bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shexiang Tongxin Dropping Pill Protects Against Chronic Heart Failure in Mice via Inhibiting the ERK/MAPK and TGF-β Signaling Pathways
Authors: Zhang Shuying , Liu Hanbing , Fang Qianqian , He Houhong , Lu Xiaoyan , Wang Yi , Fan Xiaohui 
Published: December 2021

Background: Chronic heart failure (CHF) is a major public health problem with high mortality and morbidity worldwide. Shexiang Tongxin Dropping Pill (STDP) is a widely used traditional Chinese medicine preparation for coronary heart disease and growing evidence proves that STDP exerts beneficial effects on CHF in the clinic. However, the molecular mechanism of the therapeutic effects of STDP on CHF remains largely unknown.Objective: This study aimed to elucidate the mechanism of action of STDP against CHF by integrating network pharmacology analysis and whole-transcriptome sequencing.Methods: First, the mouse model of CHF was established by the transverse aortic constriction (TAC) surgery, and the efficacy of STDP against CHF was evaluated by assessing the alterations in cardiac function, myocardial fibrosis, and cardiomyocyte hypertrophy with echocardiography, Masson’s trichrome staining, and wheat germ agglutinin staining. Next, a CHF disease network was constructed by integrating cardiovascular disease-related genes and the transcriptome sequencing data, which was used to explore the underlying mechanism of action of STDP. Then, the key targets involved in the effects of STDP on CHF were determined by network analysis algorithms, and pathway enrichment analysis was performed to these key genes. Finally, important targets in critical pathway were verified in vivo.Results: STDP administration obviously improved cardiac function, relieved cardiomyocyte hypertrophy, and ameliorated myocardial fibrosis in CHF mice. Moreover, STDP significantly reversed the imbalanced genes that belong to the disease network of CHF in mice with TAC, and the number of genes with the reverse effect was 395. Pathway analysis of the crucial genes with recovery efficiency revealed that pathways related to fibrosis and energy metabolism were highly enriched, while TGF-β pathway and ERK/MAPK pathway were predicted to be significantly affected. Consistently, validation experiments confirmed that inhibiting ERK/MAPK and TGF-β signaling pathways via reduction of the phosphorylation level of Smad3 and ERK1/2 is the important mechanism of STDP against CHF.Conclusion: Our data demonstrated that STDP can recover the imbalanced CHF network disturbed by the modeling of TAC through the multi-target and multi-pathway manner in mice, and the mechanisms are mainly related to inhibition of ERK/MAPK and TGF-β signaling pathways.
Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis
Authors: Boudart Céline , Su Fuhong , Pitisci Lorenzo , Dhoine Arnaud , Duranteau Olivier , Jespers Pascale , Herpain Antoine , Vanderpool Rebecca , Brimioulle Serge , Creteur Jacques , Naeije Robert , Van Obbergh Luc , Dewachter Laurence 
Published: December 2021

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis.Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation.Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor.Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.
Cost-Effectiveness of Portable Electrocardiogram for Screening Cardiovascular Diseases at a Primary Health Center in Ahmedabad District, India
Authors: Shah Komal , Pandya Apurvakumar , Kotwani Priya , Saha Somen , Desai Chintan , Tyagi Kirti , Saxena Deepak , Puwar Tapasvi , Gaidhane Shilpa 
Published: December 2021

