bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality trends and geographic distribution of kidney cancer in Peru: a secondary analysis
Authors: Torres-Roman J. Smith , De la Cruz-Ku Gabriel , Juárez-Leon Valeria , Calderón-Solano Delahnie , Bazalar-Palacios Janina , Vecchia Carlo La , Pinheiro Paulo S.
Published: March 2023

Background

The incidence of kidney cancer has been increasing worldwide, with variable patterns in mortality due to improved diagnostic techniques and increased survival. The mortality rates, geographical distribution and trends of kidney cancer in South America remain poorly explored. This study aims to illustrate mortality by kidney cancer in Peru.

Methods

A secondary data analysis of the Deceased Registry of the Peruvian Ministry of Health database, from 2008 to 2019 was conducted. Data for kidney cancer deaths were collected from health facilities distributed throughout the country. We estimated age-standardized mortality rates (ASMR) per 100,000 persons and provided an overview of trends from 2008 to 2019. A cluster map shows the relationships among 3 regions.

Results

A total of 4221 deaths by kidney cancer were reported in Peru between 2008 and 2019. ASMR for Peruvian men ranged from 1.15 to 2008 to 1.87 in 2019, and from 0.68 to 2008 to 0.82 in 2019 in women. The mortality rates by kidney cancer rose in most regions, although they were not significant. Callao and Lambayeque provinces reported the highest mortality rates. The rainforest provinces had a positive spatial autocorrelation and significant clustering (p < 0.05) with the lowest rates in Loreto and Ucayali.

Conclusion

Mortality by kidney cancer has increased in Peru, being a trend that disproportionally affects more men than women. While the coast, especially Callao and Lambayeque, present the highest kidney cancer mortality rates, the rainforest has the lowest rates, especially among women. Lack of diagnosis and reporting systems may confound these results.
Impact of unilateral removable partial dentures versus removable partial dentures with major connector on oral health-related quality of life of elder patients: a clinical study
Authors: Goguta Luciana , Frandes Mirela , Candea Adrian , Ille Codruta , Jivanescu Anca
Published: March 2023

Objective

This study aimed to establish the survival rate of unilateral removable partial dentures (u-RPD) comparative with bilateral RPD (bi-RPD) with major connector in elder patients, as well as to determine both their treatment satisfaction and oral health.

Methods

The study sample included 17 patients treated with u-RPD and 17 patients treated with bi-RPD with a major connector. The patients were followed over five years with recalls every 6 months. A 5- points Likert scale was used to determine the satisfaction of the patients. The Oral Health Impact Profile-14 (OHIP-14) questionnaire was used to evaluate their oral health after each type of administrated treatment. The local oral examined aspects included the maintenance of the abutment teeth periodontal health, the fractures of the removable dentures, the fractures of the connectors, the chipping of the aesthetic material. Kaplan–Meier survival analysis was conducted to evaluate the performance of the two treatments.

Results

The mean survival time in years was 4.882 ± 0.114, 95% CI (4.659; 5.106) and 4.882 ± 0.078, 95% CI (4.729; 5.036), for the u-RPD and the bi-RPD, respectively. The five-year survival rates for the two dentures were 94.1% for u-RPD vs. 88.2% for bi-RPD with a major connector, without a statistically significant difference between them (Log-rank test χ2(1) = 0.301, p = 0.584). The patients receiving u-RPD presented significantly higher satisfaction scores compared to the patients receiving bi-RPD, 4.88 ± 0.48 vs. 4.41 ± 0.62, Mann-Whitney U test, p = 0.026.

Conclusion

Patients receiving u-RPD presented higher levels of treatment satisfaction and better oral health than patients receiving bi-RPD. The survival rates of the treatments u-RPD and bi-RPD were similar.
De novo myeloid sarcoma mimicking gynecological tumors: a retrospective case series of eight patients
Authors: Gu Yu , Zheng Haoran , Mo Shengwei , Guo Tao , Chen Lihua , Yang Junjun , Xiang Yang
Published: March 2023

Objective

To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients.

Methods

This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022.

Results

There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60–90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056–1.000). The median OS was 26 months (range: 3–82).

Conclusion

For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.
Non-invasive measurements of respiration and heart rate across wildlife species using Eulerian Video Magnification of infrared thermal imagery
Authors: Rzucidlo Caroline L. , Curry Erin , Shero Michelle R.
Published: March 2023

Background

An animal’s metabolic rate, or energetic expenditure, both impacts and is impacted by interactions with its environment. However, techniques for obtaining measurements of metabolic rate are invasive, logistically difficult, and costly. Red–green–blue (RGB) imaging tools have been used in humans and select domestic mammals to accurately measure heart and respiration rate, as proxies of metabolic rate. The purpose of this study was to investigate if infrared thermography (IRT) coupled with Eulerian video magnification (EVM) would extend the applicability of imaging tools towards measuring vital rates in exotic wildlife species with different physical attributes.

