bluuebunny/crossref_metadata_2025 huggingface dataset:
Radical radiotherapy for cervical cancer and meningioma with a history of Guillain-Barré syndrome: A case report
Authors: Deng Kangli , Yu Yanxin , Ge Liben , Deng Kangyan , Zhang Mo
Published: December 2022

Rationale:

Guillain-Barré syndrome (GBS) is a rare autoimmune disease. Patients with cervical malignancies and intracranial meningiomas after the course of GBS are even rarer. There are no relevant reports at present.

Patient concerns:

We report a patient who developed cervical cancer (CC) and intracranial meningioma simultaneously after the course of GBS.

Diagnoses:

The history, pelvic enhanced magnetic resonance imaging (MRI) and pathology confirmed cervical squamous cell carcinoma, and the head enhanced MRI confirmed meningioma.

Intervention:

After multi-disciplinary team, the patient received head stereotactic radiosurgery for meningioma and radical radiotherapy for CC.

Outcomes:

The follow up for 1 year after treatment revealed a complete remission of the cervical tumor, stable disease of the meningioma, and no signs of GBS recurrence. Up to now, the general condition of the patient is acceptable and the curative effect is satisfactory.

Lessons:

This case report aims to improve the oncologists’ understanding of malignant tumors with rare autoimmune diseases and provide treatment reference for similar diseases in the future.
Carbohydrate antigen 125 combined with N-terminal pro-B-type natriuretic peptide in the prediction of acute heart failure following ST-elevation myocardial infarction
Authors: Xu Kaizu , Wu Meifang , Huang Meinv , Zhuo Xiuping , Weng Yujuan , Chen Xi
Published: December 2022

The value of serum carbohydrate antigen 125 (CA125) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the evaluation of acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) remains unclear. The aim of this study was to evaluate the efficacy of CA125 combined with NT-proBNP in predicting AHF following STEMI. A total of 233 patients with STEMI were evaluated, including 39 patients with Killip II-IV and 194 patients with Killip I. The optimal cutoff point for predicting AHF was determined by receiver operating characteristic (ROC) curve, and the independent predictors of AHF were evaluated by multiple logistic regression. According to the cutoff value, it was divided into three groups: C1 = CA125 < 13.20 and NT-proBNP < 2300 (n = 138); C2 = CA125 ≥ 13.20 or NT-proBNP ≥ 2300 (n = 59); C3 = CA125 ≥ 13.20 and NT-proBNP ≥ 2300 (n = 36). Differences between groups were compared by odds ratio (OR). The levels of CA125 and NT-proBNP in AHF group were higher than those in non-AHF group (19.90 vs 10.00, P < .001; 2980.00 vs 1029.50, P < .001, respectively). The optimal cutoff values of CA125 and NT-proBNP for predicting AHF were 13.20 and 2300, both of which were independent predictors of AHF. The incidence of AHF during hospitalization was highest in C3 (69.44%), middle in C2 (20.34%) and lowest in C1 (1.45%). After adjustment for clinical confounding variables, compared with C1: C2 (OR = 6.41, 95% CI: 1.22–33.84, P = .029), C3 (OR = 19.27, 95% CI: 3.12–118.92, P = .001). Elevated CA125 and NT-proBNP are independent predictors of AHF in STEMI patients, and their combination can improve the recognition efficiency.
Unilateral thalamic infarction onset with lethargy: A case report and literature review
Authors: Kong Wei , Ma Lei , Yin Changyou , Zhao Wei , Wang Yanbin
Published: December 2022

Introduction:

Infarct-induced lethargy is a common disabling symptom that lacks a consensual definition and a standardized method of care. Identifying the causes of the infarct in the thalamic reticular nucleus (TRN) induced lethargy is crucial in stroke patients.

Case presentation:

A 68-year-old female patient was admitted to the hospital with lethargy and weakness in the right limb. A computed tomography (CT) scan performed at the presentation showed no bleeding. She was given intravenous thrombolysis. A head computed tomography (CT) scan clearly showed that the infarct was located in the TRN. After 1 hour of treatment, the weakness in the patient’s limb was relieved. However, she was still lethargic, but her lethargy symptoms improved after 3 days.

Discussion and conclusions:

Our case highlights that despite the small size of the infarct, the patient was unconscious, which makes it difficult for physicians to understand and treat the condition, resulting in trouble managing the case. We performed a literature review and proposed that the infarction located in the TRN causes lethargy. However, further clinical and pathophysiological research is still needed to improve patient care.
Treatment-resistant idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly managed with Janus kinase inhibitors: A case report
Authors: Kakutani Takuya , Nunokawa Takahiro , Chinen Naofumi , Tamai Yotaro
Published: December 2022

Rationale:

Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are nonmalignant but life-threatening systemic inflammatory disorders. However, many patients are refractory to treatment, resulting in significant morbidity and mortality. Additionally, established treatment options are unavailable. Therefore, we present 2 cases of adults with the iMCD-TAFRO syndrome refractory to initial treatment but responded to Janus kinase (JAK) inhibitors with ruxolitinib. The report reveals that these rare adult cases of the refractory and treatment-resistant iMCD-TAFRO syndrome can be treated using JAK inhibitors.

