bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a risk prediction model for pulmonary tuberculosis among presumptive tuberculosis cases in Ethiopia
Authors: Wolde Haileab Fekadu , Clements Archie C A , Alene Kefyalew Addis
Published: December 2023

Background

Early diagnosis and treatment of tuberculosis (TB) is one of the key strategies to achieve the WHO End TB targets. This study aimed to develop and validate a simple, convenient risk score to diagnose pulmonary TB among presumptive TB cases.

Methods

This prediction model used Ethiopian national TB prevalence survey data and included 5459 presumptive TB cases from all regions of Ethiopia. Logistic regression was used to determine which variables are predictive of pulmonary TB. A risk prediction model was developed, incorporating significant variables (p<0.05). The Youden Index method was used to choose the optimal cut-off point to separate the risk score of the patients as high and low. Model performance was assessed using discrimination power and calibration. Internal validation of the model was assessed using Efron’s enhanced bootstrap method, and the clinical utility of the risk score was assessed using decision curve analysis.

Results

Of total participants, 94 (1.7%) were confirmed to have TB. The final prediction model included three factors with different scores: (1) TB contact history, (2) chest X-ray (CXR) abnormality and (3) two or more symptoms of TB. The optimal cut-off point for the risk score was 6 and was found to have a good discrimination accuracy (c-statistic=0.70, 95% CI: 0.65 to 0.75). The risk score has sensitivity of 51.1%, specificity of 79.9%, positive predictive value of 4.3% and negative predictive value of 98.9%. After internal validation, the optimism coefficient was 0.003, which indicates the model is internally valid.

Conclusion

We developed a risk score that combines TB contact, number of TB symptoms and CXR abnormality to estimate individual risk of pulmonary TB among presumptive TB cases. Though the score is easy to calculate and internally validated, it needs external validation before widespread implementation in a new setting.
Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial
Authors: Estiasari Riwanti , Tiksnadi Amanda , Tunjungsari Dyah , Maharani Kartika , Aninditha Tiara , Sofyan Henry Riyanto , Savitri Irma , Pangeran David , Jeremia Ivan , Widhani Alvina , Ariane Anna
Published: December 2023

Background

Chronic headache is a ‘silent’ neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches.

Methods and analysis

SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement.

Ethics and dissemination

Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals.

Trial registration number

NCT05613582.
Non-specific effects of Pneumococcal and Haemophilus vaccines in children aged 5 years and under: a systematic review
Authors: Geraghty Keith , Rooney Darragh , Watson Chris , Ledwidge Mark T , Glynn Liam , Gallagher Joe
Published: December 2023

Objective

To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under.

Data sources

A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023.

Study eligibility criteria

Randomised controlled trials (RCTs), quasi-RCT or cohort studies.

Participants

Children aged 5 or under.

Study appraisal and synthesis methods

Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed.

Results

Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1–3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found.

Conclusions and implications

In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings.

PROSPERO registration number

CRD42020146640.
Health outcomes in those who have been victims of knife crime: a protocol for a systematic review and meta-analysis
Authors: Gani Illin , Chandan Joht Singh , Bandyopadhyay Siddhartha , Pathmanathan Anna , Martin James
Published: December 2023

Introduction

Knife-enabled crime is a UK public health issue leading to substantial impacts on society, victims and their families, as well as additional strain on the healthcare system. Despite the increase in knife-enabled crime and the overwhelming consequences, there is a lack of comprehensive studies exploring the long-term health outcomes of knife crime victims in the UK. The research gap hinders the development of more targeted secondary preventative interventions, resource allocation and public awareness campaigns. This systematic review aims to identify the long-term health outcomes of knife crime victims, therefore providing valuable knowledge for stakeholders, health practitioners and policymakers for a more effective public health response.

Methods and analysis

A comprehensive search strategy was developed, focusing on four key concepts: study design, knife-related offences, outcomes and risk. Databases being searched include MEDLINE, EMBASE, PsycINFO, ProQuest Criminology Collection, Web of Science Core Collection, Google Scholar and OpenGrey. Reference lists and forward citations will be inspected for further suitable literature. The study selection will involve two independent reviewers screening the studies from the search, with disagreements resolved by a third reviewer. All UK quantitative research on long-term health outcomes of knife crime victims will be included in the review. Covidence will be used to efficiently manage data. A data extraction form has been developed which will summarise key aspects of each study that will be included in the review. Methodological Index for Non-Randomised Studies quality assessment checklist will be used to assess the studies and the Newcastle-Ottawa Scale will assess the risk of bias in each study. Findings will be narratively synthesised, and if heterogeneity is sufficient, a meta-analysis will be conducted.

