bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random-effect based test for multinomial logistic regression: choice of the reference level and its impact on the testing
Authors: He Qianchuan , Liu Yang , Liu Meiling , Wu Michael C. , Hsu Li 
Published: April 2021

ABSTRACTRandom-effect score test has become an important tool for studying the association between a set of genetic variants and a disease outcome. While a number of random-effect score test approaches have been proposed in the literature, similar approaches for multinomial logistic regression have received less attention. In a recent effort to develop random-effect score test for multinomial logistic regression, we made the observation that such a test is not invariant to the choice of the reference level. This is intriguing because binary logistic regression is well-known to possess the invariance property with respect to the reference level. Here, we investigate why the multinomial logistic regression is not invariant to the reference level, and derive analytic forms to study how the choice of the reference level influences the power. Then we consider several potential procedures that are invariant to the reference level, and compare their performance through numerical studies. Our work provides valuable insights into the properties of multinomial logistic regression with respect to random-effect score test, and adds a useful tool for studying the genetic heterogeneity of complex diseases.
A Cryptochrome adopts distinct moon- and sunlight states and functions as sun- versus moonlight interpreter in monthly oscillator entrainment
Authors: Poehn Birgit , Krishnan Shruthi , Zurl Martin , Coric Aida , Rokvic Dunja , Häfker N. Sören , Arboleda Enrique , Orel Lukas , Raible Florian , Wolf Eva , Tessmar-Raible Kristin 
Published: April 2021

AbstractThe moon’s monthly cycle synchronizes reproduction in countless marine organisms. The mass-spawning bristle wormPlatynereis dumeriliiuses an endogenous monthly oscillator to phase reproduction to specific days. Classical work showed that this oscillator is set by full moon. But how do organisms recognize such a specific moon phase? We uncover that the light receptor L-Cryptochrome (L-Cry) is able to discriminate between different moonlight durations, as well as between sun- and moonlight. Consistent with L-Cry’s function as light valence interpreter, its genetic loss leads to a faster re-entrainment under artificially strong nocturnal light. This suggests that L-Cry blocks “wrong” light from impacting on the monthly oscillator. A biochemical characterization of purified L-Cry protein, exposed to naturalistic sun- or moonlight, reveals the formation of distinct sun- and moonlight states characterized by different photoreduction- and recovery kinetics of L-Cry’s co-factor Flavin Adenine Dinucleotide.In vivo,L-Cry’s sun-versus moonlight states correlate with distinct sub-cellular localizations, indicating different signalling. In contrast, r-Opsin1, the most abundant ocular opsin, is not required for monthly oscillator entrainment. Our work reveals a new concept for correct moonlight interpretation involving a “valence interpreter” that provides entraining photoreceptor(s) with light source and moon phase information. These findings advance our mechanistic understanding of a fundamental biological phenomenon: moon-controlled monthly timing. Such level of understanding is also an essential prerequisite to tackle anthropogenic threats on marine ecology.
Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase
Authors: Zurl Martin , Poehn Birgit , Rieger Dirk , Krishnan Shruthi , Rokvic Dunja , Rajan Vinoth Babu Veedin , Gerrard Elliot , Schlichting Matthias , Orel Lukas , Lucas Robert J. , Wolf Eva , Helfrich-Förster Charlotte , Raible Florian , Tessmar-Raible Kristin 
Published: April 2021

AbstractMany species synchronize their physiology and behavior to specific hours. It is commonly assumed that sunlight acts as the main entrainment signal for ~24h clocks. However, the moon provides similarly regular time information, and increasingly studies report correlations between diel behavior and lunidian cycles. Yet, mechanistic insight into the possible influences of the moon on ~24hr timers is scarce.We studiedPlatynereis dumeriliiand uncover that the moon, besides its role in monthly timing, also schedules the exact hour of nocturnal swarming onset to the nights’ darkest times. Moonlight adjusts a plastic clock, exhibiting <24h (moonlit) or >24h (no moon) periodicity. Abundance, light sensitivity, and genetic requirement indicatePlatynereisr-Opsin1 as receptor to determine moonrise, while the cryptochrome L-Cry is required to discriminate between moon- and sunlight valence. Comparative experiments inDrosophilasuggest that Cryptochrome’s requirement for light valence interpretation is conserved. Its exact biochemical properties differ, however, between species with dissimilar timing ecology.Our work advances the molecular understanding of lunar impact on fundamental rhythmic processes, including those of marine mass spawners endangered by anthropogenic change.
Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling
Authors: Messerschmidt Victoria L. , Kuriakose Aneetta E. , Chintapula Uday , Laboy Samantha , Truong Thuy Thi Dang , Kydd LeNaiya A. , Jaworski Justyn , Nguyen Kytai T. , Lee Juhyun 
Published: April 2021

AbstractNotch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domain-containing plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.
Invasive grass fuel loads suppress native species by increasing fire intensity and soil heating
Authors: Tomat‐Kelly Giovanna , Dillon Whalen W. , Flory Stephen Luke 
Published: April 2021

Abstract

Non‐native invasive grasses are driving intense fires across the globe but the impacts of native versus invader‐fuelled fires on community assemblages are poorly understood. By increasing fire intensity, grass invasions might increase below‐ground mortality of heat‐sensitive seeds and buds, thereby shifting community composition.

