bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal and Chemical Evolution of an Archean Collision Zone: Insights from P–T–t History of Mafic Granulites from the Coorg Block, S. India
Authors: Basak Sampriti , Hasenstab Eric , Bhowmik Santanu Kumar , Gerdes Axel , Dasgupta Somnath , Münker Carsten , Kumar Gr. Ravindra , Chakraborty Sumit 
Published: April 2023

Abstract
Knowledge of pressure–temperature–time (P–T–t) evolution of Archean high-grade (deep crustal) metamorphic rocks is important for deciphering the nature of Archean tectonic processes. However, exposures of such rocks are limited in the present rock record. Here, we study a suite of high-grade, mafic rocks that are present along a crustal-scale shear zone (called the Mercara Shear Zone) between two Archean terrains of India, the Coorg block and the Dharwar Craton. Given that the Mercara Shear Zone is dated to be Mesoarchean, these shear zone rocks are well suited to elucidate Archean orogenic processes. Petrological investigation shows that these mafic rocks are characterized by a granulitic assemblage of orthopyroxene, clinopyroxene, plagioclase, quartz and amphibole ± garnet, and with accessory phases such as apatite, ilmenite, magnetite and rutile in some cases. We distinguish the investigated rocks into low-Mg and high-Mg varieties based on their whole-rock composition as well as their mode of occurrence in the field and mineral chemistry. This difference in the bulk composition led to different reaction histories—for example, the low-Mg mafic granulites underwent partial melting while high-Mg granulites were less fertile. Combining these observations with the results of geothermobarometry, phase equilibria modeling, geochronology (U–Pb in zircon and Lu–Hf in garnet ) and diffusion modeling, we have reconstructed a multi-stage P–T–t history for these rocks. The first phase (Stage 1) is represented by granulite-grade metamorphism at ~750–900°C and 8–13 kbar during ~3100 Ma (with uncertainties permitting a timing as recent as ~2700 Ma), after which they resided at T &lt;500°C, likely at lower crustal levels (Stage 2). Subsequently, these rocks were reheated to a T of 700–750°C at 7–10 kbar at ~2400 Ma (Stage 3) and then again cooled down to ~500–600°C at 6–8 kbar (Stage 4). Application of diffusion chronometry shows that (1) the cooling rates of these granulites at high temperatures (&gt;600°C) varied in the range of 25–50°C/Ma, and (2) the rocks resided for a long duration (~500 million years) at the Stage 2 metamorphic conditions, i.e. at T &lt;500°C. We infer that such a protracted, high-T metamorphic history involving at least two heating pulses, and the relatively slow cooling rates on the order of 10’s °C/Ma are consistent with the operation of peel-back styled orogenesis (an embryonic form of plate tectonics) on an early hotter Earth (Mesoarchean to Paleoproterozoic). Moreover, the controls of bulk rock compositions on reaction histories provide a mechanism for intracrustal differentiation and generating Mg-rich, refractory material that may have eventually formed the lower continental crust over a protracted and pulsed thermal evolution spanning several hundred million years.
ENHANCED DISEASE SUSCEPTIBILITY 1 promotes hydrogen peroxide scavenging to enhance rice thermotolerance
Authors: Liao Min , Ma Zemin , Kang Yuanrong , Zhang Biaoming , Gao Xuanlin , Yu Feng , Yang Pingfang , Ke Yinggen 
Published: April 2023

Abstract
Heat stress is a major factor limiting the production and geographic distribution of rice (Oryza sativa), and breeding rice varieties with tolerance to heat stress is of immense importance. Although extensive studies have revealed that reactive oxygen species (ROS) play a critical role in rice acclimation to heat stress, the molecular basis of rice controlling ROS homeostasis remains largely unclear. In this study, we discovered a novel heat-stress-responsive strategy that orchestrates ROS homeostasis centering on an immune activator, rice ENHANCED DISEASE SUSCEPTIBILITY 1 (OsEDS1). OsEDS1, which confers heat stress tolerance, promotes hydrogen peroxide (H2O2) scavenging by stimulating catalase activity through the OsEDS1-catalase association. The loss-of-function mutation in OsEDS1 causes increased sensitivity to heat stress, whereas the overexpression of OsEDS1 enhances thermotolerance. Furthermore, overexpression lines greatly improved rice tolerance to heat stress during the reproductive stage, which was associated with substantially increased seed setting, grain weight, and plant yield. Rice CATALASE C (OsCATC), whose activity is promoted by OsEDS1, degrades H2O2 to activate rice heat stress tolerance. Our findings greatly expand our understanding of heat stress responses in rice. We reveal a molecular framework that promotes heat tolerance through ROS homeostasis regulation, suggesting a theoretical basis and providing genetic resources for breeding heat-tolerant rice varieties.
Evolution-strengthened knowledge graph enables predicting the targetability and druggability of genes
Authors: Quan Yuan , Xiong Zhan-Kun , Zhang Ke-Xin , Zhang Qing-Ye , Zhang Wen , Zhang Hong-Yu 
Published: April 2023

