bluuebunny/crossref_metadata_2025 huggingface dataset:
A gene based combination test using GWAS summary data
Authors: Zhang Jianjun , Liang Xiaoyu , Gonzales Samantha , Liu Jianguo , Gao Xiaoyi Raymond , Wang Xuexia
Published: January 2023

Background

Gene-based association tests provide a useful alternative and complement to the usual single marker association tests, especially in genome-wide association studies (GWAS). The way of weighting for variants in a gene plays an important role in boosting the power of a gene-based association test. Appropriate weights can boost statistical power, especially when detecting genetic variants with weak effects on a trait. One major limitation of existing gene-based association tests lies in using weights that are predetermined biologically or empirically. This limitation often attenuates the power of a test. On another hand, effect sizes or directions of causal genetic variants in real data are usually unknown, driving a need for a flexible yet robust methodology of gene based association tests. Furthermore, access to individual-level data is often limited, while thousands of GWAS summary data are publicly and freely available.

Results

To resolve these limitations, we propose a combination test named as OWC which is based on summary statistics from GWAS data. Several traditional methods including burden test, weighted sum of squared score test [SSU], weighted sum statistic [WSS], SNP-set Kernel Association Test [SKAT], and the score test are special cases of OWC. To evaluate the performance of OWC, we perform extensive simulation studies. Results of simulation studies demonstrate that OWC outperforms several existing popular methods. We further show that OWC outperforms comparison methods in real-world data analyses using schizophrenia GWAS summary data and a fasting glucose GWAS meta-analysis data. The proposed method is implemented in an R package available athttps://github.com/Xuexia-Wang/OWC-R-package

Conclusions

We propose a novel gene-based association test that incorporates four different weighting schemes (two constant weights and two weights proportional to normal statisticZ) and includes several popular methods as its special cases. Results of the simulation studies and real data analyses illustrate that the proposed test, OWC, outperforms comparable methods in most scenarios. These results demonstrate that OWC is a useful tool that adapts to the underlying biological model for a disease by weighting appropriately genetic variants and combination of well-known gene-based tests.
Individual patient data to allow a more elaborated comparison of trial results with real-world outcomes from second-line immunotherapy in NSCLC
Authors: Ismail R. K. , Schramel F. M. N. H. , van Dartel M. , Pasmooij A. M. G. , Cramer-van der Welle C. M. , Hilarius D. L. , de Boer A. , Wouters M. W. J. M. , van de Garde E. M. W.
Published: January 2023

Background

Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD.

Methods

This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial.

Results

Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively).

Conclusions

This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.
Anti-IgLON5 disease complicated with rectal adenocarcinoma: a case report
Authors: Li Yi , Zhang Lili , Wang Yuzhong
Published: January 2023

Background

Anti-IgLON5 disease is a rare chronic autoimmune-mediated tauopathy, featured by the sleep disturbance. Several studies have described its clinical characteristics, however, the simultaneous occurrence of anti-IgLON5 disease and rectal cancer has not been reported. We described an unusual entity of anti-IgLON5 disease complicated with rectal cancer.

Case presentation

A 76-year-old man initially presented with slurred speech and limb tremors, followed by epileptic-like seizures, lethargy, and sleep apnea. IgG anti-IgLON5 antibodies were positive in both serum and cerebrospinal fluid. The patient responded well to the treatment of plasma exchange and a pulse and gradual reduction of steroids therapy. When the oral steroids started, mycophenolate mofetil was added. Two months later, the patient had bloody stools and pathological-confirmed moderately differentiated adenocarcinoma of the rectum.

Conclusions

Whereas sleep disturbance is the most common feature in patients with anti-IgLON5 disease, our case presented with slurred speech and limb tremors. Anti-IgLON5 disease complicated with rectal cancer is very rare. Tumor screening should be considered in patients with anti-IgLON5 disease to investigate the association between tumor and this disease.
Clinical characteristics and prognostic factors affecting survival after radical radiotherapy for early and late post-treatment metastatic nasopharyngeal carcinoma
Authors: Jia Guo-Dong , Sun Xue-Song , Li Xiao-Yun , Liu Sai-Lan , Yang Jin-Hao , Chen Qiu-Yan , Yuan Li , Mai Hai-Qiang
Published: January 2023

Objective

We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies.

Methods

This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan–Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models.

Results

The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease.

