bluuebunny/crossref_metadata_2025 huggingface dataset:
Solitude can be good—If you see it as such: Reappraisal helps lonely people experience solitude more positively
Authors: Rodriguez Micaela , Pratt Samuel , Bellet Benjamin W. , McNally Richard J.
Published: September 2023

Objective

Solitude is a common experience that can elicit both positive (e.g., relaxation) and negative (e.g., loneliness) emotions. But can changing the way we think about solitude improve its emotional effects? In a previous study, our team found that positively reframing solitude buffers against a reduction in positive affect when alone. Yet, it is unknown whether people who are lonely—and thus more likely to experience solitude negatively—benefit from modifying their beliefs about being alone.

Method

Here, we test whether reframing solitude as a beneficial experience or de‐stigmatizing loneliness helps people experiencing moderate‐to‐severe loneliness (N = 224) feel more positive emotion and less negative emotion during solitude. We randomly assigned participants to read about either the benefits of solitude, the high prevalence of loneliness, or a control topic. Then, participants spent 10 min alone in the laboratory. State affect was assessed before and after the solitude period.

Results

Across conditions, the solitude period reduced high‐arousal positive (e.g., excited) and high‐arousal negative (e.g., anxious) affect. Notably, people who read about the benefits of solitude experienced a significantly larger increase in low‐arousal positive affect compared with the control condition.

Conclusion

Our findings indicate that lonely individuals can more readily reap the emotional benefits of solitude when they reframe solitude as an experience that can enhance their well‐being.
Equivalence and non‐inferiority tests using replicated discrimination and preference data
Authors: Meyners Michael , Carr B. Thomas , Kunert Joachim
Published: September 2023

Using replications in discrimination tests is becoming more common in times of strict budgetary and time constraints. For the proof of differences, it is well‐known that the standard binomial test can be used. However, it is no longer applicable if the objective is to show equivalence or non‐inferiority, as potential differences among assessors (assessor heterogeneity/overdispersion) might invalidate the binomial test. We reapply ideas described earlier for the development of a confidence interval to derive a direct asymptotic test for equivalence or non‐inferiority using replicated discrimination and preference data, both for the cases of equal and unequal numbers of replications among assessors. The suggested test is largely model‐free, that is, does not require any assumptions that cannot be easily warranted by the test design and execution. At the same time, implementation is surprisingly easy by using the R code provided or any simple spreadsheet editor, or even manually.

Practical Applications

Showing equivalence in perception between stimuli becomes increasingly important in applications, for example, in cost‐savings or product‐matching. The suggested approach is statistically valid without potentially doubtful model assumptions, yet at the same time simple and easy to use. Tables with critical values and R code for the evaluations further ease adoption, as illustrated by three small examples. The power assessments indicate that the loss in power is only moderate as long as the number of replications is not excessive, making replicate evaluations in discrimination tests a viable option for showing equivalence. The common approach of concluding for equivalence when a test for differences does not turn out to be statistically significant is heavily flawed; given that a valid yet simple approach to establish equivalence from replicated discrimination and preference data is provided here, such practice should be abandoned.
Transcriptomic response of Cinachyrella cf. cavernosa sponges to spatial competition
Authors: Deshpande Aabha , Rivera‐Vicéns Ramón E. , Thakur Narsinh L. , Wörheide Gert
Published: September 2023

Spatial competition in the intertidal zones drives the community structure in marine benthic habitats. Organisms inhabiting these areas not only need to withstand fluctuations in temperature, water level, pH, and salinity but also need to compete for the best available space. Sponges are key members of the intertidal zones, and their life history processes (e.g. growth, reproduction, and regeneration) are affected by competition. Here, we used transcriptomics to investigate the effects of interspecific competition between the tetillid sponge Cinachyrella cf. cavernosa, the zoantharid Zoanthus sansibaricus and the macroalgae Dictyota ciliolata in the field. The analysis of differentially expressed genes showed that Z. sansibaricus was the more stressful competitor to C. cf. cavernosa, which showed an upregulation of cellular respiration under stress of competition. Similarly, an upregulation of energy metabolism, lipid metabolism and the heat‐shock protein (HSP) 70 was also observed along with an increase in viral load and decreased ability to synthesize protein. A downregulation of purine and pyrimidine metabolism indicated a reduction in the physiological activities of the competing sponges. Moreover, a putative case of possible kleptocnidism, not previously reported in C. cf. cavernosa, was also observed. This study offers a glimpse into the inner workings of marine organisms competing for spatial resources using transcriptome data.
Small collections remembered: Sámi material culture and community‐based digitization at the Smithsonian Institution
Authors: Magnani Matthew , Porsanger Jelena , Laiti Sami , Magnani Natalia , Olli Anne May , Rauhala Paula , Valkeapää Samuel , Hollinger Eric
Published: September 2023

