bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of prognostic nomograms based on De Ritis ratio and clinicopathological features for patients with stage II/III colorectal cancer
Authors: Fu Jinming , Du Fenqi , Tian Tian , Huang Hao , Zhang Lei , Li Dapeng , Liu Yupeng , Zhang Ding , Gao Lijing , Zheng Ting , Liu Yanlong , Zhao Yashuang
Published: July 2023

Background

Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility.

Methods

A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses.

Results

Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging.

Conclusions

De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.
Pan-cancer analysis of whole-genome doubling and its association with patient prognosis
Authors: Kikutake Chie , Suyama Mikita
Published: July 2023

Background

Whole-genome doubling (WGD) is a common mutation in cancer. Various studies have suggested that WGD is associated with a poor prognosis in cancer. However, the detailed association between WGD occurrence and prognosis remains unclear. In this study, we aimed to elucidate the mechanism by which WGD affects prognosis using sequencing data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) and The Cancer Genome Atlas.

Methods

Whole-genome sequencing data of 23 cancer types were downloaded from PCAWG project. We defined the WGD event in each sample using the WGD status annotated using PCAWG. We used MutationTimeR to predict the relative timings of mutations and loss of heterozygosity (LOH) in WGD, thus evaluating their association with WGD. We also analyzed the association between WGD-associated factors and patient prognosis.

Results

WGD was associated with several factors, e.g., length of LOH regions. Survival analysis using WGD-associated factors revealed that longer LOH regions and LOH in chr17 were associated with poor prognosis in samples with WGD (WGD samples) and samples without WGD (nWGD samples). In addition to these two factors, nWGD samples showed that the number of mutations in tumor suppressor genes was associated with prognosis. Moreover, we explored the genes associated with prognosis in both samples separately.

Conclusion

The prognosis-related factors in WGD samples differed significantly compared with those in nWGD samples. This study emphasizes the need for different treatment strategies for WGD and nWGD samples.
Clinicopathological characteristics of Non-Small Cell Lung Cancer (NSCLC) patients with c-MET exon 14 skipping mutation, MET overexpression and amplification
Authors: Ding Caixia , Qiu Yanyi , Zhang Juan , Wei Wei , Gao Hongbian , Yuan Yong , Wang Xiaomin
Published: July 2023

Purpose

MET exon 14 skipping is one of the rare mutations in non-small cell lung cancer (NSCLC), involving its pathogenesis and progression. The performances of several MET inhibitors in clinical trials have been validated based on NGS, immunohistochemistry (IHC), and gene copy number assessments. Thus, a detailed understanding of the relationship between these markers and prognosis is required.

Methods

This study has recruited patients (n = 17) with MET exon 14 skipping mutation and initially screened genes (n = 10) by polymerase chain reaction (PCR) from 257 specimens of NSCLC, including small biopsies and surgical resection. Further, the IHC analysis detected MET overexpression and recorded the score using the MetMAb trial (rial ( recruited patients (n = 17) with MET exstainings). Finally, the fluorescence in situ hybridization (FISH) resulted in the MET amplification with a MET copy number initially screened genes (n = 10) by p.

Results

PCR results indicated strong MET staining ( 3+) in more than 50% of tumor cells. Among the recruited 17 cases of MET exon 14 skipping, 9 cases presented MET amplification, and 10 cases with MET overexpression. These attributes were not correlated to the clinicopathological characteristics and overall survival. In addition, 4 cases showed gene amplification, and 3 cases presented polyploidy condition. The correlation analysis showed a significant relationship between MET amplification and MET overexpression (Pearson’s r2 = 0.4657, P < 0.005).

Conclusion

Together, these findings indicated a significant correlation between MET overexpression and MET amplification in NSCLC patients but no correlation to prognosis.
Risk factors for mortality in patients with acute exacerbation of cor pulmonale in plateau
Authors: Feng Xiaokai , Yang Chenlu , Sun Zerui , Kan Wanrong , He Xiang , Chen Yongxin , Tuo Yajun
Published: July 2023

Background

The risk factors for mortality might differ between patients with acute exacerbation of chronic pulmonary heart disease in plains and plateaus, while there is a lack of evidence.

Method

Patients diagnosed with cor pulmonale at Qinghai Provincial People’s Hospital were retrospectively included between January 2012 and December 2021. The symptoms, physical and laboratory examination findings, and treatments were collected. Based on the survival within 50 days, we divided the patients into survival and death groups.

