bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza a virus regulates interferon signaling and its associated genes; MxA and STAT3 by cellular miR-141 to ensure viral replication
Authors: Alalem Mai , Dabous Emad , Awad Ahmed M. , Alalem Nedaa , Guirgis Adel A. , El-Masry Samir , Khalil Hany 
Published: August 2023

AbstractThe antiviral response against influenza A virus (IAV) infection includes the induction of the interferon (IFN) signaling pathway, including activation of the STATs protein family. Subsequently, antiviral myxovirus resistance (MxA) protein and other interferon-stimulated genes control virus replication; however, the molecular interaction of viral-mediated IFN signaling needs more investigation. Host microRNAs (miRNAs) are small non-coding molecules that posttranscriptionally regulate gene expression. Here, we sought to investigate the possible involvement of miR-141 in IAV-mediated IFN signaling. Accordingly, the microarray analysis of A549 cells transfected with precursor miR-141 (pre-miR-141) was used to capture the potentially regulated genes in response to miR-141 overexpression independent of IAV infection. The downregulation of targeted genes by miR-141, in addition to viral gene expression, was investigated by quantitative real-time PCR, western blot analysis, and flow cytometric assay. Our findings showed a significant upregulation of miR-141 in infected A549 cells with different strains of IAV. Notably, IAV replication was firmly interrupted in cells transfected with the miR-141 inhibitor. While its replication significantly increased in cells transfected with pre-miR-141 confirming the crucial role of miRNA-141 in supporting virus replication. Interestingly, the microarray data of miR-141 transduced A549 cells showed many downregulated genes, including MxA, STAT3, IFI27, and LAMP3. The expression profile of MxA and STAT3 was significantly depleted in infected cells transfected with the pre-miR-141, while their expression was restored in infected cells transfected with the miR-141 inhibitor. Unlike interleukin 6 (IL-6), the production of IFN-β markedly decreased in infected cells that transfected with pre-miR-141, while it significantly elevated in infected cells transfected with miR-141 inhibitor. These data provide evidence for the crucial role of miR-141 in regulating the antiviral gene expression induced by IFN and IL-6 signaling during IAV infection to ensure virus replication.
Mid-term results of endoscopic mitral valve repair and insights in surgical techniques for isolated posterior prolapse
Authors: Squiccimarro Enrico , Margari Vito , Kounakis Georgios , Visicchio Giuseppe , Pascarella Clemente , Rotunno Crescenzia , Carbone Carmine , Paparella Domenico 
Published: August 2023

Abstract
Background
The adoption of minimally invasive techniques to perform mitral valve repair surgery is increasing. This is enhanced by the compelling evidence of satisfactory short-term results and lower major morbidity. We analyzed mid-term follow-up results of our experience, and further compared two techniques: isolated leaflet resection and neochord implantation for posterior leaflet prolapse.

Methods
Data for all consecutive endoscopic mitral valve repairs via video-assisted right anterior mini-thoracotomy were analyzed between December 2012 and September 2021. The early and mid-term follow-up results were ascertained. The main outcome was the incidence of mortality and the recurrence of significant mitral regurgitation during follow-up which were summarized by the Kaplan-Meier estimator and compared between treatment arms using the stratified log-rank test. Secondary outcomes were the early-postoperative results including 30-days mortality and the occurrence of major complications.

Results
A total of 309 patients were included. Along with ring annuloplasty, 136 (44.4%) patients received posterior leaflet resection (122 isolated) whereas 97 (31.1%) underwent posterior leaflet chords implantation (88 isolated). Forty-nine patients had annuloplasty alone. In-hospital mortality was 1.0%. Mean follow-up was 28.8 ± 22.0 months (maximum 8.3 years). Kaplan–Meier survival rate at 5 years was 97.3 ± 1.0%, mitral regurgitation ($$\ge$$3+) or valve reoperation free-survival at 5 years was estimated as 94.5 ± 2.3%. Subgroup time-to-event analysis for the indexed outcomes showed no statistical significance between the techniques.

