bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas
Authors: Backman Samuel , Åkerström Tobias , Maharjan Rajani , Cupisti Kenko , Willenberg Holger S. , Hellman Per , Björklund Peyman 
Published: April 2019

AbstractAldosterone producing adenomas (APAs) occur in the adrenal glands of around 30% of patients with primary aldosteronism, the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1 have been described in ~60% of these tumours. We subjected 15 aldosterone producing adenomas (13 with known mutations and two without) to RNA Sequencing and Whole Genome Sequencing (n = 2). All known mutations were detected in the RNA-Seq reads, and mutations in ATP2B3 (G123R) and CACNA1D (S410L) were discovered in the tumours without known mutations. Adenomas with CTNNB1 mutations showed a large number of differentially expressed genes (1360 compared to 106 and 75 for KCNJ5 and ATP1A1/ATP2B3 respectively) and clustered together in a hierarchical clustering analysis. RT-PCR in an extended cohort of 49 APAs confirmed higher expression of AFF3 and ISM1 in APAs with CTNNB1 mutations. Investigation of the expression of genes involved in proliferation and apoptosis revealed subtle differences between tumours with and without CTNNB1 mutations. Together our results consolidate the notion that CTNNB1 mutations characterize a distinct subgroup of APAs.
Structures and functions linked to genome-wide adaptation of human influenza A viruses
Authors: Klingen Thorsten R. , Loers Jens , Stanelle-Bertram Stephanie , Gabriel Gülsah , McHardy Alice C. 
Published: April 2019

AbstractHuman influenza A viruses elicit short-term respiratory infections with considerable mortality and morbidity. While H3N2 viruses circulate for more than 50 years, the recent introduction of pH1N1 viruses presents an excellent opportunity for a comparative analysis of the genome-wide evolutionary forces acting on both subtypes. Here, we inferred patches of sites relevant for adaptation, i.e. being under positive selection, on eleven viral protein structures, from all available data since 1968 and correlated these with known functional properties. Overall, pH1N1 have more patches than H3N2 viruses, especially in the viral polymerase complex, while antigenic evolution is more apparent for H3N2 viruses. In both subtypes, NS1 has the highest patch and patch site frequency, indicating that NS1-mediated viral attenuation of host inflammatory responses is a continuously intensifying process, elevated even in the longtime-circulating subtype H3N2. We confirmed the resistance-causing effects of two pH1N1 changes against oseltamivir in NA activity assays, demonstrating the value of the resource for discovering functionally relevant changes. Our results represent an atlas of protein regions and sites with links to host adaptation, antiviral drug resistance and immune evasion for both subtypes for further study.
High frequencies of Non Allelic Homologous Recombination (NAHR) events at the AZF loci and male infertility risk in Indian men
Authors: Rani Deepa Selvi , Rajender Singh , Pavani Kadupu , Chaubey Gyaneshwer , Rasalkar Avinash A. , Gupta Nalini J. , Deendayal Mamta , Chakravarty Baidyanath , Thangaraj Kumarasamy 
Published: April 2019

AbstractDeletions in the AZoospermia Factor (AZF) regions (spermatogenesis loci) on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility, yet not much data is available for Indian infertile men. Therefore, we screened for AZF region deletions in 973 infertile men consisting of 771 azoospermia, 105 oligozoospermia and 97 oligoteratozoospermia cases, along with 587 fertile normozoospermic men. The deletion screening was carried out using AZF-specific markers: STSs (Sequence Tagged Sites), SNVs (Single Nucleotide Variations), PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) analysis of STS amplicons, DNA sequencing and Southern hybridization techniques. Our study revealed deletion events in a total of 29.4% of infertile Indian men. Of these, non-allelic homologous recombination (NAHR) events accounted for 25.8%, which included 3.5% AZFb deletions, 2.3% AZFbc deletions, 6.9% complete AZFc deletions, and 13.1% partial AZFc deletions. We observed 3.2% AZFa deletions and a rare long AZFabc region deletion in 0.5% azoospermic men. This study illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.
Transperitoneal radical nephroureterectomy is associated with worse disease progression than retroperitoneal radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma
Authors: Kim Tae Heon , Suh Yoon Seok , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Choi Han Yong , Sung Hyun Hwan 
Published: April 2019