Ethics and dissemination

Ethics approval is not required for this study as no original data will be collected. The results will be disseminated through a peer-reviewed publication and conference presentation.
Financial hardship for patients with cancer and caregivers at end of life in the USA: narrative review
Authors: Salazar Marisa Martinez , Khera Nandita , Chino Fumiko , Johnston Emily
Published: December 2023

Background

Patients and their families face financial hardship during cancer treatment, which may intensify at end of life (EOL) due to increased symptoms and care needs. We undertook a narrative literature review to describe the current understanding of the causes, impacts and factors associated with financial hardship at EOL. We identify gaps in research, policy and clinical practice and propose steps to mitigate financial hardship for patients and caregivers at EOL.

Methods

We conducted a Medline search to identify US studies since 2000 that examined EOL financial hardship for patients with cancer and their caregivers.

Results

Twenty-seven adult and four paediatric studies met review criteria. Adults with cancer and their caregivers face significant financial hardship at EOL and in bereavement, especially due to employment changes and informal caregiving time costs. Financial hardship may be higher for younger caregivers and for patients who are uninsured, low income, rural, with high symptom burdens or with certain cancer types. The few paediatric studies showed high financial hardship and employment impact lasting well beyond a child’s death.

Conclusions

There is limited literature examining financial hardship at EOL in the USA, especially in paediatrics. Priorities for future research include longitudinal studies in diverse populations of patients with cancer and informal caregivers using standardised financial hardship measures. Policies to address financial hardship at EOL, especially with hospice care, should include insurance coverage for family caregiving and medical leave policies. There is need for increased financial hardship screening at EOL and in bereavement and a need for financial navigation interventions.
From the Editor: Herding Cats
Authors: Kelly Rob G.
Published: December 2023

“Leadership of a group of people, be it in the commercial sector, on community boards, or at an academic institution, is one of the hardest tasks one can tackle. I have often been asked by others, many not in academia, why it seems that “nothing gets done” or “change takes forever” at universities. It’s easy to point fingers at the leaders (e.g., department chairs, deans, provosts) as their job descriptions could be summarized as “make sure stuff gets done.” The poor saps have to do that with people who think they are all that and a bag of chips.”
Winter 2023 - Connect with ECS News
Authors: Chaves Frances N.
Published: December 2023

Your connection to the ECS community, career opportunities, and industry-related news and events
2023 Edward G. Weston Research Fellowship – Summary Report: Exploring Chemical Speciation and Catalyst Behavior for the Electrochemical Interconversion of Formate and Bicarbonate
Authors: Quinn Alexander H.
Published: December 2023

The water-soluble formate/bicarbonate redox couple holds promise for electrochemical energy storage, hydrogen transportation, and carbon dioxide (CO2) management. Because electrochemical transformations in these electrolytes are accompanied by homogeneous reactions, we investigate electrolyte speciation as a function of reaction environment. In addition, we study the electrocatalytic oxidation of formate in the absence of supporting salt.
2023 Joseph W. Richards Fellowship – Summary Report: Toward High-throughput Electrochemical Screening of in vivo Synthesized Metalloenzymes
Authors: Alden Sasha Elena
Published: December 2023

In recent years, bioinspired metalloenzymes have proven a viable and sustainable method for hydrogen production via the hydrogen evolution reaction (HER). By using in vivo directed evolution synthetic techniques, hydrogenase systems based on rubredoxin (Rd) scaffolds with Ni substituted metal centers have proven promising molecular catalysts. However, insight into the mechanism of hydrogen production between different mutants has proven tricky, as electrochemical characterization of the high number of mutants is slow. High-throughput electrochemistry has started to emerge at the nano and macroscale in the form of scanning electrochemical methods and by using an array of electrochemical cells. Here we utilize the array microcell method (AMCM)to electrochemically investigate each enzyme at one array.
2023 F. M. Becket Fellowship Fellowship – Summary Report: Illuminating Photo-enhanced Bioelectrocatalysis in Purple Bacteria
Authors: Beaver Kevin
Published: December 2023

Purple bacteria are a special subclass of photosynthetic bacteria known for their metabolic versatility, resistance to salinity, and bright red-violet pigmentation responsible for photosynthesis. Previous work by the Minteer group has demonstrated purple bacteria to be a viable electrochemical solution for sustainable decontamination of saline wastewater, in addition to biosensing and bio-electrosynthesis applications. Notably, the bacteria’s mechanism of transferring electrons to electrodes is directly related to their photosynthetic electron transfer chain, and current density is significantly enhanced in the presence of light. Often, the light sources used for photo-bioelectrochemistry experimental studies are high-intensity (∼100 mW per cm2) and not wavelength-specific. This leads to uncertainty of the mechanism of photo-enhanced bioelectrocatalysis and may also lead to photo-inhibition at higher light intensities. A novel method was developed to study the effect of isolated light wavelengths on photo-enhanced current.
Reports from the Frontier: Advanced Sensing Strategies for Chemical Characterization
Authors: Zhao Yaoli , Thundat Thomas , Cushing Scott
Published: December 2023

