bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rhythm of Many: Biological Rhythms in the Marine Environment, From Macro-Scale Planktonic Ecosystems to Micro-Scale Holobionts
Authors: Hewitt Olivia H. , Shaikh Hisham M.
Published: November 2021

Daily environmental oscillations that follow Earth’s rotation around the Sun set a metronome for life, under which all organisms have evolved. Entrainment to these cues allow organisms to rhythmically set the pace of their own endogenous biological clocks with which the timings of diverse cellular activities are coordinated. In recent years, our knowledge of biological rhythms has extended across all domains of life. This includes both free-living and symbiotic life forms. With the insurgence of metagenomic sequencing tools, the field of holobiont chronobiomics (encompassing chronobiology of host and its associated microbiota) has recently opened and gained significant traction. Here, we review current knowledge regarding free-living prokaryote rhythmic regulation before exploring active areas of research that consider the coordinated rhythmic regulatory activities of hosts and their symbionts as a single entity, i.e., holobiont, and even the extent to which rhythmicity influences virus–host interactions. We describe rhythmicity within non-photosynthetic bacteria, cyanobacteria, and archaea, before investigating the effect of light, and, thus, diel cycle, on viral life cycles and host–virus population dynamics in marine planktonic ecosystems along with their potential to influence host cyanobacterial circadian clocks. We then explore current evidence outlining coordinated rhythmic regulation within marine holobionts and the significance of this for holobiont health and adaptive fitness that, in turn, optimizes their success within their local environments. Finally, we assess the critical role of circadian regulation for holobiont innate immunity and metabolism within well-studied non-marine mammalian systems, and, thus, assess how this can guide us within understudied marine chronobiomics research.
Inflammatory Biomarkers Are Inaccurate Indicators of Bacterial Infection on Admission in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease—A Systematic Review and Diagnostic Accuracy Network Meta-Analysis
Authors: Pázmány Piroska , Soós Alexandra , Hegyi Péter , Dohos Dóra , Kiss Szabolcs , Szakács Zsolt , Párniczky Andrea , Garami András , Péterfi Zoltán , Molnár Zsolt
Published: November 2021

Introduction: The value of inflammatory biomarkers in the diagnosis of bacterial infection induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is currently unclear. Our objective was to investigate the diagnostic accuracy of on-admission inflammatory biomarkers in differentiating bacterial origin in AECOPD.

Methods: Systematic literature search was performed to include cross-sectional studies on AECOPD patients with microbiological culture results as gold standard, and at least one on-admission inflammatory biomarker determined from serum: C-reactive protein (CRP), procalcitonin (PCT), neutrophil/lymphocyte ratio, eosinophil percentage, CD64index; or sputum: neutrophil elastase, tumor necrosis factor alfa, interleukin-1-beta (IL-1b), interleukin-8, sputum color, as index tests. We ranked index tests by superiority indices in a network meta-analysis and also calculated pooled sensitivity and specificity.

Results: Altogether, 21 eligible articles reported data on 2,608 AECOPD patients (44% bacterial). Out of the 14 index tests, sputum IL-1b showed the highest diagnostic performance with a pooled sensitivity of 74% (CI: 26–97%) and specificity of 65% (CI: 19–93%). Pooled sensitivity for CRP and PCT were: 67% (CI: 54–77%) and 54% (CI: 39–69%); specificity 62% (CI: 52–71%) and 71% (CI: 59–79%), respectively.

Conclusion: Admission inflammatory biomarkers are inaccurate indicators of bacterial infection in AECOPD.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#myprospero, identifier: 42020161301.
Distribution of White-to-White Corneal Diameter and Anterior Chamber Depth in Chinese Myopic Patients
Authors: Xu Guihua , Wu Guanrong , Du Zijing , Zhu Shanqing , Guo Yunxiang , Yu Honghua , Hu Yijun
Published: November 2021

Purpose: To investigate the distribution of white-to-white (WTW) corneal diameter and anterior chamber depth (ACD) in Chinese myopia patients.

Methods: This was a cross-sectional observational study conducted at five ophthalmic centers. Anterior segment biometry was performed in 7,893 eyes of the 7,893 myopic patients using Pentacam, and the WTW and ACD were recorded. The distribution patterns of WTW and ACD were evaluated and the correlation between WTW and ACD was analyzed statistically.

Results: There were 4416 (55.95%) males and 3477 (44.05%) females. The age of the study population was 25.14 ± 5.41 years. Distribution of WTW was slightly positively skewed (Skewness = 0.0076, Kurtosis = 0.3944, KS P = 0.020) with a mean of 11.65 ± 0.38 mm and a 95% normal range of 10.91–12.39 mm. A significant difference in WTW was found among different myopia groups (P < 0.001). The ACD was normally distributed (Skewness = 0.899, Kurtosis = 0.027, KS P = 0.086). The mean ACD was 3.25 ± 0.26 mm and the 95% normal range of was 2.74–3.75 mm. A significant difference in ACD was also found among different myopia groups (P = 0.030). There was a significant correlation between WTW and ACD (r = 0.460, P < 0.001).

