bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear analysis of the efficiency and saturation length of free electron laser with realistic helical wiggler and ion-channel guiding
Authors: kheiri golshad
Published: April 2022

A nonlinear study of the efficiency, power, and the saturation length of a free-electron laser with realistic helical wiggler and ion-channel guiding using numerical simulation is presented. A set of coupled nonlinear differential equations is derived using the Lorentz force equation for the ensemble of electrons and Maxwell’s equations for radiation waves. To calculate the efficiency, power, and the saturation length of the amplifier, these equations are solved simultaneously using a code developed in this study. By choosing different values of the plasma frequency of ion-channel guiding, the dominant mode for the group I and group II orbits is found. The effect of ion-channel guiding on efficiency and saturation length was studied, and the results show that ion-channel guiding increases efficiency and reduces saturation length. Moreover, the efficiency increases, and the saturation length decrease when the annular electron beam is substituted for a solid electron beam. Finally, the results show that the efficiency of a realistic wiggler free-electron laser is higher than that of an idealized one, while the saturation length is lower.
Immunofluorescence and Biochemical Investigation of the Protective Effects of Naringin and Diosmin on the Freezability of Merino Ram Semen
Authors: Ömür Ali Doğan , Kaynar Özgür , İleritürk Mustafa , Özkaraca Mustafa , Öztürk Ali Erdem , Bodu Mustafa , Şahin İpek Nur , akarsu serkan
Published: April 2022

In this study, the effects of diosmin and naringin on freezability of ram semen were investigated. For this purpose, 6 Merino rams were used during the breeding season. The ejaculates were pooled after being collected from the rams. Pooled ejaculates were divided into 6 groups as control (C; no additive) Naringin (1, 2, and 4 mM) and Diosmin (2 and 4 mM) groups, and then reconstituted with TRIS-based diluent. Pooled semen was equilibrated, placed in 0,25 mL straws with 10 × 107 sperm cells in each straw and frozen in liquid nitrogen vapor. After waiting for 24 hours, the straws were thawed at 37 oC for 25 s and analyzes were made. There was no statistical difference in total motility between the groups. D2 and D4 preserved the integrity of the plasma membrane better than the other groups. D4 showed better effect than other groups in terms of acrosome integrity, there was no difference between the groups in terms of mitochondrial activity. In the analysis of the sperm membrane lipid profile, it was observed that the diosmin added group had the highest lipid-phospholipid ratio. In the sperm membrane protein profile analysis, it was observed that both additives had protective effects at different levels. The highest total protein amount was seen in D4 and N4 groups. 8-OhDG positivity was more common in the control group than in the diosmin and naringin groups. Cu-Zn SOD positivity was less in the control group but more intense in all other groups. The positives were especially in the acrosome parts of the sperm cells.
The Impact of COVID-19 on Autologous Stem Cell Transplantation in Multiple Myeloma A single-centre service evaluation
Authors: Camilleri Marquita , Bekris Georgios , Sidhu Govundeep , Buck Caroline , Elsden Esme , McCourt Orla , Horder Jackie , Newrick Fiona , Lecat Catherine , Sive Jonathan , Papanikolaou Xenofon , Popat Rakesh , Lee Lydia , Xu Ke , Kyriakou Charalampia , Rabin Neil , Yong Kwee , Fisher Abi
Published: April 2022

Autologous stem cell transplantation (ASCT) is standard of care in biologically fit, newly diagnosed multiple myeloma (MM) patients, offering better therapeutic outcomes and improved quality of life (QoL). However, with the UK’s 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to patients’ treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QoL. We conducted a qualitative study using semi-structured interviews to gain insight into MM patients’ understanding of their disease, initial therapy and ASCT, and their response to therapy changes. A clinical snapshot of how COVID-19 affected the MM ASCT service in a single UK institution is also provided, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. Framework analysis identified 6 overarching themes: 1) beliefs about ASCT, 2) perceptions of information provided about MM and ASCT, 3) high levels of fear and anxiety due to COVID-19, 4) feelings about ASCT disruption or delay due to COVID-19, 5) perceptions of care and 6) importance of social support. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment, and devastation at COVID-related treatment delays (despite high anxiety about infection) and exceptionally high levels of trust in the transplant team. Such insights will help us adjust our service and counselling approaches to be more in tune with patients’ priorities and expectations.
A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature
Authors: Bryant Maria C , Spencer L. Terry , Yalcindag Ali
Published: April 2022

