bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of cefaclor in human plasma using SIL‐IS LC‐ESI‐MS/MS for pharmacokinetics study in healthy Chinese volunteers
Authors: Chen Xinyan , Liu Gege , Wang Changmao , Liu Ran , Wang Minhui , Huang Yunzhe , Shen Jie , Jia Yuanwei
Published: April 2023

A steady, high‐efficiency, and precise liquid chromatography‐electrospray ionization‐tandem mass spectrometry method was established and validated using cefaclor‐d5 as the stable isotope‐labeled internal standard for quantification of cefaclor in human plasma. One‐step protein precipitation was applied to extract human plasma samples using methanol as precipitant. An Ultimate XB C18 column (2.1 × 50.0 mm, 5.0 μm) was used to achieve chromatographic separation. Mobile phases of gradient elution were an aqueous solution containing 0.1% formic acid (mobile phase A) and an acetonitrile solution containing 0.1% formic acid (mobile phase B). Electrospray ionization in positive‐ion mode was applied to detect under multiple reaction monitoring mode. Target fragment ion pairs of cefaclor and stable isotope‐labeled internal standard, respectively, were m/z 368.2 → 191.1 and m/z 373.2 → 196.1. Linear range of this method was between 20.0 and 10,000.0 ng/ml, with coefficient of determination (R2) >0.9900. Seven concentrations of quality control samples were used: 20.0 ng/ml (lower limit of quantitation), 60.0 ng/ml (low quality control), 650 ng/ml (middle quality control), 5000 ng/ml (arithmetic average middle quality control [AMQC]), 7500 ng/ml (high quality control), 10,000 ng/ml (upper limit of quantification), and 40,000 ng/ml (dilution quality control [DQC]). The method was validated for selectivity, lower limit of quantitation, linearity, accuracy, precision, recovery, matrix effect, dilution reliability, stability, carryover, and incurred sample reanalysis. This stable isotope‐labeled internal standard liquid chromatography‐electrospray ionization‐tandem mass spectrometry approach has been successfully applied to study the pharmacokinetics of cefaclor dry suspension among healthy Chinese volunteers.
Randomized clinical trial on the effect of intermittent vibrational force application during orthodontic treatment with aligners on RANKL and OPG concentrations in crevicular fluid
Authors: Pérez Idarraga Alicia , Yeste Ojeda Fara , Virto Ruiz Leire , Lacasa Litner Miguel , Cacho Casado Alberto , Martin Conchita
Published: April 2023

Application of intermittent forces by vibration is proposed as an easy‐to‐use accelerator of dental movement. The purpose of this study was to determine the effect of intermittent vibrational force application during orthodontic aligner treatment on receptor activator of nuclear factor‐kappa B ligand (RANKL) and osteoprotegerin (OPG) concentrations in crevicular fluid as markers of bone remodeling. This three‐arm parallel randomized clinical trial included 45 candidates for malocclusion treatment with aligners, randomly assigned to: Group A (vibrational forces from onset of treatment); Group B (vibrational forces at 6 weeks after treatment onset); or Group C (no vibration). The frequency of aligner adjustment also differed among groups. At different time points, a paper tip was used to draw crevicular fluid samples from a moving lower incisor for RANKL and OPG analysis using ELISA kits. Mixed‐model ANOVA found no significant differences in RANKL (A: p = 0.31, B: p = 0.8, C: p = 0.49) or OPG (A: p = 0.24, B: p = 0.58, C: p = 0.59) over time in any group or as a function of the application/non‐application of vibration or the frequency of aligner adjustments. Application of this accelerator device did not significantly affect bone remodeling in patients undergoing orthodontic treatment with aligners. However, a nonsignificant improvement in biomarker concentrations was observed when aligners were changed every 7 days and vibration was also applied. Further research is warranted to establish protocols for the application of vibration and the timing of aligner adjustments.
Management of failed stenting of the unprotected left main coronary artery
Authors: Moroni Alice , Marin Federico , Venturi Gabriele , Scarsini Roberto , Ribichini Flavio , De Maria Giovanni Luigi , Banning Adrian P.
Published: April 2023

