bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypocalcemia and bone mineral changes in hemodialysis patients with low bone mass treated with denosumab: a 2-year observational study
Authors: Hiramatsu Rikako , Ubara Yoshifumi , Sawa Naoki , Sakai Akinori 
Published: February 2021

Abstract

Background
Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients.

Methods
An observational noncontrolled study involving 47 hemodialysis patients was conducted to determine the independent risk factors related to percentage changes in serum calcium (Ca) levels associated with denosumab using multivariate regression analysis. Optimal predictive markers for DAAH were explored by receiver operating characteristic analysis. Percentage changes of BMD at the lumbar spine (LS) and femoral neck (FN) at 24 months were investigated.

Results
The incidence of DAAH [serum corrected Ca (cCa) ≤8 mg/dL] following denosumab was 25.5%. Multivariate regression analysis showed that baseline bone alkaline phosphatase was independently related to percentage changes in cCa levels (β = −0.407, P = 0.008). Tartrate-resistant acid phosphatase-5b was found to be the most accurate marker to predict DAAH, with an area under the curve of 0.750 (95% confidence interval 0.546–0.954; P = 0.02), and the optimal cut-off level was 670 mU/mL with sensitivity: 0.727 and specificity: 0.733. BMD significantly increased by 5.9 ± 1.7% (P = 0.01) at LS and 4.2 ± 1.5% (P = 0.04) at FN at 24 months.

Conclusions
In hemodialysis patients, high bone turnover was an independent risk factor for the Ca declines induced by denosumab. Denosumab significantly increased BMD at LS and FN at 24 months.
Systematic review of the nuclear factor erythroid 2-related factor 2 (NRF2) system in human chronic kidney disease: alterations, interventions and relation to morbidity
Authors: Juul-Nielsen Christoffer , Shen Jianlin , Stenvinkel Peter , Scholze Alexandra 
Published: February 2021

AbstractBackgroundNuclear factor erythroid 2-related factor 2 (NRF2) and its effectors NAD(P)H:quinoneoxidoreductase 1 (NQO1) and haem oxygenase 1 (HO-1) are of interest in kidney disease. We therefore reviewed studies about their status in patients with chronic kidney disease (CKD).MethodsWe undertook systematic searches of PubMed and Excerpta Medica dataBASE (EMBASE) databases. Alterations of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their relation to clinically relevant parameters were reported.ResultsWe identified 1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were decreased in the majority of analyses of CKD patients. Half of the analyses showed a similar or increased NQO1 level versus control, whereas in half of the analyses NQO1 was decreased. Most of the studies reported either an increased or similar HO-1 level in CKD patients compared with controls. For patients with CKD Stages 1–4, studies reported positive correlations to markers of kidney disease severity. Also, positive associations of NQO1/HO-1 levels to inflammation and comorbidities were reported. One-third of the studies showed discordant changes between gene expression and protein level of NRF2 system components. Two-thirds of intervention studies (50% dietary, such as using resistant starch) reported an increase of NRF2, NQO1 or HO-1.ConclusionsIn patients with CKD, NRF2 expression was downregulated, while NQO1 and HO-1 showed varying alterations related to inflammation, comorbidities and severity of kidney damage. Interventions that increased NRF2 system components were described, but their effectiveness and clinical relevance require further clinical studies of high quality. Research on gene expression together with protein analyses is indispensable to understand NRF2 system alterations in CKD.
Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status
Authors: Wei Chih-Fu , Lin Ching-Chun , Tsai Meng-Shan , Guo Yueliang Leon , Lin Shio-Jean , Liao Hua-Fang , Hsieh Wu-Shiun , Chen Mei-Huei , Chen Pau-Chung 
Published: February 2021

AbstractIntroductionSecondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population.Aims and MethodsTerm singleton mother–infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification.ResultsHigher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye.ConclusionsSecondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status.ImplicationsThe study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.
Mental health, reporting bias and economic transitions
Authors: Brown Sarah , Harris Mark N , Srivastava Preety , Taylor Karl 
Published: February 2021

