bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinesiophobia Severity Categories and Clinically Meaningful Symptom Change in Persons With Achilles Tendinopathy in a Cross-Sectional Study: Implications for Assessment and Willingness to Exercise
Authors: Chimenti Ruth L. , Post Andrew A. , Silbernagel Karin Grävare , Hadlandsmyth Katherine , Sluka Kathleen A. , Moseley G. Lorimer , Rio Ebonie
Published: September 2021

Objectives: (1) Validate thresholds for minimal, low, moderate, and high fear of movement on the 11-item Tampa Scale of Kinesiophobia (TSK-11), and (2) Establish a patient-driven minimal clinically important difference (MCID) for Achilles tendinopathy (AT) symptoms of pain with heel raises and tendon stiffness.

Methods: Four hundred and forty-two adults with chronic AT responded to an online survey, including psychosocial questionnaires and symptom-related questions (severity and willingness to complete heel raises and hops). Kinesiophobia subgroups (Minimal ≤ 22, Low 23–28, Moderate 29–35, High ≥ 36 scores on the TSK-11), pain MCID subgroups (10-, 20-, 30-, >30-points on a 0- to 100-point scale), and stiffness MCID subgroups (5, 10, 20, >20 min) were described as median [interquartile range] and compared using non-parametric statistics.

Results: Subgroups with higher kinesiophobia reported were less likely to complete three heel raises (Minimal = 93%, Low = 74%, Moderate = 58%, High = 24%). Higher kinesiophobia was associated with higher expected pain (Minimal = 20.0 [9.3–40.0], Low = 43.0 [20.0–60.0], Moderate = 50.0 [24.0–64.0], High = 60.5 [41.3–71.0]) yet not with movement-evoked pain (Minimal = 25.0 [5.0–43.0], Low = 31.0 [18.0–59.0], Moderate = 35.0 [20.0–60.0], High = 43.0 [24.0–65.3]). The most common pain MCID was 10 points (39% of respondents). Half of respondents considered a 5-min (35% of sample) or 10-min (16%) decrease in morning stiffness as clinically meaningful.

Conclusions: Convergent validity of TSK-11 thresholds was supported by association with pain catastrophizing, severity of expected pain with movement, and willingness to complete tendon loading exercises. Most participants indicated that reducing their pain severity to the mild range would be clinically meaningful.
All You Need Is Evidence: What We Know About Pneumonia in Children With Neuromuscular Diseases
Authors: Cherchi Claudio , Chiarini Testa Maria B. , Deriu Daniele , Schiavino Alessandra , Petreschi Francesca , Ullmann Nicola , Paglietti Maria G. , Cutrera Renato
Published: September 2021

Neuromuscular diseases may involve all major respiratory muscles groups including inspiratory, expiratory, and bulbar muscles. Respiratory complications are the major cause of morbidity and mortality. Pneumonia represents a frequent cause of morbidity in children with neuromuscular disease. The aim of this review is to collect knowledge about pneumonia in children with neuromuscular diseases. Pneumonia usually follows viral respiratory infections of the upper respiratory tract, due to the combination of an increased amount of nasal and oral secretions and an impairment of the cough efficiency and of the clearance of secretions due to the muscle weakness, further compromised by the infection itself. The accumulation of bronchial secretions leads to atelectasis and promote bacterial infection. Moreover, dysfunction of swallowing mechanism exposes these children to the risk of developing aspiration pneumonia. However, etiology of viral and bacterial respiratory infection in these patients is still poorly studied.
Fetal Heart Rate Fragmentation
Authors: Costa Matilde , Xavier Mariana , Nunes Inês , Henriques Teresa S.
Published: September 2021

Intrapartum fetal monitoring's primary goal is to avoid adverse perinatal outcomes related to hypoxia/acidosis without increasing unnecessary interventions. Recently, a set of indices were proposed as new biomarkers to analyze heart rate (HR), termed HR fragmentation (HRF). In this work, the HRF indices were applied to intrapartum fetal heart rate (FHR) traces to evaluate fetal acidemia. The fragmentation method produces four indices: PIP-Percentage of inflection points; IALS-Inverse of the average length of acceleration/deceleration segments; PSS-Percentage of short segments; PAS-Percentage of alternating segments. On the other hand, the symbolic approach studied the existence of different patterns of length four. We applied the measures to 246 selected FHR recordings sampled at 4 and 2 Hz, where 39 presented umbilical artery's pH ≤ 7.15. When applied to the 4 Hz FHR, the PIP, IASL, and PSS showed significantly higher values in the traces from acidemic fetuses. In comparison, the percentage of “words” W1h and W2s showed lower values for those traces. Furthermore, when using the 2 Hz, only IASL, W0, and W2m achieved significant differences between traces from both acidemic and normal fetuses. Notwithstanding, the ideal sampling frequency is yet to be established. The fragmentation indices correlated with Sisporto variability measures, especially short-term variability. Accordingly, the fragmentation indices seem to be able to detect pathological patterns in FHR tracings. These indices have the advantage of being suitable and straightforward to apply in real-time analysis. Future studies should combine these indexes with others used successfully to detect fetal hypoxia, improving the power of discrimination in a larger dataset.
Initial Esophageal Anastomosis Diameter Predicts Treatment Outcomes in Esophageal Atresia Patients With a High Risk for Stricture Development
Authors: Baghdadi Osama , Clark Susannah , Ngo Peter , Yasuda Jessica , Staffa Steven , Zendejas Benjamin , Hamilton Thomas , Jennings Russell , Manfredi Michael
Published: September 2021

