bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent advances in targeted drug delivery systems for resistant colorectal cancer
Authors: Sharifi-Azad Masoumeh , Fathi Marziyeh , Cho William C. , Barzegari Abolfazl , Dadashi Hamed , Dadashpour Mehdi , Jahanban-Esfahlan Rana 
Published: May 2022

AbstractColorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.
Restorative biodegradable two-layered hybrid microneedles for melanoma photothermal/chemo co-therapy and wound healing
Authors: Shan Yue , Tan Bowen , Zhang Min , Xie Xi , Liao Jinfeng 
Published: May 2022

AbstractTumor killing and wound healing are two complementary and influential processes during the treatment of melanoma. Herein, a two-layered microneedle platform was developed with bifunctional effect of chemo-photothermal synergistic melanoma therapy and skin regeneration. The bifunctional platform composed of embeddable curcumin nanodrugs/new Indocyanine Green/hyaluronic acid (Cur NDs/IR820/HA) microneedles and sodium alginate/gelatin/hyaluronic acid (SA/Ge/HA) supporting backing layer was prepared through a two-step casting process. With uniform incorporation of curcumin nanodrugs and IR820, the microneedles exhibited excellent photothermal performance under external near-infrared (NIR) light stimulation and tumor co-therapy ability. Once the embeddable microneedles were inserted into skin, they would rapidly dissolve and activate drug release successfully for tumor treatment. Moreover, the SA/Ge/HA supporting backing layer was left behind to cover the wound and promote the proliferation of endothelial and fibroblasts cells for enhanced skin regeneration. The two-layered microneedles platform can simultaneously eliminate the tumor and accelerate wounding healing, which may be potentially employed as a competitive strategy for the treatment of melanoma.
Graphical Abstract
Total systems failure: police officers’ perspectives on the impacts of the justice, health, and social service systems on people who use drugs
Authors: Butler Amanda , Zakimi Naomi , Greer Alissa 
Published: May 2022

Abstract
Background
Police in Canada have become main responders to behavioural health concerns in the community—a role that disproportionately harms people who use drugs (PWUD). Recent calls to defund the police emphasize the need to shift responsibility for non-criminal health issues from police to health and social services. This study explores the role of police interactions in responding to PWUD within the broader institutional and structural contexts in which they operate.

Methods
We conducted a qualitative thematic analysis of interviews with sixteen police officers across nine jurisdictions in British Columbia, Canada. We examined police officers’ everyday policing experiences interacting with PWUD, enforcing drug laws, and working alongside other service sectors.

Results
Officers explained that the criminal justice system is one component of a wider network of systems that collectively fail to meet the needs of PWUD. They recognized that PWUD who interact with police often experienced intersecting structural vulnerabilities such as poverty, homelessness, and intergenerational trauma. Harmful drug laws in conjunction with inadequate treatment and housing resources contributed to a funnelling of PWUD into interactions with police. They provided several recommendations for reform including specialized health and justice roles, formalized intersectoral collaboration, and poverty reduction.

Conclusions
Overall, this study provides unique insights into the positioning and role of police officers within a “total systems failure” that negatively impact PWUD. Police have become responders-by-default for issues that are fundamentally related to people’s health conditions and socioeconomic circumstances. Addressing failures across the health, social, and justice systems to meet the needs of PWUD will require an examination of the shortcomings across these systems, as well as substantial funding and system reforms.
tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma
Authors: Xu Weiguo , Zheng Junyu , Wang Xiao , Zhou Bin , Chen Huanqiu , Li Gang , Yan Feng 
Published: May 2022

Abstract
Background
As a new kind of non-coding RNAs (ncRNAs), tRNA derivatives play an important role in gastric carcinoma (GC). Nevertheless, the underlying mechanism tRNA derivatives were involved in was rarely illustrated.

Methods
We screened out the tRNA derivative, tRF-Val-CAC-016, based on the tsRNA sequencing and demonstrated the effect tRF-Val-CAC-016 exerted on GC proliferation in vitro and in vivo. We applied Dual-luciferase reporter assay, RIP assay, and bioinformatic analysis to discover the downstream target of tRF-Val-CAC-016. Then CACNA1d was selected, and the oncogenic characteristics were verified. Subsequently, we detected the possible regulation of the canonical MAPK signaling pathway to further explore the downstream mechanism of tRF-Val-CAC-016.

Results
As a result, we found that tRF-Val-CAC-016 was low-expressed in GC, and upregulation of tRF-Val-CAC-016 could significantly suppress the proliferation of GC cell lines. Meanwhile, tRF-Val-CAC-016 regulated the canonical MAPK signaling pathway by targeting CACNA1d.

