bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term forecasting of a motor outcome following rehabilitation in chronic stroke via a hierarchical bayesian dynamic model
Authors: Schweighofer Nicolas , Ye Dongze , Luo Haipeng , D’Argenio David Z. , Winstein Carolee
Published: June 2023

Background

Given the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a hierarchical Bayesian dynamic (i.e., state-space) model (HBDM) to forecast long-term changes in a motor outcome due to rehabilitation in the chronic phase post-stroke.

Methods

The model incorporates the effects of clinician-supervised training, self-training, and forgetting. In addition, to improve forecasting early in rehabilitation, when data are sparse or unavailable, we use the Bayesian hierarchical modeling technique to incorporate prior information from similar patients. We use HBDM to re-analyze the Motor Activity Log (MAL) data of participants with chronic stroke included in two clinical trials: (1) the DOSE trial, in which participants were assigned to a 0, 15, 30, or 60-h dose condition (data of 40 participants analyzed), and (2) the EXCITE trial, in which participants were assigned a 60-h dose, in either an immediate or a delayed condition (95 participants analyzed).

Results

For both datasets, HBDM accounts well for individual dynamics in the MAL during and outside of training: mean RMSE = 0.28 for all 40 DOSE participants (participant-level RMSE 0.26 ± 0.19—95% CI) and mean RMSE = 0.325 for all 95 EXCITE participants (participant-level RMSE 0.32 ± 0.31), which are small compared to the 0-5 range of the MAL. Bayesian leave-one-out cross-validation shows that the model has better predictive accuracy than static regression models and simpler dynamic models that do not account for the effect of supervised training, self-training, or forgetting. We then showcase model’s ability to forecast the MAL of “new” participants up to 8 months ahead. The mean RMSE at 6 months post-training was 1.36 using only the baseline MAL and then decreased to 0.91, 0.79, and 0.69 (respectively) with the MAL following the 1st, 2nd, and 3rd bouts of training. In addition, hierarchical modeling improves prediction for a patient early in training. Finally, we verify that this model, despite its simplicity, can reproduce previous findings of the DOSE trial on the efficiency, efficacy, and retention of motor therapy.

Conclusions

In future work, such forecasting models can be used to simulate different stages of recovery, dosages, and training schedules to optimize rehabilitation for each person.

Trial registration This study contains a re-analysis of data from the DOSE clinical trial ID NCT01749358 and the EXCITE clinical trial ID NCT00057018
Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders
Authors: Fiore Mathieu , Giraudet Janine-Sophie , Alessi Marie-Christine , Falaise Céline , Desprez Dominique , d’Oiron Roseline , Voisin Sophie , Hurtaud Marie-Françoise , Boutroux Hélène , Saultier Paul , Lavenu-Bombled Cécile , Bagou Gilles , Dubucs Xavier , Chauvin Anthony , Leroy Christophe , Meckert Francine , Kerbaul François , Giraud Nicolas , Pühler Ambra , Rath Ana
Published: June 2023

Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients’ associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT.
Differences in perceived threat and trauma in children during the COVID-19 pandemic
Authors: Kohlboeck Gabriele , Wenter Anna , Sevecke Kathrin , Exenberger Silvia
Published: June 2023

Background

The past 2 years of the COVID-19 pandemic were stressful for most children and adolescents; some children may have experienced a high level of stress and trauma. To date, no study has examined self-reported stress and trauma levels due to COVID-19 in children. This study aimed to assess perceived threat, exposure and trauma symptoms in children aged 7–13 years. In addition, we explored whether parent-reported factors could predict a higher risk of COVID-19 vulnerability in their children.

Method

Cross-sectional data were collected from 752 children to assess COVID-19 threat, exposure and trauma symptoms using the self- and parent-reported Child and Adolescent Trauma Screening Self-Report (CATS) Trauma questionnaire. We used exploratory analyses (factor analysis of mixed data and hierarchical clustering) to identify subgroups (i.e., clusters) of children sharing similar characteristics in the dataset. Linear regression modeling was applied to determine the likelihood of higher threat and vulnerability in children with parent-reported COVID-19 threat, exposure, CATS trauma symptoms, behaviors on the Child Behavior Checklist (CBCL), and posttraumatic growth (PTG).

Results

We identified a high-risk group of children reporting clinically relevant trauma symptoms and COVID-19-related fears. Parents’ reports of trauma could be used to identify children at high risk.

