bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists
Authors: Glewis Sarah , Lingaratnam Senthil , Krishnasamy Mei , H Martin Jennifer , Tie Jeanne , Alexander Marliese , Michael Michael
Published: April 2023

Background

Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians’ views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation.

Methods

A study-specific 17-question survey was emailed (01 February–12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics.

Results

Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation.

Conclusion

PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians’ hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.
A serial mediation model testing associations between teacher–student relationship, resilience, autonomous learning and academic performance in the Chinese EFL context
Authors: Cui Tianxue , Wang Chuang , Yang Yanchao , Shao Yueyang
Published: April 2023

The current study investigated the relationship between students’ perceived teacher–student relationship (SPTSR) and their performance in English via multiple mediation effects of resilience and autonomous learning in the Chinese English as a foreign language (EFL) context. The participants were 15,184 eighth-graders from China. Results of the multilevel mediation model revealed that after controlling for students’ gender, socioeconomic status (SES), and school type, the positive association between SPTSR and students’ academic outcomes in English was partially and serially mediated by the resilience and autonomous learning. The current study sheds new light on the crucial mediating roles of resilience and autonomous learning in improving EFL learners’ English proficiency. We recommend that English language teachers establish a friendly and equal classroom climate, which may enhance students’ resilience to cope with learning setbacks. Such positive beliefs help stimulate students’ autonomy in English language learning, which in turn promotes performance in learning English.
Unpacking support: A strengths-based investigation into the needs of incarcerated individuals’ loved ones
Authors: Tadros Eman , Henson Abigail , Presley Sarah
Published: April 2023

The United States incarcerates more people than any other country in the world. As a result, a growing body of critical research has sought to understand the impact of the carceral experience, not only on those currently or previously incarcerated, but also on those connected to incarcerated individuals. Much of this research identifies the barriers and difficulties loved ones of incarcerated individuals (LOIs) encounter; however, few of these studies highlight the ways LOIs navigate and overcome such barriers. By using this deficits-framework, LOIs can be mischaracterized as solely powerless or disordered. Also, while many studies importantly identify difficulties in navigating the carceral experience of a loved one, few allow LOIs to speak directly to their needs. Drawing upon deidentified Facebook posts from an online LOI group, the current study takes a strengths-based approach to showcase how LOIs attempt to address their needs and assuage difficulties by engaging in storytelling, advice and information sharing, and advocacy work.
Realignment Surgery for Failed Osteochondral Autologous Transplantation in Osteochondral Lesions of the Talus Associated With Malalignment
Authors: Kim Jaeyoung , Rajan Lavan , Gagne Oliver , Kim Ji-Beom , Lee Woo-Chun
Published: April 2023

Background

While osteochondral autologous transplantation (OAT) offers favorable results in most patients with osteochondral lesions of the talus (OLT), some patients continue to experience persistent pain following the procedure. Information regarding the etiology of this pain and outcomes of revision surgery are limited. This study aimed to report results of revision surgery with realignment procedures in patients with failed OAT who demonstrated concomitant malalignment at the distal tibia or hindfoot.

Methods

Eight patients (8 ankles), who had been experiencing persistent pain for more than 1 year following OAT, underwent realignment procedures during revision surgery. All patients underwent primary OAT for the treatment of medial OLTs. Patients were divided into 2 groups based on the main location of deformity: the supramalleolar realignment group (SRG, 5 ankles) and the hindfoot realignment group (HRG, 3 ankles). No direct procedure was performed on the osteochondral lesion at the time of revision surgery. Ankle and hindfoot alignment were evaluated using 6 parameters in weightbearing radiographs. Computed tomography (CT) was used to assess for medial gutter narrowing, spur formation, and cyst volume around transplanted osteochondral plug preoperatively and postoperatively. Clinical outcomes were assessed using Foot Function Index and Visual Analogue Scale.

Results

All patients had medial gutter narrowing or spur formation, which are early signs of ankle arthritis. The SRG had varus distal tibial alignment with a median medial distal tibial angle of 85.7 degrees (interquartile range [IQR], 3.2). The HRG had valgus hindfoot alignment and a lower medial longitudinal arch with a median hindfoot moment arm of 8.4 mm (IQR, 6.1) and a median Meary’s angle of 11.8 degrees (IQR, 1.4). Spontaneous restoration of the osteochondral lesion was observed after realignment surgery, with cyst volume decreasing from 0.2592 to 0.0873 cm3 (P < .05). Clinical scores improved in all patients.

