bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scoping review of the literature featuring research ethics and research integrity cases
Authors: Armond Anna Catharina Vieira , Gordijn Bert , Lewis Jonathan , Hosseini Mohammad , Bodnár János Kristóf , Holm Soren , Kakuk Péter 
Published: April 2021

Abstract
Background
The areas of Research Ethics (RE) and Research Integrity (RI) are rapidly evolving. Cases of research misconduct, other transgressions related to RE and RI, and forms of ethically questionable behaviors have been frequently published. The objective of this scoping review was to collect RE and RI cases, analyze their main characteristics, and discuss how these cases are represented in the scientific literature.

Methods
The search included cases involving a violation of, or misbehavior, poor judgment, or detrimental research practice in relation to a normative framework. A search was conducted in PubMed, Web of Science, SCOPUS, JSTOR, Ovid, and Science Direct in March 2018, without language or date restriction. Data relating to the articles and the cases were extracted from case descriptions.

Results
A total of 14,719 records were identified, and 388 items were included in the qualitative synthesis. The papers contained 500 case descriptions. After applying the eligibility criteria, 238 cases were included in the analysis. In the case analysis, fabrication and falsification were the most frequently tagged violations (44.9%). The non-adherence to pertinent laws and regulations, such as lack of informed consent and REC approval, was the second most frequently tagged violation (15.7%), followed by patient safety issues (11.1%) and plagiarism (6.9%). 80.8% of cases were from the Medical and Health Sciences, 11.5% from the Natural Sciences, 4.3% from Social Sciences, 2.1% from Engineering and Technology, and 1.3% from Humanities. Paper retraction was the most prevalent sanction (45.4%), followed by exclusion from funding applications (35.5%).

Conclusions
Case descriptions found in academic journals are dominated by discussions regarding prominent cases and are mainly published in the news section of journals. Our results show that there is an overrepresentation of biomedical research cases over other scientific fields compared to its proportion in scientific publications. The cases mostly involve fabrication, falsification, and patient safety issues. This finding could have a significant impact on the academic representation of misbehaviors. The predominance of fabrication and falsification cases might diverge the attention of the academic community from relevant but less visible violations, and from recently emerging forms of misbehaviors.
Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study
Authors:   RISE Study Group, Vasunilashorn Sarinnapha M. , Ngo Long H. , Dillon Simon T. , Fong Tamara G. , Carlyle Becky C. , Kivisäkk Pia , Trombetta Bianca A. , Vlassakov Kamen V. , Kunze Lisa J. , Arnold Steven E. , Xie Zhongcong , Inouye Sharon K. , Libermann Towia A. , Marcantonio Edward R. 
Published: April 2021

Abstract
Background
Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation.

Methods
We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids.

Results
Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline.

Conclusions
In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.
Identification of aberrant innate and adaptive immunity based on changes in global gene expression in the blood of adults with autism spectrum disorder
Authors: Horiuchi Fumie , Yoshino Yuta , Kumon Hiroshi , Hosokawa Rie , Nakachi Kiwamu , Kawabe Kentaro , Iga Jun-ichi , Ueno Shu-ichi 
Published: April 2021

Abstract
Background
Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder, and one of the main hypotheses regarding its cause is genetic factors. A previous meta-analysis of seven microarray studies and one RNA sequencing (RNA-seq) study using the blood of children with ASD identified dysregulation of gene expressions relevant to the immune system. In this study, we explored changes in global gene expression as the phenotype of ASD in the blood of adults with ASD.

Methods
We recruited an RNA-seq cohort (ASD vs. control; n = 6 each) and a replication cohort (ASD vs. control; n = 19 each) and conducted RNA-seq to explore changes in global gene expression. We then subjected the significantly up- and downregulated genes to gene ontology (GO) and core analyses. Weighted gene correlation network analysis (WGCNA) was performed with all 11,617 genes detected in RNA-seq to identify the ASD-specific gene network.

Results
In total, 117 significantly up- and 83 significantly downregulated genes were detected in the ASD compared with the control group, respectively (p < 0.05 and q < 0.05). GO analysis revealed that the aberrant innate and adaptive immunity were more obvious in the 117 upregulated than in the 83 downregulated genes. WGCNA with core analysis revealed that one module including many immune-related genes was associated with the natural killer cell signaling pathway. In the results for the replication cohort, significant changes with same trend found in RNA-seq data were confirmed for MAFB (p = 0.046), RPSAP58 (p = 0.030), and G2MK (p = 0.004).

Limitations
The sample size was relatively small in both the RNA-seq and replication cohorts. This study examined the mRNA expression level, so the interaction between mRNA and protein remains unclear. The expression changes between children and adults with ASD were not compared because only adults with ASD were targeted.

Conclusions
The dysregulated gene expressions confirmed in the blood of adults with ASD were relevant to the dysfunction of innate and adaptive immunity. These findings may aid in understanding the pathogenesis of ASD.
Acute high-grade acromioclavicular joint dislocation patients treated with titanium cable insertion under a homemade guider
Authors: Wang Jun , Cui Yongfeng , Zhang Yuhang , Yin Hang 
Published: April 2021

Abstract
Backgrounds
To describe a new technique for implanting a double-bundle titanium cable to treat acromioclavicular (AC) joint dislocation via the new guider, and evaluate clinic outcomes.

