bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-Class Anti-immunoglobulin–like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors
Authors: Siu Lillian L. , Wang Ding , Hilton John , Geva Ravit , Rasco Drew , Perets Ruth , Abraham Anson K. , Wilson Douglas C. , Markensohn Julia F. , Lunceford Jared , Suttner Leah , Siddiqi Shabana , Altura Rachel A. , Maurice-Dror Corinne 
Published: October 2021

Abstract

Purpose:
In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab.

Patients and Methods:
Patients with histologically/cytologically confirmed advanced solid tumors, measurable disease by RECIST v1.1, and evaluable baseline tumor sample received escalating doses of intravenous MK-4830 every 3 weeks as monotherapy (parts A and B) and in combination with pembrolizumab (part C). Safety and tolerability were the primary objectives. Pharmacokinetics, objective response rate per RECIST v1.1, and molecular biomarkers were also evaluated.

Results:
Of 84 patients, 50 received monotherapy and 34 received combination therapy. No dose-limiting toxicities were observed; maximum tolerated dose was not reached. MK-4830 showed dose-related target engagement. Eleven of 34 patients in the dose-escalation phase who received combination therapy achieved objective responses; 5 previously had progressive disease on anti–PD-1/PD-L1 therapies. Exploratory evaluation of the association between response and pretreatment gene expression related to interferon-gamma signaling in tumors suggested higher sensitivity to T-cell inflammation with combination therapy than historically expected with pembrolizumab monotherapy, with greater response at more moderate levels of inflammation.

Conclusions:
This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid-suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti–PD-1/PD-L1 agent.
The Rhetoric of Digital Presentation Tools in Politics: The Case of Visual Knowledge in President Obama's Enhanced State Of the Union
Authors: Kjeldsen Jens E. 
Published: October 2021

Abstract
President Barack Obama's State of the Union speeches were distributed online as so–called Enhanced versions, where the television images of Obama delivering the speech were accompanied by pictures, graphs, and tables used to convince the audience about the factual state of affairs in the United States. The article explores this combination of the rhetoric and epistemology of visuality and information design on the one hand and political oratory on the other. The article demonstrates how the Enhanced State of the Union is a hybrid genre using visuals to create a rhetoric of reification and reality, apparently aiming not to argue but only to establish facts.
A geno-clinical decision model for the diagnosis of myelodysplastic syndromes
Authors: Radakovich Nathan , Meggendorfer Manja , Malcovati Luca , Hilton C. Beau , Sekeres Mikkael A. , Shreve Jacob , Rouphail Yazan , Walter Wencke , Hutter Stephan , Galli Anna , Pozzi Sara , Elena Chiara , Padron Eric , Savona Michael R. , Gerds Aaron T. , Mukherjee Sudipto , Nagata Yasunobu , Komrokji Rami S. , Jha Babal K. , Haferlach Claudia , Maciejewski Jaroslaw P. , Haferlach Torsten , Nazha Aziz 
Published: October 2021

Abstract
The differential diagnosis of myeloid malignancies is challenging and subject to interobserver variability. We used clinical and next-generation sequencing (NGS) data to develop a machine learning model for the diagnosis of myeloid malignancies independent of bone marrow biopsy data based on a 3-institution, international cohort of patients. The model achieves high performance, with model interpretations indicating that it relies on factors similar to those used by clinicians. In addition, we describe associations between NGS findings and clinically important phenotypes and introduce the use of machine learning algorithms to elucidate clinicogenomic relationships.
Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers
Authors: Rodríguez Marta , Alonso-Alonso Ruth , Tomás-Roca Laura , Rodríguez-Pinilla Socorro M. , Manso-Alonso Rebeca , Cereceda Laura , Borregón Jennifer , Villaescusa Teresa , Córdoba Raúl , Sánchez-Beato Margarita , Fernández-Miranda Ismael , Betancor Isabel , Bárcena Carmen , García Juan F. , Mollejo Manuela , García-Cosio Mónica , Martin-Acosta Paloma , Climent Fina , Caballero Dolores , de la Fuente Lorena , Mínguez Pablo , Kessler Linda , Scholz Catherine , Gualberto Antonio , Mondéjar Rufino , Piris Miguel A. 
Published: October 2021

