bluuebunny/crossref_metadata_2025 huggingface dataset:
Associaion of Gout with Crohn’s disease, and Inflammatory Bowel Disease with IgA Nephropathy: A Mendelian Randomization
Authors: Ye Chuyuan , Lu Jianhua , Liang Danna , Zhou Gongting , Yang Chenxin , Zhang Wei , Wu Hao , Huang Xiufeng , Yi Yongdong , Lin Limiao , Sun Weijian
Published: March 2022

Background: Gout and IgA nephropathy (IgAN) are two prevalent extra-intestinal symptoms of inflammatory bowel disease (IBD). However, no randomized controlled experiment has found a link between Crohn's disease (CD) and gout or IBD and IgAN. Thus, the causal relationship between IBD, gout, and IgAN is studied using two-sample Mendelian Randomization and Genome-wide association studies (GWAS) summary statistics. Methods: Several quality control processes were used to select qualified instrumental SNPs associated with exposure. To ensure the trustworthiness of the conclusion, inverse variance weighted, MR Egger, weighted median, and weighted mode methods were used. To estimate eligible instruments' stability, horizontal pleiotropy, and heterogeneity, leave-one-out analysis, MR-Egger intercept, and Cochran's Q test were used. Results: At a genetic level, MR analysis revealed that gout was associated with CD (IVW: P = 0.01). IBD was also found to increase the probability of IgAN (IVW: P = 4.77e-7). Conclusions: Gout increased the likelihood of CD, and IBD caused IgAN, according to a Mendelian randomization study. A larger sample size is required to discuss further the causal influence of gout on Crohn's disease.
RETRACTED: Isolation and Identification of Fungi from Egyptian Ras Cheese Made with some Probiotic Lactobacillus spp. with Reference to Their Toxins and Enzymes
Authors: Moneeb Asmaa H. M. , Zohri Abdel-Naser A. , Abd-Elmonem Mohammed A. , Tammam Adel A. , El-Desoki Wahid I.
Published: March 2022

The authors have requested that this preprint be removed from Research Square.
Hepatic and gastrointestinal manifestations in Mexican patients with juvenile systemic lupus erythematosus
Authors: Chavez Elizabeth Hernández , Coronel José María Alarid , Nuñez Myriam Mendez
Published: March 2022

Background: Systemic lupus erythematosus (SLE) is a multisystem disorder which can affect the gastrointestinal system (GI), symptoms can manifest in 50% of patients with systemic lupus erythematosus (SLE), these have barely been reviewed due to difficulty in identifying different causes [1]. The causes of abdominal pain in SLE patients are diverse, including lupus-related and non–lupus-related etiologies, as well as infections and medication side effects [2]. Children more often have lupus-related causes such as lupus mesenteric vasculitis, ascites peritonitis, and pancreatitis [2,3]. Liver manifestations, generally mild elevations in liver transaminases, have been reported in approximately 25-57.9% in paediatric-onset SLE (pSLE).Methods: Retrospective study, with review of 63 medical records of patients diagnosed with paediatric-onset SLE (pSLE) according to ACR 1997 criteria treated at the UMAE Hospital Pediatría CMNO, during the period from 2018 to 2020. Results: 63 patients were included, 49 (77.8%) girls and 14 (22.2%) boys, age range 5-17 years, mean 14 years (DS±2.9). Gastrointestinal involvement was recorded in 50.8% (n= 32) children. Lupus hepatitis, the most frequent digestive disorder (12.7%). Elevation of liver enzymes was detected in 31.7% with a higher elevation in patients with digestive disorders, in the case of AST (p= 0.001) and ALT (p= 0.024) Abdominal pain was the most frequent symptom, present in 38.1% (n= 24) patients, especially related to multiple medication 46% (n= 29), pancreatitis 7.9% (n=5), lupus enteritis 3.2% (n=2), intestinal pseud occlusion 1.6% (n=1) and ascites 1.6% (n= 1). A significant association was found (p= 0.03), among those patients with gastrointestinal affection and management with 4 or more drugs. Azathioprine was the drug most associated with abdominal pain (p= 0.07). Pancreatitis was associated with higher levels of disease activity by MEX SLEDAI score (p= 0.016). Of the manifestations not related to SLE, gastritis was the most frequent in 7.9% which was associated with a longer disease evolution time (p= 0.01).The decrease in C4 was the only immunological parameter significantly associated in patients with lupus and digestive disorders (P = 0.033). Conclusions: Gastrointestinal manifestations are common in paediatric-onset SLE (pSLE), but most of them are mild and due to adverse reactions to medications. Moderate elevation of liver enzymes occurred in 31.7% with significantly higher mean values of ALT and AST in patients with digestive disorders.
Trauma-informed care in UK: where are we? A qualitative study of health policies and professional perspectives
Authors: Emsley Elizabeth , Smith Joshua , Martin David , Lewis Natalia V
Published: March 2022

