bluuebunny/crossref_metadata_2025 huggingface dataset:
Population-level health and economic impacts of introducing Vaccae vaccination in China: a modelling study
Authors: Mao Jun-Jie , Zang Xiao , Yue Wan-Lu , Zhai Pei-Yao , Zhang Qiong , Li Chun-Hu , Zhuang Xun , Liu Min , Qin Gang
Published: May 2023

Introduction

Given the ageing epidemic of tuberculosis (TB), China is facing an unprecedented opportunity provided by the first clinically approved next-generation TB vaccine Vaccae, which demonstrated 54.7% efficacy for preventing reactivation from latent infection in a phase III trial. We aim to assess the population-level health and economic impacts of introducing Vaccae vaccination to inform policy-makers.

Methods

We evaluated a potential national Vaccae vaccination programme in China initiated in 2024, assuming 20 years of protection, 90% coverage and US$30/dose government contract price. An age-structured compartmental model was adapted to simulate three strategies: (1) no Vaccae; (2) mass vaccination among people aged 15–74 years and (3) targeted vaccination among older adults (60 years). Cost analyses were conducted from the healthcare sector perspective, discounted at 3%.

Results

Considering postinfection efficacy, targeted vaccination modestly reduced TB burden (~20%), preventing cumulative 8.01 (95% CI 5.82 to 11.8) million TB cases and 0.20 (0.17 to 0.26) million deaths over 2024–2050, at incremental cost-effectiveness ratio of US$4387 (2218 to 10 085) per disability adjusted life year averted. The implementation would require a total budget of US$22.5 (17.6 to 43.4) billion. In contrast, mass vaccination had a larger bigger impact on the TB epidemic, but the overall costs remained high. Although both preinfection and postinfection vaccine efficacy type might have a maximum impact (>40% incidence rate reduction in 2050), it is important that the vaccine price does not exceed US$5/dose.

Conclusion

Vaccae represents a robust and cost-effective choice for TB epidemic control in China. This study may facilitate the practice of evidence-based strategy plans for TB vaccination and reimbursement decision making.
Prediction model of adjacent vertebral compression fractures after percutaneous kyphoplasty: a retrospective study
Authors: Mao Yi , Wu Wangsheng , Zhang Junchao , Ye Zhou
Published: May 2023

Objectives

The purpose of this study was to develop a prediction model to assess the risk of adjacent vertebral compression fractures (AVCFs) after percutaneous kyphoplasty (PKP) surgery.

Design

A retrospective chart review.

Setting and participants

Patients were collected from the Quzhou People’s Hospital, from March 2017 to May 2019. Patients were included if they suffered from osteoporotic vertebral compression fractures (OVCFs), underwent PKP surgery and were followed up for 2 years.

Interventions

None.

Methods

This was a retrospective cohort study of all PKP surgery procedures of the thoracic, lumbar and thoracolumbar (TL) spine that have been performed for OVCF from 1 March 2017 up to 1 May 2019. The least absolute shrinkage and selection operator (LASSO) regression model was used to optimise feature selection for the AVCF risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the LASSO regression model. The C-index, calibration plot and decision curve analysis were applied to assess this model.

Results

Gender, age, the number of surgical vertebrae, cement volume, bone mineral density, diabetes, hypertension, bone cement leakage, duration of anti-osteoporosis treatment after surgery and TL junction were identified as predictors. The model displayed good discrimination with a C-index of 0.886 (95% CI 0.828–0.944) and good calibration. High C-index value of 0.833 could still be reached in the interval validation. Decision curve analysis showed that the AVCF nomogram was clinically useful when intervention was decided at the AVCF possibility threshold of 1%.

Conclusions

This study developed a clinical prediction model to identify the risk factors for AVCF after PKP surgery, and this tool is of great value in sharing surgical decision-making among patients consulted before surgery.

Trial registration number

researchregistry7716.
Compassion fatigue in healthcare providers during the COVID-19 pandemic: a scoping review protocol
Authors: Hui Lucy , Garnett Anna , Oleynikov Christina , Boamah Sheila A
Published: May 2023

Introduction

The COVID-19 pandemic has negatively impacted the psychological health and well-being of healthcare providers. An amplification in chronic stressors, workload and fatalities may have increased the risk of compassion fatigue and disrupted the quality of patient care. Although current studies have explored the general psychological status of healthcare providers during the COVID-19 pandemic, few have focused on compassion fatigue. The purpose of this review is to explore the impacts of the COVID-19 pandemic on compassion fatigue in healthcare providers and the repercussions of compassion fatigue on patient care.

Methods and analysis

This scoping review will follow Joanna Briggs Institute and Arksey and O’Malley scoping review methodology. Comprehensive searches will be conducted in the following relevant databases: MEDLINE (Ovid), PsycINFO (Ovid), Embase (Ovid), CINAHL, Scopus, Web of Science. To expand the search, reference lists of included studies will be handsearched for additional relevant studies. Included studies must report on the impact of COVID-19 pandemic on compassion fatigue in healthcare providers and have been published in English since January 2020.

