bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world patient characteristics and treatment patterns of polycythemia vera in Taiwan between 2016 and 2017: a nationwide cross-sectional study
Authors: Tsai Tsung-Hsien , Yu Lennex Hsueh-Lin , Yu Ming-Sun , Huang Shih-Hao , Lin Alex Jia-Hong , Lee Kuan-Der , Chen Min-Chi 
Published: June 2023

Background: Polycythemia vera (PV) patients often experience constitutional symptoms and are at risk of thromboembolism as well as disease progression to myelofibrosis or acute myeloid leukemia. Not only is PV often overlooked but treatment options are also limited, however. Objectives: To explore the patient characteristics and treatment pattern of PV patients in Taiwan, and compare with other countries reported in the literature. Design: This is a nationwide cross-sectional study. Methods: The National Health Insurance Research Database in Taiwan, which covers 99% of the population, was utilized. Patients were identified during the cross-sectional period between 2016 and 2017, and their retrospective data were retrieved from 2001 to 2017. Results: A total of 2647 PV patients were identified between 1 January 2016 and 31 December 2017. This study described the demographic information of these patients, including number of patients by risk stratification and by sex, age at diagnosis, age at cross-sectional period, rate of bone marrow aspiration/biopsy at diagnosis, comorbidities, number of postdiagnosis thrombosis, number of disease progression, and death. The mortality rate of PV patients (4.1%) over 60 of age was higher than the general population of the same age group (2.8%). This study also compared the different treatment patterns between sexes and risk groups. Hydroxyurea was deferred to an older age, but conversely was prescribed at higher dose to younger patients. Alarmingly, a high proportion of patients did not receive phlebotomy or hydroxyurea for at least 2 years. Furthermore, discrepancies in prevalence, age at diagnosis, sex ratio, incidence of thrombosis and mortality were also found when compared with data reported in other countries. Conclusion: The clinical landscape of PV in Taiwan between 2016 and 2017 was examined. Distinctive patterns of phlebotomy and hydroxyurea were identified. Overall, these findings highlight the importance of understanding the patient characteristics and treatment patterns of PV in different regions to better inform clinical practice and improve patient outcomes.
A phase 2 study of pembrolizumab after autologous stem cell transplantation in patients with T-cell non-Hodgkin lymphoma
Authors: Merrill Mwanasha H. , Dahi Parastoo B. , Redd Robert A. , McDonough Mikaela M. , Chen Yi-Bin , DeFilipp Zachariah , Herrera Alex F. , Fisher David C. , LaCasce Ann S. , Odejide Oreofe O. , Ng Samuel Y. , Jacobson Caron A. , Merryman Reid W. , Kim Austin I. , Nieto Yago L. , Sauter Craig S. , Shah Gunjan L. , Zain Jasmine M. , Armand Philippe , Jacobsen Eric D. 
Published: June 2023

Abstract
Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti–PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study’s primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997.
Arterial spin labeling MRI applied to migraine: current insights and future perspectives
Authors: Russo Antonio , Silvestro Marcello , Tessitore Alessandro , Orologio Ilaria , De Rosa Alessandro Pasquale , De Micco Rosa , Tedeschi Gioacchino , Esposito Fabrizio , Cirillo Mario 
Published: June 2023

AbstractIntroductionAdvanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes.Main bodyConverging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures.Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as “migraine generators” from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura.ConclusionAlthough ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.
A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines
Authors: Desire Suzanne , Johnsson Martin , Ros-Freixedes Roger , Chen Ching-Yi , Holl Justin W. , Herring William O. , Gorjanc Gregor , Mellanby Richard J. , Hickey John M. , Jungnickel Melissa K. 
Published: June 2023

Abstract
Background
Genome-wide association studies (GWAS) aim at identifying genomic regions involved in phenotype expression, but identifying causative variants is difficult. Pig Combined Annotation Dependent Depletion (pCADD) scores provide a measure of the predicted consequences of genetic variants. Incorporating pCADD into the GWAS pipeline may help their identification. Our objective was to identify genomic regions associated with loin depth and muscle pH, and identify regions of interest for fine-mapping and further experimental work. Genotypes for ~ 40,000 single nucleotide morphisms (SNPs) were used to perform GWAS for these two traits, using de-regressed breeding values (dEBV) for 329,964 pigs from four commercial lines. Imputed sequence data was used to identify SNPs in strong ($$\ge$$
≥
0.80) linkage disequilibrium with lead GWAS SNPs with the highest pCADD scores.