Conclusion

The current study demonstrates the effectiveness of realignment surgery in a selected patient group who experienced persistent pain and showed radiographic evidence of malalignment after primary OAT. Our study provides evidence supporting the use of realignment procedures in these cases, with results indicating improved patient-reported outcomes and spontaneous restoration of osteochondral lesions.

Levels of Evidence:

Level IV: Case series
Geographic Cluster or Global Linkages? What Accelerates Emerging Market Firms Foreign Entry Speed
Authors: Yadav Sandeep , Upadhyayula Rajesh Srinivas
Published: April 2023

This study examines whether emerging market firms use global linkages as a substitute to the location in geographical clusters to promote the speed of foreign market entry. Drawing from economic geography, we find a slower speed of foreign market entry by firms located outside geographical clusters in the home country as compared to firms inside clusters. This relationship is further moderated by the firm’s cognitive proximity in the foreign markets (measured as a firm’s extent of informal global linkages). Cognitive proximity increases the transfer of tacit knowledge and weakens the negative impact of firm cluster absence on the speed of foreign entry. We test the proposed hypotheses using the cox proportional hazard model based on a longitudinal sample of 602 Indian firms in the information technology industry (IT) from 2000 to 2019.
A new horizon for possibility thinking: A conceptual case study of Human × AI collaboration
Authors: Beghetto Ronald A.
Published: April 2023

Possibility thinking (PT) can be described as an imaginative and action-oriented process that drives movement from what is to what could be. The promise of PT is most fully realized in collaboration with others. With recent advances in AI, it can be argued that natural language models (e.g. OpenAI’s GPT models) represent a possible “other” for such collaborations. This article aims to illustrate, through a conceptual case study, how Human × AI collaboration can support PT. The article opens with a brief overview of the basic principles of PT and how those principles can be applied in Human × AI collaboration. Next, a conceptual case study will be presented, which reports on six examples of Human × AI collaborations used for PT. The article closes with a brief discussion of implications and future directions, including the importance of developing a principled approach when using AI for PT. This article likely will be of interest to broad audiences within and across domains, including readers focused on human-centered AI collaborations and anyone interested in learning more about new and emerging ways to generate possibilities in their learning, work, and lives.
Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension
Authors: Chakraborty Ananya , Nathan Abinaya , Orcholski Mark , Agarwal Stuti , Shamskhou Elya A. , Auer Natasha , Mitra Ankita , Guardado Eleana Stephanie , Swaminathan Gowri , Condon David F. , Yu Joyce , McCarra Matthew , Juul Nicholas H. , Mallory Alden , Guzman-Hernandez Roberto A. , Yuan Ke , Rojas Vanesa , Crossno Joseph T. , Yung Lai-Ming , Yu Paul B. , Spencer Thomas , Winn Robert A. , Frump Andrea , Karoor Vijaya , Lahm Tim , Hedlin Haley , Fineman Jeffrey R. , Lafyatis Robert , Knutsen Carsten N.F. , Alvira Cristina M. , Cornfield David N. , de Jesus Perez Vinicio A.
Published: April 2023

Introduction:

Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH.

Methods:

Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specificWnt7a−/–mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx).

Results:

Healthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specificWnt7a−/–mice under either chronic hypoxia or SuHx, globalWnt7a+/–mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH,Wnt7a+/–PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a.

Conclusions:

Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.
Characteristics of severe asthma patients on biologics: a real-life European registry study
Authors: Principe Stefania , Richards Levi B. , Hashimoto Simone , Kroes Johannes Anthon , Van Bragt Job J.M.H. , Vijverberg Susanne J. , Sont Jacob K. , Scichilone Nicola , Bieksiene Kristina , Ten Brinke Anneke , Csoma Zsuzsanna , Dahlén Barbro , Gemicioglu Bilun , Grisle Ineta , Kuna Piotr , Lazic Zorica , Mihaltan Florin , Popović-Grle Sanja , Škrgat Sabina , Marcon Alessandro , Caminati Marco , Djukanovic Ratko , Porsbjerg Celeste , Maitland Van Der Zee Anke-Hilse
Published: April 2023

Background

The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs.

