bluuebunny/crossref_metadata_2025_split huggingface dataset:
The regulatory role of CARBON STARVED ANTHER-mediated photoperiod-dependent male fertility in rice
Authors: Li Jingbin , Wang Duoxiang , Sun Shiyu , Sun Linlin , Zong Jie , Lei Yaqi , Yu Jing , Liang Wanqi , Zhang Dabing 
Published: March 2022

Abstract
Environmental signals, especially daylength, play important roles in determining fertility in photoperiod-sensitive genic male sterile (PGMS) lines that are critical to sustain production of high-yielding hybrid rice (Oryza sativa) varieties. However, the mechanisms by which PGMS lines perceive changes in photoperiod and transmit those signals to elicit downstream effects are not well understood. In this study, we compared the transcriptomes from the leaves and anthers of carbon starved anther (csa), a PGMS line, to wild-type (WT) tissues under different photoperiods. Components of circadian clock in the leaves, including Circadian Clock-Associated 1 and Pseudo-Response Regulator (PRR95), played vital roles in sensing the photoperiod signals. Photoperiod signals were weakly transduced to anthers, where gene expression was mainly controlled by the CSA allele. CSA played a critical role in regulating sugar metabolism and cell wall synthesis in anthers under short-day conditions, and transcription of key genes inducing csa-directed sterility was upregulated under long-day (LD) conditions though not to WT levels, revealing a mechanism to explain the partial restoration of fertility in rice under LD conditions. Eight direct targets of CSA regulation were identified, all of which were genes involved in sugar metabolism and transport (cell wall invertases, SWEETs, and monosaccharide transporters) expressed only in reproductive tissues. Several hub genes coordinating the effects of CSA regulation were identified as critical elements determining WT male fertility and further analysis of these and related genes will reveal insights into how CSA coordinates sugar metabolism, cell wall biosynthesis, and photoperiod sensing in rice anther development.
Causal cascade of direct and indirect effects of anifrolumab on patient-reported outcomes: structural equation modelling of two Phase 3 trials
Authors: Stull Donald , O’Quinn Sean , Williams Betsy , Bean Stephanie , Schwetje Erik , Abreu Gabriel , Tummala Raj 
Published: March 2022

Abstract

Objectives
SLE significantly impairs health-related quality of life (HRQoL). In this post hoc analysis, structural equation modelling was used to examine the ‘causal cascade’ of interaction between anifrolumab, disease activity and patient-reported outcomes (PROs) in pooled data from the phase 3 TULIP-1 and TULIP-2 trials.

Methods
Data were pooled from the TULIP-1 (n = 364) and TULIP-2 (n = 362) randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks for 48 weeks). We evaluated changes from baseline to week 24 and week 52 in four clinical (BICLA, BILAG-2004, SLEDAI-2K and changes in glucocorticoid dosage) and six PRO measures (SF-36, FACIT-F, EQ-5D, LupusQoL, PHQ-8 and pain NRS) in our hypothesized model of interactions.

Results
Our hypothesized model had an acceptable fit to the pooled TULIP trial data. At week 24, significant paths revealed that when compared with placebo, anifrolumab treatment improved disease activity as measured by BICLA, BILAG-2004, SLEDAI-2K and changes to glucocorticoid dosage. In turn, these clinical measures reduced pain, which improved fatigue, physical functioning, mood/emotions and HRQoL. When the model incorporated number of glucocorticoid tapers as the measure of change in glucocorticoid dosage, treatment effects of anifrolumab on glucocorticoid tapers were not retained at week 52. However, at week 52 treatment indirectly improved HRQoL through its direct effects on BICLA.

Conclusions
Anifrolumab is associated with significant patient-reported improvements in aspects of HRQoL including pain, fatigue, mood and physical function. These benefits are from the direct effect of anifrolumab treatment on disease activity and reduction in glucocorticoid dosage.
Investigating characteristics of idiopathic inflammatory myopathy flares using daily symptom data collected via a smartphone app
Authors: Oldroyd Alexander G S , Krogh Niels Steen , Dixon William G , Chinoy Hector 
Published: March 2022

Abstract

Objective
The objective of this study was to use daily data collected via a smartphone app for characterization of patient-reported and symptom-based (using an a priori definition) flares in an adult idiopathic inflammatory myopathy (IIM) cohort.

Methods
UK adults with an IIM answered patient-reported outcome measurements (PROMs) daily via a smartphone app during a 91-day study. Daily symptom PROMs addressed global activity, overall pain, myalgia, fatigue, and weakness (on a 0–100 visual analogue scale). Patient-reported flares were recorded via a weekly app question. Symptom-based flares were defined via an a priori definition related to increase in daily symptom data from the previous 4-day mean.