Conclusions
Endoscopic mitral valve repair is safe and associated with excellent short- and mid-term outcomes. No differences were found between leaflet resection and gore-tex chords implantation for posterior leaflet prolapse.
GTM-decon: guided-topic modeling of single-cell transcriptomes enables sub-cell-type and disease-subtype deconvolution of bulk transcriptomes
Authors: Swapna Lakshmipuram Seshadri , Huang Michael , Li Yue 
Published: August 2023

AbstractCell-type composition is an important indicator of health. We present Guided Topic Model for deconvolution (GTM-decon) to automatically infer cell-type-specific gene topic distributions from single-cell RNA-seq data for deconvolving bulk transcriptomes. GTM-decon performs competitively on deconvolving simulated and real bulk data compared with the state-of-the-art methods. Moreover, as demonstrated in deconvolving disease transcriptomes, GTM-decon can infer multiple cell-type-specific gene topic distributions per cell type, which captures sub-cell-type variations. GTM-decon can also use phenotype labels from single-cell or bulk data to infer phenotype-specific gene distributions. In a nested-guided design, GTM-decon identified cell-type-specific differentially expressed genes from bulk breast cancer transcriptomes.
Statistical modeling of gut microbiota for personalized health status monitoring
Authors: Zhu Jinlin , Xie Heqiang , Yang Zixin , Chen Jing , Yin Jialin , Tian Peijun , Wang Hongchao , Zhao Jianxin , Zhang Hao , Lu Wenwei , Chen Wei 
Published: August 2023

Abstract
Background
The gut microbiome is closely associated with health status, and any microbiota dysbiosis could considerably impact the host’s health. In addition, many active consortium projects have generated many reference datasets available for large-scale retrospective research. However, a comprehensive monitoring framework that analyzes health status and quantitatively present bacteria-to-health contribution has not been thoroughly investigated.

Methods
We systematically developed a statistical monitoring diagram for personalized health status prediction and analysis. Our framework comprises three elements: (1) a statistical monitoring model was established, the health index was constructed, and the health boundary was defined; (2) healthy patterns were identified among healthy people and analyzed using contrast learning; (3) the contribution of each bacterium to the health index of the diseased population was analyzed. Furthermore, we investigated disease proximity using the contribution spectrum and discovered multiple multi-disease-related targets.

Results
We demonstrated and evaluated the effectiveness of the proposed monitoring framework for tracking personalized health status through comprehensive real-data analysis using the multi-study cohort and another validation cohort. A statistical monitoring model was developed based on 92 microbial taxa. In both the discovery and validation sets, our approach achieved balanced accuracies of 0.7132 and 0.7026, and AUC of 0.80 and 0.76, respectively. Four health patterns were identified in healthy populations, highlighting variations in species composition and metabolic function across these patterns. Furthermore, a reasonable correlation was found between the proposed health index and host physiological indicators, diversity, and functional redundancy. The health index significantly correlated with Shannon diversity ($$\rho = 0.07$$

ρ
=
0.07

) and species richness ($$\rho = 0.44$$

ρ
=
0.44

) in the healthy samples. However, in samples from individuals with diseases, the health index significantly correlated with age ($$\rho = 0.12$$

ρ
=
0.12

), species richness ($$\rho = 0.46$$

ρ
=
0.46

), and functional redundancy ($$\rho = - 0.16$$

ρ
=
-
0.16

). Personalized diagnosis is achieved by analyzing the contribution of each bacterium to the health index. We identified high-contribution species shared across multiple diseases by analyzing the contribution spectrum of these diseases.