Conclusions

Approximately 25% of children reported moderate to clinically relevant levels of trauma symptom. It is especially important to offer adequate support to these children to ease the trauma and prevent their symptoms from developing into psychopathology.
Breast cancer brain metastasis: from etiology to state-of-the-art modeling
Authors: Farahani Mohammad Kamalabadi , Gharibshahian Maliheh , Rezvani Alireza , Vaez Ahmad
Published: June 2023

Currently, breast carcinoma is the most common form of malignancy and the main cause of cancer mortality in women worldwide. The metastasis of cancer cells from the primary tumor site to other organs in the body, notably the lungs, bones, brain, and liver, is what causes breast cancer to ultimately be fatal. Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%. Many researchers have focused on brain metastasis, but due to its complexities, many aspects of this process are still relatively unclear. To develop and test novel therapies for this fatal condition, pre-clinical models are required that can mimic the biological processes involved in breast cancer brain metastasis (BCBM). The application of many breakthroughs in the area of tissue engineering has resulted in the development of scaffold or matrix-based culture methods that more accurately imitate the original extracellular matrix (ECM) of metastatic tumors. Furthermore, specific cell lines are now being used to create three-dimensional (3D) cultures that can be used to model metastasis. These 3D cultures satisfy the requirement for in vitro methodologies that allow for a more accurate investigation of the molecular pathways as well as a more in-depth examination of the effects of the medication being tested. In this review, we talk about the latest advances in modeling BCBM using cell lines, animals, and tissue engineering methods.
A gene signature can predict risk of MGUS progressing to multiple myeloma
Authors: Sun Fumou , Cheng Yan , Ying Jun , Mery David , Al Hadidi Samer , Wanchai Visanu , Siegel Eric R. , Xu Hongwei , Gai Dongzheng , Ashby Timothy Cody , Bailey Clyde , Chen Jin-Ran , Schinke Carolina , Thanendrarajan Sharmilan , Zangari Maurizio , Janz Siegfried , Barlogie Bart , Van Rhee Frits , Tricot Guido , Shaughnessy John D. , Zhan Fenghuang
Published: June 2023

Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Serum markers are currently used to stratify MGUS patients into clinical risk groups. A molecular signature predicting MGUS progression has not been produced. We have explored the use of gene expression profiling to risk-stratify MGUS and developed an optimized signature based on large samples with long-term follow-up. Microarrays of plasma cell mRNA from 334 MGUS with stable disease and 40 MGUS that progressed to MM within 10 years, was used to define a molecular signature of MGUS risk. After a three-fold cross-validation analysis, the top thirty-six genes that appeared in each validation and maximized the concordance between risk score and MGUS progression were included in the gene signature (GS36). The GS36 accurately predicted MGUS progression (C-statistic is 0.928). An optimal cut-point for risk of progression by the GS36 score was found to be 0.7, which identified a subset of 61 patients with a 10-year progression probability of 54.1%. The remainder of the 313 patients had a probability of progression of only 2.2%. The sensitivity and specificity were 82.5% and 91.6%. Furthermore, combination of GS36, free light chain ratio and immunoparesis identified a subset of MGUS patients with 82.4% risk of progression to MM within 10 years. A gene expression signature combined with serum markers created a highly robust model for predicting risk of MGUS progression. These findings strongly support the inclusion of genomic analysis in the management of MGUS to identify patients who may benefit from more frequent monitoring.
Risk-reducing salpingo-oophorectomy among Chinese women at increased risk of breast and ovarian cancer
Authors: Feng Zheng , Zuo Ke , Ju Xingzhu , Chen Xiaojun , Yang Wentao , Wen Hao , Yu Lin , Wu Xiaohua
Published: June 2023

Background

Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of breast and ovarian cancer. We launched a prospective study of women receiving RRSO, including those with mutations in genes beyond BRCA1/2.

Patients and methods

80 women were enrolled for RRSO with sectioning and extensively examining the fimbriae (SEE-FIM) protocol between October 2016 and June 2022. The majority of participants had inherited susceptibility gene mutations or a family history suggesting ovarian cancer risk, while patients with isolated metastatic high-grade serous cancer of unknown origin were also included.

Results

Overall, two patients had isolated metastatic high-grade serous cancer with unknown origin, and four patients had family histories but refused to take genetic tests. The rest 74 patients harbored deleterious susceptible gene, including 43 (58.1%) with BRCA1 mutation, and 26 (35.1%) with BRCA2 mutation, respectively. Other mutated genes included ATM (1), BRIP1(1), PALB2(1), MLH1(1) and TP53 (1) in each patient. Among the 74 mutation carriers, three (4.1%) cancers were recognized, one (1.4%) was found to have serous tubal intraepithelial carcinoma (STIC), and five patients (6.8%) was diagnosed with serous tubal intraepithelial lesions (STILs). P53 signature was recognized in 24 patients (32.4%). For other genes, MLH1 mutation carrier had endometrial atypical hyperplasia and p53 signature in fallopian tubes. The germline TP53 mutation carrier had STIC in the surgical specimens. Evidence for precursor escape was also recognized in our cohort.