Background and Aims: Children with esophageal atresia (EA) who undergo surgical repair are at risk for anastomotic stricture, which may need multiple dilations or surgical resection if the stricture proves refractory to endoscopic therapy. To date, no studies have assessed the predictive value of anastomotic diameter on long-term treatment outcomes. Our aim was to evaluate the relationship between anastomotic diameter in the early postoperative period and need for frequent dilations and stricture resection within 1 year of surgical repair.

Methods: A retrospective chart review was performed of patients who had EA repair or stricture resection (SR). Medical records were reviewed to evaluate the diameter of the anastomosis at the first endoscopy after surgery, number and timing of dilations needed to treat the anastomotic stricture, and need for stricture resection. A generalized estimating equations (GEE) modeling with a logit link and binomial family was done to analyze the relationship between initial endoscopic anastomosis diameter and the outcome of needing a stricture resection. Median regression was implemented to estimate the association between number of dilations needed based on initial diameter.

Results: A total of 121 patients (56 females) with a history of EA (64% long-gap EA) were identified who either underwent Foker repair at 46% or stricture resection with end-to-end esophageal anastomosis at 54%. The first endoscopy occurred a median of 22 days after surgery. Among all cases, a narrower anastomoses were more likely to need stricture resection with an OR of 12.9 (95% CI, 3.52, 47; p < 0.001) in patients with an initial diameter of <3 mm. The number of dilations that patients underwent also decreased as anastomotic diameter increased. This observation showed a significant difference when comparing all diameter categories when looking at all surgeries taken as a whole (p < 0.008).

Conclusion: Initial anastomotic diameter as assessed via endoscopy performed after high-risk EA repair predicts which patients will require more esophageal dilations as well as the likelihood for stricture resection. This data may serve to stratify patients into different endoscopic treatment plans.
Ten-Year Trend of Retinopathy of Prematurity Among Extremely Preterm Infants in One Neonatal Intensive Care Unit in China
Authors: Dai Yi , Zhu Li , Zhou Yequn , Chen Chao , Zhang Shulian
Published: September 2021

Background: Extremely preterm (EP) infants are at the highest risk of retinopathy of prematurity (ROP). With more EP infants survived in China, recent data of ROP is lacking. The aim of the study is to report the trend of incidence of ROP among EP infants in a large neonatal intensive care unit in China over the past 10-year period, in relation with the overall survival rate and the change of oxygen saturation targets.

Methods: This retrospective cohort study enrolled all EP infants born before 28 weeks' gestation and admitted to one of the largest tertiary neonatal intensive care units in China from 2010 to 2019. Data were compared between two time periods according to different oxygen saturation targets: 2010–2014 (P1) with low saturation target and 2015–2019 (P2) with higher target.

Results: Of 630 EP infants admitted during the 10 years, 447 (71.0%) infants survived to discharge. The survival rate increased significantly from 61.6% in P1 to 75.8% in P2 (P < 0.05). Of the 472 infants who had ROP data, 318 (67.4%) developed ROP of any stage, 67 (14.2%) developed severe ROP, and 44 (9.3%) received treatment. The incidence of any ROP increased significantly from 51.7% in P1 to 74.3% in P2 (P < 0.05). The incidence of severe ROP increased from 11.0% in P1 to 15.6% in P2, and ROP treatment increased from 6.9% in P1 to 10.4% in P2, but neither reached statistical significance (both P > 0.05).

Conclusions: We observed an increasing trend in the incidence of ROP across the 10-year period in one of the largest neonatal care units in China. The increased survival rate and the use of high-target oxygen saturation in the later period may partly explain this trend. Further investigations are needed to improve the care practices and to reduce the incidence of severe ROP.
Genetic Testing in Various Neurodevelopmental Disorders Which Manifest as Cerebral Palsy: A Case Study From Iran
Authors: Nejabat Marzieh , Inaloo Soroor , Sheshdeh Afsaneh Taghipour , Bahramjahan Shima , Sarvestani Fatima Masoomi , Katibeh Pegah , Nemati Hamid , Tabei Seyed Mohammad Bagher , Faghihi Mohammad Ali
Published: September 2021

Purpose: Cerebral palsy (CP) is a heterogeneous permanent disorder impacting movement and posture. Investigations aimed at diagnosing this disorder are expensive and time-consuming and can eventually inconclusive. This study aimed to determine the diagnostic yield of next generation sequencing in patients with atypical CP (ACP).

