bluuebunny/crossref_metadata_2025 huggingface dataset:
To Explore the Herbal Combinations and Pharmacological Mechanisms of Yourong Huang in the Treatment of Cervical Spondylosis Based on Data Mining and Network Pharmacology
Authors: Chai Yuan , Huang Yourong , Han Jie , Chen Feng , Zhu Jicong , Zeng Hao , Li Wenhua , Zhang Xiaoyun
Published: June 2023

Objective: Yourong Huang's drug administration pattern in treating cervical spondylosis (CS) was discussed and evaluated, and the likely mechanism of the high-frequency drug in the treatment of CS to give a reference for the clinical treatment of CS. Materials & methods: The cases of Yourong Huang treating CS were collected, to provide association rules between high-frequency drug pairs, IBM SPSS Statistics 22.0 and IBM SPSS Modeler18.0 were employed. Build a network relationship between “CS core target-active ingredient-drug” was constructed. Results: Two hundred and sixty-two prescriptions were collected, 117 drugs were used, and 2882 doses were taken. Through systematic analysis, the core drug Shaoyao-Mugua Decoction (SYMGD) was discovered. A total of 206 active ingredients were found in the 8 high-frequency prescription drugs. There were 71 potential targets for SYMGD treatment of CS. A total of 158 items were identified by KEGG enrichment analysis, the most important of which were 5 signaling pathways. According to the molecular docking results, SYMGD had good binding activity to its therapeutic targets. Discussion & conclusion: Yourong Huang treated CS with Chinese medicine by “reinforcing liver and kidney, warmly invigorating spleen and stomach, activating blood and resolving stasis.” SYMGD, a core drug group, treats CS through a multicomponent, multitarget, and multipathway comprehensive intervention. Comprehensive analysis calculate the minimum binding energy between 5 key active ingredients and 5 key targets, knowable that SYMGD had good binding activity to its therapeutic target, proving that the prediction of this study was reliable.
Can ❤s Change Minds? Social Media Endorsements and Policy Preferences
Authors: Conzo Pierluigi , Taylor Laura K. , Morales Juan S. , Samahita Margaret , Gallice Andrea
Published: June 2023

We investigate the effect of social media endorsements (likes, retweets, shares) on individuals’ policy preferences. In two pre-registered online experiments ( N = 1,384), we exposed participants to non-neutral policy messages about the COVID-19 pandemic (emphasizing either public health or economic activity as a policy priority) while varying the level of endorsements of these messages. Our experimental treatment did not result in aggregate changes to policy views. However, our analysis indicates that active social media users did respond to the variation in engagement metrics. In particular, we find a strong positive treatment effect concentrated on a minority of individuals who correctly answered a factual manipulation check regarding the endorsements. Our results suggest that though only a fraction of individuals appear to pay conscious attention to endorsement metrics, they may be influenced by these social cues.
Influence of Metabolic Syndrome on Small, Dense LDL, and Subclinical Atherosclerosis in Older Subjects
Authors: Yoshino Hiroshi , Matsumoto Tomoko , Yoshino Gen
Published: June 2023

Aging is known as one of the important risk factors for coronary artery disease (CAD). We explore whether an association of metabolic syndrome (Met- S) increases subclinical atherosclerosis among elderly diabetic subjects estimating the plaque score ( PS) of the carotid artery. A total of 187 subjects were enrolled. Middle-aged and older groups were divided into two groups. T-test and Chi-square test were also employed. Simple regression analysis for the PS was performed with respective risk factors as independent variables. After selection of independent variables, multiple regression analysis was performed to estimated the association of PS and dependent variable of the study. There were significant differences in body mass index (BMI) ( p < .001), HbA1c ( p < .01), TG ( p < .05), and PS ( p < .001) . Multiple regression analysis in middle-aged subjects showed that the determinant of PS were age ( p < .001), BMI ( p = .006), Met- S ( p = .004), and hs-CRP ( p = .019). Multiple regression analysis in older subjects showed that neither age nor Met- S was included as significant determinant of PS. An association of Met- S is an important factor for progression of subclinical atherosclerosis, but it cannot be a significant determinant of PS if the subjects are limited within older group.
Magnitude of Incapability and Pain Intensity are Associated More with Unhelpful Thoughts Than Stressful Life Events
Authors: Broekman Melle M , Brinkman Niels , Ramtin Sina , Ngoue Marielle , Ring David , Jayakumar Prakash
Published: June 2023

