bluuebunny/crossref_metadata_2025 huggingface dataset:
Does a new case-based payment system promote the construction of the ordered health delivery system? Evidence from a pilot city in China
Authors: Shi Huanyu , Cheng Zhichao , Liu Zhichao , Zhang Yang , Zhang Peng
Published: March 2024

Background

The construction of the ordered health delivery system in China aims to enhance equity and optimize the efficient use of medical resources by rationally allocating patients to different levels of medical institutions based on the severity of their condition. However, superior hospitals have been overcrowded, and primary healthcare facilities have been underutilized in recent years. China has developed a new case-based payment method called “Diagnostic Intervention Package” (DIP). The government is trying to use this economic lever to encourage medical institutions to actively assume treatment tasks consistent with their functional positioning and service capabilities.

Methods

This study takes Tai’an, a DIP pilot city, as a case study and uses an interrupted time series analysis to analyze the impact of DIP reform on the case severity and service scope of medical institutions at different levels.

Results

The results show that after the DIP reform, the proportion of patients receiving complicated procedures (tertiary hospitals: β3 = 0.197, P < 0.001; secondary hospitals: β3 = 0.132, P = 0.020) and the case mix index (tertiary hospitals: β3 = 0.022, P < 0.001; secondary hospitals: β3 = 0.008, P < 0.001) in tertiary and secondary hospitals increased, and the proportion of primary-DIP-groups cases decreased (tertiary hospitals: β3 = -0.290, P < 0.001; secondary hospitals: β3 = -1.200, P < 0.001), aligning with the anticipated policy objectives. However, the proportion of patients receiving complicated procedures (β3 = 0.186, P = 0.002) and the case mix index (β3 = 0.002, P < 0.001) in primary healthcare facilities increased after the reform, while the proportion of primary-DIP-groups cases (β3 = -0.515, P = 0.005) and primary-DIP-groups coverage (β3 = -2.011, P < 0.001) decreased, which will reduce the utilization efficiency of medical resources and increase inequity.

Conclusion

The DIP reform did not effectively promote the construction of the ordered health delivery system. Policymakers need to adjust economic incentives and implement restraint mechanisms to regulate the behavior of medical institutions.
A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation
Authors: Peng Xin , Huang Xin , Lulu Talal Ben , Jia Wenqing , Zhang Shaolu , Cohen Limor , Huang Shengfan , Fan Jindian , Chen Xi , Liu Shanshan , Wang Yongzhe , Wang Kailin , Isoyama Sho , Dan Shingo , Wang Feng , Zhang Zhe , Elkabets Moshe , Kong Dexin
Published: March 2024

Background

Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models.

Methods

KTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC–MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR.

Results

KTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8+ T cells and innate immune cells. An intermittent dosing regimen of KTC1101 enhanced these effects. Notably, KTC1101 synergized with anti-PD-1 therapy, significantly boosting antitumor immunity and extending survival in preclinical models.

Conclusion

KTC1101's dual mechanism of action—directly inhibiting tumor cell growth and dynamically enhancing the immune response— represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations.
Injectable Bombyx mori (B. mori) silk fibroin/MXene conductive hydrogel for electrically stimulating neural stem cells into neurons for treating brain damage
Authors: Yang Zhangze , You Yuxin , Liu Xiangyu , Wan Quan , Xu Zongpu , Shuai Yajun , Wang Jie , Guo Tingbiao , Hu Jiaqi , Lv Junhui , Zhang Meng , Yang Mingying , Mao Chuanbin , Yang Shuxu
Published: March 2024

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.

Graphical Abstract
Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies
Authors: Xie Zhiying , Liu Chang , Yu Haiyan , Xie Zhihao , Sun Chengyue , Zhu Ying , Hu Xiaoyu , Bai Li , Wei Luhua , Sun Peng , Lu Yanyu , Lu Yunlong , Zhao Yawen , Zhang Wei , Wang Zhaoxia , Meng Lingchao , Yuan Yun
Published: March 2024

Background

Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies.

Methods

Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them.

Results

Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively.