Methods: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following conditions: severe intellectual disability, positive family history, brain imaging findings not typical for cerebral palsy, abnormal neurometabolic profile, intractable seizure, normal neuroimaging despite severe psychomotor disability, after pediatric neurologist assessment including neuroimaging and biochemical-metabolic study offered for genetic study.

Results: Exome sequencing was done for 66 patients which revealed pathogenic, likely pathogenic, and variants of unknown significance in 36.2, 9, and 43.9%, respectively. We also found 10 new mutations and were able to suggest specific and personalized treatments for nine patients. We also found three different mutations with different phenotypical spectrum in one gene that have not been reported for cerebral palsy.

Conclusion: An accurate history and physical examination and determination of patients with atypical cerebral palsy for doing exome sequencing result in improved genetic counseling and personalized management.
Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study
Authors: Blaser Lea S , Duthaler Urs , Bouitbir Jamal , Leuppi-Taegtmeyer Anne B , Liakoni Evangelia , Dolf Reto , Mayr Michael , Drewe Jürgen , Krähenbühl Stephan , Haschke Manuel
Published: September 2021

Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α.

Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing.

Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC50 0.69 ± 0.27 µM) compared with naproxen (EC50 0.034 ± 0.033 µM).

Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.
Serum Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Early Prognosis Markers After ST-Segment Elevation Myocardial Infarction
Authors: Paccalet Alexandre , Crola Da Silva Claire , Mechtouff Laura , Amaz Camille , Varillon Yvonne , de Bourguignon Charles , Cartier Regine , Prieur Cyril , Tomasevic Danka , Genot Nathalie , Leboube Simon , Derimay François , Rioufol Gilles , Bonnefoy-Cudraz Eric , Mewton Nathan , Ovize Michel , Bidaux Gabriel , Bochaton Thomas
Published: September 2021

Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity.

Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outcomes in STEMI patients.

Methods: We enrolled into a prospective cohort 251 consecutive STEMI patients referred to our hospital for percutaneous coronary intervention revascularization. Blood samples were collected at five time points: admission and 4, 24, 48 h, and 1 month after admission to assess sTNFR1 and sTNFR2 serum concentrations. Patients underwent cardiac magnetic resonance imaging at 1 month.

Results: sTNFR1 concentration increased at 24 h with a median of 580.5 pg/ml [95% confidence interval (CI): 534.4–645.6]. sTNFR2 increased at 48 h with a median of 2,244.0 pg/ml [95% CI: 2090.0–2,399.0]. Both sTNFR1 and sTNFR2 peak levels were correlated with infarct size and left ventricular end-diastolic volume and inversely correlated with left ventricular ejection fraction. Patients with sTNFR1 or sTNFR2 concentration above the median value were more likely to experience an adverse clinical event within 24 months after STEMI [hazards ratio (HR): 8.8, 95% CI: 4.2–18.6, p < 0.0001 for sTNFR1; HR: 6.1, 95% CI: 2.5 –10.5, p = 0.0003 for sTNFR2]. Soluble TNFR1 was an independent predictor of major adverse cardiovascular events and was more powerful than troponin I (p = 0.04 as compared to the troponin AUC).

Conclusion: The circulating sTNFR1 and sTNFR2 are inflammatory markers of morphological and functional injury after STEMI. sTNFR1 appears as an early independent predictor of clinical outcomes in STEMI patients.
Platinum Accumulation and Cancer-Related Fatigue, Correlation With IL-8, TNF-α and Hemocytes
Authors: Zhang Yuling , Huang Xiaoting , Feng Shanna , Chen Chen , Guo Dainian , Fang Ling
Published: September 2021

Platinum-based chemotherapy drugs cause platinum accumulation and result in cancer-related fatigue (CRF), which is related to immune response through still ambiguous mechanisms. We aimed to explore the correlation between platinum and CRF from the perspective of platinum accumulation. After allowing for complete metabolism of the administered platinum drugs, we collected blood samples from 135 patients who had at least two platinum chemotherapy rounds, correlated the platinum concentration (C-Pt), pro-inflammatory cytokines IL-8 and TNF-α, hematological index with therapeutic effect, adverse reactions and fatigue. The median platinum concentration was higher in patients treated with cisplatin than oxaliplatin (424.0 vs 211.3 μg/L), and the occurrence of fatigue was 64.4% in all subjects. Separately, the incidence and degree of fatigue were 74.1% and 9.5 in the patients with higher platinum concentration compared to 57.1% and 2.0 in the lower group. C-Pt, IL-8 and TNF-α were positively correlated with the degree of CRF, while erythrocyte count and hemoglobin were negatively correlated with the degree of CRF. Mediating effect analysis showed that increased IL-8 concentration mediated 57.4%, while decreased erythrocyte count mediated 24.1% of the C-Pt effect on CRF. Platinum accumulation may involve increasing IL-8, cause inflammation or aggravate anemia, which in combination lead to CRF.
Houttuynia cordata Thunb: An Ethnopharmacological Review
Authors: Wu Zhao , Deng Xinyu , Hu Qichao , Xiao Xiaolin , Jiang Jing , Ma Xiao , Wu Mingquan
Published: September 2021