Conclusion

Our study demonstrated clinic-pathological findings of patients at increased risk of breast and ovarian cancer, and expand the clinical application of SEE-FIM protocol.
Effects of a biomechanical-based Tai Chi program on gait and posture in people with Parkinson’s disease: study protocol for a randomized controlled trial
Authors: Law Nok-Yeung , Li Jing Xian , Zhu Qingguang , Nantel Julie
Published: June 2023

Background

Parkinson’s disease (PD) is associated with changes in gait and posture, which increases the rate of falls and injuries in this population. Tai Chi (TC) training enhances the movement capacity of patients with PD. However, the understanding of the effect of TC training on gait and postural stability in PD is lacking. This study aims to examine the effect of biomechanical-based TC training on dynamic postural stability and its relationship with walking performance.

Methods/design

A single-blind, randomized control trial of 40 individuals with early-stage PD was conducted (Hoehn and Yahr stages 1 to 3). Patients with PD will be randomly assigned to either the TC or control group. The TC group will participate in a biomechanical-based TC training program that is formed based on the movement analysis of TC and will be practiced thrice a week for 12 weeks. The control group will be required to engage in at least 60 min of regular physical activity (PA) on their own for three times per week for 12 weeks. The primary and secondary outcomes will be assessed at baseline and at 6 and 12 weeks after commencing the study protocol. The primary outcome measures will include dynamic postural stability indicated by the center of mass and center of pressure separation distance and clearance distance of the heel and toe measured during fixed-obstacle crossing. The secondary measures are gait speed, cadence, step length during level surface walking (simple task), and fixed-obstacle crossing (challenging task). The Unified Parkinson’s Disease Rating Scale, single leg-stance test with eyes open and closed, and three cognitive scores (Stroop Test, Trail Making Test Part B, and the Wisconsin Card Sorting Test) were also employed.

Discussion

This protocol could lead to the development of a biomechanics TC training program for the improvement of gait and postural stability among individuals with PD. The program could enhance the understanding of the effect of TC training on gait and postural stability and could help improve or preserve the postural stability, self-confidence, and active participation in social activities of the participants, thus enhancing their overall quality of life.

Trial registration

ClinicalTrials.gov NCT04644367. Registered on 25 November 2020.
12,13-diHOME and noradrenaline are associated with the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus
Authors: Cao Ning , Wang Yichun , Bao Boyi , Wang Man , Li Jiayu , Dang Wenxi , Hua Bing , Song Lijin , Li Hongwei , Li Weiping
Published: June 2023

Background

Acute myocardial infarction (AMI) is the most prevalent cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). However, strict blood glucose control does not always prevent the development and progression of AMI. Therefore, the present study aimed to explore potential new biomarkers associated with the occurrence of AMI in T2DM patients.

Methods

A total of 82 participants were recruited, including the control group (n = 28), T2DM without AMI group (T2DM, n = 30) and T2DM with initial AMI group (T2DM + AMI, n = 24). The untargeted metabolomics using liquid chromatography-mass spectrometry (LC–MS) analysis was performed to evaluate the changes in serum metabolites. Then, candidate metabolites were determined using ELISA method in the validation study (n = 126/T2DM group, n = 122/T2DM + AMI group).

Results

The results showed that 146 differential serum metabolites were identified among the control, T2DM and T2DM + AMI, Moreover, 16 differentially-expressed metabolites were significantly altered in T2DM + AMI compared to T2DM. Amino acid and lipid pathways were the major involved pathways. Furthermore, three candidate differential metabolites, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), noradrenaline (NE) and estrone sulfate (ES), were selected for validation study. Serum levels of 12,13-diHOME and NE in T2DM + AMI were significantly higher than those in T2DM. Multivariate logistic analyses showed that 12,13-diHOME (OR, 1.491; 95% CI 1.230–1.807, P < 0.001) and NE (OR, 8.636; 95% CI 2.303–32.392, P = 0.001) were independent risk factors for AMI occurrence in T2T2DM patients. The area under receiver operating characteristic (ROC) curve (AUC) were 0.757 (95% CI 0.697–0.817, P < 0.001) and 0.711(95% CI 0.648–0.775, P < 0.001), respectively. The combination of both significantly improved the AUC to 0.816 (95% CI 0.763–0.869, P < 0.001).