Conclusion

Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.
Community-based rehabilitation for people with psychosocial disabilities in low- and middle-income countries: a systematic review of the grey literature
Authors: Butura Ana-Maria , Ryan Grace K. , Shakespeare Tom , Ogunmola Olusegun , Omobowale Olubukola , Greenley Rachel , Eaton Julian
Published: March 2024

Background

Community based rehabilitation (CBR) aims to promote the inclusion and participation of people with disabilities, particularly in low- and middle-income countries (LMICs). Yet people with psychosocial disabilities are often excluded from CBR programmes. The restrictive inclusion criteria used by previous reviews make it difficult to identify promising examples that could otherwise help to inform the uptake of CBR for people with psychosocial disabilities. We aim to address this gap using gold standard methods for the review and synthesis of grey literature on CBR for people with psychosocial disabilities in LMICs.

Methods

Our search strategy was developed in consultation with an expert advisory group and covered seven grey literature databases, two customised Google Advanced searches, 34 targeted websites and four key reports. A single reviewer screened the search results and extracted relevant data using a standardised format based on the World Health Organisation’s CBR matrix. The included programmes were then checked by a second reviewer with experience in CBR to ensure they met the review’s criteria. A narrative synthesis with summative content analysis was performed to synthesise the findings.

Results

The 23 CBR programmes identified for inclusion spanned 19 countries and were mostly located in either rural areas or urban areas where a large proportion of the population was living in poverty. 13 were classified as livelihood programmes, eight as empowerment programmes, seven as social programmes, seven as health programmes and four as education programmes. Only two addressed all five of these components. 12 of the included programmes reported challenges to implementation, with stigma and lack of resources emerging as two of the most prominent themes.

Conclusion

This grey literature review identified several CBR programmes and synthesised key learning that would have otherwise been missed by a more traditional review of the published literature. However, as evaluation by implementing organisations is not always conducted to a high standard, the quality of this evidence is generally poor. A flexible monitoring and evaluation framework for CBR programmes could help to reduce heterogeneity in terms of the quality and content of reporting.
11p13 microduplication: a differential diagnosis of Silver–Russell syndrome?
Authors: Amin Asmaa K. , Krause Jeremias , Eggermann Thomas
Published: March 2024

Background

Silver–Russel syndrome (SRS) is a congenital disorder which is mainly characterized by intrauterine and postnatal growth retardation, relative macrocephaly, and characteristic (facial) dysmorphisms. The majority of patients shows a hypomethylation of the imprinting center region 1 (IC1) in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat), but in addition a broad spectrum of copy number variations (CNVs) and monogenetic variants (SNVs) has been reported in this cohort. These heterogeneous findings reflect the clinical overlap of SRS with other congenital disorders, but some of the CNVs are recurrent and have therefore been suggested as SRS-associated loci. However, this molecular heterogeneity makes the decision on the diagnostic workup of patients with SRS features challenging.

Case presentation

A girl with clinical features of SRS but negatively tested for the IC1 hypomethylation and upd(7)mat was analyzed by whole genome sequencing in order to address both CNVs and SNVs in the same run. We identified a 11p13 microduplication affecting a region overlapping with a variant reported in a previously published patient with clinical features of Silver–Russel syndrome.

Conclusions

The identification of a 11p13 microduplication in a patient with SRS features confirms the considerable contribution of CNVs to SRS-related phenotypes, and it strengthens the evidence for a 11p13 microduplication syndrome as a differential diagnosis SRS. Furthermore, we could confirm that WGS is a valuable diagnostic tool in patients with SRS and related disorders, as it allows CNVs and SNV detection in the same run, thereby avoiding a time-consuming diagnostic testing process.
Unraveling the molecular mechanisms of lymph node metastasis in ovarian cancer: focus on MEOX1
Authors: Li Jiajia , Sun Yihua , Zhi Xiuling , Sun Yating , Abudousalamu Zulimire , Lin Qianhan , Li Bin , Yao Liangqing , Chen Mo
Published: March 2024

Background

Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome.

Results

Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells.

Conclusions

The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.
Real-time machine learning model to predict short-term mortality in critically ill patients: development and international validation
Authors: Lim Leerang , Gim Ukdong , Cho Kyungjae , Yoo Dongjoon , Ryu Ho Geol , Lee Hyung-Chul
Published: March 2024

Background

A real-time model for predicting short-term mortality in critically ill patients is needed to identify patients at imminent risk. However, the performance of the model needs to be validated in various clinical settings and ethnicities before its clinical application. In this study, we aim to develop an ensemble machine learning model using routinely measured clinical variables at a single academic institution in South Korea.