AbstractThis study aimed to compare the oncologic outcomes between retroperitoneal radical nephroureterectomy (rRNU) and transperitoneal radical nephroureterectomy (tRNU) for the treatment of patients with upper urinary tract urothelial carcinoma (UTUC). Medical records of 743 eligible patients who underwent rRNU or tRNU between 1995 and 2015 were reviewed retrospectively. Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were compared according to the surgical approach using the Kaplan–Meier method. Predictors of PFS, CSS, and OS were analyzed with a multivariable Cox regression model. Overall, 620 (83.4%) and 123 (16.6%) patients were treated with rRNU and tRNU, respectively. Five-year CSS and OS rates were equivalent between rRNU and tRNU groups, but 5-year PFS was lower in the tRNU group than the rRNU group (P = 0.005). When patients were stratified by pathological T stage, PFS was significantly different between the two groups in favor of the rRNU group for both organ-confined disease (pTis/pTa/pT1/T2) (P = 0.022) and locally advanced disease (pT3/pT4) (P = 0.039). However, no significant differences in CSS or OS was observed when comparing the two surgical types in patients with organ-confined disease (P = 0.336 and P = 0.851) or patients with locally advanced disease (P = 0.499 and P = 0.278). tRNU was a significant predictor of PFS (hazard ratio = 1.54; P = 0.023), but not CSS or OS. Our findings indicate that the rRNU approach resulted in better PFS than the tRNU approach in patients with UTUC.
Anti-HERV-WEnv antibodies are correlated with seroreactivity against Mycobacterium avium subsp. paratuberculosis in children and youths at T1D risk
Authors: Niegowska Magdalena , Wajda-Cuszlag Małgorzata , Stępień-Ptak Grażyna , Trojanek Joanna , Michałkiewicz Jacek , Szalecki Mieczysław , Sechi Leonardo A. 
Published: April 2019

AbstractRecent evidence points at the role that human endogenous retroviruses (HERVs) may play through the activation of genes integrated across the human genome. Although a variety of genetic/epigenetic mechanisms maintain most HERVs silenced, independent environmental stimuli including infections may transactivate endogenous elements favoring pathogenic conditions. Several studies associated exposures to Mycobacterium avium subsp. paratuberculosis (MAP) with increased anti-MAP seroreactivity in T1D patients. Here, we assessed humoral responses against HERV envelope antigens (HERV-KEnv and HERV-WEnv) and four MAP-derived peptides with human homologs in distinct populations: Sardinian children at T1D risk (rT1D) (n = 14), rT1D from mainland Italy (n = 54) and Polish youths with T1D (n = 74) or obesity unrelated to autoimmunity (OB) (n = 26). Unlike Sardinian rT1D, youths displayed increased anti-HERV-WEnv Abs prevalence compared to age-matched OB or healthy controls (24.32 vs. 11.54%, p = 0.02 for Polish T1D/OB and 31.48 vs. 11.90%, p = 0.0025 for Italian rT1D). Anti-HERV-KEnv responses showed variable trends across groups. A strong correlation between Abs levels against HERV-WEnv and homologous peptides was mirrored by time-related Abs patterns. Elevated values registered for HERV-WEnv overlaped with or preceded the detection of T1D diagnostic autoantibodies. These results support the hypothesis of MAP infection leading to HERV-W antigen expression and enhancing the production of autoantibodies in T1D.
30 Gb/s integrated receiver array for parallel optical interconnects
Authors: Nguyen Nga T.H. , Ukaegbu Ikechi A. , Park Hyo‐Hoon 
Published: April 2019

A 30 Gb/s integrated receiver array for parallel optical interconnects with four channels have been designed and implemented in a 0.13 μm CMOS technology. To achieve small area and low power consumption while maintaining large bandwidth and high gain, the integrated receiver has been implemented with a regulated cascode (RGC) transimpedance amplifier (TIA), resistive and capacitive degeneration and inductorless limiting amplifier (LA), which employs active feedback and negative capacitance. From the measurement results of the optical module using 850 nm photodiode (PD), the receiver showed a constant single‐ended output swing of 320 mV up to 7.5 Gb/s/ch with clear eye diagrams and BER of <10−12. With a voltage supply of 1.2 V, a figure of merit (FOM) of 8 mW/Gb/s was obtained with a small chip area per channel of 0.28 mm2 /ch.
S1-Leitlinie Diagnostik und Therapie der erektilen Dysfunktion
Authors: Haensch Carl-Albrecht , Hilz Max , Jost Wolfgang , Kaufmann Albert , Kessler Thomas , Lahrmann Heinz 
Published: April 2019

