bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with hepatic cirrhosis and hepatocellular carcinoma
Authors: Elghoroury Eman A , Abdelghaffar Esmat E , Awadallah Eman , Kamel Solaf A , Kandil Dina , Hassan Eman M , Hassan Mirhane , Kamel Mahmoud M , Gomaa Mohammed M , Fathalla Lamiaa A 
Published: April 2022

Background Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. Aims This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. Methods This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. Results miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group ( p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis ( p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients ( p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients ( p < 0.001). Conclusion miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.
Development and fabrication of continuous carbon fiber reinforced thermoplastic porous composite structures with different infill patterns by using additive manufacturing
Authors: Maqsood Nabeel , Rimašauskas Marius 
Published: April 2022

Additive manufacturing is a development of fabricating 3D parts layer by layer with complex geometries and utilized in numerous engineering structural applications. Fused deposition modeling technology provides higher design flexibility with aim of low cost and simplicity of material conversion to generate the composite parts. Previous studies have mainly focused on the manufacturing and characterization of continuous carbon fiber reinforced polymer composites (CCFRPCs) structure for fully dense and solid part structures and no study has been reported for porous CCFRPC parts. In this study, CCFRPCs porous structures were manufactured using FDM technology. The porous structures were fabricated with one perimeter shell by using two different types of infill patterns (grid and triangular) at three different infill densities levels (20%, 40%, and 60%). The reasons for developing such lightweight porous composite structures with continuous carbon fiber are the reduction of mass, efficient material utilization, energy consumption, and less waste generation. This study investigated the effects on tensile and flexural properties of composite specimens under uniaxial tensile loading and flexural loading, respectively. Fracture interface of the printed porous composites were examined and explored using optical microscope after performing mechanical tests. The experimental results demonstrated that infill pattern and density levels greatly affect the mechanical properties. The specimen printed using grid infill pattern with 60% infill density exhibited highest strength level in term of mechanical test and showed maximum tensile and flexural strength of 162.9 MPa and 127.24 MPa, respectively. While triangular infill pattern with 60% infill density level revealed the maximum tensile and flexural strength of 152.62 MPa and 117.53 MPa, respectively. Hence, from the results achieved in this study showed great potential and ability to replace fully dense and solid structure by the porous structure.
Early detection of anxiety problems in childhood: Spanish validation of the brief Spence Children’s Anxiety Scale for parents
Authors: Orgilés Mireia , Morales Alexandra , Espada José P , Rodríguez-Menchón Miriam 
Published: April 2022

The small percentage of children with anxiety problems who receive psychological treatment, and the negative psychological consequences associated with these problems highlight the need for early detection. Although assessment instruments with appropriate measurement properties exist, they tend to be extensive, making it difficult to apply them in clinical settings, schools, or primary care practices. This study aimed to adapt the Spanish brief version for parents of the Spence Children’s Anxiety Scale (SCAS-P-8). For this purpose, information on 215 children between 8 and 12 years of age was reported by 163 parents. The Spanish version of the SCAS-P-8 adequately fit a one-factor structure, χ2 = 44.25; df = 19; comparative fit index = .97; Tucker–Lewis index = .96; root mean square error of approximation: .07 (.04, .09); standardized root mean squared residual = .08. Evidence of internal consistency of the total SCAS-P-8 score was good ( α = 0.82), and the direct correlations obtained between the SCAS-P-8 and internalizing problems showed evidence of convergent validity. Moreover, the appropriate measurement properties of the SCAS-P-8 were shown to be independent of gender. Differences in sociodemographic variables and SDQ-P between children with anxiety symptoms and those without anxiety symptoms were also discussed. Information reported by parents can help the clinician carry out an accurate diagnosis. A brief assessment scale can be easily applied in schools or primary care settings.
Drug safety of frequently used drugs and substances for self-medication in COVID-19
Authors: Baracaldo-Santamaría Daniela , Pabón-Londoño Santiago , Rojas-Rodriguez Luis Carlos 
Published: April 2022