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare form of vasculitis in children. SARS-CoV-2, the virus that causes COVID-19 infection, seems to trigger autoimmunity and new-onset autoimmune disease in pediatric and adult patients. We present a case of new-onset AAV following COVID-19 infection in an adolescent patient, and we review the literature of AAV following COVID-19 infection. Case presentation: An adolescent female with a history of asthma was diagnosed with mild COVID-19 infection and subsequently developed persistent cough, wheezing, hearing loss, arthralgias, and rash. Her imaging and laboratory workup showed pulmonary nodules and cavitary lesions, elevated inflammatory markers, negative infectious testing, and positive ANCA. She was treated with corticosteroids, rituximab, and mycophenolate. At six-month follow-up, she had improvement in her symptoms, pulmonary function tests, imaging findings, and laboratory markers. Conclusions: We report the second case of new-onset anti-PR3, C-ANCA vasculitis and the fourth case of pediatric-onset AAV following COVID-19 infection. A systematic review of the literature found 6 cases of new-onset AAV in adults after COVID-19 infection. Pediatric and adult patients who develop AAV post COVID-19 infection have few, if any, comorbidities, and show marked radiographic and symptomatic improvement after treatment. There is increasing evidence for COVID-19-induced autoimmunity in children and our case highlights the importance of considering AAV in a child following a recent COVID-19 infection because timely treatment may improve clinical outcomes.
Characterizing the effects of stormwater runoff on dissolved organic matter in an urban river (Jiujiang, Jiangxi Province, China) using spectral analysis
Authors: Yuan Keting , Wan Qiong , Chai Beibei , Lei Xiaohui , Kang Aiqing , Chen Jianghai , Chen Xiang , Shi Hongwei , He Lixin , Li Ming
Published: April 2022

The effect of stormwater runoff on dissolved organic matter (DOM) in rivers is one of the central topics in water environment research. Jiujiang is one of the first cities established in the Green Development Demonstration Zone of the Yangtze River Economic Belt (Jiangxi Province, China). Three-dimensional excitation–emission matrix fluorescence with parallel factor analysis (3DEEM-PARAFAC) and ultraviolet–visible (UV-Vis) spectroscopy were used to explore the effects of runoff on organic matter in Shili River (Jiujiang, Jiangxi Province, China). The results show that the runoff led to an increase of some critical pollutants and DOM concentrations, especially in the middle reaches of the river. The concentration and relative molecular weight of DOM in water increased as a result of runoff. Three humic-like (C1–C3) and two protein-like (C4 and C5) components of DOM were identified using the PARAFAC model. The sources of the three humic-like components were consistent, unlike those of the protein-like component C4. The runoff contained lower amounts of humic compounds which caused the relative content and proportion of humic substances little change and protein-like species increasing. The DOM mainly derived from autochthonous sources, and runoff had limited effect on its characteristics. The PARAFAC components could adequately represent different indicators and sources of DOM in urban rivers, providing an important reference for urban river management.
Anxiety in Autism Spectrum Disorder: clinical characteristics and the role of the family.
Authors: Guerrera Silvia , Pontillo Maria , Tata Maria Cristina , Vincenzo Cristina Di , bellantoni domenica , Napoli Eleonora , Valeri Giovanni , Vicari Stefano
Published: April 2022

Background: Anxiety Disorder (AD) is among the most common psychiatric comorbidities in children and adolescents with Autism Spectrum Disorder (ASD). However, findings regarding the characterization of anxiety symptoms and the use of validated measures for children with ASD and AD are inconsistent. Parental psychological distress (PPD) has been linked to anxiety symptoms in children with ASD. This study aims to identify and to explore clinical characteristics of anxiety symptoms in ASD. Furthermore we shed light on the possible presence of PPD involving families of children and adolescents with ASD and AD. Methods: The final sample consisted of 75 children and adolescents (Mean age: 11,8 ± 2,3 years; Range age: 8-16 years) and their parents. Participants were divided into three groups based on the diagnosis: children and adolescents with a diagnosis of Autism Spectrum Disorder and Anxiety Disorders in comorbidity, children and adolescents with a diagnosis of Anxiety Disorders but without a diagnosis of Autism Spectrum Disorder, children and adolescents with a diagnosis of Autism Spectrum Disorder but without a diagnosis of Anxiety Disorders.Results: Results show the presence of clinical phenotype ASD+AD with specific features than AD group (p = 0,00003). A major functional impairment is reported for ASD+AD group compared the other groups. Finally, parents of the ASD+AD group reveal higher levels of PPD than AD (p = 0,005). Conclusions: Understanding clinical characteristics of anxiety disorder and the role of PPD could define individualized treatments and a better prognosis in children and adolescents with ASD and AD
Quantitative study of medical doctors’ professional identity formation: General picture and importance of experiences in the ‘community of practice’
Authors: Tagawa Masami
Published: April 2022