Ethics and dissemination

This review does not require research ethics board approval. By examining the impacts of the COVID-19 pandemic on compassion fatigue in healthcare providers, this scoping review can offer important insight into the possible risks, protective factors and strategies to support healthcare providers’ psychological health and patient care amidst persisting stressful conditions.
Cross-sectional study examining household factors associated with SARS-CoV-2 seropositivity in low-income children in Los Angeles
Authors: Doctor Jason N , Berg Anders H , Knight Tara K , Kadono Mika , Stewart Emily , Sonik Rajan , Hochman Michael , Sood Neeraj
Published: May 2023

Objectives

This study aims to quantify the degree to which an underserved, Hispanic population in Los Angeles is impacted by SARS-CoV-2, and determine factors associated with paediatric seropositivity.

Design

Cross-sectional.

Setting

AltaMed, a Federally Qualified Health Center in Los Angeles.

Participants

A random sample of households who had received healthcare at AltaMed Medical Group was invited to participate. Households with at least one adult and one paediatric participant between 5 and 17 years of age were eligible to participate. Consented participants completed a survey on social determinants of health and were tested for antibodies using Abbott Architect SARS-CoV-2-IgG and SARS-CoV-2-IgM tests.

Primary outcome measure

Seropositive status.

Results

We analysed 390 adults (mean age in years, 38.98 (SD 12.11)) and 332 paediatric participants (11.26 (SD 3.51)) from 196 households. Estimated seropositivity was 52.11% (95% CI 49.61% to 55.19%) in paediatric participants and 63.58% (95% CI 60.39% to 65.24%) in adults. Seropositivity was 11.47% (95% CI 6.82% to 14.09%) lower in paediatric participants, but high relative to other populations. A household member with type 2 diabetes (OR 2.94 (95% CI 1.68 to 5.14)), receipt of food stamps (OR 1.66 (95% CI 1.08 to 2.56)) and lower head-of-household education (OR 1.73 (95% CI 1.06 to 2.84)) were associated with paediatric seropositivity.

Conclusions

SARS-CoV-2 seropositivity is high in Hispanic children and adolescents in Los Angeles. Food insecure households with low head-of-household education, and at least one household member with type 2 diabetes, had the highest risk. These factors may inform paediatrician COVID-19 mitigation recommendations.

Trial registration number

NCT04901624.
Developing and delivering a hybrid Cardiac Rehabilitation Phase II exercise program during the COVID-19 pandemic: a quality improvement program
Authors: Loureiro Diaz Javier , Foster Liam David , Surendran Praveen Jayaprabha , Jacob Prasobh , Ibrahim Omar , Gupta Poonam
Published: May 2023

The COVID-19 pandemic resulted in the cessation of approximately 75% of cardiac rehabilitation (CR) programmes worldwide. In March 2020, CR phase II (CRP2) services were stopped in Qatar. Multiple studies had shown safety, effectiveness, reduced cost of delivery and improved participation with hybrid CR. A multidisciplinary team reviewed various alternative models for delivery and decided to implement a hybrid CRP2 exercise programme (HCRP2-EP) to ensure continuation of our patient care. Our aim was to enrol in the HCRP2-EP 70% of all eligible patients by 30 September 2020. Institute for Health Care Improvement’s collaborative model was adopted. Multiple plan–do–study–act cycles were used to test change ideas. The outcomes of the project were analysed using standard run chart rules to detect the changes in outcomes over time. This project was implemented from March 2020, and the male patients enrolled between August 2020 and April 2021, with sustained monthly median enrolment above target of 70% throughout. As for our secondary outcome, 75.8% of the male patients who completed HCRP2-EP showed a meaningful change in peak exercise capacity of ≥10% (mean change 17%±6%). There were no major adverse events reported, and the median Patient Satisfaction Score was 96% well above the institutional target of 90%. This shows a well-designed quality improvement programme is an appropriate strategy for implementing HCRP2-EP in a clinical setting, and HCRP2-EP is a feasible, effective and safe intervention in eligible male patients with cardiovascular disease.
Emerging interleukin targets in the tumour microenvironment: implications for the treatment of gastrointestinal tumours
Authors: Dickerson Lindsay Kathleen , Carter Jason A , Kohli Karan , Pillarisetty Venu G
Published: May 2023

The effectiveness of antitumour immunity is dependent on intricate cytokine networks. Interleukins (ILs) are important mediators of complex interactions within the tumour microenvironment, including regulation of tumour-infiltrating lymphocyte proliferation, differentiation, migration and activation. Our evolving and increasingly nuanced understanding of the cell type-specific and heterogeneous effects of IL signalling has presented unique opportunities to fine-tune elaborate IL networks and engineer new targeted immunotherapeutics. In this review, we provide a primer for clinicians on the challenges and potential of IL-based treatment. We specifically detail the roles of IL-2, IL-10, IL-12 and IL-15 in shaping the tumour-immune landscape of gastrointestinal malignancies, paying particular attention to promising preclinical findings, early-stage clinical research and innovative therapeutic approaches that may properly place ILs to the forefront of immunotherapy regimens.
Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer treated with systemic neoadjuvant therapy
Authors: Huerta-Rosario Mariela , Mir Mariam , Quispe-Vicuña Carlos , Hwang Helena , Sarode Venetia , Peng Yan , Fang Yisheng , Leitch Marilyn , Sahoo Sunati
Published: May 2023

Aims

Touch preparation (TP) and frozen section (FS) are the two methods routinely used in the intraoperative evaluation (IOE) of sentinel lymph nodes (SLNs) to detect metastases in patients with breast cancer. Both methods are extremely sensitive and specific in the primary surgery (non-neoadjuvant systemic therapy (non-NST)) setting. Since NST introduces unique challenges in the IOE of SLNs, the aim was to determine the accuracy of TP and FS in the IOE of SLNs in the NST setting and compare the results with the non-NST setting and to examine factors that contribute to any differences.

