bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine intelligence-driven framework for optimized hit selection in virtual screening
Authors: Kumar Neeraj , Acharya Vishal 
Published: July 2022

AbstractVirtual screening (VS) aids in prioritizing unknown bio-interactions between compounds and protein targets for empirical drug discovery. In standard VS exercise, roughly 10% of top-ranked molecules exhibit activity when examined in biochemical assays, which accounts for many false positive hits, making it an arduous task. Attempts for conquering false-hit rates were developed through either ligand-based or structure-based VS separately; however, nonetheless performed remarkably well. Here, we present an advanced VS framework—automated hit identification and optimization tool (A-HIOT)—comprises chemical space-driven stacked ensemble for identification and protein space-driven deep learning architectures for optimization of an array of specific hits for fixed protein receptors. A-HIOT implements numerous open-source algorithms intending to integrate chemical and protein space leading to a high-quality prediction. The optimized hits are the selective molecules which we retrieve after extreme refinement implying chemical space and protein space modules of A-HIOT. Using CXC chemokine receptor 4, we demonstrated the superior performance of A-HIOT for hit molecule identification and optimization with tenfold cross-validation accuracies of 94.8% and 81.9%, respectively. In comparison with other machine learning algorithms, A-HIOT achieved higher accuracies of 96.2% for hit identification and 89.9% for hit optimization on independent benchmark datasets for CXCR4 and 86.8% for hit identification and 90.2% for hit optimization on independent test dataset for androgen receptor (AR), thus, shows its generalizability and robustness. In conclusion, advantageous features impeded in A-HIOT is making a reliable approach for bridging the long-standing gap between ligand-based and structure-based VS in finding the optimized hits for the desired receptor. The complete resource (framework) code is available at https://gitlab.com/neeraj-24/A-HIOT.
Graphical Abstract
Single-cell RNA sequencing reveals the potential mechanism of heterogeneity of immunomodulatory properties of foreskin and umbilical cord mesenchymal stromal cells
Authors: Cai Siyu , Fan Chuiqin , Xie Lichun , Zhong Huifeng , Li Aijia , Lv Siyu , Liao Maochuan , Yang Xixi , Su Xing , Wang Yue , Wang Hongwu , Wang Manna , Huang Peng , Liu Yulin , Wang Yu , Liu Yufeng , Wang Tianyou , Zhong Yong , Ma Lian 
Published: July 2022

AbstractBackgroundMesenchymal stromal cells (MSCs) are heterogeneous populations. Heterogeneity exists within the same tissue and between different tissues. Some studies have found enormous heterogeneity in immunomodulatory function among MSCs derived from different tissues. Moreover, the underlying mechanism of heterogeneity in immunomodulatory abilities is still unclear.MethodsForeskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured until the third passage. According to the International Association for Cell Therapy standard, we confirmed the cell type. Then, FSMSCs and HuMSCs were cocultured with human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) in vitro. Furthermore, the supernatant was sampled for an enzyme-linked immunosorbent assay to investigate the secretion of IL-1β, IL-6, IL-10, TNF-α, and TGF-β1. Finally, we performed single-cell RNA sequencing (scRNA-seq) of FSMSCs and HuMSCs.ResultsWe successfully identified FSMSCs and HuMSCs as MSCs. When cocultured with LPS pretreated PBMCs, FSMSCs and HuMSCs could effectively reduced the secretion of IL-1β and TNF-α. However, FSMSCs stimulated the PBMCs to secrete more IL-10, TGF-β1, and IL-6. Furthermore, 4 cell subsets were identified from integrated scRNA-seq data, including proliferative MSCs (MKI67+,CD146low+,NG2+,PDGFRB−), pericytes (CD146high+,PDGFRB+,MKI67−,CD31−,CD45−,CD34−), immune MSCs (CXCL12high+,PTGIShigh+,PDGFRB+,CD146−,MKI67−) and progenitor proliferative MSCs (CXCL12low+,PTGISlow+,PDGFRB+,CD146−,MKI67−). Among them, we found that immune MSCs with strengthened transcriptional activity were similar to pericytes with regard to the degree of differentiated. Various of immune-related genes, gene sets, and regulons were also enriched in immune MSCs. Moreover, immune MSCs were determined to be close to other cell subsets in cell–cell communication analysis. Finally, we found that the proportion of immune MSCs in foreskin tissue was highest when comparing the subset compositions of MSCs derived from different tissues.ConclusionsFSMSCs show better immunomodulatory capacity than HuMSCs in vitro. Moreover, immune MSCs may play a vital role in the heterogeneity of immunoregulatory properties. This study provides new insights suggesting that immune MSCs can be isolated to exert stable immunoregulatory functions without being limited by the heterogeneity of MSCs derived from different tissues.
SENP6 induces microglial polarization and neuroinflammation through de-SUMOylation of Annexin-A1 after cerebral ischaemia–reperfusion injury
Authors: Mao Meng , Xia Qian , Zhan Gao-Feng , Chu Qin-Jun , Li Xing , Lian Hong-Kai 
Published: July 2022