Of the 158 million things housed by the Smithsonian Institution, about 56 objects originate from Sámi communities. By all accounts a small group of objects—even by the standards of the Arctic collections at the Institution—it may be easily overlooked or dismissed as insignificant, based on entrenched ideologies about idealized collections. Presenting a community‐based methodology for the engagement of distant museum collections using three‐dimensional technologies, this article establishes the latent potential of small collections for Indigenous communities. We demonstrate how a group of 56 objects not only chronicles complex histories of exchange and colonialism, but also provides a manageable conduit for learning and exchange to facilitate the continued restructuring of relationships between museums and descendent stakeholders, from the individual to community level. Small collections, far from incomplete, may not only contain materials significant to descendent groups on their own terms, but provide the grounds to generate new forms of Indigenous initiated, balanced reciprocity.
Tackling redundancy: genetic mechanisms underlying paralog compensation in plants
Authors: Iohannes Sessen Daniel , Jackson David
Published: September 2023

Gene duplication is a powerful source of biological innovation giving rise to paralogous genes that undergo diverse fates. Redundancy between paralogous genes is an intriguing outcome of duplicate gene evolution, and its maintenance over evolutionary time has long been considered a paradox. Redundancy can also be dubbed ‘a geneticist's nightmare’: It hinders the predictability of genome editing outcomes and limits our ability to link genotypes to phenotypes. Genetic studies in yeast and plants have suggested that the ability of ancient redundant duplicates to compensate for dosage perturbations resulting from a loss of function depends on the reprogramming of gene expression, a phenomenon known as active compensation. Starting from considerations on the stoichiometric constraints that drive the evolutionary stability of redundancy, this review aims to provide insights into the mechanisms of active compensation between duplicates that could be targeted for breaking paralog dependencies – the next frontier in plant functional studies.
Ethanol infusion therapy for peri‐mitral atrial tachycardia through the Marshall bundle with electrical irrelevance of left atrial appendage and mitral isthmus
Authors: Kimura Kohki , Nakamura Kohki , Sasaki Takehito , Naito Shigeto
Published: September 2023

A 62‐year‐old man with a history of catheter ablation for atrial fibrillation and atrial tachycardia (AT) received a line of block of the mitral isthmus (MI) and electrical isolation of the left atrial appendage (LAA). Upon entrainment pacing, AT recurred and was diagnosed as peri‐mitral AT (PMAT) with electrical irrelevance of MI, LAA, and left pulmonary vein, having a critical isthmus identified as Marshall bundle (MB). MB was then infused with ethanol, leading to the successful treatment of the PMAT.
Non‐vascular intracranial lesions in three children with PHACE association
Authors: Mologousis Mia A. , Balkin Daniel M. , Smith Edward R. , Lidov Hart G. W. , Li Alice M. , Yang Edward , Liang Marilyn G.
Published: September 2023

PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac anomalies, eye anomalies) association has many recognized clinical features. A link between PHACE and non‐vascular intracranial lesions has not been well‐described. We report three pediatric patients with PHACE and non‐vascular intracranial lesions.
Adjustment disorder and its risk factors during the solid organ pre‐transplant period for children: A retrospective analysis of the last 10 years
Authors: Kaba Duygu , Sarı Burcu Akın , Taner Hande Ayraler
Published: September 2023

Background

Adjustment disorder (AD) in individuals suffering from end‐stage organ failure can negatively impact treatment adherence and overall quality of life. Previous research focusing on adults has suggested that AD might serve as a precursor to major mental disorders. However, although it is frequently used as a diagnosis in consultation‐liaison psychiatry, our understanding of AD in pediatric transplant candidates remains limited. Therefore, the objective of this study is to assess AD and identify its associated risk factors among children who are candidates for heart, kidney, and liver transplantation.

Methods

Data were collected retrospectively from a cohort of 155 children, aged between 6 months and 18 years (mean age 9.4), who had undergone consultations for child and adolescent psychiatry at a hospital with a transplant center within the past 10 years.

Results

The predominant diagnosis among children assessed during the pre‐transplant period was AD (20%), with the subtype “with depressed mood” being the most commonly observed (35.5%). Organ type and length of hospital stay were identified as significant independent predictors of AD. Being a heart transplant candidate was determined as the strongest predictor of AD among children who underwent consultations with child and adolescent psychiatry within the population of transplant candidates.