Materials and methods

We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies.

Results

Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids.

Conclusion

A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.
Diffuse alveolar haemorrhage in children: an international multicentre study
Authors: Ring Astrid Madsen , Schwerk Nicolaus , Kiper Nural , Aslan Ayse Tana , Aurora Paul , Ayats Roser , Azevedo Ines , Bandeira Teresa , Carlens Julia , Castillo-Corullon Silvia , Cobanoglu Nazan , Elnazir Basil , Emiralioğlu Nagehan , Eyuboglu Tugba Sismanlar , Fayon Michael , Gursoy Tugba Ramaslı , Hogg Claire , Kötz Karsten , Karadag Bülent , Látalová Vendula , Krenke Katarzyna , Lange Joanna , Manali Effrosyni D. , Osona Borja , Papiris Spyros , Proesmans Marijke , Reix Philippe , Roditis Lea , Rubak Sune , Rumman Nisreen , Snijders Deborah , Stehling Florian , Weiss Laurence , Yalcın Ebru , Zirek Fazilcan , Bush Andrew , Clement Annick , Griese Matthias , Buchvald Frederik Fouirnaies , Nathan Nadia , Nielsen Kim Gjerum
Published: April 2023

Background

Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome.

Methods

A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years.

Results

Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0–12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function.

Conclusions

Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.
Genomic adaptation to extreme climate conditions in beef cattle as a consequence of cross-breeding program
Authors: Tian Rugang , Asadollahpour Nanaie Hojjat , Wang Xiao , Dalai Baolige , Zhao Meng , Wang Feng , Li Hui , Yang Ding , Zhang Hao , Li Yuan , Wang Tingyue , Luan Tu , Wu Jianghong
Published: April 2023

Background

Understanding the evolutionary forces related to climate changes that have been shaped genetic variation within species has long been a fundamental pursuit in biology. In this study, we generated whole-genome sequence (WGS) data from 65 cross-bred and 45 Mongolian cattle. Together with 62 whole-genome sequences from world-wide cattle populations, we estimated the genetic diversity and population genetic structure of cattle populations. In addition, we performed comparative population genomics analyses to explore the genetic basis underlying variation in the adaptation to cold climate and immune response in cross-bred cattle located in the cold region of China. To elucidate genomic signatures that underlie adaptation to cold climate, we performed three statistical measurements, fixation index (FST), log2 nucleotide diversity (θπ ratio) and cross population composite likelihood ratio (XP-CLR), and further investigated the results to identify genomic regions under selection for cold adaptation and immune response-related traits.

Results

By generating WGS data, we investigated the population genetic structure and phylogenetic relationship of studied cattle populations. The results revealed clustering of cattle groups in agreement with their geographic distribution. We detected noticeable genetic diversity between indigenous cattle ecotypes and commercial populations. Analysis of population structure demonstrated evidence of shared genetic ancestry between studied cross-bred population and both Red-Angus and Mongolian breeds. Among all studied cattle populations, the highest and lowest levels of linkage disequilibrium (LD) per Kb were detected in Holstein and Rashoki populations (ranged from ~ 0.54 to 0.73, respectively). Our search for potential genomic regions under selection in cross-bred cattle revealed several candidate genes related with immune response and cold shock protein on multiple chromosomes. We identified some adaptive introgression genes with greater than expected contributions from Mongolian ancestry into Molgolian x Red Angus composites such as TRPM8, NMUR1, PRKAA2, SMTNL2 and OXR1 that are involved in energy metabolism and metabolic homeostasis. In addition, we detected some candidate genes probably associated with immune response-related traits.