Methods

We developed an ensemble model using deep learning and light gradient boosting machine models. Internal validation was performed using the last two years of the internal cohort dataset, collected from a single academic hospital in South Korea between 2007 and 2021. External validation was performed using the full Medical Information Mart for Intensive Care (MIMIC), eICU-Collaborative Research Database (eICU-CRD), and Amsterdam University Medical Center database (AmsterdamUMCdb) data. The area under the receiver operating characteristic curve (AUROC) was calculated and compared to that for the National Early Warning Score (NEWS).

Results

The developed model (iMORS) demonstrated high predictive performance with an internal AUROC of 0.964 (95% confidence interval [CI] 0.963–0.965) and external AUROCs of 0.890 (95% CI 0.889–0.891) for MIMIC, 0.886 (95% CI 0.885–0.887) for eICU-CRD, and 0.870 (95% CI 0.868–0.873) for AmsterdamUMCdb. The model outperformed the NEWS with higher AUROCs in the internal and external validation (0.866 for the internal, 0.746 for MIMIC, 0.798 for eICU-CRD, and 0.819 for AmsterdamUMCdb; p < 0.001).

Conclusions

Our real-time machine learning model to predict short-term mortality in critically ill patients showed excellent performance in both internal and external validations. This model could be a useful decision-support tool in the intensive care units to assist clinicians.
A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity
Authors: Shanley Harrison T. , Taki Aya C. , Byrne Joseph J. , Nguyen Nghi , Wells Tim N. C. , Jabbar Abdul , Sleebs Brad E. , Gasser Robin B.
Published: March 2024

Background

Infection with parasitic nematodes (helminths), particularly those of the order Strongylida (such as Haemonchus contortus), can cause significant and burdensome diseases in humans and animals. Widespread drug (anthelmintic) resistance in livestock parasites, the absence of vaccines against most of these nematodes, and a lack of new and effective chemical entities on the commercial market demands the discovery of new anthelmintics. In the present study, we searched the Global Health Priority Box (Medicines for Malaria Venture) for new candidates for anthelmintic development.

Methods

We employed a whole-organism, motility-based phenotypic screening assay to identify compounds from the Global Health Priority Box with activity against larvae of the model parasite H. contortus, and the free-living comparator nematode Caenorhabditis elegans. Hit compounds were further validated via dose–response assays, with lead candidates then assessed for nematocidal activity against H. contortus adult worms, and additionally, for cytotoxic and mitotoxic effects on human hepatoma (HepG2) cells.

Results

The primary screen against H. contortus and C. elegans revealed or reidentified 16 hit compounds; further validation established MMV1794206, otherwise known as ‘flufenerim’, as a significant inhibitor of H. contortus larval motility (half-maximal inhibitory concentration [IC50] = 18 μM) and development (IC50 = 1.2 μM), H. contortus adult female motility (100% after 12 h of incubation) and C. elegans larval motility (IC50 = 0.22 μM). Further testing on a mammalian cell line (human hepatoma HepG2 cells), however, identified flufenerim to be both cytotoxic (half-maximal cytotoxic concentration [CC50] < 0.7 μM) and mitotoxic (half-maximal mitotoxic concentration [MC50] < 0.7 μM).

Conclusions

The in vitro efficacy of MMV1794206 against the most pathogenic stages of H. contortus, as well as the free-living C. elegans, suggests the potential for development as a broad-spectrum anthelmintic compound; however, the high toxicity towards mammalian cells presents a significant hindrance. Further work should seek to establish the protein–drug interactions of MMV1794206 in a nematode model, to unravel the mechanism of action, in addition to an advanced structure–activity relationship investigation to optimise anthelmintic activity and eliminate mammalian cell toxicity.

