bluuebunny/crossref_metadata_2025 huggingface dataset:
Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis
Authors: van Winden Tijn M. S. , Nijman Tobias A. J. , Kleinrouweler C. Emily , Salim Raed , Kashanian Maryam , Al-Omari Wafa R. , Pajkrt Eva , Mol Ben W. , Oudijk Martijn A. , Roos Carolien
Published: July 2022

Background

Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA).

Methods

We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks’ gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata.

Results

We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47–1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80–5.1).

Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69–0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14–0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73–1.4) or 7 days (OR 1.3, 95% CI 0.85–5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60–3.4).

Conclusions

In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug.

Study registration

We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.
Evaluation of an implementation strategy for Individual Placement and Support in the Netherlands: a 30-month observational study
Authors: Vukadin Miljana , Schaafsma Frederieke G. , Michon Harry W. C. , Cillekens Bart , van de Ven Peter M. , Juurlink Trees , Anema Johannes R.
Published: July 2022

Background

Individual Placement and Support (IPS) is an evidence-based, effective approach to help people with severe mental illness (SMI) obtain and maintain competitive employment. The aim of the present study was to examine employment outcomes and associations with an organizational and a financial factor in people with SMI who participated in Individual Placement and Support using a multifaceted implementation strategy (IPS + MIS). The goal of this strategy was to improve IPS implementation by enhancing collaboration among mental health care and vocational rehabilitation stakeholders, and realizing secured IPS funding.

Methods

An observational cohort study including 103 participants was conducted, with a 30-month follow-up. Descriptive analyses were used to examine employment outcomes. Multivariable logistic and linear regression analyses were performed to study associations with an organizational and a financial factor: the level of experience of mental health agencies with providing IPS + MIS and the type of IPS funding (i.e. municipality funding (reference group) and the Dutch Social Security Institute: the Institute for Employee Benefits Schemes (UWV) funding).

Results

Forty-six percent of the participants were competitively employed at any time during the 30-month follow-up; the median number of days until competitive job obtainment and in competitive jobs was 201 and 265, respectively. The majority of all jobs obtained (81%) were categorized as ‘elementary occupations’, ‘clerical support workers’, and ‘service and sales workers’. A higher level of experience of the mental health agencies with providing IPS + MIS was found to be positively associated with job obtainment (OR = 3.83, 95% CI 1.42–10.30, p = 0.01) and the number of days worked in competitive jobs (B = 1.21, 95% CI 0.36–2.07, p = 0.01). UWV funding was found to be negatively associated with job obtainment (OR = 0.30, 95% CI 0.11–0.77, p = 0.01). No association was found for the type of IPS funding and the number of days worked in competitive jobs (B = -0.73, 95% CI -1.48–0.02, p = 0.06).

Conclusions

This study shows that almost half of the people who participate in IPS + MIS obtain a competitive job within 30 months. The results further suggest that both the level of experience of mental health agencies with providing IPS + MIS, and funding may play a role in employment outcomes.
Mathematical modelling of vaccination rollout and NPIs lifting on COVID-19 transmission with VOC: a case study in Toronto, Canada
Authors: Aruffo Elena , Yuan Pei , Tan Yi , Gatov Evgenia , Moyles Iain , Bélair Jacques , Watmough James , Collier Sarah , Arino Julien , Zhu Huaiping
Published: July 2022

Background

Since December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategies focused on vaccinating the elderly to prevent hospitalizations and deaths, but with vaccines becoming available to the broader population, it became important to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence.

Methods

We extended the classic deterministic SIR compartmental disease-transmission model to simulate the lifting of NPIs under different vaccine rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020, and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity.

Results

We found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20–39 and 40–59 years, wherein first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% coverage by mid-June, along with postponing reopening from August 2021 to September 2021) can reduce case counts and severe outcomes by roughly 57% by December 31, 2021.

Conclusions

Our results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, increasing contacts and easing protective personal behaviours is not advisable since a resurgence is expected to occur, especially with an earlier reopening.
Incidence and mortality trends of nasopharynx cancer from 1990 to 2019 in China: an age-period-cohort analysis
Authors: Bai Ruhai , Sun Jianzhong , Xu Yan , Sun Zhonghe , Zhao Xiaoyan
Published: July 2022

Background

Nasopharynx cancer (NPC) is a great health burden in China. This study explored the long-term trends of NPC incidence and mortality in China.

Methods

We retrospectively analyzed data from the Global Burden of Disease Study 2019 using an age-period-cohort framework.