Conclusions: In our study, 95% of the Chinese myopic patients had a WTW within 10.91–12.39 mm and an ACD within 2.74–3.75 mm. ACD and WTW were significantly different among different myopia, gender and age groups. WTW was positively correlated with ACD.
Urine Output Is Associated With In-hospital Mortality in Intensive Care Patients With Septic Shock: A Propensity Score Matching Analysis
Authors: Hu Tianyang , Qiao Zhao , Mei Ying
Published: November 2021

Background: The relationship between urine output (UO) and in-hospital mortality in intensive care patients with septic shock is currently inconclusive.

Methods: The baseline data, UO, and in-hospital prognosis of intensive care patients with septic shock were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. By drawing receiver operating characteristic (ROC) curves and comparing the areas under the ROC curves (AUC) to determine the predictive value of UO for in-hospital mortality, and by drawing the Kaplan-Meier curves to compare the difference in in-hospital mortality between different groups of UO.

Results: Before and after the propensity score matching (PSM) analysis, UO was always a risk factor for in-hospital mortality in patients with septic shock. The AUC of UO was comparable to the Sequential Organ Failure Assessment (SOFA) scoring system, while the AUC of combining UO and SOFA was greater than that of SOFA. The median survival time of the high-UO group (UO > 0.39 ml/kg/h, before PSM; UO > 0.38 ml/kg/h, after PSM) was longer than that of the low-UO group. Compared with the high-UO group, the hazard ratios (HR) of the low-UO group were 2.6857 (before PSM) and 1.7879 (after PSM).

Conclusions: UO is an independent risk factor for septic shock. Low levels of UO significantly increase the in-hospital mortality of intensive care patients with septic shock. The predictive value of UO is comparable to the SOFA scoring system, and the combined predictive value of the two surpasses SOFA alone.
Discrimination of SARS-CoV-2 Infections From Other Viral Respiratory Infections by Scent Detection Dogs
Authors: ten Hagen Nele Alexandra , Twele Friederike , Meller Sebastian , Jendrny Paula , Schulz Claudia , von Köckritz-Blickwede Maren , Osterhaus Ab , Ebbers Hans , Pink Isabell , Welte Tobias , Manns Michael Peter , Illig Thomas , Fathi Anahita , Addo Marylyn Martina , Nitsche Andreas , Puyskens Andreas , Michel Janine , Krause Eva , Ehmann Rosina , von Brunn Albrecht , Ernst Christiane , Zwirglmaier Katrin , Wölfel Roman , Nau Alexandra , Philipp Eva , Engels Michael , Schalke Esther , Volk Holger Andreas
Published: November 2021

Background: Testing of possibly infected individuals remains cornerstone of containing the spread of SARS-CoV-2. Detection dogs could contribute to mass screening. Previous research demonstrated canines' ability to detect SARS-CoV-2-infections but has not investigated if dogs can differentiate between COVID-19 and other virus infections.

Methods: Twelve dogs were trained to detect SARS-CoV-2 positive samples. Three test scenarios were performed to evaluate their ability to discriminate SARS-CoV-2-infections from viral infections of a different aetiology. Naso- and oropharyngeal swab samples from individuals and samples from cell culture both infected with one of 15 viruses that may cause COVID-19-like symptoms were presented as distractors in a randomised, double-blind study. Dogs were either trained with SARS-CoV-2 positive saliva samples (test scenario I and II) or with supernatant from cell cultures (test scenario III).

Results: When using swab samples from individuals infected with viruses other than SARS-CoV-2 as distractors (test scenario I), dogs detected swab samples from SARS-CoV-2-infected individuals with a mean diagnostic sensitivity of 73.8% (95% CI: 66.0–81.7%) and a specificity of 95.1% (95% CI: 92.6–97.7%). In test scenario II and III cell culture supernatant from cells infected with SARS-CoV-2, cells infected with other coronaviruses and non-infected cells were presented. Dogs achieved mean diagnostic sensitivities of 61.2% (95% CI: 50.7–71.6%, test scenario II) and 75.8% (95% CI: 53.0–98.5%, test scenario III), respectively. The diagnostic specificities were 90.9% (95% CI: 87.3–94.6%, test scenario II) and 90.2% (95% CI: 81.1–99.4%, test scenario III), respectively.

Conclusion: In all three test scenarios the mean specificities were above 90% which indicates that dogs can distinguish SARS-CoV-2-infections from other viral infections. However, compared to earlier studies our scent dogs achieved lower diagnostic sensitivities. To deploy COVID-19 detection dogs as a reliable screening method it is therefore mandatory to include a variety of samples from different viral respiratory tract infections in dog training to ensure a successful discrimination process.
The Application of a SaCoVLMTM Visual Intubation Laryngeal Mask for the Management of Difficult Airways in Morbidly Obese Patients: Case Report
Authors: Sun Yongtao , Huang Linlin , Xu Lingling , Zhang Min , Guo Yongle , Wang Yuelan
Published: November 2021