During the COVID-19 pandemic, the behavior of self-medication has increased. The dissemination of misleading information regarding the efficacy of certain drugs or substances for the prevention and treatment of COVID-19 has been the major contributing factor for this phenomenon. Alongside with the increase in self-medication behavior, the inherent risks to this act such as drug–drug interactions, adverse events, drug toxicity, and masking of symptoms have also increased. Self-medication in the context of COVID-19 has led to drug misuse leading in some cases to the development of fatal adverse drug reactions. It is important that during this ongoing pandemic drugs with potential clinical efficacy against COVID-19 are adequately analyzed regarding their efficacy, safety, and monitoring. The aim of this review is to describe the available evidence regarding the efficacy, safety, and monitoring of the drugs and substances that have been shown to be frequently used for self-medication in patients with COVID-19 (hydroxychloroquine, non-steroidal anti-inflammatory drugs, ivermectin, azithromycin, vitamins, aspirin, and chlorine dioxide) to adequately characterize their risks, safe use, monitoring strategies, and to reinforce the concept that these substances should not be used for self-medication and require a medical prescription. Plain Language Summary Drug safety of frequently used drugs and substances for self-medication in COVID-19 Dissemination of information about potential COVID-19 treatments has led individuals to self-medicate and expose themselves to risks such as drug–drug interactions, side effects, antibiotic resistance, and misdiagnosis. There is a need to review the medical literature to evaluate the safety and efficacy of the drugs and substances commonly used by the population for the treatment and prevention of SARS CoV-2 infection. In this review, we included drugs that are frequently used for self-medication and commonly advertised such as ivermectin, hydroxychloroquine, chlorine dioxide, azithromycin, and non-steroidal anti-inflammatory drugs, among others. A brief introduction of the drug and its mechanism of action, followed by a summary of the efficacy in COVID-19 and safety, will be described for each drug in order to promote their responsible use.
Thoracic Outlet Syndrome in Major League Baseball Pitchers: Return to Sport and Performance Metrics After Rib Resection
Authors: Arnold Michael T. , Hart Christopher M. , Greig Danielle E. , Trikha Rishi , Gelabert Hugh A. , Jones Kristofer J. 
Published: April 2022

Background: Thoracic outlet syndrome (TOS) is a rare injury that affects Major League Baseball (MLB) pitchers and is often corrected with surgical resection of the first rib. There are limited return-to-play (RTP) data for this surgery in MLB pitchers. Hypothesis: It was hypothesized that MLB pitchers who undergo first rib resection for TOS will show (1) a high rate of RTP, (2) no difference in postoperative career length compared with controls, (3) no difference in pre- and postoperative performance, and (4) no difference in postoperative performance compared with controls. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective cohort study evaluated MLB pitchers with neurogenic or vascular TOS who underwent rib resection surgery between January 1, 2001, and December 31, 2019. Players were identified through public injury reports from press releases, the MLB website, MLB team injury reports, and blogs. A demographics- and performance-matched control group was generated for comparison. Each player in the control group was given an index year that corresponded to the surgery year of the case group. Performance data included innings pitched (IP), games played (GP), earned run average (ERA), complete GP, shutouts, saves, hits, runs, home runs (HR), walks, strikeouts (K), walks plus hits per IP (WHIP), and earned runs (ER). Results: We identified 26 MLB pitchers who underwent rib resection for neurogenic or vascular TOS; 21 players (81%) had a successful RTP. Pitchers were 30 ± 3.6 years old at the time of surgery and had played 6.2 ± 3.5 seasons before undergoing surgery. Average postoperative career length was 3.1 ± 2.0 seasons, with an average time from surgery to RTP being 10 ± 4.7 months. Pitchers who RTP showed no significant differences in performance metrics compared with controls. Players pitch 0.94 ( P < .05) more IP/GP in the season directly following RTP compared with the season before surgical intervention. Conclusion: MLB pitchers undergoing rib resection for TOS demonstrated (1) high RTP rates following rib resection, (2) no difference in postoperative career length compared with controls, (3) improvement in postoperative performance, and (4) no difference in postoperative performance compared with controls.
A Pandemic Perspective: Analyzing the Impact of COVID-19 on Diabetes Management and Mood Through the Lens of Location and Family Conflict
Authors: Moore Hailey , Abadula Fayo , Garretson Sydney , Okonkwo Nkemjika , Streisand Randi , Jaser Sarah 
Published: April 2022

Purpose: The purpose of this study was to examine the influence of COVID-19 on teens’ diabetes management and mood and their association with family conflict. Methods: One hundred and nineteen teens ages 13 to 17 (M = 15.5 ± 1.3 years, 61.3% female, 57.1% non-Hispanic White) and 119 parents (83.2% female, 75.6% married, 63.9% non-Hispanic White) enrolled in an ongoing two-site randomized behavioral clinical trial. At baseline, dyads completed the Revised Diabetes Family Conflict scale and a survey measuring the impact of COVID-19 on teens’ mood and diabetes management. Results: Parent- and teen-reported impacts of COVID-19 on diabetes management and teen mood were positively correlated. Higher levels of both parent- and teen-reported family conflict were associated with greater parent-reported impact of COVID-19 on diabetes management and teen mood. In addition, teen-reported impact of COVID-19 on their mood varied by geographical location but not population density. Conclusions: COVID-19 influenced teen diabetes management and mood, and the impact of COVID-19 was related to diabetes-related family conflict and differed by geographic location. Findings lend support for mental health interventions targeting teens with T1DM affected by COVID-19 and monitoring the long-term effects of the pandemic.
Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse
Authors: Berdel Andrew F. , Ruhnke Leo , Angenendt Linus , Wermke Martin , Röllig Christoph , Mikesch Jan-Henrik , Scheller Annika , Hemmerle Teresa , Matasci Mattia , Wethmar Klaus , Kessler Torsten , Gerwing Mirjam , Hescheler Daniel , Schäfers Michael , Hartmann Wolfgang , Altvater Bianca , Rossig Claudia , Bornhäuser Martin , Lenz Georg , Stelljes Matthias , Rueter Bjoern , Neri Dario , Berdel Wolfgang E. , Schliemann Christoph 
Published: April 2022

