bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB535: A novel IL12-based immunocytokine targeting fibroblast activation protein (FAP) for the treatment of cancer
Authors: Nadal Lisa , Peissert Frederik , Elsayed Abdullah , Libbra Chiara , Neri Dario , De Luca Roberto
Published: June 2022

Immunocytokines, which consist of the fusion of cytokines to tumor targeting antibodies, represent a novel class of biopharmaceuticals that have great potential for cancer treatment. The use of these products improves the efficacy of the delivered drug by reducing related side effects and significantly enhances the therapeutic index of the payload. Over the past years, nuclear medicine studies have validated the Fibroblast Activation Protein (FAP) as a pantumoral antigen, with more than 28 different cancer types successfully imaged in patients. Since FAP is mostly undetectable in healthy organs, it has been considered as an attractive target for both imaging and therapeutic applications. For this reason, here we describe the generation of a novel fully human monoclonal antibody targeting FAP. The antibody was isolated from a synthetic antibody phage display library and its tumor recognition properties were validated by immunofluorescence performed on a commercial tissue microarray as well as on freshly frozen colon cancer biopsies from human patients. An ex vivo biodistribution analysis in mice confirmed the ability of anti-FAP in IgG1 format to selectively localize to solid tumors while sparing healthy organs. Furthermore, Pharmacokinetics (PK) studies in Cynomolgus Monkey showed no sink effects at early time points and a slow clearance from bloodstream as expected for IgG1 antibodies. Encouraged by these results, an antibody cytokine fusion (mIL12-FAP) based on the novel anti-FAP antibody was generated and characterized in vitro and in vivo, showing activation of the immune system both in immunocompetent and immunodeficient mouse models bearing FAP-positive tumors. mIL12-FAP exhibited strong anticancer activity in mice bearing CT26-FAP colon carcinomas which could be boosted by the combination with immune checkpoint inhibitors, leading to durable cancer eradication. The targeted delivery of mIL12 to the tumor microenvironment increased the infiltrate of tumor-specific lymphocytes and Natural Killer (NK) cells as compared to the control group without apparent evidence of toxicity.

Citation Format: Lisa Nadal, Frederik Peissert, Abdullah Elsayed, Chiara Libbra, Dario Neri, Roberto De Luca. A novel IL12-based immunocytokine targeting fibroblast activation protein (FAP) for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB535.
Abstract LB549: LncRNA PCAT1 activates SOX2 and suppresses radioimmune responses via regulating cGAS/STING signaling in non-small cell lung cancer
Authors: Gao Yanping , Zhang Nannan , Gong Yan , Xie Conghua
Published: June 2022

Background: The long non-coding RNA (lncRNA) PCAT1 is upregulated in non-small cell lung cancer (NSCLC), and promotes tumor growth and metastasis, but its roles in the radioimmune responses remain unknown. We aimed to investigate the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC.

Methods: Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumor invasion in NSCLC. The expression levels of PCAT1 were analyzed by in situ hybridization in 55 paired NSCLC and adjacent normal tissues. Both loss- and gain-of-function assays were performed to evaluate the functions of PCAT1 and SOX2 in NSCLC cell behaviors in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification and dual-luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase, and rescue assays were utilized to identify the relationship between SOX2 and the cGAS/STING signaling.

Results: PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and inhibited cell migration and invasion in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumor growth through inhibiting cytotoxic T cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I IFN-induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumor growth, and activated the cGAS/STING signaling pathway, which enhanced the immune responses of radiotherapy in NSCLC.

Conclusions: PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signaling-mediated T-cell activation. Inhibition of PCAT1 and SOX2 synergized with radiotherapy to activate the immune response and could serve as potential therapeutic targets.

Citation Format: Yanping Gao, Nannan Zhang, Yan Gong, Conghua Xie. LncRNA PCAT1 activates SOX2 and suppresses radioimmune responses via regulating cGAS/STING signaling in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB549.
Abstract LB557: Multiphoton phosphorescence quenching microscopy reveals kinetics of tumor oxygenation during anti-angiogenesis and angiotensin signaling inhibition
Authors: Martin John , Lanning Ryan , Fukumura Dai , Padera Timothy , Jain Rakesh
Published: June 2022

Purpose: The abnormal function of tumor blood vessels causes hypoxia fueling disease progression and conferring treatment resistance. The local level of oxygen experienced by a cell will determine its response, making it critical to understand tissue oxygen levels with a spatial resolution on the order of the size of a cell. While microenvironment normalization strategies alleviate global hypoxia, how local oxygen levels change are not known because there are no in vivo techniques to longitudinally assess tumor vessels and interstitial oxygen in tumors with sufficient resolution. Understanding the heterogeneity of oxygen levels after microenvironmental normalization will help improve the efficacy of various normalization strategies.

