bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the potential molecular biology of triptolide in the treatment of diabetic nephropathy: A narrative review
Authors: Gao Ying , Guo Zhaoan , Liu Yingying 
Published: December 2022

Objective:
To explore the potential mechanism of triptolide in diabetic nephropathy (DN) treatment using network pharmacology.

Methods:
The main targets of triptolide were screened using the TCMSP, DrugBank, and NCBI databases, and gene targets of DN were searched using the DrugBank, DisGeNET, TTD, and OMIM databases. All of the above targets were normalized using the UniProt database to obtain the co-acting genes. The co-acting genes were uploaded to the STRING platform to build a protein-protein interaction network and screen the core acting targets. Gene ontology and Kyoto encyclopedia of genes and genomes analyses of the core targets were performed using Metascape. Molecular docking validation of triptolide with the co-acting genes was performed using the Swiss Dock platform.

Results:
We identified 76 potential target points for triptolide, 693 target points for DN-related diseases, and 24 co-acting genes. The main pathways and biological processes involved are lipids and atherosclerosis, IL-18 signaling pathway, TWEAK signaling pathway, response to oxidative stress, hematopoietic function, and negative regulation of cell differentiation. Both triptolide and the active site of the core target genes can form more than 2 hydrogen bonds, and the bond energy is less than -5kJ/mol. Bioinformatics analysis showed that triptolide had a regulatory effect on most of the core target genes that are aberrantly expressed in DKD.

Conclusion:
Triptolide may regulate the body’s response to cytokines, hormones, oxidative stress, and apoptosis signaling pathways in DN treatment by down-regulating Casp3, Casp8, PTEN, GSA3B and up-regulating ESR1, and so forth.
Efficacy and safety of 400 mg efavirenz versus standard 600 mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: An open-label, interventional, randomized, non-inferiority trial
Authors: Dravid Ameet , Pilawan Anant S. , S. Anuradha , Morkar Dnyanesh N. , Ramapuram John T , Madhukarrao Kulkarni Milind , Naik K. Sunil , Bhrusundi Milind , K. R Raveendra , Nageswaramma Siddabathuni , Kulkarni Vinay 
Published: December 2022

Background:
To evaluate the non-inferiority of low dose efavirenz (400 mg) to standard dose efavirenz (600 mg), when taken in combination with tenofovir and lamivudine in Indian patients with HIV-1 infection.

Methods:
An open-label, interventional phase IV study with blinded assessment was conducted across 17 sites in India. HIV-1-infected antiretroviral therapy-naive adult patients (≥18 years of age) with a plasma HIV-1 viral load of at least 1000 copies per mL were randomized to receive either tenofovir/lamivudine/efavirenz (TLE) 400 or TLE 600. The primary endpoint was the difference in the proportion of patients achieving < 200 copies per mL at the end of 24 weeks.

Results:
A total of 265 patients were enrolled and were randomized in 1:1 ratio to TLE 400 group (130 patients) and TLE 600 group (135 patients). At week 24, the proportion of patients with a viral load of less than 200 copies per mL was 80.70% for TLE 400 and 78.95% for TLE 600 (difference 1.75%, 90% confidence interval: −7.01, 10.49) which was within the predefined margin of −10% (90% confidence interval). Significantly lower study drug-related adverse events were observed in TLE 400 group compared to TLE 600 group (52.30%, n = 68 vs 64.92%, n = 87; P = .037). The treatment discontinuation percentage was marginally higher by 2.08% in TLE 600 group.

Conclusion:
The fixed-dose combination of TLE 400 is non-inferior to TLE 600 in terms of viral suppression and has an improved safety profile over 24 weeks in adult Indian patients with HIV-1 infection.
Two-year follow-up of a young male with possible acute hemorrhagic leukoencephalitis: A case report
Authors: Wu Chen , Zhang Weiliang , Jiao Yan , Dong Minhui , Zhou Heng , Lv Yun , Yang Jun 
Published: December 2022

Rationale:
Acute hemorrhagic leukoencephalitis (AHLE) is a rare but fetal fulminant demyelinating disease of unknown etiology. It is commonly regarded as a severe variant of acute demyelinating encephalomyelitis (ADEM). Its rapid clinical deterioration and high mortality appeal to clinicians to attach importance to early diagnosis. Immunosuppressive therapy is the main management to attenuate the autoimmune process, but with varied response and prognosis.