Percutaneous coronary intervention (PCI) is increasingly accepted as treatment for unprotected left main coronary artery (ULMCA) disease especially in those patients who are unsuitable for cardiac surgery. Treatment of any stent failure is associated with increased complexity and worse clinical outcomes when compared with de novo lesion revascularization. Intracoronary imaging has provided new insight into mechanisms of stent failure and treatment options have developed considerably over the last decade. There is paucity of evidence on the management strategy for stent failure in the specific setting of ULMCA. Treating any left main with PCI requires careful consideration and consequently treatment of failed stents in ULMCA is complex and provides unique challenges. Consequently, we provide an overview of ULMCA stent failure, proposing a tailored algorithm to guide best management and decision in daily clinical practice, with a special focus on intracoronary imaging characterization of causal mechanisms and specific technical and procedural considerations.
Synthesis and Anti‐Mycobacterium tuberculosis Activity of Imidazo[2,1‐b][1,3]oxazine Derivatives against Multidrug‐Resistant Strains
Authors: Fernandes Guilherme F. S. , Manieri Karyn F. , Bonjorno Andressa F. , Campos Debora L. , Ribeiro Camila M. , Demarqui Fernanda M. , Ruiz Daniel A. G. , Nascimento‐Junior Nailton M. , Denny William A. , Thompson Andrew M. , Pavan Fernando R. , Dos Santos Jean L.
Published: April 2023

The emergence of multidrug‐resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2‐nitro‐6,7‐dihydro‐5H‐imidazo[2,1‐b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb‐infected macrophages, several compounds demonstrated a 1‐log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1‐b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin‐dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1‐b][1,3]oxazines and their promising potential against MDR‐TB.
Drop coating deposition Raman (DCDR) spectroscopy of biologically important molecules
Authors: Kuižová Alžbeta , Kočišová Eva
Published: April 2023

Drop coating deposition Raman (DCDR) spectroscopy introduces a simple and easily accessible approach to studying biologically important molecules and their mixtures. The method is based on drying a small drop of solution or suspension of studied molecules deposited on a special hydrophobic surface. The drying process efficiently accumulates the molecules in the ‘coffee‐ring’ or any small pattern from which the Raman spectrum can be measured. In this way, a significant (several orders of magnitude) improvement of the Raman detection sensitivity compared with Raman measurement from solution can be reached. Therefore, a small sample volume (several microliters), as well as a low initial concentration of studied molecules in deposited droplets, are important advantages of the DCDR method over the normal Raman one. Recently, many relevant DCDR applications on biomolecules and related molecules have been reported. The mini‐review covers a brief overview of the DCDR method (principle, short history, suitable hydrophobic surfaces and state‐of‐the‐art). It will be followed by a summary of the studies over the last 15–20 years on different biologically important molecules, including proteins, lipids (in the form of liposomes) and small molecules (e.g., porphyrins, anthrax marker dipicolinic acid and food and environmental contaminants). Finally, the application potential and further perspectives of the DCDR method for biomolecular studies will be discussed.
Synthesis of Multifunctional Protein‐Polymer Conjugates via Oxygen‐tolerant, Aqueous Copper‐Mediated Polymerization, and Bioorthogonal Click Chemistry
Authors: Voutyritsa Errika , Gryparis Charis , Theodorou Alexis , Velonia Kelly
Published: April 2023

Oxygen‐tolerant, aqueous copper‐mediated polymerization approaches are combined with click chemistry in either a sequential or a simultaneous manner, to enable the synthesis of multifunctional protein‐polymer conjugates. Propargyl acrylate (PgA) and propargyl methacrylate (PgMA) grafting from a bovine serum albumin (BSA) macroinitiator is thoroughly optimized to synthesize chemically addressable BSA‐poly(propargyl acrylate) and BSA‐poly(propargyl methacrylate) respectively. The produced multifunctional bioconjugates bear pendant terminal 1‐alkynes which can be readily post‐functionalized via both [3+2] Huisgen cycloaddition and thiol‐yne click chemistry under mild reaction conditions. Simultaneous oxygen‐tolerant, aqueous copper‐catalyzed polymerization, and click chemistry mediate the in situ multiple chemical tailoring of biomacromolecules in excellent yields.
Renewing the resource‐based view: New contexts, new concepts, and new methods
Authors: Helfat Constance E. , Kaul Aseem , Ketchen David J. , Barney Jay B. , Chatain Olivier , Singh Harbir
Published: April 2023

The resource‐based view is an enduring and impactful mainstay of research within strategic management and beyond. This editors' introduction to the special issue on “new directions for the resource‐based view” accomplishes two main tasks. First, we describe the contributions offered by the seven articles contained in the special issue. Second, we explain the potential value to research of incorporating into resource‐based inquiry new contexts (artificial intelligence and digitization, distributed organizations, and stakeholders and sustainability); new concepts (resource redeployment, market shaping through resources and capabilities); and new methods (text analysis and machine learning, formal models, policy capturing). The overall aim of this introduction is to help invigorate the resource‐based view by spotlighting a series of promising new directions.
Effect of flowing water on the pharmacokinetic properties of norfloxacin in channel catfish (Ictalurus punctatus) after single‐dose oral administration
Authors: Yu Yali , Dong Lixue , Zhang Lang , Gan Jinhua , Peng Jie , Liu Ting , Chen Jianwu , Lu Xiaorong , He Li , Cheng Bo
Published: April 2023

Background

The recirculating aquaculture system (RAS) is a widely used, water‐saving and efficient aquaculture model. However, bacterial diseases are common in farmed fish reared at high densities. Although antibiotics effectively treat these diseases, developing efficient methods to increase drug clearance in fish and decrease the concentrations of antibiotic residues in aquatic products is essential.