Conclusion

The study identified candidate genes involved in responses to cold adaptation and immune response in cross-bred cattle, including new genes or gene pathways putatively involved in these adaptations. The identification of these genes may clarify the molecular basis underlying adaptation to extreme environmental climate and as such they might be used in cattle breeding programs to select more efficient breeds for cold climate regions.
Application of TraDIS to define the core essential genome of Campylobacter jejuni and Campylobacter coli
Authors: Stoakes Emily , Turner Keith , Baker Dave J. , Suau Sans Maria , Yasir Muhammad , Kalmar Lajos , Costigan Ruby , Lott Martin , Grant Andrew J.
Published: April 2023

Campylobacter species are the major cause of bacterial gastroenteritis. As there is no effective vaccine, combined with the rapid increase in antimicrobial resistant strains, there is a need to identify new targets for intervention. Essential genes are those that are necessary for growth and/or survival, making these attractive targets. In this study, comprehensive transposon mutant libraries were created in six C. jejuni strains, four C. coli strains and one C. lari and C. hyointestinalis strain, allowing for those genes that cannot tolerate a transposon insertion being called as essential. Comparison of essential gene lists using core genome analysis can highlight those genes which are common across multiple strains and/or species. Comparison of C. jejuni and C. coli, the two species that cause the most disease, identified 316 essential genes. Genes of interest highlighted members of the purine pathway being essential for C. jejuni whilst also finding that a functional potassium uptake system is essential. Protein–protein interaction networks using these essential gene lists also highlighted proteins in the purine pathway being major ‘hub’ proteins which have a large number of interactors across the network. When adding in two more species (C. lari and C. hyointestinalis) the essential gene list reduces to 261. Within these 261 essential genes, there are many genes that have been found to be essential in other bacteria. These include htrB and PEB4, which have previously been found as core virulence genes across Campylobacter species in other studies. There were 21 genes which have no known function with eight of these being associated with the membrane. These surface-associated essential genes may provide attractive targets. The essential gene lists presented will help to prioritise targets for the development of novel therapeutic and preventative interventions.
Association between intraoperative pulmonary artery pressure and cardiovascular complications after off-pump coronary artery bypass surgery: a single-center observational study
Authors: Matsuo Mitsuhiro , Doi Toshio , Katsuki Masahito , Yoshimura Yuichiro , Ito Hisakatsu , Fukahara Kazuaki , Yoshimura Naoki , Yamazaki Mitsuaki
Published: April 2023

Background

The impact of intraoperative pulmonary hemodynamics on prognosis after off-pump coronary artery bypass (OPCAB) surgery remains unknown. In this study, we examined the association between intraoperative vital signs and the development of major adverse cardiovascular events (MACE) during hospitalization or within 30 days postoperatively.

Methods

This retrospective study analyzed data from a university hospital. The study cohort comprised consecutive patients who underwent isolated OPCAB surgery between November 2013 and July 2021. We calculated the mean and coefficient of variation of vital signs obtained from the intra-arterial catheter, pulmonary artery catheter, and pulse oximeter. The optimal cut-off was defined as the receiver operating characteristic curve (ROC) with the largest Youden index (Youden index = sensitivity + specificity – 1). Multivariate logistic regression analysis ROC curves were used to adjust all baseline characteristics that yielded P values of < 0.05.

Results

In total, 508 patients who underwent OPCAB surgery were analyzed. The mean patient age was 70.0 ± 9.7 years, and 399 (79%) were male. There were no patients with confirmed or suspected preoperative pulmonary hypertension. Postoperative MACE occurred in 32 patients (heart failure in 16, ischemic stroke in 16). The mean pulmonary artery pressure (PAP) was significantly higher in patients with than without MACE (19.3 ± 3.0 vs. 16.7 ± 3.4 mmHg, respectively; absolute difference, 2.6 mmHg; 95% confidence interval, 1.5 to 3.8). The area under the ROC curve of PAP for the prediction of MACE was 0.726 (95% confidence interval, 0.645 to 0.808). The optimal mean PAP cut-off was 18.8 mmHg, with a specificity of 75.8% and sensitivity of 62.5% for predicting MACE. After multivariate adjustments, high PAP remained an independent risk factor for MACE.