Background: Trauma-informed (TI) approach is a framework for a system change intervention that transforms the organisational culture and practices to address the high prevalence and impact of trauma on patients and healthcare providers and prevent re-traumatisation in healthcare services. Our systematic review of TI approaches in primary and community mental healthcare identified limited evidence for its effectiveness in the UK, despite endorsement in various policies. We aimed to explain the evidence-policy gap by analysing how and why TI approaches are represented, understood, and implemented in the UK.Methods: A qualitative study comprising of a document analysis of UK health policies followed by semi-structured interviews with key informants with direct experience of developing and implementing TI approaches. We used the Ready Extract Analyse Distil (READ) approach, and framework method.Results: We analysed 25 documents and interviewed 11 professionals from healthcare organisations and local authorities. Policies from healthcare organisations, local authorities, and Scottish and Welsh governments recommended TI approaches. However, there was no UK-wide strategy, agreed terminology and framework, or robust evidence base. Despite growing endorsement of TI approaches in policies, positive statements were not backed up with legislation, funding or resource allocation. Documents and interviews revealed differing understandings of TI approaches between geographical areas and across services, with disconnected, piecemeal implementation. Professionals explained the current landscape of TI approaches by the lack of high-level strategy and leadership, a need for adequate evaluation funding, and a lack of understanding of the term, existing frameworks and evidence available. They wanted more coordination and collaboration between organisations and regions. We identified factors that affected implementation of TI approaches at the level of organisation (leadership support, bottom-up and top-down development, presence of systemic thinking, organisational culture, resource allocation, competing priorities) and wider context (government support, funding, impact of the COVID-19 pandemic). Professionals had conflicting views on the future of TI approaches, however all agreed that government backing is essential for implementing policies into practice.Conclusions: A coordinated, centralised strategy on TI approaches in health systems, improved funding for evaluation, and education through professional networks about evidence-based TI health systems can increase value and reduce waste in research and implementation of TI approaches in the UK.
Validity of the methods evaluating the association between psychosocial stress and diabetes incidence and/ or control
Authors: shoher Shira , Toker Sharon , Cantrell Dror , Perl Kobi , Rapoport Micha J
Published: March 2022

Aims: Assessment of psychosocial stress remains a major obstacle in understanding its association with diabetes. We examined the validity of methods used to measure psychosocial stress in relation to diabetes incidence and control. Methods: 125 studies of psychosocial stress and diabetes published between 1983 and 2017 were evaluated. Evaluation included the stress type definition, study’s design, methodology of stress assessment and diabetes outcomes (incidence and/or control).Results: An association between stress and diabetes outcomes was found in 89% of studies. Prospective designs were commonly employed (38%), followed by cross-section designs (18%). More studies (64%) focused on psychosocial stress than sleep disorder related stress (22%). More studies explored diabetes incidence as an outcome (74%) than diabetes control (22%). The most common measure for stress assessment was a self-administered questionnaire (64%), followed by physiological indicators (7%). An analysis of the validity of the measures used, indicates that 67% of the studies used valid measures, with self-administered questionnaires exhibited a similar validity as other tools. Interestingly, the validity of tools used to evaluate sleep disorders severity was generally higher than those used to evaluate psychosocial stress.Conclusion: The majority of studies evaluating the association between anteceding stress and diabetes outcome applied valid measures.
The biological activities of 5,15-diaryl-10,20-dihalogeno porphyrins for photodynamic therapy
Authors: Li Man-Yi , Mi Le , Meerovich Gennady , Soe Thin Wut , Chen Ting , Than Ni-Ni , Yan Yi-Jia , Chen Zhi-Long
Published: March 2022

Purpose Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy.Methods The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I1-6, II1-4) were tested. The cytotoxicity of I1-6 and II1-4 were measured by MTT assay. The pathway of cell death was studied by ﬂow cytometry. In vivo photodynamic efficacy of I3 and II2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined.Results 5,15-Diaryl-10,20-dihalogeno porphyrins I1-6 and II1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λmax = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS1 (λmax = 630 nm). The singlet oxygen generation rates of I1-6 and II1-4 were significantly higher than PS1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II4 exhibited appropriate absorption in the phototherapeutic window, higher 1O2 generation rate (k = 0.0061 s-1), the strongest phototoxicity (IC50 = 0.4 μM), lower dark toxicity in vitro on Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II4 mediated PDT.Conclusion All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.
Flood Prediction and Risk Assessment at the South-western Region of Bangladesh
Authors: Meraz Md Musfike , Hossain Md. Riad , Sultana Rabeya , Esraz-Ul-Zannat Md.
Published: March 2022

Although Bangladesh has been experiencing frequent flooding that has made colossal damages to lives and properties, overseeing floods remains a difficult task. Due to the complexity, scale, and multidisciplinary nature of flood management, it is a multisectoral activity. Khulna and Satkhira districts, located in the south-western region of Bangladesh, are considered as one of the most vulnerable areas to flooding due to their economic potential, demographic makeup, and adaptive capacity of the population. This research focused on finding the most vulnerable areas to flooding for each polder within the study area. Water level data from fourteen stations of seven rivers (Sibsa, Rupsa-Pasur, Kobadak, Bhadra, Kobadak, Ichamati (Western Border), Betna-Kholpetua, and Satkhira Khal) were analyzed to calculate water levels for 2, 5, 10, 25, and 100-year return period applying normal distribution, Extreme Value Type-I (EV-I), and Log Person Type- III (LP-III) distribution methods. The EV-I distribution method was showing the best fit. The study revealed that station SW243 (Rupsa-Pasur river) in the Dacope region has the most extreme water level, station SW259 (Sibsa river) has the second-highest water level, and station SW254.5 (Satkhira Khal) in Satkhira Sadar has the third-highest water level for the return period of 100 years. A flood inundation map was prepared using the EV-I method's 10-year return period value. The Analytic Hierarchy Process (AHP) was used to demonstrate the polders' vulnerability depending on several factors. Overall, polder15 (Ghubra, Satkhira) is the most vulnerable polder, while polder 33 and polder 32 respectively are the second and third most vulnerable polders for flooding, both located in the Dacope region.
The Relationship Among Adolescents’ Self-esteem, Emotional Intelligence and Friendship Quality
Authors: Ye WEI
Published: March 2022

