bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes
Authors: Chen Lixian , Wu Nan , Kennedy Lindsey , Francis Heather , Ceci Ludovica , Zhou Tianhao , Samala Niharika , Kyritsi Konstantina , Wu Chaodong , Sybenga Amelia , Ekser Burcin , Dar Wasim , Atkins Constance , Meadows Vik , Glaser Shannon , Alpini Gianfranco 
Published: April 2021

Background and Aims
Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down‐regulation of miR‐125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR‐125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH.

Approach and Results

In vivo, 4‐week‐old male wild‐type, Sct
−/− and Sctr
−/− mice were fed a control diet or high‐fat diet (HFD) for 16 weeks. The expression of SCT/SCTR/miR‐125b axis was measured in human NAFLD/NASH liver samples and HFD mouse livers by immunohistochemistry and quantitative PCR. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were evaluated in mouse liver and human NAFLD/NASH liver samples. miR‐125b target lipogenesis genes in hepatocytes were screened and validated by custom RT2 Profiler PCR array and luciferase assay. Biliary SCT/SCTR expression was increased in human NAFLD/NASH samples and in livers of HFD mice, whereas the expression of miR‐125b was decreased. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were observed in human NAFLD/NASH samples as well as HFD mice, which were decreased in Sct
−/− and Sctr
−/− HFD mice. Elovl1 is a lipogenesis gene targeted by miR‐125b, and its expression was also decreased in HFD mouse hepatocytes following Sct or Sctr knockout. Bile acid profile in fecal samples have the greatest changes between wild‐type mice and Sct
−/−/Sctr
−/− mice.

Conclusion
The biliary SCT/SCTR/miR‐125b axis promotes liver steatosis by up‐regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR‐125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.
Using isotopes to understand landscape‐scale connectivity in a groundwater‐dominated, lowland catchment under drought conditions
Authors: Kleine Lukas , Tetzlaff Doerthe , Smith Aaron , Goldhammer Tobias , Soulsby Chris 
Published: April 2021

AbstractThe Demnitzer Millcreek catchment (DMC), is a 66 km2 long‐term experimental catchment located 50 km SE of Berlin. Monitoring over the past 30 years has focused on hydrological and biogeochemical changes associated with de‐intensification of farming and riparian restoration in the low‐lying landscape dominated by rain‐fed farming and forestry. However, the hydrological function of the catchment, which is closely linked to nutrient fluxes and highly sensitive to climatic variability, is still poorly understood. In the last 3 years, a prolonged drought period with below‐average rainfall and above‐average temperatures has resulted in marked hydrological change. This caused low soil moisture storage in the growing season, agricultural yield losses, reduced groundwater recharge, and intermittent streamflows in parts of an increasingly disconnected channel network. This paper focuses on a two‐year long isotope study that sought to understand how different parts of the catchment affect ecohydrological partitioning, hydrological connectivity and streamflow generation during drought conditions. The work has shown the critical importance of groundwater storage in sustaining flows, basic in‐stream ecosystem services and the dominant influence of vegetation on groundwater recharge. Recharge was much lower and occurred during a shorter window of time in winter under forests compared to grasslands. Conversely, groundwater recharge was locally enhanced by the restoration of riparian wetlands and storage‐dependent water losses from the stream to the subsurface. The isotopic variability displayed complex emerging spatio‐temporal patterns of stream connectivity and flow duration during droughts that may have implications for in‐stream solute transport and future ecohydrological interactions between landscapes and riverscapes. Given climate projections for drier and warmer summers, reduced and increasingly intermittent streamflows are very likely not just in the study region, but in similar lowland areas across Europe. An integrated land and water management strategy will be essential to sustaining catchment ecosystem services in such catchment systems in future.
How realistic are water‐balance closure assumptions? A demonstration from the southern sierra critical zone observatory and kings river experimental watersheds
Authors: Safeeq Mohammad , Bart Ryan R. , Pelak Norman F. , Singh Chandan K. , Dralle David N. , Hartsough Peter , Wagenbrenner Joseph W. 
Published: April 2021

