bluuebunny/crossref_metadata_2025_split huggingface dataset:
XRCC2 Arg188His polymorphism and colorectal cancer risk: a meta-analysis
Authors: Wang Zhiyu , Wei Yaning , An Lin , Xi Chenglin , Wang Kunjie , Hong Dan , Shi Yan , Zang Aiming , Su Shenyong , Li Wenwen 
Published: October 2021

Objective To investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 ( XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear. Methods The CNKI, PubMed, EMBASE and Cochrane library databases were systematically searched for relevant studies published up to July 2021. Data were extracted from included studies, and analysed for pooled or subgroup odds ratios (ORs) with 95% confidence intervals (CIs) using STATA 12.0 software. Results Seven published studies were included. Pooled analysis revealed that the XRCC2 Arg188His polymorphism was associated with increased CRC risk (His versus Arg: OR 1.14, 95% CI 1.01, 1.29). Trial Sequential Analysis to test the power of the results showed that they were unreliable and the meta-analysis required additional studies. Conclusion The current meta-analysis suggests that the XRCC2 Arg188His polymorphism may be a risk factor for CRC.
Doxycycline sensitizes renal cell carcinoma to chemotherapy by preferentially inhibiting mitochondrial translation
Authors: Wang Bo , Ao Jinsong , Li Xiaoyan , Yu Weimin , Yu Dan , Qiu Chengjun 
Published: October 2021

Objectives The anti-cancer activity of doxycycline has been reported in many cancers but not renal cell carcinoma (RCC). This study aimed to determine the efficacy of doxycycline alone and in combination with paclitaxel and analyze the underlying mechanism in RCC. Methods Proliferation, colony formation and apoptosis assays were performed in RCC cell lines after drug treatments. An RCC xenograft mouse model was generated, and tumor growth was monitored. Mechanistic studies focused on mitochondrial translation and functions. Results Doxycycline at clinically achievable concentrations inhibited proliferation and colony formation and induced apoptosis in RCC cell lines. In normal kidney cells, doxycycline at the same concentrations either had no effect or was less effective. The combination index value demonstrated that doxycycline and paclitaxel were synergistic in vitro. Consistently, this combination therapy was significantly more effective than the monotherapy in RCC xenograft mice without causing significant toxicity. Mechanistic studies revealed that doxycycline acts on RCC cells via preferentially inhibiting mitochondrial DNA translation, thereby disrupting multiple mitochondrial complexes and impairing mitochondrial respiration. Conclusions Doxycycline is a useful addition to the treatment strategy for RCC. Our work also highlights the therapeutic value of mitochondrial translation inhibition in sensitizing RCC to chemotherapy.
Survival after multiple nail gun injuries to the brain, lung, and heart: a case report and a review of the literature
Authors: Wang Suo-Hsien , Chen Mao-Yu , Yan Jiun-Lin , Huang Tzu-Yen , Chang Che-Chia , Chien Chih-Ying 
Published: October 2021

Most nail gun injuries involve the extremities and result from work-related accidents. Injuries to the brain or thorax are relatively rare, and cases with injuries to both regions are even rarer and often lethal. Initial evaluation, resuscitation, and surgical planning can be challenging for emergency physicians and surgeons. We present the details of a man with multiple nail gun injuries to the brain, lung, and heart following a suicide attempt. The patient presented to the emergency department in shock. After immediate resuscitation, emergent sternotomy, and subsequent craniotomy, he was discharged without significant morbidity. According to the literature, this is the only reported case involving multiple nail gun injuries to the brain, lungs, and heart. The mortality rate of multiple nail gun injuries involving the head and chest is approximately 20%. Rapid evaluation, immediate resuscitation, and appropriate imaging and surgery are crucial for increasing survival and achieving a good prognosis. Emergency sternotomy for cardiac injury is the foremost priority, and the timing of craniotomy depends on the patient’s vital sign status and whether brain injury is evident. A preprint of this article is available online: DOI: 10.21203/rs.3.rs-35448/v1.
Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families
Authors: Häppölä Paavo , Gormley Padhraig , Nuottamo Marjo E , Artto Ville , Sumelahti Marja-Liisa , Nissilä Markku , Keski-Säntti Petra , Ilmavirta Matti , Kaunisto Mari A , Hämäläinen Eija I , Ripatti Samuli , Pirinen Matti , Wessman Maija , Palotie Aarno , Kallela Mikko ,   International Headache Genetics Consortium (IHGC)
Published: October 2021