Abstract
Measures of mental health are heavily relied upon to identify at-risk individuals. However, self-reported mental health metrics might be unduly affected by mis-reporting (perhaps stemming from stigma effects). In this article, we consider this phenomenon by focusing upon the mis-reporting of mental health using UK panel data from 1991 to 2018. In separate analyses of males and females, we examine how inaccurate reporting of the General Health Questionnaire (GHQ-12) measure, specifically its sub-components, can adversely affect the distribution of the index. The analysis suggests that individuals typically over report their mental health (especially so for males). The results are then used to adjust the GHQ-12 score to take mis-reporting into account. We then compare the effects of the adjusted/unadjusted GHQ-12 index when modelling a number of important economic transitions. Using the original index typically leads to an underestimate of the effect of poor mental health on transitions into improved economic states, for example, unemployment to employment.
Function of the HYDROXYCINNAMOYL-CoA:SHIKIMATE HYDROXYCINNAMOYL TRANSFERASE is evolutionarily conserved in embryophytes
Authors: Kriegshauser Lucie , Knosp Samuel , Grienenberger Etienne , Tatsumi Kanade , Gütle Desirée D , Sørensen Iben , Herrgott Laurence , Zumsteg Julie , Rose Jocelyn K C , Reski Ralf , Werck-Reichhart Danièle , Renault Hugues 
Published: February 2021

AbstractThe plant phenylpropanoid pathway generates a major class of specialized metabolites and precursors of essential extracellular polymers that initially appeared upon plant terrestrialization. Despite its evolutionary significance, little is known about the complexity and function of this major metabolic pathway in extant bryophytes, which represent the non-vascular stage of embryophyte evolution. Here, we report that the HYDROXYCINNAMOYL-CoA:SHIKIMATE HYDROXYCINNAMOYL TRANSFERASE (HCT) gene, which plays a critical function in the phenylpropanoid pathway during seed plant development, is functionally conserved in Physcomitrium patens (Physcomitrella), in the moss lineage of bryophytes. Phylogenetic analysis indicates that bona fide HCT function emerged in the progenitor of embryophytes. In vitro enzyme assays, moss phenolic pathway reconstitution in yeast and in planta gene inactivation coupled to targeted metabolic profiling, collectively indicate that P. patens HCT (PpHCT), similar to tracheophyte HCT orthologs, uses shikimate as a native acyl acceptor to produce a p-coumaroyl-5-O-shikimate intermediate. Phenotypic and metabolic analyses of loss-of-function mutants show that PpHCT is necessary for the production of caffeate derivatives, including previously reported caffeoyl-threonate esters, and for the formation of an intact cuticle. Deep conservation of HCT function in embryophytes is further suggested by the ability of HCT genes from P. patens and the liverwort Marchantia polymorpha to complement an Arabidopsis thaliana CRISPR/Cas9 hct mutant, and by the presence of phenolic esters of shikimate in representative species of the three bryophyte lineages.
An alternative splicing variant of PtRD26 delays leaf senescence by regulating multiple NAC transcription factors in Populus
Authors: Wang Hou-Ling , Zhang Yi , Wang Ting , Yang Qi , Yang Yanli , Li Ze , Li Bosheng , Wen Xing , Li Wenyang , Yin Weilun , Xia Xinli , Guo Hongwei , Li Zhonghai 
Published: February 2021

Abstract
During leaf senescence, the final stage of leaf development, nutrients are recycled from leaves to other organs, and therefore proper control of senescence is thus critical for plant fitness. Although substantial progress has been achieved in understanding leaf senescence in annual plants, the molecular factors that control leaf senescence in perennial woody plants are largely unknown. Using RNA sequencing, we obtained a high-resolution temporal profile of gene expression during autumn leaf senescence in poplar (Populus tomentosa). Identification of hub transcription factors (TFs) by co-expression network analysis of genes revealed that senescence-associated NAC family TFs (Sen-NAC TFs) regulate autumn leaf senescence. Age-dependent alternative splicing (AS) caused an intron retention (IR) event in the pre-mRNA encoding PtRD26, a NAC-TF. This produced a truncated protein PtRD26IR, which functions as a dominant-negative regulator of senescence by interacting with multiple hub Sen-NAC TFs, thereby repressing their DNA-binding activities. Functional analysis of senescence-associated splicing factors identified two U2 auxiliary factors that are involved in AS of PtRD26IR. Correspondingly, silencing of these factors decreased PtRD26IR transcript abundance and induced early senescence. We propose that an age-dependent increase of IR splice variants derived from Sen-NAC TFs is a regulatory program to fine tune the molecular mechanisms that regulate leaf senescence in trees.
Magnesium maintains the length of the circadian period in Arabidopsis
Authors: de Melo J Romário F , Gutsch Annelie , Caluwé Thomas De , Leloup Jean-Christophe , Gonze Didier , Hermans Christian , Webb Alex A R , Verbruggen Nathalie 
Published: February 2021