Experimental Design: We developed a multiphoton phosphorescence quenching microscopy system using a low-molecular weight palladium porphyrin probe to measure perfused vessels, oxygen tension and their spatial correlations in vivo in mouse skin, bone marrow, and tumors. Further, we measured the temporal and spatial changes in oxygen and vessel perfusion in tumors in response to microenvironmental normalization.

Results: We found that vessel function was highly dependent on tumor type. Although some tumors had vessels with greater oxygen carrying ability than normal skin, most tumors had inefficient vessels. Further, inter-vessel heterogeneity in tumors coincided with heterogeneous response to microenvironmental normalizing agents. Using both vascular and stromal normalizing agents, we show that spatial heterogeneity in oxygen levels persist, even with global reductions in hypoxia.

Conclusions: We present the first study to examine the high-resolution spatial and temporal response of tumor vessels to two agents known to improve vascular perfusion globally. Our measurements demonstrate that the heterogeneities in the local imbalance of pro- and anti-angiogenic signaling lead to spatially heterogeneous changes in vessel structure and function. Microscale dynamic vascular changes should be considered in optimizing the dose and schedule of microenvironment normalizing therapies to improve function.

Citation Format: John Martin, Ryan Lanning, Dai Fukumura, Timothy Padera, Rakesh Jain. Multiphoton phosphorescence quenching microscopy reveals kinetics of tumor oxygenation during anti-angiogenesis and angiotensin signaling inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB557.
Risk Factors for Nephrotoxicity due to Tacrolimus Therapy for Ulcerative Colitis
Authors: Nakata Satoshi , Kakimoto Kazuki , Numa Keijiro , Kinoshita Naohiko , Kawasaki Yuka , Tatsumi Yoshihiro , Tawa Hideki , Koshiba Ryoji , Hirata Yuki , Ota Kazuhiro , Sakiyama Naokuni , Kojima Yuichi , Nishikawa Hiroki , Inoue Takuya , Takeuchi Toshihisa , Fukunishi Shinya , Miyazaki Takako , Nakamura Shiro , Higuchi Kazuhide
Published: June 2022

Background and Aims: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. Methods: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10–15 ng/mL) for 2 weeks and low trough levels (5–10 ng/mL) for 3 months. Results: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69–11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). Conclusion: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.
Comparison of Lipid Foam Cream and Basic Cream on Epidermal Reconstruction in Mild Atopic Eczema
Authors: Dähnhardt Dorothee , Dähnhardt-Pfeiffer Stephan , Schulte-Walter Judith , Hanisch Eckhard , Neubourg Thomas , Fölster-Holst Regina
Published: June 2022

Introduction: Basic therapy is of central importance in the treatment of atopic eczema. Using electron microscopic images, the morphology of epidermal skin barrier and its lipids was investigated after application of a lipid foam cream and basic cream. Methods: Patients with two contralateral comparable atopic eczema (local SCORAD 1–10) on the forearms were tested. Eczema was treated with a lipid foam cream or basic cream twice daily for 28 days. At the beginning, after 14 days, and at the end of application, the local SCORAD, trans-epidermal water loss (TEWL), skin hydration, intercellular lipid length in the intercellular space of the stratum corneum (SC), and skin lipids were determined. Results: After application of the foam cream, the epidermal skin barrier could be completely restored and corresponded to healthy skin, while the epidermal skin barrier could not reach this state after care with the basic cream. The content of lipids in the SC increases significantly by 31% after basic cream treatment, whereas they are significantly increased by 85% after application of the lipid foam cream. The local SCORAD improved for both treatments to about the same extent, and no significant results could be shown for TEWL and skin hydration. Conclusion: In subjects with mild atopic eczema, the lipid foam cream leads to a measurable recovery of the skin barrier which is much more pronounced in comparison to the basic cream.
Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis
Authors: Zhu Yifan , Tang Yuyan , Peng Yinshun , Hu Ping , Sun Weiqian , Jin Meiping , Liu Ping , Wu Jiajun , He Haidong , Xu Xudong
Published: June 2022

Introduction: Kidney transplantation (KT) has surpassed dialysis as the optimal therapy for end-stage kidney disease. Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods: To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and nonrejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus database. Then, we used weighted gene coexpression network analysis (WGCNA) to analyze the coexpression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. Results: As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. Three key modules had 21 mutual Gene Ontology term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes, Yip1 interacting factor homolog B, membrane trafficking protein, toll like receptor 8, neutrophil cytosolic factor 4, glutathione peroxidase 8, mesenteric estrogen dependent adipogenesis, decorin, serpin family F member 1, integrin subunit beta like 1, SRY-box transcription factor 15, trophinin associated protein, SRY-box transcription factor 1, metallothionein 3, lysosomal protein transmembrane, FERM domain containing kindlin 3, and cathepsin S, had a great diagnostic performance (AUC > 0.7). Conclusion: This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.
A Prospective Study on Defining the Indications of Prophylactic Level IB Radiotherapy in Nasopharyngeal Carcinoma Based on a Risk Score Model
Authors: Zhang Xue , Yuan Jing-Jing , Ding Jian-Wu , Zhang Shou-Hua , Zhang Zhi-Lin , Hu Rong-Huan , Gong Dan , Hu Jia-Li , Tu Zi-Wei , Zeng Lei
Published: June 2022