Results
Twenty participants (65% female) participated. Patient-reported flares occurred on a median of 5 weeks (IQR 3, 7) per participant, out of a possible 13. The mean of each symptom score was significantly higher in flare weeks, compared with non-flare weeks (e.g. mean flare week myalgia score 34/100, vs 21/100 during non-flare week, t test P-value &lt;0.01). Fatigue accounted for the most symptom-based flares [incidence-rate 23/100 person-days (95% CI 19, 27)], and myalgia the fewest [incidence rate 13/100 person-days (95% CI 11, 16)]. Symptom-based flares typically resolved after 3 days, although fatigue-predominant flares lasted 2 days. The majority (69%) of patient-reported flare weeks coincided with at least one symptom-based flare.

Conclusions
IIM flares are frequent and associated with increased symptom scores. This study has demonstrated the ability to identify and characterize patient-reported and symptom-based flares (based on an a priori definition), using daily app-collected data.
Sleep architecture based on sleep depth and propensity: patterns in different demographics and sleep disorders and association with health outcomes
Authors: Younes Magdy , Gerardy Bethany , Pack Allan I , Kuna Samuel T , Castro-Diehl Cecilia , Redline Susan 
Published: March 2022

Abstract

Study Objectives
Conventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics.

Methods
We analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP &lt; 0.50) and in full-wakefulness (ORP &gt; 2.25) were each assigned a rank, 1–3, representing first and second digits, respectively, of nine distinct types (“1,1”, “1,2” … ”3,3”). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined.

Results
Three types (“1,1”, “1,2”, “1,3”) were prevalent in OSA and were associated with reduced QOL. Two (“1,3” and “2,3”) were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only “1,3” was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types “1,1” and “1,2”, and low in “1,3” and “2,3”. Prevalence of some types increased with age while in others it decreased. Other types were either rare (“1,1” and “3,3”) or high (“2,2”) at all ages.

Conclusions
The proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders.
Delayed autumnal leaf senescence following nutrient fertilization results in altered nitrogen resorption
Authors: Wang Peilin , Fu Chen , Wang Liying , Yan Tao 
Published: March 2022

Abstract
Increased atmospheric nitrogen (N) deposition could create an imbalance between N and phosphorus (P), which may substantially impact ecosystem functioning. Changes in autumnal phenology (i.e., leaf senescence) and associated leaf nutrient resorption may profoundly impact plant fitness and productivity. However, we know little about how and to what extent nutrient addition affects leaf senescence in tree species, or how changes in senescence may influence resorption. We thus investigated the impacts of N and P addition on leaf senescence and leaf N resorption in 2-year-old larch (Larix principisrupprechtii) seedlings in northern China. Results showed that nutrient addition (i.e., N, P or N + P addition) significantly delayed autumnal leaf senescence, and decreased leaf N resorption efficiency (NRE) and proficiency (NRP), particularly in the N and N + P treatments. Improved leaf N concentrations were correlated with delayed leaf senescence, as indicated by the positive relationship between mature leaf N concentrations and the timing of leaf senescence. Following nutrient addition, larch seedlings shifted toward delayed onset, but more rapid, leaf senescence. Additionally, we observed an initial negative correlation between the timing of leaf senescence and NRE and NRP, followed by a positive correlation, indicating delayed and less efficient remobilization during the early stages of senescence, followed by accelerated resorption in the later stages. However, the latter effect was potentially impaired by the increased risk of early autumn frost damage, thus failed to fully compensate for the negative effects observed during the early stages of senescence. Improved soil P availability increased leaf N resorption and thus weakened the negative impact of delayed leaf senescence on leaf N resorption, so P addition had no significant impact on leaf N resorption. Overall, our findings clarify the relationship between nutrient addition–resorption and the linkage with leaf senescence, and would have important implications for plant nutrient conservation strategy and nutrient cycling.
Aridity and cold temperatures drive divergent adjustments of European beech xylem anatomy, hydraulics and leaf physiological traits
Authors: Vicente Eduardo , Didion-Gency Margaux , Morcillo Luna , Morin Xavier , Vilagrosa Alberto , Grossiord Charlotte 
Published: March 2022

