bluuebunny/crossref_metadata_2025 huggingface dataset:
Morusin shows potent antitumor activity for melanoma through apoptosis induction and proliferation inhibition
Authors: Liu Wei , Ji Yacong , Wang Feng , Li Chongyang , Shi Shaomin , Liu Ruochen , Li Qian , Guo Leiyang , Liu Yaling , Cui Hongjuan
Published: June 2023

Background

The discovery of new anti-melanoma drugs with low side effect is urgently required in the clinic. Recent studies showed that morusin, a flavonoid compound isolated from the root bark of Morus Alba, has the potential to treat multiple types of cancers, including breast cancer, gastric cancer, and prostate cancer. However, the anti-cancer effect of morusin on melanoma cells has not been investigated.

Methods

We analyzed the effects of morusin on the proliferation, cell cycle, apoptosis, cell migration and invasion ability of melanoma cells A375 and MV3, and further explored the effects of morusin on tumor formation of melanoma cell. Finally, the effects of morusin on the proliferation, cycle, apoptosis, migration and invasion of A375 cells after knockdown of p53 were detected.

Results

Morusin effectively inhibits the proliferation of melanoma cells and induces cell cycle arrest in the G2/M phase. Consistently, CyclinB1 and CDK1 that involved in the G2/M phase transition were down-regulated upon morusin treatment, which may be caused by the up-regulation of p53 and p21. In addition, morusin induces cell apoptosis and inhibits migration of melanoma cells, which correlated with the changes in the expression of the associated molecules including PARP, Caspase3, E-Cadherin and Vimentin. Moreover, morusin inhibits tumor growth in vivo with little side effect on the tumor-burden mice. Finally, p53 knockdown partially reversed morusin-mediated cell proliferation inhibition, cell cycle arrest, apoptosis, and metastasis.

Conclusion

Collectively, our study expanded the spectrum of the anti-cancer activity of morusin and guaranteed the clinical use of the drug for melanoma treatment.
Infantile fibrosarcoma of the perineum with dorsal metastasis in a neonate: a case report original
Authors: Geng Juan , Chen Dan , Wang Limin , Liu Xiangjiao , Chen Wenjing , Gao Hongyi , Xiao Shangjie
Published: June 2023

Background

Infantile fibrosarcoma is a rare pediatric soft tissue tumor and usually appears in children before one year of age. Distal extremities constitute the most frequently affected locations, and other tissues such as the trunk, head and neck, gut, sacrococcygeal region, and viscera are uncommon sites.

Case presentation

We describe a rare case of infantile fibrosarcoma arising from the perineum. First, a cystic mass was detected using prenatal ultrasonography, and then an echo was changed in serial ultrasound examinations. A solid cystic lesion was found at term; a hypoechoic lesion occurred in the back. The tumor became so large that massive bleeding occurred, which then underwent surgical resection. Pathological examination confirmed infantile fibrosarcoma.

Conclusion

Our report demonstrates not all ultrasonographic findings in cases of infantile fibrosarcoma exhibit a solid mass during the initial examination — an early-stage lesion may reveal a cystic echo. Infantile fibrosarcoma has a good prognosis and surgery constitute the main treatment, with adjuvant chemotherapy being received if necessary.
Functional abdominal pain disorders in children in southern Anhui Province, China are related to academic stress rather than academic performance
Authors: Bao Xiaoshuang , Yu Wenchao , Chu Ziyan , Gao Jie , Zhou Meimei , Gu Yong
Published: June 2023

Background

Functional abdominal pain disorders (FAPDs) are one of the most common gastrointestinal disorders in children. The aim of this study was to investigate the prevalence of FAPDs in children in southern Anhui Province, China and their association with academic stress.

Methods

In this cross-sectional survey, we randomly selected children aged 6–17 years from 11 public schools in southern Anhui Province. FAPDs were diagnosed according to the Rome IV criteria, and a custom-designed questionnaire was used to investigate the association between academic stress and FAPDs in children.

Results

A total of 2,344 children aged 6–17 years were enrolled. The mean age was 12.4 ± 3.0 years. Of these children, 335 (14.3%) were diagnosed with FAPDs according to the Rome IV criteria. Among the children with FAPDs, 156 (46.6%) were boys, and 179 (53.4%) were girls. The prevalence was higher in girls than in boys. The most common disorder was irritable bowel syndrome (IBS) (n = 182 (7.8%)). Other types of FAPDs included functional abdominal pain–not otherwise specified (FAPNOS) (n = 70 (3.0%)), functional dyspepsia (FD) (n = 55 (2.3%)), and abdominal migraine (AM) (n = 28 (1.2%)). Academic stress, not meeting parental expectations, poor relationships with parents, and sleep disturbances were independent risk factors for FAPDs in children; academic performance was not associated with the development of FAPDs.

