bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-sectional study: mindset towards Coronavirus in developing countries and lessons learned: the case of Sudan
Authors: Omer Zeinab , Khalid Yousra , Zakaria Goffran , Sabir Shahd , MohamedAbdallah Abrar
Published: April 2024

Introduction:

People’s mindset towards COVID-19 in developing countries has an impact on how they perceive and react to the preventative measures taken by the governments to contain the virus. Understanding the factors influencing the mindset and identifying lessons learned amidst COVID-19 are critical to inform any future intervention strategy.

Methods:

This was a cross-sectional, community-based study conducted to assess the mindset changes and lessons learned post-COVID-19 in developing countries, focusing on Sudan. The study adopted a sequential mixed approach (SMA), combining qualitative and quantitative methods. The study used a structured questionnaire with 300 respondents and in-depth interviews with two experts. To identify the factors influencing the mindset of the people towards COVID-19, the study employed logistic regression. The data was analyzed using SPSS software.

Results:

Of the total (N = 300) respondents, 59.0% are female, 59.3% are between the ages of 20 and 39, 79.7% have a university education, 25.3% have the Coronavirus, and 42.3% has their family or relative contracted the virus. Further, only 22.7% had taken the vaccine. Reasons for vaccine hesitancy include lack of trust (29.5%), fear of side effects (24.1%), and absence of the need to travel outside the country (25.5%). When the virus first appeared, 77.3% thought it posed a health risk, while 22.7% perceived it as a hoax or conspiracy. After 3 years, 73% still regarded it as a health threat, while 27% believed it was a hoax or conspiracy. The mindset was found to be influenced by age, history of the disease, the extent of trust in foreign media coverage, and the belief in the effectiveness of the vaccination.

Conclusion:

Assessing the mindset towards the virus and identifying the lessons learned from the pandemic could be of vital importance to control the spread of the virus in developing countries. Making use of such lessons and influencing the mindset of the people towards positive attitudes and behaviours are required to enhance the effectiveness of the health precaution measures adopted. Further research is required on the public’s mistrust of foreign media coverage and the contribution of local media to educate the public about the virus, particularly among the elderly.
Electrodiagnostic Findings Using Radial Motor Segmental Conduction Study and Inching Test in Patients With Radial Neuropathy
Authors: Kwon Jeha , Kang Jong Woo , Park Hong Bum , Kim Dong Hwee
Published: April 2024

Objectives

The aims of this study were to characterize the electrodiagnostic findings of radial neuropathy using motor segmental conduction study and to determine the utility of subsequent inching test in precise lesion localization.

Design

Twenty-three patients with radial neuropathy were evaluated using radial neuropathy using motor segmental conduction study with three-point stimulation. The pathomechanism of the lesions according to the radial neuropathy using motor segmental conduction study was classified into three groups: conduction block, mixed lesion (combination of conduction block and axonal degeneration), and axonal degeneration. Inching test was performed in patients with conduction block to localize the lesion site, and needle electromyography identified the most proximal radial nerve-innervated muscles affected.

Results

Out of 23 cases, the radial neuropathy using motor segmental conduction study demonstrated probable partial conduction block in 10, mixed lesions in 2, and axonal degeneration in 10. One case could not be categorized with radial neuropathy using motor segmental conduction study alone. As determined by radial neuropathy using motor segmental conduction study and inching test, the most common cause of conduction block was compression, while the most common cause of axonal degeneration was iatrogenic. In the conduction block group, the lesion locations identified by radial neuropathy using motor segmental conduction study and inching test were consistent with needle electromyography localization.

Conclusions

The combined radial neuropathy using motor segmental conduction study and inching test technique can precisely localize radial motor nerve injuries and provide detailed information on electrodiagnostic characteristics of radial mononeuropathy.
Positive Bacterial Cultures on Spinal Wound Closure Do Not Predict Postoperative Outcomes
Authors: VanDolah Hunter B. , Li Karen R. , Kim Kevin G. , Berger Lauren E. , Tefera Eshetu A. , Acuna Kelly A. , Attinger Christopher E. , Fan Kenneth L. , Evans Karen K.
Published: April 2024

Background

Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management.

Methods

This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days.

Results

The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio [OR], 1.772; 95% confidence interval [CI], 1.045–3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078–0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034–0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547–8.613).

Conclusions

Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.
The Application of Reverse Z-Plasty Design in Medial Canthal Skin Redundancy Reconstruction Surgery
Authors: Huahui Zhang , Dan Xue , Jiange Qian , Yuxiang Zhang , Qiming Zhao , Xiaohui Long
Published: April 2024

Purpose:

To investigate the clinical outcomes of reverse Z-plasty in the reconstruction of epicanthal fold.