Conclusions

The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.
Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report
Authors: Tsang Vivian W. L. , Bhanot Saundarai , Jia Lingsa
Published: January 2023

Background

Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.

Case presentation

In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.

Conclusion

The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.
Policy to expand hospital utilization in disadvantaged areas in Indonesia: who should be the target?
Authors: Laksono Agung Dwi , Megatsari Hario , Senewe Felly Philipus , Latifah Leny , Ashar Hadi
Published: January 2023

Background

The disadvantaged areas are one of the government’s focuses in accelerating development in Indonesia, including the health sector. The study aims to determine the target for expanding hospital utilization in disadvantaged areas in Indonesia.

Methods

The study employed the 2018 Indonesian Basic Health Survey data. This cross-sectional study analyzed 42,644 respondents. The study used nine independent variables: residence, age, gender, marital, education, employment, wealth, insurance, and travel time, in addition to hospital utilization, as a dependent variable. The study employed binary logistic regression to evaluate the data.

Results

The results found that average hospital utilization in disadvantaged areas in Indonesia in 2018 was 3.7%. Urban areas are 1.045 times more likely than rural areas to utilize the hospital (95% CI 1.032–1.058). The study also found age has a relationship with hospital utilization. Females are 1.656 times more likely than males to use the hospital (95% CI 1.639–1.673). Moreover, the study found marital status has a relationship with hospital utilization. The higher the education level, the higher the hospital utilization. Employed individuals have a 0.748 possibility to use the hospital compared with those unemployed (95% CI 0.740–0.757). Wealthy individuals have more chances of using the hospital than poor individuals. Individuals with all insurance types are more likely to utilize the hospital than those uninsured. Individuals with travel times of ≤ 1 h are 2.510 more likely to use the hospital than those with > 1 h (95% CI 2.483–2.537).

Conclusion

The specific targets to accelerate the increase in hospital utilization in disadvantaged areas in Indonesia are living in a rural area, being male, never in a union, having no education, being employed, being the poorest, uninsured, and having a travel time of > 1 h. The government should make a policy addressing the problem based on the research findings.
Association of internalised homonegativity with partner notification after diagnosis of syphilis or gonorrhoea among men having sex with men in 49 countries across four continents
Authors: Marcus Ulrich , Jonas Kai , Berg Rigmor , Veras Maria Amelia , Caceres Carlos F. , Casabona Jordi , Schink Susanne B. , Schmidt Axel J.
Published: January 2023

Background

Partner notification (PN) after a sexually transmitted infection (STI) diagnosis is being promoted as a means to interrupt transmission chains. We investigated whether Internalised Homonegativity (IH) is associated with PN among men having sex with men (MSM).

Methods

PN, defined as notifying at least one partner after diagnosis of syphilis and gonorrhoea, was queried in two internet-based self-completion surveys conducted between Oct 2017 and May 2018 in 68 countries in Europe, Latin America, Canada, and the Philippines. IH is defined by a man’s level of agreement or disagreement with negative social beliefs about male homosexuality. Covariates included in a multivariate regression model with a random intercept at country level were age, HIV diagnosis, partnership status, sexual self-efficacy, HIV serostatus communication during last sex with a non-steady partner, place where this partner was met, and PN-related socio-historical background of the country of residence. We grouped countries in three areas: North- and Central-Western European countries plus Canada, former socialist countries, and Latin-American/Mediterranean countries plus the Philippines. In each of the three areas individuals were assigned to 4 subgroups based on IH quartiles and PN rates were determined for each subgroup.

Results

PN rates were calculated for 49 countries (excluding countries with less than 10 diagnoses). Mean proportions of MSM notifying their partners were 68.1% and 72.9% after syphilis and gonorrhoea diagnoses, respectively. PN rates were lower in Latin American countries and the Philippines compared to European countries. Within Europe, a North–South divide with lower PN rates in Mediterranean countries was observed. In each of the three regions we mostly observed a stepwise increase of PN rates with decreasing IH.

Regression analysis showed lower IH scores associated with higher PN rates. Higher perceived self-efficacy, living in a partnership, and HIV status communication were positively associated with PN. Men who had met their last partner in a gay social venue were more likely to have notified their partners of a syphilis diagnosis compared to men who had met this partner online. Men with diagnosed HIV were less likely to report PN.

