bluuebunny/crossref_metadata_2025_split huggingface dataset:
Big Health Data Research and Group Harm: The Scope of IRB Review
Authors: Doerr Megan , Meeder Sara 
Published: July 2022

ABSTRACTMuch of precision medicine is driven by big health data research—the analysis of massive datasets representing the complex web of genetic, behavioral, environmental, and other factors that impact human well‐being. There are some who point to the Common Rule, the regulation governing federally funded human subjects research, as a regulatory panacea for all types of big health data research. But how well does the Common Rule fit the regulatory needs of this type of research? This article suggests that harms that may arise from artificial intelligence and machine‐learning technologies used in big health data research—and the increased likelihood that this research will affect public policy—mean it is time to consider whether the current human research regulations prohibit comprehensive, ethical review of big health data research that may result in group harm.
Developing and Implementing Electronic Consent Procedures in Response to Covid‐19 Restrictions
Authors: Bromberg Julie R. , Nimaja Evelyn , Kiragu Andrew W. , Lawson Karla A. , Lee Lois , Nasr Isam W. , Pruitt Charles , Ruest Stephanie M. , Mello Michael J. 
Published: July 2022

ABSTRACTThe Covid‐19 pandemic resulted in unprecedented restrictions on many public, private, and workplace activities throughout the United States and elsewhere. When restrictions were imposed, we were conducting a type III hybrid effectiveness‐implementation trial in 10 pediatric trauma centers. In response to several pandemic‐based restrictions, we had to develop procedures for engaging with potential research participants while limiting nonclinical, in‐person interactions. This manuscript describes the procedures and challenges of obtaining electronic informed consent and assent in a multisite trauma center‐based research study. We developed, tested, and trained staff to implement three options for obtaining informed consent. Twenty‐five participants were enrolled in the effectiveness‐implementation multisite trial during the first six months of utilization of the consent options, with eleven of these individuals enrolled using hybrid or electronic consent procedures. The challenges we identified involving electronic consent procedures included confusion over who would complete the electronic consent process and difficulties reconnecting with families. Lessons learned can strengthen electronic consent and assent procedures for future studies. More research is needed to further strengthen this process and increase its utilization.
How intensive revegetation affects runoff in semiarid watersheds: A case study based on an integrated modelling framework
Authors: Chang Yiming , Lei Huimin 
Published: July 2022

AbstractRevegetation projects are beneficial measures used to control soil erosion, though they can adversely affect the water yield of semiarid watersheds. In this study, Dali River basin that is a semiarid basin with intensive ecological restoration strategies on the Loess Plateau of China was selected as an extreme condition to examine how revegetation projects affect watershed runoff. In the study watershed, the vegetation indicator Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Total Vegetation Index (SATVI) increased by 6.9% and 189.1% after 2000, respectively. Human activities contributed most to vegetation increase (77.1% for NDVI and 98.6% for SATVI). We quantified the response of runoff change to revegetation within a physically based modelling framework that incorporated the effects of check‐dam construction and was constrained by the observed runoff data. The results showed that revegetation explained 29.2% of the runoff decrease in the impact period 2 (2000–2010), but its contribution was lower than that of check‐dam construction (75.2%). Compared with climatic factors, implementation of the two ecological restoration projects was the dominant driver of runoff reduction after 2000. This study demonstrates the importance of attribution analysis in an integrated modelling framework with revegetation and other ecological restoration projects and constrained by the observed runoff data.
Pleistocene glacial and interglacial ecosystems inferred from ancient DNA analyses of permafrost sediments from Batagay megaslump, East Siberia
Authors: Courtin Jérémy , Perfumo Amedea , Andreev Andrei A. , Opel Thomas , Stoof‐Leichsenring Kathleen R. , Edwards Mary E. , Murton Julian B. , Herzschuh Ulrike 
Published: July 2022