Conclusion

There was a high prevalence of FAPDs among children in southern Anhui Province, China, and IBS was the most common subtype of functional abdominal pain. Academic stress, rather than academic performance, was associated with FAPDs in children.
Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis
Authors: Zhang Qin , Chen Bing , Zhang Jinghui , Dong Jingyi , Ma Jianglin , Zhang Yuyan , Jin Kangyu , Lu Jing
Published: June 2023

Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.
The impact of physical activity on electronic media use among chinese adolescents and urban-rural differences
Authors: Bai Shengchao , Yin Yutong , Chen Shengju
Published: June 2023

Objective

With the prevalence of electronic media use among Chinese adolescents and concerns regarding its potential negative consequences on their health and development, this study investigated the relationship between physical exercise and electronic media use. Utilizing data from the China Education Panel Survey, we examine the impact of physical activity on adolescents’ electronic media use.

Methods

A simultaneous equation model, including two-stage least square and three-stage least square, was employed to estimate the impact of physical activity on electronic media use among adolescents. Self-control theory and media addiction theory were also used to analyze electronic media use in adolescents. Descriptive statistics were used to analyzed the data.

Results

Chinese adolescents dedicated a substantial amount of time, averaging 2.95 hours per day, to electronic media activities. Increasing physical activity demonstrated an effective means to reduce electronic media use. Furthermore, the impact of physical activity on electronic media use exhibited urban-rural stratification, with family factors related to social class status primarily influencing electronic media use among urban students, while physical activity has a more pronounced influence among rural students.

Conclusions

Promoting physical activity represents a compelling and effective strategy for curbing excessive electronic media use among Chinese adolescents, particularly in rural areas where physical activity has a stronger influence. In addition, controlling media entertainment and recreation time and enhancing social cohesion can help to weaken media interest. While changing the social class status of families in urban areas may be difficult in the short term, parents should be aware that physical exercise is an effective way to reduce their children’s use of electronic media. Our findings suggested that promoting physical activity may be a promising strategy for reducing excessive electronic media use among Chinese adolescents, particularly in rural areas where physical activity has a stronger influence.
Vaccine coverage and effectiveness against laboratory-confirmed symptomatic and severe Covid-19 in indigenous people in Brazil: a cohort study
Authors: Pescarini Julia M. , Cardoso Andrey M. , Santos Ricardo Ventura , Scaff Priscila F. , Paixao Enny S. , Ranzani Otavio T. , Cerqueira-Silva Thiago , Boaventura Viviane S. , Bertoldo-Junior Juracy , de Oliveira Vinicius A. , Werneck Guilherme L. , Barreto Mauricio L. , Barral-Netto Manoel
Published: June 2023

Background

Indigenous people have historically suffered devastating impacts from epidemics and continue to have lower access to healthcare and be especially vulnerable to respiratory infections. We estimated the coverage and effectiveness of Covid-19 vaccines against laboratory-confirmed Covid-19 cases among indigenous people in Brazil.

Methods

We linked nationwide Covid-19 vaccination data with flu-like surveillance records and studied a cohort of vaccinated indigenous people aged ≥ 5 years between 18th January 2021 and 1st March 2022. We considered individuals unexposed from the date they received the first dose of vaccine until the 13th day of vaccination, partially vaccinated from the 14th day after the first dose until the 13th day after receiving the second dose, and fully vaccinated onwards. We estimated the Covid-19 vaccination coverage and used Poisson regression to calculate the relative risks (RR) and vaccine effectiveness (VE) of CoronaVac, ChAdOx1, and BNT162b2 against Covid-19 laboratory-confirmed cases incidence, mortality, hospitalisation, and hospital-progression to Intensive Care Unit (ICU) or death. VE was estimated as (1-RR)*100, comparing unexposed to partially or fully vaccinated.

Results

By 1st March 2022, 48.7% (35.0-62.3) of eligible indigenous people vs. 74.8% (57.9–91.8) overall Brazilians had been fully vaccinated for Covid-19. Among fully vaccinated indigenous people, we found a lower risk of symptomatic cases (RR: 0.47, 95%CI: 0.40–0.56) and mortality (RR: 0.47, 95%CI: 0.14–1.56) after the 14th day of the second dose. VE for the three Covid-19 vaccines combined was 53% (95%CI:44–60%) for symptomatic cases, 53% (95%CI:-56-86%) for mortality and 41% (95%CI:-35-75%) for hospitalisation. In our sample, we found that vaccination did not reduce Covid-19 related hospitalisation. However, among hospitalised patients, we found a lower risk of progression to ICU (RR: 0.14, 95%CI: 0.02–0.81; VE: 87%, 95%CI:27–98%) and Covid-19 death (RR: 0.04, 95%CI:0.01–0.10; VE: 96%, 95%CI: 90–99%) after the 14th day of the second dose.