Conclusions

The study found that AD was the most common diagnosis among transplant candidates who underwent psychiatric consultations. Additionally, the study identified the length of hospital stay and the type of organ needed as independent predictors of AD. Screening for AD by considering risk factors may provide an opportunity for early intervention before the occurrence of major mental disorders in transplant candidates.
Strategic social media marketing: An empirical analysis of sequential advertising
Authors: Hotkar Parshuram , Garg Rajiv , Sussman Kristen
Published: September 2023

Social media platforms like Facebook and Twitter have emerged as effective channels for advertising that enable consumer targeting based on demographics, interests, and user behavior. Social media marketers have utilized information spillover within these platforms to reach a larger customer base. This information spillover also exists across groups of users within the platform and enhances returns from social media advertising. Thus, this information spillover can be utilized to strategically sequence targeted advertising to amplify the returns from social media ads. In this paper, we present a theoretical model for information retention and show that the sequential advertising strategy is effective in targeting groups of users on a social media platform. In addition, we provide empirical evidence through two series of randomized field experiments. From experiments for a health services organization, we find that sequential advertising campaigns provide 23% more clicks when compared to campaigns that target groups simultaneously, which translates to a saving of 18.7% in the advertising budget to achieve similar results as simultaneous advertising. Additionally, we found that sequential advertising campaigns targeting a smaller group first followed by a larger group provide 10.7% additional clicks when compared to targeting a larger group first followed by a smaller group. These results were consistent for consumer packaged goods that were advertised on Facebook and Twitter. These results provide implications for social media advertising research and practice.
Advances in understanding canine pregnancy: Endocrine and morpho‐functional regulation
Authors: Kowalewski Mariusz P.
Published: September 2023

Canine pregnancy relies on luteal steroidogenesis for progesterone (P4) production. The canine placenta responds to P4, depending on the nuclear P4 receptor (PGR). This has sparked interest in investigating the interaction between ovarian luteal steroids and the placenta in dogs. Canine placentation is characterized by restricted (shallow) trophoblast invasion, making the dog an interesting model for studying decidua‐derived modulation of trophoblast invasion, compared with the more invasive (hemochorial) placentation. The PGR is expressed in maternally derived decidual cells and plays a crucial role in feto‐maternal communication during pregnancy maintenance. Understanding PGR‐mediated signalling has clinical implications for improving reproductive performance control in dogs. Altering the PGR signalling induces the release of PGF2α from the foetal trophoblast, hindering placental homeostasis, which can also be achieved with antigestagens like aglepristone. Consequently, luteolysis, both natural and antigestagen‐induced, involves apoptosis, vascular lesion, and immune cell infiltration in the placenta, resulting in placentolysis and foetal membranes expulsion. Our laboratory developed the immortalized dog uterine stromal (DUS) cell line to study canine‐specific decidualization. We study canine reproduction by observing physiological processes and investigating evidence‐based mechanisms of decidualization and feto‐maternal interaction. Our focus on morphology, function and molecular aspects enhances understanding and enables targeted and translational studies.
Compost promotes biocrust and plant growth in greenhouse cocultures for dryland restoration
Authors: Garibotti Irene A. , Gonzalez Polo Marina , Satti Patricia
Published: September 2023

Biocrusts and plants are the main ground cover and provide multiple ecosystem functions in arid and semiarid areas. As land degradation worsens and waste management is ever more pressing, the use of composted waste appears as a sustainable restoration practice to enhance vegetation reestablishment, but its effects on biocrusts still remain largely understudied. Moreover, developing appropriate methods for the co‐introduction of plants and biocrusts can be an emerging approach to reconstruct the biocrust/plant interaction and their associated functions. We evaluated the effect of different compost types on biocrust and plant cocultivations. We performed a greenhouse mesocosm experiment using urban organic solid waste and sewage sludge composts to grow a moss‐dominated biocrust and seedlings of two pioneer shrubs (Senecio filaginoides and Acaena splendens) in the Patagonian steppe. Both compost types successfully enhanced biocrust cover and chlorophyll a development, with cultured biocrusts being compositionally similar to the natural inoculum. Only the addition of composted sewage sludge enhanced seedling growth, and biocrusts had significant but opposite effects (positive/negative) on the two plant species we used for experimentation. This difference in the biocrust/plant interaction outcome was likely mediated by the significant influence of biocrusts on the relative availability of ammonium and nitrate and possible plant species‐specific preferences for different inorganic nitrogen forms. We conclude that the application of sewage sludge compost effectively improves the success of biocrust and plant cocultures, but species‐specific differences in the performance of seedlings growing in biocrusted soils impose limits on attempts to promote biocrust and plant joint restoration.
Slackline training for Paralympic alpine sit skiers: Development of human‐device multi‐joint coordination
Authors: Liu Kaiqi , Ji Linhong , Capelli Dario , Lu Yijia
Published: September 2023

Purpose

Para‐alpine sit skiers face unique challenges in balance control due to their disabilities and the use of sit skis. This study assessed their multi‐joint coordination before and after slackline training.

