bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Theory to Practice: Reflections on How We Can Meaningfully Measure Human Rights Impact
Authors: Gubbioni Natalia , Vannucchi Danny 
Published: November 2023

Abstract
What are the biggest challenges and opportunities when an organization is trying to understand the human rights impact it has achieved? Building on more than 12 years combined years of practical evaluation and impact assessment experience across various organizations in the human rights field, the authors reflect on the key lessons learnt while trying to balance organizational needs of reporting, planning, and accountability with the substantive need of understanding how to break down human rights progress and how it happens. Reflections will be articulated in four key challenges, each with practical ideas to build on: the data challenge—what kind of information can give us the most meaningful view of human rights impact; the progress challenge—how we might capture the incremental nature and gradual pace of human rights impact; the target challenge—how best to balance the need to work towards realistic targets with setting an ambitious agenda for change; and finally, the context challenge—how we might compare human rights impact across countries and acknowledge different operating contexts.
Nord-Ost: Russia’s Medical Failure in the 2002 Crisis
Authors: Turner Matthew D , Sapp Jason 
Published: November 2023

ABSTRACT
The 2002 hostage crisis at a Moscow theater transfixed the attention of the world. While the initial assault, led by Spetsnaz commandos, successfully secured the building, the Russian security force’s utter failure at coordinating with medical services led to the preventable deaths of over 100 hostages.
Passive Movements Do Not Appear to Prevent or Reduce Joint Stiffness in Medium to Long-Stay ICU Patients: A Randomized, Controlled, Within-Participant Trial
Authors: Stiller Kathy R. , Dafoe Simone , Jesudason Christabel S. , McDonald Tony M. , Callisto Rocky J. 
Published: November 2023

OBJECTIVES:
ICU patients have an increased risk of joint stiffness because of their critical illness and reduced mobility. There is a paucity of evidence evaluating the efficacy of passive movements (PMs). We investigated whether PMs prevent or reduce joint stiffness in ICU patients.

DESIGN:
A randomized, controlled, within-participant, assessor-blinded study.

SETTING:
A 48-bed tertiary care adult ICU.

PATIENTS:
Intubated patients who were expected to be invasively mechanically ventilated for greater than 48 hours with an ICU length of stay greater than or equal to 5 days, and unable to voluntarily move their limbs through full range of motion (ROM).

INTERVENTIONS:
The ankle and elbow on one side of each participant’s body received PMs (10 min each joint, morning and afternoon, 5 d/wk). The other side acted as the control. The PMs intervention continued for as long as clinically indicated to a maximum of 4 weeks.

MEASUREMENTS:
The primary outcome was ankle dorsiflexion ROM at cessation of PMs. Plantarflexion, elbow flexion and extension ROM, and participant-reported joint pain and stiffness (verbal analog scale [VAS]) were also measured. Outcomes were recorded at baseline and cessation of PMs. For participants whose PMs intervention ceased early due to recovery, additional post-early-cessation of PMs review measurements were undertaken as near as possible to 4 weeks.

MAIN RESULTS:
We analyzed data from 25 participants with a median (interquartile range) ICU stay of 15.6 days (11.3–25.4). The mean (95% CI) between-side difference for dorsiflexion ROM (with knee extension) at cessation of PMs was 0.4 degrees (–4.4 to 5.2; p = 0.882), favoring the intervention side, indicating there was not a clinically meaningful effect of 5 degrees. No statistically significant differences were found between the intervention and control sides for any ROM or VAS data.

CONCLUSIONS:
PMs, as provided to this sample of medium to long-stay ICU patients, did not prevent or reduce joint stiffness.
A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus for Tunisian Adults after Renal Transplantation
Authors: Abderahmene Amani , Francke Marith I. , Andrews Louise M. , Hesselink Dennis A. , Amor Dorra , Sahtout Wissal , Ajmi Marwa , Mastouri Hayfa , Bouslama Ali , Zellama Dorsaf , Omezzine Asma , De Winter Brenda C. M. 
Published: November 2023

Background:
Tacrolimus is the most frequently used immunosuppressive drug for preventing renal rejection. However, its use is hampered by its narrow therapeutic index and large intra and interpatient variability in pharmacokinetics. The objective of this study was to externally validate a tacrolimus population pharmacokinetic model developed for the Dutch population and adjust the model for the Tunisian population for use in predicting the starting dose requirement after kidney transplantation.

