16 years.

Conclusions

The risk of new-onset Long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those ≥16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset Long Covid after a second infection, with around 1 in 40 of those ≥16 years and 1 in 165 of those <16 years reporting Long Covid after a second infection.
Selenium reduction of ubiquinone via SQOR suppresses ferroptosis
Authors: Lee Namgyu , Park Sung Jin , Lange Mike , Tseyang Tenzin , Doshi Mihir B. , Kim Tae Yong , Song Yoseb , Kim Dong In , Greer Paul L. , Olzmann James A. , Spinelli Jessica B. , Kim Dohoon
Published: April 2023

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here, we demonstrate that selenium, via its metabolic intermediate hydrogen selenide, efficiently donates its electrons to ubiquinone to form ubiquinol in the mitochondria through catalysis by sulfide quinone oxidoreductase (SQOR). Hydrogen selenide is superior to hydrogen sulfide as an electron donor owing to its larger valence shell. We show that this mechanism, independently of selenoprotein production, protects against ferroptosis via ubiquinol production in a manner that depends on xCT mediated selenide formation and SQOR activity. Our findings identify a regulatory mechanism against ferroptosis that implicates SQOR and expands our understanding of selenium in biology.
Efficient Fisher Information Computation and Policy Search in Sampled Stochastic Chemical Reaction Networks through Deep Learning
Authors: Badolle Quentin , Berrada Gabrielle , Khammash Mustafa
Published: April 2023

Markov jump processes constitute the central class of Chemical Reaction Network models used to account for the intrinsic stochasticity observed in the dynamics of molecular species abundance throughout Molecular Biology. These models are specified in a parametric form, and their identification requires the use of inference procedures, and in particular the estimation of the Fisher Information. Here, a fast and accurate computation method is introduced in the case of partial observations at discrete time points, based on the use of a Mixture Density Network. We also demonstrate how this Neural Network can be used to perform fast policy search. The efficiency of these approaches is illustrated on a set of examples, and is compared to that of the current state-of-the-art.
Extracellular thiamine concentration influences thermogenic competency of differentiating neck area-derived human adipocytes
Authors: Vinnai Boglárka Ágnes , Arianti Rini , Győry Ferenc , Fésüs László , Kristóf Endre
Published: April 2023

Brown adipose tissue (BAT) dissipates energy in the form of heat majorly via the mitochondrial uncoupling protein 1 (UCP1). The activation of BAT, which is enriched in the neck area and contains brown and beige adipocytes in humans, was considered as a potential therapeutic target to treat obesity. Therefore, finding novel agents that can stimulate the differentiation and recruitment of brown or beige thermogenic adipocytes are important subjects for investigation. The current study investigated how the availability of extracellular thiamine (vitamin B1), an essential cofactor of mitochondrial enzyme complexes that catalyze key steps in the catabolism of nutrients, affects the expression of thermogenic marker genes and proteins and subsequent functional parameters duringex vivoadipocyte differentiation. Therefore, we differentiated primary human adipogenic progenitors that were cultivated from subcutaneous (SC) or deep neck (DN) adipose tissues in the presence of gradually increasing thiamine concentrations during their 14 day long differentiation program. Higher thiamine levels resulted in increased expression of thiamine transporter 1 and 2 both at mRNA and protein levels in human neck area-derived adipocytes. Gradually increasing concentrations of thiamine led to increased basal, cAMP-stimulated, and proton-leak respiration along with elevated mitochondrial biogenesis of the differentiated adipocytes. The extracellular thiamine availability during adipogenesis determined the expression levels of UCP1, PGC1a, CKMT2, and other browning-related genes and proteins in primary SC and DN-derived adipocytes in a concentration-dependent manner. Providing abundant amounts of thiamine further increased the thermogenic competency of the adipocytes. Our study raises the possibility of a novel strategy with long-term thiamine supplementation, which can enhance the thermogenic competency of differentiating neck area-derived adipocytes for preventing or combating obesity.