Prior studies show that stressful life events are associated with greater magnitude of incapability and symptom intensity. We sought to understand the association of such events (i.e., both adverse childhood experiences and recent difficult life events [DLEs]) alongside feelings of worry or despair and unhelpful, on the magnitude of incapability and symptom intensity in musculoskeletal patients. One hundred and thirty-six patients presenting for musculoskeletal specialty care completed measures of incapability, pain intensity, adverse childhood experiences, DLEs in the last year, unhelpful thoughts, symptoms of anxiety and depression, and sociodemographic factors. Factors associated with the magnitude of incapability and pain intensity were sought in multivariable analysis. Accounting for potential confounders, greater incapability was associated with greater unhelpful thoughts (RC  =  −0.81; 95% CI  =  −1.2 to −0.42; P  ≤  .001), but not with stressful life events (either during childhood or more recently). Greater pain intensity was associated with greater unhelpful thoughts(RC  =  0.25; 95% CI  =  0.16 to 0.35; P  ≤  .001) and being divorced or widowed (RC  =  1.8; 96% CI  =  0.43 to 3.2; P  =  .011), but again, not with stressful life events. The strong association of unhelpful thoughts with magnitude of incapability and pain intensity can motivate musculoskeletal specialists to anticipate patients expressing negative pain thoughts and behaviors. Future studies might account for social and environmental context behind stressful life events and the influence of resiliency and pain-coping strategies on these interactions.

Level of Evidence:

Level III, prognostic study
Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial
Authors: Reddy Amit K. , Miller D. Claire , Sura Amol A. , Rathinam SR , Gonzales John A , Thundikandy Radhika , Kanakath Anuradha , Murugan Bala , Vedhanayaki Rajesh , Lim Lyndell L. , Suhler Eric B. , Doan Thuy , Al-Dhibi Hassan A. , Goldstein Debra A. , Arellanes-Garcia Lourdes , Acharya Nisha R
Published: June 2023

Background

The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis.

Main body

This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF.

Conclusion

Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.
Deep learning-based classification model for GPR151 activator activity prediction
Authors: Xu Huangchao , Zhang Baohua , Liu Qian
Published: June 2023

Background

GPR151 is a kind of protein belonging to G protein-coupled receptor family that is closely associated with a variety of physiological and pathological processes.The potential use of GPR151 as a therapeutic target for the management of metabolic disorders has been demonstrated in several studies, highlighting the demand to explore its activators further. Activity prediction serves as a vital preliminary step in drug discovery, which is both costly and time-consuming. Thus, the development of reliable activity classification model has become an essential way in the process of drug discovery, aiming to enhance the efficiency of virtual screening.

Results

We propose a learning-based method based on feature extractor and deep neural network to predict the activity of GPR151 activators. We first introduce a new molecular feature extraction algorithm which utilizes the idea of bag-of-words model in natural language to densify the sparse fingerprint vector. Mol2vec method is also used to extract diverse features. Then, we construct three classical feature selection algorithms and three types of deep learning model to enhance the representational capacity of molecules and predict activity label by five different classifiers. We conduct experiments using our own dataset of GPR151 activators. The results demonstrate high classification accuracy and stability, with the optimal model Mol2vec-CNN significantly improving performance across multiple classifiers. The svm classifier achieves the best accuracy of 0.92 and F1 score of 0.76 which indicates promising applications for our method in the field of activity prediction.

Conclusion

The results suggest that the experimental design of this study is appropriate and well-conceived. The deep learning-based feature extraction algorithm established in this study outperforms traditional feature selection algorithm for activity prediction. The model developed can be effectively utilized in the pre-screening stage of drug virtual screening.
Probing stress-regulated ordering of the plant cortical microtubule array via a computational approach
Authors: Li Jing , Szymanski Daniel B. , Kim Taeyoon
Published: June 2023

Background

Morphological properties of tissues and organs rely on cell growth. The growth of plant cells is determined by properties of a tough outer cell wall that deforms anisotropically in response to high turgor pressure. Cortical microtubules bias the mechanical anisotropy of a cell wall by affecting the trajectories of cellulose synthases in the wall that polymerize cellulose microfibrils. The microtubule cytoskeleton is often oriented in one direction at cellular length-scales to regulate growth direction, but the means by which cellular-scale microtubule patterns emerge has not been well understood. Correlations between the microtubule orientation and tensile forces in the cell wall have often been observed. However, the plausibility of stress as a determining factor for microtubule patterning has not been directly evaluated to date.

