bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric tuberculosis outcomes and factors associated with unfavorable treatment outcomes in Botswana, 2008–2019: a retrospective analysis
Authors: Siamisang Keatlaretse , Rankgoane-Pono Goabaone , Madisa Tumisang Malebo , Mudiayi Tantamika Kabamba , Tlhakanelo John Thato , Mubiri Paul , Kadimo Khutsafalo , Banda Francis Msume , Setlhare Vincent
Published: November 2022

Introduction

Globally, the amount of research on the outcomes of pediatric tuberculosis (TB) is disproportionately less than that of adult TB. The diagnosis of paediatric TB is also problematic in developing countries. The aim of this study was to describe the outcomes of pediatric TB in Botswana and to identify the factors associated with unfavorable outcomes.

Methods

This was a retrospective analysis of pediatric TB outcomes in Botswana, over a 12-year period from January 2008 to December 2019. Treatment success (treatment completion or cured) was considered a favorable outcome, while death, loss to follow-up and treatment failure were considered unfavorable outcomes. Program data from drug-sensitive TB (DS-TB) cases under the age of 15 years were included. Sampling was exhaustive. Binary logistic regression was used to determine the factors associated with unfavorable outcomes during TB treatment. A p value of < 0.05 was considered a statistically significant association between the predictor variables and unfavorable outcomes.

Results

The data of 6,004 paediatric TB cases were extracted from the Botswana National TB Program (BNTP) electronic registry and analyzed. Of these data, 2,948 (49.4%) were of female patients. Of the extracted data, 1,366 (22.8%) were of HIV positive patients and 2,966 (49.4%) were of HIV negative patients. The rest of the data were of patients with unknown HIV status. Pulmonary TB accounted for 4,701 (78.3%) of the cases. Overall, 5,591 (93.1%) of the paediatric TB patient data showed treatment success, 179 (3.0%) were lost to follow-up, 203 (3.4%) records were of patients who died, and 31 (0.5%) were of patients who experienced treatment failure. The factors associated with unfavorable outcomes were positive HIV status (AOR 2.71, 95% CI: 2.09–3.52), unknown HIV status (AOR 2.07, 95% CI: 1.60–2.69) and retreatment category (AOR 1.92, 95% CI: 1.30–2.85). Compared with the 0–4 years age category, the 5–9 years (AOR 0.62, 95% CI: 0.47–0.82) and 10–14 years (AOR 0.76, 95% CI: 0.60–0.98) age categories were less likely to experience the unfavorable outcomes.

Conclusion

This study shows a high treatment success rate among paediatric TB cases in Botswana. The government under the National TB Program should maintain and consolidate the gains from this program. Public health interventions should particularly target children with a positive or unknown HIV status, those under 5 years, and those who have been previously treated for TB.
Increased diaphragm echodensity correlates with postoperative pulmonary complications in patients after major abdominal surgery: a prospective observational study
Authors: Fu Xin , Wang Zhen , Wang Luping , Lv Guangxuan , Cheng Yisong , Wang Bo , Zhang Zhongwei , Jin Xiaodong , Kang Yan , Zhou Yongfang , Wu Qin
Published: November 2022

Background

Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery.

Methods

Diaphragm ultrasound images of patients after major abdominal surgery were collected during spontaneous breathing trials. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes including occurrence of PPCs, reintubation rate, duration of ventilation, and length of ICU stay were recorded.

Results

Diaphragm echodensity was measured serially in 117 patients. Patients who developed PPCs exhibited a higher ED50 (35.00 vs. 26.00,p < 0.001), higher ED85 (64.00 vs. 55.00,p < 0.001) and higher EDmean (39.32 vs. 33.98,p < 0.001). In ROC curve analysis, the area under the curve of ED50 for predicting PPCs was 0.611. The optimal ED50 cutoff value for predicting the occurrence of PPCs was 36. According to this optimal ED50 cutoff value, patients were further divided into a high-risk group (ED50 > 36, n = 35) and low-risk group (ED50 ≤ 36, n = 82). Compared with the low-risk group, the high-risk group had a higher incidence of PPCs (unadjustedp = 0.003; multivariate-adjustedp < 0.001).