Conclusions

12,13-diHOME and NE may lead to understanding the possible metabolic alterations associated with AMI onset in T2DM population and serve as promising risk factors and therapeutic targets.
Comparison of optimized machine learning approach to the understanding of medial tibial stress syndrome in male military personnel
Authors: Sobhani Vahid , Asgari Alireza , Arabfard Masoud , Ebrahimpour Zeynab , Shakibaee Abolfazl
Published: June 2023

Purpose

This study investigates the applicability of optimized machine learning (ML) approach for the prediction of Medial tibial stress syndrome (MTSS) using anatomic and anthropometric predictors.

Method

To this end, 180 recruits were enrolled in a cross-sectional study of 30 MTSS (30.36 ± 4.80 years) and 150 normal (29.70 ± 3.81 years). Twenty-five predictors/features, including demographic, anatomic, and anthropometric variables, were selected as risk factors. Bayesian optimization method was used to evaluate the most applicable machine learning algorithm with tuned hyperparameters on the training data. Three experiments were performed to handle the imbalances in the data set. The validation criteria were accuracy, sensitivity, and specificity.

Results

The highest performance (even 100%) was observed for the Ensemble and SVM classification models while using at least 6 and 10 most important predictors in undersampling and oversampling experiments, respectively. In the no-resampling experiment, the best performance (accuracy = 88.89%, sensitivity = 66.67%, specificity = 95.24%, and AUC = 0.8571) was achieved for the Naive Bayes classifier with the 12 most important features.

Conclusion

The Naive Bayes, Ensemble, and SVM methods could be the primary choices to apply the machine learning approach in MTSS risk prediction. These predictive methods, alongside the eight common proposed predictors, might help to more accurately calculate the individual risk of developing MTSS at the point of care.
Infinitely many solutions for quasilinear Schrödinger equation with general superlinear nonlinearity
Authors: Li Jiameng , Chen Huiwen , He Zhimin , Ouyang Zigen
Published: June 2023

In this article, we study the quasilinear Schrödinger equation $$ -\triangle (u)+V(x)u-\triangle \bigl(u^{2}\bigr)u=g(x,u), \quad x\in \mathbb{R}^{N}, $$
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Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints
Authors: Lu Jiaying , Ma Xiaoxi , Zhang Huiwei , Xiao Zhenxu , Li Ming , Wu Jie , Ju Zizhao , Chen Li , Zheng Li , Ge Jingjie , Liang Xiaoniu , Bao Weiqi , Wu Ping , Ding Ding , Yen Tzu-Chen , Guan Yihui , Zuo Chuantao , Zhao Qianhua ,   on behalf of the Shanghai Memory Study (SMS), Chen Keliang , Shi Langfeng , Wu Wanqing , Zhou Yan , Zhang Yan , Pei Fang
Published: June 2023

Background

Gaining more information about the reciprocal associations between different biomarkers within the ATN (Amyloid/Tau/Neurodegeneration) framework across the Alzheimer’s disease (AD) spectrum is clinically relevant. We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography (PET) ATN biomarkers in subjects with cognitive complaints.

Methods

A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging (18F-florbetapir for A,18F-Florzolotau for T, and18F-fluorodeoxyglucose [18F-FDG] for N) was enrolled (n = 137). The β-amyloid (Aβ) status (positive versus negative) and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.

Results

Plasma phosphorylated tau 181 (p-tau181) level was found to be associated with PET imaging of ATN biomarkers in the entire cohort. Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+ and Aβ− subjects. An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+ subjects. Additionally, glucose hypometabolism – along with elevated plasma neurofilament light chain level – was related to more severe cognitive impairment in Aβ− subjects.

Conclusion

Plasma p-tau181, as well as18F-florbetapir and18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβ status in symptomatic stages of AD.18F-Florzolotau and18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment. Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.
Effects of ice slurry ingestion on body temperature and softball pitching performance in a hot environment: a randomized crossover trial
Authors: Numata Urara , Yanaoka Takuma , Kurosaka Shiho , Hasegawa Hiroshi
Published: June 2023

Background

Although softball players are often required to play in hot environments, scarce evidence is available regarding the effects of ice slurry ingestion on body temperature and pitching performance in softball pitchers in a hot environment. Thus, this study investigated the effects of ice slurry ingestion before and between innings on body temperature and softball pitching performance in a hot environment.

Methods

In a randomized crossover design, seven heat-acclimatized amateur softball pitchers (four males and three females) completed simulated softball games consisting of 15 best-effort pitches per inning for seven innings with between-pitch rest intervals of 20 s. Participants were assigned to either a control trial (CON: ingestion of 5.0 g·kg−1 of cool fluid [9.8 ± 2.2 °C] before simulated softball games and 1.25 g·kg−1 of cool fluid between inning intervals) or an ice trial (ICE: ingestion of ice slurry [− 1.2 ± 0.1 °C] based on the same timings and doses as the CON). Participants performed both trials in an outdoor ground during the summer season (30.8 ± 2.7 °C, 57.0 ± 7.9% relative humidity).