Results

Here, we simulated how different attributes of tensile forces in the cell wall can orient and pattern the microtubule array in the cortex. We implemented a discrete model with transient microtubule behaviors influenced by local mechanical stress in order to probe the mechanisms of stress-dependent patterning. Specifically, we varied the sensitivity of four types of dynamic behaviors observed on the plus end of microtubules – growth, shrinkage, catastrophe, and rescue – to local stress. Then, we evaluated the extent and rate of microtubule alignments in a two-dimensional computational domain that reflects the structural organization of the cortical array in plant cells.

Conclusion

Our modeling approaches reproduced microtubule patterns observed in simple cell types and demonstrated that a spatial variation in the magnitude and anisotropy of stress can mediate mechanical feedback between the wall and of the cortical microtubule array.
Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges
Authors: Sato Daisuke , Takami Hirokazu , Takayanagi Shunsaku , Taoka Kazuki , Tanaka Mariko , Matsuura Reiko , Tanaka Shota , Saito Nobuhito
Published: June 2023

Background

Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described.

Case presentation

A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and “other iatrogenic immunodeficiency-associated lymphoproliferative disorder” (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD.

Conclusions

This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.
The role of gender inequities in women's access to reproductive health services: a population-level study of Simiyu Region Tanzania
Authors: Tesha Jane , Fabian Agatha , Mkuwa Serafina , Misungwi Gaspery , Ngalesoni Frida
Published: June 2023

Background

Amref Health Africa, with support from Global Affairs Canada, examines if women's access to reproductive health services in Tanzania is affected by Gender social norms, decision-making power, roles and responsibility, and access to resources in relation to the utilization of reproductive Health Services in Tanzania. A Gender Need Assessment (GNA) was conducted in five districts in ' 'Tanzania Simiyu Region to improve the infrastructure, supply, quality, and demand for integrated Reproductive, Maternal, Newborn, and Child and Adolescent Health (RMNCAH), Nutrition, and Water, Sanitation, and Hygiene (WASH) services. The analysis identifies gender as a fundamental maternal and child health driver through existing gender inequality at the household and community levels that dictates women's status.

Methods

The qualitative assessment involved data collected from gender- and age-desegregated focus group discussions (FGDs) and in-depth interviews (IDIs) of key informants in three districts; Bariadi, Busega, and Meatu, in Simiyu region, Tanzania. Participants comprised 8-10 married women and men, unmarried women and men, and adolescent boys and girls. A total of 129 participants were involved in the FGDs.

Results

This paper reports the critical drivers influencing gender inequality in Simiyu by detailing how Gender inequality affected women's access to reproductive health care in relation to; gender social norms, decision-making power, access to resources at the household and community level, roles and responsibilities, including men's and 'boys' roles are more valued than the roles and responsibilities of women and girls resulted to limited free time to do things for themselves, such as visiting the health facilities for RMNCAH.

Conclusions

This paper explored gender-based enablers and/or barriers influencing women and girls' realization of their sexual and reproductive health and rights. It was found that social norms, decision-making powers, and lack of access to and control over resources presented as key barriers. In contrast, continuous community sensitization and increased scope of women's participation in decision-making served as enabling environment to overcome gender inequities that influence woman's use of RMNCAH services in Tanzania. Such insights will shape interventions geared towards valuing differences in a manner that overcome gender inequities that influence woman's use of RMNCAH services in Tanzania.
The predictors of unsuppressed viremia among PLHIV: a cross-sectional study in Ghana
Authors: Owusu Lydia Boampong , Ababio Christiana , Boahene Selina , Zakaria Abdul-Fatawu Suglo , Emikpe Abigael Omowumi , Dwumfour Catherine Kroamah , Appiagyei Kofi Antwi , Apiribu Felix
Published: June 2023

Background

Unsuppressed viremia in HIV infected patients is generally associated with increased rates of disease transmission and poor patient survival. This study assessed the socio-demographic determinants of People Living with HIV/AIDS, having viral load non-suppression and who are receiving antiretroviral therapy in a District Hospital in Ghana.