Conclusion

Diaphragm echodensity can be feasibly and reproducibly measured in mechanically ventilated patients. The increase in diaphragm echodensity during spontaneous breathing trials was related to an increased risk of PPCs in patients after major abdominal surgery.
Comparing efficacy of a single intraarticular injection of platelet-rich plasma (PRP) combined with different hyaluronans for knee osteoarthritis: a randomized-controlled clinical trial
Authors: Huang Hung-Ya , Hsu Chien-Wei , Lin Guan-Chyun , Lin Huey-Shyan , Chou Yi-Jiun , Liou I-Hsiu , Sun Shu-Fen
Published: November 2022

Background

Intraarticular plasma-rich platelet (PRP) and hyaluronic acid (HA) have each been shown to be effective for treating knee osteoarthritis (OA). Evidence supporting the combination therapy is controversial. This study aimed to investigate the efficacy of a single intraarticular PRP injection combined with different HAs in patients with knee OA.

Methods

In this prospective randomized-controlled trial, 99 patients with Kellgren-Lawrence grade 2 knee OA with average knee pain ≥ 30 mm on a 0-100 mm pain visual analog scale (VAS) were randomized into two groups. The PRP + Artz group received a single intraarticular HA (Artz, 2.5 ml, 10 mg/ml) followed by 3 ml PRP (n = 50). The PRP + HYAJOINT Plus group received a single intraarticular cross-linked HA (HYAJOINT Plus, 3 ml, 20 mg/ml) followed by 3 ml PRP (n = 49). All patients were evaluated before and at 1, 3 and 6 months after injections. The primary outcome was the VAS pain reduction from baseline at 6 months. Secondary outcome measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, single leg stance (SLS) test and patient satisfaction.

Results

Ninety-five patients were analyzed by intention-to-treat analysis. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at 1, 3 and 6 months post intervention (p < 0.05). Between-group comparisons showed no significant differences at most follow-up time points, except better improvements in Lequesne index at 1 month (p = 0.003) and WOMAC-stiffness score at 6 months (p = 0.020) in the PRP + Artz group, and superiority in SLS at 1, 3 and 6 months in the PRP+ HYAJOINT Plus group (p < 0.001, p = 0.003 and p = 0.004). Additional Johnson-Neyman analyses showed that among the patients with baseline WOMAC-pain score > 8.5, WOMAC-function score > 21.7 and WOMAC-total score > 32.0, respectively, those treated with PRP + HYAJOINT Plus injections had better effects in WOMAC-pain, WOMAC-function and WOMAC-total scores than those treated with PRP + Artz at 3 months postinjection (p < 0.05). Both groups reported high satisfaction. No serious adverse events occurred during the study.

Conclusions

A single PRP injection combined with Artz or HYAJOINT Plus is effective and safe for 6 months in patients with knee OA. Both injection regimens are potential treatment options for knee OA. Further studies are needed to confirm these results.

Trial registration

The study was registered at ClinicalTrials.gov (NCT04931719), retrospectively. Date of registration 18/6/2021.

Name of trial registry

Comparing efficacy of single PRP combined with different hyaluronans for knee osteoarthritis.

Level of evidence

Therapeutic Level 1.
Factors associated with depression among young female migrants in Ethiopia
Authors: Erulkar Annabel , Medhin Girmay
Published: November 2022

Background

Mental health disorders represent a significant share of disease burden for adolescents and young people and depression is among the leading causes of morbidity within this age group. With rural-urban migration increasing in many settings, and young females being among the main migrants, few studies have examined the impact of such major transitions on mental health. This paper measures levels of depression among young women who are rural-urban migrants in Ethiopia, as well as factors associated with depression.

Methods

This was part of a largescale study of urban migrant females aged 15–24 in Ethiopia, which took place in seven cities. Multiple categories of migrants were interviewed. We used modified PHQ-9 questions to measure depression and logistic regression models to examine its association with various characteristics including patterns of migration and violence. In all, 4,495 migrant females were interviewed.

Results

Twenty-one percent of migrant young women displayed symptoms of moderate or severe depression. Symptoms of depression were more common among commercial sex workers (37%) than among other categories of migrants. Factors significantly associated with depression were being in commercial sex work (OR 1.70), migrating before age 15 (OR 1.37), using a broker to find a job (OR 1.53), experiencing forced first sex (OR 2.16) and experiencing beating in the last three months (OR 2.16).