Abstract
Background
Previous data have reported that Sentrin/SUMO-specific protease 6 (SENP6) is involved in ischaemic brain injury and induces neuronal apoptosis after cerebral ischaemia, but the role of SENP6 in microglia-induced neuroinflammation and its underlying mechanism remain poorly understood. This research systematically explored the function and potential mechanism of SENP6 in microglia-induced neuroinflammation after ischaemic stroke.

Results
We first identified an increased protein level of SENP6 in microglia after cerebral ischaemia. Then, we demonstrated that SENP6 promoted detrimental microglial phenotype polarization. Specifically, SENP6-mediated de-SUMOylation of ANXA1 targeted the IκB kinase (IKK) complex and selectively inhibited the autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression. In addition, downregulation of SENP6 in microglia effectively reduced cocultured neuronal damage induced by ischaemic stroke. More importantly, we employed an AAV-based technique to specifically knockdown SENP6 in microglia/macrophages, and in vivo experiments showed that SENP6 inhibition in microglia/macrophages notably lessened brain ischaemic infarct size, decreased neurological deficit scores, and ameliorated motor and cognitive function in mice subjected to cerebral ischaemia surgery.

Conclusion
We demonstrated a previously unidentified mechanism by which SENP6-mediated ANXA1 de-SUMOylation regulates microglial polarization and our results strongly indicated that in microglia, inhibition of SENP6 may be a crucial beneficial therapeutic strategy for ischaemic stroke.

Graphical Abstract
FBXL17/spastin axis as a novel therapeutic target of hereditary spastic paraplegia
Authors: Kang Hyun Mi , Kim Dae Hun , Kim Mijin , Min Yoohong , Jeong Bohyeon , Noh Kyung Hee , Lee Da Yong , Cho Hyun-Soo , Kim Nam-Soon , Jung Cho-Rok , Lim Jung Hwa 
Published: July 2022

Abstract
Background
Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy.

Results
As evidenced by protein chip analysis, FBXL17 inversely correlated with SPAST-M1 at the protein level in vitro and, also in vivo during embryonic developmental stage. SPAST-M1 protein interacted with FBXL17 specifically via the BTB domain at the N-terminus of SPAST-M1. The SCFFBXL17 E3 ubiquitin ligase complex degraded SPAST-M1 protein in the nuclear fraction in a proteasome-dependent manner. SPAST phosphorylation occurred only in the cytoplasmic fraction by CK2 and was involved in poly-ubiquitination. Inhibition of SCFFBXL17 E3 ubiquitin ligase by small chemical and FBXL17 shRNA decreased proteasome-dependent degradation of SPAST-M1 and induced axonal extension. The SPAST Y52C mutant, harboring abnormality in BTB domain could not interact with FBXL17, thereby escaping protein regulation by the SCFFBXL17 E3 ubiquitin ligase complex, resulting in loss of functionality with aberrant quantity. Although this mutant showed shortening of axonal outgrowth, low rate proliferation, and poor differentiation capacity in a 3D model, this phenotype was rescued by inhibiting SCFFBXL17 E3 ubiquitin ligase.