Objective: The aim of the study was to investigate clinical evidence for defining the indications of prophylactic level IB radiotherapy (RT) in nasopharyngeal carcinoma (NPC). Methods: We conducted a phase 2 prospective study in 116 newly diagnosed patients with NPC treated by intensity-modulated RT. Whether level IB was irradiated is based on the risk score model (RSM). Two groups based on RSM were obtained: low risk and high risk. Omission of level IB irradiation was conducted in the low-risk group, otherwise level IB was contoured as part of the treatment target. Grade 2 or worse xerostomia at 12 months was assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-H&N35 questionnaire. Results: At a median follow-up of 16 months (range, 1–26 months), none of the patients developed failures at level IB. The 1-year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 98.3%, 97.2%, and 95.8%, respectively. At 12 months xerostomia side-effects were reported in 90 of 116 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the low-risk group than in the high-risk group. Conclusion: Omission of level IB irradiation was feasible for patients with low-risk IB lymph nodes metastasis.
Sex-Dependent Gliovascular Interface Abnormality in the Hippocampus following Postnatal Immune Activation in Mice
Authors: Ardalan Maryam , Chumak Tetyana , Quist Alexandra , Jabbari Shiadeh Seyedeh Marziyeh , Mallard Anna-Jean , Rafati Ali Hoseinpoor , Mallard Carina
Published: June 2022

The neuro-gliovascular unit is a crucial structure for providing a balanced well-functioning environment for neurons and their synapses. Activation of the immune system during the developmental period is believed to affect the gliovascular unit, which may trigger neurodevelopmental and neurological/neuropsychiatric diseases. In this study, we hypothesized that vulnerability of the male brain to a neonatal insult was conditioned by sex-dependent differences in the impairment of the hippocampal gliovascular unit. Male and female C57BL/6J pups received lipopolysaccharide (LPS) (1 mg/kg) or saline on postnatal day (P) 5. Brains were collected at P12 and morphological quantifications of hippocampal fibrillary glial acid protein (GFAP+) astrocytes and ionized calcium-binding adaptor molecule 1 protein (Iba1+) microglia were performed by using 3-D image analysis together with measuring the length of CD31+ and aquaporin-4 (AQP4+) vessels. We found a significant increase in the length of CD31+ capillaries in the male LPS group compared to the saline group; however, coverage of capillaries by astrocytic end-feet (AQP4+) was significantly reduced. In contrast, there was a significant increase in AQP4+ capillary length in female pups 1 week after LPS injection. GFAP+ astrocytes via morphological changes in the hippocampus showed significant enhancement in the activity 1 week following LPS injection in male mice. We propose that neonatal inflammation could induce susceptibility to neurodevelopmental disorders through modification of hippocampal gliovascular interface in a sex-dependent manner.
Oratórios públicos: monumentos erigidos para o exercício religioso nas ruas da cidade de Salvador, Bahia, nos séculos XVIII e XX
Authors: Souza Claudio Rafael Almeida de
Published: June 2022

Nosso artigo estuda quatro oratórios monumentos: Oratório Cruz do Pascoal, Oratório de São Benedito, Oratório da Mãe Rainha de Schoenstatt e Oratório de Nossa Senhora de Fátima, todos na cidade de Salvador, Bahia. Procura-se correlacionar sua estima enquanto cultura material e de memória visual que emerge dos lugares onde se localizam. O resultado permite ter conhecimento e explicitação da associação entre o que é monumento, a religiosidade baiana, a devoção aos santos e as construções, que são frutos da devoção popular na Bahia.
A atuação das CAPs E IAPs em cidades médias: o caso de Passo Fundo, RS
Authors: Souza Edgar de
Published: June 2022

No Brasil, até as primeiras décadas do século XX, os campos previdenciário e habitacional eram controlados essencialmente pelo setor privado. Frente à ineficiência do setor privado em atender a demanda nacional por esses serviços, e pressionado pela população, o poder púbico decidiu assumir efetivamente como sua responsabilidade a promoção da assistência e habitação social com a criação das Caixas e dos Institutos de Aposentadoria e Pensões (CAPs/IAPs). Assim, este artigo tem como objetivo compreender a atuação das CAPs e dos IAPS no campo da habitação social de Passo Fundo, cidade média localizada ao noroeste do estado do Rio Grande do Sul, entre 1945 e 1964. Os procedimentos metodológicos foram divididos em três etapas: pesquisa bibliográfica; pesquisa documental; e análise dos dados. A partir do levantamento de 5.276 processos imobiliários nos arquivos do INSS/RS das cidades de Passo Fundo e Porto Alegre, encontrou-se um volume de 144 processos de financiamento imobiliários concedidos por meio de seis diferentes órgãos previdenciários em Passo Fundo durante o recorte temporal especificado.
Risk factors for asthma exacerbations during pregnancy: a systematic review and meta-analysis
Authors: Robijn Annelies L. , Bokern Marleen P. , Jensen Megan E. , Barker Daniel , Baines Katherine J. , Murphy Vanessa E.
Published: June 2022

Background

Conflicting literature exists regarding the risk factors for exacerbations among pregnant women with asthma. This systematic review and meta-analysis aimed to determine risk factors for asthma exacerbations during pregnancy.

