bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low baseline plasma PCSK9 level is associated with good clinical outcomes of immune checkpoint inhibitors in advanced non‐small cell lung cancer
Authors: Xie Mengqing , Yu Xin , Chu Xiangling , Xie Huikang , Zhou Juan , Zhao Jing , Su Chunxia 
Published: December 2021

AbstractBackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein involved in the metabolism of low‐density lipoprotein cholesterol. However, the role of plasma PCSK9 in predicting the efficacy of ICIs in advanced non‐small cell lung cancer (NSCLC) remains to be clarified.MethodsWe retrospectively reviewed the medical records of NSCLC patients who presented at Shanghai Pulmonary Hospital between April 2019 and June 2020. ELISA was conducted to detect the concentration of PCSK9. Clinical efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).ResultsA total of 55 patients were enrolled in the study. The median progression‐free survival (PFS) following treatment with ICIs in all patients was 9.9 months. The optimal threshold of baseline plasma PCSK9 was 232.2 ng/ml. Patients with low baseline plasma PCSK9 had a longer PFS (NR vs. 7.37 months, p = 0.017, HR = 0.207, 95% CI: 0.086–0.498) and a better response (ORR 71.4% vs. 43.9%, p = 0.075, DCR 100% vs. 80.5%, p = 0.098) to ICIs. Younger patients (≤66 years) with a lower PCSK9 had a significantly longer PFS and higher treatment response than those with a high baseline level of PCSK9 (NR vs. 5.83 months, p = 0.021, HR = 0.134, 95% CI: 0.044–0.409; ORR 66.7% vs. 30.0%, p = 0.106, DCR 100% vs. 75%, p = 0.153). The situation was similar in patients who received first‐line therapy (NR vs. 8.97 months, p = 0.022, HR = 0.138, 95% CI: 0.047–0.400; ORR 63.6% vs. 46.4%, p = 0.480, DCR 100% vs. 89.3%, p = 0.545). Multivariate analysis showed that low PCSK9 concentration was independently associated with PFS (p = 0.032, HR = 0.201).ConclusionsLow baseline plasma PCSK9 level may predict good outcomes in patients with advanced NSCLC treated with ICIs.
Naltrexone moderates the association of alcohol use and affect among adolescent drinkers in daily life
Authors: Carpenter Ryan W. , Emery Noah N. , Meisel Samuel N. , Miranda Robert 
Published: December 2021

AbstractBackgroundNaltrexone is an efficacious medication for the treatment of alcohol use disorder in adults. As an opioid receptor antagonist, naltrexone blocks activation of the endogenous opioid system, which is involved in the affectively reinforcing properties of substance use. Few studies, however, have examined the moderating effect of naltrexone on the association between affect and alcohol use. Additionally, most existing research on naltrexone has been with adults in the human laboratory.MethodWe conducted a secondary analysis of ecological momentary assessment data from a randomized, double‐blinded, placebo‐controlled cross‐over study that compared naltrexone (50 mg/daily) and placebo in 26 adolescents (15 to 19 years old) who exhibited problematic drinking patterns. Multilevel models tested whether naltrexone moderated associations of alcohol use with both positive and negative affect (PA, NA).ResultsResults indicated that, during naltrexone treatment, greater estimated blood alcohol concentration (eBAC) levels were associated with greater NA further into drinking episodes. In turn, greater NA after the first drink of an episode was associated with reduced subsequent eBAC values during naltrexone treatment. Low PA was also associated with lower subsequent eBAC levels in the naltrexone condition after the first drink.ConclusionsThese findings support the idea that naltrexone can disrupt the association between affect and alcohol use, effects that emerge later in drinking episodes. Greater attention to the effects of naltrexone on affect and reinforcement may help to tailor psychotherapy to maximize the benefits of naltrexone. However, in the present study, as most drink reports were in the first 2 h of the drinking episode and participants reported affect only at the first three end‐drink reports of a drinking episode (limiting the number of drinks reported), we had reduced power to detect effects in the continuation phase. Thus, replication of the findings is needed using a design that assesses the impact of naltrexone across the entire episode.
A mutation modulating DDX3Y gene expression cosegregates with the major Y‐chromosomal haplogroups and with testis size in Hu sheep
Authors: Zhang Xueying , Liao Zhi , Tang Shijie , Yuan Zehu , Li Fadi , Yue Xiangpeng 
Published: December 2021