Results

We collected IRT and RGB video of 52 total species (39 mammalian, 7 avian, 6 reptilian) from 36 taxonomic families at zoological institutions and used EVM to amplify subtle changes in temperature associated with blood flow for respiration and heart rate measurements. IRT-derived respiration and heart rates were compared to ‘true’ measurements determined simultaneously by expansion of the ribcage/nostrils and stethoscope readings, respectively. Sufficient temporal signals were extracted for measures of respiration rate in 36 species (85% success in mammals; 50% success in birds; 100% success in reptiles) and heart rate in 24 species (67% success in mammals; 33% success in birds; 0% success in reptiles) using IRT-EVM. Infrared-derived measurements were obtained with high accuracy (respiration rate, mean absolute error: 1.9 breaths per minute, average percent error: 4.4%; heart rate, mean absolute error: 2.6 beats per minute, average percent error: 1.3%). Thick integument and animal movement most significantly hindered successful validation.

Conclusion

The combination of IRT with EVM analysis provides a non-invasive method to assess individual animal health in zoos, with great potential to monitor wildlife metabolic indices in situ.
NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer
Authors: Wang Shunyi , Kuai Yihe , Lin Simin , Li Li , Gu Quliang , Zhang Xiaohan , Li Xiaoming , He Yajun , Chen Sishuo , Xia Xiaoru , Ruan Zhang , Lin Caixia , Ding Yi , Zhang Qianqian , Qi Cuiling , Li Jiangchao , He Xiaodong , Pathak Janak L. , Zhou Weijie , Liu Side , Wang Lijing , Zheng Lingyun
Published: March 2023

Background

Adenoma-adenocarcinoma transition is a key feature of colorectal cancer (CRC) occurrence and is closely regulated by tumor-associated macrophages (TAMs) and CD8+ T cells. Here, we investigated the effect of the NF-κB activator 1 (Act1) downregulation of macrophages in the adenoma-adenocarcinoma transition.

Methods

This study used spontaneous adenoma-developing ApcMin/+, macrophage-specific Act1-knockdown (anti-Act1), and ApcMin/+; anti-Act1 (AA) mice. Histological analysis was performed on CRC tissues of patients and mice. CRC patients’ data retrieved from the TCGA dataset were analyzed. Primary cell isolation, co-culture system, RNA-seq, and fluorescence-activated cell sorting (FACS) were used.

Results

By TCGA and TISIDB analysis, the downregulation of Act1 expression in tumor tissues of CRC patients negatively correlated with accumulated CD68+ macrophages in the tumor. Relative expression of EMT markers in the tumor enriched ACT1lowCD68+ macrophages of CRC patients. AA mice showed adenoma-adenocarcinoma transition, TAMs recruitment, and CD8+ T cell infiltration in the tumor. Macrophages depletion in AA mice reversed adenocarcinoma, reduced tumor amounts, and suppressed CD8+ T cell infiltration. Besides, macrophage depletion or anti-CD8a effectively inhibited metastatic nodules in the lung metastasis mouse model of anti-Act1 mice. CRC cells induced activation of IL-6/STAT3 and IFN-γ/NF-κB signaling and the expressions of CXCL9/10, IL-6, and PD-L1 in anti-Act1 macrophages. Anti-Act1 macrophages facilitated epithelial-mesenchymal-transition and CRC cells’ migration via CXCL9/10-CXCR3-axis. Furthermore, anti-Act1 macrophages promoted exhaustive PD1+ Tim3+ CD8+ T cell formation. Anti-PD-L1 treatment repressed adenoma-adenocarcinoma transition in AA mice. Silencing STAT3 in anti-Act1 macrophages reduced CXCL9/10 and PD-L1 expression and correspondingly inhibited epithelial-mesenchymal-transition and CRC cells’ migration.

Conclusions

Act1 downregulation in macrophages activates STAT3 that promotes adenoma-adenocarcinoma transition via CXCL9/10-CXCR3-axis in CRC cells and PD-1/PD-L1-axis in CD8+ T cells.
Diagnostic performance of NxTek™ Eliminate Malaria-Pf test for the detection of Plasmodium falciparum in school children with asymptomatic malaria
Authors: Biruksew Abdissa , Demeke Ashenafi , Birhanu Zewdie , Kebede Estifanos , Golassa Lemu , Mathebula Evans Mantiri , Yewhalaw Delenasaw
Published: March 2023

Background

One of the major roadblocks to the falciparum malaria elimination programme is the presence of a portion of the population, such as school children, with asymptomatic malaria infection. Targeting such reservoirs of infections is critical to interrupting transmission and enhancing elimination efforts. The NxTek™ Eliminate Malaria Pf test is a highly sensitive rapid diagnostic test (hsRDT) for the detection of HRP-2. However, knowledge gaps exist in Ethiopia on the diagnostic performance of hsRDT for the detection of Plasmodium falciparum in school children with asymptomatic malaria.

