bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Comparison of 3-Factor Prothrombin Complex Concentrate Products for Warfarin Reversal
Authors: Jones G. Morgan , Cave Brandon , Cook Ryan 
Published: March 2020

Background and Purpose: Current guidelines suggest that 3-factor prothrombin complex concentrate is a possible alternative to 4-factor products for the emergent reversal of bleeding secondary to warfarin. While multiple observational studies have evaluated various forms of 3-factor prothrombin complex concentrate individually, no study has compared the efficacy of the 2 products. The purpose of this study is to compare the efficacy and safety of Bebulin™ and Profilnine™ for the emergent reversal of warfarin-associated major bleeding. Methods: We conducted a retrospective cohort study of patients receiving both Bebulin™ and Profilnine™ at an urban, academic medical center with comprehensive stroke center designation and a neurosurgical center of excellence. All patients were treated at a single center that utilized a fixed, weight-based dosing protocol. The primary outcome was the percentage of patients in each group achieving a goal international normalization ratio of 1.4 or less. Results: There was a significant difference in goal international normalization ratio achieved favoring Bebulin™ (85.5% vs 27.3%; P < .001) over Profilnine™. Median dose per kilogram of actual body weight was the same between the groups. When we assessed results by baseline™ international normalization ratio subgroup, more patients in the Bebulin™ group achieved goal when baseline values were 6 or less. No thrombotic events were documented in either group. Conclusions: We found that patients treated with Bebulin™ experienced significantly higher rates of successful international normalization ratio reversal when compared to those who received Profilnine™. Further research is needed to determine the comparative efficacy between the 2 agents.
Factors associated with plasma antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide concentrations in acute heart failure
Authors: Miñana Gema , de la Espriella Rafael , Mollar Anna , Santas Enrique , Núñez Eduardo , Valero Ernesto , Bodí Vicent , Chorro Francisco J , Fernández-Cisnal Agustin , Martí-Cervera Jorge , Sanchis Juan , Bayés-Genís Antoni , Núñez Julio 
Published: March 2020

Background:
Plasma amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 levels are positively associated with a higher risk of adverse clinical outcomes in acute heart failure. As a proxy of congestion, antigen carbohydrate 125 has also been proposed as a right-sided heart failure marker. Thus, we aimed to determine in this population the main factors – including echocardiographic right-sided heart failure parameters – associated with antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide.

Methods and results:
We prospectively included 2949 patients admitted with acute heart failure. Amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were used as dependent variables in a multivariable linear regression analysis. The mean age of the sample was 73.9±11.1 years; 48.9% were female, 35.8% showed ischaemic aetiology, and 51.6% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were 4840 (2111–9204) pg/ml and 58 (26–129) U/ml, respectively. In a multivariable setting, and ranked in order of importance (R2), estimated glomerular filtration rate (43.7%), left ventricle ejection fraction (15.1%), age (12.4%) and high-sensitivity troponin T (10.9%) emerged as the most important factors associated with amino-terminal pro-B-type natriuretic peptide. The five main factors associated with antigen carbohydrate 125 were, in order of importance: the presence of pleural effusion (36.8%), tricuspid regurgitation severity (25.1%), age (11.9%), amino-terminal pro-B-type natriuretic peptide (6.5%) and peripheral oedema (4.3%).

Conclusion:
In patients with acute heart failure the main factors associated with amino-terminal pro-B-type natriuretic peptide were renal dysfunction, left ventricle ejection fraction and age. For antigen carbohydrate 125, clinical parameters of congestion and the severity of tricuspid regurgitation were the most important predictors. These results endorse the value of antigen carbohydrate 125 as a useful marker of right-sided heart failure.
One-year follow-up of efficacy and cost of repeated doses versus single larger dose of intra-articular hyaluronic acid for knee osteoarthritis
Authors: Suppan Vijaya Kumar L , Tew Mei Mei , Wong Bor Chern , Chan Huan Keat , Chew Yu Wei , Tan Chin Siong , Nanta Kumar Vijay Kumar , Shafie Asrul Akmal , Sadashiva Rao Ashutosh 
Published: March 2020