Conclusions

Our findings provide the first evidence that intraoperative borderline pulmonary hypertension may affect the prognosis of patients undergoing OPCAB surgery. Future large-scale prospective studies are needed to verify the present findings.
Impact of vitamin D receptor gene polymorphisms (TaqI and BsmI) on the incidence and severity of coronary artery disease: a report from southern Iran
Authors: Akhlaghi Boshra , Firouzabadi Negar , Foroughinia Farzaneh , Nikparvar Marzieh , Dehghani Pouyan
Published: April 2023

Background

The association of vitamin D level and vitamin D receptor (VDR) gene polymorphisms with the prevalence of coronary artery disease (CAD) has been evaluated in various studies; however, the reported results were inconsistent. Hence, we aimed to investigate the impact of two VDR gene polymorphisms, TaqI (rs731236) and BsmI (rs1544410), on the incidence and severity of CAD in Iranian population.

Methods

Blood samples were collected from 118 CAD patients underwent elective percutaneous coronary intervention (PCI) and 52 control subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping. SYTNAX score (SS) was calculated as a grading tool for complexity of CAD by an interventional cardiologist.

Results

TaqI polymorphism of VDR was not associated with the incidence of CAD. A significant difference was observed between CAD patients and controls regarding BsmI polymorphism of VDR (p < 0.001). GA and AA genotypes was significantly associated with a decreased risk of CAD (p = 0.01, p-adjusted = 0.01 and p < 0.001, p-adjusted = 0.001 respectively). A allele of BsmI polymorphism was shown to have a protective effect against CAD (p < 0.001, p-adjusted = 0.002). No association was found between TaqI and BsmI polymorphisms of VDR and SS as a measure of CAD severity.

Conclusion

Association of BsmI genotypes with the incidence of CAD revealed that the genetic variation of VDR might play a role in the pathogenesis of CAD.
Accounting for expected attrition in the planning of cluster randomized trials for assessing treatment effect heterogeneity
Authors: Tong Jiaqi , Li Fan , Harhay Michael O. , Tong Guangyu
Published: April 2023

Background

Detecting treatment effect heterogeneity is an important objective in cluster randomized trials and implementation research. While sample size procedures for testing the average treatment effect accounting for participant attrition assuming missing completely at random or missing at random have been previously developed, the impact of attrition on the power for detecting heterogeneous treatment effects in cluster randomized trials remains unknown.

Methods

We provide a sample size formula for testing for a heterogeneous treatment effect assuming the outcome is missing completely at random. We also propose an efficient Monte Carlo sample size procedure for assessing heterogeneous treatment effect assuming covariate-dependent outcome missingness (missing at random). We compare our sample size methods with the direct inflation method that divides the estimated sample size by the mean follow-up rate. We also evaluate our methods through simulation studies and illustrate them with a real-world example.

Results

Simulation results show that our proposed sample size methods under both missing completely at random and missing at random provide sufficient power for assessing heterogeneous treatment effect. The proposed sample size methods lead to more accurate sample size estimates than the direct inflation method when the missingness rate is high (e.g., ≥ 30%). Moreover, sample size estimation under both missing completely at random and missing at random is sensitive to the missingness rate, but not sensitive to the intracluster correlation coefficient among the missingness indicators.

Conclusion

Our new sample size methods can assist in planning cluster randomized trials that plan to assess a heterogeneous treatment effect and participant attrition is expected to occur.
A novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma
Authors: Chen Yusheng , Lin Xuan , Zou Xuan , Qian Yunzhen , Liu Yu , Wang Ruijie , Wang Xu , Yu Xianjun , Liu Chen , Cheng He
Published: April 2023

Background

Pancreatic adenocarcinoma (PAAD) remains a lethal malignancy making the detection of novel prognostic biomarkers urgent. Limited studies have investigated the predictive capability of immune checkpoints in PAAD.

Method

Gene expression data and correlative clinical information of PAAD cohort were obtained from public databases, including TCGA, ICGC, GTEX and GEO databases. Risk factors were screened and used to establish a risk score model through LASSO and Cox regression analyses. The prognostic ability of the risk score model was demonstrated. The association between risk score with immune cells infiltration, immune checkpoint genes expression, immunogenic cell death, somatic mutations and signaling pathways enrichment were analysed. scRNA-seq data were collected to confirmed the immune checkpoints expression in PAAD samples. The prognosis prediction ability of OX40/TNFRSF4 was identified. The mRNA and protein expression of OX40 in our clinical specimens were examined by RT-PCR and IHC method and its prognosis ability was verified.