Patient concerns:

Case 1 is a 36-year-old previously healthy male patient who presented with fever and general fatigue for 2 weeks. Case 2 is a 42-year-old previously healthy female patient who presented with fever and general fatigue.

Diagnosis:

The diagnosis met the 2015 criteria for TAFRO syndrome, as determined by All Japan TAFRO Syndrome Research Group in the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW) Japan.

Interventions:

Treatment with tocilizumab and several immunosuppressants were ineffective. So, we performed ruxolitinib.

Outcomes:

Each patient received ruxolitinib, the general condition improved, and CRP levels decreased.

Lessons:

These cases showed that ruxolitinib was effective for treatment-resistant/ refractory TAFRO syndrome. Further prospective studies are needed on using ruxolitinib with a small number of cases.
A case report of multiple extramedullary plasmacytoma of the head and neck
Authors: Zhang Jin , Ding Detao , Sun Juxing , Zhang Hui , Dai YunBing , Li Xiaoying , Ma Xu , Li Xiaoyu , Wu Yungang
Published: December 2022

Rationale:

Multiple extramedullary plasmacytoma (EMP) of the head and neck is rare and a definitive first-line treatment has not been established. EMP successively as a benign mass occurring in multiple areas of the head and neck is rare. This report describes an atypical case with EMP occurring in multiple areas of the head and neck.

Patient concerns:

A 35-year-old woman was admitted due to complaints of sore throat discomfort accompanied by hoarseness. The patient had undergone surgical excision of the thyroid gland and parotid gland excision several years ago. Postoperative pathological examination both indicated EMP. This time, the woman suffered EMP in head and neck who was treated with a simple surgery.

Diagnosis:

Postoperative pathological examination of the tumor indicated EMP, and histopathological findings revealed the tumor to be a plasmacytoma. Immunopathological examination were consistent with the diagnosis of EMP.

Interventions:

The patient underwent surgical resection without radiotherapy.

Outcomes:

Histopathological and immunopathological examination findings revealed the tumor to be EMP. The patient was recurrence-free and did not progress to multiple myeloma (MM) during 19 months follow-up.

Lessons:

Increasing the awareness of EMP of head and neck is warranted. Our case confirmed that surgical excision is beneficial in the treatment of small, localized EMP.
Expanding Medicaid to Reduce Human Immunodeficiency Virus Transmission in Houston, Texas
Authors: Lee Francis , Khanna Aditya S. , Hallmark Camden J. , Lavingia Richa , McNeese Marlene , Zhao Jing , McNeese Melanie L. , Khuwaja Salma , Ardestani Babak M. , Collier Nicholson , Ozik Jonathan , Hotton Anna L. , Harawa Nina T. , Schneider John A. , Fujimoto Kayo
Published: December 2022

Context:

Medicaid expansion has been nationally shown to improve engagement in the human immunodeficiency virus (HIV) treatment and prevention continua, which are vital steps to stopping the HIV epidemic. New HIV infections in the United States are disproportionately concentrated among young Black men who have sex with men (YBMSM). Houston, TX, is the most populous city in the Southern United States with a racially/ethnically diverse population that is located in 1 of 11 US states that have not yet expanded Medicaid coverage as of 2021.

Methods:

An agent-based model that incorporated the sexual networks of YBMSM was used to simulate improved antiretroviral treatment and pre-exposure prophylaxis (PrEP) engagement through Medicaid expansion in Houston, TX. Analyses considered the HIV incidence (number of new infections and as a rate metric) among YBMSM over the next 10 years under Medicaid expansion as the primary outcome. Additional scenarios, involving viral suppression and PrEP uptake above the projected levels achieved under Medicaid expansion, were also simulated.

Results:

The baseline model projected an HIV incidence rate of 4.96 per 100 person years (py) and about 368 new annual HIV infections in the 10th year. Improved HIV treatment and prevention continua engagement under Medicaid expansion resulted in a 14.9% decline in the number of annual new HIV infections in the 10th year. Increasing viral suppression by an additional 15% and PrEP uptake by 30% resulted in a 44.0% decline in new HIV infections in the 10th year, and a 27.1% decline in cumulative infections across the 10 years of the simulated intervention.

Findings:

Simulation results indicate that Medicaid expansion has the potential to reduce HIV incidence among YBMSM in Houston. Achieving HIV elimination objectives, however, might require additional effective measures to increase antiretroviral treatment and PrEP uptake beyond the projected improvements under expanded Medicaid.
Factors Affecting Breast Screening Behavior of First-Degree Relatives of Breast Cancer Patients in China
Authors: Lu Ningning , Zhang Chi , You Hua , Ma Zhuyue , Zhu Ping , Cheng Fang
Published: December 2022

Background

Breast cancer is the most common cancer in women, and first-degree relatives (FDRs) of breast cancer patients have a significantly higher risk of developing breast cancer. However, the factors affecting breast cancer screening behavior of FDRs in China remain unclear.

