bluuebunny/crossref_metadata_2025 huggingface dataset:
An e-consent framework for tiered informed consent for human genomic research in the global south, implemented as a REDCap template
Authors: Tamuhla Tsaone , Tiffin Nicki , Allie Taryn
Published: November 2022

Research involving human participants requires their consent, and it is common practice to capture consent information on paper and store those hard copies, presenting issues such as long-term storage requirements, inefficient retrieval of consent forms for reference or future use, and the potential for transcription errors when transcribing captured informed consent. There have been calls to move to electronic capture of the consent provided by research participants (e-consent) as a way of addressing these issues. A tiered framework for e-consent was designed using the freely available features in the inbuilt REDCap e-consent module. We implemented ‘branching logic’, ‘wet signature’ and ‘auto-archiver’ features to the main informed consent and withdrawal of consent documents. The branching logic feature streamlines the consent process by making follow-up information available depending on participant response, the ‘wet signature’ feature enables a timestamped electronic signature to be appended to the e-consent documents and the ‘auto-archiver’ allows for PDF copies of the e-consent documents to be stored in the database. When designing the content layout, we provided example participant information text which can be modified as required. Emphasis was placed on the flow of information to optimise participant understanding and this was achieved by merging the consent and participant information into one document where the consent questions were asked immediately after the corresponding participant information. In addition, we have provided example text for a generic human genomic research study, which can be easily edited and modified according to specific requirements. Building informed consent protocols and forms without prior experience can be daunting, so we have provided researchers with a REDCap template that can be directly incorporated into REDCap databases. It prompts researchers about the types of consent they can request for genomics studies and assists them with suggestions for the language they might use for participant information and consent questions. The use of this tiered e-consent module can ensure the accurate and efficient electronic capture and storage of the consents given by participants in a format that can be easily queried and can thus facilitate ethical and effective onward sharing of data and samples whilst upholding individual participant preferences.
Nurse-led consultations reinforced with eHealth technology: a qualitative study of the experiences of patients with gynecological cancer
Authors: Skorstad Mette , Vistad Ingvild , Fegran Liv , Berntsen Sveinung , Johannessen Berit
Published: November 2022

Background

During the last decade, the health care profession has moved toward personalized care and has focused on the diversity of survivorship needs after initial cancer treatment. Health care providers encourage empowering patients to participate actively in their own health management and survivorship. Consequently, we developed and piloted a new follow-up model for patients at a Norwegian hospital, referred to as the Lifestyle and Empowerment Techniques in Survivorship of Gynecologic Oncology (LETSGO) model. Using LETSGO, a dedicated nurse replaces the physician in every second follow-up consultation, providing patients who have undergone cancer treatment with self-management techniques that are reinforced with eHealth technology via a specially designed app. Encouraging behavioral change and evaluating the late effects of treatment and recurrence symptoms are central components of self-management techniques. In addition, the app encourages physical activity and positive lifestyle changes, helps identify recurrence-related symptoms, and provides reminders of activity goals. This study aims to investigate experiences with nurse-led consultations supported by eHealth technology among the patients who piloted the LETSGO intervention.

Methods

Semi-structured qualitative interviews were conducted to analyze the participants’ experiences with the LETSGO intervention after six to seven months.

Results

The participants in the LETSGO pilot felt safe and well cared for. They thought the nurse was less busy than the doctors appear to be, which made it easy for them to share any cancer-related challenges. Many participants reported increased empowerment and confidence in recognizing symptoms of cancer recurrence, and participants who used the app regularly were motivated to increase their physical activity levels. However, the participants also experienced some limitations and technical errors with the app.

Conclusions

Generally, the participants positively received the nurse-led consultations and eHealth technology, but an intervention study is required for further evaluation. In addition, the reported technical app errors should be resolved and tested prior to eHealth application implementation. Regardless, this study may be useful in planning personalized survivorship care studies.