BackgroundProfessional identity formation (PIF), the development of professional values, actions, and aspirations, is the process of personal and professional development. PIF of medical doctors is now recognized as the goal of medical education and the construction of professional identity (PI) has been discussed. To evaluate medical trainees’ and doctors’ PI, a scale to evaluate overall professional development (developing scale, DS) and Kegan’s stage attributes specific scales (SASs) have been developed. Using these scales, this research aimed to reveal PI from young medical trainees to experienced doctors, and elucidate factors related to PIF.MethodsMedical students, residents, and medical doctors who have diverse clinical experiences working in Kagoshima University Hospital were asked to respond to a self-administered anonymous questionnaire and to list up to three important events and experiences that affected their present attitude as a medical doctor, in addition to answer items on demographic characteristics.Scores on the PIF scales were compared among respondent groups, and factors related to scale scores were analyzed. Listed experiences were categorized by topic themes and timing and the number of respondents listed in each category were analyzed by their scale scores and by estimated PI stage.ResultsMean DS scores of medical students, residents, and medical doctors were 68.8, 72.2, and 73.8, respectively, and scores were higher in medical doctors with longer clinical experience. Age for students’ DS and SAS-2 scores, and length of clinical experience for medical doctors’ DS, SAS-3, and SAS-h scores were significant factors.Respondents who were estimated to be at a higher stage of PI listed more professional related experiences. Respondents with high scores on each PIF scale reported more professional related experiences than lower scoring groups.ConclusionsQuantitative research indicated that PIF of medical doctors continued for decades after graduation, and the length of clinical experience might be an important factor for PIF. Professional and personal experiences were recognized as important by medical trainees and doctors, especially people at higher stages of PI. The experiences of medical trainees and doctors at different training phases showed a tendency to link to specific attributes.
Effect of different preparation conditions on the properties of nano-hydroxyapatite/bamboo fiber composite membrane
Authors: Liuyun Jiang , Jiang Zhihong , Ma Bingli , Ma Yingjun , Wen Yue , Zhang Na , Zhang Yan , Su Shengpei , Tang Xionggui , Hu Xiang
Published: April 2022

A novel nano-hydroxyapatite/bamboo fiber (n-HA/BF) composite membrane was obtained by a simple casting technique. The membrane forming mechanism and the effects of different forming membrane methods, drying methods and n-HA amounts on the properties of n-HA/BF composite membrane were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), contact angle, electromechanical universal tester, in vitro soaking in simulated body fluid (SBF) and in vitro cell culture experiment. The results demonstrated that the dispersity of n-HA nanoparticles in BF matix was not affected by the prepartion condition, however, the morphologies of membrane was determined by the different preparation conditions owing to different hydrogen bond shrinkage. Moreover, the hydrophilicity of the composite membrane was improved under the condition of the membrane formation in oven, freeze drying and high addition content of n-HA, and the mechanical properties of composite membrane depended on n-HA content. In vitro soaking behavior indicated that the degradability and bone-like apatite deposition could be controlled by different preparation conditions. And the cell proliferation experiment showed that the n-HA/BF composite membranes obtained under different preparation conditions were all non-toxic. The above results indicated that the casting technique could be used to prepare n-HA/BF composite membrane, and the properties of the composite membrane could be controlled by adopting different preparation conditions, which would have a great promising as guide bone tissue regeneration (GBR) membrane, and the study would provide a new application for BF in biomedical field.
Effects of the appearance care on psychosocial outcomes for breast cancer: a systematic review and meta-analysis
Authors: Zhu Mengyao , Sun Shihao , Zhang Yiheng , Chen Lili , He Haiyan , Chen Juanjuan , zhang Ni , Zhang Meifen
Published: April 2022

Purpose To synthesize the evidence for the immediate and short-term effects of appearance care on psychosocial outcomes in breast cancer patients in order to inform the design of future research and clinical practice.Methods A search of four databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science). The JBI Critical Appraisal Checklists were used by two reviewers to assess methodology quality. Subgroup analysis was conducted for the different time points measured after intervention.Results Seven studies were eligible for the meta-analysis, including two RCTs and five quasi-experimental studies, from 1994 to 2022. The type of intervention was mainly grouped-education, led by beauty specialists, and the dose and frequency varied. The quality of included studies was moderate to high. The results showed that appearance care had positive immediate effect on self-esteem (SMD = 0.63, 95% CI 0.37 to 0.89), anxiety (SMD = -0.46, 95% CI -0.60 to -0.31), and depression (SMD = -0.41, 95% CI -0.62 to -0.19), with short-term effects on anxiety (SMD = -0.42, 95% CI -0.54 to -0.34), depression (SMD = -0.41, 95% CI -0.55 to -0.26) and sexual function (SMD = 0.50, 95% CI 0.18 to 0.81).The effect of appearance care on body image and quality of life was uncertain.Conclusion Appearance care could be a promising intervention to improve self-esteem, anxiety, depression, and sexual function among patients with breast cancer. More high-quality RCTs are needed to validate these findings. Online appearance care programs and exploration of long-term effects should also be considered.
Construction of antibacterial nano-silver embedded bioactive hydrogel to repair infectious skin defects
Authors: Dong Qi , Zu Dan , Kong Lingqiang , Chen Sunfang , Yao Jun , Lin Jiawei , Lu Lei , Wu Bing , Fang Bin
Published: April 2022