Conclusions
tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma. This study discussed the function and mechanism of tRF-Val-CAC-016 in GC for the first time. The pioneering work has contributed to our present understanding of tRNA derivative, which might provide an alternative mean for the targeted therapy of GC.
Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer
Authors: Luo Wenqin , Xiang Wenqiang , Gan Lu , Che Ji , Li Jing , Wang Yichao , Han Lingyu , Gu Ruiqi , Ye Li , Wang Renjie , Zhang Xiuping , Xu Ye , Dai Weixing , Mo Shaobo , Li Qingguo , Cai Guoxiang 
Published: May 2022

Abstract
Background
Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively.

Methods
In this study, we obtained NRGs and performed consensus molecular subtyping by “ConsensusClusterPlus” to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients’ survival outcomes with low-throughput validation in a patients’ cohort from Fudan University Shanghai Cancer Center.

Results
We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy.

Conclusions
Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients’ prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.
Worked to the bone: antibody-based conditioning as the future of transplant biology
Authors: Griffin James M. , Healy Fiona M. , Dahal Lekh N. , Floisand Yngvar , Woolley John F. 
Published: May 2022

AbstractConditioning of the bone marrow prior to haematopoietic stem cell transplant is essential in eradicating the primary cause of disease, facilitating donor cell engraftment and avoiding transplant rejection via immunosuppression. Standard conditioning regimens, typically comprising chemotherapy and/or radiotherapy, have proven successful in bone marrow clearance but are also associated with severe toxicities and high incidence of treatment-related mortality. Antibody-based conditioning is a developing field which, thus far, has largely shown an improved toxicity profile in experimental models and improved transplant outcomes, compared to traditional conditioning. Most antibody-based conditioning therapies involve monoclonal/naked antibodies, such as alemtuzumab for graft-versus-host disease prophylaxis and rituximab for Epstein–Barr virus prophylaxis, which are both in Phase II trials for inclusion in conditioning regimens. Nevertheless, alternative immune-based therapies, including antibody–drug conjugates, radio-labelled antibodies and CAR-T cells, are showing promise in a conditioning setting. Here, we analyse the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.
Transcranial electric and acoustic stimulation for tinnitus: study protocol for a randomized double-blind controlled trial assessing the influence of combined transcranial random noise and acoustic stimulation on tinnitus loudness and distress
Authors: Martins Mariana Lopes , Kleinjung Tobias , Meyer Martin , Raveenthiran Vithushika , Wellauer Zino , Peter Nicole , Neff Patrick 
Published: May 2022

Abstract
Background
Tinnitus is the result of aberrant neuronal activity. As a novel treatment form, neuromodulation is used to modify neuronal activity of brain areas involved in tinnitus generation. Among the different forms of electric stimulation, transcranial random noise stimulation (tRNS) has been shown to be a promising treatment option for tinnitus. In addition, recent studies indicate that the reduction in tinnitus can be more pronounced when different modalities of stimulation techniques are combined (“bimodal stimulation”). TRNS can be used in combination with acoustic stimulation (AS), a further treatment option recognized in the literature. The aim of the proposed study is to investigate whether simultaneous tRNS and AS improve levels of tinnitus loudness and distress.

Methods
The intervention consists of bilateral high-definition tRNS (HD-tRNS) over the auditory cortex combined with the application of AS which is studied in a crossover design. The visits will be performed in 26 sessions. There will be 20 treatment sessions, divided into two blocks: active and sham HD-tRNS. Within the blocks, the interventions are divided into group A: HD-tRNS and AS, and group B: HD-tRNS alone. Furthermore, in addition to the assessments directly following the intervention sessions, there will be six extra sessions performed subsequently at the end of each block, after a period of some days (follow-ups 1 and 2) and a month after the last intervention (C). Primary outcome measures are analog scales for evaluation of subjective tinnitus loudness and distress, and the audiological measurement of minimum masking level (MML). Secondary outcome measures are brain activity as measured by electroencephalography and standardized questionnaires for evaluating tinnitus distress and severity.

Discussion
To the best of our knowledge, this is the first study which uses HD-tRNS combined with AS for tinnitus treatment. The crossover design permits the comparison between HD-tRNS active vs. sham and with vs. without AS. Thus, it will be possible to evaluate the efficacy of the combined approach to HD-tRNS alone. In addition, the use of different objective and subjective evaluations for tinnitus enable more reliable and valid results.