Graphical Abstract
Robotic resection for splenic artery aneurysm associated with neurofibromatosis type 1: a case report
Authors: Ueda Akihiko , Saito Kenta , Murase Hiromichi , Kato Tomokatsu , Imafuji Hiroyuki , Morimoto Mamoru , Ogawa Ryo , Takahashi Hiroki , Matsuo Yoichi , Takiguchi Shuji
Published: March 2024

Background

Neurofibromatosis type 1 is an autosomal-dominant disease characterized by café-au-lait spots and neurofibromas, as well as various other symptoms in the bones, eyes, and nervous system. Due to its connection with vascular fragility, neurofibromatosis type 1 has been reported to be associated with vascular lesions, such as aneurysms. However, there have been few reports of abdominal visceral aneurysms associated with neurofibromatosis type 1. Furthermore, there have been no reports of robotic treatment of aneurysms associated with neurofibromatosis type 1. In this report, we describe the case of a patient with neurofibromatosis type 1 with a splenic artery aneurysm who was successfully treated with robotic surgery.

Case presentation

This report describes a 41-year-old Asian woman with a history of neurofibromatosis type 1 who was referred to our hospital for evaluation of a 28 mm splenic artery aneurysm observed on abdominal ultrasound. The aneurysm was in the splenic hilum, and transcatheter arterial embolization was attempted; however, this was difficult due to the tortuosity of the splenic artery. Thus, we suggested minimally invasive robotic surgery for treatment and resection of the splenic artery aneurysm with preservation of the spleen. The postoperative course was uneventful, and the patient was discharged on the eighth day after surgery. At 1 year of follow-up, the patient was doing well, with no evidence of recurrence.

Conclusion

We encountered a rare case of splenic artery aneurysm in a patient with neurofibromatosis type 1 who was successfully treated with robotic surgery. There is no consensus on treatment modalities for neurofibromatosis-related aneurysms, and endovascular treatment is considered safe and effective; however, surgery remains an important treatment modality. Especially in patients with stable hemodynamic status, robotic surgery may be considered as definitive treatment. To our knowledge, this is the first successfully treated case of a splenic artery aneurysm in a patient with neurofibromatosis type 1.
XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
Authors: Amato-Menker Carly J. , Hopen Quinn , Pettit Andrea , Gandhi Jasleen , Hu Gangqing , Schafer Rosana , Franko Jennifer
Published: March 2024

Background

Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation.

Methods

Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation.

Results

XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies.

Conclusions

FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism.
Advancing material property prediction: using physics-informed machine learning models for viscosity
Authors: Chew Alex K. , Sender Matthew , Kaplan Zachary , Chandrasekaran Anand , Chief Elk Jackson , Browning Andrea R. , Kwak H. Shaun , Halls Mathew D. , Afzal Mohammad Atif Faiz
Published: March 2024

In materials science, accurately computing properties like viscosity, melting point, and glass transition temperatures solely through physics-based models is challenging. Data-driven machine learning (ML) also poses challenges in constructing ML models, especially in the material science domain where data is limited. To address this, we integrate physics-informed descriptors from molecular dynamics (MD) simulations to enhance the accuracy and interpretability of ML models. Our current study focuses on accurately predicting viscosity in liquid systems using MD descriptors. In this work, we curated a comprehensive dataset of over 4000 small organic molecules’ viscosities from scientific literature, publications, and online databases. This dataset enabled us to develop quantitative structure–property relationships (QSPR) consisting of descriptor-based and graph neural network models to predict temperature-dependent viscosities for a wide range of viscosities. The QSPR models reveal that including MD descriptors improves the prediction of experimental viscosities, particularly at the small data set scale of fewer than a thousand data points. Furthermore, feature importance tools reveal that intermolecular interactions captured by MD descriptors are most important for viscosity predictions. Finally, the QSPR models can accurately capture the inverse relationship between viscosity and temperature for six battery-relevant solvents, some of which were not included in the original data set. Our research highlights the effectiveness of incorporating MD descriptors into QSPR models, which leads to improved accuracy for properties that are difficult to predict when using physics-based models alone or when limited data is available.

Graphical Abstract
Operational strategies for achieving comprehensive cancer center community outreach and engagement objectives: impact and logic models
Authors: Odedina Folakemi T. , Salinas Manisha , Albertie Monica , Murrell Doug , Munoz Kristin
Published: March 2024

Background

The National Cancer Institute’s (NCI) Cancer Center Support Grants (CCSGs) encourages Cancer Centers to address health disparities and reduce the cancer burden in their Catchment Area (CA) through an organized Community Outreach and Engagement (COE) structure. This paper shares the development of two guide models that fosters the operations of the Mayo Clinic Comprehensive Cancer Center (MCCCC) COE Office and programs, the MCCCC COE Impact Model and the MCCCC COE Logic Model.

