bluuebunny/crossref_metadata_2025 huggingface dataset:
Open-label, dose-escalation phase 1a study of SPH5030, a tyrosine kinase inhibitor (TKI) targeting HER2, in patients with HER2 positive advanced solid tumors.
Authors: Wang Jiayu , Wang Wenna , Tong Zhongsheng , Shi Yehui , Shi Yanxia , Zheng Qiufan , Yu Shunjiang , Cao Yuanyuan , Xie Ning , Fan Jianru , Xu Binghe
Published: June 2024

3117

Background: Although existing HER2-targeted agents have driven treatment strategies of HER2-overexpressed advanced solid tumor, unmet need still occurred in clinical setting. SPH5030, is a novel tyrosine kinase inhibitor targeting HER2, with a modified structure from tucatinib and pyrotinib. It has advantages such as target selectivity of tucatinib and the irreversible inhibitory effect of pyrotinib. Methods: This Phase Ia, open-label, multi-center study was conducted to evaluate the safety, pharmacokinetics and preliminary activity of SPH5030 in patients (pts) with HER2-positive advanced solid tumor. A 3+3 dose-escalation was conducted with six dose levels of SPH5030 (50,100,200,300,400,600 mg) administered orally once every day (QD) to evaluate dose limiting toxicity (DLT). Adverse events were assessed using CTCAE V5.0; tumor response per RECIST 1.1 every 6 weeks. Results: As of Feb 2, 2024, 30 pts were enrolled with a median age of 51 years, including 28 (93.3%) pts with breast cancer (BC) and 2 (6.7%) pts with colorectal cancer (CRC). All pts were heavily treated with a median of 4 (range, 1-9) prior lines of therapy. All the 28 BC pts received previous anti-HER2 therapy, and 23 of them received anti-HER2-TKI therapy. Treatment-emerged adverse events (TEAEs) and ≥grade (G) 3 TEAEs occurred in 30 pts (100.0%) and 10 pts (33.3%), respectively. Treatment-related adverse events (TRAEs) and ≥G3 TRAEs occurred in 28 pts (93.3%) and 8 pts (26.7%), respectively; the most common TRAEs (≥20%) were diarrhea (66.7%, 16.7% ≥ G3), creatinine increased (30.0%, 0% ≥ G3), hypokalemia (23.3%, 3.3% ≥ G3), fatigue (23.3%, 3.3% ≥ G3), AST increased (20.0%, 0% ≥ G3), and bilirubin increased (20.0%, 0% ≥ G3). One in 6 pts receiving 600 mg dose experienced a DLT (diarrhea, G3). SPH5030 plasma exposures from single-dose and steady-state showed a proportional dose increase, but absorption of SPH5030 was found to reach a plateau from 400 to 600mg. Of the 28 evaluable pts for efficacy (BC = 26, CRC = 2),6 pts (21.4%) achieved partial response (PR, BC = 5, CRC = 1), while 16 pts (57.1%) achieved stable disease (4 pts SD≥ 24 weeks,14.3%). Objective response rate (ORR) was 21.4%, disease control rate was 78.6%, and clinical benefit rate was 35.7%. Three pts in the 600 mg dose group achieved PR, with ORR of 50.0%. Conclusions: This study demonstrated that SPH5030 was well tolerated at doses ranging from 50 to 600mg. A dose of 600 mg QD regimen could be considered for further clinical trials. Clinical trial information: NCT05245058 .
Socioeconomic disparities in survival outcomes of patients with SCLC with brain metastases: A nationwide analysis.
Authors: Bellur Shreyas S , Jayram Diya , Ahmad Shahzaib , Bhat Vivek , Ozair Ahmad , Ganiyani Mohammad Arfat , Khosla Atulya Aman , Podder Vivek , Ahluwalia Manmeet Singh
Published: June 2024

e20133

Background: Despite advances in the management of cancer, socioeconomic disparities have been reported to impact survival outcomes. However, recent state of disparities in SCLC patients with brain metastases (BM) remains unknown. We explored socioeconomic disparities in survival outcomes of SCLC BM patients. Methods: We conducted a retrospective cohort study and included patients diagnosed with SCLC BM in 2018-2019 in the National Cancer Database. Patients were grouped as White, Black, American Indian, Aleutian or Pacific Islander (AAPI), or Asian. Socioeconomic and survival outcomes were analyzed and reported using median overall survival (mOS) (95% CI). Cox proportional hazard models adjusted for sex, race, facility type, education, and income and reported using hazard ratios for death (HR) (95% CI). Results: Of 2369 SCLC BM patients, 85% (N=2018) were White, 11% (N=259) Black, 0.4% (N=10), and 1.8% (N=43) Asian. 58% were Medicare-insured, and 21% earned >$74,063. 40% were treated at comprehensive cancer care centers (CCC). Log-rank test revealed no significant difference in survival between races. Hispanic did not have a significant survival benefit compared to non-Hispanic patients. Medicare-insured patients have a significantly worse mOS of 7.56 months (6.90-8.28) compared to 13.77 months (12.62-16.07) in private-insured patients. Cox multivariate analysis (Table) showed improved survival in Asian (HR - 0.55, 0.34-0.89, P=0.014) and Black (HR- 0.82, 0.69-0.98, P=0.029) compared to White patients. Patients treated at CCCC had worse survival (HR-1.26, 1.11-1.42, P<0.001) than in academic centers. Patients who earn more reported higher survival (HR-0.82, 0.68-0.98, P=0.030). Conclusions: Race did not significantly impact survival based on unadjusted analysis. Medicare-insured patients have unfavorable outcomes. On adjusted analysis, Asian and Black patients appear to have better survival. Treatment at community centers has worse survival. Focused efforts are warranted to bridge this gap and reduce disparities due to socioeconomic factors. [Table: see text]
Clinical outcomes, demographics and associative analysis of lung cancer patients with Lambert-Eaton myasthenic syndrome: Insights from the National Inpatient Sample (NIS) database.
Authors: Laxmidhar Fehmida , Patel Rushin , Patel Darshil , Patel Zalak , Patel Mrunal , Lakhatariya Khushboo , Gadhiya Dhruvkumar
Published: June 2024