Conclusions

Lower coverage but similar Covid-19 VE among indigenous people than overall Brazilians suggest the need to expand access, timely vaccination, and urgently offer booster doses to achieve a great level of protection among this group.
It can be unnecessary to combine common synovial fluid analysis and alpha-defensin tests for periprosthetic joint infection diagnosis
Authors: Li Hao , Li Rui , Erlong Niu , Chai Wei , Hao LiBo , Xu Chi , Fu Jun , Chen Jiying , Zhu Fangzheng
Published: June 2023

Background

Periprosthetic joint infection is a serious complication after total joint arthroplasty. Despite that alpha-defensin was used as diagnostic test in the 2018 ICM (international consensus meeting) criteria, its position in the PJI diagnostic pipeline was controversial. Therefore, we performed a retrospective pilot study to identify whether synovial fluid alpha-defensin test was necessary when corresponding synovial fluid analysis (WBC count, PMN% and LE tests) was performed.

Methods

Between May 2015 and October 2018, a total of 90 suspected PJI patients who underwent revisions after TJA were included in this study. Based on the 2018 ICM criteria, the interobserver agreements between preoperative diagnostic results and postoperative diagnostic results and the interobserver reliability between preoperative diagnostic results and postoperative diagnostic results with or without synovial fluid alpha-defensin tests were calculated. After that, the ROC analysis, and the direct cost-effectiveness of adding alpha-defensin was performed.

Results

There were 48,16 and 26 patients in the PJI group, inconclusive group and non-PJI group, respectively. Adding the alpha-defensin tests into 2018 ICM criteria can’t change the preoperative diagnostic results, postoperative diagnostic results, and the concordance between preoperative and postoperative diagnostic results. Moreover, the Risk–benefit Ratio is over 90 per changed decision and the direct cost-effectiveness of alpha-defensin was more than $8370($93*90) per case.

Conclusions

Alpha-defensin assay exhibit high sensitivity and specificity for PJI detection as a standalone test based on the 2018 ICM criteria. However, the additional order of Alpha-defensin can’t offer additional evidence for PJI diagnosis when corresponding synovial fluid analysis was performed (synovial fluid WBC count, PMN% and LE strip tests).

Evidence level

Level II, Diagnostic study.
Exploring the correlation between serum fibroblast growth factor-21 levels and Sarcopenia: a systematic review and meta-analysis
Authors: Liu Hao , He Xia , Deng Xiao-Yan , Yan Jing-Lu
Published: June 2023

Background

Fibroblast growth factor 21 (FGF-21) plays an important role in the growth and metabolism of skeletal muscle cells. This study aims to systemically review the evidence regarding the relationship between FGF-21 levels and Sarcopenia, as well as the related influential factors.

Methods

This review was conducted according to the PRISMA guidelines. We comprehensively searched PubMed, EMBASE, the Web of Science, Scopus, and Chinese Databases (CNKI, Wan Fang, VIP, and CBM) up to 1 May 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and two investigators performed an independent quality assessment of case-control studies using the Joanna Briggs Institute (JBI) tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot.

Results

Five studies with a total of 625 cases were included in the review. Meta-analysis showed lower BMI in the sarcopenia group [MD= -2.88 (95% CI, -3. 49, -2.27); P < 0.00001; I2 = 0%], significantly reduced grip strength in the sarcopenia group compared to the non-sarcopenia group [MD = -7.32(95% CI, -10.42,-4.23); P < 0.00001; I2 = 93%]. No statistically significant differences in serum FGF21 levels were found when comparing the two groups of subjects [SMD = 0.31(95% CI, -0.42, 1.04); P = 0.41; I2 = 94%], and no strong correlation was found between the onset of sarcopenia and serum FGF21 levels.

Conclusion

The diagnosis of sarcopenia is followed by a more significant decrease in muscle mass and strength, but there is a lack of strong evidence to support a direct relationship between elevated organismal FGF21 and sarcopenia, and it is not convincing to use FGF21 as a biological or diagnostic marker for sarcopenia. The currently used diagnostic criteria for sarcopenia and setting of cut-off values for each evaluation parameter no longer seem to match clinical practice.
Menopausal symptoms by HIV status and association with health-related quality of life among women in Zimbabwe: a cross-sectional study
Authors: Madanhire Tafadzwa , Hawley Samuel , Dauya Ethel , Bandason Tsitsi , Rukuni Ruramayi , Ferrand Rashida A , Gregson Celia L
Published: June 2023

Background

The scale-up of antiretroviral therapy programmes has resulted in increased life expectancy of people with HIV in Africa. Little is known of the menopausal experiences of African women, including those living with HIV. We aimed to determine the prevalence and severity of self-reported menopause symptoms in women at different stages of menopause transition, by HIV status, and evaluate how symptoms are related to health-related quality of life (HRQoL). We further sought to understand factors associated with menopause symptoms.