Abstract
Identifying promising targets is a critical step in modern drug discovery, with causative genes of diseases that are an important source of successful targets. Previous studies have found that the pathogeneses of various diseases are closely related to the evolutionary events of organisms. Accordingly, evolutionary knowledge can facilitate the prediction of causative genes and further accelerate target identification. With the development of modern biotechnology, massive biomedical data have been accumulated, and knowledge graphs (KGs) have emerged as a powerful approach for integrating and utilizing vast amounts of data. In this study, we constructed an evolution-strengthened knowledge graph (ESKG) and validated applications of ESKG in the identification of causative genes. More importantly, we developed an ESKG-based machine learning model named GraphEvo, which can effectively predict the targetability and the druggability of genes. We further investigated the explainability of the ESKG in druggability prediction by dissecting the evolutionary hallmarks of successful targets. Our study highlights the importance of evolutionary knowledge in biomedical research and demonstrates the potential power of ESKG in promising target identification. The data set of ESKG and the code of GraphEvo can be downloaded from https://github.com/Zhankun-Xiong/GraphEvo.
Inequalities in smoking among pregnant women in North West London
Authors: Pinho-Gomes Ana-Catarina , Mullins Edward 
Published: April 2023

Abstract

Background
London has the lowest smoking prevalence among pregnant women in England. However, it was unclear whether the low overall prevalence masked inequalities. This study investigated the prevalence of smoking among pregnant women in North West London stratified by ethnicity and deprivation.

Methods
Data regarding smoking status, ethnicity and deprivation were extracted from electronic health records collected by maternity services at Imperial Healthcare NHS Trust between January 2020 and August 2022.

Results
A total of 25 231 women were included in this study. At the time of booking of antenatal care (mean of 12 weeks), 4% of women were current smokers, 17% were ex-smokers and 78% never smokers. There were marked differences in the smoking prevalence between ethnic groups. Women of Mixed—White and Black Caribbean ethnicity and White Irish women had the highest prevalence of smoking (12 and 9%, respectively). There was an over 4-fold increase in the prevalence of smoking between the most and the least deprived groups (5.6 versus 1.3%).

Conclusions
Even in a population with an overall low prevalence of smoking in pregnancy, women experiencing deprivation and from certain ethnic backgrounds have a high smoking prevalence and hence are the most likely to benefit from smoking cessation interventions.
Role of activated p21-activated kinase 2 in methylmercury-induced embryotoxic effects on mouse blastocysts
Authors: Lee Cheng-Kai , Wang Fu-Ting , Huang Chien-Hsun , Chan Wen-Hsiung 
Published: April 2023

AbstractMethylmercury (MeHg), a biotransformation product derived from mercury or inorganic mercury compounds in waterways, is a potent toxin that exerts hazardous effects on human health via environmental contamination. Previous studies have reported MeHg-induced impairment of nerve development in embryogenesis and placental development. However, the potential deleterious effects and regulatory mechanisms of action of MeHg on pre- and post-implantation embryo development are yet to be established. Experiments from the current study clearly demonstrate that MeHg exerts toxic effects on early embryonic development processes, including the zygote to blastocyst stage. Induction of apoptosis and decrease in embryo cell number were clearly detected in MeHg-treated blastocysts. Additionally, intracellular reactive oxygen species (ROS) generation and activation of caspase-3 and p21-activated protein kinase 2 (PAK2) were observed in MeHg-treated blastocysts. Importantly, prevention of ROS generation by pre-treatment with Trolox, a potent antioxidant, significantly attenuated MeHg-triggered caspase-3 and PAK2 activation as well as apoptosis. Notably, the downregulation of PAK2 via transfection of specifically targeted siRNA (siPAK2) led to marked attenuation of PAK2 activity and apoptosis and the deleterious effects of MeHg on embryonic development in blastocysts. Our findings strongly suggest that ROS serve as an important upstream regulator to trigger the activation of caspase-3, which further cleaves and activates PAK2 in MeHg-treated blastocysts. Activated PAK2 promotes apoptotic processes that, in turn, cause sequent impairment of embryonic and fetal development.
Descriptive Analysis of Documentation Time for the National Developmental-Behavioral Pediatric Physician Workforce Using a Commercial Electronic Health Record System
Authors: Patel Rohan , Yang Yumei , Lin Feng-Chang , Shumaker Amanda , Nash Patricia , Newmeyer Amy , Baum Rebecca , Hoffman Jeffrey 
Published: April 2023

Abstract:

Objective:
The national developmental-behavioral pediatric (DBP) workforce struggles to meet current service demands because of several factors. Lengthy and inefficient documentation processes are likely to contribute to service demand challenges, but DBP documentation patterns have not been sufficiently studied. Identifying clinical practice patterns may inform strategies to address documentation burden in DBP practice.