e20134

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder that may present as a paraneoplastic syndrome or a primary autoimmune disorder. Approximately 60% of LEMS patients have an underlying tumor, with the paraneoplastic form predominantly associated with small cell lung cancer (SCLC). Understanding the clinical outcomes and risks associated in lung cancer patients with LEMS is crucial in effective management of such patients. Methods: This retrospective study utilized inpatient hospitalization data from the National Inpatient Sample (NIS) between January 1, 2016, and December 31, 2019. Data of patients with a primary or secondary discharge diagnosis of lung cancer (ICD10-CM codes C34, C78.0, C46.5, D02.2) were obtained. Then, out of this population, we identified Lambert-Eaton myasthenic syndrome with ICD-10 codes (G70.80, G70.81, G73.1). The objective was to run a descriptive analysis of clinical outcomes, risks, demographics and associations of LEMS in patients with lung cancer. Results: A total of 204 cases of lung cancer hospitalizations with LEMS were analyzed. The mean age was 68.23 years, with a slight female (51.72%) preponderance as compared to male (48.28%). Race distribution revealed increased prevalence in White Caucasians (83%), followed by Black (7%), Hispanic (4.5%), Asian or Pacific Islander (3%), Native American (0.5%), and Other (2%). The majority were covered by Medicare (66.33%), followed by private insurance (26.13%). The mortality rate was 8.9%, with a mean length of stay of 10.35 days and mean hospital charges of $118,676. Clinical outcomes and risks were analyzed, with sepsis occurring in 17.6% of cases, pneumonia in 22.5%, and acute respiratory failure in 26.9%. Intubation/mechanical ventilation was necessary in 18.1% of cases. The incidence of urinary tract infection (UTI) was 16.7%, acute kidney injury (AKI) was 17.2%, and venous thromboembolism (VTE) was 6.4%. Additionally, interventions such as intravenous immunoglobulin (IVIG) therapy and blood transfusions were also noted. Conclusions: This study provides insights into the demographic characteristics and clinical outcomes of lung cancer patients with Lambert-Eaton myasthenic syndrome (LEMS). The findings highlight the need for comprehensive management strategies targeting associated complications like acute respiratory failure, intubation and need for mechanical ventilation, pneumonia, UTI, AKI, and VTE to improve patient outcomes, quality of care and effective patient education with regards to their diagnosis of LEMS in lung cancer.
Real world outcomes of patients with small cell lung cancer (SCLC) presenting with brain metastasis at diagnosis in a single institution health system.
Authors: Joseph Julia K. , Matera Robert M , Park Henry Soo-Min , Chiang Veronica , Chiang Anne C.
Published: June 2024

e20136

Background: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive lung cancer subtype with high propensity for brain metastases (mets). Despite this, there is no consensus on the treatment of brain mets especially in the setting of frontline chemoimmunotherapy and advanced radiation techniques like Gamma Knife radiosurgery (GKRS). Methods: In this single-institution retrospective study, we queried the Yale Tumor registry for all patients diagnosed with ES-SCLC in 1/2016-4/2023. Patients with brain mets at the time of presentation were identified and underwent manual chart review for abstraction of clinical information specifically pertaining to brain mets and treatment modalities. Survival outcomes including median progression free survival (mPFS), median central nervous system-progression free survival (mcPFS) and median overall survival (mOS) measured in months were also captured. Results: 423 ES-SCLC patients were identified. Of those, 92 (22%) had brain mets at initial presentation and were reviewed. 44 (48%) of patients with brain mets were treated with frontline chemotherapy (platinum doublet) while 42 (46%) were treated with chemoimmunotherapy (platinum doublet with atezolizumab or durvalumab). Patients treated with upfront chemotherapy had mPFS 6.4 (95% CI -1.2, 14.1), mcPFS 7.7 (95% CI -1.2, 17.1), and mOS 9.3 (95% CI -13.7, 36.4), compared to patients treated with chemoimmunotherapy, who had mPFS 4.9 (p=0.23; 95% CI -3.5, 15.4), mcPFS 6.7 (p=0.99; 95% CI 3.3, 20.8), and mOS 7.7 (p=0.89; 95% CI -11.4, 33.9). 63 (68%) of patients underwent upfront brain radiation. 44 (48%) had whole brain radiation (WBRT) while 19 (30%) underwent GKRS. Of the patients undergoing GKRS, 8 (42%) were symptomatic. 7 patients (37%) presented with 1 brain met, and 12 (63%) patients presented with 2-5 brain mets. For patients treated with GKRS, mPFS 6.8 (95% CI 2.3, 10.4), mcPFS 7.2 (95% CI 2.9, 12.6), and mOS 11.1 (95% CI -13.0, 40.9). For patients undergoing WBRT, mPFS 6.5 (p = 1.0; 95% CI -4.5, 20.2), mcPFS 6.5 (p = 0.96; 95% CI -3.9, 21.6), and mOS 8.6 (p = 0.21; 95% CI -17.7, 39.9). Conclusions: GKRS is a viable option for SCLC patients presenting with brain metastases, especially in those with a low number of mets. Further studies are required to determine the optimal ES-SCLC candidates for upfront GKRS. [Table: see text]
Gestational Age-specific Reference Intervals for Androgens in Pregnancy
Authors: Lau So Ling , Yuen Lai Yuk , Ho Chung Shun , Chan Michael Ho Ming , Ma Ronald Ching Wan , Tam Wing Hung
Published: June 2024

