bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience
Authors: Diarra Ava , Duployez Nicolas , Fournier Elise , Preudhomme Claude , Coiteux Valérie , Magro Leonardo , Quesnel Bruno , Heiblig Maël , Sujobert Pierre , Barraco Fiorenza , Balsat Marie , Scanvion Quentin , Hachulla Eric , Launay David , Yakoub-Agha Ibrahim , Terriou, Louis 
Published: October 2021

Abstract
The recently described vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by somatic mutations in UBA1. Patients with VEXAS syndrome display late-onset autoinflammatory symptoms, usually refractory to treatment, and hematologic abnormalities. The identification of an easily-accessible specific marker (UBA1 mutations) is of particular interest as it allows the convergence of various inflammatory and hematological symptoms in a unique clinico-biological entity and gives the opportunity to design specific treatment strategies. Here we retrospectively identified 6 patients with VEXAS syndrome who underwent allogeneic hematopoietic stem cell transplantation (ASCT). To date, no treatment guidelines have been validated. In 4 patients, ASCT was guided by life-threatening autoinflammatory symptoms that were refractory to multiple therapies. Three patients are in durable complete remission 32, 38, and 37 months after ASCT. Two others are in complete remission response after 3 and 5 months. One unfortunately died post-ASCT. This report suggests that ASCT could be a curative option in patients with VEXAS syndrome and severe manifestations. Considering the complications and side effects of the procedure as well as the existence of other potential treatment, clinical trials are needed to define the subgroup of patients who will benefit from this strategy and its place in the therapeutic arsenal against VEXAS syndrome.
Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways
Authors: Witte Hanno M. , Künstner Axel , Hertel Nadine , Bernd Heinz-Wolfram , Bernard Veronica , Stölting Stephanie , Merz Hartmut , von Bubnoff Nikolas , Busch Hauke , Feller Alfred C. , Gebauer Niklas 
Published: October 2021

AbstractPlasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype–phenotype correlation in Epstein-Barr virus–positive (EBV+) and EBV– PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-κB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6/JAK/STAT signaling, NF-κB activity, and MYC signaling. Moreover, class I major histocompatibility complex–mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase/AKT/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV– PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas.
Modeling of radial variations of wood properties in naturally regenerated trees of Betula platyphylla grown in Selenge, Mongolia
Authors: Erdene-Ochir Togtokhbayar , Ishiguri Futoshi , Nezu Ikumi , Tumenjargal Bayasaa , Baasan Bayartsetseg , Chultem Ganbaatar , Ohshima Jyunichi , Yokota Shinso 
Published: October 2021

AbstractWood properties, such as annual ring width, wood fiber length, vessel element length, basic density, air-dry density, dynamic Young’s modulus, modulus of elasticity (MOE), modulus of rupture (MOR), absorbed energy in impact bending, compressive strength parallel to grain, and shearing strength, were investigated for wood from 10 naturally regenerated trees of Betula platyphylla Sukaczev in Mandal, Selenge, Mongolia. Mixed-effects models were used to evaluate the radial variations in the wood properties. The mean values of wood properties obtained in the present study were in almost the same range, with a few exceptions, as those reported by other researchers for other Betula species. The radial variations of wood properties in B. platyphylla were well-fitted to a nonlinear mixed-effects model (logarithmic formula); all examined wood properties increased from the pith and then became constant toward the bark side. The wood properties significantly differed between the core and outer wood. Basic density, air-dry density, and dynamic Young’s modulus were significantly correlated with MOE, MOR, and compressive strength. It is concluded that when the wood of B. platyphylla is utilized as raw materials for solid wood products, the differences between the core wood and outer wood should be considered. In addition, the selection of wood with higher strength properties can be achieved using the wood density and dynamic Young’s modulus as indicators.
Extracellular matrix alterations in the skin of patients affected by psoriasis
Authors: Wagner Mariana Fatima Muaccad Gama , Theodoro Thérèse Rachell , Filho Carlos D’. Apparecida Santos Machad , Oyafuso Luiza Keiko Matsuka , Pinhal Maria Aparecida Silva 
Published: October 2021

Abstract
Background
Psoriasis is a chronic inflammatory disease dependent upon a complex interaction between genetic predisposition and immunological factors. It is characterized by skin lesions throughout the body, causing great morbidity and affecting life quality. The present study aimed to evaluate the protein and mRNA expression of heparanase-1 (HPSE), heparanase-2 (HPSE2), syndecan-1 (SYND1), metalloproteinases (MMP2, MMP9), and tissue inhibitor metalloproteinases 2 (TIMP2) in skin samples.