Methods:

We conducted a retrospective analysis on clinical data from patients who underwent medial canthal skin redundancy reconstruction surgery from September 2019 to January 2023. The surgical procedure involved a preoperative design for the incision line, suborbicularis oculi dissection to create a muscle flap, and the use of a reverse Z-flap for the reconstruction of the lateral canthal fold. Postoperative follow-up assessments focused on the intercanthal distance, positional changes of the medial canthus point, alterations in the medial canthus angle, and patient satisfaction levels. The statistical evaluation was carried out utilizing paired t-tests, with a P-value of less than 0.05 denoting statistical significance.

Results:

Postsurgery, the lacrimal prominences were less exposed, and inner canthal angles naturally reshaped. Inconspicuous scarring with diminished reverse Z-plasty marks was noted within 3 months. The average ICD has increased by 3 to 6 mm, corresponding to elongation ratios of 9.09% to 28.30%. Preoperatively, the ICD averaged 31.25±2.32 mm, expanding postoperatively to 35.19±2.26 mm. The canthal angle enlarged significantly from 49.031±6.627 to 62.188±6.662. Inner canthal points shifted notably postsurgery, with a decrease in x-value and an increase in y-value, signalling a movement upwards and away from the nose. Patient satisfaction is high.

Conclusion:

The reverse Z-plasty technique has proven to be an effective approach for reconstructing the epicanthal fold. The clarity and precision of the incision design, coupled with the stability of postoperative results, demonstrate that this method can reliably achieve successful epicanthal fold reconstruction.
Congenital Upper Lip Sinus
Authors: Zhang Jiarui , Li Zengjian , Pang Pai
Published: April 2024

Congenital upper lip sinus (CULS) is an extremely rare anomaly. The aim of the study is to present a new case and compile the present knowledge of CULS to help foster a deeper understanding of this disease. A 9-year-old girl with a midline CULS, a prolonged maxillary labial frenulum, and a palatal epulis is presented. Thirty-nine papers met the eligibility criteria and 45 cases were included in the systematic review. CULS shows typical clinical and pathologic characteristics. It tends to occur at the midline region horizontally (n=35; 78%) and the upper part of the white lip (n=23; 51%) vertically. No ethnic predilection is found, but it tends to show a female predilection (n=28; 62%). Twenty-six cases (58%) are symptomatic. Thirteen cases (29%) are accompanied by other maxillofacial defects. In all cases, the sinus was lined with stratified squamous epithelium. The etiology remains unknown but 3 theories have been put forward: the fusion theory, the merging theory, and the invagination theory. The authors believe that CULS shows homogeneity with cleft lip to some extent and maybe a microform of it. Primary treatment is surgical excision and the prognosis is favorable, with no complications or recurrence.
Mastoid Emissary Foramina in Dry Skulls: Its Morphometry, Topography, and Associated Clinical Implications
Authors: Singh Rajani
Published: April 2024

Mastoid emissary foramen transmitting mastoid emissary vein connects the posterior auricular vein with the sigmoid sinus. This foramen and so the mastoid emissary vein varies in prevalence, number, size and location, knowledge of which is essential for carrying out uneventful surgeries, especially retrosigmoid, mastoidectomy, and skull base surgeries. There is a paucity of literature on this foramen in the Indian context, so the study was done. The purpose of the study is to elaborate on the prevalence, number, size, and location of mastoid foramen in dry adult skulls. The study was conducted in the Department of Anatomy using 90 dry skulls of unknown age and sex, and prevalence, number, size, and location in these skulls were noted. The mastoid foramen was detected in 27.8% of skulls, with an incidence of 31.1% and 12.2% on right and left sides of skulls, respectively. The number of foramina ranged between 1 and 4. The mean diameter of this foramen was 0.9 mm, and the most frequent location was mastoid process. The detailed morphology and morphometry of mastoid foramen are of utmost use to neurosurgeons, ENT surgeons, radiologists, and vascular surgeons as it transmits mastoid emissary vein and meningeal branch of the occipital artery, which may be injured during various surgical procedures involving mastoid region and skull base causing catastrophic hemorrhage. In addition to this, mastoid emissary vein may be the source of thrombus, causing thrombus of sigmoid sinus creating helm of neurological complications.
Usefulness of the Glove Finger Pad for Ultrasonography in Nasal Fracture Reduction
Authors: Kashimura Tsutomu , Sugawara Takashi , Soejima Kazutaka
Published: April 2024