Methods

Nine alpine sit skiers (6 M/3 F; 27 ± 8 years; height: 168.3 ± 6.0 cm; body mass: 55.4 ± 6.9 kg) with different disabilities (LW10‐LW12) volunteered for the experiment. All subjects performed slackline training for 5 weeks (20 sessions). Joint kinematics were captured by vision‐based markerless motion analysis. Root mean square (RMS) amplitude, mean velocity and mean power frequency (MPF) were evaluated.

Results

After training, performance improved significantly with an increase in balance time (1041%, p = 0.002), and a decrease in joint angular velocities and RMS amplitude of the sit ski foot (p < 0.05). Joint synergies were developed through in‐ or anti‐phase movements between joint pairs, particularly involving the hip joints (continuous relative phase angles ~0° or 180°, p < 0.001). Multi‐joint coordination shifted from large‐RMS amplitude of elbows to low‐MPF large‐RMS amplitude of the hip and shoulders (p < 0.05), with a significant increase of hip weighting (77.61%, p = 0.031) in the principal component analysis. The coordination was maintained with the change of slackline tension (p < 0.05). Athletes with severe trunk disabilities (LW10) had shorter balance time and poorer coordination than athletes with full trunk functions (LW12).

Conclusions

Our findings showed the development of joint coordination involving better control of the hip and sit skis during the challenging slackline training task.
Rock‐like strength enhancement of Indian desert sand using commercially available polysaccharide biopolymers
Authors: Dagliya Monika , Satyam Neelima , Garg Ankit
Published: September 2023

Biopolymers are a nature‐friendly solution that can impart rock‐like strength in sand by developing bonds between grains. In this study, we assessed the behaviour of desert sand treated with commercially available pectin (P), acacia gum (AG) and sodium alginate (SA) polysaccharide biopolymers (1%, 2% and 3% concentrations) applied at 0.75 and 1 pore volume (PV). Non‐destructive ultrasonic pulse velocity (UPV) tests recorded maximum values of 1579 m/s for AG samples, 1490 m/s for SA samples and 1400 m/s for P samples, all showing rock‐like behaviour. Unconfined compressive strength (UCS) and split tensile strength (STS) tests showed that the strength level generally increased with biopolymer concentration. The minimum UCS value was 173 kPa for the P (1%) 0.75 PV composition, and the maximum was 1287 kPa for the AG (2%) 0.75 PV composition. The UCS value for the AG (1%) 0.75 PV was 1178 kPa, with optimal results compared with other compositions. Scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDX) and X‐ray diffraction (XRD) tests were performed for microstructural analysis. SEM revealed a strong bond between sand particles and biopolymers. EDX and XRD showed that the strength stemmed from gel formation in the pores, rather than mineralogical changes. The study results indicate the level of strength attained with varying biopolymer percentages and PVs and are useful for desert sand stabilization.
Age‐related changes in P2Y receptor signalling in mouse cochlear supporting cells
Authors: Hool Sarah A. , Jeng Jing‐Yi , Jagger Daniel J. , Marcotti Walter , Ceriani Federico
Published: September 2023

Our sense of hearing depends on the function of a specialised class of sensory cells, the hair cells, which are found in the organ of Corti of the mammalian cochlea. The unique physiological environment in which these cells operate is maintained by a syncitium of non‐sensory supporting cells, which are crucial for regulating cochlear physiology and metabolic homeostasis. Despite their importance for cochlear function, the role of these supporting cells in age‐related hearing loss, the most common sensory deficit in the elderly, is poorly understood. Here, we investigated the age‐related changes in the expression and function of metabotropic purinergic receptors (P2Y1, P2Y2 and P2Y4) in the supporting cells of the cochlear apical coil. Purinergic signalling in supporting cells is crucial during the development of the organ of Corti and purinergic receptors are known to undergo changes in expression during ageing in several tissues. Immunolabelling and Ca2+ imaging experiments revealed a downregulation of P2Y receptor expression and a decrease of purinergic‐mediated calcium responses after early postnatal stages in the supporting cells. An upregulation of P2Y receptor expression was observed in the aged cochlea when compared to 1 month‐old adults. The aged mice also had significantly larger calcium responses and displayed calcium oscillations during prolonged agonist applications. We conclude that supporting cells in the aged cochlea upregulate P2Y2 and P2Y4 receptors and display purinergic‐induced Ca2+ responses that mimic those observed during pre‐hearing stages of development, possibly aimed at limiting or preventing further damage to the sensory epithelium.

image

Key points

Age‐related hearing loss is associated with lower hearing sensitivity and decreased ability to understand speech.