Abstract
Understanding plant trait coordination and variance across climatic gradients is critical for assessing forests’ adaptive potential to climate change. We measured 11 hydraulic, anatomical and leaf-level physiological traits in European beech (Fagus sylvatica L.) along a moisture and temperature gradient in the French Alps. We assessed how traits covaried, and how their population-level variances shifted along the gradient. The intrapopulation variances of vessel size and xylem-specific conductivity reduced in colder locations as narrow vessels were observed in response to low temperature. This decreased individual-level water transport capacity compared with the warmer and more xeric sites. Conversely, the maximum stomatal conductance and Huber value variances were constrained in the arid and warm locations, where trees showed restricted gas exchange and higher xylem-specific conductivity. The populations growing under drier and warmer conditions presented wide variance for the xylem anatomical and hydraulic traits. Our results suggest that short-term physiological acclimation to raising aridity and heat in southern beech populations may occur mainly at the leaf level. Furthermore, the wide variance of the xylem anatomical and hydraulic traits at these sites may be advantageous since more heterogeneous hydraulic conductivity could imply populations’ greater tree–tree complementarity and resilience against climatic variability. Our study highlights that both intrapopulation trait variance and trait network analysis are key approaches for understanding species adaptation and the acclimation potential to a shifting environment.
XenostrobusorVignadula(Bivalvia: Mytilidae)? A taxonomic re-evaluation of small black mussels inhabiting the upper intertidal zone of the estuaries of Southeast Asia
Authors: Tan Koh Siang , Tan Samuel Hui Ming , Sanpanich Kitithorn , Duangdee Teerapong , Ambarwati Reni 
Published: March 2022

AbstractThe presence of small black mussels in the upper intertidal zone of estuarine seashores in Southeast Asia is often overlooked, despite their numerical dominance. Here, we clarify their species identities, taxonomy, geographical distributions and genetic relationships. Our molecular results suggest that three closely related species in East and Southeast Asia form a sister clade to Australian and New Zealand Xenostrobus. Given their distinctness, we resurrect the genus Vignadula to distinguish these two clades. Vignadula atrata, first described from Japan and type species of the genus, is confined to north-east Asia, whilst two other Vignadula species occur natively in Southeast Asia. Of these two species, one is found throughout Thailand, Malaysia, Singapore and Java. We show that this species corresponds to Xenostrobus balani and Xenostrobus mangle described from the Malacca Strait, which are genetically indistinguishable and here considered as one and the same species, Vignadula mangle comb. nov. The other species, Vignadula kuraburiensis sp. nov., described in this study, has so far been found only in south-west Thailand. Members of Vignadula are, in turn, all clearly different from their closest morphological equivalent in Australia, Xenostrobus pulex. A new subfamily Xenostrobinae is proposed to accommodate the two genera Xenostrobus and Vignadula.
Cow's milk allergy
Authors: Arasi Stefania , Cafarotti Arianna , Fiocchi Alessandro 
Published: March 2022

Purpose of review
To highlight the most recent insights on cow's milk allergy (CMA), its treatment, and management.

Recent findings
CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction, CMA may imply also a severe impairment of health-related quality of life at individual and family level as well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against Cow's Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-of-the-art specifically on CMA, including international evidence-based recommendations. The current results from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high degree of cross-reactivity with cow's milk proteins and risk for allergic reactions, goats’ milk or other mammals’ milk should not be used.

Summary
The adoption and implementation of evidence-based recommendations may guide a proper diagnostics and management and awaited advances in knowledge will allow the development of a personalized treatment tailored on the specific CMA patient's profile.
Association of Obesity With Longer Time to Pregnancy
Authors: Burger Taylor , Li Joanna , Zhao Qiuhong , Schreiber Courtney A. , Teal Stephanie , Turok David K. , Natavio Melissa , Peipert Jeffrey F. 
Published: March 2022

OBJECTIVE:
To assess whether obesity is associated with increased time to pregnancy in a cohort of participants who were stopping their contraceptive method to attempt pregnancy.

METHODS:
We performed a secondary analysis of the FACT (Fertility After Contraceptive Termination) study. This prospective analysis included 432 participants, aged 18–35 years, who discontinued contraception to become pregnant, were sexually active with a male partner, and provided pregnancy status data within the first 12 months in the study. The primary outcome, time to pregnancy, was measured beginning with discontinuation of contraception to estimated pregnancy date. We used Cox proportional hazard models to assess associations of normal (lower than 25.0), overweight (25.0–29.9), and obese (30 or higher) body mass index (BMI) and time to pregnancy while controlling for potential confounding factors.

RESULTS:
After adjusting for confounders, participants with BMIs 30 or higher were noted to have prolonged time to pregnancy compared with those with BMIs lower than 25 (adjusted hazard ratio [aHR] 0.62; 95% CI 0.44–0.89). The median time to pregnancy for participants with normal BMIs was 5.3 months (95% CI 3.8–6.4) compared with 8.2 months (95% CI 6.8–10.8) for participants with obesity. Pregnancy rates at 1 year were 76.4% (95% CI 69.7–82.6%), 69.5% (95% CI 60.5–78.1%), and 59.1% (95% CI 51.0–67.4%) for participants with BMIs lower than 25, 25–29.9, and 30 or higher, respectively. Menstrual irregularity was also associated with decreased fertility (aHR 0.67; 95% CI 0.46–0.97).