“This feature is intended to let ECS award-winning students and post-docs write primary author perspectives on their field, their work, and where they believe things are going. This month we highlight the work of Yaoli Zhao, the 2023 Sensor Division Graduate Student Award Winner.”
Overview: Multifunctional Sensors for Smart Agriculture
Authors: Sekhar Praveen
Published: December 2023

Introduction to the Special Issue of Interface on Sensors for Smart Agriculture and Beyond
Advanced Multi-functional Sensors for In-situ Soil Parameters for Sustainable Agriculture
Authors: Venkadesh Vagheeswari , Kamat Vivek , Bhansali Shekhar , Jayachandran Krish
Published: December 2023

“The agronomic practices of agricultural science in recent years have become more accurate, precise, and data-driven than ever before. The stable performance of an intelligent and sustainable system relies on precise monitoring that provides critical information for constructing site-specific information for evaluating soil parameters, environmental conditions, and plant growth. By implementing advanced systems like sensors, agriculture can become technology driven, more productive, and more efficient by optimizing fertilizer application and minimizing environmental impacts. As a result, multi-functional sensors are extensively used and increasingly in demand to provide accurate information to farmers, ensuring agricultural strategies tailored to specific needs and enhancing yields.”
Progress in Inkjet-Printed Sensors and Antennas
Authors: Sandry Caden Tyler , Shila Sharmin , Gonzalez-Jimenez Leobardo , Martinez Sebastian , Sekhar Praveen
Published: December 2023

In recent years, inkjet printing has become a popular form for creating sensors and antennas. These devices are fabricated using different materials with inkjet printing using various (conductive, oxide, biological) inks on predominantly flexible substrate. This form of fabrication has attracted much attention for a variety of reasons such as relatively cheap cost of manufacturing and materials, as well as the ease of use and high customization. These devices also provide a lighter frame and added flexibility allowing them to be incorporated as devices on non-planar surfaces. It is also possible for inkjet printing to be used as a sustainable manufacturing method, providing a method of reducing electronic waste. In this article, several topics related to inkjet printing are covered. These topics include a general overview of the fabrication process of inkjet devices through an inkjet printer, recent applications of inkjet-printed sensors, applications of inkjet-printed antennae, challenges in inkjet printing, and an outlook on the inkjet printing. In the fabrication section, the different materials and printing process are explored. Topics covered in the application section include gas sensors, biomedical sensors, pressure sensors, temperature sensors, glucose sensors, and more. In the inkjet antennas portion of the article, RFID tagging and 5G applications are highlighted. The main challenges covered are specific to fabrication that are being currently addressed.
Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study
Authors: Pellegrino Alessio , Toncelli Loira , Pasquini Lucia , Masini Giulia , Mecacci Federico , Pedrizzetti Gianni , Modesti Pietro Amedeo
Published: December 2023

These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.
Persistent, Poorly Responsive Immune Thrombocytopenia Secondary to Asymptomatic COVID-19 Infection in a Child
Authors: Mettananda Chamila , Williams Senani
Published: December 2023

Immune thrombocytopenic purpura (ITP) secondary to asymptomatic COVID-19 infection, especially in children, is not reported. Furthermore, persistent, treatment-resistant ITP secondary to COVID-19 is not reported. We report a previously healthy 14-year-old Asian boy who developed secondary ITP following an asymptomatic COVID-19 infection and is having a relapsing and remitting cause with poor response to immunosuppressants even after 21 months following the diagnosis. This case emphasizes the importance of testing for COVID-19 in newly diagnosed ITP patients and the need for follow-up platelet counts in patients who recover from COVID-19 as it may follow into developing secondary ITP yet being asymptomatic until you present with a bleeding complication of ITP. The poor response to standard immunosuppression warrants more understanding of the pathophysiology of persistently low platelets following COVID-19 infection. Long-term sequelae of the disease highlight the importance of getting vaccinated for COVID-19 despite COVID-19 being no longer a global emergency.
A Comparative Analysis of the Nutritional Quality of Salmon Species in Canada among Different Production Methods and Regions
Authors: Gillies Caroline R. , Jung Euichan , Colombo Stefanie M.
Published: December 2023

