bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis
Authors: Lu Qing-Bo , Fu Xiao , Liu Yao , Wang Zi-Chao , Liu Shi-Yi , Li Yu-Chao , Sun Hai-Jian
Published: November 2023

Background

Periostin is an extracellular matrix protein that plays a critical role in cell fate determination and tissue remodeling, but the underlying role and mechanism of periostin in diabetic cardiomyopathy (DCM) are far from clear. Thus, we aimed to clarify the mechanistic participation of periostin in DCM.

Methods

The expression of periostin was examined in DCM patients, diabetic mice and high glucose (HG)-exposed cardiac fibroblasts (CF). Gain- and loss-of-function experiments assessed the potential role of periostin in DCM pathogenesis. RNA sequencing was used to investigate the underlying mechanisms of periostin in DCM.

Results

A mouse cytokine antibody array showed that the protein expression of periostin was most significantly upregulated in diabetic mouse heart, and this increase was also observed in patients with DCM or HG-incubated CF. Periostin-deficient mice were protected from diabetes-induced cardiac dysfunction and myocardial damage, while overexpression of periostin held the opposite effects. Hyperglycemia stimulated the expression of periostin in a TGF-β/Smad-dependent manner. RNA sequencing results showed that periostin upregulated the expression of nucleosome assembly protein 1-like 2 (NAP1L2) which recruited SIRT3 to deacetylate H3K27ac on the promoters of the branched-chain amino acid (BCAA) catabolism-related enzymes BCAT2 and PP2Cm, resulting in BCAA catabolism impairment. Additionally, CF-derived periostin induced hypertrophy, oxidative injury and inflammation in primary cardiomyocytes. Finally, we identified that glucosyringic acid (GA) specifically targeted and inhibited periostin to ameliorate DCM.

Conclusion

Overall, manipulating periostin expression may function as a promising strategy in the treatment of DCM.
A cell abundance analysis based on efficient PAM clustering for a better understanding of the dynamics of endometrial remodelling
Authors: Domingo Juan , Kutsyr-Kolesnyk Oleksandra , Leon Teresa , Perez-Moraga Raul , Ayala Guillermo , Roson Beatriz
Published: November 2023

Background

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for investigating cell abundance changes during tissue regeneration and remodeling processes. Differential cell abundance supports the initial clustering of all cells; then, the number of cells per cluster and sample are evaluated, and the dependence of these counts concerning the phenotypic covariates of the samples is studied. Analysis heavily depends on the clustering method. Partitioning Around Medoids (PAM or k-medoids) represents a well-established clustering procedure that leverages the downstream interpretation of clusters by pinpointing real individuals in the dataset as cluster centers (medoids) without reducing dimensions. Of note, PAM suffers from high computational costs and memory requirements.

Results

This paper proposes a method for differential abundance analysis using PAM as a clustering method and negative binomial regression as a statistical model to relate covariates to cluster/cell counts. We used this approach to study the differential cell abundance of human endometrial cell types throughout the natural secretory phase of the menstrual cycle. We developed a new R package-scellpam-, that incorporates an efficient parallel C++ implementation of PAM, and applied this package in this study. We compared the PAM-BS clustering method with other methods and evaluated both the computational aspects of its implementation and the quality of the classifications obtained using distinct published datasets with known subpopulations that demonstrate promising results.

Conclusions

The implementation of PAM-BS, included in thescellpampackage, exhibits robust performance in terms of speed and memory usage compared to other related methods. PAM allowed quick and robust clustering of sets of cells with a size ranging from 70,000 to 300,000 cells.https://cran.r-project.org/web/packages/scellpam/index.html. Finally, our approach provides important new insights into the transient subpopulations associated with the fertile time frame when applied to the study of changes in the human endometrium during the secretory phase of the menstrual cycle.
Cohort study investigating gout flares and management in UK general practice
Authors: Finnikin Samuel , Mallen Christian D. , Roddy Edward
Published: November 2023

Background

Gout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT.

Methods

Using the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression.

Results

Fifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5–36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1–17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03–5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3–28.0%): 5.7% (95%CI 5.5–5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares.