Methods

A school-based cross-sectional study was conducted from September 2021 to January 2022 on 994 healthy school children (aged 6–15 years). Finger-pricked whole blood samples were collected for microscopy, hsRDT, conventional RDT (cRDT or SD Bioline Malaria Ag Pf/P.v), and QuantStudio™ 3 Real—Time PCR system (qPCR). The hsRDT was compared to cRDT and microscopy. qPCR and microscopy were used as reference methods.

Results

The prevalence of Plasmodium falciparum was 1.51%, 2.2%. 2.2% and 4.52%, by microscopy, hsRDT, cRDT and qPCR, respectively. Using qPCR as reference, the sensitivity of hsRDT was higher (48.89%) than the microscopy (33.3%), and showed 100% specificity and a positive predictive value (PPV). Microscopy showed similar specificity and PPV as hsRDT. Using microscopy as a reference, the diagnostic perforrmances of both hsRDT and cRDT were similar. Both RDTs demonstrated identical diagnostic performances in both comparison methods.

Conclusions

hsRDT has the same diagnostic performance as cRDT but improved diagnostic characteristics than microscopy for detection of P. falciparum in school children with asymptomatic malaria. It can be a useful tool for the national malaria elimination plan of Ethiopia.
Perception and awareness towards malaria vaccine policy implementation in Nigeria by health policy actors
Authors: Nnaji Adaugo , Ozdal Macide Artac
Published: March 2023

Background

This study aimed to assess the perception and awareness of malaria vaccine policy implementation among health policy actors in Nigeria.

Methods

A descriptive study was conducted to assess the opinions and perceptions of policy actors on the implementation of a vaccination programme against malaria in Nigeria. Descriptive statistics were carried out to study the characteristics of the population and the univariate analysis of the responses to questions presented to the participants. Multinomial logistic regression was conducted to evaluate the association between demographic characteristics and the responses.

Results

The study revealed that malaria vaccine awareness was poor, with only 48.9% of the policy actors having previous knowledge of the malaria vaccine. The majority of participants (67.8%) declared that they were aware of the importance of vaccine policy in efforts to manage disease transmission. As the number of years of work experience of the participants increased, the odds of being more likely to be aware of the malaria vaccine increased [OR 2.491 (1.183–5.250), p value < 0.05].

Conclusion

It is recommended that policy-makers develop methods of educating populations, increase awareness of the acceptability of the vaccine and ensure that an affordable malaria vaccine programme is implemented in the population.
Development and validation of an online dynamic nomogram based on the atherogenic index of plasma to screen nonalcoholic fatty liver disease
Authors: Peng Hewei , Zhang Junchao , Huang Xianhua , Xu Miao , Huang Jingru , Wu Yunli , Peng Xian-E.
Published: March 2023

Background

Nonalcoholic fatty liver disease (NAFLD), a common liver disease worldwide, can be reversed early in life with lifestyle and medical interventions. This study aimed to develop a noninvasive tool to screen NAFLD accurately.

Methods

Risk factors for NAFLD were identified using multivariate logistic regression analysis, and an online NAFLD screening nomogram was developed. The nomogram was compared with reported models (fatty liver index (FLI), atherogenic index of plasma (AIP), and hepatic steatosis index (HSI)). Nomogram performance was evaluated through internal and external validation (National Health and Nutrition Examination Survey (NHANES) database).

Results

The nomogram was developed based on six variables. The diagnostic performance of the present nomogram for NAFLD (area under the receiver operator characteristic curve (AUROC): 0.863, 0.864, and 0.833, respectively) was superior to that of the HSI (AUROC: 0.835, 0.833, and 0.810, respectively) and AIP (AUROC: 0.782, 0.773, and 0.728, respectively) in the training, validation, and NHANES sets. Decision curve analysis and clinical impact curve analysis presented good clinical utility.

Conclusion

This study establishes a new online dynamic nomogram with excellent diagnostic and clinical performance. It has the potential to be a noninvasive and convenient method for screening individuals at high risk for NAFLD.
Machine learning prognosis model based on patient-reported outcomes for chronic heart failure patients after discharge
Authors: Tian Jing , Yan Jingjing , Han Gangfei , Du Yutao , Hu Xiaojuan , He Zixuan , Han Qinghua , Zhang Yanbo
Published: March 2023

Background

Patient-reported outcomes (PROs) can be obtained outside hospitals and are of great significance for evaluation of patients with chronic heart failure (CHF). The aim of this study was to establish a prediction model using PROs for out-of-hospital patients.