Results

Ice slurry ingestion before the simulated softball game (pre-cooling) resulted in a greater reduction in rectal temperature compared with cool fluid ingestion (p = 0.021, d = 0.68). No significant differences were observed between the trials in rectal temperature changes during the simulated softball game (p > 0.05). Compared to the CON, heart rate during the game was significantly decreased (p < 0.001, d = 0.43), and handgrip strength during the game was significantly increased (p = 0.001, d = 1.16) in the ICE. Ratings of perceived exertion, thermal comfort, and thermal sensation were improved in the ICE compared to those in the CON (p < 0.05). Ball velocity and pitching accuracy were not affected by ICE.

Conclusions

Ice slurry ingestion before and between innings reduced thermal, cardiovascular, and perceptual strain. However, it did not affect softball pitching performance compared to cool fluid ingestion.
Endoscopic sinus surgery outcomes in patients with chronic rhinosinusitis and immunoglobulin deficiencies
Authors: Samargandy Shireen , Grose Elysia , Yip Jonathan , Lee John M.
Published: June 2023

Background

Patients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical management for their CRS. However, there is a paucity of literature on the surgical outcomes in this patient population and appropriate treatment algorithms for CRS in patients with ID. The objective of this study was to better elucidate the outcomes of endoscopic sinus surgery (ESS) in patients with ID in terms of disease-specific quality-of-life scores and the need for revision surgery.

Methods

A case–control study was performed comparing adult patients with ID and healthy controls that had undergone ESS for CRS. Patients were matched based on age, sex, CRS phenotype, and preoperative Lund-Mackay score. The revision surgery rates, time to revision surgery, and changes in sinonasal outcome tests (SNOT-22) were evaluated.

Results

Thirteen patients with CRS and ID were matched to 26 control patients with CRS. The revision surgery rate for cases and controls was 31% and 12%, respectively, but there was no statistical difference ( p > 0.05). There was a clinically meaningful reduction in SNOT-22 scores in both groups from the preoperative to postoperative period [mean of 12 points in patients with ID ( p = 0.323) and 25 points in controls ( p < 0.001)], however, there was again no significant difference between cases and controls ( p > 0.05).

Conclusion

Our data suggests that patients with ID have clinically meaningful improvement in SNOT-22 scores after ESS but may have higher revision rates than immunocompetent patients with CRS. ID are rare disease entities, thus most attempts at studying this cohort would be limited by sample size. Further homogenous data on immunoglobulin deficient patients is required for future meta-analysis to better understand the impact of ESS in patients with ID.
Exploring the Xylariaceae and its relatives
Authors: Suwannasai Nuttika , Sangvichien Ek , Phosri Cherdchai , McCloskey Sirirath , Wangsawat Niwana , Thamvithayakorn Pisit , Ruchikachorn Nutthaporn , Thienhirun Surang , Mekkamol Sureewan , Sihanonth Prakitsin , Whalley Margaret A. , Whalley Anthony J. S.
Published: June 2023

The Xylariaceae and its relatives rank as one of the best-known members of the Ascomycota. They are now well recognized for their diversity, global distribution, ecological activities and their outstanding novel metabolites with wide ranging bioactivity.
Pediatric outdoor recreational injuries: another hidden concern during the COVID-19 pandemic
Authors: Blumberg Melissa P. , Gittelman Michael A. , Pomerantz Wendy J.
Published: June 2023

Background

Recreational equipment sales rose significantly during the COVID-19 pandemic. This study investigated changes in the incidence of pediatric emergency department (PED) visits related to outdoor recreational activities during the COVID-19 pandemic.

Methods

A retrospective cohort study was conducted at a large children’s hospital with a level 1 trauma center. Data were obtained from PED electronic medical records of children 5–14 years with a visit from March 23-September 1 in years 2015–2020. Patients with an ICD-10 code for injury associated with recreation and use of common outdoor recreational equipment were included. Initial pandemic year, 2020, was compared with pre-pandemic years (2015–2019). Data collected included patient demographics, injury characteristics, deprivation index, and disposition. Descriptive statistics were used to characterize the population and Chi-squared analysis was used determine relationships between groups.