Background: District Health Authority in Ahmedabad, Gujarat has introduced Project Lifeline, 12-lead portable ECG devices across all primary health centers (PHC) in the district to screen cardiac abnormalities among high-risk and symptomatic adults for providing primary management and proper timely referral. The prime purpose of the study was to assess the cost-effectiveness of portable ECG for the screening of cardiovascular diseases (CVD) among high-risk and symptomatic adults at the PHC in Ahmedabad, Gujarat.Methods: Cost-effective analysis was conducted using a societal perspective. An incremental costing approach was adapted, and cost-effectiveness analysis was done using a decision-analytic model. We surveyed 73 patients who screened positive for cardiac abnormality, documented the type of ECG abnormalities, and diagnosed CVD. The program cost was obtained from the implementers. Transition probabilities were derived from primary data supported by expert opinion for the intervention arm, while a systematic search of the literature was undertaken to derive transition probabilities for the control arm.Results: The ECG screening at PHC saves 2.90 life years at an incremental cost of 89.97 USD (6657.47 INR), yielding a cost-effectiveness ratio of 31.07 USD (2,299.06 INR) per life-year saved, which is below the willingness to pay threshold. The budget impact analysis was also performed. Results are sensitive to the relative risk reduction associated with the non-participation and the cost of initial screening.Conclusion: Cost-effectiveness analysis clearly shows that the facility to screen cardiac abnormality at the PHC level is highly recommended for high-risk adults and symptomatic cases.
SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation, A Dynamical Mathematical Model
Authors: Bensussen Antonio , Álvarez-Buylla Elena R. , Díaz José 
Published: December 2021

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL−1 s−1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5. To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.
Talking about premature ejaculation in primary care: the GET UP cluster randomised controlled trial
Authors: Barais Marie , Costa Marine , Montalvo Camille , Rannou Vincent , Vaillant-Roussel Hélène , Costa David , Cadier Sébastien , Pereira Bruno 
Published: December 2021

BackgroundPremature ejaculation (PE) is the most common sexual dysfunction in males. A previous qualitative study identified six communication strategies described by GPs to tackle this topic during consultations.AimTo determine whether these six strategies are more effective than usual care for promoting discussion about PE between patients and their GPs.Design and settingCluster randomised controlled trial, stratified in four French regions, with an intervention group (GPs who received a training session on the six communication strategies) and a control group (routine medical care). Participants were males aged 18–80 years consulting for a sexual, urogenital, or psychological reason.MethodThe efficacy of the training session in communication skills, compared with usual care, was evaluated by determining the percentage of patients who discussed PE with their GP (primary outcome). The percentage of enrolled patients with PE was calculated using a cut-off score >9 of the premature ejaculation diagnostic tool (PEDT) completed by the enrolled patients at Week 4 after the consultation. The quality-of-life changes were evaluated as the SF-12 scale score difference between baseline and Week 4 post-consultation.ResultsIn total, 130 patients were included by 32 GPs (n= 16 in the intervention andn= 16 in the control group). The percentage of patients who discussed PE was higher in the intervention group than in the control group (42.0% versus 4.9%, absolute difference = 37.1%; 95% confidence intervals [CI] = 24% to 50%,P<0.001).ConclusionTraining GPs in communication strategies about PE improves its detection.
Implementation of remote asthma consulting in general practice in response to the COVID-19 pandemic: an evaluation using extended Normalisation Process Theory
Authors: Stewart Jonathan , McCorry Noleen , Reid Helen , Hart Nigel , Kee Frank 
Published: December 2021

BackgroundThe COVID-19 pandemic has led to the rapid and reactive deployment of remote consulting in UK general practice. The delivery of acute and chronic asthma care has been affected. Extended Normalisation Process Theory (eNPT) provides a framework for evaluating the implementation of new complex interventions in routine practice, including examination of how context–intervention interactions affect implementation.AimTo explore the implementation of remote asthma consulting in UK general practice in response to the COVID-19 pandemic.Design & settingMixed-methods evaluation, which was informed by eNPT, in general practice in Northern Ireland.MethodData were collected from a range of healthcare professionals who provide asthma care using online questionnaires, interviews, and multidisciplinary focus groups. Analysis was informed by eNPT.ResultsTen themes were identified to describe and explain the contribution of general practice staff to implementation of remote asthma consulting. Staff identified novel alternatives to in-person review. Having a practice champion to drive implementation forward, and engage other practice staff, was important. Patient, staff, and healthcare system-contextual factors influencing implementation were identified including access to, understanding of, and willingness to use the technology required for remote consulting.ConclusionThe experiences of frontline healthcare professionals in this study indicate that remote asthma consulting has potential benefits in terms of access and effectiveness when implementation integrates seamlessly with face-to-face care for those who want or need it. Work is required at practice and healthcare system levels to realise this potential, and ensure implementation does not exacerbate existing healthcare inequalities.
Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor UBE-1099 Ameliorates Progressive Phenotype in Alport Syndrome Mouse Model
Authors: Kaseda Shota , Sannomiya Yuya , Horizono Jun , Kuwazuru Jun , Suico Mary Ann , Ogi Sayaka , Sasaki Ryoko , Sunamoto Hidetoshi , Fukiya Hirohiko , Nishiyama Hayato , Kamura Misato , Niinou Saki , Koyama Yuimi , Nara Futoshi , Shuto Tsuyoshi , Onuma Kazuhiro , Kai Hirofumi 
Published: December 2021