Methods

CHF-PRO were collected in 941 patients with CHF from a prospective cohort. Primary endpoints were all-cause mortality, HF hospitalization, and major adverse cardiovascular events (MACEs). To establish prognosis models during the two years follow-up, six machine learning methods were used, including logistic regression, random forest classifier, extreme gradient boosting (XGBoost), light gradient boosting machine, naive bayes, and multilayer perceptron. Models were established in four steps, namely, using general information as predictors, using four domains of CHF-PRO, using both of them and adjusting the parameters. The discrimination and calibration were then estimated. Further analyze were performed for the best model. The top prediction variables were further assessed. The Shapley additive explanations (SHAP) method was used to explain black boxes of the models. Moreover, a self-made web-based risk calculator was established to facilitate the clinical application.

Results

CHF-PRO showed strong prediction value and improved the performance of the models. Among the approaches, XGBoost of the parameter adjustment model had the highest prediction performance with an area under the curve of 0.754 (95% CI: 0.737 to 0.761) for death, 0.718 (95% CI: 0.717 to 0.721) for HF rehospitalization and 0.670 (95% CI: 0.595 to 0.710) for MACEs. The four domains of CHF-PRO, especially the physical domain, showed the most significant impact on the prediction of outcomes.

Conclusion

CHF-PRO showed strong prediction value in the models. The XGBoost models using variables based on CHF-PRO and the patient’s general information provide prognostic assessment for patients with CHF. The self-made web-based risk calculator can be conveniently used to predict the prognosis for patients after discharge.

Clinical Trial Registration

URL: http://www.chictr.org.cn/index.aspx; Unique identifier: ChiCTR2100043337.

Graphical abstract
Identification of transcription factors related to diabetic tubulointerstitial injury
Authors: Liu Jialu , Duan Guangzhong , Yang Wenxia , Zhang Shumin , Liu Fuyou , Peng Youming , Sun Lin , Liu Yu , Xiao Li
Published: March 2023

Background

Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury.

Methods

A microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS.

Results

The regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury.

Conclusions

(1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN.
Fighting female genital mutilation/cutting (FGM/C): towards the endgame and beyond
Authors: Sabi Boun Saidou , Otu Akaninyene , Yaya Sanni
Published: March 2023

Despite the criminalization of the practice by numerous laws and international treaties in most countries concerned, female genital mutilation/cutting (FGM/C), although on the decline overall, is stagnating or tending to increase in some parts Africa. This relative failure in the fight against FGM/C could be explained from an institutional perspective. Although these struggles affect the regulatory mechanisms, which include laws, they hardly touch the normative mechanisms, which constitute the set of values deemed socially acceptable by a society, and the cultural and cognitive mechanisms, which are the manifestations of the ideologies or beliefs of a group. The naming of FGM/C among certain ethnic groups, which is part of the normative character of the social institution, rather valorizes them and makes uncut girls/women feel "dirty" or "unfit”. In these communities, women who have undergone FGM/C are viewed by society as women of honour while uncut girls are perceived as promiscuous and victims of mockery, rejection, or exclusion by the community. In addition, since excision ceremonies and rituals are exclusively reserved for women, many see them as a way of freeing themselves from the rules of patriarchy and male domination that are omnipresent in the societies concerned. Informal mechanisms such as the use of witchcraft, gossip, and beliefs related to the supernatural power of the excisors underpin the cultural-cognitive nature of FGM/C practice. As a result, many families are reluctant to challenge the cutters. The fight against FGM/C can be more effective by addressing the normative and cultural-cognitive roots that form the basis for its perpetuation. This can be achieved by avoiding moralizing the practice, involving those who resist the practice in a context of high prevalence, known as "positive deviants," and using productive methods from the societies concerned. This will create a social environment in which FGM/C is increasingly perceived as less favourable and will ultimately allow for a gradual reform of the normative and cultural-cognitive character of societies that practice FGM/C. Education of women and social mobilisation are critical tools which can act as powerful levers in shifting attitudes about FGM/C.
Pathogenic role of Twist-1 protein in hydatidiform molar pregnancies and investigation of its potential diagnostic utility in complete moles
Authors: Jahanbin Behnaz , Sarmadi Soheila , Ghasemi Dorsa , Nili Fatemeh , Moradi Jafar-Ali , Ghasemi Soha
Published: March 2023

Background

Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary.

Methods

In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score.

Results

Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p < 0.001). Moderate to strong staining intensity in more than 50% of villous stromal cells, can differentiate CM and PM with 89.5% sensitivity and 75% specificity. In syncytiotrophoblasts of CM, Twist-1 expression was significantly lower than PM (p < 0.001). Negative or weak staining intensity in less than 10% of syncytiotrophoblasts, can distinguish CM and PM with 82.9% sensitivity and 60% specificity.