Nutritional information of fresh seafood, including salmon, is not commonly available to the public, which can lead to misconceptions. The aim of this study was to determine the nutritional content of salmon fillets, comparing: (1) Canadian salmon, both wild (pink, chinook, and sockeye) and farmed (Atlantic salmon); (2) Canadian farmed Atlantic salmon grown in ocean net pens or land-based recirculating aquaculture systems (RAS); and (3) farmed Atlantic salmon raised in Canada compared with Scotland, Chile, and Ireland. Samples were purchased from retail stores in Canada and analyzed for moisture, crude protein, total lipid, fatty acids, amino acids, cholesterol, mercury, and color. The greatest differences in nutritional content were between species, rather than if it was wild or farmed. Compared to salmon raised in net pens, salmon raised in RAS had three times more eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) per serving (0.7/100 g vs. 2.3/100 g, respectively), twice as much omega-3s (14% vs. 30%) and redder in color (24.7 vs. 30.1) but higher in saturated fats (18% vs. 24%). Scottish salmon had over double the amount of EPA + DHA per 100 g (1.6 g) than salmon from Canada (0.70 g), Chile (0.66 g), and Ireland (0.61 g). While nutritional content differed among salmon types, each type can provide dietary essential nutrients that can benefit consumers.
“Complete Venous Shutdown:” A Rare Case of Combined Superior Vena Cava (SVC) and Inferior Vena Cava (IVC) Occlusion
Authors: Malik M. Kasim , Humayun Wajahat , Darki Amir
Published: December 2023

Independently, superior vena cava (SVC) occlusion and inferior vena cava (IVC) occlusion are usually seen in the setting of SVC syndrome and iliocaval venous obstruction (ICVO), respectively. Concomitant occlusion of the SVC and IVC is rare and most commonly seen in the setting of malignancy or other hypercoagulable states. Venous hypertension can lead to the formation of “downhill” varices in the esophagus and can be a rare source of gastrointestinal bleeding. We present a rare case of combined SVC and IVC occlusion and its management.
Interventions Aimed at Alleviating Loneliness and Social Isolation among the Older Population: Perspectives of Service Providers
Authors: Fakoya Olujoke , McCorry Noleen K. , Donnelly Michael
Published: December 2023

Background. Older people are one of the groups particularly vulnerable to loneliness due to factors such as deteriorating health, widowhood and death of friends/family, fewer confiding relationships, and being more likely to live alone. In the United Kingdom, services to alleviate and/or prevent loneliness can be classified as foundation services, direct interventions, gateway services, and structural enablers. Service managers and personnel involved in the delivery of interventions for older people are well-positioned to report on the mechanisms that contribute to the effectiveness of interventions. This study aimed to elicit from the perspective of a range of service providers, the barriers and facilitators of successful service provision, and the reduction of loneliness among older people. Methods. Semistructured interviews were conducted with 23 service managers of services providing an intervention to older people in Northern Ireland. Services were eligible for inclusion if they reported a goal of preventing or reducing loneliness and/or social isolation among older people. Transcripts were analysed using thematic analysis. Results. Eight themes were produced representing barriers or facilitators of successful service delivery, including characteristics of the service (person-centred approach, empowerment of service users and staff/volunteers, personal qualities of staff and volunteers, and funding for service provision) and characteristics of the wider community were services were located (hard to identify and/or reach lonely people; education and awareness of services; family and community structures; and accessible, affordable, and safe public transport). Conclusion. Developments in this area should prioritise integrated, systemic solutions that harness capacity and partnership working within communities, grounded in the principles of empowerment, inclusion, self-determination, and collective action.
Data from Methylation Mediated Silencing of MicroRNA-1 Gene and Its Role in Hepatocellular Carcinogenesis
Authors: Datta Jharna , Kutay Huban , Nasser Mohd W. , Nuovo Gerard J. , Wang Bo , Majumder Sarmila , Liu Chang-Gong , Volinia Stefano , Croce Carlo M. , Schmittgen Thomas D. , Ghoshal Kalpana , Jacob Samson T.
Published: December 2023

Abstract
MicroRNAs (miR) are a class of small (∼21 nucleotide) noncoding RNAs that, in general, negatively regulate gene expression. Some miRs harboring CGIs undergo methylation-mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRs in liver cancer, the miRNA expression profile was analyzed in hepatocellular carcinoma (HCC) cell lines treated with 5-azacytidine (DNA hypomethylating agent) and/or trichostatin A (histone deacetylase inhibitor). The results showed that these epigenetic drugs differentially regulate expression of a few miRs, particularly miR-1-1, in HCC cells. The CGI spanning exon 1 and intron 1 of miR-1-1 was methylated in HCC cell lines and in primary human HCCs but not in matching liver tissues. The miR-1-1 gene was hypomethylated and activated in DNMT1−/− HCT 116 cells but not in DNMT3B null cells, indicating a key role for DNMT1 in its methylation. miR-1 expression was also markedly reduced in primary human hepatocellular carcinomas compared with matching normal liver tissues. Ectopic expression of miR-1 in HCC cells inhibited cell growth and reduced replication potential and clonogenic survival. The expression of FoxP1 and MET harboring three and two miR-1 cognate sites, respectively, in their respective 3′-untranslated regions, was markedly reduced by ectopic miR-1. Up-regulation of several miR-1 targets including FoxP1, MET, and HDAC4 in primary human HCCs and down-regulation of their expression in 5-AzaC–treated HCC cells suggest their role in hepatocarcinogenesis. The inhibition of cell cycle progression and induction of apoptosis after re-expression of miR-1 are some of the mechanisms by which DNA hypomethylating agents suppress hepatocarcinoma cell growth. [Cancer Res 2008;68(13):5049–58]
Data from Loss of Metallothionein Predisposes Mice to Diethylnitrosamine-Induced Hepatocarcinogenesis by Activating NF-κB Target Genes
Authors: Majumder Sarmila , Roy Satavisha , Kaffenberger Thomas , Wang Bo , Costinean Stefan , Frankel Wendy , Bratasz Anna , Kuppusamy Periannan , Hai Tsonwin , Ghoshal Kalpana , Jacob Samson T.
Published: December 2023