Objectives

This study evaluates the effect of flowing water in the RAS on norfloxacin (NOR) pharmacokinetics in channel catfish (Ictalurus punctatus).

Methods

Channel catfish were randomly divided into the control group (RAS group) and the experimental group (flow‐through aquaculture system group) (120 individuals/group). A NOR dose of 20 mg/kg was then orally administered to the fish. Plasma, muscle, liver and kidney samples were collected up to 168 h after treatment. NOR concentrations were measured using liquid chromatography–mass spectrometry, and pharmacokinetic parameters were calculated using a non‐compartmental method.

Results

Flowing water had a significant effect on the plasma pharmacokinetics and tissue distribution of NOR, increasing NOR clearance in the kidney, muscle and plasma. The time to maximum concentration of NOR was shorter in the plasma and longer in the kidney and liver. Moreover, flowing water increased the maximum concentration of NOR in the kidney, muscle and plasma and decreased the area under the concentration–time curve from time 0 to the last measurable concentration in the liver and plasma. Flowing water decreased the withdrawal period in muscle from 10 to 6 days.

Conclusions

These results indicate that flowing water can potentially increase NOR clearance in channel catfish.
Expression of SATB1 and SATB2 in the brain of bony fishes: what fish reveal about evolution
Authors: Lozano Daniel , López Jesús M. , Jiménez Sara , Morona Ruth , Ruíz Víctor , Martínez Ana , Moreno Nerea
Published: April 2023

Satb1 and Satb2 belong to a family of homeodomain proteins with highly conserved functional and regulatory mechanisms and posttranslational modifications in evolution. However, although their distribution in the mouse brain has been analyzed, few data exist in other non-mammalian vertebrates. In the present study, we have analyzed in detail the sequence of SATB1 and SATB2 proteins and the immunolocalization of both, in combination with additional neuronal markers of highly conserved populations, in the brain of adult specimens of different bony fish models at key evolutionary points of vertebrate diversification, in particular including representative species of sarcopterygian and actinopterygian fishes. We observed a striking absence of both proteins in the pallial region of actinopterygians, only detected in lungfish, the only sarcopterygian fish. In the subpallium, including the amygdaloid complex, or comparable structures, we identified that the detected expressions of SATB1 and SATB2 have similar topologies in the studied models. In the caudal telencephalon, all models showed significant expression of SATB1 and SATB2 in the preoptic area, including the acroterminal domain of this region, where the cells were also dopaminergic. In the alar hypothalamus, all models showed SATB2 but not SATB1 in the subparaventricular area, whereas in the basal hypothalamus the cladistian species and the lungfish presented a SATB1 immunoreactive population in the tuberal hypothalamus, also labeled with SATB2 in the latter and colocalizing with the gen Orthopedia. In the diencephalon, all models, except the teleost fish, showed SATB1 in the prethalamus, thalamus and pretectum, whereas only lungfish showed also SATB2 in prethalamus and thalamus. At the midbrain level of actinopterygian fish, the optic tectum, the torus semicircularis and the tegmentum harbored populations of SATB1 cells, whereas lungfish housed SATB2 only in the torus and tegmentum. Similarly, the SATB1 expression in the rhombencephalic central gray and reticular formation was a common feature. The presence of SATB1 in the solitary tract nucleus is a peculiar feature only observed in non-teleost actinopterygian fishes. At these levels, none of the detected populations were catecholaminergic or serotonergic. In conclusion, the protein sequence analysis revealed a high degree of conservation of both proteins, especially in the functional domains, whereas the neuroanatomical pattern of SATB1 and SATB2 revealed significant differences between sarcopterygians and actinopterygians, and these divergences may be related to the different functional involvement of both in the acquisition of various neural phenotypes.
Renal cryoablation combined with prior transcatheter arterial embolization in non-dialysis patients with stage 4 or 5 chronic kidney disease: a retrospective study
Authors: Umakoshi Noriyuki , Iguchi Toshihiro , Matsui Yusuke , Tomita Koji , Uka Mayu , Kawabata Takahiro , Munetomo Kazuaki , Nagata Shoma , Gobara Hideo , Araki Motoo , Hiraki Takao
Published: April 2023

Purpose

To retrospectively evaluate cryoablation combined with prior transcatheter arterial embolization (TAE) for renal cell carcinoma (RCC) in non-dialysis patients with stage 4 or 5 chronic kidney disease (CKD).