Trial registration

ClinicalTrials.gov,NCT03453788. Registration March 5, 2018.
Medicine in older age—perception and assessment of ageing processes by older people and medical and nursing professionals: study protocol for a qualitative focus group design (FOR TiMed_Life)
Authors: Kleinert Evelyn , Mohacsi Laura , Heim Susanne , Hummers Eva
Published: November 2022

Background

This study is conducted by a subproject of the DFG research group "Medicine, Time and the Good Life" FOR 5022 (FOR TiMed_Life) and investigates the care preferences of individuals of advanced age and the care priorities of medical and nursing professionals in times of increasing medical options and more complex decision-making processes, especially for elderly patients. We assume that the preference for or rejection of medical treatment is shaped by individual and social age patterns and by the awareness of the finiteness of life. Just like older people themselves, professionals are also influenced by societal images of age(ing) and associated notions of age-appropriate health. These concepts are subject to constant change, which means that what was considered to be a 'normal' symptom of older age 100 years ago is now treated medically as a disease. The aim of the study is to identify the underlying perceptions of ageing and their influence on medical decisions.

Methods

By means of semi-structured focus group discussions and supplementary individual interviews with older people and medical and nursing professionals, the subproject investigates the perception of ageing processes and the resulting care preferences and priorities of these three groups. The evaluation of the interview material is carried out in two stages: First, the recorded group discussions are pre-structured using knowledge mapping. Based on the mapping results, the interview passages are selected, transcribed, and analysed in detail based on qualitative content analysis.

Discussion

Because the nature of the research question is exploratory, qualitative methods provide a suitable approach. The mapping technique provides early initial results that are used by the other subprojects. Within the research group, the results of the interviews provide an empirical basis for ethical discourses on the influence of medicine on ideas of a good life, and in particular, on successful ageing.

Trial registration

German Clinical Trials Register: DRKS00027076, 05/11/2021.
Development and initial testing of a multi-stakeholder intervention for Lynch syndrome cascade screening: an intervention mapping approach
Authors: Passero Lauren , Srinivasan Swetha , Grewe Mary E. , Leeman Jennifer , Berg Jonathan , Reuland Daniel , Roberts Megan C.
Published: November 2022

Background

Lynch syndrome is an underdiagnosed hereditary condition carrying an increased lifetime risk for colorectal and endometrial cancer and affecting nearly 1 million people in the United States. Cascade screening, systematic screening through family members of affected patients, could improve identification of Lynch syndrome, but this strategy is underused due to multi-level barriers including low knowledge about Lynch syndrome, low access to genetics services, and challenging family dynamics.

Methods

We used intervention mapping, a 6-step methodology to create stakeholder-driven interventions that meet the needs of a target population, to develop an intervention to improve cascade screening for Lynch syndrome. The intervention development process was guided by input from key stakeholders in Lynch syndrome care and patients. We conducted usability testing on the intervention with Lynch syndrome patients using qualitative semi-structured interviewing and rapid qualitative analysis.

Results

We developed a workbook intervention named Let’s Talk that addresses gaps in knowledge, skills, self-efficacy, outcome expectancy and other perceived barriers to cascade screening for Lynch syndrome. Let’s Talk contained educational content, goal setting activities, communication planning prompts and supplemental resources for patients to plan family communication. Evidence-based methods used in the workbook included information chunking, guided practice, goal setting and gain-framing. We conducted usability testing focused on the complexity and relative advantage of the intervention through 45-min virtual interviews with 10 adult patients with Lynch syndrome recruited from a national advocacy organization in the United States. Usability testing results suggested the intervention was acceptable in terms of complexity and relative advantage to other available resources, but additional information for communication with young or distant family members and a web-based platform could enhance the intervention’s usability.

Conclusions

Intervention mapping provided a framework for intervention development that addressed the unique needs of Lynch syndrome patients in overcoming barriers to cascade screening. Future work is needed to transform Let’s Talk into a web-based tool and evaluate the effectiveness of the intervention in clinical practice with patients and genetic counselors. Intervention mapping can be useful to researchers as an evidence-based technique to develop stakeholder-centered interventions for addressing the needs of other unique populations.
Effective hospital readmission prediction models using machine-learned features
Authors: Davis Sacha , Zhang Jin , Lee Ilbin , Rezaei Mostafa , Greiner Russell , McAlister Finlay A. , Padwal Raj
Published: November 2022

Background:

Hospital readmissions are one of the costliest challenges facing healthcare systems, but conventional models fail to predict readmissions well. Many existing models use exclusively manually-engineered features, which are labor intensive and dataset-specific. Our objective was to develop and evaluate models to predict hospital readmissions using derived features that are automatically generated from longitudinal data using machine learning techniques.

Methods:

We studied patients discharged from acute care facilities in 2015 and 2016 in Alberta, Canada, excluding those who were hospitalized to give birth or for a psychiatric condition. We used population-level linked administrative hospital data from 2011 to 2017 to train prediction models using both manually derived features and features generated automatically from observational data. The target value of interest was 30-day all-cause hospital readmissions, with the success of prediction measured using the area under the curve (AUC) statistic.