Background

Androgen could impact cervical remodeling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism.

Methods

We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models.

Results

A4 and TT levels increased across the gestation, and they closely correlated with each other (R = .90, P = <.001), whereas the 17-OHP level decreased from the 5th gestational week to the 16th gestational week and then increased afterward toward the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with P≤ .01, whereas mothers carrying male vs female fetuses have comparable levels of A4, TT, and 17-OHP.

Conclusion

The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE.
microRNA-guided immunity against respiratory virus infection in human and mouse lung cells
Authors: Shibamoto Ayaka , Kitsu Yoshiaki , Shibata Keiko , Kaneko Yuka , Moriizumi Harune , Takahashi Tomoko
Published: June 2024

Viral infectivity depends on multiple factors. Recent studies showed that the interaction between viral RNAs and endogenous microRNAs (miRNAs) regulates viral infectivity; viral RNAs function as a sponge of endogenous miRNAs and result in upregulation of its original target genes, while endogenous miRNAs target viral RNAs directly and result in repression of viral gene expression. In this study, we analyzed the possible interaction between parainfluenza virus RNA and endogenous miRNAs in human and mouse lungs. We showed that the parainfluenza virus can form base pairs with human miRNAs abundantly than mouse miRNAs. Furthermore, we analyzed that the sponge effect of endogenous miRNAs on viral RNAs may induce the upregulation of transcription regulatory factors. Then, we performed RNA-sequence analysis and observed the upregulation of transcription regulatory factors in the early stages of parainfluenza virus infection. Our studies showed how the differential expression of endogenous miRNAs in lungs could contribute to respiratory virus infection and species- or tissue-specific mechanisms and common mechanisms could be conserved in humans and mice and regulated by miRNAs during viral infection.
Linking in vivo muscle dynamics to force–length and force–velocity properties reveals that guinea fowl lateral gastrocnemius operates at shorter than optimal lengths
Authors: Janneke Schwaner M. , Mayfield Dean L. , Azizi Emanuel , Daley Monica A.
Published: June 2024

The isometric force–length (F–L) and isotonic force–velocity (F–V) relationships characterize the contractile properties of skeletal muscle under controlled conditions, yet it remains unclear how these properties relate to in vivo muscle function. Here, we map the in situ F–L and F–V characteristics of guinea fowl (Numida meleagris) lateral gastrocnemius (LG) to the in vivo operating range during walking and running. We test the hypothesis that muscle fascicles operate on the F–L plateau, near the optimal length for force (L0) and near velocities that maximize power output (Vopt) during walking and running. We found that in vivo LG velocities are consistent with optimizing power during work production, and economy of force at higher loads. However, LG does not operate near L0 at higher loads. LG length was near L0 at the time of electromyography (EMG) onset but shortened rapidly such that force development during stance occurred on the ascending limb of the F–L curve, around 0.8L0. Shortening across L0 in late swing might optimize potential for rapid force development near the swing–stance transition, providing resistance to unexpected perturbations that require rapid force development. We also found evidence of in vivo passive force rise in late swing, without EMG activity, at lengths where in situ passive force is zero, suggesting that dynamic viscoelastic effects contribute to in vivo force development. Comparison of in vivo operating ranges with F–L and F–V properties suggests the need for new approaches to characterize muscle properties in controlled conditions that more closely resemble in vivo dynamics.
Chronic changes in developmental oxygen have little effect on mitochondria and tracheal density in the endothermic moth Manduca sexta
Authors: Wilmsen Sara M. , Dzialowski Edward M.
Published: June 2024

Oxygen availability during development is known to impact the development of insect respiratory and metabolic systems. Drosophila adult tracheal density exhibits developmental plasticity in response to hypoxic or hyperoxic oxygen levels during larval development. Respiratory systems of insects with higher aerobic demands, such as those that are facultative endotherms, may be even more responsive to oxygen levels above or below normoxia during development. The moth Manduca sexta is a large endothermic flying insect that serves as a good study system to start answering questions about developmental plasticity. In this study, we examined the effect of developmental oxygen levels (hypoxia: 10% oxygen, and hyperoxia: 30% oxygen) on the respiratory and metabolic phenotype of adult moths, focusing on morphological and physiological cellular and intercellular changes in phenotype. Mitochondrial respiration rate in permeabilized and isolated flight muscle was measured in adults. We found that permeabilized flight muscle fibers from the hypoxic group had increased mitochondrial oxygen consumption, but this was not replicated in isolated flight muscle mitochondria. Morphological changes in the trachea were examined using confocal imaging. We used transmission electron microscopy to quantify muscle and mitochondrial density in the flight muscle. The respiratory morphology was not significantly different between developmental oxygen groups. These results suggest that the developing M. sexta trachea and mitochondrial respiration have limited developmental plasticity when faced with rearing at 10% or 30% oxygen.
O impacto da depressão pós-parto no desenvolvimento cognitivo infantil
Authors: Araújo Antônio César Costa , Alves Elisa Isabella Rodrigues , Araújo Julyana Alcantara Silva de , Oliveira Matheus Felipe de , Mendes Nícolas Ventura da Silva , Duarte Pedro Lucas Silveira , Zanuzzi Tamara Rodrigues Lima , Oliveira Fábio Morato de
Published: June 2024