Methods
From each psoriasis patient, two samples were collected, one sample from a psoriasis plaque (n = 23) and the other sample from non-affected skin (n = 23), as well as tissue collected by blepharoplasty from control individuals (n = 18). Protein expression was investigated by immunohistochemistry, followed by digital quantification. Quantitative RT-PCR obtained mRNA expression. Statistical analyses were done, and p values < 0.05 were considered significant.

Results
A significant increase in protein and mRNA expression was observed in both heparanases (HPSE and HPSE2), and higher protein levels of MMP9 and TIMP2 were observed in the psoriasis plaque compared to the non-affected skin. The data point to a probable activation of MMP2 by TIMP2. Moreover, there was a significant increase in HPSE2, SYND1, MMP9, and TIMP2 in non-affected skin samples from patients with psoriasis than in the control sample (tissue obtained by individuals who do not have psoriasis).

Conclusions
These results show a possible correlation between the characteristic inflammatory process and alterations in the expression of the extracellular matrix in psoriasis. The increased expression of HPSE2, SYND1, MMP9, and TIMP2, even in the absence of psoriatic plaque, indicates that these molecules may be involved with extracellular matrix changes in the initial alterations the psoriatic process and may be candidates for the development of target treatments.
Genome-wide association study uncovers major genetic loci associated with seed flooding tolerance in soybean
Authors: Sharmin Ripa Akter , Karikari Benjamin , Chang Fangguo , Al Amin G.M. , Bhuiyan Mashiur Rahman , Hina Aiman , Lv Wenhuan , Chunting Zhang , Begum Naheeda , Zhao Tuanjie 
Published: October 2021

Abstract
Background
Seed flooding stress is one of the threatening environmental stressors that adversely limits soybean at the germination stage across the globe. The knowledge on the genetic basis underlying seed-flooding tolerance is limited. Therefore, we performed a genome-wide association study (GWAS) using 34,718 single nucleotide polymorphism (SNPs) in a panel of 243 worldwide soybean collections to identify genetic loci linked to soybean seed flooding tolerance at the germination stage.

Results
In the present study, GWAS was performed with two contrasting models, Mixed Linear Model (MLM) and Multi-Locus Random-SNP-Effect Mixed Linear Model (mrMLM) to identify significant SNPs associated with electrical conductivity (EC), germination rate (GR), shoot length (ShL), and root length (RL) traits at germination stage in soybean. With MLM, a total of 20, 40, 4, and 9 SNPs associated with EC, GR, ShL and RL, respectively, whereas in the same order mrMLM detected 27, 17, 13, and 18 SNPs. Among these SNPs, two major SNPs, Gm_08_11971416, and Gm_08_46239716 were found to be consistently connected with seed-flooding tolerance related traits, namely EC and GR across two environments. We also detected two SNPs, Gm_05_1000479 and Gm_01_53535790 linked to ShL and RL, respectively. Based on Gene Ontology enrichment analysis, gene functional annotations, and protein-protein interaction network analysis, we predicted eight candidate genes and three hub genes within the regions of the four SNPs with Cis-elements in promoter regions which may be involved in seed-flooding tolerance in soybeans and these warrant further screening and functional validation.

Conclusions
Our findings demonstrate that GWAS based on high-density SNP markers is an efficient approach to dissect the genetic basis of complex traits and identify candidate genes in soybean. The trait associated SNPs could be used for genetic improvement in soybean breeding programs. The candidate genes could help researchers better understand the molecular mechanisms underlying seed-flooding stress tolerance in soybean.
Acute stroke treatment and outcome in the oldest old (90 years and older) at a tertiary care medical centre in Germany-a retrospective study showing safety and efficacy in this particular patient population
Authors: Kauffmann Jil , Grün Daniel , Yilmaz Umut , Wagenpfeil Gudrun , Faßbender Klaus , Fousse Mathias , Unger Marcus M. 
Published: October 2021

Abstract
Background
Stroke is among the most common causes of death and disability worldwide. Despite the relevance of stroke-related disease burden, which is constantly increasing due to the demographic change in industrialized countries with an ageing population and consecutively an increase in age-associated diseases, there is sparse evidence concerning acute stroke treatment and treatment-related outcome in the elderly patient group. This retrospective study aimed at analysing patient characteristics, therapy-related complications and functional outcome in stroke patients aged 90 years or older who underwent acute stroke treatment (i.e. intravenous thrombolysis, mechanical thrombectomy, or both).