Conclusion

A higher expression of Twist-1 in villous stromal cells of hydatidiform moles is a sensitive and specific marker for the diagnosis of CMs. An elevated expression of this marker in villous stromal cells suggests another pathogenic mechanism for more aggressiveness of CMs in addition to the characteristics of trophoblast cells. The opposite result was obtained in the expression of Twist-1 in the syncytiotrophoblasts, compatible with defects in the process of formation of these supportive cells in CMs.
Hospital mortality of blunt abdominal aortic injury (BAAI): a systematic review and meta-analysis
Authors: Li Mingxuan , Yan Yu , Wang Chaonan , Tu Haixia
Published: March 2023

Background

Studies on the mortality of blunt abdominal aortic injury (BAAI) are rare and have yielded inconsistent results. In the present study, we aimed to quantitatively analyse the retrieved data to more accurately determine the hospital mortality of BAAI.

Methods

The Excerpta Medica Database, PubMed, Web of Science and Cochrane Library databases were searched to identify relevant publications without date restrictions. The overall hospital mortality (OHM) of BAAI patients was set as the primary outcome measure. English publications with data that met the selection criteria were included. The quality of all included studies was assessed by the Joanna Briggs Institute checklist and the American Agency for Health Care Quality and Research’s cross-sectional study quality evaluation items. After data extraction, a meta-analysis of the Freeman–Tukey double arcsine transformation of data was performed using the Metaprop command in Stata 16 software. Heterogeneity was assessed and reported as a percentage using the I2 index value and as a P value using the Cochrane Q test. Various methods were used to determine the sources of heterogeneity and to analyse the sensitivity of the computation model.

Results

Of the 2147 references screened, 5 studies that involved 1593 patients met the selection criteria and were included. There were no low-quality references after assessment. One study that only included 16 juvenile BAAI patients was excluded from the meta-analysis of the primary outcome measure due to high heterogeneity. Due to the low heterogeneity (I2 = 47.6%, P = 0.126 for Q test) that was observed after using the random effects model, the fixed model was subsequently used to pool the effect sizes of the remaining four studies, thus yielding an OHM of 28.8% [95% confidence interval (CI) 26.5–31.1%]. The stability of the model was verified by sensitivity analysis, and Egger’s test (P = 0.339) indicated a low level of publication bias. In addition, we also performed meta-analyses and obtained a pooled hospital mortality of operation (13.5%, 95% CI 8.0–20.0%), a pooled hospital mortality of non-operation (28.4%, 95% CI 25.9–31.0%), and a pooled rate of aortic rupture (12.2%, 95% CI 7.0–18.5%) of BAAI.

Conclusions

The present study indicated that BAAI has an OHM of 28.8%, indicating that this disease deserves more attention and research.
Rates of discontinuation and non-publication of upper and lower extremity fracture clinical trials
Authors: Shepard Samuel , Anderson J. Michael , Heigle Benjamin , Thompson Jay C. , Detweiler Byron , Hartwell Micah , Vassar Matt
Published: March 2023

Purpose

To our knowledge, no study has quantified the rate of discontinuation and nonpublication of randomized controlled trials (RCTs) regarding upper and lower extremity fractures.

Methods

We searched ClinicalTrials.gov on September 9th, 2020, for phase 3 and 4 RCTs pertaining to upper and lower extremity fractures. Trial completion status was determined using records available on ClinicalTrials.gov. Publication status was determined using records on ClinicalTrials.gov and by searching PubMed (MEDLINE), Embase, and Google Scholar. We queried corresponding authors on trial status if a peer-reviewed publication was not identified.

Results

Our final analysis included 142 RCTs, of which 57 (40.1%) were discontinued and 71 (50%) were unpublished. Thirty-six (of 57, 63.2%) discontinued trials failed to provide a reason for discontinuation, the most commonly identified reason for discontinuation was due to inadequate recruitment (13/21, 61.9%). Completed trials were more likely to reach publication (59/85; 69.4%; X2 = 32.92; P ≤ 0.001) than discontinued trials. Trials with more than 80 participants were less likely not to reach publication (AOR: 0.12; 95% CI 0.15–0.66).

Conclusion

Our analysis of 142 upper and lower extremity fracture RCTs demonstrated one-half failed to reach publication and two-fifths were discontinued prior to trial completion. These findings indicate the need for increased guidance in developing, completing, and publishing RCTs in upper and lower extremity fractures. Discontinuation and nonpublication of orthopaedic RCTs hinder the public’s access to collected data and negate the valued contribution from study participants. Discontinuation and non-publication of clinical trials may subject participants to potentially harmful interventions, limit the advancement of clinical research, and contribute to research waste.