Methods:
Nearly 500 DBP physicians in the United States use a single commercial electronic health record (EHR) system (EpicCare Ambulatory, Epic Systems Corporation, Verona WI). We evaluated descriptive statistics using the US Epic DBP provider data set. We then compared DBP documentation metrics against those of pediatric primary care and selected pediatric subspecialty providers who provide similar types of care. One-way analyses of variance (ANOVAs) were conducted to determine whether outcomes differed among provider specialties.

Results:
We identified 4 groups for analysis from November 2019 through February 2020: DBP (n = 483), primary care (n = 76,423), pediatric psychiatry (n = 783), and child neurology (n = 8589). Post hoc pairwise comparisons revealed statistically significant differences between multiple outcome-specialty combinations. Time in notes per appointment and progress note length demonstrated the strongest evidence of an increased burden on DBP providers compared with other similar provider groups.

Conclusion:
DBP providers spend a significant amount of time documenting progress notes both during and outside of normal clinic hours. This preliminary analysis highlights the utility of using EHR user activity data to quantitatively measure documentation burden.
Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans
Authors: Mateza Somila , Bradford Yuki , Maartens Gary , Sokhela Simiso , Chandiwana Nomathemba C. , Venter Willem D.F. , Post Frank A. , Ritchie Marylyn D. , Haas David W. , Sinxadi Phumla 
Published: April 2023

Objective
Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans.

Methods
Genetic sub-study of adults randomized to initiate TAF or TDF together with dolutegravir and emtricitabine was conducted. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine β2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations.

Results
336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7).

Conclusion
Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.
Comparing outcomes of ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery versus laparoendoscopic single-site surgery: A retrospective cohort study
Authors: Chang Chi-Han , Ding Dah-Ching 
Published: April 2023

Background:
We aimed to compare the outcomes of ovarian cystectomy (OC) performed by vaginal natural orifice transluminal endoscopic surgery (vNOTES) vs transumbilical laparoendoscopic single-site surgery (LESS).

Methods:
We retrospectively analyzed the data of patients in our hospital who underwent OC either by vNOTES or LESS between January 2015 and September 2021. Demographic data were collected. The primary outcome was the conversion rate. The secondary outcomes were the duration of surgery, length of hospital stay, estimated blood loss, maximum body temperature within 48 hours after operation, and duration of maximum body temperature (hours), among others. Statistical analysis was done using the SPSS software.

Results:
Exactly 284 patients were screened. The vNOTES and LESS groups consisted of 21 and 47 patients, respectively. There was no significant difference in the conversion rates between the two groups (0 vs 8.5% in vNOTES and LESS, respectively; p = 0.303). Compared with the vNOTES group, the LESS group had a larger cyst diameter (6.00 ± 2.32 vs 4.69 ± 1.29 cm; p = 0.004), more endometriotic cysts (42.6% vs 9.5%; p < 0.001), and more pelvic adhesions requiring adhesiolysis (57.4% vs 19.0%; p = 0.003). At baseline, there were no other differences between the groups. The secondary outcomes included a shorter duration of surgery (70.14 ± 27.30 vs 99.57 ± 36.26 minutes; p = 0.001) and lower estimated blood loss (64.29 ± 39.19 vs 163.43 ± 251.20 mL; p = 0.011) in the vNOTES group. Regression analysis showed the diameter of the ovarian cyst correlated with surgical time. The complication was comparable between the two groups.

Conclusion:
Above all, the advantages of vNOTES include an absence of visible scars, shorter surgical duration, and less blood loss when compared with LESS. Further large-scale prospective trials should confirm the results of our study.
Simultaneous Cochlear Implantation and Salvage Translabyrinthine Resection of Vestibular Schwannoma after Radiotherapy
Authors: Choi Jonathan S. , Fritz Christian G. , Babu Kavan C. , Fan Caleb J. , Babu Seilesh C. 
Published: April 2023

Objective
To report on the novel use of simultaneous cochlear implantation (CI) during salvage translabyrinthine resection of vestibular schwannoma (VS) after failed stereotactic radiosurgery (SRS).

