bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐reported outcomes in a large North American cohort living with chronic hepatitis B virus: a cross‐sectional analysis
Authors: Evon Donna M. , Lin Hsing‐Hua S. , Khalili Mandana , Fontana Robert J. , Yim Colina , Wahed Abdus S. , Fried Michael W. , Hoofnagle Jay H. ,   for the Hepatitis B Research Network (HBRN)
Published: January 2020

SummaryBackgroundPatient‐reported outcomes (PROs) such as health‐related quality of life (HRQoL) and symptoms associated with chronic hepatitis B viral (HBV) infection have not been well‐described in North American cohorts.AimsTo evaluate several PROs and associations with HBV disease activity markers.MethodsCross‐sectional analysis including 876 adults who completed PRO measures during the Hepatitis B Research Network Adult Cohort Study. Participants on HBV treatment were excluded. Outcomes included: HRQoL using the SF‐36 mental component summary and physical component summary scores; symptom burden using a 10‐item Total Symptom Checklist and fatigue using an instrument from the Patient‐Reported Outcomes Measurement Information System®. Covariates included laboratory markers of disease severity, virological status, comorbidities and medications.ResultsMedian age was 42 (range: 19‐79), 51% were female, 73% Asian, 19% HBeAg (+), 2% had AST‐platelet ratio index (APRI) ≥1.5 and 74% without comorbidities. Mean mental component summary T‐score = 52, physical component summary T‐score = 54 and PROMIS Fatigue T‐score = 47. On a scale from 0 (none) to 40 (extreme), the mean Symptom Checklist score = 3 and 25% reported no symptoms. The most frequent symptoms were fatigue (60%), irritability (32%) and itching (32%). Most symptoms were ‘a little bit’ bothersome. In multivariable regressions, APRI ≥1.50 and more comorbidities were associated with worse patient‐reported outcomes; virological markers were not. Adding the Total Symptom Checklist score to original regression models increased explanation of variation in the mental component summary score from 4% to 44% and the Physical Component Summary Score from 17% to 34%.ConclusionsUntreated North American HBV patients with mild liver disease report favourable health‐related quality of life and minimal symptoms. HBV does not impact health‐related quality of life unless advanced liver disease or comorbidities are present. High symptom burden explains substantial variation in health‐related quality of life. (CT.gov identifier: NCT01263587).
A missense variant in complement factor B (CFB) is a potential predictor of 24‐week off‐treatment response to PegIFNα therapy in Chinese HBeAg‐positive chronic hepatitis B patients
Authors: Chen Haitao , Sun Jian , Zhou Bin , Peng Jinxin , Xie Qing , Liang Xieer , Fan Rong , Conran Carly , Xu Jianfeng , Ji Yuan , Zhang Xinxin , Sun Li , Jia Jidong , Wang Guiqiang , Hou Jinlin , Jiang De‐Ke 
Published: January 2020

SummaryBackgroundTo date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB).AimTo investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients.MethodsWe performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed.ResultsWe found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P‐trend = 4.000 × 10−4) and HBsAg loss (P‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients.ConclusionsCFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.
The natural flavonoid galangin ameliorates dextran sulphate sodium–induced ulcerative colitis in mice: Effect on Toll‐like receptor 4, inflammation and oxidative stress
Authors: Gerges Samar H. , Tolba Mai F. , Elsherbiny Doaa A. , El‐Demerdash Ebtehal 
Published: January 2020

AbstractThis study was carried out to investigate the potential therapeutic effect of galangin, a promising active principle of honeybee propolis, in dextran sulphate sodium (DSS)–induced colitis in mice. We explored the possible underlying mechanisms for galangin action and the therapeutic benefit of adding galangin to the standard therapy sulphasalazine. A galangin dose of 40 mg/kg was selected based on a preliminary dose‐selection study for investigation in a 4‐week cyclical model of DSS‐induced colitis. Mice received 3% DSS in their drinking water during the first and third weeks and were administered the treatments (40 mg/kg galangin, 100 mg/kg sulphasalazine and a combination of 20 mg/kg galangin and 50 mg/kg sulphasalazine) daily starting from the second week. Galangin significantly ameliorated DSS‐induced histopathological alterations and tissue injury, down‐regulated Toll‐like receptor 4 expression, suppressed NF‐κB p65 activation, lowered inflammatory cytokine levels and demonstrated antioxidant effects. The combination of galangin and sulphasalazine at half doses yielded comparable results to either drug alone at full dose. This study highlights galangin as a promising therapy for colitis management.
Safety and efficacy of eltrombopag plus pulsed dexamethasone as first‐line therapy for immune thrombocytopenia
Authors: Zhang Lunqing , Zhang Mingjie , Du Xin , Cheng Yunfeng , Cheng Gregory 
Published: January 2020