Methods
A retrospective study of patients treated for acute high-grade acromioclavicular joint dislocation from June 2016 to January 2020 in our trauma center, twenty patients with AC joint dislocation were managed with double-bundle titanium cable. It includes the following steps: (1) Put the guider under the coracoid close to the cortical; (2) drill proximal clavicle; (3) place the titanium cable; (4) perforate distal clavicle, (5) reset the acromioclavicular joint and lock titanium cable; and (6) suture the acromioclavicular ligament. An independent reviewer conducted functional testing of these patients, including the use of coracoclavicular distance (CCD), visual analog scale (VAS) scores, and Constant–Murley scores (CMS).

Results
All patients are presented following at a median duration of 15 months (12-24months) after the surgery. All patients based on X-ray evaluation and clinic evaluation. The median CCD was 7.5 (6–14) mm, the VAS score was 0.55 (0-2), the CMS score was 95.5 (92-99). One patient had subluxation again at the final follow-up based on X-ray examination.

Conclusions
This study demonstrates that the AC joint fixation anatomically with double-bundle titanium, acquired excellent outcomes in terms of the recovery of shoulder joint function and radiographic outcomes. It has a low complication rate and need not remove the hardware.
Five semi analytical and numerical simulations for the fractional nonlinear space-time telegraph equation
Authors: Khater Mostafa M. A. , Park Choonkil , Lee Jung Rye , Mohamed Mohamed S. , Attia Raghda A. M. 
Published: April 2021

AbstractThe accuracy of analytical obtained solutions of the fractional nonlinear space–time telegraph equation that has been constructed in (Hamed and Khater in J. Math., 2020) is checked through five recent semi-analytical and numerical techniques. Adomian decomposition (AD), El Kalla (EK), cubic B-spline (CBS), extended cubic B-spline (ECBS), and exponential cubic B-spline (ExCBS) schemes are used to explain the matching between analytical and approximate solutions, which shows the accuracy of constructed traveling wave solutions. In 1880, Oliver Heaviside derived the considered model to describe the cutting-edge or voltage of an electrified transmission. The matching between solutions has been explained by plotting them in some different sketches.
The impact of central foveal thickness and integrity of the outer retinal layers in the visual outcome of uveitic macular edema
Authors: Alvarez-Guzman Carlos , Bustamante-Arias Andres , Colorado-Zavala Maria F. , Rodriguez-Garcia Alejandro 
Published: April 2021

Abstract
Background
To analyze the relationship between the central foveal thickness (CFT) and the integrity of the ellipsoid portion of inner segments (EPIS) and interdigitating zone (IZ) retinal layers in the visual outcome of uveitic macular edema (UME).

Methods
Prospective, observational, and cross-sectional study of eyes with UME. Spectral-domain optical coherence tomography (SD-OCT) macular morphological pattern, CFT, and integrity of the outer retinal layers were analyzed. We arranged the data by EPIS or IZ integrity and contrasted it with student t-test (quantitative variables) and Fisher exact test or χ² distribution (categorical variables) to evaluate visual impairment and retinal measures. Receiver operator curve (ROC) estimation and logistic regression (probit) assessed if the sample´s variance could be associated with IZ or EPIS integrity.

Results
We included 145 SD-OCT macular scans from 45 patients at different stages of UME. Cystoid macular edema (CME) increased the risk of severe (P ≤ 0.0162) and moderate visual loss (P ≤ 0.0032). The highest CFT values occurred in patients with moderate (478.11 ± 167.62 μm) and severe (449.4 ± 224.86 μm) visual loss. Of all morphological patterns of macular edema, only CME showed a statistically significant relationship with severe visual impairment (44.92%, p = 0.0035, OR 4.29 [1.62–11.4]). Likewise, an increased probability of severe visual loss correlated negatively with both, IZ (37.93%, P ≤ 0.001, OR 10.02) and EPIS (38.98%, P ≤ 0.001, OR 13.1) disruption. A CFT > 337 μm showed a higher probability of IZ (AUROC = 0.7341, SEN 77.59%, ESP 65.52) and EPIS (AUROC = 0.7489, SEN 76.37%, ESP 65.12%) loss of integrity. Moreover, when BCVA reached 0.44 LogMAR (≤ 20/50 Snellen eq.), it was more likely to have IZ (AUROC = 0.8706, ESP 88.51%, SEN 77.59%) and EPIS (AUROC = 0.8898, ESP 88.3%, SEN 76.27) disruption.