Methods

The study utilized the cross-sectional research design with both primary and secondary data conducted from September to October 2021 in Ghana. Data were collected from 331 PLHIV who were placed on Anti-Retroviral Therapy (ART) for more than 12 months at the ART centre at a District Hospital in Ghana. Unsuppressed viremia was defined as plasma viral load of ≥ 1000 copies/mL after 12 months on an ART with effective adherent support. A structured questionnaire was used to collect primary data on participants and a Secondary data was also collected from patients’ folders, hospital registers and the computerized health information systems at the study site. SPSS was used to analyse descriptive and inferential data. Pearson’s chi-square and Fisher’s exact test were used to assess the independent determinants of viral load non-suppression. Pearson’s chi-square test was used for tests giving ≤ 20% of expected cell counts less than five while Fisher’s exact test was used for tests giving > 20% of expected cell counts less than five. A p value of < 0.05 was considered statistically significant.

Results

Out of the 331 PLHIV who participated in the study, 174 (53%) were female and 157 (47%) were Male. The study found viral load non-suppression of 19% with age (p = 0.03), income (p = 0.02), employment (p = 0.04), means of transportation (p = 0.02), cost of transportation to the ART centre (p = 0.03) and level of medication adherence (p = 0.02) as determinants of viral load non-suppression.

Conclusion

There was a low level of viral load non-suppression among PLHIV after 12 months of active antiretroviral therapy with age, income, employment, means of transportation, cost of transportation and level of medication adherence influencing viral non-suppression. Thus, ART drugs and services should be decentralized to the community health workers’ level within the various localities of patients to decrease the economic consequences involved in accessing health care for PLHIV/AIDS. This will minimize defaulting, improve adherence and promote viral load suppression.
Single-use flexible bronchoscopes vs traditional reusable flexible bronchoscopes: a prospective controlled study
Authors: He Shuzhen , Xie Lihua , Liu Jianming , Zou Lijun
Published: June 2023

Background

Single-use flexible bronchoscopes(SFB) eliminate the risk of bronchoscopy-related infection compared with traditional reusable flexible bronchoscopes(RFB). At present, there is no comparative study between SFB and RFB in the aspects of biopsy and interventional therapy. This study aims to explore whether SFB can perform complex bronchoscopic procedures such as transbronchial biopsies just like RFB.

Methods

We conducted a prospective controlled study. A total of 45 patients who required bronchoscopic biopsy in our hospital from June 2022 to December 2022 were enrolled. The patients were divided into the SFB group and the RFB group, and routine bronchoscopy, bronchoalveolar lavage, and biopsy were performed respectively. Data on the time of routine bronchoscopy, the recovery rate of bronchoalveolar lavage fluid(BALF), biopsy time, and bleeding volume were collected. Then we used the two-sample t-test and the χ2 test to assess the performance differences between SFB and RFB. We also designed a questionnaire to compare the performance between SFB and RFB by different bronchoscope operators.

Results

The routine examination time of SFB and RFB was 3.40 ± 0.50 min and 3.55 ± 0.42 min, respectively. There was no significant difference between the two groups (P = 0.308). The recovery rate of BALF was (46.56 ± 8.22) % in the SFB group and (47.00 ± 8.07) in the RFB group, without a significant difference between the two groups(P = 0.863). The biopsy time was similar(4.67 ± 0.51 min VS 4.57 ± 0.45 min) in both groups, with no significant difference(P = 0.512). The positive biopsy rate was 100% in both groups, with no significant difference. Overall, the bronchoscope operators were generally satisfied with SFB.

Conclusion

SFBs are non-inferior to RFBs in routine bronchoscopy, bronchoalveolar lavage, and biopsy. It is suggested that SFBs have a wider clinical application.
Development and validation of a machine learning model to predict imminent new vertebral fractures after vertebral augmentation
Authors: Jiang Yang , Cai Jinhui , Zeng Yurong , Ye Haoyi , Yang Tingqian , Liu Zhifeng , Liu Qingyu
Published: June 2023

Background

Accurately predicting the occurrence of imminent new vertebral fractures (NVFs) in patients with osteoporotic vertebral compression fractures (OVCFs) undergoing vertebral augmentation (VA) is challenging with yet no effective approach. This study aim to examine a machine learning model based on radiomics signature and clinical factors in predicting imminent new vertebral fractures after vertebral augmentation.