Methods:
Data on tacrolimus exposure were obtained from kidney transplant recipients (KTRs) during the first 3 months post-transplantation. External validation of the Dutch model and its adjustment for the Tunisian population was performed using nonlinear mixed-effects modeling.

Results:
In total, 1901 whole-blood predose tacrolimus concentrations from 196 adult KTRs were analyzed. According to a visual predictive check, the Dutch model underestimated the starting dose for the Tunisian adult population. The effects of age, together with the CYP3A5*3 and CYP3A4*22 genotypes on tacrolimus clearance were significantly different in the Tunisian population than in the Dutch population. Based on a bodyweight-based dosing, only 21.9% of tacrolimus concentrations were within the target range, whereas this was estimated to be 54.0% with the newly developed model-based dosing. After adjustment, the model was successfully validated internally in a Tunisian population.

Conclusions:
A starting-dose population pharmacokinetic model of tacrolimus for Tunisian KTRs was developed based on a previously published Dutch model. Using this starting dose could potentially increase the percentage of patients achieving target tacrolimus concentrations after the initial starting dose.
Assessing health care leadership and management for resilience and performance during crisis: The HERO-36
Authors: Atkinson Mariam Krikorian , Biddinger Paul D. , Chughtai Mah-Afroze , Hayirli Tuna C. , Hick John L. , Cagliuso Nicholas V. , Singer Sara J. 
Published: November 2023

Background
Whereas organizational literature has provided much insight into the conceptual and theoretical underpinnings of organizational leadership and management during emergencies, measures to operationalize related effective practices during crises remain sparse.

Purpose
To address this need, we developed the Healthcare Emergency Response Optimization survey, which set out to examine the leadership and management practices in health care organizations that support resilience and performance during crisis.

Methodology
We administered an online survey in April to May 2022 to health care administrators and frontline staff intimately involved in their hospital’s emergency response during the COVID-19 pandemic, which included a sample of 379 respondents across nine rural and urban hospitals (response rate: 44.4%). We used confirmatory factor analysis and quantile regressions to examine the results.

Results
Applying confirmatory factor analysis, we retained 36 items in our survey that comprised eight measures for formal and informal practices to assess crisis leadership and management. To test effectiveness of the specified practices, we regressed self-reported resilience and performance measures on the formality and informality scores. Findings show that informal practices mattered most for resilience, whereas formal practices mattered most for performance. We also identified specific practices (anticipation, transactional and relational interactions, and ad hoc collaborations) for resilience and performance.

Practice Implications
These validated measures of organizational practices assess emergency response during crisis, with an emphasis on the actions and decisions of leadership as well as the management of organizational structures and processes. Organizations using these measures may subsequently modify preparedness and planning approaches to better manage future crises.
Impact of smoking on glaucoma
Authors: Mahmoudinezhad Golnoush , Meller Leo , Moghimi Sasan 
Published: November 2023

Purpose of reviewAssessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation.Recent findingsWhile the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression.SummarySmoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies.
Case Series: Mixed Infectious Keratitis by Pythium insidiosum and Fungal Species
Authors: Singh Nimish Kumar , Barik Manas Ranjan , Das Sujata , Sahu Srikant Kumar , Priyadarshini Smruti Rekha , Sharma Savitri , Sahu Soumya Sucharita , Behera Himansu Sekhar 
Published: November 2023

SIGNIFICANCE
This case series is the first to illustrate mixed infection from Pythium sp. and fungal species in corneal ulcer.

PURPOSE
This case series aimed to alert all toward the possibility of both Pythium sp. and fungal species infection in case of nonresponding corneal ulcer treated with either antifungals or antipythium drugs alone. Increased suspicion of mixed infection in case of nonresponding fungal/Pythium keratitis may facilitate early and prompt management.