Methods

Following a less than stellar CCSG rating for COE in 2018, the MCCCC developed a transition team to specifically address the critique and create a transformative plan for engaging communities to address cancer burden in the CA. A qualitative research approach was employed, focusing on organizing and displaying the relationship between MCCCC COE processes and outcomes through impact and logic models. An impact model was developed to illustrate the components of the CCSG and connect those components to short- and long-term COE outcomes. A logic model was developed to track and monitor activities for continuous process improvement for all COE activities.

Results

The impact and logic model serve as a roadmap to monitor progress towards short- and long-term COE goals of the MCCCC. The COE operational strategies draw upon bidirectional partnership, evidence-based practices, and research facilitation to respond to the CCSG critique.

Conclusion

These strategies demonstrate successful practices in addressing cancer burden, promoting health equity and eliminating cancer disparities in the MCCCC CA.
Adaptive capability and socioecological traps: a bioenergy case in communities of Irapuato, Guanajuato, Mexico
Authors: Reyes-Santiago María del Rosario , Maruri Montes de Oca Ana Elizabeth , Olalde Portugal Victor , Hernández-Rosales Maribel
Published: March 2024

Background

Energy poverty, which is the deprivation of a series of energy services that satisfy human needs, affects over 2 billion individuals who rely on the combustion of biomass and other solid fuels to fulfill their energy needs. While certain communities address their energy shortfall by harnessing local natural resources, these alternatives fail to provide access to more advantageous and sustainable conditions, thus leading to what are commonly referred to as socioecological traps.

Results

This research studies the relationships between the energy alternatives that two communities have developed, the bioenergy capability that would allow the system to access more desirable and sustainable states, and the costs and benefits that are perceived from this new use of their residues and resources. A quantitative methodology was employed by designing and applying a structured questionnaire applied to 207 households in two energy-poor communities in the municipality of Irapuato, Guanajuato, Mexico: San Agustín de los Tordos and El Comedero Grande. We have inferred that the alternatives generated by the communities function as socioecological traps. On the one hand, these options generate adverse effects on the health of people and the environment, while discouraging the construction of bioenergy capabilities; on the other hand, they allow them to cover some training costs, at least in the short term. These discoveries suggest that the system is currently in an advantageous phase of the cultivation of new capabilities.

Conclusions

The outcomes of this study contribute significantly to enhancing our comprehension of socioecological traps and capabilities within the realm of energy, thereby offering valuable insights for the effective management of successful bioenergy implementation initiatives. Moreover, these findings enable the development of frameworks for theoretical interpretation and methodological application within specific contexts, exemplified in our case by rural communities in Irapuato, Guanajuato Mexico. The holistic approach reveals that while individuals may have alternatives to fulfill their energy requirements, many of these alternatives can inadvertently become socioecological traps. For instance, the use of firewood as a short-term solution for household energy needs can generate adverse health and environmental consequences in the long run. In the light of these considerations, a study of their nature becomes imperative and relevant as it delves deeply into the intricate relationship between compensatory alternatives and capacities. Simultaneously, it scrutinizes the community’s perception of bioenergy in terms of costs and benefits, with the overarching goal of transitioning toward a sustainable energy system.
Analysis of inappropriate prophylactic use of proton pump inhibitors during the perioperative period: an observational study
Authors: Liu Pengpeng , Li Guangyao , Wu Qian , Han Mei , Zhang Chao
Published: March 2024

Background

The prevalence and characteristics of inappropriate use of proton pump inhibitors (PPIs) to prevent stress-related mucosal disease (SRMD) during the perioperative period and its associated factors are rarely reported. This study aimed to investigate the prevalence and characteristics of inappropriate prophylactic use of proton pump inhibitors (PPIs) during the perioperative period and identify its associated factors in a tertiary care and academic teaching hospital in China and to provide evidence for regulation authorities and pharmacists to take targeted measures to promote rational drug use.

Methods

Inpatients who underwent surgical operations and received prophylactic use of PPIs from June 2022 to November 2022 were included in this retrospective study. The appropriateness of perioperative prophylactic use of PPIs was evaluated by clinical pharmacists. Associated factors with inappropriate perioperative prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression.