Patient concerns:
A young male presented with moderate fever, headache and seizures after extraction of impacted teeth, and then deteriorated rapidly to deep coma. Initial magnetic resonance imaging (MRI) revealed multiple plaque-like lesions in bilateral cerebra, right thalamus and pontobulbar region with massive edematous swelling and multifocal small hemorrhagic foci. Inflammatory parameters in the peripheral blood were only mild higher with a pleocytosis in CSF.

Diagnosis:
His clinical presentation, laboratory evaluation and radiological features were consistent with a suspected diagnosis of AHLE.

Interventions:
He underwent pulse corticosteroids initially but failed to respond to it. However, his consciousness improved obviously when he was treated with multiple courses of intravenous injection of immunoglobulin (IVIG) combined with mycophenolate mofetil (MMF).

Outcomes:
The patient regained consciousness gradually on day 180 and was in minimally conscious state (MCS) during the two-year follow-up.

Lessons:
AHLE presents distinctly from classical ADEM, and the situation may pose a diagnostic challenge. Clinicians should be vigilant in recognizing AHLE because of its rapid clinical deterioration and high mortality. We highlight the critical role of multimodal MRI, particularly susceptibility-weighted imaging (SWI) in the diagnosis of AHLE if cerebral biopsies are unavailable. Multiple courses of IVIG with MMF may be effective when early single pulse of corticosteroids fails. Individual who survives the initial insult may carry relatively good prognosis.
Treatment of heterotopic cervical pregnancy by ultrasound-guided hysteroscopy: A case report and literature review
Authors: Sheng Shuman , Zhang Haomeng , Pan Zhengwu , Li Tao , Wang Xin , Shi Min , Wang Fei 
Published: December 2022

Background:
Heterotopic cervical pregnancy is a rare event of ectopic pregnancy with an incidence rate of < 1%. Herein, we report a rare case of successful treatment of heterotopic pregnancy following an in vitro fertilization-embryo transfer using ultrasound-guided hysteroscopy. In order to choose the best treatment option, we reviewed the clinical treatments and discussion of heterotopic cervical pregnancy over the last 15 years.

Methods:
The heterotopic pregnancy was terminated using ultrasound-guided hysteroscopy; however, the intrauterine pregnancy was maintained. We searched for the keywords “cervical pregnancy combined with intrauterine pregnancy,” “compound pregnancy,” “assisted reproductive technology,” “cervical pregnancy,” and “ectopic pregnancy” on PubMed to include articles published in the last 15 years.

Results:
The patient underwent an emergency cervical cerclage at 22 weeks’ gestation for cervical insufficiency and delivered a healthy newborn at 38 weeks’ gestation by transvaginal compliance. Twenty-one relevant case reports were selected. After analysis and discussion, we found that assisted reproductive technology is more likely to lead to heterotopic pregnancy than unassisted reproduction. Most women requesting the preservation of intrauterine embryos opted for surgical termination of cervical pregnancy and achieved the ideal outcomes.

Conclusion:
More attention should be paid to the diagnosis and treatment of heterotopic pregnancies to obtain the most optimal pregnancy outcome and long-term prognosis. Hysteroscopic surgery is a completely feasible cervical pregnancy treatment option with less postoperative impact on the mother and the intrauterine fetus.
The Physiatrist’s Guide to Cyclist Palsy: A Narrative Review
Authors: Farag Jordan , Sherwood David , Kuwabara Anne , Kumbhare Dinesh 
Published: December 2022

Abstract
Ulnar neuropathy at the wrist is a common consequence of long-duration cycling, a condition termed ‘Cyclist Palsy’. Although Cyclist Palsy has been clinically well-described in the literature, a gap exists regarding its electrodiagnostic evaluation and management. Patients with Cyclist Palsy present with a wide variety of sensory or motor impairments, depending on the location of the lesion. Electrodiagnostic studies are essential for accurate localization, with studies suggesting that pure motor lesions sparing the hypothenar muscles are most common among cyclists. This paper aims to provide the electromyographer and physiatrist with a clinical approach to Cyclist Palsy, and management strategies including patient education, equipment changes, and alterations to bicycle fit.
Fostering integration among students with different backgrounds using an orthotic community service program
Authors: Hassan Beygi Babak , Wang Kubert Tianghang , Chan Hiu Lam , Wu Hui Dong , Hung Percy Ho Tim , So Mike Ka Pui , Kwong Theresa , Wong Man Sang 
Published: December 2022

Background:
In this globalization era, institutions are developing strategies including international service-learning pedagogies to integrate global perspectives and dimensions into the learning and teaching processes to develop students' capacity in intercultural competence.