Background: Hydrogels loaded with antimicrobial agents have been widely developed for the treatment of infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of a AgNP-impregnated PADM (AgNPs-PADM) hydrogel in the treatment of infected wound defects. Methods: A AgNPs-PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of PADM and AgNPs-PADM hydrogels to treat infected wounds in animals. Results: The PADM and AgNPs-PADM hydrogels were pH-sensitive, which made them flow dynamically under acidic conditions and become solid under neutral conditions. They also demonstrated porous network structures, satisfactory moisture retention, and slow degradation rates. Meanwhile, the AgNPs-PADM hydrogel showed a slow and sustained release of AgNPs for at least seven days without changing the size of the particles, so that they could exhibit adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNPs-PADM hydrogel successfully promoted the angiogenesis and wound healing of infected skin defects in vivo. Conclusions: A AgNPs-PADM hydrogel is a promising bioderived antibacterial material for clinical infected wound dressings.
The accuracy of first metatarsophalangeal joint palpation guided injections. An arthrography cadaveric study
Authors: Reilly Ian Neil , Naemi Roozbeh , Chockalingam Nachiappan
Published: April 2022

BackgroundInjectable glucocorticoids are widely used in the management of foot pathology, in particular for the treatment of osteoarthritis of the great toe - hallux limitus/rigidus. Injections can be performed using anatomical (blind) guided methods or performed with needle placement aided by the use diagnostic imaging with ultrasound or fluoroscopy, with or without the use of contrast media.AimPalpation and image guided injection techniques have been studied in other joints of the body but less so for the first metatarsophalangeal joint of the foot, where palpation guidance is commonly performed. The aim of this study was to investigate the injection accuracy of palpation guided injections of the first metatarsophalangeal joint in six cadaveric feet using radio-opaque contrast media.MethodsThe injection equipment consisted of a 2.5ml Luer lock syringe and a 23-gauge needle used to inject iohexol (Omnipaque 300) into the first metatarsophalangeal joint in six cadaveric specimens. The needle was placed into the joint space by a single practitioner using palpation guidance. The contrast media was injected under live (cine) view without further movement or ingress of the needle. The injectate was considered accurate if the media coated the inside of the synovial membrane and/or outlined the joint shape.FindingsFailure of technique was seen in one of six feet, and extravasation of contrast media beyond the joint margins noted in three out of six feet.ConclusionsFurther study on a large sample of live subjects using a variance of technique is required to expand the confidence of these findings but the high failure rate calls into question the confidence of palpation guided techniques for injection of the first metatarsophalangeal joint.
Patient dissatisfaction associated with physician-patient linguistic discordance in California clinics: An analytical cross-sectional study
Authors: Fernández-Ortega Miguel Ángel , Juárez-Flores Arturo , Olaiz-Fernández Gustavo Adolfo , Muñiz-Salinas Daniel Alejandro ,   AB1045 Law Analysis Group, Rodríguez-Mendoza Omar
Published: April 2022

Background: Patient satisfaction is considered as a product of two psychological processes, a cognitive one, including expectations and perceptions, and an emotional one resulting from the congruence between expectation and subjective perception of the user. The objective was to identify the factors associated with the level of perceived satisfaction in patients treated in 36 nonprofit health clinics that offer comprehensive health care services in four counties in the state of California, United States.Methods: Cross-sectional analytical study in 14 clinics in four California counties. It consisted of the application of a 30-question questionnaire to determine the degree of patient satisfaction with the clinic. The factorial composition of the quality of care and clinic quality components was analyzed and two factors with an Eigen value greater than 1 were obtained.Results: A total of 846 responses were registered. Factor analysis identified two underlying dimensions: Physician Attitude and Empathy. It was found that the discordance in language between the physician and the patient generates a difference in the perception of satisfaction. Patients who prefer to speak English have better satisfaction than those who speak Spanish. Spanish speakers who do not have a translator have lower satisfaction than those who do. (p<0,01)Conclusions: The most important sociodemographic cofactor was language. Satisfaction decreased in Spanish-speaking patients who were not proficient in the use of English since they expressed fewer comments and doubts. Other associated cofactors were: age, sex, schooling, and occupation.
Healthcare provider and patient perspectives on access to and management of atrial fibrillation in the Northern Province, Sri Lanka: A rapid evaluation of barriers and facilitators to care
Authors: Sheron Vethanayagam Antony , Shanmugathas Shivany , Gooden Tiffany E , Guruparan Mahesan , Kumarendran Balachandran , Lip Gregory Y.H. , Manaseki-Holland Semira , Nirantharakumar Krishnarajah , Shribavan Kaneshamoorthy , Subaschandren Kumaran , Haniffa Rashan , Surenthirakumaran Rajendra , Thomas G. Neil , Uruthirakumar Powsiga , Greenfield Sheila , Lane Deirdre A. , Beane Abi
Published: April 2022