ZusammenfassungDie S1-Leitlinie „Diagnostik und Therapie der erektilen Dysfunktion“ (AWMF-Registernummer 030 / 112) steht in einer vollständig überarbeiteten Neufassung zur Verfügung. Erektile Dysfunktion ist definiert als die fortwährende Unfähigkeit, eine penile Erektion, die für einen befriedigenden Geschlechtsverkehr ausreicht, zu erreichen oder aufrechtzuerhalten. Betroffen sind Millionen Bundesbürger: Bei Männern mit regelmäßiger sexueller Aktivität nimmt die erektile Dysfunktion von 2,3 Prozent in der dritten Lebensdekade auf 53,4 Prozent in der siebten Lebensdekade zu. Die Leitlinie gibt dezidierte Empfehlungen zur adäquaten Diagnose und zur Therapie der erektilen Dysfunktion, die seit der Einführung der Phosphodiesterase-5-(PDE-5-)Hemmer häufig unkritisch erfolgt.
Neue Arzneimittel für Pferde und landwirtschaftliche
Nutztiere 2018
Authors: Emmerich Ilka Ute 
Published: April 2019

ZusammenfassungIm Jahr 2018 kam für Pferde und landwirtschaftliche Nutztiere kein neuer
Wirkstoff auf den deutschen Tierarzneimittelmarkt. Ein Wirkstoff erhielt eine
Tierartenerweiterung. So wurde das Inhalationsanästhetikum Isofluran (Isofluran
Baxter® vet) aus der Gruppe der halogenierten
Kohlenwasserstoffverbindungen auch für Schweine (Ferkel) zugelassen. Mit
Acepromazin, Mepivacain und Oxyclozanid wurden drei zwischenzeitlich nicht mehr
erhältliche Wirkstoffe wieder zugelassen. Außerdem kamen ein Präparat mit einer
neuen Wirkstoffkombination und ein Wirkstoff in einer neuen Darreichungsform für
Pferde und landwirtschaftliche Nutztiere auf den Markt.
Langzeit-Follow-up nach Exokryokoagulation bei Frühgeborenenretinopathie in Nordgriechenland: 3-Jahres-Ergebnisse
Authors: della Volpe Waizel Maria , Gatzioufas Zisis , Iraklis Vastardis , Soubasi Vasiliki , Drossou-Agakidou Vasiliki , Pruente Christian , Scholl Hendrik , Kozeis Nikos 
Published: April 2019

Zusammenfassung
Hintergrund Untersucht werden soll retrospektiv die Effektivität der Behandlung mit Exokryokoagulation bei Frühgeborenen (FG) mit Retinopathia praematurorum (ROP) bez. der morphologischen Netzhautstrukturen und der visuellen Funktion.
Material und Methoden Von insgesamt 3103 untersuchten FG hatten 304 (9,8%) eine ROP. Von diesen wurden 66 behandelt. Alle FG wurden über 3 Jahre nach dieser Behandlung beobachtet. Als nicht erfolgreich wurden eine Ablatio retinae und eine Makulaverziehung (dragging of the macula) gewertet. Bestkorrigierte Gittersehschärfe und bestkorrigierte Sehschärfen wurden mittels Lea-Symbolen und Kay Pictures geprüft.
Ergebnisse Die 66 behandelten FG (132 Augen) hatten ein Gestationsalter von weniger als 28 Wochen und ein Geburtsgewicht < 1280 g. 28 FG hatten eine ROP in Zone 1, die übrigen in Zone 2. Von diesen 66 FG zeigten 64 (128 Augen) eine Visusverbesserung. 37 FG (74 Augen) zeigten ebenso eine morphologische Besserung. Nur bei einem FG kam es zu einer bilateralen Amotio retinae.
Schlussfolgerung Eine frühe Behandlung mit Kryropexie bei FG mit ROP kann zu einer Visusverbesserung wie auch zu einer anatomischen Stabilisierung der Netzhautsituation führen.
Modular, stereocontrolled C
β
–H/C
α
–C activation of alkyl carboxylic acids
Authors: Shang Ming , Feu Karla S. , Vantourout Julien C. , Barton Lisa M. , Osswald Heather L. , Kato Nobutaka , Gagaring Kerstin , McNamara Case W. , Chen Gang , Hu Liang , Ni Shengyang , Fernández-Canelas Paula , Chen Miao , Merchant Rohan R. , Qin Tian , Schreiber Stuart L. , Melillo Bruno , Yu Jin-Quan , Baran Phil S. 
Published: April 2019

