bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the drivers of syphilis among men who have sex with men in Switzerland reveals a key impact of testing frequency: A modelling study
Authors: Balakrishna Suraj , Salazar-Vizcaya Luisa , Schmidt Axel J. , Kachalov Viacheslav , Kusejko Katharina , Thurnheer Maria Christine , Roth Jan A. , Nicca Dunja , Cavassini Matthias , Battegay Manuel , Schmid Patrick , Bernasconi Enos , Günthard Huldrych F. , Rauch Andri , Kouyos Roger D. ,   the Swiss HIV Cohort Study (SHCS)
Published: January 2021

AbstractBackgroundOver the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions.Methods and FindingsWe set up an epidemiological model to assess the drivers of syphilis in MSM in Switzerland between 2006 and 2017. We stratified the model by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used ‘reported non-steady partners’ (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health.The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two-years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017).ConclusionsThe model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.
Network-based modeling of herb combinations in Traditional Chinese Medicine
Authors: Wang Yinyin , Yang Hongbin , Chen Linxiao , Jafari Mohieddin , Tang Jing 
Published: January 2021

AbstractTraditional Chinese Medicine (TCM) has been practiced for thousands of years for treating human diseases. In comparison to modern medicine, one of the advantages of TCM is the principle of herb compatibility, known as TCM formulae. A TCM formula usually consists of multiple herbs to achieve the maximum treatment effects, where their interactions are believed to elicit the therapeutic effects. Despite being a fundamental component of TCM, the rationale of combining specific herb combinations remains unclear. In this study, we proposed a network-based method to quantify the interactions in herb pairs. We constructed a protein-protein interaction network for a given herb pair by retrieving the associated ingredients and protein targets, and determined multiple network-based distances including the closest, shortest, center, kernel, and separation, both at the ingredient and at the target levels. We found that the frequently used herb pairs tend to have shorter distances compared to random herb pairs, suggesting that a therapeutic herb pair is more likely to affect neighboring proteins in the human interactome. Furthermore, we found that the center distance determined at the ingredient level improves the discrimination of top-frequent herb pairs from random herb pairs, suggesting the rationale of considering the topologically important ingredients for inferring the mechanisms of action of TCM. Taken together, we have provided a network pharmacology framework to quantify the degree of herb interactions, which shall help explore the space of herb combinations more effectively to identify the synergistic compound interactions based on network topology.
Ubiquitin ligase RIPLET mediates polyubiquitination of RIG-I and LGP2 and regulates the innate immune responses to SARS-CoV-2 infection
Authors: Kouwaki Takahisa , Nishimura Tasuku , Wang Guanming , Nakagawa Reiko , Oshiumi Hiroyuki 
Published: January 2021

SummaryRIG-I, a cytoplasmic viral RNA sensor, is crucial for innate antiviral immune responses; however, there are controversies about RIG-I’s regulatory mechanism by several ubiquitin ligases and LGP2. Our genetic study revealed that the RIPLET ubiquitin ligase was a general activating factor for RIG-I signaling, whereas another ubiquitin ligase, TRIM25, activated RIG-I in a cell-type-specific manner. These RIPLET and TRIM25 functions were modulated by accessory factors, such as ZCCH3C and NLRP12. Interestingly, we found an additional role of RIPLET in innate immune responses. RIPLET induced delayed polyubiquitination of LGP, resulting in the attenuation of excessive cytokine expression at the late phase. Moreover, RIPLET was involved in the innate immune responses against SARS-CoV-2 infection, a cause of the recent COVID-19 pandemic. Our data indicate that RIPLET fine-tunes innate immune responses via polyubiquitination of RIG-I and LGP2 against virus infection, including SARS-CoV-2.
Identifying outlier patterns of inconsistent ambulance billing in Medicare
Authors: Sanghavi Prachi , Jena Anupam B. , Newhouse Joseph P. , Zaslavsky Alan M. 
Published: January 2021

AbstractObjectiveTo illustrate a method that accounts for sampling variation in identifying suppliers and counties with outlying rates of a particular pattern of inconsistent billing for ambulance services to Medicare.Data SourcesUS Medicare claims for a 20% simple random sample of 2010‐2014 fee‐for‐service beneficiaries.Study DesignWe identified instances in which ambulance suppliers billed Medicare for transporting a patient to a hospital, but no corresponding hospital visit appeared in billing claims. We estimated the distributions of outlier supplier and county rates of such “ghost rides” by fitting a nonparametric empirical Bayes model with flexible distributional assumptions to account for sampling variation.Data CollectionWe included Basic and advanced life support ground emergency ambulance claims with a hospital destination.Principal Findings“Ghost ride” rates varied considerably across both ambulance suppliers and counties. We estimated 6.1% of suppliers and 5.0% of counties had rates that exceeded 3.6%, which was twice the national average of “ghost rides” (1.8% of all ambulance transports).ConclusionsHealth care fraud and abuse are frequently asserted but can be difficult to detect. Our data‐driven approach may be a useful starting point for further investigation.
Probiotic Lactobacillus casei Shirota prevents acute liver injury by reshaping the gut microbiota to alleviate excessive inflammation and metabolic disorders
Authors: Yan Ren , Wang Kaicen , Wang Qiangqiang , Jiang Huiyong , Lu Yingfeng , Chen Xiaoxiao , Zhang Hua , Su Xiaoling , Du Yiling , Chen Lifeng , Li Lanjuan , Lv Longxian 
Published: January 2021