Conclusion

Approximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought.
The cross-sectional area of erector spinae muscle and the liver-to-spleen ratio are associated with frailty in older patients with diabetes: a cross-sectional study
Authors: Sato Motoya , Tamura Yoshiaki , Murao Yuji , Yorikawa Fumino , Katsumata Yuu , Watanabe So , Zen Shugo , Kodera Remi , Oba Kazuhito , Toyoshima Kenji , Chiba Yuko , Araki Atsushi
Published: November 2023

Background

Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported.

Methods

A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty.

Results

The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men.

Conclusions

The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.
Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents
Authors: Paniskaki Krystallenia , Goretzki Sarah , Anft Moritz , Konik Margarethe J. , Lechtenberg Klara , Vogl Melanie , Meister Toni L. , Pfaender Stephanie , Zettler Markus , Jäger Jasmin , Dolff Sebastian , Westhoff Timm H. , Rohn Hana , Felderhoff-Mueser Ursula , Stervbo Ulrik , Witzke Oliver , Dohna-schwake Christian , Babel Nina
Published: November 2023

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.
Factor structure and measurement invariance of the 8-item CES-D: a national longitudinal sample of Chinese adolescents
Authors: Liu Shuxia , Fang Yuan , Su Zhongyan , Cai Jimin , Chen Zhiyan
Published: November 2023

Background

The 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents.

Methods

The data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale.

Results

A two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance.

Conclusions

The factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.
Asthma and COPD as co-morbidities in patients hospitalised with Covid-19 disease: a global systematic review and meta-analysis
Authors: Finnerty James Patrick , Hussain A. B. M. Arad , Ponnuswamy Aravind , Kamil Hafiz Gulzeb , Abdelaziz Ammar
Published: November 2023

Background

Factors predisposing to increased mortality with COVID-19 infection have been identified as male sex, hypertension, obesity, and increasing age. Early studies looking at airway diseases gave some contradictory results. The purpose of our study was to determine global variation in studies in patients hospitalized with COVID-19 in the prevalence of COPD and asthma; and to determine whether the presence of asthma or COPD affected mortality in the same hospital population.

Methods

A systematic review and meta-analysis of the published literature of COPD and asthma as co-morbidities in patients hospitalized with COVID-19 was performed, looking firstly at the prevalence of these diseases in patients hospitalized with COVID-19, and secondly at the relative risk of death from any cause for patients with asthma or COPD.

Results

Prevalence of both airway diseases varied markedly by region, making meaningful pooled global estimates of prevalence invalid and not of clinical utility. For individual studies, the interquartile range for asthma prevalence was 4.21 to 12.39%, and for COPD, 3.82 to 11.85%. The relative risk of death with COPD for patients hospitalized with COVID-19 was 1.863 (95% CI 1.640–2.115), while the risk with asthma was 0.918 (95% CI 0.767 to 1.098) with no evidence of increased mortality.

Conclusions

For asthma and COPD, prevalence in patients hospitalized with COVID-19 varies markedly by region. We found no evidence that asthma predisposed to increased mortality in COVID-19 disease. For COPD, there was clear evidence of an association with increased mortality.

Trial registration

The trial was registered with PROSPERO: registration number CRD42021289886.
Tea consumption and risk of lung diseases: a two‑sample Mendelian randomization study
Authors: Chen Linjie , Deng Yaru , Wang Tiexu , Lin Xinyu , Zheng Lukun , Chen Xiaohong , Chen Tongsheng
Published: November 2023

Background

Numerous studies have reported the association between tea intake and lung diseases. However, the probable relationship between tea consumption on lung diseases still remain controversial and it is unclear whether these findings are due to reverse causality or confounding factor.

Methods

In order to systematically investigate the causal connection between tea intake on respiratory system disorders, we employed a two-sample Mendelian randomized (MR) study. Genetic instruments for tea intake were identified from a genome-wide association study (GWAS) involving 447,385 individuals. Data on lung diseases were collected from a variety of publicly available genome-wide association studies. The main method used for MR analysis is the inverse variance weighting (IVW) method. To ensure the accuracy of the findings, further sensitivity analysis was conducted.