CASE REPORTS
Six patients presented with signs of either fungal or Pythium keratitis. They underwent ophthalmological examinations, smear examinations, cultures, and polymerase chain reaction (PCR). Therapeutic penetrating keratoplasty was performed in cases where symptoms worsened after treatment with either antifungal or antipythium drugs. The half corneal button (HCB) was shared for histopathological and microbiological examinations. In the first case, smear examination from corneal scraping (CS) revealed Pythium-like filaments, which were confirmed with PCR; however, Aspergillus nidulans grew in culture. In the second case, iodine–potassium iodide (IKI) staining was positive for Pythium; however, PCR was positive for both Pythium and fungus, which was further confirmed by DNA sequencing. In the third case, IKI staining and HCB were positive for Pythium; however, PCR was positive for fungus, which was identified as Candida saitoana with DNA sequencing. In the fourth case, Pythium grew in the CS culture; however, Candida sp. grew in the HCB culture. In the fifth case, Cladosporium sp. grew in culture from CS; however, Pythium insidiosum grew from the anterior chamber exudate after therapeutic penetrating keratoplasty. In the sixth case, smear examination revealed septate fungal filaments, and Cladosporium sp. grew in culture; however, HCB on histopathological examination showed features of Pythium keratitis.

CONCLUSIONS
In unresponsive cases of Pythium or fungal keratitis, diagnostic modalities such as IKI and PCR should be implemented as a routine practice, in addition to smears and cultures.
Cell-Specific Transposable Element Gene Expression Analysis Identifies Associations with Systemic Lupus Erythematosus Phenotypes
Authors: Cutts Zachary , Patterson Sarah , Maliskova Lenka , Taylor Kimberly E. , Ye Chun , Dall’Era Maria , Yazdany Jinoos , Criswell Lindsey , Fragiadakis Gabriela K. , Langelier Charles , Capra John A. , Sirota Marina , Lanata Cristina M 
Published: November 2023

AbstractThere is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to production of type I IFNs and generation of autoantibodies. We profiled cell-sorted RNA-seq data (CD4+ T cells, CD14+ monocytes, CD19+ B cells, and NK cells) from PBMCs of 120 SLE patients and quantified TE expression identifying 27,135 TEs. We tested for differential TE expression across 10 SLE phenotypes including autoantibody production and disease activity and discovered 731 differentially expressed (DE) TEs whose effects were mostly cell-specific and phenotype-specific. DE TEs were enriched for specific families and viral genes encoded in TE sequences. Increased expression of DE TEs was associated with genes involved in antiviral activity such as LY6E, ISG15, TRIM22 and pathways such as interferon signaling. These findings suggest that expression of TEs contributes to activation of SLE-related mechanisms in a cell-specific manner, which can impact disease diagnostics and therapeutics.
Sex matters: the MouseX DW-ALLEN Atlas for mice diffusion-weighted MR imaging
Authors: Martínez-Tazo Patricia , Santos Alexandra , Kotb Selim Mohamed , Espinós-Soler Elena , De Santis Silvia 
Published: November 2023

AbstractOvercoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis. To fill this gap, we build a mouse MRI template of both structural and diffusion contrasts, with anatomical annotation according to the Allen Mouse Brain Atlas, the most detailed public resource for mouse brain investigation. To achieve a standardized resource, we use a large cohort of animalsin vivo, and include animals of both sexes. To prove the utility of this resource to integrate imaging and molecular data, we demonstrate significant association between the mean diffusivity from MRI and gene expression-based glial counting. To demonstrate the need of equitable sex representation, we compared across sexes the warp fields needed to match a male-based template, and our template built with both sexes. Then, we use both templates for analysing mice imaging data obtained in animals of different ages, demonstrating that using a male-based template creates spurious significant sex effects, not present otherwise. All in all, our MouseX DW-ALLEN Atlas will be a widely useful resource getting us one step closer to equitable healthcare.Graphical abstract
mBARq: a versatile and user-friendly framework for the analysis of DNA barcodes from transposon insertion libraries, knockout mutants and isogenic strain populations
Authors: Sintsova Anna , Ruscheweyh Hans-Joachim , Field Christopher M. , Feer Lilith , Nguyen Bidong D. , Daniel Benjamin , Hardt Wolf-Dietrich , Vorholt Julia A. , Sunagawa Shinichi 
Published: November 2023

ABSTRACTDNA barcoding has become a powerful tool for assessing the fitness of strains in a variety of studies, including random transposon mutagenesis screens, attenuation of site-directed mutants, and population dynamics of isogenic strain pools. However, the statistical analysis, visualization and contextualization of the data resulting from such experiments can be complex and require bioinformatic skills. Here, we developed mBARq, a user-friendly tool designed to simplify these steps for diverse experimental setups. The tool is seamlessly integrated with an intuitive web app for interactive data exploration via the STRING and KEGG databases to accelerate scientific discovery.
HUNGER DRIVES SWITCHING AND SEARCHING RESPONSE IN A SOCIAL PREDATOR
Authors: Prokopenko CM , Zabihi-Seissan S , Dupont DLJ , Kingdon KA , Turner JW , Vander Wal E 
Published: November 2023