Results

The age-standardized incidence rate (ASIR) of NPC increased by 72.7% and age-standardized mortality rate (ASMR) of NPC decreased by 51.7% for both sexes between 1990 and 2019. For males, the local drift for incidence was higher than 0 (P < 0.05) in those aged 20 to 79 years. For females, the local drift was higher than 0 (P < 0.05) in those aged 30 to 59 years, and lower than 0 (P < 0.05) in those aged 65 to 84 years. The local drift for mortality rates were less than 0 (P < 0.05) in every age group for both sexes. The estimated period relative risks (RRs) for incidence of NPC were increased monotonically for males, and increased for females after 2000. The increasing trend of cohort RRs of incidence was ceased in recent birth cohorts. Both period and cohort effects of NPC mortality in China decreased monotonically.

Conclusions

Over the last three decades, the ASMR and crude mortality rate (CMR) of NPC has decreased, but the ASIR and crude incidence rate (CIR) increased in China. Although the potential mortality risk of NPC decreased, the risk of NPC incidence was found to increase as the period move forward, and suggested that control and prevention efforts should be enhanced.
Investigation of pilots' mental health and analysis of influencing factors in China: based on structural equation model
Authors: Yu Feifei , Li Xuxia , Yang Jishun
Published: July 2022

Background

Pilots' physical and mental health might be significant contributing factors to flight safety. Exploring pilots’ health-related quality of life (HRQoL) is crucial for aviation security, health management, and psychological security. This study aimed to explore HRQoL and mental health of pilots and analyze the health characteristics and influencing factors, such as demographic data, personality traits, social support, and resilience. It may provide data for a theoretical basis for aviation security work and health management strategy.

Methods

This is a cross-sectional study using quantitative approaches. Two hundred twenty male pilots with an average age of 33.31 years participated. They answered a social demographic questionnaire, Symptom Checklist-90, Short Form 36 Health Survey Questionnaire, Perceived social support scale, Connor-Davidson resilience scale, and Big Five Personality Inventories, whose data were analyzed using descriptive and inferential statistics.

Results

The mediating effect of personality factors between resilience and the HRQoL of pilots was observed. Personality factors also mediated the relationship between social support and the mental health of pilots.

Conclusion

Pilots’ mental health and quality of life need to be taken seriously. Social support, resilience, and personality factors affect pilots’ mental health and quality of life.
Comparison of accuracy and safety between second-generation TiRobot-assisted and free-hand thoracolumbar pedicle screw placement
Authors: Yan Kai , Zhang Qi , Tian Wei
Published: July 2022

Background

Robot-assisted spine surgery aims to improve the accuracy of screw placement. We compared the accuracy and safety between a novel robot and free hand in thoracolumbar pedicle screw placement.

Methods

Eighty patients scheduled to undergo robot-assisted (40 patients) and free-hand (40 patients) pedicle screw placement were included. The patients’ demographic characteristics, radiographic accuracy, and perioperative outcomes were compared. The accuracy of screw placement was based on cortical violation and screw deviation. Safety outcomes mainly included operative time, blood loss, revision, and complications.

Results

A total of 178 and 172 screws were placed in the robot-assisted and free-hand groups, respectively. The rate of perfect screw position (grade A) was higher in the robot-assisted group than in the free-hand group (91.0% vs. 75.6%; P < 0.001). The rate of clinically acceptable screw position (grades A and B) was also higher in the robot-assisted group than in the free-hand group (99.4% vs. 90.1%; P < 0.001). The robot-assisted group had significantly lower screw deviation than the free-hand group [1.46 (0.94, 1.95) mm vs. 2.48 (1.09, 3.74) mm, P < 0.001]. There was no robot abandonment in the robot-assisted group. No revision was required in any of the groups.

Conclusions

Robot-assisted pedicle screw placement is more accurate than free-hand placement. The second-generation TiRobot–assisted thoracolumbar pedicle screw placement is an accurate and safe procedure.

Trial registration retrospectively registered
RNA-seq reveals co-dysregulated circular RNAs in the adenomyosis eutopic endometrium and endometrial–myometrial interface
Authors: Guo Zhengchen , Duan Hua , Wang Sha , Wang Sirui , Lin Qi , Li Yazhu
Published: July 2022

Background

Uterine adenomyosis is associated with chronic pelvic pain, abnormal uterine bleeding, and infertility. The pathogenesis of adenomyosis is still unclear. Circular RNAs (circRNAs) have been implicated in several benign diseases and malignant tumors. We aimed to explore the co-dysregulated circular RNA profile in the eutopic endometrium and endometrial–myometrial interface (EMI) of adenomyosis.

Methods

Total RNA was extracted from the eutopic endometrium and EMI of 5 patients with adenomyosis and 3 patients without adenomyosis. Next-generation sequencing was performed to identify the circRNA expression profile of the two tissue types. Bioinformatics analysis was performed to predict circRNA-binding miRNAs and miRNA-binding mRNAs and construct ceRNA networks, and functional enrichment analysis was performed to predict the biological functions of circRNAs.