The treatment of nasal bone fractures involves closed reduction, in which the reduction position is generally evaluated indirectly by visual examination and palpation. While more direct evaluation methods using ultrasonography can improve treatment outcomes, ultrasonography of the nasal bones requires acoustic coupling materials to hold the entire ultrasonography probe in close contact with the nose. We report the use of the Glove Finger Pad, a homemade acoustic coupling material made from a medical glove. The Glove Finger Pad is easy to prepare and use and produces good images. We believe that the Glove Finger Pad will further enhance the usefulness of ultrasonography for the treatment of nasal fractures.
Using implementation science to decrease variation and high opioid administration in a surgical ICU
Authors: Kalkwarf Kyle J. , Bailey Brett J. , Wells Allison , Jenkins Allison K. , Smith Rebecca R. , Greer Jordan W. , Yeager Richard , Bruce Nolan , Margolick Joseph , Kost Melissa R. , Kimbrough Mary K. , Roberts Matthew L. , Davis Benjamin L. , Privratsky Anna , Curran Geoffrey M.
Published: April 2024

BACKGROUND

High doses and prolonged duration of opioids are associated with tolerance, dependence, and increased mortality. Unfortunately, despite recent efforts to curb outpatient opioid prescribing because of the ongoing epidemic, utilization remains high in the intensive care setting, with intubated patients commonly receiving infusions with a potency much higher than doses required to achieve pain control. We attempted to use implementation science techniques to monitor and reduce excessive opioid prescribing in ventilated patients in our surgical intensive care unit (SICU).

METHODS

We conducted a prospective study investigating opioid administration in a closed SICU at an academic medical center over 18 months. Commonly accepted conversions were used to aggregate daily patient opioid use. Patients with a history of chronic opioid use and those being treated with an intracranial pressure monitor/drain, neuromuscular blocker, or extracorporeal membrane oxygenation were excluded. If the patient spent a portion of a day on a ventilator, that day's total was included in the “vent group.” morphine milligram equivalents per patient were collected for each patient and assigned to the on-call intensivist. Intensivists were blinded to the data for the first 7 months. They were then provided with academic detailing followed by audit and feedback over the subsequent 11 months, demonstrating how opioid utilization during their time in the SICU compared with the unit average and a blinded list of the other attendings. Student's t tests were performed to compare opioid utilization before and after initiation of academic detailing and audit and feedback.

RESULTS

Opioid utilization in patients on a ventilator decreased by 20.1% during the feedback period, including less variation among all intensivists and a 30.9% reduction by the highest prescribers.

CONCLUSION

Implementation science approaches can effectively reduce variation in opioid prescribing, especially for high outliers in a SICU. These interventions may reduce the risks associated with prolonged use of high-dose opioids.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Normothermic Ex Vivo Heart Perfusion With Exosomes From Human Umbilical Cord Mesenchymal Stem Cells Improves Graft Function in Donation After Circulatory Death Hearts
Authors: Zhang Zhong , Ji Jianqiang , Pan Xuan , Niu Chuanjie , Xu Liwei , Lei Wenrui , Zeng Zifeng , Chen Qiong , Peng Qingbao , Zheng Shaoyi , Lu Jun , Zhou Pengyu
Published: April 2024

Background.

This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death (DCD) hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model.

Methods.

Thirty-two male Lewis rats were divided into 2 groups: the control group and the exosome group. The donor-heart rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 90 min, and then transplanted into recipients via abdominal heterotopic heart transplantation. Vehicle or exosome was added into the perfusate of normothermic EVHP in the control or exosome group. We evaluated left ventricular graft function, myocardial inflammation, and myocardial apoptosis of the donor heart 1.5 h after heart transplantation. Furthermore, we investigate the alternation of myocardial gene expression in the donor hearts between both groups by transcriptome sequencing.

Results.

The treatment with exosome significantly enhanced cardiac function through increasing left ventricular developed pressure, dp/dtmax, and dp/dtmin of DCD hearts at 90 min after heart transplantation compared with the control group. The myocardial cells in the exosome group exhibited an orderly arrangement without obvious edema. Furthermore, exosome added into perfusate in the exosome group significantly attenuated the level of inflammatory response and apoptosis. Transcriptome sequencing and RT-qPCR showed the phosphoinositide 3-kinase/protein kinase B pathway was activated after exosome treatment.

Conclusions.

Normothermic EVHP combined with exosome can be a promising and novel DCD heart preservation strategy, alleviating myocardial ischemia–reperfusion injury in the DCD heart.
Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia–Reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain
Authors: Concors Seth J. , Hernandez Paul T. , O’Brien Ciaran , DePaolo John , Murken Douglas R. , Aufhauser David D. , Wang Zhonglin , Xiong Yan , Krumeich Lauren , Ge Guanghui , Beier Ulf H. , Bhatti Tricia R. , Kozikowski Alan P. , Avelar Leandro A. Alves , Kurz Thomas , Hancock Wayne W. , Levine Matthew H.
Published: April 2024

Background.