AbstractHunger is a frequent state for many predators and increasing hunger is likely to motivate costly behaviour to acquire necessary resources. Generalist predators must balance the costs and gains of hunting different prey, including increasing encounter rates and improving success rates by seeking areas with greater prey catchability. Large carnivores face threats when they interact with humans or conspecifics. We use integrated step selection analysis to describe spatiotemporal factors that influence wolf (Canis lupus) hunting behavior in Riding Mountain National Park, a natural area that wolves share with moose (Alces alces) and elk (Cervus canadensis). If hunger generates more risky behavior by wolves, as time-from-kill increases we expect wolves will: (1) search for and kill a prey that poses higher risk of injury, (2) use the periphery of their range, (3) use areas closer to the park boundary. Hunger alters wolf space use and drives a fine scale change in prey tracking. Movement patterns of hungry wolves are indicative of search behavior, i.e., shorter steps and more turning. Contrary to our predictions, hungry wolves moved further into the park. As wolves become hungrier, they switch their response from a weak selection to avoidance of elk. In contrast, the response to the primary and emergent prey, moose varied between individuals with some pack level similarities. Therefore, the state-based response to a pervasive risk and a historical resource was conserved in a population residing in a prey rich ‘island’ interfacing with human disturbance.
Translation elongation as a rate limiting step of protein production
Authors: Lyons Elijah F , Devanneaux Lou C , Muller Ryan Y , Freitas Anna V , Meacham Zuriah A , McSharry Maria V , Trinh Van N , Rogers Anna J , Ingolia Nicholas T , Lareau Liana F 
Published: November 2023

AbstractThe impact of synonymous codon choice on protein output has important implications for understanding endogenous gene expression and design of synthetic mRNAs. Synonymous codons are decoded at different speeds, but simple models predict that this should not drive protein output. Instead, translation initiation should be the rate limiting step for production of protein per mRNA, with little impact of codon choice. Previously, we used a neural network model to design a series of synonymous fluorescent reporters and showed that their protein output in yeast spanned a seven-fold range corresponding to their predicted translation elongation speed. Here, we show that this effect is not due primarily to the established impact of slow elongation on mRNA stability, but rather, that slow elongation further decreases the number of proteins made per mRNA. We combine simulations and careful experiments on fluorescent reporters to show that translation is limited on non-optimally encoded transcripts. Using a genome-wide CRISPRi screen, we find that impairing translation initiation attenuates the impact of slow elongation, showing a dynamic balance between rate limiting steps of protein production. Our results show that codon choice can directly limit protein production across the full range of endogenous variability in codon usage.
Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening
Authors: Chandraghatgi Rohan , Ji Hai-Feng , Rosen Gail L. , Sokhansanj Bahrad A. 
Published: November 2023

ABSTRACTRecent advances in computational methods provide the promise of dramatically accelerating drug discovery. While math-ematical modeling and machine learning have become vital in predicting drug-target interactions and properties, there is untapped potential in computational drug discovery due to the vast and complex chemical space. This paper advances a novel computational fragment-based drug discovery (FBDD) method called Fragment Databases from Screened Ligands Drug Discovery (FDSL-DD), which aims to streamline drug design by applying a two-stage optimization process. In this ap-proach,in silicoscreening identifies ligands from a vast library, which are then fragmentized while attaching specific at-tributes based on predicted binding affinity and interaction with the target sub-domain. This process both shrinks the search space and focuses on promising regions within it. The first optimization stage assembles these fragments into larger com-pounds using evolutionary strategies, and the second stage iteratively refines resulting compounds for enhanced bioac-tivity. The methodology is validated across three diverse protein targets involved in human solid cancers, bacterial antimi-crobial resistance, and SARS-CoV-2 viral entry, demonstrating the approach’s broad applicability. Using the proposed FDSL-DD and two-stage optimization approach yields high-affinity ligand candidates more efficiently than other state-of-the-art computational methods. Furthermore, a multiobjective optimization method is presented that accounts for druglikeness while still producing potential candidate ligands with high binding affinity. Overall, the results demonstrate that integrat-ing detailed chemical information with a constrained search framework can markedly optimize the initial drug discovery process, offering a more precise and efficient route to developing new therapeutics.