Trial registration
Swiss Ethics Committee (BASEC-Nr. 2020-02027); Swiss Federal Complementary Database (kofam.ch: SNCTP000004051); and ClinicalTrials.gov (clinicaltrials.gov: NCT04551404).
Cephalopod palaeobiology: evolution and life history of the most intelligent invertebrates
Authors: Klug Christian , Bonnaud-Ponticelli Laure , Nabhitabhata Jaruwat , Fuchs Dirk , De Baets Kenneth , Cheng Ji , Hoffmann René 
Published: May 2022

AbstractSigurd von Boletzky was a cephalopod researcher who was world-renowned for his enthusiasm for his field of research, for his friendly and calm personality, and, of course, his publications. He dedicated most of his life as active researcher on the development, biology and evolution of coleoids. Nevertheless, he was always curious to learn about other cephalopods as well. Sigurd passed away in Switzerland on September 28th 2020. We dedicate this text and volume to his memory.
Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases
Authors: Liu Zonghan , Sun Yi , Qi Zhengtang , Cao Lu , Ding Shuzhe 
Published: May 2022

AbstractMitochondria play a pivotal role in energy generation and cellular physiological processes. These organelles are highly dynamic, constantly changing their morphology, cellular location, and distribution in response to cellular stress. In recent years, the phenomenon of mitochondrial transfer has attracted significant attention and interest from biologists and medical investigators. Intercellular mitochondrial transfer occurs in different ways, including tunnelling nanotubes (TNTs), extracellular vesicles (EVs), and gap junction channels (GJCs). According to research on intercellular mitochondrial transfer in physiological and pathological environments, mitochondrial transfer hold great potential for maintaining body homeostasis and regulating pathological processes. Multiple research groups have developed artificial mitochondrial transfer/transplantation (AMT/T) methods that transfer healthy mitochondria into damaged cells and recover cellular function. This paper reviews intercellular spontaneous mitochondrial transfer modes, mechanisms, and the latest methods of AMT/T. Furthermore, potential application value and mechanism of AMT/T in disease treatment are also discussed.
Ginkgolic acid and anacardic acid are reversible inhibitors of SARS-CoV-2 3-chymotrypsin-like protease
Authors: Li Dongsheng , Yan Gangan , Zhou Wenwen , Si Shuyi , Liu Xiaoping , Zhang Jing , Li Yan , Chen Yunyu 
Published: May 2022

AbstractBecause of the emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different regions of the world, the battle with infectious coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been seesawing. Therefore, the identification of antiviral drugs is of particular importance. In order to rapidly identify inhibitors for SARS-CoV-2 3-chymotrypsin-like protease (3CLpro), an enzyme essential for viral replication, we combined the fluorescence polarization (FP) technique with biotin-avidin system (BAS) and developed a novel sandwich-like FP screening assay. Through high-throughput screening, two hits of 3CLpro inhibitors, ginkgolic acid (GA) and anacardic acid (AA) were identified, which showed IC50 values of 11.29 ± 0.48 and 12.19 ± 0.50 μM, respectively. Their binding modes were evaluated by HPLC-Q-TOF–MS. There was no mass increase detected for SARS-CoV-2 3CLpro incubated with either GA or AA, indicating the absence of covalent adducts. The kinetic analysis clearly demonstrated that both GA and AA inhibit SARS-CoV-2 3CLpro via reversible and mixed-inhibition manner. Our results argue against conclusion that GA and AA act as irreversible and covalent inhibitors against SARS-CoV-2 3CLpro, which is based on the studies by Chen et al.
Mitochondrial gene expression in different organs of Hoplobatrachus rugulosus from China and Thailand under low-temperature stress
Authors: Jin Wan-Ting , Guan Jia-Yin , Dai Xin-Yi , Wu Gong-Ji , Zhang Le-Ping , Storey Kenneth B. , Zhang Jia-Yong , Zheng Rong-Quan , Yu Dan-Na 
Published: May 2022

Abstract
Background
Hoplobatrachus rugulosus (Anura: Dicroglossidae) is distributed in China and Thailand and the former can survive substantially lower temperatures than the latter. The mitochondrial genomes of the two subspecies also differ: Chinese tiger frogs (CT frogs) display two identical ND5 genes whereas Thai tiger frogs (TT frogs) have two different ND5 genes. Metabolism of ectotherms is very sensitive to temperature change and different organs have different demands on energy metabolism at low temperatures. Therefore, we conducted studies to understand: (1) the differences in mitochondrial gene expression of tiger frogs from China (CT frogs) versus Thailand (TT frogs); (2) the differences in mitochondrial gene expression of tiger frogs (CT and TT frogs) under short term 24 h hypothermia exposure at 25 °C and 8 °C; (3) the differences in mitochondrial gene expression in three organs (brain, liver and kidney) of CT and TT frogs.

Results
Utilizing RT-qPCR and comparing control groups at 25 °C with low temperature groups at 8 °C, we came to the following results. (1) At the same temperature, mitochondrial gene expression was significantly different in two subspecies. The transcript levels of two identical ND5 of CT frogs were observed to decrease significantly at low temperatures (P < 0.05) whereas the two different copies of ND5 in TT frogs were not. (2) Under low temperature stress, most of the genes in the brain, liver and kidney were down-regulated (except for COI and ATP6 measured in brain and COI measured in liver of CT frogs). (3) For both CT and TT frogs, the changes in overall pattern of mitochondrial gene expression in different organs under low temperature and normal temperature was brain > liver > kidney.