Significance
The combination of two newly emerging methods for chemical synthesis enables access to molecular space that was previously challenging or impossible to access. Thus, a C–H activation of ubiquitous carboxylic acids followed by their decarboxylative functionalization provides modular access to difunctionalized carbon frameworks with distinctly controlled stereochemistry. Application of this strategy to simplify the synthesis of medicinally important entities and to discover potent antimalarial compounds is described.
The role of input in native Spanish Late learners’ production and perception of English phonetic
segments
Authors: Flege James E. , Wayland Ratree 
Published: April 2019

Abstract
This study evaluated the effect of input variation on the production and perception of English phonetic segments by native Spanish
adults who had immigrated to the United States after the age of 16 years. The native Spanish (NS) participants were assigned to
three groups of 20 each according to years of English input (years of U.S. residence multiplied by percent English use outside the
home). Experiment 1 assessed the perceived relation between English and Spanish vowels. It yielded similar results for the NS
groups designated “Low input” (M = 0.2 years of input), “Mid” (M = 1.2 years) and “High”
(M = 3.0 years). Experiments 2–4 examined English vowel discrimination, vowel production and consonant
discrimination. Apart from a modest improvement in vowel discrimination, these experiments showed little improvement as years of
English input increased. One possible explanation for the essentially null finding of this study is that input matters little or
not at all when an L2 is learned naturalistically following the closure of a critical period. Another possibility is that adequate
native speaker input is crucial for L2 speech learning but the input differences evaluated here were insufficient to yield
measurable improvements in performance. We conclude the article by illustrating a new technique that might be used to choose
between these competing explanations.
Enacting voices
Authors: LaScotte Darren K. 
Published: April 2019

Abstract
The present study supports the idea of heteroglossia and its contributions to language learning in second language
acquisition (SLA) theory and bilingualism. Bakhtin’s (1934/1981) theory of
heteroglossia differs from variety and register in that when acquiring a language, one internalizes the voices of others. Viewing
interlanguage through a heteroglossic lens, it is possible that these voices in heteroglossia may have an effect on second
language (L2) users’ language production. By blending sociolinguistic and sociocultural frameworks, this study analyzed the
complexity, accuracy, and fluency of two French-English bilinguals’ narratives. Findings demonstrate a clear shift in all three
measures of the CAF framework when participants enacted the voice of a perceived interlocutor or perceived self, versus when they
recounted a narrative. These findings support the notion that an individual may have variable linguistic systems, and raise other
important theoretical and practical implications for SLA research and L2 instruction.
What is effective second language exposure and how does it relate to content-based instruction and language across the curriculum?
Authors: Chu Edward Y. W. 
Published: April 2019

AbstractSecond language acquisition cannot take place in the absence of exposure to input. However, despite extensive L2 instruction and/or learning content subjects in L2, many struggle to communicate adequately in their L2 in social and/or academic contexts. A clearer delineation of the concept of ‘exposure’, which requires a review of relevant language acquisition theories and findings, is needed. As such, substantial bodies of work in L2 acquisition by well-known language educators, namely Jim Cummins (‘BICS’ and ‘CALP’), Stephen Krashen (‘Comprehensible Input Hypothesis’), Michael Long (Interaction Hypothesis) and Merril Swain (Output Hypothesis) are reviewed. A review is also made of relevant neuroscience research. Two educational approaches, Content-based instruction (CBI) and Language across the curriculum (LAC), are discussed in relation to the insights obtained, with special reference to contexts influenced by Confucian heritage culture (CHC). To allow subject networking to take place, school managers/L2 policy makers need to actively revamp the curriculum.
Recovery profiles following single and multiple matches per week in professional football
Authors: Howle Kieran , Waterson Adam , Duffield Rob 
Published: April 2019

