bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver saturated fat content associates with hepatic DNA methylation in obese individuals
Authors: Sehgal Ratika , Perfilyev Alexander , Männistö Ville , Ågren Jyrki , Nilsson Emma , Käkelä Pirjo , Ling Charlotte , de Mello Vanessa D. , Pihlajamäki Jussi 
Published: February 2023

Abstract
Background
Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals.

Results
We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA).

Conclusions
Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations.
Imidacloprid poisoning in a young female: a case report
Authors: Bhatta Om Prakash , Chand Sabita , Chand Hemant , Poudel Ram Chandra , Lamichhane Ram Prasad , Singh Abhi Kumar , Subedi Nuwadatta 
Published: February 2023

Abstract
Background
Imidacloprid, a neonicotinoid insecticide, is widely used in agricultural settings. Consequently, cases of accidental and suicidal poisoning are increasingly seen in clinical practice. Although cases with varied clinical presentations and toxicological profiles have been reported, standard management principles are lacking.

Case presentation
We present a case of Imidacloprid poisoning in a 25-year-old previously healthy indigenous Tamang female without a classic toxidrome requiring ventilatory support, complicated by a prolonged neuropsychiatric sequela.

Conclusions
Although uncommonly reported, imidacloprid toxicity may lead to life-threatening complications and hence should be suspected in cases of unidentified poisoning with a relevant toxidrome. Vigilance on the part of treating physicians plays a crucial role in appropriate management.
HIV co-opts a cellular antiviral mechanism, activation of stress kinase PKR by its RNA, to enable splicing of rev/tat mRNA
Authors: Namer Lise Sarah , Harwig Alex , Heynen Stephan P. , Das Atze T. , Berkhout Ben , Kaempfer Raymond 
Published: February 2023

Abstract
Background
Activation of RNA-dependent stress kinase PKR, especially by viral double-stranded RNA, induces eukaryotic initiation factor 2 α-chain (eIF2α) phosphorylation, attenuating thereby translation. We report that this RNA-mediated negative control mechanism, considered a cornerstone of the cell’s antiviral response, positively regulates splicing of a viral mRNA.

Results
Excision of the large human immunodeficiency virus (HIV) rev/tat intron depends strictly on activation of PKR by the viral RNA and on eIF2α phosphorylation. Rev/tat mRNA splicing was blocked by viral PKR antagonists Vaccinia E3L and Ebola VP35, as well as by a trans-dominant negative mutant of PKR, yet enhanced by overexpressing PKR. Expression of non-phosphorylatable mutant eIF2αS51A, but not of wild type eIF2α, abrogated efficient splicing of rev/tat mRNA. By contrast, expression of eIF2αS51D, a phosphomimetic mutant of eIF2α, left rev/tat mRNA splicing intact. Unlike eIF2αS51A, eIF2αS51D does not inhibit eIF2α phosphorylation by activated PKR. All HIV mRNA species contain terminal trans-activation response (TAR) stem-loop sequences that potentially could activate PKR, yet even upon TAR deletion, HIV mRNA production remained sensitive to inhibitors of PKR activation. Bioinformatic and mutational analyses revealed a compact RNA pseudoknot upstream of 3′-terminal TAR that promotes splicing by activating PKR. Supporting its essential role in control of splicing, this pseudoknot is conserved among diverse HIV and nonhuman primate SIVcpz isolates. The pseudoknot and 3′-terminal TAR collaborate in mediating PKR-regulated splicing of rev/tat intron, the pseudoknot being dominant.

Conclusions
Our results on HIV provide the first example of a virus co-opting activation of PKR by its RNA, a cellular antiviral mechanism, to promote splicing. They raise the question whether other viruses may use local activation of host kinase PKR through RNA elements within their genome to achieve efficient splicing of their mRNA. Our experiments reveal an indispensable role for eIF2α phosphorylation in HIV rev/tat mRNA splicing that accounts for the need for PKR activation.
A randomized controlled trial of an intervention to reduce stigma toward people with opioid use disorder among primary care clinicians
Authors: Hooker Stephanie A. , Crain A. Lauren , LaFrance Amy B. , Kane Sheryl , Fokuo J. Konadu , Bart Gavin , Rossom Rebecca C. 
Published: February 2023

Abstract
Background
Many primary care clinicians (PCCs) hold stigma toward people with opioid use disorder (OUD), which may be a barrier to care. Few interventions exist to address PCC stigma toward people with OUD. This study examined whether an online training incorporating patient narratives reduced PCCs’ stigma toward people with OUD (primary) and increased intentions to treat people with OUD compared to an attention-control training (secondary).