We investigated age‐related changes in the expression and function of metabotropic purinergic (P2Y) receptors in cochlear non‐sensory supporting cells of mice displaying early‐onset (C57BL/6N) and late‐onset (C3H/HeJ) hearing loss.

The expression of P2Y1, P2Y2 and P2Y4 receptors in the supporting cells decreased during cochlear maturation, but that of P2Y2 and P2Y4 was upregulated in the aged cochlea.

P2Y2 and P2Y4 receptors were primarily responsible for the ATP‐induced Ca2+ responses in the supporting cells.

The degree of purinergic expression upregulation in aged supporting cells mirrored hearing loss progression in the different mouse strains.

We propose that the upregulation of purinergic‐mediated signalling in the aged cochlea is subsequent to age‐related changes in the hair cells and may act as a protective mechanism to limit or to avoid further damage to the sensory epithelium.
Reynolds Number Effects on Turbulent Wakes Generated by Rectangular Cylinders With Streamwise Aspect Ratios Between 1 and 4
Authors: Liu Manqi , Kumahor Sedem , Tachie Mark F.
Published: September 2023

The effects of streamwise aspect ratio and Reynolds number on the separated shear layer and near wake of rectangular cylinders in uniform flow are investigated experimentally using a particle image velocimetry system. Four length-to-height ratios (AR = 1, 2, 3, and 4) were examined at Reynolds numbers (based on freestream velocity and cylinder height) of 3000, 7200, 14,700, and 21,000. The results show that the separated shear layer is either shed directly into the wake region (AR1 and AR2) or reattaches onto the cylinder (AR4), regardless of the Reynolds number. Meanwhile, a transitional regime occurs for AR3 where mean flow reattachment on the cylinder is highly dependent on the Reynolds number. The peak magnitudes of the Reynolds stresses, turbulent kinetic energy, turbulence production, and its transport are highest for AR1 owing to stronger vortex shedding. Aspect ratio and Reynolds number also have significant effects on shear layer transitioning from laminar to turbulence but the transition lengths, when normalized by the corresponding value at Re = 3000, follow a universal power decay law. The wake characteristics, including the recirculation length and wake formation lengths, are independent of Reynolds number for AR1 but decrease with Reynolds number for the longer cylinders, while AR2 shows the largest values. The probability density functions and joint probability density functions are used to examine the effects of Reynolds number on the fluctuating velocities and momentum transport in the shear layer and near-wake region.
Effects of Hydraulic Parameters on the Retrieved Hydrothermal Dynamics of Unsaturated Soil Using a Synthetic Inverse Model
Authors: Lemoubou Ernest Léontin , Bogning Jean Roger
Published: September 2023

Hydraulic parameters are required indicators to quantify characteristic properties in agricultural fields. This technical brief analyses numerically the effects of soil hydraulic parameters on the retrieved responses of thermal, moisture, and solute dynamics using a synthetic inverse modeling. The goal was to provide analysis insight into the role of hydraulic parameters as tool for interpretation of soil thermal and hydrochemical responses. The inverse results show good agreement and present excellent accuracy when compared to the retrieved responses and true values. Several simulations reveal relevant contributions of the saturated hydraulic conductivity and moisture content, the shape parameter as well as the pore-size indicator on the special distributions of thermal and hydraulic responses.
On the Centennial of the Academic Careers (1919–2019) of Llewellyn M. K. Boelter and William H. McAdams: American Pioneers in Heat and Mass Transfer
Authors: Marner W. J. , Manglik Raj M.
Published: September 2023

In the early 1900s, the heat transfer state of the art in the United States of America (U.S.) lagged far behind that in Europe, especially in Germany. The initial 35 years of the 20th century, however, saw major changes take place as the process industry and other research institutions increasingly began requiring a better understanding of heat and mass transfer. While many individuals have since made important contributions to the field, both past and contemporary peers in the heat and mass transfer community have identified two pioneers as having played key roles in this effort in the U.S.: Llewellyn Michael Kraus Boelter of the University of California—Berkley (UC-Berkley) and the University of California—Los Angeles (UCLA), and William Henry McAdams of the Massachusetts Institute of Technology (MIT). They both started their respective academic positions in 1919, one on the East Coast and the other on the West Coast of U.S. In this paper, the centenary (1919–2019) of their seminal contributions is celebrated by highlighting the early heat and mass transfer developments in the U.S. and the careers of both McAdams and Boelter, which have been integral to this rich history. Many of their heat transfer contributions to the evolution of the field, up to the prevailing times in the 21st century, are documented, along with commentaries and annotations.
Effects of microphone mounting location and gender on accuracy in speech recognition using a throat microphone
Authors: Konuma Y. , Asakura T.
Published: September 2023