Results

After 1:10 matching according to gender, age, and altitude, 673 patients were included in the study, 69 of whom died. The multivariable Cox proportional hazards analysis showed that NYHA class IV (HR = 2.03, 95%CI: 1.21–3.40, P = 0.007), type II respiratory failure (HR = 3.57, 95%CI: 1.60–7.99, P = 0.002), acid-base imbalance (HR = 1.82, 95%CI: 1.06–3.14, P = 0.031), C-reactive protein (HR = 1.04, 95%CI: 1.01–1.08, P = 0.026), and D-dimer (HR = 1.07, 95%CI: 1.01–1.13, P = 0.014) were risk factors for death in patients with cor pulmonale at high altitude. Among patients living below 2500 m, cardiac injury was a risk factor for death (HR = 2.47, 95%CI: 1.28–4.77, P = 0.007), while no significant association was observed at ≥ 2500 m (P = 0.057). On the contrary, the increase of D-dimer was only a risk factor for the death of patients living 2500 m and above (HR = 1.23, 95% CI: 1.07–1.40, P = 0.003).

Conclusion

NYHA class IV, type II respiratory failure, acid-base imbalance, and C- reactive protein may increase the risk of death in patients with cor pulmonale. Altitude modified the association between cardiac injury, D-dimer, and death in patients with cor pulmonale.
Clinical significance of high monocyte counts for the continuous treatment with nintedanib
Authors: Tsuneyoshi Shingo , Zaizen Yoshiaki , Tominaga Masaki , Matama Goushi , Umemoto Shushi , Ohno Shuuhei , Takaki Reiko , Yano Ryo , Murotani Kenta , Okamoto Masaki , Hoshino Tomoaki
Published: July 2023

Background

Nintedanib is now widely used to treat interstitial lung disease (ILD). Adverse events, which occur in not a few patients, make it difficult to continue nintedanib treatment, but the risk factors for adverse events are not well understood.

Methods

In this retrospective cohort study, we enrolled 111 patients with ILDs treated with nintedanib and investigated the factors involved in starting dosage reduction, withdrawal, or discontinuation within 12 months, even with appropriate symptomatic treatment. We also examined the efficacy of nintedanib in reducing the frequency of acute exacerbations and the prevention of pulmonary function reduction.

Results

Patients with high monocyte counts (> 0.454 × 109/L) had a significantly higher frequency of treatment failure, such as dosage reduction, withdrawal, or discontinuation. High monocyte count was as significant a risk factor as body surface area (BSA). Regarding efficacy, there was no difference in the frequency of acute exacerbations or the amount of decline in pulmonary function within 12 months between the normal (300 mg) and reduced (200 mg) starting dosage groups.

Conclusion

Our study results indicate that patients with higher monocyte counts (> 0.454 × 109/L) should very careful about side effects with regard to nintedanib administration. Like BSA, a higher monocyte count is considered a risk factor for nintedanib treatment failure. There was no difference in FVC decline and frequency of acute exacerbations between the starting doseage of nintedanib, 300 mg and 200 mg. Considering the risk of withdrawal periods and discontinuation, a reduced starting dosage may be acceptable in the patients with higher monocyte counts or small body sizes.
Clinical evaluation of resin infiltration treatment masking effect on hypomineralised enamel surfaces
Authors: Altan Halenur , Yilmaz Rabia Erağca
Published: July 2023

Background

Resin infiltration is a micro-invasive treatment for molar incisor hypomineralisation (MIH). In this study it was aimed to evaluate the masking effect of resin infiltration treatment (ICON) on hypomineralised enamel surface of permanent anterior teeth by using laser fluorescence, spectrophotometer, and cross-polarisation photography.

Methods

A total of 116 permanent central incisors in 37 patients were included in the study. The resin infiltration treatment (Icon®) was applied to the teeth with MIH; the healthy teeth received no treatment (control). Hypomineralised enamel lesions were evaluated by ICDAS II criteria. DIAGNOdent Pen was used to assess the lesions and healthy enamel surface quantitatively. Colour changes in enamel lesions were evaluated by using a spectrophotometer (VITA EasyShare). Each enamel lesion was imaged using a cross-polarization technique before and after treatment. All photos were assessed using Image J to evaluate the changes in lesion size. Enamel lesions were evaluated before; immediately after; 1; 3; and 6 months after treatment. Statistical significance was set asp < 0.05.

Results

After the resin infiltration, significant decreases were found in the mean DIAGNOdent values for the treatment group (p < 0.05). The colour differences before and after treatment significantly differed in all follow-ups (p < 0.05). In the treatment group, lesion areas decreased significantly after treatment (p < 0.05).

Conclusions

The resin infiltration treatment has a masking effect on MIH lesions without cavities, with stable outcomes after six months. The cross-polarization photography technique may be use to evaluate the lesion size instead of photography with flash.

Trial registration.

