bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global opioid agonist treatment: a review of clinical practices by country
Authors: Jin Harry , Marshall Brandon D. L. , Degenhardt Louisa , Strang John , Hickman Matt , Fiellin David A. , Ali Robert , Bruneau Julie , Larney Sarah 
Published: April 2020

ABSTRACTAimsWe assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine‐naloxone, is delivered in routine clinical practice, with a focus on factors that affect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally.MethodsWe completed searches of PubMed, Embase, and grey literature databases for cross‐sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted from eligible studies were compared with guidelines provided by WHO.ResultsWe found 140 reports from 41 countries that contained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was the most common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadone ranged from 16–131 mg whereas range for buprenorphine was 2.5–19 mg. Access to unsupervised dosing under some conditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several times a week to eight times per year (methadone) or as clinically indicated.ConclusionsOpioid agonist treatment practices, including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lower dose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinical benefits.
Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study
Authors: Wallace Sebastian J. , Swann Rachael , Donnelly Mhairi , Kemp Linda , Guaci Julia , Murray Aimee , Spoor Johannes , Lin Nan , Miller Michael , Dalton Harry R. , Hussaini S. Hyder , Gunson Rory , Simpson Kenneth , Stanley Adrian , Fraser Andrew 
Published: April 2020

SummaryBackgroundHepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states.AimsTo record the morbidity and mortality of HEV in Scotland.MethodsDemographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018.ResultsFive hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre‐existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV‐related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40‐782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85‐594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01‐1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02‐0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty‐five (6.7%) patients developed acute or acute‐on‐chronic liver failure with two requiring transplant. Thirty‐seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain‐Barré and 2 encephalitis. Forty‐four (8.6%) patients developed acute kidney injury.ConclusionIn Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.
Comparison of the fecal microbiota of two monogastric herbivorous and five omnivorous mammals
Authors: Kobayashi Rana , Nagaoka Kentaro , Nishimura Naomichi , Koike Satoshi , Takahashi Eiki , Niimi Kimie , Murase Harutaka , Kinjo Teruo , Tsukahara Takamitsu , Inoue Ryo 
Published: April 2020

AbstractFecal microbiota in seven different monogastric animal species, elephant, horse, human, marmoset, mouse, pig and, rat were compared using the same analytical protocol of 16S rRNA metagenome. Fecal microbiota in herbivores showed higher alpha diversity than omnivores except for pigs. Additionally, principal coordinate analysis based on weighted UniFrac distance demonstrated that herbivores and pigs clustered together, whereas other animal species were separately aggregated. In view of butyrate‐ and lactate‐producing bacteria, predominant genera were different depending on animal species. For example, the abundance of Faecalibacterium, a known butyrate producer, was 8.02% ± 3.22% in human while it was less than 1% in other animal species. Additionally, Bifidobacterium was a predominant lactate producer in human and marmoset, while it was rarely detected in other omnivores. The abundance of lactate‐producing bacteria in herbivores was notably lower than omnivores. On the other hand, herbivores as well as pig possess Fibrobacter, a cellulolytic bacterium. This study demonstrated that fecal microbiota in herbivorous animals is similar, sharing some common features such as higher alpha diversity and higher abundance of cellulolytic bacterium. On the other hand, omnivorous animals seem to possess unique fecal microbiota. It is of interest that pigs, although omnivore, have fecal microbiota showing some common features with herbivores.
Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant
Authors: Sweiss Karen , Vemu Bhaskar , Hofmeister Craig C. , Wenzler Eric , Calip Gregory Sampang , Galvin John P. , Mahmud Nadim , Rondelli Damiano , Johnson Jeremy James , Patel Pritesh 
Published: April 2020