We report insertion of the SaCoVLMTM in three awake morbidly obese patients (BMI 46. 7–52.1 kg/m2). The patients were given intravenous atropine and midazolam injections after entering the operating room and then inhaled an anesthetic with 2% lidocaine atomization. After SaCoVLMTM insertion while patients were awake, when the vocal cords were visualized, controlled anesthetic induction commenced with spontaneous ventilation. The entire anesthesia induction and intubation process was completed under visualization, and no adverse events such as hypoxemia occurred. No patient had an unpleasant recall of the procedure. We conclude that the SaCoVLMTM is easy to use, well tolerated and suitable for awake orotracheal intubation in patients with known difficult airways.
Effects of Exercise Intervention on Peripheral Skeletal Muscle in Stable Patients With COPD: A Systematic Review and Meta-Analysis
Authors: Li Peijun , Li Jian , Wang Yingqi , Xia Jun , Liu Xiaodan
Published: November 2021

Objectives: Peripheral skeletal muscle dysfunction is an important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) that can be counteracted by exercise training. This study aimed to review the effect of three major exercise training modalities, which are used in pulmonary rehabilitation to improve on skeletal muscle mass, function, and exercise capacity in COPD.

Methods: PubMed, Embase, EBSCO, Web of Science, and the PEDro database were searched on April 25, 2020. Only randomized controlled studies published in English evaluating the effects of exercise interventions on peripheral skeletal muscle mass, strength, and exercise capacity in stable COPD patients were included. The quality of included studies was evaluated using the PEDro scale. The mean difference (MD) or the standardized mean difference (SMD) with 95% CI was calculated to summarize the results. Subgroup meta-analysis was used to investigate the effects of different exercise training modalities and different outcome measures. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to rate evidence quality.

Results: A total of 30 randomized controlled trials involving 1,317 participants were included. Data from trials investigating endurance exercise (EE), resistance exercise (RE), and combined aerobic and resistance exercise (CE) were pooled into a meta-analysis, and the differences compared with the non-exercising COPD control were improvement in the muscle strength and exercise capacity in stable COPD patients. Subgroup meta-analysis for different exercise training modalities showed that RE significantly improved muscle strength (SMD = 0.6, 95% CI 0.35–0.84, I2 = 61%), EE and CE significantly increased VO2peak (EE: MD = 3.5, 95% CI 1.1–5.91, I2 = 92%; CE: MD = 1.66, 95% CI 0.22–3.1, I2 = 1%). Subgroup meta-analysis for different outcome measures showed that only isotonic strength was improved after exercise interventions (SMD = 0.89, 95% CI 0.51–1.26, I2 = 71%).

Conclusion: Moderate evidence supports that exercise training in stable COPD patients has meaningful and beneficial effects on peripheral skeletal muscle strength and exercise capacity. Peripheral skeletal muscle shows a higher response to RE, and the isotonic test is relatively sensitive in reflecting muscle strength changes. The proportion of aerobic and resistance exercise components in a combined exercise program still needs exploration.

Systematic Review Registration: The review was registered with the PROSPERO: (The website is https://www.crd.york.ac.uk/PROSPERO/, and the ID is CRD42020164868).
The Experiences of Functioning and Health of Patients With Primary Sjögren's Syndrome: A Multicenter Qualitative European Study
Authors: Unger Julia , Mattsson Malin , Drăgoi Răzvan G. , Avram Claudiu , Boström Carina , Buttgereit Frank , Lackner Angelika , Witte Torsten , Raffeiner Bernd , Peichl Peter , Durechova Martina , Hermann Josef , Stamm Tanja A. , Dejaco Christian
Published: November 2021

Objective:To identify a spectrum of perspectives on functioning and health of patients with primary Sjögren's syndrome (pSS) from the five European countries in order to reveal commonalities and insights in their experiences.

Methods:A multicenter focus group study on the patients with pSS about their perspectives of functioning and health was performed. Focus groups were chaired by trained moderators based on an interview guide, audiotaped, and transcribed. After conducting a meaning condensation analysis of each focus group, we subsequently combined the extracted concepts from each country and mapped them to the International Classification of Functioning, Disability and Health (ICF).

Results:Fifty-one patients with pSS participated in 12 focus groups. We identified a total of 82 concepts meaningful to people with pSS. Of these, 55 (67%) were mentioned by the patients with pSS in at least four of five countries and 36 (44%) emerged in all the five countries. Most concepts were assigned to the ICF componentsactivities and participation(n= 25, 30%), followed by 22 concepts (27%) that were considered to benot definableornot coveredby the ICF; 15 concepts (18%) linked tobody structures and functions. Participants reported several limitations in the daily life due to a mismatch between the capabilities of the person, the demands of the environment and the requirements of the activities.

Conclusion:Concepts that emerged in all the five non-English speaking countries may be used to guide the development and adaption of the patient-reported outcome measures and to enhance the provision of treatment options based on the aspects meaningful to patients with pSS in clinical routine.
Sex-Specific Association Between Socioeconomic Status, Lifestyle, and the Risk of Frailty Among the Elderly in China
Authors: Wang Huai-yu , Zhang Mufan , Sun Xiaojing
Published: November 2021

Background: Lifestyle contributors to frailty among the elderly were previously reported in the developed Western countries, while evidence from the less developed East Asian regions was still lacking. Due to the well-acknowledged sex-based disparity of frailty and sex-difference of socioeconomic status and lifestyle, it is worth investigating the sex-specific association between the social and behavioral contributors and the risk of frailty among the East Asian longevous population.