Results

The IVW method in our MR analysis revealed no evidence to support a causal relationship between tea intake and lung diseases (IPF: OR = 0.997, 95% CI = 0.994-1.000, p = 0.065; Lung cancer: OR = 1.003, 95% CI = 0.998–1.008, P = 0.261; COPD: OR = 1.001, 95% CI = 0.993–1.006, p = 0.552; acute bronchitis: OR = 0.919, 95% CI = 0.536–1.576, p = 0.759; tuberculosis: OR = 1.002, 95% CI = 0.998–1.008, p = 0.301; pneumonia: OR = 0.789, 95% CI = 0.583–1.068, p = 0.125). The reliability of the results was further demonstrated by four additional MR analysis techniques and additional sensitivity testing.

Conclusion

We found no evidence of a link between tea intake on lung diseases in our MR results based on genetic information.
Laboratory and clinical findings in mouse models of diabetic nephropathy induced with streptozotocin
Authors: Wahono Aditya Mahardika , Harnanik Titut , Pasaribu Irma A. , Adiwinoto Ronald Pratama , Octavianda Yohana
Published: November 2023

Background

Diabetic nephropathy (DN) represents a microvascular complication of diabetes mellitus (DM). Despite the increasing incidence and prevalence of DN, conservative therapy only reduces risk factors and hemodialysis. This research aimed at finding DN animal model that can be tried to be given an alternative treatment. DN was assessed by evaluating body weight, blood glucose, proteinuria, and kidney histopathology.

Methods

Wistar novergicus male rats were induced with 75 mg of streptozotocin per kg BW to obtain a diabetic nephropathy model. The 18 rats were divided into 2 groups consisting of 9 rats in the negative group (G0) and 9 rats in the positive group (G1). Indicators of body weight, blood glucose levels, urine protein and kidney histopathology determine the incidents of DN animal models.

Result

Rats induced using 75 mg of streptozotocin per kg body weight (BW) indicated weight loss, increased blood glucose, urine protein levels and histopathological features of DN.

Conclusion

Seventy-five mg of streptozotocin per kg BW can induce a diabetic nephropathy animal model in Wistar norvegicus rats.
Innovations in online classes introduced during the COVID-19 pandemic and their educational outcomes in Japan
Authors: Yamamoto Kyoko , Akiyoshi Kumiko , Kondo Hidekazu , Akioka Hidefumi , Teshima Yasushi , Yufu Kunio , Takahashi Naohiko , Nakagawa Mikiko
Published: November 2023

Background

The novel coronavirus disease (COVID-19) pandemic emerged in Japan in February 2020, forcing the adoption of online education by university medical schools across Japan. The advantages and disadvantages of online education have been studied in Japan; however, the educational outcome of online classes conducted during the COVID-19 pandemic has not been completely evaluated. In this study, we examined the relationship between lecture format (e.g., face-to-face or online) and performance of third-year university students in their organ-specific cardiovascular course examination.

Methods

This retrospective, nonclinical, and noninterventional comparative educational study included 550 third-year medical students who took a cardiovascular course between April 2018 and May 2022. Cardiovascular coursework was conducted in-person in 2018 and 2019, online in 2020 and 2021, and again in-person in 2022. The course comprised 62 lecture and 2 problem-based learning (PBL) sessions. A quiz was set up in advance on Moodle based on all lectures conducted in 2021 and 2022. A written examination was administered at the end of the course to evaluate the knowledge of students. The student online course evaluation questionnaires were administered in 2020 and 2021. Examination scores and proportion of failures in each year were compared.

Results

The mean examination scores were significantly higher in 2021 and 2022 than in 2018, 2019, and 2020 (p < 0.05). Univariate and multivariate analyses adjusted for the class type, online quiz, and PBL revealed that only online quiz was significantly associated with better examination results (p < 0.05). A student course evaluation survey indicated that the online format did not interfere with the students’ learning and was beneficial.