Conclusions
We mainly drew the following conclusions: (1) The differences in the structure and expression of the ND5 gene between CT and TT frogs could result in the different tolerances to low temperature stress. (2) At low temperatures, the transcript levels of most of mitochondrial protein-encoding genes were down-regulated, which could have a significant effect in reducing metabolic rate and supporting long term survival at low temperatures. (3) The expression pattern of mitochondrial genes in different organs was related to mitochondrial activity and mtDNA replication in different organs.
Quality of life during COVID-19 pandemic: a community-based study in Dakahlia governorate, Egypt
Authors: Mohsen Shorouk , El-Masry Ragaa , Ali Olfat Farag , Abdel-Hady Doaa 
Published: May 2022

Abstract
Background
The sudden transmission of the novel coronavirus along with instant measures taken in response to the Coronavirus Disease 2019 (COVID-19) pandemic caused many new challenges adversely disturbing quality of life (QoL). The objective of this study is to measure quality of life of the public during the COVID-19 pandemic and factors affecting it among adults.

Methods
This is a community-based cross-sectional household study with analytic component conducted in an agricultural area in Dakahlia governorate, Egypt and included 500 individuals. Data were collected through a structured interview, and the collected data included socio-demographic characteristics as well as some data related to their habits and comorbidities, their experience with COVID-19 and data about QoL using the COV19-Impact on Quality of Life (COV19-QoL) scale Arabic version, after assessing Content validity and reliability.

Results
The total QoL score (mean ± standard deviation) is 2.3 ± 0.6 and the score for QoL in general and perception of danger on personal safety show the highest mean with 2.6 ± 0.7. The lowest mean score is related to the perception of mental health deterioration (1.9 ± 0.8). Independent predictors of the total QoL scale are sex (regression coefficient (95% CI) = 0.1 (0.02 to 0.2), p value = 0.02), monthly income (regression coefficient (95% CI) = 0.1 (0.004 to 0.2), p value = 0.04), knowing someone infected with COVID-19 (regression coefficient (95% CI) = 0.15 (0.08 to 0.3), p value = 0.001), and data collection time (regression coefficient (95% CI) = 0.1 (0.006 to 0.2), p value = 0.04).

Conclusions
COVID-19 pandemic has impacted the public quality of life, particularly in terms of general quality of life and personal safety. People with substantial predictors of lower quality of life should be given more attention.
Prediction of glioma-subtypes: comparison of performance on a DL classifier using bounding box areas versus annotated tumors
Authors: Ali Muhaddisa Barat , Gu Irene Yu-Hua , Lidemar Alice , Berger Mitchel S. , Widhalm Georg , Jakola Asgeir Store 
Published: May 2022

AbstractBackgroundFor brain tumors, identifying the molecular subtypes from magnetic resonance imaging (MRI) is desirable, but remains a challenging task. Recent machine learning and deep learning (DL) approaches may help the classification/prediction of tumor subtypes through MRIs. However, most of these methods require annotated data with ground truth (GT) tumor areas manually drawn by medical experts. The manual annotation is a time consuming process with high demand on medical personnel. As an alternative automatic segmentation is often used. However, it does not guarantee the quality and could lead to improper or failed segmented boundaries due to differences in MRI acquisition parameters across imaging centers, as segmentation is an ill-defined problem. Analogous to visual object tracking and classification, this paper shifts the paradigm by training a classifier using tumor bounding box areas in MR images. The aim of our study is to see whether it is possible to replace GT tumor areas by tumor bounding box areas (e.g. ellipse shaped boxes) for classification without a significant drop in performance.MethodIn patients with diffuse gliomas, training a deep learning classifier for subtype prediction by employing tumor regions of interest (ROIs) using ellipse bounding box versus manual annotated data. Experiments were conducted on two datasets (US and TCGA) consisting of multi-modality MRI scans where the US dataset contained patients with diffuse low-grade gliomas (dLGG) exclusively.ResultsPrediction rates were obtained on 2 test datasets: 69.86% for 1p/19q codeletion status on US dataset and 79.50% for IDH mutation/wild-type on TCGA dataset. Comparisons with that of using annotated GT tumor data for training showed an average of 3.0% degradation (2.92% for 1p/19q codeletion status and 3.23% for IDH genotype).ConclusionUsing tumor ROIs, i.e., ellipse bounding box tumor areas to replace annotated GT tumor areas for training a deep learning scheme, cause only a modest decline in performance in terms of subtype prediction. With more data that can be made available, this may be a reasonable trade-off where decline in performance may be counteracted with more data.