bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-species functional compatibility of the Theobroma cacao and Arabidopsis FT orthologs: 90 million years of functional conservation of meristem identity genes
Authors: Prewitt S. F. , Shalit-Kaneh A. , Maximova S. N. , Guiltinan M. J. 
Published: May 2021

AbstractBackgroundIn angiosperms the transition to flowering is controlled by a complex set of interacting networks integrating a range of developmental, physiological, and environmental factors optimizing transition time for maximal reproductive efficiency. The molecular mechanisms comprising these networks have been partially characterized and include both transcriptional and post-transcriptional regulatory pathways. Florigen, encoded byFLOWERING LOCUS T(FT) orthologs, is a conserved central integrator of several flowering time regulatory pathways. To characterize the molecular mechanisms involved in controlling cacao flowering time, we have characterized a cacao candidate florigen gene,TcFLOWERING LOCUS T(TcFT). Understanding how this conserved flowering time regulator affects cacao plant’s transition to flowering could lead to strategies to accelerate cacao breeding.ResultsBLAST searches of cacao genome reference assemblies identified seven candidate members of theCENTRORADIALIS/TERMINAL FLOWER1/SELF PRUNINGgene family including a single florigen candidate. cDNA encoding the predicted cacao florigen was cloned and functionally tested by transgenic genetic complementation in the Arabidopsisft-10mutant. Transgenic expression of the candidateTcFTcDNA in late flowering Arabidopsisft-10partially rescues the mutant to wild-type flowering time. Gene expression studies reveal thatTcFTis spatially and temporally expressed in a manner similar to that found in Arabidopsis, specifically,TcFTmRNA is shown to be both developmentally and diurnally regulated in leaves and is most abundant in floral tissues. Finally, to test interspecies compatibility of florigens, we transformed cacao tissues withAtFTresulting in the remarkable formation of flowers in tissue culture. The morphology of these in vitro flowers is normal, and they produce pollen that germinates in vitro with high rates.ConclusionWe have identified the cacaoCETSgene family, central to developmental regulation in angiosperms. The role of the cacao’s singleFT-like gene (TcFT) as a general regulator of determinate growth in cacao was demonstrated by functional complementation of Arabidopsisft-10late-flowering mutant and through gene expression analysis. In addition, overexpression ofAtFTin cacao resulted in precocious flowering in cacao tissue culture demonstrating the highly conserved function ofFTand the mechanisms controlling flowering in cacao.
Combining targeted metabolite analyses and transcriptomics to reveal the specific chemical composition and associated genes in the incompatible soybean variety PI437654 infected with soybean cyst nematode HG1.2.3.5.7
Authors: Shi Xue , Chen Qiansi , Liu Shiming , Wang Jiajun , Peng Deliang , Kong Lingan 
Published: May 2021

Abstract
Background
Soybean cyst nematode, Heterodera glycines, is one of the most devastating pathogens of soybean and causes severe annual yield losses worldwide. Different soybean varieties exhibit different responses to H. glycines infection at various levels, such as the genomic, transcriptional, proteomic and metabolomic levels. However, there have not yet been any reports of the differential responses of incompatible and compatible soybean varieties infected with H. glycines based on combined metabolomic and transcriptomic analyses.

Results
In this study, the incompatible soybean variety PI437654 and three compatible soybean varieties, Williams 82, Zhonghuang 13 and Hefeng 47, were used to clarify the differences in metabolites and transcriptomics before and after the infection with HG1.2.3.5.7. A local metabolite-calibrated database was used to identify potentially differential metabolites, and the differences in metabolites and metabolic pathways were compared between the incompatible and compatible soybean varieties after inoculation with HG1.2.3.5.7. In total, 37 differential metabolites and 20 KEGG metabolic pathways were identified, which were divided into three categories: metabolites/pathways overlapped in the incompatible and compatible soybeans, and metabolites/pathways specific to either the incompatible or compatible soybean varieties. Twelve differential metabolites were found to be involved in predicted KEGG metabolite pathways. Moreover, 14 specific differential metabolites (such as significantly up-regulated nicotine and down-regulated D-aspartic acid) and their associated KEGG pathways (such as the tropane, piperidine and pyridine alkaloid biosynthesis, alanine, aspartate and glutamate metabolism, sphingolipid metabolism and arginine biosynthesis) were significantly altered and abundantly enriched in the incompatible soybean variety PI437654, and likely played pivotal roles in defending against HG1.2.3.5.7 infection. Three key metabolites (N-acetyltranexamic acid, nicotine and D,L-tryptophan) found to be significantly up-regulated in the incompatible soybean variety PI437654 infected by HG1.2.3.5.7 were classified into two types and used for combined analyses with the transcriptomic expression profiling. Associated genes were predicted, along with the likely corresponding biological processes, cellular components, molecular functions and pathways.