Methods: The present study was an observational study based on the four waves of interviews of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. The participants aged ≥65 years and without frailty at baseline were included. Fried criteria (exhaustion, shrink, weakness, low mobility, and inactivity) were adopted to identify the incidence of frailty (≥3 domains) and pre-frailty (1–2 domains) during the follow-up. The sex-specific association between lifestyle (smoke status, drinking status, food intake, sleep, exercise, and physical activity) and the risk of incident pre-frailty and frailty was analyzed using the multinomial logistic regression models.

Results: Altogether, 3,327 participants aged 81.2 ± 10.3 (range 65–116) years were included. In total, 964 (29.0%) and 1,249 (37.5%) participants were recognized as having incident pre-frailty and frailty, respectively. Older women were disproportionately uneducated, frequently did housework and labor work, but seldom did exercise. Men had diverse dietary and recreational activities but were frequently exposed to tobacco and alcohol. The protective effects of higher income, exercise, doing housework, and daily intake of fresh fruits/vegetables were found in both the sexes (P < 0.05). Sleep disorders (odds ratio [OR] = 2.16, 95% CI: 1.28–3.62) and labor work (OR = 2.18, 95% CI: 1.42–3.33) were associated with the increased risk of frailty among women. For men, diverse dietary (four types of food added: OR = 0.21, 95% CI: 0.09–0.50) showed a protective effect on the risk of frailty, but daily intake of pickled vegetables showed the opposite effect (OR = 1.86, 95% CI: 1.12–3.07).

Conclusion: Socioeconomic status, lifestyle, and the association with the risk of frailty showed substantial difference between the sexes among the longevous population in China. To establish the individualized strategy of behavioral improvement for the frailty prevention should consider the sex disparity.
Microbial Transglutaminase Improves ex vivo Adhesion of Gelatin Methacryloyl Hydrogels to Human Cartilage
Authors: Trengove Anna , Duchi Serena , Onofrillo Carmine , O'Connell Cathal D. , Di Bella Claudia , O'Connor Andrea J.
Published: November 2021

Current surgical techniques to treat articular cartilage defects fail to produce a satisfactory long-term repair of the tissue. Regenerative approaches show promise in their ability to generate hyaline cartilage using biomaterials in combination with stem cells. However, the difficulty of seamlessly integrating the newly generated cartilage with the surrounding tissue remains a likely cause of long-term failure. To begin to address this integration issue, our strategy exploits a biological enzyme (microbial transglutaminase) to effect bioadhesion of a gelatin methacryloyl implant to host tissue. Mechanical characterization of the bioadhesive material shows that enzymatic crosslinking is compatible with photocrosslinking, allowing for a dual-crosslinked system with improved mechanical properties, and a slower degradation rate. Biocompatibility is illustrated with a 3D study of the metabolic activity of encapsulated human adipose derived stem cells. Furthermore, enzymatic crosslinking induced by transglutaminase is not prevented by the presence of cells, as measured by the bulk modulus of the material. Adhesion to human cartilage is demonstrated ex vivo with a significant increase in adhesive strength (5.82 ± 1.4 kPa as compared to 2.87 ± 0.9 kPa, p < 0.01) due to the addition of transglutaminase. For the first time, we have characterized a bioadhesive material composed of microbial transglutaminase and GelMA that can encapsulate cells, be photo crosslinked, and bond to host cartilage, taking a step toward the integration of regenerative implants.
Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
Authors: Shen Chunmei , Shen Ying , Zhang Hui , Xu Maosuo , He Leqi , Qie Jingbo
Published: November 2021

Antibiotic resistance (AMR) has always been a hot topic all over the world and its mechanisms are varied and complicated. Previous evidence revealed the metabolic slowdown in resistant bacteria, suggesting the important role of metabolism in antibiotic resistance. However, the molecular mechanism of reduced metabolism remains poorly understood, which inspires us to explore the global proteome change during antibiotic resistance. Here, the sensitive, cotrimoxazole-resistant, amikacin-resistant, and amikacin/cotrimoxazole -both-resistant KPN clinical isolates were collected and subjected to proteome analysis through liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). A deep coverage of 2,266 proteins were successfully identified and quantified in total, representing the most comprehensive protein quantification data by now. Further bioinformatic analysis showed down-regulation of tricarboxylic acid cycle (TCA) pathway and up-regulation of alcohol metabolic or glutathione metabolism processes, which may contribute to ROS clearance and cell survival, in drug-resistant isolates. These results indicated that metabolic pathway alteration was directly correlated with antibiotic resistance, which could promote the development of antibacterial drugs from “target” to “network.” Moreover, combined with minimum inhibitory concentration (MIC) of cotrimoxazole and amikacin on different KPN isolates, we identified nine proteins, including garK, uxaC, exuT, hpaB, fhuA, KPN_01492, fumA, hisC, and aroE, which might contribute mostly to the survival of KPN under drug pressure. In sum, our findings provided novel, non-antibiotic-based therapeutics against resistant KPN.
Development of Methodology to Investigate the Surface SMALPome of Mammalian Cells
Authors: Morrison Kerrie A. , Heesom Kate J. , Edler Karen J. , Doutch James , Price Gareth J. , Koumanov Francoise , Whitley Paul
Published: November 2021