Conclusions
Our research revealed that the proposed monitoring framework could promote a deep understanding of healthy microbiomes and unhealthy variations and served as a bridge toward individualized therapy target discovery and precise modulation.
Prevalence of subclinical systolic dysfunction in Takayasu’s arteritis and its association with disease activity: a cross-sectional study
Authors: de Lourdes Castro de Oliveira Figue Maria , Costa Maria Carolina Moura , Costa Maria Clara Moura , Lobo Paulo Rocha , Sanches Leonardo Vinicius , Martins Kátia Maria Alves , Sousa Anna Paula Mota Duque , Pedreira Ana Luisa Souza , Barreto Santiago Mittermayer 
Published: August 2023

Abstract
Background
Takayasu’s arteritis (TA) is a vasculitis that affects the aorta and its branches and causes stenosis, occlusion, and aneurysms. Up to 60% of TA patients are associated with cardiac involvement which confers a poor prognosis. Global longitudinal strain (GLS) analysis is an echocardiographic technique that can detect the presence of subclinical systolic dysfunction. Hence, this study aimed to describe the prevalence of subclinical systolic dysfunction in patients with TA using the GLS method and to correlate this finding with disease activity using the ITAS-2010 (Indian Takayasu Activity Score).

Methods
Thirty patients over 18 years of age who met the American College of Rheumatology (ACR) 1990 criteria for TA were included. The sample was submitted for medical record review, clinical and echocardiographic evaluation, and application of ITAS-2010. The cutoff for systolic dysfunction was GLS > – 20%.

Results
Of the 30 patients analyzed, 25 (83.3%) were female, and the mean age was 42.6 years (± 13.2). The median time since diagnosis was 7.5 years [range, 3–16.6 years], and the type V angiographic classification was the most prevalent (56.7%). Regarding echocardiographic findings, the median ejection fraction (EF) was 66% [61–71%] and the GLS was − 19.5% [-21.3 to -15.8%]. Although half of the participants had reduced GLS, only two had reduced EF. Eleven patients (33.%) met the criteria for activity. An association was found between disease activity and reduced GLS in eight patients (P = 0.02) using the chi-square test.

Conclusion
GLS seems to be an instrument capable of the early detection of systolic dysfunction in TA. The association between GLS and disease activity in this study should be confirmed in a study with a larger sample size.
Increasing Quality and Efficiency of the Radiotherapy Treatment Planning Process by Constructing and Implementing a Workflow-Monitoring Application
Authors: Heilemann Gerd , Georg Dietmar , Dobiasch Matthias , Widder Joachim , Renner Andreas 
Published: August 2023

PURPOSE To demonstrate how the efficiency of the treatment planning processes of a university radiation oncology department (2,500 new patients/year) could be improved by constructing and implementing a workflow-monitoring application. METHODS A web-based application was developed in house, which enhanced the process management tools of the clinic's oncology information system. The application calculates the days left for the next task in the treatment planning process and visualizes the information on a browser-based whiteboard. Workflow monitoring considers tumor types (breast, prostate, lung, etc) and treatment techniques and is backward planned from the planned start of treatment. The effect of introducing this application was analyzed over four phases: (1) baseline data without the workflow-monitoring application, (2) after introducing workflow visualization via a browser-based whiteboard, (3) after upgrading the whiteboard and introducing backend rules, and (4) after updating these rules on the basis of data from the previous phase. RESULTS Implementing the workflow-monitoring application and the introduced measures significantly reduced delays and, consequently, stress and a negative working atmosphere in the treatment planning process. Most notably, the amount of last-minute physics checks (on the day of the treatment start) could be reduced by 50%. CONCLUSION The study showed what measures can help organize and prioritize the treatment planning workflow. The increased efficiency is believed to improve the quality and reduce the risk of human error.
Implementation of Brachytherapy for Patients With Cervical Cancer in Ethiopia: A 3-Year Practice Report
Authors: Kibret Yitbarek M. , Tigeneh Wondemagegnehu , Jemal Ahmedin , Kantelhardt Eva J. 
Published: August 2023