NCT04685889 (registered 28 December 2020).
Predictors and outcomes of patient safety culture at King Abdulaziz Medical City, Jeddah, Saudi Arabia. A nursing perspective
Authors: Rawas Hawazen , Abou Hashish Ebtsam Aly
Published: July 2023

Background

Patient safety culture assessment is viewed as the starting point from which action planning begins and helps hospitals get a good idea of the patient safety features that need immediate attention, identify the strengths and weaknesses of their safety culture, help units find their most common patient safety problems, and compare their scores to those of other hospitals. This study aimed to assess nurses’ perceptions of patient safety culture composites in a Saudi hospital in the Western region and to explore the association between patient safety culture predictors and outcomes, taking into consideration nurses' characteristics.

Methods

This study employed a cross-sectional descriptive design with a convenience sample of 184 nurses who are working at inpatient care units at King Khaled Hospital- King Abdulaziz Medical City in Jeddah, Western region, Saudi Arabia. The data were collected through a structured questionnaire consisting of nurses’ demographics and work characteristics, and the Patient Safety Culture Hospital Questionnaire (HSOPSC), which proved valid and reliable. Descriptive status, correlation, and regression analysis were applied to patient safety culture composites for statistical analysis.

Results

The overall positive response rate of the predictors of patient safety culture in the HSOPSC survey was 63.46%. The mean percent score for predictors ranged from 39.06% to 82.95%. "Teamwork within units" (82.95%) was the highest mean, followed by "organizational learning" (81.88%) and "feedback and communication about errors" (81.25%). In addition to the overall perceived patient safety (59.0%), safety grade, frequency, and number of events are also reported as safety outcome measures.

Conclusions and recommendations

Regardless of the percentage of the safety culture domains, this study agrees that all the domains should be considered high-priority and focused areas for continuous improvement. The results confirmed the need for continuous staff safety training programs to improve their perception and performance of the safety culture.
Association between caregiver type and catastrophic health expenditure among households using inpatient medical services: using Korean health panel
Authors: Park Yu shin , Kim Hyunkyu , Yun Il , Park Eun-Cheol , Jang Suk-Yong
Published: July 2023

Background

Caregiving services often place a financial burden on individuals and households that use inpatient medical services. Consequently, this study aimed to examine the association between the type of caregiver and catastrophic health expenditure among households utilizing inpatient medical services.

Methods

Data were extracted from the Korea Health Panel Survey conducted in 2019. This study included 1126 households that used inpatient medical and caregiver services. These households were classified into three groups: formal caregivers, comprehensive nursing services, and informal caregivers. Multiple logistic regression was used to analyze the association between caregiver type and catastrophic health expenditure (CHE).

Results

Households receiving formal caregiving had an increased likelihood of CHE at threshold levels of 40% compared to those who received care from family (formal caregiver: OR 3.11; CI 1.63–5.92). Compared to those who received formal caregiving, households using comprehensive nursing services (CNS) had a decreased likelihood of CHE (CNS: OR, 0.35; CI 0.15–0.82). In addition, considering the economic value associated with informal care, there was no significant relationship between households received formal caregiving and informal caregiving.

Conclusion

This study found that the association with CHE differed based on the type of caregiving used by each household. Households using formal care had a risk of developing CHE. Households using CNSs were likely to have a decreased association with CHE, compared to households using informal and formal caregivers. These findings highlight the need to expand policies to mitigate the burden on caregivers for households forced to use formal caregivers.
Differential expression of the circadian clock network correlates with tumour progression in gliomas
Authors: Petkovic Marina , Yalçin Müge , Heese Oliver , Relógio Angela
Published: July 2023

Background

Gliomas are tumours arising mostly from astrocytic or oligodendrocytic precursor cells. These tumours are classified according to the updated WHO classification from 2021 in 4 grades depending on molecular and histopathological criteria. Despite novel multimodal therapeutic approaches, the vast majority of gliomas (WHO grade III and IV) are not curable. The circadian clock is an important regulator of numerous cellular processes and its dysregulation had been found during the progression of many cancers, including gliomas.

Results

In this study, we explore expression patterns of clock-controlled genes in low-grade glioma (LGG) and glioblastoma multiforme (GBM) and show that a set of 45 clock-controlled genes can be used to distinguish GBM from normal tissue. Subsequent analysis identified 17 clock-controlled genes with a significant association with survival. The results point to a loss of correlation strength within elements of the circadian clock network in GBM compared to LGG. We further explored the progression patterns of mutations in LGG and GBM, and showed that tumour suppressor APC is lost late both in LGG and GBM. Moreover, HIF1A, involved in cellular response to hypoxia, exhibits subclonal losses in LGG, and TERT, involved in the formation of telomerase, is lost late in the GBM progression. By examining multi-sample LGG data, we find that the clock-controlled driver genes APC, HIF1A, TERT and TP53 experience frequent subclonal gains and losses.