Houttuynia cordata Thunb (H. cordata; Saururaceae) is widely distributed in Asian regions. It plays an important role in traditional health care and disease treatment, as its aboveground stems and leaves have a long medicinal history in China and are used in the treatment of pneumonia and lung abscess. In clinical treatment, it can usually be combined with other drugs to treat dysentery, cold, fever, and mumps; additionally, H. cordata is an edible plant. This review summarizes detailed information on the phytochemistry and pharmacological effects of H. cordata. By searching the keywords “H. cordata and lung”, “H. cordata and heart”, “H. cordata and liver”, and “H. cordata and inflammation” in PubMed, Web of Science and ScienceDirect, we screened out articles with high correlation in the past ten years, sorted out the research contents, disease models and research methods of the articles, and provided a new perspective on the therapeutic effects of H. cordata. A variety of its chemical constituents are characteristic of medicinal plants, the chemical constituents were isolated from H. cordata, including volatile oils, alkaloids, flavonoids, and phenolic acids. Flavonoids and volatile oils are the main active components. In pharmacological studies, H. cordata showed organ protective activity, such as reducing the release of inflammatory factors to alleviate lung injury. Moreover, H. cordata regulates immunity, enhances the immune barriers of the vagina, oral cavity, and intestinal tract, and combined with the antibacterial and antiviral activity of its extract, effectively reduces pathogen infection. Furthermore, experiments in vivo and in vitro showed significant anti-inflammatory activity, and its chemical derivatives exert potential therapeutic activity against rheumatoid arthritis. Antitumour action is also an important pharmacological activity of H. cordata, and studies have shown that H. cordata has a notable effect on lung tumour, liver tumour, colon tumour, and breast tumour. This review categorizes the biological activities of H. cordata according to modern research papers, and provides insights into disease prevention and treatment of H. cordata.
MicroRNA-21: An Emerging Player in Bone Diseases
Authors: Chen Chen , Liu Ya-Mei , Fu Bin-Lan , Xu Liang-Liang , Wang Bin
Published: September 2021

MicroRNAs (MiRNAs) are small endogenous non-coding RNAs that bind to the 3′-untranslated region of target genes and promote their degradation or inhibit translation, thereby regulating gene expression. MiRNAs are ubiquitous in biology and are involved in many biological processes, playing an important role in a variety of physiological and pathological processes. MiRNA-21 (miR-21) is one of them. In recent years, miR-21 has received a lot of attention from researchers as an emerging player in orthopedic diseases. MiR-21 is closely associated with the occurrence, development, treatment, and prevention of orthopedic diseases through a variety of mechanisms. This review summarizes its effects on osteoblasts, osteoclasts and their relationship with osteoporosis, fracture, osteoarthritis (OA), osteonecrosis, providing a new way of thinking for the diagnosis, treatment and prevention of these bone diseases.
Gut Microbiota Modulation as a Potential Target for the Treatment of Lung Infections
Authors: Cruz Clênio Silva , Ricci Mayra Fernanda , Vieira Angélica Thomaz
Published: September 2021

The gastrointestinal and respiratory systems are colonized by a complex ecosystem of microorganisms called the microbiota. These microorganisms co-evolved over millions of years with the host, creating a symbiotic relationship that is fundamental for promoting host homeostasis by producing bioactive metabolites and antimicrobial molecules, and regulating the immune and inflammatory responses. Imbalance in the abundance, diversity, and function of the gut microbiota (known as dysbiosis) have been shown to increase host susceptibility to infections in the lungs, suggesting crosstalk between these organs. This crosstalk is now referred to as the gut-lung axis. Hence, the use of probiotics, prebiotics, and synbiotics for modulation of gut microbiota has been studied based on their effectiveness in reducing the duration and severity of respiratory tract infections, mainly owing to their effects on preventing pathogen colonization and modulating the immune system. This review discusses the role and responses of probiotics, prebiotics, and synbiotics in the gut-lung axis in the face of lung infections.
Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice
Authors: Zhang Qi , Jin Linbo , Jin Quanxin , Wei Qiang , Sun Mingyuan , Yue Qi , Liu Huan , Li Fangfang , Li Honghua , Ren Xiangshan , Jin Guihua
Published: September 2021

