bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percentage of Adherence Correlates with the Risk of Protease Inhibitor (PI) Treatment Failure in HIV-Infected Patients
Authors: Casado Jose L , Sabido Raquel , Perez-Elías María J , Antela Antonio , Oliva Jesús , Dronda Fernando , Mejía Blanca , Fortún Jesús 
Published: April 2022

Objectives To determine the effect of adherence on the rate of protease inhibitor (PI) treatment failure among human immunodeficiency virus (HIV)-infected patients. Methods A prospective study of a cohort of 282 patients who initiated PI therapy from March 1996 to December 1997. Adherence was quantified as the percentage of prescribed doses reportedly taken and treatment failure was defined as HIV RNA levels above 200 copies/ml after 1 year on therapy. Results Overall, 190 patients (67%) missed prescribed doses. However, mean percentage of doses taken was 91% (range, 21–100%). Demographic, virological and immunological characteristics could not predict adherence outcomes. The causes of non-adherence included intolerance or side effects (35%), complexity of treatment (23%), or recurrence in active drug abuse (17%), whereas abandonment owing to HIV-related disease was uncommon (6%). A degree of adherence above 90% correlated significantly with viral suppression [relative risk (RR) 1.69; 95% confidence interval (CI) 1.1–2.56; P<0.01]. In a multivariate analysis, a lower degree of adherence (RR, 0.96; P=0.006), a higher HIV viral load (RR, 2.03; P=0.0001), prior antiretroviral therapy (RR, 2.5; P=0.01), and use of saquinavir-hard gel capsules (saquinavir-HGC) (RR, 1.77; P=0.03) were strongly associated with treatment failure. Conclusion The percentage of adherence and initial HIV viral load are the most important determinants of virological response to PI therapy and non-adherence is related to treatment-related factors in the majority of cases.
Standardized Preoperative Pathways Determining Preoperative Echocardiogram Usage Continue to Improve Hip Fracture Quality
Authors: Esper Garrett , Anil Utkarsh , Konda Sanjit , Furgiuele David , Zaretsky Jonah , Egol Kenneth 
Published: April 2022

Introduction The purpose of this study was to assess the hospital quality measures and outcomes of operative hip fracture patients before and after implementation of an anesthesiology department protocol assigning decision for a preoperative transthoracic echocardiogram (TTE) to the hospitalist co-managing physician. Materials and Methods Demographics, injury details, hospital quality measures, and outcomes were reviewed for a consecutive series of patients presenting to our institution with an operative hip fracture. In May of 2019, a new protocol assigning the responsibility to indicate a patient for preoperative TTE was mandated to the co-managing hospitalist at the institution. Patients were split into pre-protocol and post-protocol cohorts. Linear regression modeling and comparative analyses were conducted with a Bonferroni adjusted alpha as appropriate. Results Between September 2015 and June 2021, 1002 patients presented to our institution and were diagnosed with a hip fracture. Patients in the post-protocol cohort were less likely to undergo a preoperative echocardiogram, experienced a shorter time (days) to surgery, shorter length of stay, an increase in amount of home discharges, and lower complication risks for urinary tract infection and acute blood loss anemia as compared to those in the pre-protocol cohort. There were no differences seen in inpatient or 30-day mortality. Multivariable linear regression demonstrated a patient’s comorbidity profile (Charlson Comorbidity Index (CCI)) and their date of presentation (pre- or post-protocol), were both associated with (P<0.01) a patients' time to surgery. Conclusion A standardized preoperative work flow protocol regarding which physician evaluates and determines which patients require a preoperative TTE allows for a streamlined perioperative course for hip fracture patients. This allows for a shortened time to surgery and length of stay with an increase in home discharges and was associated with a reduced risk of common index hospitalization complications including UTI and anemia.
Influence of surface functionalization of ceramic nanofibers on morphological, physical and mechanical properties of unsaturated polyester nanocomposites
Authors: Kallagunta Harish , Tate Jitendra S 
Published: April 2022