Results
Fifteen distinct regions were associated with loin depth and one with loin pH at genome-wide significance. Regions on chromosomes 1, 2, 5, 7, and 16, explained between 0.06 and 3.55% of the additive genetic variance and were strongly associated with loin depth. Only a small part of the additive genetic variance in muscle pH was attributed to SNPs. The results of our pCADD analysis suggests that high-scoring pCADD variants are enriched for missense mutations. Two close but distinct regions on SSC1 were associated with loin depth, and pCADD identified the previously identified missense variant within the MC4R gene for one of the lines. For loin pH, pCADD identified a synonymous variant in the RNF25 gene (SSC15) as the most likely candidate for the muscle pH association. The missense mutation in the PRKAG3 gene known to affect glycogen content was not prioritised by pCADD for loin pH.

Conclusions
For loin depth, we identified several strong candidate regions for further statistical fine-mapping that are supported in the literature, and two novel regions. For loin muscle pH, we identified one previously identified associated region. We found mixed evidence for the utility of pCADD as an extension of heuristic fine-mapping. The next step is to perform more sophisticated fine-mapping and expression quantitative trait loci (eQTL) analysis, and then interrogate candidate variants in vitro by perturbation-CRISPR assays.
In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function
Authors: Shinwari Khyber , Wu Yurong , Rehman Hafiz Muzzammel , Xiao Ningkun , Bolkov Mikhail , Tuzankina Irina , Chereshnev Valery 
Published: June 2023

AbstractHennekam Lymphangiectasia–Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.
Pan-genome of Citrullus genus highlights the extent of presence/absence variation during domestication and selection
Authors: Sun Yang , Kou Dou-Rong , Li Yan , Ni Jiang-Ping , Wang Jing , Zhang Yong-Mei , Wang Qing-Nan , Jiang Bin , Wang Xu , Sun Yue-Xin , Xu Xin-Tong , Tan Xiao-Juan , Zhang Yong-Jun , Kong Xiang-dong 
Published: June 2023

AbstractThe rich genetic diversity in Citrullus lanatus and the other six species in the Citrullus genus provides important sources in watermelon breeding. Here, we present the Citrullus genus pan-genome based on the 400 Citrullus genus resequencing data, showing that 477 Mb contigs and 6249 protein-coding genes were absent in the Citrullus lanatus reference genome. In the Citrullus genus pan-genome, there are a total of 8795 (30.5%) genes that exhibit presence/absence variations (PAVs). Presence/absence variation (PAV) analysis showed that a lot of gene PAV were selected during the domestication and improvement, such as 53 favorable genes and 40 unfavorable genes were identified during the C. mucosospermus to C. lanatus landrace domestication. We also identified 661 resistance gene analogs (RGAs) in the Citrullus genus pan-genome, which contains 90 RGAs (89 variable and 1 core gene) located on the pangenome additional contigs. By gene PAV-based GWAS, 8 gene presence/absence variations were found associated with flesh color. Finally, based on the results of gene PAV selection analysis between watermelon populations with different fruit colors, we identified four non-reference candidate genes associated with carotenoid accumulation, which had a significantly higher frequency in the white flesh. These results will provide an important source for watermelon breeding.
Prematurely delivering mothers show reductions of lachnospiraceae in their gut microbiomes
Authors: Yang Ru , Li Xiaoyu , Ying Zhiye , Zhao Zicheng , Wang Yinan , Wang Qingyu , Shen Bairong , Peng Wentao 
Published: June 2023

Abstract
Background
Preterm birth is the leading cause of perinatal morbidity and mortality. Despite evidence shows that imbalances in the maternal microbiome associates to the risk of preterm birth, the mechanisms underlying the association between a perturbed microbiota and preterm birth remain poorly understood.