Conclusions

We could demonstrate that IH was associated with PN among MSM across all countries included in our analysis. Reducing cultural homophobia and ensuring inclusive policies may contribute to STI prevention and control.
Relationship between BMI and risk of impaired glucose tolerance and impaired fasting glucose in Chinese adults: a prospective study
Authors: Zhang Xin , Yue Yankun , Liu Shaobo , Cong Xiangfeng , Wang Wenjuan , Li Jianhong
Published: January 2023

Background

Current studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them.

Methods

The baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI < 18.5 kg/m2), normal weight (18.5–23.9 kg/m2), overweight (24.0–27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG.

Results

During an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08–1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27–1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39–3.54).

Conclusions

In China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage.
Technical aspects of virtual augmented reality-based rehabilitation systems for musculoskeletal disorders of the lower limbs: a systematic review
Authors: Kiani Shamim , Rezaei Iman , Abasi Sanaz , Zakerabasali Somayyeh , Yazdani Azita
Published: January 2023

Introduction

Musculoskeletal disorders are one of the most common causes of physical disability. The rehabilitation process after musculoskeletal disorders is long and tedious, and patients are not motivated to follow rehabilitation protocols. Therefore, new systems must be used to increase patient motivation. Virtual reality (VR) and augmented reality (AR) technologies can be used in this regard. In developing such systems, various technologies and methods of movement recognition are used; therefore, this study aims to summarize the technical aspects of using VR/AR in rehabilitation and evaluate and discuss efficient methods of investigating studies using the Statement of Standards for Reporting Implementation Studies (StaRI).

Methods

Search in four scientific databases was done systematically based on PRISMA through online search engines from inception to June 2021. These databases include Medline (PubMed), Scopus, IEEE, and Web of Science. An updated search was also conducted on 17 December 2021. The research used keywords and MeSH terms associated with VR/AR, musculoskeletal disorder, and rehabilitation. Selected articles were evaluated qualitatively using the Standards for Reporting Implementation Studies (StaRI) statement.

Results

A total of 2343 articles were found, and 20 studies were included. We found that 11 (55%) studies used Kinect technology as input tools, and 15 (75%) studies have described the techniques used to analyze human movements, such as dynamic time warping (DTW) and support vector machines (SVM). In 10 (50%) studies, the Unity game engine was used for visualization. In 8 studies (40%), usability was assessed, and high usability was reported. Similarly, the results of the review of studies according to the StaRI checklist showed poor reporting in the title and discussion of the studies.

Conclusions

We found that academic studies did not describe the technical aspects of rehabilitation systems. Therefore, a good description of the technical aspects of the system in such studies should be considered to provide repeatability and generalizability of these systems for investigations by other researchers.
No association between different in tibial resection level and clinical outcomes six months after Oxford unicompartmental knee arthroplasty: a prospective cohort study
Authors: Pornrattanamaneewong Chaturong , Ruangsillapanan Naruepol , Ruangsomboon Pakpoom , Narkbunnam Rapeepat , Chareancholvanich Keerati , Udomkiat Pacharapol
Published: January 2023

Background

Localized tibial strain is one of the hypotheses to explain residual pain after Oxford UKA. We evaluate whether the depth of the vertical cut during tibial resection correlates with
medial knee pain. We aimed to investigate the association between the depth of tibial resection and medial knee pain after OUKA.

Methods

This prospective cohort study enrolled 85 patients (mean age: 64.5 ± 7.7 years) who underwent cemented OUKA at our institute during October 2018–June 2019. The depth of tibial resection was measured intraoperatively as the thickness of the anterior, middle, and posterior parts. The greatest of the three thicknesses was recorded. Medial knee pain was assessed at 6 weeks and followed to 6 months. Patients were divided into the pain (P) and no pain (NP) groups. Preoperative and postoperative radiographic findings and OKS were compared between groups. We used logistic regression to analyze the independent association.

Results

The mean preoperative Oxford Knee Score (OKS) was 27.2 ± 7.6. The incidence of medial knee pain was 23.5% at 6 weeks after OUKA. The P group had a significantly lower OKS at 6 weeks compared to the NP group (28.9 ± 9.7 vs 33.7 ± 6.5, p = 0.049). There was no significant difference in the depth of tibial resection between groups. Medial knee pain had resolved by 6 months in all patients, and the 6-month OKS was similar between groups.

Conclusion

Medial knee pain was found to be common in the early postoperative period after OUKA, but this pain spontaneously resolved by 6 months. As a range of tibial resection level, post-operative pain is not associated with tibial resection thickness in this study.