Results:

Data from 428,669 patients (62% female, 38% male, 27% 65 years or older) were used for training and evaluating models: 24,974 (5.83%) were readmitted within 30 days of discharge for any reason. Patients were more likely to be readmitted if they utilized hospital care more, had more physician office visits, had more prescriptions, had a chronic condition, or were 65 years old or older. The LACE readmission prediction model had an AUC of 0.66 ± 0.0064 while the machine learning model’s test set AUC was 0.83 ± 0.0045, based on learning a gradient boosting machine on a combination of machine-learned and manually-derived features.

Conclusion:

Applying a machine learning model to the computer-generated and manual features improved prediction accuracy over the LACE model and a model that used only manually-derived features. Our model can be used to identify high-risk patients, for whom targeted interventions may potentially prevent readmissions.
Noninvasive detection of pancreatic ductal adenocarcinoma using the methylation signature of circulating tumour DNA
Authors: Wu Huanwen , Guo Shiwei , Liu Xiaoding , Li Yatong , Su Zhixi , He Qiye , Liu Xiaoqian , Zhang Zhiwen , Yu Lianyuan , Shi Xiaohan , Gao Suizhi , Wang Huan , Pan Yaqi , Ma Chengcheng , Liu Rui , Dai Menghua , Jin Gang , Liang Zhiyong
Published: November 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood.

Methods

Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility.

Results

In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001).

Conclusions

The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.

Graphic Abstract
Does intraoperative cyst rupture of malignant cystic renal masses really have no negative impact on oncologic outcomes?
Authors: Xu Peirong , Zhang Sihong , Cao Bohong , Huang Jiaqi , Li Yaohui , Cheng Jiangting , Lin Wenyao , Cheng Jie , Chen Weijie , Zhu Yanjun , Jiang Shuai , Hu Xiaoyi , Guo Jianming , Wang Hang
Published: November 2022

Background

To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes.

Methods

The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture.

Results

Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839–29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804–36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183–42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018–0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029).

Conclusions

Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.
Assessment of antibody responses against SARS-CoV-2 in unvaccinated individuals and vaccinees from Omicron-BA.2 infection in Zhaoqing, Guangdong Province, China
Authors: Zhang Huan , Jiang Yushan , Tan Hanqing , Zou Lirong , Zheng Zhonghua , Huang Yushi , Lin Shujian , Su Lebin , Yu Jianxiang , Deng Xiaoling , He Jianfeng , Liu Chang , Shen Chenguang , Li Baisheng
Published: November 2022

Currently, the majority of the global population has been vaccinated with the COVID-19 vaccine, and characterization studies of antibodies in vivo from Omicron breakthrough infection and naive infection populations are urgently needed to provide pivotal clues about accurate diagnosis, treatment, and next-generation vaccine design against SARS-CoV-2 infection. We showed that after infection with Omicron-BA.2, the antibody levels of specific IgM against the Wuhan strain and specific IgG against Omicron were not significantly elevated within 27 days of onset. Interestingly, in this study, the levels of humoral immunity against Omicron-specific IgM were significantly increased after breakthrough infection, suggesting that the detection of Omicron-specific IgM antibodies can be used as a test criterion of Omicron breakthrough infection. In addition, we observed that serums from unvaccinated individuals and the majority of vaccinated infections possessed only low or no neutralizing activity against Omicron at the onset of Omicron breakthrough infections, and at the later stage of Omicron-BA.2 breakthrough infection, levels of neutralization antibody against the Wuhan and Omicron strains were elevated in infected individuals. The findings of this study provide important clues for the diagnosis of Omicron breakthrough infections, antibody characterization studies and vaccine design against COVID-19.
Transcriptomic analysis of a 3D blood–brain barrier model exposed to disturbed fluid flow
Authors: Bouhrira Nesrine , DeOre Brandon J. , Tran Kiet A. , Galie Peter A.
Published: November 2022