Conclusions
We discovered that a novel pathway, FBXL17-SPAST was involved in pathogenicity of HSP by the loss of function and the quantitative regulation. This result suggested that targeting FBXL17 could provide new insight into HSP therapeutics.
Alternative transcription start sites contribute to acute-stress-induced transcriptome response in human skeletal muscle
Authors: Makhnovskii Pavel A. , Gusev Oleg A. , Bokov Roman O. , Gazizova Guzel R. , Vepkhvadze Tatiana F. , Lysenko Evgeny A. , Vinogradova Olga L. , Kolpakov Fedor A. , Popov Daniil V. 
Published: July 2022

Abstract
Background
More than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress-induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise).

Results
We identified 44,680 CAGE TSS clusters (including 3764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of “classic” transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors.

Conclusions
Transcriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.
Impact of the COVID-19 Pandemic on Exercise Physiology Services in Australia: A Retrospective Audit
Authors: Owen Patrick J. , Keating Shelley E. , Askew Christopher D. , Clanchy Kelly M. , Jansons Paul , Maddison Ralph , Maiorana Andrew , McVicar Jenna , Robinson Suzanne , Mundell Niamh L. 
Published: July 2022

AbstractIntroductionThe COVID-19 pandemic has led to a shift in healthcare towards telehealth delivery, which presents challenges for exercise physiology services. We aimed to examine the impact of the COVID-19 pandemic on the reach, efficacy, adoption and implementation of telehealth delivery for exercise physiology services by comparing Australian practises before (prior to 25 January 2020) and during the COVID-19 pandemic (after 25 January 2020).MethodsThis retrospective audit included 80 accredited exercise physiology clinicians. We examined relevant dimensions of the RE-AIM framework (reach, effectiveness, adoption and implementation) from the clinician perspective.ResultsDuring the COVID-19 pandemic, 91% (n = 73/80) of surveyed clinicians offered telehealth delivery service, compared to 25% (n = 20/80) prior. Mean (SD) telehealth delivery per week doubled from 5 (7) to 10 (8) hours. In-person delivery decreased from 23 (11) to 15 (11) hours per week. Typical reasons for not offering telehealth delivery were client physical/cognitive incapacity (n = 33/80, 41%) and safety (n = 24/80, 30%). Clinician-reported reasons for typical clients not adopting telehealth delivery were personal preference (n = 57/71, 80%), physical capacity (n = 35/71, 49%) and access to reliable delivery platforms (n = 27/71, 38%). Zoom (n = 54/71, 76%) and telephone (n = 53/71, 75%) were the most commonly used platforms. Of the reasons contributing to incomplete treatment, lack of confidence in delivery mode was sevenfold higher for telehealth compared to in-person delivery. No serious treatment-related adverse events were reported.ConclusionsDuring the COVID-19 pandemic, telehealth delivery of exercise physiology services increased and in-person delivery decreased, which suggests the profession was adaptable and agile. However, further research determining comparative efficacy and cost-effectiveness is warranted.
Coacervate-mediated novel pancreatic cancer drug
Aleuria Aurantia
lectin delivery for augmented anticancer therapy
Authors: Kim Sungjun , Choi Yunyoung , Kim Kyobum 
Published: July 2022

Abstract

Background

Pancreatic cancer, one of the cancers with the highest mortality rate, has very limited clinical treatment. Cancer cells express abnormal glycans on the surface, and some lectins with a high affinity for the glycans induce apoptosis in cancer. In this study, the efficacy of
Aleuria Aurantia
lectin (AAL) for the treatment of pancreatic cancer was evaluated and the efficacy improvement through AAL delivery with mPEGylated coacervate (mPEG-Coa) was investigated.

Methods
AAL was treated with pancreatic cancer cells, PANC-1, and the expression level of caspase-3 and subsequent apoptosis was analyzed. In particular, the anticancer efficacy of AAL was compared with that of concanavalin A, one of the representative anticancer lectins. Then, methoxypolyethylene glycol-poly(ethylene arginylaspartate diglyceride), a polycation, was synthesized, and an mPEG-Coa complex was prepared with polyanion heparin. The AAL was incorporated into the mPEG-Coa and the release kinetics of the AAL from the mPEG-Coa and the cargo protection capacity of the mPEG-Coa were evaluated. Finally, improved anticancer ability through Coa-mediated AAL delivery was assessed.