Level of evidence

Level II.

Trial registration

The study was approved by the Institutional review board of Siriraj Hospital, Mahidol university. [SIRB 691/2560(EC4)].
The relationship between spinal alignment and activity of paravertebral muscle during gait in patients with adult spinal deformity: a retrospective study
Authors: Asada Tomoyuki , Miura Kousei , Kadone Hideki , Sakashita Kotaro , Funayama Toru , Takahashi Hiroshi , Noguchi Hiroshi , Sato Kosuke , Eto Fumihiko , Gamada Hisanori , Inomata Kento , Koda Masao , Yamazaki Masashi
Published: January 2023

Background

Spinal alignment in patients with adult spinal deformity (ASD) changes between rest and during gait. However, it remains unclear at which point the compensated walking posture breaks down and how muscles respond. This study used time-synchronized electromyography (EMG) to investigate the relationship between dynamic spinal alignment and muscle activity during maximum walking duration to reveal compensation mechanisms.

Methods

This study collected preoperative three-dimensional gait analysis data from patients who were candidates for corrective surgery for ASD from April 2015 to May 2019. We preoperatively obtained dynamic spinal alignment parameters from initiation to cessation of gait using a motion capture system with time-synchronized surface integrated EMG (iEMG). We compared chronological changes in dynamic spinal alignment parameters and iEMG values 1) immediately after gait initiation (first trial), 2) half of the distance walked (half trial), and 3) immediately before cessation (last trial).

Results

This study included 26 patients (22 women, four men) with ASD. Spinal sagittal vertical axis distance during gait (SpSVA) increased over time (first vs. half vs. last, 172.4 ± 74.8 mm vs. 179.9 ± 76.8 mm vs. 201.6 ± 83.1 mm; P < 0.001). Cervical paravertebral muscle (PVM) and gluteus maximus activity significantly increased (P < 0.01), but thoracic and lumbar PVM activity did not change. Dynamic spinal alignment showed significant correlation with all muscle activity (cervical PVM, r = 0.41–0.54; thoracic PVM, r = 0.49–0.66; gluteus maximus, r = 0.54–0.69; quadriceps, r = 0.46–0.55) except lumbar PVM activity.

Conclusion

Spinal balance exacerbation occurred continuously in patients with ASD over maximum walking distance and not at specific points. To maintain horizontal gaze, cervical PVM and gluteus maximus were activated to compensate for a dynamic spinal alignment change. All muscle activities, except lumbar PVM, increased to compensate for the spinal malalignment over time.
Interprofessional collaboration and patient-reported outcomes: a secondary data analysis based on large scale survey data
Authors: Kaiser Laura , Neugebauer Edmund A. M. , Pieper Dawid
Published: January 2023

Background

While interprofessional collaboration (IPC) is widely considered a key element of comprehensive patient treatment, evidence focusing on its impact on patient-reported outcomes (PROs) is inconclusive. The aim of this study was to investigate the association between employee-rated IPC and PROs in a clinical inpatient setting.

Methods

We conducted a secondary data analysis of the entire patient and employee reported data collected by the Picker Institute Germany in cross-sectional surveys between 2003 and 2016. Individual patient data from departments within hospitals was matched with employee survey data from within 2 years of treatment at the department-level. Items assessing employee-rated IPC (independent variables) were included in Principal Component Analysis (PCA). All questions assessing PROs (overall satisfaction, less discomforts, complications, treatment success, willingness to recommend) served as main dependent variables in ordered logistic regression analyses. Results were adjusted for multiple hypothesis testing as well as patients’ and employees’ gender, age, and education.

Results

The data set resulted in 6154 patients from 19 hospitals respective 103 unique departments. The PCA revealed three principal components (department-specific IPC, interprofessional organization, and overall IPC), explaining 67% of the total variance. The KMO measure of sampling adequacy was .830 and Bartlett’s test of sphericity highly significant (p < 0.001). An increase of 1 SD in department-specific IPC was associated with a statistically significant chance of a higher (i.e., better) PRO-rating about complications after discharge (OR 1.07, 95% CI 1.00–1.13, p = 0.029). However, no further associations were found. Exploratory analyses revealed positive coefficients of department-specific IPC on all PROs for patients which were treated in surgical or internal medicine departments, whereas results were ambiguous for pediatric patients.