Methods
PCCs from 15 primary care clinics were invited to complete a 30 min online training for an electronic health record-embedded clinical decision support (CDS) tool that alerts PCCs to screen, diagnose, and treat people with OUD. PCCs were randomized to receive a stigma-reduction version of the training with patient narrative videos or a control training without patient narratives and were blinded to group assignment. Immediately after the training, PCCs completed surveys of stigma towards people with OUD and intentions and willingness to treat OUD. CDS tool use was monitored for 6 months. Analyses included independent samples t-tests, Pearson correlations, and logistic regression.

Results
A total of 162 PCCs were randomized; 88 PCCs (58% female; 68% white) completed the training (Stigma = 48; Control = 40) and were included in analyses. There was no significant difference between intervention and control groups for stigma (t = − 0.48, p = .64, Cohen’s d = − 0.11), intention to get waivered (t = 1.11, p = .27, d = 0.26), or intention to prescribe buprenorphine if a waiver were no longer required (t = 0.90, p = 0.37, d = 0.21). PCCs who reported greater stigma reported lower intentions both to get waivered (r = − 0.25, p = 0.03) and to prescribe buprenorphine with no waiver (r = − 0.25, p = 0.03). Intervention group and self-reported stigma were not significantly related to CDS tool use.

Conclusions
Stigma toward people with OUD may require more robust intervention than this brief training was able to accomplish. However, stigma was related to lower intentions to treat people with OUD, suggesting stigma acts as a barrier to care. Future work should identify effective interventions to reduce stigma among PCCs.
Trial Registration: ClinicalTrials.gov NCT04867382. Registered 30 April 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04867382
Bile acid predicts congenital portosystemic venous shunt in patients with pulmonary arterial hypertension
Authors: Li Yunyan , Deng Xiaoxian , Zhou Hongmei , Zheng Xuan , Zhang Gangcheng , Xiong Qingfeng 
Published: February 2023

AbstractThe etiology of pulmonary arterial hypertension (PAH) is complex, especially the investigation of rare pathogeny is difficult. Congenital portosystemic venous shunt (CPSS) is a rare congenital anomaly in which the portal blood completely or partially bypasses the liver through a congenital portosystemic shunt, and drains directly into the inferior vena cava (IVC) (Howard and Davenport in J Pediatr Surg 32:494–497, 1997).CPSS is an uncommon cause of PAH (Christiane et al. in J Pediatr Gastroenterol Nutr 56:675–681, 2013), and often covered by other pathogenic factors. The clinical manifestations of CPSS-associated PAH are not specific, thus making it difficult to distinguish from PAH caused by other pathogenetic factors based on clinical presentations alone. This is a retrospective analysis of data from six patients with CPSS at a single center. Of these, five were diagnosed as PAH: four were also associated with other predisposing factors of pulmonary hypertension (PH). All patients had high serum bile concentration and high cardiac output. The aim of this retrospective study was to investigate the clinical recognition of PAH secondary to CPSS. The concentration of serum bile acid and cardiac output can be used as two important non-invasive indicators in clinical practice. Thus far, few studies have reported the clinical outcomes of CPSS-associated PAH specifically (Anna et al. in Hepatology 71:658–669, 2020;Franchi-Abella et al. in J Pediatr Gastroenterol Nutr 51:322–330, 2010;Uike et al. in Pediatr Pulmonol 53:505–511, 2018;). In the current study, such patients carried a poor prognosis if left untreated, or treated with pulmonary vasodilators alone.
Biological function of resveratrol and its application in animal production: a review
Authors: Meng Qingwei , Li Jiawei , Wang Chunsheng , Shan Anshan 
Published: February 2023

AbstractWith the prohibition of antibiotics in feed, plant functional substances have been widely studied as feed additives. Resveratrol, a natural stilbene, and a non-flavonoid polyphenol found in plants, possesses antioxidant, anti-inflammatory, and metabolic regulatory features. Resveratrol generated intense scientific and public interest, primarily due to its widely reported ability to prevent cancer, delay aging and alleviate related metabolic diseases. Recently, resveratrol has been studied and applied as a feed additive in animal production. This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present, including pigs, poultry, and ruminants. In pigs, dietary resveratrol improved intestinal health, mitochondrial function, meat quality, and more. In poultry, studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects. There are few studies on dietary resveratrol in ruminants; however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep. It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.
Signals of sustainability transition: Sensing enabling factors through cultural initiatives
Authors: Concilio Grazia , Bianchi Irene , Tosoni Ilaria 
Published: February 2023