AimsHigh dose melphalan (HDM) and autologous stem cell transplant (ASCT) is standard of care for multiple myeloma (MM), but there is significant variability in melphalan exposure (area under the plasma drug concentration–time curve, AUC) when using body surface area‐based dosing. Our aim was to establish a method of pharmacokinetic (PK) testing for real‐time melphalan dose adjustments.MethodsWe performed a prospective PK study of melphalan 140 or 200 mg/m2 in MM patients undergoing ASCT. Twenty MM patients were administered HDM on days −2 and − 1, with PK sampling at 8–10 time points. PK testing was performed on day −2 in all patients, and on day −1 in 5 patients.ResultsLess than 20% interpatient variation in the day −2 and − 1 AUC was observed. The day −2 range in AUC (4.95–11.28 mg h/L) confirmed significant interpatient variability. The hypothetical total dose ranged from 133–302 mg/m2 to achieve the total median AUC. A 4‐time point AUC (0, 30, 150 and 240 min) highly correlated with the AUC from the 8‐time point schedule. A higher AUC correlated with increased risk of febrile neutropenia (P = .05).ConclusionHere we outline the methods to establish novel melphalan dosing using PK testing in MM patients undergoing ASCT to target a desired melphalan AUC.
Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1)
Authors: Papp K. , Menter A. , Leonardi C. , Soung J. , Weiss S. , Pillai R. , Jacobson A. 
Published: April 2020

Summary

Background
Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks.

Objectives
To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment.

Methods
At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re-treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events.

Results
Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed.

Conclusions
These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.
Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency
Authors: Fernández Cecilia S. , Taboas Melisa , Bruque Carlos D. , Benavides‐Mori Belén , Belli Susana , Stivel Mirta , Oneto Adriana , Pasqualini Titania , Delea Marisol , Espeche Lucía D. , Kolomenski Jorge E. , Alba Liliana , Buzzalino Noemí , Dain Liliana 
Published: April 2020

AbstractContext21‐hydroxylase deficiency is the most common cause of Congenital Adrenal Hyperplasia. It presents as severe or classical forms—salt wasting and simple virilizing—and a mild or nonclassical (NC). Several studies have reported the frequency of pathogenic variants in different populations, although few of them included a large number of NC patients.ObjectiveTo analyse the CYP21A2 gene defects in a large cohort of Argentine patients.DesignMolecular characterization of 628 patients (168 classical, 460 nonclassical, representing 1203 nonrelated alleles), 398 relatives, 126 partners.MethodsGenetic variants were assessed by allele‐specific PCR, PCR‐RFLP or direct sequencing. Deletions, duplications and large gene conversions (LGC) were studied by Southern blot/MLPA or long‐range PCR. Biological implications of novel variants were analysed by structure‐based in silico studies.ResultsThe most frequent pathogenic variants were p.V282L (58%) in NC alleles and c.293‐13C>G (31.8%) and p.I173N (21.1%) in classical. Deletions and LGC were found at low frequency (6.2%), 57 alleles had rare pathogenic variants, and 3 had novel variants: p.(S166F); p.(P189R), p.(R436L). Genotype‐phenotype correlation was observed in 98.6% of the cases, 11 asymptomatic first‐degree relatives had pathogenic variants in both alleles, and 21/126 partners were carriers.ConclusionsWe conducted a comprehensive genetic characterization of the largest cohort of 21‐hydroxylase patients from the region. In particular, we add to the molecular characterization of a large number of NC patients and to the estimation of the disease carrier's frequency in our population.
Diagnostic significance of DNA methylation of PTEN and DAPK in thyroid tumors
Authors: Wei Feng , Wu Yun , Wang Zhaoxia , Li Yongchao , Wang Jing , Shao Guo , Yang Ying , Shi Bingyin 
Published: April 2020