PURPOSE Although cervical cancer is the second most commonly diagnosed cancer in Ethiopia, brachytherapy (BT) was not a component in patient treatment until 2015. The purpose of this study was to identify the patterns of utilization as well as to describe the practice of BT in Ethiopia. MATERIALS AND METHODS A retrospective descriptive data analysis of 138 patients with cervical cancer treated with a curative potential using BT from 2015 to 2018 at Tikur Anbassa Specialized Hospital, which housed the only BT facility in Ethiopia during the study period. RESULTS During the first 3-year period of BT service commencement, each year n = 37, n = 36, and n = 65 patients with cervical cancer were treated, respectively, with curative intention treatment. The median age of these 138 patients was 50 years (range, 22-75). All the patients were in International Federation of Gynecology and Obstetrics stage Ib–IIIb group, and stage IIb (66.4%) was the predominant. Majority (79%) of the patients were treated primarily with radiotherapy (RT), while 21% received RT after surgery. More than half of these patients (62%) received a total RT dose of 82 Gy in equivalent dose in 2 Gy fractions (EQD2), while the rest received a dose ranging from 76 to 86 Gy. Concurrent cisplatin with RT was given only for 36% of the patients for undocumented reasons. The overall treatment time including both external-beam RT and BT was greater than 8 weeks in 21% of the patients. CONCLUSION The utilization of BT service increased gradually and BT enabled the delivery of a higher RT dose to patients with cervical cancer (mostly stage IIB). However, there was protracted treatment duration and low concurrent chemotherapy utilization.
Organizational Impact of Immunotherapies in Advanced Cancers in France
Authors: Grumberg Valentine , Chouaïd Christos , Gaudin Anne-Françoise , Le Tourneau Christophe , Marabelle Aurélien , Bongiovanni-Delarozière Isabelle , Cotté François-Emery , Borget Isabelle 
Published: August 2023

PURPOSE In 2020, the French National Authority for Health ( Haute Autorité de Santé) published a methodologic guide called organizational impact (OI) cartography to define and structure assessment of the OI of health technologies. As immunotherapies are associated with extended survival and improved quality of life in advanced cancer, we aimed to identify OIs that immunotherapies had on health care systems and professionals. To our knowledge, we suggest the first implementation for OI assessment on the basis of the cartography. METHODS A literature review was conducted, and interviews with health care professionals (HCPs) were performed to identify OIs of immunotherapies. They were asked if immunotherapies had OIs classified into three macrocriteria, namely, impact on the care process (six criteria), impact on capacities and skills required (six criteria), and impact on society (four criteria). If an OI was mentioned for a criterion, information on its impact (minor/moderate/major) and its timing was collected. We considered that an OI existed when 75% of HCPs mentioned an impact for a given criterion. RESULTS Overall, 27 HCPs were interviewed. For 12 of 16 criteria, most HCPs mentioned an impact, whereas the literature identified impacts for 11 criteria. Four criteria (skills and transfer between HCPs, scheduling capabilities, and social relationship) had consensus among HCPs and a high impact; two criteria (rhythm or care duration, working/living conditions) showed consensus but a moderate impact; two criteria (funding and scheduling capabilities cross-structure) had a high impact but no consensus. For eight criteria (as environment or inequity), there was no consensus and moderate impact. CONCLUSION The introduction of immunotherapies for advanced cancer has had an important OI in France, regarding capacities and skills. Further research using qualitative analysis of interviews will provide more information regarding OI.
Outcome of Patients With Early-Stage Mismatch Repair Deficient Colorectal Cancer Receiving Neoadjuvant Immunotherapy: A Systematic Review
Authors: Chakrabarti Sakti , Grewal Udhayvir Singh , Vora Kruti Bhagirath , Parikh Aparna Raj , Almader-Douglas Diana , Mahipal Amit , Sonbol Mohamad (Bassam) B. 
Published: August 2023

PURPOSE We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)–based regimens. METHODS MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti–PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.
Transcriptomic Signatures Associated With Outcomes in Recurrent Prostate Cancer Treated With Salvage Radiation, Androgen-Deprivation Therapy, and Enzalutamide: Correlative Analysis of the STREAM Trial
Authors: Bitting Rhonda L. , Wu Yuan , Somarelli Jason A. , Proudfoot James A. , Liu Yang , Davicioni Elai , George Daniel J. , Armstrong Andrew J. 
Published: August 2023