Background Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. Methods We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. Results Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02–0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08–0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14–0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26–0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31–0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. Conclusions The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.
The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice
Authors: Kang Li , Tang Wenjing , Zhang Yaofen , Zhang Mingjie , Liu Jing , Li Yingji , Kong Shanshan , Zhao Dengfa , Yu Shengyuan 
Published: October 2021

Background Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Methods Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. Results In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Conclusion Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.
Formaldehyde induces ferritinophagy to damage hippocampal neuronal cells
Authors: Hu Yu , Wu Lei , Yang San-Qiao , Wei Hai-Jun , Wang Chun-Yan , Kang Xuan , Jiang Jia-Mei , Zhang Ping , Tang Xiao-Qing 
Published: October 2021

Formaldehyde (FA) causes neurotoxicity and contributes to the occurrence of neurodegenerative diseases. However, the mechanism of FA-induced neurotoxicity has not been fully elucidated. Ferritinophagy, an autophagy process of ferritin mediated by the nuclear receptor coactivator 4 (NCOA4), is a potential mechanism of neurotoxicity. In this study, we explored whether ferritinophagy is associated with the neurotoxicity of FA. Our results showed that FA (50, 100, 200 μM; 24 h) exposure upregulated ferritinophagy in the mouse hippocampal neuronal HT22 cells, which was evidenced by the upregulated autophagic flux, the increased colocalizations of NCOA4 with ferritin heavy chain (FTH1) and NCOA4 with microtubule-associated protein 1 light chain-3B (LC3B), the augmented expression of NCOA4, and the reduced content of FTH1. We also found that FA (0.1, 1, and 10 μmol, i.c.v., 7d) administration boosted ferritinophagy in the hippocampus of Sprague-Dawley (SD) rats, which was demonstrated by the accumulated autophagosomes, the increased expressions of LC3II/I and NCOA4, and the decreased contents of p62 and FTH1 in the hippocampus. Further, we confirmed that inhibition of ferritinophagy by silencing the expression of NCOA4 decreased FA-induced toxic damage in HT22 cells. These results indicated that FA induces neurotoxicity by promoting ferritinophagy. Our findings suggest a potential mechanism insight into the FA-induced neurotoxicity, which in turn provides a new thought for the treatment of FA-related neurodegenerative diseases.
Type 2 diabetes mellitus potentiates acute acrylonitrile toxicity: Potentiation reduction by phenethyl isothiocyanate
Authors: Zhou Jie , Zhu Xueyu , Dong Ying , Yang Bobo , Lu Rongzhu , Xing Guangwei , Wang Suhua , Li Fang 
Published: October 2021

Acrylonitrile (AN) is a known animal carcinogen and suspected human carcinogen. Recently, occupational exposure to AN has considerably increased. Previously, we demonstrated that streptozotocin-induced diabetes potentiates AN-induced acute toxicity in rats and that the induced cytochrome P450 2E1 (CYP2E1) is responsible for this effect. In the present study, we examined whether induction of CYP2E1 is also the underlying mechanism for the potentiation of AN-induced acute toxicity in type 2 diabetes in db/db mice. The effect of phenethyl isothiocyanate (PEITC) in reducing potentiation was also investigated. The mice were randomly divided into the normal control, diabetic control, AN, diabetes + AN, PEITC + AN, and diabetes + PEITC + AN groups. PEITC (40 mg/kg) was orally administered to rats for 3 days, and 1 h after the last PEITC gavage, 45 mg/kg AN was intraperitoneally injected. Time to death was observed. The CYP2E1 level and enzymatic activity, cytochrome c oxidase (CCO) activity, and reactive oxygen species (ROS) levels were measured. The survival rate was decreased in AN-treated db/db mice compared with that in AN-treated wild-type mice. The hepatic CYP2E1 level and enzymatic activity remained unaltered in db/db mice. Phenethyl isothiocyanate alleviated AN-induced acute toxicity in db/db mice as evident in the increased survival rate, restored CCO activity, and decreased ROS level in both the liver and brain. The study results suggested that CYP2E1 may not be responsible for the sensitivity to AN-induced acute toxicity in db/db mice and that PEITC reduced the potentiation of AN-induced acute toxicity in db/db mice.
Blood lead levels, calcium metabolism and bone-turnover among automobile technicians in Sagamu, Nigeria: Implications for elevated risk of susceptibility to bone diseases
Authors: Nwobi Nnenna L , Nwobi Joseph C , Adejumo Esther N , Usiobeigbe Osahon S , Adetunji Opeyemi A , Atulomah Nnodimele O , Anetor John I 
Published: October 2021