Abstract
Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P &lt; .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.
TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders
Authors: Merli Pietro , Pagliara Daria , Galaverna Federica , Li Pira Giuseppina , Andreani Marco , Leone Giovanna , Amodio Donato , Pinto Rita Maria , Bertaina Alice , Bertaina Valentina , Mastronuzzi Angela , Strocchio Luisa , Boccieri Emilia , Pende Daniela , Falco Michela , Di Nardo Matteo , Del Bufalo Francesca , Algeri Mattia , Locatelli Franco 
Published: October 2021

Abstract
Several nonmalignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders, or metabolic diseases, lacking a fully matched donor or requiring urgent transplantation underwent TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study. The median age at transplant was 3.5 years (range 0.3-16.1); the median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (eg, aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/recent infections at the time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade 1-2 acute GVHD was 14.4% (no patient developed grade 3-4 acute GVHD). Only one patient at risk developed mild chronic GVHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment of children with NMDs. Prompt donor availability, low incidence of GVHD, and TRM make this strategy an attractive option in NMDs patients. The study is registered at ClinicalTrial.gov as NCT01810120.
Anticoagulant therapy in patients with congenital FXI deficiency
Authors: Bravo-Pérez Carlos , Serna María Jose , Esteban Julio , Fernandez-Mellid Eugenia , Fontanes-Trabazo Emilia , Lorenzo Alvaro , Calviño-Suárez Michael , Miñano Antonia , Padilla José , Roldán Vanessa , Vicente Vicente , Corral Javier , de la Morena-Barrio María Eugenia 
Published: October 2021

Abstract
The bleeding phenotype of factor XI (FXI) deficiency is unpredictable. Bleeding is usually mild and mostly occurs after injury. Although FXI deficiency renders antithrombotic protection, some patients might eventually develop thrombosis or atrial fibrillation, requiring anticoagulant therapy. There is almost no evidence on the bleeding risk in this scenario. Our retrospective study of 269 white FXI-deficient subjects (1995-2021) identified 15 cases requiring anticoagulation. They harbored 8 different F11 variants, mainly in heterozygosis (1 case was homozygote), and had mild to moderate deficiency (FXI:C: 20% to 70%). Two subjects (13.3%) had bleeding history before anticoagulation. Atrial fibrillation was the main indication (12/15; 80%). Fourteen patients started therapy with vitamin K antagonists (VKA), but 4 subjects were on direct oral anticoagulants (DOACs) at the end of follow-up. Over &gt;1000 months of anticoagulation, 2 mild bleeding episodes in 2 patients (13.3%, 95% confidence interval: 3.7% to 37.9%) were recorded. No major/fatal events were reported. “Pre-post” bleeding localization and severity did not change despite treatment. On VKA, drug dosing and management were also standard, unaltered by FXI deficiency. We provide the largest description of anticoagulant use in FXI deficiency, and the first cases receiving DOACs. Although further studies are needed, our observations suggest that moderate FXI deficiency does not interfere with anticoagulant management nor bleeding risk.
Book reviews in the age of social media
Authors: Johnson Norman A. 
Published: October 2021

AbstractDespite the large quantity and wide variety of popular science books available in biology, most undergraduate biology majors seldom read full-length books outside of class. To ensure that the students in my Writing in Biology class are exposed to such books, I assign a book review essay and provide an annotated list of a few dozen books in genetics, evolution, and other areas of biology. The assignment also includes a section on the book author’s style, in which students use material discussed earlier in the class. Informal presentations of the books provide opportunities for various discussions. The assignment (including the list of books) is included in an Additional file 1.
Evaluation of selected carotenoids of Lycopersicon esculentum variants as therapeutic targets for ‘Alzheimer’s disease: an in silico approach
Authors: Bakare Olalekan Olanrewaju , Fadaka Adewale Oluwaseun , Akanbi Musa Oyebowale , Akinyede Kolajo Adedamola , Klein Ashwil , Keyster Marshall 
Published: October 2021

