bluuebunny/crossref_metadata_2025 huggingface dataset:
The fungal-derived compound AM3 modulates pro-inflammatory cytokine production and skews the differentiation of human monocytes
Authors: Geckin Büsra , Kilic Gizem , Debisarun Priya A. , Föhse Konstantin , Rodríguez-Luna Azahara , Fernández-González Pablo , Sánchez Ana López , Domínguez-Andrés Jorge
Published: October 2023

The proper functioning of the immune system depends on an appropriate balance between pro-inflammation and anti-inflammation. When the balance is disrupted and the system is excessively biased towards inflammation, immune responses cannot return within the normal range, which favors the onset of diseases of autoimmune or inflammatory nature. In this scenario, it is fundamental to find new compounds that can help restore this balance and contribute to the normal functioning of the immune system in humans. Here, we show the properties of a fungal compound with a strong safety profile in humans, AM3, as an immunomodulatory molecule to decrease excessive cytokine production in human cells. Our results present that AM3 treatment of human peripheral blood mononuclear cells and monocytes decreased their pro-inflammatory cytokine secretion following the challenge with bacterial lipopolysaccharide. Additionally, AM3 skewed the differentiation profile of human monocytes to macrophages towards a non-inflammatory phenotype without inducing tolerance, meaning these cells kept their capacity to respond to different stimuli. These effects were similar in young and elderly individuals. Thus, the fungal compound, AM3 may help reduce excessive immune activation in inflammatory conditions and keep the immune responses within a normal homeostatic range, regardless of the age of the individual.
Systemic cytokine and viral antigen-specific responses in hepatitis D virus RNA positive versus HDV RNA negative patients
Authors: Joshi Shivali S. , Sadler Matthew , Patel Nishi H. , Osiowy Carla , Fonseca Kevin , Coffin Carla S.
Published: October 2023

Background

Hepatitis B virus (HBV)/Hepatitis D Virus (HDV) co-infection increases the risk of severe liver disease compared to HBV mono-infection. Adaptive immune responses to HDV are weakly detectable, and the involvement of innate immunity in the progression of HDV-related liver fibrosis is suggested. We hypothesize that an overall innate immune activation in HBV/HDV co-infection plays a role in liver disease progression and also impacts virus specific T cell response.

Methods

Sixteen HBV/HDV-co-infected-patients (median age 42y/7F/6 Asian/4 White/6 Black/15 HBeAg-) and 8 HBV monoinfected-patients (median age 39y/4F/4 Asian/3 Black/1 White/HBeAg-) with median follow-up of 5 years were enrolled. Liver fibrosis was assessed by liver stiffness measurement (LSM, FibroScan®). Proliferation of CD3 + CD4+ T cells in response to viral antigens using CFSE assays and cytokine secreting monocytes was analyzed by flow cytometry.

Results

Of 16 HBV/HDV, 11 were HDV-RNA+ (HBV-DNA 0–1,040 IU/mL), 5/11 Interferon (IFN) + Nucleos/tide Analog (NA), 3/11 NA monotherapy, median ALT 77 U/L at the time of sample collection, median LSM of 9.8. In 5 HDV RNA−, median HBV DNA 65 IU/mL, 4/5 prior IFN and/or NA, ALT 31 U/L, and median LSM 8.5 kPa. In 8 HBV controls, median HBV-DNA, ALT, LSM was 69 IU/mL, 33 U/L,5 kPa, respectively. PBMC stimulation with HBV core antigen (HBcAg) and HDV antigen (HDAg) showed weaker CD3 + CD4 + T-cell proliferation in HDV-RNA+ vs. HDV RNA− and HBV-mono-infected patients (p < 0.05). In HDV-RNA+ patients, a correlation between ALT and TNF-α (r = 0.76, p = 0.008), higher IL-10 levels and increased proportion of CD14 + TNF-α+ cells were found.

Conclusion

In summary, during HBV/HDV coinfection, HDV RNA+ patients had weaker HBV and HDV specific responses, associated with increased TNF-α + monocytes irrespective of IFN treatment.
Investigating autonomic nervous system dysfunction among patients with post-COVID condition and prolonged cardiovascular symptoms
Authors: da Silva Fernanda Stábile , Bonifácio Lívia Pimenta , Bellissimo-Rodrigues Fernando , Joaquim Luis Fernando , Martins Dias Daniel Penteado , Dias Romano Minna Moreira , Schmidt André , Crescêncio Júlio César , Buzinari Tereza C. , Fazan Rubens , Salgado Helio Cesar
Published: October 2023