Conclusion

This study reveals significant levels of depression among young women in Ethiopia who are rural-urban migrants. The study highlights the need to expand measurement of mental health conditions in health surveys and underscores the need for additional investments in mental health infrastructure, programs and services for marginalized groups in sub-Saharan Africa.
Development and psychometric evaluation of a new brief scale to measure eHealth literacy in people with type 2 diabetes
Authors: Lee Eun-Hyun , Lee Young Whee , Lee Kwan-Woo , Kim Hae Jin , Hong Seongbin , Kim So Hun , Kang Eun Hee
Published: November 2022

Background

The internet has become a major source of health information, and obtaining appropriate information requires various abilities and skills, labeled as electronic health literacy (eHealth literacy). The existing instruments for measuring eHealth literacy are outdated because they were developed during the Web 1.0 era, or not sufficiently sensitive for people with a specific condition or disease because they were designed to assess eHealth literacy over a broad range for a general population. Approximately one in ten adults worldwide live with diabetes. Health professionals have a responsibility to identify patients with low eHealth literacy to prevent them from obtaining misleading internet diabetes information.

Aims

The aims were to develop a condition-specific eHealth literacy scale for diabetes and to evaluate its psychometric properties among people with type 2 diabetes.

Methods

An instrument development design was used. This study recruited 453 people diagnosed with type 2 diabetes at the outpatient clinics of hospitals in 2021. Psychometric properties (internal consistency, measurement invariance, and content, structural, convergent, and known-groups validities) were analyzed.

Results

An expert panel assessed content validity. Exploratory factor analysis, exploratory graph analysis, and confirmatory factor analysis (CFA) for structural validity yielded a two-factor solution (CFI = 0.977, SRMR = 0.029, RMSEA = 0.077). Cronbach’s alpha and omega values were excellent for each factor (0.87–0.94). Multigroup CFA yielded configural and metric measurement invariance across the gender, age, and glycemic control status groups. Convergent validity with a comparator instrument to measure health literacy was supported by a moderate correlation, and known-groups validity determined using groups with different internet-use frequencies was satisfied with a high effect size.

Conclusion

A new condition-specific eHealth literacy scale for people with type 2 diabetes was developed, comprising 10 items. The scale exhibited good psychometric properties; however, test–retest reliability must be determined for the stability of the scale and cross-cultural validity is required among different languages. The brief scale has the merits of being feasible to use in busy clinical practice and being less burdensome to respondents. The scale can be applied in clinical trials of internet-based diabetes interventions for assessing the eHealth literacy of respondents.
Prevalence and influence factors of occupational exposure to blood and body fluids in registered Chinese nurses: a national cross-sectional study
Authors: Zhang Lihui , Li Qi , Guan Ling , Fan Lu , Li Yunxia , Zhang Zhiyun , Yuan Sue
Published: November 2022

Background

Occupational exposure to blood and body fluids poses a threat to medical providers and to nurses especially. This harm is not only physical, but psychology as well and can ultimately impact patient safety. This study aims to understand the prevalence of occupational exposure to blood and body fluids among Chinese registered nurses and explores the factors that influence this exposure.

Methods

A cross-sectional online survey was conducted for 31 province-level divisions in China, using a self-created questionnaire entitled Status Survey on Occupational Exposure in Nurses. Descriptive statistics were used to describe both the demographic characteristics of the respondents and the characteristics of occupational exposure. Categorical variables were presented as frequencies and percentage, and the relationship between possible influential factors and the occurrence of occupational exposure was determined using binary logistic regression.

Results

Out of a total of 20,791 nurses analyzed, over half (52.1%) of them had experienced occupational exposure to blood or body fluids, but over 1/3 (34.6%) of them did not ever report their exposures to a supervisor/official. The top three causes of under-reporting were: the source patient failed to test positive for infectious pathogens (43.6%), perception of a burdensome reporting process (24.6%), and indifferent attitude towards being infected (16.9%). Nurses who worked over 8 hours per day had higher risks of exposure (OR 1.199, 95% CI 1.130 to 1.272, P < 0.001, respectively). The occupational exposure risk from providing 1–2 types of PPE is 1.947 times that of providing 9–10 types of PPE (OR 1.947, 95% CI 1.740 to 2.178, P < 0.001). Likewise, the occupational exposure risk of providing 1–2 types of safety-engineered injection devices is 1.275 times of that of providing 5–6 types (OR 1.275, 95% CI 1.179 to 1.379, P < 0.001).