Results

Among the adenomyosis patients, 760 circRNAs were significantly upregulated and 119 circRNAs were significantly downregulated in the EMI of adenomyosis, while 47 circRNAs were significantly upregulated and 17 circRNAs were significantly downregulated in the eutopic endometrium of adenomyosis. We identified hsa_circ_0002144 and hsa_circ_0005806 as co-upregulated and hsa_circ_0079536 and hsa_circ_0024766 as co-downregulated in the eutopic endometrium and EMI. Bioinformatics analysis was performed to construct a ceRNA network of codifferentially expressed circRNAs. The MAPK signaling pathway is the most important signaling pathway involved in the function of the ceRNA network.

Conclusions

Co-dysregulated circRNAs were present in the eutopic endometrium and EMI of adenomyosis. MiRNA binding sites were observed for all of these circRNAs and found to regulate gene expression. Co-dysregulated circRNAs may induce the eutopic endometrial invagination process through the MAPK signaling pathway and promote the progression of adenomyosis.
Protein expression profiling identifies a prognostic model for ovarian cancer
Authors: Xiong Luyang , Tan Jiahong , Feng Yuchen , Wang Daoqi , Liu Xudong , Feng Yun , Li Shusheng
Published: July 2022

Background

Owing to the high morbidity and mortality, ovarian cancer has seriously endangered female health. Development of reliable models can facilitate prognosis monitoring and help relieve the distress.

Methods

Using the data archived in the TCPA and TCGA databases, proteins having significant survival effects on ovarian cancer patients were screened by univariate Cox regression analysis. Patients with complete information concerning protein expression, survival, and clinical variables were included. A risk model was then constructed by performing multiple Cox regression analysis. After validation, the predictive power of the risk model was assessed. The prognostic effect and the biological function of the model were evaluated using co-expression analysis and enrichment analysis.

Results

394 patients were included in model construction and validation. Using univariate Cox regression analysis, we identified a total of 20 proteins associated with overall survival of ovarian cancer patients (p < 0.01). Based on multiple Cox regression analysis, six proteins (GSK3α/β, HSP70, MEK1, MTOR, BAD, and NDRG1) were used for model construction. Patients in the high-risk group had unfavorable overall survival (p < 0.001) and poor disease-specific survival (p = 0.001). All these six proteins also had survival prognostic effects. Multiple Cox regression analysis demonstrated the risk model as an independent prognostic factor (p < 0.001). In receiver operating characteristic curve analysis, the risk model displayed higher predictive power than age, tumor grade, and tumor stage, with an area under the curve value of 0.789. Analysis of co-expressed proteins and differentially expressed genes based on the risk model further revealed its prognostic implication.

Conclusions

The risk model composed of GSK3α/β, HSP70, MEK1, MTOR, BAD, and NDRG1 could predict survival prognosis of ovarian cancer patients efficiently and help disease management.
Knowledge, practice and associated factors of nurses towards prevention of catheter-associated urinary tract infection in intensive care unit of public hospitals administered by Federal Government in Addis Ababa, Ethiopia: a cross-sectional institutional-based study
Authors: Teshager Tilahun , Hussien Heyria , Kefyalew Merahi , Wondimneh Fenta , Ketema Indeshaw , Habte Sisay
Published: July 2022

Background

Urinary catheterization is one of the most common procedures performed in hospitals specifically, in the intensive care units and is associated with a high risk for acquired urinary tract infections. More than 70% of acquired urinary tract infections are due to catheter use. Nurses are the primary healthcare providers responsible for inserting and maintaining urinary catheters. The data regarding nurses’ knowledge, practice and associated factors towards prevention of catheter-associated urinary tract infections are limited in Ethiopia. Therefore, this study aimed to assess the knowledge, practice, and associated factors of nurses towards prevention of catheter-associated UTIs in the Intensive Care Unit (ICU) of public hospitals in Addis Ababa, Ethiopia.

Methods

An institutional-based descriptive cross-sectional study was conducted from March 01 to April 15, 2021, among nurses working in the ICU of public hospitals in Addis Ababa, Ethiopia. All 204 nurses working in the ICU of four public hospitals were included in the study using the census sampling method. Data were collected using a pretested self-administered semi-structured questionnaire. Data were cleaned and entered into Epi data version 4.6 and analyzed using Statistical Package for Social Sciences version 26.0. Pearson Chi-square and Fischer exact tests were performed to see the association between independent and dependent variables. The level of significance is considered at P-value less than 0.05.

Results

A total of 184 nurses participated in the study, making a response rate of 90.2%. The mean (±SD) age of the study participant was 29.07(±4.78). The study findings showed that more than half (63.04%) of nurses had poor knowledge and 88(47.83%) of nurses had poor practice towards prevention of catheter-associated UTIs. In this study, there was a statistically significant association between professional work experience and nurses’ knowledge in preventing catheter-associated UTIs (at P-value = 0.031).