Lead is an occupational toxicant and a recognised health threat particularly in developing countries. Hence, this study explored the interaction of blood lead level (BLL), a conventional marker of lead exposure, with indices of calcium metabolism and biomarkers of bone-turnover in 120 adult male automobile technicians (AT) with ≥ 1 year duration in professional practice. The AT as well as the control group, which comprised 120 age, body-size and socio-economically matched male administrative workers, were recruited from Sagamu, South West Nigeria. Levels of blood lead, serum indices of calcium metabolism [total calcium (tCa), ionised calcium (iCa), phosphate, albumin, magnesium (Mg) and 25-Hydroxycholecalceferol (25-OHCC)], biomarkers of bone formation [bone alkaline phosphatase (BALP) and osteocalcin (OC)] and biomarkers of bone resorption [tartarate-resistant acid phosphatase-5b (TACRP-5b) and urinary hydroxyproline (UHYP)] were determined in all participants. The BLL, 25-OHCC, TRACP-5b and UHYP significantly increased while tCa and iCa significantly reduced in AT compared to control. However, no significant difference was observed in phosphate, albumin, Mg, BALP and OC in AT compared to control. Interestingly, BLL demonstrated a significant negative association with tCa and iCa but a significant positive association with 25-OHCC, TRACP-5b and UHYP. However, BLL did not show significant association with phosphate, albumin, Mg, BALP and OC. Increased lead exposure as well as altered calcium metabolism and bone-turnover demonstrated by the automobile technicians may be suggestive of lead-induced accelerated bone demineralisation. These workers may be predisposed to high risk of increased susceptibility to bone diseases if this sub-clinical picture is sustained.
Mesothelial Cell Transplantation in Models of Acute Inflammation and Chronic Peritoneal Dialysis
Authors: Hekking Liesbeth H.P. , Harvey V. Susan , Havenith Carin E.G. , van den Born Jacob , Beelen Robert H.J. , Jackman Robert W. , Nagy Janice A. 
Published: October 2021

♦ Objectives Mesothelial cell (MC) injury caused by continuous exposure to unphysiological peritoneal dialysis (PD) fluid and by episodes of peritonitis can eventually lead to peritoneal adhesions and peritoneal fibrosis. In the present study, we evaluated the possibility of using autologous genetically modified MCs for transplantation after the induction of peritoneal injury by acute inflammatory mediators or chronic instillation of PD fluid. ♦ Methods Rats were injected intraperitoneally either once with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or thioglycollate, or PD fluid [ i.e., Dianeal (Baxter Healthcare, Deerfield, Illinois, USA) or Physioneal (Baxter, Nivelles, Belgium)], or chronically (up to 8 weeks) with Dianeal. From 2 to 48 hours later, animals were injected with syngeneic MCs genetically modified to express the LacZ reporter gene. Rats were sacrificed 2 days later and expression of β-galactosidase (β-Gal) was visualized by X-Gal staining of excised tissues. Quantification of the percent area of β-Gal–positive MCs on part of the parietal peritoneum was performed using computerized image analysis. ♦ Results The highest numbers of repopulated genetically modified MCs were observed 8 hours after a single thioglycollate injection, approximately 0.66% of a representative 2-cm2 area selected for study (corresponding to approximately 10% of the peritoneal surface). The number of genetically modified MCs found to repopulate the peritoneal surface following short-term injury varied with inflammatory mediator (thioglycollate > PD fluid > fMLP) and duration of exposure. No obvious difference's were observed between the two PD fluids tested. Reimplantation of syngeneic genetically modified MCs was also observed after chronic instillation of PD fluid. ♦ Conclusions These data demonstrate that transplanted genetically modified MCs repopulate the denuded areas on the peritoneal surface that were caused by acute or chronic inflammation. This technique opens possibilities of MC transplantation and gene therapy in order to prevent complications relevant to the continuous ambulatory PD setting.
Effect of Peritoneal Dialysis on Plasma and Peritoneal Fluid Concentrations of Isoniazid, Pyrazinamide, and Rifampin
Authors: Ahn Curie , Oh Kook-Hwan , Kim Kiwon , Lee Kyung Yi , Lee Jung Geon , Oh Myung Don , Kim Yonsu , Han Jin Suk , Kim Suhnggwon , Lee Jung Sang , Jang In-jin , Shin Sang-Goo 
Published: October 2021