Cerebral aneurysms are more likely to form at bifurcations in the vasculature, where disturbed fluid is prevalent due to flow separation at sufficiently high Reynolds numbers. While previous studies have demonstrated that altered shear stress exerted by disturbed flow disrupts endothelial tight junctions, less is known about how these flow regimes alter gene expression in endothelial cells lining the blood–brain barrier. Specifically, the effect of disturbed flow on expression of genes associated with cell–cell and cell–matrix interaction, which likely mediate aneurysm formation, remains unclear. RNA sequencing of immortalized cerebral endothelial cells isolated from the lumen of a 3D blood–brain barrier model reveals distinct transcriptional changes in vessels exposed to fully developed and disturbed flow profiles applied by both steady and physiological waveforms. Differential gene expression, validated by qRT-PCR and western blotting, reveals that lumican, a small leucine-rich proteoglycan, is the most significantly downregulated gene in endothelial cells exposed to steady, disturbed flow. Knocking down lumican expression reduces barrier function in the presence of steady, fully developed flow. Moreover, adding purified lumican into the hydrogel of the 3D blood–brain barrier model recovers barrier function in the region exposed to fully developed flow. Overall, these findings emphasize the importance of flow regimes exhibiting spatial and temporal heterogeneous shear stress profiles on cell–matrix interaction in endothelial cells lining the blood–brain barrier, while also identifying lumican as a contributor to the formation and maintenance of an intact barrier.
Prevalence and impact of peer victimisation among youth seeking treatment at a tertiary psychiatric institution in Singapore: a cross-sectional study
Authors: Subramaniam Mythily , Shahwan Shazana , Abdin Edimansyah , Verma Swapna , Gupta Bhanu , Chua Boon Yiang , Zhang Yunjue , Sambasivam Rajeswari , Chong Siow Ann
Published: November 2022

Background

Peer victimization is common among adolescents and leads to negative consequences. However, few studies have examined the extent of peer-victimization and its correlates among adolescent patients in a psychiatric setting. The current study aimed to examine the prevalence and correlates of peer victimisation among youth with mental illness and to examine its association with depressive symptoms and health-related quality of life (HRQOL).

Methods

A sample of 239 youths aged 15–24 years were recruited from the outpatient clinics of a tertiary psychiatric hospital in Singapore using convenience sampling. All participants were administered the Multidimensional Peer Victimisation Scale (MPVS), Short Form 12 (SF-12) questionnaire and the Patient Health Questionnaire-8 (PHQ-8). The effect of MPVS  total and subscores on depression scores, quality of life subscores and quality of life total scores were examined using multiple linear regression analyses.

Results

The majority of the patients reported that they had experienced at least one form of peer victimisation (95.8%, n = 229) during their school years. Higher levels of ‘verbal victimisation’, ‘attacks on property’ and higher total MPVS scores were significantly associated with lower social functioning; additionally, higher levels of ‘verbal victimisation’ were significantly associated with lower mental component summary scores in the quality of life assessment. Higher scores on all four subscales as well as higher total scores on the MPVS were significantly associated with more severe depressive symptoms.

Conclusions

Given the high prevalence of peer victimisation in our sample and its associations with more severe depressive symptoms and lower quality of life, it is vital to implement interventions that prevent peer victimisation in educational and other social settings and to provide youth with strategies to more effectively manage instances of peer victimisation.
Exclusive breastfeeding rate and related factors among mothers within maternal health WeChat groups in Jiaxing, Zhejiang province, China: a cross-sectional survey
Authors: Fu Chun-Yan , Tang Xue-Juan , Pan Ling-Pei , Jin Hai-Ying , Yao Juan-Feng , Wang Li-Zhong
Published: November 2022

Background

The health workers in Jiaxing of China have established maternal health WeChat groups for maternal health education and management since 2019. Pregnant women in Jiaxing are invited to join the WeChat groups and a health worker as the group manager provides health education and individual counselling for women within the group. This study aimed to investigate the exclusive breastfeeding (EBF) status up to six months and its associated factors among the mothers of infants aged 7-12 months within the WeChat groups.

Methods

This was a cross-sectional survey on healthy mothers with infants aged 7-12 months from seven maternal health WeChat groups in October 2021 in Jiaxing, China. EBF was defined as breastfeeding infants exclusively up to six months. Data including breastfeeding practice from birth to six months, maternal sociodemographic and obstetric characteristics, hospitalization information, work related factors and reasons for non-EBF up to six months were collected using an online self-administered questionnaire. A multivariable logistic regression analysis was performed to identify the factors independently associated with EBF up to 6 months.