Abstract
Metallothioneins (MT) are potent scavengers of free radicals that are silenced in primary hepatocellular carcinomas (HCC) of human and rodent origin. To examine whether loss of MT promotes hepatocarcinogenesis, male Mt-1 and Mt-2 double knockout (MTKO) and wild-type (WT) mice were exposed to diethylnitrosamine (DEN) and induction of HCC was monitored at 23 and 33 weeks. The size and number of liver tumors, the ratio between liver and body weight, and liver damage were markedly elevated in the MTKO mice at both time points compared with the WT mice. At 23 weeks, MTKO mice developed HCC whereas WT mice developed only preneoplastic nodules suggesting that loss of MT accelerates hepatocarcinogenesis. MTKO tumors also exhibited higher superoxide anion levels. Although NF-κB activity increased in the liver nuclear extracts of both genotypes after DEN exposure, the complex formed in MTKO mice was predominantly p50/65 heterodimer (transcriptional activator) as opposed to p50 homodimer (transcriptional repressor) in WT mice. Phosphorylation of p65 at Ser276 causing its activation was also significantly augmented in DEN-exposed MTKO livers. NF-κB targets that include early growth response genes and proinflammatory cytokines were significantly upregulated in MTKO mice. Concurrently, there was a remarkable increase (∼100-fold) in Pai-1 expression; significant increase in c-Jun, c-Fos, c-Myc, Ets2, and ATF3 expressions; and growth factor signaling that probably contributed to the increased tumor growth in MTKO mice. Taken together, these results demonstrate that MTs protect mice from hepatocarcinogen-induced liver damage and carcinogenesis, underscoring their potential therapeutic application against hepatocellular cancer. Cancer Res; 70(24); 10265–76. ©2010 AACR.
Data from Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)
Authors: Haigentz Missak , Lee Jeannette Y. , Chiao Elizabeth Y. , Aboulafia David M. , Ratner Lee , Ambinder Richard F. , Baiocchi Robert A. , Mitsuyasu Ronald T. , Wachsman William , Sparano Joseph A. , Rudek Michelle A.
Published: December 2023

AbstractPurpose:
To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with human immunodeficiency virus and cancer receiving antiretrovirals (ARV).
Patients and Methods:
Patients received a reduced dose of cabozantinib (20 mg orally daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or noninteracting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed on the basis of tolerability.
Results:
36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib doses for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with noninteracting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared with 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared with 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma.
Conclusions:
Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

See related commentary by Eisenmann and Sparreboom, p. 4999
Data from Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment
Authors: Wrenn Emma D. , Apfelbaum April A. , Rudzinski Erin R. , Deng Xuemei , Jiang Wei , Sud Sudha , Van Noord Raelene A. , Newman Erika A. , Garcia Nicolas M. , Miyaki Aya , Hoglund Virginia J. , Bhise Shruti S. , Kanaan Sami B. , Waltner Olivia G. , Furlan Scott N. , Lawlor Elizabeth R.
Published: December 2023

AbstractPurpose:
Despite limited genetic and histologic heterogeneity, Ewing sarcoma (EwS) tumor cells are transcriptionally heterogeneous and display varying degrees of mesenchymal lineage specification in vitro. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo.
Experimental Design:
Single-cell proteogenomic-sequencing of EwS cell lines was performed and integrated with patient tumor transcriptomic data. Cell subpopulations were isolated by FACS for assessment of gene expression and phenotype. Digital spatial profiling and human whole transcriptome analysis interrogated transcriptomic heterogeneity in EwS xenografts. Tumor cell subpopulations and matrix protein deposition were evaluated in xenografts and patient tumors using multiplex immunofluorescence staining.
Results:
We identified CD73 as a biomarker of highly mesenchymal EwS cell subpopulations in tumor models and patient biopsies. CD73+ tumor cells displayed distinct transcriptional and phenotypic properties, including selective upregulation of genes that are repressed by EWS::FLI1, and increased migratory potential. CD73+ cells were distinguished in vitro and in vivo by increased expression of matrisomal genes and abundant deposition of extracellular matrix (ECM) proteins. In epithelial-derived malignancies, ECM is largely deposited by cancer-associated fibroblasts (CAF), and we thus labeled CD73+ EwS cells, CAF-like tumor cells. Marked heterogeneity of CD73+ EwS cell frequency and distribution was detected in tumors in situ, and CAF-like tumor cells and associated ECM were observed in peri-necrotic regions and invasive foci.
Conclusions:
EwS tumor cells can adopt CAF-like properties, and these distinct cell subpopulations contribute to tumor heterogeneity by remodeling the tumor microenvironment.