Alumina nanofibers at 0.25wt%, 0.5wt%, 0.75wt%, and 1wt% concentration were used to modify unsaturated polyester resin. Additionally, vinyl silane treated alumina nanofibers were used at the same concentrations and were compared to pristine alumina nanofibers. The SEM images showed a variation in the surface morphology when alumina nanofibers and the BET measurement showed surface area increase from 111 m2/g to 122 m2/g when nanofibers were treated with silane agent. The dispersion of alumina nanofibers into the host unsaturated polyester resin was successfully achieved by three roll mill dispersion. The TEM images showed good dispersion of alumina nanofibers in polyester resin. Although pristine nanofibers showed greater agglomeration at 1wt% concentration, the effect of agglomeration was reduced in the 1wt% concentration. The weight loss measurements from TGA showed that the thermal stability of nanocomposites increased with addition of nanofibers and the lower onset degradation temperature can be tailored to improve by a maximum of 5.5% for silane treated nanofiber. Viscosity and contact angle which are key factors affecting the processability has seen to be positively altered by silane treatment. Additional tensile, flexural, and Izod impact properties were evaluated for the nine material systems and the properties were summarized.
First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results
Authors: Königs Christoph , Ozelo Margareth C. , Dunn Amy , Kulkarni Roshni , Nolan Beatrice , Brown Simon A. , Schiavulli Michele , Gunawardena Sriya , Mukhopadhyay Sutirtha , Jayawardene Deepthi , Winding Bent , Carcao Manuel 
Published: April 2022

Abstract
PUPs A-LONG evaluated the safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously untreated patients (PUPs) with hemophilia A. This open-label, phase 3 study enrolled male PUPs (&lt;6 years) with severe hemophilia A to receive rFVIIIFc. The primary endpoint was the occurrence of inhibitor development. Secondary endpoints included annualized bleed rate (ABR). Of 103 subjects receiving ≥1 dose of rFVIIIFc, 80 (78%) were aged &lt;1 year at the study start, 20 (19%) had a family history of inhibitors, and 82 (80%) had high-risk F8 mutations. Twenty subjects began on prophylaxis, while 81 began an on-demand regimen (69 later switched to prophylaxis). Eighty-seven (81%) subjects completed the study. Inhibitor incidence was 31.1% (95% confidence interval [CI], 21.8% to 41.7%) in subjects with ≥10 exposure days (or inhibitor); high-titer inhibitor incidence was 15.6% (95% CI, 8.8% to 24.7%). The median (range) time to high-titer inhibitor development was 9 (4-14) exposure days. Twenty-eight (27%) subjects experienced 32 rFVIIIFc treatment-related adverse events; most were inhibitor development. There was 1 nontreatment-related death due to intracranial hemorrhage (onset before the first rFVIIIFc dose). The overall median (interquartile range [IQR]) ABR was 1.49 (0.00-4.40) for subjects on variable prophylaxis dosing regimens. In this study of rFVIIIFc in pediatric PUPs with severe hemophilia A, overall inhibitor development was within the expected range, although high-titer inhibitor development was on the low end of the range reported in the literature. rFVIIIFc was well-tolerated and effective for prophylaxis and treatment of bleeds. This trial is registered at www.clinicaltrials.gov (NCT02234323).
BMP2/SMAD pathway activation in JAK2/p53-mutant megakaryocyte/erythroid progenitors promotes leukemic transformation
Authors: Li Bing , An Wenbin , Wang Hua , Baslan Timour , Mowla Shoron , Krishnan Aishwarya , Xiao Wenbin , Koche Richard P. , Liu Ying , Cai Sheng F. , Xiao Zhijian , Derkach Andriy , Iacobucci Ilaria , Mullighan Charles G. , Helin Kristian , Lowe Scott W. , Levine Ross L. , Rampal Raajit K. 
Published: April 2022