Results

There were 29,044 total injury visits during the study months with 4715 visits (16.2%) due to recreational mechanisms. A higher proportion of visits due to recreational injury visits occurred during the COVID pandemic (8.2%) compared to before (4.9%). Comparing patients included within the two times, were no differences in sex, ethnicity, or ED disposition. During the COVID pandemic, there was a higher percentage of White patients (80% vs 76%) and patients with commercial insurance (64% vs 55%). There was a significantly lower deprivation index for patients injured during the COVID pandemic. There were more injuries due to bicycles, ATV/motorbike, and non-motorized wheeled vehicles during the COVID pandemic.

Conclusions

During the COVID-19 pandemic, there was an increase in bicycle, ATV/motorbike, and non-motorized wheeled vehicle injuries. White patients with commercial insurance were more likely to be injured compared to years prior. A targeted approach to injury prevention initiatives should be considered.
Magnitude of bottle-feeding practice and associated factors among mothers of 0–24 months’ children in Asella town, Oromia region, Ethiopia
Authors: Hunde Belachew M. , Sitotaw Ismael K. , Elema Teshome B.
Published: June 2023

Background

Since bottle feeding has an impact on the effectiveness of breastfeeding and appropriate supplemental feeding, the World health organization recommends being avoided for infant and early child feeding. Thus, this study aimed to assess the level of the bottle-feeding practice and its associated factors among mothers of 0–24 month’s children in Asella town, Oromia region, Ethiopia.

Methods

Community-based cross-sectional study design was conducted from March 8-April 8, 2022, among a sample of 692 mothers of children aged 0–24 months. A multi-stage sampling technique was used to select the study subjects. Data were collected using a pretested and structured questionnaire by face-to-face interview technique questionnaire. The outcome variable bottle-feeding practice (BFP) was assessed using WHO and UNICEF UK healthy baby initiative BF assessment tools. Binary logistic regression analysis was used to identify the association between explanatory and outcome variables. Adjusted Odds ratio (AOR) with a 95% confidence interval was used to measure the strength of the association and a p-value < 0.05 was used to declare statistical significance.

Results

A total of 692 mothers with mean age and standard deviation (SD) of 31.86 (± 4.87) participated in the study. The prevalence of bottle-feeding practice was 246(35.5% with 95% CI: (31.8, 39.5). Mothers who were government-employed (AOR: 1.64, 95% CI: 1.02, 2.64), mothers who delivered at home (AOR: 3.74, 95% CI: 2.58–5.42), mothers who did not attend postnatal care (AOR: 3.76, 95% CI: 2.60,5.44) and mother who had negative attitude (AOR: 1.94, 95%CI: 1.34,2.8) were significantly associated with bottle feeding practices.

Conclusion

The BFP were higher in the study area when compared with national reports of practices. The occupational status of the mothers, place of delivery, attending postnatal care, and attitude of the mothers were factors that increased bottle-feeding practice in the study area. Strengthening dietary behavioral modification for mothers who have children 0–24 months of the child to practice appropriate feeding is recommended.
Alzheimer’s disease biomarkers in cerebrospinal fluid are stable with the Elecsys immunoassay to most pre-analytical influencing factors except freezing at -80 °C
Authors: Konen Franz Felix , Maier Hannah Benedictine , Neyazi Alexandra , Bleich Stefan , Neumann Konstantin , Skripuletz Thomas
Published: June 2023

Background

Alzheimer´s disease is considered a neurodegenerative disease and is diagnosed by exclusion, while the detection of specific cerebrospinal fluid (CSF) biomarkers, namely amyloid-beta (Aβ) peptides Aβ1–42 (Aß42), phospho-tau (181P; P-tau), and total-tau (T-tau), has been shown to improve diagnostic accuracy. Recently, a new generation of sample tubes (Sarstedt false-bottom tubes) for the Elecsys CSF immunoassay for the determination of Alzheimer´s disease biomarkers in CSF was introduced, promising better measurability. However, the pre-analytic influencing factors have not yet been sufficiently investigated.

Methods

In 29 patients without Alzheimer’s disease diagnosis, CSF concentrations of Aß42, P-tau and T-tau were examined in native CSF and after different influencing interventions using the Elecsys immunoassay test method. The following influencing factors were analyzed: contamination with blood (10,000 and 20,000 erythrocytes/µl CSF), 14-day storage at 4 °C, blood contamination of CSF and 14-day storage at 4 °C, 14-day freezing at -80 °C in Sarstedt tubes or glass vials, 3-month intermediate storage at -80 °C in glass vials.

Results

Both storage at -80 °C for 14 days in Sarstedt false-bottom tubes and in glass vials and storage at -80 °C for 3 months in glass vials resulted in significant decreases in Aß42 (13% after 14 days in Sarstedt and 22% in glass vials, 42% after 3 months in glass vials), P-tau (9% after 14 days in Sarstedt and 13% in glass vials, 12% after 3 months in glass vials) and T-tau (12% after 14 days in Sarstedt and 19% in glass vials, 20% after 3 months in glass vials) concentrations in CSF. No significant differences were found for the other pre-analytical influencing factors.