Abstract
The circadian clock coordinates the physiological responses of a biological system to day and night rhythms through complex loops of transcriptional/translational regulation. It can respond to external stimuli and adjust generated circadian oscillations accordingly to maintain an endogenous period close to 24 h. However, the interaction between nutritional status and circadian rhythms in plants is poorly understood. Magnesium (Mg) is essential for numerous biological processes in plants, and its homeostasis is crucial to maintain optimal development and growth. Magnesium deficiency in young Arabidopsis thaliana seedlings increased the period of circadian oscillations of the CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) promoter (pCCA1:LUC) activity and dampened their amplitude under constant light in a dose-dependent manner. Although the circadian period increase caused by Mg deficiency was light dependent, it did not depend on active photosynthesis. Mathematical modeling of the Mg input into the circadian clock reproduced the experimental increase of the circadian period and suggested that Mg is likely to affect global transcription/translation levels rather than a single component of the circadian oscillator. Upon addition of a low dose of cycloheximide to perturb translation, the circadian period increased further under Mg deficiency, which was rescued when sufficient Mg was supplied, supporting the model’s prediction. These findings suggest that sufficient Mg supply is required to support proper timekeeping in plants.
Persistent Post-Mastectomy Pain: The Impact of Regional Anesthesia Among Patients with High vs Low Baseline Catastrophizing
Authors: Zinboonyahgoon Nantthasorn , Patton Megan E , Chen Yun-Yun K , Edwards Rob R , Schreiber Kristin L 
Published: February 2021

Abstract

Background
Persistent post-mastectomy pain (PPMP) varies both in its severity and impact, with psychosocial factors such as catastrophizing conferring greater risk. Preoperative regional anesthesia (RA) is an important nonopioid therapy, but with variable success at preventing PPMP in previous reports. We previously reported that RA was associated with lower acute post-mastectomy pain and opioid use, but more prominently among patients with higher baseline catastrophizing. The current longitudinal investigation at 3, 6, and 12 months postop aimed to detect differential long-term impact of RA on PPMP among patients with high vs low catastrophizing.

Methods
In this prospective observational study, patients (n = 123) completed preoperative psychosocial assessment and underwent mastectomy either with (n = 56) or without (n = 67) preoperative RA. Generalized estimating equation (GEE) regression analysis assessed impact of baseline catastrophizing, RA, and their interaction, on the primary outcome of pain severity index, as well as secondary outcomes including cognitive and emotional impact of pain, and persistent opioid use.

Results
We observed a significant interaction between the effect of catastrophizing and RA on PPMP. Specifically, RA was associated with reduced pain severity and pain impact 3, 6, and 12 months postoperatively, but only among those with high baseline catastrophizing scores. In addition, both RA and lower catastrophizing scores were associated with lower incidence of persistent opioid use.

Conclusions
The efficacy of therapies to prevent PPMP may be importantly influenced by pain-modulatory psychosocial characteristics. These findings underscore the importance of considering individual patient factors when applying preventive treatments, and of including their assessment in future trials.
Radiofrequency Ablation for Chronic Hip Pain: A Comprehensive, Narrative Review
Authors: Cheney Cole W , Ahmadian Amir , Brennick Caroline , Zheng Patricia , Mattie Ryan , McCormick Zachary L , Nagpal Ameet 
Published: February 2021

Abstract
Chronic hip pain can be treated with physical therapy, oral medications, injections, and, definitively, total hip arthroplasty. Enough patients have contraindications to and refractory pain even after total hip arthroplasty, that there is a need to develop alternative managements for this disabling condition. This article examines the state of hip radiofrequency ablation literature including relevant anatomy, patient selection, and treatment outcomes.
Self-reported medicinal plant use by Ghanaian women during pregnancy is associated with poor neonatal health
Authors: Busse Clara E , Wilson Mark L , Bakari Ashura , Moyer Cheryl A 
Published: February 2021

ABSTRACT

Background
More than a third of pregnant women in Africa use medicinal plants (hereafter, ‘herbs’) during pregnancy, yet little is known about herb use among urban African women, or about the potential impact on newborns.

Methods
This cross-sectional study of 504 women giving birth at an urban government hospital in Kumasi, Ghana (May–July 2018) collected data via chart reviews and maternal interviews. Data were analyzed using conditional logistic regression.

Results
Of 380 singleton births with complete data, 102 mothers (26.84%) reported using herbs during pregnancy and/or delivery. Herb users and non-users did not differ significantly across a range of sociodemographic variables. Controlling for age, education, neonatal birthweight and household running water (socioeconomic status (SES) indicator), herb-using women were twice as likely to have their newborn admitted to the hospital (odds ratio (OR) = 2.05; confidence interval (CI) 95% 1.17, 3.60) and four times as likely to bear a child with a low Apgar score (OR = 4.09; CI 95% 1.66, 10.07) compared with non-users.