Ischemia–reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation.

Methods.

Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors.

Results.

Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT).

Conclusions.

Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.
Caspase-1 deletion reveals pyroptosis participates in neural damage induced by cerebral ischemia/reperfusion in tMCAO model mice
Authors: Hao Qing-Na , Xue Xiao-Bo , Zhou Heng , Hu Zhao-Li
Published: April 2024

Pyroptosis, a form of programmed cell death, drives inflammation in the context of cerebral ischemia/reperfusion. The molecular mechanism of pyroptosis underlying ischemia/reperfusion, however, is not fully understood. The transient middle cerebral artery occlusion was applied to wild-type and caspase-1 knockout mice. 2,3,5-Triphenyltetrazolium chloride-staining and immunohistochemistry were used to identify the ischemic region, and western blot and immunofluorescence for the examination of neuronal pyroptosis. The expression of inflammatory factors and the behavioral function assessments were further conducted to examine the effects of caspase-1 knockout on protection against ischemia/reperfusion injury. Ischemia/reperfusion injury increased pyroptosis-related signals represented by the overexpression of pyroptosis-related proteins including caspase-1 and gasdermin D (GSDMD). Meanwhile, the number of GSDMD positive neurons increased in penumbra by immunofluorescence staining. Compared with wild-type mice, those with caspase-1 knockout exhibited decreased levels of pyroptosis-related proteins following ischemia/reperfusion. Furthermore, ischemia/reperfusion attack-induced brain infarction, cerebral edema, inflammatory factors, and neurological outcomes were partially improved in caspase-1 knockout mice. The data indicate that pyroptosis participates in ischemia/reperfusion induced-damage, and the caspase-1 might be involved, it provides some new insights into the molecular mechanism of ischemia.
ICTV Virus Taxonomy Profile: Nairoviridae 2024
Authors: Kuhn Jens H. , Alkhovsky Sergey V. , Avšič-Županc Tatjana , Bergeron Éric , Burt Felicity , Ergünay Koray , Garrison Aura R. , Marklewitz Marco , Mirazimi Ali , Papa Anna , Pawęska Janusz T. , Spengler Jessica R. , Palacios Gustavo
Published: April 2024

Nairoviridae is a family for negative-sense RNA viruses with genomes of about 17.2–21.1 kb. These viruses are maintained in and/or transmitted by arthropods among birds, reptiles and mammals. Norwaviruses and orthonairoviruses can cause febrile illness in humans. Several orthonairoviruses can infect mammals, causing mild, severe and sometimes, fatal diseases. Nairovirids produce enveloped virions containing two or three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), sometimes a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Nairoviridae, which is available at www.ictv.global/report/nairoviridae.
Stochastic epidemic models and their link with methods from survival analysis
Authors: Putter Hein , Goeman Jelle , Wallinga Jacco
Published: April 2024

Compartmental models based on ordinary differential equations (ODE’s) quantifying the interactions between susceptible, infectious, and recovered individuals within a population have played an important role in infectious disease modeling. The aim of the present paper is to explain the link between stochastic epidemic models based on the susceptible-infectious-recovered (SIR) model, and methods from survival analysis. We illustrate how standard software for survival analysis in the statistical language R can be used to estimate pivotal parameters in the stochastic SIR model in the very much idealized situation where the epidemic is completely observed. Extensions incorporating interventions, age structure and heterogeneity are explored and illustrated.
Complementary methods for the study of interactions between eosinophils and cancer cells
Authors: Antonucci Caterina , Gambardella Adriana Rosa , Tirelli Valentina , Mattei Fabrizio , Schiavoni Giovanna
Published: April 2024

Eosinophils are a rare immune cell subset with important roles in Th2 immunity and, recently, in cancer. Interleukin IL-33 (IL-33) is well recognized for its important roles in the activation of eosinophils in Th2 immunity. On the other hand, IL-33 has been recently discovered to play central roles in cancer, in particular by activating eosinophils and increase their degranulation consequent to an intrinsic tumor cell killing function. We propose a dual approach methodology to extrapolate functional interactions of eosinophils with tumor cells, as a result of eosinophil stimulation. Human eosinophils (Eos) isolated from the blood of healthy donors by dextran sedimentation followed by magnetic sorting are exposed to IL-33 (Eos33) or IL-5 (Eos5, control) for 18 h. These pre-conditioned cells are then co-cultured with A375P melanoma cells to monitor cell-cell interactions. Acoustic focusing flow cytometry analysis is employed to evaluate the presence of Eos-tumor cell conjugates after 1h incubation of human eosinophils and A375P melanoma cells. Moreover, a 24 h time-lapse video recording approach is employed to obtain single cell tracking Eos profiles. This allows to quantitatively determine the interaction extent of Eos33, as opposed to Eos5 (control condition), with tumor cells. In conclusion, our protocols easily and quickly allow the extrapolation of relevant kinematic and biologically relevant parameters for tumor reactive eosinophils. Furthermore, these methods are adaptable to various models with other types of immune cell subsets and cancer cells and can be implemented on different video microscopy platforms and advanced flow cytometry systems.
Ubiquitin-specific protease 8 controls B-cell proteostasis and survival representing a target in multiple myeloma
Authors: Dufner Almut , Thery Fabien , Monaco Gianni , Lazarevic Jelena , Gorka Oliver , Chevalier Nina , Frosch Maximilian , van der Heden van Noort Gerbrand J. , Allmeroth Kira , Prinz Marco , Groß Olaf , Ovaa Huib , Geurink Paul P. , Schamel Wolfgang W. , Heissmeyer Vigo , Denzel Martin S. , Bruns Heiko , Schemionek Mirle , Impens Francis , Knobeloch Klaus-Peter
Published: April 2024