Methods

We analysed 871 SLNs from 232 patients (615 SLNs from NST and 256 SLNs from non-NST settings) between 2016 through 2019.

Results

In the NST group, TP alone (n=366) had a sensitivity of 45.7% and specificity of 99.7%; FS alone (n=90) had a sensitivity of 83.3% and specificity of 100%. When both TP and FS (n=135) were used, the sensitivity was 80.3% and the specificity was 98.6%.

In the non-NST group, TP alone (n=193) had a sensitivity of 66.7% and specificity of 100%; FS alone (n=22) had a sensitivity and specificity of 100%; and combined TP and FS (n=34) had a sensitivity and specificity of 100% and 96%, respectively.

Conclusions

Evaluating SLNs intraoperatively in the NST setting can be challenging secondary to therapy-related changes. In the NST setting, FS has higher sensitivity and specificity compared with TP for the IOE of SLNs and should be the preferred method.
Do not attempt cardiopulmonary resuscitation documentation: a quality improvement project
Authors: Haire Ellen , Bralesford Catherine , Botting Joanna , Beasant Elizabeth , Taubert Mark
Published: May 2023

Objectives

This quality improvement project looked at enhancing do not attempt cardiopulmonary resuscitation (DNACPR) documentation in a Welsh National Health Service trust.

Methods

A full clinical review cycle was carried out, evaluating 50 DNACPR forms in each data collection, totalling 100 forms. The all Wales DNACPR audit template was used to ensure standardised audit criteria. After completion of the first data collection, several changes were introduced: a new version national form was adopted by the trust; a series of education events was launched to improve understanding of the all Wales DNACPR policy. Electronic learning resources, such as the TalkCPR videos and electronic staff record modules, were widely disseminated.

Results

The evaluation of data demonstrated consistency in completion of forms. The introduction of the new national form in phase 2 of the audit resulted in clearer documentation of discussions held with patients and their significant others and documented reasons why and when conversations had not taken place.

Conclusion

Documentation of DNACPR discussions in the trust demonstrably improved in several domains. A central electronic record for advance and future care plans, accessible by all relevant healthcare providers, patients and carers, may be an effective way of improving further on the current paper-based model.
Short-term effects of camera trap installation on incubation constancy in cranes
Authors: Jaworski Jessica A. , Strobel Bradley N. , Dubay Shelli A.
Published: May 2023

Research regarding how birds respond to the installation of cameras at nest sites is limited. We installed cameras at nests of Sandhill Cranes Antigone canadensis ( Linnaeus, 1758 ) and federally endangered Whooping Cranes Grus americana Linnaeus, 1758 in Juneau County, WI, as part of an ongoing study monitoring the reproductive success of Whooping Cranes in WI. The eastern population of Sandhill Cranes has grown, while Whooping Crane population growth has been slow, prompting the need to monitor the reproductive success of cranes on the refuge. We recorded the flight initiation distance during camera installation, the return time after camera installation, as well as measured the distance at which cameras were placed from each nest. We included temperature at camera deployment, age of nest, mode of access, ordinal date, and year in statistical regression models. We found an apparent difference in the observed flight initiation distances between the two species. Sandhill Cranes allowed researchers to approach their nests closer than Whooping Cranes prior to flushing. The post-disturbance return time was influenced by how far away the cameras were placed from the nest and the ambient temperature during camera deploy. Our study may help inform decisions regarding species response to methods and distance when deploying cameras, especially for endangered or disturbance-sensitive species.
Stability analysis and novel optical pulses to Kundu–Mukherjee–Naskar model in birefringent fibers
Authors: Shafqat-ur-Rehman  , Ahmad Jamshad
Published: May 2023

The concern of this study is to investigate the optical solitons pluses. The [Formula: see text]-dimensional Kundu–Mukherjee–Naskar (KMN) mathematical model in birefringent fibers is taken under consideration for this sake because this model has great importance in optics and delineate the propagation of soliton dynamics in optical fiber communication system and the rogue waves in the oceans and the bending of the light beam. Two newly developed approaches first extended rational sinh-Gordon method which is formulated from the well-known sinh-Gordon equation and second [Formula: see text]-expansion function method are manipulated for the construction of optical solitons in distinct formats. Bright, dark, and singular along their combined forms, periodic and plane wave solutions are extracted with the aid of proposed methods. Moreover, the modulation instability of investigated model is also carried out via linear stability theory. To endorse the physical compatibility of the results, the 2D, 3D, contour, and density plots have been delineated using appropriate parametric values. According to our literature research, these two methods that we are working on have not been applied to the KMN equation in birefringent fibers before, and we believe that the new solutions we have obtained will be useful to researchers working in modeling in this field. The evaluated results suggested that the techniques employed in this research to recover inclusive and standard solutions are approachable, efficient, and speedier in computing and can be considered a handy tool in solving more complex phenomena with the assistance of symbolic computation.
The Global Forest Health Crisis: A Public-Good Social Dilemma in Need of International Collective Action
Authors: Williams Geoffrey M. , Ginzel Matthew D. , Ma Zhao , Adams Damian C. , Campbell Faith , Lovett Gary M. , Pildain María Belén , Raffa Kenneth F. , Gandhi Kamal J.K. , Santini Alberto , Sniezko Richard A. , Wingfield Michael J. , Bonello Pierluigi
Published: May 2023