See related commentary by Kuo and Amatruda, p. 5002
OFFSPRING: A SPRING Follow-Up Study Assessing the Efficacy of Maternal Probiotics and Allergic Disease in the Child
Authors: Shipton Emma V. , Foxcroft Katie , Dekker Nitert Marloes , McIntyre H. David , Barrett Helen , Tang Mimi , Callaway Leonie
Published: December 2023

Introduction: There are a variety of factors that contribute to the development of allergic diseases in children, including environmental exposures during the maternal prenatal period. It has been proposed that probiotic supplementation during pregnancy could be used as a possible preventative measure to target childhood allergic disease. Methods: Participants from a previously conducted prospective double-blind randomised control trial of probiotics versus placebo study (Study of PRrobiotics IN Gestation) were sent electronic questionnaires to complete about their child, who are now between 3 and 7 years of age. Demographic data and rates of allergic diseases were compared between the two groups. Results: One hundred and seven women responded to the questionnaires. Between the two groups, there was no difference in the frequency of allergic diseases, with similar rates of eczema, asthma, and hospital presentations seen. Conclusion: In this follow-up study, infants of mothers who were exposed to probiotics during their pregnancy do not appear to have any paediatric health advantages in terms of allergic diseases.
Factors Affecting the Second Complete Atypical Femoral Fracture after the First Atypical Fracture
Authors: Tsuchie Hiroyuki , Kasukawa Yuji , Nozaka Koji , Kinoshita Hayato , Sasaki Ken , Aizawa Toshiaki , Mita Motoki , Ouchi Kentaro , Yuasa Yusuke , Miura Takanori , Tomite Takenori , Maekawa Shigeto , Abe Hidekazu , Akagawa Manabu , Shibata Nobusuke , Fujii Masashi , Takeshima Masaaki , Inoue Jyunichi , Saito Hikaru , Miyakoshi Naohisa
Published: December 2023

Objectives: Atypical femoral fracture (AFF) is an atypical low-energy subtrochanteric and diaphyseal femoral fracture. Even if bone fusion is achieved in patients with AFF, the risk of AFF in the contralateral femur must be considered. This study aimed to investigate the factors affecting complete AFF in the contralateral femur and conservatively treated incomplete AFF. Subject and Methods: Radiographs of 111 femurs in 104 AFF cases were examined, and the femurs were classified as follows: 85 contralateral femurs with complete AFF; 18 contralateral femurs with incomplete AFF; 8 femurs with incomplete AFF without surgical treatment. Various patients’ clinical data were collected, and we investigated the factors affecting the second complete AFF. Results: Complete fractures occurred in 10 (9.7%) of 103 femurs without incomplete AFF at the first visit and in 3 (37.5%) of 8 femurs with incomplete AFF. The Kaplan-Meier curve revealed that lateral cortical bone thickening and thigh pain were associated with significantly poorer prognoses (p = 0.026 and p = 0.013, respectively). Multivariate analyses revealed that eldecalcitol usage after AFF onset (p = 0.0094) and previous use of bisphosphonate or denosumab (p = 0.0126) were protective factors for second complete AFF and that the presence of thigh pain (p = 0.0134) was a risk factor for second complete AFF. Conclusions: Eldecalcitol administration after bone union of first AFF may prevent AFF recurrence. In addition, painful incomplete AFF has a high risk of developing a complete fracture.
Diversity in Renal Mass Data Cohorts: Implications for Urology AI Researchers
Authors: Cen Harmony Selena , Dandamudi Siddhartha , Lei Xiaomeng , Weight Chris , Desai Mihir , Gill Inderbir , Duddalwar Vinay
Published: December 2023