Background
Bardoxolone methyl activates nuclear factor erythroid 2–related factor 2 (Nrf2) via covalent binding and irreversible inhibition of Kelch-like ECH-associated protein 1 (Keap1), the negative regulator of Nrf2. Ongoing clinical trials of bardoxolone methyl show promising effects for patients with CKD. However, the direct inhibition of Keap1-Nrf2 protein-protein interaction (PPI) as an approach to activate Nrf2 is less explored.

Methods
We developed a noncovalent Nrf2 activator UBE-1099, which highly selectively inhibits Keap1-Nrf2 PPI, and evaluated its efficacy on the progressive phenotype in an Alport syndrome mouse model (Col4a5-G5X).

Results
Similar to bardoxolone methyl, UBE-1099 transiently increased proteinuria and reduced plasma creatinine in Alport mice. Importantly, UBE-1099 improved the glomerulosclerosis, renal inflammation, and fibrosis, and prolonged the life span of Alport mice. UBE-1099 ameliorated the dysfunction of Nrf2 signaling in the renal tissue of Alport mice. Moreover, transcriptome analysis in the glomerulus showed that UBE-1099 induced the expression of genes associated with the cell cycle and cytoskeleton, which may explain its unique mechanism of improvement such as glomerular morphologic change.

Conclusions
UBE-1099 significantly ameliorates the progressive phenotype in Alport mice. Our results revealed the efficacy of Keap1-Nrf2 PPI inhibitor for glomerulosclerosis and present a potential therapeutic drug for CKD.
A Propensity Score–Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease
Authors: Seethapathy Rituvanthikaa , Zhao Sophia , Long Joshua D. , Strohbehn Ian A. , Sise Meghan E. 
Published: December 2021

Key Points

Remdesivir was not approved in patients with eGFR <30 ml/min per 1.73 m2, and safety data are extremely limited.Compared with matched controls who did not receive remdesivir, there was no increased risk of cardiac, kidney, liver, or neurologic adverse events.Hyperglycemia was more common in remdesivir-treated patients; this may be explained by concomitant dexamethasone use.

Background
Remdesivir is not currently approved for patients with eGFR <30 ml/min per 1.73 m2. We aimed to determine the safety of remdesivir in patients with kidney failure.

Methods
This study was a retrospective cohort study of patients with COVID-19 hospitalized between May 2020 and January 2021 with eGFR <30 ml/min per 1.73 m2 who received remdesivir and historical controls with COVID-19 hospitalized between March 1, 2020 and April 30, 2020 prior to the emergency use authorization of remdesivir within a large health care system. Patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. Adverse events and hospital outcomes were recorded by manual chart review.

Results
The overall cohort included 34 hospitalized patients who initiated remdesivir within 72 hours of hospital admission with eGFR<30 ml/min per 1.73 m2 and 217 COVID-19 controls with eGFR <30 ml/min per 1.73 m2. The propensity score–matched cohort included 31 remdesivir-treated patients and 31 nonremdesivir-treated controls. The mean age was 74.0 (SD=13.8) years, 57% were women, and 68% were white participants. A total of 26% had ESKD. Among patients who were not on dialysis prior to initiating remdesivir, one developed worsening kidney function (defined as ≥50% increase in creatinine or initiation of KRT) compared with three in the historical control group. There was no increased risk of cardiac arrythmia, cardiac arrest, altered mental status, or clinically significant anemia or liver function test abnormalities. There was a significantly increased risk of hyperglycemia, which may be partly explained by the increased use of dexamethasone in the remdesivir-treated population.