Objective:
This study aimed to assess the students' intercultural learning outcome through provision of orthotic community service to the less-privileged children.

Methods:
A Hong Kong–based university collaborated with 2 American universities to conduct an orthotic community service program for the children with cerebral palsy in mainland China. In the process of service delivery, the students with different backgrounds worked closely and students' professional knowledge, intercultural understanding, and communication skills were evaluated. A mixed-method approach was adopted to investigate on how this international program could facilitate meaningful interactions in clinical practices. Preprogram and postprogram surveys and focus group interviews were conducted. Statistical analyses were performed on the quantitative data, while interview data were analyzed thematically.

Results:
A comparison of preprogram and postprogram surveys showed that the students perceived this community service program important for enhancement of their capabilities to communicate with people from other cultures (n = 39, p < 0.05). It also showed an increase in local students' willingness to work with people from other cultures. Some themes related to intercultural competences were identified from the interview: “intercultural awareness, understanding, and communication” as well as openness to work/socialize with people from other cultures.”

Conclusions:
This study demonstrated that an international community service program could initiate positive changes in students' intercultural communication capability and interest to work with culturally different people.
T-cell responses induced by ChAdOx1 nCoV-19 (AZD1222) vaccine to wild-type severe acute respiratory syndrome coronavirus 2 among people with and without HIV in South Africa
Authors: McMahon William C. , Kwatra Gaurav , Izu Alane , Koen Anthonet L. , Greffrath Johann , Fairlie Lee , Patel Faeezah , Mukendi Christian K. , Mbele Nkululeko J. , Lala Rushil , Burgers Wendy A. , Nunes Marta C. , Cutland Clare L. , Gilbert Sarah C. , Lambe Teresa , Pollard Andrew J. , Madhi Shabir A. 
Published: December 2022

Objective(s):
This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses 14 days after single-dose ChAdOx1 nCoV-19 (AZD1222) vaccination in black Africans with and without HIV in South Africa, as well as determine the effect of AZD1222 vaccination on cell-mediated immune responses in people with HIV (PWH) with prior SARS-CoV-2 infection.

Methods:
A total of 70 HIV-uninfected people and 104 PWH were prospectively enrolled in the multicentre, randomized, double-blinded, placebo-controlled, phase Ib/IIa trial (COV005). Peripheral blood mononuclear cells (PBMCs) were collected from trial participants 14 days after receipt of first dose of study treatment (placebo or AZD1222 vaccine). T-cell responses against the full-length spike (FLS) glycoprotein of wild-type SARS-CoV-2 and mutated S-protein regions found in the Alpha, Beta and Delta variants were assessed using an ex-vivo ELISpot assay.

Results:
Among AZD1222 recipients without preceding SARS-CoV-2 infection, T-cell responses to FLS of wild-type SARS-CoV-2 were similarly common in PWH and HIV-uninfected people (30/33, 90.9% vs. 16/21, 76.2%; P = 0.138); and magnitude of response was similar among responders (78 vs. 56 SFCs/106 PBMCs; P = 0.255). Among PWH, AZD1222 vaccinees with prior SARS-CoV-2 infection, displayed a heightened T-cell response magnitude compared with those without prior infection (186 vs. 78 SFCs/106 PBMCs; P = 0.001); and similar response rate (14/14, 100% vs. 30/33, 90.9%; P = 0.244).