Ubiquitin-specific protease 8 is involved in endosomal/lysosomal trafficking, exerts multiple cellular functions, and was identified as a vulnerability gene for multiple myeloma, a disease characterized by clonal expansion of malignant plasma cells in the bone marrow. Here we characterized USP8 function in B cells and multiple myeloma, and analyzed its impact on the global and ubiquitin-modified proteome.

Usp8depletion inUsp8f/fCd19-Cre mice affected B-cell survival and development favoring immature and innate-like B cells, as well as germinal center and plasma cells. This effect was accompanied by elevated immune-responses and Roquin depletion. Moreover, low USP8 expression at diagnosis correlated with decreased survival of multiple myeloma patients. B cells expressing catalytically inactive USP8 accumulated proteins modified with mixed ubiquitin/NEDD8 chains as hallmarks of proteotoxic stress, which we identified as favored USP8 substrates. Efficient USP8 knockdown reduced survival of multiple myeloma cells resistant to proteasome inhibition by bortezomib in a lysosomal dysfunction-dependent manner. Of note, the inhibitor DUB-IN-2 even more potently resensitized bortezomib-resistant multiple myeloma cells in an ER stress response-synergistic manner, and we confirmed applicability of DUB-IN-2/bortezomib combination treatment in a mouse transplantation model. Our analyses uncovered the potential of USP8 inhibition and of DUB-IN-2/bortezomib combination treatment in multiple myeloma.
Vocal and musical emotion perception, voice cue discrimination, and quality of life in cochlear implant users with and without acoustic hearing
Authors: Harding Eleanor E. , Gaudrain Etienne , Tillmann Barbara , Maat Bert , Harris Robert L. , Free Rolien H. , Başkent Deniz
Published: April 2024

This study aims to provide a comprehensive picture of auditory emotion perception in cochlear implant (CI) users by (1) investigating emotion categorization in both vocal (pseudo-speech) and musical domains and (2) how individual differences in residual acoustic hearing, sensitivity to voice cues (voice pitch, vocal tract length), and quality of life (QoL) might be associated with vocal emotion perception and, going a step further, also with musical emotion perception. In 28 adult CI users, with or without self-reported acoustic hearing, we showed that sensitivity (d’) scores for emotion categorization varied largely across the participants, in line with previous research. However, within participants, the d’ scores for vocal and musical emotion categorization were significantly correlated, indicating similar processing of auditory emotional cues across the pseudo-speech and music domains and robustness of the tests. Only for musical emotion perception, emotion d’ scores were higher in implant users with residual acoustic hearing compared to no acoustic hearing. The voice pitch perception did not significantly correlate with emotion categorization in either domain, while the vocal tract length significantly correlated in both domains. For QoL, only the subdomain of Speech production ability, but not the overall QoL scores, correlated with vocal emotion categorization, partially supporting previous findings. Taken together, results indicate that auditory emotion perception is challenging for some CI users, possibly a consequence of how available the emotion-related cues are via electric hearing. Improving these cues, either via rehabilitation or training, may also help auditory emotion perception in CI users.
How weedyArabidopsis thalianadominated the world: ancestral variation and polygenic adaptation
Authors: Lo Cheng-Yu , Chien Chih-Cheng , Lin Ya-Ping , Yeh Pei-Min , Lee Cheng-Ruei
Published: April 2024