We compared fuel loads in native and non‐native invasive (cogongrass, Imperata cylindrica) plant‐dominated areas of pine savannas in Florida. Then, we conducted a field experiment to examine how fuel loads and native and invasive fuel types affected soil heating and seedling emergence or resprouting of native and invasive plant species.

Average fuel loads in invaded communities were 152% greater than that in native communities. Soil heating, including heating duration >60°C, maximum temperature and heat flux >60°C, increased, and seedling emergence and resprouting decreased with greater fuel loads; these relationships were similar across the overlapping range of native and invasive fuel loads. However, longer durations of soil heating at the higher average fuel loads of invaded communities resulted in 23% lower predicted probability of seedling emergence compared to average fuel loads of native communities.

Invasive cogongrass resprouting was not affected by fuel loads, indicating that cogongrass tolerates the intense fires it generates. In contrast, seedling emergence and resprouting of most other species was reduced by greater fuel loads.

Synthesis and applications. By increasing fuel loading and soil heating, grass invasions may alter post‐fire community assemblages and facilitate invasive grass dominance at the expense of native species via an invasion‐fire cycle. Fuel loads can be used to predict soil heating duration and depth, and these data, combined with information on species tolerances to heating, can be used to forecast the impacts of invasions on post‐fire community composition. To maintain fire regimes that promote native communities and resist invader dominance, it is critical to manage invasive species that increase fuel loads.
Update on pregnancy in Takayasu arteritis—A narrative review
Authors: Padiyar Shivraj , Manikuppam Prathyusha , Kabeerdoss Jayakanthan , Rathore Swati , Danda Debashish 
Published: April 2021

AbstractTakayasu arteritis (TA) is a chronic, idiopathic large‐vessel vasculitis that affects women of reproductive age, and has significant maternal and fetal implications. Although there are contrasting data on the effect of TA on fertility, most studies have shown that fertility outcomes remain unaffected. The disease activity of TA usually either remains stable or decreases during pregnancy. The important fetomaternal complications are maternal hypertension, pre‐eclampsia, prematurity, and intrauterine growth restriction. To reduce maternal and fetal morbidity, controlling the disease before conception is important. This review article discusses the various implications, challenges, and medical and endovascular management of TA during pregnancy.
Microbial rhodopsins are increasingly favoured over chlorophyll in High Nutrient Low Chlorophyll waters
Authors: Hassanzadeh Babak , Thomson Blair , Deans Fenella , Wenley Jess , Lockwood Scott , Currie Kim , Morales Sergio E. , Steindler Laura , Sañudo‐Wilhelmy Sergio A. , Baltar Federico , Gómez‐Consarnau Laura 
Published: April 2021

AbstractMicrobial rhodopsins are simple light‐harvesting complexes that, unlike chlorophyll photosystems, have no iron requirements for their synthesis and phototrophic functions. Here, we report the environmental concentrations of rhodopsin along the Subtropical Frontal Zone off New Zealand, where Subtropical waters encounter the iron‐limited Subantarctic High Nutrient Low Chlorophyll (HNLC) region. Rhodopsin concentrations were highest in HNLC waters where chlorophyll‐a concentrations were lowest. Furthermore, while the ratio of rhodopsin to chlorophyll‐a photosystems was on average 20 along the transect, this ratio increased to over 60 in HNLC waters. We further show that microbial rhodopsins are abundant in both picoplankton (0.2–3 μm) and in the larger (>3 μm) size fractions of the microbial community containing eukaryotic plankton and/or particle‐attached prokaryotes. These findings suggest that rhodopsin phototrophy could be critical for microbial plankton to adapt to resource‐limiting environments where photosynthesis and possibly cellular respiration are impaired.
The perceptions of pregnant women about cervical length screening for preterm birth prevention
Authors: Pedretti Michelle K. , Dickinson Jan E. , Doherty Dorota A. 
Published: April 2021