Conclusions

Measurements of the concentrations of Aß42, P-tau, and T-tau in CSF with use of the Elecsys immunoassay are robust to the pre-analytical influencing factors of blood contamination and duration of storage. Freezing at -80 °C results in significant reduction of biomarker concentrations regardless of the storage tube and must be considered in retrospective analysis.
Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology
Authors: Chopra Supriya , Gupta Ankita , Aoyama Hidefumi , Wu Hong-Gyun , Mahmood Humera , Tharavichitkul Ekkasit , Khine Aung , Gandhi Ajeet , Faruque Golam Mohiuddin , Cruz Misael , Kodrat Henry , Xue Xiaoying , Abeysinghe Prasad , Ho Gwo Fuang , Minjgee Minjmaa , Tey Jeremy , Gao Xianshu
Published: June 2023

PURPOSE

This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations.

MATERIALS AND METHODS

A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO.

RESULTS

Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created.

CONCLUSION

The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.
Characterizing Referrals for Prostate Cancer Genetic Services in a Safety-Net Hospital
Authors: Gunn Christine M. , Gignac Gretchen , Hardy Brianna , Zayhowski Kimberly , Pankowska Magdalena , Loo Stephanie , Wang Catharine
Published: June 2023

A new JCO Onc Practice paper inspects trends in PCa genetic testing referrals before & after guideline changes
Clinical and Genomic Features of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients With Advanced KRAS G12C-Mutant Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Bernstein Ezra , Herzberg Benjamin , Li Bob T. , Iqbal Afsheen , Preeshagul Isabel , Santini Fernando C. , Eng Juliana , Ladanyi Marc , Yang Soo-Ryum , Shen Ronglai , Lito Piro , Riely Gregory J. , Sabari Joshua K. , Arbour Kathryn C.
Published: June 2023

PURPOSE

With the recent approval of the KRAS G12C inhibitor sotorasib for patients with advanced KRAS G12C-mutant non–small cell lung cancer (NSCLC), there is a new need to identify factors associated with activity and toxicity among patients treated in routine practice.

MATERIALS AND METHODS

We conducted a multicenter retrospective study of patients treated with sotorasib outside of clinical trials to identify factors associated with real-world progression free survival (rwPFS), overall survival (OS), and toxicity.

RESULTS

Among 105 patients with advanced KRAS G12C-mutant NSCLC treated with sotorasib, treatment led to a 5.3-month median rwPFS, 12.6-month median OS, and 28% real-world response rate. KEAP1 comutations were associated with shorter rwPFS and OS (rwPFS hazard ratio [HR], 3.19; P = .004; OS HR, 4.10; P = .003); no significant differences in rwPFS or OS were observed across TP53 (rwPFS HR, 1.10; P = .731; OS HR, 1.19; P = .631) or STK11 (rwPFS HR, 1.66; P = .098; OS HR, 1.73; P = .168) comutation status. Notably, almost all patients who developed grade 3 or higher treatment-related adverse events (G3+ TRAEs) had previously been treated with anti–PD-(L)1 therapy. Among these patients, anti–PD-(L)1 therapy exposure within 12 weeks of sotorasib was strongly associated with G3+ TRAEs ( P < .001) and TRAE-related sotorasib discontinuation ( P = .014). Twenty-eight percent of patients with recent anti–PD-(L)1 therapy exposure experienced G3+ TRAEs, most commonly hepatotoxicity.

CONCLUSION

Among patients treated with sotorasib in routine practice, KEAP1 comutations were associated with resistance and recent anti–PD-(L)1 therapy exposure was associated with toxicity. These observations may help guide use of sotorasib in the clinic and may help inform the next generation of KRAS G12C-targeted clinical trials.
Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer
Authors: Wadensten Elisabeth , Wessman Sandra , Abel Frida , Diaz De Ståhl Teresita , Tesi Bianca , Orsmark Pietras Christina , Arvidsson Linda , Taylan Fulya , Fransson Susanne , Vogt Hartmut , Poluha Anna , Pradhananga Sailendra , Hellberg Maria , Lagerstedt-Robinson Kristina , Raj Somarajan Praveen , Samuelsson Sofie , Orrsjö Sara , Maqbool Khurram , Henning Karin , Strid Tobias , Ek Torben , Fagman Henrik , Olsson Bontell Thomas , Martinsson Tommy , Puls Florian , Kogner Per , Wirta Valtteri , Pronk Cornelis Jan , Wille Joakim , Rosenquist Richard , Nistér Monica , Mertens Fredrik , Sabel Magnus , Norén-Nyström Ulrika , Grillner Pernilla , Nordgren Ann , Ljungman Gustaf , Sandgren Johanna , Gisselsson David ,   for the Genomic Medicine Sweden Childhood Cancer Working Group
Published: June 2023

PURPOSE

Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.