Level of Evidence: III.
Effects of eight-week high-intensity interval training on some metabolic, hormonal and cardiovascular indices in women with PCOS: a randomized controlled trail
Authors: Mohammadi Somayeh , Monazzami Amirabbas , alavimilani Solmaz
Published: March 2023

Background

Studies have revealed that high-intensity interval training (HIIT) has beneficial effect on hormonal, cardiovascular indices in women with polycystic ovary syndrome (PCOS). There, however, is still no comprehensive data on the type, intensity and duration of training for these women.

Objective

The current study aimed to investigate the effects of high-intensity interval training (HIIT) on metabolic, hormonal and cardiovascular indices in women with PCOS compared to a control group.

Methods

In a randomized controlled study, 28 patients (age: 23.8 ± 5.3 years, weight: 82.4 ± 9.7 kg, BMI: 30.33 ± 3.99 kg/m2) were divided into two groups including HIIT (n = 14) and the control (n = 14). The training protocol was performed with 100–110 maximum aerobic velocity (MAV), 4–6 sets, 4 laps, 3 sessions per week for eight weeks. Anthropometric indices, aerobic performance, insulin resistance and sensitivity, lipid profiles, testosterone, cortisol and hs-CRP were evaluated.

Results

The HIIT intervention decreased BMI, waist to hip ratio (WHR), visceral fat, insulin, insulin resistance, low density lipoprotein (LDL), atherogenic index, cholesterol and cortisol (P < 0.05). All variables remained unchanged in the control group (P > 0.05). Except for VAI, FBG, HDL, TG and AIP, the rest of the variables in the training and control groups show a significant difference (P < 0.05).

Conclusion

The results of the present study indicate that eight weeks of HIIT has beneficial effects on anthropometric, insulin sensitivity, fat profile, and inflammatory and cardiovascular indices in PCOS patients. It seems that the intensity of HIIT (100–110 MAV) is a determining factor in creating optimal adaptations in PCOS patients.

Trail registration: IRCT20130812014333N143. Registration date: 22/03/2020. URL: https://en.irct.ir/trial/46295.
Distinguishable DNA methylation defines a cardiac-specific epigenetic clock
Authors: Mongelli A. , Panunzi S. , Nesta M. , Gottardi Zamperla M. , Atlante S. , Barbi V. , Mongiardini V. , Ferraro F. , De Martino S. , Cis L. , Re A. , Maltese S. , Bachetti T. , La Rovere M. T. , Martelli F. , Pesce M. , Nanni S. , Massetti M. , Pontecorvi A. , Farsetti A. , Gaetano C.
Published: March 2023

Background

The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age.

Results

Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume.

Conclusion

This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.
A clinical–radiomics model based on noncontrast computed tomography to predict hemorrhagic transformation after stroke by machine learning: a multicenter study
Authors: Ren Huanhuan , Song Haojie , Wang Jingjie , Xiong Hua , Long Bangyuan , Gong Meilin , Liu Jiayang , He Zhanping , Liu Li , Jiang Xili , Li Lifeng , Li Hanjian , Cui Shaoguo , Li Yongmei
Published: March 2023

Objective

To build a clinical–radiomics model based on noncontrast computed tomography images to identify the risk of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT).

Materials and methods

A total of 517 consecutive patients with AIS were screened for inclusion. Datasets from six hospitals were randomly divided into a training cohort and an internal cohort with an 8:2 ratio. The dataset of the seventh hospital was used for an independent external verification. The best dimensionality reduction method to choose features and the best machine learning (ML) algorithm to develop a model were selected. Then, the clinical, radiomics and clinical–radiomics models were developed. Finally, the performance of the models was measured using the area under the receiver operating characteristic curve (AUC).

Results

Of 517 from seven hospitals, 249 (48%) had HT. The best method for choosing features was recursive feature elimination, and the best ML algorithm to build models was extreme gradient boosting. In distinguishing patients with HT, the AUC of the clinical model was 0.898 (95% CI 0.873–0.921) in the internal validation cohort, and 0.911 (95% CI 0.891–0.928) in the external validation cohort; the AUC of radiomics model was 0.922 (95% CI 0.896–0.941) and 0.883 (95% CI 0.851–0.902), while the AUC of clinical–radiomics model was 0.950 (95% CI 0.925–0.967) and 0.942 (95% CI 0.927–0.958) respectively.