Heart Rate Variability (HRV) and arterial pressure (AP) variability and their responses to head-up tilt test (HUTT) were investigated in Post-COVID-19 syndrome (PCS) patients reporting tachycardia and/or postural hypotension. Besides tachycardia, PCS patients also showed attenuation of the following HRV parameters: RMSSD [square root of the mean of the sum of the squares of differences between adjacent normal-to-normal (NN) intervals] from statistical measures; the power of RR (beat-to-beat interval) spectra at HF (high frequency) from the linear method spectral analysis; occurrence of 2UV (two unlike variation) pattern of RR from the nonlinear method symbolic analysis; and the new family of statistics named sample entropy, when compared to control subjects. Basal AP and LF (low frequency) power of systolic AP were similar between PCS patients and control subjects, while 0 V (zero variation) patterns of AP from the nonlinear method symbolic analysis were exacerbated in PCS patients. Despite tachycardia and a decrease in RMSSD, no parameter of HRV changed during HUTT in PCS patients compared to control subjects. PCS patients reassessed after 6 months showed higher HF power of RR spectra and a higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0 V patterns of AP, while the HUTT elicited HR (heart rate) and AP responses identical to control subjects. The HRV and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients. In contrast, the lack of responses of HRV and AP variability indices during HUTT indicates a marked impairment of autonomic control. Of note, the reassessment of PCS patients showed that the noxious effect of COVID-19 on autonomic control tended to fade over time.
Case report: Dupilumab therapy for alopecia areata in a 4-year-old patient resistant to baricitinib
Authors: Cai Lu , Wei Yi , Zhao Min , Zhuo Jia , Tao Xiao , Lin Mao
Published: October 2023

Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.
The role of gut archaea in the pig gut microbiome: a mini-review
Authors: Yang Jianbo , Chen Routing , Peng Yunjuan , Chai Jianmin , Li Ying , Deng Feilong
Published: October 2023

The gastrointestinal microbiota of swine harbors an essential but often overlooked component: the gut archaea. These enigmatic microorganisms play pivotal roles in swine growth, health, and yield quality. Recent insights indicate that the diversity of gut archaea is influenced by various factors including breed, age, and diet. Such factors orchestrate the metabolic interactions within the porcine gastrointestinal environment. Through symbiotic relationships with bacteria, these archaea modulate the host’s energy metabolism and digestive processes. Contemporary research elucidates a strong association between the abundance of these archaea and economically significant traits in swine. This review elucidates the multifaceted roles of gut archaea in swine and underscores the imperative for strategic interventions to modulate their population and functionality. By exploring the probiotic potential of gut archaea, we envisage novel avenues to enhance swine growth, health, and product excellence. By spotlighting this crucial, yet under-investigated, facet of the swine gut microbiome, we aim to galvanize further scientific exploration into harnessing their myriad benefits.
miR-431 secreted by human vestibular schwannomas increases the mammalian inner ear’s vulnerability to noise trauma
Authors: Fujita Takeshi , Seist Richard , Kao Shyan-Yuan , Soares Vitor , Panano Lorena , Khetani Radhika S. , Landegger Lukas D. , Batts Shelley , Stankovic Konstantina M.
Published: October 2023

Introduction

Vestibular schwannoma (VS) is an intracranial tumor that arises on the vestibular branch of cranial nerve VIII and typically presents with sensorineural hearing loss (SNHL). The mechanisms of this SNHL are postulated to involve alterations in the inner ear’s microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model in vivo.

Methods

VS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores. Next-generation sequencing was performed on RNA isolated from cultured primary human VS cells and EVs from VS-conditioned media, stratified by patients’ hearing ability. microRNA expression levels were compared between VS-PH and VS-GH samples to identify differentially expressed candidates for packaging into a synthetic adeno-associated viral vector (Anc80L65). Viral vectors containing candidate microRNA were infused to the semicircular canals of mice to evaluate the effects on hearing, including after noise exposure.

Results

Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH). Newborn mice receiving intracochlear injection of viral vectors over-expressing hsa-miR-431-GFP, hsa-miR-192-GFP, or GFP only (control) had similar hearing 6 weeks post-injection. However, after acoustic trauma, the miR-431 group displayed significantly worse hearing, and greater loss of synaptic ribbons per inner hair cell in the acoustically traumatized cochlear region than the control group.

Conclusion

Our results suggest that miR-431 contributes to VS-associated hearing loss following cochlear stress. Further investigation is needed to determine whether miR-431 is a potential therapeutic target for SNHL.
Nanoparticles loaded with natural medicines for the treatment of Alzheimer’s disease
Authors: Liu Nanyang , Ruan Juanjuan , Li Hao , Fu Jianhua
Published: October 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that disrupts cognitive function and severely affects the quality of life. Existing drugs only improve cognitive function and provide temporary relief of symptoms but do not stop or delay disease progression. Recently, natural medicines, especially Chinese herbal medicines, have gained attention in the treatment of AD due to their antioxidant, anti-inflammatory, and neuroprotective effects. However, conventional oral dosage forms lack brain specificity and have side effects that lead to poor patient compliance. Utilizing nanomedicine is a promising approach to improve brain specificity, bioavailability, and patient compliance. This review evaluates recent advances in the treatment of AD with nanoparticles containing various natural medicines. This review highlights that nanoparticles containing natural medicines are a promising strategy for the treatment of AD. It is believed that this technology can be translated into the clinic, thereby providing opportunities for AD patients to participate in social activities.
Development and validation of radiomics models for the prediction of diagnosis of classic trigeminal neuralgia
Authors: Wang Fuxu , Ma Anbang , Wu Zeyu , Xie Mingchen , Lun Peng , Sun Peng
Published: October 2023