Introduction: We examine the heterogeneity and distribution of the cohort populations in two publicly used radiological image cohorts, the Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCIA TCGA KIRC) collection and 2019 MICCAI Kidney Tumor Segmentation Challenge (KiTS19), and deviations in real-world population renal cancer data from the National Cancer Database (NCDB) Participant User Data File (PUF) and tertiary center data. PUF data are used as an anchor for prevalence rate bias assessment. Specific gene expression and, therefore, biology of RCC differ by self-reported race, especially between the African American and Caucasian populations. AI algorithms learn from datasets, but if the dataset misrepresents the population, reinforcing bias may occur. Ignoring these demographic features may lead to inaccurate downstream effects, thereby limiting the translation of these analyses to clinical practice. Consciousness of model training biases is vital to patient care decisions when using models in clinical settings. Methods: Data elements evaluated included gender, demographics, reported pathologic grading, and cancer staging. American Urological Association risk levels were used. Poisson regression was performed to estimate the population-based and sample-specific estimation for prevalence rate and corresponding 95% confidence interval. SAS 9.4 was used for data analysis. Results: Compared to PUF, KiTS19 and TCGA KIRC oversampled Caucasian by 9.5% (95% CI, −3.7 to 22.7%) and 15.1% (95% CI, 1.5 to 28.8%), undersampled African American by −6.7% (95% CI, −10% to −3.3%), and −5.5% (95% CI, −9.3% to −1.8%). Tertiary also undersampled African American by −6.6% (95% CI, −8.7% to −4.6%). The tertiary cohort largely undersampled aggressive cancers by −14.7% (95% CI, −20.9% to −8.4%). No statistically significant difference was found among PUF, TCGA, and KiTS19 in aggressive rate; however, heterogeneities in risk are notable. Conclusion: Heterogeneities between cohorts need to be considered in future AI training and cross-validation for renal masses.
Similarity in evoked responses does not imply similarity in macroscopic network states
Authors: Rasero Javier , Betzel Richard , Sentis Amy Isabella , Kraynak Thomas E. , Gianaros Peter J. , Verstynen Timothy
Published: December 2023

It is commonplace in neuroscience to assume that if two tasks activate the same brain areas in the same way, then they are recruiting the same underlying networks. Yet computational theory has shown that the same pattern of activity can emerge from many different underlying network representations. Here we evaluated whether similarity in activation necessarily implies similarity in network architecture by comparing region-wise activation patterns and functional correlation profiles from a large sample of healthy subjects (N = 242). Participants performed two executive control tasks known to recruit nearly identical brain areas, the color-word Stroop task and the Multi-Source Interference Task (MSIT). Using a measure of instantaneous functional correlations, based on edge time series, we estimated the task-related networks that differed between incongruent and congruent conditions. We found that the two tasks were much more different in their network profiles than in their evoked activity patterns at different analytical levels, as well as for a wide range of methodological pipelines. Our results reject the notion that having the same activation patterns means two tasks engage the same underlying representations, suggesting that task representations should be independently evaluated at both node and edge (connectivity) levels.
Altered topological structure of the brain white matter in maltreated children through topological data analysis
Authors: Chung Moo K. , Azizi Tahmineh , Hanson Jamie L. , Alexander Andrew L. , Pollak Seth D. , Davidson Richard J.
Published: December 2023

Childhood maltreatment may adversely affect brain development and consequently influence behavioral, emotional, and psychological patterns during adulthood. In this study, we propose an analytical pipeline for modeling the altered topological structure of brain white matter in maltreated and typically developing children. We perform topological data analysis (TDA) to assess the alteration in the global topology of the brain white matter structural covariance network among children. We use persistent homology, an algebraic technique in TDA, to analyze topological features in the brain covariance networks constructed from structural magnetic resonance imaging and diffusion tensor imaging. We develop a novel framework for statistical inference based on the Wasserstein distance to assess the significance of the observed topological differences. Using these methods in comparing maltreated children with a typically developing control group, we find that maltreatment may increase homogeneity in white matter structures and thus induce higher correlations in the structural covariance; this is reflected in the topological profile. Our findings strongly suggest that TDA can be a valuable framework to model altered topological structures of the brain. The MATLAB codes and processed data used in this study can be found at https://github.com/laplcebeltrami/maltreated.
The Quality of Hasmonaean Biblical Manuscripts
Authors: Popović Mladen , Tigchelaar Eibert
Published: December 2023

Recent research has introduced the categories of deluxe or high-quality Dead Sea Scrolls. We reconsider this category and propose a classification of manuscripts on the basis of handwriting quality. As a test case, we classify all Hasmonaean-type biblical manuscripts as elegant, professional, or substandard. We discuss eleven scrolls with elegant handwriting and consider other physical, scribal, and textual features of these scrolls. Our study calls into question the idea that especially biblical manuscripts would have been copied according to the highest standards. We show that different quality standards were in operation for Hasmonaean-type biblical manuscripts.
First reports of inland water benthic crustaceans for a Mediterranean-climate river (Claro River basin, Chile)
Authors: De los Ríos-Escalante Patricio R. , Esse Carlos , Ulloa-Yáñez Alfredo , Santander-Massa Rodrigo , Peña-Farfal Carlos , Corsini Acuña Gino , Guerra Emilio , Correa-Araneda Francisco , Martin Juan
Published: December 2023