AbstractObjectives: To investigate player responses 48 h post single (SM) and multi‐match (MM) weeks on two subjective and three objective outcome measures to infer recovery status. Methods: From 42 professional players over 2 seasons, outcome measures relevant to recovery status were collected 48 h following matches, as well as during pre‐season training weeks as a comparative baseline. These included (1) 5‐item subjective wellness questionnaire, (2) total quality recovery (TQR) scale, (3) hip adduction squeeze test, ankle knee to wall (KTW) test, and active knee extension (AKE) flexibility test. These outcome measures 48 h post‐match were compared for SM (n = 79) and MM (n = 86) weeks where players completed >75 min of match time in only one (SM) or if both matches were played and had <96 h recovery (MM). Internal match load was collected from each match based on session rating of perceived exertion (sRPE) multiplied by match duration. Results: Subjective wellness (specifically fatigue, sleep and soreness), TQR and hip adduction squeeze test were all significantly reduced following match 1 at 48 h post for both SM and MM (p < 0.05), and further reduced following match 2 in MM (p < 0.05). No other outcome measures to infer recovery showed significant differences (p > 0.05) within or between‐conditions. Conclusions: Subjective wellness, TQR and hip adduction strength showed reduction 48 h post match for players competing in multiple matches with <96 h recovery. Therefore, these outcome measures may be of use to practitioners to assess readiness to compete during congested competition schedules.
Source or Sink? A comparison of Landfire- and FIA-based estimates of change in aboveground live tree carbon in California’s forests
Authors: Holland Tim G , Stewart William , Potts Matthew D 
Published: April 2019

Abstract
Forests play a central role in addressing climate change, and accurate estimates of forest carbon are critical for the development of actions that reduce emissions from forests and that maximize sequestration by forests. Methodological challenges persist regarding how best to estimate forest carbon stocks and flux at regulatory-relevant scales. Using California, USA as a case study, we compare two approaches to stock-difference forest carbon estimation for aboveground live trees: one based on ground inventories and one on land cover classification of remotely-sensed data. Previous work using ground inventory data from the Forest Inventory and Analysis Program (FIA) showed net aboveground carbon (AGC) sequestration by live trees in California forests, while estimates using land cover classification from the Landscape Fire and Resource Management Planning Tools (Landfire) showed net reductions in live tree AGC over a similar time period. We examined the discrepancy by re-analyzing the FIA inventory data through the lens of a category-change analysis based on Landfire. This analysis showed more than 50% of the live tree AGC in fewer than 4% of Landfire-equivalent categories and that the overwhelming majority (>80%) of forest area did not change height category between measurement periods. Despite the lack of categorical change, the majority of FIA plots increased in both 95th percentile tree height and in live tree AGC. These findings suggest that an approach based on observing categorical changes risks undercounting AGC sequestration resulting from growth and thus overstating the relative importance of AGC reductions that result from disturbances. This would bias AGC flux estimates downward, leading us to validate the conclusion that live trees in California were a net sink of aboveground carbon in the decade ending in 2016. Our findings suggest an inventory-based or hybrid approach is preferable to methods that depend on categorical bins for estimating AGC in disturbance-prone forest ecosystems.
Shorter time to achieve endoscopic eradication is not associated with improved long-term outcomes in Barrett's esophagus
Authors: Soroush Ali , Poneros John M , Lightdale Charles J , Abrams Julian A 
Published: April 2019

SUMMARY
Quality indicators have been proposed for endoscopic eradication therapy of Barrett's esophagus (BE). One such measure suggests that complete eradication of intestinal metaplasia (CE-IM) should be achieved within 18 months of starting treatment. The aim of this study was to assess whether achievement of CE-IM within 18 months is associated with improved long-term clinical outcomes. This was a retrospective cohort study of BE patients who underwent endoscopic eradication. Time to CE-IM was recorded and categorized as ≤ or > 18 months. The main outcome measures were recurrence of IM and of dysplasia after CE-IM, defined as a single endoscopy without endoscopic evidence of BE or histologic evidence of intestinal metaplasia. Recurrence was analyzed using the Kaplan–Meier method and multivariable Cox proportional hazards modeling. A total of 290 patients were included in the analyses. The baseline histology was high-grade dysplasia or intramucosal carcinoma in 74.2% of patients. CE-IM was achieved in 85.5% of patients, and 54.1% of the cohort achieved CE-IM within 18 months. Achieving CE-IM within 18 months was not associated with reduced risk of recurrence of IM or dysplasia in both unadjusted and adjusted analyses. In this cohort, older age and increased BE length were associated with IM recurrence, and increased hiatal hernia size was associated with dysplasia recurrence. Compared to longer times, achieving CE-IM within 18 months was not associated with a reduced risk of recurrence of IM or dysplasia. Alternative evidence-based quality metrics for endoscopic eradication therapy should be identified.