AbstractThis article reports a first attempt to combine the analysis of socio-technical mechanisms and initiative-based learning to sense sustainability transition signals in cities. Relying on the analysis of cultural initiatives in six European Cities, the study identifies those factors that enabled social impact generation. It then formulates hypotheses about their contribution to the inception and rooting of sustainability transition dynamics. As a result, the article proposes a set of analytical categories of enabling factors acting across niches and regimes. The same factors are then reinterpreted by referring to scaling mechanisms (scaling up, out and deep). The proposed analytical scheme seeks to offer a broader reflection on the conceptual and methodological challenges related to sensing and interpreting urban sustainability transition pathways.
The association of dietary acid load (DAL) with estimated skeletal muscle mass and bone mineral content: a cross-sectional study
Authors: Gholami Fatemeh , Bahrampour Niki , Samadi Mahsa , Rasaei Niloufar , Yarizadeh Habib , Naghshi Sina , Mirzaei Khadijeh 
Published: February 2023

Abstract
Background & Aims
Dietary patterns that promote mild metabolic acidosis may have a negative effect on bone and muscle, and a high dietary acid load (DAL) may be detrimental to skeletal muscle mass and bone mineral content. However, the association between skeletal muscle mass and bone mineral content with dietary acid load has not been consistently reported in previous studies. The objective of the study was to evaluate the association of potential renal net acid load (PRAL) and net endogenous acid production (NEAP) with bone mineral content and skeletal muscle mass in pre-menopause women with overweight or obesity in Iran.

Method
Three hundred and ninety women with a body mass index (BMI) of 25 were included in this cross-sectional study. We used a validated 147-item semi-quantitative food frequency questionnaire (FFQ) for evaluating the dietary intake. Based on the dietary data, potential renal net acid load (PRAL) and net endogenous acid production (NEAP) were calculated. Muscle mass and bone mineral content were estimated by a bioelectrical impedance analyzer (BIA).

Results
After controlling for potential confounders, we discovered a significant linear relationship between PRAL (β = -0.027, 95%CI = -0.049 to -0.004, P = 0.02) and NEAP (β = -0.05, 95%CI = -0.097 to -0.003, P = 0.03) and skeletal muscle mass index. However, there was no significant difference between SMM and BMC across PRAL and NEAP tertiles.

Conclusion
PRAL and NEAP were found to be inversely related to skeletal muscle mass index among overweight/obese women. Further research is required to establish whether this relationship is important for musculoskeletal health in these populations.
Associations of Physical and Social Workplace Characteristics with Movement Behaviors at Work
Authors: Holmes Anthony J. , Quinn Tyler D. , Conroy Molly B. , Paley Joshua L. , Huber Kimberly A. , Barone Gibbs Bethany 
Published: February 2023

ABSTRACT

Introduction/Purpose
Sedentary behavior (SB) is common in desk-based work, and prolonged periods of SB are associated with negative health outcomes. This study assessed associations between workplace characteristics and setting and movement patterns during working hours.

Methods
This secondary analysis used baseline data from the Reducing Sedentary Behavior to Decrease Blood Pressure clinical trial, which enrolled inactive, desk-based workers with elevated blood pressure (n = 271; mean age, 45.3 ± 11.6 yr; body mass index, 30.66 ± 7.1 kg·m−2; 59.4% women). Physical and social workplace characteristics were assessed by a study-developed questionnaire and the Office Environment and Sitting Scale. Participants also wore an activPAL activity monitor for 7 d and reported working hours in a diary to measure SB and physical activity (PA) specifically while working. Linear regression was used to analyze cross-sectional associations between workplace characteristics and SB and PA. A stratified analysis was also conducted to assess associations among home-based and in-office desk workers separately. Analyses were adjusted for age, gender, body mass index, and work wear time.

Results
Participants spent 77% of working hours in SB. Public versus private offices, working in-office versus at home, higher local connectivity, and greater overall connectedness were associated with lower SB and/or greater PA (all P < 0.05). Higher frequency of face-to-face interactions, and greater visibility and proximity to coworkers were associated with less SB and more PA (all P < 0.05). For example, home-based workers had more total SB (+17.2 ± 8.4 min per day), more SB bouts ≥30 min (+39.1 ± 12.8 min per day), and less steps (695 ± 201 steps per day) than in-office employees. Stratification by office setting revealed differences in associations between SB and PA and workplace characteristics.

Conclusions
More public, open spaces with more social interactions and physical walkways could improve SB and PA patterns during work. Home-based workers had more SB, less PA, and unique associations of these activities with workplace characteristics, suggesting a need for tailored interventions.
The influence of genetic and environmental factors on the incidence of prostate cancer in men
Authors: Olko Paweł , Licak Gabriela , Tomkiewicz Julia , Tomkiewicz Michał , Paluch Michał , Sałata Piotr , Żuchnik Magda , Radulski Jakub , Szczuraszek Hugo , Bętkowska Paulina , Dadziak Mikołaj 
Published: February 2023