The composition of a species could change with demographic turnovers, where dominant populations quickly expanded and replaced others. However, whether such events have a genetic basis remains to be investigated. Previous studies showed thatArabidopsis thalianaexperienced a significant demographic turnover, where “non-relicts” replaced “relicts” throughout Eurasia. Here, we showed that non-relicts have smaller seeds, more seeds per fruit, and a higher germination rate, making them more competitive over relicts. Using a unique population enriching relict alleles while minimizing population structure, we identified candidate loci and showed that such trait divergence was caused by the divergent sorting of multiple ancient haplotypes in a Mendelian gene and joint allele frequency change of polygenes affecting single-trait divergence and multi-trait covariance. This study is one of the few genetic investigations of species-wide demographic turnover, emphasizing the importance of processes different from the much-focused hard selective sweep.
Host range of naturally and artificially evolved symbiotic bacteria for a specific host insect
Authors: Sugiyama Ryuga , Moriyama Minoru , Koga Ryuichi , Fukatsu Takema
Published: April 2024

Diverse insects are intimately associated with specific symbiotic bacteria, where host and symbiont are integrated into an almost inseparable biological entity. These symbiotic bacteria usually exhibit host specificity, uncultivability, reduced genome size, and other peculiar traits relevant to their symbiotic lifestyle. How host-symbiont specificity is established at the very beginning of symbiosis is of interest but poorly understood. To gain insight into the evolutionary issue, we adopted an experimental approach using the recently developed evolutionary model of symbiosis between the stinkbugPlautia staliandEscherichia coli. Based on the laboratory evolution ofP. stali-E. colimutualism, we selected ΔcyaAmutant ofE. colias an artificial symbiont ofP. stalithat has established mutualism by a single mutation. In addition, we selected a natural cultivable symbiont ofP. staliof relatively recent evolutionary origin. These artificial and natural symbiotic bacteria ofP. staliwere experimentally inoculated to symbiont-deprived newborn nymphs of diverse stinkbug species. Strikingly, the mutualisticE. coliwas unable to establish infection and support growth and survival of all the stinkbug species except forP. stali, uncovering that host specificity can be established at a very early stage of symbiotic evolution. Meanwhile, the natural symbiont was able to establish infection and support growth and survival of several stinkbug species in addition toP. stali, unveiling that a broader host range of the symbiont has evolved in nature. Based on these findings, we discuss what factors are relevant to the establishment of host specificity in the evolution of symbiosis.

IMPORTANCE

How does host-symbiont specificity emerge at the very beginning of symbiosis? This question is difficult to address, because it is generally difficult to directly observe the onset of symbiosis. However, recent development of experimental evolutionary approaches to symbiosis has brought about a breakthrough. Here we tackled this evolutionary issue using a symbioticEscherichia colicreated in laboratory and a naturalPantoeasymbiont, which are both mutualistic to the stinkbugPlautia stali. We experimentally replaced essential symbiotic bacteria of diverse stinkbugs by the artificial and natural symbionts ofP. stali, and evaluated whether the symbiotic bacteria evolved for a specific host can establish infection and support growth and survival of heterospecific hosts. Strikingly, the artificial symbiont showed strict host specificity toP. staliwhereas the natural symbiont was capable of symbiosis with diverse stinkbugs, which provide insight into how host-symbiont specificity can be established at early evolutionary stages of symbiosis.
Perceptions of children and young people in England on the smokefree generation policy: a focus group study
Authors: Davies Nathan P , Murray Rachael L , Langley Tessa , Morling Joanne R , Bains Manpreet
Published: April 2024

Background

This study investigates perceptions of young people towards the planned smokefree generation (SFG) policy in England, which will ban sale of tobacco products to those born in or after 2009. It focuses on SFG policy acceptability, design and implementation.

Methods

We conducted 7 semi-structured focus groups with 36 participants aged 12 - 21 (mean = 15) in England over video call and in person. 21 participants were female and 15 male. Participants were purposively sampled to include those from areas of greater deprivation and for use of tobacco or e-cigarettes. Data was analysed using the framework approach.

Results

Participants expressed broadly negative perceptions towards tobacco and its manufacturers. Most participants supported SFG policy goals and its focus on freedom from addiction and harm. Many believed the law would benefit from stringent enforcement, inclusion of e-cigarette products, tobacco licensing, and input from young people. A minority raised concerns about the loss of freedom to purchase tobacco and believed it would have little effect on smoking rates.

Conclusion

Communication of the freedom-giving nature of SFG is likely to resonate with many young people. Enforcement, communication, and involvement of young people in SFG should be considered carefully to maximise policy impact.

What is already known on this topic

Observational and modelling studies of raising the legal age of sale of tobacco show its effectiveness in reducing smoking rates in target populations. The UK is currently on track to be the first nation to introduce a generational ban on tobacco products, but little is known about young people’s perceptions on this policy.

What this study adds

The overarching goal and preventative approach of SFG has the power to resonate with young people, including nicotine product users, but there is likely to be a small minority opposed to SFG on philosophical principles and perceptions of limited effectiveness. Young people may have mixed feelings about e-cigarettes being excluded from SFG due to misperceptions of equivalent harm between products.

