bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heroin and fentanyl in Dallas County: A 5‐year retrospective review of toxicological, seized drug, and demographical data
Authors: Glicksberg Lindsay , Dempsey Sara K. , Casey Brittany K. 
Published: October 2022

AbstractThe opioid epidemic resulted in an increase in identifications of fentanyl, fentanyl analogs, and heroin, among other opioids, in the toxicology and seized drug analysis fields over the past several years. The Dallas County Southwestern Institute of Forensic Sciences, comprised of the Toxicology Laboratory and Drug Analysis Laboratory, observed a rise in fentanyl‐positive analyses in both laboratories. Fentanyl positivity increased from 1.1% to 3.4% in the Toxicology Laboratory over the five years of this study, whereas 6‐monoacetylmorphine (6‐MAM) positivity remained relatively stable at approximately 2%. Similarly, in the Drug Analysis Laboratory, the fentanyl positivity rate changed from 0.03% to 0.60%, whereas heroin identification remained stable at approximately 8–9%. Based on data obtained from toxicology submissions, a typical fentanyl or heroin user was a white male in their late 30s. The average concentration of fentanyl in postmortem cases, antemortem cases, and 6‐MAM in postmortem specimens was 9.7 ng/ml, 5.5 ng/ml, and 68.4 ng/ml, respectively. Poly‐drug use was evident, with benzodiazepines being the most commonly co‐administered drug with fentanyl (49.4%). Multiple drugs were identified via analysis of clandestine tablets submitted to the Drug Analysis Laboratory, including fentanyl and/or heroin in combination with compounds such as cocaine, etizolam, and acetaminophen. The most frequently identified clandestine tablet was “M367,” typically manufactured to contain acetaminophen and hydrocodone, but was found to contain fentanyl or heroin. The results from this study aid in the understanding of the current opioid trends in Dallas County and provides an opportunity for comparison to other populations and geographical regions.
Outcomes of early‐start peritoneal dialysis (PD) and the comparison with urgent‐start hemodialysis and conventional‐start PD
Authors: Yeter Hasan Haci , Izgi Aybuke , Yildirim Saliha , Akcay Omer Faruk , Derici Ulver 
Published: October 2022

AbstractBackgroundLimited data in the literature is comparing early‐start peritoneal dialysis (PD), urgent‐start hemodialysis (HD) with the jugular central venous catheter (CVC), and conventional‐start PD.MethodsThis retrospective study was conducted with 148 patients with early‐start PD, 104 patients with conventional‐start PD, and 100 patients with urgent‐start HD. Early‐start PD was defined as catheter break‐in time between 3 and 14 days.ResultsThe occurrence of dialysate‐leakage was similar between PD groups (p = 0.1). Bleeding at the catheter site was detected in 8 (2.3%) patients with CVC. There was no significant difference in catheter dysfunction and revision. PD groups had statistically similar peritonitis rates (p = 0.5). 19% (19/100) of patients suffered CVC‐related bloodstream infection and one patient died due to septic shock. Technique survival was significantly higher at early‐start PD than the conventional‐start PD at 6 months (p = 0.02).ConclusionInitiating early‐start PD is comparable with conventional‐start PD, and it may be an alternative dialysis modality to avoid bloodstream infections in suitable patients.
Accumulation by dispossession and hazardscape production in post‐corporate gold mining in Itogon, Philippines
Authors: Ocampo Lou Angeli , Schmitz Serge 
Published: October 2022

AbstractThis study investigates the experience of a gold mining community two decades after corporate mining activities ceased and were replaced by informal subcontract small‐scale mining in Itogon, Philippines. Drawing on David Harvey’s accumulation by dispossession and Daanish Mustafa’s hazardscape, we consider the lasting effects, from 1903, of dispossession upon the establishment of the first commercial mines in the Philippines as experienced by traditional miners in Itogon. Despite the closure of mining operations, mineral lands remain privately owned, resulting in the persistence of legal land dispossession among local small‐scale gold miners. Mining activities still continue as small‐scale miners are able to access abandoned mines through subcontract mining. Subcontract mining has changed the source of capital that funds mining activities from mining corporation to rent‐seeking small‐scale mining financiers, but the new economic relations still benefit from the capitalist logic of low natural resources and labour value. We argue that the production of hazardscapes is a consequence of accumulation by dispossession through (1) processes of expropriation of mineral lands and the consequent creation of free labour among local miners; (2) the externalisation environmental cost as an accumulation strategy that results in the production of socionatural hazards; and (3) exploitation of those who labour and who are made to work in precarious work environment while contributing to the production of hazardscapes.
Interleukin 23 receptor gene polymorphisms and their role in the inflammatory status of rheumatoid arthritis patients in an Iranian population
Authors: Abbasifard Mitra , Mirzaei Mohammad Reza , Abade Mahsa , Bagheri‐Hosseinabadi Zahra 
Published: October 2022