METHODS

We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.

RESULTS

During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).

CONCLUSION

Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration
Authors: Bailey Christine N. , Martin Brian J. , Petkov Valentina I. , Schussler Nicola C. , Stevens Jennifer L. , Bentler Suzanne , Cress Rosemary D. , Doherty Jennifer A. , Durbin Eric B. , Gomez Scarlett L. , Gonsalves Lou , Hernandez Brenda Y. , Liu Lihua , Morawski Bożena M. , Schymura Maria J. , Schwartz Stephen M. , Ward Kevin C. , Wiggins Charles , Wu Xiao-Cheng , Goldberg Matthew S. , Siegel Jennifer J. , Cook Robert W. , Covington Kyle R. , Kurley Sarah J.
Published: June 2023

PURPOSE

The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level.

METHODS

Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score–matched to a cohort of non–31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling.

RESULTS

Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients.

CONCLUSION

In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.
Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis
Authors: Dave Biren M. , Chen Xin , McCready Fraser , Charton Connor S. , Morley Rachel M. , Tailor Jignesh K. , Ellis James , Huang Xi , Dirks Peter B.
Published: June 2023

Cerebellar granule neurons (CGNs) are the most abundant neurons in the human brain. Dysregulation of their development underlies movement disorders and medulloblastomas. It is suspected that these disorders arise in progenitor states of the CGN lineage, for which human models are lacking. Here, we have differentiated human hindbrain neuroepithelial stem (hbNES) cells to CGNs in vitro using soluble growth factors, recapitulating key progenitor states in the lineage. We show that hbNES cells are not lineage committed and retain rhombomere 1 regional identity. Upon differentiation, hbNES cells transit through a rhombic lip (RL) progenitor state at day 7, demonstrating human specific sub-ventricular cell identities. This RL state is followed by an ATOH1+ CGN progenitor state at day 14. By the end of a 56-day differentiation procedure, we obtain functional neurons expressing CGN markers GABAARα6 and vGLUT2. We show that sonic hedgehog promotes GABAergic lineage specification and CGN progenitor proliferation. Our work presents a new model with which to study development and diseases of the CGN lineage in a human context.
Optimal Policy under Dollar Pricing
Authors: Egorov Konstantin , Mukhin Dmitry
Published: June 2023

Empirical evidence shows that most international prices are sticky in dollars. This paper studies the policy implications of this fact in the context of an open economy model with general preferences, technologies, asset markets, nominal rigidities, and a rich set of shocks. We show that although monetary policy is less efficient and cannot implement the flexible-price allocation, inflation targeting and a floating exchange rate remain robustly optimal in non-US economies. The capital controls cannot unilaterally improve the allocation and are useful only when coordinated across countries. International cooperation benefits other economies, but is not in the self-interest of the United States. (JEL E31, E52, F14, F31, F38, F41)
The Old Boys’ Club: Schmoozing and the Gender Gap
Authors: Cullen Zoë , Perez-Truglia Ricardo
Published: June 2023

Offices are social places. Employees and managers take breaks together and talk about family and hobbies. In this study, we show that employees’ social interactions with their managers can be advantageous for their careers, and that this phenomenon contributes to the gender pay gap. We use administrative and survey data from a large financial institution and exploit quasi-random variation induced by the rotation of managers. We provide evidence that when employees have more face-to-face interactions with their managers, they are promoted at a higher rate. This mechanism could explain a third of the gender gap in promotions at this firm. (JEL G21, J16, J31, J71, M12, M51, Z13)
Heroes and Villains: The Effects of Heroism on Autocratic Values and Nazi Collaboration in France
Authors: Cagé Julia , Dagorret Anna , Grosjean Pauline , Jha Saumitra
Published: June 2023

We measure how a network of heroes can legitimize and diffuse extreme political behaviors. We exploit newly declassified intelligence files, novel voting data, and regimental histories to show that home municipalities of French line regiments arbitrarily rotated under Philippe Pétain’s generalship through the heroic World War I battlefield of Verdun diverge politically thereafter, particularly following Pétain’s own overt espousal of authoritarian views. Further, under Pétain’s collaborationist Vichy regime (1940–1944), they raise 7 percent more active Nazi collaborators per capita. These effects extend across all forms of Nazi collaboration and diffuse beyond the veterans themselves. (JEL D72, D74, N34, N44, Z13)