Conclusions

Our results show a higher level of disrgulation at the gene expression level in GBM compared to LGG, and indicate an association between the differentially expressed clock-regulated genes and patient survival in both LGG and GBM. By reconstructing the patterns of progression in LGG and GBM, our data reveals the relatively late gains and losses of clock-regulated glioma drivers. Our analysis emphasizes the role of clock-regulated genes in glioma development and progression. Yet, further research is needed to asses their value in the development of new treatments.
A semi-field evaluation in Thailand of the use of human landing catches (HLC) versus human-baited double net trap (HDN) for assessing the impact of a volatile pyrethroid spatial repellent and pyrethroid-treated clothing on Anopheles minimus landing
Authors: Vajda Élodie A. , Saeung Manop , Ross Amanda , McIver David J. , Tatarsky Allison , Moore Sarah J. , Lobo Neil F. , Chareonviriyaphap Theeraphap
Published: July 2023

Background

The mosquito landing rate measured by human landing catches (HLC) is the conventional endpoint used to evaluate the impact of vector control interventions on human-vector exposure. Non-exposure based alternatives to the HLC are desirable to minimize the risk of accidental mosquito bites. One such alternative is the human-baited double net trap (HDN), but the estimated personal protection of interventions using the HDN has not been compared to the efficacy estimated using HLC. This semi-field study in Sai Yok District, Kanchanaburi Province, Thailand, evaluates the performance of the HLC and the HDN for estimating the effect on Anopheles minimus landing rates of two intervention types characterized by contrasting modes of action, a volatile pyrethroid spatial repellent (VSPR) and insecticide-treated clothing (ITC).

Methods

Two experiments to evaluate the protective efficacy of (1) a VPSR and (2) ITC, were performed. A block randomized cross-over design over 32 nights was carried out with both the HLC or HDN. Eight replicates per combination of collection method and intervention or control arm were conducted. For each replicate, 100 An. minimus were released and were collected for 6 h. The odds ratio (OR) of the released An. minimus mosquitoes landing in the intervention compared to the control arm was estimated using logistic regression, including collection method, treatment, and experimental day as fixed effects.

Results

For the VPSR, the protective efficacy was similar for the two methods: 99.3%, 95% CI (99.5–99.0) when measured by HLC, and 100% (100, Inf) when measured by HDN where no mosquitoes were caught (interaction test p = 0.99). For the ITC, the protective efficacy was 70% (60–77%) measured by HLC but there was no evidence of protection when measured by HDN [4% increase (15–27%)] (interaction test p < 0.001).

Conclusions

Interactions between mosquitoes, bite prevention tools and the sampling method may impact the estimated intervention protective efficacy. Consequently, the sampling method must be considered when evaluating these interventions. The HDN is a valid alternative trapping method (relative to the HLC) for evaluating the impact of bite prevention methods that affect mosquito behaviour at a distance (e.g. VPSR), but not for interventions that operate through tarsal contact (e.g., ITC).
Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus
Authors: Liu Jia , Qi Wenqian , Wang Song , Zhang Yonggui , Wang Xu , Sun Derong , Xu Yanhui , Shi Jingyi , Duan Honglei , Zhang Qian , Wang Hongguang , Wang Jiangbin
Published: July 2023

Background

Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients.

Methods

Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD.

Results

There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD.

Conclusion

Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.
Hunting practices in southwestern Amazonia: a comparative study of techniques, modalities, and baits among urban and rural hunters
Authors: Oliveira Marcela Alvares , Braga-Pereira Franciany , El Bizri Hani Rocha , Morcatty Thais Queiroz , Doria Carolina Rodrigues da Costa , Messias Mariluce Rezende
Published: July 2023

Background

Hunting is a vital means of obtaining animal in various human populations. Hunters rely on their knowledge of species ecology and behavior to develop and employ hunting techniques and increase their chances of success. The comparison of the hunting practices of different human societies can shed light on the sustainability of hunting and the impact it has on species’ populations. In this study, we examine and compare the techniques, modalities, and baits used by urban and rural hunters in Rondônia, a state in southwestern Amazonia, Brazil. We expected that rural hunters would use these elements and have greater knowledge when compared to urban hunters. We also expect that the use of specific hunting techniques and modalities will have greater selectivity and specificity of capture for rural hunters and that this knowledge will differ between groups.

Methods

We conducted 106 semi-structured interviews with rural and urban hunters from October 2018 to February 2020. We analyzed the data using PERMANOVA and Network analyses to compare and contrast the hunting practices of each group.