AbstractBackgroundSeveral investigations have disclosed the involvement of the interleukin (IL)‐23/IL‐17 pathway in rheumatoid arthritis (RA) pathogenesis. Here we investigated the association of single nucleotide polymorphisms (SNPs) in the IL23 receptor (IL23R) gene with RA risk. In addition, the role of these SNPs with the inflammatory state of the patients were determined.MethodsIn this case‐control study, 200 RA cases and 200 healthy subjects were recruited. Using allelic discrimination real‐time polymerase chain reaction, both IL23R rs10489629 and rs1004819 SNPs were genotyped. The messenger RNA (mRNA) expression levels of IL‐23R, IL‐23, and IL‐17A were determined in peripheral blood mononuclear cells (PBMCs). The serum levels of IL‐23 and IL‐17A were also determined.ResultsThe A allele (odds ratio [OR] = 1.52, 95% CI: 1.15‐2.01; P = .0030), AA genotype (OR = 2.41, 95% CI: 1.33‐4.35; P = .0035), and AG genotype (OR = 2.55, 95% CI: 1.56‐4.16, P = .0002) of rs1004819 SNP was significantly associated with increased RA risk. The mRNA expression of IL‐17A (fold change = 2.55, P = .00027), IL‐23 (fold change = 1.62, P = .0081), and IL‐23R (fold change = 1.59, P = .0077) was significantly upregulated in the PBMCs from RA patients compared to that of healthy controls. Serum levels of IL‐17A (P = .00019) and IL‐23 (P = .00055) was significantly higher in the RA patients compared to the controls. No significant association was detected between patient data and SNPs.ConclusionsThe IL‐23/IL‐27 pathway plays a role in RA pathogenesis, but IL23R gene rs1004819 SNP might not be regulating this pathway in RA disease.
Distinct clinicopathological characteristics, genomic alteration and prognosis in breast cancer with concurrent TP53 mutation and MYC amplification
Authors: Lin Xiaoyi , Lin Xin , Guo Lijuan , Wang Yulei , Zhang Guochun 
Published: October 2022

AbstractBackgroundBoth TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well‐characterized.MethodsA total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next‐generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse‐free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy.ResultsIn GDPH cohort, patients with TP53/MYC co‐alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF‐β signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019–14.579; p < 0.001). They maintained independent significance for relapse‐free (HR, 1.310; 95% CI: 1.012–1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093–1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553–25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088–0.788; p = 0.020) were associated with pCR, while the co‐alteration did not serve as an independent predictor (p = 0.199).ConclusionsTP53/MYC co‐alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.
Bromelain‐based endodontic irrigant: preparation, properties, and biocompatibility: An in‐vitro study
Authors: Aldoski Mohammed Rashed Nabi , Selivany Bahar Jaafar , Sulaiman Taiseer 
Published: October 2022

AbstractThe aim of the study was to determine the properties, efficacy and biocompatibility of combining bromelain enzyme, chlorohexidine and EDTA (BCE) to create a novel endodontic irrigant. Fourier transform infrared spectrometry was performed to confirm the stability of the BCE and direct contact inhibition test was performed to determine antibacterial action. Baseline pH and surface tension of irrigants was compared with determine stability. Subcutaneous injection to dorsal skin of rabbits was graded for presence of inflammation, oedema, granulation and fibrosis. BCE caused less overall irritation, less oedematous and was earlier to heal than 2.5% NaOCl. The pH stability of BCE was also superior to 2.5% NaOCl. A one‐way ANOVA test was performed for the direct contact inhibition and microleakage test. A significant difference was determined (p ≤ 0.05) between BCE and 2.5% NaOCl for antibacterial action. BCE irrigant is effective in preparing dentinal surfaces for root canal without adverse effects and promising longevity.
Early phase oncology clinical trials in Malaysia: current status and future perspectives
Authors: Voon Pei‐Jye , Lai Wei‐Hong , Bustaman Ros Suzanna , Siu Lillian L. , Razak Albiruni R. Abdul , Yusof Akhmal , Abdullah Noor Hisham 
Published: October 2022

AbstractHistorically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia‐Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry‐sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.
Whistleblower: How One Man Tried to Stop a Famous Cancer Center from Suppressing an Effective Treatment
Authors: Castuera Ignacio 
Published: October 2022