Existing studies on central Chilean inland waters only mention records of decapods, but there are no ecological studies about decapods and other crustacean groups. The aim of the present study was a first characterization of inland water crustaceans in Claro River, a Mediterranean-climate river from Chile. The results of redundance analysis (RDA) revealed that the crab Aegla affinis inhabits waters of high pH and low temperature values, whereas amphipods of the genus Hyalella inhabit habitats with high pH, high temperatures, and low values of dissolved oxygen. Finally, ostracods (family Cyprididae), isopods (Heterias sp.) and the southern river crayfish (Samastacus spinifrons) inhabit water systems with moderate values of pH, temperature, dissolved oxygen, and conductivity. This paper represents the first ecological report for crustaceans of central Chilean inland waters, and the results appear to be similar to comparable descriptions for northern Patagonian rivers.
Pinnotheres onychodactylus Tesch, 1918: a junior synonym of Magnotheres Globosus (Hombron & Jacquinot, 1846) (Decapoda, Brachyura, Pinnotheridae)
Authors: Ng Peter K. L. , Ahyong Shane T.
Published: December 2023

The pea crab, Pinnotheres onychodactylus Tesch, 1918, is only known on the basis of the types collected from the Moluccas, Indonesia. A re-examination of the type specimens shows that the species is actually a junior subjective synonym of Magnotheres globosus (Hombron & Jacquinot, 1846), a widely distributed Indo-West Pacific species associated with horse mussels of the family Pinnidae.
L’établissement de la mission méthodiste en Côte d’Ivoire (c. 1924-1940)
Authors: Miran-Guyon Marie
Published: December 2023

Cet article revisite l’histoire des débuts de la Mission méthodiste wesleyenne en Côte d’Ivoire coloniale, depuis les prémices de la présence protestante sur le sol ivoirien à la fin du XIXe siècle, puis en resserrant la focale sur la période d’après la tournée « héroïque » du pasteur Platt en 1924 – ayant permis une complète refondation de la mission – jusqu’à la transition des années 1940. La conversion ivoirienne au christianisme est l’œuvre du prophète William Wadé Harris, dont la mission prophétique en 1913-1914 révolutionna la société de la Basse-Côte. L’article interroge comment la mission méthodiste se fit l’héritière d’Harris, en entrant en concurrence avec des communautés prophétiques locales et la mission catholique des pères de la Société des missions africaines. L’article explore aussi les stratégies linguistiques et éducatives mises en œuvre par les missionnaires méthodistes pour aller à la rencontre d’Africains et d’Africaines qui tentèrent, par leur conversion religieuse, de se convertir aussi à une certaine modernité coloniale, en se frayant un chemin incertain d’émancipation sous la double contrainte d’un ordre colonial et d’un ordre missionnaire exogènes.
Enacting the Mythical through Architecture
Authors: Spellerberg Jonathan
Published: December 2023

The beginning of the Third Reich saw the construction of large architectural structures to host and aesthetically frame Nazi mass events. The significance of these buildings cannot be understood without the propaganda and mass performances that constituted their contemporary frame of reception. This article discusses the Gauforum project in Weimar, constructed from 1937 until 1944. Combining an analysis of common architecture-related propaganda tropes with an examination of architectural design and a reading of the ceremony of laying the first foundation stone, it shows how these elements performed the longed-for Volksgemeinschaft. By framing construction works as the expression of national achievement and an ongoing revolutionary renewal of the nation, Nazi-era architecture propaganda discursively primed the ground for interplay between the material arrangements of architecture and events that afforded an experience of the mythical spatiotemporality of the Volksgemeinschaft. In this way, Nazi architectural propaganda played an efficacious part in the politics of mass events.
Reinventing Romanitas
Authors: Plantzos Dimitris , Balaskas Vasileios
Published: December 2023

Based on fresh archival research this article examines the exchange of Romanizing statuary between Italy and Spain during the ventennio fascista. Between 1933 and 1943, Italy and Spain exchanged copies of Roman statues as symbolic gestures, to substantiate their claims to a shared classical heritage of ‘imperial greatness’. Using press reports and documentary film excerpts the article reconstructs public events that took place in Merida, Tarragona, Palma, and Zaragoza and assesses their impact. Behind these exchanges, and public ceremonies staged on their occasion, lay the Fascist concept of romanità: an archaeologically and aesthetically charged discourse placing Late-Republican and Early-Imperial Roman heritage in the epicentre of Fascist identity politics. Through improvised public performances of romanità, classical materialities, monumental as well as spatial, were imbued with Fascist dynamics, as the past turned into the present and projected into the future. Through individual and collective performance these ceremonies embodied a primeval Fascist ideal that appeared at once spectacular and modern.