AbstractNatural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but deficiency of environmental signals and insufficient tumor recognition may limit their activity. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to a spliced isoform of the extracellular matrix (ECM) glycoprotein tenascin-C would potentiate NK-cell–mediated antibody-dependent cellular cytotoxicity against leukemic blasts. In this novel-novel combination, dose-escalation, phase 1 trial, we enrolled patients with posttransplant acute myeloid leukemia (AML) relapse to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of the antibody-cytokine fusion F16IL2 (10 × 106 to 20 × 106 IU IV; days 1, 8, 15, and 22 of each 28-day cycle) in combination with the anti-CD33 antibody BI 836858 (10-40 mg IV, 2 days after each F16IL2 infusion). Among the 15 patients (median [range] age, 50 [20-68] years) treated across 4 dose levels (DLs), 6 (40%) had received 2 or 3 prior transplantations. The most frequent adverse events were pyrexia, chills, and infusion-related reactions, which were manageable, transient and of grade ≤2. One dose-limiting toxicity occurred at each of DLs 3 (pulmonary edema) and 4 (graft-versus-host disease). Three objective responses were observed among 7 patients treated at the 2 higher DLs, whereas no responses occurred at the 2 starting DLs. Combination therapy stimulated the expansion and activation of NK cells, including those expressing the FcγRIIIA/CD16 receptor. ECM-targeted IL-2 combined with anti-CD33 immunotherapy represents an innovative approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. This trial was registered at EudraCT as 2015-004763-37.
Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma
Authors: Frigault Matthew J. , Bishop Michael R. , Rosenblatt Jacalyn , O’Donnell Elizabeth K. , Raje Noopur , Cook Daniella , Yee Andrew J. , Logan Emma , Avigan David E. , Jakubowiak Andrzej , Shaw Kit , Daley Heather , Nikiforow Sarah , Griffin Faith , Cornwell Christine , Shen Angela , Heery Christopher , Maus Marcela V. 
Published: April 2022

Abstract
Relapsed and refractory multiple myeloma (RRMM) is a plasma cell neoplasm defined by progressively refractory disease necessitating chronic and increasingly intensive therapy. Despite recent advances, limited treatment options exist for RRMM. This single-arm, open label phase 1 study aimed to evaluate the safety of novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T construct that leverages a completely synthetic antigen-binding domain (CART-ddBCMA), which was specifically engineered to reduce immunogenicity and improve CAR cell surface stability. Thirteen patients ≥18 years with RRMM who received at least 3 prior regimens of systemic therapy were enrolled in the study. Patients received a single dose of 100 × 106 CART-ddBCMA (DL1) or 300 × 106 CART-ddBCMA (DL2) following standard lymphodepleting chemotherapy. The primary endpoints of the study were to evaluate the incidence of treatment emergent adverse events, including dose-limiting toxicities, and establish a recommended phase 2 dose. Results showed that CART-ddBCMA was well tolerated and demonstrated a favorable toxicity profile. Only 1 case of grade ≥3 cytokine release syndrome and 1 case of immune effector cell–associated neurotoxicity were reported; both were at DL2 and were manageable with standard treatment. No atypical neurological toxicities and Parkinson disease-like movement disorders were observed. The maximum tolerated dose was not reached. All infused patients responded to CART-ddBCMA, and 9/12 (75%) patients achieved complete response/stringent complete response. Responses deepened over time, and at the time of last data-cut (median follow-up 56 weeks), 8/9 (89%) evaluable patients achieved minimal residual disease negativity. In conclusion, the findings demonstrate the safety of CART-ddBCMA cells and document durable responses to CART-ddBCMA in patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT04155749.
Oxford Nanopore and Bionano Genomics technologies evaluation for plant structural variation detection
Authors: Canaguier Aurélie , Guilbaud Romane , Denis Erwan , Magdelenat Ghislaine , Belser Caroline , Istace Benjamin , Cruaud Corinne , Wincker Patrick , Le Paslier Marie-Christine , Faivre-Rampant Patricia , Barbe Valérie 
Published: April 2022