Methods

A total of 235 eligible patients with OVCFs who underwent VA procedures were recruited from two independent institutions and categorized into three groups, including training set (n = 138), internal validation set (n = 59), and external validation set (n = 38). In the training set, radiomics features were computationally retrieved from L1 or adjacent vertebral body (T12 or L2) on T1-w MRI images, and a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm (LASSO). Predictive radiomics signature and clinical factors were fitted into two final prediction models using the random survival forest (RSF) algorithm or COX proportional hazard (CPH) analysis. Independent internal and external validation sets were used to validate the prediction models.

Results

The two prediction models were integrated with radiomics signature and intravertebral cleft (IVC). The RSF model with C-indices of 0.763, 0.773, and 0.731 and time-dependent AUC (2 years) of 0.855, 0.907, and 0.839 (p < 0.001 for all) was found to be better predictive than the CPH model in training, internal and external validation sets. The RSF model provided better calibration, larger net benefits (determined by decision curve analysis), and lower prediction error (time-dependent brier score of 0.156, 0.151, and 0.146, respectively) than the CPH model.

Conclusions

The integrated RSF model showed the potential to predict imminent NVFs following vertebral augmentation, which will aid in postoperative follow-up and treatment.
Investigating discrimination in the workplace. Translation and validation of the Everyday Discrimination Scale for nursing staff in Germany
Authors: Ulusoy Nazan , Nienhaus Albert , Brzoska Patrick
Published: June 2023

Background

The Everyday Discrimination Scale (EDS) is a frequently used questionnaire in the field of health and social psychology that aims to explore perceptions of discrimination, especially instances of injustice related to various diversity characteristics. No adaptation to health care staff exists. The present study translates and adapts the EDS to nursing staff in Germany and examines its reliability and factorial validity as well as its measurement equivalence between men and women and different age groups.

Methods

The study was based on an online survey conducted among health care staff of two hospitals and two inpatient care facilities in Germany. The EDS was translated using a forward-backward translation approach. Direct maximum likelihood confirmatory factor analysis (CFA) was conducted to examine the factorial validity of the adapted EDS. Differential item functioning (DIF) related to age and sex was investigated by means of multiple indicators, multiple causes (MIMIC) models.

Results

Data on 302 individuals was available, of whom 237 (78.5%) were women. The most commonly employed one-factor, 8-item baseline model of the adapted EDS showed a poor fit (RMSEA = 0.149; CFI = 0.812; TLI = 0.737; SRMR = 0.072). The model fit improved considerably after including three error covariances between items 1 and 2, items 4 and 5, and items 7 and 8 (RMSEA = 0.066; CFI = 0.969; TLI = 0.949; SRMR = 0.036). Item 4 showed DIF related to sex and age, item 6 showed DIF related to age. DIF was moderate in size and did not bias the comparison between men and women or between younger and older employees.

Conclusions

The EDS can be considered a valid instrument for the assessment of discrimination experiences among nursing staff. Given that the questionnaire, similar to other EDS adaptations, may be prone to DIF and also considering that some error covariances need to be parameterized, latent variable modelling should be used for the analysis of the questionnaire.
Regulation of dental consultations in primary health care and performance of services in dental speciality centers
Authors: da Silva Bárbara Campos , Buzinaro Giovana Soares , Cabral Jhenyffer Andrade Viana , da Cunha Inara Pereira , de Lacerda Valéria Rodrigues , Bomfim Rafael Aiello
Published: June 2023

Objective

This study analyzed the regulation of dental specialty centers (CEOs) coordinated exclusively by Primary Health Care (PHC) in four primary outcomes: access and dental consultation, reception services, bonding and responsibility, and social participation.

Methods

A cross-sectional study was carried out using secondary data from the National Program for the Improvement of Access and Quality of Dental Specialty Centers (PMAQ-CEO): second cycle, using multilevel logistic regression to calculate the odds ratio (OR) and individual covariates.

Results

The analytical sample consisted of 9,599 CEO users who had completed all the variables analyzed. Of these, 63.5% were referred to the CEO by PHC. Dental care regulated by PHC was related to better access (OR 1.36, CI 95% 1.10–1.68), better reception (OR 1.33, CI 95% 1.03–1.71), better bonding and responsibility (OR 1.36, CI 95% 0.91–2.04), and social participation (OR 1.13, CI 95% 0.93–1.35) compared to those not regulated by primary health care as the exclusive pathway.