Conclusion
Urban-dwelling Ghanaian women from diverse backgrounds use herbs during pregnancy. Maternal herb use was associated with poor neonatal outcomes, regardless of the baby’s birthweight and mother’s age, education or SES, suggesting the importance of educating all women about the possible negative impacts of herb use during pregnancy and delivery.
Incorporating Hierarchical Characters into Phylogenetic Analysis
Authors: Hopkins Melanie J , St. John Katherine 
Published: February 2021

Abstract
Popular optimality criteria for phylogenetic trees focus on sequences of characters that are applicable to all the taxa. As studies grow in breadth, it can be the case that some characters are applicable for a portion of the taxa and inapplicable for others. Past work has explored the limitations of treating inapplicable characters as missing data, noting that this strategy may favor trees where internal nodes are assigned impossible states, where the arrangement of taxa within subclades is unduly influenced by variation in distant parts of the tree, and/or where taxa that otherwise share most primary characters are grouped distantly. Approaches that avoid the first two problems have recently been proposed. Here, we propose an alternative approach which avoids all three problems. We focus on data matrices that use reductive coding of traits, that is, explicitly incorporate the innate hierarchy induced by inapplicability, and as such our approach extend to hierarchical characters, in general. In the spirit of maximum parsimony, the proposed criterion seeks the phylogenetic tree with the minimal changes across any tree branch, but where changes are defined in terms of dissimilarity metrics that weigh the effects of inapplicable characters. The approach can accommodate binary, multistate, ordered, unordered, and polymorphic characters. We give a polynomial-time algorithm, inspired by Fitch’s algorithm, to score trees under a family of dissimilarity metrics, and prove its correctness. We show that the resulting optimality criteria is computationally hard, by reduction to the NP-hardness of the maximum parsimony optimality criteria. We demonstrate our approach using synthetic and empirical data sets and compare the results with other recently proposed methods for choosing optimal phylogenetic trees when the data includes hierarchical characters. [Character optimization, dissimilarity metrics, hierarchical characters, inapplicable data, phylogenetic tree search.]
Bladder Cancer Immunotherapy by BCG is associated with a significantly reduced risk of Alzheimer‘s disease
Authors: Klinger Danielle , Hill Brian L. , Barda Noam , Halperin Eran , Gofrit Ofer N. , Greenblatt Charles L. , Rappoport Nadav , Linial Michal , Bercovier Hervé 
Published: February 2021

ABSTRACTIMPORTANCEDespite years of investigation and billions of dollars, there is no cure or even a disease-slowing remedy for Alzheimer’s disease (AD). Most studies thus far have focused on amyloid beta plaques (Aβ) and neurofibrillary tangles as therapeutic targets, and only a few on modulating the associated inflammatory process.OBJECTIVETo determine if exposure to Bacillus Calmette–Guérin (BCG) during treatment of non-muscle-invasive bladder cancer (NMIBC) is associated with a lower risk of developing AD.DESIGN, SETTING AND PARTICIPANTSMulticenter retrospective study of 12,185 bladder cancer patients including 2301 BCG-treated patients between 2000 and 2019 meeting all inclusion criteria. Data was retrieved from two tertiary hospital systems in Israel and the United States, and the largest Israeli health provider database, with a median follow up of 3.5 to 7 years.MAIN OUTCOMES AND MEASURESThe primary outcome was time to the first occurrence of AD/Dementia events following a diagnosis of bladder cancer by trans-urethral resection (TURBT) in BCG treated patients, and in bladder cancer patients not receiving BCG (control group).RESULTSBCG treatment was associated with a significantly reduced risk of developing AD in bladder cancer patients of ≥75 years following BCG treatment. A competing risk model using Cox Proportional-Hazard (PH) analysis applied to the largest medical records data showed a Hazard Ratio (HR) of 0.726 (95% CI: 0.529 – 0.996, P = 0.0473). The results were duplicated in analyzing NMIBC patients from a tertiary hospital with a HR of 0.416 (95% CI: 0.203 – 0.853, P = 0.017). A reduction in the risk (by 28%) for developing Parkinson’s disease (PD) was also shown in bladder cancer patients subjected to BCG immunotherapy.CONCLUSIONS AND RELEVANCEBCG treatment for bladder cancer patients was associated with a significantly reduced risk for developing AD and PD in the elderly population (>75 years), and in NMIBC patients from a tertiary hospital. Prospective studies in elderly inoculated with intradermic BCG should be initiated to evaluate the potential protective effect of BCG against AD and PD.KEY POINTSQuestionWhether bladder cancer patients treated with BCG immunotherapy have a lower risk to develop AD than bladder cancer patients that do not receive such treatment.FindingsIn a multicenter retrospective study composed of three cohorts covering >12,000 bladder cancer patients, those receiving intravesical BCG immunotherapy had a significantly lower risk of developing AD.MeaningIntradermal inoculation of BCG to elderly people should be tested as a potential preventive approach against AD.