Society is confronted by interconnected threats to ecological sustainability. Among these is the devastation of forests by destructive non-native pathogens and insects introduced through global trade, leading to the loss of critical ecosystem services and a global forest health crisis. We argue that the forest health crisis is a public-good social dilemma and propose a response framework that incorporates principles of collective action. This framework enables scientists to better engage policymakers and empowers the public to advocate for proactive biosecurity and forest health management. Collective action in forest health features broadly inclusive stakeholder engagement to build trust and set goals; accountability for destructive pest introductions; pooled support for weakest-link partners; and inclusion of intrinsic and nonmarket values of forest ecosystems in risk assessment. We provide short-term and longer-term measures that incorporate the above principles to shift the societal and ecological forest health paradigm to a more resilient state.
Purification and characterization of a serine protease from organic dust and elucidation of its inductive effects on lung inflammatory mediators
Authors: Kusampudi Shilpa , Meganathan Velmurugan , Keshava Shiva , Boggaram Vijay
Published: May 2023

Inhalation of dust in industrial agricultural operations is linked to the development of lung diseases. Our studies have isolated for the first time a trypsin protease from poultry farm dust and have shown that it stimulates lung inflammation. The protease stimulates the production of oxidants and cell signaling pathways to increase inflammatory mediator production. Targeting trypsin protease in poultry farm environment may be a useful strategy to counter the harmful effects of dust.
Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice
Authors: Waiden Julia , Heydarian Motaharehsadat , Oak Prajakta , Koschlig Markus , Kamgari Nona , Hagemann Michael , Wjst Matthias , Hilgendorff Anne
Published: May 2023

Vitamin D-enriched diet during gestation resulted in reduced lung inflammation and matrix remodeling in neonatal mice exposed to clinically relevant, postnatal injury. The results underscore the need to monitor the subclinical effects of vitamin D insufficiency that impact health in the offspring when other risk factors come into play.
Investigation on Machine Learning Approaches for Environmental Noise Classifications
Authors: Albaji Ali Othman , Rashid Rozeha Bt. A. , Abdul Hamid Siti Zeleha
Published: May 2023

This project aims to investigate the best machine learning (ML) algorithm for classifying sounds originating from the environment that were considered noise pollution in smart cities. Sound collection was carried out using necessary sound capture tools, after which ML classification models were utilized for sound recognition. Additionally, noise pollution monitoring using Python was conducted to provide accurate results for sixteen different types of noise that were collected in sixteen cities in Malaysia. The numbers on the diagonal represent the correctly classified noises from the test set. Using these correlation matrices, the F1 score was calculated, and a comparison was performed for all models. The best model was found to be random forest.
Coinfection with SARS-CoV-2 and Cytomegalovirus in a Patient with Mild COVID-19
Authors: Ura Kazuya , Goubaru Yumi , Motoya Misato , Ishii Hidehiro
Published: May 2023

Persistent fever due to coronavirus disease 2019 (COVID-19) is a considerable issue for patients and physicians that requires a broad differential diagnosis and evaluation of complications. Coinfections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various respiratory viruses have also been reported. In severe cases of COVID-19, cytomegalovirus (CMV) reactivation or CMV coinfection with SARS-CoV-2 has been reported in association with critical illnesses and immunosuppressive therapy; however, in mild COVID-19 cases, CMV coinfection with SARS-CoV-2 has been reported only in severely immunocompromised patients, and its incidence and clinical importance remain unclear. Herein, we report a rare case of coinfection with SARS-CoV-2 and CMV in a patient with mild COVID-19 and untreated diabetes mellitus, which led to persistent fever for approximately 4 weeks. CMV coinfection should be considered in patients with COVID-19 who exhibit persistent fever.
Analysis of the Multiwalled Carbon Nanotubes Reinforced Polymethyl Methacrylate Bone Cement’s Characteristics and In Vitro Bioactivity to Prolong Its Functionality in Orthopedic Application
Authors: Kumar T. V. Vineeth , Shanmugapriya N. , Arun S. , Ramasubramanian G.
Published: May 2023