Conclusions
Our results not only identified potential novel metabolites and associated genes involved in the incompatible response of PI437654 to soybean cyst nematode HG1.2.3.5.7, but also provided new insights into the interactions between soybeans and soybean cyst nematodes.
Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis
Authors: Chen Yaw-Sen , Hsieh Pei-Min , Lin Hung-Yu , Hung Chao-Ming , Lo Gin-Ho , Hsu Yao-Chun , Lu I.-Cheng , Lee Chih-Yuan , Wu Tsung-Chin , Yeh Jen-Hao , Hsiao Pojen , Li Yu-Chan , Wang Ya-Chin , Hsieh Kun-Chou , Lin Chih-Wen 
Published: May 2021

Abstract
Background
The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.

Methods
Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.

Results

In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.

Conclusions
SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.
Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real-world study
Authors: Jeong Su Jin , Lee Seung Eun , Shin Dong Hyun , Park Ie Byung , Lee Hui Seung , Kim Kyoung-Ah 
Published: May 2021

Abstract
Background
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice.

Methods
A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60–89; G3ab, 30–59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30–300; A3, > 300 mg/g) were used to define CKD status.

Results
Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %).
Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation.

Conclusions
Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.
The association between ambient air pollution and birth defects in five major ethnic groups in Liuzhou, China
Authors: Huang Xiaoli , Chen Jichang , Zeng Dingyuan , Lin Zhong , Herbert Carly , Cottrell Lesley , Liu Liu , Ash Arlene , Wang Bo 
Published: May 2021

Abstract
Background
Studies suggest that exposure to ambient air pollution during pregnancy may be associated with increased risks of birth defects (BDs), but conclusions have been inconsistent. This study describes the ethnic distribution of major BDs and examines the relationship between air pollution and BDs among different ethnic groups in Liuzhou city, China.

Methods
Surveillance data of infants born in 114 registered hospitals in Liuzhou in 2019 were analyzed to determine the epidemiology of BDs across five major ethnic groups.
Concentrations of six air pollutants (PM2.5, PM10, SO2, CO, NO2, O3) were obtained from the Liuzhou Environmental Protection Bureau. Logistic regression was used to examine the associations between ambient air pollution exposure and risk of BDs.

Results
Among 32,549 infants, 635 infants had BDs, yielding a prevalence of 19.5 per 1000 perinatal infants. Dong ethnic group had the highest prevalence of BDs (2.59%), followed by Yao (2.57%), Miao (2.35%), Zhuang (2.07%), and Han (1.75%). Relative to the Han ethnic group, infants from Zhuang, Miao, Yao and Dong groups had lower risks of congenital heart disease, polydactyly, and hypospadias. The Zhuang ethnic group had higher risks of severe thalassemia, cleft lip and/or palate, and syndactyls. Overall BDs were positively correlated with air pollutants PM10 (aOR =1.14, 95% CI:1.12 ~ 2.43; aOR =1.51, 95% CI:1.13 ~ 2.03 for per 10μg/mg3 increment) and CO (aOR =1.36, 95% CI:1.14 ~ 2.48; aOR =1.75, 95% CI:1.02 ~ 3.61 for every 1 mg /m3 increment) in second and third month of pregnancy. SO2 was also significantly associated with BDs in the second month before the pregnancy (aOR = 1.31; 95% CI: 1.20 ~ 3.22) and third month of pregnancy (aOR =1.75; 95% CI:1.02 ~ 3.61). Congenital heart disease, polydactyl, cleft lip and/or palate were also significantly associated with PM10, SO2 and CO exposures. However, no significant association was found between birth defects and O3, PM2.5 and NO2 exposures (P > 0.05).