The study aims to develop a magnetic resonance imaging (MRI)-based radiomics model for the diagnosis of classic trigeminal neuralgia (cTN). This study involved 350 patients with cTN and 100 control participants. MRI data were collected retrospectively for all the enrolled subjects. The symptomatic side trigeminal nerve regions of patients and both sides of the trigeminal nerve regions of control participants were manually labeled on MRI images. Radiomics features of the areas labeled were extracted. Principle component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) regression were utilized as the preliminary feature reduction methods to decrease the high dimensionality of radiomics features. Machine learning methods were established, including LASSO logistic regression, support vector machine (SVM), and Adaboost methods, evaluating each model’s diagnostic abilities using 10-fold cross-validation. All the models showed excellent diagnostic ability in predicting trigeminal neuralgia. A prospective study was conducted, 20 cTN patients and 20 control subjects were enrolled to validate the clinical utility of all models. Results showed that the radiomics models based on MRI can predict trigeminal neuralgia with high accuracy, which could be used as a diagnostic tool for this disorder.
Case Report: Primary osteosarcoma of the kidney
Authors: Chen Junyong , Liao Hongxian , Zhan Rungen , Zheng Qiaoli , Deng Jian , Wang Guojie , Zhang Jie
Published: October 2023

Extraosseous osteosarcoma is a rare malignant tumor, most commonly occurring in the thigh, upper limbs, and retroperitoneum. However, there are only a few reported cases of renal osteosarcoma. Herein, we present the case of a 54-year-old woman with malignant extraosseous osteosarcoma of the left kidney. CT and MR imaging revealed a soft tissue mass originating from the left kidney.
Human antibody VH domains targeting uPAR as candidate therapeutics for cancers
Authors: Chu Xiaojie , Li Wei , Hines Margaret G. , Lyakhov Ilya , Mellors John W. , Dimitrov Dimiter S.
Published: October 2023

The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ovarian cancer, and melanoma. In our study, two high-affinity and specific human VH domain antibody candidates, designed as clones 3 and 115, were isolated from a phage-displayed human VH antibody library. Domain-based bispecific T- cell engagers (DbTE) based on these two antibodies exhibited potent killing of uPAR-positive cancer cells. Thus, these two anti-uPAR domain antibodies are promising candidates for treating uPAR positive cancers.
Nuclear medicine imaging methods of early radiation-induced cardiotoxicity: a ten-year systematic review
Authors: Eber Jordan , Blondet Cyrille , Le Fevre Clara , Chambrelant Isabelle , Hubele Fabrice , Morel Olivier , Antoni Delphine , Noel Georges
Published: October 2023

Introduction

Radiotherapy has significantly improved cancer survival rates, but it also comes with certain unavoidable complications. Breast and thoracic irradiation, for instance, can unintentionally expose the heart to radiation, leading to damage at the cellular level within the myocardial structures. Detecting and monitoring radiation-induced heart disease early on is crucial, and several radionuclide imaging techniques have shown promise in this regard.

Method

In this 10-year review, we aimed to identify nuclear medicine imaging modalities that can effectively detect early cardiotoxicity following radiation therapy. Through a systematic search on PubMed, we selected nineteen relevant studies based on predefined criteria.

Results

The data suggest that incidental irradiation of the heart during breast or thoracic radiotherapy can cause early metabolic and perfusion changes. Nuclear imaging plays a prominent role in detecting these subclinical effects, which could potentially serve as predictors of late cardiac complications.

Discussion

However, further studies with larger populations, longer follow-up periods, and specific heart dosimetric data are needed to better understand the relationship between early detection of cardiac abnormalities and radiation-induced heart disease.
Is there a sex difference in mortality rates in paediatric intensive care units?: a systematic review
Authors: Almossawi Ofran , Friend Amanda , Palla Luigi , Feltbower Richard G. , Sardo-Infiri Sofia , O’Brien Scott , Harron Katie , Nadel Simon , Saunders Paul , De Stavola Bianca
Published: October 2023

Introduction

Mortality rates in infancy and childhood are lower in females than males. However, for children admitted to Paediatric Intensive Care Units (PICU), mortality has been reported to be lower in males, although males have higher admission rates. This female mortality excess for the subgroup of children admitted in intensive care is not well understood. To address this, we carried out a systematic literature review to summarise the available evidence. Our review studies the differences in mortality between males and females aged 0 to <18 years, while in a PICU, to examine whether there was a clear difference (in either direction) in PICU mortality between the two sexes, and, if present, to describe the magnitude and direction of this difference.

Methods

Any studies that directly or indirectly reported the rates of mortality in children admitted to intensive care by sex were eligible for inclusion. The search strings were based on terms related to the population (those admitted into a paediatric intensive care unit), the exposure (sex), and the outcome (mortality). We used the search databases MEDLINE, Embase, and Web of Science as these cover relevant clinical publications. We assessed the reliability of included studies using a modified version of the risk of bias in observational studies of exposures (ROBINS-E) tool. We considered estimating a pooled effect if there were at least three studies with similar populations, periods of follow-up while in PICU, and adjustment variables.