Conclusion:
Our results indicate comparable T-cell responses following AZD1222 vaccination in HIV-uninfected people and PWH on stable antiretroviral therapy. Our results additionally show that hybrid immunity acquired through SARS-CoV-2 infection and AZD1222 vaccination, induce a heightened T-cell response.
rcCAE: a convolutional autoencoder method for detecting intra-tumor heterogeneity and single-cell copy number alterations
Authors: Yu Zhenhua , Liu Furui , Shi Fangyuan , Du Fang 
Published: December 2022

AbstractIntra-tumor heterogeneity (ITH) is one of the major confounding factors that result in cancer relapse, and deciphering ITH is essential for personalized therapy. Single-cell DNA sequencing (scDNA-seq) now enables profiling of single-cell copy number alterations (CNAs) and thus aids in high-resolution inference of ITH. Here, we introduce an integrated framework called rcCAE, to accurately infer cell subpopulations and single-cell CNAs from scDNA-seq data. A convolutional autoencoder (CAE) is employed in rcCAE to learn latent representation of the cells as well as distill copy number information from noisy read counts data. This unsupervised representation learning via the CAE model makes it convenient to accurately cluster cells over the low-dimensional latent space, and detect single-cell CNAs from enhanced read counts data. Extensive performance evaluations on simulated datasets show rcCAE outperforms existing CNA calling methods, and is highly effective in inferring clonal architecture. Furthermore, evaluations of rcCAE on two real datasets demonstrate it is able to provide more refined clonal structure, of which some details are lost in clonal inference based on integer copy numbers.
NetGO 3.0: Protein Language Model Improves Large-scale Functional Annotations
Authors: Wang Shaojun , You Ronghui , Liu Yunjia , Xiong Yi , Zhu Shanfeng 
Published: December 2022

AbstractAs one of the state-of-the-art automated function prediction (AFP) methods, NetGO 2.0 integrates multi-source information to improve the performance. However, it mainly utilizes the proteins with experimentally supported functional annotations without leveraging valuable information from a vast number of unannotated proteins. Recently, protein language models have been proposed to learn informative representations (e.g., Evolutionary Scale Modelling (ESM)-1b embedding) from protein sequences based on self-supervision. We represent each protein by ESM-1b and use logistic regression (LR) to train a new model, LR-ESM, for AFP. The experimental results show that LR-ESM achieves comparable performance with the best-performing component of NetGO 2.0. Therefore, by incorporating LR-ESM into NetGO 2.0, we develop NetGO 3.0 to improve the performance of AFP extensively. NetGO 3.0 is freely accessible athttps://dmiip.sjtu.edu.cn/ng3.0.
ERBB-activated myofibroblastic cancer-associated fibroblasts promote local metastasis of pancreatic cancer
Authors: Mucciolo Gianluca , Henríquez Joaquín Araos , Teles Sara Pinto , Manansala Judhell S. , Jihad Muntadher , Li Wenlong , Lloyd Eloise G. , Cheng Priscilla S.W. , Biffi Giulia 
Published: December 2022

SUMMARYPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective treatment strategies. We previously identified TGF-β as a main driver of myofibroblastic CAFs (myCAFs). Here, we show that EGFR/ERBB2 signaling is induced by TGF-β in myCAFs through an autocrine process mediated by the ERBB ligand amphiregulin. Inhibition of this ERBB-signaling network in PDAC organoid-derived cultures and mouse models impacts distinct CAF subtypes, providing insights into mechanisms underpinning their heterogeneity. Remarkably, ERBB-activated myCAFs promote local PDAC metastasis in mice, unmasking functional significance in myCAF heterogeneity. Finally, analyses of other cancer datasets suggest these processes might operate in other malignancies. These data provide functional relevance to CAF heterogeneity and identify a potential target for preventing local tumor invasion in PDAC.
Rapid Restoration of Cell Phenotype and Matrix Forming Capacity Following Transient Nuclear Softening
Authors: Locke Ryan C. , Miller Liane , Lemmon Elisabeth A. , Assi Sereen S. , Jones Dakota L. , Bonnevie Eddie D. , Burdick Jason A. , Heo Su Jin , Mauck Robert L. 
Published: December 2022