AbstractPronounced glacial and interglacial climate cycles characterized northern ecosystems during the Pleistocene. Our understanding of the resultant community transformations and past ecological interactions strongly depends on the taxa found in fossil assemblages. Here, we present a shotgun metagenomic analysis of sedimentary ancient DNA (sedaDNA) to infer past ecosystem‐wide biotic composition (from viruses to megaherbivores) from the Middle and Late Pleistocene at the Batagay megaslump, East Siberia. The shotgun DNA records of past vegetation composition largely agree with pollen and plant metabarcoding data from the same samples. Interglacial ecosystems at Batagay attributed to Marine Isotope Stage (MIS) 17 and MIS 7 were characterized by forested vegetation (Pinus, Betula, Alnus) and open grassland. The microbial and fungal communities indicate strong activity related to soil decomposition, especially during MIS17. The local landscape likely featured more open, herb‐dominated areas, and the vegetation mosaic supported birds and small omnivorous mammals. Parts of the area were intermittently/partially flooded as suggested by the presence of water‐dependent taxa. During MIS 3, the sampled ecosystems are identified as cold‐temperate, periodically flooded grassland. Diverse megafauna (Mammuthus, Equus, Coelodonta) coexisted with small mammals (rodents). The MIS 2 ecosystems existed under harsher conditions, as suggested by the presence of cold‐adapted herbaceous taxa. Typical Pleistocene megafauna still inhabited the area. The new approach, in which shotgun sequencing is supported by metabarcoding and pollen data, enables the investigation of community composition changes across a broad range of taxonomic groups and inferences about trophic interactions and aspects of soil microbial ecology.
An Isolable Phosphaborene Stabilized by an Intramolecular Lewis Base
Authors: Li Jiancheng , Mei Yanbo , Liu Liu Leo 
Published: July 2022

AbstractPhosphaborenes are P/B analogs of alkynes. Herein, we describe the isolation of a phosphaborene stabilized by an intramolecular Lewis base. This species is achieved via the installation of the phosphaborene with a sterically encumbering phosphino substituent. Although this species features an aromatic P2B three‐membered ring, the ring strain allows the hemi‐labile behavior of the P−B donor‐acceptor bond, thereby exhibiting frustrated Lewis pair reactivity. Our finding paves the way for further exploration of the reactivity patterns of monomeric phosphaborenes.
A UV‐C LED‐based unit for continuous decontamination of the sheath fluid in a flow‐cytometric cell sorter
Authors: Kirsch Jenny , Heinrich Kerstin , Kage Daniel , Glaab Johannes , Grothe Benjamin , Volkmann Konrad v. , Kaiser Toralf 
Published: July 2022

AbstractAseptic cell sorting is challenging, especially when a flow‐cytometric cell sorter is not operated in a sterile environment. The sheath fluid system of a cell sorter may be contaminated with germs such as bacteria, yeasts, viruses, or fungi. Thus, a regular chemical cleaning procedure is required to prepare a sorter for aseptic cell sorting by flushing the fluidic system. However, this procedure is time consuming, and most importantly, the researcher can never be sure that the cleaning process was successful. Here we present a method in which the sheath fluid of a cell sorter was decontaminated by irradiation with UV‐C light using a flow‐through principle. Using this principle, we were able to achieve a 5 log reduction of bacteria in the sheath fluid.
The political economy of China's GMO commercialization dilemma
Authors: Xiao Zhihua , Kerr William A. 
Published: July 2022

AbstractWhy has China delayed commercialization of genetically modified (GM) crops over the last decade given its heavy public R&D investment in biotechnology and maturing GM capacity? Further, imports of GM products for consumption are allowed while similar domestic GM‐crops cannot be commercialized. The paper analyzes, from a political economy perspective, how the delay of commercialization arises from the government balancing interests and conflicts among vested interests to keep social stability based on comprehensive secondary data and unique primary survey data. Anti‐GMO activists have, over time, been able to shape the public perception of biotechnology. Their efforts have garnered widespread acceptance among interest groups and have been sufficient to raise the specter of underlying social instability, which is always near the top of mind for China's government. As a result, no movement on commercialization has been made since 2010—more than a decade ago. The failure to commercialize is important because food production would increase considerably if China were able to commercialize GM crops and the resolution of the biotechnology issue has broad implications for food security.
Prognostic value of computed tomography scan detection of cartilage invasion in advanced laryngeal cancer treated with primary total laryngectomy
Authors: Lee Maxwell Y. , Lee Jonathan , Stock Sarah , Belfiglio Mario , Matia Brian , Koyfman Shlomo , Joshi Nikhil P. , Burkey Brian B. , Lamarre Eric , Prendes Brandon , Scharpf Joseph , Lorenz Robert R. , Woody Neil M. , Adelstein David J. , Geiger Jessica L. , Chute Deborah J. , Ku Jamie A. 
Published: July 2022