Methods
We identified files of all inpatient stays at the Department of Neurology at Saarland University Medical Center (tertiary care level with a comprehensive stroke unit) between June 2011 and December 2018 and filtered for subjects aged 90 years or older at the time of admission. We reviewed patient files for demographic data, symptoms upon admission, (main) diagnoses, comorbidities, and administered therapies. For patients admitted due to acute stroke we reviewed files for therapy-related complications and functional outcome. We compared the modified Rankin scale (mRS) scores upon admission and at discharge for these patients.

Results
We identified 566 inpatient stays of subjects aged 90 years or older. Three hundred sixty-seven of the 566 patients (64.8%) were admitted and discharged due to symptoms indicative of stroke. Two hundred eleven patients received a diagnosis of ischaemic stroke. These 211 patients were analysed subsequently. Sixty-four patients qualified for acute stroke treatment (intravenous thrombolysis n = 22, mechanical thrombectomy n = 26, intravenous thrombolysis followed by mechanical thrombectomy n = 16) and showed a significant improvement in their functional status as measured by change in mRS score (admission vs. discharge, p 0.001) with 7 (10.9%) observed potentially therapy-related complications (relevant drop in haemoglobin n = 2, subarachnoidal haemorrhage n = 1, cerebral haemorrhage n = 3, extracranial bleeding n = 1). One intravenous thrombolysis was stopped because of an uncontrollable hypertensive crisis. Patients who did not qualify for these treatments (including those declining acute treatment) did not show a change of their functional status between admission and discharge (p 0.064).

Conclusion
Our data indicate that acute stroke treatment is effective and safe in the oldest old. Age alone is no criterion to withhold an acute intervention even in oldest old stroke patients.
Comparison of clinical manifestation of dengue fever in Bangladesh: an observation over a decade
Authors: Hasan Mohammad Jahid , Tabassum Tamanna , Sharif Mohiuddin , Khan Md. Abdullah Saeed , Bipasha Akhi Roy , Basher Ariful , Islam Mohammad Rafiqul , Amin Mohammad Robed 
Published: October 2021

AbstractBackgroundThe clinical presentation of dengue fever had been observed to change with time since its first outbreak in 2000 in Bangladesh. This report showed the clinical presentation of the 2019 outbreak in Bangladesh along with its comparison to previous outbreaks witnessed in this region.MethodsThis hospital-based cross-sectional study was conducted in one of the largest tertiary care hospitals in Dhaka city. A total of 553 laboratory-confirmed and 194 probable dengue cases were interviewed. The clinical manifestation of the confirmed cases of the current outbreak was compared with three of the outbreak reports retrieved from the databases. R version 3.6.3 was used for data analysis.ResultsAmong the confirmed cases, two-thirds were male (63.2%) and the average age was 27(± 11) years. Positive tests for NS1 and IgM were present in 99.6% (n = 525/527) and 82.6% (n = 38/46) of the cases, respectively. Thrombocytopenia was present in 66.1% of cases. Fever (100%) was common for all. Gastrointestinal (GIT) features, including abdominal pain (86.5%), anorexia and/or vomiting (69.6%), and Diarrhea (> 3 motions/day) (26.2%) were more frequent than typical rash and other pain symptoms. Hypotension was present in approximately a quarter of patients (25%). GIT features (anorexia, nausea, and/or vomiting) and hypotension were more common among adult participants while bleeding manifestation (melena and vaginal bleeding, p = 0.009 & 0.032) was more frequent in pediatric patients. Compared to outbreaks of 2008, 2016, and 2018, increasing trends in GIT symptoms e.g. anorexia, abdominal pain, and diarrhea were observed. While a negative trend in hemorrhagic manifestations (skin rash, melena, and conjunctival hemorrhage/hemorrhagic sclera) and arthralgia/joint pain were found.ConclusionThe present outbreak was noticeably characterized by GIT symptoms and hypotension in addition to the typical clinical features like rash and pain symptoms. An increasing trend in GIT features and decreasing trend in hemorrhagic manifestations was noted over the last decade of dengue outbreaks.
Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma – the phase III “PREVENT”- (FLOT9) trial of the AIO /CAOGI /ACO
Authors: Götze Thorsten O. , Piso Pompiliu , Lorenzen Sylvie , Bankstahl Ulli S. , Pauligk Claudia , Elshafei Moustafa , Amato Giuseppe , Reim Daniel , Bechstein Wolf O. , Königsrainer Alfred , Mönig Stefan P. , Rau Beate , Schwarzbach Matthias , Al-Batran Salah-Eddin 
Published: October 2021