♦ Objective This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients. ♦ Patients Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study. ♦ Methods After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis. ♦ Results Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time. ♦ Conclusion For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.
Prospective Observational Evaluation of Predatory Journals in Critical Care Pharmacy Practice: Defining Characteristics Associated With Receiving Unsolicited Invitations to Publish
Authors: Peppard William J. , Peppard Sarah R. , Feih Joel T. , Kim Andy K. , Obenberger Steve J. , Mulvey Ashley F. , Teng Bi Qing , Brazauskas Ruta , Pape Kate O. , Gibson Gabrielle A. , Dzierba Amy L. , Dobesh Paul P. 
Published: October 2021

Open-access publishing promotes accessibility to scholarly research at no cost to the reader. The emergence of predatory publishers, which exploit the author-pay model by charging substantial publication fees for publication in journals with questionable publishing processes, is on the rise. Authors are solicited through aggressive marketing tactics, though who is targeted is not well described. The purpose of this study was to identify characteristics associated with critical care pharmacists that make them targets of unsolicited invitations to publish. A prospective, observational study of critical care pharmacists was performed. Participants archived emails received by their professional email that were unsolicited invitations to submit their original work for publication in a journal (unsolicited journals). Variables were evaluated to determine which were associated with unsolicited invitations; these were compared to legitimate journals, defined as all PubMed-indexed journals in which the participants were previously published. Twenty-three pharmacist participants were included, all of whom were residency and/or fellowship trained and practicing in an academic medical center. Participants had a median of 7 years of experience since their post-graduate training, 6 years since their last change in professional email address, and 2 years since their first PubMed-indexed publication. From these participants, 136 unsolicited and 59 legitimate journals were included. The average number of invitations increased 1.04 (95% CI, 1.02–1.05) times for every additional PubMed-indexed publication ( P < .001). Most unsolicited journals were considered predatory. Legitimate and unsolicited journals differed significantly. The number of previous PubMed-indexed publications strongly correlates with the likelihood of critical care pharmacists receiving unsolicited publication invitations, often from predatory journal.
An Empirical Model for Assessing the Impact of Air Quality on Urban Residents’ Loyalty to Place of Residence
Authors: Karaca Ferhat , Turkyilmaz Ali , Myrzagali Alikhan , Kerimray Aiymgul , Bell Phillip 
Published: October 2021

There has been a growing interest in the impact of environmental awareness on ‘green’ or ‘environmentally friendly’ consumption patterns, and this has been the subject of much research by environmental psychologists. However, the effect of environmental awareness on residents and their attachment to their homes and their environment has received little attention and is worthy of closer examination. Outdoor air quality can be considered one of the most critical environmental factors impacting the value of a residential location. This research investigates how air pollution-related environmental factors influence residents’ attachment to the place of residence and their willingness to move. It defines the structural relationship between air pollution awareness parameters, which are later employed in the proposed structural equation model (SEM), to explain ‘district loyalty’. A survey was carried out in Almaty, Kazakhstan, one of the most populated and polluted cities in Central Asia. A total of 550 respondents responded. Based on the overall model’s test results, the factors relating to district loyalty explained the 17.5% variation in the samples, which suggests that the perception of residents to their district air quality has a low-level impact on loyalty to their place of residence. The power of perceived environmental risks appears to have little relation to district loyalty. The most influential factor on the model is environmental behaviour parameter, which is about adopting attitudes and behaviours aimed at minimizing negative impacts on the environment. When the perceived environmental risk increased, their place attachment levels only slightly decreased. However, the obtained results do not confirm that district loyalty significantly correlates with their readiness/unreadiness to move to another residence in order to enjoy improved air quality. To sum up, environmental awareness of local air quality seems not to directly affect residents’ attachment to place. Nevertheless, indirect effects can be presented in research relating to urban residents’ place attachment. Research, policy and sectoral implications of the findings are addressed and discussed in detail.