Method
Applying shotgun metagenomic analysis on 80 gut microbiotas of 43 mothers, we analyzed the taxonomic composition and metabolic function in gut microbial communities between preterm and term mothers.

Results
Gut microbiome of mothers delivering prematurely showed decreased alpha diversity and underwent significant reorganization, especially during pregnancy. SFCA-producing microbiomes, particularly species of Lachnospiraceae, Ruminococcaceae, and Eubacteriaceae, were significantly depleted in preterm mothers. Lachnospiraceae and its species were the main bacteria contributing to species’ differences and metabolic pathways.

Conclusion
Gut microbiome of mothers delivering prematurely has altered and demonstrates the reduction of Lachnospiraceae.
Comparison of bispectral index and patient state index as measures of sedation depth during surgeries using remimazolam tosilate
Authors: Zhao Tang-yuan-meng , Chen Di , Xu Zhi-xin , Wang Huan-liang , Sun Hu 
Published: June 2023

Abstract
Background

The Bispectral Index (BIS) and the Patient State Index (PSI) are commonly used measures to assess intraoperative sedation depth. However, model differences lead to different results, which in turn interferes with clinicians’ judgment on the depth of anesthesia. Remimazolam tosilate (RT) for injection is a new benzodiazepine used in sedation. In its clinical application, there are few effective indicators for sedation depth monitoring. To close this gap, this study aims to compare BIS and PSI in measuring the sensitivity and specificity of intraoperative RT and to explore the safety of RT for intraspinal anesthesia in elderly patients.

Methods
This study included 40 patients undergoing elective electro-prostatectomy with intraspinal anesthesia, who were monitored by BIS and PSI simultaneously during operation. Remimazolam tosylate 0.1 mg/kg was intravenously administered after the intraspinal anesthesia when patients were in a completely painless status. Then BIS, PSI, the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scores and vital signs were observed and recorded per minute for 10 min. Pearson’s correlation analysis and linear regression model were used to compare BIS and PSI sedation scores, and to test their associations with the MOAA/S score, respectively. ROC curves were drawn to compare the sensitivity and specificity of BIS and PSI. Changes of vital signs were presented as mean ± standard deviation. Perioperative liver and kidney function indicators were analyzed using a paired t-test to evaluate the safety of RT for intraspinal anesthesia in the elderly patients.

Results
According to Pearson’s correlation analysis, a significant (P < 0.01) correlation between BIS and PSI was found when used to monitor intraoperative sedation of RT (r = 0.796). Significant associations between BIS and MOAA/S (r = 0.568, P < 0.01), and between PSI and MOAA/S (r = 0.390, P < 0.01) were also found. The areas under the ROC curves of BIS and PSI were 0.801 ± 0.022 and 0.734 ± 0.026, respectively, suggesting that both measures may predict patients’ state of consciousness and BIS was more accurate than PSI. Vital signs remained stable throughout the study. No abnormal changes of clinical significance were found based on laboratory test results of liver and kidney function.

Conclusion
BIS and PSI are strongly associated for monitoring the sedation of RT intraoperatively. Both methods can accurately reflect sedation depth. According to correlation analyses with MOAA/S scale and ROC curves, BIS is more accurate than PSI during such intraoperative monitoring. In addition, RT can be safely used in elderly patients under intraspinal anesthesia for supportive sedation, with stable vital signs and sound kidney and liver safety profiles.

Trial registration
http://www.chictr.org.cn (ChiCTR2100051912).
Metrics of care and cardiovascular outcomes in patients with ST-elevation myocardial infarction treated with pharmacoinvasive strategy: a decade-long network in a populous city in Brazil
Authors: De Marqui Moraes Pedro Ivo , Galhardo Attilio , Barbosa Adriano Henrique Pereira , de Sousa Jose Marconi Almeida , Alves Claudia Maria Rodrigues , Bianco Henrique Tria , dos Santos Povoa Rui Manuel , Stefanini Edson , Goncalves Iran , de Almeida Dirceu Rodrigues , Fonseca Francisco Antonio Helfenstein , de Oliveira Izar Maria Cristina , Moises Valdir Ambrosio , Lopes Renato Delascio , Carvalho Antonio Carlos , Caixeta Adriano 
Published: June 2023

Abstract
Background
Pharmacoinvasive strategy is an effective myocardial reperfusion therapy when primary percutaneous coronary intervention (p-PCI) cannot be performed in a timely manner.