Background: The purpose of this study is to analyze the relationship among self-esteem, emotional intelligence and friendship quality of adolescents. Methods: A total of 333 adolescents were investigated with the help of a questionnaire and the qualitative data of interviews were used to demonstrate the results. The data were analyzed by exploratory analysis and typical correlation analysis. Results: Self-esteem can explain 21.3% of the variance of friendship quality. All levels of self-esteem are positively correlated with company help, intimate communication, positive value, trust and respect in friendship quality, but negatively correlated with conflict and betrayal in friendship quality. Emotional intelligence can explain 36.4% of the variance of friendship quality, and all levels of emotional intelligence are positively related to the level of companionship, intimate communication, positive value, trust and respect in friendship quality, but negatively related to the level of conflict and betrayal in friendship quality. Conclusion: There is a typical relationship among self-esteem, emotional intelligence and friendship quality, and interpersonal self-esteem, trust and respect, companionship and help, and intimate communication are the main explanatory factors. Emotional adjustment, cognitive reappraisal, emotional control and company help, trust and respect, positive value, intimate communication are the main explanatory factors.
Dimorphic life cycle through transverse division in burrowing hard corals
Authors: SENTOKU ASUKA , Shimizu Keisuke , Naka Tsubasa , Tokuda Yuki
Published: March 2022

The azooxanthellate solitary scleractinian Deltocyathoides orientalis (Family Turbinoliidae), which has bowl-shaped costate corallites, exhibits burrowing behavior on soft substrates and adapts to an infaunal mode of life. Here, we describe the previously unknown aspects of their life history and asexual mode of reproduction based on morphological and molecular phylogenetic analyses. The findings revealed that (1) D. orientalis exhibits asexual reproduction by transverse division; (2) smaller bowl-shaped costate anthocyathus derived from cylindrical to tympanoid anthocaulus attached to hard substrates, including shell fragments and gravels on soft substrates; (3) the anthocyathus only reproduces sexually after division and the anthocaulus regrew and repeatedly produces anthocyathi through transverse division. The bowl-shaped corallum morphology of the anthocyathus just after division might reduce and time of skeletal formation for infaunal adaptation after transverse division. Immediately after division, D. orientalis is able to smoothly shift to a burrowing lifestyle that efficiently utilizes soft-substrate environments, increasing its survival rate. Thus, morphological formation of prospective anthocyathus in the anthocaulus stage is thought to involve not only increasing clonal individuals but also adaptation to the necessarily burrowing free-living mode of life in the anthocyathus stage.
The value of percutaneous ultrasound-guided subacromial bursography in the diagnosis of rotator cuff tears
Authors: Li Ruochen , Li Miao , Cui Yipeng , Yang Pei , Zhang Chen
Published: March 2022

PurposeTo determine the feasibility and diagnostic value of percutaneous ultrasound-guided subacromial bursography (PUSB) in the diagnosis of rotator cuff tears.MethodsBetween July 2019 to October 2021, 78 patients who had suspected rotator cuff injury and who were admitted to the Second Affiliated Hospital of Xi'an Jiaotong University were selected, including 32 males and 46 females, aged 31–70 years (mean age 53.9 ± 9.1 years), with a course of 1D-2 years. The MRI, US and PUSB images of patients were retrospectively analyzed to obtain the diagnostic and predictive indexes (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) of these three methods for different rotator cuff tears types (full-thickness tears, partial-thickness tears and no tears of rotator cuff ). With the results of shoulder arthroscopy serving as the standard, PUSB results were compared with MRI and US results using the X2 -test (α = 0.05, two-sided).ResultsIn all 78 patients, the overall accuracy of MRI, US, and PUSB in diagnosing rotator cuff tears was 82.1% (64/78), 75.6% (59/78) and 96.2% (75/78), respectively (P < 0.001). Among 21 patients with full-thickness tears, the numbers of cases correctly diagnosed by MRI, US and PUSB were 19, 19 and 21, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing full-thickness tears were 90.5%, 90.5%, 100% and 98.2%, 93.0%, 100%, respectively. The diagnostic accuracies of full-thickness rotator cuff tears were 90.5%, 90.5% and 100%, respectively, with no statistical difference (P = 0.344). Among 42 patients with partial-thickness tears, the numbers of patients whose cases were correctly diagnosed on MRI, US and PUSB were 32, 27 and 40, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing partial-thickness tears were 76.2%, 64.3%, and 95.2% and 88.9%, 88.9%, and 97.2%, respectively. The diagnostic accuracies of partial-thickness rotator cuff tears were 76.2% (32/42), 64.3% (27/42) and 95.2% (40/42), respectively (P<0.05). Among the 15 patients without tears, the numbers of misdiagnosed cases by MRI, US and PUSB were 2, 2, and 1, respectively, and they were all misdiagnosed as partial-thickness tears. The sensitivity and specificity of MRI, US and PUSB in the diagnosis of complete rotator cuff were 86.7%, 86.7%, and 93.3% and 85.7%, 82.5% and 96.8%, respectively, and the accuracies in diagnosing no tears were 86.7% (13/15), 86.7% (13/15) and 87.5% (14/15), respectively (P = 0.997).ConclusionsIt is feasible to diagnose rotator cuff tears by PUSB, and its overall effect is superior to MRI and US, especially for patients with partial-thickness tears, which can be used as an important imaging method to evaluate rotator cuff tears.
Burden of adult neurofibromatosis 1: Translation, cultural adaption, and psychometric properties of the Iranian version
Authors: Jahanshahi Reza , Yasaghi Zahra , Mirzaei Fatemeh , Ghasemi Shohreh , Sanagoo Akram , Jouybari Leila , Foji Samira
Published: March 2022