Abstract
Leukemic transformation (LT) of myeloproliferative neoplasm (MPN) has a dismal prognosis and is largely fatal. Mutational inactivation of TP53 is the most common somatic event in LT; however, the mechanisms by which TP53 mutations promote LT remain unresolved. Using an allelic series of mouse models of Jak2/Trp53 mutant MPN, we identify that only biallelic inactivation of Trp53 results in LT (to a pure erythroleukemia [PEL]). This PEL arises from the megakaryocyte-erythroid progenitor population. Importantly, the bone morphogenetic protein 2/SMAD pathway is aberrantly activated during LT and results in abnormal self-renewal of megakaryocyte-erythroid progenitors. Finally, we identify that Jak2/Trp53 mutant PEL is characterized by recurrent copy number alterations and DNA damage. Using a synthetic lethality strategy, by targeting active DNA repair pathways, we show that this PEL is highly sensitive to combination WEE1 and poly(ADP-ribose) polymerase inhibition. These observations yield new mechanistic insights into the process of p53 mutant LT and offer new, clinically translatable therapeutic approaches.
CD34+CD19−CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies
Authors: Bueno Clara , Barrera Susana , Bataller Alex , Ortiz-Maldonado Valentín , Elliot Natalina , O’Byrne Sorcha , Wang Guanlin , Rovira Montse , Gutierrez-Agüera Francisco , Trincado Juan L. , González-González María , Morgades Mireia , Sorigué Marc , Bárcena Paloma , Zanetti Samanta Romina , Torrebadell Montse , Vega-Garcia Nerea , Rives Susana , Mallo Mar , Sole Francesc , Mead Adam J. , Roberts Irene , Thongjuea Supat , Psaila Bethan , Juan Manel , Delgado Julio , Urbano-Ispizúa Alvaro , Ribera Josep María , Orfao Alberto , Roy Anindita , Menendez Pablo 
Published: April 2022

Abstract
CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19− (pre)-leukemic cells represent an “early progenitor origin-related” mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19−CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19−CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19−CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19−CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19− relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged.
The dynamic alteration of transcriptional regulation by crucial TFs during tumorigenesis of gastric cancer
Authors: Yu Beiqin , Dai Wentao , Pang Li , Sang Qingqing , Li Fangyuan , Yu Junxian , Feng Haoran , Li Jianfang , Hou Junyi , Yan Chao , Su Liping , Zhu Zhenggang , Li Yuan-Yuan , Liu Bingya 
Published: April 2022

AbstractBackgroundThe mechanisms of Gastric cancer (GC) initiation and progression are complicated, at least partly owing to the dynamic changes of gene regulation during carcinogenesis. Thus, investigations on the changes in regulatory networks can improve the understanding of cancer development and provide novel insights into the molecular mechanisms of cancer.MethodsDifferential co-expression analysis (DCEA), differential gene regulation network (GRN) modeling and differential regulation analysis (DRA) were integrated to detect differential transcriptional regulation events between gastric normal mucosa and cancer samples based on GSE54129 dataset. Cytological experiments and IHC staining assays were used to validate the dynamic changes of CREB1 regulated targets in different stages.ResultsA total of 1955 differentially regulated genes (DRGs) were identified and prioritized in a quantitative way. Among the top 1% DRGs, 14 out of 19 genes have been reported to be GC relevant. The four transcription factors (TFs) among the top 1% DRGs, including CREB1, BPTF, GATA6 and CEBPA, were regarded as crucial TFs relevant to GC progression. The differentially regulated links (DRLs) around the four crucial TFs were then prioritized to generate testable hypotheses on the differential regulation mechanisms of gastric carcinogenesis. To validate the dynamic alterations of gene regulation patterns of crucial TFs during GC progression, we took CREB1 as an example to screen its differentially regulated targets by using cytological and IHC staining assays. Eventually, TCEAL2 and MBNL1 were proved to be differentially regulated by CREB1 during tumorigenesis of gastric cancer.ConclusionsBy combining differential networking information and molecular cell experiments verification, testable hypotheses on the regulation mechanisms of GC around the core TFs and their top ranked DRLs were generated. Since TCEAL2 and MBNL1 have been reported to be potential therapeutic targets in SCLC and breast cancer respectively, their translation values in GC are worthy of further investigation.
Roles of ARID1A variations in colorectal cancer: a collaborative review
Authors: Zhao Shankun , Wu Weizhou , Jiang Zufu , Tang Fuqin , Ding Lingzhi , Xu Weifang , Ruan Libin 
Published: April 2022