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 60 million people worldwide. Limited evidence on AF management exists from low- and middle-income countries and none from Sri Lanka. We aimed to investigate the existing AF care pathway and patients’ perception on AF management to identify barriers and enablers for optimal AF care in Northern Province, Sri Lanka.Methods: A rapid evaluation was undertaken with use of qualitative methods. Local healthcare providers (HCPs) mapped the intended pathway of care for AF patients which was then explored and annotated through 12 iterative sessions with additional HCPs. Topics of inefficiencies identified from the finalised map were used to guide focus group discussions (FGDs) with AF patients. AF patients who were attending the anticoagulation clinic at the only tertiary hospital in Northern Province were recruited and invited to participate using purposive sampling. The topic guide was developed in collaboration with local clinicians and qualitative experts. FGDs were conducted in the native Tamil language and all sessions were recorded, transcribed verbatim and thematically analysed using a deductive approach. Results: The mapped pathway revealed inefficiencies in referral, diagnosis and ongoing management. These were explored through three FGDs conducted with 25 AF patients aged 25 to 70 years. Two key themes that contributed to and resulted in delays in accessing care and ongoing management were health seeking behaviours and atomistic healthcare structures. Four cross-cutting sub-themes identified were decision making, paternalistic approach to care, cost impacts and lifestyle impacts. These are discussed across 10 unique categories with consideration of the local context. Conclusions: Strengthening primary healthcare services, improving public health literacy regarding AF and building patient autonomy whilst understanding the importance of their daily life and family involvement may be advantageous in tackling the inefficiencies in the current AF care pathway in Sri Lanka.
A Scoping Review of Gay Family Networks: HIV Preventative Implications for Black MSM
Authors: Smith Martez Dexter Ray , Leblanc Natalie M , McMahon James M , Nelson LaRon E
Published: April 2022

Gay family networks (GFNs) are social supports that have been shown to influence protective and risk factors for HIV transmission among Black men who have sex with men (MSM). The purpose of this scoping review is to provide a conceptual overview and mapping of HIV-related prevention research with Black MSM belonging to GFNs. We identified 352 articles for title and abstract review; of these, 28 were included in the final analysis. Our review includes a discussion of identified themes including, social network characteristics of GFNs, psychosocial factors affecting vulnerability for HIV transmission, and HIV prevention interventions. Research suggests the potential to bolster GFN assets to promote protective factors against HIV acquisition for Black MSM. The few HIV prevention interventions involving GFNs show promise, but only quasi-experimental studies have been completed to date. Identifying and strengthening assets among Black MSM’s GFNs, as well as utilizing experimental study designs should be a priority for future research.
Effects of perfluoroalkyl substances (PFAS) and benzo[a]pyrene (BaP) co-exposure on phase I biotransformation in rainbow trout (Oncorhynchus mykiss)
Authors: Solan Megan E. , Franco Marco E. , Lavado Ramon
Published: April 2022

The presence of perfluoroalkyl substances (PFAS) in the environment, especially in aquatic ecosystems, continues to be a significant concern for human and environmental health. Previous studies have suggested that several PFAS do not undergo biotransformation due to their chemical stability, yet perfluorooctanesulfonic acid (PFOS)- and perfluorooctanoic acid (PFOA)-exposed organisms have presented altered activity of important biotransformation pathways. Given the fundamental role of biotransformation in biological organisms and the significant distribution of PFAS in aquatic environments, the present study investigated the influence of PFOA and PFOS on phase I biotransformation enzymes in vitro using the rainbow trout liver RTL-W1 cell line and in vivo using juvenile rainbow trout. Cells and fish were exposed and co-exposed to environmentally relevant concentrations of PFOA, PFOS, and benzo[a]pyrene (BaP), for 72 h and 10 days, respectively, prior to measurements of cytotoxicity and biotransformation ability through measurements of CYP1A1-, CYP1A2- and CYP3A4-like activities. Our results indicate that exposure to PFAS-BaP binary mixtures altered CYP1A-like activity in vivo; however, those alterations were not observed in vitro. Similarly, while BaP did not significantly induce CYP3A4, exposure to the PFAS led to significantly lower enzymatic activity relative to basal levels. These observations may have implications for organisms simultaneously exposed to PFAS and other environmental pollutants for which biotransformation is necessary, especially in detoxification mechanisms. Furthermore, the interference with biotransformation pathways could potentially increase adverse outcomes, compromising the stability of fish populations inhabiting PFOA- and PFOS-polluted environments.
The Virgin and Child with the Infant St. John the Baptist by Sandro Botticelli (1445-1510): does the child have Pompe Disease?
Authors: de Campos Deivis
Published: April 2022

Purpose: Current literature describes that art can be used to teach observation skills in medical students. In this way, many medical schools have developed formal observational training on works of art to improve their students' visual diagnostic skills. In this context, this description presents unprecedented evidence that Sandro Botticelli (1445-1510) may have represented a rare neuromuscular disorder, known as Pompe Disease (accumulation of lysosomal glycogen primarily in the heart, skeletal muscles, and the nervous system) in one of the characters that make up Virgin and Child with the Infant St. John the Baptist (1490-1500).Methods: Observational study.Results: The painting reveals that the Infant Jesus has facial features consistent with some of the main clinical manifestations of Pompe Disease (poor head control, facial weakness with open mouth posture, tongue protrusion and eyelid ptosis). Conclusion: These results may indicate that Botticelli in 1500 may have made the first pictorial representation of Pompe's Disease that was only described in the medical literature in 1932. Furthermore, this description demonstrates the importance of the medico-artistic field for the study of any disease during the Renaissance period, which will be essential for the learning process of visual diagnostic.
Comparative efficacy and tolerability of target agents and immune checkpoint inhibitors in combination with chemotherapy as First-line treatment for advanced gastric cancer: A Bayesian network meta-analysis
Authors: Liu Shu , Wong Heung Yan , Xie Li , Kim Yoojin , Shu Danhua , Zheng Beishi , Liu Naxin , Xing Chungen , Chen Xiaolei , Dong Qiantong
Published: April 2022