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8+CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8+CTLs. Moreover, DHA impacts STAT3-induced EMT and MMPS in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo. These results have important implications for the potential use of DHA in the treatment of melanoma in humans.
Targeting of Protein’s Messenger RNA for Viral Replication, Assembly and Release in SARS-CoV-2 Using Whole Genomic Data From South Africa: Therapeutic Potentials of Cannabis Sativa L
Authors: Erukainure Ochuko L. , Matsabisa Motlalepula G. , Muhammad Aliyu , Abarshi Musa M. , Amaku James F. , Katsayal Sanusi B. , Nde Adeline Lum
Published: September 2021

The possible evolutionary trend of COVID-19 in South Africa was investigated by comparing the genome of SARS-CoV-2 isolated from a patient in KwaZulu-Natal, South Africa with those isolated from China, Spain, Italy, and United States, as well as the genomes of Bat SARS CoV, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mouse Hepatitis Virus (MHV), and Infectious Bronchitis Virus (IBV). Phylogenetic analysis revealed a strong homology (96%) between the genomes of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from the study countries as well as those isolated from bat SARS CoV, MERS-CoV, MHV and IBV. The ability of phytocannabinoids fromCannabis sativainfusion to interact with gene segments (mRNAs) coding for proteins implicated in viral replication, assembly and release were also investiagted using computational tools. Hot water infusion ofC. sativaleaves was freeze-dried and subjected to Gas Chromatography-Mass Spectroscopy analysis which revealed the presence of tetrahydrocannabivarin, cannabispiran, cannabidiol tetrahydrocannabinol, cannabigerol, and cannabinol. Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids. These results depict the spread of SARS-CoV-2 is intercontinental and might have evolved from other coronaviruses. The results also portray the phytocannabinoids ofC. sativainfusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2. However, further studies are needed to verify these activities in pre-clinical and clinical studies.
Metformin Reduces the Risk of Diverticula of Intestine in Taiwanese Patients with Type 2 Diabetes Mellitus
Authors: Tseng Chin-Hsiao
Published: September 2021

Aim: To investigate the risk of diverticula of intestine associated with metformin use.

Methods: This retrospective cohort study used the Taiwan’s National Health Insurance database to enroll 307,548 ever users and 18,839 never users of metformin. The patients were followed up starting on January 1, 2006 and ending on a date up to December 31, 2011. To address confounding by indication, hazard ratios were derived from Cox regression based on the inverse probability of treatment weighting using propensity score.

Results: During follow-up, newly diagnosed cases of diverticula were identified in 1,828 ever users (incidence rate: 125.59 per 100,000 person-years) and 223 never users (incidence rate: 268.17 per 100,000 person-years). Ever users had an approximately 54% lower risk, as shown by the overall hazard ratio of 0.464 (95% confidence interval 0.404–0.534). While patients categorized in each tertile of cumulative duration of metformin therapy were compared to never users, a dose-response pattern was observed with hazard ratios of 0.847 (0.730–0.983), 0.455 (0.391–0.531) and 0.216 (0.183–0.255) for the first (<27.37 months), second (27.37–59.70 months) and third (>59.70 months) tertiles, respectively. The findings were similar when the diagnosis of diverticula was restricted to the small intestine or to the colon. Subgroup analyses suggested that the lower risk of diverticula of intestine associated with metformin use was significant in all age groups of <50, 50–64 and ≥65 years, but the magnitude of risk reduction attenuated with increasing age.

Conclusion: Metformin treatment is associated with a significantly reduced risk of diverticula of intestine.
High Fidelity Spatial Light Modulator Configuration for Photo-Stimulation
Authors: Aghayee Samira , Weikert Mitchell , Alvarez Phillip , Frank Gabriel A. , Losert Wolfgang
Published: September 2021

For their capacity to shape optical wavefronts in real time into any desired illumination pattern, phase-only Spatial Light Modulators (SLM) have proven to be powerful tools for optical trapping and micromanipulation applications. SLMs are also becoming increasingly utilized in selective photo-stimulation of groups of neurons in the brain. However, conventional SLM based wavefront modulation introduces artifacts that are particularly detrimental for photo-stimulation applications. The primary issue is the unmodulated light that travels along the 0th order of diffraction. This portion of light is commonly blocked at the center of the object plane, which prevents photo-stimulation in the blocked region. We demonstrate a virtual lens configuration that moves the 1st order diffraction with the desired illumination pattern into the Fourier plane of the 0th order light. This virtual lens setup makes the whole field of view accessible for photo-stimulation and eliminates the need for removing the 0th order light in two-photon applications. Furthermore, in an example application to reconstruct a pattern consisting of an array of points, the virtual lens configuration increases the uniformity of the intensities these points. Moreover, diffraction-induced artifacts are also significantly reduced within the target plane. Therefore, our proposed high fidelity configuration yields target points with high signal to noise ratio.
Auto Recognition of Solar Radio Bursts Using the C-DCGAN Method
Authors: Zhang Weidan , Yan Fabao , Han Fuyun , He Ruopu , Li Enze , Wu Zhao , Chen Yao
Published: September 2021