Results

First of all, the difference of immune microenvironment between pancreatic cancer and adjacent tissues was shown. A risk score system based on three immune checkpoints (OX40, TNFSF14 and KIR3DL1) was established. The risk score model was an independent prognostic factor and performed well regarding overall survival (OS) predictions among PAAD patients. A nomogram was established to facilitate the risk model application in clinical prognosis. Immune cells including naive B cells, CD8+ T cells and Tregs were negatively correlated with the risk score. The risk score was associated with expression of immune checkpoint genes, immunogenic cell death related genes and somatic mutations. Glycolysis processes, IL-2-STAT5, IL-6-STAT3, and mTORC1 signaling pathways were enriched in the high-risk score group. Furthermore, scRNA-seq data confirmed that TNFRSF4, TNFSF14 and KIR3DL1 were expressed on immune cells in PAAD samples. We then identified OX40 as an independent prognosis-related gene, and a higher OX40 expression was associated with increased survival rate and immune environment change. In 84 PAAD clinical specimens collected from our center, we confirmed that higher OX40 mRNA expression levels were related to a good prognosis. The protein expression of OX40 on tumor-infiltrating immune cells (TIICs), endothelial cells and tumor cells was verified in PAAD tissues by immunohistochemistry (IHC) method.

Conclusions

Overall, our findings strongly suggested that the three-immune checkpoints score system might be useful in the prognosis and design of personalized treatments for PAAD patients. Finally, we identified OX40 as an independent potential biomarker for PAAD prognosis prediction.
Diagnostic performance of the IMMY cryptococcal antigen lateral flow assay on serum and cerebrospinal fluid for diagnosis of cryptococcosis in HIV-negative patients: a systematic review
Authors: Macrae Catriona , Ellis Jayne , Keddie Suzanne H. , Falconer Jane , Bradley John , Keogh Ruth , Baerenbold Oliver , Hopkins Heidi , Jarvis Joseph N.
Published: April 2023

Background

The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid.

Methods

We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity.

Results

Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68–100%) with a pooled specificity estimate of 96% (95%CrI 84–100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95–100%) with a pooled specificity median of 99% (95%CrI 95–100%).

Conclusions

This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test.
Multiple rib and vertebral fractures associated with Bordetella pertussis infection: a case report
Authors: Wang Jingqiao , Gao Junxiang , Fan Hongwei , Guo Haonan , Yin Zundong , Dong Mei , Huang Xiaoming
Published: April 2023

Background

Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult.

Case presentation

A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient’s bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient’s symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain.

Conclusions

Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.
Does design change in total knee arthroplasty implants affect patient-reported outcomes?
Authors: Toossi Nader , Bucklen Brandon , Meding Lindsey K. , Meding John B.
Published: April 2023

Purpose

The purpose of this study is to compare the early results of patient-reported outcomes between two generations of a total knee system.

Methods

Between June 2018 and April 2020, 121 first-generation, cemented TKAs (89 patients) and 123 s-generation, cemented TKAs (98 patients) were performed by a single surgeon. Demographic and surgical data were collected from all patients. Starting at the 6-month follow-up, patient-reported outcome measures Knee Injury and Osteoarthritis Outcome Score, Joint Reconstruction (KOOS-JR) and Knee Society (KS) clinical and radiographic scores were prospectively recorded. This study represents a retrospective review of these prospectively collected data.

Results

There were no statistically significant differences between the two groups in terms of demographic variables such as age, body mass index, gender and race. KOOS-JR and Knee Society (KS) scores improved significantly (p < 0.001) from their preoperative values in both device generations. There were no differences, pre-operatively, between the two groups in terms of KOOS-JR, KS functional, KS objective, patient satisfaction, and expectation scores; however, there were statistically significant (p < 0.001) lower values of KOOS-JR and KS functional scores for first versus second generation at 6 months (81 vs. 89 and 69 vs. 74, respectively).