Results

We recorded four main hunting techniques divided into ten modalities with three techniques and seven modalities being the preferred choices among hunters. Waiting for at a Fruit Tree was cited as the primary technique employed by hunters living in urban and rural areas indicated. While the techniques and modalities were similar among hunters, the composition of species targeted and baits used differed between groups. Our network approach showed that modularity in urban areas was numerically lower than in rural areas. All species had one to more techniques associated with their capture.

Conclusions

Hunters living in urban and rural environments showed high similarity in their practices, probably due to sharing similar environments to hunt containing similar species, as well as targeting preferably the same species.
A CNN-LSTM-att hybrid model for classification and evaluation of growth status under drought and heat stress in chinese fir (Cunninghamia lanceolata)
Authors: Xing Dong , Wang Yulin , Sun Penghui , Huang Huahong , Lin Erpei
Published: July 2023

Background

Cunninghamia lanceolata(Chinese fir), is one of the most important timber trees in China. With the global warming, to develop new resistant varieties to drought or heat stress has become an essential task for breeders of Chinese fir. However, classification and evaluation of growth status of Chinese fir under drought or heat stress are still labor-intensive and time-consuming.

Results

In this study, we proposed a CNN-LSTM-att hybrid model for classification of growth status of Chinese fir seedlings under drought and heat stress, respectively. Two RGB image datasets of Chinese fir seedling under drought and heat stress were generated for the first time, and utilized in this study. By comparing four base CNN models with LSTM, the Resnet50-LSTM was identified as the best model in classification of growth status, and LSTM would dramatically improve the classification performance. Moreover, attention mechanism further enhanced performance of Resnet50-LSTM, which was verified by Grad-CAM. By applying the established Resnet50-LSTM-att model, the accuracy rate and recall rate of classification was up to 96.91% and 96.79% for dataset of heat stress, and 96.05% and 95.88% for dataset of drought, respectively. Accordingly, the R2value and RMSE value for evaluation on growth status under heat stress were 0.957 and 0.067, respectively. And, the R2value and RMSE value for evaluation on growth status under drought were 0.944 and 0.076, respectively.

Conclusion

In summary, our proposed model provides an important tool for stress phenotyping in Chinese fir, which will be a great help for selection and breeding new resistant varieties in future.
Hospital-based retrospective analysis of 224 surgical cases of lung hydatid cyst from southern Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Ebrahimi Kamyar , Rastegarian Mohammad , Eskandarisani Mehrdad , Ziaian Bizhan , Sarkari Bahador
Published: July 2023

Background

The lungs are considered the second-most frequent location for hydatid cyst in human. The current retrospective hospital-based study aimed to assess the epidemiological data, clinical presentation, and treatment outcomes of lung hydatid cyst in patients who underwent surgery for this disease in Fars province, southern Iran.

Methods

In this retrospective study, hospital records of 224 pulmonary hydatid cyst patients were assessed in two main university-affiliated hospitals in Fars Province, southern Iran. Clinical features of patients, epidemiological data, cyst features, surgical interventions, and treatment outcomes were reviewed and analyzed.

Results

A total of 224 hydatid cyst cases of the lung were reviewed. Male patients accounted for the majority of cases (60.4%). The average age of the patients was 31.13 (± 19.6), ranging from 2 to 94 years old. Of the 224 patients, 145 (75.9%) cases had only one single cyst and mostly 110 (53.9%) located in the right lung. Also, 6 (2.9%) cases had cysts in both lungs. The lower lobe of the lungs was the most common location of the hydatid cyst. The average size of lung hydatid cyst was 7.37 cm (SD = 3.86; rang: 2–24) while for the cyst areas was 42.87cm2 (SD = 52.76; range: 2–488). Regarding the surgical method, 86 (38.6%) cases were operated by lung resection surgery while 137 (61.4%) cases had lung preserving one. The chief complaints of the patients were cough (55.4%) and dyspnea (32.6%). Relapse was documented in 25 (11.16%) of cases.

Conclusions

Lung hydatid cyst is a common infection in southern Iran. Lung preserving surgery is the method of choice for the management of hydatid cyst. Relapse, which was not uncommon in our study, is a challenging feature of hydatid cyst management.
mTORC1-mediated acquisition of reward-related representations by hippocampal somatostatin interneurons
Authors: Michon François-Xavier , Laplante Isabel , Bosson Anthony , Robitaille Richard , Lacaille Jean-Claude
Published: July 2023

Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, “reward off sustained”, “reward off transient”, “reward on sustained” and “reward on transient”, and these responses showed reorganization after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent reward- related activity during learning. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location.
A study to evaluate association of nuclear grooving in benign thyroid lesions with RET/PTC1 and RET/PTC3 gene translocation
Authors: Ashwini Basavaraj Rangalakshmi , Nirmala Chandran , Natarajan Muthuvelu , Biligi Dayananda S
Published: July 2023