Conclusions

The association between department-level IPC and patient-level PROs remains – as documented in previous literature - unclear and results are of marginal effect sizes. Future studies should keep in mind the different types of IPC, their specific characteristics and possible effect mechanisms.

Trial registration

Study registration: Open Science Framework (DOI https://doi.org/10.17605/OSF.IO/2NYAX); Date of registration: 09 November 2021.
C2 pedicle screw placement on 3D-printed models for the performance assessment of CTA-based screw preclusion
Authors: Wu Yuelin , Liang Zhaoquan , Bao Junhao , Wen Ling , Zhang Li
Published: January 2023

Background

3-D printing technology has a large spectrum of applications in upper cervical spinal surgery, but none have evaluated the radiological analysis of the feasibility of C2 pedicle screw placement. Thus, this study aimed to perform 3.5-mm-diameter C2 pedicle screw placement on models for performance assessment of CTA-based preoperative screw preclusion.

Methods

We enrolled 152 patients who underwent CTA of the cervical spine between April 2020 and December 2020. Transverse pediculoisthmic width (TPW), oblique pediculoisthmic width (OPW), minimum pediculoisthmic diameter (MPD), internal height, and isthmus height were measured preoperatively. Subsequently, 1:1 3D-printed bone models were created, and a 3.5-mm-diameter C2 pedicle screw was placed on the models. All 3D-printed models underwent postoperative CT multiplanar reconstruction to evaluate the screw trajectory for the performance assessment of CTA-based preoperative screw preclusion.

Results

The ROC curves of the MPD, TPW, OPW, Internal height and Isthmus height showed that the optimal cutoff values for each of the five groups were measured values of 4.78, 4.44, 4.37, 4.22 and 5.59 mm, respectively. The AUC, sensitivity, and specificity of MPD were 0.992, 95.1% and 100%, respectively. The MPD had higher metrics than the TPW (AUC, 0.949; sensitivity, 87.9%), internal height (AUC, 0.885; sensitivity, 80.8%; specificity, 84.6%), and isthmus height (AUC, 0.941; sensitivity, 87.2%). We found no evidence of a difference between MPD and OPW in terms of the AUC and sensitivity (0.93 and 95.5%, respectively).

Conclusions

C2 pedicle screw placement on 3D-printed models is useful for performance assessment of CTA-based preoperative screw preclusion. MPD measurement with CTA multiplanar reconstruction showed the best performance for judging acceptable or unacceptable screws. However, the definition of HRVA could be modified by a 4.2 mm-internal height or by measuring only the isthmus height for judging the preclusion of C2 pedicle screw placement.
PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies
Authors: Chen Saisai , Paul Matt R. , Sterner Christopher J. , Belka George K. , Wang Dezhen , Xu Peining , Sreekumar Amulya , Pan Tien-chi , Pant Dhruv K. , Makhlin Igor , DeMichele Angela , Mesaros Clementina , Chodosh Lewis A.
Published: January 2023

Background

Breast cancer mortality is principally due to recurrent disease that becomes resistant to therapy. We recently identified copy number (CN) gain of the putative membrane progesterone receptor PAQR8 as one of four focal CN alterations that preferentially occurred in recurrent metastatic tumors compared to primary tumors in breast cancer patients. Whether PAQR8 plays a functional role in cancer is unknown. Notably, PAQR8 CN gain in recurrent tumors was mutually exclusive with activating ESR1 mutations in patients treated with anti-estrogen therapies and occurred in > 50% of both patients treated with anti-estrogen therapies and those treated with chemotherapy or anti-Her2 agents.

Methods

We used orthotopic mouse models to determine whether PAQR8 overexpression or deletion alters breast cancer dormancy or recurrence following therapy. In vitro studies, including assays for colony formation, cell viability, and relative cell fitness, were employed to identify effects of PAQR8 in the context of therapy. Cell survival and proliferation were quantified by immunofluorescence staining for markers of apoptosis and proliferation. Sphingolipids were quantified by liquid chromatography-high resolution mass spectrometry.

Results

We show that PAQR8 is necessary and sufficient for efficient mammary tumor recurrence in mice, spontaneously upregulated and CN gained in recurrent tumors that arise following therapy in multiple mouse models, and associated with poor survival following recurrence as well as poor overall survival in breast cancer patients. PAQR8 promoted resistance to therapy by enhancing tumor cell survival following estrogen receptor pathway inhibition by fulvestrant or estrogen deprivation, Her2 pathway blockade by lapatinib or Her2 downregulation, and treatment with chemotherapeutic agents. Pro-survival effects of PAQR8 were mediated by a Gi protein-dependent reduction in cAMP levels, did not require progesterone, and involved a PAQR8-dependent decrease in ceramide levels and increase in sphingosine-1-phosphate levels, suggesting that PAQR8 may possess ceramidase activity.