Polymethyl methacrylate (PMMA) bone cement is being used to fill voids that are created due to vertebral compression fractures. It is also a grouting medium in orthopedic joint replacement surgeries as they possess fast primary fixation to the bone. Considering the cement properties and in vitro bioactivity of bone cement is essential for cemented hip and knee joint replacement surgeries. In this study, commercial Simplex P bone cement (SPBC) is modified with carboxyl- (-COOH-) functionalized multiwalled carbon nanotubes (MWCNTs) to overcome high polymerization temperature, volumetric shrinkage, surface wettability, and in vitro bioactivity. A geometric dilution method is used to incorporate MWCNTs with the PMMA powder, which is in unequal proportions. The PMMA/MWCNT nanocomposite with different concentrations of reinforcements, such as 0.1, 0.3, 0.5, and 0.7 weight percentages, is prepared for the investigation. It was observed that the MWCNTs had a beneficial impact on PMMA bone cement (PMMA-BC) by enhancing its setting time (2.94%↑) and surface wettability (23.58%↑). Also, diminished polymerization temperature (29%↓) and volumetric shrinkage (40.9%↓) are observed for an optimum concentration of 0.7 wt. %. The bioactivity of the cement surface is validated by the in vitro bioactivity observed in simulated body fluid (SBF) through the development of primary and secondary apatite. It is concluded that the synthesized PMMA/MWCNT nanocomposites are found to have enhanced cement properties compared to PMMA-BC.
Comparison of the Nutritional Status of Swiss Albino Mice Fed on Either a Purified or Cereal-Based Diet for 15 weeks
Authors: Kinyi Hellen W. , Kato Charles Drago , Tusubira Deusdedit , Kiwanuka Gertrude N.
Published: May 2023

Background. Laboratory animals are commonly fed on cereal-based diets (CBDs) whose nutrient composition is unknown and may confound the metabolic response to study interventions. Purified diets such as AIN-93M are therefore recommended, as their nutrient composition is known. However, few studies have evaluated their use as adequate control diets. The aim of this study was to compare the nutrition status of Swiss albino mice fed on either CBD or AIN-93M for 15 weeks. Methods. Twenty Swiss albino mice aged 6–8 weeks and weighing 21.7 g ± 0.6 were fed on either CBD or AIN-93M diet for 15 weeks. Their nutritional status was evaluated using anthropometric and hematological indices, serum glucose, total protein, albumin, and total cholesterol to select an appropriate normal control diet. Results. The CBD had low-calorie content (2.57 kcal/g) and protein (11 ± 3.8 g/100 g) compared to AIN-93M (3.8 kcal/g and 14 g/100 g, respectively). The BMI of male mice fed on CBD and AIN-93M diets was significantly higher (

P
=
0.0139

and

P
=
0.0325

, respectively) compared to that of females fed on similar diets. Animals in the CBD group had lower hemoglobin (15.1–16.9 g/dl) compared to those in the AIN-93M group (18.1–20.8 g/dl). Serum albumin levels were higher in both male

P
=
0.001

and female

P
=
3
×

10

−
6

mice fed on AIN-93M compared to those fed on CBD. Females in the AIN-93M group had higher cholesterol

P
=
0.026

than those in the CBD group. Conclusion. The AIN-93 diet of caloric value 3.85 kcal/g (total protein 14 g, total fat 4 g of soy bean oil, fibre 5 g, and total carbohydrate 42 g per 100 g) can be safely used as a normal control diet in long-term research studies using Swiss albino mice.
Single-Cell Evolutionary Analysis Reveals Drivers of Plasticity and Mediators of Chemoresistance in Small Cell Lung Cancer
Authors: Wollenzien Hannah , Afeworki Tecleab Yohannes , Szczepaniak-Sloane Robert , Restaino Anthony , Kareta Michael S.
Published: May 2023

Small cell lung cancer (SCLC) is often a heterogeneous tumor, where dynamic regulation of key transcription factors can drive multiple populations of phenotypically different cells which contribute differentially to tumor dynamics. This tumor is characterized by a very low 2-year survival rate, high rates of metastasis, and rapid acquisition of chemoresistance. The heterogeneous nature of this tumor makes it difficult to study and to treat, as it is not clear how or when this heterogeneity arises. Here we describe temporal, single-cell analysis of SCLC to investigate tumor initiation and chemoresistance in both SCLC xenografts and an autochthonous SCLC model. We identify an early population of tumor cells with high expression of AP-1 network genes that are critical for tumor growth. Furthermore, we have identified and validated the cancer testis antigens (CTA) PAGE5 and GAGE2A as mediators of chemoresistance in human SCLC. CTAs have been successfully targeted in other tumor types and may be a promising avenue for targeted therapy in SCLC.

Implications:

Understanding the evolutionary dynamics of SCLC can shed light on key mechanisms such as cellular plasticity, heterogeneity, and chemoresistance.
FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Authors: Wilde Blake R. , Chakraborty Nishma , Matulionis Nedas , Hernandez Stephanie , Ueno Daiki , Gee Michayla E. , Esplin Edward D. , Ouyang Karen , Nykamp Keith , Shuch Brian , Christofk Heather R.
Published: May 2023

Fumarate accumulation due to loss of fumarate hydratase (FH) drives cellular transformation. Germline FH alterations lead to hereditary leiomyomatosis and renal cell cancer (HLRCC) where patients are predisposed to an aggressive form of kidney cancer. There is an unmet need to classify FH variants by cancer-associated risk. We quantified catalytic efficiencies of 74 variants of uncertain significance. Over half were enzymatically inactive, which is strong evidence of pathogenicity. We next generated a panel of HLRCC cell lines expressing FH variants with a range of catalytic activities, then correlated fumarate levels with metabolic features. We found that fumarate accumulation blocks de novo purine biosynthesis, rendering FH-deficient cells reliant on purine salvage for proliferation. Genetic or pharmacologic inhibition of the purine salvage pathway reduced HLRCC tumor growth in vivo. These findings suggest the pathogenicity of patient-associated FH variants and reveal purine salvage as a targetable vulnerability in FH-deficient tumors.