SummaryCurrent first‐line treatments for immune thrombocytopenia (ITP) usually have transient effects and sustained platelet response off therapy remains low. We evaluated whether eltrombopag plus pulsed dexamethasone as first‐line therapy can increase the proportion of patients maintaining platelet counts >50 × 109/l for a prolonged period without further ITP therapy. Treatment consisted of eltrombopag 25–75 mg daily according to platelet response for 12 weeks plus dexamethasone, 40 mg daily for four consecutive days every four weeks for 1–3 courses. Primary endpoint was durable response off therapy defined as maintaining platelet counts >50 × 109/l for more than six months without further ITP therapy. Fifty ITP subjects were enrolled between November 2014 and March 2019. Out of 46 evaluable subjects, 26 (56·5%) had achieved the primary endpoint. The median platelet counts at six months off‐treatment follow‐up were 158 × 109/l. Only two out of 26 responders had relapsed at eight‐ and nine‐month follow‐up. The remaining 24 are still maintaining platelet counts >50 × 109/l, the longest over three years. All subjects tolerated treatment well and no Grade 3 or above adverse effects were reported. Eltrombopag plus pulsed dexamethasone as a first‐line therapy could result in durable response off therapy in a significant number of ITP subjects.
The role of the Polochic Fault as part of the North American and Caribbean Plate boundary: Insights from the infill of the Lake Izabal Basin
Authors: Obrist‐Farner Jonathan , Eckert Andreas , Locmelis Marek , Crowley James L. , Mota‐Vidaure Byron , Lodolo Emanuele , Rosenfeld Joshua , Duarte Edward 
Published: January 2020

AbstractThe Lake Izabal Basin in Guatemala is a major pull‐apart basin along the sinistral Polochic Fault, which is part of the North American and Caribbean plate boundary. The basin infill contains information about the tectonic and sedimentological processes that have imparted a significant control on its sedimentary section. The inception of the basin has been linked to the relative importance of the Polochic Fault in the tectonic history of the plate boundary; yet, its sedimentological record and its inception age have been poorly documented. This study integrates diverse datasets, including industry reports, well logs and reports, well cuttings, vintage seismic data, outcrop observations and geochronological data to constrain the initial infill and age of inception of the basin. The integrated data show that during the Oligocene–Miocene, a marine carbonate platform was established in the region which was later uplifted and eroded in the early Miocene. The fluvial–lacustrine deposits above this carbonate platform are part of the initial infill of the basin and are constrained with zircon weighted‐mean 206Pb/238U ages of 12.060 ± 0.008 from a volcanic tuff ~30 m above the unconformity. Sandstone, mudstone and coal dominate the interval from 12 to 4 Ma, with an increase in conglomerate correlating to the uplift of the Mico Mountains and San Gil Hill at 4 Ma. Fault switch activity between the Polochic and Motagua faults has been hypothesized to explain total offset along the Polochic Fault and the geologic and geodetic slip rates along the two faults. The 12 Ma age determined for the initial infill of the basin confirms this hypothesis. Consequently, our study confirms that at ~12 Ma the Polochic Fault served as the main fault of the plate boundary with inferred slip rates ranging from 13 to 21 mm/yr with a strong possibility that the Polochic Fault was, at some point between 15 Ma and 7 Ma, the only active fault of the plate boundary. The results of this study show that tectonic records preserved in sediments of strike‐slip basins improve the understanding of the relative significance of individual faults and the implications with respect to strain partitioning throughout its tectonic history.
Insect herbivory and herbivores ofFicusspecies along a rain forest elevational gradient in Papua New Guinea
Authors: Sam Katerina , Koane Bonny , Sam Legi , Mrazova Anna , Segar Simon , Volf Martin , Moos Martin , Simek Petr , Sisol Mentap , Novotny Vojtech 
Published: January 2020