Conclusions

Our data provide in vivo evidence that PAQR8 plays a functional role in cancer, implicate PAQR8, cAMP, and ceramide metabolism in breast cancer recurrence, and identify a novel mechanism that may commonly contribute to the acquisition of treatment resistance in breast cancer patients.
Distinct gene signatures of monocytes and B cells in patients with giant cell arteritis: a longitudinal transcriptome analysis
Authors: Matsumoto Kotaro , Suzuki Katsuya , Yoshida Hiroto , Magi Mayu , Matsumoto Yoshihiro , Noguchi-Sasaki Mariko , Yoshimoto Keiko , Takeuchi Tsutomu , Kaneko Yuko
Published: January 2023

Background

Giant cell arteritis (GCA) is a primary large-vessel vasculitis (LVV) of unknown origin. Its management is a challenge due to the late onset of disease symptoms and frequent relapse; therefore, clarifying the pathophysiology of GCA is essential to improving treatment. This study aimed to identify the transition of molecular signatures in immune cells relevant to GCA pathogenesis by analyzing longitudinal transcriptome data in patients.

Methods

We analyzed the whole blood transcriptome of treatment-naive patients with GCA, patients with Takayasu arteritis (TAK), age-matched, old healthy controls (HCs), and young HCs. Characteristic genes for GCA were identified, and the longitudinal transition of those genes was analyzed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT).

Results

Repeated measures analysis of variance revealed 739 differentially expressed genes among all patients and HCs. Of the 739 genes, 15 were characteristically upregulated and 36 were downregulated in patients with GCA compared to those with TAK and HCs. Pathway enrichment analysis showed that downregulated genes in GCA were associated with B cell activation. CIBERSORT analysis revealed that upregulation of “M0-macrophages” and downregulation of B cells were characteristic of GCA. Upregulation of “M0-macrophages” reflects the activation of monocytes in GCA toward M0-like phenotypes, which persisted under 6 weeks of treatment. Combined treatment with prednisolone and an interleukin-6 receptor antagonist normalized molecular profiles more efficiently than prednisolone monotherapy.

Conclusions

Gene signatures of monocyte activation and B cell inactivation were characteristic of GCA and associated with treatment response.
Transcatheter aortic valve implantation against conventional aortic valve replacement surgery in high-risk patients with aortic stenosis; a cost-effectiveness analysis
Authors: Ghiasvand Hesam , Khaleghparast Shiva , Kachoueian Naser , Tirgarfakheri Kourosh , Mortazian Meysam , Toloueitabar Yaser , Gorjipour Farhad , Naghdi Seyran
Published: January 2023

Background

Aortic stenosis is a prevalent heart valvular disorder in Iran. Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR) are two common procedures for treating the disease in the current clinical pathway. However, TAVI is an expensive procedure, and for Iran with severe limitations in financial resources, it is crucial to investigate the cost-effectiveness of the technology against other competing alternatives with the same purpose. This study aims to analyse the cost-effectiveness of TAVI vs SAVR in elderly patients who are at a higher risk of surgery.

Methods

This study is a decision economic evaluation modeling, with a lifetime horizon and a healthcare payer (health insurer) perspective. The utility values are from a previous study, transitional probabilities come from an established clinical trial called PARTNER-1, and the unit costs are from Iran’s national fee schedule for medical services. The probabilistic and one-way sensitivity analyses have been performed to mitigate the uncertainty.

Results

The incremental cost, effectiveness, and cost-effectiveness ratio for the base case were: 368,180,101 Iranian Rial, (US$ 1,473), 0.37 QALY-per-patient, and, 995,081,354 Iranian Rial (US$ 3,980), respectively. The probabilistic sensitivity analysis yielded 981,765,302 I.R.I Rials (US$ 3,927) per patient for the ICER. The probability of being cost-effective at one and three times the country’s Gross Domestic Production (GDP) is 0.31 and 0.83, respectively.