Conclusions

Occupational exposure to blood and body fluids in registered nurses is common, but the rate of under-reporting such exposure is high. Implementing engineered “sharp” injury prevention devices, following exposure prevention procedures, giving sufficient education and training to healthcare personnel on exposure prevention and control, and developing exposure reporting policies are all steps that can both reduce exposure and increase its reporting.
Budget impact analysis of the subcutaneous infliximab (CT-P13 SC) for treating inflammatory bowel disease in the Big-5 European (E5) countries
Authors: Yoo Hyun Kyeong , Byun Han Geul , Caprioli Flavio , Fumery Mathurin , Peyrin-Biroulet Laurent , Sreedhar Subramanian , Potter James , Jang Minyoung
Published: November 2022

Background

In 2020, the European Medicines Agency approved infliximab subcutaneous (SC) for the treatment of inflammatory bowel disease. This new mode of infliximab administration will reduce outpatient visits and costs of intravenous (IV) administration. This article describes a budget impact analysis of introducing infliximab SC to the Big-5 European (E5) market (Germany, France, Italy, Spain and UK) for 5 years, from the healthcare payer’s perspective.

Methods

A prevalence-based budget impact model was developed to examine the financial impact of infliximab SC. “World with” versus “world without” infliximab SC scenarios were compared, including the potential administration costs of IV administration.

Results

Introducing infliximab SC in patients with Crohn’s disease (CD) for 5 years resulted in cost savings of €42.0 million in the UK, €59.4 million in Germany, and €46.4 million in France and Italy, but increased budget expenditure in Spain by €3.8 million. For ulcerative colitis (UC), cost savings of €42.7 million in the UK, €44.9 million in Germany, €44.3 million in France, and €53.0 million in Italy occurred, but with no savings in Spain for 5 years. Cost-savings per patient was calculated by diving the net budget saving by number of treatment eligible patients. Maximum and minimum saving per patient per year ranged between €38.25 and €575.74 in CD, both from Germany, and €105.06 (France) and €647.25 (Germany) in UC.

Conclusion

Healthcare payers in the UK, Germany, France, and Italy, but not in Spain, will make budget savings by using infliximab SC for the treatment of inflammatory bowel disease.
The pathogenic roles of lncRNA-Taurine upregulated 1 (TUG1) in colorectal cancer
Authors: Azizidoost Shirin , Nasrolahi Ava , Ghaedrahmati Farhoodeh , Kempisty Bartosz , Mozdziak Paul , Radoszkiewicz Klaudia , Farzaneh Maryam
Published: November 2022

Colorectal cancer (CRC) is a gastrointestinal tumor that develops from the colon, rectum, or appendix. The prognosis of CRC patients especially those with metastatic lesions remains unsatisfactory. Although various conventional methods have been used for the treatment of patients with CRC, the early detection and identification of molecular mechanisms associated with CRC is necessary. The scientific literature reports that altered expression of long non-coding RNAs (lncRNAs) contributed to the pathogenesis of CRC cells. LncRNA TUG1 was reported to target various miRNAs and signaling pathways to mediate CRC cell proliferation, migration, and metastasis. Therefore, TUG1 might be a potent predictive/prognostic biomarker for diagnosis of CRC.
Mitochondrial protective effects caused by the administration of mefenamic acid in sepsis
Authors: Dominguini Diogo , Michels Monique , Wessler Leticia B. , Streck Emilio L. , Barichello Tatiana , Dal-Pizzol Felipe
Published: November 2022