Results
These results indicated that AAL is a potential effective pancreatic cancer treatment. Moreover, mPEG-Coa rapidly released AAL at pH 6.5, an acidic condition in the cancer microenvironment. The initial rapid release of AAL effectively suppressed pancreatic cancer cells, and the continuous supply of AAL through the Coa transporter effectively inhibited proliferation recurrence of cancer cells.

Conclusion
AAL is a potential novel drug for the treatment of pancreatic cancer therapeutic agent. In addition, a continuous supply of drugs above the therapeutic threshold using mPEG-Coa could improve therapeutic efficacy.
Urinary dipeptidyl peptidase-4 is a useful marker for tubulitis, and it is released from the tubular cells of kidney transplant recipients
Authors: Yamagishi Atsushi , Nishida Hayato , Ito Hiromi , Fukuhara Hiroki , Tsuchiya Norihiko 
Published: July 2022

Abstract
Background
Biomarkers are needed to diagnose kidney rejection in transplant recipients. We evaluated whether dipeptidyl peptidase-4 (DPP-4) could serve as a biomarker of rejection.

Methods
We determined DPP-4 concentrations and enzymatic activities in serum and urine, as well as DPP-4 expression in 49 kidney biopsy samples from 28 kidney transplant recipients. This study was approved by the ethical standards of the institutional research committee and comply with Helsinki declaration. All patients provided their informed consent. Donors were not from prisoners and were not paid or coerced.

Results
Serum and urinary DPP-4 activities closely correlated with DPP-4 concentrations, but were suppressed by DPP-4 inhibitors. Urinary DPP-4 concentrations increased with acute T cell-mediated rejection (ATCMR; p = 0.030) and higher Banff t and i scores (p < 0.001), and correlated with urinary protein/creatinine ratios (r = 0.450), and inversely with estimated glomerular filtration rate (r =  − 0.604). The area under the receiver operator characteristics curves for urinary DPP-4 concentrations with either Banff t3 or i3 scores were 0.811 (95% confidence interval: 0.687–0.934). The expression of DPP-4 in renal tubular cells was decreased in patients with ATCMR and higher in those with Banff t, i, ct, ci, ah, and ti scores, but was not associated with interstitial fibrosis/tubular atrophy.

Conclusions
We speculated that ATCMR leads to DPP-4 release from tubular cells into urine, resulting in a decrease in tubular cell expression. If so, then ATCMR would induce the elevation of urinary DPP-4 and could therefore serve as a biomarker of tubulitis.
Safeguarding equitable HIV service delivery at the health facility-level in a resource-limited setting during the pandemic
Authors: Tactacan-Abrenica Rosario Jessica , Almonte Dennis Gregg , Agrupis Kristal An , Malijan Greco Mark , Suzuki Shuichi , dela Cruz Ralph , Valdez Rich King , Arcangel Lalaine , Ariyoshi Koya , Smith Chris 
Published: July 2022

AbstractThe COVID-19 pandemic had a severe impact on delivering essential health services, including HIV service delivery. Among the challenges encountered and addressed by the HIV and AIDS Department of the San Lazaro Hospital were ensuring continued access to antiretroviral therapy and ensuring continuity of client education and empowerment. Two years into the pandemic, challenges still ensue, such as protecting health care providers from COVID-19 and regular clinical monitoring of clients. This highlights the importance of urgent action to strengthen the resilience of health systems at all its levels, not only to respond to sudden disturbances, but also to transform and evolve to be able to better face future pandemics.
How does face mask in COVID-19 pandemic disrupt face learning and recognition in adults with autism spectrum disorder?
Authors: Tso Ricky V. , Chui Celine O. , Hsiao Janet H. 
Published: July 2022