Conclusion

In this study, nurses’ knowledge and practice towards the prevention of catheter-associated urinary tract infection was relatively poor. Professional work experience had a significant statistical association with the level of knowledge. Therefore, increasing the knowledge of nurses through appropriate educational programs and training on the preventive measures of device-associated infections was recommended to prevent catheter-associated UTIs.
Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway
Authors: Xu Zhipeng , Chen Shuqiu , Liu Ruiji , Chen Hui , Xu Bin , Xu Weizhang , Chen Ming
Published: July 2022

Background

Increasing evidence has demonstrated that circular RNAs (circRNAs) are implicated in cancer progression. However, the aberrant expression and biological functions of circRNAs in clear cell renal cell carcinoma (cRCC) remain largely elusive.

Method

Differentially expressed circRNAs in cRCC were filtered via bioinformatics analysis. Aberrant circPOLR2A expression was validated in cRCC tissues and cell lines via qRT-PCR. Sanger sequencing was used to identify the backsplicing site of circPOLR2A. In vitro and in vivo functional experiments were performed to evaluate the role of circPOLR2A in cRCC malignancy. RNA pull-down, mass spectrometry, RIP, FISH and immunofluorescence assays were used to identify and validate the circPOLR2A-interacting proteins. Ubiquitination modification and interaction between proteins were detected via Co-IP and western blotting. The m6A modification in circPOLR2A was validated by the meRIP assay.

Results

Bioinformatics analysis revealed that circPOLR2A was highly expressed in cRCC tissues and metastatic cRCC tissues. CircPOLR2A expression was associated with tumor size and TNM stage in cRCC patients. In vitro and in vivo functional assays revealed that circPOLR2A accelerated cRCC cell proliferation, migration, invasion and angiogenesis, while inhibiting apoptosis. Further mechanistic research suggested that circPOLR2A could interact with UBE3C and PEBP1 proteins, and that UBE3C could act as a specific ubiquitin E3 ligase for the PEBP1 protein. The UBE3C/circPOLR2A/PEBP1 protein-RNA ternary complex enhanced the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein which could inactivate the ERK signaling pathway. Rescue experiments revealed that the PEBP1 protein was the functional downstream target of circPOLR2A. Furthermore, m6A modification in circPOLR2A was confirmed, and the m6A reader YTHDF2 could regulate circPOLR2A expression.

Conclusion

Our study demonstrated that circPOLR2A modulated the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein, and further activated the ERK pathway during cRCC progression and metastasis. The m6A reader, YTHDF2, regulated circPOLR2A expression in cRCC. Hence, circPOLR2A could be a potential target for the diagnosis and treatment of cRCC.
CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p
Authors: Xi Yong , Shen Yaxing , Wu Donglei , Zhang Jingtao , Lin Chengbin , Wang Lijie , Yu Chaoqun , Yu Bentong , Shen Weiyu
Published: July 2022

Rationale

Circular RNAs (circRNAs) have been demonstrated to contribute to esophageal cancer progression. CircBCAR3 (hsa_circ_0007624) is predicted to be differentially expressed in esophageal cancer by bioinformatics analysis. We investigated the oncogenic roles and biogenesis of circBCAR3 in esophageal carcinogenesis.

Methods

Functions of circBCAR3 on cancer cell proliferation, migration, invasion, and ferroptosis were explored using the loss-of-function assays. A xenograft mouse model was used to reveal effects of circBCAR3 on xenograft growth and lung metastasis. The upstream and downstream mechanisms of circBCAR3 were investigated by bioinformatics analysis and confirmed by RNA immunoprecipitation and luciferase reporter assays. The dysregulated genes in hypoxia-induced esophageal cancer cells were identified using RNA-seq.

Results

CircBCAR3 was highly expressed in esophageal cancer tissues and cells and its expression was increased by hypoxia in vitro. Silencing of circBCAR3 repressed the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro, as well as inhibited the growth and metastasis of esophageal xenograft in mice in vivo. The hypoxia-induced promotive effects on esophageal cancer cell migration and ferroptosis were rescued by circBCAR3 knockdown. Mechanistically, circBCAR3 can interact with miR-27a-3p by the competitive endogenous RNA mechanism to upregulate transportin-1 (TNPO1). Furthermore, our investigation indicated that splicing factor quaking (QKI) is a positive regulator of circBCAR3 via targeting the introns flanking the hsa_circ_0007624-formed exons in BCAR3 pre-mRNA. Hypoxia upregulates E2F7 to transcriptionally activate QKI.

Conclusion

Our research demonstrated that splicing factor QKI promotes circBCAR3 biogenesis, which accelerates esophageal cancer tumorigenesis via binding with miR-27a-3p to upregulate TNPO1. These data suggested circBCAR3 as a potential target in the treatment of esophageal cancer.