Conclusions

TAVI does not seem a cost-effective procedure in comparison with SAVR at the current willingness to pay thresholds of the country. However, by increasing the WTP threshold to 3 times the GDP per capita the probability of being cost-effective will raise to 83%.
Zebrafish: a convenient tool for myelopoiesis research
Authors: Hu Yang-Xi , Jing Qing
Published: January 2023

Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and deteriorate a variety of hematopoietic malignancies such as leukemia. Myeloid cells and their precursors are difficult to capture in circulation, let alone observe them in real time. For decades, researchers had to face these difficulties, particularly in in-vivo studies. As a unique animal model, zebrafish possesses numerous advantages like body transparency and convenient genetic manipulation, which is very suitable in myelopoiesis research. Here we review current knowledge on the origin and regulation of myeloid development and how zebrafish models were applied in these studies.
Partial-fraction decomposition of a rational function and its application
Authors: Zhu Jun-Ming , Luo Qiu-Ming
Published: January 2023

In this paper, by using the residue method of complex analysis, we obtain an explicit partial fraction decomposition for the general rational function $\frac{x^{M}}{(x+1)^{\lambda}_{n}}$

x
M

(
x
+
1
)

n
λ

(M is any nonnegative integer, λ and n are any positive integers). As applications, we deduce the corresponding algebraic identities and combinatorial identities which are the corresponding extensions of Chu’ results. We also give some explicit formulas of Apostol-type polynomials and harmonic Stirling numbers of the second kind.
HCV serostatus and injection sharing practices among those who obtain syringes from pharmacies and directly and indirectly from syringe services programs in rural New England
Authors: Romo Eric , Rudolph Abby E. , Stopka Thomas J. , Wang Bo , Jesdale Bill M. , Friedmann Peter D.
Published: January 2023

Background

Among people who inject drugs (PWID), obtaining syringes via syringe services programs (SSPs) and pharmacies reduces injection sharing practices associated with hepatitis C virus (HCV). Whether indirect use of SSPs via secondary exchange confers a similar benefit remains unknown, particularly in rural settings. We compared HCV serostatus and injection sharing practices by primary syringe source among a sample of rural PWID.

Methods

Data are from a cross-sectional study of adults who use drugs recruited from eleven rural counties in New Hampshire, Vermont, and Massachusetts using respondent-driven sampling (2018–2019). Study staff performed HCV antibody testing. An audio computer-assisted self-interview assessed sociodemographic characteristics, past 30-day injection practices, and past 30-day primary syringe source. Primary syringe source was classified as direct SSP, pharmacy, indirect SSP (secondary exchange), or “other” (friend/acquaintance, street seller, partner/relative, found them). Mixed effects modified Poisson models assessed the association of primary syringe source with HCV seroprevalence and injection sharing practices.

Results

Among 397 PWID, the most common primary syringe source was “other” (33%), then pharmacies (27%), SSPs (22%), and secondary exchange (18%). In multivariable models, compared with those obtaining most syringes from “other” sources, those obtaining most syringes from pharmacies had a lower HCV seroprevalence [adjusted prevalence ratio (APR):0.85, 95% confidence interval (CI) 0.73–0.9985]; however, the upper bound of the 95% CI was close to 1.0. Compared with those obtaining most syringes from other sources, PWID obtaining most syringes directly from SSPs or pharmacies were less likely to report borrowing used syringes [APR(SSP):0.60, 95% CI 0.43–0.85 and APR(Pharmacies):0.70, 95% CI 0.52–0.93], borrowing used injection equipment [APR(SSP):0.59, 95% CI 0.50–0.69 and APR (Pharmacies):0.81, 95% CI 0.68–0.98], and backloading [APR(SSP):0.65, 95% CI 0.48–0.88 and APR(Pharmacies):0.78, 95% CI 0.67–0.91]. Potential inverse associations between obtaining most syringes via secondary exchange and injection sharing practices did not reach the threshold for statistical significance.

Conclusions

PWID in rural New England largely relied on informal syringe sources (i.e., secondary exchange or sources besides SSPs/pharmacies). Those obtaining most syringes from an SSP or pharmacy were less likely to share injection equipment/syringes and had a lower HCV seroprevalence, which suggests using these sources reduces the risk of new HCV infections or serves as proxy for past injection behavior.
Clinical characteristics and outcomes of cervical lymph node metastasis from unknown primary sites: a single institution’s 14-year experience
Authors: Zhou Mengqian , Wu Yansheng , Wu Yue , Li Hong , Ye Beibei , Yue Kai , Jing Chao , Duan Yuansheng , Wang Xudong
Published: January 2023

Background

Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles.