Background
The use of target agents and immune checkpoint inhibitors have changed the treatment landscape for AGC in the first-line setting. However, the crosswise comparison between each regimen is rare. Therefore, we estimated the efficacy and safety of targeted therapy or immunotherapy with chemotherapy in AGC patients as the first-line treatment;
Method
Included studies were divided into “unselected” or “selected” group according to whether the patients were selected by a certain pathological expression. We conducted a Bayesian network meta-analysis for all regimens in both groups;
Results
In unselected group, no regimen showed significant improvements in overall survival (OS) and progression free survival (PFS), while pembrolizumab and nivolumab combined with chemotherapy were ranked first and second respectively without an obvious safety difference. In selected group, zolbetuximab plus chemo-therapy significantly prolonged OS (HR 0.53, 95%CI 0.31–0.89) and PFS (HR 0.45, 95%CI 0.23–0.89). The top three regimens were zolbetuximab-chemotherapy, tratuzumab plus pertuzumab-chemotherapy and nivolumab-chemotherapy respectively, with no significant safety risk.
Conclusion
For average patients, immune checkpoint inhibitor PD-1 plus chemotherapy will be the promising regimen. For patients with overexpression of HER-2 or CLDN18.2, dual HER-2 targeting strategy or zolbetuximab combined with chemotherapy comes with greater survival benefits.
Adaptive MHC-E restricted tissue-resident NK cells are associated with persistent low antigen load in alveolar macrophages after SARS-CoV-2 infection
Authors: HUOT Nicolas , Planchais Cyril , Contreras Vanessa , Jacquelin Beatrice , PETITDEMANGE Caroline , Lazzerini Marie , ROSENBAUM Pierre , Rey Félix , Reeves R. Keith , Grand Roger Le , Mouquet Hugo , Müller-Trutwin Michaela
Published: April 2022

Natural killer (NK) cells are innate lymphocytes with potent activity against a wide range of viruses. In SARS-CoV-2 infection, NK cell activity might be of particular importance within lung tissues. Here, we investigated whether NK cells with activity against Spike+ cells are induced during SARS-CoV-2 infection and have a role in modulating viral persistence beyond primary clearance from nasopharyngeal and tracheal tissues. We performed an integrated analysis of NK cells and macrophages in blood and bronchoalveolar lavage fluids (BALF) of COVID-19 convalescent non-human primates in comparison to uninfected control animals. SARS-CoV-2 protein expression was detected for at least 9–18 months post-infection in alveolar macrophages. Convalescent animals segregated into two groups based on cellular phenotypes and viral persistence profiles in BALF. The animals with lower persistent antigen displayed macrophages with a regulatory phenotype and enhanced MHC-E restricted NK cell activity toward cells presenting peptides derived from the SARS-CoV-2 Spike protein leader sequence, while NK cell activity from the other convalescent animals, control animals and healthy humans were strongly inhibited by these Spike peptides. The adaptive NK cell activity was not detected in blood but in tissue-resident NK cells, and cross-reacted against MERS-CoV and SARS-CoV Spike-derived peptides.
Perinatal Characteristics and Neonatal Outcomes of Singletons and Twins in Chinese Very Preterm Birth Infants: A Cohort Study
Authors: Yang Min , Fang Lingyu , Wang Yanchen , Li Xiaoying , Cao Yun , Sun Jianhua , Ting Joseph , Chen Xiafang , Fan Xiaobo , Dai Jiale , Tong Xiaomei , Chen Dongmei , Wang Jimei
Published: April 2022

Background: The prevalence of preterm birth has been raising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. Methods: The study population comprised all infants born before 32 weeks in Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Results: During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weight of 1333.70g and 1294.63g, respectively. Twins were significantly more likely to be delivered by cesarean section (p<0.01), to have antenatal steroid usage (p=0.048), to have received assisted reproductive technology (ART) (p<0.01), and have higher prevalence of maternal diabetes (p<0.01) and more were inborn (p<0.01) compared with singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, primigravida compared to singletons (all p<0.01). After adjusting for the potential confounders, twins had higher mortality (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10-1.49), short term composite outcome (AOR 1.28, 95% CI 1.09-1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12-1.50), bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01-1.21), surfactant usage (AOR 1.22, 95% CI 1.05-1.41) and prolonged hospital stay (adjusted mean ratio 1.03, 95% CI 1.00-1.06), compared to the singletons. Conclusion: Our work suggest that twins have a greater risk of mortality, higher incidence of RDS and BPD, more surfactant usage, and longer NICU stay compared with singletons among VPIs in China.
Intramuscular delivery of formulated RNA encoding six linked single-domain antibodies is highly protective for exposures to three Botulinum neurotoxin serotypes
Authors: Mukherjee Jean , Ondeck Celinia A. , Tremblay Jacqueline M. , Archer Jacob , Debatis Michelle , Foss Alexa , Awata Junya , Erasmus Jesse H. , McNutt Patrick M. , Shoemaker Charles B.
Published: April 2022

Single domain antibodies (sdAbs) have substantial biophysical advantages over conventional antibodies and are increasingly being employed as components of immunotherapeutic agents. One particularly favorable property is the ability to link different sdAbs into heteromultimers. This feature allows production of single molecules capable of simultaneously targeting more than one antigen. In particular, cooperative binding of multiple linked sdAbs to non-overlapping epitopes on the same target can produce synergistic improvements in target affinity, variant specificity, and in vivo potencies. Here we seek to test the option of increased component sdAbs in these heteromultimers by testing different sdAb heterohexamers in which each of the six camelid sdAb components (VHHs) can neutralize one of three different Botulinum neurotoxin (BoNT) serotypes, A, B or E. Each heterohexamer bound all three targeted BoNT serotypes and protected mice from at least 100 MIPLD50 of each serotype. To test the potential of mRNA therapeutics encoding long sdAb heteromultimers, one heterohexamer was encoded as replicating RNA (repRNA), formulated with a cationic nanocarrier, and delivered to mice via intramuscular injection. Heterohexamer antitoxin serum expression levels were easily detected by 8 hours post-treatment, peaked at 5-10 nM around two days, and persisted for more than three days. Mice treated with the formulated repRNA one day post-treatment survived challenge with 100 MIPLD50 of each toxin serotype, demonstrating the function of all six component VHHs. Use of long sdAb multimers, administered as proteins or repRNA, offer the potential for substantially improved versatility in the development of antibody-based therapeutics.
Functional improvement and satisfaction with a wearable hip exoskeleton in community- living adults
Authors: Kim Jihye , Chun Hyelim , Lee Su-Hyun , Lee Hwang-Jae , Kim Yun-Hee
Published: April 2022

Background: Demand for wearable devices and supportive technology is growing as these devices have the potential to enhance physical function and quality of life in users. The purpose of this study was to investigate usability and satisfaction after performing functional and gait exercise with a wearable hip exoskeleton in community-living adults. Methods: Two-hundred and twenty-five adults (mean age 67.52 ±10.99) residing in the local community participated in this study. All participants (middle-aged group, n=75; old-aged group, n=150) performed 40-minutes of exercise once with a wearable hip exoskeleton in various environments. The EX1 (Samsung Electronics Co., Ltd., Suwon, Republic of Korea), which functions as a wearable hip exoskeleton, was used. Physical function was assessed before and after exercise with the EX1 using the 10-meter walking test (10MWT), four square step test (FSST), timed up and go test (TUG), 6-minute walking test (6MWT), and short physical performance battery (SPPB). In addition, after completing exercise with the EX1, the usability and satisfaction questionnaires were evaluated.Results: Gait speed, TUG, and FSST showed statistically significant improvements after exercise with the EX1 in both groups (p<0.05). In 6MWT, a significant increase was observed in the middle-aged group (p<0.05) but not in the old-aged group. In SPPB, there was a significant improvement in the old-aged group (p<0.05) but not in the middle-aged group. On the other hand, positive results in usability and satisfaction were noticed in both groups. In preference between resistance and assist mode of the EX1, the old-aged group preferred the assist mode and the middle-aged group preferred the resistance mode.Conclusion: These results demonstrate that a single session of exercise with the EX1 was effective in improving physical performance of both middle- and old-aged adults, with positive feedback from most of the participants.Trial registration: Clinical trials registration information: ClinicalTrials.gov Identifier: NCT05106881 (03/11/2021).
‘Tropicalization’ of megafauna community in a South Atlantic warming hot spot: evidences from demersal fisheries off Brazil
Authors: PEREZ JOSE ANGEL , Sant'Ana Rodrigo
Published: April 2022

The Southwest Atlantic Ocean comprises a major ‘marine warming hotspot’ subject to significant marine ecosystem changes. Among them, a process of ‘tropicalization’ of demersal fauna has been proposed, as determined by the increasing influence of the warm Brazil Current, gradually expanding towards higher latitudes. We identified signals of fauna ‘tropicalization’ analysing commercial catches of 29,021 multispecies demersal fishing operations conducted in the Brazilian Meridional Margin between 2000 and 2019. These signals included changes in species catch composition and patterns of biomass gains and losses of species with affinities for warm- and cold-waters, respectively. In addition, annual variability of the Mean Temperature of the Catches increased sharply from 2013 onwards at a rate of 0.41°C yr− 1, explained by increasing sea bottom temperatures (with 0 and 1-year time-lag) and the transport volumes of the Brazil Current (4-year time-lag).
Relationship between Helicobacter pylori infection and white matter lesions in patients with migraine
Authors: Öcal Serkan , Öcal Ruhsen , Suna Nuretdin
Published: April 2022