Methods

A cross-sectional study recruited women resident in Harare, Zimbabwe, sampled by age group (40–44/45–49/50–54/55–60 years) and HIV status. Women recruited from public-sector HIV clinics identified two similarly aged female friends (irrespective of HIV status) with phone access. Socio-demographic and medical details were recorded and women staged as pre-, peri- or post-menopause. The Menopausal Rating Scale II (MRS), which classified symptom severity, was compared between those with and without HIV. Linear and logistic regression determined factors associated with menopause symptoms, and associations between symptoms and HRQoL.

Results

The 378 women recruited (193[51.1%] with HIV), had a mean (SD) age of 49.3 (5.7) years; 173 (45.8%), 51 (13.5%) and 154 (40.7%) were pre-, peri and post-menopausal respectively. Women with HIV reported more moderate (24.9% vs. 18.1%) and severe (9.7% vs. 2.6%) menopause symptoms than women without HIV. Peri-menopausal women with HIV reported higher MRS scores than those pre- and post-menopausal, whereas in HIV negative women menopausal stage was not associated with MRS score (interaction p-value = 0.014). With increasing severity of menopause symptoms, lower mean HRQoL scores were observed. HIV (OR 2.02[95% CI 1.28, 3.21]), mood disorders (8.80[2.77, 28.0]), ≥ 2 falls/year (4.29[1.18, 15.6]), early menarche (2.33[1.22, 4.48]), alcohol consumption (2.16[1.01, 4.62]), food insecurity (1.93[1.14, 3.26]) and unemployment (1.56[0.99, 2.46]), were all associated with moderate/severe menopause symptoms. No woman reported use of menopausal hormone therapy.

Conclusions

Menopausal symptoms are common and negatively impact HRQoL. HIV infection is associated with more severe menopause symptoms, as are several modifiable factors, including unemployment, alcohol consumption, and food insecurity. Findings highlight an unmet health need in ageing women in Zimbabwean, especially among those living with HIV.
When theory beats practice: the implementation of competency-based education at healthcare workplaces
Authors: Janssens Oona , Embo Mieke , Valcke Martin , Haerens Leen
Published: June 2023

Background

Work-integrated learning constitutes a large part of current healthcare education. During the last decades, a competency-based educational (CBE) approach has been introduced to reduce the theory-practice gap and to promote continuous competency development. Different frameworks and models have been developed to support CBE implementation in practice. Although CBE is now well-established, implementation at healthcare workplaces remains complex and controversial. This study aims to explore how students, mentors, and educators from different healthcare disciplines perceive the implementation of CBE at the workplace. The six-step model of Embo et al. (2015) was used as a base: (1) competency selection, (2) formulating learning goals, (3) self-monitoring performance, (4) self-assessing competency development, (5) summative assessment of individual competencies, and (6) summative assessment of global professional competence.

Methods

Three semi-structured focus group interviews were conducted with (1) five students, (2) five mentors, and (3) five educators. We recruited participants from six different educational programs: audiology, midwifery, nursing (associate degree and bachelor), occupational therapy, or speech therapy. We used thematic analysis combining an inductive and deductive approach.

Results

An overview of the predefined competencies was hard to find which complicated CBE implementation and resulted in a lack of consistency between the steps; e.g., the link between the selection of relevant competencies (step 1) and the formulation of learning goals based on these selected competencies (step 2) was absent. Furthermore, the analysis of the data helped identifying seven barriers for CBE implementation: (1) a gap between the educational program and the workplace, (2) a lacking overview of predefined competencies, (3) a major focus on technical competencies at the expense of generic competencies, (4) weak formulation of the learning goals, (5) obstacles related to reflection, (6) low feedback quality, and (7) perceived subjectivity of the assessment approach.

Conclusion

The present barriers to CBE implementation lead to a fragmentation of current work-integrated learning. In this way, theory beats practice when it comes to CBE implementation as the theory of CBE is not effectively implemented. However, the identification of these barriers might help to find solutions to optimize CBE implementation. Future research seems critical to optimize CBE so that theory can meet practice and the opportunities of CBE optimize healthcare education.
Professional autonomy among nurses in Saudi Arabian critical care units
Authors: Alruwaili Majed M. , Abuadas Fuad H.
Published: June 2023

Background

Professional autonomy is essential in expanding the scope of nursing practice and has been recognized as a top nursing priority.