The pathophysiology of sepsis may involve the activation of the NOD-type receptor containing the pyrin-3 domain (NLPR-3), mitochondrial and oxidative damages. One of the primary essential oxidation products is 8-oxoguanine (8-oxoG), and its accumulation in mitochondrial DNA (mtDNA) induces cell dysfunction and death, leading to the hypothesis that mtDNA integrity is crucial for maintaining neuronal function during sepsis. In sepsis, the modulation of NLRP-3 activation is critical, and mefenamic acid (MFA) is a potent drug that can reduce inflammasome activity, attenuating the acute cerebral inflammatory process. Thus, this study aimed to evaluate the administration of MFA and its implications for the reduction of inflammatory parameters and mitochondrial damage in animals submitted to polymicrobial sepsis. To test our hypothesis, adult male Wistar rats were submitted to the cecal ligation and perforation (CLP) model for sepsis induction and after receiving an injection of MFA (doses of 10, 30, and 50 mg/kg) or sterile saline (1 mL/kg). At 24 h after sepsis induction, the frontal cortex and hippocampus were dissected to analyze the levels of TNF-α, IL-1β, and IL-18; oxidative damage (thiobarbituric acid reactive substances (TBARS), carbonyl, and DCF-DA (oxidative parameters); protein expression (mitochondrial transcription factor A (TFAM), NLRP-3, 8-oxoG; Bax, Bcl-2 and (ionized calcium-binding adaptor molecule 1 (IBA-1)); and the activity of mitochondrial respiratory chain complexes. It was observed that the septic group in both structures studied showed an increase in proinflammatory cytokines mediated by increased activity in NLRP-3, with more significant oxidative damage and higher production of reactive oxygen species (ROS) by mitochondria. Damage to mtDNA it was also observed with an increase in 8-oxoG levels and lower levels of TFAM and NGF-1. In addition, this group had an increase in pro-apoptotic proteins and IBA-1 positive cells. However, MFA at doses of 30 and 50 mg/kg decreased inflammasome activity, reduced levels of cytokines and oxidative damage, increased bioenergetic efficacy and reduced production of ROS and 8-oxoG, and increased levels of TFAM, NGF-1, Bcl-2, reducing microglial activation. As a result, it is suggested that MFA induces protection in the central nervous system early after the onset of sepsis.
Levonorgestrel-releasing intrauterine device plus metformin, or megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma: a prospective, randomized, blind-endpoint design trial protocol
Authors: Zhao Xin , Niu Jumin , Shi Cong , Liu Zhihui
Published: November 2022

Background

Endometrial adenocarcinoma (EC) is the fifth most common cancer in women worldwide, standard treatment for EC includes hysterectomy, but it results in the loss of reproductive function. Thus, conservative treatment for these patients is strongly demanded, progestin therapy is widely accepted as the main fertility-sparing treatment for young women with endometrial hyperplasia with atypia (EHA) and well-differentiated endometrioid endometrial cancer. This trial will investigate the effectiveness of conservative treatment for obese women with early-stage EC.

Method and design

This will be an open-label, 2-armed, randomized, phase-II single-center trial of LNG-IUD plus metformin or megestrol acetate (MA) plus metformin. A total of 88 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound and radiology data, will be collected at baseline, and then at 3, 6, 9, 12, 18, and 24 months. EC biomarkers will be collected at baseline. The primary aim is to determine the efficacy of a levonorgestrel-releasing intrauterine device (LNG-IUD) plus metformin, or megestrol acetate (MA) plus metformin in achieving pathological complete response (pCR) at 12 months, as well as post-treatment pregnancy outcomes and recurrence rate. The secondary aims are to predict the response to an LNG-IUD plus metformin and MA plus metformin via clinical, blood, and tissue predictive biomarkers.

Conclusions

Prospective evidence for conservative treatment of EC is limited. New methods to achieve better CR rates with fewer side effects are needed. This trial will investigate the effectiveness of LNG-IUD plus metformin, and MA plus metformin, in obese women with early-stage EC, providing a non-surgical treatment option for these patients.

Trial registration ChiCTR2200055624. The trial was registered at http://www.chictr.org.cn/listbycreater.aspx on January 15, 2022
JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis
Authors: Li Zhenyang , Zhou Ye , Jia Kaiwei , Yang Yingyun , Zhang Liyuan , Wang Suyuan , Dong Yue , Wang Mu , Li Yunhui , Lu Shan , Zhang Wannian , Zhang Luxin , Fan Yiwen , Zhang Dingji , Li Nan , Yu Yizhi , Cao Xuetao , Hou Jin
Published: November 2022

Background

Hepatocarcinogenesis is driven by necroinflammation or metabolic disorders, and the underlying mechanisms remain largely elusive. We previously found that retinoic acid-inducible gene-I (RIG-I), a sensor for recognizing RNA virus in innate immune cells, is mainly expressed by parenchymal hepatocytes in the liver. However, its roles in hepatocarcinogenesis are unknown, which is intensively investigated in this study.