AbstractThe dense extracellular matrix of connective tissues impedes cell migration and subsequent matrix formation at sites of injury. We recently employed transient nuclear softening via histone deacetylase inhibition with trichostatin A (TSA) treatment to overcome the stiff nuclear impediments to cell migration through dense tissues and electrospun matrices. Despite these positive findings, the long-term implications of transient nuclear softening on cell transcriptional phenotype and matrix formation capacity are unknown. To address this, we investigated the influence of transient TSA treatment on porcine meniscal cell behavior, beginning with the efficacy and reproducibility of transient TSA treatment on histone acetylation and chromatin remodeling in vitro and cell migration through native meniscus tissue. Within 3 days after cessation of transient TSA treatment, histone acetylation and chromatin remodeling returned to control levels. Following TSA treatment, endogenous cell migration through native meniscus tissue increased greater than 3-fold compared to controls. Importantly, meniscal cells completely restored their transcriptional phenotype and maintained their capacity to respond transcriptionally and functionally to a secondary pro-matrix stimuli (i.e., transforming growth factor β3) within 7 days after cessation of TSA treatment. Towards translation, we also showed the feasibility of biomaterial-delivered TSA to increase endogenous cell migration to a wound edge ex vivo. Together, this work defines the efficacy, reproducibility, safety, and feasibility of future translational approaches for nuclear softening to treat dense connective tissue injuries.
Redundant representations are required to disambiguate simultaneously presented complex stimuli
Authors: Johnston W. Jeffrey , Freedman David J. 
Published: December 2022

AbstractAn individual observing a barking dog and purring cat together in a field has distinct pairs of representations of the two animals in their visual and auditory systems. Without prior knowledge, how does the observer infer that the dog barks and the cat purrs? This integration of distributed representations is called the assignment problem, and it must be solved to integrate distinct representations across but also within sensory modalities. Here, we identify and analyze a solution to the assignment problem: the representation of one or more common stimulus features in pairs of relevant brain regions – for example, estimates of the spatial position of both the cat and the dog represented in both the visual and auditory systems. We characterize how the reliability of this solution depends on different features of the stimulus set (e.g., the size of the set and the complexity of the stimuli) and the details of the split representations (e.g., the precision of each stimulus representation and the amount of overlapping information). Next, we implement this solution in a biologically plausible receptive field code and show how constraints on the number of neurons and spikes used by the code force the brain to navigate a tradeoff between local and catastrophic errors. We show that, when many spikes and neurons are available, representing stimuli from a single sensory modality can be done more reliably across multiple brain regions, despite the risk of assignment errors. Finally, we show that a feedforward neural network can learn the optimal solution to the assignment problem. We also discuss relevant results on assignment errors from the human working memory literature and show that several key predictions of our theory already have support.
Gremlin 1 is required for macrophage M2 polarization
Authors: Mthunzi Liberty , Rowan Simon C , Knaus Ulla G , McLoughlin Paul 
Published: December 2022

AbstractPro-proliferative, M2-like polarization of macrophages is a critical step in the development of fibrosis and remodeling in chronic lung diseases such as pulmonary fibrosis and pulmonary hypertension. Macrophages in healthy and diseased lungs express gremlin 1 (Grem1), a secreted glycoprotein that acts in both paracrine and autocrine manners to modulate cellular function. Increased Grem1 expression plays a central role in pulmonary fibrosis and remodelling, however, the role of Grem1 in M2-like polarization of macrophages has not previously been explored. The results reported here show that recombinant Grem1 potentiated M2-like polarization of mouse macrophages and bone marrow derived macrophages (BMDM) in response to the Th2 cytokines IL4 and IL13. Genetic depletion of Grem1 in BMDMs inhibited M2 polarization while exogenous gremlin 1 could partially rescue this effect. Taken together, these findings reveal that gremlin 1 is required for M2-like polarization of macrophages.
Low-pass sequencing plus imputation using avidity sequencing displays comparable imputation accuracy to sequencing by synthesis while reducing duplicates
Authors: Li Jeremiah H. , Findley Karrah , Pickrell Joseph K. , Blease Kelly , Zhao Junhua , Kruglyak Semyon 
Published: December 2022

AbstractLow-pass sequencing with genotype imputation has been adopted as a cost-effective method for genotyping. The most widely used method of short-read sequencing uses sequencing by synthesis (SBS). Here we perform a study of a novel sequencing technology — avidity sequencing. In this short note, we compare the performance of imputation from low-pass libraries sequenced on an Element AVITI system (which utilizes avidity sequencing) to those sequenced on an Illumina NovaSeq 6000 (which utilizes SBS) with an SP flow cell for the same set of biological samples across a range of genetic ancestries. We observed dramatically lower duplication rates in the data deriving from the AVITI system compared to the NovaSeq 6000, resulting in higher effective coverage given a fixed number of sequenced bases, and comparable imputation accuracy performance between sequencing chemistries across ancestries. This study demonstrates that avidity sequencing is a viable alternative to the standard SBS chemistries for applications involving low-pass sequencing plus imputation.