Conclusions

The introduction of online classes into medical education due to the COVID-19 pandemic was as effective as face-to-face classes owing to learning management system and other innovations, such as online quizzes. Online education may confer more benefits when provided in a combination with face-to-face learning after COVID-19 pandemic.
Mushroom consumption and hyperuricemia: results from the National Institute for Longevity Sciences-Longitudinal Study of Aging and the National Health and Nutrition Examination Survey (2007-2018)
Authors: Ba Djibril M. , Zhang Shu , Nishita Yukiko , Tange Chikako , Qiu Tian , Gao Xiang , Muscat Joshua , Otsuka Rei
Published: November 2023

Background

Prior study reported that mushroom consumption was associated with a lower incidence of hyperuricemia, but there is limited evidence on this association. We conducted a collaborative study to investigate the association between mushroom intake and hyperuricemia in middle-aged and older populations.

Methods

We used data from the National Health and Nutrition Examination Survey (NHANES) in the U.S. (2007–2018) and the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan (1997–2012). Consumption of mushroom (g/day) were measured by one- or two-day dietary recall in NHANES and by 3-day dietary records in the NILS-LSA. Hyperuricemia was defined using uric acid levels as > 420 μmol/L and > 350 μmol/L in NHANES for men and women, respectively; in the NILS-LSA, serum uric acid was repeatedly measured at baseline and follow-up surveys. Hyperuricemia was defined as uric acid levels > 416.4 μmol/L for men and ≥ 356.9 μmol/L for women. Logistic regression models in NHANES (cross-sectionally) and Generalized Estimation Equations in NILS-LSA (longitudinally) were performed.

Results

A total of 5,778 NHANES participants (mean (SD) age: 53.2 (9.6) years) and 1,738 NILS-LSA (mean (SD) age: 53.5 (11.2) years) were included. Mushrooms were consumed by 5.7% of participants in NHANES and 81.2% in NILS-LSA. We did not observe a significant association between mushroom intakes and hyperuricemia in the NHANES men and women. However, in the NILS-LSA, compared to non-consumers, a higher mushroom intake was associated with a lower risk of incident hyperuricemia in men under 65 years old. The adjusted odds ratio (95% CI) for non-consumers, participants with middle, and the highest consumption of mushrooms were 1.00 (Ref.), 0.77 (0.44, 1.36), and 0.55 (0.31, 0.99), respectively (P-trend = 0.036). No association was found in women in NILS-LSA.

Conclusions

Mushroom consumption was associated with a lower risk of incident hyperuricemia in Japanese men.
The effect of clinical guidelines on the utilisation of radiographs in chiropractic clinics in Denmark - an interrupted time series analysis
Authors: Reibke Pernille Schaldemose , Godskesen Henriette , Jensen Rikke Krüger , French Simon D , Bussières André , Christensen Henrik Wulff , Jensen Tue Secher
Published: November 2023

Background

In Denmark, chiropractors have a statutory right to use radiography and the government-funded national Health Insurance provides partial reimbursement. Danish National Clinical Guidelines recommends against routine use of imaging for uncomplicated spinal pain; however, it is not clear if clinical imaging guidelines recommendations have had an effect on the utilisation of spinal radiography. This study aimed to describe the utilisation rate of radiographs in Danish chiropractic clinics in the period from 2010 to 2020 and to assess the impact of clinical guidelines and policy changes on the utilisation of radiographs in Danish chiropractic clinics.

Methods

Anonymised data from January 1st, 2010, to December 31st, 2020, were extracted from the Danish Regions register on health contacts in primary care. Data consisted of the total number of patients consulting one of 254 chiropractic clinics and the total number of patients having or being referred for radiography. Data were used to investigate the radiography utilisation per month from 2010 to 2020. An ‘interrupted time series’ analysis was conducted to determine if two interventions, the dissemination of 1) Danish clinical imaging guidelines recommendations and policy changes related to referral for advanced imaging for chiropractors in 2013 and 2) four Danish clinical guidelines recommendations in 2016, were associated with an immediate change in the level and/or slope of radiography utilisation.