Results

We identified 124 studies of which 114 reported counts of deaths by males and females which gave a population of 278,274 children for analysis, involving 121,800 (44%) females and 156,474 males (56%). The number of deaths and mortality rate for females were 5,614 (4.61%), and for males 6,828 (4.36%). In the pooled analysis, the odds ratio of female to male mortality was 1.06 [1.01 to 1.11] for the fixed effect model, and 1.10 [1.00 to 1.21] for the random effects model.

Discussion

Overall, males have a higher admission rate to PCU, and potentially lower overall mortality in PICU than females.

Systematic Review Registration

www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=203009, identifier (CRD42020203009).
The role of blood pressure variability indicators combined with cerebral blood flow parameters in predicting intraventricular hemorrhage in very low birth weight preterm infants
Authors: Jiang Lijun , Yu Qian , Wang Fudong , Wu Mingfu , Liu Feng , Fu Mingfeng , Gao Junyan , Feng Xing , Zhang Longfeng , Xu Zhenxing
Published: October 2023

Background

Hemodynamic instability is the main factor responsible for the development of intraventricular hemorrhage (IVH) in premature newborns. Herein, we evaluated the predictive ability of blood pressure variability (BPV) and anterior cerebral artery (ACA) blood flow parameters in IVH in premature infants with gestational age (GA) ≤32 weeks and birth weight (BW) ≤ 1,500 g.

Methods

Preterm infants with GA ≤32 weeks and BW ≤ 1,500 g admitted to the neonatal intensive care unit (NICU) of the hospital affiliated to Yangzhou University from January 2020 to January 2023 were selected as the research subjects. All preterm infants were admitted within 1 h after birth, and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) were monitored at 1-h intervals. The difference between maximum and minimum values (max-min), standard deviation (SD), coefficient of variation (CV), and successive variation (SV) were used as BPV indicators. On the 1st, 3rd, and 7th day after birth, transcranial ultrasound examination was performed to screen for the occurrence of IVH. On the 24 ± 1 h after birth, systolic velocity (Vs), diastolic velocity (Vd), and resistance index (RI) of the ACA were measured simultaneously. Preterm infants were divided into the IVH group and non-IVH group based on the results of transcranial ultrasound examination, and the correlation between BPV indicators, ACA blood flow parameters, and development of IVH was analyzed.

Results

A total of 92 premature infants were enrolled, including 49 in the IVH group and 43 in the non-IVH group. There was no statistically significant difference in baseline characteristics such as BW, GA, sex, and perinatal medical history between the two groups of preterm infants (P > 0.05). The SBP SD (OR: 1.480, 95%CI: 1.020–2.147) and ACA-RI (OR: 3.027, 95%CI: 2.769–3.591) were independent risk factors for IVH in premature newborns. The sensitivity and specificity of combined detection of SBP SD and ACA-RI in predicting IVH were 61.2% and 79.1%, respectively.

Conclusion

High BPV and ACA-RI are related to IVH in premature infants with GA ≤32 w and BW ≤1,500 g. Combined detection of SBP SD and ACA-RI has a certain predictive effect on early identification of IVH.
Proteomic and single-cell analysis shed new light on the anti-inflammatory role of interferonβ in chronic periodontitis
Authors: Liu Jieying , Li Tianle , Zhang Shunhao , Lu Eryi , Qiao Wei , Chen Huimin , Liu Peng , Tang Xiaoyue , Cheng Tianfan , Chen Hui
Published: October 2023

Periodontitis, a condition that results in periodontal attachment loss and alveolar bone resorption, contributes to the global burden of oral disease. The underlying mechanism of periodontitis involves the dysbiosis and dyshomeostasis between host and oral microbes, among which the macrophage is one of the major innate immune cell players, producing interferon β (IFNβ) in response to bacterial infection. The objective of this research was to examine the interaction of macrophages with periodontitis and the role and mechanism of IFNβ on macrophages. IFNβ has been shown to have the potential to induce the differentiation of M1 to M2 macrophages, which are stimulated by low levels of lipopolysaccharide (LPS). Additionally, IFNβ has been demonstrated to promote the production of ISG15 by macrophages, which leads to the inhibition of the innate immune response. Moreover, our investigation revealed that IFNβ has the potential to augment the secretion of ISG15 and its downstream cytokine, IL10, in LPS-stimulated macrophages. Single-cell analysis was conducted on the gingival tissues of patients with periodontitis, which revealed a higher proportion of macrophages in the periodontitis-diseased tissue and increased expression of IFNβ, ISG15, and IL10. Gene Set Enrichment Analysis indicated that bacterial infection was associated with upregulation of IFNβ, ISG15, and IL10. Notably, only IL10 has been linked to immunosuppression, indicating that the IFNβ-ISG15-IL10 axis might promote an anti-inflammatory response in periodontitis through IL10 expression. It is also found that macrophage phenotype transitions in periodontitis involve the release of higher levels of IFNβ, ISG15, and IL10 by the anti-inflammatory M2 macrophage phenotype compared to the pro-inflammatory M1 phenotype and myeloid-derived suppressor cells (MDSCs). This implies that the IFNβ-induced production of IL10 might be linked to the M2 macrophage phenotype. Furthermore, cell communication analysis demonstrated that IL10 can promote fibroblast proliferation in periodontal tissues via STAT3 signaling.
Model-informed precision dosing in vancomycin treatment
Authors: Yoon Sukyong , Guk Jinju , Lee Sang-Guk , Chae Dongwoo , Kim Jeong-Ho , Park Kyungsoo
Published: October 2023