Results

Four-hundred seventy-two patients were finally included in this study, of which 131 (27.75%) patients had at least one problem with inappropriate perioperative prophylactic use of PPIs. The three most common problems were drug use without indication (52.0%), inappropriate usage and dosage (34.6%), and inappropriate duration of medication (6.7%). Multiple logistic regression analysis showed that oral dosage form of PPIs [OR = 18.301, 95% CI (7.497, 44.671), p < 0.001], discharge medication of PPIs [OR = 11.739, 95% CI (1.289, 106.886), p = 0.029], and junior doctors [OR = 9.167, 95% CI (3.459, 24.299), p < 0.001] were associated with more inappropriate prophylactic use of PPIs. Antithrombotics [OR = 0.313, 95% CI (0.136, 0.721), p = 0.006] and prolonged postoperative hospital stay (longer than 15 days) [OR = 0.262, 95% CI (0.072, 0.951), p = 0.042] were associated with less inappropriate prophylactic use of PPIs.

Conclusions

The inappropriate prophylactic use of PPIs during the perioperative period is common. Regulation authorities and pharmacists should take more targeted measures to promote the rational prophylactic use of PPIs during the perioperative period.
Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling
Authors: Zhao Le , Yang Haili , Li Minhao , Xiao Min , Li Xingchun , Cheng Lei , Cheng Wenqiang , Chen Meixi , Zhao Yongju
Published: March 2024

Background

Brown adipose tissue (BAT) is known to be capable of non-shivering thermogenesis under cold stimulation, which is related to the mortality of animals. In the previous study, we observed that goat BAT is mainly located around the kidney at birth, and changes to white adipose tissue (WAT) in the perirenal adipose tissue of goats within one month after birth. However, the regulatory factors underlying this change is remain unclear. In this study, we systematically studied the perirenal adipose tissue of goat kids in histological, cytological, and accompanying molecular level changes from 0 to 28 d after birth.

Results

Our study found a higher mortality rate in winter-born goat kids, with goat birthing data statistics. Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d. This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids. Additionally, we found a series of changes of BAT during the first 28 d after birth, such as whitening, larger lipid droplets, decreased mitochondrial numbers, and down-regulation of key thermogenesis-related genes (UCP1, DIO2, UCP2, CIDEA, PPARGC1a, C/EBPb, and C/EBPa). Then, we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats. Furthermore, 12 candidate genes were found to potentially regulate goat BAT thermogenesis. The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes. While apoptosis may play a limited role, it is largely not critical in this transition process.

Conclusions

We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids, with notable species differences in the expression of adipose tissue marker genes, and we highlighted some potential marker genes for goat BAT and WAT. Additionally, the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.
Not a passive learner but an active one: a focus on the efficacy of philosophy-based language instruction and its consequences on EFL learners’ critical thinking, engagement, and academic achievement
Authors: Li Lingxi , Ismail Sayed M. , Patra Indrajit , Lami Desta
Published: March 2024

This study investigates the impact of Philosophy-Based Language Teaching (PBLT) on the critical thinking skills and learner engagement of English as a Foreign Language (EFL) students. A concurrent mixed-methods approach, including semi-structured interviews, document analysis, and academic achievement tests, was employed with an experimental group (EG) exposed to PBLT and a control group (CG) receiving traditional instruction. The results reveal a substantial positive effect of PBLT on the critical thinking abilities of EFL learners, as evidenced by thematic analyses of interviews and document content. Themes include heightened critical thinking awareness, collaborative knowledge construction, and increased learner engagement. Academic achievement tests further demonstrate significant improvement in the experimental group’s performance. A comparison with existing literature underscores the novelty of our mixed-methods approach. Implications for language teachers, materials developers, syllabus designers, and policy-makers are discussed, highlighting the potential of PBLT in cultivating critical thinking and learner engagement.
The scientific analysis of the bronze mous excavated from Wushan, Chongqing, China: new perspectives from alloy composition analysis and proteomic method
Authors: Tan Liwei , Fan Xiaopan , Rao Huiyun , Zhang Hui , Yang Yimin
Published: March 2024