How this study might affect research, practice or policy

Our study suggests involvement of young people in SFG’s design and accompanying communication is likely to strengthen its legitimacy and appeal. Our sample were largely supportive of well-resourced, consistent enforcement of SFG law with strong penalties for retailers who break the law.
Gastric modulation of food reward, olfaction and taste in obesity and bariatric surgery: an artificial intelligence assisted scoping review protocol
Authors: Ritsch Nina , Bourque Camille , Bergeron Frederic , Nazare Julie-Anne , Dougkas Anestis , Iceta Sylvain
Published: April 2024

Objective

To understand the extent and nature of the available research on gastric modulation of food reward, olfaction, and taste in people with obesity or those who have undergone bariatric surgery.

Introduction

Bariatric surgery-induced weight loss is partially attributed to shifts in food preferences resulting from alterations in sensory perceptions and changes in reward system. The stomach’s innervation and mechanical function have been theorized to play a significant role in these modifications, as suggested by numerous preclinical studies. However, the extent and nature of these connections in clinical settings require further elucidation.

Inclusion criteria

This review will examine studies on the influence of gastric innervation and/or mechanical function on food reward, olfaction, and taste. Selected studies will include participants of all ages with obesity or bariatric surgery. Both observational studies and controlled experiments will be considered, while study protocols, opinion articles, letters to the editor, book chapters, oral communication or poster abstracts and systematic reviews will be excluded.

Methods

The search will be undertaken in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Google Scholar, and gray literature. No date parameters will be set, and all languages will be considered. Citations will be uploaded into EndNote 20.0 and duplicates removed using Covidence. The remaining studies will be analyzed by 3 reviewers using a two-stage procedure with the ASReview python package. The full-text screening and the data extraction will be conducted by 2 reviewers on Covidence. An additional reviewer will be consulted in the event of disagreement. Tabulated results will be accompanied by a narrative summary.
The RESIST Senior Individuals Cohort: Design, participant characteristics and aims
Authors: Roesner LM , Gupta KM , Kopfnagel V , van Unen N , Kemmling Y , Heise J , Castell S , Jiang X , Riemann L , Traidl S , Lange B , Sühs KW , Illig T , Strowig T , Li Y , Förster R , Huehn J , Schulz TF , Werfel T ,   the RESIST SI Cohort Investigators
Published: April 2024

The number of older adults worldwide is growing exponentially. However, while living longer, older individuals are more susceptible to both non-infectious and infectious diseases, at least in part due to alterations of the immune system. Here, we report on a prospective cohort study investigating the influence of age on immune responses and susceptibility to infection. The RESIST Senior Individuals (SI) cohort was established as a general population cohort with a focus on the elderly, enrolling an age- and sex-stratified sample of 650 individuals (n=100 20-39y, n=550 61-94y, 2019-2023, Hannover, Germany). It includes clinical, demographic, and lifestyle data and also extensive biomaterial sampling. Initial insights indicate that the SI cohort exhibits characteristics of the aging immune system and the associated susceptibility to infection, thereby providing a suitable platform for the decoding of age-related alterations of the immune system and unraveling the molecular mechanisms underlying the impaired immune responsiveness in aging populations by exploring comprehensive, unbiased multi-omics datasets.
Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states
Authors: Okada Junichi , Landgraf Austin , Xiaoli Alus M. , Liu Li , Horton Maxwell , Schuster Victor L. , Yang Fajun , Sidoli Simone , Qiu Yunping , Kurland Irwin J. , Eliscovich Carolina , Shinoda Kosaku , Pessin Jeffrey E.
Published: April 2024

The liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule. Here, using single cell analysis of hepatocytes across the liver lobule, we demonstrate that gluconeogenic gene expression (Pck1andG6pc) is relatively low in the fed state and gradually increases first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases, and following entry into the starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression to the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting state but only 1.5-fold higher in the starvation state. In parallel, starvation suppresses canonical beta-catenin signaling and modulates expression of pericentral and periportal glutamine synthetase and glutaminase, resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These findings demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule, underscoring the critical importance of using well-defined feeding and fasting conditions to define the basis of hepatic insulin resistance and glucose production.
Molecular mechanism of the endothelin receptor type B interactions with Gs, Gi, and Gq
Authors: Ham Donghee , Shihoya Wataru , Nureki Osamu , Inoue Asuka , Chung Ka Young
Published: April 2024