AbstractThe seriousness and menace of the worldwide weight of ‘Alzheimer’s disease have been related to a few factors, which incorporate antioxidant system depletion, mutation of proteins, and high expression of cholinesterases due to aging, environmental influence, diet, infectious agents, and hormonal imbalance. Overexpression of cholinesterases has been emphatically connected to ‘Alzheimer’s disease because of the unreasonable hydrolysis of acetylcholine and butyrylcholine. Certain plant phytochemicals, for example, beta-carotenoids, lutein, neoxanthin, and viola-xanthine fromLycopersicon esculentumMill. Var. esculentum (ESC) andLycopersicon esculentumMill. Var. cerasiforme (CER) has been utilized altogether as a therapeutic candidate for the treatment of ‘Alzheimer’s disease. Therefore, this research sought to investigate the drug-likeness of the individual carotenoids as detailed for cholinesterase inhibition in the treatment of ‘Alzheimer’s disease. Four potential cholinesterase inhibitors from ESC and CER were retrieved from the PubChem database. Investigation of their drug-likeness, toxicity prediction, molecular docking, and dynamic simulations were carried out using Molinspiration, PreADMET V.2.0, Patchdock server, and Schrodinger Maestro software respectively. Neoxanthin was ranked the safest with a greater tendency to inhibit the cholinesterases with high binding affinity. In addition, its stability after simulation in a mimicked biological environment suggests its relevance as a potential drug candidate for the treatment of ‘Alzheimer’s disease through the inhibition of cholinesterases.
Association between serum alanine and aspartate aminotransferase and blood pressure: a cross-sectional study of Chinese freshmen
Authors: Zhu Lijun , Fang Zhengmei , Jin Yuelong , Chang Weiwei , Huang Mengyun , He Lianping , Chen Yan , Yao Yingshui 
Published: October 2021

Abstract
Background
High blood pressure is a well-recognized risk factor for cardiovascular events, and the incidence of hypertension is increasing among young people. This study investigated the relationship between ALT and AST levels and hypertension among freshmen in China.

Methods
This cross-sectional study was conducted in the Anhui Province from September to November 2018. A total of 3114 freshmen underwent a physical examination including testing of biochemical indicators and a standardized questionnaire.

Results
The overall prevalence of elevated ALT and AST were 6.8% and 2.3% among freshmen. The mean ALT and AST levels were higher in males (22.59 ± 21.98 vs.12.62 ± 10.30 U/L; 23.55 ± 12.24 vs. 20.02 ± 5.75 U/L, respectively). The prevalence of hypertension was significantly higher in men (16.1%) than in women (1.9%). The mean values of BMI, SBP, DBP, TC, TG, and LDL-C were found to be increased with elevated levels of serum ALT and AST in the quartiles (P for trend < 0.05). After adjusting for covariates, the risk of hypertension was significantly higher in the highest ALT quartile than in the lowest quartile (OR (95% CI) of 1.681 (1.028, 2.751) in males; 2.802 (1.102, 7.124) in females). A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders only in total population and females (P for trend < 0.05).

Conclusions
These findings suggest that ALT level is significantly associated with hypertension both in male and female freshmen.
Operationalizing respectful maternity care at the healthcare provider level: a systematic scoping review
Authors: Jolivet R. Rima , Gausman Jewel , Kapoor Neena , Langer Ana , Sharma Jigyasa , Semrau Katherine E. A. 
Published: October 2021

Abstract
Background
Ensuring the right to respectful care for maternal and newborn health, a critical dimension of quality and acceptability, requires meeting standards for Respectful Maternity Care (RMC). Absence of mistreatment does not constitute RMC. Evidence generation to inform definitional standards for RMC is in an early stage. The aim of this systematic review is clear provider-level operationalization of key RMC principles, to facilitate their consistent implementation.

Methods
Two rights-based frameworks define the underlying principles of RMC. A qualitative synthesis of both frameworks resulted in seven fundamental rights during childbirth that form the foundation of RMC. To codify operational definitions for these key elements of RMC at the healthcare provider level, we systematically reviewed peer-reviewed literature, grey literature, white papers, and seminal documents on RMC. We focused on literature describing RMC in the affirmative rather than mistreatment experienced by women during childbirth, and operationalized RMC by describing objective provider-level behaviors.

Results
Through a systematic review, 514 records (peer-reviewed articles, reports, and guidelines) were assessed to identify operational definitions of RMC grounded in those rights. After screening and review, 54 records were included in the qualitative synthesis and mapped to the seven RMC rights. The majority of articles provided guidance on operationalization of rights to freedom from harm and ill treatment; dignity and respect; information and informed consent; privacy and confidentiality; and timely healthcare. Only a quarter of articles mentioned concrete or affirmative actions to operationalize the right to non-discrimination, equality and equitable care; less than 15%, the right to liberty and freedom from coercion. Provider behaviors mentioned in the literature aligned overall with seven RMC principles; yet the smaller number of available research studies that included operationalized definitions for some key elements of RMC illustrates the nascent stage of evidence-generation in this area.