Conclusion

While significant improvement in KS objective, subjective, and patient satisfaction scores were noted with both knee systems, KOOS-JR and KS function scores were significantly higher at the early (6-month) follow-up in the second-generation group. Patients responded acutely to the design change as evidenced by significantly improved patient-reported outcome scores for the second generation.
Exploring the microbiome of oral epithelial dysplasia as a predictor of malignant progression
Authors: Wright Robyn J. , Pewarchuk Michelle E. , Marshall Erin A. , Murrary Benjamin , Rosin Miriam P. , Laronde Denise M. , Zhang Lewei , Lam Wan L. , Langille Morgan G. I. , Rock Leigha D.
Published: April 2023

A growing body of research associates the oral microbiome and oral cancer. Well-characterized clinical samples with outcome data are required to establish relevant associations between the microbiota and disease. The objective of this study was to characterize the community variations and the functional implications of the microbiome in low-grade oral epithelial dysplasia (OED) using 16S rRNA gene sequencing from annotated archival swabs in progressing (P) and non-progressing (NP) OED. We characterised the microbial community in 90 OED samples — 30 swabs from low-grade OED that progressed to cancer (cases) and 60 swabs from low-grade OED that did not progress after a minimum of 5 years of follow up (matched control subjects). There were small but significant differences between P and NP samples in terms of alpha diversity as well as beta diversity in conjunction with other clinical factors such as age and smoking status for both taxa and functional predictions. Across all samples, the most abundant genus was Streptococcus, followed by Haemophilus, Rothia, and Neisseria. Taxa and predicted functions were identified that were significantly differentially abundant with progression status (all Ps and NPs), when samples were grouped broadly by the number of years between sampling and progression or in specific time to progression for Ps only. However, these differentially abundant features were typically present only at low abundances. For example, Campylobacter was present in slightly higher abundance in Ps (1.72%) than NPs (1.41%) and this difference was significant when Ps were grouped by time to progression. Furthermore, several of the significantly differentially abundant functions were linked to the Campylobacteraceae family in Ps and may justify further investigation. Larger cohort studies to further explore the microbiome as a potential biomarker of risk in OED are warranted.
Women in a safe and healthy urban environment: environmental top priorities for the women’s presence in urban public spaces
Authors: Sadeghi Ali Reza , Baghi Elahe Sadat Mousavi Sarvine , Shams Fatemeh , Jangjoo Sina
Published: April 2023

Today, in developing countries, women's need to be present in urban public spaces and the establishment of everyday social interactions seem to be ignored more than other groups. Therefore, the present study aims to achieve the environmental components related to women’s presence in urban spaces and prioritize them. In this study, by scrutinizing the criteria obtained from the interviews, a questionnaire was prepared and randomly distributed among 256 women in the population. IBM SPSS has been used to analyze the data and explain the priorities. The results of the T-test show that security (T-value = 6.508 in T1 test), compatibility with behavioral patterns (T-value = 4.975 in T2 test), eventuality (T-value = 11.064 in T3 test), permeability (T-value = 10.220 in T4 test), attention to climate (T-value = 5.692 in T5 test), liberty (T-value = 11.184 in T6 test), collective memory (T-value = 7.367 in T7 test), variety (T-value = 1.816 in T8 test), complexity (T-value = 13.228 in T9 test), and identity (T-value of 18.905 in T10 test) are the most important criteria in motivating presence in urban public spaces, respectively. According to the results, among the individual characteristics of the respondents, the components of collective memory (r = 0.805), identity (r = 0.784), liberty (r = 0.703), and safety and security (r = 0.644) have had a positive correlation with the age of the respondents. The results of this study indicated that improving security (individual, social, and psychological) is the main environmental priority for women over 18 to be present in urban public spaces.
Gender-based violence and its associated factors among internally displaced women in Northwest Ethiopia: a cross-sectional study
Authors: Workie Keralem , Tinsae Techilo , Salelew Endalamaw , Asrat Biksegn
Published: April 2023

Background

Gender-based violence (GBV) is a common human right violence in conflict-affected communities. Women with GBV are prone to experience mental health problems such as post-traumatic stress disorder, depression, and anxiety. However, there is a paucity of evidence as to what extent the problem is affecting internally displaced women (IDW) in Ethiopia. This study aimed to assess the prevalence of GBV and its associated factors among IDW in Northwest Ethiopia.