Introduction

Papillary thyroid carcinoma (PTC) is the most common malignant lesion of the thyroid characterized by unique histological features like nuclear grooving, nuclear clearing, and intra-nuclear inclusions. However, nuclear grooves are observed even in benign thyroid lesions (BTL) like nodular goiter (NG), Hashimoto's thyroiditis (HT), and follicular adenoma (FA) resulting in diagnostic dilemma of the presence of PTC in such BTL. RET/PTC gene translocation is one of the most common oncogenic rearrangements seen in PTC, known to be associated with nuclear grooving. Among different types of RET/PTC translocations, RET/PTC1 and RET/PTC3 gene translocations are the most common types. These translocations have also been identified in many BTL like hyperplastic nodules and HT. Our study aimed to determine the frequency of nuclear grooving in BTL and evaluate their association with RET/PTC1 and RET/PTC3 gene translocation.

Methods

Formalin-fixed, paraffin-embedded (FFPE) tissue blocks of NG, HT, and FA were included in the study. The hematoxylin and eosin (H&E) stained sections were evaluated for the presence of nuclear grooving/high power field (hpf) and a scoring of 0 to 3 was used for the number of grooves. Sections of 10 μ thickness were cut and the cells containing the nuclear grooves were picked using Laser-Capture microdissection. About 20 to 50 such cells were microdissected in each of the cases followed by RNA extraction, cDNA conversion, realtime-polymerase chain reaction (RQ-PCR) for RET/PTC1 and RET/PTC3 gene translocation, and the findings were analyzed for statistical significance.

Results

Out of 87 BTL included in the study, 67 (77.0%) were NG, 12 (13.7%) were HT, and 8 (9.2%) were FA. Thirty-two cases (36.8%) had nuclear grooving with 18 out of 67 NG, 6 out of 12 HT, and all 8 cases of FA showing a varying number of nuclear grooves. A significant association between the number of nuclear grooves with RET/PTC gene translocation (p-value of 0.001) was obtained. A significant association of HT with RET/PTC gene translocation (p-value of 0.038) was observed. RET/PTC1 and RET/PTC3 translocation were seen in 5 out of 87 cases, with HT showing positivity in 2 and FA in 1 case for RET/PTC1 and HT in 1 and FA in 2 cases for RET/PTC3 gene translocation with 1 case of FA being positive for both RET/PTC1 and RET/PTC3 gene translocation.

Conclusions

The frequency of nuclear grooving among BTLs in our study was 36.8%. Our study shows, that when BTLs, show nuclear grooves, with an increase in the nuclear size, oval and elongated shape, favors the possibility of an underlying genetic aberration like RET/PTC gene translocation, which in turn supports the reporting pathologist to suggest a close follow up of the patients on seeing such nuclear features on cytology or histopathology sample, particularly in HT.
Genotype–phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome
Authors: Papadopulos M. E. , Plazzer J. P. , Macrae F. A.
Published: July 2023

Background

Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45–60% of JPS cases, with BMPR1a DCVs accounting for 17–38% of JPS cases. Within those with either a BMPR1a or SMAD4 DCV, there is phenotypic variability in location of polyps, risk of malignancy and extra-intestinal manifestations with limited published reports of gene-phenotype association or genotype–phenotype correlation.

We aimed to identify any gene-phenotype association or genotype–phenotype correlation in BMPR1a to inform surveillance recommendations, and gene-specific modification to the ACMG classification of pathogenicity of DCVs.

Methods

A literature search was performed through EMBASE, MEDLINE and PubMed. Studies that were included explored BMPR1a DCV-related JPS or contiguous deletion of PTEN and BMPR1a. Data was also drawn from the BMPR1a specific databases on LOVD and ClinVar.

Results

There were 211 DCVs in BMPR1a identified, 82 from patients with JPS in the literature, and 17 from LOVD and 112 from ClinVar classified as pathogenic or likely pathogenic. These included missense, nonsense and frameshift variants and large deletions, occurring across all functional domains of the gene.

Unlike in SMAD4 carriers, gastric polyposis and malignancy were not identified in our review in BMPR1a carriers, but colonic polyposis and malignancy occurred in carriers of either BMPR1a or SMAD4 DCVs. Those with contiguous deletion of PTEN and BMPR1a can present with JPS of infancy, with a severe phenotype of GI bleeding, diarrhoea, exudative enteropathy and rectal prolapse.

No specific BMPR1a genotype–phenotype correlation could be ascertained including by variant type or functional domain.