Solar radio bursts can be used to study the properties of solar activities and the underlying coronal conditions on the basis of the present understanding of their emission mechanisms. With the construction of observational instruments, around the world, a vast volume of solar radio observational data has been obtained. Manual classifications of these data require significant efforts and human labor in addition to necessary expertise in the field. Misclassifications are unavoidable due to subjective judgments of various types of radio bursts and strong radio interference in some events. It is therefore timely and demanding to develop techniques of auto-classification or recognition of solar radio bursts. The latest advances in deep learning technology provide an opportunity along this line of research. In this study, we develop a deep convolutional generative adversarial network model with conditional information (C-DCGAN) to auto-classify various types of solar radio bursts, using the solar radio spectral data from the Culgoora Observatory (1995, 2015) and the Learmonth Observatory (2001, 2019), in the metric decametric wavelengths. The technique generates pseudo images based on available data inputs, by modifying the layers of the generator and discriminator of the deep convolutional generative adversarial network. It is demonstrated that the C-DCGAN method can reach a high-level accuracy of auto-recognition of various types of solar radio bursts. And the issue caused by inadequate numbers of data samples and the consequent over-fitting issue has been partly resolved.
A Baseline Model For Estimating the Risk of Gas Embolism in Sea Turtles During Routine Dives
Authors: Robinson Nathan J. , García-Párraga Daniel , Stacy Brian A. , Costidis Alexander M. , Blanco Gabriela S. , Clyde-Brockway Chelsea E. , Haas Heather L. , Harms Craig A. , Patel Samir H. , Stacy Nicole I. , Fahlman Andreas
Published: September 2021

Sea turtles, like other air-breathing diving vertebrates, commonly experience significant gas embolism (GE) when incidentally caught at depth in fishing gear and brought to the surface. To better understand why sea turtles develop GE, we built a mathematical model to estimate partial pressures of N2 (PN2), O2 (PO2), and CO2 (PCO2) in the major body-compartments of diving loggerheads (Caretta caretta), leatherbacks (Dermochelys coriacea), and green turtles (Chelonia mydas). This model was adapted from a published model for estimating gas dynamics in marine mammals and penguins. To parameterize the sea turtle model, we used values gleaned from previously published literature and 22 necropsies. Next, we applied this model to data collected from free-roaming individuals of the three study species. Finally, we varied body-condition and cardiac output within the model to see how these factors affected the risk of GE. Our model suggests that cardiac output likely plays a significant role in the modulation of GE, especially in the deeper diving leatherback turtles. This baseline model also indicates that even during routine diving behavior, sea turtles are at high risk of GE. This likely means that turtles have additional behavioral, anatomical, and/or physiologic adaptions that serve to reduce the probability of GE but were not incorporated in this model. Identifying these adaptations and incorporating them into future iterations of this model will further reveal the factors driving GE in sea turtles.
Exploring the Anthropometric, Cardiorespiratory, and Haematological Determinants of Marathon Performance
Authors: Christou Georgios A. , Pagourelias Efstathios D. , Deligiannis Asterios P. , Kouidi Evangelia J.
Published: September 2021

Aim

We aimed to investigate the main anthropometric, cardiorespiratory and haematological factors that can determine marathon race performance in marathon runners.

Methods

Forty-five marathon runners (36 males, age: 42 ± 10 years) were examined during the training period for a marathon race. Assessment of training characteristics, anthropometric measurements, including height, body weight (n = 45) and body fat percentage (BF%) (n = 33), echocardiographic study (n = 45), cardiopulmonary exercise testing using treadmill ergometer (n = 33) and blood test (n = 24) were performed. We evaluated the relationships of these measurements with the personal best marathon race time (MRT) within a time frame of one year before or after the evaluation of each athlete.

Results

The training age regarding long-distance running was 9 ± 7 years. Training volume was 70 (50–175) km/week. MRT was 4:02:53 ± 00:50:20 h. The MRT was positively associated with BF% (r = 0.587, p = 0.001). Among echocardiographic parameters, MRT correlated negatively with right ventricular end-diastolic area (RVEDA) (r = −0.716, p < 0.001). RVEDA was the only independent echocardiographic predictor of MRT. With regard to respiratory parameters, MRT correlated negatively with maximum minute ventilation indexed to body surface area (VEmax/BSA) (r = −0.509, p = 0.003). Among parameters of blood test, MRT correlated negatively with haemoglobin concentration (r = −0.471, p = 0.027) and estimated haemoglobin mass (Hbmass) (r = −0.680, p = 0.002). After performing multivariate linear regression analysis with MRT as dependent variable and BF% (standardised β = 0.501, p = 0.021), RVEDA (standardised β = −0.633, p = 0.003), VEmax/BSA (standardised β = 0.266, p = 0.303) and Hbmass (standardised β = −0.308, p = 0.066) as independent variables, only BF% and RVEDA were significant independent predictors of MRT (adjusted R2 = 0.796, p < 0.001 for the model).