Methods

DEN-induced necroinflammation-driven hepatocarcinogenesis and STAM NASH-hepatocarcinogenesis were carried out in hepatocyte-specific RIG-I knockout mice. The post-translational modification of RIG-I was determined by mass spectrometry, and specific antibodies against methylated lysine sites and the RIG-I lysine mutant mice were constructed to identify the functions of RIG-I methylation.

Results

We interestingly found that DEN-induced hepatocarcinogenesis was enhanced, while NASH-induced hepatocarcinogenesis was suppressed by hepatocyte-specific RIG-I deficiency. Further, IL-6 decreased RIG-I expression in HCC progenitor cells (HcPCs), which then viciously promoted IL-6 effector signaling and drove HcPCs to fully established HCC. RIG-I expression was increased by HFD, which then enhanced cholesterol synthesis and steatosis, and the in-turn NASH and NASH-induced hepatocarcinogenesis. Mechanistically, RIG-I was constitutively mono-methylated at K18 and K146, and demethylase JMJD4-mediated RIG-I demethylation suppressed IL-6-STAT3 signaling. The constitutive methylated RIG-I associated with AMPKα to inhibit HMGCR phosphorylation, thus promoting HMGCR enzymatic activity and cholesterol synthesis. Clinically, RIG-I was decreased in human hepatic precancerous dysplastic nodules while increased in NAFLD livers, which were in accordance with the data in mouse models.

Conclusions

Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC.
Electrical impedance tomography for titration of positive end-expiratory pressure in acute respiratory distress syndrome patients with chronic obstructive pulmonary disease
Authors: Liu Xuesong , Liu Xiao , Meng Jue , Liu Dongdong , Huang Yongbo , Sang Ling , Xu Yonghao , Xu Zhiheng , He Weiqun , Chen Sibei , Zhang Rong , Liu Xiaoqing , Li Yimin
Published: November 2022

Background

Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration.

Methods

To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol.

Results

A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001).

Conclusion

Titrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics.
The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing
Authors: Wang Yu-Hao , Zhao Cheng-Zhi , Wang Ren-Yi , Du Qian-Xin , Liu Ji-Yuan , Pan Jian
Published: November 2022

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.
Sex and age differences in the association of fatty liver index-defined non-alcoholic fatty liver disease with cardiometabolic risk factors: a cross-sectional study
Authors: Fresneda Sergio , Abbate Manuela , Busquets-Cortés Carla , López-González Arturo , Fuster-Parra Pilar , Bennasar-Veny Miquel , Yáñez Aina M.
Published: November 2022

Background

Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults.

Methods

This cross-sectional study included data from 33,216 Spanish adult workers (18–65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression.

Results

The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3–28.5%) for men and 6.8% (95% CI 6.4–7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses.

Conclusions

Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.
The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate
Authors: Li Zili , Fang Fang , Long Yuting , Zhao Qian , Wang Xiaotong , Ye Zhen , Meng Tianqing , Gu Xiuli , Xiang Wenpei , Xiong Chengliang , Li Honggang
Published: November 2022

Background

Human primordial germ cells (hPGCs) initiate from the early post-implantation embryo at week 2–3 and undergo epigenetic reprogramming during development. However, the regulatory mechanism of DNA methylation during hPGC specification is still largely unknown due to the difficulties in analyzing early human embryos. Using an in vitro model of hPGC induction, we found a novel function of TET proteins and NANOG in the hPGC specification which was different from that discovered in mice.

Methods

Using the CRISPR–Cas9 system, we generated a set of TET1, TET2 and TET3 knockout H1 human embryonic stem cell (hESC) lines bearing a BLIMP1-2A-mKate2 reporter. We determined the global mRNA transcription and DNA methylation profiles of pluripotent cells and induced hPGC-like cells (hPGCLCs) by RNA-seq and whole-genome bisulfite sequencing (WGBS) to reveal the involved signaling pathways after TET proteins knockout. ChIP-qPCR was performed to verify the binding of TET and NANOG proteins in the SOX17 promoter. Real-time quantitative PCR, western blot and immunofluorescence were performed to measure gene expression at mRNA and protein levels. The efficiency of hPGC induction was evaluated by FACS.