Results

A total of 822 mothers were included in this study. Among them, 586 mothers (71.3%) exclusively breastfed infants up to six months. Multivariable logistic regression analysis showed that older maternal age (adjusted odds ratio [AOR] 0.956; 95% confidence interval [CI] 0.917, 0.997) and perceived insufficient breast milk (AOR 0.104; 95% CI 0.072, 0.149) were associated with lower odds of EBF up to six months. The five of common reasons for non-EBF up to six months were no or insufficient breast milk (59.8%), return to work (23.9%), no flexible nursing breaks at work (18.2 %), infant crying or feeling tired or troubled with breastfeeding (9.7%), and nipple and breast problems (9.3%).

Conclusion

About 71.3% of infants were exclusively breastfed until six months of age in our WeChat groups. Perceived insufficient breast milk and work related factors are the main barriers to EBF up to six months in this setting. However, further comparative study is needed to confirm the effect of WeChat groups on breastfeeding.
Stimulant use disorder diagnosis and opioid agonist treatment dispensation following release from prison: a cohort study
Authors: Palis Heather , Zhao Bin , Young Pam , Korchinski Mo , Greiner Leigh , Nicholls Tonia , Slaunwhite Amanda
Published: November 2022

Background

Concurrent opioid and stimulant use is on the rise in North America. This increasing trend of use has been observed in the general population, and among people released from prison in British Columbia (BC), who face an elevated risk of overdose post-release. Opioid agonist treatment is an effective treatment for opioid use disorder and reduces risk of overdose mortality. In the context of rising concurrent stimulant use among people with opioid use disorder, this study aims to investigate the impact of stimulant use disorder on opioid agonist treatment dispensation following release from prison in BC.

Methods

Linked health and corrections records were retrieved for releases between January 1st 2015 and December 29th 2018 (N = 13,380). Hospital and primary-care administrative health records were used to identify opioid and stimulant use disorder and mental illness. Age, sex, and health region were derived from BC’s Client Roster. Incarceration data were retrieved from provincial prison records. Opioid agonist treatment data was retrieved from BC’s provincial drug dispensation database. A generalized estimating equation produced estimates for the relationship of stimulant use disorder and opioid agonist treatment dispensation within two days post-release.

Results

Cases of release among people with an opioid use disorder were identified (N = 13,380). Approximately 25% (N = 3,328) of releases ended in opioid agonist treatment dispensation within two days post-release. A statistically significant interaction of stimulant use disorder and mental illness was identified. Stratified odds ratios (ORs) found that in the presence of mental illness, stimulant use disorder was associated with lower odds of obtaining OAT [(OR) = 0.73, 95% confidence interval (CI) = 0.64–0.84)] while in the absence of mental illness, this relationship did not hold [OR = 0.89, 95% CI = 0.70–1.13].

Conclusions

People with mental illness and stimulant use disorder diagnoses have a lower odds of being dispensed agonist treatment post-release compared to people with mental illness alone. There is a critical need to scale up and adapt opioid agonist treatment and ancillary harm reduction, and treatment services to reach people released from prison who have concurrent stimulant use disorder and mental illness diagnoses.
Risk factors for insufficient reduction after short-segment posterior fixation for thoracolumbar burst fractures: Does the interval from injury onset to surgery affect reduction of fractured vertebrae?
Authors: Aono Hiroyuki , Takenaka Shota , Okuda Akinori , Kikuchi Takeshi , Takeshita Hiroshi , Nagata Keiji , Ito Yasuo
Published: November 2022

Background

Many surgeons have encountered patients who could not immediately undergo surgery to treat spinal fractures because they had associated injuries and/or because a complete diagnosis was delayed. For such patients, practitioners might assume that delays could mean that the eventual reduction would be insufficient. However, no report covered risk factors for insufficient reduction of fractured vertebra including duration from injury onset to surgery. The purpose of this study is to investigate the risk factors for insufficient reduction after short-segment fixation of thoracolumbar burst fractures.

Methods

Our multicenter study included 253 patients who sustained a single thoracolumbar burst fracture and underwent short-segment fixation. We measured the local vertebral body angle (VBA) on roentgenograms, before and after surgery, and then calculated the reduction angle and reduction rate of the fractured vertebra by using the following formula: $$\left[ {\left( {{\text{Preoperative}}\;{\text{VBA }}{-}{\text{ Postoperative}}\;{\text{VBA}}} \right)/{\text{Preoperative}}\;{\text{VBA}}} \right] \, \times \, 100.$$

Preoperative

VBA

-

Postoperative

VBA

/
Preoperative

VBA

×

100
.