Conclusion

The regulation of access to the CEO coordinated by PHC presented the best performance. It is suggested that this form of PHC regulation, as a route for dental specialty centers, can be established in the national oral health care policy for better service performance.
Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing
Authors: Singh Ashish Kumar , Talseth-Palmer Bente , Xavier Alexandre , Scott Rodney J. , Drabløs Finn , Sjursen Wenche
Published: June 2023

Background

Hereditary genetic mutations causing predisposition to colorectal cancer are accountable for approximately 30% of all colorectal cancer cases. However, only a small fraction of these are high penetrant mutations occurring in DNA mismatch repair genes, causing one of several types of familial colorectal cancer (CRC) syndromes. Most of the mutations are low-penetrant variants, contributing to an increased risk of familial colorectal cancer, and they are often found in additional genes and pathways not previously associated with CRC. The aim of this study was to identify such variants, both high-penetrant and low-penetrant ones.

Methods

We performed whole exome sequencing on constitutional DNA extracted from blood of 48 patients suspected of familial colorectal cancer and used multiple in silico prediction tools and available literature-based evidence to detect and investigate genetic variants.

Results

We identified several causative and some potentially causative germline variants in genes known for their association with colorectal cancer. In addition, we identified several variants in genes not typically included in relevant gene panels for colorectal cancer, includingCFTR,PABPC1andTYRO3, which may be associated with an increased risk for cancer.

Conclusions

Identification of variants in additional genes that potentially can be associated with familial colorectal cancer indicates a larger genetic spectrum of this disease, not limited only to mismatch repair genes. Usage of multiple in silico tools based on different methods and combined through a consensus approach increases the sensitivity of predictions and narrows down a large list of variants to the ones that are most likely to be significant.
Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial
Authors: Li Xiao , Li Wen , Sun Lianjie , Ren Junyi , Xu Ying , Zheng Yuanyi , Bai Wenkun
Published: June 2023

Background

Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia.

Methods

Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded.

Discussion

This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body’s self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia.

Trial registration

ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.
Safety and efficacy in pediatric secondary intraocular lens implantation, in-the-bag versus sulcus implantation: a multicenter, single-blinded randomized controlled trial
Authors: Zou Yingshi , Jin Ling , Qu Bo , Chen Hui , Zeng Mingbing , Li Xia , Liu Xinhua , Luo Lixia , Liu Zhenzhen , Liu Yizhi
Published: June 2023

Background

Treatment of pediatric cataract remains challenging because of the extremely high incidence of postoperative adverse events (AEs), especially the AEs related to the locations of secondary implanted intraocular lens (IOL). There are two common locations for secondary IOL implantation in pediatric aphakic eyes: ciliary sulcus or in-the-bag implantation. However, there are currently no large, prospective studies comparing complication rates and visual prognosis of in-the-bag versus ciliarysulcus secondary IOL implantation in pediatric patients. Whether or how much secondary in-the-bag IOL implantation benefits the pediatric patients more than sulcus implantation and deserves to be performed routinely by surgeons remains to be elucidated. Here, we describe the protocol of a randomized controlled trial (RCT) designed to evaluate the safety and efficacy of two approaches of IOL implantation in pediatric aphakia.

Methods

The study is a multicenter, single-blinded RCT with 10 years of follow-up. Overall, a minimum of 286 eyes (approximately 228 participants assuming 75% have two study eyes) will be recruited. This study will be carried out in four eye clinics across China. Consecutive eligible patients are randomized to undergo either secondary in-the-bag IOL implantation or secondary sulcus IOL implantation. Participants with two eyes eligible will receive the same treatment. The primary outcomes are IOL decentration and the incidence of glaucoma-related AEs. The secondary outcomes include the incidence of other AEs, IOL tilt, visual acuity, and ocular refractive power. Analysis of the primary and secondary outcomes is to be based on the intention-to-treat and per-protocol analysis. Statistical analyses will include the χ2 test or Fisher’s exact test for the primary outcome, mixed model and generalized estimated equation (GEE) model for the secondary outcome, Kaplan–Meier survival curves for the cumulative probability of glaucoma-related AEs over time in each group.

Discussion

To the best of our knowledge, this study is the first RCT to evaluate the safety and efficacy of secondary IOL implantation in pediatric aphakia. The results will provide high-quality evidence for the clinical guidelines for the treatment of pediatric aphakia.