AbstractObjectiveDNA Methylation of the tumour suppressor gene leading to gene silencing plays an important role in thyroid tumour development. The purpose was to determine the DNA methylation status of phosphatase and tensin homolog (PTEN) and death‐associated protein kinase (DAPK) in patients with thyroid nodules and to explore whether they can be used as molecular diagnostic tools to differentiate benign and malignant thyroid nodules.Design, patients and measurementsThyroid tissue and blood samples were obtained from normal healthy individuals (controls) and patients suffering from clinically diagnosed thyroid nodular disease [papillary thyroid carcinoma (PTC), adenoma and nodular goitre]. DNA methylation level, mRNA expression and protein expression of PTEN and DAPK in the thyroid tissues and peripheral blood were detected using methylation‐specific PCR, semi‐quantitative reverse transcription PCR and Western blot, respectively. Diagnostic sensitivity, specific and accuracy of detection were evaluated between blood and thyroid tissue.ResultsThere was a significant increase in the level of DNA methylation of PTEN and DAPK in PTC (P < .05) compared with controls and other types of thyroid nodules. Levels of the mRNA of both PTEN and DAPK were lower in PTC in both peripheral blood and tissue samples compared with controls, while there was concomitant decrease of both PTEN and DAPK protein expression in PTC tissues (P < .05). There was no significant difference in diagnostic specificity, sensitivity and accuracy between blood sample and thyroid tissues.ConclusionsHypermethylated status of both PTEN and DAPK in peripheral blood and tissue samples can be useful biomarkers for clinical diagnosis and, distinguishing of benign and malignant thyroid nodules.
Primary stability of narrow‐diameter dental implants with a multiple condensing thread design placed in bone with and without osteotomes: An in vitro study
Authors: Romanos Georgios E. , Lau Jessica , Delgado‐Ruiz Rafael , Javed Fawad 
Published: April 2020

AbstractBackgroundThe authors hypothesized that there is no difference in the primary stability (PS) of multiple condensing thread design (MCTD) implants placed in simulated type‐IV bone with and without using osteotomes.PurposeThis in vitro study assessed the PS of narrow‐diameter dental implants with MCTD placed in simulated soft (type‐IV) bone with and without using osteotomes.Materials and MethodsSixty MCT‐designed implants (diameter: 3.0 mm; length: 11.5 mm) were placed using 800 rpm drilling speed in cellular rigid polyurethane foam bone‐blocks that simulated type‐IV bone. Prior to placement, the implants were divided into three groups (20 implants per group) depending upon the protocol used for osteotomy preparation—Group‐1: Conventional drilling (CD); Group‐2: CD followed by osseous condensation using a chisel‐shaped tapered osteotome with maximum diameter of 3 mm; and Group‐3: CD followed by osseous condensation using a cylindrical osteotome with maximum diameter of 3 mm. Abutments were connected to all implants and PS was recorded using resonance frequency analysis (RFA) and the periotest (PTV). Group comparisons were performed using analysis and Bonferroni post‐hoc adjustment tests. Level of significance was set at P < .05.ResultsThere was no statistically significant difference in the RFA values for the MCT‐designed implants placed in groups 1, 2, and 3 (59.85 ± 0.72, 59.67 ± 0.76 and 59.42 ± 0.92, respectively). There was no statistically significant difference in the PTV values for MCT‐designed implants in groups 1, 2, and 3 (1.655 ± 0.82, 1.405 ± 0.57, and 1.078 ± 0.63, respectively).ConclusionThe MCTD implants with narrow diameters have a high PS in artificial soft bone in vitro. Due to the condensation effect of the thread design, there is no need for additional condensation of the peri‐osteotomy bone in order to improve implant stability.
Biodiversity policy beyond economic growth
Authors: Otero Iago , Farrell Katharine N. , Pueyo Salvador , Kallis Giorgos , Kehoe Laura , Haberl Helmut , Plutzar Christoph , Hobson Peter , García‐Márquez Jaime , Rodríguez‐Labajos Beatriz , Martin Jean‐Louis , Erb Karl‐Heinz , Schindler Stefan , Nielsen Jonas , Skorin Teuta , Settele Josef , Essl Franz , Gómez‐Baggethun Erik , Brotons Lluís , Rabitsch Wolfgang , Schneider François , Pe'er Guy 
Published: April 2020

AbstractIncreasing evidence—synthesized in this paper—shows that economic growth contributes to biodiversity loss via greater resource consumption and higher emissions. Nonetheless, a review of international biodiversity and sustainability policies shows that the majority advocate economic growth. Since improvements in resource use efficiency have so far not allowed for absolute global reductions in resource use and pollution, we question the support for economic growth in these policies, where inadequate attention is paid to the question of how growth can be decoupled from biodiversity loss. Drawing on the literature about alternatives to economic growth, we explore this contradiction and suggest ways forward to halt global biodiversity decline. These include policy proposals to move beyond the growth paradigm while enhancing overall prosperity, which can be implemented by combining top‐down and bottom‐up governance across scales. Finally, we call the attention of researchers and policy makers to two immediate steps: acknowledge the conflict between economic growth and biodiversity conservation in future policies; and explore socioeconomic trajectories beyond economic growth in the next generation of biodiversity scenarios.
Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy
Authors: Chen Yudi , Nong Lin , Li Xin , Wang Yang 
Published: April 2020