Methods

Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*) and (exacerb* or flare up or morbidit* or attack*).

All studies published between 2000 and 24 August 2021 were considered for inclusion if they reported at least one potential risk factor of asthma exacerbations in pregnant women with asthma. Of the 3337 references considered, 35 publications involving 429 583 pregnant women with asthma were included. Meta-analyses were conducted to determine mean difference in risk factor between exacerbation groups, or the relative risks of exacerbation with certain risk factors. Good study quality was found through the Newcastle-Ottawa Scale (median score 8, interquartile range 7–9).

Results

Increased maternal age (mean difference 0.62, 95% CI 0.11–1.13), obesity (relative risk 1.25, 95% CI 1.15–1.37), smoking (relative risk 1.35, 95% CI 1.04–1.75), black ethnicity (relative risk 1.62, 95% CI 1.52–1.73), multiparity (relative risk 1.31, 95% CI 1.01–1.68), depression/anxiety (relative risk 1.42, 95% CI 1.27–1.59), moderate–severe asthma (relative risk 3.44, 95% CI 2.03–5.83,versusmild) and severe asthma (relative risk 2.70, 95% CI 1.85–3.95,versusmild–moderate) were associated with an increased risk of asthma exacerbations during pregnancy.

Conclusions

Future interventions aimed at reducing exacerbations in pregnancy could address the modifiable factors, such as smoking and depression/anxiety, and introduce more regular monitoring for those with nonmodifiable risk factors such as obesity and more severe asthma.
Suitability of accelerometry as an objective measure for upper extremity use in stroke patients
Authors: Heye Anne-Lisa , Kersting Christine , Kneer Malte , Barzel Anne
Published: June 2022

Background

Upper limb (UL) paresis is one of the most common stroke consequences and significantly restricts patients in everyday life. Instruments objectively measuring direct arm use in stroke patients are lacking, but might be helpful to understand patients’ impairment. Aiming to examine whether accelerometry is a suitable objective measure for everyday UL use in stroke patients, we conducted a systematic review on the association between accelerometer-derived measurements and clinical scales.

Methods

Articles were systematically searched in PubMed, Scopus, Cochrane Library, PeDro and LIVIVO through December 12th, 2021, screened for inclusion by AH, and subsequently independently screened by CK and MK. Disagreements were discussed until consensus. We included English and German peer-reviewed articles dealing with the validity of accelerometers as a measurement of UL use in stroke patients and eligible systematic reviews. Studies exclusively using accelerometry as an outcome parameter, book contributions, conference abstracts and case studies were excluded. Data extraction was conducted by AH and confirmed by CK focussing on study type, objective, accelerometer device, sample size, stroke status, assessments conducted, measurement method, wearing time and key results. We analysed all eligible articles regarding the correlation between accelerometry and other clinical assessments and the validity in accordance with the type of accelerometer.

Results

Excluding duplicates, the initial search yielded 477 records. In the 34 eligible studies accelerometers was used with a predominance of tri-axial accelerometery (n = 12) and only few with two-axial application (n = 4). Regarding measures to examine association to accelerometer data different clinical scales were applied depending on the setting, the degree of impairment and/or the status of stroke. Cut-off values to determine correlations varied largely; most significant correlations are reported for the MAL [Range 0.31- 0.84] and the ARAT [Range 0.15–0.79].

Conclusions

Accelerometers can provide reliable data about daily arm use frequency but do not supply information about the movements´ quality and restrictions on everyday activities of stroke patients. Depending on the context, it is advisable to use both, accelerometry and other clinical measures. According to the literature there is currently no accelerometer device most suitable to measure UL activity. High correlations indicate that multi-dimensional accelerometers should be preferred.
Hiccups in patients with cancer: a multi-site, single-institution study of etiology, severity, complications, interventions, and outcomes
Authors: Ehret Christopher J. , Almodallal Yahya , Le-Rademacher Jennifer G. , Martin Nichole A. , Moynagh Michael R. , Rajotia Arush , Jatoi Aminah
Published: June 2022

Background

To our knowledge, previous studies have not investigated hiccups in patients with cancer with detailed patient-level data with the goal of capturing a broad spectrum of hiccup symptomatology.

Methods

This multi-site, single institution study examined consecutive medical records to better understand hiccups in patients with cancer.