Results

In total, 336,128 unique patients consulted a chiropractor in 2010 of which 55,449 (15.4%) had radiography. In 2020, the number of patients consulting a chiropractor had increased to 366,732 of which 29,244 (8.0%) had radiography. The pre-intervention utilisation decreased by two radiographs per 10,000 patients per month. Little absolute change, but still statistically significant for Intervention 1, in the utilisation was found after the dissemination of the clinical guidelines and policy changes in 2013 or 2016.

Conclusions

The proportion of Danish chiropractic patients undergoing radiography was halved in the period from 2010 to 2020. However, the dissemination of clinical imaging guidelines recommendations and policy changes related to referrals for advanced imaging showed little meaningful change in the monthly utilisation of radiographs in the same period.
Exosomal miR-331-3p derived from chemoresistant osteosarcoma cells induces chemoresistance through autophagy
Authors: Meng Chenyang , Yang Yun , Feng Wei , Ma Penglei , Bai Rui
Published: November 2023

Background

Osteosarcoma is a common malignant bone tumor, and chemotherapy can effectively improve the prognosis. MicroRNA-331 (MiR-331) is associated with poor cancer outcomes. However, the role of miR-331 in osteosarcoma remains to be explored.

Methods

Drug-resistant osteosarcoma cells were cultured, and their exosomes were purified. The secretion and uptake of exosomes by drug-resistant osteosarcoma and osteosarcoma cells were confirmed using a fluorescence tracking assay and Transwell experiments. The effects of drug-resistant exosomes on cell proliferation were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. siRNA-Drosha and neutral sphingomyelinase inhibitor GW4869 were used to determine the transfer of miRNAs. qRT-PCR and western blotting were used to detect the role of autophagy in the regulation of drug-resistant cell-derived exosomal miR-331-3p.

Results

Exosomal miR-331-3p levels in drug-resistant cells were higher than in exosomes from osteosarcoma cells. The exosomes secreted by the drug-resistant osteosarcoma cells could be absorbed by osteosarcoma cells, leading to acquired drug resistance in previously non-resistance cells. Inhibition of miRNAs resulted in reduced transmission of drug resistance transmission by exosomes. Exosomes from drug-resistant osteosarcoma cells transfected with siRNA-Drosha or treated by GW4869 could not enhance the proliferation of MG63 and HOS cells. Finally, miR-331-3p in the exosomes secreted by drug-resistant osteosarcoma cells could induce autophagy of osteosarcoma cells, allowing them to acquire drug resistance. The inhibition of miR-331-3p decreased drug resistance of osteosarcoma cells.

Conclusion

Exosomes secreted from chemoresistant osteosarcoma cells promote drug resistance through miR-331-3p and autophagy. Inhibition of miR-331-3p could be used to alleviate drug resistance in osteosarcoma.
Docking site complications analysis of Ilizarov bone transport technique in the treatment of tibial bone defects
Authors: Feng Dongwei , Zhang Yaxin , Wu Weize , Jia Heping , Ma Chuang
Published: November 2023

Background

Treating long bone defects of the extremities caused by trauma, infection, tumours, and nonunion has been challenging for clinical orthopaedic surgeons. Bone transport techniques have the potential to treat bone defects. However, inevitable docking site complications related to bone transport techniques have been reported in many studies. The purpose of this study was to investigate the risk factors associated with docking site complications in patients who underwent the Ilizarov bone transport technique for the treatment of tibial bone defects.

Methods

This retrospective study included 103 patients who underwent bone transport for the treatment of large bone defects in the tibia from October 2012 to October 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, univariate analysis and logistic regression analysis were used to analyse the factors that may affect the development of docking site complications in patients with tibial bone defects treated with the Ilizarov bone transport technique. The clinical outcomes were evaluated using the Association for the Study and Application of the Ilizarov criteria (ASAMI) at the last clinical follow-up.