Speech recognition using air-conduction microphones is less accurate under high noise conditions and when the volume of the speaker's voice is relatively low. In this study, the effect of mounting location of throat microphones (which are less susceptible to ambient noise) on recognition accuracy was experimentally investigated. The results confirmed that mounting position and speaker gender affected recognition accuracy, regardless of any other factor or speech recognition system. In addition, relatively lower recognition accuracy was observed in the upper part of the neck near the mandibular angle for both males and females.
Novel bacterial topoisomerase inhibitors: unique targeting activities of amide enzyme-binding motifs for tricyclic analogs
Authors: Mann Chelsea A. , Carvajal Moreno Jessika J. , Lu Yanran , Dellos-Nolan Sheri , Wozniak Daniel J. , Yalowich Jack C. , Mitton-Fry Mark J.
Published: September 2023

Antimicrobial resistance has made a sizeable impact on public health and continues to threaten the effectiveness of antibacterial therapies. Novel bacterial topoisomerase inhibitors (NBTIs) are a promising class of antibacterial agents with a unique binding mode and distinct pharmacology that enables them to evade existing resistance mechanisms. The clinical development of NBTIs has been plagued by several issues, including cardiovascular safety. Herein, we report a sub-series of tricyclic NBTIs bearing an amide linkage that displays promising antibacterial activity, potent dual-target inhibition of DNA gyrase and topoisomerase IV (TopoIV), as well as improved cardiovascular safety and metabolic profiles. These amide NBTIs induced both single- and double-strand breaks in pBR322 DNA mediated byStaphylococcus aureusDNA gyrase, in contrast to prototypical NBTIs that cause only single-strand breaks. Unexpectedly, amides1aand1btargeted human topoisomerase IIα (TOP2α) causing both single- and double-strand breaks in pBR322 DNA, and induced DNA strand breaks in intact human leukemia K562 cells. In addition, anticancer drug-resistant K/VP.5 cells containing decreased levels of TOP2α were cross-resistant to amides1aand1b. Together, these results demonstrate broad spectrum antibacterial properties of selected tricyclic NBTIs, desirable safety profiles, an unusual ability to induce DNA double-stranded breaks, and activity against human TOP2α. Future work will be directed toward optimization and development of tricyclic NBTIs with potent and selective activity against bacteria. Finally, the current results may provide an additional avenue for development of selective anticancer agents.
Disrupting the infectious disease ecosystem in the digital precision health era innovations and converging emerging technologies
Authors: Abbo Lilian M. , Vasiliu-Feltes Ingrid
Published: September 2023

This commentary explores the convergence of precision health and evolving technologies, including the critical role of artificial intelligence (AI) and emerging technologies in infectious diseases (ID) and microbiology. We discuss their disruptive impact on the ID ecosystem and examine the transformative potential of frontier technologies in precision health, public health, and global health when deployed with robust ethical and data governance guardrails in place.
Therapeutic potential of rWnt5A in curbing
Leishmania donovani
infection
Authors: Maity Shreyasi , Sengupta Soham , Sen Malini
Published: September 2023

In view of the antagonism of Wnt5A signaling toward microbial pathogens, we were interested in evaluating the therapeutic potential of recombinant Wnt5A (rWnt5A) in curbing
Leishmania donovani
infection. Initially, using
L. donovani
-infected RAW 264.7 and peritoneal macrophages, we demonstrated that application of rWnt5A as opposed to the vehicle control to the infected cells significantly dampens
L. donovani
infection. Inhibition of infection was associated with increase in cell-associated reactive oxygen species (ROS), and blocked by the ROS production inhibitor diphenylene iodonium chloride (DPI). rWnt5A, but not the vehicle control (PBS: phosphate-buffered saline) administration to
L. donovani
-infected mice appreciably reduced the infection load, and inhibited disease progression as evident from the preservation of splenic white pulp architecture. rWnt5A administration, moreover, led to elevation of both cell-associated ROS and the activation of splenic T cells. Substantial increase in T cell-associated Interleukin-2 (IL-2) and Granzyme B (GRB) upon exposure of splenic lymphocytes harvested from rWnt5A-treated mice to
L. donovani
-infected RAW 264.7 macrophages
in vitro
validated the occurrence of
L. donovani
-responsive T cell activation
in vivo
. In summary, this study unveils the therapeutic potential of rWnt5A in curbing
L. donovani
infection and the progression of experimental visceral leishmaniasis possibly through increase in cellular ROS and T cell activation. Accordingly, it opens up a new avenue of investigation into the use of rWnt5A as a therapeutic agent for restraining the progression of drug-resistant
L. donovani
infection.
Roles of host SUMOylation in bacterial pathogenesis
Authors: Ma Xin , Zhao Chenhao , Xu Yuyao , Zhang Haifang
Published: September 2023