Graphical Abstract

Hypoxia induces the upregulation of E2F7, which transcriptionally activates QKI in esophageal cancer cells. QKI increases the formation of circBCAR3 by juxtaposing the circularized exons. CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.
Increased levels of a pro-inflammatory IgG receptor in the midbrain of people with schizophrenia
Authors: Petty A. , Glass L. J. , Rothmond D. A. , Purves-Tyson T. , Sweeney A. , Kondo Y. , Kubo S. , Matsumoto M. , Weickert C. Shannon
Published: July 2022

Background

There is growing evidence that neuroinflammation may contribute to schizophrenia neuropathology. Elevated pro-inflammatory cytokines are evident in the midbrain from schizophrenia subjects, findings that are driven by a subgroup of patients, characterised as a “high inflammation” biotype. Cytokines trigger the release of antibodies, of which immunoglobulin G (IgG) is the most common. The level and function of IgG is regulated by its transporter (FcGRT) and by pro-inflammatory IgG receptors (including FcGR3A) in balance with the anti-inflammatory IgG receptor FcGR2B. Testing whether abnormalities in IgG activity contribute to the neuroinflammatory abnormalities schizophrenia patients, particularly those with elevated cytokines, may help identify novel treatment targets.

Methods

Post-mortem midbrain tissue from healthy controls and schizophrenia cases (n = 58 total) was used to determine the localisation and abundance of IgG and IgG transporters and receptors in the midbrain of healthy controls and schizophrenia patients. Protein levels of IgG and FcGRT were quantified using western blot, and gene transcript levels of FcGRT, FcGR3A and FcGR2B were assessed using qPCR. The distribution of IgG in the midbrain was assessed using immunohistochemistry and immunofluorescence. Results were compared between diagnostic (schizophrenia vs control) and inflammatory (high vs low inflammation) groups.

Results

We found that IgG and FcGRT protein abundance (relative to β-actin) was unchanged in people with schizophrenia compared with controls irrespective of inflammatory subtype. In contrast, FcGRT and FcGR3A mRNA levels were elevated in the midbrain from “high inflammation” schizophrenia cases (FcGRT;p = 0.02, FcGR3A;p < 0.0001) in comparison to low-inflammation patients and healthy controls, while FcGR2B mRNA levels were unchanged. IgG immunoreactivity was evident in the midbrain, and approximately 24% of all individuals (control subjects and schizophrenia cases) showed diffusion of IgG from blood vessels into the brain. However, the intensity and distribution of IgG was comparable across schizophrenia cases and control subjects.

Conclusion

These findings suggest that an increase in the pro-inflammatory Fcγ receptor FcGR3A, rather than an overall increase in IgG levels, contribute to midbrain neuroinflammation in schizophrenia patients. However, more precise information about IgG-Fcγ receptor interactions is needed to determine their potential role in schizophrenia neuropathology.
Diagnosis and treatment of congenital tricuspid valve malformation in a case of monozygotic twins
Authors: Shen Pin , Xie Qin , Ma Runwei , Dong Yunxing , Wang Qiang , Sun Yi
Published: July 2022

Background

Congenital tricuspid valve malformations are known to occur, but tricuspid valve malformations associated with twins are rarely reported. We report this case from the point of view of a medical history, an auxiliary examination and a genetic pathogenesis to provide a reference for our peers.

Case presentation

We report a rare case of congenital heart disease in monozygotic twins of Hui nationality in Yunnan-Guizhou Plateau, they are normal conception. Twin 1 had Ebstein’s anomaly, and received surgical treatment and recovered satisfactorily. Twin 2 had only partial tricuspid septal prolapse, and pulmonary hypertension occurred during follow-up.

Conclusions

It is necessary to carry out individualized diagnosis and treatment for twins and follow-up observation by echocardiography for a long time. Choosing the right time for cardiac surgery is of great significance to the treatment of the disease.
Clinical manifestation, economic burden, and mortality in patients with transthyretin cardiac amyloidosis
Authors: Jang Suk-Chan , Nam Jin Hyun , Lee Seung-Ah , An Dasom , Kim Hye-Lin , Kwon Sun-Hong , Lee Eui-Kyung
Published: July 2022

Background

Transthyretin cardiac amyloidosis, also known as transthyretin cardiomyopathy (ATTR-CM) is a poorly-recognized disease with delayed diagnosis and poor prognosis. This nationwide population-based study aimed to identify disease manifestations, economic burden, and mortality of patients with ATTR-CM.

Methods

Data of newly diagnosed patients with ATTR-CM between 2013 and 2018 from the Korean National Health Insurance Service were used, covering the entire population. Patient characteristics included comorbidities, medical procedures, and medication. Healthcare resource utilization and medical costs were observed as measures of the economic burden. The Kaplan–Meier survival curve and years of potential life lost (YPLL) from the general population were estimated for disease burden with ATTR CM.