BackgroundThe Western Australian Preterm Birth Prevention Initiative was officially launched in November 2014. It demonstrated an initial decrease in the preterm birth rate in Western Australia. One of the key points of this initiative is the routine ultrasound measurement of the cervical length in mid‐pregnancy.AimThe aim of this study was to evaluate the perceptions and attitudes of Western Australian women regarding transvaginal cervical length (TVCL) screening for preterm birth prevention.Materials and methodsSelf‐administered questionnaires were completed by pregnant women before and after their mid‐trimester obstetric ultrasound. Maternal demographical and medical data were collected in addition to opinions of TVCL screening.ResultsA total of 598 women participated with the maternal age range representative of the Western Australian obstetric population. There was a high rate of acceptance of TVCL imaging, with 2% of the 149 women declining a transvaginal ultrasound (TVU) offered in this study, 1.5% refusing a TVU in the past and 5.7% reporting that they would have a concern in having a TVU in the future. Women stated that they either had declined TVCL in the past (11%) or would decline in the future (30.7%) as they wanted to discuss the procedure with their clinician first, had been advised not to have a TVU by their clinician (11% in the past and 47.7% in the future) or felt uncomfortable with the operator (22% at a previous TVU and 34.4% in the future).ConclusionPregnant women participating in this study had a high acceptance of TVCL screening for preterm birth prevention.
Serum carcinoembryonic antigen pre‐operative level in colorectal cancer: revisiting risk stratification
Authors: Iacuzzo Cristiana , Germani Paola , Troian Marina , Cipolat Mis Tommaso , Giudici Fabiola , Osenda Edoardo , Bortul Marina , de Manzini Nicolò 
Published: April 2021

AbstractBackgroundBiomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre‐operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut‐off values.MethodsA retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease‐free survival at 3‐years and risk of local, loco‐regional and distant recurrence during follow‐up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre‐operative values and follow‐up data in order to estimate the optimal cut‐off values.ResultsA total of 559 patients were considered. The mean CEA value was 12.1 ± 54.1 ng/mL, and the median 29.3 (0–4995) ng/mL. The ROC curve analysis identified 12.5 ng/mL as the best CEA cut‐off value to predict the risk of metastatic development after surgery in stage I–III colorectal cancer patients, and 10 ng/mL as the best CEA cut‐off value to predict overall survival and disease‐free survival in stage III–IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA <10 ng/mL), a moderate risk class (CEA 10–12.5 ng/mL) and a high risk class (CEA >12.5 ng/mL).ConclusionIn conclusion, pre‐operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy.
Outcomes of diverting loop ileostomy reversal in the elderly: a case–control study
Authors: Segev Lior , Assaf Dan , Elbaz Nadav , Schtrechman Gal , Westrich Gal , Adileh Mohammad , Nissan Aviram , Goitein David 
Published: April 2021

AbstractBackgroundAlthough diverting loop ileostomy (DLI) reversal is considered to be a relatively simple procedure, it is not immune from major morbidity. We aimed to compare outcomes of DLI reversal between elderly and non‐elderly patients.MethodsRetrospective review of all patients who underwent DLI reversal at a single tertiary medical centre between 2010 and 2020. The elderly group consisted of patients 70 or older compared to a control group of those younger than 70 years.ResultsDuring the study period, 307 patients underwent DLI reversal. Of these, 76 patients were in the elderly group (mean age 75.6) and 231 in the control group (mean age 55.3). The groups were comparable in terms of mean time interval between the creation of the ileostomy and reversal (242 versus 255 days, respectively, P = 0.5), choice between stapled and hand‐sewn anastomoses (97.4% stapled anastomosis versus 93.1%, P = 0.086), median post‐operative length of stay (5 days in both, P = 0.086), rates of post‐operative complications (26.3% versus 26.8%, P = 0.99), severe complications (5.3% versus 6.9%, P = 0.81) and 30‐day readmission rates (13.2% versus 10.8%, P = 0.58). Multivariate analysis found the time interval between the creation of the stoma and its reversal to be the only significant risk factor for major post‐operative morbidity. Age was not found to be correlated with post‐operative morbidity.ConclusionThe outcomes of loop ileostomy reversal in elderly patients are similar to non‐elderly patients. Efforts should be made to decrease the time interval between the creation of the stoma and its reversal as this is a significant risk factor for major post‐operative morbidity.
Experience of treating biliary atresia with laparoscopic‐modified Kasai and laparoscopic conventional Kasai: a cohort study
Authors: Li Bing , Chen Bing Wei , Xia Lin Shun 
Published: April 2021

AbstractBackgroundComplete mobilization of the left and right portal veins had been seldom utilized in the laparoscopic Kasai procedures. The purpose of this study was to evaluate the feasibility and efficacy of the key technique in detail.MethodsA total of 82 patients with type III biliary atresia were operated by laparoscopic Kasai at our hospital during January 2012 to October 2019. Forty‐two patients underwent modified laparoscopic Kasai (group 1), and 40 patients of control group underwent general laparoscopic Kasai (group 2). The clinical data between the two groups were compared.ResultsThe early clearance of jaundice was significantly higher for group 1 (88.1%) versus group 2 (68.4%) (P < 0.05), the incidence of repeated cholangitis was significantly lower in group 1 (11.9%) versus group 2 (31.6%) (P < 0.05). The native liver survival rate was (85.7%) in group1 versus in group 2 (65.8%) (P < 0.05). In addition, there were no significant differences regarding the resumption oral intake and the post‐operative hospital stay in the two groups.ConclusionThe key technique of the complete mobilization of the left and right portal veins would improve the outcome of biliary atresia treated by laparoscopic Kasai.
The correlates of social phobia in OCD: Findings from a large clinical sample
Authors: Tibi Lee , Asher Sapir , van Oppen Patricia , van Balkom Anton J. L. M. , Eikelenboom Merijn , Visser Henny A. , Penninx Brenda W. , Anholt Gideon E. 
Published: April 2021

ObjectivesObsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder, often complicated with comorbidities. Social phobia (SP) is the most frequent co‐occurring anxiety disorder in OCD, associated with increased clinical severity. However, no study had examined the relevance of interpersonal processes in this comorbidity, which are at the core of SP. This study characterized the clinical (i.e., symptom profile, age of onset, chronicity, and comorbidity), vulnerability (i.e., childhood trauma, negative life events), and interpersonal (attachment style, expressed emotion, and social support) correlates of comorbid SP in a large sample of OCD patients.MethodsWe analysed the data of 382 OCD patients participating in the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. We examined the correlates of SP in OCD using self‐report questionnaires and structured clinical interviews. In addition, data of 312 non‐OCD SP patients were drawn from the Netherlands Study of Depression and Anxiety (NESDA), to compare the age of onset of SP between groups. Descriptive univariate analyses were followed by backward stepwise logistic regression analyses.ResultsSocial phobia was present among approximately 20% of OCD patients. Social phobia in OCD was associated with increased depression severity and decreased ratings of secure attachment style. Among OCD patients, SP had a significantly earlier age onset as compared to SP in non‐OCD patients.ConclusionSocial phobia in OCD might render a vulnerable clinical picture, characterized with early onset of SP symptoms, insecure attachment style, and increased depressive symptoms. Future studies should use prospective designs to better understand the nature of comorbid SP in OCD.Practitioner points

Approximately one fifth of OCD patients were diagnosed with comorbid social phobia in a large representative clinical sample.

OCD patients with comorbid social phobia presented with a vulnerable clinical picture, characterized with increased depression severity and decreased ratings of secure attachment style.

Social phobia in OCD was associated with an earlier AOO as compared to the AOO of social phobia without OCD.

The findings are limited by a cross‐sectional design; thus, causality could not be assessed.

Research is needed to further examine the mechanisms of comorbid social phobia in OCD.
Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis
Authors: Gao Lin , Dong Xiaowu , Gong Weijuan , Huang Wei , Xue Jing , Zhu Qingtian , Ma Nan , Chen Weiwei , Fu Xianghui , Gao Xiang , Lin Zhaoyu , Ding Yanbing , Shi Juanjuan , Tong Zhihui , Liu Tingting , Mukherjee Rajarshi , Sutton Robert , Lu Guotao , Li Weiqin 
Published: April 2021

Background and PurposePyroptosis is a lytic form of pro‐inflammatory cell death characterised as caspase 1 dependent with canonical NLRP3 inflammasome‐induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyroptotic cell death in pancreatic injury and systemic inflammation in AP.Experimental ApproachPancreatic acinar pyroptotic cell death pathway activation upon pancreatic toxin stimulation in vitro and in vivo was investigated. Effects of pharmacological (NLRP3 and caspase‐1 inhibitors), constitutive (Nlrp3−/−, Casp1−/− and Gsdmd−/−) and acinar cell conditional (Pdx1CreNlrp3Δ/Δ and Pdx1CreGsdmdΔ/Δ) genetic inhibition on pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation were assessed using mouse AP models (caerulein, sodium taurocholate and l‐arginine). Effects of Pdx1CreGsdmdΔ/Δ versus myeloid conditional knockout (Lyz2CreGsdmdΔ/Δ) and Gsdmd−/− versus receptor‐interacting protein 3 (RIP3) inhibitor were compared in CER‐AP.Key ResultsThere was consistent pyroptotic acinar cell death upon pancreatic toxin stimulation both in vitro and in vivo, which was significantly reduced by pharmacological or genetic pyroptosis inhibition. Pdx1CreGsdmdΔ/Δ but not Lyz2CreGsdmdΔ/Δ mice showed significantly reduced pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation in caerulein‐AP. Co‐application of RIP3 inhibitor on Gsdmd−/− mice further increased protection on caerulein‐AP.Conclusion and ImplicationsThis work demonstrates a critical role for NLRP3 inflammasome and GSDMD activation‐mediated pyroptosis in acinar cells, linking pancreatic necrosis and systemic inflammation in AP. Targeting pyroptosis signalling pathways holds promise for specific AP therapy.