Introduction: While vancomycin remains a widely prescribed antibiotic, it can cause ototoxicity and nephrotoxicity, both of which are concentration-associated. Overtreatment can occur when the treatment lasts for an unnecessarily long time. Using a model-informed precision dosing scheme, this study aims to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin to determine the optimal dosage regimen and treatment duration in order to avoid drug-induced toxicity.

Methods: The data were obtained from electronic medical records of 542 patients, including 40 children, and were analyzed using NONMEM software. For PK, vancomycin concentrations were described with a two-compartment model incorporating allometry scaling.

Results and discussion: This revealed that systemic clearance decreased with creatinine and blood urea nitrogen levels, history of diabetes and renal diseases, and further decreased in women. On the other hand, the central volume of distribution increased with age. For PD, C-reactive protein (CRP) plasma concentrations were described by transit compartments and were found to decrease with the presence of pneumonia. Simulations demonstrated that, given the model informed optimal doses, peak and trough concentrations as well as the area under the concentration-time curve remained within the therapeutic range, even at doses smaller than routine doses, for most patients. Additionally, CRP levels decreased more rapidly with the higher dose starting from 10 days after treatment initiation. The developed R Shiny application efficiently visualized the time courses of vancomycin and CRP concentrations, indicating its applicability in designing optimal treatment schemes simply based on visual inspection.
Evidence for benefits and risks of tadalafil as a non-prescription medicine: review and evaluation using the Group Delphi technique to achieve consensus amongst clinical experts
Authors: Miller Kurt , May Uwe , Beecken Wolf-Dietrich , Hatzichristodoulou Georgios , Böhm Michael , Fink Stefan
Published: October 2023

An evidence-based consensus meeting was held with urologists, a pharmacist and a cardiologist to perform a structured benefit-risk analysis of reclassifying tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor for treatment of erectile dysfunction (ED), to be available without prescription in Germany. As per the Brass process endorsed by regulatory authorities, an evidence-based Brass value tree was developed, which identified the incremental benefits and risks that should be considered above the safety and efficacy evidence required for prescription medicines. During the Group Delphi consensus meeting, the expert panel rated the likelihood and clinical impact of each benefit and risk on a scale of 0 (none) to 3 (high). Overall attribute scores were calculated from the product of the mean likelihood and mean clinical impact scores giving a possible score of 0–9. The overall benefit attribute scores ranged from 2.8 to 5.4. The overall risk attribute scores ranged from 0.2 to 2.2 though most were 1.0 or less (3 or more is generally considered to be of concern). On balance, the independent meeting scored the benefits of reclassification of tadalafil higher than the risks and considered the risk mitigation strategies of the packaging label and patient information leaflet (PIL) sufficient.
Synchronous multi-wavelength mode-locked laser at 2-μm based on Mamyshev cavity
Authors: Gong Rui , Geng Yalin , Pei Li , Wei Huai
Published: October 2023

In recent years, 2-μm band lasers have developed rapidly due to their wide range of usage. It is a challenging problem to realize the synchronization of multi-wavelength multi-channel ultrashort pulses for many important applications. In this paper, a 2-μm synchronous multi-wavelength fiber laser is proposed. The laser was constructed based on cascaded Mamyshev regenerators. The multi-cascade nonlinear broadening and offset filtering can act as a saturable absorber, enabling mode locking, and resolving the issues of gain competition and synchronous output encountered in traditional multi-wavelength lasers. A stable synchronous multi-wavelength mode-locked laser was realized through numerical simulation. The laser can provide six-channel ultrashort pulses with a wavelength interval of 5 nm (the central wavelengths range from 2000 nm to 2025 nm). The peak power and duration of the output pulses are respectively 0.1–0.25 kW (intracavity peak power 0.4–1.1 kW for coupler ratio is 20:80) and ∼1.1 ps. Design principles and the effects of various parameters such as the filter, the fiber length, etc., on the optimization of the laser are analyzed and discussed.
Agronomic and hormonal approaches for enhancing flowering intensity in white Guinea yam (Dioscorea rotundata Poir.)
Authors: Mondo Jean M. , Agre Paterne A. , Chuma Géant B. , Asiedu Robert , Akoroda Malachy O. , Asfaw Asrat
Published: October 2023