Background/aim: White matter lesions (WMLs) are more frequently observed in migraine patients than in the average population. Associations between Helicobacter pylori (H. pylori) infection and different extraintestinal pathologies have been identified. Here, we aimed to examine the effect of H. pylori infection on WML in patients diagnosed with migraine.Materials and methods: A retrospective study was conducted with 526 subjects with a diagnosis of migraine. Hyperintensity of WML had been previously evaluated in these patients with brain magnetic resonance imaging (MRI) examinations. Previous endoscopic gastric biopsy histopathological examination of the same patients and reports on H. pylori findings were recorded. The demographic characteristics of the patients, such as age, drugs, and gender, were recorded. Statistical evaluation was made.Results: Evaluation was made among 526 migraine patients who met the inclusion criteria, comprising 397 (75.5%) females and 129 (24.5%) males with a mean age of 45.57 ± 13.46 years (range, 18-69 years). Of the 211 (40.1%) subjects who were negative for H. pylori, WML was not detected in 140 (26.6%) and was detected in 71 (13.5%) on brain MRI. WML was not detected in 137 (26.0%) of 315 (59.9%) subjects who were positive for H. pylori and was detected in 178 (33.8%) on brain MRI (p <0.05). Subjects who are H. pylori-positive migraine were observed at a 2.5-fold higher incidence of brain MRI WML (odds ratio: 2.562, 95% CI 1.784-3.680). WML was found to be more significant in patients with hypertension and migraine than those without (p <0.001). Conclusion: It was concluded that H. pylori infection, a chronic infection, can be considered a risk factor in developing WML in subjects with migraine.
Universal structures for embedded integral control in biological adaptation
Authors: Araujo Robyn , Liotta Lance
Published: April 2022

At the molecular level, the evolution of life is driven by the generation and diversification of adaptation mechanisms. A universal description of adaptation-capable chemical reaction network (CRN) structures has remained elusive until now, since currently-known criteria for adaptation apply only to a tiny subset of possible CRNs. While adaptation is known to require some form of embedded integral control, current approaches can only identify an internal integral structure in simple special cases. Here we identify the definitive structural requirements that characterize all adaptation-capable collections of interacting molecules, however large or complex. We show that these network structures implement a form of integral control in which multiple independent integrals can collaborate to confer the capacity for adaptation on specific molecules. We present a universal method to test for adaptation capacity, and for detecting the adaptation-conferring integrals, in any CRN. Using this new approach, we demonstrate the existence of embedded integrals in a variety of biologically important CRNs that have eluded previous methods, and for which adaptation has been observed experimentally. This definitive picture of biological adaptation at the level of intermolecular interactions represents a blueprint for adaptation-capable signalling networks across all domains of life, and for the design of synthetic biosystems.
Functional stemness-related genes revealed by single-cell profiling of naïve and stimulated human CD34 + cells from CB and mPB
Authors: Dong Guoyi , Xu Xiaojing , Li Yue , Ouyang Wenjie , Zhao Weihua , Gu Ying , Li Jie , Liu Tianbin , Zeng Xinru , Zou Huilin , Wang Shuguang , Liu Sixi , Sun Hai-Xi , Liu Chao
Published: April 2022

Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long-time ex vivo culture. However, the underlying mechanisms of the stemness differences because of the cell sources and the culture stimulation are not fully understood. Here, we applied single-cell RNA-seq (scRNA-seq) to analyze the naïve and stimulated human CD34+ cells from cord blood (CB) and (mPB). We collected over 16,000 single-cell data to construct a comprehensive trajectory inference map and characterized the HSC population on the hierarchy top, which is under quiescent state. Then we compared HSCs in CB to those in mPB and HSCs of naïve samples to those of cultured samples, and identified stemness-related genes (SRGs) associated with culture time (CT-SRGs) and cell source (CS-SRGs), respectively. Interestingly, CT-SRGs and CS-SRGs share genes enriched in the signaling pathways such as mRNA catabolic process, Translational initiation, Ribonucleoprotein complex biogenesis and Cotranslational protein targeting to membrane, suggesting dynamic protein translation and processing may be a common requirement for stemness maintenance. Meanwhile, CT-SRGs are enriched in pathways involved in glucocorticoid and corticosteroid response that affect HSCs homing and engraftment. In contrast, CS-SRGs specifically contain genes related purine and ATP metabolic process which is important to initiate hematopoiesis. Finally, we presented an application through a small-scale drug screening using Connectivity Map (CMap) against CT-SRGs and found a small molecule cucurbitacin I, targeting STAT3/JAK2, can efficiently expand HSCs ex vivo while maintaining its stemness. These results indicate SRGs revealed by scRNA-seq can provide helpful insights to understand the stemness differences under diverse circumstances, and CT-SRGs can be a valuable database to identify candidates enhancing functional HSC expansion during ex vivo culture.