A multiple logistical regression analysis was performed to identify risk factors for insufficient reduction. The factors that we evaluated were age, gender, affected spine level, time elapsed from injury to surgery, inclusion of vertebroplasty with surgery, load-sharing score (LSS), AO classification (type A or B), preoperative VBA, and the ratio of canal compromise before surgery.

Results

There were 140 male and 113 female patients, with an average age of 43 years, and the mean time elapsed between injury and surgery was 3.8 days. The mean reduction angle was 12°, and the mean reduction rate was 76%. The mean LSS was 6.4 points. Multiple linear regression analysis revealed that a higher LSS, a larger preoperative VBA, a younger age, and being female disposed patients to having a larger reduction angle and reduction rate. The time elapsed from injury to surgery had no relation to the quality of fracture reduction in the acute period.

Conclusions

Our findings indicate that if there is no neurologic deficit, we might not need to hurry surgical reduction of fractured vertebrae in the acute phase.
A superior articular process morphology of 5th lumbar vertebra prone to screws placement failure: an anatomical study of 299 patients
Authors: Liu Xiang-Ge , Liang Pei-Jie , Liu Han-Hui , Chen Guang-Fu , Zhao Xiao-Dong
Published: November 2022

Purposes

This study aimed to investigate whether the morphology of the superior articular processes of L5 vertebra affected the accuracy of pedicle screw placement by reviewing 299 patients who had undergone L5 pedicle screw fixation over the past 12 months and measuring relevant parameters.

Methods

We retrospectively analyzed patients who underwent L5 vertebra fixation at our spine surgery department from October 20, 2020 to October 20, 2021. Patients with spondylolisthesis, spondylolysis, and scoliosis were excluded. Parameters associated with the superior articular process were analyzed, including Mammillary process-Spinal canal Distance (MCD), Inter-Facet Distance (IFD), Inter-Pedicle Distance (IPD), Zygapophysial Joints Angle (ZJA), Superior Articular Width, and Lateral Recess Transverse Diameter. The L5 vertebral body was reconstructed by Mimics 21.0, and the simulated L5 screws were inserted at multiple entry points to measure the Maximum Safe Transverse Angle (STAmax).

Results

A total of 299 patients who underwent L5 vertebra fixation with 556 pedicle screws were analyzed. An MCD < 6 mm was associated with a significant increase in screw placement failure rate and decrease in ZJA. The MCD was positively correlated with IFD. No significant change in IPD was observed. Mimics software analysis showed that the STAmax decreased with a decrease of MCD. When WBV < 6 mm, 93% of the trans-mammillary vertical line was located within 50% of the pedicle.

Conclusions

The superior articular process tended to narrow the spinal canal and exhibit a steep and a “cloverleaf” morphology when the MCD was < 6 mm. This morphology increased the risk of operator mis-judgement resulting in screw placement failure. Assessment of the relationship between the trans-mammillary vertical line and the pedicle represents a simple method to predict abnormal morphology of the superior articular process before surgery.
Genetic variant in SPAG16 is associated with the susceptibility of ACPA-positive rheumatoid arthritis possibly via regulation of MMP-3
Authors: Lin Qingxi , Zhou Bingxiang , Song Xiaoxiao , Ye Wei , Li Qinglong , Shi Tong , Cheng Chen , Li Yetian , Wei Xing
Published: November 2022

Objectives

In two previously published genome-wide association studies, a cluster of variants of sperm-associated antigen16 (SPAG16) were reported to be associated with the radiological progression rate of ACPA-positive rheumatoid arthritis (RA) patients from North American and Southern European ancestry. In this study, we aimed to investigate whether the reported RA-risk loci in SPAG16 are associated with the disease in the Chinese population and to further validate the functional role of the susceptible locus in RA tissues.

Methods

A total of 500 ACPA-positive RA patients and 1000 age-matched healthy subjects were recruited. Two SNPs of SPAG16, including rs7607479 (C/T) and rs6435818 (A/C), were genotyped, and the genotyping data were compared with chi-square test. Gene expression analysis was performed in synovial tissues obtained from 40 RA patients and 30 non-RA controls surgically treated for bone fracture. The tissue expression of SPAG16 and matrix metalloproteinase 3 (MMP-3) was compared between the two groups by the Student’s t test. The relationship between serum indexes and mRNA expression of SPAG16 and MMP-3 were evaluated by Spearman’s correlation analysis.