The bronze mou was an important artifact commonly used in the Ba-Shu region (now in Chongqing and Sichuan Province) during the Spring and Autumn Period and the Han Dynasty. Although extensive archaeological study of the bronze mou has been conducted, scientific analysis of the bronze mou has been limited, and no organic residue analysis has been performed on the bronze mou. In this study, four bronze mous dated to the Han dynasty (206 BC–220 AD) with organic residues unearthed in three archaeological sites in Wushan, Chongqing, were selected for analysis by portable X-ray fluorescent spectrometer (P-XRF) and liquid chromatograph-tandem mass spectrometry (LC/MS/MS). The results of the alloy composition indicated that all the samples are copper-tin-lead ternary alloys. The proteomic analysis results confirmed that the bronze mou had been used as cooking utensils or containers. At the Tuchengpo Cemetery, soybeans were found in both bronze mou M32:27 and M38:39, and vigna was discovered in M32:27. No useful protein was discovered in the bronze mou from the Shennvmiao Cemetery. Proteins of ginkgo and chicken were found in M16:12 at the Gaotangguan Cemetery. The discovery indicated that residents in Wushan, Chongqing, had access to a diverse range of food sources around 2000 years ago. Furthermore, this study demonstrates that proteomic analysis is highly effective in studying archaeological organic residues.
Food insecurity is associated with low diet quality and unhealthy cooking and eating habits in Iranian women
Authors: Kohanmoo Ali , Hashemzadeh Maral , Teymouri Maryam , Zare Morteza , Akhlaghi Masoumeh
Published: March 2024

Background

Food insecurity affects diet and nutrition intakes. We explored the relationship between food insecurity and dietary intakes in a group of Iranian women.

Methods

The cross-sectional study was performed on 190 healthy females aged 20–55 years attending primary healthcare centers in Shiraz. Food insecurity was evaluated by Household Food Insecurity Access Scale, which is a validated tool for assessing food insecurity in developing countries. Diet was assessed using a food frequency questionnaire. The association of dietary patterns and food insecurity was assessed by linear regression.

Results

Assessment of dietary intakes revealed that consumption of red meat, poultry, fish, dairy, fruits, non-starchy vegetables, and nuts decreased whereas that of grains, processed meats, potato, and sugary foods increased with increasing food insecurity. Among nutrients, carbohydrates, fiber, vitamin A, vitamin C, folic acid, potassium, calcium, and magnesium decreased while fat and sodium increased as food insecurity increased. Three major dietary patterns were detected. Healthy dietary patterns showed inverse associations with food insecurity in the crude (β = -0.422 and − 0.435, P < 0.001) and adjusted (adjusted for age, marital status, and educational level) (β = -0.475 and − 0.341, P < 0.001) models of regression analysis but unhealthy pattern did not show an association with food insecurity. Compared to food secure participants, a higher percentage of food insecure individuals indicated unhealthy eating habits, such as skipping breakfast, lower snack ingestion, more fast and fried food consumption, and using unhealthy cooking methods.

Conclusion

Overall, this study showed that food insecurity was associated with less healthy diet and unhealthy cooking and eating habits.
H3K4 methylation regulates development, DNA repair, and virulence in Mucorales
Authors: Osorio-Concepción Macario , Lax Carlos , Lorenzo-Gutiérrez Damaris , Cánovas-Márquez José Tomás , Tahiri Ghizlane , Navarro Eusebio , Binder Ulrike , Nicolás Francisco Esteban , Garre Victoriano
Published: March 2024

Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.
Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India
Authors: Mathew Aju , Davis Sissmol , Boby Jeffrey Mathew , R I Anu , Suryavanshi Moushumi , Dawood Shaheenah S. , Panda Pankaj Kumar , Nag Shona Milon , Das Arunangshu , Rohatgi Nitesh , Popat Sanjay , Shah Riyaz N.H. , Thampy Cherian , Parikh Aparna Raj , Yadav Siddhartha , Mehta Prashant , Singh Randeep , Mukherji Deborah , Shilpakar Ramila , Mullapally Sujith Kumar , Sirohi Bhawna
Published: March 2024

PURPOSE

Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non–high-income setting, with international input to evaluate the necessity of MTB in clinical practice.

METHODS

We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented.

RESULTS

Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases).

CONCLUSION

The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.