Abstract
Background
The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40–50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60–70% of tumors of diffuse type, compared to only 20–30% of intestinal type.
Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction.
No results from a PCRT from the Western hemisphere have yet been published.

Methods
This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens’s classification) adenocarcinoma of the stomach and Type II/III GEJ.
All enrolled pts. will have received 3–6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk).
Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life.
The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed.
Recruitment has already started and first patient in was on January 18th, 2021.

Discussion
If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery.

Trial registration
The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352; EudraCT: 2017-003832-35.
Survival improvement and prognosis for hepatocellular carcinoma: analysis of the SEER database
Authors: Ding Jingli , Wen Zhili 
Published: October 2021

Abstract
Background
Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S. population.

Methods
The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval).
Results
A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35–0.56), hepatic resection (HR = 0.35, 95% CI: 0.33–0.37), and transplantation (HR = 0.14, 95% CI: 0.13–0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages.

Conclusions
Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.
Clinical spectrum and predictors of severity of dengue among children in 2019 outbreak: a multicenter hospital-based study in Bangladesh
Authors: Khan Md. Abdullah Saeed , Al Mosabbir Abdullah , Raheem Enayetur , Ahmed Ahsan , Rouf Rashawan Raziur , Hasan Mahmudul , Alam Fawzia Bente , Hannan Nahida , Yesmin Sabrina , Amin Robed , Ahsan Nazmul , Anwar Sayeeda , Afroza Syeda , Hossain Mohammad Sorowar 
Published: October 2021

AbstractBackgroundThe mosquito-borne arboviral disease dengue has become a global public health concern. However, very few studies have reported atypical clinical features of dengue among children. Because an understanding of various spectrums of presentation of dengue is necessary for timely diagnosis and management, we aimed to document the typical and atypical clinical features along with predictors of severity among children with dengue during the largest outbreak in Bangladesh in 2019.MethodsWe conducted a cross-sectional study between August 15 and September 30, 2019. in eight tertiary level hospitals in Dhaka city. Children (aged < 15 years) with serologically confirmed dengue were conveniently selected for data collection through a structured questionnaire. Descriptive, inferential statistics, and multivariable logistic regression were used to analyze data.ResultsAmong the 190 children (mean age 8.8 years, and male-female ratio 1.22:1) included in the analysis, respectively 71.1 and 28.9% children had non-severe and severe dengue. All children had fever with an average temperature of 103.3 ± 1.2 F (SD). Gastrointestinal symptoms were the most common associated feature, including mostly vomiting (80.4%), decreased appetite (79.5%), constipation (72.7%), and abdominal pain (64.9%). Mouth sore, a less reported feature besides constipation, was present in 28.3% of children. Atypical clinical features were mostly neurological, with confusion (21.3%) being the predominant symptom. Frequent laboratory abnormalities were thrombocytopenia (87.2%), leucopenia (40.4%), and increased hematocrit (13.4%). Age (AOR 0.86, 95%CI 0.75–0.98,p = 0.023), mouth sore (AOR 2.69, 95%CI 1.06–6.96,p = 0.038) and a decreased platelet count (< 50,000/mm3) with increased hematocrit (> 20%) (AOR 4.94, 95%CI 1.48–17.31,p = 0.01) were significant predictors of severity.ConclusionsDengue in children was characterized by a high severity, predominance of gastrointestinal symptoms, and atypical neurological presentations. Younger age, mouth sores, and a decreased platelet with increased hematocrit were significant predictors of severity. Our findings would contribute to the clinical management of dengue in children.