Results

In humans, TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) impaired the NODAL signaling pathway and impeded hPGC specification in vitro, while the hyperactivated NODAL signaling pathway led to gastrulation failure when Tet proteins were inactivated in mouse. Specifically, TET proteins stimulated SOX17 through the NODAL signaling pathway and directly regulates NANOG expression at the onset of hPGCLCs induction. Notably, NANOG could bind to SOX17 promoter to regulate its expression in hPGCLCs specification. Furthermore, in TKO hESCs, DNMT3B-mediated hypermethylation of the NODAL signaling-related genes and NANOG/SOX17 promoters repressed their activation and inhibited hPGCLC induction. Knockout of DNMT3B in TKO hESCs partially restored NODAL signaling and NANOG/SOX17 expression, and rescued hPGCLC induction.

Conclusion

Our results show that TETs-mediated oxidation of 5-methylcytosine modulates the NODAL signaling pathway and its downstream genes, NANOG and SOX17, by promoting demethylation in opposition to DNMT3B-mediated methylation, suggesting that the epigenetic balance of DNA methylation and demethylation in key genes plays a fundamental role in early hPGC specification.
Pterostilbene attenuates intrauterine growth retardation-induced colon inflammation in piglets by modulating endoplasmic reticulum stress and autophagy
Authors: Chen Yanan , Zhang Hao , Li Yue , Ji Shuli , Jia Peilu , Wang Tian
Published: November 2022

Background

Endoplasmic reticulum (ER) stress and autophagy are implicated in the pathophysiology of intestinal inflammation; however, their roles in intrauterine growth retardation (IUGR)-induced colon inflammation are unclear. This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha (TNF-α)-treated human colonic epithelial cells (Caco-2) by targeting ER stress and autophagy.

Results

Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses, ER stress, and impaired autophagic flux (P < 0.05). The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells (P < 0.05). Conversely, pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells (P < 0.05). Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65, reduced intestinal permeability and cell apoptosis, and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells (P < 0.05). Importantly, treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response, cell apoptosis, and intestinal barrier function in the TNF-α-exposed Caco-2 cells (P < 0.05).

Conclusion

Pterostilbene mitigates ER stress and promotes autophagic flux, thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.
Stem cell phenotype predicts therapeutic response in glioblastomas with MGMT promoter methylation
Authors: Lakis Nelli S. , Brodsky Alexander S. , Karashchuk Galina , Audesse Amanda J. , Yang Dongfang , Sturtevant Ashlee , Lombardo Kara , Wong Ian Y. , Webb Ashley E. , Anthony Douglas C.
Published: November 2022

A growing body of evidence supports the presence of a population of cells in glioblastoma (GBM) with a stem cell-like phenotype which shares certain biological markers with adult neural stem cells, including expression of SOX2, CD133 (PROM1), and NES (nestin). This study was designed to determine the relationship between the expression of these stem cell markers and the clinical outcome in GBM patients. We quantified the intensity of expression of the proteins CD133 and SOX2 by immunohistochemistry (IHC) in a cohort of 86 patients with IDH-wildtype GBM, and evaluated patient outcomes using Kaplan–Meier and Cox proportional hazards analysis. In our patients, MGMT promoter methylation status and age were predictors of overall survival and progression free survival. The levels of SOX2 and CD133 were not associated with outcome in univariate analysis; however, stratification of tumors based on low or high levels of CD133 or SOX2 expression revealed that MGMT methylation was a predictor of progression-free survival and overall survival only for tumors with high levels of expression of CD133 or SOX2. Tumors with low levels of expression of CD133 or SOX2 did not show any relationship between MGMT methylation and survival. This relationship between MGMT and stem cell markers was confirmed in a second patient cohort, the TCGA dataset. Our results show that stratification of GBM by the level of expression of CD133 and SOX2 improved the prognostic power of MGMT promoter methylation status, identifying a low-expressing group in which the clinical outcome is not associated with MGMT promoter methylation status, and a high-expressing group in which the outcome was strongly associated with MGMT promoter methylation status. These findings support the concept that the presence of a high stem cell phenotype in GBM, as marked by expression of SOX2 or CD133, may be associated with the clinical response to treatment.
Weakening behavior of the shallow megasplay fault in the Nankai subduction zone
Authors: Roesner Alexander , Ikari Matt J. , Hüpers Andre , Kopf Achim J.
Published: November 2022