Conclusions
Lack of systematic codification, grounded in empirical evidence, of operational definitions for RMC at the provider level has limited the study, design, implementation, and comparative assessment of respectful care. This qualitative systematic review provides a foundation for maternity healthcare professional policy, training, programming, research, and program evaluation aimed at studying and improving RMC at the provider level.
Effect of stereotactic body radiotherapy on regional metabolic liver function investigated in patients by dynamic [18F]FDGal PET/CT
Authors: Sørensen Michael , Fode Mette Marie , Petersen Jørgen Baltzer , Holt Marianne Ingerslev , Høyer Morten 
Published: October 2021

Abstract
Purpose
Stereotactic body radiotherapy (SBRT) is increasingly used for treatment of liver tumors but the effect on metabolic liver function in surrounding tissue is largely unknown. Using 2-deoxy-2-[18F]fluoro-d-galactose ([18F]FDGal) positron emission tomography (PET)/computed tomography (CT), we aimed to determine a dose–response relationship between radiation dose and metabolic liver function as well as recovery.
Procedures.
One male subject with intrahepatic cholangiocarcinoma and five subjects (1 female, 4 male) with liver metastases from colorectal cancer (mCRC) underwent [18F]FDGal PET/CT before SBRT and after 1 and 3 months. The dose response was calculated using the data after 1 month and the relative recovery was evaluated after 3 months. All patients had normal liver function at time of inclusion.

Results
A linear dose–response relationship for the individual liver voxel dose was seen until approximately 30 Gy. By fitting a polynomial curve to data, a mean TD50 of 18 Gy was determined with a 95% CI from 12 to 26 Gy. After 3 months, a substantial recovery was observed except in tissue receiving more than 25 Gy.

Conclusions
[18F]FDGal PET/CT makes it possible to determine a dose–response relationship between radiation dose and metabolic liver function, here with a TD50 of 18 Gy (95% CI 12–26 Gy). Moreover, the method makes it possible to estimate metabolic recovery in liver tissue.
A randomised controlled trial of a family-group cognitive-behavioural (FGCB) preventive intervention for the children of parents with depression: short-term effects on symptoms and possible mechanisms
Authors: Löchner Johanna , Starman-Wöhrle Kornelija , Takano Keisuke , Engelmann Lina , Voggt Alessandra , Loy Fabian , Bley Mirjam , Winogradow Dana , Hämmerle Stephanie , Neumeier Esther , Wermuth Inga , Schmitt Katharina , Oort Frans , Schulte-Körne Gerd , Platt Belinda 
Published: October 2021

Abstract
Objective
Parental depression is one of the biggest risk factors for youth depression. This parallel randomized controlled trial evaluates the effectiveness of the German version of the family-group-cognitive-behavioral (FGCB) preventive intervention for children of depressed parents.

Methods
Families with (i) a parent who has experienced depression and (ii) a healthy child aged 8–17 years (mean = 11.63; 53% female) were randomly allocated (blockwise; stratified by child age and parental depression) to the 12-session intervention (EG; n = 50) or no intervention (CG; usual care; n = 50). Self-reported (unblinded) outcomes were assessed immediately after the intervention (6 months). We hypothesized that CG children would show a greater increase in self-reported symptoms of depression (DIKJ) and internalising/externalising disorder (YSR/CBCL) over time compared to the EG. Intervention effects on secondary outcome variables emotion regulation (FEEL-KJ), attributional style (ASF-KJ), knowledge of depression and parenting style (ESI) were also expected. Study protocol (Belinda Platt, Pietsch, Krick, Oort, & Schulte-Körne, 2014) and trial registration (NCT02115880) reported elsewhere.

Results
We found significant intervention effects on self-reported internalising ($$\eta_{p}^{2}$$

η

p

2

= 0.05) and externalising ($$\eta_{p}^{2}$$

η

p

2

= 0.08) symptoms but did not detect depressive symptoms or parent-reported psychopathology. Parental depression severity did not modify these effects. Both groups showed equally improved knowledge of depression ($$\eta_{p}^{2}$$

η

p

2

= 0.06). There were no intervention effects on emotion regulation, attributional style or parenting style.

Conclusion
The German version of the FGCB intervention is effective in reducing symptoms of general psychopathology. There was no evidence that the mechanisms targeted in the intervention changed within the intervention period.