Methods

A cross-sectional study was conducted among IDW residing at three humanitarian sites from May to June 2022 in Northwest Ethiopia. Study participants were selected using a stratified simple random sampling technique from the three sites. GBV was assessed using a 6-item Assessment Screen to Identify Survivors Toolkit questionnaire for Gender-based violence (ASIST-GBV). Data were analyzed using binary logistic regression. All variables with ap-value of ≤ 0.05 in the multivariable analysis were defined to have a statistically significant association with GBV at a 95% confidence interval (CI).

Results

Of 424 approached candidates, 412 (97.2%) of them participated in the study. A one-year prevalence of GBV was 37.9% (95%CI = 33.2–42.6) among IDW in Northwest Ethiopia. The mean age of the participants was 31.3 (± 7.6) years. Young women, 18–24 years old (AOR = 3.52, 95%CI = 2.15–5.34,p ≤ 0.001) and 25–29 years old (AOR = 2.41, 95%CI = 1.57–3.24,p ≤ 0.001) had a statistically significant association with GBV. Moreover, having no social protection (AOR = 3.18, 95%CI = 2.65–6.22,p ≤ 0.001), being current alcohol user (AOR = 2.54, 95%CI = 1.22–4.78,p ≤ 0.001) and being single in marital status (AOR = 1.69, 95%CI = 1.18–2.87,p < 0.01) showed a statistical association with GBV.

Conclusion

We found a high prevalence of GBV among IDW in Northwest Ethiopia which indicates that IDW are prone to GBV. We call for immediate action and special attention to young women in conflict-affected parts of Ethiopia. It is crucial to establish a system that ensures the safety, security, and well-being of women in humanitarian settings.
Accurate breast cancer diagnosis using a stable feature ranking algorithm
Authors: Yu Shaode , Jin Mingxue , Wen Tianhang , Zhao Linlin , Zou Xuechao , Liang Xiaokun , Xie Yaoqin , Pan Wanlong , Piao Chenghao
Published: April 2023

Background

Breast cancer (BC) is one of the most common cancers among women. Since diverse features can be collected, how to stably select the powerful ones for accurate BC diagnosis remains challenging.

Methods

A hybrid framework is designed for successively investigating both feature ranking (FR) stability and cancer diagnosis effectiveness. Specifically, on 4 BC datasets (BCDR-F03, WDBC, GSE10810 and GSE15852), the stability of 23 FR algorithms is evaluated via an advanced estimator (S), and the predictive power of the stable feature ranks is further tested by using different machine learning classifiers.

Results

Experimental results identify 3 algorithms achieving good stability ($$S \ge 0.55$$S≥0.55) on the four datasets and generalized Fisher score (GFS) leading to state-of-the-art performance. Moreover, GFS ranks suggest that shape features are crucial in BC image analysis (BCDR-F03 and WDBC) and that using a few genes can well differentiate benign and malignant tumor cases (GSE10810 and GSE15852).

Conclusions

The proposed framework recognizes a stable FR algorithm for accurate BC diagnosis. Stable and effective features could deepen the understanding of BC diagnosis and related decision-making applications.
Development and user testing of a patient decision aid for cancer patients considering treatment for anxiety or depression
Authors: Rayner Rebecca , Shaw Joanne , Hunt Caroline
Published: April 2023

Background

Despite high rates of mental health disorders among cancer patients, uptake of referral to psycho-oncology services remains low. This study aims to develop and seek clinician and patient feedback on a patient decision aid (PDA) for cancer patients making decisions about treatment for anxiety and/or depression.

Methods

Development was informed by the International Patient Decision Aid Standards and the Ottawa Decision Support Framework. Psycho-oncology professionals provided feedback on the clinical accuracy, acceptability, and usability of a prototype PDA. Cognitive interviews with 21 cancer patients/survivors assessed comprehensibility, acceptability, and usefulness. Interviews were thematically analysed using Framework Analysis.

Results

Clinicians and patients strongly endorsed the PDA. Clinicians suggested minor amendments to improve clarity and increase engagement. Patient feedback focused on clarifying the purpose of the PDA and improving the clarity of the values clarification exercises (VCEs).

Conclusions

The PDA, the first of its kind for psycho-oncology, was acceptable to clinicians and patients. Valuable feedback was obtained for the revision of the PDA and VCEs.