The Nankai Trough megasplay fault hosts diverse modes of fault slip, ranging from slow slip events to megathrust earthquakes, and is responsible for related phenomena such as tsunamis and submarine landslides. All types of slip events require some kind of frictional weakening process in order to nucleate and propagate. We tested fluid-saturated, powdered megasplay fault samples in a direct shear apparatus under effective normal stresses of 2–18 MPa to investigate their friction velocity- and slip-dependence. The experiments show that for short distances (1 mm) after a velocity step, there is an evolution from velocity weakening at low effective normal stress to velocity strengthening at high effective normal stresses. Over a longer distance (5 mm), large velocity weakening is observed over all tested effective normal stresses. In all experiments, slip weakening behavior occurred with relatively large weakening rates at low effective normal stresses and smaller weakening rates at higher effective normal stresses. Critical stiffnesses for slip instability were calculated for both the velocity and slip dependence of friction to determine their relative importance. At shallow depths, velocity weakening would be the main cause of frictional instability for both small and large slip perturbations, whereas at greater depth instability requires either slip weakening over small slip distances, or velocity weakening induced by larger slip. Regardless of the underlying mechanism, the observed slip instability at lower effective stresses increases the likelihood for fault slip events to travel to the seafloor which may cause submarine landslides and tsunamis.

Graphical Abstract
Minos and Restless transposon insertion mutagenesis of psychrotrophic fungus for red pigment synthesis adaptive to normal temperature
Authors: Lu Fengning , Ren Yanna , Ding Lulu , Lu Jian , Zhou Xiangshan , Liu Haifeng , Wang Nengfei , Cai Menghao
Published: November 2022

The polar psychrotrophic fungus Geomyces sp. WNF-15A can produce high-quality natural red pigment for the potential use as edible pigment. However, it shows low-temperature-dependent synthesis of red pigment, which limits its large-scale industrial applications due to the difficult and high-cost bioprocess control. This study aims to develop transposon-mediated mutagenesis methods to generate mutants that are able to synthesize red pigment at normal temperature. Four transposable systems, including single and dual transposable systems, were established in this fungus based on the Minos from Drosophila hydei and the Restless from Tolypocladium inflatum. A total of 23 production-dominant mutants and 12 growth-dominant mutants were thus obtained by constructed transposable systems. At 14 °C and 20 °C, the MPS1 mutant strain achieved the highest level of red pigment (OD520 of 43.3 and 29.7, respectively), which was increased by 78.4% and 128.7% compared to the wild-type, respectively. Of note, 4 mutants (MPS1, MPS3, MPS4 and MPD1) successfully synthesized red pigment (OD520 of 5.0, 5.3, 4.7 and 4.9, respectively) at 25 °C, which broke the limit of the wild-type production under normal temperature. Generally, the dual transposable systems of Minos and Restless were more efficient than their single transposable systems for mutagenesis in this fungus. However, the positive mutation ratios were similar between the dual and single transposable systems for either Minos or Restless. This study provides alternative tools for genetic mutagenesis breeding of fungi from extreme environments.

Graphical Abstract
Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties
Authors: Amer Maggie E. , Othman Azza I. , Abozaid Hajer Mohammed , El-Missiry Mohamed A.
Published: November 2022

Background

Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis.

Methods

Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation.

Results

Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology.

Conclusions

These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.
Obesity and total joint arthroplasty: Does weight loss in the preoperative period improve perioperative outcomes?
Authors: Laperche Jacob , Feinn Richard , Myrick Karen , Halawi Mohamad J.
Published: November 2022

Background

The obese population is more likely to develop degenerative joint disease requiring total joint arthroplasty (TJA) and also experience increased rates of adverse post-surgical outcomes. This study assessed whether a quantifiable weight loss prior to TJA had any impact on perioperative and 30-day outcomes in obese patients.

Method

Using the American College of Surgeons-National Surgical Quality Improvement Program database, obese patients who underwent total hip or total knee arthroplasty and lost at least 10% of their total body weight prior to surgery were identified and matched to other obese individuals undergoing the same procedures without weight loss. Perioperative outcomes, including operative time, length of stay, discharge destination, or 30-day adverse events, including complications, re-admissions, re-operations, and mortality, were then compared using conditional Logistic regression analysis.

Results

Analysis showed no difference between the two groups in terms of operative time, length of stay, discharge destination, or 30-day adverse events, including complications, re-admissions, re-operations, and mortality.

Conclusion

The results of this study suggest that weight loss alone in the preoperative period may not be sufficient to mitigate the effects of obesity on immediate post-TJA outcomes.