Results

A total of 320 patients are the focus of this report. The median age of patients when hiccups were first reported in the medical record was 63 years (range: 21, 97 years) with 284 (89%) men and 36 (11%) women. The most common diagnose was gastrointestinal cancer. Hiccups most frequently occurred daily, as seen in 194 patients (62%), and the most common duration was less than 1 week, as seen in 146 patients (47%). However, nine patients had had daily hiccups for greater than 6 weeks, and 5 had symptoms for years. Cited etiology was non-chemotherapy medications in 36 (11%) and cancer chemotherapy in 19 (6%). Complications occurred in approximately a third and included insomnia in 51 patients (16%); hospitalization or emergency department visit in 34 (11%); and musculoskeletal pain in 23 (7%). Baclofen was the single most prescribed agent for hiccup palliation, but 100 patients received more than one medication. Medical procedures, which included acupuncture, paracentesis, or phrenic nerve block, were performed in 5 patients. In 234 patients (73%), the medical record documented hiccup cessation.

Conclusions

Hiccups appear to be highly problematic in a small subset of patients with cancer with no well-defined palliative approaches.
Prevalence and determinants of aggressive behavior among adults with problematic substance use in Northwest Ethiopia: a cross-sectional survey
Authors: Legas Getasew , Belete Habte , Asnakew Sintayehu
Published: June 2022

Background

The recent WHO data reported that a high treatment gap for behavioral illnesses (70%) in low- and- middle-income countries and the mortality rate of aggressive behavior reaches up to 32.1 per 100,000 populations in the region. However, the magnitude of aggressive behavior is not well stated in resource-limited settings. Therefore, the aim of this study was to assess the prevalence and determinant factors of aggressive behavior among adults with problematic substance use in northwest Ethiopia.

Methods

A community-based cross-sectional study was employed from January to March 2019. A multi-stage cluster sampling method was used to screen a total of 4028 adults for problematic substance use by using the Cutdown, Annoyed, Guilty, and Eye-opener questionnaire (CAGE AID). Finally, 838 participants were positive for problematic substance use and interviewed for aggressive behavior using a modified overt aggression scale. Multiple logistic regression analysis was used to show the adjusted odds ratios (AOR) and p-value < 0.05 considered statistically significant. A multilevel binary logistic regressions model was employed for the hierarchical structure of two-level data for the individual and woreda/district levels.

Results

The prevalence of aggressive behavior was found to be 37.9% (301/795, 95% CI: 34.5, 41.3). Stressful life events (AOR = 2.209, 95 CI; 1.423, 3.429), family history of mental illness (AOR = 4.038, 95 CI; 2.046, 7.971), comorbid physical illness (AOR = 2.01, 95 CI; 1.332, 3.032) and depressive symptoms (AOR = 2.342, 95 CI; 1.686, 3.253) were associated with aggressive behavior among individual with problem substance use.

Conclusion

Aggressive behavior was found to be high among problematic substance uses. An individual with problematic substance use is recommended to be screened by health extension workers for aggressive behavior at the community level.
Neighborhood social cohesion and serious psychological distress among Asian, Black, Hispanic/Latinx, and White adults in the United States: a cross-sectional study
Authors: Gullett Lauren R. , Alhasan Dana M. , Gaston Symielle A. , Jackson W. Braxton , Kawachi Ichiro , Jackson Chandra L.
Published: June 2022

Background

Serious psychological distress (SPD) is common and more prevalent in women, older adults, and individuals with a low-income. Prior studies have highlighted the role of low neighborhood social cohesion (nSC) in potentially contributing to SPD; however, few have investigated this association in a large, nationally representative sample of the United States. Therefore, our objective was to investigate the overall and racial/ethnic-, sex/gender-, self-rated health status-, age-, and household income-specific relationships between nSC and SPD.

Methods

We used data from survey years 2013 to 2018 of the National Health Interview Survey to investigate nSC and SPD among Asian, Non-Hispanic (NH)-Black, Hispanic/Latinx, and NH-White men as well as women in the United States (N = 168,573) and to determine modification by race/ethnicity, sex/gender, self-rated health status, age, and annual household income. nSC was measured by asking participants four questions related to the trustworthiness and dependability of their neighbors. nSC scores were trichotomized into low (< 12), medium (12–14), and high (15–16). SPD was measured using the Kessler 6 psychological distress scale with scores ≥ 13 indicating SPD. After adjusting for sociodemographic, health behavior, and clinical confounders, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs).

Results

Among 168,573 participants, most were Non-Hispanic (NH)-White (69%), and mean age was 47 ± 0.01 years. After adjustment, low vs. high nSC was associated with a 75% higher prevalence of SPD overall (PR = 1.75 [1.59–1.92]), 4 times the prevalence of SPD among Asian men (PR = 4.06 [1.57–10.50]), 2 times the prevalence of SPD among participants in at least good health (PR = 2.02 [95% CI: 1.74–2.35]), 92% higher prevalence of SPD among participants ≥ 50 years old (PR = 1.92 [1.70–2.18]), and approximately 3 times the prevalence of SPD among Hispanic/Latinx participants with household incomes ≥ $75,000 (PR = 2.97 [1.45–6.08]).