Objective

This study aims to assess Saudi nurses’ autonomy level in critical care settings and examine the influence of sociodemographic and clinical characteristics on their autonomy level.

Methods

A correlational design and a convenience sampling approach were used to recruit 212 staff nurses from five Saudi governmental hospitals in Jouf region of Saudi Arabia. The data were collected through a self-administered questionnaire composed of two sections, including sociodemographic characteristics and the Belgen autonomy scale. The Belgen autonomy scale used in this study measures nurses’ autonomy levels and consists of 42 items rated on an ordinal scale. The scale’s minimum score of 1 indicates nurses with no authority, while the maximum score of 5 indicates nurses with full authority.

Results

Descriptive statistics revealed that nurses in the sample had a moderate overall work autonomy (M = 3.08), with higher autonomy in patient care decisions (M = 3.25) compared to unit operations decisions (M = 2.91). Nurses had the highest level of autonomy in tasks related to preventing patient falls (M = 3.84), preventing skin breakdown (M = 3.69), and promoting health activities (M = 3.62), while they had the lowest level of autonomy in ordering diagnostic tests (M = 2.27), determining the day of discharge (M = 2.61), and planning the unit’s annual budget (M = 2.22). The multiple linear regression model (R2 = 0.32, F (16, 195) = 5.87, p < .001) showed that education level and years of experience in critical care settings were significantly related to nurses’ work autonomy.

Conclusion

Saudi nurses in acute care settings have moderate professional autonomy, with higher autonomy in making patient care decisions than unit operations decisions. Investing in nurses’ education and training could increase their professional autonomy, leading to improved patient care. Policymakers and nursing administrators can use the study’s results to develop strategies that promote nurses’ professional development and autonomy.
Were SARS-CoV-2 self-tests used for their intended purpose? The experience in Belgium
Authors: Lafort Yves , Cornelissen Laura , Van Cauteren Dieter , Verboven Barbara , Drieskens Sabine , Couvreur Simon , Hermans Lize , Straetmans Koen , Lernout Tinne
Published: June 2023

Background

Self-testing has been promoted as a means of increasing COVID-19 test coverage. In Belgium, self-testing was recommended as a complement to the formal, provider-administered indications, such as out of courtesy before meeting others and when feared to be infected. More than a year after the introduction of self-testing their place in the test strategy was evaluated.

Methods

We assessed trends in the number of self-tests sold, the number of positive self-tests reported, the proportion sold self-tests/total tests, and the proportion of all positive tests that were confirmed self-tests. To evaluate the reason why people use self-tests, we used the results of two online surveys among members of the general population: one among 27,397 people, held in April 2021, and one among 22,354 people, held in December 2021.

Results

The use of self-tests became substantial from end 2021 onwards. In the period mid-November 2021 – end-of-June 2022, the average proportion of reported sold self-tests to all COVID-19 tests was 37% and 14% of all positive tests were positive self-tests. In both surveys, the main reported reasons for using a self-test were having symptoms (34% of users in April 2021 and 31% in December 2021) and after a risk contact (27% in both April and December). Moreover, the number of self-tests sold, and the number of positive self-tests reported closely followed the same trend as the provider-administered tests in symptomatic people and high risk-contacts, which reinforces the hypothesis that they were mainly used for these two indications.

Conclusions

From end 2021 onwards, self-testing covered a significant part of COVID-19 testing in Belgium, which increased without doubt the testing coverage. However, the available data seem to indicate that self-testing was mostly used for indications outside of official recommendations. If and how this affected the control of the epidemic remains unknown.
DNA replication stress and mitotic catastrophe mediate sotorasib addiction in KRASG12C-mutant cancer
Authors: Chiou Li-Wen , Chan Chien-Hui , Jhuang Yu-Ling , Yang Ching-Yao , Jeng Yung-Ming
Published: June 2023

Background

Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.

Methods

Sotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo.

Results

In the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo.

Conclusions

We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
The use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists versus sulfonylureas and the risk of lower limb amputations: a nation-wide cohort study
Authors: Werkman Nikki C. C. , Driessen Johanna H. M. , Stehouwer Coen D. A. , Vestergaard Peter , Schaper Nicolaas C. , van den Bergh Joop P. , Nielen Johannes T. H.
Published: June 2023

Background

Numerous studies have investigated the potential association of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) with an increased risk of lower limb amputations (LLAs), but have produced conflicting results. Particularly studies comparing SGLT2-Is to glucagon-like peptide-1 receptor agonists (GLP1-RAs) seem to find a higher LLA risk with SGLT2-I use. This raises the question whether the results are driven by a protective GLP1-RA-effect rather than a harmful SGLT2-I-effect. GLP1-RAs could promote wound healing and therefore reduce the risk of LLAs, but the associations between both drug classes and LLA remain uncertain. Therefore, the aim of the current study was to investigate the risk of LLA and diabetic foot ulcer (DFU) with SGLT2-I use and GLP1-RA use versus sulfonylurea use.