Significance:

This study functionally characterizes patient-associated FH variants with unknown significance for pathogenicity. This study also reveals nucleotide salvage pathways as a targetable feature of FH-deficient cancers, which are shown to be sensitive to the purine salvage pathway inhibitor 6-mercaptopurine. This presents a new rapidly translatable treatment strategy for FH-deficient cancers.

This article is featured in Selected Articles from This Issue, p. 1949
Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Bertucci François , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: May 2023

Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that MELK mRNA levels were higher in TNBC tumors [8.11 (3.79–10.95)] than in HR+HER2− tumors [6.54 (2.90–9.26)]; P < 0.001]. In univariate analysis, patients with breast cancer with high-MELK–expressing tumors had worse overall survival (P < 0.001) and distant metastasis-free survival (P < 0.01) than patients with low-MELK–expressing tumors. In a multicovariate Cox regression model, high MELK expression was associated with shorter overall survival after adjusting for other baseline risk factors. MELK knockdown using siRNA or MELK inhibition using the MELK inhibitor MELK-In-17 significantly reduced invasiveness, reversed epithelial-to-mesenchymal transition, and reduced CSC self-renewal and maintenance in TNBC cells. Nude mice injected with CRISPR MELK-knockout MDA-MB-231 cells exhibited suppression of lung metastasis and improved overall survival compared with mice injected with control cells (P < 0.05). Furthermore, MELK-In-17 suppressed 4T1 tumor growth in syngeneic BALB/c mice (P < 0.001). Our findings indicate that MELK supports metastasis by promoting epithelial-to-mesenchymal transition and the CSC phenotype in TNBC.

Significance:

These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.
Desmoplastic Reaction Associates with Prognosis and Adjuvant Chemotherapy Response in Colorectal Cancer: A Multicenter Retrospective Study
Authors: Hu Qingru , Wang Yiting , Yao Su , Mao Yun , Liu Liu , Li Zhenhui , Chen Yonghe , Zhang Shenyan , Li Qian , Zhao Yingnan , Fan Xinjuan , Cui Yanfen , Zhao Ke , Liu Zaiyi
Published: May 2023

Desmoplastic reaction (DR) is one of many tumor–host interactions and is associated with the overall survival (OS) of patients with colorectal cancer. However, the clinical significance of DR requires further study in large multicenter cohorts and its predictive value in adjuvant chemotherapy (ACT) response remains unclear. Here, a total of 2,225 patients with colorectal cancer from five independent institutions were divided into primary (N = 1,012 from two centers) and validation (N = 1,213 from three centers) cohorts. DR was classified as immature, middle, or mature depending on the presence of myxoid stroma and hyalinized collagen bundles at the invasive front of the primary tumor. OS among different subgroups were compared, and the correlations of DR type with tumor-infiltrating lymphocytes (TILs) within stroma, tumor stroma ratio (TSR), and Stroma AReactive Invasion Front Areas (SARIFA) were also analyzed. In the primary cohort, patients with mature DR had the highest 5-year survival rate. These findings were confirmed in validation cohort. In addition, for stage II colorectal cancer, patients classified as non-mature DR would benefit from ACT compared with surgery alone. Furthermore, immature and middle DR were more associated with high TSR, less distribution of TILs within stroma and positive SARIFA compared with mature. Taken together, these data suggest that DR is a robust-independent prognostic factor for patients with colorectal cancer. For patients with stage II colorectal cancer, non-mature DR could be a potential marker for recognizing high-risk patients who may benefit from ACT.

Significance:

DR has the potential to identify patients with high-risk colorectal cancer and predict the efficacy of adjuvant chemotherapy in patients with stage II colorectal cancer. Our findings support reporting DR types as additional pathologic parameters in clinical practice for more precise risk stratification.
Enhancing Seasonal Forecast Skills by Optimally Weighting the Ensemble from Fresh Data
Authors: Brajard Julien , Counillon François , Wang Yiguo , Kimmritz Madlen
Published: May 2023