Conclusion

Phenotypic characteristics cannot be used to inform variant location in BMPR1a. However, the phenotypic characteristics of BMPR1a DCV carriers, being almost exclusively related to the colon and rectum, can assist in pathogenicity assessment of BMPR1a variants.

Given these findings, we propose that carriers of BMPR1a DCVs should only require surveillance for colorectal polyps and malignancy, and that surveillance for gastric polyps and malignancy may be unnecessary. However variant location within BMPR1a does not support differential surveillance recommendations.
Potent anthelmintic activity of a colloidal nano-silver formulation (Silversol®) against the model worm Caenorhabditis elegans
Authors: Gajera Gemini , Godse Chhaya , DeSouza Anselm , Mehta Dilip , Kothari Vijay
Published: July 2023

Objective

In the background of a very small number of effective anthelmintics available today with a narrow activity spectrum, and a rise in resistance against them among parasitic helminths, there is an urgent need for discovery of novel broad-spectrum anthelmintics displaying no or minimal toxicity towards the host. Silver being used since centuries for therapeutic purposes and considered safe for human consumption, we investigated anthelmintic activity of a colloidal nanosilver formulation Silversol®. Anthelmintic efficacy of the test formulation was assayed employing the nematode Caenorhabditis elegans as a model worm through a live-dead count.

Results

Silversol® exerted anthelmintic action superior to one of the positive controls (Benzimidazole), and almost at par to another positive control (Ivermectin). At concentrations ≥ 2 ppm, it could kill all the worms present in the experimental well. Lower concentrations of silver were found to have a cuticle-damaging action on worms. Further investigation is warranted to assess whether Silversol® can exert similar potent activity against different species of parasitic helminths, and elucidate the underlying molecular mechanisms of action.
Downregulation of circ-Foxo3 in breast cancer stem-like cells
Authors: Kamalabadi-Farahani Mohammad , Atashi Amir , Eslami Mohammad Masoud
Published: July 2023

Objective

Cancer cells having stem cell characteristics are linked to metastasis and relapse in breast cancer. Circ-Foxo3, as a circular RNA, has been linked to the breast cancer lethal traits. This study’s objective was to assess circ-Foxo3 expression in breast cancer stem-like cells. After isolation from tumor mass, breast cancer cells were subjected to the reliable in vitro assay of spheroid formation to determine the presence cancer stem cells (CSCs). We used a quantitative real-time polymerase chain reaction to examine circ-Foxo3 expression in spheroids.

Results

Circ-Foxo3 expression was significantly downregulated in spheroid-forming tumor cells, according to our data. This study demonstrated that breast CSCs have downregulated circ-Foxo3 expression, which may allow these cells to evade apoptosis. A precise analysis of this circRNA’s role could be exploited to develop focused therapeutic approaches to fight breast CSCs.
Dataset development of pre-formulation tests on fast disintegrating tablets (FDT): data aggregation
Authors: Momeni Mehri , Rakhshani Saleh , Abbaspour Mohammadreza , Alizadeh Faezeh , Sheikhi Nafiseh , GhorbanZadeh Faezeh , Habibi Zahra , Tabesh Hamed
Published: July 2023

Objectives

Tablet manufacturing development is costly, laborious, and time-consuming. Technologies related to artificial intelligence like ,predictive model ,can be used in the control process to facilitate and accelerate the tablet manufacturing process. predictive models have become popular recently. However, predictive models need a comprehensive dataset of related data in the field, due to the lack of a dataset of tablet formulations, the aim of this study is to aggregate and integrate fast disintegration tablet’s formulation into a comprehensive dataset.

Data description

The search strategy has been prepared between the years of 2010 to 2020, consisting of the keyword’s ‘formulation’ ,‘disintegrating’ and ‘Tablet’, as well as their synonyms. By searching four databases, 1503 articles were retrieved, from these articles only 232 articles met all of the study’s criteria. By reviewing 232 articles, 1982 formulations have been extracted, afterward pre-processing and cleaning data, contain steps of unifying the name and units, removing inappropriate formulations by an expert, and finally, data tidying was done on data. The developed dataset contains valuable information from various FDT’s formulations, which can be used in pharmaceutical studies that are critical to the discovery and development of new drugs. this method can be applied to aggregate datasets from the other dosage forms.
American College of Radiology Appropriateness Criteria®: a bibliometric analysis of panel members
Authors: Malhotra Ajay , Bajaj Suryansh , Garg Tushar , Khunte Mihir , Pahwa Bhavya , Wu Xiao , Payabvash Seyedmehdi , Mukherjee Suresh , Gandhi Dheeraj , Forman Howard P.
Published: July 2023

Objective

To assess the features of panel members involved in the writing of the ACR-AC and identify alignment with research output and topic-specific research publications.