Abstract
Background
Structural Variations (SVs) are genomic rearrangements derived from duplication, deletion, insertion, inversion, and translocation events. In the past, SVs detection was limited to cytological approaches, then to Next-Generation Sequencing (NGS) short reads and partitioned assemblies. Nowadays, technologies such as DNA long read sequencing and optical mapping have revolutionized the understanding of SVs in genomes, due to the enhancement of the power of SVs detection.
This study aims to investigate performance of two techniques, 1) long-read sequencing obtained with the MinION device (Oxford Nanopore Technologies) and 2) optical mapping obtained with Saphyr device (Bionano Genomics) to detect and characterize SVs in the genomes of the two ecotypes of Arabidopsis thaliana, Columbia-0 (Col-0) and Landsberg erecta 1 (Ler-1).

Results
We described the SVs detected from the alignment of the best ONT assembly and DLE-1 optical maps of A. thaliana Ler-1 against the public reference genome Col-0 TAIR10.1. After filtering (SV > 1 kb), 1184 and 591 Ler-1 SVs were retained from ONT and Bionano technologies respectively. A total of 948 Ler-1 ONT SVs (80.1%) corresponded to 563 Bionano SVs (95.3%) leading to 563 common locations. The specific locations were scrutinized to assess improvement in SV detection by either technology. The ONT SVs were mostly detected near TE and gene features, and resistance genes seemed particularly impacted.

Conclusions
Structural variations linked to ONT sequencing error were removed and false positives limited, with high quality Bionano SVs being conserved. When compared with the Col-0 TAIR10.1 reference genome, most of the detected SVs discovered by both technologies were found in the same locations. ONT assembly sequence leads to more specific SVs than Bionano one, the latter being more efficient to characterize large SVs. Even if both technologies are complementary approaches, ONT data appears to be more adapted to large scale populations studies, while Bionano performs better in improving assembly and describing specificity of a genome compared to a reference.
Influenza virus-like particle vaccine containing both apical membrane antigen 1 and microneme-associated antigen proteins of Plasmodium berghei confers protection in mice
Authors: Kim Min-Ju , Chu Ki-Back , Kang Hae-Ji , Yoon Keon-Woong , Lee Dong-Hun , Lee Su-Hwa , Moon Eun-Kyung , Quan Fu-Shi 
Published: April 2022

Abstract
Background
Apical membrane antigen 1 (AMA1) and microneme-associated antigen (MIC) of Plasmodium parasites are important factors involved in host cell invasion.

Methods
In this study, influenza VLP vaccines containing both codon-optimized AMA1 and MIC were generated and the vaccine efficacy was evaluated in mice.

Results
VLPs vaccine immunization elicited higher levels of parasite-specific IgG and IgG2a antibody responses in sera. CD4+ and CD8+ T cells and germinal center B cells in blood, inguinal lymph nodes (ILN) and spleen were found to be significantly increased. Importantly, VLPs vaccination significantly reduced the levels of pro-inflammatory cytokines IFN-γ and TNF-α, decreased parasitemia in blood, resulting in lower body weight loss and longer survival time compared to control.

Conclusion
These results indicated that VLPs containing P. berghei AMA1 and MIC could be a candidate for malaria blood-stage vaccine design.
Comparison of surgical and oncologic outcomes in very elderly patients (≥ 80 years old) and elderly (65–79 years old) colorectal cancer patients: a propensity score matching
Authors: Cheng Yu-Xi , Liu Xiao-Yu , Kang Bing , Tao Wei , Wei Zheng-Qiang , Peng Dong 
Published: April 2022

Abstract
Purpose
The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM).

Methods
This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65–79 years old).

Results
A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p < 0.01, HR = 1.878, 95% CI 1.488–2.371), tumor stage (p < 0.01, HR = 1.865, 95% CI 1.603–2.170), overall complications (p < 0.01, HR = 1.514, 95% CI 1.224–1.872) and major complications (p = 0.001, HR = 2.012, 95% CI 1.319–3.069) were independent prognostic factors. For DFS, age (p < 0.01, HR = 1.816, 95% CI 1.579–2.088), tumor stage (p < 0.01, HR = 1.816, 95% CI 1.579–2.088), overall complications (p = 0.002, HR = 1.379, 95% CI 1.128–1.685) and major complications (p = 0.002, HR = 1.902, 95% CI 1.259–2.874) were found to be independent prognostic factors. Moreover, elderly patients had a better OS and DFS than very elderly patients.

Conclusion
Very elderly patients had a poorer prognosis than elderly patients after primary CRC surgery. Surgeons should be cautious when treating very elderly CRC patients.