Conclusion
This study provides a comprehensive description of ethnic differences in BDs in Southwest China and broadens the evidence of the association between air pollution exposure during gestation and BDs.
Osteitis Fibrosa Cystica and pathological fractures—the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report
Authors: Vanitcharoenkul Ekasame , Singsampun Nontouch , Unnanuntana Aasis , Sirinvaravong Sirinart 
Published: May 2021

Abstract
Background
Osteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT.

Case presentation
A 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6–10.0] mg/dl), low serum phosphate (2.2 [2.5–4.5] mg/dL), high serum alkaline phosphatase (1482 [35–105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15–65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device.

Conclusions
PHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.
Newly designed solid coupling medium for reducing trapped air pockets during extracorporeal shock wave lithotripsy_ a phantom study
Authors: Wang Chien-Sheng , Li Ching-Chia , Wu Wen-Jeng , Liou Wen-Chin , Lin Yusen Eason , Chen Wei-Chuan 
Published: May 2021

Abstract
Introduction
Air pockets between the lithotripter head and body surface are almost inevitably generated when applying a handful of gel onto the contact portion of the treatment head and that on the patient’s skin during coupling procedure. These air pockets can compromise the transmission of acoustic energy of shock wave and may significantly affect efficacy of stone disintegration. Comparing to conventional gel, this study aims to investigate efficacy of stone disintegration by using a proprietary isolation-coupling pad (“icPad”) as the coupling medium to reduce trapped air pockets during ESWL procedure.

Method
In this phantom study, Dornier lithotripter (Delta-2 RC, Dornier MedTech Europe GmbH Co., Germany) was used with a proprietary gel pads (icPad, Diameter = 150 mm, Thickness = 4 mm and 8 mm). The lithotripter was equipped with inline camera to observe the trapped air pockets between the contact surface of the lithotripter head. A testing and measuring device were used to observe experimental stone disintegration using icPad and semi-liquid gel. The conventional semi-liquid gel was used as control for result comparison.

Results
The stone disintegration rate of icPad 4 mm and 8 mm after 200 shocks of energy at level 2 were significantly higher than that of the semi-liquid gel (disintegration rate 92.3%, 85.0% vs. 45.5%, respectively, p < 0.001). The number of shocks for complete stone disintegration by icPad of 4 mm and 8 mm at the same energy level 2 were significantly lower than that of the semi-liquid gel (the number of shocks 242.0 ± 13.8, 248.7 ± 6.3 vs. 351.0 ± 54.6, respectively, p = 0.011). Furthermore, quantitative comparison of observed air pockets under Optical Coupling Control (OCC) system showed that the area of air pockets in semi-liquid group was significantly larger than that of the group using icPad (8 mm) and that of the group using icPad (8 mm) after sliding (332.7 ± 91.2 vs. 50.3 ± 31.9, 120.3 ± 21.5, respectively, p < 0.05).

Conclusion
The advantages of icPad includes: (1) reduced the numbers of shock wave and increased stone disintegration rate due to icPad’s superior efficacy; (2) significantly reduce trapped air pockets in ESWL coupling. Due to the study limitation, more data are needed to confirm our observations before human trials.
A qualitative study on continuous deep sedation until death as an alternative to assisted suicide in Switzerland
Authors: Tomczyk Martyna , Dieudonné-Rahm Nathalie , Jox Ralf J. 
Published: May 2021

Abstract
Background
According to the European Association for Palliative Care, decisions regarding palliative sedation should not be made in response to requests for assisted dying, such as euthanasia or assisted suicide. However, several studies show that continuous deep sedation until death (CDSUD) – a particular form of sedation – has been considered as an alternative to these practices in some countries. In Switzerland, where assisted suicide is decriminalized and CDSUD is not legally regulated, no studies have comprehensively investigated their relation. Our study aimed to identify and describe the experience among palliative care physicians of CDSUD as a potential alternative to assisted suicide in the French-speaking part of Switzerland.