Objetivo: avaliar as consequências da depressão pós-parto no desenvolvimento cognitivo infantil. Métodos: trata-se de uma revisão narrativa, com caráter analítico quantitativo, realizada por meio da busca de artigos científicos publicados, nas plataformas Google Acadêmico, Scielo e PubMed, sobre a relação entre depressão pós-parto e desenvolvimento infantil. Resultados: foi selecionado um total de 23 artigos entre os três bancos de dados. Os resultados apontam que filhos de mães deprimidas são mais propensos a ter alterações no desenvolvimento cognitivo, social e linguístico do que filhos de mães não deprimidas. Entretanto, deve-se lembrar que essa alteração não acontece exclusivamente pela depressão pós-parto, uma vez que ela pode estar associada a outros fatores de risco, como condições socioeconômicas e apoio marital. Conclusão: a depressão pós-parto como fator isolado afeta o bebê de maneira sutil, mas, diante de diversos fatores ambientais e conduta parental, o efeito nocivo pode ser intensificado, o que pode prejudicar os desempenhos nos testes cognitivos, de atenção e aprendizagem. Desse modo, compreende-se que é importante incentivar um acompanhamento pré-natal que valorize a saúde mental das gestantes, para que qualquer manifestação psicológica negativa seja prontamente identificada e receba o apoio necessário o mais rápido possível.
Self-transcendence and the dialectic of the finite-infinite in the philosophy of Bernard Bosanquet
Authors: Παναγάκου Σταματούλα
Published: June 2024

Η διδακτορική μου διατριβή προσφέρει μια νέα ερμηνεία της φιλοσοφίας του Βρετανού Ιδεαλιστή φιλοσόφου Bernard Bosanquet (1848-1923). Η ανάλυσή μου εστιάζει σε ζητήματα πολιτικής φιλοσοφίας, ηθικής, θρησκείας, μεταφυσικής και οντολογίας στο έργο του Bosanquet. Καταδεικνύει τη σημασία της λογικής και μεταφυσικής θεώρησης του Bosanquet για την ορθή κατανόηση και αποτίμηση της ηθικής, κοινωνικής και πολιτικής του φιλοσοφίας. Οι θεμελιώδεις αρχές που στηρίζουν την ανάλυσή μου πηγάζουν από τη φιλοσοφία του Bosanquet και κυρίως από τα έργα του The Principle of Individuality and Value (London: Macmillan, 1912) και The Value and Destiny of the Individual (London: Macmillan, 1913). Πρόκειται για (α) την αρχή της αυτό-υπέρβασης και (β) την αρχή της διαλεκτικής του πεπερασμένου – απείρου. Οι αρχές αυτές συνεπικουρούνται από τα εννοιολογικά σύνολα της «μεταφυσικής του εαυτού» και της «γενεαλογίας του εαυτού» οι οποίες βοηθούν στην κατανόηση της οντολογικής δυναμικής του ατόμου στο περιβάλλον των ηθικών, αισθητικών και κοινωνικοπολιτικών αλληλεπιδράσεών του με την πνευματική και υλική ολότητα της οποίας είναι αναπόσπαστο τμήμα. Το πρώτο κεφάλαιο είναι αφιερωμένο στην ανάλυση της θεωρίας της ατομικότητας και υποστηρίζεται ότι η αυτό-υπέρβαση είναι δυνατή λόγω της διαλεκτικής σχέσης του πεπερασμένου – απείρου που χαρακτηρίζει την ανθρώπινη οντολογία και καθορίζεται στην πνευματικότητα του ανθρώπου. Στο δεύτερο και τρίτο κεφάλαιο διερευνώ τη σύνδεση θρησκείας και ηθικής (θρησκευτικής και ηθικής συνείδησης) που επεξεργάζεται ο Bosanquet στη φιλοσοφία του. Η θεώρηση της θρησκείας του Bosanquet είναι συνδεδεμένη με τη μεταφυσική του εαυτού και την επίτευξη της ιδέας του αγαθού στον ατομικό και κοινωνικό βίο. Στη συνέχεια επεξεργάζομαι εκτενώς τη σχέση φιλοσοφίας της θρησκείας και ηθικής στην πραγματεία του Bosanquet, What Religion Is (London: Macmillan, 1920). Το τέταρτο κεφάλαιο είναι αφιερωμένο στη διαφωνία μεταξύ του Bosanquet και του Honbhouse σχετικά με τη φιλοσοφική θεωρία του κράτους που διατύπωσε ο Bosanquet στο magnum opus της πολιτικής του φιλοσοφίας, The Philosophical Theory of the State (1899). Στόχος μου είναι η υπεράσπιση της φιλοσοφίας του κράτους του Bosanquet από τις άδικες και ανεδαφικές κατηγορίες του Hobhouse και η διερεύνηση της σχέσης ατόμου και κράτους στην πολιτειολογία του Bosanquet. Ανατρέπω τον ισχυρισμό του Hobhouse ότι ο Bosanquet θεωρεί το κράτος αυτοσκοπό (an end in itself) επισημαίνοντας ότι ο Bosanquet ορίζει ξεκάθαρα στο έργο του The Philosophical Theory of the State ότι ο σκοπός του κράτους, της κοινωνίας, και του ατόμου είναι η επίτευξη του ορθού βίου στο πλαίσιο της πολιτικής κοινωνίας, δηλαδή του βίου που συνδυάζει αρμονικά το καλό του ατόμου με το κοινό καλό.
Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan
Authors: Adam Mosab , Shen Hongwei , Enan Khalid-A , Wang Hao , Musa Azza B. Musa , El Hussein Abdel R. , Khidir Isam M. , Ma Xuejun
Published: June 2024