Results

All 103 patients with an average follow-up of 27.5 months. The docking site complications rate per patient was 0.53, and delayed union occurred in 22 cases (21.4%), axial deviation occurred in 19 cases (18.4%) and soft tissue incarceration occurred in 10 cases (9.7%). According to the results of the logistic regression analysis, the bone defect length (P = 0.001, OR = 1.976), and bone defect of distal 1/3 (P = 0.01, OR = 1.976) were significantly correlated with delayed union. Bone defect length (P < 0.001, OR = 1.981) and external fixation time (P = 0.012, OR = 1.017) were significantly correlated with axial deviation. Soft tissue defects (P = 0.047, OR = 6.766) and the number of previous operations (P = 0.001, OR = 2.920) were significantly correlated with soft tissue incarceration. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.1% and a rate of excellent functional results of 90.3%.

Conclusion

The Ilizarov bone transport technique is a practical and effective method for the treatment of tibial bone defects. However, the incidence of complications at the docking site is high, of which bone defect length, external fixation time, the number of previous operations, soft tissue defects and the bone defect of distal 1/3 are statistically significantly associated with the occurrence of docking site complications.
Implantation of ascyrus medical dissection stent, our first-hand experience
Authors: Kanj Mouhammad , Cosset Benoit , Oliny Alexandre , Farhat Fadi
Published: November 2023

Background

Acute type A aortic dissection is associated with high perioperative morbidity and mortality. Ascyrus Medical Dissection Stent (Cryolife, Kennesaw, USA) is a novel uncovered hybrid stent graft developed to be used as an adjunct to standard surgical approach to promote true lumen expansion and enhance aortic remodeling.

Methods

From March 2021 to March 2022, four consecutive patients presented with acute Debakey type I aortic dissection and underwent emergent surgical repair with Tirone David procedure and implantation of Ascyrus Medical Dissection Stent. We reviewed patient’s files retrospectively and described the perioperative outcomes.

Results

All four device implantations were successful. Overall 30-day mortality was 0%. Malperfusion that was present in two patients pre-operatively improved after Ascyrus Medical Dissection Stent implantation. No aortic reinterventions were needed. No aortic injury related to the device was noted. Favourable changes in aortic true lumen and false lumen dimensions were found in most of our patients but the stent was compressed at the isthmus in one patient.

Conclusion

Ascyrus Medical Dissection Stent is a reliable and secure device. However, its benefits remain unclear when it comes to a positive remodeling and seems less likelihood comparable to a frozen elephant trunk. The main reason seems to be an insufficient radial force of the stent.
Radical mediastinal lipectomy for tamponade-like cardiac physiology
Authors: Malik Mohsyn Imran , Jae James Changhyun , Sefein Osama Sedky Shehata , Zamper Raffael Pereira Cezar , Nagpal A. Dave
Published: November 2023

Background

Re-opening the chest is an unwanted and potentially morbid complication after open heart surgery, most commonly required for refractory bleeding or tamponade. In this report, we present a unique case of a postoperative coronary artery bypass patient, demonstrating clinical features of cardiac tamponade of the right atrium and ventricle with inconclusive findings on imaging.

Case presentation

A 62 year-old male presented to hospital with exertional angina and a coronary angiogram found severe three-vessel coronary artery disease with preserved left ventricular function. He underwent an uncomplicated triple coronary artery bypass surgery. Over the following hours in the cardiac intensive care unit, the patient had a climbing serum lactate level and increasing vasopressor requirements. On investigations, there was evidence of compression of the right heart. The patient was taken back to the operating room where very little clot or bleeding was identified, rather there was significant amounts of mediastinal fat surrounding the heart which was subsequently resected with wide margins. The patient had complete resolution of their symptoms and an uncomplicated postoperative course thereafter.

Conclusions

To our knowledge, this case is the first reported occurrence of cardiac constriction from excessive mediastinal fat after open heart surgery. Identifying patients at high-risk for excessive pericardial fat, as well as considering alternative modalities of imaging appear to be the main stay in diagnosis at this point. Current treatment is a mediastinal lipectomy with wide margins, avoiding injury to surrounding structures such as the phrenic nerve and innominate vein. Future study might consider the value of prophylactic mediastinal lipectomy at time of surgery, and methods to improve detection with current and future imaging modalities.
Total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert II AEG
Authors: Yin Qifan , Zhang Guibin , Qie Peng , Han Shaohui , Liu Lijun
Published: November 2023

Purpose

The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG.