Conclusion

The proposed clinical–radiomics model is a dependable approach that could provide risk assessment of HT for patients who receive IVT after stroke.
Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration
Authors: Lu Ye , Mai Zizhao , Cui Li , Zhao Xinyuan
Published: March 2023

Mesenchymal stem cell-based therapy has become an effective therapeutic approach for bone regeneration. However, there are still limitations in successful clinical translation. Recently, the secretome of mesenchymal stem cells, especially exosome, plays a critical role in promoting bone repair and regeneration. Exosomes are nanosized, lipid bilayer-enclosed structures carrying proteins, lipids, RNAs, metabolites, growth factors, and cytokines and have attracted great attention for their potential application in bone regenerative medicine. In addition, preconditioning of parental cells and exosome engineering can enhance the regenerative potential of exosomes for treating bone defects. Moreover, with recent advancements in various biomaterials to enhance the therapeutic functions of exosomes, biomaterial-assisted exosomes have become a promising strategy for bone regeneration. This review discusses different insights regarding the roles of exosomes in bone regeneration and summarizes the applications of engineering exosomes and biomaterial-assisted exosomes as safe and versatile bone regeneration agent delivery platforms. The current hurdles of transitioning exosomes from bench to bedside are also discussed.
TMED3 promotes the development of malignant melanoma by targeting CDCA8 and regulating PI3K/Akt pathway
Authors: Guo Xianling , Yin Xiaolan , Xu Yu , Li Liang , Yuan Min , Zhao Huaxin , Jiang Yuxiong , Shi Xiujuan , Bi Hongda , Liu Yeqiang , Chen Yong , Xu Qing
Published: March 2023

Background

Transmembrane emp24 domain containing (TMED) proteins are known to play pivotal roles in normal development, but have been reported to be implicated in pancreatic disease, immune system disorders, and cancers. As far as TMED3 is concerned, its roles in cancers are controversial. However, evidence describing TMED3 in the context of malignant melanoma (MM) is scarce.

Results

In this study, we characterized the functional significance of TMED3 in MM and identified TMED3 as a tumor-promoting factor in MM development. Depletion of TMED3 arrested the development of MM in vitro and in vivo. Mechanistically, we found that TMED3 could interact with Cell division cycle associated 8 (CDCA8). Knocking down CDCA8 suppressed cell events associated with MM development. On the contrary, elevating CDCA8 augmented cell viability and motility and even reversed the inhibitory effects of TMED3 knockdown on MM development. On the other hand, we found that the levels of P-Akt and P-PI3K were decreased in response to TMED3 downregulation, which was partially abolished following SC79 treatment. Thus, our suspicion was that TMED3 exacerbates MM progression via PI3K/Akt pathway. More notably, previously decreased P-Akt and P-PI3K in TMED3-depleted cells were rescued after overexpressing CDCA8. Also, previously impaired cell events due to CDCA8 depletion were ameliorated after SC79 addition, implying that TMED3 regulates PI3K-AKT pathway via CDCA8, thereby promoting MM development.

Conclusions

Collectively, this study established the link between TMED3 and MM, and provides a potential therapeutic intervention for patients with MM harboring abundant TMED3.
“Sign Me Up”: a qualitative study of video observed therapy (VOT) for patients receiving expedited methadone take-homes during the COVID-19 pandemic
Authors: Darnton James B. , Bhatraju Elenore P. , Beima-Sofie Kristin , Michaels Alyssa , Hallgren Kevin A. , Soth Sean , Grekin Paul , Woolworth Steve , Tsui Judith I.
Published: March 2023

Background

Federal and state regulations require frequent direct observation of methadone ingestion at an Opioid Treatment Program (OTP)—a requirement that creates barriers to patient access. Video observed therapy (VOT) may help to address public health and safety concerns of providing take-home medications while simultaneously reducing barriers to treatment access and long-term retention. Evaluating user experiences with VOT is important for understanding the acceptability of this strategy.

Methods

We conducted a qualitative evaluation of a clinical pilot program of VOT via smartphone that was rapidly implemented between April and August 2020 during the COVID-19 pandemic within three opioid treatment programs. In the program, selected patients submitted video recordings of themselves ingesting methadone take-home doses, which were asynchronously reviewed by their counselor. We recruited participating patients and counselors for semi-structured, individual interviews to explore their VOT experiences after program completion. Interviews were audio recorded and transcribed. Transcripts were analyzed using thematic analysis to identify key factors influencing acceptability and the effect of VOT on the treatment experience.

Results

We interviewed 12 of the 60 patients who participated in the clinical pilot and 3 of the 5 counselors. Overall, patients were enthusiastic about VOT, noting multiple benefits over traditional treatment experiences, including avoiding frequent travel to the clinic. Some noted how this allowed them to better meet recovery goals by avoiding a potentially triggering environment. Most appreciated having increased time to devote to other life priorities, including maintaining consistent employment. Participants described how VOT increased their autonomy, allowed them to keep treatment private, and normalized treatment to align with other medications that do not require in-person dosing. Participants did not describe major usability issues or privacy concerns with submitting videos. Some participants reported feeling disconnected from counselors while others felt more connected. Counselors felt some discomfort in their new role confirming medication ingestion but saw VOT as a useful tool for select patients.