Introduction Diarrhea is a significant health problem in the Third World. Identification of the pathogen that causes diarrhea is vital for measures to prevent and control this disease. There are also very few reports of diarrhea in Sudan. Our study aimed to determine the Prevalence of specific protozoan pathogens (Entamoeba histolytica, Cryptosporidium parvum., and Giardia spp) in children in Khartoum, Sudan. Methods We conducted a cross-sectional survey among children under five years of age who were hospitalized with acute diarrhea between April and December 2014. Diarrheal stool samples were collected and E. histolytica, C. parvum, and Giardia spp were examined using multiplex real-time PCR. Results Four hundred and thirty-seven children with acute diarrheawere included in this study; the higher Prevalence of diarrhea was in the age less than ≤ 2 years old (403,92.2%). The male-to-female ratio in this study was 1:1.7. infection with intestinal parasite was found in 155 (35.5%) cases, and co-infection was detected in 16 (10.3%) cases. Giardia spp(18.8%) and C. parvum (15.8 %) were the most frequently identified parasites, followed by E. histolytica (0.9). The parasite infection rate was highest and lowest in the under 2-year-old group (92.3%) and the 2–4-year-old group (7.3%). The infection rate was higher in boys (67.1%) than in girls (32.9%). The incidence of protozoan infection was higher in the rainy season (August to December) (92.2%), corresponding with that in the dry Season (April to June). (7.8%). Discussion Our present study demonstrated the high prevalence of Giardia spp and C. parvum in children with diarrhea in the Khartoum region and the usefulness of the multiplex real-time method in disclosing pathogenic protozoal agents. Our result highlighted the necessity of developing intervention measurement and control strategies to deal with childhood parasitic diarrhea in this region.
Cigarette smoke alters circRNA expression in human T-cells
Authors: Hong So Jin , Liao Zhaohao , Witwer Kenneth W. , Russell Ashley E.
Published: June 2024

Circular RNAs (circRNAs), once thought to be a result of splicing errors, have been found to be involved in various molecular processes and the pathology of various diseases, including cancer and neurodegenerative diseases. Additionally, circRNA expression was found to be altered by lifestyle habits, such as smoking cigarettes. Past studies have revealed that the rate of smoking remains high in people living with human immunodeficiency virus (HIV). In this study, we isolated total RNA from uninfected T-cells that have been exposed to cigarette smoke and compared the expression levels of circRNAs to those of T-cells that were not exposed to cigarette smoke. We identified certain circRNAs that were upregulated or downregulated in T-cells when exposed to cigarette smoke. These data indicate that the study of circRNAs is warranted within the context of HIV.
Securing data on the move
Authors: Vanover Rick
Published: June 2024

Organisations are not only moving much of their data to the cloud, many are adopting hybrid or multi-cloud models. This can result in a lot of data being on the move at any given time. But enabling that kind of data portability is not simple, especially when it comes to making sure it’s secure.
The Future of Off-Highway: What Lies Ahead?
Authors: Smith David
Published: June 2024

AS 2023 DREW TO A CLOSE IVT CELEBRATED COMPLETING ITS 30TH YEAR. BUT RATHER THAN LOOKING BACK, WE DECIDED TO DO WHAT WE’VE ALWAYS DONE BEST AND LOOK FORWARD – PREDICTING WHAT’S NEXT FOR THE OFF-HIGHWAY INDUSTRY IN THE YEARS AND DECADES TO COME. OVER THE FOLLOWING PAGES FOUR SEASONED INDUSTRY SPECIALISTS – OEM VETERAN, ACADEMIC, FUTURIST AND ANALYST – TELL US WHAT THEY BELIEVE ARE THE SIGNIFICANT CHANGES AHEAD AND HOW WE CAN PREPARE FOR THEM NOW
IMPACTOS DO PROGRAMA INSTITUCIONAL DE BOLSAS DE INICIAÇÃO À DOCÊNCIA NA FORMAÇÃO INICIAL EM EDUCAÇÃO FÍSICA: UM RELATO DE EXPERIÊNCIA.
Authors: Rocha Raphael , Lima de Oliveira Mateus , Amorim Cruz Santos Wilker , Alves Nogueira Souza Suzana
Published: June 2024