AbstractComposite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T‐cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed‐Sternberg (R‐S) cells were interspersed among these atypical T‐cells in the deep dermis. Immunophenotyping suggested a HL origin of these R‐S cells. Monoclonality of T‐cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R‐S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.
‘In This Profession We Eat Dust’: Informal and Formal Solidarity among Women Urban Transportation Workers in Nepal
Authors: Grossman‐Thompson Barbara 
Published: April 2020

ABSTRACTThis article considers the working lives of women who drive electric rickshaws, known as tempos, in Kathmandu, Nepal. Drawing on ethnographic fieldwork, the author examines drivers’ precarious working conditions and the strategies they use in an effort to secure better conditions and job security. This case study illuminates the particulars of women tempo drivers’ day‐to‐day experiences and also speaks to larger debates in feminist political economy surrounding women's entrance into the paid labour force, especially in South Asia. Women drivers provide a compelling example of how socio‐economically disadvantaged women in industrializing and urbanizing cities of the global South find ways to create and protect spaces of dignified work and worker solidarity despite myriad challenges. Evidence from the research suggests that both informal and more formalized coping and resistance strategies are important mechanisms through which women seek to change the terms of their labour.
Neutrophil recruitment and intracellular vesicle transport: A short overview
Authors: Masgrau‐Alsina Sergi , Sperandio Markus , Rohwedder Ina 
Published: April 2020

AbstractRecruitment of neutrophils from the intravascular compartment into injured tissue is an essential component of the inflammatory response. It involves intracellular trafficking of vesicles within neutrophils and endothelial cells, both containing numerous proteins that have to be distributed in a tightly controlled and precise spatiotemporal fashion during the recruitment process. Rab proteins, a family of small GTPases, together with their effectors, are the key players in guiding and regulating the intracellular vesicle trafficking machinery during neutrophil recruitment. This review will provide a short overview on this process and highlight new findings as well as current controversies in the field.
Normal regression of the internal umbilical remnant structures in Standardbred foals
Authors: McCoy Annette M. , Lopp Christine T. , Kooy Sarah , Migliorisi Alessandro C. , Austin Scott M. , Wilkins Pamela A. 
Published: April 2020

AbstractBackgroundDiseases affecting the internal umbilical remnant are common in foals. Ultrasound is used to diagnose abnormalities of these structures, and to monitor treatment. However, little is known about the progression of normal internal umbilical remnant regression.ObjectivesTo document normal regression of the umbilical remnant in foals over the first 6 weeks of life.Study designProspective, longitudinal cohort study.MethodsWeekly ultrasound examinations were performed beginning at 1 day of age in 34 healthy Standardbred foals. The umbilical vein was measured in cross section just cranial to the external umbilicus, at the level of the liver and midway between these points. The umbilical arteries were measured in cross section just caudal to the external umbilicus, at the apex of the bladder and at the midpoint of the bladder. The urachus was imaged longitudinally as it exited the bladder. Reduction in size over time was evaluated as percentage change in diameter.ResultsStructure diameter decreased linearly over time. The largest measurements were at 24 hours of age with a median umbilical vein diameter of 0.83 cm (IQR 0.77‐1.02 cm), median umbilical artery diameter of 0.61 cm (IQR 0.56‐0.70 cm) and median urachal diameter of 1.07 cm (IQR 1.02‐1.14 cm). There was a significant reduction in diameter for all structures (16.0%‐21.9%; corrected P < .001) within the first week of life.Main limitationsAll foals were of a single breed, and examinations and measurements were performed by multiple individuals.ConclusionsThe internal umbilical remnants (umbilical vein/arteries, and urachus) rapidly regress over the first few weeks of life. The median internal umbilical remnant diameters reported here are smaller than previously reported values, emphasising the importance of accounting for age when diagnosing umbilical abnormalities. In a healthy Standardbred foal, normal structures are difficult to definitively identify via transcutaneous ultrasound by 5‐6 weeks of age.