Background: The notion of "burden" has taken a key place in the evaluation of care, and particular in the case of rare diseases. The aim of study was to evaluate the psychometric properties of the burden of neurofibromatosis 1 (BoN) questionnaire and the perceived disease burden.Results: BoN with 15 items was translated into Persian and no items were removed from it based on content validity. The adequacy of sample was acceptable (KMO = 0.902), and Bartlett's test of sphericity revealed statistically significant results (P<0.001). Three factors were explored for the questionnaire based on exploratory factor analysis. Reliability of the scale was good (Cronbach’s alpha: 0.90) and Intra-class reliability was 0.85. The severity of burden of neurofibromatosis was moderate and the total mean score of burden was 33.12 ±16.12.Conclusions: The Persian version of BoN is an acceptable tool in terms of structure and content that specifically addresses the practical aspects of daily activities for patients with neurofibromatosis.
Patterns of the physical, cognitive, and mental health status of older individuals in a real-life primary care setting and differences in coping styles
Authors: Wittlinger Thomas , Bekić Sanja , Guljaš Silva , Periša Vlatka , Volarić Mile , Majnarić Ljiljana Trtica
Published: March 2022

BackgroundThe types of older patients with multimorbidity (coexisting diseases) are highly heterogeneous and complex, which hampers delivering of individualized and patient-centered care to these patients.PurposeThe aim of this study was to show how physical frailty, mental disorders, and cognitive impairment cluster together and how these clusters are associated with comorbidities, stressful events, and coping styles.MethodsParticipants were older individuals (≥60), attenders of PC, who were mobile and not suffering from dementia. For screening participants on physical frailty, cognitive impairment, and mental disorders, we used Fried`s phenotype model, the Mini-Mental State Examination (MMSE), the Geriatric Anxiety Scale (GAS) and the Geriatric Depression Scale (GDS). For testing participants on coping styles, we used the 14-scale questionnaire Brief COPE. To identify clusters, we used the algorithm fuzzy k-means. To further describe the clusters, we examined differences in age, gender, number of chronic diseases and medications prescribed, some diagnoses of chronic diseases, life events, body mass index, renal function, expressed as the glomerular filtration rate, and coping styles.ResultsThe most appropriate cluster solution was the one with three clusters, that were termed as: functional (FUN) (N=139), dysfunctional (DFUN) (N=81), and cognitively impaired (COG-IMP) (N=43). The cluster FUN was associated with positive reframing coping style. Religion and self-blame were coping mechanisms specifically associated only with cluster DFUN; self-distraction only with cluster COG-IMP; and these two latter clusters shared the mechanisms of behavioral disengagement and denial.ConclusionsThe research approach presented in this study could provide a new framework for decoding patient complexity. Gaining insights into this complexity is expected to improve personalized prevention and treatment strategies for older individuals with multimorbidity.
Ultrashort time-to-echo T2* and R2* relaxometry for evaluation of lumbar disk degeneration: A comparative study
Authors: Wu Li-Lan , Liu Li-Heng , Rao Sheng-Xiang , Wu Pu-Yeh , Zhou Jian-Jun
Published: March 2022

Background: To compare potential of ultrashort time-to-echo (UTE) T2* mapping and R2* values from T2*-weighted imaging for assessing lumbar intervertebral disk degeneration (IVDD) ,with Pfirrmann grading as a reference standard.Methods: UTE-T2* and R2* values of 366 lumbar disks (L1/2-L5/S1) in 76 subjects were measured in 3 segmented regions: anterior annulus fibrosus, nucleus pulposus (NP), and posterior annulus fibrosus. Lumbar intervertebral discs were divided into 3 categories based on 5-level Pfirrmann grading: normal (Pfirrmann grade I),early disk degeneration (Pfirrmann grades II-III), and advanced disk degeneration (Pfirrmann grades IV-V). Regional differences between UTE-T2* and R2* relaxometry and correlation with degeneration were statistically analyzed.Results: UTE-T2* value correlated negatively with Pfirrmann grades; R2* value correlated positively (all P < 0.001). In NP, correlations with Pfirrmann grade were high with UTE-T2* values (r = −0.733; P < 0.001) and moderate with R2* values (r = 0.654; P < 0.001). Diagnostic accuracy of detecting early IVDD was better with UTE-T2* mapping than R2* mapping (P < 0.05),with receiver operating characteristic analysis area under the curve of 0.715–0.876.Conclusions: UTE-T2* relaxometry provides another promising magnetic resonance imaging sequence for quantitatively evaluate lumbar IVDD and was more accurate than R2* in the earlier stage degenerative process.
Seasonal bacterial niche structures and chemolithoautotrophic ecotypes in a North Atlantic fjord
Authors: Raes Eric , Tolman Jennifer , Desai Dhwani , Ratten Jenni-Marie , Zorz Jackie , Robicheau Brent M. , Haider Diana , LaRoche Julie
Published: March 2022