SummaryVariations in the Y‐chromosome are usually correlated with male‐specific traits. However, this condition has been described only sporadically, even in human genetics. The present study was conducted to clone the full‐length gene sequence of ovine DEAD‐box helicase 3, Y‐linked (DDX3Y), and investigate the effect of the expression and variation of DDX3Y on the reproductive traits of Hu sheep. Consequently, we identified the full coding sequence and genomic sequence of ovine DDX3Y. Quantitative PCR (qPCR) analysis showed that ovine DDX3Y was highly expressed in testis, and the expression level increased during testicular development. Furthermore, individuals with larger testis at 6 months expressed significantly more DDX3Y mRNA in the testis than individuals with smaller testis. Notably, a novel SNP (g. 12657 C>A) in the 3′ untranslated region was identified in Hu sheep and Tan sheep according to the investigation of the full DDX3Y genomic sequence of 1069 individuals from nine sheep breeds. Association analysis revealed that the SNP was significantly related to testis size in Hu sheep. Meanwhile, Hu rams with the derived C allele showed significantly higher expression levels of DDX3Y in testis than those with the ancestral A allele. In addition, data mining in a previous study showed that the C allele cosegregated with the globally major Y‐chromosomal haplogroups y‐HA and y‐HC, and the A allele is found in all rams with haplogroups y‐HB1, y‐HB2 and y‐HD. This study suggests that the association of the Y‐chromosomal haplogroups with testis size in Hu sheep can be extrapolated to the sheep population worldwide.
The molecular landscape of progressive familial intrahepatic cholestasis in Turkey: Defining the molecular profiles and expanding the variant spectrum
Authors: Bakır Abdullatif , Topçu Vehap , Çavdarlı Büşranur 
Published: December 2021

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a rare genetically heterogeneous group of autosomal recessive liver disorders that manifests as intrahepatic cholestasis during the neonatal period. ATP8B1, ABCB11, and ABCB4 genes are responsible for PFIC type 1, PFIC type 2, and PFIC type 3, respectively. To determine the underlying molecular etiology of PFIC, 80 patients from 77 families were investigated. The molecular genetic diagnosis was applied by using next‐generation sequencing (NGS) and revealed 29 different variants from 32 patients. In this study, we evaluated these variants according to mechanisms, clinical sub‐groups, and genotype‐phenotype correlation.
There’s more to a vessel than meets the eye: Organic residue analysis of ‘wine’ containers from shipwrecks and settlements of ancient Cyprus (4th–1st century bce)
Authors: Briggs Lisa , Demesticha Stella , Katzev Susan , Wylde Swiny Helena , Craig Oliver E. , Drieu Léa 
Published: December 2021

AbstractDespite growing evidence to the contrary, wine remains the assumed content of many types of ancient pottery. Vessels from the Kyrenia and Mazotos shipwrecks, and Yeronisos island presumed to have contained wine were subjected to three different extraction protocols to test the assumption that these vessels were used to import and serve wine. Chemical extracts reveal grapevine products but also other fruit juice, beeswax and plant oil, sometimes mixed with grapevine products due to intentional mixing or reuse. Biomarkers detected in sediment samples from Mazotos and Yeronisos demonstrate why quantification is vital. Analyses show that even seemingly identical ceramics from the same shipwreck contained different commodities.
Nanomedicine targets iron metabolism for cancer therapy
Authors: Lin Liangru , Chen Hanqing , Zhao Ruifang , Zhu Motao , Nie Guangjun 
Published: December 2021

AbstractIron is an essential element for cell proliferation and homeostasis by engaging in cell metabolism including DNA synthesis, cell cycle, and redox cycling; however, iron overload could contribute to tumor initiation, proliferation, metastasis, and angiogenesis. Therefore, manipulating iron metabolisms, such as using iron chelators, transferrin receptor 1 (TFR1) Abs, and cytotoxic ligands conjugated to transferrin, has become a considerable strategy for cancer therapy. However, there remain major limitations for potential translation to the clinic based on the regulation of iron metabolism in cancer treatment. Nanotechnology has made great advances for cancer treatment by improving the therapeutic potential and lowering the side‐effects of the proved drugs and those under various stages of development. Early studies that combined nanotechnology with therapeutic means for the regulation of iron metabolism have shown certain promise for developing specific treatment options based on the intervention of cancer iron acquisition, transportation, and utilization. In this review, we summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron‐regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers.
The dietary inflammatory index is directly associated with polycystic ovary syndrome: A case‐control study
Authors: Zirak Sharkesh Elnaz , Keshavarz Seyed A. , Nazari Leila , Abbasi Behnood 
Published: December 2021