AbstractBackgroundWe sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy.MethodsRetrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis.ResultsAssessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease‐free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS.ConclusionGestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.
Mast cells selectively target large cholangiocytes during biliary injury via H2HR‐mediated cAMP/pERK1/2 signaling
Authors: Zhou Tianhao , Meadows Vik , Kundu Debjyoti , Kyritsi Konstantina , Owen Travis , Ceci Ludovica , Carpino Guido , Onori Paolo , Gaudio Eugenio , Wu Nan , Glaser Shannon , Ekser Burcin , Alpini Gianfranco , Kennedy Lindsey , Francis Heather 
Published: July 2022

Abstract
Bile ducts are heterogenous in structure and function, and primary sclerosing cholangitis (PSC) damages specific bile ducts leading to ductular reaction (DR), mast cell (MC) infiltration, increased histamine release, inflammation, and fibrosis. Bile duct ligation (BDL) induces large duct damage via cyclic adenosine monophosphate (cAMP)/extracellular signal‐related protein kinase (ERK) signaling, and large cholangiocytes express H2 histamine receptor (H2HR). We evaluated how MCs interact with large cholangiocytes during cholestasis. Male wild‐type (WT) and MC‐deficient (Kit

W‐sh
) mice 10–12 weeks of age were subjected to BDL for 7 days. Select Kit

W‐sh
mice were injected with MCs pretreated with control or H2HR antagonist (ranitidine, 25 μm, 48 h) via tail vein injection. In vitro, MC migration toward small mouse cholangiocytes (SMCCs) and large mouse cholangiocytes (LMCCs) treated with lipopolysaccharide or histamine (±ranitidine) was measured. LMCCs were stimulated with MC supernatants pretreated with control, α‐methyl‐dl‐histidine (to block histamine release), or ranitidine. Liver damage, large duct DR/senescence, inflammation, fibrosis, and cAMP/ERK immunoreactivity increased in BDL WT and Kit

W‐sh
+MC mice but decreased in BDL Kit

W‐sh
and Kit

W‐sh
+MC‐H2HR mice. In vitro, MCs migrate toward damaged LMCCs (but not SMCCs) blocked by inhibition of H2HR. Loss of MC histamine or MC‐H2HR decreases LMCC proliferation, senescence, H2HR, and cAMP/ERK levels. Human PSC livers have increased MC number found near DR, senescent ducts, and H2HR‐positive ducts. Conclusion: Infiltrating MCs preferentially interact with large ducts via H2HR signaling promoting biliary and liver damage. Mediation of MCs may be a therapeutic strategy for PSC.
A hybrid design for dose‐finding oncology clinical trials
Authors: Liao Jason J. Z. , Zhou Feng , Zhou Heng , Petruzzelli Lilli , Hou Kevin , Asatiani Ekaterine 
Published: July 2022

AbstractIdentifying the maximum tolerated dose (MTD) and recommending a Phase II dose for an investigational treatment is crucial in cancer drug development. A suboptimal dose often leads to a failed late‐stage trial, while an overly toxic dose causes harm to patients. There is a very rich literature on trial designs for dose‐finding oncology clinical trials. We propose a novel hybrid design that maximizes the merits and minimizes the limitations of the existing designs. Building on two existing dose‐finding designs: a model‐assisted design (the modified toxicity probability interval) and a dose‐toxicity model‐based design, a hybrid design of the modified toxicity probability interval design and a dose‐toxicity model such as the logistic regression model is proposed, incorporating optimal properties from these existing approaches. The performance of the hybrid design was tested in a real trial example and through simulation scenarios. The hybrid design controlled the overdosing toxicity well and led to a recommended dose closer to the true MTD due to its ability to calibrate for an intermediate dose. The robust performance of the proposed hybrid design is illustrated through the real trial dataset and simulations. The simulation results demonstrated that the proposed hybrid design can achieve excellent and robust operating characteristics compared to other existing designs and can be an effective model for determining the MTD and recommended Phase II dose in oncology dose‐finding trials. For practical feasibility, an R‐shiny tool was developed and is freely available to guide clinicians in every step of the dose finding process.
σ versus π‐radical: Tuning the electronic nature of neutral carbon (I) compounds with three non‐bonding electrons
Authors: Muhasina Puthan Veetil , Parameswaran Pattiyil 
Published: July 2022