Conclusions
In this propensity score–matched study, remdesivir was well tolerated in patients with eGFR <30 ml/min per 1.73 m2.
Teaching Mathematical Modeling of Cellular Systems with the VCell MathModel
Authors: King Jasia , Eroumé Kerbaï Saïd , Truckenmüller Roman , Giselbrecht Stefan , Cowan Ann , Loew Leslie M. , Carlier Aurélie 
Published: December 2021

ABSTRACT
Mathematical biology has emerged as a powerful approach to describe and understand biological systems. Here, we introduce an interactive teaching tool with a practical hands-on skill session plan to introduce students to the various components of a mathematical model with 4 different mathematical approaches (i.e., ordinary differential equations, partial differential equations, stochastic differential equations, and spatial stochastic differential equations) and their advantages and disadvantages. As such, we provide a didactic summary for instructors and students interested in using VCell MathModels for mathematical modeling; this work is also valuable for mathematics-savvy users who would like to exploit fully the capabilities of the VCell software.
PENINGKATAN KUALITAS PRODUK OLAHAN JAMU TRADISIONAL PADA MASA PANDEMI COVID-19 DI DESA KOLAM
Authors: Ritonga Winsyahputra , Fitrawaty Fitrawaty , Panggabean Deo Demonta , Oktora Maya , Harahap Mukti Hamjah , Irfandi Irfandi , Syah Dedy Husrizal 
Published: December 2021

Kegiatan pengabdian pada masyarakat ini dilaksanakan di Desa Kolam Kecamatan Percut Sei Tuan Kabupaten Deli Serdang, Sumatera Utara. Permasalahan yang dihadapi mitra yaitu teknologi pengolahan masih tradisional sehingga mitra mengalami kesusahan dalam memenuhi kuantitas yang dibutuhkan dalam waktu singkat, khususnya teknologi dalam pemerasan dan penggiling bahan baku, dan penyusunan laporan keuangan. Sehubungan dengan permasalahan yang dihadapi mitra, maka pada program pengabdian kepada masyarakat ini akan diwujudkan dengan mentransferkan alat/mesin penggiling jamu, pelatihan pembukuan dan manajemen keuangan. Metode yang digunakan untuk mencapai tujuan kegiatan pengabdian ini adalah metode pendidikan, sosialisasi, pendampingan peningkatan produk, pelatihan pembukuan dan manajemen usaha. Hasil kegiatan ini berupa telah diberikannya alat TTG Mesin penggiling jamu, serta diadakannya pelatihan serta pendampingan manajemen usaha dan pembukuan keuangan. Tingkat keberhasilan dari kegiatan pengabdian pada masyarakat di buktikan dengan peningkatan produksi, pendapatan dan pengetahuan mitra
Conexão entre múltiplas representações em atividades de função polinomial do 1º Grau
Authors: Aparecida de Faria Renata , Laburú Carlos Eduardo 
Published: December 2021

O presente artigo apresenta 3 (três) das atividades componentes de uma pesquisa de mestrado que está fundamentada nos referenciais das Múltiplas Representações e na Teoria dos Registros de Representação Semiótica. Considerando que os objetos matemáticos são acessíveis somente por representações e que não podemos confundir o objeto matemático com sua representação (Duval,2009), o objetivo da pesquisa foi investigar a mobilização de representações em diferentes registros do objeto matemático Função Polinomial do 1° Grau , com alunos do 1° ano do Ensino Médio em uma escola da Rede Pública do Norte do Paraná .A pesquisa denominada qualitativa apresentou os instrumentos de coletas de informações anotações em diário de campo da pesquisadora- , gravações em áudio e protocolo dos estudantes.As interações dialógicas ocorridas no desenvolvimento das atividades,permitiram a inferência das Funções Pedagógicas (Ainsworth,2006) de complementar, restringir e/ou aprofundar a cada nova representação em conexão com a atividade cognitiva de conversão.
$r$-Critical Numbers of Natural Intervals
Authors: Herzog Marcel , Kaplan Gil , Lev Arieh , Zigdon Romina 
Published: December 2021