Quantifying the temporal change of bacterial communities is essential to understanding how both natural and anthropogenic pressures impact the functions of coastal ecosystems. Here we use weekly microbial DNA sampling across four years, to show that bacterial phyla have distinct seasonal niches, with a richness peak in winter (i.e., an inverse relationship with daylength). Our results suggest that seasonal fluctuations rather than the kinetic energy or resource hypotheses, dominate the pattern of bacterial diversity. These findings supplement those from global analyses which lack temporal replication and present few data from winter months in polar and temperate regions. Centered log ratio transformed data provided new insights into the seasonal niche partitioning of conditionally rare phyla, such as Modulibacteria, Verrucomicrobiota, Synergistota, Deinococcota, and Fermentibacterota. These patterns could not be identified using the standard practice of generation of ASVs followed by rarefaction. Our study provided evidence that five globally-relevant ecotypes of the chemolithoautotrophic bacteria from the SUP05 lineage comprise a significant functional group with varying seasonal dominance patterns in the Bedford Basin.
Association between outpatient examinations and upgrading treatments for pediatric constipation
Authors: Yang Jixin , Zhao Xiaoli , Zhu Tianqi , Zhang Hongyi , Wu Xiaojuan , Xiang Lei , Sun Xiaoyi , Wei Mingfa , Yi Bin , Wang Guo , Feng Jiexiong
Published: March 2022

Purpose: This study aims to investigate risk factors of BE, ARM and acetylcholinesterase staining related to failure of treatments and diagnostic value of Hirschsprung’s disease (HSCR) or intractable constipation (IC). Methods: A single-center retrospective cohort study of children with constipation was conducted. All patients were followed up until significant improvement of defecation. Patients initially received general/conservative treatment or surgery. Upgraded treatments were adopted if the initial treatment failed. The risk factors including transitional zone, barium residue, absence of recto-anal inhibitory reflex (RAIR) and acetylcholinesterase staining. A p value <0.1 or <0.05 was considered to be statistically significant in Logistic regression. Chi-square test was used to calculate the sensitivity and specificity when analyzing the diagnostic value.Results: This study enrolled 4869 cases. Acetylcholinesterase staining +++ had the highest risk (OR, 177.613[95%CI 92.178~273.526]) leading to failure of general treatment, followed by absence of RAIR ((OR, 158.786[95%CI 92.178~273.526]) and severe barium residue (OR, 153.829[70.004~338.028]). The leading risk factors causing failure of conservative therapy were severe barium residue (OR, 15.530[95%CI 5.337~45.191]) and acetylcholinesterase staining +++ (OR, 13.242[6.657~26.337]). In children ≤3 years, the transitional zone, absence of RAIR and acetylcholinesterase staining ++/+++ had similar specificity (80.0%, 75.6% and 73.3%), whereas the acetylcholinesterase staining ++/+++ had the highest sensitivity (95.5%). The sensitivity was generally lower in children ＞ 3 years, however the specificity was similar between each age group.Conclusion: This real-world study validates that the performance of 3 examinations is of great significance in guiding upgrading treatments, predicting clinical outcomes and identifying HSCR and IC.Trial Number: NCT02216994 (registered on October 27, 2014)
CD58 as a biomarker for prognosis and immune infiltration in hepatocellular carcinoma
Authors: Cai Mengjiao , Chen Jie , Wang Jin , Ji Chao , Zhang Xinyue , Pan Jue , Ma Jinlu
Published: March 2022