Extraction of membrane proteins from biological membranes has traditionally involved detergents. In the past decade, a new technique has been developed, which uses styrene maleic acid (SMA) copolymers to extract membrane proteins into nanodiscs without the requirement of detergents. SMA nanodiscs are compatible with analytical techniques, such as small-angle scattering, NMR spectroscopy, and DLS, and are therefore an attractive medium for membrane protein characterization. While mass spectrometry has also been reported as a technique compatible with copolymer extraction, most studies have focused on lipidomics, which involves solvent extraction of lipids from nanodiscs prior to mass-spectrometry analysis. In this study, mass spectrometry proteomics was used to investigate whether there are qualitative or quantitative differences in the mammalian plasma membrane proteins extracted with SMA compared to a detergent control. For this, cell surface proteins of 3T3L1 fibroblasts were biotinylated and extracted using either SMA or detergent. Following affinity pull-down of biotinylated proteins with NeutrAvidin beads, samples were analyzed by nanoLC-MS. Here, we report for the first time, a global proteomics protocol for detection of a mammalian cell “SMALPome”, membrane proteins incorporated into SMA nanodiscs. Removal of SMA from samples prior to processing of samples for mass spectrometry was a crucial step in the protocol. The reported surface SMALPome of 3T3L1 fibroblasts consists of 205 integral membrane proteins. It is apparent that the detergent extraction method used is, in general, quantitatively more efficient at extracting proteins from the plasma membrane than SMA extraction. However, samples prepared following detergent extraction contained a greater proportion of proteins that were considered to be “non-specific” than in samples prepared from SMA extracts. Tantalizingly, it was also observed that proteins detected uniquely or highly preferentially in pull-downs from SMA extracts were primarily multi-spanning membrane proteins. These observations hint at qualitative differences between SMA and detergent extraction that are worthy of further investigation.
A Novel Biotinylated Homotryptamine Derivative for Quantum Dot Imaging of Serotonin Transporter in Live Cells
Authors: Tomlinson Ian D. , Kovtun Oleg , Torres Ruben , Bellocchio Laurel G. , Josephs Travis , Rosenthal Sandra J.
Published: November 2021

The serotonin transporter (SERT) is the primary target for selective serotonin reuptake inhibitor (SSRI) antidepressants that are thought to exert their therapeutic effects by increasing the synaptic concentration of serotonin. Consequently, probes that can be utilized to study cellular trafficking of SERT are valuable research tools. We have developed a novel ligand (IDT785) that is composed of a SERT antagonist (a tetrahydro pyridyl indole derivative) conjugated to a biotinylated poly ethylene glycol (PEG) via a phenethyl linker. This compound was determined to be biologically active and inhibited SERT-mediated reuptake of IDT307 with the half-maximal inhibitory concentration of 7.2 ± 0.3 μM. We demonstrated that IDT785 enabled quantum dot (QD) labeling of membrane SERT in transfected HEK-293 cultures that could be blocked using the high affinity serotonin reuptake inhibitor paroxetine. Molecular docking studies suggested that IDT785 might be binding to the extracellular vestibule binding site rather than the orthosteric substrate binding site, which could be attributable to the hydrophilicity of the PEG chain and the increased loss of degrees of freedom that would be required to penetrate into the orthosteric binding site. Using IDT785, we were able to study the membrane localization and membrane dynamics of YFP-SERT heterologously expressed in HEK-293 cells and demonstrated that SERT expression was enriched in the membrane edge and in thin cellular protrusions.
Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
Authors: Ikezawa Jun , Yokochi Fusako , Okiyama Ryoichi , Kumada Satoko , Tojima Maya , Kamiyama Tsutomu , Hanakawa Takashi , Matsuda Hiroshi , Tanaka Fumiaki , Nakata Yasuhiro , Isozaki Eiji
Published: November 2021

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia.

Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT).

Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined.

Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10−6).

Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD.
Differences in Brain Functional Networks of Executive Function Between Cantonese-Mandarin Bilinguals and Mandarin Monolinguals
Authors: Cai Lei , Xu Xiaoyu , Fan Xiaoxuan , Ma Jingwen , Fan Miao , Wang Qingxiong , Wu Yujia , Pan Ning , Yin Zhixin , Li Xiuhong
Published: November 2021

It remains controversial whether long-term logographic-logographic bilingual experience shapes the special brain functional subnetworks underlying different components of executive function (EF). To address this question, this study explored the differences in the functional connections underlying EF between the Cantonese-Mandarin bilinguals and Mandarin monolinguals. 31 Cantonese-Mandarin bilinguals and 31 Mandarin monolinguals were scanned in a 3-T magnetic resonance scanner at rest. 4 kinds of behavioral tasks of EF were tested. Network-based statistics (NBS) was performed to compare the connectomes of fronto-parietal (FP) and cingulo-opercular (CO) network between groups. The results showed that the bilinguals had stronger connectivity than monolinguals in a subnetwork located in the CO network rather than the FP network. The identified differential subnetwork referred to as the CO subnetwork contained 9 nodes and 10 edges, in which the center node was the left mid-insula with a degree centrality of 5. The functional connectivity of the CO subnetwork was significantly negatively correlated with interference effect in bilinguals. The results suggested that long-term Cantonese-Mandarin bilingual experience was associated with stronger functional connectivity underlying inhibitory control in the CO subnetwork.
Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats
Authors: Vincent Kathleen F. , Zhang Edlyn R. , Kato Risako , Cho Angel , Moody Olivia A. , Solt Ken
Published: November 2021