SummaryMillions of people die from liver diseases annually, and liver failure is one of the three major outcomes of liver disease. The gut microbiota plays a crucial role in liver diseases. This study aimed to explore the effects of Lactobacillus casei strain Shirota (LcS), a probiotics used widely around the world, on acute liver injury (ALI), as well as the underlying mechanism. Sprague Dawley rats were intragastrically administered LcS suspensions or placebo once daily for 7 days before induction of ALI by intraperitoneal injection of D‐galactosamine (D‐GalN). Histopathological examination and assessments of liver biochemical markers, inflammatory cytokines, and the gut microbiota, metabolome and transcriptome were conducted. Our results showed that pretreatment with LcS reduced hepatic and intestinal damage and reduced the elevation of serum gamma‐glutamyltranspeptidase (GGT), total bile acids, IL‐5, IL‐10, G‐CSF and RANTES. The analysis of the gut microbiota, metabolome and transcriptome showed that LcS lowered the ratio of Firmicutes to Bacteroidetes; reduced the enrichment of metabolites such as chenodeoxycholic acid, deoxycholic acid, lithocholic acid, d‐talose and N‐acetyl‐glucosamine, reduce the depletion of d‐glucose and l‐methionine; and alleviated the downregulation of retinol metabolism and PPAR signalling and the upregulation of the pyruvate metabolism pathway in the liver. These results indicate the promising prospect of using LcS for the treatment of liver diseases, particularly ALI.
An unusual overrepresentation of genetic factors related to iron homeostasis in the genome of the fluorescent Pseudomonas sp. ABC1
Authors: Valenzuela‐Heredia Daniel , Henríquez‐Castillo Carlos , Donoso Raúl , Lavín Paris , Ringel Michael T. , Brüser Thomas , Campos José Luis 
Published: January 2021

SummaryMembers of the genus Pseudomonas inhabit diverse environments, such as soil, water, plants and humans. The variability of habitats is reflected in the diversity of the structure and composition of their genomes. This cosmopolitan bacterial genus includes species of biotechnological, medical and environmental importance. In this study, we report on the most relevant genomic characteristics of Pseudomonas sp. strain ABC1, a siderophore‐producing fluorescent strain recently isolated from soil. Phylogenomic analyses revealed that this strain corresponds to a novel species forming a sister clade of the recently proposed Pseudomonas kirkiae. The genomic information reveals an overrepresented repertoire of mechanisms to hoard iron when compared to related strains, including a high representation of fecI‐fecR family genes related to iron regulation and acquisition. The genome of the Pseudomonas sp. ABC1 contains the genes for non‐ribosomal peptide synthetases (NRPSs) of a novel putative Azotobacter‐related pyoverdine‐type siderophore, a yersiniabactin‐type siderophore and an antimicrobial betalactone; the last two are found only in a limited number of Pseudomonas genomes. Strain ABC1 can produce siderophores in a low‐cost medium, and the supernatants from cultures of this strain promote plant growth, highlighting their biotechnological potential as a sustainable industrial microorganism.
Deep brain stimulation versus ablative surgery for treatment‐refractory obsessive‐compulsive disorder: A meta‐analysis
Authors: Hageman Sarah Babette , van Rooijen Geeske , Bergfeld Isidoor O. , Schirmbeck Frederike , de Koning Pelle , Schuurman P. Rick , Denys Damiaan 
Published: January 2021