Este trabalho se trata de um relato de experiência que abrange a discussão dos efeitos do Programa Institucional de Bolsas de Iniciação à Docência (PIBID) na formação inicial de estudantes do Curso de Licenciatura em Educação Física de uma universidade estadual no interior da Bahia. Nesse sentido, esse relato tem como objetivo analisar os impactos na formação docente ao promover reflexões acerca das práticas pedagógicas utilizadas na  Escola Municipal Doutor Clóvis Ramos Lima (EMDCRL). Trata-se   de  relato de experiência de natureza descritiva, que se configura como uma narrativa escrita sobre vivências, capaz de enriquecer a construção de conhecimento em contextos educacionais. Buscou-se aprofundar a compreensão dos impactos iniciais dos bolsistas do PIBID, que, por sua vez, influenciam os saberes pedagógicos da formação e a construção da identidade docente. Essa experiência proporcionou uma jornada de aprendizado enriquecedora, promovendo a integração entre teoria e prática, aprofundando a compreensão dos desafios da formação docente que podem contribuir na construção da identidade docente dos bolsistas.
Irreducible Complex Posterior Elbow Dislocation with Varus Posteromedial Rotary Instability – A Case Report
Authors:   Department of Orthopaedics, PGIMER, Chandigarh, India,, Sharma Siddhartha , Dadra Ankit ,   Department of Orthopaedics, PGIMER, Chandigarh, India,, Rana Anurag ,   Department of Trauma and Orthopaedics, Whiston Hospital, Rainhill, Prescot, United Kingdom., Aggarwal Sameer ,   Department of Orthopaedics, PGIMER, Chandigarh, India,, Patel Sandeep ,   Department of Orthopaedics, PGIMER, Chandigarh, India,, Kumar Prasoon ,   Department of Orthopaedics, PGIMER, Chandigarh, India,
Published: June 2024

Introduction: Elbow dislocations, particularly those associated with varus posteromedial rotary instability, are relatively uncommon. We present the case of a 25-year-old male initially managed nonoperatively for a posterior elbow dislocation, who subsequently experienced irreducible re-dislocation with characteristic fractures of the anteromedial facet and tip of the coronoid, indicative of varus posteromedial rotary instability. Case Report: Following an unsuccessful attempt at closed reduction under general anesthesia, open reduction was performed, revealing the interposition of the posterior capsule of the humero-ulnar joint as the cause of irreducibility. Fixation of the coronoid fracture was undertaken, and the patient exhibited excellent functional outcomes at a 4.5-year follow-up. Conclusion: This case underscores the rarity of irreducible elbow dislocation in the context of varus posteromedial rotary instability and highlights the crucial role of capsular interposition in such cases. Successful open reduction, coronoid fixation, and attentive postoperative care contributed to the patient’s favorable long-term functional outcome. Keywords: Varus posteromedial rotary instability, elbow dislocation, capsular Interposition, open reduction, coronoid fracture.
"As accurate as memory": The Making of Basil H. Johnston's Indian School Days
Authors: Panofsky Ruth
Published: June 2024

Abstract: This article unveils the personal dedication of author Basil H. Johnston, together with the professional commitment of his publisher Anna Porter and agent Beverley Slopen, that led to the production and dissemination of Indian School Days . Published in 1988 by Toronto's Key Porter Books, Indian School Days was the first memoir to focus entirely on the Indian residential school experience in Canada and the first written by an Anishinaabemowin speaker. Drawing on primary material—archival documents held in the Basil H. Johnston fonds at McMaster University in Hamilton, Ontario, as well as my 2022 interview with his daughter, Tibby Johnston—the article argues for the distinctive allyship of Porter and Slopen with Johnston, three figures united in sensibility and purpose. Individually, each valued mutual understanding alongside career success and sought to challenge the prevailing bias against Indigenous writing within mainstream publishing. Collectively, they grasped the corrective significance of Indian School Days —as a work of remembrance, history, and art—and fostered awareness for a book that was central to the rise of Indigenous writing in Canada.
Posverdad: / Posverdad: Geographies of Post-Truth in Latin America / Gegrafías de posverdad en América Latina
Authors: Warf Barney
Published: June 2024

abstract: Post-truth has become a widespread but malevolent force throughout Latin America. While it has received attention from sociologists and philosophers, its spatial dimensions have been overlooked. This essay first outlines the fundamentals of post-truth. Second, it ties post-truth to neoliberalism. Third, it sketches the social bases of post-truth in Latin America, including the corporatization of media and the explosion of social media. It links post-truth to the hegemony of neoliberalism in the region. Then it offers a series of vignettes designed to illustrate that post-truth takes varying forms in different national contexts, including Donald Trump's border wall, Jair Bolsonaro's Brazil, Venezuela under Hugo Chávez and Nicolás Maduro, and several other countries. resumen: La posverdad se ha convertido en una fuerza ampliamente extendida pero maligna en toda América Latina. Mientras es cierto que sociólogos y filósofos le han prestado atención, sus dimensiones espaciales han sido pasadas por alto. Este ensayo comienza delineando los fundamentos de la posverdad. En segundo lugar, establece la relación de la posverdad con el neoliberalismo. En tercer lugar, delinea las bases sociales de la posverdad en América Latina, incluyendo la corporatización de los medios de comunicación y la explosión de las redes sociales. Seguidamente se establece un vínculo de la posverdad con la hegemonía del neoliberalismo en la región. Luego ofrece una serie de viñetas diseñadas para ilustrar que la posverdad adquiere formas variadas en diferentes contextos nacionales, incluido el muro fronterizo de Donald Trump, el Brasil de Jair Bolsonaro, Venezuela bajo Hugo Chávez y Nicolás Maduro, y varios otros países.
A new statistical fading model for loss factor induced by angle-of-arrival fluctuations in free space optical communication
Authors: Du Hairui , Cao Kairui , Ding Junrong , Hao Guanglu , Li Zekun , Zhang Jie , Wu Hongyu , Ran Qiwen , Yang Qingbo , Ma Jing
Published: June 2024

The impact of angle-of-arrival (AOA) fluctuations on the loss factor is investigated, and a new fading model is proposed to describe the associated attenuation. Distinct decay characteristics induced by AOA fluctuations are revealed, which depend on the ratio of detector size to beam width (M). The fading model can be divided into two sub-models based on the value of M0, where M0 is the value of M when the root-mean-square errors of the two sub-models are equal. In the case of M⩾M0, this fading model follows an inverse S-shaped pattern to describe the impact of AOA fluctuations. When M < M0, an exponential function to characterize the attenuation induced by AOA fluctuations. The numerical computation results indicate that the proposed fading model offers higher accuracy compared to traditional methods. Furthermore, the continuous analytical expressions for the probability density function (PDF) and cumulative density function (CDF) of the presented fading model caused by AOA are derived. Based on the proposed PDF and CDF models, the outage probability of inter-satellite laser link is analyzed.
Multi-excitation photoluminescence spectroscopy system for gemstone analysis
Authors: Tsai Tsung-Han , D’Haenens-Johansson Ulrika F. S. , Smith Tyler , Zhou Chunhui , Xu Wenxing
Published: June 2024

Luminescence spectra can reveal important chemical and structural information that can be used for gemstone characterization and identification. Traditionally, gemstone UV-excited luminescence is evaluated visually under mercury vapor lamp illumination. This approach is limited by several factors, including the mixture of mercury’s emission peaks, possible filter degradation, an inability to separate overlapping emission features, and the sensitivity and subjectivity of human vision and color interpretation. A multi-excitation photoluminescence (PL) spectroscopy system has been built for gemstone analysis, incorporating 261 and 405 nm laser excitations to study gemstone emission features between 270 to 1000 nm. This system presents significant improvements, extending the detection spectral range, increasing the sensitivity, accuracy and reproducibility of gemstone luminescence analysis. Luminescence analysis of commercially valuable gemstones are presented to demonstrate the system’s suitability for gemstone identification. Examples include distinguishing natural from laboratory-grown diamonds, thermal and color treatment detection for corundum and pearls, respectively, and mineral type separation of emeralds and other green gemstones.
Threshold-awareness in adaptive cancer therapy
Authors: Wang MingYi , Scott Jacob G. , Vladimirsky Alexander
Published: June 2024

Although adaptive cancer therapy shows promise in integrating evolutionary dynamics into treatment scheduling, the stochastic nature of cancer evolution has seldom been taken into account. Various sources of random perturbations can impact the evolution of heterogeneous tumors, making performance metrics of any treatment policy random as well. In this paper, we propose an efficient method for selecting optimal adaptive treatment policies under randomly evolving tumor dynamics. The goal is to improve the cumulative “cost” of treatment, a combination of the total amount of drugs used and the total treatment time. As this cost also becomes random in any stochastic setting, we maximize the probability of reaching the treatment goals (tumor stabilization or eradication) without exceeding a pre-specified cost threshold (or a “budget”). We use a novel Stochastic Optimal Control formulation and Dynamic Programming to find such “threshold-aware” optimal treatment policies. Our approach enables an efficient algorithm to compute these policies for a range of threshold values simultaneously. Compared to treatment plans shown to be optimal in a deterministic setting, the new “threshold-aware” policies significantly improve the chances of the therapy succeeding under the budget, which is correlated with a lower general drug usage. We illustrate this method using two specific examples, but our approach is far more general and provides a new tool for optimizing adaptive therapies based on a broad range of stochastic cancer models.
Astroviruses in terrestrial Malagasy mammals
Authors: Carcauzon Victoria , Herrera James P. , Kaufman Kayla , Baudino Fiona , Wickenkamp Natalie , Randriamoria Toky M. , Soarimalala Voahangy , Goodman Steven M. , Nunn Charles L. , Lebarbenchon Camille , Tortosa Pablo
Published: June 2024

Small terrestrial mammals are major hosts of infectious agents responsible for zoonotic diseases. Astroviruses (AstVs)–the cause of non-bacterial gastroenteritis mainly affecting young children–have been detected in a wide array of mammalian and avian host species. However, understanding the factors that influence AstV infection within and across hosts is limited. Here, we investigated the impact of land use changes on AstVs in terrestrial small mammals in rural northeastern Madagascar. We sampled 515 small mammals, representing seven endemic and four introduced species. Twenty-two positive samples were identified, all but one of which were found in the introduced species Mus musculus and Rattus rattus (family Muridae), with a positivity rate of 7.7% (6/78) and 5.6% (15/266), respectively. The non-introduced rodent case was from an endemic shrew-tenrec (family Tenrecidae). We found the highest positivity rate of AstVs infection in brushy regrowth (17.5%, 7/40) as compared to flooded rice fields (4.60%, 8/174), secondary forest (4.1%, 3/74), agroforest (3.6%, 1/28), village (2.61%, 3/115), and semi-intact forest (0%, 0/84). A phylogenetic analysis revealed an association between AstVs and their rodent host species. None of the viruses were phylogenetically related to AstVs previously described in Malagasy bats. This study supports AstV circulation in synanthropic animals in agricultural habitats of Madagascar and highlights the need to assess the spillover risk to human populations in rural areas.
The association of systemic immune-inflammation index with lung function, risk of COPD and COPD severity: A population-based study
Authors: Song Ying-da , Bai Xiao-ming , Ma Jun
Published: June 2024

Purpose

The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults.

Methods

Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships.

Results

Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3.

Conclusions

In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity.
Effects of activity-oriented physiotherapy with and without eye movement training on dynamic balance, functional mobility, and eye movements in patients with Parkinson’s disease: An assessor-blinded randomised controlled pilot trial
Authors: Mildner Sarah , Hotz Isabella , Kübler Franziska , Rausch Linda , Stampfer-Kountchev Michaela , Panzl Johanna , Brenneis Christian , Seebacher Barbara
Published: June 2024

Objectives

To describe changes in balance, walking speed, functional mobility, and eye movements following an activity-oriented physiotherapy (AOPT) or its combination with eye movement training (AOPT-E) in patients with Parkinson’s disease (PD). To explore the feasibility of a full-scale randomised controlled trial (RCT).

Methods

Using an assessor-blinded pilot RCT, 25 patients with PD were allocated to either AOPT or AOPT-E. Supervised interventions were performed 30 minutes, 4x/weekly, for 4 weeks, alongside inpatient rehabilitation. Outcomes were assessed at baseline and post-intervention, including dynamic balance, walking speed, functional and dual-task mobility, ability to safely balance, health-related quality of life (HRQoL), depression, and eye movements (number/duration of fixations) using a mobile eye tracker. Freezing of gait (FOG), and falls-related self-efficacy were assessed at baseline, post-intervention, and 4-week follow-up. Effect sizes of 0.10 were considered weak, 0.30 moderate, and ≥0.50 strong. Feasibility was assessed using predefined criteria: recruitment, retention and adherence rates, adverse events, falls, and post-intervention acceptability using qualitative interviews.

Results

Improvements were observed in dynamic balance (effect size r = 0.216–0.427), walking speed (r = 0.165), functional and dual-task mobility (r = 0.306–0.413), ability to safely balance (r = 0.247), HRQoL (r = 0.024–0.650), and depression (r = 0.403). Falls-related self-efficacy (r = 0.621) and FOG (r = 0.248) showed varied improvements, partly sustained at follow-up. Eye movement improvements were observed after AOPT-E only. Feasibility analysis revealed that recruitment was below target, with less than two patients recruited per month due to COVID-19 restrictions. Feasibility targets were met, with a retention rate of 96% (95% confidence interval [CI]: 77.68–99.79) and a 98.18% (95% CI: 96.12–99.20) adherence rate, exceeding the targets of 80% and 75%, respectively. One adverse event unrelated to the study intervention confirmed intervention safety, and interview data indicated high intervention acceptability.

Conclusions

AOPT-E and AOPT appeared to be effective in patients with PD. Feasibility of a larger RCT was confirmed and is needed to validate results.
Isolation and screening of fungi for enhanced agarwood formation in Aquilaria sinensis trees
Authors: Liu Chuang , Zhou Guoying , Liu Junang
Published: June 2024

Agarwood is a resinous heartwood of Aquilaria sinensis that is formed in response to mechanical wounding. In the present study pre-treatment of Aquilaria sinensis was carried out, and then the dominant fungi were isolated and purified from the surface and electroshock holes of trees. The isolated Trichoderma sp. and Neurospora sp. were then screened for resistance against benzyl acetone and then inoculated into healthy Aquilaria sinensis trees. After six months, the agarwood was collected for analysis. The chemical composition of incense was analyzed using gas chromatography-mass spectroscopy, and 82 chemical constituents were identified. Agarwood products formed by using Trichoderma sp. and Neurospora sp. consisted of 50.22% and 48.71% ether extracts, respectively, which surpassed the 10% threshold specified by the Chinese Pharmacopoeia. Similarly, relative aromatic contents in the two agarwood products were 30.1% and 32.86%, while proportions of sesquiterpene constituents were 10.21% and 11.19%, respectively. These two agarwood-specific chemical constituents accounted for a large proportion of the total chemical composition, which showed that the generated agarwood was of good quality. The results of the study revealed that both Trichoderma sp. and Neurospora sp. were able to effectively induce agarwood production in Aquilaria sinensis trees in 6 months. This study expands the library of fungi that promote the production of agarwood from Aquilaria sinensis trees.
Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department—Convenience or necessity?
Authors: Willis Michael , Colonetti Efrem , Bakir Ali , Alame Yousef Jamal , Annetts Megan , Aygin Deren T. , Daou Amina , Farooq Sultan , Fine Nicholas A. , Firat Gozde , Goozee Benjamin , Gupta Anuj Neelesh , Hubbett Charlotte , Loi Nicole Shun Yee , Maciejec-Biskup Laura , Muthukumar Merline Gabriela , Pott Jason , Bloom Benjamin M. , Muiesan Maria Lorenza , Harris Tim
Published: June 2024

Background

Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary.

Methods

The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose.

Results

A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink.

Conclusions

More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.