AbstractThe bonding and reactivity of the hypo‐coordinated compounds with one, two, and four non‐bonding electrons namely, carbon‐centered free radical, carbenes, and carbones were well earlier established. Here, we report stability, bonding and reactivity of compounds RCL, where R is one‐electron donor group (R = CH3 (a), CHO (b), and NO2 (c)) and L is two‐electron donor ligand (L = cAAC (1), CO (2), NHC (3) and PMe3 (4)), having three non‐bonding electrons. The ground states of molecules exist in a doublet with a lone pair of electrons and an unpaired electron at the central carbon atom (C1). The spin hops over from π‐ to σ‐type orbitals is observed as the π‐acceptor strength of the donor ligand increases. The replacement of the methyl group by CHO and NO2 indicate that the cAAC and CHO substituted compounds gives a σ‐radical except in compound 2c. These molecules show very high proton affinity and exothermic reaction energy for the hydrogen atom addition indicating dual reactivity namely, radical and lone pair reactivity.
Costs and benefits of cooperative learning as a universal school‐based approach to adolescent substance use prevention
Authors: Van Ryzin Mark J. , Cil Gulcan , Roseth Cary J. 
Published: July 2022

AbstractSubstance use during early adolescence implies a greater likelihood of abuse and dependence in later adolescence or adulthood. In turn, substance abuse and dependence are linked to a variety of maladaptive long‐term health‐related outcomes that imply significant individual and societal costs. In this paper, we evaluated an approach to substance use prevention that relies on the vital role of peers, who comprise a key risk factor for adolescent substance use. This approach (i.e., cooperative learning, CL) focuses on interrupting the process of deviant peer clustering and providing at‐risk youth with the opportunity to build social skills and cultivate friendships with low‐risk youth. In addition to testing the efficacy of CL in reducing the number of students who become regular substance users, we also conducted a cost–benefit analysis. Using four waves of data from a cluster‐randomized trial (N = 15 middle schools, 1890 students, 47.1% female, 75.2% White, 13.9% of students were receiving special education services), we found that significantly lower percentages of students in the intervention (CL) schools became regular users of tobacco, alcohol, and marijuana. We estimated that the reduction in substance use associated with the implementation of CL resulted in total lifetime benefits of between $1027 and $4621 per student (in 2019 dollars), or between $8.79 and $39.54 for each dollar invested in CL. Benefit/cost ratios would go up to $22.54–$101.39 per dollar invested with the continual implementation of CL, assuming retraining every 5 years. Implications and future research directions are discussed.
Assessment of the Effect of Organ Impairment on the Pharmacokinetics of 2′‐MOE and Phosphorothioate Modified Antisense Oligonucleotides
Authors: Wang Yanfeng , Diep John K. , Yu Rosie Z. , Hurh Eunju , Karwatowska‐Prokopczuk Ewa , Schneider Eugene , Henry Scott , Bhanot Sanjay , Geary Richard S. 
Published: July 2022

AbstractThe pharmacokinetics (PK) of 2′‐O‐methoxyethyl and phosphorothioate antisense oligonucleotides (ASOs), with or without N‐acetyl galactosamine conjugation, have been well characterized following subcutaneous or intravenous drug administration. However, the effect of organ impairment on ASO PK, primarily hepatic or renal impairment, has not yet been reported. ASOs distribute extensively to the liver and kidneys, where they are metabolized slowly by endo‐ and exonucleases, with minimal renal excretion as parent drug (<1%–3%). This short review evaluated the effect of organ impairment on ASO PK using 3 case studies: (1) a phase 1 renal impairment study evaluating a N‐acetyl galactosamine–conjugated ASO in healthy study participants and study participants with moderate renal impairment, (2) a phase 2 study evaluating an unconjugated ASO in patients with end‐stage renal disease; and (3) a phase 3 study evaluating an unconjugated ASO, which included patients with mild hepatic or renal impairment. Results showed that patients with end‐stage renal disease had a mild increase (≈34%) in total plasma exposure, whereas mild or moderate renal impairment showed no effect on plasma PK. The effect of hepatic impairment on ASO PK could not be fully evaluated due to lack of data in moderate and severe hepatic impairment study participants. Nonetheless, available data suggest that mild hepatic impairment had no effect on ASO exposure.
Heterogeneous genetic and non‐genetic mechanisms contribute to response and resistance to azacitidine monotherapy
Authors: Symeonidou Vasiliki , Metzner Marlen , Usukhbayar Batchimeg , Jackson Aimee E. , Fox Sonia , Craddock Charles F. , Vyas Paresh 
Published: July 2022