Conclusions

The main physiological determinants of better marathon performance appear to be low BF% and RV enlargement. Upregulation of both maximum minute ventilation during exercise and haemoglobin mass may have a weaker effect to enhance marathon performance.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT04738877.
RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice
Authors: Lee Kyuwon , Yu Hyeonju , Shouse Stephanie , Kong Byungwhi , Lee Jihye , Lee Seong-Ho , Ko Kwang Suk
Published: September 2021

Prohibitin 1 (PHB1) is an evolutionarily conserved and ubiquitously expressed protein that stabilizes mitochondrial chaperone. Our previous studies showed that liver-specific Phb1 deficiency induced liver injuries and aggravated lipopolysaccharide (LPS)-induced innate immune responses. In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1−/−, Phb1+/−, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/− and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/− compared with WT. Diseases and biofunctions analyses conducted by IPA verified that hepatic system diseases, including liver fibrosis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death, which may be caused by hepatotoxicity, were highly associated with liver-specific Phb1 deficiency in mice. Interestingly, of liver disease-related 5 DE genes between Phb1+/− and WT, the mRNA expressions of forkhead box M1 (Foxm1) and TIMP inhibitor of metalloproteinase (Timp1) were matched with validation for RNA-seq in liver tissues and AML12 cells transfected with Phb1 siRNA. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with hepatic Phb1.
Metabolic Cost of the Immune Response During Early Ontogeny of the Scallop Argopecten purpuratus
Authors: Rojas Isis , Rivera-Ingraham Georgina A. , Cárcamo Claudia B. , Jeno Katherine , de la Fuente-Ortega Erwin , Schmitt Paulina , Brokordt Katherina
Published: September 2021

The scallop Argopecten purpuratus is an important resource for Chilean and Peruvian aquaculture. Seed availability from commercial hatcheries is critical due to recurrent massive mortalities associated with bacterial infections, especially during the veliger larval stage. The immune response plays a crucial role in counteracting the effects of such infections, but being energetically costly, it potentially competes with the physiological and morphological changes that occur during early development, which are equally expensive. Consequently, in this study, energy metabolism parameters at the individual and cellular levels, under routine-basal status and after the exposure to the pathogenic strain bacteria (Vibrio splendidus VPAP18), were evaluated during early ontogeny (trochophore, D-veliger, veliger, pediveliger, and early juveniles) of A. purpuratus. The parameters measured were as follows: (1) metabolic demand, determined as oxygen consumption rate and (2) ATP supplying capacity measured by key mitochondrial enzymes activities [citrate synthase (CS), electron transport system (ETS), and ETS/CS ratio, indicative of ATP supplying efficiency], mitochondrial membrane potential (ΔΨm), and mitochondrial density (ρm) using an in vivo image analysis. Data revealed that metabolic demand/capacity varies significantly throughout early development, with trochophores being the most efficient in terms of energy supplying capacity under basal conditions. ATP supplying efficiency decreased linearly with larval development, attaining its lowest level at the pediveliger stage, and increasing markedly in early juveniles. Veliger larvae at basal conditions were inefficient in terms of energy production vs. energy demand (with low ρm, ΔΨm, enzyme activities, and ETS:CS). Post-challenged results suggest that both trochophore and D-veliger would have the necessary energy to support the immune response. However, due to an immature immune system, the immunity of these stages would rely mainly on molecules of parental origin, as suggested by previous studies. On the other hand, post-challenged veliger maintained their metabolic demand but decreased their ATP supplying capacity, whereas pediveliger increased CS activity. Overall, results suggest that veliger larvae exhibit the lowest metabolic capacity to overcome a bacterial challenge, coinciding with previous works, showing a reduced capacity to express immune-related genes. This would result in a higher susceptibility to pathogen infection, potentially explaining the higher mortality rates occurring during A. purpuratus farming.
Airway Sensory Nerve Plasticity in Asthma and Chronic Cough
Authors: Drake Matthew G. , Cook Madeline , Fryer Allison D. , Jacoby David B. , Scott Gregory D.
Published: September 2021

Airway sensory nerves detect a wide variety of chemical and mechanical stimuli, and relay signals to circuits within the brainstem that regulate breathing, cough, and bronchoconstriction. Recent advances in histological methods, single cell PCR analysis and transgenic mouse models have illuminated a remarkable degree of sensory nerve heterogeneity and have enabled an unprecedented ability to test the functional role of specific neuronal populations in healthy and diseased lungs. This review focuses on how neuronal plasticity contributes to development of two of the most common airway diseases, asthma and chronic cough, and discusses the therapeutic implications of emerging treatments that target airway sensory nerves.
A Simple Method for Automatic 3D Reconstruction of Coronary Arteries From X-Ray Angiography
Authors: Hwang Minki , Hwang Sa-Bin , Yu Hyosang , Kim Jaehyeok , Kim Daehyun , Hong Wonjae , Ryu Ah-Jin , Cho Han Yong , Zhang Jinlong , Koo Bon Kwon , Shim Eun Bo
Published: September 2021