Purpose: A recent 3-month randomized, open-label controlled trial found that the intra-articular hyaluronic acid injection (GO-ON®) given as a single dose of 5 mL is as effective and safe as three repeated doses of 2.5 mL in patients with knee osteoarthritis. However, the information on the long-term efficacy and economic implications of the single-dose regimen is still limited. Hence, this follow-up study was designed to compare the effectiveness and costs of the two regimens 12 months following the treatment. Methods: All the 127 patients, who received either three repeated doses ( n = 64) or a single dose ( n = 63) of GO-ON in the previous trial, were followed up in month 12 following the treatment. The effectiveness of both the regimens was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the mean WOMAC scores were compared with those recorded at the baseline and in month 3. Additionally, the total treatment costs of the two regimens, taking account of both direct and indirect costs, were computed and compared. Results: A total of 125 patients (98.4%) completed the assessment. Despite the reduction of the overall mean WOMAC score from 39.24 to 19.93 ( p < 0.001) in the first 3 months following the treatment with GO-ON, no further changes were observed up to month 12 ( p > 0.95). In the meantime, the two regimens did not differ in the mean WOMAC scores ( p = 0.749) and in the subscale scores for pain ( p = 0.970), stiffness ( p = 0.526), and physical functioning ( p = 0.667) in month 12. The cost for single-dose injection was found to be approximately 30% lower compared to the repeated doses. Conclusion: These findings indicate that the single larger dose of GO-ON is as effective as the repeated doses over 12 months, and yet the total treatment cost is lowered.
Achillon versus modified minimally invasive repair treatment in acute Achilles tendon rupture
Authors: Liu Jun-Yi , Duan Wei-Feng , Shen Sheng , Ye Ye , Sun Yong-Qiang , He Wei 
Published: March 2020

Purpose: To date, the best treatment of acute Achilles tendon rupture (AATR) is still inconclusive. Achillon seems to be a promising approach with satisfactory function and low complication rate. We hypothesize a modified minimally invasive repair (MMIR), which provides direct visualization of proximal tendon stump without specialized equipment that could provide comparable results. This trial is aimed to evaluate the functional and surgical outcomes of MMIR comparing with Achillon. Methods: From February 2013 to February 2017, 114 patients with AATR were enrolled in this trial, underwent an alternative operation (Achillon or MMIR), and accelerated rehabilitation protocol. Forty-four patients took the Achillon and the other 70 patients took the MMIR at their subjective choice. One hundred eleven full follow-up data were obtained including Achilles tendon total rupture score (ATRS), time back to work, rerupture rate, overall complication rate, and operation time. Results: There was no significant difference between groups in demographic characters. There was no statistical difference between both groups regarding to time return to work and ATRS at 3rd, 6th, 12th, and 24th month, respectively. Five reruptures and two Achilles tendons tethering to skins were found in the Achillon group, and two reruptures and one sural nerve injury in the MMIR group. No wound infection and dehiscence occurred. Overall complication rate in the Achillon group is higher (16.3% vs. 4.4%, p = 0.044). The operation time of Achillon is less than MMIR (34.84 vs. 39.71, p < 0.001). Conclusion: Both techniques combining with accelerated rehabilitation showed to be reliable and effective. MMIR is safer and more economical, and Achillon is faster.
Factor VIII exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulum
Authors: Poothong Juthakorn , Pottekat Anita , Siirin Marina , Campos Alexandre Rosa , Paton Adrienne W. , Paton James C. , Lagunas-Acosta Jacqueline , Chen Zhouji , Swift Mark , Volkmann Niels , Hanein Dorit , Yong Jing , Kaufman Randal J. 
Published: March 2020

AbstractHemophilia A, an X-linked bleeding disorder caused by deficiency of factor VIII (FVIII), is treated by protein replacement. Unfortunately, this regimen is costly due to the expense of producing recombinant FVIII as a consequence of its low-level secretion from mammalian host cells. FVIII expression activates the endoplasmic reticulum (ER) stress response, causes oxidative stress, and induces apoptosis. Importantly, little is known about the factors that cause protein misfolding and aggregation in metazoans. Here, we identified intrinsic and extrinsic factors that cause FVIII to form aggregates. We show that FVIII forms amyloid-like fibrils within the ER lumen upon increased FVIII synthesis or inhibition of glucose metabolism. Significantly, FVIII amyloids can be dissolved upon restoration of glucose metabolism to produce functional secreted FVIII. Two ER chaperone families and their cochaperones, immunoglobulin binding protein (BiP) and calnexin/calreticulin, promote FVIII solubility in the ER, where the former is also required for disaggregation. A short aggregation motif in the FVIII A1 domain (termed Aggron) is necessary and sufficient to seed β-sheet polymerization, and BiP binding to this Aggron prevents amyloidogenesis. Our findings provide novel insight into mechanisms that limit FVIII secretion and ER protein aggregation in general and have implication for ongoing hemophilia A gene-therapy clinical trials.
Progression of AITL-like tumors in mice is driven by Tfh signature proteins and T-B cross talk
Authors: Witalis Mariko , Chang Jinsam , Zhong Ming-Chao , Bouklouch Yasser , Panneton Vincent , Li Joanna , Buch Thorsten , Kim Seok Jin , Kim Won Seog , Ko Young Hyeh , Veillette André , Suh Woong-Kyung 
Published: March 2020

Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma driven by a pool of neoplastic cells originating from T follicular helper (Tfh) cells and concomitant expansion of B cells. Conventional chemotherapies for AITL have shown limited efficacy, and as such, there is a need for improved therapeutic options. Because AITL originates from Tfh cells, we hypothesized that AITL tumors continue to rely on essential Tfh components and intimate T-cell–B-cell (T-B) interactions. Using a spontaneous AITL mouse model (Roquinsan/+ mice), we found that acute loss of Bcl6 activity in growing tumors drastically reduced tumor size, demonstrating that AITL-like tumors critically depend on the Tfh lineage–defining transcription factor Bcl6. Because Bcl6 can upregulate expression of signaling lymphocytic activation molecule–associated protein (SAP), which is known to promote T-B conjugation, we next targeted the SAP-encoding Sh2d1a gene. We observed that Sh2d1a deletion from CD4+ T cells in fully developed tumors also led to tumor regression. Further, we provide evidence that tumor progression depends on T-B cross talk facilitated by SAP and high-affinity LFA-1. In our study, AITL-like tumors relied heavily on molecular pathways that support Tfh cell identity and T-B collaboration, revealing potential therapeutic targets for AITL.
Insight into unique somitogenesis of yak (Bos grunniens) with one additional thoracic vertebra
Authors: Wang Yu , Cai Haoyang , Luo Xiaolin , Ai Yi , Jiang Mingfeng , Wen Yongli 
Published: March 2020

Abstract
Background
The yak is a species of livestock which is crucial for local communities of the Qinghai-Tibet Plateau and adjacent regions and naturally owns one more thoracic vertebra than cattle. Recently, a sub-population of yak termed as the Jinchuan yak has been identified with over half its members own a thoracolumbar vertebral formula of T15L5 instead of the natural T14L5 arrangement. The novel T15L5 positioning is a preferred genetic trait leading to enhanced meat and milk production. Selective breeding of this trait would have great agricultural value and exploration of the molecular mechanisms underlying this trait would both accelerate this process and provide us insight into the development and regulation of somitogenesis.

Results
Here we investigated the genetic background of the Jinchuan yak through resequencing fifteen individuals, comprising five T15L5 individuals and ten T14L5 individuals with an average sequencing depth of > 10X, whose thoracolumbar vertebral formulae were confirmed by anatomical observation. Principal component analysis, linkage disequilibrium analysis, phylogenetic analysis, and selective sweep analysis were carried out to explore Jinchuan yak’s genetic background. Three hundred and thirty candidate markers were identified as associated with the additional thoracic vertebrae and target sequencing was used to validate seven carefully selected markers in an additional 51 Jinchuan yaks. The accuracies of predicting 15 thoracic vertebrae and 20 thoracolumbar vertebrae with these 7 markers were 100.00 and 33.33% despite they both could only represent 20% of all possible genetic diversity. Two genes, PPP2R2B and TBLR1, were found to harbour the most candidate markers associated with the trait and likely contribute to the unique somitic number and identity according to their reported roles in the mechanism of somitogenesis.

Conclusions
Our findings provide a clear depiction of the Jinchuan yak’s genetic background and a solid foundation for marker-assistant selection. Further exploitation of this unique population and trait could be promoted with the aid of our genomic resource.
Novel pathogenic VPS13A mutation in Moroccan family with Choreoacanthocytosis: a case report
Authors: Ouchkat Fatima , Regragui Wafaa , Smaili Imane , Naciri Darai Hajar , Bouslam Naima , Rahmani Mounia , Melhaoui Adyl , Arkha Yasser , El Fahime Elmostafa , Bouhouche Ahmed 
Published: March 2020

Abstract
Background
Choreoacanthocytosis (ChAc), is a rare neurodegenerative disease, characterized by movement disorders and acanthocytosis in the peripheral blood smears, and various neurological, neuropsychiatric and neuromuscular signs. It is caused by mutations in VPS13A gene with autosomal recessive pattern of inheritance.

Case presentation
Here we report two patients belonging to a consanguineous Moroccan family who present with movement disorder pathology. They were suspected to have choreoacanthocytosis according to biological, clinical and radiological finding. Thus, whole-exome sequencing was performed for precise diagnosis and identified a homozygous novel nonsense mutation c.337C > T (p.Gln113*) in exon 5 of VPS13A in the two affected siblings.