Result

For rs7607479, the frequency of genotype TT was significantly higher in RA patients than in the controls (49.0% vs. 40.4%, p = 0.002). The RA patients were found to have significantly lower frequency of allele C than the controls (30.9% vs. 36.8%, p = 0.001). As for rs6435818, there was no significant difference of genotype or allele frequency between the two groups. The mRNA expression of MMP-3 was 1.63-fold higher in the RA patients than in the controls (p < 0.001). The expression of SPAG16 was comparable between the two groups (p = 0.43). The mRNA expression of MMP-3 was 1.39-fold higher in patients with genotype TT than in the patients with genotype CC (p = 0.006). The mRNA expression level of MMP-3 was significantly correlated with serum rheumatoid factor (r = 0.498, p < 0.001) and C-reactive protein (r = 0.272, p = 0.01), weakly correlated with erythrocyte sedimentation rate (r = 0.236, p = 0.09).

Conclusions

We validated a common genetic risk factor in ACPA-positive patients with RA, which is associated with the tissue production of MMP-3 and disease progression. Further functional analysis into the role of rs7607479 in MMP-3 expression can shed new light on the genetic architecture of ACPA-positive RA.
Preoperative inhalation therapy for patients with chronic obstructive pulmonary disease undergoing lung surgery: a retrospective study
Authors: Machino Ryusuke , Shimoyama Koichiro , Nagayasu Takeshi , Tagawa Tsutomu
Published: November 2022

Background

Research shows that even the short-term administration of inhaled drugs immediately before surgery can improve respiratory function in surgical candidates with chronic obstructive pulmonary disease (COPD). However, the long-term efficacies of different types of long-acting inhaled agents when used during a short preoperative period remain unclear. Therefore, we evaluated the efficacies of short-term, preoperative long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids with long-acting β2-agonists (ICSs/LABAs), and long-acting muscarinic antagonists with long-acting β2-agonists (LAMAs/LABAs) in patients with COPD after lung resection.

Methods

Patients who underwent anatomical lung resections between April 2010 and March 2020 were divided into the non-COPD (193 patients) and COPD (241 patients) groups. The COPD group underwent preoperative treatment with either a LAMA (51 patients), an ICS/LABA (112 patients), or a LAMA/LABA (78 patients) for almost 1 month, with pulmonary function tests performed initially, just before surgery, and at 1 and 6 months after surgery. Improvement in preoperative respiratory function by inhalation therapy and the maintenance of improvement in respiratory function after surgery were examined in each group.

Results

The COPD group had significantly higher proportions of men, older patients, smokers, and histopathologic types except for adenocarcinoma than the non-COPD group; however, there were neither differences in sex, age, percentage of smokers, or histopathologic type among the inhalant groups within the COPD group nor were there differences in percentage of GOLD stage, preoperative inhalation period, or percentage of resected lobes in lobectomy. Preoperative increases in forced expiratory volume in 1.0 s (FEV1.0) were significantly higher in the COPD group (129.07 ± 11.29 mL) than in the non-COPD group (-2.32 ± 12.93 mL) (p < 0.0001). At 6 months, there was no significant difference in residual FEV1.0 between the COPD-LAMA/LABA (2017.46 ± 62.43 mL) and non-COPD groups (2046.93 ± 40.53 mL). The FEV1.0 reduction rate was more suppressed in the COPD-LAMA/LABA group than in the non-COPD group at 1 and 6 months after surgery.

Conclusions

Short-term, preoperative, inhaled pharmacotherapies, particularly LAMAs/LABAs, were effective at improving respiratory function in patients with COPD; thus, these agents are recommended for use in this population.
Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury
Authors: Xu Han , Xu Sicong , Li Liyan , Wu Yuhuang , Mai Shiying , Xie Yiqiang , Tan Yinfeng , Li Ailing , Xue Fengming , He Xiaoning , Li Yonghui
Published: November 2022

Background

Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI.

Methods

Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays.

Results

DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered.

Conclusion

This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.