Methods

All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis.

Results

365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy.

Conclusions

Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.
Case report: tracking data from foraging hawksbill turtles in the northern Red Sea
Authors: Tanabe Lyndsey K. , Cochran Jesse E. M. , Williams Collin T. , Garzon Francesco , Langner Ute , Hardenstine Royale S. , Hawkes Lucy A. , Brainard Russell E. , Eweida Ameer A. , Marshall Paul A. , Berumen Michael L.
Published: January 2023

Background

Hawksbill turtles (Eretmochelys imbricata) are Critically Endangered throughout their global range, and concerningly little is known about this species in the Red Sea. With large-scale coastal development projects underway in the northern Red Sea, it is critical to understand the movement and habitat use patterns of hawksbill turtles in this environmentally unique region, so that effective conservation strategies can be implemented. We satellite tagged three hawksbill turtles, one 63 cm curved carapace length adult male captured near Wahlei Island, one 55 cm turtle captured in the Gulf of Aqaba, and one 56 cm turtle suffering from a floating syndrome which was captured at Waqqadi Island, rehabilitated, and released at Waqqadi Island. Turtles were tracked for 156, 199, and 372 days between October 2020 and November 2021.

Results

We calculated the home ranges and core use areas of hawksbill turtles using kernel-density estimations and found that each turtle showed high fidelity to their foraging sites. Home ranges calculated with GPS-derived locations ranged between 13.6 and 2.86 km2, whereas home ranges calculated with Argos-derived locations ranged from 38.98 to 286.45 km2. GPS-derived locations also revealed a higher proportion of time spent in coral and rock habitats compared to Argos, based on location overlap with the Allen Coral Reef Atlas. We also found that turtles were making shallow dives, usually remaining between 0 and 5 m.

Conclusions

While the number of tracked turtles in this study was small, it represents an important contribution to the current understanding of spatial ecology among foraging hawksbill turtles globally, and provides the first-ever reported hawksbill turtle tracking data from the Red Sea. Our results suggest that protecting coral reef habitats and implementing boating speed limits near reefs could be effective conservation measures for foraging hawksbill turtles in the face of rapid coastal development.
High-precision deformation analysis of yingxian wooden pagoda based on UAV image and terrestrial LiDAR point cloud
Authors: Guo Ming , Sun Mengxi , Pan Deng , Wang Guoli , Zhou Yuquan , Yan Bingnan , Fu Zexin
Published: January 2023

The monitoring of wooden pagodas is a very important task in the restoration of wooden pagodas. Traditionally, this labor has always been carried out by surveying personnel, who manually check all parts of the pagoda, which not only consumes huge manpower, but also suffers from low efficiency and measurement errors. This article evaluates the feasibility of combining portable 3D light detection and ranging (LiDAR) scanning and unmanned aerial vehicle (UAV) photogrammetry to perform these inspection tasks easily and accurately. The wooden pagoda's exterior picture and inside point cloud are acquired using a UAV and a LiDAR scanner, respectively. We propose a feature−based global alignment method to register the site point cloud. The error equation of the column of observed values is utilized as the beginning value of the feature constraint for global leveling. The beam method leveling model solves the spatial transformation parameters and the unknown point leveling values. Then, the Structure from Motion (SfM) algorithm of computer vision is used to realize the fusion of the dense point cloud of the exterior of the wooden pagoda generated from multiple non−measured images by global optimization and the LiDAR point cloud of the interior of the wooden pagoda to obtain the complete point cloud of the wooden pagoda, which makes the deformation monitoring of the pagoda more detailed and comprehensive. After experimental verification, the overall registration accuracy of the Yingxian wooden pagoda reaches 0.006 m. Compared with the scanning point cloud data in 2018, the model is more accurate and complete. By analyzing and comparing the data of the second floor of the wooden pagoda, we knew that the inclination of a second bright layer and a second dark layer is still developing steadily. Overall, the western outer trough inclines thoughtfully, and the column frame slopes from southwest to northeast. Some internal columns showed a negative offset in 2020, and the deformation analysis of a single column was realized by comparing it with the standard column model. The main contribution of this method lies in the effective integration of UAV images and point cloud data to provide accurate data sources for good modeling. This research will provide theoretical and methodological support for the digital protection of architectural heritage and GIS data modeling. The analysis results can provide a scientific basis for the restoration scheme design.