Results

A total of 175 newly diagnosed patients with ATTR-CM were identified. The most common cardiac manifestation was hypertension (51.3%), while the most common non-cardiac manifestation was musculoskeletal disease (68.0%). Mean medical costs at the post-cohort entry date were significantly higher than those at the pre-cohort entry date ($1,864 vs. $400 per patient per month (PPPM), p < 0.001). Of the total medical costs during the study period, the proportion of inpatients cost was 12.9 times higher than the outpatients cost ($1,730 and $134 PPPM, respectively). The median survival time was 3.53 years from the first diagnosis of ATTR-CM, and the mean (SD) YPLL was 13.0 (7.7).

Conclusions

Patients with ATTR-CM had short survival and high medical costs. To reduce the clinical and economic burdens, carefully examining manifestations of disease in patients can help with early diagnosis and treatment.
Impact of a digital manual for guidance on malignant hyperthermia: patient education
Authors: Rodrigues Gislene , de Andrade Pamela Vieira , dos Santos Joilson Moura , do Amaral José Luiz Gomes , da Silva Helga Cristina Almeida
Published: July 2022

Background

Malignant hyperthermia (MH) is a rare, hereditary disease with a hypermetabolic response to volatile anesthetics/succinylcholine. Susceptible patients face difficulties due to a lack of knowledge about MH. As informational materials could increase knowledge and adherence to prevention/therapy, digital information about rare diseases validated for patients is needed. Our objective was to evaluate the following: (1) the impact of digital manuals on the knowledge/quality of life of MH patients and (2) access to MH services.

Materials and methods

Fifty MH-susceptible patients filled out a virtual questionnaire twice (demographic/economic/clinical data, MH knowledge and impact on daily life, and SF-36 quality of life). Test groups 1 (n = 17) and 2 (n = 16) were evaluated 30 and 180 days after receiving a digital manual, and the control group (n = 17; without manual) was evaluated after 180 days. We collected the MH service data about the number of contacts.

Results

Twenty-four (48%) patients reported problems in personal/professional life, sports, clinical/surgical/dental treatments, and military service, in addition to concerns about emergency care and complaints of sequelae. The percentage of correct answers in the second MH knowledge questionnaire increased for test group 2 (62% vs. 74.1%; unpaired t test, p < 0.01), was significantly greater in test groups 1 (68.1%) and 2 (74.1%) than in the control group (56.5%; Kruskal–Wallis, p < 0.05), and correlated with more time studying the manual and reports of MH-related problems (multiple regression, p < 0.05).

Conclusions

The digital manual improved patients’ MH knowledge. Online contacts with the MH service increased, allowing greater information dissemination. As informational materials could increase knowledge/adherence to prevention/therapy, digital information about MH validated for patients should be implemented.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
Authors: Bowles Kathryn R. , Pugh Derian A. , Liu Yiyuan , Patel Tulsi , Renton Alan E. , Bandres-Ciga Sara , Gan-Or Ziv , Heutink Peter , Siitonen Ari , Bertelsen Sarah , Cherry Jonathan D. , Karch Celeste M. , Frucht Steven J. , Kopell Brian H. , Peter Inga , Park Y. J. ,   International Parkinson’s Disease Genomics Consortium (IPDGC), Charney Alexander , Raj Towfique , Crary John F. , Goate A. M.
Published: July 2022

Background

Parkinson’s disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified.

Methods

To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain tissue.

Results

We identified three novel H1 sub-haplotype blocks across the 17q21.31 locus associated with PD risk. Protective sub-haplotypes were associated with increased LRRC37A/2 copy number and expression in human brain tissue. We found that LRRC37A/2 is a membrane-associated protein that plays a role in cellular migration, chemotaxis and astroglial inflammation. In human substantia nigra, LRRC37A/2 was primarily expressed in astrocytes, interacted directly with soluble α-synuclein, and co-localized with Lewy bodies in PD brain tissue.

Conclusion

These data indicate that a novel candidate gene, LRRC37A/2, contributes to the association between the 17q21.31 locus and PD via its interaction with α-synuclein and its effects on astrocytic function and inflammatory response. These data are the first to associate the genetic association at the 17q21.31 locus with PD pathology, and highlight the importance of variation at the 17q21.31 locus in the regulation of multiple genes other than MAPT and KANSL1, as well as its relevance to non-neuronal cell types.
Eraldo Antonini Lectures, 1983–2019
Authors: Brunori Maurizio
Published: July 2022