Trial registration

ClinicalTrials.gov NCT05136950. Registered on 1 November 2021.
Management of preexisting pelvic organ prolapse in pregnancy complicated with preterm premature rupture of membrane: a case report
Authors: Arusi Muhudin , Abdulhakim Elham , Awol Yasin , Mosa Hassen
Published: June 2023

Background

Pregnancy management is difficult when pelvic organ prolapse already exists. During pregnancy, childbirth, and the days following, clinicians may come across situations that present management dilemmas. Here, we present conservative management of preexisting pelvic organ prolapse in pregnancy complicated with preterm premature rupture of membrane up to term.

Case presentation

A 35-year-old Ethiopian woman, gravida V, para IV, visited our emergency obstetrics and gynecology department at 32 weeks and 1 day of pregnancy in a prolapsed uterus on the 4th of April 2022. She was referred from primary hospital as a case of preterm pregnancy, pelvic organ prolapse, and preterm premature rupture of membrane after she presented with complaints of passage of clear liquor of 10 hours duration. She was successfully managed conservatively without application of pessary until she gave birth to a 3200 g healthy male neonate by elective cesarean section at 37 weeks of gestational age. At the same operation, cesarean hysterectomy was done.

Conclusion

Women with preexisting pelvic organ prolapse complicated by premature rupture of membrane during the third trimester of pregnancy can be treated without the use of a pessary. Our case shows the importance of conservative management, which includes strict antenatal follow-ups, lifestyle modifications, and manual uterine reduction. Due to potential intrapartum problems from induction of labor with the occurrence of severe pelvic organ prolapse, we recommend cesarean delivery. However, to determine the optimal mode of delivery, additional comprehensive study with a large sample size is vital. If definitive management is warranted after delivery, we need to take a consideration of the status of prolapse, patient’s choice, and family size.
Analysis of white-light imaging-based features predictive for determination of lesion depths of superficial flat esophageal squamous cell carcinoma: a retrospective multicenter study from China
Authors: Wang Bin , Feng Yadong , Song Jie , Ma Jifeng , Liang Yan , Li Mengjie , Wang Xiaofen , Cheng Cui-e , Shi Ruihua
Published: June 2023

Objectives

Endoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC.

Methods

A two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth.

Results

Among 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2–3/4 and 1/4–1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort.

Conclusions

Our study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.
Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
Authors: Mao Shiqi , Yang Shuo , Liu Xinyu , Li Xingya , Wang Qiming , Zhang Yiping , Chen Jianhua , Wang Yan , Gao Guanghui , Wu Fengying , Jiang Tao , Zhang Jiao , Yang Ying , Lin Xiang , Zhu Xiaoyu , Zhou Caicun , Ren Shengxiang
Published: June 2023

Background

Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.

Methods

Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.

Results

This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.

Conclusion

Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.

Trial registration: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).
Response of pink bollworm Pectinophora gossypiella (Saunders) to Cry1Ac and Cry2Ab toxin
Authors: Likhitha P. , Undirwade D. B. , Kulkarni U. S. , Kolhe A. V. , Moharil M. P.
Published: June 2023

Background

During field surveillance in Gujarat, India, in 2009, scientists found that pink bollworm was surviving in the first generation of Bollgard cotton, which contains a single protein. This survival was observed in four districts of Gujarat. From 2012 to 2014, surveys revealed that pink bollworm larvae had higher survival rates on Bollgard II cotton in Amreli and Bhavnagar districts. In 2016, a pink bollworm outbreak in Maharashtra caused significant losses in cotton production, leading to damage, yield losses, and increased management costs in several regions. The objective of the present study was to determine the reaction of Pectinophora gossypiella to Cry1Ac and Cry2Ab toxins.

Results

Neonates of P. gossypiella collected from six distinct locations in Vidarbha were subjected to seven different concentrations of Cry1Ac. The highest LC50 value was recorded in the population collection of Yavatmal (1.362 μg/ml diet) but the lowest LC50 value of 0.600 μg/ml diet in Buldana population. The highest MIC50 value was recorded in the population collected from Yavatmal (0.743 μg/ml diet) and the lowest MIC50 value of 0.413 μg/ml diet in the Buldana population (0.431 μg/ml diet). The highest IC50 value was recorded in the population collected from Yavatmal (0.303 μg/ml diet) but the lowest IC50 value of 0.127 μg/ml diet in the Buldana population. Neonates of P. gossypiella collected from six different locations in Vidarbha were exposed to seven different concentrations (9.0, 3.0, 1.0, 0.333, 0.111, 0.037 and 0.012 for Cry1Ac and 27.0, 9.0, 3.0, 1.0, 0.333, 0.111 and 0.037 μg/ml for Cry2Ab) which revealed that the Yavatmal population had the highest LC50 value of 94.294 μg/ml diet and the lowest LC50 value was recorded in the Amravati population (42.144 μg/ml diet). The highest MIC50 value of 27.258 μg/ml diet was recorded in Buldana population, but the lowest MIC50 value was recorded in the Amravati population (12.881 μg/ml diet). The highest IC50 value of 3.209 μg/ml diet was observed in Yavatmal population, and the lowest one was recorded in the Amravati population (1.574 μg/ml diet).