AbstractWhile working at Sloan Kettering Institute (SKI) in the 1970s, Ralph Moss discovered that the top research scientist there was impressed with the anti‐cancer properties of amygdalin, the synthetic form of which is laetrile. At that time, laetrile was a topic of national interest as a low‐cost way of treating cancer. It would have been big news if SKI announced that laetrile was effective in animal studies and then conducted human trials of its efficacy. But due to pressure from unknown sources, Moss’s superiors chose to publicly deny the validity of their scientist’s research. Moss and other dissenting staff tried to gain press attention for the cover‐up going on at SKI, but their efforts failed. In 1979, the FDA ban on the interstate sale of laetrile was upheld by the U.S. Supreme Court, effectively ending the common use of it. It has been classified by the cancer establishment as a classic case of “quackery,” meaning that those who claim it has anti‐cancer properties are frauds. Thus, this case study shows how easily information about potentially effective cancer treatments can be suppressed by a handful of people in positions of authority. It also shows how politics can change the scientific information available to the public.
When Will theFDADo What Is in People’s Best Interests?
Authors: Ordman Alfred B. 
Published: October 2022

ABSTRACTThe national effort to reduce the incidence and severity of cancer and other chronic diseases in the United States has suffered from political influences that undermine the interests of the public. As one example, the medical profession has not made adequate use of nutritional information to improve the health of the population. Daily values for vitamins were established in the United States during World War II, when the goal was to avoid short‐term deficiencies so soldiers could continue to fight. But there is more to health than short‐term survival. Linus Pauling advocated megadoses of vitamin C to reduce the risk of cancer and to improve long‐term health. Despite numerous studies demonstrating that better nutrition and exercise are vital to a longer span of good health, the U.S. Food and Drug Administration (FDA) does not permit claims to be made about the health benefits of specific nutritional supplements. The FDA is responsive to political pressures, including pressures to reduce public knowledge of supplements and their benefits. Pharmaceutical companies contribute to members of Congress to influence health policy. Those companies promote legislation and regulations that favor the use of expensive medical treatments and that limit the provision of cost‐effective public health measures. This article reviews many examples of failures of our current medical system, and methods that could prevent the current expense and suffering in this nation.
Autoimmune regulator (AIRE): Takes a hypoxia‐inducing factor 1A (HIF1A) route to regulate FOXP3 expression in PCOS
Authors: Padmanabhan Renjini Ambika , Johnson Betcy Susan , Dhyani Ajay Kumar , Pillai Sathy M. , Jayakrishnan K. , Laloraya Malini 
Published: October 2022

AbstractProblemAutoimmune polyendocrinopathy‐candidiasis‐ ectodermal dystrophy (APECED) pathology due to autoimmune regulator (AIRE) gene mutations leads to loss of central tolerance triggering immune attack, a factor causing infertility. One of the targets of autoimmune attack is ovary and its repercussion results in polycystic ovarian syndrome (PCOS). Although reduced Tregs have been reported in PCOS, a lacunae exists on the status of AIRE gene expression and its role in treg insufficiency via HIF1A‐FOXP3 axis in PCOS.Method of studyThis is a case‐control cohort study recruiting 40 normal and 40 PCOS volunteers for peripheral blood sample collection and PCOS diagnoses were based on Rotterdam Consensus criteria. AIRE and HIF1A expression status was analysed by qRT PCR and western blot. FACS analyses was conducted on AIRE silenced peripheral blood mononuclear cells (PBMCs) after Treg induction.ResultsOur results indicate a reduced AIRE (fold change log2 (RQ) = –2.6, P < .01) and increased HIF1A (fold change log2 (RQ) = 3.6, P < .02) in PBMCs of PCOS subjects compared to age‐matched controls. Western blot of AIRE and HIF1A corroborates with qRT PCR data. Our CHIP data demonstrate AIRE mediated HIF1A promoter regulation. Silencing of AIRE in PBMCs contributes to the upregulation of HIF1A transcripts by two‐fold (P < .0015) and downregulation in FOXP3 expression by three‐fold (P < .0017). FACS analyses revealed that silencing of AIRE reduces Tcell to Treg conversion.ConclusionsOur consolidated results derive a new connection among AIRE‐HIF1A‐FOXP3 with AIRE reduction enabling increased HIF1A resulting in reduced FOXP3 in PBMCs of PCOS patients leading to Treg insufficiency.
Testis‐specific serine kinase 3 is required for sperm morphogenesis and male fertility
Authors: Nozawa Kaori , Garcia Thomas X. , Kent Katarzyna , Leng Mei , Jain Antrix , Malovannaya Anna , Yuan Fei , Yu Zhifeng , Ikawa Masahito , Matzuk Martin M. 
Published: October 2022