Method

Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation.

Result

A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196–347 min); The median surgical blood loss was 250 ml (20–2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17–36); The median duration of drainage tube was 5 days (3–7days); The median length of stay in ICU was 18 h(10–34 h); The median time of resume oral feeding was 6 days (5–7days); The median postoperative hospital stay was 11 days (8–15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4–8.5 cm) from the upper margin of the tumor to the resection margin.

Conclusion

The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.
Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma
Authors: Zhou Lingyun , He Linye , Liu Chang-Hai , Qiu Huandi , Zheng Li , Sample Klarke Michael , Wu Qin , Li Jiaxin , Xie Kunlin , Ampuero Javier , Li Zhihui , Lv Duoduo , Liu Miao , Romero-Gómez Manuel , Hu Yiguo , Tang Hong
Published: November 2023

Background

Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims to reveal the contributions of NRCAM to LCSC function and HCC metastasis, and further explore its mechanism in detail.

Methods

117 HCC and 29 non-HCC patients with focal liver lesions were collected and analyzed to assess the association between NRCAM and HCC metastasis. Single-cell RNA sequencing (scRNA-seq) was used to explore the biological characteristics of cells with high NRCAM expression in metastatic HCC. The role and mechanism of NRCAM in LCSC dissemination and metastasis was explored in vitro and in vivo using MYC-driven LCSC organoids from murine liver cells.

Results

Serum NRCAM is associated with HCC metastasis and poor prognosis. A scRNA-seq analysis identified that NRCAM was highly expressed in LCSCs with MYC activation in metastatic HCC. Moreover, NRCAM facilitated LCSC migration and invasion, which was confirmed in MYC-driven LCSC organoids. The in vivo tumor allografts demonstrated that NRCAM mediated intra-hepatic/lung HCC metastasis by enhancing the ability of LCSCs to escape from tumors into the bloodstream. Nrcam expression inhibition in LCSCs blocked HCC metastasis. Mechanistically, NRCAM activated epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) through the MACF1 mediated β-catenin signaling pathway in LCSCs.

Conclusions

LCSCs typified by high NRCAM expression have a strong ability to invade and migrate, which is an important factor leading to HCC metastasis.
CRISPR/Cas9: a powerful tool in colorectal cancer research
Authors: Hu Yang , Liu Liang , Jiang Qi , Fang Weiping , Chen Yazhu , Hong Yuntian , Zhai Xiang
Published: November 2023

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.
The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome
Authors: Amin Mutaz , Gragnoli Claudia
Published: November 2023

The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results.
Cut-off point of mature oocyte for routine clinical application of rescue IVM: a retrospective cohort study
Authors: Wei Jianbo , Luo Zhongyu , Dong Xiyuan , Jin Huizi , Zhu Lixia , Ai Jihui
Published: November 2023

Background

The rescue in vitro mature(Rescue IVM) technique allows the use of immature oocytes collected in conventional COH to obtain more mature oocytes for fertilization through in vitro maturation. Some studies have shown that Rescue IVM could improve clinical outcomes in patients undergoing IVF/ICSI, but the effectiveness and the indications for the clinical application of this technique remain controversial. It remains to be studied whether Rescue IVM should be universally applied in all conventional IVF/ICSI cycles.

Method

This is a large retrospective cohort study that included a total of 22,135 female patients undergoing their first IVF treatment cycles. The effect of the number of mature oocytes(metaphaseII[MII]) on the cumulative live birth rate was investigated in a population with routine IVF/ICSI first. The receiver operating characteristic curve(ROC) analysis was used to explore the cut-off point of the number of MII affecting CLBR. Secondly, Patients undergoing ICSI with Rescue IVM were included in the analysis with those who underwent ICSI only during the same period, grouped according to the MII cut-off values. Multi-factor binary logistic regression and inverse probability weighting (IPW) were used to investigate whether Rescue IVM influenced the final cumulative live birth rate(CLBR).