Introduction
The prostate gland is a small reproductive organ found in men. It consists of 3 zones: central, peripheral and transitional. The most common localization of prostate cancer in elderly men is the peripheral zone. Prostate cancer is one of the most common cancers in men. It ranks second in terms of incidence and fifth in terms of lethality among men worldwide. There are many factors that contribute to the development of prostate cancer in men. We can divide them into two large groups: genetic factors and environmental factors. These include, among others: older age, ethnicity / race, positive family history, genetic predisposition, type of diet, obesity, smoking or higher height. Each of the above factors has a different impact on the incidence of prostate cancer, which has been demonstrated on the basis of the results of numerous studies and will be summarized in the following review.
Materiał and Methods
This review was based on available data collected in the PubMed database, using the following keywords: „Prostate Cancer”, „Epidemiology of Prostate Cancer” and „Risk factors of Prostate Cancer”.
Conclusions
Prostate cancer is a serious problem affecting men all over the world. Every year we observe an increasing incidence of this disease, which makes prostate cancer one of the most common cancers affecting men. There are many factors affecting the occurrence of this cancer, but it is extremely difficult to study their exact impact on the development of prostate cancer. Therefore, new initiatives and research should be undertaken to broadly understand the etiology and risk factors of this cancer.
The role of the designated prescribing supervisor: an evaluation
Authors: Jarmain Sally , Moreno-Chamorro Deborah , Piggin Catherine 
Published: February 2023

Aim To understand the experience of non-medical prescribers undertaking the role of designated prescribing supervisor with students on the non-medical prescribing course for the first time. Methods Questionnaire completed by 34 designated prescribing supervisors, followed by semi-structured interviews with 10 designated prescribing supervisors. Findings There were four themes identified from the data. These were: knowledge and experience prior to undertaking the designated prescribing supervisor role; how the role of designated prescribing supervisor was enacted in practice; interactions and engagements necessary to support the designated prescribing supervisor and underpin students' professional development; and the way in which the designated prescribing supervisor role supports personal growth. Conclusion Designated prescribing supervisors in this evaluation described their role as consisting of coaching, advice and pastoral support. The supervision which they provided tended to be unscheduled and informal. Designated prescribing supervisors valued the support they received from the University and their Employer. Undertaking the role of designated prescribing supervisors was described as beneficial to their continuing professional development, it enhanced job satisfaction and provided a greater sense of self-worth.
The Weak Hybrid Equilibria of an Exchange Economy with a Continuum of Agents and Externalities
Authors: Yang Zhe 
Published: February 2023

Abstract
Inspired by Zhao, J. 1996. “The Hybrid Equilibria and Core Selection in Exchange Economies with Externalities.” Journal of Mathematical Economics 26 (4): 387–407, Askoura, Y. 2011. “The Weak-Core of a Game in Normal Form with a Continuum of Players.” Journal of Mathematical Economics 47: 43–7, Askoura, Y. 2017. “On the Core of Normal Form Games with a Continuum of Players.” Mathematical Social Sciences 89: 32–42, Yang, Z. 2020. “The Weak α-core of Exchange Economies with a Continuum of Players and Pseudo-utilities.” Journal of Mathematical Economies 91: 43–50 and Yang, Z., and X. Zhang. 2021. “A Weak α-core Existence Theorem of Games with Nonordered Preferences and a Continuum of Agents.” Journal of Mathematical Economics 94: 102464, we establish an exchange economy with externalities and a continuum of agents. We define the weak hybrid equilibrium in this model and prove the existence theorem under the regular conditions. Furthermore, we analyze the relation between the set of hybrid equilibria and the set of competitive equilibria in an exchange economy without externalities and with a continuum of agents.
An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma
Authors: Sleumer Bas , Zwerwer Jordan , van Faassen Martijn , Vos Michel J. , Bischoff Rainer , Kema Ido P. , van de Merbel Nico C. 
Published: February 2023

Abstract

Objectives
Sex hormone binding globulin (SHBG) is a hormone binding protein which plays an important role in regulating the transport and availability of biologically active androgens and estradiol to target cells and used to calculate free testosterone concentrations.

Methods
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, featuring an albumin removal step followed by a tryptic digestion. After a reduction step with dithiothreitol and alkylation with iodoacetamide three signature peptides were used for the quantification of SHBG.

Results
The method enables the quantification of serum and plasma SHBG over the clinically relevant range of 200–20,000 ng/mL and was validated according to the most recent guidelines. The LC-MS/MS method correlates well with the Abbott Alinity immunoassay (R2>0.95), but the LC-MS/MS results are on average 16–17% lower than the immunoassay results, which is consistent for all three signature peptides.

Conclusions
The LC-MS/MS method which includes an albumin depletion step allows quantification of SHBG in serum and plasma without an immunocapture step at clinically relevant SHBG levels, thus contributing to better lab-to-lab consistency of results.