Methods

A retrospective population-based cohort study was conducted using data from the Danish National Health Service (2013–2018). The study population (N = 74,475) consisted of type 2 diabetes patients aged 18 + who received a first ever prescription of an SGLT2-I, GLP1-RA or sulfonylurea. The date of the first prescription defined the start of follow-up. Time-varying Cox proportional hazards models estimated the hazard ratios (HRs) of LLA and DFU with current SGLT2-I use and GLP1-RA use versus current SU use. The models were adjusted for age, sex, socio-economic variables, comorbidities and concomitant drug use.

Results

Current SGLT2-I use was not associated with a higher risk of LLA versus sulfonylureas {adjusted HR 1.10 [95% confidence interval (CI) 0.71–1.70]}. Current GLP1-RA use, on the other hand, was associated with a lower risk of LLA [adjusted HR 0.57 (95%CI 0.39–0.84)] compared to sulfonylureas. The risk of DFU was similar to that with sulfonylureas with both exposures of interest.

Conclusion

SGLT2-I use was not associated with a higher risk of LLA, but GLP1-RAs with a lower risk of LLA. Previous studies reporting a higher risk of LLA with SGLT2-I use compared to GLP1-RA use might have been looking at a protective GLP1-RA effect, rather than a harmful SGLT2-I effect.
Association between non-insulin-based insulin resistance indices and cardiovascular events in patients undergoing percutaneous coronary intervention: a retrospective study
Authors: Zhang Zenglei , Zhao Lin , Lu Yiting , Meng Xu , Zhou Xianliang
Published: June 2023

Background

Insulin resistance (IR) has been confirmed that getting involved in the pathophysiological process of cardiovascular diseases (CVD). Recently, increasing evidence suggests metabolic score for insulin resistance (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index are simple and reliable surrogates for IR. However, their abilities in predicting cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) are not well explored. Therefore, this study aimed to investigate the association and evaluate the predictive performance of each index.

Methods

A total of 2533 consecutive participants undergoing PCI were included in this study, and the data from 1461 patients were used to determine the correlation of these non-insulin-based IR indices with major adverse cardiac and cerebrovascular events (MACCEs) via performing the multivariate logistic models and restricted cubic splines (RCS).

Results

During a median of 29.8 months follow-up, 195 cases of 1461 patients experienced incident MACCEs. In the overall population, both univariate and multivariate logistic regression analyses indicated no statistically significant connection between these IR indices and MACCEs. Subgroup analyses revealed significant interactions between age subgroups and TyG-BMI index, as well as METS-IR, and between sex subgroups and TyG index. In elderly patients, per 1.0-SD increment in TyG-BMI index and METS-IR had a significant association with MACCEs, with odds ratios (ORs) [95% confidence interval (CI)] of 1.24 (1.02–1.50) and 1.27 (1.04–1.56), respectively (both P < 0.05). Moreover, in female patients, all the IR indices showed significant associations with MACCEs. Multivariable-adjusted RCS curves demonstrated a linear relationship between METS-IR and MACCEs in elderly and female patients, respectively. However, all the IR indices failed to enhance the predictive performance of the basic risk model for MACCEs.

Conclusion

All the four IR indices showed a significant association with MACCEs in female individuals, whereas only TyG-BMI index and METS-IR showed associations in elderly patients. Although the inclusion of these IR indices did not improve the predictive power of basic risk model in either female or elderly patients, METS-IR appears to be the most promising index for secondary prevention of MACCEs and risk stratification in patients undergoing PCI.
Pilot-scale bioethanol production from the starch of avocado seeds using a combination of dilute acid-based hydrolysis and alcoholic fermentation by Saccharomyces cerevisiae
Authors: Caballero-Sanchez Luis , Lázaro-Mixteco Pedro E. , Vargas-Tah Alejandra , Castro-Montoya Agustín J.
Published: June 2023

Background

A processing methodology of raw starch extraction from avocado seeds (ASs) and a sequential hydrolysis and fermentation bioprocess in just a few steps was successfully obtained for the bioethanol production by a single yeast Saccharomyces cerevisiae strain and this research was also to investigate the optimum conditions for the pretreatment of biomass and technical procedures for the production of bioethanol. It successfully resulted in high yields and productivity of all the experiments from the laboratory scale and the pilot plant. Ethanol yields from pretreated starch are comparable with those in commercial industries that use molasses and hydrolyzed starch as raw materials.