AbstractBackgroundThe importance of phosphorylation in sperm during spermatogenesis has not been pursued extensively. Testis‐specific serine kinase 3 (Tssk3) is a conserved gene, but TSSK3 kinase functions and phosphorylation substrates of TSSK3 are not known.ObjectiveThe goals of our studies were to understand the mechanism of action of TSSK3.Materials and methodsWe analyzed the localization of TSSK3 in sperm, used CRISPR/Cas9 to generate Tssk3 knockout (KO) mice in which nearly all of the Tssk3 open reading frame was deleted (ensuring it is a null mutation), analyzed the fertility of Tssk3 KO mice by breeding mice for 4 months, and conducted phosphoproteomics analysis of male testicular germ cells.ResultsTSSK3 is expressed in elongating sperm and localizes to the sperm tail. To define the essential roles of TSSK3 in vivo, heterozygous (HET) or homozygous KO male mice were mated with wild‐type females, and fertility was assessed over 4 months; Tssk3 KO males are sterile, whereas HET males produced normal litter sizes. The absence of TSSK3 results in disorganization of all stages of testicular seminiferous epithelium and significantly increased vacuolization of germ cells, leading to dramatically reduced sperm counts and abnormal sperm morphology; despite these histologic changes, Tssk3 null mice have normal testis size. To elucidate the mechanisms causing the KO phenotype, we conducted phosphoproteomics using purified germ cells from Tssk3 HET and KO testes. We found that proteins implicated in male infertility, such as GAPDHS, ACTL7A, ACTL9, and REEP6, showed significantly reduced phosphorylation in KO testes compared to HET testes, despite unaltered total protein levels.ConclusionsWe demonstrated that TSSK3 is essential for male fertility and crucial for phosphorylation of multiple infertility‐related proteins. These studies and the pathways in which TSSK3 functions have implications for human male infertility and nonhormonal contraception.
Prevention of thrombus formation in blood pump by mechanical circular orbital excitation of impeller in magnetically levitated centrifugal pump
Authors: Hatakenaka Kohei , Hijikata Wataru , Fujiwara Tatsuki , Ohuchi Katsuhiro , Inoue Yusuke 
Published: October 2022

AbstractBackgroundMechanical circulatory support devices, such as left ventricular assist devices, have recently been used in patients with heart failure as destination therapy but the formation of thrombus in blood pumps remains a critical problem. In this study, we propose a mechanical antithrombogenic method by impeller excitation using a magnetically levitated (Maglev) centrifugal pump. Previous studies have shown that one‐directional excitation prevents thrombus; however, it is effective in only one direction. In this study, we aimed to obtain a better effect by vibrating it in a circular orbit to induce uniform changes in the shear‐rate field entirely around the impeller.MethodsThe blood coagulation time was compared using porcine blood. (1) The flow rate was set to 1 L/min, and applied excitation was at a frequency of 280 Hz and amplitude of 3 μm. (2) Moreover, the effect was compared by varying the frequency, amplitude, and direction of the excitation. In this experiment, the flow rate was set to 0.3 L/min.Results(1) The thrombus formation time was 77 min without excitation and 133 min with excitation, which was 1.7 times longer. (2) The results showed no difference between (280 Hz, 3 μm) and (50 Hz, 16 μm) circular orbital excitations, and no directional difference, with thrombus formation of 2.5 times longer under all conditions than that without excitation.ConclusionIn the case of simple reciprocating excitation, the time was approximately 1.2 times longer. This indicated that the circular orbital excitation is more effective.
South Korean social enterprises and their networks: On their organizational linkages at the interstice between the third, public, and corporate sectors
Authors: Claassen Casper Hendrik , Bidet Eric , Kim Junki 
Published: October 2022

AbstractSocial enterprise and government interactions have become an increasingly prominent theme in the literature on social entrepreneurship, due in part to the pressures confronting the welfare state and the rise of precarious work. This analysis is motivated by the efforts of the government of South Korea to incubate social enterprises since 2007. The constant scaling of the South Korean government's monitored social enterprise certification scheme had led to the registration of approximately 3440 social enterprises as of May 2021. This study documents the interorganizational network behaviour of these enterprises relative to the public sector, corporate sector, and civil society and the social economy. A cluster analysis approach is utilized to analyse network data obtained from a self‐administered survey of 103 government‐certified social enterprises operating in South Korea. We find that a sizeable number of government‐certified social enterprises have diversified networks, as opposed to public sector‐centric networks, although such social enterprises are in the minority. This study references social innovation cluster theory to argue that the aforementioned scheme has attained a partial degree of success in facilitating the emergence of social enterprises with diversified networks.However, the majority remain quasi‐governmental implementers of government contracts and, generally, do not engage in networking.