Automatic three-dimensional (3-D) reconstruction of the coronary arteries (CA) from medical imaging modalities is still a challenging task. In this study, we present a deep learning-based method of automatic identification of the two ends of the vessel from X-ray coronary angiography (XCA). We also present a method of using template models of CA in matching the two-dimensional segmented vessels from two different angles of XCA. For the deep learning network, we used a U-net consisting of an encoder (Resnet) and a decoder. The two ends of the vessel were manually labeled to generate training images. The network was trained with 2,342, 1,907, and 1,523 labeled images for the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), respectively. For template models of CA, ten reconstructed 3-D models were averaged for each artery. The accuracy of correspondence using template models was compared with that of manual matching. The deep learning network pointed the proximal region (20% of the total length) in 97.7, 97.5, and 96.4% of 315, 201, and 167 test images for LAD, LCX, and RCA, respectively. The success rates in pointing the distal region were 94.9, 89.8, and 94.6%, respectively. The average distances between the projected points from the reconstructed 3-D model to the detector and the points on the segmented vessels were not statistically different between the template and manual matchings. The computed FFR was not significantly different between the two matchings either. Deep learning methodology is feasible in identifying the two ends of the vessel in XCA, and the accuracy of using template models is comparable to that of manual correspondence in matching the segmented vessels from two angles.
Nordic Walking at Maximal Fat Oxidation Intensity Decreases Circulating Asprosin and Visceral Obesity in Women With Metabolic Disorders
Authors: Kantorowicz Malgorzata , Szymura Jadwiga , Szygula Zbigniew , Kusmierczyk Justyna , Maciejczyk Marcin , Wiecek Magdalena
Published: September 2021

Objective

Excess visceral adipose tissue is associated with insulin resistance and other metabolic disorders, including deregulation of adipokine secretion, which may be corrected by aerobic exercise training. Asprosin is a novel adipokine responsible for the regulation of appetite and the release of glucose from the liver, and its levels are pathologically elevated in obesity. The aim of the study was to evaluate the effects of 8-week Nordic walking (NW) training at maximal fat oxidation intensity (FATmax) on changes in body mass, as well as those in insulin resistance and asprosin levels among young women with visceral obesity and metabolic disorders.

Materials and Methods

The study was completed by 14 women (30.14 ± 3.63 years) representing low levels of physical activity, visceral obesity (waist circumference 105.50 ± 14.87 cm, BMI 33.85 ± 5.48 kg/m2) and with metabolic disorders, who for 8 weeks (three times a week, 60 min), participated in NW training at the FATmax intensity (61.92 ± 6.71% HRmax, 42.33 ± 8.69% VO2max) controlled on the basis of heart rate (114.21 ± 14.10 bpm).

Results

After 4 and 8 weeks of NW training, a significant decrease in the concentration of asprosin, waist and hip circumference (HC), waist-to-height ratio and body adiposity index (BAI) (p < 0.05, large effect size) were found.

Conclusion

The 8-week NW training at an FATmax intensity decreases the concentration of asprosin in the blood as well as visceral obesity in young women with metabolic disorders.
Mitochondrial tRNA-Derived Fragments and Their Contribution to Gene Expression Regulation
Authors: Shaukat Athanasios-Nasir , Kaliatsi Eleni G. , Stamatopoulou Vassiliki , Stathopoulos Constantinos
Published: September 2021

Mutations in human mitochondrial tRNAs (mt-tRNAs) are responsible for several and sometimes severe clinical phenotypes, classified among mitochondrial diseases. In addition, post-transcriptional modifications of mt-tRNAs in correlation with several stress signals can affect their stability similarly to what has been described for their nuclear-encoded counterparts. Many of the perturbations related to either point mutations or aberrant modifications of mt-tRNAs can lead to specific cleavage and the production of mitochondrial tRNA-derived fragments (mt-tRFs). Although mt-tRFs have been detected in several studies, the exact biogenesis steps and biological role remain, to a great extent, unexplored. Several mt-tRFs are produced because of the excessive oxidative stress which predominantly affects mitochondrial DNA integrity. In addition, mt-tRFs have been detected in various diseases with possible detrimental consequences, but also their production may represent a response mechanism to external stimuli, including infections from pathogens. Finally, specific point mutations on mt-tRNAs have been reported to impact the pool of the produced mt-tRFs and there is growing evidence suggesting that mt-tRFs can be exported and act in the cytoplasm. In this review, we summarize current knowledge on mitochondrial tRNA-deriving fragments and their possible contribution to gene expression regulation.