Methods
We performed an exploratory multicentre qualitative study based on interviews with palliative care physicians in the French-speaking part of Switzerland and conducted linguistic and thematic analysis of all interview transcripts. The study is described in accordance with COREQ guidelines.

Results
We included 10 interviews conducted in four palliative care units. Our linguistic analysis shows four main types of sedation, which we called ‘rapid CDSUD’, ‘gradual CDSUD’, ‘temporary sedation’ and ‘intermittent sedation’. CDSUD (rapid or gradual) was not considered an alternative to assisted suicide, even if a single situation has been reported. In contrast, ‘temporary’ or ‘intermittent sedation’, although not medically indicated, was sometimes introduced in response to a request for assisted suicide. This was the fact when there were barriers to an assisted suicide at home (e.g., when transfer home was impossible or the patient wished not to burden the family).

Conclusion
These preliminary results can guide clinical, ethical, linguistic and legal reflection in this field and be used to explore this question more deeply at the national and international levels in a comparative, interdisciplinary and multiprofessional approach. They can also be useful to update Swiss clinical guidelines on palliative sedation in order to include specific frameworks on various sedation protocols and sedation as an alternative to assisted suicide. Potential negative impacts of considering palliative sedation as an alternative to assisted suicide should be nuanced by open and honest societal debate.
Effectiveness of self-managed continuous monitoring for maintaining high-quality early essential newborn care compared to supervision visit in Lao PDR: a cluster randomised controlled trial
Authors: Horiuchi Sayaka , Rattana Sommana , Saysanasongkham Bounnack , Kounnavongsa Outhevanh , Kubota Shogo , Inoue Mariko , Yamaoka Kazue 
Published: May 2021

Abstract
Background
Thousands of neonatal deaths are expected to be averted by introducing the Early Essential Newborn Care (EENC) in the Western Pacific Region. In Lao People’s Democratic Republic (Lao PDR), the government adopted the EENC programme and expanded it to district hospitals. With the expansion, maintaining the quality of EENC has become difficult for the government.

Methods
A cluster randomised controlled trial with four strata based on province and history of EENC coaching was implemented to evaluate the effectiveness of self-managed continuous monitoring compared with supervisory visit in Lao PDR between 20 July 2017 and 2 April 2019. Health workers who were routinely involved in maternity care were recruited from 15 district hospitals in Huaphanh (HP) and Xiangkhouang (XK) provinces. The primary endpoint was the score on the determinants of EENC performance measured by the Theory of Planned Behaviour (TPB). Secondary endpoints were set as the knowledge and skill scores. A linear mixed-effects model was applied to test the effects of intervention over time on the endpoints.

Results
Among 198 recruited health workers, 46 (23.2%) did not complete the final evaluation. TPB scores were 180.9 [Standard Deviation: SD 38.6] and 182.5 [SD 37.7] at baseline and 192.3 [SD 30.1] and 192.3 [SD 28.4] at the final evaluation in the intervention and control groups, respectively. There was no significant difference in changes between the groups in the adjusted model (2.4, p = 0.650). Interviews with participants revealed that district hospitals in HP regularly conducted peer reviews and feedback meetings, while few hospitals did in XK. Accordingly, in stratified analyses, the TPB score in the intervention group significantly increased in HP (15.5, p = 0.017) but largely declined in XK (− 17.7, p = 0.047) compared to the control group after adjusting for covariates. Skill scores declined sharper in the intervention group in XK (− 8.78, p = 0.026), particularly in the practice of managing nonbreathing babies.

Conclusions
The study indicates that self-managed continuous monitoring is effective in improving behaviour among district health workers; however, additional measures are necessary to support its proper implementation. To maintain resuscitation skills, repeated practice is necessary.

Trial registration
This trial was registered at UMIN Clinical Trials Registry on 15/6/2017. Registration number is UMIN000027794.