AbstractThe water balance is an essential tool for hydrologic studies and quantifying water‐balance components is the focus of many research catchments. A fundamental question remains regarding the appropriateness of water‐balance closure assumptions when not all components are available. In this study, we leverage in‐situ measurements of water fluxes and storage from the Southern Sierra Critical Zone Observatory (SSCZO) and the Kings River Experimental Watersheds (KREW) to investigate annual water‐balance closure errors across large (1016–5389 km2) river basins and small (0.5–5 km2) headwater‐catchment scales in the southern Sierra Nevada. The results showed that while long‐term water balance in river basins can be closed within 10% of precipitation, in the smaller headwater catchments as much as a quarter of precipitation remained unaccounted for. A detailed diagnosis of this water‐balance closure error using distributed soil moisture measurements in the top 1 m suggests an unaccounted deeper storage and a net groundwater export from the headwater catchments. This imbalance was also found to be very sensitive to the timescales over which water‐balance closures were attempted. While some of the closure errors in the simple water balance can be attributed to measurement uncertainties, we argue for a broader consideration of groundwater exchange when evaluating hydrological processes at headwater scales, as the assumption of negligible net groundwater exchange may lead to an overestimation of fluxes derived from the water balance method.
Gender‐neutral HPV elimination, cervical cancer screening, and treatment: Experience from Bhutan
Authors: Dorji Thinley , Tshomo Ugyen , Gyamtsho Sonam , Tamang Saran Tenzin , Wangmo Sangay , Pongpirul Krit 
Published: April 2021

AbstractCervical cancer is preventable and also curable when detected early and treated adequately, yet it remains a leading cause of morbidity and mortality among women. In Bhutan, cervical cancer is the most common cancer among women. Bhutan was the first country among the low‐ and middle‐income economies to have instituted a national HPV vaccination program, in 2010, and has achieved >90% coverage. In 2019, Bhutan launched a cervical cancer elimination flagship program well ahead of WHO’s launch of the global strategy for accelerated elimination of cervical cancer. Bhutan initiated vaccination of adolescent boys and adopted a gender‐neutral vaccination program beginning September 2020 through its well‐established network of primary healthcare centres. The flagship program aims to screen women aged 30–69 years with HPV testing using liquid‐based cytology (LBC) as triaging for screen positive women. For women aged 25–29 years, LBC will be continued as per American Society of Colposcopy and Cervical Pathology guidelines. Colposcopy and treatment will be performed in camps to decrease loss of follow up of screen positive women. This program is also expected to improve early diagnosis of cervical cancer and provide timely and adequate cancer treatment and palliative care services. This article reviews the progress made and the challenges facing the 2030 cervical cancer elimination targets in Bhutan.
Evaluation of 17 genetic variants in association with leukemia in the north Indian population using MassARRAY Sequenom
Authors: Bhat Amrita , Bhat Gh. Rasool , Verma Sonali , Sharma Bhanu , Bakshi Divya , Abrol Deepak , Singh Supinder , Qadri Raies Ahmed , Shah Ruchi , Kumar Rakesh 
Published: April 2021

AbstractLeukemia is a heterogeneous disorder, characterized by elevated proliferation of white blood cells. In this study, we explored the association of 17 genetic variants with leukemia patients in the Jammu and Kashmir region of north India. The variants were genotyped by using a high‐throughput Agena MassARRAY platform in 758 individuals (166 cases and 592 controls). Of the 17 single‐nucleotide polymorphisms (SNPs) studied, five SNPs were showing significant association with the high risk of leukemia in the north Indian population, which includes rs10069690 of telomere reverse transcriptase (TERT) with OR = 0.34 (95% CI, 0.20–0.58; p = .0008), rs2972392 (​​​PSCA) with OR 1.86 (95% CI, 1.04–3.81; p = .035), rs4986764 (BRIP1) with OR 1.34 (95% CI, 1.00–1.80; p = .04), rs6990097 (TNKS) with OR 1.81 (95% CI, 1.2–2.6; p = .001) and rs12190287 (TCF21) with OR 2.87 (95% CI, 1.72–4.7; p = .0001) by allelic association using Plink and analyzed by SPSS. This is the first study to explore these variants with leukemia in the studied population.
Crystal structure and quantum chemical calculations of (E)1‐benzyl‐3‐((4‐methoxyphenyl)imino)‐5‐methylindolin‐2‐one
Authors: Abdel El‐wahab Hend A. A. , Hamdy Ahmed K. , Schulzke Carola , Aboul‐Fadl Tarek , Qayed Wesam S. 
Published: April 2021

AbstractThe known Schiff base compound, (E)1‐benzyl‐3‐((4‐methoxyphenyl)imino)‐5‐methylindolin‐2‐one, was prepared as before by reacting 1‐benzyl‐5‐methylindoline‐2,3‐dione with 4‐methoxyaniline. The product was unambiguously characterized using elemental analysis,1H and13C‐NMR spectroscopy, and its new single‐crystal X‐ray structural analysis. Molecular orbital calculations were conducted in order to investigate the structures and relative stabilities of the (E) and (Z) isomers of 1‐benzyl‐3‐([4 methoxyphenyl]‐imino)‐5‐methylindolin‐2‐one. Specific attention was paid to the (E) isomer. The available crystallographic experimental data for the latter ensured also validation of the model structures computationally derived at the theoretical B3LYP/6‐31G(d,p) level.
A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics
Authors: Chen Jane S , Matoga Mitch , Pence Brian W , Powers Kimberly A , Maierhofer Courtney N , Jere Edward , Massa Cecilia , Khan Shiraz , Rutstein Sarah E , Phiri Sam , Hosseinipour Mina C , Cohen Myron S , Hoffman Irving F , Miller William C , Lancaster Kathryn E 
Published: April 2021

AbstractIntroductionHIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi.MethodsWe conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant.ResultsA total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant.ConclusionsCombining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.
The breadth of concomitant virological features in a family cluster outbreak of COVID‐19 pneumonia
Authors: Lei Guanglin , Meng Fanping , Wang Cheng , Yan Jin , Sun Fang , Shi Lei , Li Wengang , Luan Junqing , Wang Siyu , Yang Penghui 
Published: April 2021

AbstractAn outbreak of a novel coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) had emerged in 2019 and rapidly posed a global epidemic. Here, we report the breadth of concomitant virological features of a family cluster with COVID‐19. The period of virus shedding is significantly different between upper respiratory and feces samples. Even the SARS‐CoV‐2 virus titers were undetectable in feces, it could be positive again soon and likely related to fluctuated inflammation levels (interleukin‐6, etc.) and lowered immune responses (CD4 + T lymphocyte, etc.). Our findings expand the novel understanding of the breadth of concomitant virological features during a non‐severe family cluster of COVID‐19.
Do you value or worry about feedback? Tradeoffs between cost and value perceptions and dual feedback‐seeking strategies toward creativity
Authors: Sung Sun Young , Choi Jin Nam 
Published: April 2021

SummaryThis study advances the literature by elaborating on how disparate tradeoffs between cost and value perceptions targeted at FSB lead to distinct feedback‐seeking strategies. Specifically, the cost–value framework is employed to explain the emergence of two forms of feedback‐seeking behavior (FSB), namely, inquiry and monitoring. An interplay between the two FSB strategies is also proposed to predict employee creativity. Data collected from 194 individuals across 76 work teams reveal that high cost–low value perceptions are negatively related and low cost–high value perceptions are positively related to inquiry strategy. Such incongruence between cost and value perceptions shows no significant effect on monitoring strategy. Instead, employees adopt a monitoring strategy when they perceive congruence or ambiguous tradeoffs related to FSB (high cost–high value, low cost–low value). Analysis indicates the interplay between the two FSB strategies in which the highest level of creativity is observed when employees use both inquiry and monitoring strategies at high levels. This study complements and enriches the feedback literature by theorizing and empirically validating comparative effects of cost and value perceptions toward FSB as well as the interplay between the two FSB strategies in predicting employee creativity.
Confidence, ability to meet return to sport criteria, and second ACL injury risk associations after ACL‐reconstruction
Authors: Paterno Mark V. , Thomas Staci , VanEtten Karen Thatcher , Schmitt Laura C. 
Published: April 2021

AbstractThis study tested the hypotheses that participants with high knee‐related confidence at the time of return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction (ACLR) would have a greater likelihood of meeting RTS criteria and would have a higher likelihood of second ACL injury. Participants completed RTS testing when cleared to RTS. Success was defined as an IKDC score more than or equal to 90 and all limb symmetry index (LSI) scores more than or equal to 90%. Confidence groups were created based on response to the KOOS Quality of Life subscale. Incidence of second ACL injury was tracked for 24 months after RTS. Associations among confidence, success in meeting RTS criteria, and second ACL injury were evaluated. At RTS, 37.7% were classified with high knee‐related confidence, 26.4% met RTS criteria and 22.0% sustained a second ACL injury post‐RTS. A higher proportion of confident participants met all RTS criteria (p = 0.001). Confident participants were over two times more likely to suffer a second ACL injury (odds ratio [OR] = 2.40; 95% confidence interval [CI]:1.21–5.20) (p = 0.02) and participants who were both confident and met all RTS criteria were 10 times more likely to suffer a second ACL injury (OR = 9.6; 95% CI:1.1, 84.2) (p = 0.02) than those who passed all RTS criteria but lacked knee‐related confidence. Clinical significance: Confident, young athletes at the time of RTS after ACLR are more likely to meet all RTS criteria and more likely to sustain a second ACL injury after RTS. Future work must consider how the inclusion of additional factors into RTS criteria may better identify those at high risk for poor outcome after ACLR.
Optimal Strategies for Managing Wildlife Harvest Under System Change
Authors: Tucker Anna M. , Runge Michael C. 
Published: April 2021