As the number of individuals undergoing general anesthesia rises globally, it becomes increasingly important to understand how consciousness and cognition are restored after anesthesia. In rodents, levels of consciousness are traditionally captured by physiological responses such as the return of righting reflex (RORR). However, tracking the recovery of cognitive function is comparatively difficult. Here we use an operant conditioning task, the 5-choice serial reaction time task (5-CSRTT), to measure sustained attention, working memory, and inhibitory control in male and female rats as they recover from the effects of several different clinical anesthetics. In the 5-CSRTT, rats learn to attend to a five-windowed touchscreen for the presentation of a stimulus. Rats are rewarded with food pellets for selecting the correct window within the time limit. During each session we tracked both the proportion of correct (accuracy) and missed (omissions) responses over time. Cognitive recovery trajectories were assessed after isoflurane (2% for 1 h), sevoflurane (3% for 20 min), propofol (10 mg/kg I.V. bolus), ketamine (50 mg/kg I.V. infusion over 10 min), and dexmedetomidine (20 and 35 μg/kg I.V. infusions over 10 min) for up to 3 h following RORR. Rats were classified as having recovered accuracy performance when four of their last five responses were correct, and as having recovered low omission performance when they missed one or fewer of their last five trials. Following isoflurane, sevoflurane, and propofol anesthesia, the majority (63–88%) of rats recovered both accuracy and low omission performance within an hour of RORR. Following ketamine, accuracy performance recovers within 2 h in most (63%) rats, but low omission performance recovers in only a minority (32%) of rats within 3 h. Finally, following either high or low doses of dexmedetomidine, few rats (25–32%) recover accuracy performance, and even fewer (0–13%) recover low omission performance within 3 h. Regardless of the anesthetic, RORR latency is not correlated with 5-CSRTT performance, which suggests that recovery of neurocognitive function cannot be inferred from changes in levels of consciousness. These results demonstrate how operant conditioning tasks can be used to assess real-time recovery of neurocognitive function following different anesthetic regimens.
Fully Automated 68Ga-Labeling and Purification of Macroaggregated Albumin Particles for Lung Perfusion PET Imaging
Authors: Blanc-Béguin Frédérique , Masset Julien , Robin Philippe , Tripier Raphaël , Hennebicq Simon , Guilloux Valérie , Vriamont Charles , Warnier Corentin , Cogulet Virginie , Eu Peter , Salaün Pierre-Yves , Le Roux Pierre-Yves
Published: November 2021

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [68Ga]Ga-MAA labeling procedure, using a commercially available [99mTc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [68Ga]Ga-MAA.

Method: The synthesis parameters (pH, heating temperature) were manually determined. Automated 68Ga-labeling of MAA was then developed on a miniAIO (Trasis®, Ans, Belgium) module. An innovative automated process was developed for the purification. The process was then optimized and adapted to automate both the [68Ga]Ga-MAA synthesis and the isolation of gallium-68 eluate required for the pulmonary ventilation PET/CT.

Results: The 15-min process demonstrated high reliability and reproducibility, with high synthesis yield (>95 %). Mean [68Ga]Ga-MAA radiochemical purity was 99 % ± 0.6 %. The 68Ga-labeled MAA particles size and morphology remained unchanged.

Conclusion: A fast, user friendly, and fully automated process to produce GMP [68Ga]Ga-MAA for clinical use was developed. This automated process combining the advantages of using a non-modified MAA commercial kit, a gallium-68 eluate without pre-purification and an efficient final purification of the [68Ga]Ga-MAA may facilitate the implementation of lung PET/CT imaging in nuclear medicine departments.
Evaluating the Effect of Appropriate Complementary Feeding Practices on Child Growth in Malawi Using Cross-Sectional Data: An Application of Propensity Score Matching
Authors: Twabi Halima S. , Manda Samuel O. M. , Small Dylan S.
Published: November 2021

Introduction: Appropriate complementary foods have been found to provide infants and young children with nutritional needs for their growth and development. In the absence of a randomized control trial (RCT), this study used observational data to evaluate the effect of appropriate complementary feeding practices on the nutritional status of children aged 6–23 months in Malawi using a propensity score matching statistical technique.

Methods: Data on 4,722 children aged 6 to 23 months from the 2015–16 Malawi Demographic and Health Survey (MDHS) were analyzed. Appropriate complementary feeding practices were assessed using the core indicators recommended by the World Health Organization (WHO)/United Nations Children's Fund (UNICEF), and consist of the introduction of complementary feeding, minimum dietary diversity, minimum meal frequency and minimum acceptable diet based on a dietary intake during a most recent 24-h period.