Bacteria frequently interfere with the post-translational modifications of host cells to facilitate their survival and growth after invasion. SUMOylation, a reversible post-translational modification process, plays an important role in biological life activities. In addition to being critical to host cell metabolism and survival, SUMOylation also regulates gene expression and cell signal transmission. Moreover, SUMOylation in eukaryotic cells can be used by a variety of bacterial pathogens to advance bacterial invasion. In this minireview, we focused on the role and mechanism of host SUMOylation in the pathogenesis of six important clinical bacterial pathogens (
Listeria monocytogenes
,
Shigella flexneri
,
Salmonella
Typhimurium
, Klebsiella pneumoniae
,
Staphylococcus aureus
, and
Escherichia coli
). Taken together, this review provided new insights for understanding the unique pathogen-host interaction based on host SUMOylation and provided a novel perspective on the development of new strategies to combat bacterial infections in the future.
Early antibody treatment, inflammation, and risk of post-COVID conditions
Authors: Gebo Kelly A. , Heath Sonya L. , Fukuta Yuriko , Zhu Xianming , Baksh Sheriza , Abraham Allison G. , Habtehyimer Feben , Shade David , Ruff Jessica , Ram Malathi , Laeyendecker Oliver , Fernandez Reinaldo E. , Patel Eshan U. , Baker Owen R. , Shoham Shmuel , Cachay Edward R. , Currier Judith S. , Gerber Jonathan M. , Meisenberg Barry , Forthal Donald N. , Hammitt Laura L. , Huaman Moises A. , Levine Adam , Mosnaim Giselle S. , Patel Bela , Paxton James H. , Raval Jay S. , Sutcliffe Catherine G. , Anjan Shweta , Gniadek Thomas , Kassaye Seble , Blair Janis E. , Lane Karen , McBee Nichol A. , Gawad Amy L. , Das Piyali , Klein Sabra L. , Pekosz Andrew , Bloch Evan M. , Hanley Daniel , Casadevall Arturo , Tobian Aaron A. R. , Sullivan David J. ,   on behalf of the CSSC-004 Consortium
Published: September 2023

Post-COVID conditions (PCCs) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about treatment, inflammation, and PCC. Among 882 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of COVID-19 convalescent plasma (CCP) vs control plasma with available biospecimens and symptom data, the association between early CCP treatment, cytokine levels, and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14, and day 90 using a multiplexed sandwich immunoassay (Meso Scale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between CCP treatment, cytokine levels, and PCC were examined using multivariate logistic regression models. One third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and anosmia (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis, female sex (adjusted odds ratio [AOR] = 2.69 [1.93–3.81]), older age (AOR = 1.32 [1.17–1.50]), and elevated baseline levels of IL-6 (AOR = 1.59 [1.02–2.47]) were independently associated with development of PCC. Those who received early CCP treatment (≤5 days after symptom onset) compared to late CCP treatment had statistically significant lower odds of PCC.

IMPORTANCE

Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical characteristics. Future treatment studies should be considered to evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
Bacteriophages limitedly contribute to the antimicrobial resistome of microbial communities in wastewater treatment plants
Authors: Sabatino Raffaella , Sbaffi Tomasa , Sivalingam Periyasamy , Corno Gianluca , Fontaneto Diego , Di Cesare Andrea
Published: September 2023

Bacteriophages are known as players in the transmission of antimicrobial resistance genes (ARGs) by horizontal gene transfer. In this study, we characterized the bacteriophage community and the associated ARGs to estimate the potential for phages to spread ARGs in aquatic ecosystems analyzing the intra- and extracellular DNA isolated from two wastewater treatment plants (WWTPs) by shotgun metagenomics. We compared the phage antimicrobial resistome with the bacterial resistome and investigated the effect of the final disinfection treatment on the phage community and its resistome. Phage community was mainly composed by
Siphoviridae
and other members of the order
Caudovirales
. The final disinfection only marginally affected the composition of the phage community, and it was not possible to measure its effect on the antimicrobial resistome. Indeed, only three phage metagenome-assembled genomes (pMAGs) annotated as
Siphoviridae
,
Padoviridae
, and
Myoviridae
were positive for putative ARGs. Among the detected ARGs, i.e.,
dfr
B6,
rpo
B mutants, and EF-Tu mutants, the first one was not annotated in the bacterial MAGs. Overall, these results demonstrate that bacteriophages limitedly contribute to the whole antimicrobial resistome. However, in order to obtain a comprehensive understanding of the antimicrobial resistome within a microbial community, the role of bacteriophages needs to be investigated.