Graphical Abstract
Upregulation of Ca2+-binding proteins contributes to VTA dopamine neuron survival in the early phases of Alzheimer’s disease in Tg2576 mice
Authors: La Barbera Livia , Nobili Annalisa , Cauzzi Emma , Paoletti Ilaria , Federici Mauro , Saba Luana , Giacomet Cecilia , Marino Ramona , Krashia Paraskevi , Melone Marcello , Keller Flavio , Mercuri Nicola Biagio , Viscomi Maria Teresa , Conti Fiorenzo , D’Amelio Marcello
Published: November 2022

Background

Recent clinical and experimental studies have highlighted the involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons for the early pathogenesis of Alzheimer’s Disease (AD). We have previously described a progressive and selective degeneration of these neurons in the Tg2576 mouse model of AD, long before amyloid-beta plaque formation. The degenerative process in DA neurons is associated with an autophagy flux impairment, whose rescue can prevent neuronal loss. Impairments in autophagy can be the basis for accumulation of damaged mitochondria, leading to disturbance in calcium (Ca2+) homeostasis, and to functional and structural deterioration of DA neurons.

Methods

In Tg2576 mice, we performed amperometric recordings of DA levels and analysis of dopaminergic fibers in the Nucleus Accumbens – a major component of the ventral striatum precociously affected in AD patients – together with retrograde tracing, to identify the most vulnerable DA neuron subpopulations in the VTA. Then, we focused on these neurons to analyze mitochondrial integrity and Apoptosis-inducing factor (AIF) localization by electron and confocal microscopy, respectively. Stereological cell count was also used to evaluate degeneration of DA neuron subpopulations containing the Ca2+-binding proteins Calbindin-D28K and Calretinin. The expression levels for these proteins were analyzed by western blot and confocal microscopy. Lastly, using electrophysiology and microfluorometry we analyzed VTA DA neuron intrinsic properties and cytosolic free Ca2+ levels.

Results

We found a progressive degeneration of mesolimbic DA neurons projecting to the ventral striatum, located in the paranigral nucleus and parabrachial pigmented subnucleus of the VTA. At the onset of degeneration (3 months of age), the vulnerable DA neurons in the Tg2576 accumulate damaged mitochondria, while AIF translocates from the mitochondria to the nucleus. Although we describe an age-dependent loss of the DA neurons expressing Calbindin-D28K or Calretinin, we observed that the remaining cells upregulate the levels of Ca2+-binding proteins, and the free cytosolic levels of Ca2+ in these neurons are significantly decreased. Coherently, TUNEL-stained Tg2576 DA neurons express lower levels of Calbindin-D28K when compared with non-apoptotic cells.

Conclusion

Overall, our results suggest that the overexpression of Ca2+-binding proteins in VTA DA neurons might be an attempt of cells to survive by increasing their ability to buffer free Ca2+. Exploring strategies to overexpress Ca2+-binding proteins could be fundamental to reduce neuronal suffering and improve cognitive and non-cognitive functions in AD.
Regulation of N-type calcium channels by nociceptin receptors and its possible role in neurological disorders
Authors: Caminski Emanuelle Sistherenn , Antunes Flavia Tasmin Techera , Souza Ivana Assis , Dallegrave Eliane , Zamponi Gerald W.
Published: November 2022

Activation of nociceptin opioid peptide receptors (NOP, a.k.a. opioid-like receptor-1, ORL-1) by the ligand nociceptin/orphanin FQ, leads to G protein-dependent regulation of Cav2.2 (N-type) voltage-gated calcium channels (VGCCs). This typically causes a reduction in calcium currents, triggering changes in presynaptic calcium levels and thus neurotransmission. Because of the widespread expression patterns of NOP and VGCCs across multiple brain regions, the dorsal horn of the spinal cord, and the dorsal root ganglia, this results in the alteration of numerous neurophysiological features. Here we review the regulation of N-type calcium channels by the NOP-nociceptin system in the context of neurological conditions such as anxiety, addiction, and pain.
Proteogenomic insights into the biology and treatment of pancreatic ductal adenocarcinoma
Authors: Tong Yexin , Sun Mingjun , Chen Lingli , Wang Yunzhi , Li Yan , Li Lingling , Zhang Xuan , Cai Yumeng , Qie Jingbo , Pang Yanrui , Xu Ziyan , Zhao Jiangyan , Zhang Xiaolei , Liu Yang , Tian Sha , Qin Zhaoyu , Feng Jinwen , Zhang Fan , Zhu Jiajun , Xu Yifan , Lou Wenhui , Ji Yuan , Zhao Jianyuan , He Fuchu , Hou Yingyong , Ding Chen
Published: November 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.

Methods

We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression.

Results

A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway.

Conclusions

This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.