AbstractUse of face masks is one of the measures adopted by the general community to stop the transmission of disease during this ongoing COVID-19 pandemic. This wide use of face masks has indeed been shown to disrupt day-to-day face recognition. People with autism spectrum disorder (ASD) often have predisposed impairment in face recognition and are expected to be more vulnerable to this disruption in face recognition. Here, we recruited typically developing adult participants and those with ASD, and we measured their non-verbal intelligence, autism spectrum quotient, empathy quotient, and recognition performances of faces with and without a face mask covering the lower halves of the face. When faces were initially learned unobstructed, we showed that participants had a general reduced face recognition performance for masked faces. In contrast, when masked faces were first learned, typically developing adults benefit with an overall advantage in recognizing both masked and unmasked faces; while adults with ASD recognized unmasked faces with a significantly more reduced level of performance than masked faces—this face recognition discrepancy is predicted by a higher level of autistic traits. This paper also discusses how autistic traits influence processing of faces with and without face masks.
Making decisions about health information on social media: a mouse-tracking study
Authors: Lowry Mark , Trivedi Neha , Boyd Patrick , Julian Anne , Treviño Melissa , Lama Yuki , Heley Kathryn , Perna Frank 
Published: July 2022

AbstractHealth misinformation is a problem on social media, and more understanding is needed about how users cognitively process it. In this study, participants’ accuracy in determining whether 60 health claims were true (e.g., “Vaccines prevent disease outbreaks”) or false (e.g., “Vaccines cause disease outbreaks”) was assessed. The 60 claims were related to three domains of health risk behavior (i.e., smoking, alcohol and vaccines). Claims were presented as Tweets or as simple text statements. We employed mouse tracking to measure reaction times, whether processing happens in discrete stages, and response uncertainty. We also examined whether health literacy was a moderating variable. The results indicate that information in statements and tweets is evaluated incrementally most of the time, but with overrides happening on some trials. Adequate health literacy scorers were equally certain when responding to tweets and statements, but they were more accurate when responding to tweets. Inadequate scorers were more confident on statements than on tweets but equally accurate on both. These results have important implications for understanding the underlying cognition needed to combat health misinformation online.
Isolation and evaluation of bacteria associated with entomopathogenic nematode Heterorhabditis spp. against the spider mite, Tetranychus truncatus Ehara (Acari: Tetranychidae)
Authors: Ashwini M. N. , Bhaskar Haseena , Mathew Deepu , Shylaja M. R. , Girija D. 
Published: July 2022

Abstract
Background
Entomopathogenic nematodes (EPNs) belonging to the Heterorhabditis spp. harbour symbiotically associated bacteria which are toxic to a wide range of insect pests. Isolation, purification, characterization and mass multiplication of such bacteria will be a promising strategy in the management of the pests. This study was carried out to isolate the EPN from different locations, isolate and purify the bacterial colonies, characterize the bacteria through morphological and molecular strategies and to test the efficacy of different bacteria in the control of polyphagous Tetranychus truncatus Ehara mites.

Results
EPNs were isolated from soil samples at 11 localities of Kerala State, India, and used to infect the Galleria mellonella L. larvae. Bacteria associated with the haemolymph of the infected larvae were isolated, which on NBTA medium have produced circular to irregular, entire, opaque and smooth colonies. Sequence characterization of the 16S rRNA revealed nine isolates namely: one symbiotic bacterium Photorhabdus luminescens, two Pseudomonas aeruginosa, five Ochrobactrum sp. and one Stenotrophomonas maltophilia. Phylogenetic analysis using the sequences has further confirmed the bacterial identity. Evaluation of the cell suspension (CS) and cell-free supernatant (CFS) of P. luminescens, P. aeruginosa and Ochrobactrum sp. for their adulticidal and ovicidal efficiencies on T. truncatus had identified significant adulticidal effects by P. luminescens, followed by P. aeruginosa. After 96 h of treatment, P. luminescens at 108 cells/ml resulted in a significantly higher mortality rate of adult mites (64.00 and 60.67%, respectively, for CFS and CS), compared to that resulted by P. aeruginosa (38.67 and 33.33%).

Conclusions
Results of this study showed that P. luminescens associated with the EPN Heterorhabditis spp. is a promising biocontrol agent for T. truncatus.