PURPOSE Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive systemic approach. METHODS We performed a retrospective analysis of a prospective phase II multicenter trial of enzalutamide, ADT, and salvage radiotherapy in men with rising PSA after RP. Tumor tissue was analyzed using the Decipher platform for gene expression, including a novel prostate subtyping classifier, PTEN loss, homologous recombination deficiency (HRD), and ADT response. Cox models were used to associate signature scores with progression-free survival (PFS). RESULTS Of the 38 men enrolled, 31 had tissue with sufficient-quality RNA for genomic analysis. Luminal differentiated (LD) subtype tumors had the longest 3-year PFS at 89% compared with 19% in the luminal proliferating subtype. Men with signatures of PTEN loss (hazard ratio [HR], 1.32; 95% CI, 1.07 to 1.64; P = .01) or HRD (HR, 1.21; 95% CI, 1.05 to 1.39; P = .009) had worse PFS, while those with higher ADT response signature scores (HR, 0.75; 95% CI, 0.61 to 0.94; P = .01) were associated with improved PFS. Analysis of these signatures in a large cohort (n = 5,330) of RP samples from patients with biochemical recurrence found that these signatures provide complementary information related to outcomes with salvage radiation. CONCLUSION Despite aggressive systemic therapy with salvage radiation, nearly 50% of high-risk men relapse within 3 years. We show that LD and higher ADT sensitivity tumors had favorable outcomes. Those with a luminal proliferating subtype, PTEN loss, and/or HRD signatures had poor outcomes despite ADT/radiation and enzalutamide and may benefit from alternative approaches.
Thinking Out to In: Psychological Considerations and Strategies for Optimal Sport and Exercise Performance
Authors: Mellano Kathleen T. 
Published: August 2023

Apply It!
By reading this article, you will learn how:
• To choose or design a task that is challenging but presents some opportunity for success.
• Working in groups can foster or inhibit motivation and how to pair people based on skill level and existing relationships.
• To set aside a few mindful minutes before engaging in sport or exercise to warm-up mentally; similar to how one physically warms-up.
The Use of Botulinum Toxin in Medicine: Safety and Efficacy Based on the Latest Research
Authors: Jaremek Anna , Kępa Joanna , Kandefer Norbert , Wyszkowski Michał , Grabarczyk Aleksandra , Pawlak Anna , Grad Sylwia , Gregorek Małgorzata , Gregorek Paweł 
Published: August 2023

Introduction and aim of the study: Botulinum toxin, produced by anaerobic bacteria of the Clostridium botulinum family, is one of the most potent organic compounds known to man. Despite its toxicity, it has found widespread use in medicine. From applications in aesthetic medicine, through the treatment of various disease entities, botulinum toxin has become an extremely valuable tool in the hands of doctors. The aim of this study is to review the latest research on the use of botulinum in medicine, with an emphasis on its safety and effectiveness.

Methodology: The review work is mainly based on articles searched in the Pubmed and Google Scholar databases in the years 2016-2023. The study was conducted by reviewing keywords such as "botulin", "botulin toxin", "botulin treatment", "botulin aesthetic".
Current state of knowledge: Botulinum is used in the treatment of such disease entities as hyperhidrosis, cervical dystonia, migraines, neurogenic bladder, as well as in the treatment of scars and wrinkles. The use of botulinum in medicine is safe, provided that it is used by qualified specialists and in appropriate doses. An area that requires further research is the impact of long-term botulinum therapy on the antibodies produced against the toxin. Additionally, an important area for further research is patient monitoring, appropriate dose adjustment and frequency of administration, which in turn can increase the effectiveness of treatment.
Summary: Botulinum toxin is an effective tool in medicine, which has many applications. However, as with any drug, it requires appropriate use and understanding of potential side effects. Further research and education are key to fully exploiting its potential and assessing the risk associated with long-term use.