Conclusions
Significantly increased CFT has a higher probability for EPIS and IZ disruption, which significantly increases the risk for irreversible visual loss in eyes with UME. Evaluating these layers’ integrity by optical coherence tomography helps predict the visual outcome and make the right therapeutic decisions.
Trial registration The study was registered on April 13, 2020, at the Instituto Tecnologico y de Estudios Superiores de Monterrey Research Committee (License No. COFEPRIS 20 CI 19 039 002), project registration No. P000338-CAVICaREMU-CI-CR002, and the Ethics Committee (License No. CONBIOETICA 19 CEI 011-2016-10-17), project registration No. P000338-CAVICaREMU-CEIC-CR002
TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors
Authors: Tagawa Scott T. , Balar Arjun V. , Petrylak Daniel P. , Kalebasty Arash Rezazadeh , Loriot Yohann , Fléchon Aude , Jain Rohit K. , Agarwal Neeraj , Bupathi Manojkumar , Barthelemy Philippe , Beuzeboc Philippe , Palmbos Phillip , Kyriakopoulos Christos E. , Pouessel Damien , Sternberg Cora N. , Hong Quan , Goswami Trishna , Itri Loretta M. , Grivas Petros 
Published: April 2021

PURPOSE Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC. METHODS TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973 ) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety. RESULTS Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade ≥ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events. CONCLUSION SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population.
On quarks and the origin of QCD: Partons and baryons from intrinsic states
Authors: Trinhammer Ole L. 
Published: April 2021

Abstract
We create quarks from baryons in stead of constituting baryons from quarks. The quantum fields of QCD are generated via the exterior derivative (momentum form) of baryon wave functions on an intrinsic configuration space, the Lie group U(3). Local gauge transformations correspond to coordinate translations in the intrinsic space. A proton spin structure function and a proton magnetic moment are derived. We show how the spectrum of unflavoured baryons, the N and Delta resonances, can be understood from a mass Hamiltonian on the intrinsic space and note how our model resolves the problem of colour confinement. We calculate an approximate value for the relative neutron-to-proton mass shift and give an exact value for the neutron mass. We predict neutral charge singlets that may be interpreted as neutral pentaquarks at LHCb.
The Effect of Chloroacetophenone on the Inducing Capacity of Hensen’s Node
Authors: Lakshmi M. S. 
Published: April 2021

ABSTRACT
The effect of chloroacetophenone at concentrations of 0·0005 M, 0·001 M, and 0·0015 M on the capacity of induction of Hensen’s node has been studied. A fall in the percentage of induction with increase of concentration of CAP is seen. A qualitative fall of induction is also observed as evidenced by a reduction in the number of strong inductions and increase in cases of absence of induction with increase of concentration from 0·0005 M to 0·0015 M. There were no strong inductions after 0·0015 M CAP treatment.
Identification of dividing, determined sensory neuron precursors in the mammalian neural crest
Authors: Greenwood Amy L. , Turner Eric E. , Anderson David J. 
Published: April 2021

Abstract
Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo.
Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling
Authors: Chen Yang , Cardinaux Jean-René , Goodman Richard H. , Smolik Sarah M. 
Published: April 2021

Abstract
Hedgehog (HH) is an important morphogen involved in pattern formation during Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a transcription factor responsible for transducing the hh signal in the nucleus and activating hh target gene expression. Previous studies have shown that CI exists in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form. The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression. In this paper, we demonstrate that the exogenous expression of CI that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression of wingless (wg) in vivo and a phenotype consistent with wg overexpression. Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and restore wg expression in hh mutant embryos. When PKA activity is suppressed by expressing a dominant negative PKA mutant, the exogenous expression of CI(wt) results in overexpression of wg and lethality in embryogenesis, defects that are similar to those caused by the exogenous expression of CI(m1-4). In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI. We also show that PKA directly phosphorylates the four consensus phosphorylation sites in vitro. Taken together, our results suggest that positive hh and negative PKA regulation of wg gene expression converge on the regulation of CI phosphorylation.
Refined analysis of early symbiotic steps of the Rhizobium-Medicago interaction in relationship with microtubular cytoskeleton rearrangements
Authors: Timmers Antonius C. J. , Auriac Marie-Christine , Truchet Georges 
Published: April 2021

Abstract
In situ immunolocalization of tubulin revealed that important rearrangements occur during all the early symbiotic steps in the Medicago/R. meliloti symbiotic interaction. Microtubular cytoskeleton (MtC) reorganizations were observed in inner tissues, first in the pericycle and then in the inner cortex where the nodule primordium forms. Subsequently, major MtC changes occurred in outer tissues, associated with root hair activation and curling, the formation of preinfection threads (PITs) and the initiation and the growth of an infection network. From the observed sequence of MtC changes, we propose a model which aims to better define, at the histological level, the timing of the early symbiotic stages. This model suggests the existence of two opposite gradients of cell differentiation controlling respectively the formation of division centers in the inner cortex and plant preparation for infection. It implies that (i) MtC rearrangements occur in pericycle and inner cortex earlier than in the root hair, (ii) the infection process proceeds prior to the formation of the nodule meristem, (iii) the initial primordium prefigures the future zone II of the mature nodule and (iv) the nodule meristem derives from the nodule primordium. Finally, our data also strongly suggest that in alfalfa PIT differentiation, a stage essential for successful infection, requires complementary signaling additional to Nod factors.