“Can order spring from Chaos?” is the title of an extensive Report on Italian science published by NATURE on 12 May 1983 and written by Robert Walgate, the Chief European Correspondent. It is a twenty pages complete paper touching all aspects of the struggle of Italian scientists to work in the “curious amalgam of ingenuity and muddle, a reflection of the political system”. (Nature, 1983; 303: 109–128). To read it after four decades is interesting but somewhat depressing since the main problems unfolded in the paper have not been solved, starting with the largely insufficient support of fundamental curiosity driven research. At page 114 you could find a item called: ITALY’s TOP SCIENTISTS: Four in the top one thousand. The Author refers to the data reported by the ISI (Institute of Scientific Information) that took two years to scan 3,000 major journals over the period 1965–78 and covered 5 millions articles and 67 millions references. The four top Italian scientists working in Italy were: Eraldo Antonini (3127 citations), Enrico Clementi (4001), Silvio Garattini (2833), and Giorgio Giacomelli (2483); 3 out of four were 52 years old, and one 55. Antonini did not see the Report since he passed away on March 18, 1983. However the information leaked before the publication of Nature because I remember the Messaggero of Rome reporting a whole page with the ranking of the four Italians, and even a picture of Eraldo. The students of the first year Medical course, his Class, welcomed the Professor with a standing ovation. After a short time the Board of the SIB (Società Italiana di Biochimica) casted a unanimous vote in favour of the motion of President Noris Siliprandi to begin the annual Congress with an Antonini Lecture, forever. As reported below, the tradition began immediately at the Congress in Saint-Vicent, Italy, and is continuing. In this paper I report an account of the Eraldo Antonini Lectures that I attended over the years and until September 2019, a few months before the pandemics lock down.
IL-6 gene rs1800795 polymorphism and diabetes mellitus: a comprehensive analysis involving 42,150 participants from a meta-analysis
Authors: Cheng Zhiying , Zhang Chunmin , Mi Yuanyuan
Published: July 2022

Background

Over the past two decades, several studies have focused on the association between a common polymorphism (rs1800795) from interleukin-6 (IL-6) gene and Diabetes Mellitus (DM) risk. However, the results remain ambiguous and indefinite.

Methods

A comprehensive analysis was performed to explore this relationship. A search was conducted in the PubMed, Embase, Chinese (CNKI and Wanfang), and GWAS Catalog databases, covering all publications until February 10, 2022. Odds ratios (OR) with 95% confidence intervals (CI) were used to evaluate the strength of the association. Publication bias was assessed using both Begg and Egger tests.

Results

Overall, 34 case–control studies with 7257 T2DM patients and 15,598 controls, and 12 case–control studies (10,264 T1DM patients and 9031 health controls) were included in the analysis. A significantly lower association was observed between the rs1800795 polymorphism and T2DM risk in Asians, mixed population, and hospital-based (HB) subgroups (C-allele vs. G-allele: OR = 0.76, 95% CI  0.58–0.99, P = 0.039 for Asians; CG vs. GG: OR = 0.74, 95% CI  0.58–0.94, P = 0.014 for mixed population; CC vs. GG: OR = 0.61, 95% CI  0.41–0.90, P = 0.014 for HB). However, increased associations were found from total, mixed population, and HB subgroups between rs1800795 polymorphism and T1DM susceptibility (CG vs. GG: OR = 1.32, 95% CI 1.01–1.74, P = 0.043 for total population, CC vs. GG: OR = 2.45, 95% CI 1.18–5.07, P = 0.016 for mixed individuals; C-allele vs. G-allele: OR = 1.29, 95% CI 1.07–1.56, P = 0.0009 for HB subgroup).

Conclusions

In summary, there is definite evidence to confirm that IL-6 rs1800795 polymorphism is associated with susceptibility to decreased T2DM and increased T1DM.
Bilateral simultaneous asymmetric hip fracture without major trauma in an elderly patient: a case report
Authors: Takagi Yasutaka , Yamada Hiroshi , Ebara Hidehumi , Hayashi Hiroyuki , Inatani Hiroyuki , Toyooka Kazu , Ima Musashi , Kitano Yoshiyuki , Ryu Yasuji , Nakanami Aki , Yahata Tetsutaro , Tsuchiya Hiroyuki
Published: July 2022

Background

Simultaneous bilateral hip fractures without major trauma in the elderly are rare and usually symmetrical. To the best of our knowledge, only two cases of bilateral simultaneous asymmetric hip fracture in the elderly without major trauma have been reported.

Case presentation

We present the case of a 90-year-old Japanese man with simultaneous bilateral asymmetric hip fractures with trochanteric fracture on the right side and greater trochanteric fracture on the left side. He complained of dyspnea at midnight and was referred to our emergency department. He was admitted to the internal medicine department for bacterial pneumonia treatment. On the 8th day of hospitalization, he was referred to our orthopedic surgery department for hip pain and was found to have fractures of both hips. Computed tomography findings showed that the left femoral neck fracture was an old fracture, while the left greater trochanteric fracture and the right trochanteric fracture were fresh fractures. He was surgically treated through open reduction and internal fixation with an intramedullary nail on the right and hemiarthroplasty on the left in supine position, performed during the same surgical sessions on the 12th day of hospitalization.