Methods
Authors sought to evaluate metrics of care and cardiovascular outcomes in a decade-long registry of a pharmacoinvasive strategy network for the treatment of ST-elevation myocardial infarction (STEMI). Data from a local network including patients undergoing fibrinolysis in county hospitals and systematically transferred to the tertiary center were accessed from March 2010 to September 2020. Numerical variables were described as median and interquartile range. Area under the curve (AUC-ROC) was used to analyze the predictive value of TIMI and GRACE scores for in-hospital mortality.

Results
A total of 2,710 consecutive STEMI patients aged 59 [51–66] years, 815 women (30.1%) and 837 individuals with diabetes (30.9%) were analyzed. The time from symptom onset to first-medical-contact was 120 [60–210] minutes and the door-to-needle time was 70 [43–115] minutes. Rescue-PCI was required in 929 patients (34.3%), in whom the fibrinolytic-catheterization time was 7.2 [4.9–11.8] hours, compared to 15.7 [6.8–22,7] hours in those who had successful lytic reperfusion. All cause in-hospital mortality occurred in 151 (5.6%) patients, reinfarction in 47 (1.7%) and ischemic stroke in 33 (1.2%). Major bleeding occurred in 73 (2.7%) patients, including 19 (0.7%) cases of intracranial bleeding. C-statistic confirmed that both scores had high predictive values for in-hospital mortality, demonstrated by TIMI AUC-ROC of 0.80 [0,77–0.84] and GRACE AUC-ROC of 0.86 [0.83—0.89].

Conclusion
In a real world registry of a decade-long network for the treatment of ST-elevation myocardial infarction based on the pharmacoinvasive strategy, low rates of in-hospital mortality and cardiovascular outcomes were observed, despite prolonged time metrics for both fibrinolytic therapy and rescue-PCI. Register Clinicaltrials.gov NCT02090712 date of first registration 18/03/2014.
Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study
Authors: Cho Heejin , Lee Yun Bin , Ha Yeonjung , Chon Young Eun , Kim Mi Na , Lee Joo Ho , Park Hana , Rim Kyu Sung , Hwang Seong Gyu 
Published: June 2023

Abstract
Background/Aims
Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients.

Methods
This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline.

Results
A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5–55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P < 0.001). At week 96, virological and biochemical responses were achieved in 34 (94.4%) patients and 20 (76.9%) patients, respectively. Moreover, 21 of 36 (58.3%) patients showed a significant decline in LS value. A higher baseline LS value was a single independent predictor for the reduction in LS value at week 96 from baseline (P < 0.001).

Conclusions
During the 144-week TDF therapy, LS values declined significantly in treatment-naïve CHB patients.
Reply to: “The partner-an underutilized facilitator to support healthy gestational weight gain”
Authors: Escañuela Sánchez Tamara , Meaney Sarah , O’Donoghue Keelin , Byrne Molly , Matvienko-Sikar Karen 
Published: June 2023

AbstractFacilitators and barriers influencing weight management behaviours were identified in our meta-synthesis of qualitative research entitled “Facilitators and barriers influencing weight management behaviours during pregnancy: a meta-synthesis of qualitative research”. This manuscript is in response to the letter submitted by Sparks et al. regarding that work. The authors highlight the importance of including partners into intervention design when addressing weight management behaviours. We agree with the authors that it is important to include partners into intervention design and further research is granted to identify facilitators and barriers affecting their influence over women. As per our findings, the influence of the social context goes beyond the partner and we suggest that future interventions should address other relevant people in women’s contexts such as parents, other relatives, and close friends.