BACKGROUND
The glycoprotein CD58, is a co-stimulatory receptor distributed on a wide range of human tissue cells. CD2 interacts with CD58 to promote important adhesion between T cells and target cells and to induce signaling events involved in the regulation of T cell responses. However, the relevance of CD58 to the prognosis of different tumors and to tumor-infiltrating lymphocytes is unclear.
RESULTS
Analysis of CD58 expression through the Tumor Immune Evaluation Resource (TIMER) website and UALCAN, revealed meaningful differential expression of CD58 between hepatocellular carcinoma (LIHC) tumor tissue and normal tissue, with higher levels of CD58 expression in hepatocellular carcinoma than in normal tissue. We used Kaplan-Meier plotter and gene expression profiling interaction analysis (GEPIA) to assess the impact of CD58 on clinical prognosis and found that high CD58 expression was associated with a poorer prognosis in hepatocellular carcinoma. The correlation between CD58 and tumor immune infiltration by TIMER revealed that CD58 expression was negatively correlated with tumor purity and positively correlated with the level of immune infiltration of B cell, Neutrophil, Macrophage, Myeloid dendritic cell and T cell CD4+. Furthermore, we analyzed the correlation between CD58 expression and the gene marker sets for immune infiltration using TIMER and GEPIA and found that in hepatocellular carcinoma, the expression levels of most monocytes, TAM, M1 macrophages, M2 macrophages, dendritic cells, Th1, Th2 and Treg marker sets correlated strongly with CD58 expression in LIHC.
CONCLUSION
CD58 is associated with the level of immune infiltration and prognosis of B cell, Neutrophil, Macrophage, Myeloid dendritic cell, T cell CD4 + in a variety of tumors, especially in patients with hepatocellular carcinoma. In addition, CD58 expression may help regulate the expression levels of most monocytes, TAM, M1 macrophages, M2 macrophages, dendritic cells, Th1, Th2, and Treg marker groups in hepatocellular carcinoma. It is suggested that CD58 may be used as a biomarker to determine the prognosis and immune infiltration of hepatocellular carcinoma.
Single-cell RNA Sequencing Reveals the Tissue-specific Immune Signatures of Lung Cancer with COPD Overlapped
Authors: Meng Heng , Chang# Jiwei , Wang# Bo , Geng Boxin , He Ruyuan , Hao Bo , Lin Weichen , Song Congkuan , Li Ning , Geng Qing
Published: March 2022

COPD is one of the high-risk factors for lung cancer, but the underlying mechanism is still unclear. Here, we performed single-cell RNA sequencing analysis on three COPD tissues, and three COPD-based lung cancer tissue (LCCOPD), and enrolled the scRNA-seq data of normal lung tissues, COPD tissues, lung cancer tissues, and LCCOPD tissues from the public database. We found that most immune cell types were significantly enriched in COPD groups, and the LCCOPD showed a differential enrichment of T-regs and macrophage subtypes in comparison with COPD. FOXP3 mRNA expression was significantly increased in LCOPD-related T-regs and positively associated with CTLA-4 and PD-1 to form an immunosuppressive environment. Macrophages from different pathological environments show significant differences in cell composition, pseudo-time trajectories, and phenotypic dominance. COPD-related macrophages were dominated by M1-type with increased cell proliferation. LCCOPD-related macrophages, dominated by M2-type and tumor-associated macrophages, had progressively enhanced immune population chemotaxis along the trajectory. Based on the public data, we found the overlap of COPD accelerated infiltration of T-regs and M2 macrophages. Several metabolic and cytokine pathways were down-regulated in COPD tissues and up-regulated in LCCOPD groups, such as the SREBP pathway, IL2, IFN-γ, glycolysis, and glutamine metabolism. Our study provided an extensive description of lung cancer overlapping COPD and revealed the association between COPD status and the formation of an immunosuppressive environment, which elucidates the role of COPD, as a high-risk factor, in the development of lung cancer.
Impact of Managed Entry Agreements on availability of and timely access to medicines: an ex-post evaluation of agreements implemented for oncology therapies in four countries
Authors: Efthymiadou Olina , Kanavos Panos
Published: March 2022

Background: Despite the increased utilisation of Managed Entry Agreements (MEAs), empirical studies assessing their impact on achieving better access to medicines remains scarce. In this study we evaluated the role of MEAs on enhancing availability of and timely access to a sample of oncology medicines that had received at least one prior rejection from reimbursement. Methods: Funding decisions and their respective timelines for all oncology medicines approved between 2009 and 2018 in Australia, England, Scotland and Sweden were studied. A number of binary logit models captured the probability (Odds ratio (OR)) of a previous coverage rejection being reversed to positive after resubmission with vs. without a MEA. Gamma generalised linear models were used to understand if there is any association between time to final funding decision and the presence of MEA, among other decision-making variables, and if so, the strength and direction of this association (Beta coefficient (B)). Results: Of the 59 previously rejected medicine-indication pairs studied, 88.2% (n=45) received a favourable decision after resubmission with MEA vs. 11.8% (n=6) without. Average time from original submission to final funding decision was 404 (±254) and 452 (±364) days for submissions without vs. with MEA respectively. Resubmissions with a MEA had a higher likelihood of receiving a favourable funding decision compared to those without MEA (43.36<OR<202, p<0.05), although approval specifically with an outcomes-based agreement was associated with an increase in the time to final funding decision (B=0.89, p<0.01). A statistically significant decrease in time to final funding decision was observed for resubmissions in Australia and Scotland compared to England and Sweden, and for resubmissions with a clinically relevant instead of a surrogate endpoint.Conclusions: MEAs can improve availability of medicines by increasing the likelihood of reimbursement for medicines that would have otherwise remained rejected from reimbursement due to their evidentiary uncertainties. Nevertheless, approval with a MEA can increase the time to final funding decision, while the true, added value for patients and healthcare systems of the interventions approved with MEAs in comparison to other available interventions remains unknown.
Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models
Authors: Song Young , Leem Joseph , Dhanani Mehul , McKirnan M. Dan , Ichikawa Yasuhiro , Braza Julie , Harrington Elizabeth O. , Hammond H. Kirk , Roth David M. , Patel Hemal H.
Published: March 2022