Conclusions

We report a new form of simultaneous bilateral asymmetric hip fracture in the elderly. The fracture types of the case were femoral trochanteric fracture and greater trochanteric fracture of the femur, which were different from the fracture types in the previously reported two cases. Clinicians should be aware of the possibility of simultaneous bilateral hip fractures, especially in the elderly.
Reproducing ancient Chinese ink depending on gelatin/chitosan and modern experimental methodology
Authors: Liu Zhen , Liu Kun
Published: July 2022

Chinese ink has very special significance for presentation of artistic effects and preservation of works of art; however, wasted nonrenewable resources, potential toxicity, and complex and inefficient production technologies have limited the development of inks for traditional Chinese culture. Herein, environmentally friendly, practical and antibacterial Chinese ink was prepared by facile heating-stirring of gelatin and the natural polysaccharide chitosan. The internal composition, viscosity, morphology, particle size and antibacterial properties of the ink were characterized by Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and bacteriostatic zone tests. The results showed that commercial ink (CM) spread easily on Xuan paper and led to imperfect artwork, while the chitosan and gelatin ink (CG) showed good adhesion and stability on Xuan paper. Based on this study, we believe that the good performance of CG ink should be attributed to restrictions arising from its internal chitosan and gelatin network, which restrict diffusion. Finally, the author used CG ink to display traditional Chinese calligraphy and landscape painting and believes that it has significant application prospects and will be used in large-scale production.
Simulating Colorectal Cancer Trials Using Real-World Data
Authors: Chen Zhaoyi , Zhang Hansi , George Thomas J. , Guo Yi , Prosperi Mattia , Guo Jingchuan , Braithwaite Dejana , Wang Fei , Kibbe Warren , Wagner Lynne , Bian Jiang
Published: July 2022

PURPOSE

Using real-world data (RWD)–based trial simulation approach, we aim to simulate colorectal cancer (CRC) trials and examine both effectiveness and safety end points in different simulation scenarios.

METHODS

We identified five phase III trials comparing new treatment regimens with an US Food and Drug Administration–approved first-line treatment in patients with metastatic CRC (ie, fluorouracil, leucovorin, and irinotecan) as the standard-of-care (SOC) control arm. Using Electronic Health Record–derived data from the OneFlorida network, we defined the study populations and outcome measures using the protocols from the original trials. Our design scenarios were (1) simulation of the SOC fluorouracil, leucovorin, and irinotecan arm and (2) comparative effectiveness research (CER) simulation of the control and experimental arms. For each scenario, we adjusted for random assignment, sampling, and dropout. We used overall survival (OS) and severe adverse events (SAEs) to measure effectiveness and safety.

RESULTS

We conducted CER simulations for two trials, and SOC simulations for three trials. The effect sizes of our simulated trials were stable across all simulation runs. Compared with the original trials, we observed longer OS and higher mean number of SAEs in both CER and SOC simulation. In the two CER simulations, hazard ratios associated with death from simulations were similar to that reported in the original trials. Consistent with the original trials, we found higher risk ratios of SAEs in the experiment arm, suggesting potentially higher toxicities from the new treatment regimen. We also observed similar SAE rates across all simulations compared with the original trials.

CONCLUSION

In this study, we simulated five CRC trials, and tested two simulation scenarios with several different configurations demonstrated that our simulations can robustly generate effectiveness and safety outcomes comparable with the original trials using real-world data.
Chimera states in coupled memristive chaotic systems: Effects of control parameters
Authors: Ramamoorthy Ramesh , Shahriari Zahra , Natiq Hayder , Rajagopal Karthikeyan , Li Chunbiao
Published: July 2022

The study of the collective behavior of oscillators has attracted great attention in recent years. Among all dynamical systems, multi-stable systems have received particular attention. This paper considers a ring network of non-locally coupled VB5 chaotic systems exhibiting multistability with linear coupling. The collective patterns of the oscillators are investigated by taking various internal parameters of memristors as the bifurcation parameter. The network's state is characterized by computing the strength of incoherence. Moreover, the variations of the coupling strength and the number of neighbors in connections are considered to check out the coupling effects. The synchronous, chimera, and asynchronous states are visible in the network under different parameters. It is observed that as the dynamics of the oscillators become more complex, the behavior of the network transits to more asynchrony. The results also show that the network represents the chimera state both in monostable and multistable modes. In monostable mode, the oscillators of the synchronized and asynchronized groups belong to one attractor. In contrast, in the multistable mode, each group oscillates in one of the existing attractors.
Generalized quantum oscillator under harmonic-type central potential effects induced by Lorentz symmetry violation environment(a)
Authors: Ahmed Faizuddin
Published: July 2022

In this paper, we study a relativistic quantum oscillator model via the generalized Klein-Gordon oscillator equation under harmonic-type central potential effects induced by the violation of the Lorentz symmetry. We determine solutions of the wave equation for Coulomb- and Cornell-type potential functions using the Nikiforov-Uvarov method and analyze the effects on the energy profile and the wave function of the oscillator fields.