AbstractObjectiveAblative surgery (ABL) and deep brain stimulation (DBS) are last‐resort treatment options for patients suffering from treatment‐refractory obsessive‐compulsive disorder (OCD). The aim of this study was to conduct an updated meta‐analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation.MethodsWe conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta‐analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale‐Brown Obsessive‐Compulsive Scale (Y‐BOCS) score and the responder rate (≥35% reduction in Y‐BOCS score).ResultsWith responder rates of 48% and 53% after 12–16 months and 56% and 57% at last follow‐up for ABL and DBS, respectively, and large effect sizes in the reduction in Y‐BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta‐regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS.ConclusionThis meta‐analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.
Paradoxical effect of SARS‐CoV‐2 infection in patients with immune thrombocytopenia
Authors: de la Cruz‐Benito Beatriz , Rivas‐Pollmar María I. , Álvarez Román María T. , Trelles‐Martínez Roberto , Martín‐Salces Monica , Lázaro‐del Campo Paula , Ramírez‐López Andrés , García‐Barcenilla Sara , Cebanu Tamara , Acuña‐Butta Paula , Monzón‐Manzano Elena , González‐Zorrilla Elena , Jiménez‐Yuste Victor , Butta Nora V. 
Published: January 2021

SummaryThrombocytopenia has been identified as a common complication of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the general population. In an attempt to determine the impact of coronavirus disease 2019 (COVID‐19) in patients with immune thrombocytopenia (ITP), a retrospective single‐centre study was performed. Thrombocytosis was observed in patients with chronic ITP after SARS‐CoV‐2 infection, frequently needing treatment adjustment or even discontinuation of therapy. Relapses and newly diagnosed cases showed a fast response after initial treatment compared to ITP. Reduced immune activity due to lymphopenia during COVID‐19 could explain this paradoxical effect, although further studies are needed.
Efficacy of parthenium hysterophorus waste biomass compared with activated charcoal for the removal of CI Reactive Red 239 textile dye from wastewater
Authors: Bapat Shreyas , Jaspal Dipika , Malviya Arti 
Published: January 2021

AbstractIn the quest to find an eco‐friendly, cost‐effective and efficient alternative to expensive and non‐biodegradable activated charcoal (AC), in the current study the potential of a weed, parthenium hysterophorus (PH), has been explored as a bio‐adsorbent for purification of textile wastewater. Root, stem and leaves of PH weed have been used as bio‐adsorbents in raw and surface‐treated forms and compared with AC for removal of toxic textile dye CI Reactive Red 239 (Remazol Brilliant Red 3BS [RBR 3BS]) from wastewater. The surface treatment carried out using QAS (N‐Cetyl‐N,N,N–trimethylammonium bromide) in the current study is a novel way to enhance the dye adsorption capacity of raw adsorbents of PH. Characterisation tools like Fourier Transform–infrared spectroscopy, scanning electron microscopy, elemental analysis and potential of zero charge have been used to confirm the surface treatment. The impact of various process variables like pH, dosage of adsorbent, contact time, solution temperature and dye concentration have been studied. Isothermal, kinetic and thermodynamics modelling for adsorption data have been thoroughly investigated to ascertain the mechanism of adsorption. Statistical error functions like root mean square error, chi‐square test, sum of absolute error and normalized standard deviation (NSD) have been used to validate the adsorption data. Results revealed that novel surface treatment significantly improved the dye adsorption capacity of raw PH adsorbents (ca. 15‐16 times). Of all the weed bio‐adsorbents, surface‐treated PH stem showed the highest dye adsorption capacity (105 mg/g), which was 10‐folds greater than commercial grade AC (10.4 mg/g at 27°C). For both adsorbents, surface‐treated PH stem and AC, adsorption followed pseudo‐second order kinetics, and the Langmuir isotherm was the best fit with film diffusion as a rate‐controlling step. Thermodynamic parameters infer the spontaneous and exothermic nature of adsorption. Therefore, in the current study, surface‐treated PH stem bio‐adsorbent has been revealed as a superior alternative to AC for the removal of RBR 3BS dye from wastewater, opening a new gateway to the utilisation of waste weeds for the purpose of wastewater treatment.
Population pharmacokinetic and exposure‐response analyses of ivosidenib in patients with IDH1‐mutant advanced hematologic malignancies
Authors: Jiang Xuemin , Wada Russ , Poland Bill , Kleijn Huub Jan , Fan Bin , Liu Guowen , Liu Hua , Kapsalis Stephanie , Yang Hua , Le Kha 
Published: January 2021