Developing novel white Guinea yam (Dioscorea rotundata) varieties is constrained by the sparse, erratic, and irregular flowering behavior of most genotypes. We tested the effectiveness of nine agronomic and hormonal treatments to enhance flowering on D. rotundata under field conditions. Genotypes responded differently to flower-inducing treatments (p<0.001). Of the test treatments, pruning and silver thiosulfate (STS) were effective in increasing the number of spikes per plant and the flowering intensity on both sparse flowering and monoecious cultivars. STS and tuber removal treatments promoted female flowers on the monoecious variety while pruning and most treatments involving pruning favored male flowers. None of the treatments induced flowering on Danacha, a non-flowering yam landrace. Flower-enhancing treatments had no significant effect on flower fertility translated by the fruit set, since most treatments recorded fruit sets above the species’ average crossability rate. Flower-enhancing techniques significantly influenced number of tubers per plant (p = 0.024) and tuber dry matter content (DMC, p = 0.0018) but did not significantly affect plant tuber yield. Nevertheless, treatments that could enhance substantially flowering intensity, such as pruning and STS, reduced tuber yield. DMC had negative associations with all flowering-related traits. This study provided insights into white yam flower induction and suggests promising treatments that can be optimized and used routinely to increase flowering in yam crop, without significantly affecting flower fertility and tuber yield.
Transcriptome and metabolome analyses of anthocyanin biosynthesis in post-harvest fruits of a full red-type kiwifruit (Actinidia arguta) ‘Jinhongguan’
Authors: Ye Lixia , Bai Fuxi , Zhang Lei , Luo Minmin , Gao Lei , Wang Zhi , Peng Jue , Chen Qinghong , Luo Xuan
Published: October 2023

Anthocyanin is the main component of pigment in red-fleshed kiwifruit. ‘Jinhongguan’ is a new cultivar of Actinidia arguta with red peel and flesh after harvest. However, the specific types of anthocyanin in the ‘Jinhongguan’ fruit and its biosynthesis pathways remain largely unknown. Here, the total anthocyanin content in the fruit color conversion process was determined. The results showed that total anthocyanin content increased with the deepening color of the peel and flesh. To identify the genes related to anthocyanin biosynthesis and the types of anthocyanins in the ‘Jinhongguan’ fruit, a combined analysis of transcriptome and anthocyanin-targeted metabolome was carried out. A total of 5751 common differentially expressed genes (DEGs) at different stages of peel and flesh were identified, of which 2767 were common up-DEGs and 2976 were common down-DEGs. KEGG and GO enrichment analyses showed that the common up-DEGs were significantly enriched in anthocyanin synthesis-related pathways, suggesting some up-DEGs are involved in anthocyanin biosynthesis. In total, 29 metabolites were detected in the flesh by anthocyanin-targeted metabolome. Among these, nine were differential accumulation metabolites (DAMs) in comparison to red flesh vs green flesh. Six DAMs were up-regulated, with five of them were cyanidins. The content of cyanidin-3-O-galactoside was much higher than that of other DAMs, making it the main pigment in ‘Jinhongguan’. Moreover, a total of 36 anthocyanin synthesis-related structural genes, 27 MYB transcription factors (TFs), 37 bHLH TFs and 9 WDR TFs were screened from the common DEGs. Correlation analysis of transcriptome and metabolome revealed that 9 structural genes, 6 MYB TFs, 6 bHLH TFs and 1 WDR TF were significantly associated with cyanidin-3-O-galactoside. Further, qRT-PCR analysis demonstrated that structural genes (AaPAL3, Aa4CL3, AaCHS2/3/8/9/11, AaDFR1/2, AaANR1, UFGT3a and UFGT6b) and TFs (MYB108, bHLH30, bHLH94-1 and WD43) play important roles in cyanidin biosynthesis. Overall, this study identified cyanidin-3-O-galactoside as the main anthocyanin type and revealed key candidate genes of red coloration of post-harvest fruit in Actinidia arguta. These findings provided new insights into the color formation mechanism of post-harvest fruit and offered a theoretical basis for color regulation in kiwifruit.
Agenda-setting in first sessions of business coaching—a focus on coaches’ practices to manage the agenda and establish the working alliance
Authors: Jautz Sabine , Graf Eva-Maria , Fleischhacker Melanie , Dionne Frédérick
Published: October 2023

Introduction

Agenda-setting is a central communicative task for professionals and a joint activity of all participants particularly at the onset of helping interactions such as coaching. Agreeing on goal(s) and assigning tasks alongside establishing a trustful bond prepare the ground for the success of the interaction. The professional agent initiates and sets the agenda as part of their professional role and responsibility, i.e., based on their professional epistemic and deontic authority. Concurrently, by orienting to clients’ epistemic authority and by yielding power, control, and agency to clients to co-manage the ensuing interaction, agenda-setting is the first opportunity for client-centeredness, which is a central characteristic and success factor for the working alliance in coaching.

Procedure and Methods

We take first steps in filling a research gap by providing a first analysis of the interactional unfolding of agenda-setting in coaching and by showcasing that and how agenda-setting as a joint activity of coach and client contributes to their working alliance. More precisely, we investigate agenda-management practices in five first sessions of business coaching to (1) document and analyze how the joint activity ‘agenda-setting’ is implemented via various (coach-initiated) social actions, (2) detail their contribution to establishing the working alliance, and (3) to interpret the emerging practices of agenda-management against the concept of ‘client-centeredness’. For the analysis, we draw on conceptual and methodological resources from interactional linguistics alongside linguistic pragmatics and conversation analysis.