AbstractColorectal cancer (CRC), a common malignancy, is one of the leading cause of cancer death in adults. AT-rich interaction domain 1A (ARID1A), a critical portion of the SWItch/sucrose non-fermentation (SWI/SNF) chromatin remodeling complexes, shows one of the most frequent mutant genes across different human cancer types. Deleterious variations of ARID1A has been recognized to be correlated the tumorigenesis and the poor prognosis of CRC. Here, we summarize recent advances in the clinical implications and molecular pathogenesis of ARID1A variations in CRC. According to independent data of 23 included studies, ARID1A is mutated in 3.6–66.7%. Consistently, all of the 23 relevant studies report that ARID1A functions as a specific tumor suppressor in CRC. Clinically, ARID1A variation status serves as a biomarker for survival prognosis and various therapies for CRC. Mechanistically, the pathophysiologic impacts of ARID1A variations on CRC may be associated with the co-occurrence variations of other genes (i.e., TP53, KRAS, APC, FBXW7, and PIK3CA) and the regulation of several signaling pathways being affected (i.e., WNT signaling, Akt signaling, and MEK/ERK pathway), leading to cell cycle arrest, chromatin remodeling, chromosome organization, and DNA hypermethylation of the cancer cells. The present review highlights ARID1A serving as a potent tumor suppressor and an important prognostic factor in CRC. ARID1A variations hint towards a promising tool for diagnostic tumor profiling and individualized therapeutic targets for CRC in the future.
A comparison of mRNA sequencing (RNA-Seq) library preparation methods for transcriptome analysis
Authors: Ura Hiroki , Togi Sumihito , Niida Yo 
Published: April 2022

AbstractBackgroundmRNA sequencing is a powerful technique, which is used to investigate the transcriptome status of a gene of interest, such as its transcription level and splicing variants. Presently, several RNA sequencing (RNA-Seq) methods have been developed; however, the relative advantage of each method has remained unknown. Here we used three commercially available RNA-Seq library preparation kits; the traditional method (TruSeq), in addition to full-length double-stranded cDNA methods (SMARTer and TeloPrime) to investigate the advantages and disadvantages of these three approaches in transcriptome analysis.ResultsWe observed that the number of expressed genes detected from the TeloPrime sequencing method was fewer than that obtained using the TruSeq and SMARTer. We also observed that the expression patterns between TruSeq and SMARTer correlated strongly. Alternatively, SMARTer and TeloPrime methods underestimated the expression of relatively long transcripts. Moreover, genes having low expression levels were undetected stochastically regardless of any three methods used. Furthermore, although TeloPrime detected a significantly higher proportion at the transcription start site (TSS), its coverage of the gene body was not uniform. SMARTer is proposed to be yielded for nonspecific genomic DNA amplification. In contrast, the detected splicing event number was highest in the TruSeq. The percent spliced in index (PSI) of the three methods was highly correlated.ConclusionsTruSeq detected transcripts and splicing events better than the other methods and measured expression levels of genes, in addition to splicing events accurately. However, although detected transcripts and splicing events in TeloPrime were fewer, the coverage at TSS was highest. Additionally, SMARTer was better than TeloPrime with regards to the detected number of transcripts and splicing events among the understudied full-length double-stranded cDNA methods. In conclusion, for short-read sequencing, TruSeq has relative advantages for use in transcriptome analysis.
Ventricular tachycardia ablation guided or aided by scar characterization with cardiac magnetic resonance: rationale and design of VOYAGE study
Authors: Lilli Alessio , Parollo Matteo , Mazzocchetti Lorenzo , De Sensi Francesco , Rossi Andrea , Notarstefano Pasquale , Santoro Amato , Aquaro Giovanni Donato , Cresti Alberto , Lapira Federica , Faggioni Lorenzo , Tessa Carlo , Pauselli Luca , Bongiorni Maria Grazia , Berruezo Antonio , Zucchelli Giulio 
Published: April 2022