Methods

A cross-sectional analysis was performed on the research output of panel members of 34 ACR-AC documents published in 2021. For each author, we searched Medline to record total number of papers (P), total number of ACR-AC papers (C) and total number of previously published papers that are relevant to the ACR-AC topic (R).

Results

Three hundred eighty-three different panel members constituted 602 panel positions for creating 34 ACR-AC in 2021 with a median panel size of 17 members. Sixty-eight (17.5%) of experts had been part of ≥10 previously published ACR-AC papers and 154 (40%) were members in ≥ 5 published ACR-AC papers. The median number of previously published papers relevant to the ACR-AC topic was 1 (IQR: 0–5). 44% of the panel members had no previously published paper relevant to the ACR-AC topic. The proportion of ACR-AC papers (C/P) was higher for authors with ≥ 5 ACR-AC papers (0.21) than authors with < 5 ACR-AC papers (0.11, p < 0.0001); however, proportion of relevant papers per topic (R/P) was higher for authors with < 5 ACR-AC papers (0.10) than authors with ≥ 5 ACR-AC papers (0.07).

Conclusion

The composition of the ACR Appropriateness Criteria panels reflects many members with little or no previously published literature on the topic of consideration. Similar pool of experts exists on multiple expert panels formulating imaging appropriateness guidelines.

Key Points

There were 68 (17.5%) panel experts on ≥ 10 ACR-AC panels.

Nearly 45% of the panel experts had zero median number of relevant papers.

Fifteen panels (44%) had > 50% of members having zero relevant papers.
A clinician’s guide to understanding aortic 4D flow MRI
Authors: Ramaekers Mitch J. F. G. , Westenberg Jos J. M. , Adriaans Bouke P. , Nijssen Estelle C. , Wildberger Joachim E. , Lamb Hildo J. , Schalla Simon
Published: July 2023

Four-dimensional flow magnetic resonance imaging is an emerging technique which may play a role in diagnosis and risk-stratification of aortic disease. Some knowledge of flow dynamics and related parameters is necessary to understand and apply this technique in clinical workflows. The purpose of the current review is to provide a guide for clinicians to the basics of flow imaging, frequently used flow-related parameters, and their relevance in the context of aortic disease.

Clinical relevance statement Understanding normal and abnormal aortic flow could improve clinical care in patients with aortic disease.

Graphical abstract
Exogenous melatonin ameliorates steroid-induced osteonecrosis of the femoral head by modulating ferroptosis through GDF15-mediated signaling
Authors: Li Wenming , Li Wenhao , Zhang Wei , Wang Hongzhi , Yu Lei , Yang Peng , Qin Yi , Gan Minfeng , Yang Xing , Huang Lixin , Hao Yuefeng , Geng Dechun
Published: July 2023

Background

Ferroptosis is an iron-related form of programmed cell death. Accumulating evidence has identified the pathogenic role of ferroptosis in multiple orthopedic disorders. However, the relationship between ferroptosis and SONFH is still unclear. In addition, despite being a common disease in orthopedics, there is still no effective treatment for SONFH. Therefore, clarifying the pathogenic mechanism of SONFH and investigating pharmacologic inhibitors from approved clinical drugs for SONFH is an effective strategy for clinical translation. Melatonin (MT), an endocrine hormone that has become a popular dietary supplement because of its excellent antioxidation, was supplemented from an external source to treat glucocorticoid-induced damage in this study.

Methods

Methylprednisolone, a commonly used glucocorticoid in the clinic, was selected to simulate glucocorticoid-induced injury in the current study. Ferroptosis was observed through the detection of ferroptosis-associated genes, lipid peroxidation and mitochondrial function. Bioinformatics analysis was performed to explore the mechanism of SONFH. In addition, a melatonin receptor antagonist and shGDF15 were applied to block the therapeutic effect of MT to further confirm the mechanism. Finally, cell experiments and the SONFH rat model were used to detect the therapeutic effects of MT.

Results

MT alleviated bone loss in SONFH rats by maintaining BMSC activity through suppression of ferroptosis. The results are further verified by the melatonin MT2 receptor antagonist that can block the therapeutic effects of MT. In addition, bioinformatic analysis and subsequent experiments confirmed that growth differentiation factor 15 (GDF15), a stress response cytokine, was downregulated in the process of SONFH. On the contrary, MT treatment increased the expression of GDF15 in bone marrow mesenchymal stem cells. Lastly, rescue experiments performed with shGDF15 confirmed that GDF15 plays a key role in the therapeutic effects of melatonin.

Conclusions

We proposed that MT attenuated SONFH by inhibiting ferroptosis through the regulation of GDF15, and supplementation with exogenous MT might be a promising method for the treatment of SONFH.

Graphical Abstract