AbstractIvosidenib is a once daily (q.d.), orally available, potent mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor approved for treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and intensive chemotherapy ineligible AML with a susceptible IDH1 mutation. Population pharmacokinetics (PKs; N = 253), exposure‐response (efficacy [n = 201] and safety [n = 253]), and concentration‐corrected electrocardiogram QT interval (QTc; n = 171) analyses were performed using phase I data (100 mg twice daily and 300–1200 mg q.d.). Ivosidenib disposition was well‐described by a two‐compartment PK model with first‐order absorption and elimination. Between‐subject variability was moderate for PK parameters. Intrinsic factors did not affect ivosidenib PKs. Moderate/strong CYP3A4 inhibitors increased the area under the plasma ivosidenib concentration‐time curve at steady state (AUCss) by 60%. Efficacy responders and nonresponders had similar ivosidenib exposures. Based on AUCss, there was no apparent relationship between ivosidenib exposure and efficacy or adverse events. The plasma ivosidenib concentration‐QT analysis showed a mean change in QTc using Fridericia’s method (ΔQTcF) of 17.2 msec at the approved 500 mg q.d. dose. Because of the direct association between ivosidenib exposure and QTcF, patients should have their electrocardiograms and electrolytes monitored, and comedications that increase ivosidenib exposure or prolong the QT interval should be avoided. These model‐based analyses quantitatively provide a framework to describe the relationship among ivosidenib dose, exposure, and clinical end points. With precautions for QTc prolongation, the exposure‐response analyses support the 500 mg q.d. dose in patients with AML with a susceptible IDH1 mutation.
Vergleich der Wirksamkeit und Sicherheit von Biologika bei mittelstark bis stark ausgeprägter Plaque‐Psoriasis: Metaanalyse multipler Therapien
Authors: Xu Shanshan , Gao Xing , Deng Jixiang , Yang Jiajia , Pan Faming 
Published: January 2021

ZusammenfassungZielVergleich der Wirksamkeit und Sicherheit von Biologika bei Patienten mit mittelstark bis stark ausgeprägter Plaque‐Psoriasis.MethodenSystematische Auswertung von 60 randomisierten, kontrollierten Studien mit insgesamt 34 020 Teilnehmern, in denen 14 Biologika zur Behandlung der mittelstark bis stark ausgeprägten Plaque‐Psoriasis verglichen wurden. Die Hauptkriterien in der Analyse waren eine Verminderung des Schweregrades im Psoriasis Area and Severity Index um ≥ 90 % (PASI 90) sowie die Anzahl der Patienten, die unter der Behandlung aufgetretene Nebenwirkungen (NW) berichteten. Sekundäre Kriterien waren ≥ 75 % Verminderungen im Psoriasis Area and Severity Index (PASI 75), ein Physician’s Global Assessment von 0/1 (PGA 0/1) sowie Infektionen.ErgebnisseDiese Netzwerk‐Metaanalyse zeigt, dass Biologika signifikant wirksamer sind als Placebo. Ixekizumab, Risankizumab und Bimekizumab gehören zu den wirksamsten Behandlungsmöglichkeiten, während Tildrakizumab, Guselkumab und Risankizumab den anderen Arzneimitteln in der Sicherheit überlegen sind. Risankizumab und Guselkumab zeigten sowohl in der Wirksamkeit als auch in der Sicherheit stabile Ergebnisse. Betrachtet man die unterschiedlichen Wirkstoffklassen, dann erweisen sich die Interleukin (IL)‐17A‐Hemmer als besonders wirksam und die Hemmstoffe der p19‐Untereinheit des IL‐23 unter allen wirksamen Biologika als am besten verträglich.SchlussfolgerungenIxekizumab zeigte sich im PASI 90 als die wirksamste Substanz, während die IL‐23p19‐Hemmstoffe Risankizumab und Guselkumab sowohl in der Wirksamkeit als auch in der Sicherheit relativ stabile Ergebnisse erbrachten.
Comparison of patient pathways in the early detection of skin cancer – a claims data analysis
Authors: Krensel Magdalene , Petersen Jana , Stephan Brigitte , Katalinic Alexander , Augustin Jobst 
Published: January 2021

SummaryBackgroundRegarding skin cancer screening, patients in Germany have the choice between a direct screening by dermatologists or an initial screening by general practitioners followed by dermatological screening if further examination is required. The aim of this study is to evaluate whether screening by general practitioners is associated with risk selection in subsequent dermatological screenings.Patients and MethodsWe conducted a retrospective observational study based on claims data from a German health insurance company (Barmer GEK). Patient pathways in skin cancer screenings between 2008 and 2016 were analyzed, and differences between the two groups were tested at 95 % confidence intervals.ResultsA total of 495,000 initial and 111,000 secondary examinations by dermatologists were analyzed. The proportion of subsequent excisions was lower in initial screenings by dermatologists. To diagnose one person with non‐melanoma skin cancer or melanoma, five or 23 to 42 excisions were necessary, depending on the type of excision considered. The number of examinations to identify one patient ranged from 25 to 53 for non‐melanoma skin cancer and 42 to 165 for melanoma. For melanoma, the number of excisions and screenings to diagnose skin cancer was lower in secondary examinations.ConclusionsThe results indicate a risk selection through initial examinations by general practitioners. However, there are other aspects that should be taken into account when comparing the two pathways.