Results

Before the pilot-scale bioethanol production, studies of starch extraction and dilute sulfuric acid-based pretreatment was carefully conducted. The amount of starch extracted from dry and fresh avocado seed was 16.85 g ± 0.34 g and 29.79 ± 3.18 g of dry starch, representing a yield of ∼17% and 30%, respectively. After a dilute sulfuric acid pretreatment of starch, the released reducing sugars (RRS) were obtained and the hydrolysate slurries containing glucose (109.79 ± 1.14 g/L), xylose (0.99 ± 0.06 g/L), and arabinose (0.38 ± 0.01 g/L). The efficiency of total sugar conversion was 73.40%, with a productivity of 9.26 g/L/h. The ethanol fermentation in a 125 mL flask fermenter showed that Saccharomyces cerevisiae (Fali, active dry yeast) produced the maximum ethanol concentration, pmax at 49.05 g/L (6.22% v/v) with a yield coefficient, Yp/s of 0.44 gEthanol/gGlucose, a productivity or production rate, rp at 2.01 g/L/h and an efficiency, Ef of 85.37%. The pilot scale experiments of the ethanol fermentation using the 40-L fermenter were also successfully achieved with essentially good results. The values of pmax,Yp/s, rp, and Ef of the 40-L scale were at 50.94 g/L (6.46% v/v), 0.45 gEthanol/gGlucose, 2.11 g/L/h, and 88.74%, respectively. Because of using raw starch, major by-products, i.e., acetic acid in the two scales were very low, in ranges of 0.88–2.45 g/L, and lactic acid was not produced, which are less than those values in the industries.

Conclusions

The sequential hydrolysis and fermentation process of two scales for ethanol production using the combination of hydrolysis by utilizing dilute sulfuric acid-based pretreatment and fermentation by a single yeast Saccharomyces cerevisiae strain is practicable and feasible for realistic and effective scale-up strategies of bioethanol production from the starch of avocado seeds.
Effect measure modification of the association between short-term exposures to PM2.5 and hospitalizations by long-term PM2.5 exposure among a cohort of people with Chronic Obstructive Pulmonary Disease (COPD) in North Carolina, 2002–2015
Authors: Cowan Kristen N. , Wyatt Lauren H. , Luben Thomas J. , Sacks Jason D. , Ward-Caviness Cavin , Rappazzo Kristen M.
Published: June 2023

Background

Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD.

Methods

In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004–2016 (n = 520), and estimated ambient PM2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0–2 and 0–3 day lags of PM2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5 concentration at the median value.

Results

We observed generally null or low-magnitude negative associations with short-term PM2.5 exposure and respiratory-related (OR per 5 µg/m3 increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039)).

Concluisons

Differences in associations demonstrate that people in areas with higher annual PM2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5 exposure.
Community-based respondent-driven sampling as a strategy for drug use surveillance in a large French urban area
Authors: Donnadieu Hélène , Quillet Catherine , D’Ottavi Morgana , Castellani Joëlle , Debellefontaine Anne , Guichard Sylvain , Baglioni René , Langendorfer Nicolas , Faucherre Vincent , Hanslik Bertrand , Tuaillon Edouard , Laureillard Didier , Nagot Nicolas
Published: June 2023

Background

Understanding drug use and behavior within the PWUD population is crucial to adapt harm reduction and prevention strategies, and provide improved addiction and medical treatment. However, in most countries such as France, the knowledge of drug use behaviors is likely biased as it originates from addiction centers which are attended by only an unknown proportion of PWUD. The objectives of this study were to describe drug use behavior in a population of active PWUD in the urban area of Montpellier, South of France.

Methods

We implemented a community-based respondent-driven sampling survey (RDSS), a validated strategy to obtain a representative sample of a population, to recruit PWUD in the city. Adult individuals reporting frequent psychoactive drug use other than cannabis, with confirmation by urine test, were eligible. Beside HCV and HIV testing, trained peers interviewed participants on their drug consumption and behavior using standardized questionnaires. Fifteen seeds launched the RDSS.

Results

During the 11 weeks of the RDSS, 554 actives PWUD were consecutively included. They were mostly men (78.8%), had a median age of 39 years, and only 25.6% had a stable living place. On average, participants consumed 4.7 (± 3.1) different drugs, and 42.6% smoked free-base cocaine. Unexpectedly, heroin and methamphetamine were consumed by 46.8% and 21.5% of participants, respectively. Among the 194 participants injecting drugs, 33% declared sharing their equipment.