Background: Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains myriads of factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. In this study, we tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects. Methods: Blood plasma was obtained from daunorubicin- and myocardial infarction-induced HF rabbits (Dauno-HF and MI-HF) and their controls (Dauno-Control and MI-Control). Effects of plasma on bioenergetics of myocardial tissue from healthy mice and cellular cardiac components; myoblasts, fibroblasts, macrophages, and endothelial cells were assessed using high-resolution respirometry and Seahorse flux analyzer. Since endothelial cell respiration was profoundly affected by HF plasma, effects of plasma on endothelial cell barrier function and death were further evaluated. Western-blot analysis and electron microscopic assessment were performed to detect alterations in mitochondrial proteins and morphology. Results: Brief exposure to HF plasma significantly decreased cardiac tissue respiration. Endothelial cell respiration was most impacted by exposure to HF plasma. Endothelial cell monolayer integrity was significantly decreased by incubation with Dauno-HF plasma. Apoptosis and necrosis were significantly increased in cells incubated with Dauno-HF plasma for 24 h. Significant down-regulation of VDAC-1, Tom20, and MFF in cells exposed to Dauno-HF plasma and mitochondrial Stat3 and MFF in cells exposed to MI-HF plasma were observed. Mitochondrial structure was disrupted in cells exposed to HF plasma.Conclusions: These findings indicate that endothelial cells and mitochondrial structure and function may be a primary target where HF pathology manifests and accelerates. High-throughput blood-based screening of HF may provide innovative ways to advance disease diagnosis and management.
Experimental Evidence for E = n 1 2 hν Energy Transfer
Authors: P. Bhanumoorthy
Published: March 2022

Abstract.
Crystal diffraction involves energy transfer into and from the crystal.
Bragg's law defines an inter-planar spacing as $2\pi$ radians and corresponds to $E=12.4/\lambda$ which is $E=nh\nu$ energy transfer.
Energy difference between adjacent Davisson-Germer peaks observed in the historic experiment follows $E=6.2/\lambda$ which is $E=n\fr12h\nu$ energy transfer.
One-full oscillation in $2\pi$ radians is one-full quantum of energy transfer and one-half oscillation in $\pi$ radians is one-half quantum of energy transfer.
The phenomenon of $E=n\fr12h\nu$ energy transfer defines the Maxwell diffraction law $2d_{\ve k}\sin\theta_{\ve k}=\lambda$ in terms of diffraction angle $\theta_{\ve k}$ where inter-planar spacing $d_{\ve k}$ becomes $\pi$ radians characteristic of an anti-node of a standing wave.
Cartesian description cannot accommodate $\pi$ in place of $2\pi$.
Hence, the Maxwell diffraction law in place of Bragg's law becomes the starting point for the new field of partial wave quantum crystallography to use precision angles measurable in the experiment for direct method solution to phase problem for macromolecular crystallography.
Temperature, density, and velocity distribution in the mixture prepared by controlled diffusion solidification process
Authors: Khalaf Abbas
Published: March 2022

Controlled diffusion solidification (CDS) is a new casting process that depends on mixing two precursor alloys. The two precursor alloys have precisely controlled temperature and content to make a required resultant alloy. The CDS process can change the microstructure to non-dendritic happening from copious nucleation, resulting in minimizing the tendency toward the hot tearing. Contrary to the conventional casting in which the dendritic microstructure forms the entire microstructure of the product. In the present study, Pure aluminum and Al-33wt%Cu have been used to make Al-4.7wt%Cu by using the CDS technique, where the pure aluminum was mixed into Al-33wt%Cu through funnels that have 9 and 6mm diameter. The events such as the nucleation and heat transfer to the environment have been studied with aid of the temperature, density, and velocity distribution taking place during the mixing step of the CDS process. The results show that the thermal curves give better indications to predict the periods of nucleation and the heat transferring to the environment. Further, the copious nucleation that occurs in the CDS process can be improved by controlling the agitation during the mixing step by decreasing the velocity of the mixture near the crucible wall and increasing the velocity in the middle of the mixture. Ansys software was employed to simulate the temperature, density, and velocity distribution in the mixture during the mixing step. The experimental results were supported by simulation results and an optical microscopy test.
MicroRNA-34a prevents postmenopausal osteoporosis by promoting osteoclasts-induced osteoblasts differentiation and downregulating the proinflammatory cytokines
Authors: Lv Wentao , Chu Xiaojie , Bao Zhonglei , zhang Xinyuan , Jia Jia , Wang LiYan
Published: March 2022