Patient
A 52-year-old woman presented with a medium-sized right VS. She experienced continued tumor growth despite previous SRS, resulting in medial extension beyond the internal auditory canal into the cerebellopontine angle. Associated symptoms included asymmetrical right moderate to severe sensorineural hearing loss, poor word recognition, tinnitus, and dizziness.

Intervention
Simultaneous CI with translabyrinthine VS resection.

Main outcome measure
CI-aided pure-tone averages.

Results
After 4 months of device use, CI-aided speech audiometry revealed hearing thresholds in the normal range, with a four-tone pure-tone, average of 16.3 dB. Speech perception with consonant-nucleus-consonant testing in the CI-only condition was 46%, representing a 12% improvement compared with preoperatively. Tinnitus and dizziness burden were subjectively reduced.

Conclusions
Despite challenges inherent to second procedures after radiotherapy failure, successful CI outcomes can be achieved. The current study demonstrates the feasibility of simultaneous CI during salvage VS resection after SRS. A larger study should be undertaken to further substantiate these preliminary findings.
Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
Authors: Phillips John , Mikulec Anthony A. , Robinson James M. , Skarinsky David , Anderson Jeffery J. 
Published: April 2023

Objective
To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease.

Study Designs
Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease.

Setting
The United States and throughout Europe.

Patients
Individuals with Ménière's disease aged 18 to 85 years.

Interventions
All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months.

Main Outcome Measures
The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations.

Results
Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated.

Conclusions
In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated.
(Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674).
RNF26 Promotes Pancreatic Cancer Proliferation by Enhancing RBM38 Degradation
Authors: Lu Xiangyu , Zhang Yu , Wu Yilei , Lu Tao , Yang Hongji , Yang Wenhao , Pang Beichuan , Yang Chong 
Published: April 2023

Objectives
RING finger protein 26 (RNF26) plays an essential role in determining malignant tumor growth, whereas the role of which in pancreatic cancer (PC) has not been reported. This study aimed to investigate the role of RNF26 in PC cells.

Methods
The Gene Expression Profiling Interactive Analysis was applied to study the role of RNF26 in malignant tumors. The in vitro or in vivo cell proliferation assays were used to investigate the role of RNF26 on the PC. The protein-protein interaction network analysis was used to search the binding partner of RNF26. The Western blot was used to reveal whether RNF26 promoted RNA binding motif protein-38 (RBM38) degradation in PC cells.

Results
The Gene Expression Profiling Interactive Analysis tool showed that RNF26 was overexpressed in PC. Repressing RNF26 expression decreased PC cells growth, but overexpression of RNF26 increased PC proliferation. Furthermore, we demonstrated RNF26 degraded RBM38 to promote PC cell proliferation.

Conclusions
RNF26 was abnormally increased in PC, and upregulated RNF26 was correlated with a poor prognosis. RNF26 enhanced PC proliferation by inducing RBM38 degradation. We identified a novel RNF26-RBM28 axis involved in the progression of PC.
Associations Between Iron Homeostasis and Pancreatic Enzymes After an Attack of Pancreatitis
Authors: Kimita Wandia , Ko Juyeon , Li Xinye , Bharmal Sakina H. , Petrov Maxim S. 
Published: April 2023

Objectives
Dysregulation of iron homeostasis and exocrine pancreatic dysfunction are linked but remain undefined in individuals with a history of pancreatitis. The objective is to investigate the relationship between iron homeostasis and pancreatic enzymes in individuals after a pancreatitis attack.

Methods
This was a cross-sectional study of adults with a history of pancreatitis. Markers of iron metabolism (hepcidin and ferritin) and pancreatic enzymes (pancreatic amylase, pancreatic lipase, and chymotrypsin) were measured in venous blood. Habitual dietary iron intake data (total, heme, and nonheme iron) were collected. Multivariable linear regression analyses were performed while considering covariates.

Results
One hundred and one participants were studied at a median of 18 months after their last pancreatitis attack. Hepcidin was significantly associated with pancreatic amylase (β coefficient, −6.68; 95% confidence interval, −12.88 to −0.48; P = 0.035) and heme iron intake (β coefficient, 0.34; 95% confidence interval, 0.08 to 0.60; P = 0.012) in the adjusted model. Hepcidin was not significantly associated with pancreatic lipase or chymotrypsin. Ferritin was not significantly associated with pancreatic enzymes and dietary iron intake.

Conclusions
An iron homeostasis–exocrine pancreas crosstalk exists in individuals after an attack of pancreatitis. The role of iron homeostasis in pancreatitis warrants high-quality purposely-designed studies.