Abstract
Background
Radiofrequency ablation has been shown to be a safe and effective treatment for scar-related ventricular arrhythmias (VA). Recent preliminary studies have shown that real time integration of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images with electroanatomical map (EAM) data may lead to increased procedure efficacy, efficiency, and safety.

Methods
VOYAGE is a prospective, randomized, multicenter controlled open label study designed to compare in terms of efficacy, efficiency, and safety a CMR aided/guided workflow to standard EAM-guided ventricular tachycardia (VT) ablation. Patients with an ICD or with ICD implantation expected within 1 month, with scar related VT, suitable for CMR and multidetector computed tomography (MDCT) will be randomized to a CMR-guided or CMR-aided approach, whereas subjects unsuitable for imaging or with image quality deemed not sufficient for postprocessing will be allocated to standard of care ablation. Primary endpoint is defined as VT recurrences (sustained or requiring appropriate ICD intervention) during 12 months follow-up, excluding the first month of blanking period. Secondary endpoints will include procedural efficiency, safety, impact on quality of life and comparison between CMR-guided and CMR-aided approaches. Patients will be evaluated at 1, 6 and 12 months.

Discussion
The clinical impact of real time CMR-guided/aided ablation approaches has not been thoroughly assessed yet. This study aims at defining whether such workflow results in more effective, efficient, and safer procedures. If proven to be of benefit, results from this study could be applied in large scale interventional practice.
Trial registrationClinicalTrials.gov, NCT04694079, registered on January 1, 2021.
Nasal cartilage destruction associated to cutaneous histoplasmosis in AIDS
Authors: Escalante Luis , Granizo-Rubio Jennyfer , Pinos-León Victor , Tello Sonia , Maldonado Astrid , Cherrez-Ojeda Iván 
Published: April 2022

Abstract
Background
Systemic histoplasmosis is a disease of high morbidity and mortality in immunocompromised patients. Patients with AIDS get the infection through inhalation of spores, triggering a primary lung infection with a subsequent hematogenous spread to multiple organs, including the skin. Tissue necrosis have been documented in cutaneous histoplasmosis with multiple clinical manifestations that mimic other diseases.

Case presentation
We report the case of nasal cartilage destruction associated to cutaneous histoplasmosis in AIDS. A 24-year-old man, resident in Ecuadorian coast, with a history of HIV for 7 years without any treatment. In the last 3 months, he has been presenting a molluscum-like lesions on his nasal bridge with subsequent dissemination to the trunk and extremities. He was admitted to the emergency department for dyspnoea, cough, and malaise. Due to his respiratory failure, he was admitted to the intensive care unit (ICU) with mechanical ventilation. Physical examination reveals a crusted surface ulcer that involves the nose and cheeks, associated with erythematous papules, some with a crusted surface which are spread to the face, trunk, and upper limbs. The patient has a specific skin involvement with a butterfly-like ulcer appearance and destruction of the upper and lower lateral cartilage of the nose. At admission CD4 cell count was 11/mm3 with a HIV viral load of 322,908 copies. Mycological cultures identified Histoplasma capsulatum. A treatment with highly active antiretroviral therapy (HAART) was stablished, associated with liposomal amphotericin B at a dose of 3 mg/kg/day and itraconazole 200 mg twice a day for 12 months.

Conclusions
Cutaneous histoplasmosis is a rare manifestation of pulmonary histoplasmosis in patients with AIDS. The cutaneous manifestations included papules, nodules, plaques, and ulcers. A histology examination is required to rule out other fungal or parasitic infections. Treatment includes highly active antiretroviral therapy (HAART), amphotericin B liposomal and itraconazole, the latest for at least 12 months.