Results

We found 117 instances of ‘agenda-setting’ in our data which can be assigned to the seven social actions “Delivering Agenda Information”, “Requesting Agenda Information”, “Requesting Agenda Agreement”, “Requesting Agenda Action”, “Suggesting Agenda Action”, “Offering Agenda Action” and “Proposing Agenda Action”.

Discussion

The social actions display that agenda-setting serves to establish a common ground regarding goals, tasks and the relational bond of coach and client, and (after this has been achieved) to negotiate future coaching actions. Thus, the joint activity of ‘doing’ agenda-setting can be shown to be ‘doing’ working alliance at the same time.
Drivers of vaccine hesitancy among vulnerable populations in India: a cross-sectional multi-state study
Authors: Krishnamurthy Parthasarathy , Mulvey Michael S. , Gowda Kallana , Singh Meghna , Venkatesan Nitish Kumar , Syam Syama B. , Shah Prerak , Kumar Shiv , Chaudhuri Angela , Narayanan Raghunathan , Perne Abdul Latheef , Pangaria Aditya
Published: October 2023

Objectives

India’s Covid-19 vaccination campaign engaged frontline workers (FLWs) to encourage vaccination among vulnerable segments of society. The FLWs report encountering a variety of barriers to vaccination and are often unsuccessful despite multiple visits to the same person. This cross-sectional study aims to pinpoint which of these barriers drive vaccine hesitancy among these segments, to help streamline vaccine communication, including FLW training, to better safeguard the population.

Methods

Trained field enumerators contacted 893 individuals from five states across India and collected self-reported assessments of fifteen vaccination barriers (identified through discussions with FLWs), current vaccination status and future vaccination intentions, and covariates (demographics/comorbidities). Factor analysis of the fifteen barriers yielded two factors, one relating to fear of vaccine adverse effects and a second focused on peripheral concerns regarding the vaccine. The covariates significantly associated with current vaccination status were combined under a latent class regime to yield three cluster types (health access, financial strength, and demographics). The primary analysis examined the effect of the two barrier factors, the covariate clusters, and comorbidity, on current vaccination status and future vaccine intentions.

Results

Fear of vaccine adverse effects was the primary driver of vaccine hesitancy; peripheral concerns frequently mentioned by the FLWs had no impact. Although cluster membership and the presence of comorbidities predicted vaccine uptake, neither of them materially altered the effect of fear of vaccine adverse effects with the following exception: fear of adverse effects was not associated with vaccination status among young Muslim men.

Conclusion

Subject to limitations, these results indicate that interventions to decrease vaccine hesitancy should focus primarily on fear associated with vaccines rather than spend resources trying to address peripheral concerns.
Sciducio: a practical framework for guiding the development and leadership of the academic research environment
Authors: Stoner Lee , Paterson Craig , Perry Lane , Higgins Simon , Woolard Nathan , Pagan Lassalle Patricia , Cowley Emma , Lassalle Yolanda
Published: October 2023

The goal of this paper is to introduce Sciducio, a practical framework for guiding the development and leadership of an academic research environment. The principal audience for this framework is new academics, that is individuals beginning a tenure-track position in the U.S or a lecturing position elsewhere in the world. However, we also believe this framework will be of use to established academics searching for structure, academics moving to a new institution, and can serve as a training tool for doctoral and postdoctoral mentees. We briefly describe the theory supporting Sciducio, outline the framework and its individual components (blocks), then provide suggested instructions for use. We provide suggested instructions (i.e., descriptive rather than prescriptive), because there is no one-size-fits-all approach for ensuring success. Sciducio incorporates three domains (Plan, Manage, and Deliver), encompasses eight blocks, and is intended to fit on one-sheet of paper or one screen. The Plan domain includes the blocks: value, strategy, and leadership. The Manage domain includes the blocks: activities, key resources, and finances. The Deliver domain includes the blocks: solution and channels. Considering each of the framework blocks is complex, we cannot provide full justice to each component. This paper serves as a general overview and subsequent papers will be more topic specific. Additionally, we encourage others to contribute to and advance this framework.
Integrating intention-based systems in human-robot interaction: a scoping review of sensors, algorithms, and trust
Authors: Zhang Yifei , Doyle Thomas
Published: October 2023

The increasing adoption of robot systems in industrial settings and teaming with humans have led to a growing interest in human-robot interaction (HRI) research. While many robots use sensors to avoid harming humans, they cannot elaborate on human actions or intentions, making them passive reactors rather than interactive collaborators. Intention-based systems can determine human motives and predict future movements, but their closer interaction with humans raises concerns about trust. This scoping review provides an overview of sensors, algorithms, and examines the trust aspect of intention-based systems in HRI scenarios. We searched MEDLINE, Embase, and IEEE Xplore databases to identify studies related to the forementioned topics of intention-based systems in HRI. Results from each study were summarized and categorized according to different intention types, representing various designs. The literature shows a range of sensors and algorithms used to identify intentions, each with their own advantages and disadvantages in different scenarios. However, trust of intention-based systems is not well studied. Although some research in AI and robotics can be applied to intention-based systems, their unique characteristics warrant further study to maximize collaboration performance. This review highlights the need for more research on the trust aspects of intention-based systems to better understand and optimize their role in human-robot interactions, at the same time establishes a foundation for future research in sensor and algorithm designs for intention-based systems.
PANSATZ: pulse-based ansatz for variational quantum algorithms
Authors: Meirom Dekel , Frankel Steven H.
Published: October 2023