ABSTRACTWildlife populations are experiencing shifting dynamics due to climate and landscape change. Management policies that fail to account for non‐stationary dynamics may fail to achieve management objectives. We establish a framework for understanding optimal strategies for managing a theoretical harvested population under non‐stationarity. Building from harvest theory, we develop scenarios representing changes in population growth rate () or carrying capacity () and derive time‐dependent optimal harvest policies using stochastic dynamic programming. We then evaluate the cost of falsely assuming stationarity by comparing the outcomes of forward projections in which either the optimal policy or a stationary policy is applied. Whendeclines over time, the stationary policy leads to an underharvest of the population, resulting in less harvest over the short term but leaving the population in a higher‐value state. Whendeclines over time, the stationary policy leads to overharvest, resulting in greater harvest returns in the short term but leaving the population in a lower and potentially more vulnerable state. This work demonstrates the basic properties of time‐dependent harvest management and provides a framework for evaluating the many outstanding questions about optimal management strategies under climate change. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
The Effects of Landscape Characteristics on Northern Bobwhite Density
Authors: Howell Paige E. , Wilhite Nathan G. , Gardner Rachel , Mohlman Jessica L. , Chandler Richard B. , Parnell Ira B. , Martin James A. 
Published: April 2021

ABSTRACTThe northern bobwhite (Colinus virginianus) is an ecologically and economically valuable species in the United States. Managers rely on autumn density estimates to set harvest regulations, balancing the interests of hunters and long‐term bobwhite population viability. Spatial capture‐recapture (SCR) is a useful framework for estimating population size and modeling spatial variation in density. We used SCR to quantify the effect of landscape structure on spatial variation in density for a population of bobwhites on the Di‐Lane Wildlife Management Area in Waynesboro, Georgia, USA. Without additional telemetry or nesting data, we were also able to estimate a spatially explicit metric of productivity. To sample the population, we deployed a fixed array of 395, 262, and 268 funnel traps in 2016, 2017, and 2018, respectively. We estimated age structure, with the highest density of juveniles (0.32 birds/ha, 95% CI = 0.28–0.37) and adults (0.10 birds/ha, 95% CI = 0.08–0.12) estimated in 2016. In our top model, density was negatively related to the proportion of closed canopy hardwoods. To increase bobwhite density on the landscape, managers should reduce the amount of closed canopy hardwood forest. Furthermore, the spatially explicit age ratio we estimated could be used to target management towards increasing the recruitment of chicks into the autumn population. An SCR approach may require additional logistical and financial resources relative to other data collection methods, but it makes modeling spatial variation in density straightforward and can be used to gather data to simultaneously understand population structure, vital rates, and movement. © 2021 The Wildlife Society.
Diazotrophs modulate phycobiliproteins and nitrogen stoichiometry differently than other cyanobacteria in response to light and nitrogen availability
Authors: Wang Jingyu , Wagner Nicole D. , Fulton James M. , Scott J. Thad 
Published: April 2021

AbstractHarmful algal blooms (HABs) frequently occur in eutrophic water bodies, which are often dominated by either non‐diazotrophic or diazotrophic strains of cyanobacteria. The occurrence of HABs is associated with multiple environmental factors that affect cyanobacterial growth, though adaptations of cyanobacteria to respond to diverse growing conditions are largely unknown. One factor affecting HAB persistence is the ability of cyanobacteria to synthesize and metabolize large biomolecules such as the light harvesting pigments phycobiliproteins that can also act as nitrogen (N) storage. Here, we examined how cyanobacteria varied phycobiliprotein content in response to different light intensity and N availability in two HAB forming species, Microcystis aeruginosa (non‐diazotrophic) and Dolichospermum flos‐aquae (diazotrophic). Our results revealed both HAB forming species responded similarly to light intensity, with decreasing light causing an increased production of phycobiliproteins, although at different rates. However, we observed dissimilar phycobiliprotein responses to varied N availability. In low N conditions, M. aeruginosa degraded phycobiliproteins primarily due to the decreased need for photosynthesis, whereas D. flos‐aquae, increased phycobiliproteins production under N‐limited conditions likely caused by the increased energetic requirements for N2‐fixation. Our results indicate that M. aeruginosa stored as much as 30% of cellular N in phycobiliproteins under high N conditions, while D. flos‐aquae only allocated 5% of the cellular N in phycobiliproteins. This study reveals a fundamental physiological difference between non‐diazotrophic and diazotrophic cyanobacteria, highlighting the critical role of phycobiliproteins on the persistence of cyanobacteria blooms under scenarios with varied light intensity and N availability.