Conclusion
Here, we report a novel nonsense p.Gln113* mutation in VPS13A identified by whole-exome sequencing, which caused ChAc in a Moroccan family. This is the first description of ChAc in Morocco with genetic confirmation, that expands the mutation diversity of VPS13A and provide clinical, neuroimaging and deep brain stimulation findings.
Influence of Casein kinase II inhibitor CX-4945 on BCL6-mediated apoptotic signaling in B-ALL in vitro and in vivo
Authors: Richter Anna , Sender Sina , Lenz Annemarie , Schwarz Rico , Hinz Burkhard , Knuebel Gudrun , Sekora Anett , Murua Escobar Hugo , Junghanss Christian , Roolf Catrin 
Published: March 2020

Abstract
Background
Casein kinase II (CK2) is involved in multiple tumor-relevant signaling pathways affecting proliferation and apoptosis. CK2 is frequently upregulated in acute B-lymphoblastic leukemia (B-ALL) and can be targeted by the ATP-competitive CK2 inhibitor CX-4945. While reduced proliferation of tumor entities including B-ALL after CX-4945 incubation has been shown in vitro and in vivo, the detailed way of action is unknown. Here, we investigated the influence on the PI3K/AKT and apoptosis cascades in vivo and in vitro for further clarification.

Methods
A B-ALL xenograft model in NSG mice was used to perform in vivo longitudinal bioluminescence imaging during six day CX-4945 treatment. CX-4945 serum levels were determined at various time points. Flow cytometry of bone marrow and spleen cells was performed to analyze CX-4945-induced effects on tumor cell proliferation and distribution in B-ALL engrafted mice. ALL cells were enriched and characterized by targeted RNA sequencing. In vitro, B-ALL cell lines SEM, RS4;11 and NALM-6 were incubated with CX-4945 and gene expression of apoptosis regulators BCL6 and BACH2 was determined.

Results
In B-ALL-engrafted mice, overall tumor cell proliferation and distribution was not significantly influenced by CK2 inhibition. CX-4945 was detectable in serum during therapy and serum levels declined rapidly after cessation of CX-4945. While overall proliferation was not affected, early bone marrow and spleen blast frequencies seemed reduced after CK2 inhibition. Gene expression analyses revealed reduced expression of anti-apoptotic oncogene BCL6 in bone marrow blasts of CX-4945-treated animals. Further, BCL6 protein expression decreased in B-ALL cell lines exposed to CX-4945 in vitro. Surprisingly, levels of BCL6 opponent and tumor suppressor BACH2 also declined after prolonged incubation. Simultaneously, increased phosphorylation of direct CK2 target and tumor initiator AKT was detected at respective time points, even in initially pAKT-negative cell line NALM-6.

Conclusions
The CK2 inhibitor CX-4945 has limited clinical effects in an in vivo B-ALL xenograft model when applied as a single drug over a six day period. However, gene expression in B-ALL cells was altered and suggested effects on apoptosis via downregulation of BCL6. Unexpectedly, the BCL6 opponent BACH2 was also reduced. Interactions and regulation loops have to be further evaluated.
Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer
Authors: Lee Yong Jae , Kim Hyun-Soo , Rim John Hoon , Lee Jung-Yun , Nam Eun Ji , Kim Sang Wun , Kim Sunghoon , Kim Young Tae 
Published: March 2020

Abstract
Background
To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS).

Methods
We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated.

Results
BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients.

Conclusion
In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.
Newborn feeding recommendations and practices increase the risk of development of overweight and obesity
Authors: Watchmaker Brittany , Boyd Bridget , Dugas Lara R. 
Published: March 2020

Abstract
Background
The prevalence of obesity among infants less than 2 years of age has increased by more than 60% over the last three decades. Obese infants and toddlers are at an increased risk for staying overweight into adolescence and adulthood. Metabolic programming has been demonstrated in animal models whereby early life feeding habits result in life-long changes in hormone balance and metabolism. Our study explores if newborn over-nutrition on the first day of life (DOL1) is associated with risk for future overweight and obesity in childhood.

Methods
Retrospective chart data was collected for full term formula-fed infants born between January 2008 and December 2012 who continued care at the same institution. Data included the volume of formula (ml) consumed on DOL1 as well, as subsequent yearly BMI measures from well child checkups (WCC). Overfeeding was categorized as any feed greater than or equal to 30 ml on any of the first seven feeds while controlling for birth weight.

Results
The final data set included 1106 infants (547 male; 559 female). 1023 of the 1106 newborns (93%) were overfed at least once during DOL1, while 789 of 1106 (71%) were overfed 3 or more times during their first 7 feeds. After adjusting for birth weight, infants who were overfed 5 of the first 7 feeds were 5 times as likely to be overweight or obese at their 4th year well child check-up (p < 0.05) compared to children not overfed. Infants who were overfed on all 7 of their first 7 feeds were 7 times more likely to be overweight or obese at their 4th year WCC (p = 0.017).

Conclusions
Infants overfed on DOL1 were significantly more likely to be overweight or obese at their 4th year WCC, compared to infants not overfed on their first day of life. Newborn families may benefit from counseling regarding age-appropriate volumes of formula during this critical time period. Future studies will aim to look at effect of implementation of smaller feeding bottle size on reducing overfeeding practices and future risk of overweight and obesity.