Results: The prevalence of stunting (height-for-age z-score < −2 SD) was 31.9% (95% CI: 29.3%, 34.6%), wasting (weight-for-height z-score < −2 SD) 3.5% (95% CI: 2.6%, 4.7%) and underweight (weight-for-age z-score < −2 SD) 9.9% (95% CI: 8.4%, 11.8%). Of the 4,722 children, 7.7% (95% CI: 6.9%, 8.5%) were provided appropriate complementary foods. Appropriate complementary feeding practices were found to result in significant decrease in stunting (OR = 0.7, 95% CI: 0.4, 0.95). They also resulted in the decrease of wasting (OR = 0.4, 95% CI: 0.1, 1.7) and underweight (OR = 0.6, 95% CI: 0.2, 1.7).

Conclusion: Appropriate complementary feeding practices resulted in a reduction of stunting, wasting, and underweight among children 6 to 23 months of age in Malawi. We recommend the continued provision of appropriate complementary foods to infants and young children to ensure that the diet has adequate nutritional needs for their healthy growth.
The Effects of Exercise on Appetite in Older Adults: A Systematic Review and Meta-Analysis
Authors: Hubner Sarah , Boron Julie Blaskewicz , Koehler Karsten
Published: November 2021

Background: The effect of physical activity and exercise on hunger and satiety has been well-studied in younger adults, but the influence of aging is less understood. While some evidence suggests that acute bouts of exercise induce a compensatory eating drive, long-term activity may improve satiety sensitivity. The objective of this study was to investigate the effects of exercise on appetite in older adults.

Methods: We systematically reviewed available literature investigating the effect of exercise on appetite in older adults adults (CRD42020208953). PubMed, PsycINFO, Academic Search Complete, the Sports Medicine & Education Index, and Web of Science, were searched for peer-reviewed articles published in English with no date restriction. Included studies implemented a primary exercise or physical activity intervention with a control group, on a generally healthy population ≥60 years of age. Selected studies included at least one appetite outcome. Risk of bias was assessed using the 11-point Physiotherapy Evidence Database (PEDro) tool. Standardized mean difference summary statistics (Hedge's g effect sizes) and 95% confidence intervals were reported.

Results: We identified 15 reports (13 studies) which met all inclusion criteria (5 resistance training, 3 aerobic, 6 mixed modalities). Studies included 443 participants (Age = 68.9 ± 5.2, 82.3% female) and had generally “good” bias scores (PEDro = 6.4 ± 0.88). Random effects meta-analyses revealed that the exercising group showed statistically significant reductions in glucose [SMD = −0.34 (95% CI: −0.67, −0.02), p < 0.05, PEDro =6.4 ± 0.45] and leptin [SMD = −0.92 (95% CI: −1.28, −0.57), p < 0.00001, PEDro = 6.2 ± 0.75].

Discussion: This systematic review revealed that exercise and physical activity may modulate resting hunger and satiety in older adults. Decreases in fasting leptin and glucose hormones suggest that exercise promotes satiety sensitivity in adults aged 60+. This review highlights that engaging in exercise and activity programs may provide a meaningful avenue for improving chronic and functional disease burden in later life by promoting appetite control and balanced energy intake. Recommendations for future research include investigations of appetite in response to varied exercise modalities within more diverse and representative samples of older adults.
TRPV1 Receptor-Mediated Hypoglycemic Mechanism of Capsaicin in Streptozotocin-Induced Diabetic Rats
Authors: Zhang Shiqi , Tang Lanlan , Xu Fanshu , Hui Yonghai , Lu Hongjia , Liu Xiong
Published: November 2021

Graphical Abstract

Signal pathway of hypoglycemic mechanism of capsaicin in the pancreas of STZ-induced diabetic rats.
The Role of Segmented Filamentous Bacteria in Immune Barrier Maturation of the Small Intestine at Weaning
Authors: Oemcke Linda A. , Anderson Rachel C. , Altermann Eric , Roy Nicole C. , McNabb Warren C.
Published: November 2021

The microbiological, physical, chemical, and immunological barriers of the gastrointestinal tract (GIT) begin developing in utero and finish maturing postnatally. Maturation of these barriers is essential for the proper functioning of the GIT. Maturation, particularly of the immunological barrier, involves stimulation by bacteria. Segmented filamentous bacteria (SFB) which are anaerobic, spore-forming commensals have been linked to immune activation. The presence and changes in SFB abundance have been positively correlated to immune markers (cytokines and immunoglobulins) in the rat ileum and stool samples, pre- and post-weaning. The abundance of SFB in infant stool increases from 6 months, peaks around 12 months and plateaus 25 months post-weaning. Changes in SFB abundance at these times correlate positively and negatively with the production of interleukin 17 (IL 17) and immunoglobulin A (IgA), respectively, indicating involvement in immune function and maturation. Additionally, the peak in SFB abundance when a human milk diet was complemented by solid foods hints at a diet effect. SFB genome analysis revealed enzymes involved in metabolic pathways for survival, growth and development, host mucosal attachment and substrate acquisition. This narrative review discusses the current knowledge of SFB and their suggested effects on the small intestine immune system. Referencing the published genomes of rat and mouse SFB, the use of food substrates to modulate SFB abundance is proposed while considering their effects on other microbes. Changes in the immune response caused by the interaction of food substrate with SFB may provide insight into their role in infant immunological barrier maturation.
Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
Authors: Yehia Rana , Schaalan Mona , Abdallah Dalaal M. , Saad Amr S. , Sarhan Neven , Saleh Samira
Published: November 2021