Dynamical climate predictions are produced by assimilating observations and running ensemble simulations of Earth system models. This process is time consuming and by the time the forecast is delivered, new observations are already available, making it obsolete from the release date. Moreover, producing such predictions is computationally demanding, and their production frequency is restricted. We tested the potential of a computationally cheap weighting average technique that can continuously adjust such probabilistic forecasts—in between production intervals—using newly available data. The method estimates local positive weights computed with a Bayesian framework, favoring members closer to observations. We tested the approach with the Norwegian Climate Prediction Model (NorCPM), which assimilates monthly sea surface temperature (SST) and hydrographic profiles with the ensemble Kalman filter. By the time the NorCPM forecast is delivered operationally, a week of unused SST data are available. We demonstrate the benefit of our weighting method on retrospective hindcasts. The weighting method greatly enhanced the NorCPM hindcast skill compared to the standard equal weight approach up to a 2-month lead time (global correlation of 0.71 vs 0.55 at a 1-month lead time and 0.51 vs 0.45 at a 2-month lead time). The skill at a 1-month lead time is comparable to the accuracy of the EnKF analysis. We also show that weights determined using SST data can be used to improve the skill of other quantities, such as the sea ice extent. Our approach can provide a continuous forecast between the intermittent forecast production cycle and be extended to other independent datasets.
Readmission and Disposition in Patients With Malignant Bowel Obstructions Following Gastrostomy Tube
Authors: Yu Jingjing , Sullivan Brittany G. , Nguyen Ninh T. , Hohmann Samuel F. , Harris Alyssa H. , Micic Dejan , Turaga Kiran K. , Senthil Maheswari , Eng Oliver S.
Published: May 2023

Background

Patients with peritoneal carcinomatosis (PC) can develop malignant bowel obstructions (MBOs) requiring inpatient admission and nasogastric tube decompression. Palliative decompressive gastrostomy tubes (G-tubes) may affect patient disposition, allowing for self-management and reduction in inpatient services. Therefore, we sought to assess disposition and inpatient readmission rates in patients admitted with PC and MBO following G-tube placement.

Methods

The Vizient® Clinical Data Base was queried for inpatient admissions from October 2018 to May 2022 utilizing ICD-10 codes to identify patients admitted with PC and bowel obstruction, with or without G-tube placement. Demographics and hospital outcomes were recorded. Descriptive statistics and multivariate logistic regression analysis were performed.

Results

From 750 patients, 59 (7.9%) had a G-tube placed. Compared to patients without G-tubes, those with G-tubes had lower rates of disposition to home (32.2% vs 70.0%, P < .001) and higher rates of disposition to hospice (home: 30.5% vs 7.8%, P < .001, facility: 10.2% vs 3.9%, P = .02). There was no significant difference in the rate (17.3% vs 22.3%, P = .40) or risk (OR = 1.44, 95% CI .69-3.01) of 30-day readmissions with G-tubes. However, palliative care consultation (OR 33.77, 95% CI 19.16-59.52) and G-tube placement (OR 5.82, 95% CI 2.56-13.25) were independent predictors for hospice.

Discussion

Placement of G-tubes in patients with PC and MBO was associated with higher rates of disposition to hospice but there is no difference in 30-day readmission rates compared to those without G-tubes. Further prospective studies are needed to understand the role of G-tube placement in patients with MBO in relation to outcomes and disposition.
Book review: Samuel Paul and Kala S. Sridhar, The Paradox of India’s North–South Divide: Lessons from the States and Regions
Authors: Jaykumar H.S.
Published: May 2023

Samuel Paul and Kala S. Sridhar, The Paradox of India’s North–South Divide: Lessons from the States and Regions. New Delhi: Sage Publications, 2015, 252 pp., ₹1,095.00 (Hardback).
Is Nagorno-Karabakh no longer a frozen conflict zone after the 2020 war?
Authors: Kurt Selim , Tüysüzoğlu Göktürk
Published: May 2023

The term “frozen conflict,” which is used to describe identity-based conflicts in former Soviet republics, characterizes a situation whereby neither war nor peace exists between the conflicting parties. The most important of these conflict areas is Nagorno-Karabakh, located in the South Caucasus. As the conflict in the 1990s could not be resolved through negotiations, war broke out again in September 2020. Under the ceasefire protocol signed in November 2020 following the war, Azerbaijan has largely succeeded in liberating its occupied territories around Nagorno-Karabakh. As it is claimed that the occupied territories of Azerbaijan have been completely liberated, this situation raises the question of whether the problem is no longer a frozen conflict. However, when the protocol is considered in relation to the concept's definition, we see that the problem remains a frozen conflict.
Investigation of the effects of laser radiation on silk fabrics dyed with kermes insect (Kermes vermilio Planchon)
Authors: Pars Abdulkadir , Karadag Recep
Published: May 2023

In this study, the dyeing properties of a natural dye extracted from the kermes insect on silk were examined. Insect dye at different concentration rates of 5%, 10%, and 15% wt was applied to silk fabrics mordanted with alum [KAl(SO4)2.12H2O] and iron-(II) sulfate [FeSO4.7H2O]. Then, the Nd:YAG laser device was used to investigate the laser radiation effects on the color of the fabric. The dyed fabrics were analyzed by different analytical and technical methods. The RP-HPLC-DAD method was used for the identification of the coloring compounds of fabrics dyed with kermes. The color coordinates and fastness values of rubbing, washing, and light were investigated. Overall, the fastness results were excellent. SEM-EDX was performed for morphological examinations and CIEL*a*b* color values were measured for colorimetric examinations after laser radiation.
Urban planning and the knowledge politics of the smart city
Authors: Cook Matthew , Karvonen Andrew
Published: May 2023