Conclusion

This RDSS highlighted a high consumption of heroin, crack and methamphetamine in this PWUD population. These unexpected results can be explained by low attendance to addiction centers, the source of drug use reports. Despite free care and risk reduction equipment in the city, sharing was very frequent among injectors, challenging the current program of harm reduction.
A rapid assay for assessing bacterial effects on Arabidopsis thermotolerance
Authors: Lee Jun Hyung , Burdick Leah H. , Piatkowski Bryan , Carrell Alyssa A. , Doktycz Mitchel J. , Pelletier Dale A. , Weston David J.
Published: June 2023

Background

The role of beneficial microbes in mitigating plant abiotic stress has received considerable attention. However, the lack of a reproducible and relatively high-throughput screen for microbial contributions to plant thermotolerance has greatly limited progress in this area, this slows the discovery of novel beneficial isolates and the processes by which they operate.

Results

We designed a rapid phenotyping method to assess the effects of bacteria on plant host thermotolerance. After testing multiple growth conditions, a hydroponic system was selected and used to optimize an Arabidopsis heat shock regime and phenotypic evaluation. Arabidopsis seedlings germinated on a PTFE mesh disc were floated onto a 6-well plate containing liquid MS media, then subjected to heat shock at 45 °C for various duration. To characterize phenotype, plants were harvested after four days of recovery to measure chlorophyll content. The method was extended to include bacterial isolates and to quantify bacterial contributions to host plant thermotolerance. As an exemplar, the method was used to screen 25 strains of the plant growth promoting Variovorax spp. for enhanced plant thermotolerance. A follow-up study demonstrated the reproducibility of this assay and led to the discovery of a novel beneficial interaction.

Conclusions

This method enables rapid screening of individual bacterial strains for beneficial effects on host plant thermotolerance. The throughput and reproducibility of the system is ideal for testing many genetic variants of Arabidopsis and bacterial strains.
Ideal entry point and direction of retrograde intramedullary nailing of the tibia
Authors: He Min , Jiang Ziyu , Tan Wenfu , Li Zhengmao , Peng Bin
Published: June 2023

Purpose

To determine the ideal entry point and direction of retrograde intramedullary nailing of the tibia.

Methods

The imaging data of patients with distal tibial fractures from June 2020 to December 2021 in our hospital were collected, and computer-aided design was performed. The relevant data were imported into the software for processing, so as to obtain a distal tibial fracture model and simulate the retrograde intramedullary nail placement in the tibia. The entry points and angles at which the intramedullary nail could be inserted successfully and the fracture could be maintained in good alignment were overlapped and counted to obtain the safe entry range and angle. The center of this safe range is the ideal entry point for retrograde intramedullary nailing of the tibia, and the mean value of the angle is the ideal direction of entry.

Results

The ideal entry point of the retrograde intramedullary nailing was located at the midpoint of the medial malleolus in the C-arm fluoroscopic anteroposterior (AP) and lateral view. The ideal nail entry direction was located at the anatomic axis of the medial malleolus in the AP position and at the anatomic axis of the distal tibial metaphysis in the lateral position.

Conclusion

The ideal point and direction of nail insertion for retrograde tibial intramedullary nailing is a "double midpoint, double axis" approach.
Preoperative simulated surgery on 3D model assists osteotomy feasibility verification and surgical guidance for patients with cubitus valgus/varus deformity: a retrospective observational study
Authors: Xue Kai-Xiao , Zheng Xing-Guo , Qiao Chang , Fang Jia-Hu
Published: June 2023

Background

As the common delayed complication of supracondylar fractures in children, cubitus valgus/varus deformity might lead to pain and loss of motion of the elbow. The current corrective treatment might not be accurate enough and even contribute to postoperative deformity. This study retrospectively analyzed the clinical value of preoperative simulated surgery on 3D model-assisted osteotomy feasibility verification and surgical guidance for cubitus valgus/varus deformity.

Methods

Seventeen patients were selected from January 2017 and November 2019. Deformities were analyzed from imaging data and 3D models and corrected after the simulated operations. The radiographic evaluation comprised osseous union, carrying angle, and anteversion angle of the distal humerus. The clinical evaluation was performed according to the Hospital for Special Surgery (HSS) scoring system.

Results

All patients underwent the operation successfully and had no postoperative deformity. The carrying angle was significantly improved postoperatively (P < 0.001). The anteversion angle of the distal humerus did not change significantly (P > 0.05). The HSS score rose after surgery (P < 0.001). The function of the elbow joint was excellent in seven cases and good in ten cases.

Conclusion

Simulated surgery on 3D model plays an important role in osteotomy plan and surgical guidance, contributing to good surgical efficacy.