CONCLUSION:
Compared with participants with normal BMIs, we observed increased time to pregnancy for participants with obesity stopping contraception with the intention to become pregnant. Understanding the reasons for this association will be helpful to inform patients and guide clinical practice.

FUNDING SOURCE:
The FACT Study was funded, in part, by Bayer, CooperSurgical, and the Society of Family Planning.
Exposure to Tramadol During Early Pregnancy and Risk of Spontaneous Abortion or Major Congenital Malformations
Authors: Sørensen Anne Mette Skov , Noergaard Mia Muusfeldt , Gotfredsen Ditte Resendal , Kjærbye-Thygesen Anette , Jimenez-Solem Espen , Askaa Bjarke , Poulsen Henrik Enghusen , Horwitz Henrik , Andersen Jon Trærup 
Published: March 2022

OBJECTIVE:
To investigate whether exposure to tramadol during early pregnancy is associated with an increased risk of spontaneous abortion or major congenital malformations.

METHODS:
The study is a nationwide cohort study including all registered pregnancies in Denmark between January 1, 1997, and December 31, 2016. The Danish National Prescription Register was used to identify maternal exposure to tramadol. Pregnancies with maternal exposure to tramadol were matched with pregnancies without maternal exposure to tramadol in a ratio of up to 1:4 using propensity scoring. The primary outcomes were spontaneous abortion and major congenital malformations. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) of spontaneous abortion, and log binominal models were used to estimate the relative risk ratios (RRs) of major congenital malformations.

RESULTS:
A total of 36,467 (tramadol exposure n=7,310) and 18,907 (tramadol exposure n=3,796) pregnancies were included in the analyses of spontaneous abortion and major congenital malformations, respectively. Spontaneous abortion occurred in 893 (12.2%) pregnancies with maternal exposure to tramadol and in 3,471 (11.9%) pregnancies without maternal exposure to tramadol (HR 1.06, 95% CI 0.99–1.14). A major congenital malformation occurred in the offspring of 151 (4.0%) pregnancies with maternal exposure to tramadol, compared with 579 (3.8%) in pregnancies without maternal exposure to tramadol (RR 1.04, 95% CI 0.87–1.24).

CONCLUSION:
Exposure to tramadol during early pregnancy does not appear to be associated with an increased risk of spontaneous abortion or major congenital malformations.
Virtual orthopaedic surgery away rotation benefits both the program and applicant: a survey of participants
Authors: White Micah , Montgomery Corey , Romer Karen , Kelly Derek M. 
Published: March 2022

Background:
The COVID-19 pandemic has forced many medical education institutions to switch from in-person to online learning environments. There is an existing gap in knowledge about the effectiveness of virtual learning for medical students.

Objective:
The purpose of the study was to determine if virtual orthopaedic surgery away rotations (VOSAR) benefit medical students and programs.

Methods:
Virtual rotations were created at two large residency programs for fourth-year medical students. From October 12, 2020 through December 28, 2020, satisfaction and quality were assessed using a 22-question survey, residency interview, rank, and match data. Forty-two fourth-year medical students participated, 38 of whom responded to the survey.

Results:
Most students stated course objectives were clear and consistent with coursework. Most were pleased with the variety of cases and presentations and were able to meaningfully interact with faculty and residents. Most stated they would participate again and suggest the rotation to others. Twenty-five of 42 participants were ranked by at least one program; 39 were accepted into residency positions, 21 of which were in orthopaedic surgery.

Conclusions:
The results indicate that the VOSAR benefits students and programs. Based on the success of the VOSAR, both programs continued to offer the curriculum for 2021.

Level of Evidence:
Level IV.
Team-based strategies to prevent heart failure
Authors: Taha Mohamad B. , Patel Kershaw V. , Nasir Khurram 
Published: March 2022

Purpose of review
The burden of heart failure (HF) in the United States and worldwide is projected to rise. Prevention of HF can curb the burden of this chronic syndrome, but current approaches are limited. This review discusses team-based strategies aimed to prevent HF.

Recent findings
Individuals at high risk for developing HF can be identified using HF risk scores, biomarkers, and cardiac imaging. Electronic medical records (EMR) can integrate clinical data to estimate HF risk and identify individuals who may benefit most from preventive therapies. Team-based interventions can lead to enhanced adherence to medications, optimization of medical management, and control of risk factors. Multifaceted interventions involve EMR-based strategies, pharmacist- and nurse-led initiatives, involvement of community personnel, polypills, and digital solutions.

Summary
Team-based strategies aimed to prevent HF incorporate a broad group of personnel and tools. Despite implementation challenges, existing resources can be efficiently utilized to facilitate team-based approaches to potentially reduce the burden of HF.