Conclusions

Low nSC was associated with higher SPD in the overall population and the magnitude of the association was higher in Asian men, participants who reported good health, older participants, and Hispanic/Latinx adults with higher household incomes. Future research should continue to examine how neighborhood contexts can affect health across various sociodemographic groups, especially among groups with multiple marginalized social identities.
Preoperative serum calcium could be a prognostic factor for surgical treatment of recurrent patellar dislocation: a retrospective study
Authors: Qiao Yi , Ye Zipeng , Xu Junjie , Zhang Xiuyuan , Chen Jiebo , Xu Caiqi , Zhao Song , Zhao Jinzhong
Published: June 2022

Background

Surgical treatment for recurrent patellar dislocation (RPD) could yield good outcomes. While, unsatisfactory recovery still exists in some cases. For all prognostic factors, serum biomarkers have rarely been investigated. This study aimed to evaluate the prognostic value of preoperative serum calcium level, a widely used serum biomarker, in surgical treatment for RPD.

Study design

Retrospective study.

Methods

Ninety-nine patients with RPD were enrolled in the study. Preoperative serum calcium was acquired from routinely tested blood 1 day prior to operation. Demographic data, characteristics of RPD, postoperative functional outcomes were obtained. The association between preoperative calcium and postoperative functional outcomes (Kujala, Lysholm, Tegner, IKDC and KOOS score) was determined by correlation analysis and multivariate linear regression analysis. Poor recovery was determined as Kujala score below 80. The receiver operating characteristic (ROC) curve was used to assess the prognostic value of preoperative calcium.

Results

Patients were followed up for a mean period of 2.45 ± 1.33 years. All clinical scores showed significant improvement at the latest follow-up. Correlation and multivariate linear analyses indicated that serum calcium level was an important factor related with the prognosis of surgical treatment for RPD. According to the ROC curve, the cut-off value for preoperative calcium was 2.225 mmol/L. The clinical outcomes of patients with a preoperative blood calcium < 2.225 mmol/L was significantly worse than that with a higher calcium level. The correspondent sensitivity was 0.812 with a specificity of 0.633.

Conclusion

Operative treatment for RPD achieved good results, while in some cases the functional scores remain inferior. As a serum biomarker, preoperative calcium could be prognostic for outcomes after surgical treatment for RPD.
Analysis of factors influencing cervical lymph node metastasis of papillary thyroid carcinoma at each lateral level
Authors: Liu Wen-qing , Yang Jing-yi , Wang Xiao-hui , Cai Wei , Li Fei
Published: June 2022

Objective

To analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC) and its influence on the distribution of lymph node metastasis at each lateral level of the neck to guide precise treatment of the lateral area.

Methods

The clinicopathological data of patients with PTC initially diagnosed and treated at our hospital from February 2014 to September 2021 were collected; the metastatic status of each lateral level was recorded, and correlations were analyzed.

Results

A total of 203 patients were enrolled in this study. There were 67 males and 136 females, with an average age of 41.1 years. In the lateral cervical area, lymph node metastasis was found at level IIa in 81 patients (39.9%); level III, 171 patients (84.2%); level IV, 122 patients (60%); and level Vb, 18 patients (8.9%). Correlation analysis showed that age (r = 0.198, P < 0.01) and sex (r = 0.196, P < 0.01) were weakly correlated with the number of positive lymph nodes in the central region. The tumor size (r = 0.164, P < 0.05) was weakly correlated with lymph node metastasis at level IV. The presence of multiple tumor foci was weakly correlated with lymph node metastasis at level IIa (r = 0.163, P < 0.05) and Vb (r = 0.143, P < 0.05). The tumor location (r = − 0.168, P < 0.05) was weakly correlated with lymph node metastasis at level III. The number of positive lymph nodes in the central region (r = 0.189, P < 0.01) was weakly correlated with lymph node metastasis at level IV. Binary logistic regression analysis showed that the risk of metastasis of multifocal tumors was higher than that of unifocal tumors by 1.958 times at level IIa (P = 0.021, OR = 1.958) and 2.929 times at level Vb (P = 0.049, OR = 2.929). The higher the tumor was located, the higher the risk of metastasis at level III (P = 0.014, OR = 0.563). Every additional positive lymph node in the central region increased the risk of metastasis at level IV by 1.126 times (P = 0.009, OR = 1.126).

Conclusions

For patients with pathological evidence of lateral metastasis, standard dissection of level IIa through Vb is recommended; selective dissection requires careful consideration. Patients with multifocal tumors have a high risk of metastasis at levels IIa and Vb, which requires special attention during the operation.
Impact of the COVID-19 pandemic on emergency department visits for genitourinary trauma
Authors: Nabavizadeh Behnam , Hakam Nizar , Abbasi Behzad , Shaw Nathan M. , Breyer Benjamin N.
Published: June 2022

Introduction

The mean number of emergency department visits for all-cause traumas has declined significantly during the COVID-19 pandemic. We aim to identify how a global pandemic and social distancing could affect the trends and pattern of genitourinary traumas.