AbstractIntroductionThe association between diet and polycystic ovary syndrome (PCOS) might be mediated by the inflammatory properties of the diet. The study aimed to investigate the relationships between the dietary inflammatory index (DII) with odds of PCOS among the adult population.MethodsIn the hospital‐based case‐control study, 203 patients with PCOS and 291 non‐PCOS controls were enroled. DII was calculated via a validated 147‐item quantitative food frequency questionnaire (FFQ). Thirty‐six macro‐ and micronutrients were extracted from FFQ and used to calculate DII. Employing a case‐control design, odds ratios (ORs) and 95% confidence intervals (CIs) were obtained, with a dose‐response effect confirmed by the test for trend (p for trend).ResultsThe mean ± SD age and body mass index (BMI) of the study participants were 29.67 ± 5.92 years and 24.51 ± 4.71 kg/m2, respectively. Compared with controls subjects, PCOS patients had significantly higher weight, BMI, and waist circumferences, but had lower physical activity. PCOS subjects had higher intakes of carbohydrate, cholesterol, and refined grains, but lower intakes of polyunsaturated fatty acids, fibre, vitamin B12, vitamin D, and dairy as compared to controls. Compared with participants in the lowest quartile of DII, those in the highest quartile had a significantly higher OR for PCOS after further adjustment for potential confounders (OR = 1.75, 95% CI: 0.95–3.22).ConclusionOur data suggest that high DII was associated with an increased odds of PCOS diagnosis. Prospective dietary intervention studies and observational prospective cohorts are required to confirm these findings.
Potential role of viral infections in miscarriage and insights into the underlying molecular mechanisms
Authors: Heydarifard Zahra , Zadheidar Sevrin , Yavarian Jila , Shatizadeh Malekshahi Somayeh , Kalantari Shirin , Mokhtari‐Azad Talat , Shafiei‐Jandaghi Nazanin‐Zahra 
Published: December 2021

AbstractIntrauterine viruses can infect the decidua and placenta and cause adverse effects on the fetus during gestation. This review discusses the contribution of various viral infections to miscarriage and the molecular mechanisms by which viruses can cause devastating effects on healthy fetuses and induce miscarriage. Severe acute respiratory syndrome coronavirus 2 as newly emerged coronavirus was considered here, due to the concerns about its role during pregnancy and inducing miscarriage, as well. In this narrative review, an extensive literature search was conducted to find all studies investigating viral infections in miscarriage and their molecular mechanisms published over the past 20 years. The results of various studies investigating the roles of 20 viral infections in miscarriage are presented. Then, the mechanisms of pregnancy loss in viral infections were addressed, including alteration of trophoblast invasion and placental dysfunction, inducing excessive maternal immune response, and inducing apoptosis in the placental tissue. Viruses may cause pregnancy loss through different mechanisms and our knowledge about these mechanisms can be helpful for controlling or preventing viral infections and achieving a successful pregnancy.
Advancing procedural justice in conservation
Authors: Ruano‐Chamorro Cristina , Gurney Georgina G. , Cinner Joshua E. 
Published: December 2021

AbstractJust participation in conservation decision‐making is a moral imperative and critical to achieving social and ecological goals. However, understanding of what constitutes a just decision‐making process in conservation remains limited. Integrating key literature from environmental justice, psychology of justice, and participatory conservation, we identify 11 procedural justice criteria, many of which have been overlooked in conservation literature. We develop a framework to help promote procedural justice in conservation decision‐making which organizes the criteria into three key domains (Process properties, Agency of participants, Interpersonal treatment), which are underpinned by the justice dimension of recognition. We highlight seven policy levers that can be used to enhance procedural justice (e.g., scalar and contextual fit, conflict resolution, facilitation). However, advancing just decision‐making using this framework requires addressing a number of key challenges, in particular those related to broader structural power inequalities, and elucidating and accounting for plural and situated conceptions of procedural justice. We outline a number of pathways to overcome these challenges, including promoting knowledge coproduction and self‐reflexivity.
Changes in and correlates of Australian public attitudes toward illicit drug use
Authors: Weatherburn Don , Alexeev Sergey , Livingston Michael 
Published: December 2021