AbstractAcute myeloid leukaemia is prevalent in older patients that are often ineligible for intensive chemotherapy and treatment options remain limited with azacitidine being at the forefront. Azacitidine has been used in the clinic for decades, however, we still lack a complete understanding of the mechanisms by which the drug exerts its anti‐tumour effect. To gain insight into the mechanism of action, we defined the mutational profile of sequential samples of patients treated with azacitidine. We did not identify any mutations that could predict response and observed lack of a uniform pattern of clonal evolution. Focusing on responders, at remission, we observed three types of response: (1) an almost complete elimination of mutations (33%), (2) no change (17%), and (3) change with no discernible pattern (50%). Heterogeneous patterns were also observed at relapse, with no clonal evolution between remission and relapse in some patients. Lack of clonal evolution suggests that non‐genetic mechanisms might be involved. Towards understanding such mechanisms, we investigated the immune microenvironment in a number of patients and we observed lack of a uniform response following therapy. We identified a higher frequency of cytotoxic T cells in responders and higher frequency of naïve helper T cells in non‐responders.
Perceived burden, psychological distress, and quality of life among family caregivers of individuals with schizophrenia
Authors: Ibrahim Norhayati , Ong Hui Chien , Wahab Suzaily , Che Din Normah , Ahmad Mahadir , Amit Noh , Siau Ching Sin , Mohamad Mohd Suhaimi 
Published: July 2022

AbstractThis study assessed the burden, psychological distress and quality of life (QoL) of Malaysian family caregivers of outpatients with schizophrenia. Of the caregivers (N = 200), 49.5% reported a high burden of care. Higher psychological distress and burden correlated with lower QoL. Older, divorced/widowed, and lower educational level caregivers indicated lower physical QoL. Unemployed caregivers indicated lower mental QoL. There is a need to routinely assess these family caregivers for psychological distress and to provide psychoeducation and counseling.
In‐depth evaluation of machine learning methods for semi‐automating article screening in a systematic review of mechanistic literature
Authors: Kebede Mihiretu M. , Le Cornet Charlotte , Fortner Renée Turzanski 
Published: July 2022

AbstractWe aimed to evaluate the performance of supervised machine learning algorithms in predicting articles relevant for full‐text review in a systematic review. Overall, 16,430 manually screened titles/abstracts, including 861 references identified relevant for full‐text review were used for the analysis. Of these, 40% (n = 6573) were sub‐divided for training (70%) and testing (30%) the algorithms. The remaining 60% (n = 9857) were used as a validation set. We evaluated down‐ and up‐sampling methods and compared unigram, bigram, and singular value decomposition (SVD) approaches. For each approach, Naïve Bayes, Support Vector Machines (SVM), regularized logistic regressions, neural networks, random forest, Logit boost, and XGBoost were implemented using simple term frequency or Tf‐Idf feature representations. Performance was evaluated using sensitivity, specificity, precision and area under the Curve. We combined predictions of the best‐performing algorithms (Youden Index ≥0.3 with sensitivity/specificity≥70/60%). In a down‐sample unigram approach, Naïve Bayes, SVM/quanteda text models with Tf‐Idf, and linear SVM e1071 package with Tf‐Idf achieved >90% sensitivity at specificity >65%. Combining the predictions of the 10 best‐performing algorithms improved the performance to reach 95% sensitivity and 64% specificity in the validation set. Crude screening burden was reduced by 61% (5979) (adjusted: 80.3%) with 5% (27) false negativity rate. All the other approaches yielded relatively poorer performances. The down‐sampling unigram approach achieved good performance in our data. Combining the predictions of algorithms improved sensitivity while screening burden was reduced by almost two‐third. Implementing machine learning approaches in title/abstract screening should be investigated further toward refining these tools and automating their implementation.