Conclusions

According to the LC50 values, all of the P. gossypiella populations in Vidarbha were extremely insensitive and had field-evolved resistance to the Bt proteins found in the transgenic cotton varieties of Bollgard II.
The Desert Whale: the boom and bust of hemp in Arizona
Authors: Stats Anastasia K. , Sweat Ken G. , Masson Robert N. , Conrow Kendra D. , Frazier Amy E. , Leung Maxwell C. K.
Published: June 2023

Background

This paper examines the factors that led to the collapse of hemp grown for cannabidiol (CBD) in Arizona, the United States of America (USA), and particularly in Yuma County, which is a well-established agricultural area in the state.

Methods

This research uses a combination of mapping analysis along with a survey of hemp farmers to assess the reasons why the hemp industry collapsed as well as to foster solutions to these problems.

Results

In 2019, 5430 acres were sown with hemp seed in Arizona with 3890 acres inspected by the state to determine if they could be harvested. By 2021, there were only 156 acres planted, and only 128 of those acres were inspected by the state for compliance. (Crop mortality accounts for the difference between acres sown and acres inspected.)

Conclusions

A lack of knowledge about the hemp life cycle greatly contributed to the failure of high CBD hemp crops in Arizona. Other problems included noncompliance with tetrahydrocannabinol limits, poor sources for seeds and inconsistent genetics of the hemp varieties sold to farmers, and diseases that hemp plants were susceptible to such as Pythium crown and root rot and beet curly top virus. Addressing these factors will go far in making hemp a profitable and widespread crop in Arizona. Additionally, hemp grown for other traditional uses (e.g., fiber or seed oil) as well as new applications (e.g., microgreens, hempcrete, and phytoremediation) offers other pathways for successful hemp agriculture in this state.
Precise isolation of high-quality RNA from leaves and storage roots of cassava (Manihot esculenta Crantz) for gene expression studies
Authors: Reuben-Kalu Jane Ijeoma , Eswaran Kokiladevi , Muthurajan Raveendran , Doraiswamy Uma , Venkatasamy Balasubramani , Shanmugam Kavitha Periannagounder
Published: June 2023

Background

The isolation of Ribonucleic Acid (RNA) from leaves and storage roots of cassava (Manihot esculenta Crantz) is a challenging one, due to the presence of large amounts of polyphenolic compounds, polysaccharides, and tuber proteins. RNA with high quality and intact integrity is vital for gene expression studies. We hereby report a precise, reproducible, and less cumbersome technique for isolating high-quality RNA from leaves and storage roots of cassava with minimal contamination from polyphenols, polysaccharides, and other secondary metabolites, using affordable reagents. This protocol functions without guanidinium salts in the extraction buffer. The presence of guanidinium salts usually leads to the formation of agglomerates during the extraction of RNA from plant tissues with high starch contents.

Results

The isolated RNA from leaves and storage roots of the ten cassava genotypes yielded between 1576.1 and 2861.9 µg/ml for RNA isolated from the leaf tissues and 2761.2–3873.5 µg/ml for RNA isolated from the storage roots. The A260:A280 ratios of the total RNA were more than 2.0 for both leaf and storage root samples, indicating minimal contamination from polysaccharides and polyphenols. The RNA samples recorded intact integrity, as demonstrated by clear 28 S and 18 S rRNA bands observed on agarose gel electrophoresis. The RNA integrity number (RIN) values ranged between 7.2 and 8.0. Also, the RNA samples were successfully used for transcriptome sequencing.

Conclusion

The present method which yielded high-quality and transcriptionally competent RNA samples is suitable for use in gene expression studies and downstream applications in the molecular breeding of cassava and related root/tuber crops.