AbstractIntroductionThe present study explores Australian public support for more lenient treatment of persons found in possession of small amounts of illegal drugs for personal use.MethodsData for the study are drawn from the 2013, 2016 and 2019 National Drug Strategy Household Surveys. Bivariate associations were tested using χ2 tests corrected for survey design. Multivariate analyses of public support for legalisation and imprisonment involved logistic regression. Multivariate analyses of public preferences for various responses to those found in possession of illicit drugs involved the use of multinomial regression.ResultsSupport for legalising personal use of three drugs (cannabis, ecstasy and cocaine) has risen significantly since 2013 but remained stable (and low) for two (heroin and methamphetamine). Support for no action, a caution or a warning has grown for those found in possession of cannabis, ecstasy and heroin for personal use but not for those found in possession of methamphetamine. There is, however, more support for responding to this group with treatment, education or a small fine than there is for imprisonment.Discussion and ConclusionThere is strong support for legalising use of cannabis. There is little support for legalising use of ecstasy and cocaine but growing public support for a less punitive approach to those who use these drugs. There is little public support for a change in the current approach to heroin and methamphetamine.
Molecular diagnostics in dermatology: An online survey to study usage, obstacles and requirements in Germany
Authors: Tizek Linda , Schuster Barbara , Gebhardt Christoffer , Reich Kristian , von Kiedrowski Ralph , Biedermann Tilo , Eyerich Kilian , Zink Alexander , Garzorz‐Stark Natalie 
Published: December 2021

SummaryBackground and objectivesMolecular diagnostics (MDx) increasingly gains importance in dermatology and its application is a prerequisite for personalized medicine. The goal of this cross‐sectional study was to determine how MDx is implemented in dermatologists’ offices in the three fields of oncology, inflammation and infectiology and which hurdles office‐based dermatologists face in terms of MDx.MethodsPhysician members of the Association of the German Dermatologists (Berufsverband der Deutschen Dermatologen e. V.; BVDD) were surveyed via an online questionnaire on MDx.Results39.6 % of the 192 participants reported using MDx. Of these, the vast majority used MDx for diagnosing infectious diseases (86.5 % and 44.3 % of users perform MDx for detection of funghi and sexually transmitted diseases, respectively). Only a small minority applied MDx to answer oncological or immunological questions. The major obstacles for non‐users as compared to users were difficulties in implementation, lack of expertise as well as time, personnel, and technical availability. Reimbursement was a main issue in both groups.ConclusionsDespite availability of specific therapies requiring precision medicine, MDx has not yet been broadly implemented in office‐based dermatology. To advance MDx, more needs to be done in terms of continuous education, availability of reliable and valid tests, and reimbursability.
Comparative effectiveness of cardiovascular, renal and safety outcomes of second‐line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta‐analysis of randomised controlled trials
Authors: Sim Ruth , Chong Chun Wie , Loganadan Navin K. , Fong Alan Y. Y. , Navaravong Leenhapong , Hussein Zanariah , Khunti Kamlesh , Lee Shaun Wen Huey 
Published: December 2021

AbstractAimsTo compare the cardiovascular, renal and safety outcomes of second‐line glucose‐lowering agents used in the management of people with type 2 diabetes.MethodsMEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second‐line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non‐cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta‐analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322).ResultsWe included 38 trials from seven classes of glucose‐lowering therapies. Both sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) and glucagon‐like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3‐point major adverse cardiovascular events, 3P‐MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84–0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83–0.93; NNT, 50]), cardiovascular death, all‐cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP‐4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty).ConclusionsSGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.
High Dickkopf‐1 levels are associated with chronic inflammation in children with sickle cell disease
Authors: Giordano Paola , Vecchio Giovanni Carlo Del , Russo Giovanna , Palmieri Viviana Valeria , Piacente Laura , Fidone Carmelo , Urbano Flavia , Faienza Maria Felicia 
Published: December 2021

AbstractObjectivesSickle bone disease (SBD) is a chronic complication of sickle cell disease (SCD) whose pathogenesis is not completely understood. Chronic inflammation associated with SCD could alter bone remodeling. Our aim was to analyze the serum levels of bone remodeling markers in a group of SCD children to evaluate their involvement in the SBD.MethodsWe enrolled 26 SCD subjects and 26 age‐matched controls, who lived in the same geographic area. DKK‐1, sclerostin, RANKL, and OPG serum levels were evaluated. Neutrophil‐lymphocyte ratio (NLR) was also evaluated as a marker of inflammation.ResultsThe analysis of bone remodeling markers did not show any significant difference between the two groups except for DKK‐1 levels that were significantly higher in the patients than controls (p < .05). A significant direct correlation between NLR and DKK‐1 (p = .004) was found. An inverse correlation between NLR and osteocalcin (p = .01) has also been observed.ConclusionsThe chronic inflammation, which represents a peculiar characteristic in SCD patients, would represent the primary causal agent of the activation of osteoblastogenesis inhibitors responsible of bone impairment in these subjects. Further studies will be needed to better explain the role of these inhibitors in SCD, to prevent or treat bone damage in this population.