Quantum computers promise a great computational advantage over classical computers, which might help solve various computational challenges such as the simulation of complicated quantum systems, finding optimum in large optimization problems, and solving large-scale linear algebra problems. Current available quantum devices have only a limited amount of qubits and a high level of noise, limiting the size of problems that can be solved accurately with those devices. Variational quantum algorithms (VQAs) have emerged as a leading strategy to address these limitations by optimizing cost function based on measurement results of shallow depth circuits. Recently, various pulse engineering methods were suggested in order to improve VQA results, including optimizing pulse parameters instead of gate angles as part of the VQA optimization process. In this paper, we suggest a novel pulse-based ansatz, which is parameterized mainly by pulses’ duration of pre-defined pulse structures. This ansatz structure provides relatively low amounts of optimization parameters while maintaining high expressibility, allowing fast convergence. In addition, the ansatz has structured adaptivity to the entanglement level required by the problem, allowing low noise and accurate results. We tested this ansatz against quantum chemistry problems. Specifically, finding the ground-state energy associated with the electron configuration problem, using the variational quantum eigensolver (VQE) algorithm for several different molecules. We manage to achieve chemical accuracy both in simulation for several molecules and on one of IBM’s NISQ devices for the H2 molecule in the STO-3G basis, without the need for extensive error mitigation. Our results are compared to a common gate-based ansatz and show better accuracy and significant latency reduction—up to 7× shorter ansatz schedules.
Embryogenesis of an aquaculture fish (Dicentrarchus labrax) under simulated altered gravity
Authors: Przybyla Cyrille , Bonnefoy Julie , Paounov Raphaelle , Debiol Amelys , Dutto Gilbert , Mansuy Emmanuel , Lallement Stephane , Coste Florence , Geffroy Benjamin , Frippiat Jean Pol
Published: October 2023

Food production and balanced nutrition will be a key challenge for residents of a future base on the Moon or Mars. As a complement to photosynthetic organisms, space aquaculture could provide the range of amino acids required to maintain health. This would rely on shipping fertilized aquaculture fish eggs to the Moon. To determine the feasibility of this, this study sought to test the influence of the conditions of a lunar mission—such as hypergravity during rocket launch and microgravity during the journey—on fish embryos and young larvae. To analyze the potential effects of these gravity changes on the early developmental stages of fish, we conducted two experiments to expose them to: i) 10 min of simulated hypergravity at 5 g (launch duration) and ii) 39 h of simulated microgravity using a random positioning machine. Both experiments used European sea bass (Dicentrarchus labrax) as a model. We analyzed egg oxygen consumption and hatching rates, as well as the expression of genes related to stress and immunity. The results indicated that neither of these altered gravity conditions affected the hatching rate. Simulated microgravity did not impact fish embryo oxygen consumption and appeared to induce faster embryonic development, as the eggs hatched earlier than expected. Levels of glucocorticoid receptors (GR1 and GR2) and heat shock proteins (Hsp90) were not impacted. Only the levels of complement component protein 3 (C3) were significantly higher in simulated microgravity, while interleukin-1β (IL-1β) transcripts were significantly lower in the hypergravity group, compared to controls. This shows that proteins involved in the innate immune system are expressed under altered gravity. Although further experiments are needed, these results suggest that the European sea bass is a promising candidate for space aquaculture.
A 24-h restraint with food and water deprivation: a potential method to establish a model of depression in pigs
Authors: Yang Sen , Zheng Qiang , Yin Guoan
Published: October 2023

Adverse stress, such as the long-term restriction of food intake and activity in intensive production, leads to a depression-like mental state in sows. Mood disorder, such as depression, is a widely concerned animal welfare issue. However, little is known about the biological mechanisms that underlie mood disorders in pigs. This study is the first attempt to establish a pig depression model by acute stress. A total of 16 adult Bama pigs were divided into the control and model groups, with 8 pigs (half male and half female) per group. The pigs in the model group were restrained for 24 h in a dark and ventilated environment, with food and water deprivation. After the restraint, behavioral tests (feed intake, sucrose preference test, open field test, and novel object test) were used to evaluate apparent indicators. The levels of COR and ACTH in the serum and the levels of 5-HT, NE, and BDNF in the hippocampus and medial prefrontal cortex were detected using ELISA to identify the physiological state. After acute stress, pigs exhibited decreased feed intake and sucrose preference, increased serum COR levels, decreased hippocampal 5-HT levels, and exhibited more fear. Finally, the model was evaluated according to the weight of the test indicators. The overall score of the model was 0.57, indicating that modeling was feasible. Although the reliability and stability require further verification, this novel model revealed typical depression-like changes in behavior and provided a potential method to establish a model of depression in pigs.