The endothelin receptor type B (ETB) exhibits promiscuous coupling with various G protein subtypes including Gs, Gi/o, Gq/11, and G12/13, leading to multi-modal signal transduction. Recent fluorescence and structural studies have raised questions regarding the coupling efficiencies and determinants of these G protein subtypes. Herein, by utilizing an integrative approach, combining hydrogen/deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cellular systems, we investigated conformational changes of Gs, Gi and Gq triggered by ETBactivation. ETBcoupled to Gi and Gq but not with Gs. We underscored the critical roles of specific regions, including the C-terminus of Gα and intracellular loop 2 (ICL2) of ETBin ETB-Gi1 or ETB-Gq coupling. Although The C-terminus of Gα is essential for ETB-Gi1 and ETB-Gq coupling, ETBICL2 influences Gq-coupling but not Gi1-coupling. Our results suggest a differential coupling efficiency of ETBwith Gs, Gi1, and Gq, accompanied by distinct conformational changes in G proteins upon ETB-induced activation.
Dynamical Responses Predict a Distal Site that Modulates Activity in an Antibiotic Resistance Enzyme
Authors: Beer Michael , Oliveira Ana Sofia F. , Tooke Catherine L. , Hinchliffe Philip , Li Angie Tsz Yan , Balega Balazs , Spencer James , Mulholland Adrian J.
Published: April 2024

β-Lactamases, which hydrolyse β-lactam antibiotics, are key determinants of antibiotic resistance. Predicting the sites and effects of distal mutations in enzymes is challenging. For β-lactamases, the ability to make such predictions would contribute to understanding activity against, and development of, antibiotics and inhibitors to combat resistance. Here, using dynamical non-equilibrium molecular dynamics (D-NEMD) simulations combined with experiments, we demonstrate that intramolecular communication networks differ in three class A SulpHydryl Variant (SHV)-type β-lactamases). Differences in network architecture and correlated motions link to catalytic efficiency and β-lactam substrate spectrum. Further, the simulations identify a distal residue 89 in the clinically importantKlebsiella pneumoniaecarbapenemase 2 (KPC-2), as a participant in similar networks, suggesting that mutation at this position would modulate enzyme activity. Experimental kinetics, biophysical and structural characterisation of the naturally occurring, but previously biochemically uncharacterised, KPC-2G89Dmutant with several antibiotics and inhibitors reveals significant changes in hydrolytic spectrum, specifically reducing activity towards carbapenems without effecting major structural or stability changes. These results show that D-NEMD simulations can predict distal sites where mutation affects enzyme activity. This approach could have broad application in understanding enzyme evolution, and in engineering of natural andde novoenzymes.
A global atlas of subsurface microbiomes reveals phylogenetic novelty, large scale biodiversity gradients, and a marine-terrestrial divide
Authors: Ruff S. Emil , Hrabe de Angelis Isabella C , Mullis Megan , Payet Jérôme P , Magnabosco Cara , Lloyd Karen G , Sheik Cody , Steen Andrew D , Shipunova Anna , Morozov Aleksey , Kiel Reese Brandi , Bradley James A , Lemonnier Clarisse , Schrenk Matthew O , Joye Samantha B , Huber Julie A , Probst Alexander J , Morrison Hilary G , Sogin Mitchell L , Ladau Joshua , Colwell Frederick
Published: April 2024

Subsurface environments constitute one of Earth's largest habitats for microbial life, yet differences between surface and subsurface microbiomes and between marine and terrestrial microbiomes remain unclear. We analyzed 478 archaeal and 1054 bacterial amplicon sequence datasets and 147 metagenomes from diverse and globally distributed surface and subsurface environments. Taxonomic analyses show that archaeal and bacterial diversity is similar in marine and terrestrial microbiomes at local to global scales. However, community composition greatly differs between marine and terrestrial microbiomes, suggesting a horizontal phylogenetic divide between sea and land that mirrors patterns in plant and animal diversity. In contrast, community composition overlapped from surface to subsurface environments indicating vertical diversity continua rather than a discrete subsurface biosphere. Diversity of terrestrial microbiomes decreases from surface to subsurface environments. Marine subsurface diversity and phylogenetic novelty rivaled (bacteria) or even exceeded (archaea) that of surface environments, suggesting that the marine subsurface holds a considerable and underestimated fraction of Earth's archaeal and bacterial diversity.
Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms
Authors: Sekar Amita , Fan Yingfang , Tierney Peyton , McCanne Madeline , Jones Parker , Malick Fawaz , Kannambadi Devika , Wannomae Keith K , Inverardi Nicoletta , Muratoglu Orhun , Oral Ebru
Published: April 2024

With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilm is crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better outcomes. Here, using in-vivo and in-vitro implant-associated infection models, we demonstrate that methicillin-sensitive and resistantStaphylococcus aureus(MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA and the models could capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can guide clinical dosing to effectively prevent or treat PJI.