Objective

The aim of this study was to determine the social cognitive theory factors influencing screening behaviors of FDRs.

Methods

A cross-sectional survey was conducted, and 430 FDRs were recruited. Data were collected using demographic information and self-reported questionnaire based on the social cognitive theory. The structural equation modeling method was used to analyze the influence of social cognitive factors on breast cancer screening behavior.

Results

The model showed a good fit (goodness of fit = 0.462). Goal setting and self-regulation (β = 0.631, P < .001) and positive outcome expectation (β = 0.098, P = .042) were positively related to breast cancer screening behavior. Negative outcome expectation was negatively related to breast cancer screening behavior (β = −0.102, P = .024). In addition, positive outcome expectation, negative outcome expectation, and goal setting and self-regulation are mediators of self-efficacy (β = 0.475, P < .001) to breast cancer screening behavior.

Conclusion

Goal setting and self-regulation are important influences on breast cancer screening behavior. The social cognitive theory is both applicable to and effective in explaining and predicting breast cancer screening behavior.

Implications for Practice

Health professionals can develop appropriate intervention strategies based on the social cognitive theory among FDRs. It is necessary to focus on the people who influence women, such as spouses, mothers, or daughters.
Timing of Tracheostomy in Critically Ill Infants and Children With Respiratory Failure: A Pediatric Health Information System Study
Authors: Mehrotra Priyanka , Thomas Charlene , Gerber Linda M. , Maresh Alison , Nellis Marianne
Published: December 2022

OBJECTIVES:

Tracheostomy placement in infants and children with respiratory failure has steadily increased over time, yet there is no consensus for optimal timing. We sought to: 1) describe tracheostomy timing and associated demographic and clinical characteristics in a large ICU cohort and 2) compare clinical outcomes between subgroups based on tracheostomy timing.

DESIGN:

Retrospective observational study using the Pediatric Health Information System (PHIS).

SETTING:

Neonatal ICUs and PICUs in the United States.

PATIENTS:

PHIS was queried for patients less than 18 years who underwent tracheostomy from 2010 to 2020. Patients were included if admitted to an ICU with need for mechanical ventilation (MV) prior to tracheostomy in the same hospitalization. Patients were categorized as early tracheostomy (ET) (placement at MV day ≤ 14), late tracheostomy (LT) (MV days 15–60), and extended tracheostomy (ExT) (MV day > 60). Primary endpoints included demographic and clinical characteristics. Secondary endpoints included patient outcomes: in-hospital mortality, length of stay (LOS), hospital-acquired pneumonia (HAP), and hospital costs.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Sixteen thousand one hundred twenty-one patients underwent tracheostomy at 52 children’s hospitals. Ten thousand two hundred ninety-five had complete data and were included in the analysis. Thirty-nine percent (4,006/10,295) underwent ET, 40% (4,159/10,295) underwent LT, and 21% (2,130/10,295) underwent ExT. Majority of patients in all subgroups had complex chronic conditions. Median age was significantly different between subgroups with ET being the oldest (p < 0.001). A multivariable regression analysis showed that ET was associated with lower in-hospital mortality (p < 0.001), shorter hospital LOS (p < 0.001), shorter ICU LOS (p < 0.001), shorter post-tracheostomy LOS (p < 0.001), decreased HAP (p < 0.001), and lower hospital costs (p < 0.001) compared with those who underwent LT or ExT.

CONCLUSIONS:

In a large cohort of pediatric patients with respiratory failure, tracheostomy placement within 14 days of MV was associated with improved in-hospital outcomes. ET was independently associated with decreased mortality, LOS, HAP, and hospital costs.
The Association of Coronary Artery Calcium Score and Osteoporosis in Postmenopausal Women: A Cross-Sectional Study
Authors: Asadi Mojgan , Razi Farideh , Fahimfar Noushin , Shirani Shapour , Behzad Ghazal , Salari Pooneh
Published: December 2022

Background: The association between osteoporosis, a common metabolic bone disorder, and atherosclerosis has been reported in different studies. In this study, we aimed to investigate the association between the coronary artery calcium score (CACS) and bone mineral density (BMD) at different sites and bone biomarkers in postmenopausal women.Methods: A total of 184 participants were enrolled in this study. The CACS and BMD at different sites, including the spinal, total hip, and femoral neck, were measured using computed tomography angiography and dual energy X-ray absorptiometry, respectively. Serum levels of osteocalcin, β-C-terminal telopeptide (β-CTX), parathyroid hormone, and 25-hydroxy-vitamin D were measured.Results: A negative association between CACS and bone biomarker levels (osteocalcin, P=0.021; β-CTX, P=0.013) was noted. The univariable model showed an association between CACS and osteoporosis of the femoral neck (P=0.03). It was found that with an increase of 10 U in CACS, the odds of osteoporosis at the femoral neck escalates by 2% (odds ratio=1.02, 95% confidence interval, 1.002–1.03) using the multivariate logistic regression model, while such an association with osteoporosis could not be found at the spinal site. The best cutoff point of the calcium score was estimated to be 127.Conclusions: The results suggest that in postmenopausal women, coronary atherosclerosis is independently associated with osteoporosis of the femoral neck, but such an association could not be detected with spinal osteoporosis. The importance of screening for osteoporosis in patients with cardiovascular disease and the implications of preventive measures in the primary care setting were highlighted considering the common risk factors.
Mapping of biomarker efficacy in SARS-CoV-2: tracking the impact of viral mutations and vaccinations
Authors: Shuvo ME Rahman , Schwiening Max , Avramidis Nikos , Soares Felipe , Feng Oliver , Abreu Susana , Veale Niki , Gao Q , Thomas William , Thompson AA Roger , Samworth Richard J , Morrell Nicholas W , Baillie Kenneth , Marciniak Stefan J , Soon Elaine
Published: December 2022