Methods

We queried the National Electronic Injury Surveillance System to obtain consumer product-related genitourinary injuries leading to emergency department visits. Using three key events in 2020, we divided the study period to three intervals: January 20, when the first COVID-19 case was confirmed in the United States; March 13, when a national state of emergency was declared; April 20, when Texas became the first state to start a phased reopening of economy. We compared the injury characteristics in 2020 to their identical intervals in 2019.

Results

Daily emergency department visits dropped significantly during the national lockdown (mean 131.5 vs. 78; Δ-40.7%; p < 0.01). The genitourinary injuries decreased significantly in children ≤ 17 years (p < 0.01), males (p < 0.001), and White population (p < 0.01). However, it did not change significantly in adults 18–64 years (p = 0.92), old adults ≥ 65 years (p = 0.37), females (p = 0.60), Black population (p = 0.90), other/unknown races (p = 0.93), and for injuries sustained at home (p = 0.75) and public (p = 0.11) locations. During the lockdown period, injuries associated with toilets/toilet seats (− 320, − 74.6%), day wear (− 266, − 77.7%), beds/bedframes (− 209, − 64.2%) decreased while injuries associated with knickknacks/statues/vases (+ 154, n/a), sofas/couches/divans (+ 130, 2,684%), and razors/shavers (+ 99, n/a) increased.

Conclusions

The COVID-19 lockdown had a significant impact on genitourinary traumas. The contributing factors could be investigated further to prevent such injuries during deconfinement periods.
In vitro anti-HIV and cytotoxic effects of pure compounds isolated from Croton macrostachyus Hochst. Ex Delile
Authors: Terefe Ermias Mergia , Okalebo Faith A. , Derese Solomon , Langat Moses K. , Mas-Claret Eduard , Aljarba Nada H. , Alkahtani Saad , Batiha Gaber El-Saber , Ghosh Arabinda , El-Masry Eman A. , Muriuki Joseph
Published: June 2022

Croton macrostachyus is an important plant in traditional African medicine, widely utilized to treat a variety of diseases. In Kenya, HIV-infected patients use leaf and root decoctions of the plant as a cure for cough, back pain, bleeding, skin diseases, warts, pneumonia, and wounds. This study aimed to evaluate the anti-HIV activities and cytotoxic effects of extracts and chemical constituents isolated from C. macrostachyus. In our previous study we demonstrated that the hexane, CH2Cl2, ethyl acetate and methanol soluble fractions of a 1:1 v/v/ CH2Cl2/MeOH crude extracts of the leaves and stem bark of C. macrostachyus exhibited potent anti-HIV activities against HIV-1 with IC50 values ranging from 0.02–8.1 μg/mL and cytotoxicity effects against MT-4 cells ranging from IC50 = 0.58–174 μg/mL. Hence, hexane soluble extract of 1:1 v/v/ CH2Cl2/MeOH crude extract of the leaves of C. macrostachyus, that was more potent against HIV-1 at IC50 = 0.02 μg/mL was subjected to column chromatography leading to the isolation of 2-methoxy benzyl benzoate (1), lupenone (2), lupeol acetate (3), betulin (4), lupeol (5), sitosterol (6) and stigmasterol (7). Lupenone (2), lupeol acetate (3) and betulin (4) exhibited anti-HIV-1 inhibition at IC50 = 4.7 nM, 4.3 and 4.5 μg/mL respectively. The results obtained from this study support the potential of C. macrostachyus, as a source of anti-HIV constituents.
The use of a surgical boot camp combining anatomical education and surgical simulation for internship preparedness among senior medical students
Authors: Zhang Jifeng , Zilundu Prince Last Mudenda , Zhang Wenbin , Yu Guangyin , Li Sumei , Zhou Lihua , Guo Guoqing
Published: June 2022

Background

Senior medical students feel unprepared for surgical procedures and care for surgery patients when they begin their internship. This study sought to introduce and evaluate a surgical boot camp training for senior medical students.

Methods

A 44-h surgical boot camp program of lectures on clinical practice simulation, anatomical dissections, and simulated operation on cadavers was designed, implemented, and evaluated during the 2018 to 2019 academic year. A self-administered questionnaire was used to assess students’ perceptions of the content, delivery, and self-confidence. The mini-Clinical Evaluation Exercise (mini-CEX) and the Operative Performance Rating System were used to assess skills essential to good clinical care and to facilitate feedback.