Reduction of estrogen levels at the menopause causes the increasing of pro-inflammatory cytokines, the enhancing of bone resorption and the impairing of bone formation, leading to osteoporosis. Previous studies showed that microRNA-34a (miR-34a) was associated with the process of postmenopausal osteoporosis (PMOP). However, the exact mechanisms by which miR-34a is involved in PMOP are not fully elucidated. In the present study, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase staining, alkaline phosphatase staining and alizarin red staining were employed to investigate the role of miR-34a in PMOP. The results showed that miR-34a inhibited RANKL-induced osteoclasts differentiation. Osteoblasts differentiation was further enhanced when osteoblasts were cultured in conditioned medium (CM) from miR-34a-overexpressed osteoclasts compared with CM from miR-NC-transfected osteoclasts. Conversely, osteoblasts differentiation was decreased when osteoblasts were cultured in CM from miR-34a-silenced osteoclasts, suggesting that miR-34a could promote bone formation through indirectly affecting coupling of osteoclasts to bone formation responses. Moreover, miR-34a impaired TNF-α-induced production of pro-inflammatory cytokines in RAW264.7 cells. Taken together, miR-34a might be used as a therapeutic agent for treating PMOP by promoting osteoclasts-induced osteoblasts differentiation and downregulating the proinflammatory cytokines.
Association of TRMT2B Gene Variants with Juvenile Amyotrophic Lateral Sclerosis
Authors: Liu Yanling , He Xi , Yuan Yanchun , Li Bin , Liu Zhen , Li Wanzhen , Li Kaixuan , Tan Shuo , Zhu Quan , Tang Zhengyan , Han Feng , Wu Ziqiang , Shen Lu , Jiang Hong , Tang Beisha , Qiu Jian , Hu Zhengmao , Wang Junling
Published: March 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is characterized by progressive degeneration of motor neurons and demonstrates high clinical heterogeneity and complex genetic architecture. We identified a variation within TRMT2B (c.1356G > T; p.K452N) to be associated with ALS in a family comprising two patients with juvenile ALS. Then, two missense variations and one splicing variation were identified in 10 ALS patients in our cohort with 910 ALS patients, and three more variations were identified in a publicly ALS database (ALSdb) including 2800 ALS patients. Functionally, we detected a decrease of mitochondrial complex I activities in patients originated Epstein-Barr virus–transformed lymphoblastoid cell lines due to decreased number of mitochondria and lower expression of ND1 in mitochondria. Further, we detected increasing ROS but decreased p62 expression alteration within patients. In conclusion, we identified a novel ALS-associated gene, TRMT2B, and broaden the clinical and genetic spectrum of ALS.
Global, regional, and national burden of colorectal cancer and attributable risk factors, from 1990 to 2019: Updated results from the Global Burden of Disease Study 2019
Authors: Liu Yang , Zhang Chao , Wang Qianwen , Wu Kangze , Sun Zhouyi , Tang Zhe , Zhang Bo
Published: March 2022

Background: This study aimed to evaluate the global trends of colorectal cancer from 1990 to 2019 and the relevant risk factors for better policymaking and resource allocation.Methods: Data on CRC, including incidence, mortality, and disability adjusted life year (DALY) rates, were extracted from the 2019 Global Burden of Disease (GBD) study. The estimated annual percentage changes (EAPCs) were calculated to assess the trend of incidence, mortality, and DALYs, and the risk factor attributable deaths and DALYs were assessed based on the comparative risk assessment framework.Results: In 2019, a total of 2.166×106 CRC cases were reported worldwide, a 157% increase compared with that reported in 1990. In high-social demographic index (SDI) regions, the trend of age-standardized incidence rate has decreased, while the proportion of people younger than 50 years has increase. Although the number of deaths and DALYs increased, the age-standardized death rate and age-standardized DALY rate was decreased. The middle-SDI regions have the fastest growing CRC burden, especially in East Asia, followed by the low-SDI regions, in which the CRC burden in women has increased faster than that in man. In addition, the milk intake, High-BMI, and high fasting plasma glucose play a more important role in on CRC.Conclusion: In developed regions, the CRC burden tended to be easier, while the CRC burden became more severe in undeveloped regions. Therefore, reasonable resource allocation and prevention policies should be implemented to avoid an increase in the burden of CRC.
PET Imaging of the cannabinoid receptor type 2 in humans using [11C]MDTC
Authors: Du Yong , Coughlin Jennifer M. , Brosnan Mary Katherine , Chen Allen , Shinehouse Laura K. , Abdallah Rehab , Lodge Martin A. , Mathews William B. , Liu Chen , Wu Yunkou , Hall Andrew , Lesniak Wojciech , Dannals Robert , Horti Andrew , Pomper Martin
Published: March 2022

Purpose: We report findings from the first-in-human study of [ 11 C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET). Methods: Ten healthy adults were imaged according to a 90 min dynamic PET protocol after bolus intravenous injection of [ 11 C]MDTC. Five participants also completed a second [ 11 C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [ 11 C]MDTC in human brain was evaluated using a metabolite-corrected arterial plasma input function with compartmental modeling and graphical analysis approaches. Four additional healthy adults completed whole-body [ 11 C]MDTC PET/CT to calculate organ doses and the whole-body effective dose. Results: [ 11 C]MDTC brain PET and [ 11 C]MDTC whole body PET/CT was well-tolerated. The model of choice for fitting the time activity curves (TACs) across brain regions of interest was a two-tissue compartment model with the blood volume fraction included as a fitting parameter (2TCM-vB). Regional distribution volume (V T ) values computed from Logan graphical analysis correlated well with those estimated using the 2TCM-vB model. Cortical regions and thalamus had higher V T than brainstem, striatum, hippocampus, and corpus callosum. Test-retest reliability of V T demonstrated a mean absolute variability of 7.13%, with an intraclass correlation coefficient 0.91. The measured effective dose of [ 11 C]MDTC was 5.29 µSv/MBq. Conclusion: These data support use of [ 11 C]MDTC PET for in vivo neuroimaging of CB2R in humans. Future in vivo studies using [ 11 C]MDTC PET in neuroinflammatory conditions are needed to assess the detection of high expression of the CB2R by activated microglia in human brain.