Rationale: Sophisticated prognostic scores have been proposed for SARS-CoV-2 but do not always perform consistently. We conducted these meta-analyses to uncover why and to investigate the impact of vaccination and variants.

Methods: We searched the PubMed database for the keywords “SARS-CoV-2” with “biomarker” and “mortality” for the baseline tranche (01/12/2020-30/06/2021) and either “SARS-CoV-2” or “Covid19” with “biomarker” and either “vaccination” or “variant” from 01/12/2020 to 31/10/2023. To aggregate the data, the meta library in R was used, and a random effects model fitted to obtain pooled AUCs and 95% confidence intervals for the European/North American, Asian, and overall datasets.

Results: Biomarker effectiveness varies significantly in different continents. Admission CRP levels were a good prognostic marker for mortality due to wild-type virus in Asian countries, with a pooled area under curve (AUC) of 0.83 (95%CI 0.80-0.85), but only an average predictor of mortality in Europe/North America, with a pooled AUC of 0.67 (95%CI 0.63-0.71, P<0.0001). We observed the same pattern for D-dimer and IL-6. This variability explains why the proposed prognostic scores did not perform evenly. Notably, urea and troponin had pooled AUCs ≥0.78 regardless of location, implying that end-organ damage at presentation is a key prognostic factor. The inflammatory biomarkers (CRP, D-dimer and IL-6) have generally declined in effectiveness in the vaccinated and variant cohorts. We note a significant lag from the pandemic advent to data availability and this has no doubt impacted on patient care.

Conclusions: Biomarker efficacies vary considerably by region. It is imperative that the infrastructure for collecting clinical data should be put in place ahead of a future pandemic.
Cerebral oxygenation and cardiac output responses during short repeated-sprints exercise and modulatory effect of glucose ingestion
Authors: Armada-da-Silva Paulo A. S. , Mingzhu Hu , Zongze Wu , Linjian Wen , Ruisen Feng , Zeng Xinglin , Yuan Zhen , Kong Zhaowei
Published: December 2022

In this study we investigated changes in concentrations of cerebral oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and total haemoglobin (tHb) during repeated sprints and their relationship with cardiac output. We also examined the effect of glucose ingestion and acute hyperglycaemia on cerebral haemoglobin responses. Ten young male participants ingested either a glucose drink (70 g) or a placebo before performing a set of 10 repeated 6-second sprints on a cycle ergometer. Heart rate, stroke volume, and cardiac output were measured continuously using impedance cardiography, while changes in O2Hb, HHb, and tHb in the frontal region of the cerebral cortex were measured using near-infrared spectroscopy (NIRS). The results showed that each sprint elicited a transient increase in O2Hb and to lesser extent HHb concentrations, which was enhanced with the number of sprint repetitions and correlated with cardiac output. After each sprint, O2Hb and HHb quickly returned to baseline, while cardiac output remained elevated. At the end of the repeated sprints, O2Hb was decreased to below pre-exercise levels, while HHb and tHb were elevated. After a recovery of 10-15 min, O2Hb returned to pre-exercise values in the placebo trial, but increased to above pre-exercise values (reactive hyperaemia) in the glucose trial. Our findings suggest that short sprint exercise increases O2Hb, HHb, and tHb levels during exertion in parallel with cardiac output. However, in addition to the transient increase in cerebral haemoglobin, a progressive decline in cerebral oxygen saturation occurs during repeated sprints. Glucose ingestion does not alter cerebral haemoglobin responses to sprint exercise but appears to be associated with faster recovery of O2Hb.
The global distribution of angiosperm genome size is shaped by climate
Authors: Bureš Petr , Elliott Tammy L. , Veselý Pavel , Šmarda Petr , Forest Félix , Leitch Ilia J. , Lughadha Eimear Nic , Gomez Marybel Soto , Pironon Samuel , Brown Matilda J. M. , Šmerda Jakub , Zedek František
Published: December 2022

Angiosperms, which inhabit diverse environments across all continents, exhibit significant variation in genome sizes, making them an excellent model system for examining hypotheses about the global distribution of genome size. These include the previously proposed large-genome-constraint, mutational-hazard, polyploidy-mediated, and climate-mediated hypotheses.

We compiled the largest genome size dataset to date, encompassing >5% of known angiosperm species, and analyzed genome size distribution using a comprehensive geographic distribution dataset for all angiosperms.

We observed that angiosperms with large range sizes generally had small genomes, supporting the large-genome-constraint hypothesis. Climate was shown to exert a strong influence on genome size distribution along the global latitudinal gradient, while the frequency of polyploidy and the type of growth form had negligible effects. In contrast to the unimodal patterns along the global latitudinal gradient shown by plant size traits and polyploid proportions, the increase in angiosperm genome size from the equator to 40-50°N/S is probably mediated by different (mostly climatic) mechanisms than the decrease in genome sizes observed from 40–50°N northwards.

Our analysis suggests that the global distribution of genome sizes in angiosperms is mainly shaped by climatically-mediated purifying selection, genetic drift, relaxed selection, and environmental filtering.
Refeeding-associated AMPKγ1complex activity is a hallmark of health and longevity
Authors: Ripa Roberto , Ballhysa Eugen , Steiner Joachim D. , Annibal Andrea , Hochhard Nadine , Latza Christian , Dolfi Luca , Calabrese Chiara , Meyer Anna M. , Polidori M. Cristina , Müller Roman-Ulrich , Antebi Adam
Published: December 2022

Late-life-initiated dietary interventions negligibly extend longevity or reduce frailty, yet the reason remains unknown. We investigated the age-related changes associated with the fasting response in adipose tissue of the short-lived killifishN. furzeri. Transcriptomic analysis revealed the presence of a fasting-like transcriptional program (FLTP) in old animals that is irrespective of their nutritional status and characterized by widespread suppression of anabolic processes. FLTP is associated with reduced expression of the AMPK γ1 regulatory subunit. Accordingly, refeeding positively regulates γ1 expression in young but not in old animals. Fish having sustained AMPKγ1activation had no sign of FLTP in old age and exhibited metabolic health and longevity. In humans, we found that γ1 expression declines with age and is associated with multimorbidity and multidimensional frailty risk. Our study highlights the importance of the refeeding arm in promoting health and longevity and identifies the AMPKγ1complex as a potential target to prevent age-related diseases in humans.
Till evolution do us part: The diversity of symbiotic associations across populations ofPhilaenusspittlebugs
Authors: Kolasa Michał , Kajtoch Łukasz , Michalik Anna , Maryańska-Nadachowska Anna , Łukasik Piotr
Published: December 2022

Symbiotic bacteria have played crucial roles in the evolution of sap-feeding insects and can strongly affect host function. However, their diversity and distribution within species are not well understood; we don’t know to what extent environmental factors or associations with other species may affect microbial community profiles. Here, we sequenced host and bacterial marker gene amplicons to survey the bacterial community composition across multiple populations ofPhilaenusspittlebugs.

Host mitochondrial sequence data confirmed morphology-based identification of 6 species and revealed two divergent clades ofPhilaenus spumarius. All of them hosted the primary symbiontSulciathat was almost always accompanied bySodalis. Interestingly, populations and individuals often differed in the presence ofSodalissequence variants, suggestive of intra-genome 16S rRNA variant polymorphism combined with rapid genome evolution and/or recent additional infections or replacements of the co-primary symbiont. The prevalence of facultative endosymbionts, includingWolbachia, Rickettsia, andSpiroplasma, varied among populations.

Notably, COI amplicon data also showed that nearly a quarter ofP. spumariuswere infected by parasitoid flies (Verralia aucta). One of theWolbachiaOTUs was exclusively present inVerralia-parasitized specimens, suggestive of parasitoids as their source and highlighting the utility of host gene amplicon sequencing in microbiome studies.
Engineered superinfective Pf phage prevents dissemination ofPseudomonas aeruginosain a mouse burn model
Authors: Prokopczuk Federico I , Im Hansol , Campos-Gomez Javier , Orihuela Carlos J. , Martinez Eriel
Published: December 2022

Pf is a filamentous bacteriophage integrated in the chromosome of most clinical isolates ofPseudomonas aeruginosa. Under stress conditions, mutations occurring in the Pf genome result in the emergence of super-infective variants of Pf (SI-Pf) that are capable of circumventing phage immunity; therefore SI-Pf can even infect Pf-lysogenizedP. aeruginosa. Herein, we identified specific mutations located between the repressor and the excisionase genes that result in the emergence of SI-Pf. Based on these findings, we genetically engineered a SI-Pf (eSI-Pf) and tested it as a phage therapy tool for the treatment of life-threateningP. aeruginosainfection of burns caused by strain PAO1. eSI-Pf was able to infect PAO1 biofilms formed in vitro on polystyrene and inhibited their formation when at high concentration. eSI-Pf also infected PAO1 present in burned skin wounds on mice but was not capable of maintaining a sustained reduction in bacterial burden beyond 24 hours. Importantly, and despite not lowering CFU/g of burn skin tissue, eSI-Pf treatment completely abolished the capability ofP. aeruginosato disseminate from the burn site to internal organs. Over the course of 10 days, this resulted in bacterial clearance and survival of all treated mice. We determined that eSI-Pf induced a small colony variant ofP. aeruginosathat was unable to disseminate systemically in our burned mouse model during acute infection. Our results suggest that eSI-Pf has potential as a phage therapy against highly recalcitrant antimicrobial resistantP. aeruginosainfections of burn wounds.

IMPORTANCE

Pseudomonas aeruginosais a major cause of burn related infections. It is also the most likely bacterial infection to advance to sepsis and result in burn-linked death. Frequently,P. aeruginosastrains isolated from burn patients display a multidrug resistant phenotype necessitating the development of new therapeutic strategies and prophylactic treatments. In this context, phage therapy using lytic phages has demonstrated exciting potential in the controlP. aeruginosainfection. However, lytic phages have a set of drawbacks during phage therapy including the induction of bacterial resistance and limited bacteria-phage interactions in vivo. Here we propose an alternative approach to interfere withP. aeruginosapathogenesis in a burn infection model, i.e., using an engineered super-infective filamentous phage. Our study demonstrates that treatment with the engineered Pf phage can prevent sepsis and death in a burn mouse model.
Natural killer cell educating KIR/HLA combinations impact survival in anti-PD-L1 treated cancer patients
Authors: Roe David , Rosoff Howard , Ruan Dan Fu , Khan Zia , Dogra Pranay , Carroll Jonathan , Hunkapiller Julie , Mohindra Rajat , Srivastava Minu K. , Nabet Barzin Y. , Chandler G. Scott , Albert Matthew L. , McCarthy Mark I. , Mellman Ira , Horowitz Amir , Hammer Christian
Published: December 2022

Natural killer (NK) cells are educated through the binding of killer immunoglobulin like receptors (KIR) to human leukocyte antigen (HLA) proteins, but it is unknown whether the presence of these highly diverse KIR/HLA interactions influence responses to immunotherapy in solid tumors. We report herein two observations that shed light on NK cell function and abundance in anti-tumor immune responses. In patients with non-small cell lung cancer treated with anti-PD-L1 therapy, we found that individuals carrying HLA-C1 and HLA-Bw4 alleles and the genes coding for their receptors KIR2DL3 and KIR3DL1 showed improved overall survival (OS). Combined with our second finding that NK cell infiltration was independently associated with improved OS, our findings have important implications for precision medicine approaches and the development of NK cell-based therapies.
Quantitative differentiation of minimal-fat angiomyolipomas from renal cell carcinomas using grating-based x-ray phase-contrast computed tomography: an ex vivo study
Authors: Birnbacher Lorenz , Braunagel Margarita , Willner Marian , Marschner Mathias , De Marco Fabio , Viermetz Manuel , Auweter Sigrid , Notohamiprodjo Susan , Hellbach Katharina , Notohamiprodjo Mike , Staehler Michael , Pfeiffer Daniela , Reiser Maximilian F. , Pfeiffer Franz , Herzen Julia
Published: December 2022

Background

The differentiation of minimal-fat—or low-fat—angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples.

Materials and methods

Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner.

Results

We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a significant (p<0.05) difference between mfAML samples (58±4 HUp), hfAML (−58±17 HUp) and RCCs (ccRCCs: 40±12 HUp; pRCCs: 43±9 HUp; chrRCCs: 40±7 HUp) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI. Due to the heterogeneity and lower signal of oncocytomas (44±10 HUp), quantitative differentiation of the samples based on HUp or in combination with HUs was not possible.

Conclusions

GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from oncocytomas and RCCs in contrast to absorption-based imaging and clinical MRI.
Poverty shapes the transcriptome of immune cells
Authors: Arnold Nicole S. , Resztak Justyna , Witonsky David , Alazizi Adnan , Hooten Nicole Noren , Evans Michele K. , Odero-Marah Valerie , Dluzen Douglas F. , Pique-Regi Roger , Luca Francesca
Published: December 2022

Social factors influence health outcomes and life expectancy. Individuals living in poverty often have adverse health outcomes related to chronic inflammation that affect the cardiovascular, renal, and pulmonary systems. Negative psychosocial experiences are associated with transcriptional changes in genes associated with complex traits. However, the underlying molecular mechanisms by which poverty increases the risk of disease and health disparities are still not fully understood. To bridge the gap in our understanding of the link between living in poverty and adverse health outcomes, we performed RNA sequencing of blood immune cells from 204 participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study in Baltimore, Maryland. We identified 138 genes differentially expressed in association with poverty. Genes differentially expressed were enriched in wound healing and coagulation processes. Of the genes differentially expressed in individuals living in poverty,EEF1DP7andVIL1are also associated with hypertension in transcriptome-wide association studies. Our results suggest that living in poverty influences inflammation and the risk for cardiovascular disease through gene expression changes in immune cells.
Identifying the most probable mammal reservoir hosts for Monkeypox virus based on ecological niche comparisons
Authors: Curaudeau Manon , Besombes Camille , Nakouné Emmanuel , Fontanet Arnaud , Gessain Antoine , Hassanin Alexandre
Published: December 2022

Background

Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contacts with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered.

Methodology/Principal Findings

In this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species in order to identify the most probable animal reservoir.

Conclusions/Significance

Our results show that the MPXV niche covers three African rainforests, the Congo Basin and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels,Funisciurus anerythrus, Funisciurus pyrropus, andHeliosciurus rufobrachium, andGraphiurus lorraineus. We conclude that the most probable MPXV reservoir isF. anerythrusbased on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection.

Monkeypox (MPX) is an emerging zoonotic disease, endemic to rainforests of West and Central Africa, which manifests as a fever, swollen lymph nodes, and fatigue, followed by a rash with macular lesions progressing from papules to vesicles, pustules and scabs, usually on the face, hands, and feet for two to four weeks. The case fatality rate ranges from 1-3% in West Africa to 5-10% in Central Africa. The disease has been reported in 10 African countries between 1970 and today, with an increasing number of cases over the last decades and several exportations outside the continent, the last one in 2022 resulting in an epidemic involving mostly men who have sex with men, with more than 80,000 cases detected worldwide.

Although MPX virus has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. In this study, we compare the predicted geographic distribution (ecological niche) of the MPX virus with that of 99 mammal species, and conclude that the most probable MPX reservoir is Thomas’s rope squirrel (Funisciurus anerythrus), followed by three other arboreal rodents, including two squirrels (Funisciurus pyrropusandHeliosciurus rufobrachium) and the Lorrain dormouse (Graphiurus lorraineus).
Non-Canonical Functions of a Mutant TSC2 Protein in Mitotic Division
Authors: Chalkley Mary-Bronwen L. , Mersfelder Rachel B. , Sundberg Maria , Armstrong Laura , Sahin Mustafa , Ihrie Rebecca A. , Ess Kevin C.
Published: December 2022

Tuberous Sclerosis Complex (TSC) is a debilitating neurodevelopmental disorder characterized by a variety of clinical manifestations including epilepsy, autism, and intellectual disability. TSC is caused by mutations in theTSC1orTSC2genes, which encode the hamartin/tuberin proteins respectively. These proteins function as a heterodimer that negatively regulates mechanistic Target of Rapamycin Complex 1 (mTORC1). TSC research has focused on the effects of mTORC1, a critical signaling hub, on regulation of diverse cell processes including metabolism, cell growth, translation, and neurogenesis. However, non-canonical functions of TSC2 are not well studied, and the potential disease-relevant biological mechanisms are not well understood. We observed aberrant multipolar mitotic division, a novel phenotype, inTSC2mutant iPSCs. The multipolar phenotype is not meaningfully affected by treatment with mTORC1 inhibition, suggesting that multipolar division is an mTORC1-independent phenotype. We further observed dominant negative activity of the mutant form of TSC2 in producing the multipolar division phenotype. These data expand the knowledge of TSC2 function and pathophysiology which will be highly relevant to future treatments for patients with TSC.

Highlights

Novel multipolar division in patient-derived iPSCs with mutant form of tuberin, TSC2 encoded protein

Mutant tuberin may act in a dominant negative, mTORC1-independent manner

eTOC

Tuberous sclerosis complex (TSC) is a disorder caused by mutations inTSC1orTSC2genes leading to mTORC1 hyperactivity. Chalkley and colleagues found that a mutant microdeletion allele of TSC2 causes multipolar division in human induced pluripotent stem cells. Chalkley and colleagues also found that the multipolar division from mutant TSC2 may have a dominant negative mechanism and be mTOR1-independent.
Attention weights accurately predict language representations in the brain
Authors: Lamarre Mathis , Chen Catherine , Deniz Fatma
Published: December 2022

In Transformer-based language models (LMs) the attention mechanism converts token embeddings into contextual embeddings that incorporate information from neighboring words. The resulting contextual hidden state embeddings have enabled highly accurate models of brain responses, suggesting that the attention mechanism constructs contextual embeddings that carry information reflected in language-related brain representations. However, it is unclear whether the attention weights that are used to integrate information across words are themselves related to language representations in the brain. To address this question we analyzed functional magnetic resonance imaging (fMRI) recordings of participants reading English language narratives. We provided the narrative text as input to two LMs (BERT and GPT-2) and extracted their corresponding attention weights. We then used encoding models to determine how well attention weights can predict recorded brain responses. We find that attention weights accurately predict brain responses in much of the frontal and temporal cortices. Our results suggest that the attention mechanism itself carries information that is reflected in brain representations. Moreover, these results indicate cortical areas in which context integration may occur.
The role of preventive education on the effectiveness of responsible drinking campaigns: a qualitative study of university students
Authors: Farace Biasino , Tarabella Angela
Published: December 2022

Purpose

The purpose of the research is to evaluate the visibility and effectiveness of responsible drinking campaigns used for the sale of the product “beer” (on labels and commercials) on a sample of university students at the University of Pisa to verify whether a preventive “education” on the issue of the effects of alcohol consumption is suitable to improve the perception of responsible communication.

Design/methodology/approach

A focus group methodology was used. Three interviews were conducted with 21 university students. The interview protocol was divided into three sections and ten guiding questions were prepared to conduct the focus groups.

Findings

The study shows the weak effectiveness of responsible communication promoted by brewers, even though the sample knew aspects related to responsible communication and the adverse health effects of alcohol. Most respondents failed to remember the existence of responsibility messages placed on beverage labels, except as a result of visual stimuli, a sign that preventive education can play a role in message recognition. Commercials seem to have a more significant impact when associated with the dangers of drunk driving. However, promoting consumer awareness campaigns continues to be perceived as contradictory.

Originality/value

This study presents the results of qualitative research that focuses on university students' perceptions of the effectiveness of the most recent responsible communication campaigns conducted by brewers. The research is significant in assessing the effectiveness of communication tools, providing theoretical and industrial implications for improving the understanding of the phenomenon and the effectiveness of responsible messages.
Better safe than sorry: the role of anticipated regret and organizational ethical climate in predicting workplace safety behavior
Authors: Chen Hsien-Chun , Lin Szu-Yin , Chen I-Heng
Published: December 2022

Purpose

Based on the theory of reasoned action, this study aims to illustrate how employees’ safety behavior can be enhanced in the workplace by specifically examining how anticipated regret leads to workplace safety behavior and the contextual factor of organizational ethical climate.

Design/methodology/approach

The authors adopted a quantitative approach and designed their survey from validated scales in prior studies. Data were obtained from two different sources, including 149 employees and 31 immediate supervisors. Hierarchical linear modeling techniques were applied to test the hypotheses.

Findings

The results showed that anticipated regret was significantly related to safety compliance and safety participation; egoistic ethical climate was negatively correlated with safety compliance and safety participation, while benevolent ethical climate was only positively correlated with safety participation. For cross-level moderating effects, both benevolent and principle ethical climate moderate the relationship between anticipated regret and safety participation, whereas all three ethical climates did not moderate the relationship between anticipated regret and safety compliance.

Research limitations/implications

It contributes to current literature by identifying critical determinants of employees’ safety behavior, which would enable practitioners to manage safety in the workplace and foster a safe working environment. Specifically, fostering benevolent ethical climate can better promote employees’ perceptions of the importance of discretionary safety behavior.

Originality/value

This study suggests that organizational practitioners could use the salience of anticipated regret to promote the safety behavioral intentions of employees in the workplace. Further, the authors examined a multilevel framework, which elaborates individual- and organizational-level antecedents of employee safety behavior as well as the impact of cross-level interactions on employee safety behavior.
Green supply chain management and innovation persistence–Based on environmental turbulence perspective
Authors: Yu Ziqin , Xiao Xiang
Published: December 2022

Purpose

In recent years, environmental issues and resource depletion have posed significant challenges to firms and society. To address these environmental challenges, firms seek to build strategic alliances of green supply chain management (GSCM) with their supply chain partner. As the largest developing country in the Asia–Pacific region, China needs to take more responsibility for environmental protection, which requires more Chinese firms to participate in GSCM. Therefore, focusing on the issue of GSCM and innovation persistence in the context of an increasingly harsh ecological environment is essential.

Design/methodology/approach

To test the hypothesis, the authors perform an empirical analysis on a sample of 124 listed firms in China from 2014 to 2019. The results are robust to a battery of robustness analyses the authors performed to take care of endogeneity.

Findings

Empirical results indicate that GSCM can promote innovation persistence and both market environment turbulence and technology environment turbulence have a positive moderating effect on the relationship between the two. Mechanism tests show that GSCM can improve innovation efficiency, ensure innovation quality and alleviate financing constraints, thus promoting the innovation persistence of firms.

Originality/value

This study can provide a theoretical basis for the country to promote GSCM orientation, raise firms' awareness of the value of GSCM, convey the significance of GSCM to investors, influence firms' investment decisions and give experience to other developing countries.
Retaining consumer engagement in online retail brand communities
Authors: Wong Amy , Chung S.W.
Published: December 2022

Purpose

Integrating uses and gratifications theory with social exchange theory, this study examines the antecedents of online brand community commitment and engagement and their impact on offline purchase intention.

Design/methodology/approach

Purposive sampling was used to administer an online survey to 205 members of a Facebook brand community of a global retailer.

Findings

The results verified the significant influence of online self-congruity on commitment and engagement and confirmed the full mediating role of engagement between commitment and offline purchase intention.

Research limitations/implications

The study focused on a global chain retailer's peer-initiated online brand community as the focal data collection site.

Practical implications

The findings provide several managerial implications that can help retailers understand consumer behaviors in peer-initiated online brand communities.

Originality/value

The study offers insights into the dynamics between individual and group characteristics in online brand communities.