Smart cities promote computational and data-driven understandings of the built environment and have the potential to reconfigure urban planning and governance practices in profound ways. Smart urbanisation is often presented as a politically neutral and socially beneficial approach to achieve urban sustainability goals but the emphasis on data gathering and algorithmic analysis and decision-making has the tendency to restrict how urban stakeholders know and act upon cities. In this article, we apply Artistotle’s intellectual virtues of techne, episteme and phronesis to critique current practices of smart cities, data-driven urbanism and computational understandings of cities as they relate to urban planning theory and practice. We argue that the rise of smart cities represents a partial return to early- to mid-20th-century positivistic knowledge politics and the reassertion of technical experts as the drivers of urban change. However, we also highlight the recent emergence of citizen-centred smart cities as an opportunity to promote value rationality in urban planning activities. We conclude that there is a need for greater integration of techne, episteme and phronesis in the pursuit of smart cities to ensure that digitalisation does not foreclose on certain ways of knowing cities but instead, provides a foundation to support a progressive knowledge politics of urban development.
Kindness for Kindness: A Dual Appraisal of International Support in Response to COVID-19
Authors: Yang Fiona X. , Li Xiangping , Cai Jack Bo , Xiong Xiling , Wong IpKin Anthony
Published: May 2023

“A friend in need is a friend indeed” well elucidates international support amid the COVID-19 pandemic. Drawing on a dual-process model of emotional appraisal, this mixed-methods research aims to investigate positive psychological responses to international support. Study 1 is a multilevel investigation of the relationships between perceived support, gratitude evoked, and change in attitude toward the benefactor countries. The moderating role of motivational relevance—the province-level prevalence of COVID-19—is also examined. Study 2 uses text mining to analyze online reviews retrieved from a social media platform. The results substantiate aid-induced gratitude and reciprocity manifested through travel intentions and unravel additional factors of motivational relevance—timing, type of support, political and cultural connotations, and comparative appraisals. Study 3 employs an experimental design to validate the causal relationships and reinforces the dual-appraisal mechanism. Managerial implications are provided for destination marketers and industry practitioners to leverage positive psychology for post-pandemic promotion.
“I Love It” Versus “I Recommend It”: The Impact of Implicit and Explicit Endorsement Styles on Electronic Word-of-Mouth Persuasiveness
Authors: Liao Junyun , He Siying , Feng Wenting , Filieri Raffaele
Published: May 2023

Consumers usually endorse tourism products differently when sharing positive electronic word-of-mouth (eWOM). This research examines the relative persuasiveness of two endorsement styles, that is, explicit endorsement (e.g., “I recommend it”) and implicit endorsement (e.g., “I love it”). Drawing on the persuasion knowledge model, we propose that explicit endorsements are less persuasive than implicit endorsements because the former trigger stronger persuasion knowledge. We further argue that source trustworthiness mitigates the persuasion effect difference between the two endorsement styles. This article assesses these hypotheses across different sources (anonymous reviewers, friends, influencers), channels (online community, social commerce platform, social networking app), and products (hotels, restaurants) using secondary data analysis and two experiments. Three studies provide support for our hypotheses. By revealing the relationship between endorsement styles and eWOM persuasiveness, this article provides important implications for implementing effective product endorsement.
Real Patient Participation in Workplace-Based Assessment of Health Professional Trainees: A Scoping Review
Authors: Nemir Arwa , Pearson Marion , Kitchin Vanessa , Wilbur Kerry
Published: May 2023

The aim of this scoping review is to outline the existing landscape of how real patients participate in the workplace-based assessment of trainees across diverse healthcare professions. In 2019–2020, the authors searched MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, and Web of Science databases for studies that included descriptions of experiences whereby patients received care from a health professional trainee and participated in workplace-based assessments of that trainee. Full-text articles published in English from 2009 to 2020 were included in the search. Of the 8770 studies screened; 77 full-text articles were included. Analysis showed that strategies for patient participation in workplace-based assessment varied widely. Aspects studied ranged from validation of an assessment tool to evaluation of the impact of an educational intervention on trainees’ performance. Assessment of patient satisfaction was the most common approach to patient involvement. The majority of studies were conducted in North America and in the context of physician training. Formal patient participation in the assessment of health professional trainees appears heterogeneous across health professions. Gaps in the literature are evident; therefore, this review points to an inclusive approach to workplace-based assessment to ensure patient feedback of the trainees who care for them is represented.
Trauma apps and the making of the ‘smart’ refugee
Authors: Abdelrahman Maha
Published: May 2023

A market for mental health apps, designed to help millions of refugees manage symptoms of Post Traumatic Syndrome Disorder and other mental health issues, has proliferated since the outbreak of the so-called refugee crisis in 2015. These bite-size, on-the-go, mindfulness-based apps have emerged at the intersection of new investment models, state-of-the-art AI and surveillance and border control regimes. Conceived of as a more cost-effective approach to refugee mental health care, mental health apps are part of a larger endeavour to create the 'smart' refugee. Self-monitoring, agile, entrepreneurial and resilient in the face of adversity, the smart refugee is expected to emerge as a node in a network of information flow, constantly connected to digital technology, at once receiving and providing real-time data. Biometric and data markets, some of the fastest growing in the world, have already been eagerly collecting refugee fingerprints, iris scans, facial images and other genomic information. To add to this arsenal of data, the new apps are harvesting, storing and selling what I call the mental prints of refugee trauma, turning the human experience of loss, grief and suffering into quantifiable and marketable commodities.