Results

Over 93% of the students were satisfied with the surgical boot camp, training equipment, and learning materials provided. After six sessions of training, 85.3% reported gaining self-confidence and performed better in some surgical procedures such as major gastrectomy. The mini-CEX scores suggested significant improvement in the students’ clinical skills, attitudes, and behaviors (P < 0.01). Ninety-eight percent of students felt that the anatomical knowledge taught met their needs. The scores of the Operative Performance Rating System suggested that the students’ surgical skills such as instruments handling, incising, treatment of surrounding tissues (blood vessels, nerves), and smoothness of the whole operation had increased significantly following the surgical boot camp (All P < 0.01).

Conclusion

The surgical boot camp curriculum improved students’ satisfaction and confidence in core clinical practice competencies. Therefore, medical schools the world over should continue to seek ways to bridge the gaps between pre-clinical, clinical, and internship training.
A gossypol derivative effectively protects against Zika and dengue virus infection without toxicity
Authors: Gao Yaning , Tai Wanbo , Wang Xinyi , Jiang Shibo , Debnath Asim K. , Du Lanying , Chen Shizhong
Published: June 2022

Background

Zika virus (ZIKV) and dengue virus (DENV) cause microcephaly and dengue hemorrhagic fever, respectively, leading to severe problems. No effective antiviral agents are approved against infections of these flaviviruses, calling for the need to develop potent therapeutics. We previously identified gossypol as an effective inhibitor against ZIKV and DENV infections, but this compound is toxic and not suitable for in vivo treatment.

Results

In this study, we showed that gossypol derivative ST087010 exhibited potent and broad-spectrum in vitro inhibitory activity against infections of at least ten ZIKV strains isolated from different hosts, time periods, and countries, as well as DENV-1-4 serotypes, and significantly reduced cytotoxicity compared to gossypol. It presented broad-spectrum in vivo protective efficacy, protecting ZIKV-infected Ifnar1−/− mice from lethal challenge, with increased survival and reduced weight loss. Ifnar1−/− mice treated with this gossypol derivative decreased viral titers in various tissues, including the brain and testis, after infection with ZIKV at different human isolates. Moreover, ST087010 potently blocked ZIKV vertical transmission in pregnant Ifnar1−/− mice, preventing ZIKV-caused fetal death, and it was safe for pregnant mice and their pups. It also protected DENV-2-challenged Ifnar1−/− mice against viral replication by reducing the viral titers in the brain, kidney, heart, and sera.

Conclusions

Overall, our data indicate the potential for further development of this gossypol derivative as an effective and safe broad-spectrum therapeutic agent to treat ZIKV and DENV diseases.
Gut microbiota signatures of long-term and short-term plant-based dietary pattern and cardiometabolic health: a prospective cohort study
Authors: Miao Zelei , Du Wenwen , Xiao Congmei , Su Chang , Gou Wanglong , Shen Luqi , Zhang Jiguo , Fu Yuanqing , Jiang Zengliang , Wang Zhihong , Jia Xiaofang , Zheng Ju-Sheng , Wang Huijun
Published: June 2022

Background

The interplay among the plant-based dietary pattern, gut microbiota, and cardiometabolic health is still unclear, and evidence from large prospective cohorts is rare. We aimed to examine the association of long-term and short-term plant-based dietary patterns with gut microbiota and to assess the prospective association of the identified microbial features with cardiometabolic biomarkers.

Methods

Using a population-based prospective cohort study: the China Health and Nutrition Survey, we included 3096 participants from 15 provinces/megacities across China. We created an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). The average PDIs were calculated using repeat food frequency questionnaires collected in 2011 and 2015 to represent a long-term dietary pattern. Short-term dietary pattern was estimated using 3-day 24-h dietary recalls collected in 2015. Fecal samples were collected in 2015 and measured using 16S rRNA sequencing. We investigated the association of long-term and short-term plant-based dietary patterns with gut microbial diversity, taxonomies, and functional pathways using linear mixed models. Furthermore, we assessed the prospective associations between the identified gut microbiome signatures and cardiometabolic biomarkers (measured in 2018) using linear regression.

Results

We found a significant association of short-term hPDI with microbial alpha-diversity. Both long-term and short-term plant-based diet indices were correlated with microbial overall structure, whereas long-term estimates explained more variance. Long-term and short-term PDIs were differently associated with microbial taxonomic composition, yet only microbes related to long-term estimates showed association with future cardiometabolic biomarkers. Higher long-term PDI was associated with the lower relative abundance of Peptostreptococcus, while this microbe was positively correlated with the high-sensitivity C-reactive protein and inversely associated with high-density lipoprotein cholesterol.

Conclusions

We found shared and distinct gut microbial signatures of long-term and short-term plant-based dietary patterns. The identified microbial genera may provide insights into the protective role of long-term plant-based dietary pattern for cardiometabolic health, and replication in large independent cohorts is needed.
The role of insulin-like growth factor 2 mRNA binding proteins in female reproductive pathophysiology
Authors: Xu Xiao , Shen Hao-Ran , Zhang Jia-Rong , Li Xue-Lian
Published: June 2022

Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets.