bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors of sarcopenia in patients on maintenance hemodialysis: a retrospective cohort study
Authors: Zhao Qianyun , Zhu Yuyu , Zhao Xin , Shi Rui , Lu Tingting , Yu Ran , Wang Deguang
Published: May 2024

Background

This study aimed to explore the prevalence and related risk factors of sarcopenia in patients on maintenance hemodialysis (MHD).

Methods

This cohort study enrolled 165 patients on MHD. The patients were divided into sarcopenia and non-sarcopenia groups based on the presence of sarcopenia or not. Sarcopenia was diagnosed according to the consensus of the Asian Sarcopenia Working Group that considers reduced muscle mass and decreased muscle strength (19). The muscle mass was measured using the multi-frequency bioelectrical impedance (Inbody260) and skeletal muscle index (SMI) was used: <7.0 kg/m2 (male); <5.7 kg/m2 (female) - with muscle mass reduction. The electronic grip dynamometer was used for measuring dominant handgrip strength (HGS) to reflect muscle strength. Male patients with HGS < 28 kg and female patients with HGS < 18 kg were considered with a decrease in muscle strength. The demographic characteristics, laboratory indexes, anthropometrical measurements, body compositions, and InBody score were compared between groups. The multivariate logistic regression was used to explore the risk factors for sarcopenia.

Results

Of the 165 patients on MHD, 36 had sarcopenia, and the prevalence was 21.82%. Patients in the sarcopenia group had higher ages and lower body mass index, serum albumin level, circumference of waist, hip, and biceps, handgrip strength, total water content, protein inorganic salt concentrations, skeletal muscle mass, basal metabolic rate, obesity degree, SMI, and body fat content. The multivariate logistic regression showed that age, waist circumference, handgrip strength, and InBody score were influencing factors for sarcopenia in patients on hemodialysis.

Conclusion

The prevalence of sarcopenia was high in patients on MHD. Higher age, lower waist circumference, lower handgrip strength, and lower InBody score were independent risk factors for sarcopenia in such patients.
Effectiveness of simulation-based interprofessional education on teamwork and communication skills in neonatal resuscitation
Authors: Chae Shinhye , Shon Soonyoung
Published: May 2024

Background

The role of effective interprofessional teamwork is especially vital in the Neonatal Intensive Care Unit (NICU) where infants facing emergency situations are admitted. Proper neonatal resuscitation, facilitated by comprehensive resuscitation training, can significantly decrease the mortality rates associated with neonatal asphyxia and respiratory failure. This study aimed to develop a simulation-based interprofessional education (IPE) programme for medical staff working in a nursery and NICU and to assess its effectiveness on teamwork, communication skills, clinical performance, clinical judgement, interprofessional attitudes, and education satisfaction.

Methods

Through a demand survey, neonatal resuscitation was selected as the theme, and an IPE team comprised of one doctor and two nurses was formed. The education programme consisted of three sessions lasting a total of 140 min: two simulation exercises and one theoretical education session. Data were collected from 18 nurses working in the nursery and NICU and 9 doctors working in the paediatrics department.

Results

A comparison of the metrics before and after applying simulation-based IPE programmes revealed teamwork (Z=-2.67, p = .008), communication skills (Z=-2.68, p = .007), clinical performance (Z=-2.52, p = .012), clinical judgement (Z=-4.52, p < .001), and interprofessional attitude (Z=-3.64, p < .001) to have significantly improved. Education satisfaction scores were 4.73 points on average out of a maximum of 5. The simulation-based IPE programme was effective in improving the teamwork, communication, and clinical performance of resuscitation teams, individual clinical judgement, and interprofessional attitude.

Conclusions

Simulation-based IPE is effective for enhancing teamwork, team communication, clinical judgement skills, and clinical performance in neonatal resuscitation. This programme has the potential to contribute to the improvement of patient safety and the quality of neonatal care. Additional studies are needed to longitudinally examine the effects of the programme on patient safety and quality of neonatal care.
Impact of the universal health insurance benefits on cervical cancer mortality in Colombia
Authors: Lewis Almira G.C , Hernandez Diana M. , Garcés-Palacio Isabel C. , Soliman Amr S.
Published: May 2024

Background

Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012.

Methods

We accessed 24,491 cervical cancer mortality records for 2006–2020 from the vital statistics of Colombia’s National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013–2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods.

Results

The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%;P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC − 0.29%;P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%;P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes.

Conclusion

Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.
Care challenges and silver linings in HIV and behavioral health service delivery for individuals living with HIV and severe mental illness during the COVID-19 pandemic: a qualitative study
Authors: Dahiya Priya , Riano Nicholas S. , Dilley James W. , Olfson Mark , Cournos Francine , Mangurian Christina , Arnold Emily A.
Published: May 2024

Background

There has been a longstanding effort to integrate behavioral health and HIV care for people with comorbid HIV and behavioral health needs, including those with severe mental illness (SMI). As this population frequents both behavioral health and HIV care settings, they were likely to experience new obstacles to the quality and availability of care during the COVID-19 pandemic. This study aims to describe how clinics for HIV services or behavioral healthcare—as well as co-located sites providing both—sought to rapidly shift protocols to maintain a standard of patient care for people with comorbid HIV and SMI while adapting to the unprecedented circumstances of the pandemic.

Methods

We interviewed HIV and behavioral healthcare providers, clinic leaders, and support service agencies that served clients impacted by both HIV and SMI. Seventeen key informants across three settings (HIV care settings, behavioral health care settings, and integrated or co-located care settings) were interviewed in 2022. Interviews focused on changes in clinical services, protocols, and care provision strategies during and at the onset of the COVID-19 pandemic. Interviews were transcribed and coded using thematic analysis.

Results

Commonly endorsed themes included both positive and negative changes in care and care provision during the pandemic. Negative impacts of the pandemic included the loss of physical space, exacerbated mental health needs and disengagement in HIV care, patient barriers to telehealth and the digital divide, and increased healthcare workforce burnout. Positive changes included improved healthcare delivery and care engagement through telehealth, new opportunities to provide a wide range of social services, paradoxical increases in engagement in HIV care for certain patients, and broad institution of workforce wellness practices.

Conclusions

Though COVID-19 presented several complex barriers to care for providers serving patients with comorbid HIV and SMI, the increased flexibility afforded by telehealth and a greater focus on collaborative approaches to patient care may benefit this patient population in the future. Additionally, the focus on workforce wellness may serve to increase retention and avoid burnout among providers. The strategies and lessons learned through adapting to COVID-19 may be invaluable moving forward as healthcare systems respond to future pandemics.
Does supplemental private health insurance impact health care utilization and seeking behavior of residents covered by social health insurance? Evidence from China National Health Services Survey
Authors: Bie Fengsai , Yan Xiaoling , Qiu Wuqi , Mao Ayan , Meng Yueli , Cai Min , Yang Renke , Zhang Yaoguang
Published: May 2024

Background

Supplemental private health insurance (PHI) plays a crucial role in complementing China’s social health insurance (SHI). However, the effectiveness of incorporating PHI as supplementary coverage lacks conclusive evidence regarding its impact on healthcare utilization and seeking behavior among SHI-covered individuals. Therefore, investigating the effects of supplementary PHI on health care utilization and seeking behavior of residents covered by social health insurance is essential to provide empirical evidence for informed decision-making within the Chinese healthcare system.

Methods

Data from the 2018 China National Health Services Survey were analyzed to compare outpatient and inpatient healthcare utilization and choices between PHI purchasers and non-purchasers across three SHI schemes: urban employee-based basic medical insurance (UEBMI), urban resident-based basic medical insurance (URBMI), and the new rural cooperative medical scheme (NRCMS). Using the Andersen Healthcare Services Utilization Behavior Model as the theoretical framework,binary logistic regression and multinomial logistic regression (MNL) models were employed to assess the impact of PHI on healthcare utilization and provider preferences.

Results

Among UEBMI, URBMI, and NRCMS participants with PHI, outpatient visit rates were 17.9, 19.8, and 21.7%, and inpatient admission rates were 12.4, 9.9, and 12.9%, respectively. Participants without PHI exhibited higher rates for outpatient visits (23.6, 24.3, and 25.6%) and inpatient admissions (15.2, 12.8, and 14.5%). Binomial logistic regression analyses revealed a higher probability of outpatient visits and inpatient admissions among UEBMI participants with PHI (p < 0.05). NRCMS participants with PHI showed a lower probability of outpatient visits but a higher probability of inpatient admissions (p < 0.05). Multinomial logistic regression indicated that NRCMS participants with PHI were more likely to choose higher-level hospitals, with a 17% increase for county hospitals and 27% for provincial or higher-level hospitals compared to primary care facilities.

Conclusion

The findings indicate that the possession of PHI correlated with increased utilization of outpatient and inpatient healthcare services among participants covered by UEBMI. Moreover, for participants under the NRCMS, the presence of PHI is linked to a proclivity for seeking outpatient care at higher-level hospitals and heightened utilization of inpatient services. These results underscore the nuanced influence of supplementary PHI on healthcare-seeking behavior, emphasizing variations across individuals covered by distinct SHI schemes.
Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury
Authors: Zheng Cuixia , Niu Mengya , Kong Yueyue , Liu Xinxin , Li Junxiu , Gong Xunwei , Ren Xinyuan , Hong Chen , Yin Menghao , Wang Lei
Published: May 2024

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.
Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses
Authors: Yang Yang , Li Fang , Du Lanying
Published: May 2024

Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens.

Graphical abstract
Rapid identification of medicinal plants via visual feature-based deep learning
Authors: Tan Chaoqun , Tian Long , Wu Chunjie , Li Ke
Published: May 2024

Background

Traditional Chinese Medicinal Plants (CMPs) hold a significant and core status for the healthcare system and cultural heritage in China. It has been practiced and refined with a history of exceeding thousands of years for health-protective affection and clinical treatment in China. It plays an indispensable role in the traditional health landscape and modern medical care. It is important to accurately identify CMPs for avoiding the affected clinical safety and medication efficacy by the different processed conditions and cultivation environment confusion.

Results

In this study, we utilize a self-developed device to obtain high-resolution data. Furthermore, we constructed a visual multi-varieties CMPs image dataset. Firstly, a random local data enhancement preprocessing method is proposed to enrich the feature representation for imbalanced data by random cropping and random shadowing. Then, a novel hybrid supervised pre-training network is proposed to expand the integration of global features within Masked Autoencoders (MAE) by incorporating a parallel classification branch. It can effectively enhance the feature capture capabilities by integrating global features and local details. Besides, the newly designed losses are proposed to strengthen the training efficiency and improve the learning capacity, based on reconstruction loss and classification loss.

Conclusions

Extensive experiments are performed on our dataset as well as the public dataset. Experimental results demonstrate that our method achieves the best performance among the state-of-the-art methods, highlighting the advantages of efficient implementation of plant technology and having good prospects for real-world applications.
Biophysical properties of alveolar surfactant in drever dogs with hunting associated pulmonary edema
Authors: Viitanen Sanna Johanna , Gehani Sabrine Moya , Tilamaa Anni Maria , Rajamäki Minna Marjaana , Veldhuizen Ruud Anthonius Wilhelmus
Published: May 2024

Background

A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown. Alveolar surfactant has a critical role in preventing alveolar collapse and edema formation. The aim of this study was to investigate, whether the predisposition to hunting associated pulmonary edema in drever dogs is associated with impaired biophysical properties of alveolar surfactant. Seven privately owned drever dogs with recurrent hunting associated pulmonary edema and seven healthy control dogs of other breeds were included in the study. All affected dogs underwent thorough clinical examinations including echocardiography, laryngeal evaluation, bronchoscopy, and bronchoalveolar lavage (BAL) as well as head, neck and thoracic computed tomography imaging to rule out other cardiorespiratory diseases potentially causing the clinical signs. Alveolar surfactant was isolated from frozen, cell-free supernatants of BAL fluid and biophysical analysis of the samples was completed using a constrained sessile drop surfactometer. Statistical comparisons over consecutive compression expansion cycles were performed using repeated measures ANOVA and comparisons of single values between groups were analyzed using T-test.

Results

There were no significant differences between groups in any of the biophysical outcomes of surfactant analysis. The critical function of surfactant, reducing the surface tension to low values upon compression, was similar between healthy dogs and affected drevers.

Conclusions

The etiology of hunting associated pulmonary edema in drever dogs is not due to an underlying surfactant dysfunction.
Advances in targeting histone deacetylase for treatment of solid tumors
Authors: Shi Mu-Qi , Xu Ying , Fu Xin , Pan De-Si , Lu Xian-Ping , Xiao Yi , Jiang Yi-Zhou
Published: May 2024

Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.
The MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 Ankle Score
Authors: Schreiner Markus M. , Raudner Marcus , Winalski Carl S. , Juras Vladimir , Aldrian Silke , Kolb Alexander , Chiari Catharina , Windhager Reinhard , Trattnig Siegfried
Published: May 2024

Objectives

The aim of this study was to introduce the MOCART 2.0 ankle score and evaluate its utility and reproducibility for the radiological assessment of cartilage repair tissue in the ankle joint.

Methods

The MOCART 2.0 ankle score evaluates seven individual variables, including “volume fill of (osteo)chondral defect,” “Integration into adjacent cartilage and bone,” “surface of the repair tissue,” “signal intensity of the repair tissue,” “bony defect and bony overgrowth,” “presence of edema-like-marrow signal,” and “presence of subchondral cysts.” Overall, a MOCART 2.0 ankle score between 0 and 100 points may be reached. Two independent readers assessed the 3-T MRI examinations of 48 ankles, who had undergone cartilage repair of a talar cartilage defect using the new MOCART 2.0 ankle score. One of the readers performed two readings. Intra- and interrater reliability were assessed using intraclass correlation coefficients (ICCs) for the overall MOCART 2.0 ankle score.

Results

Forty-eight ankles (mean age at surgery 30.2 ± 11.2 years) were evaluated. The overall interrater (ICC = 0.75; 95%CI 0.60–0.85), as well as the intrarater (ICC = 0.83; 95%CI 0.72–0.90) reliability of the MOCART 2.0 ankle score was good. For individual variables the interrater reliability ranged from a kappa value of 0.29 (95%CI 0.01–0.57) for “surface of the repair tissue” to 0.83 (95%CI 0.71–0.95) for “presence of subchondral cysts”.

Conclusions

The newly introduced MOCART 2.0 ankle score, which encompasses the distinct anatomy of the ankle joint, demonstrates good intra- and interrater reliability.

Critical relevance statement

The newly introduced MOCART 2.0 ankle score may facilitate the standardized assessment of cartilage repair in the ankle joint and allow an objective comparison of the morphological outcome between alternative treatment options and between different studies.

Key Points

This study introduces the MOCART 2.0 ankle score.

The MOCART 2.0 ankle score demonstrated good intra- and interrater reliability.

Standardized reporting may improve communication between radiologists and other physicians.

Graphical Abstract
Surgical intervention of Lemierre’s syndrome: a case report and review of the literature
Authors: Pan Yiqi , Shi Zhihong , Ye Bin , Da Qian , Wang Chaofu , Shen Yilin , Xiang Mingliang
Published: May 2024

Background

Lemierre’s syndrome is a fatal and rare disease that is typically characterized by oropharyngeal infection and internal jugular vein thrombosis. Timely institution of appropriate antibiotics is the standard treatment.

Case presentation

The authors report a case of Lemierre’s syndrome. A 67-year-old male patient of Han ethnicity in China suffered from a large inflammatory neck mass involving left internal jugular vein thrombosis diagnosed as Lemierre’s syndrome and finally cured by surgical treatment. In addition, a literature review was carried out through PubMed using the terms “Lemierre’s syndrome/disease and review, meta-analysis or retrospective study” and “Lemierre’s syndrome/disease and internal jugular vein”. This search yielded six articles that recorded surgical methods such as drainage, craniotomy, tooth extraction, and ligation of the occluded vein to give clinicians more ideas about the treatment of the Lemierre’s syndrome.

Conclusion

This is the first review to summarize the conditions under which surgical treatment are conducted. Additionally, this is the first report of such a large inflammatory neck mass that was completely cured by surgical resection and internal jugular vein ligation. The authors also offer several conclusions regarding surgical intervention in Lemierre’s syndrome for the first time.
Interferon-gamma producing CD4+ T cells quantified by flow cytometry as early markers for Mycobacterium avium ssp. paratuberculosis infection in cattle
Authors: Bulun Hakan , Bridger Philip S. , Schillinger Simone , Akineden Ömer , Barth Stefanie A. , Fischer Marta , Henrich Manfred , Seeger Torsten , Doll Klaus , Bülte Michael , Bauerfeind Rolf , Menge Christian
Published: May 2024

Current diagnostic methods for Johne’s disease in cattle allow reliable detection of infections with Mycobacterium avium ssp. paratuberculosis (MAP) not before animals are 2 years of age. Applying a flow cytometry-based approach (FCA) to quantify a MAP-specific interferon-gamma (IFN-γ) response in T cell subsets, the present study sought to monitor the kinetics of the cell-mediated immune response in experimentally infected calves. Six MAP-negative calves and six calves, orally inoculated with MAP at 10 days of age, were sampled every 4 weeks for 52 weeks post-inoculation (wpi). Peripheral blood mononuclear cells (PBMC) were stimulated with either purified protein derivatives (PPD) or whole cell sonicates derived from MAP (WCSj), M. avium ssp. avium or M. phlei for 6 days followed by labeling of intracellular IFN-γ in CD4+ and CD8+ T cells. No antigen-specific IFN-γ production was detectable in CD8+ cells throughout and the responses of CD4+ cells of MAP-infected and control calves were similar up to 12 wpi. However, the mean fluorescence intensity (MFI) for the detection of IFN-γ in CD4+ cells after WCSj antigen stimulation allowed for a differentiation of animal groups from 16 wpi onwards. This approach had a superior sensitivity (87.8%) and specificity (86.8%) to detect infected animals from 16 wpi onwards, i.e., in an early infection stage, as compared to the IFN-γ release assay (IGRA). Quantification of specific IFN-γ production at the level of individual CD4+ cells may serve, therefore, as a valuable tool to identify MAP-infected juvenile cattle.
PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals
Authors: Kim Ji Young , Shin Ji Hye , Kim Mi-Jeong , Choi Bongkum , Kang Yeeun , Choi Jimin , Kim Seo Hyun , Kwan Dohee , Kim Duk-Hwan , Chun Eunyoung , Lee Ki-Young
Published: May 2024

Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγnull) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.
Non-receipt of targeted and immunotherapies in diverse patients with metastatic cancers.
Authors: Veenstra Christine M , Abrahamse Paul , Kurian Allison W. , Hawley Sarah T. , Farias Albert , Hamilton Ann S. , Ward Kevin C , Katz Steven Jay
Published: May 2024

e13563

Background: The rapid evolution of molecularly targeted kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of metastatic cancer, coupled with high drug costs, raises potential for unwarranted variation in patient management. We evaluated correlates of non-receipt of TKIs and ICIs in a diverse, population-based sample of patients with metastatic non-small cell lung cancer (NSCLC), kidney and bladder (GU) cancer, and melanoma. Methods: We identified 2240 patients diagnosed in 2019 with metastatic NSCLC, GU cancer, or melanoma and reported to the Georgia or Los Angeles SEER registries. Using SEER registry data, we linked all patients to a managing oncology physician. We collected data from the managing physician regarding receipt of TKIs and ICIs. We used bivariate analyses and multivariable logistic regression models to assess associations between non-receipt of TKIs and ICIs and patient-level factors. Results: We present results for a preliminary sample (N=894). About half (55%) of the patients had NSCLC, 31% had GU cancer, and 14% had melanoma. The mean age was 62 (SD 12); 59% were male; 65% were White, 16% were Black, 11% were Hispanic, and 7% were Asian; 52% had Medicare, 29% had private insurance, 9% had Medicaid, and 4% had no insurance; 89% resided in urban areas, 11% resided in rural areas. 22% lived in a census tract area with ≥20% of the population living below the poverty level. The Table shows that in bivariate analyses, non-receipt of TKIs was associated with NSCLC, older age, male sex, non-white race, and non-private or no insurance (all p<0.05). After adjustment, non-receipt of TKIs was associated with NSCLC, older age, male sex, and race. Asian and Hispanic patients had lower rates of non-receipt, and Black patients had higher rates. In bivariate analyses, non-receipt of ICIs was associated with NSCLC and GU cancer (p=0.004); this association remained significant after adjustment. Conclusions: Non-receipt of TKIs was associated with important non-clinical factors including race and sex. Non-receipt of ICIs was associated only with cancer type. These findings suggest that policy-relevant factors such as out-of-pocket costs for oral cancer therapies and differential access to molecular sequencing may contribute to unwarranted variation in receipt of TKIs. [Table: see text]
Identification of genes related to PD-L1 expression in non-small cell lung cancer (NSCLC) tumor samples by GFPrint, a machine learning framework (MLF).
Authors: Sanz Martín Guillermo , Dominguez Correa Juan Manuel , Mendoza Bertelli Andrea , Cantarella Maria Florencia , Dibarbora Delfina , Galmarini Carlos Maria , Salanova Ruben
Published: May 2024

e13600

Background: The advent of drugs targeting the PD-1/PD-L1 axis has revolutionized NSCLC treatment. Although promising, individual responses to these therapies can vary among individuals, and research is ongoing to better understand the mechanisms involved in PD1/PD-L1 expression to optimize treatment protocols, and identify which patients are most likely to benefit from these therapies. In this study, Genetic Fingerprint (GFPrint), a MLF, was employed to identify mutations in genes linked to PD-L1 expression in NSCLC tumor samples. Methods: Whole exome sequencing (WES) was run on samples from biopsies of 46 NSCLC patients (histologic subtypes: squamous-cell carcinoma and adenocarcinoma). WES data were encoded using GFPrint, a MLF that generates virtual representations of the tumor exomes in a latent space (LS) defined by the genetic features of the samples. Clusters of patients were identified in such LS based on the genetic similarities of their tumors. Statistical univariate analysis was run to analyze differences in the distribution among both clusters of clinical (age, smoking, and metastatic status) and pathological (histotype and PD-L1 expression) features. The mutational burden (MB) of each cluster was also examined by pathway enrichment analysis (PEA). Results: Two main clusters were identified, C0 (n=16) and C1 (n=17), with 13 unassigned patients. Main differences between clusters were related to histology and PD-L1 expression. C0 included significantly less patients with adenocarcinoma (10/16; 62.5%) compared to CL1 (17/17; 100%) (p-value=.01). In addition, C0 presented more patients expressing PD-L1 (9/16; 56.2%) compared to C1 (3/17; 17.6%) (p-value=.04). Of interest, PD-L1 positivity was significantly higher (p value=.03) in adenocarcinomas of C0 patients (6/10; 60.0%) than those of C1 (3/17; 17.6%). Moreover, C0 adenocarcinomas presented higher levels of PD-L1 expression (6.3+/-9.7 %) than those of C1 (2.3+/-7.5 %) (p value=.06). MB analysis revealed that 1,357 genes were mutated exclusively in C0 patients, and PEA allowed the identification of 3 enriched cancer-related KEGG pathways: HIF-1 signaling, Ca2+ signaling and actin cytoskeleton. Selection of non-silent mutations in these pathways enabled the identification of 10 genes, mostly included in the HIF-1 signaling pathway, with previous data suggesting their involvement in PD-L1 regulation and expression: PIK3R1, HK1, NOS2, NRAS, BRAF, ITGA1, ITGA9, EGLN1, EGLN2 and AKT1, being the first 6 the only ones found in adenocarcinomas. Conclusions: The identified genes deserve further studies to validate them as possible targets of pharmacological intervention concomitant to PD-1/PD-L1 blockade, and also as potential biomarkers for patients’ selection to improve the efficiency of immunotherapy in NSCLC treatment.
Racial and elderly disparities in receipt of guideline-concordant care in stage I-III breast cancer.
Authors: Castillo Brenda Sofia , Boadi Taussia , Han Xiaoyan , Shulman Lawrence N. , Martei Yehoda M.
Published: May 2024

e13688

Background: Elderly and non-Hispanic Black (NHB) patients have worse breast cancer specific survival outcomes. We evaluated whether guideline concordant care (GCC) and all-cause mortality in stage I-III breast cancer differed by race among patients ≥ 65 years old. Methods: We used the National Cancer Database (NCDB), to identify a cohort of 25174 NHB and 233357 non-Hispanic White patients (NHW), ≥65 years old, diagnosed with stage I-III breast cancer between 2010 and 2019. We used the National Comprehensive Cancer Network guidelines to define GCC, including surgery, radiation and systemic therapy. Specific systemic therapies and cause of death were unavailable. We used logistic regression models to assess the association between race and GCC. We used Cox proportional hazards models to estimate associations between race and all-cause mortality after adjusting for GCC. Both models adjusted for disease, demographics, income and educational attainment. We assessed the odds of not receiving timely GCC within 30, 60 and 90 days from diagnosis for NHB vs. NHW patients using logistic regression. Results: Overall, 15% of patients did not receive GCC. Being NHB compared to NHW was associated with increased odds of not receiving GCC in univariate (OR=1.24 95%CI: 1.20-1.28) and multivariate analysis (aOR=1.13, 95%CI: 1.08-1.17). Being NHB was associated with 26% increased risk of all-cause mortality in the univariate analysis (HR=1.26, p<0.001), which decreased to 4% increased risk, after adjusting for GCC, age, clinical and sociodemographic factors (aHR=1.04, p=0.027). Non-receipt of GCC (aHR=1.75, p<0.001) and lower educational attainment (aHR 1.18, p <0.001) were independently associated with higher risk of all-cause mortality. Higher median income (aHR 0.91, p<0.001) was independently associated with a decreased risk of mortality. Being NHW compared to NHB was associated with increased odds of initiating treatment within 30 (OR=1.65, 95% CI 1.6-1.69), 60 (OR=2.11, 95% CI 2.04-2.18), and 90 days of breast cancer diagnosis (OR=2.39, 95% CI 2.27-2.51). Conclusions: Among elderly patients with stage I-III BC, being NHB was associated with increased odds of not receiving GCC and less timely treatment initiation. Being NHB was associated with increased all-cause mortality, which was attenuated after adjusting for GCC. Optimizing timely receipt of GCC may reduce inferior survival outcomes among elderly NHB breast cancer patients. Identifying area-level determinants may help design targeted interventions. Limitations include lack of granular systemic therapy data, likely overestimating GCC receipt, biasing the analysis towards the null, and lack of cause-specific death among elderly patients with competing risks of death.
Mindfulness-based group medical visits: Strategies to improve equitable access and inclusion for diverse patients in cancer treatment.
Authors: Atreya Chloe Evelyn , Leung Ivan C. , Chao Maria T. , Thompson-Lastad Ariana , Pollak Christine , Dhruva Anand , Hartogensis Wendy , Lister Michael , Cheng Stephanie W. , Mishra Kavita K.
Published: May 2024

e13717

Background: The 2023 Society for Integrative Oncology-ASCO joint guideline recommends mindfulness-based interventions (MBIs) as the non-pharmacologic therapy with the highest level of evidence to improve anxiety and depression symptoms experienced by adults with cancer. However, the evidence predominately derives from White breast cancer survivors. Racial and ethnic minority patients have less access to integrative symptom support and worse cancer outcomes. To address these gaps, we designed and piloted a series of mindfulness-based group medical visits (MB-GMVs), embedded into comprehensive cancer care, for racially and ethnically diverse patients in cancer treatment. Methods: As a quality improvement project, we launched a telehealth MB-GMV series for patients undergoing cancer treatment, delivered as four weekly 2-hour visits billable to insurance. Content was concordant with evidence-based guidelines and established MBIs and adapted to improve cultural relevance and fit (e.g., access-centered, trauma-informed, with inclusive communication practices). Program structure was adapted to address barriers to participation, with ≥50% slots per series reserved for racial and ethnic minority patients. Intake surveys incorporated a demographic questionnaire and symptom assessments. Evaluations were sent following the visits. Results: In our first ten cohorts (n=78), 80% of referred patients enrolled. Participants were: 22% Asian, 14% Black, 17% Latino, 45% non-Latino White; 65% female; with median age 54 years (range 27-79); and 80% had metastatic cancer. Common baseline symptoms included lack of energy, difficulty sleeping, and worrying. Most patients (90%) attended ≥3 visits. On final evaluations, 87% patients rated the series as “excellent”; 81% “strongly agreed” that they liked the GMV format; and 92% would “definitely” recommend the series to others. Qualitative themes included empowerment and connectedness. Conclusions: Telehealth GMVs are a feasible, acceptable, and financially sustainable model for increasing access to MBIs. Diverse patients in active cancer treatment were able to participate and reported high levels of satisfaction with this series that was tailored to center health equity and inclusion.
Exceptional Response of BRAFV600E-Mutated Acinar Cell CUP to BRAF/MEK Inhibition
Authors: Kerle Irina A. , Scheuble Anne-Marie , Kobitzsch Benjamin , Stocker Gertraud , Hiller G.G. Ruth , Badendick Maja , William Doreen , Krueger Alexander , Gross Thomas , Koegler Anja , Hartig Andreas , Richter Daniela , Aust Daniela E. , Schroeck Evelin , Heining Christoph , Glimm Hanno , Hacker Ulrich T.
Published: May 2024

Complete remission of BRAF V600E-driven ACC CUP by BRAF/MEK inhibition underscores importance of precision oncology.
Breast Cancer Risk for Women With a TP53 Pathogenic Variant
Authors: Li Shuai , Hopper John L.
Published: May 2024

The article highlights that breast cancer risk for women with TP53 mutations depends on family history.
Single-Cell Analysis of Subcutaneous Fat Reveals Profibrotic Cells That Correlate With Visceral Adiposity in HIV
Authors: Bailin Samuel S , Gabriel Curtis L , Gangula Rama D , Hannah LaToya , Nair Sangeeta , Carr John Jeffrey , Terry James G , Silver Heidi J , Simmons Joshua D , Mashayekhi Mona , Kalams Spyros A , Mallal Simon , Kropski Jonathan A , Wanjalla Celestine N , Koethe John R
Published: May 2024

Context

Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH.

Objective

We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART.

Methods

We enrolled PWH on long-term ART with a spectrum of metabolic health. Ninety-two participants underwent SAT biopsy for bulk RNA sequencing and 43 had single-cell RNA sequencing. Computed tomography quantified VAT volume and insulin resistance was calculated using the Homeostasis Model Assessment 2 Insulin Resistance (HOMA2-IR).

Results

VAT volume was associated with HOMA2-IR (P < .001). Higher proportions of SAT intermediate macrophages (IMs), myofibroblasts, and MYOC+ fibroblasts were associated with greater VAT volume using partial Spearman's correlation adjusting for age, sex, and body mass index (r = 0.34-0.49, P < .05 for all). Whole SAT transcriptomics showed PWH with greater VAT volume have increased expression of extracellular matrix (ECM)– and inflammation-associated genes, and reduced expression of lipolysis- and fatty acid metabolism–associated genes.

Conclusion

In PWH, greater VAT volume is associated with a higher proportion of SAT IMs and fibroblasts, and a SAT ECM and inflammatory transcriptome, which is similar to findings in HIV-negative persons with obesity. These data identify SAT cell-type specific changes associated with VAT volume in PWH that could underlie the high rates of cardiometabolic diseases in PWH, though additional longitudinal studies are needed to define directionality and mechanisms.
A Spatial History of Seaports in South Asia
Authors: Ludden David
Published: May 2024

Seaports provide material foundations for globalization. In the long history of global mobile connectivity that now forms globalization, the Indian Ocean is the world's oldest arena of expansive long-distance sea travel. People have sailed monsoon winds among coastal environments connecting Europe, Africa, India, and China since prehistoric times. Indian Ocean ports grew in number, size, wealth, and permanence over the centuries and anchored the rise of seaborne empires connecting Asia, Africa, Europe, and the Americas. Modernity traveled among industrial port cities along with lower unit costs for shipping and a dramatically increasing scale of shipping in volume, value, distance, and speed. Capital investments in seaport infrastructure grew with the scale of mobility through ports connecting producers and consumers by land and sea in commodity chains that eventually embraced people around the world with increasingly intricate, expansive interdependence, and also with ever more entrenched spatial inequity. The result is the current global seaport space of interwoven connectivity strung along the coastlines of globalization on all the continents.
Eviscerating the Sea
Authors: Anand Nikhil , Kamath Lalitha
Published: May 2024

Contemporary infrastructure projects in the sea reterritorialize port environments, continuously discarding historic occupants and coastal occupations in their wake. In this article the authors dwell on the ongoing histories through which fish and fishers are eviscerated in Mumbai's seas via the proliferation of massive infrastructural operations currently being staged by the Indian state. In so doing, they make two arguments. First, they show how infrastructures at sea are accretive forms that are simultaneously articulated at different time scales. New infrastructures currently being built in the sea in postcolonial India only intensify the expropriations of colonial projects that were staged in the sea. Second, urban fishers work not only at sea but also on the dry land of the city. As chances for making livelihoods at sea are steadily foreclosed, fishers are increasingly turning to their small parcels of land in the city, exploring how and if these might be made real estate to secure their futures.
Estimating maximum oxygen uptake of fishes during swimming and following exhaustive chase – different results, biological bases and applications
Authors: Rees Bernard B. , Reemeyer Jessica E. , Binning Sandra A. , Brieske Samantha D. , Clark Timothy D. , De Bonville Jeremy , Eisenberg Rachel M. , Raby Graham D. , Roche Dominique , Rummer Jodie L. , Zhang Yangfan
Published: May 2024

The maximum rate at which animals take up oxygen from their environment (ṀO2,max) is a crucial aspect of their physiology and ecology. In fishes, ṀO2,max is commonly quantified by measuring oxygen uptake either during incremental swimming tests or during recovery from an exhaustive chase. In this Commentary, we compile recent studies that apply both techniques to the same fish and show that the two methods typically yield different mean estimates of ṀO2,max for a group of individuals. Furthermore, within a group of fish, estimates of ṀO2,max determined during swimming are poorly correlated with estimates determined during recovery from chasing (i.e. an individual's ṀO2,max is not repeatable across methods). One explanation for the lack of agreement is that these methods measure different physiological states, each with their own behavioural, anatomical and biochemical determinants. We propose that these methods are not directly interchangeable but, rather, each is suited to address different questions in fish biology. We suggest that researchers select the method that reflects the biological contexts of their study, and we advocate for the use of accurate terminology that acknowledges the technique used to elevate ṀO2 (e.g. peak ṀO2,swim or peak ṀO2,recovery). If the study's objective is to estimate the ‘true’ ṀO2,max of an individual or species, we recommend that pilot studies compare methods, preferably using repeated-measures designs. We hope that these recommendations contribute new insights into the causes and consequences of variation in ṀO2,max within and among fish species.
Background Risk and Small-Stakes Risk Aversion
Authors: Mu Xiaosheng , Pomatto Luciano , Strack Philipp , Tamuz Omer
Published: May 2024

Building on Pomatto, Strack, and Tamuz (2020), we identify a tight condition for when background risk can induce first-order stochastic dominance. Using this condition, we show that under plausible levels of background risk, no theory of choice under risk can simultaneously satisfy the following three economic postulates: (i) decision-makers are risk averse over small gambles, (ii) their preferences respect stochastic dominance, and (iii) they account for background risk. This impossibility result applies to expected utility theory, prospect theory, rank-dependent utility, and many other models. (JEL D81, D91)