IMPORTANCE

WWTPs are considered hotspots for the spread of ARGs by horizontal gene transfer. In this study, we evaluated the phage composition and the associated antimicrobial resistome by shotgun metagenomics of samples collected before and after the final disinfection treatment. Only a few bacteriophages carried ARGs. However, since one of the detected genes was not found in the bacterial metagenome-assembled genomes, it is necessary to investigate the phage community in order to gain a comprehensive overview of the antimicrobial resistome. This investigation could help assess the potential threats to human health.
Diagnosis and treatment of Lyme disease in children
Authors: Bahadori Atessa , Ritz Nicole , Zimmermann Petra
Published: September 2023

Lyme disease is a zoonotic infection caused by the spirocheteBorrelia burgdorferisensu lato which is transmitted to humans mainly by tick bites. The global incidence of Lyme disease is rising, and children are more frequently affected. The disease can manifest in various organs causing non-specific symptoms. The lack of sensitive and specific diagnostic tests makes the management of Lyme disease challenging. This article offers up-to-date clinical algorithms for the management of children with suspected or diagnosed Lyme disease.
Neonatal high-frequency oscillatory ventilation: where are we now?
Authors: Hibberd Jakob , Leontini Justin , Scott Thomas , Pillow J Jane , Miedema Martijn , Rimensberger Peter C , Tingay David Gerald
Published: September 2023

High-frequency oscillatory ventilation (HFOV) is an established mode of respiratory support in the neonatal intensive care unit. Large clinical trial data is based on first intention use in preterm infants with acute respiratory distress syndrome. Clinical practice has evolved from this narrow population. HFOV is most often reserved for term and preterm infants with severe, and often complex, respiratory failure not responding to conventional modalities of respiratory support. Thus, optimal, and safe, application of HFOV requires the clinician to adapt mean airway pressure, frequency, inspiratory:expiratory ratio and tidal volume to individual patient needs based on pathophysiology, lung volume state and infant size. This narrative review summarises the status of HFOV in neonatal intensive care units today, the lessons that can be learnt from the past, how to apply HFOV in different neonatal populations and conditions and highlights potential new advances. Specifically, we provide guidance on how to apply an open lung approach to mean airway pressure, selecting the correct frequency and use of volume-targeted HFOV.
Management of long bone fractures in patients with pycnodysostosis
Authors: Sharma Ajay , Mittal Samarth , Trikha Vivek , Vatsya Pulak
Published: September 2023

Pycnodysostosis is a rare genetic condition that leads to generalised bony sclerosis and increased fracture risk. Orthopaedic specialists play a crucial role in managing affected children due to their susceptibility to frequent fractures. We had a case of a middle childhood female patient with pycnodysostosis and a femur fracture. Initially, an attempt using the Titanium Elastic Nailing System was made, but the sclerotic metaphyseal bone made it challenging. So, we opted for a 4.5 mm locked compressive plate, with multiple drill bits as a backup due to potential drill breakage. Though elastic nailing is preferred for paediatric long bone fractures, surgeons must be prepared for extremely sclerotic cortices and a narrow medullary canal when dealing with patients with pycnodysostosis. Open fixation and multiple drill bits in the toolkit are essential to overcome the potential obstacles during the procedure.
Patient randomised controlled trial of technology enabled strategies to promote treatment adherence in liver transplantation: rationale and design of the TEST trial
Authors: Serper Marina , Burdzy Alexander , Schaubel Douglas E , Mason Richard , Banerjee Arpita , Goldberg David S , Martin Eric F , Mehta Shivan J , Russell Louise B , Cheung Amanda C , Ladner Daniela P , Yoshino Benavente Julia , Wolf Michael S
Published: September 2023

Background and aims

Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes.

Methods and analysis

This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated.

Ethics and dissemination

The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders.

Trial registration number

NCT05260268.
Refinement and validation of a comprehensive clinical diagnostic model (GAMAD) based on gender, age, multitarget circulating tumour DNA methylation signature and commonly used serological biomarkers for early detection of hepatocellular carcinoma: a multicentre, prospective observational study protocol
Authors: Yang Tian , Wang Nanya , Wang Fengmei , Liu Hongmei , Shen Feng , Lv Guoyue
Published: September 2023

Introduction

Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population.

Methods and analysis

This prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des-γ-carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD’s clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD’s discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD.

Ethics and dissemination

This trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally.

Trial registration number

NCT05626985.