Conclusions

VOT may be an acceptable tool to achieve equipoise between lowering barriers to treatment with methadone and protecting the health and safety of patients and their communities.
Myeloid-derived suppressor cells: key immunosuppressive regulators and therapeutic targets in hematological malignancies
Authors: Wang Shifen , Zhao Xingyun , Wu Siwen , Cui Dawei , Xu Zhenshu
Published: March 2023

The immunosuppressive tumor microenvironment (TME) supports the development of tumors and limits tumor immunotherapy, including hematological malignancies. Hematological malignancies remain a major public health issue with high morbidity and mortality worldwide. As an important component of immunosuppressive regulators, the phenotypic characteristics and prognostic value of myeloid-derived suppressor cells (MDSCs) have received much attention. A variety of MDSC-targeting therapeutic approaches have produced encouraging outcomes. However, the use of various MDSC-targeted treatment strategies in hematologic malignancies is still difficult due to the heterogeneity of hematologic malignancies and the complexity of the immune system. In this review, we summarize the biological functions of MDSCs and further provide a summary of the phenotypes and suppressive mechanisms of MDSC populations expanded in various types of hematological malignancy contexts. Moreover, we discussed the clinical correlation between MDSCs and the diagnosis of malignant hematological disease, as well as the drugs targeting MDSCs, and focused on summarizing the therapeutic strategies in combination with other immunotherapies, such as various immune checkpoint inhibitors (ICIs), that are under active investigation. We highlight the new direction of targeting MDSCs to improve the therapeutic efficacy of tumors.
Measures of success: characterizing teaching and teaching change with segmented and holistic observation data
Authors: Weston Timothy J. , Laursen Sandra L. , Hayward Charles N.
Published: March 2023

Background

Numerous studies show that active and engaging classrooms help students learn and persist in college, but adoption of new teaching practices has been slow. Professional development programs encourage instructors to implement new teaching methods and change the status quo in STEM undergraduate teaching, and structured observations of classrooms can be used in multiple ways to describe and assess this instruction. We addressed the challenge of measuring instructional change with observational protocols, data that often do not lend themselves easily to statistical comparisons. Challenges using observational data in comparative research designs include lack of descriptive utility for holistic measures and problems related to construct representation, non-normal distributions and Type-I error inflation for segmented measures.

Results

We grouped 790 mathematics classes from 74 instructors using Latent Profile Analysis (a statistical clustering technique) and found four reliable categories of classes. Based on this grouping we proposed a simple proportional measure we called Proportion Non-Didactic Lecture (PND). The measure aggregated the proportions of interactive to lecture classes for each instructor. We tested the PND and a measure derived from the Reformed Teaching Observation Protocol (RTOP) with data from a professional development study. The PND worked in simple hypothesis tests but lacked some statistical power due to possible ceiling effects. However, the PND provided effective descriptions of changes in instructional approaches from pre to post. In tandem with examining the proportional measure, we also examined the RTOP-Sum, an existing outcome measure used in comparison studies. The measure is based on the aggregated items in a holistic observational protocol. As an aggregate measure we found it to be highly reliable, correlated highly with the PND, and had more statistical power than the PND. However, the RTOP measure did not provide the thick descriptions of teaching afforded by the PND.

Conclusions

Findings suggest that useful dependent measures can be derived from both segmented and holistic observational measures. Both have strengths and weaknesses: measures from segmented data are best at describing changes in teaching, while measures derived from the RTOP have more statistical power. Determining the validity of these measures is important for future use of observational data in comparative studies.
Evaluation of reference genes for transcript analyses in Komagataella phaffii (Pichia pastoris)
Authors: Besleaga Mihail , Vignolle Gabriel A. , Kopp Julian , Spadiut Oliver , Mach Robert L. , Mach-Aigner Astrid R. , Zimmermann Christian
Published: March 2023

Background

The yeast Komagataella phaffii (Pichia pastoris) is routinely used for heterologous protein expression and is suggested as a model organism for yeast. Despite its importance and application potential, no reference gene for transcript analysis via RT-qPCR assays has been evaluated to date. In this study, we searched publicly available RNASeq data for stably expressed genes to find potential reference genes for relative transcript analysis by RT-qPCR in K. phaffii. To evaluate the applicability of these genes, we used a diverse set of samples from three different strains and a broad range of cultivation conditions. The transcript levels of 9 genes were measured and compared using commonly applied bioinformatic tools.

Results

We could demonstrate that the often-used reference gene ACT1 is not very stably expressed and could identify two genes with outstandingly low transcript level fluctuations. Consequently, we suggest the two genes, RSC1, and TAF10 to be simultaneously used as reference genes in transcript analyses by RT-qPCR in K. phaffii in future RT-qPCR assays.

Conclusion

The usage of ACT1 as a reference gene in RT-qPCR analysis might lead to distorted results due to the instability of its transcript levels. In this study, we evaluated the transcript levels of several genes and found RSC1 and TAF10 to be extremely stable. Using these genes holds the promise for reliable RT-qPCR results.