The critical number $cr(r,n)$ of natural intervals $[r,n]$ was introduced by Herzog, Kaplan and Lev in 2014. The critical number $cr(r,n)$ is the smallest integer $t$ satisfying the following conditions: (i) every sequence of integers $S=\{r_1=r\leq r_2\leq \dotsb\leq r_k\}$ with $r_1+r_2 +\dotsb +r_k=n$ and $k\geq t$ has the following property: every integer between $r$ and $n-r$ can be written as a sum of distinct elements of $S$, and (ii) there exists $S$ with $k=t$, which satisfies that property. In this paper we study a variation of the critical number $cr(r,n)$ called the $r$-critical number $rcr(r,n)$. We determine the value of $rcr(r,n)$ for all $r,n$ satisfying $r\mid n$.
Hubungan Pengetahuan Ibu Dengan Kejadian Stunting Pada Balita Umur 12-59 Bulan
Authors: Purnama AL Jumiarsih , Hasanuddin Indirwan , Sulaeman S  
Published: December 2021

Stunting adalah gangguan kronik akibat kurangnya gizi sehingga menghambat pertumbuhan dan perkembangan pada bayi. Stunting adalah kondisi dimana terjadinya suatu gangguan pertumbuhan fisik yang ditandai dengan pertumbuhan yang tidak optimal sebagai akibat dari ketidak seimbangan gizi (Apriluana & Fikawati, 2018). Stunting masih menjadi permasalahan besar untuk sebagian besar negara di dunia. Penelitian ini bertujuan untuk mengetahui hubungan pengetahuan ibu dengan kejadian stunting pada balita usia 12-59 bulan di wilayah kerja Puskesmas Lawawoi Kabupaten Sidrap. Jenis penelitian yang digunakan adalah penelitian deskriptif analitik dengan pendekatan cross sectional studi. Sampel dalam penelitian adalah 30 responden dengan teknik penarikan sampel Purposive sampling. Data hasil penelitian dianalisis dengan menggunakan uji chi square. Hasil penelitian diperoleh bahwa ada hubungan antara pengetahuan ibu dengan kejadian stunting dengan nilai p = 0,02 (p < α = 0,05) pada balita usia 12-59 bulan di wilayah kerja Puskesmas Lawawoi Kabupaten Sidrap.
Sounds familiar(?): Expertise with specific musical genres modulates timing perception and micro-level synchronization to auditory stimuli
Authors: Danielsen Anne , Nymoen Kristian , Langerød Martin Torvik , Jacobsen Eirik , Johansson Mats , London Justin 
Published: December 2021

AbstractMusical expertise improves the precision of timing perception and performance – but is this expertise generic, or is it tied to the specific style(s) and genre(s) of one’s musical training? We asked expert musicians from three musical genres (folk, jazz, and EDM/hip-hop) to align click tracks and tap in synchrony with genre-specific and genre-neutral sound stimuli to determine the perceptual center (“P-center”) and variability (“beat bin”) for each group of experts. We had three stimulus categories – Organic, Electronic, and Neutral sounds – each of which had a 2 × 2 design of the acoustic factors Attack (fast/slow) and Duration (short/long). We found significant effects of Genre expertise, and a significant interaction for both P-center and P-center variability: folk and jazz musicians synchronize to sounds typical of folk and jazz in a different manner than the EDM/hip-hop producers. The results show that expertise in a specific musical genre affects our low-level perceptions of sounds as well as their affordance(s) for joint action/synchronization. The study provides new insights into the effects of active long-term musical enculturation and skill acquisition on basic sensorimotor synchronization and timing perception, shedding light on the important question of how nature and nurture intersect in the development of our perceptual systems.