Results

The CLBR increased with the number of MIIoocytes (P < 0.001). The ROC analysis showed the cut-off point for the number of MIIoocytes to have a significant effect on CLBR was 9 (sensitivity 0.715, specificity 0.656). Furthermore, 912 patients who underwent ICSI with Rescue IVM were included and compared to those who underwent ICSI only during the same period, and found Rescue IVM significantly increased the number of available MIIoocytes. For patients with MII numbers < 9, Rescue IVM significantly improves their clinical pregnancy rate(55.6% vs. 46.7%, P = 0.001) and CLBR(65.4% vs. 48.1%, P < 0.001), but not for those patients with MII numbers ≥ 9.

Conclusion

This study further clarifies the candidates for the application of Rescue IVM technique: patients with an MII oocytes < 9 in a conventional IVF/ICSI cycle. In contrast, it is not necessary for patients who already have sufficient mature oocytes(≥ 9), to avoid over-medication.
Larval diet and temperature alter mosquito immunity and development: using body size and developmental traits to track carry-over effects on longevity
Authors: Mackay Andrew J. , Yan Jiayue , Kim Chang-Hyun , Barreaux Antoine M. G. , Stone Chris M.
Published: November 2023

Background

Estimating arbovirus transmission potential requires a mechanistic understanding of how environmental factors influence the expression of adult mosquito traits. While preimaginal exposure to environmental factors can have profound effects on adult traits, tracking and predicting these effects remains challenging.

Methods

UsingAedes albopictusand a structural equation modeling approach, we explored how larval nutrition and temperature jointly affect development rate and success, female body size, and whether these metrics capture carry-over effects on adult female longevity. Additionally, we investigated how larval diet and temperature affect the baseline expression of 10 immune genes.

Results

We found that larval development success was primarily determined by diet, while temperature and diet both affected development rate and female body size. Under a low larval diet, pupal wet weight and wing length both declined with increasing temperature. In contrast, responses of the two morphometric measures to rearing temperature diverged when females were provided higher larval nutrition, with pupal wet weight increasing and wing length decreasing at higher temperatures. Our analyses also revealed opposing relationships between adult female lifespan and the two morphometric measures, with wing length having a positive association with longevity and pupal weight a negative association. Larval diet indirectly affected adult longevity, and the time to pupation was negatively correlated with longevity. The expression of eight immune genes from the toll, JAK-STAT and Imd pathways was enhanced in mosquitoes with higher nutrition.

Conclusions

Our results highlight deficiencies from using a single body size measure to capture carry-over effects on adult traits. Further studies of larval development rate under varying environmental conditions and its potential for tracking carry-over effects on vectorial capacity are warranted.

Graphical Abstract
The speed-gene study: methods, study design and preliminary results
Authors: Htet Swam , Zannah Miftahul , Moe Thet Hnin , Wongveerakul Pongpanot , Charoenpanich Nongnapas , Saengsirisuwan Vitoon , Papadimitriou Ioannis
Published: November 2023

The Speed-Gene study aims to identify genetic variants influencing athletic performance and human locomotion using motion capture technology. Currently, 60 female participants have completed the testing protocol, and the overall aim is to recruit 283 moderately trained, healthy Southeast Asian individuals (18–45 y, BMI < 30). Participants will undergo biomechanical analysis and genetic testing. Several analyses will be performed, including (but not limited to) linear and angular kinematic analysis using motion capture technology, force plate dynamometry and genetic analyses to define novel power/torque related outcomes that would be more sensitive to allele-specific differences in athletic performance. Pretesting beverages will be provided, and activity history and current activity levels will be assessed by a questionnaire. The kinematic data will be obtained using a Qualisys Track Manager (QTM) system, and DNA will be extracted from white blood cells. The participants serve as their own controls. Although the Speed-Gene study is tightly controlled, our preliminary findings still indicate considerable individual variability. More participants and further genetic analysis are required to allow the investigation of potential underlying genetic mechanisms responsible for this individual variability.