AbstractClassic research on elevational gradients in plant–herbivore interactions holds that insect herbivore pressure is stronger under warmer climates of low elevations. However, recent work has questioned this paradigm, arguing that it oversimplifies the ecological complexity in which plant–insect herbivore interactions are embedded. Knowledge of antagonistic networks of plants and herbivores is however crucial for understanding the mechanisms that govern ecosystem functioning. We examined herbivore damage and insect herbivores of eight species of genusFicus(105 saplings) and plant constitutive defensive traits of two of these species, along a rain forest elevational gradient of Mt. Wilhelm (200–2,700 m a.s.l.), in tropical Papua New Guinea. We report overall herbivore damage 2.4% of leaf area, ranging from 0.03% inFicus endochaeteat 1,700 m a.s.l. to 6.1% inF. hombronianaat 700 m a.s.l. Herbivore damage and herbivore abundances varied significantly with elevation, as well as among the tree species, and between the wet and dry season. Community‐wide herbivore damage followed a hump‐shaped pattern with the peak between 700 and 1,200 m a.s.l. and this pattern corresponded with abundance of herbivores. For two tree species surveyed in detail, we observed decreasing and hump‐shaped patterns in herbivory, in general matching the trends found in the set of plant defenses measured here. Our results imply that vegetation growing at mid‐elevations of the elevational gradient, that is at the climatically most favorable elevations where water is abundant, and temperatures still relatively warm, suffers the maximum amount of herbivorous damage which changes seasonally, reflecting the water availability.
Hospital volume and postoperative 5‐year survival for five different cancer sites: A population‐based study in Japan
Authors: Okawa Sumiyo , Tabuchi Takahiro , Morishima Toshitaka , Koyama Shihoko , Taniyama Yukari , Miyashiro Isao 
Published: January 2020

AbstractThe relationship between hospital volume and patient outcome is globally known; thus, hospital volume is widely used as a quality indicator. In Japan, however, recent studies on this topic are scarce. The present study examined whether hospital surgery volume is associated with postoperative 5‐year survival among cancer patients. Using the Osaka Cancer Registry, we identified a sample of 86 145 patients who were diagnosed with cancer at any of five different sites (stomach, colorectum, lung, breast and uterus) and underwent surgeries between 2007 and 2011 in Osaka. We ranked hospitals by annual surgical volume, sorted patients in descending order by hospital volume, and assigned them into quartiles (high, medium, low and very low volume). We analyzed the association between hospital volume and 5‐year survival among 80 959 patients aged between 15 and 84 years using Cox proportional hazard models. Adjustments were made for characteristics of patients, type of surgery and adjuvant treatment received. The mortality hazard of patients treated at very low‐volume hospitals was 1.36‐1.82‐fold higher than that of patients treated at high‐volume hospitals. Absolute differences in adjusted survival rates between high‐volume and very low‐volume hospitals varied with the cancer site: 14.9 in stomach, 11.5 in colorectal, 10.8 in lung, 2.4 in breast and 3.3 in uterine cancers. Hospitals with lower surgery volumes showed higher mortality risks after cancer surgery than those with higher volumes. Monitoring site‐specific surgery volumes and referring patients from low‐volume to high‐volume hospitals may be beneficial for improving the long‐term survival of cancer patients.
Icariin prevents oestrogen deficiency–induced alveolar bone loss through promoting osteogenesis via STAT3
Authors: Xu Hongyuan , Zhou Siru , Qu Ranyi , Yang Yiling , Gong Xinyi , Hong Yueyang , Jin Anting , Huang Xiangru , Dai Qinggang , Jiang Lingyong 
Published: January 2020

AbstractObjectivesAlveolar bone osteoporosis has attracted more and more attention because of its profound impact on stomatognathic function and treatment, but current treatments have not been targeted to alveolar bone and might even cause severe side effects. Thus, identifying the effects of anti‐osteoporosis agents on alveolar bone is essential. Icariin ameliorates metabolic dysfunction of long bones, but its effects on alveolar bone remain unclarified.Materials and methodsBMSCs were isolated from rat mandibles (mBMSCs). The osteogenic potential of mBMSCs and the signalling pathway involved under icariin treatment were measured by ALP and alizarin red staining, reverse transcription‐polymerase chain reaction (RT‐PCR), Western blotting and immunofluorescence. Dual‐luciferase assay, chromatin immunoprecipitation (ChIP) and co‐immunoprecipitation were used to investigate the molecular mechanism. Ovariectomized and sham‐operated rats treated with or without icariin were analysed by micro‐CT, TRAP staining and calcein double labelling.ResultsWe found that icariin promoted osteoblast differentiation of mBMSCs. Furthermore, STAT3 was critical for icariin‐promoted osteoblast differentiation, as indicated by increased phosphorylation levels in icariin‐treated mBMSCs, while preventing STAT3 activation blocked icariin‐induced osteoblast differentiation. Mechanistically, icariin‐promoted transcription of the downstream osteogenic gene osteocalcin (Ocn) through STAT3 and STAT3 bound to the promoter of Ocn. Notably, icariin prevented the alveolar bone osteoporosis induced by oestrogen deficiency through promoting bone formation.ConclusionsFor the first time, our work provides evidence supporting the potential application of icariin in promoting osteogenesis and treating alveolar bone osteoporosis.
CD10 and p63 expression in a sarcomatoid undifferentiated melanoma: A cautionary (and molecularly annotated) tale
Authors: Lefferts Joel A , Loehrer Andrew P. , Yan Shaofeng , Green Donald C. , Deharvengt Sophie J. , LeBlanc Robert E. 
Published: January 2020

AbstractUndifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single‐nucleotide polymorphism (SNP) copy number arrays and targeted next‐generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA, and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component, thereby excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype.
Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain
Authors: Anam Mohammad Badrul , Ahmad Shah Adil Ishtiyaq , Kudo Mikiko , Istiaq Arif , Felemban Athary Abdulhaleem M. , Ito Naofumi , Ohta Kunimasa 
Published: January 2020

AbstractSpecialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH−/−), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH−/−. These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self‐renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.
A qualitative study of clinician attitudes towards closed‐loop systems in mainstream diabetes care in England
Authors: Farrington C. , Murphy H. R. , Hovorka R. 
Published: January 2020

AbstractAimClinicians mediate access to new technologies. Consequently, their views on specific devices may influence user access to diabetes technology in mainstream care. As yet, little is known about clinicians’ views about closed‐loop systems. This qualitative study explored clinicians’ views on the likely impacts of future closed‐loop systems in mainstream diabetes care in England.MethodsWe conducted interviews with 36 clinicians from a range of professional backgrounds in five hospital outpatient clinics (two adult, two pregnancy, one paediatric) in England to explore possible consequences of closed‐loop systems for users and clinicians. Data analysis utilized a framework approach.ResultsClinicians reported a range of expected benefits for future users, including improved glucose control and quality of life. Expected burdens included continued need for manual input and the risk of losing basic self‐care skills. In terms of future clinical workloads, three clinicians emphasized only positive impacts, seven emphasized both positive and negative impacts, and 17 mentioned only negative impacts. Our most prominent finding, expressed by 24 clinicians, was that closed‐loop systems would generate initial challenges due to the need for staff training, user education and support, and new analytical capacities, alongside existing intra‐clinic variations in technological experience.ConclusionsClinicians recognize the value of closed‐loop systems in terms of health benefits, but also identify a range of concerns for both users and healthcare staff, which could impact negatively on user access. Future implementation efforts should address these concerns by providing training and support for healthcare teams, taking varied technological expertise into account.
The changing face of agriculture in Tanzania: Indicators of transformation
Authors: Wineman Ayala , Jayne Thomas S. , Isinika Modamba Emma , Kray Holger 
Published: January 2020

AbstractMotivationThe extent to which African farming systems are undergoing transformation continues to be strongly debated.PurposeWith a focus on Tanzania, this study assesses whether recent trends in farm behaviour, the structure of farming, and agricultural commercialization and productivity conform to stylized facts about agricultural transformation. In the process, we propose an updated typology of farms that reflects recent changes in the relative importance of different farm categories and sheds light on the heterogeneity found even among smallholder farms.Approach and methodsTo this end, we refer to farm‐household survey data over the period 2008–2014.FindingsWe find that medium‐scale farms and small, farm‐focused, commercialized farms are claiming an increasingly prominent role in Tanzanian agriculture. Farmers are more likely to participate in markets for land and labour, to engage in some forms of agricultural intensification and to exhibit a commercial orientation. Over the study period, the real value of agricultural output grew substantially, mostly reflecting a remarkable expansion of cropland rather than increased land productivity. Labour productivity also grew, driven by a reduction in labour intensity. At the same time, Tanzania is experiencing a dramatic movement of labour out of agriculture.Policy implicationsTogether, the evidence suggests that Tanzania is on the cusp of larger transformational processes in the decades to come. With this knowledge, policies can be thoughtfully shaped to support agricultural growth (particularly in land productivity) and meet farmers' diverse needs.