Background

Cachexia is a frequent syndrome in pancreatic and non-small cell lung (NSCL) cancer patients. The storm of cancer-induced inflammatory cytokines, in particular TNF-α, is a crucial pathogenic mechanism. Among the molecular alterations accused of cancer-induced cachexia,TNF-α 308 G/A(rs1800629) and−1031T/C(rs1799964) are single-nucleotide polymorphisms (SNPs) within the gene encoding this pro-inflammatory cytokine. Recent studies have demonstrated the crucial role of non-coding microRNAs (miRNAs) in pathogenesis of different diseases including cachexia. Moreover, the mechanistic cytokine signaling pathway ofmiR-155, as aTNF-αregulator, supports the involvement of SOCS1, TAB2, and Foxp3, which are direct targets ofTNF-αgene.

Aim

A case–control study (NCT04131478) was conducted primarily to determine the incidence ofTNF-α 308 G/A(rs1800629) and−1031T/C(rs1799964) gene polymorphisms in adult Egyptian patients with local/advanced or metastatic pancreatic or NSCL cancer and investigate both as cachexia risk factors. The association of gene polymorphism with cachexia severity and the expression ofmiR-155in cachectic patients were analyzed. A mechanistic investigation of the cytokine signaling pathway, involving SOCS1, TAB2, and Foxp3, was also performed.

Results

In both pancreatic and NSCL cancer cohorts, the mutantTNF-αvariant of308 G/Awas positively associated with cachexia; on the contrary, that of 1031T/C was negatively associated with cachexia in the NSCL cancer patients.MiR-155was higher in cachexia and in alignment with its severity in the cachectic group as compared with the non-cachectic group in both the pancreatic and NSCL cancer patients. Though TAB2 did not change to any significant extent in cachectic patients, the levels of SOCS1 and Foxp3 were significantly lower in the cachectic group as compared with the non-cachectic group.

Conclusion

Carriers of the A allele308 G/Agene and highmiR-155are at greater risk of cachexia in both the pancreatic and NSCL cancer patients; however, the mutant variant of1031T/Cgene is protective against cachexia in the NSCL cancer patients. Finally, high levels ofmiR-155in the cachectic group lead to negative feedback inhibition of both SOCS1 and Foxp3 in both the pancreatic and NSCL cancer patients.
Pain Assessment and Management in Pediatric Intensive Care Units Around the World, an International, Multicenter Study
Authors: Grunauer Michelle , Mikesell Caley , Bustamante Gabriela , Cobo Gissela , Sánchez Sebastián , Román Ana María , Icaza-Freire Andrea P. , Gavilanes Antonio W. D. , Wang Nancy Ewen ,   The PICU-MIC Research Group
Published: November 2021

The adequate assessment and management of pain remains a challenging task in the Pediatric Intensive Care Unit (PICU). Our goal is to describe how pain is assessed and managed in PICUs around the world and to examine how human and material resources impact achievement of this goal. An international multicenter cross-sectional observational study was designed with the participation of 34 PICUs located in urban, suburban, and rural areas of 18 countries. We evaluated how PICUs around the world assessed and managed pain according to the Initiative for Pediatric Palliative Care recommendations, and how human and material resources impacted achievement of this goal. Data was collected for this study from 2016 to 2018 using questionnaires completed by medical doctors and nurses. In this paper, we focus on the indicators related to how pain is managed and assessed. The average achievement of the goal of pain relief across all centers was 72.2% (SD: 21.1). We found a statistically significant trend of more effective pain management scores, routine assessment, proper documentation, and involvement of pain management experts by increasing country income. While there are efforts being made worldwide to improve the knowledge in pain assessment and management, there is a lack of resources to do so appropriately in low-middle-income countries. There is a mismatch between the existing guidelines and policies, which are mainly designed in high income countries, and the resources available in lower resourced environments.
Congenital Visceral Vascular Variation Causing Gastrointestinal Hemorrhage: A Case Report
Authors: Wei Yingli , Ye Zhiqiu , Shang Ning , Yang Chaoxiang , Liao Minyan , Pan Yunxiang
Published: November 2021

Variations in the visceral vasculature are often encountered, but rarely cause clinical symptoms. We report a 12-year-old girl with portal hypertension caused by congenital variations in visceral vessels. The clinical manifestations included gastrointestinal hemorrhage and ascites. The common hepatic artery and splenic artery stem shared the same trunk from the aorta, and the common hepatic artery was directly connected with the main portal vein to form an arteriovenous fistula. In addition, the left hepatic artery and the left gastric artery shared a common trunk termed the “hepatic-gastric trunk” which originated from the anterior wall of the aorta, while the right hepatic artery originated from the superior mesenteric artery and supplied the right liver. The patient was treated with interventional embolization and remained in good condition throughout the follow-up and at the time of publication.