Materials and methods

Patients with stage 4 or 5 CKD undergoing TAE and cryoablation for RCC between May 2012 and October 2021 were included. TAE was selectively performed using iodized oil with absolute ethanol or gelatin sponge 1–14 days before cryoablation. Local efficacy, safety, and changes in renal function were evaluated.

Results

Nine patients (seven men and two women; median age, 64 years; range 52–88 years) with nine RCCs (mean diameter, 3.0 ± 1.0 cm; range 1.7–4.7 cm) were included. The mean pre-treatment estimated glomerular filtration rate (eGFR) was 24.2 ± 5.6 ml/min/1.73 m2 (range 10.4–29.2 ml/min/1.73 m2). The mean amount of contrast medium used in TAE was 58 ± 29 ml (range 40–128 ml). Except in one patient (grade 3 pyelonephritis), no grade ≥ 3 complications occurred. During the follow-up period (median, 18 months; range 7–54 months), no local tumor progression occurred. In two patients with pre-treatment eGFR of < 20 ml/min/1.73 m2, hemodialysis was initiated at 3 and 19 months after cryoablation. At their last follow-up, the remaining seven patients showed a decrease of 6.2 ± 5.3 ml/min/1.73 m2 (range 0.7–17.2 ml/min/1.73 m2) in their eGFR.

Conclusion

Cryoablation combined with TAE for RCC in non-dialysis patients with stage 4 or 5 CKD was effective and safe, with an acceptable impact on renal function.
Habitability of Polygonal Soils in the Hyper‐Arid Atacama Desert After a Simulated Rain Experiment
Authors: Sager Christof , Airo Alessandro , Mangelsdorf Kai , Arens Felix L. , Karger Cornelia , Schulze‐Makuch Dirk
Published: April 2023

In the hyper‐arid Atacama Desert, microbial life thrives near its “dry limit” in scarcely distributed habitats. Fracture networks of salt‐poor sand wedges outlining salt‐cemented polygons on alluvial surfaces in the Yungay region (Chile) represent potential microbial habitats. The degree of soil habitability at the surface (0–5 cm depth) and subsurface (10–15 cm depth) of a polygon and adjacent sand wedge was assessed before and up to 42 days after a 20 mm simulated rain experiment through the abundance of phospholipid fatty acids (PLFAs). Mineralogical composition, salinity, pH, electrical and thermal conductivity, water content, and water activity were analyzed for their relevance to habitability. After wetting, the PLFA content exclusively increased steadily with time in the polygon subsurface indicating the growth of an indigenous bacterial community. This increased habitability is presumably related to the soil's ability to retain water for at least 6 weeks at this depth. The lack of a continuous growth signal at the surface is likely due to rapid desiccation. In the sand wedge subsurface, the increase in PLFA content is not continuous despite the water activity being >0.9. The reason for this remains unclear but indicates that not only water availability is relevant for habitability but also the here described soil heterogeneities might impact the detection of the microbial response. Yet, the increasing PLFA trend in the polygon subsurface emphasized its relevance as a saline microbial habitat in an otherwise hostile environment, which could have implications for the assessment of soil habitability on Mars.
Distinct Hydrologic Pathways Regulate Perennial Surface Water Dynamics in a Hyperarid Basin
Authors: McKnight S. V. , Boutt D. F. , Munk L. A. , Moran B.
Published: April 2023

In water‐stressed hyperarid basins, questions mount over the impacts of anthropogenic groundwater extraction and climate‐driven perturbations on groundwater‐surface water interactions and the resilience of ecosystem‐critical surface water. Coupling groundwater with surface water observations from Sentinel‐2 data provides an unprecedented opportunity to evaluate surface water connectivity with local aquifers following intense precipitation events in arid basins. Surface water area and groundwater level data were analyzed for trends following precipitation, including peak lag time, post‐peak recession rates, and changes in hydraulic gradients. Results indicate variable connectivity following large precipitation events between surface water change and groundwater level fluctuations in the upgradient freshwater aquifer, whereas the downgradient brine‐to‐brackish area of the aquifer indicated virtually no connectivity with the aquifer. Comparison between precipitation and surface water response indicate distinct responses based on the physical relationship of the surface water body with the brine‐to‐brackish area of the aquifer. Lumped parameter modeling of surface water inundation also constrains the possible hydrologic dynamics of the post‐precipitation response. While modeled influx to surface water seems primarily controlled by watershed hydraulics rather than direct hydraulic connectivity of the aquifers, the relationship between surface water and adjacent groundwater levels coupled with surface water area indicates that local aquifers are primarily connected to the surface water bodies through discharge via subsurface infiltration. Modeling results imply that the existence of brine‐adjacent surface water in arid basins relies on upgradient discharge from freshwater aquifers. Our results further support that marginal surface water systems can serve as a critical recharge mechanism to local aquifers.
Rapid detection of neurons in widefield calcium imaging datasets after training with synthetic data
Authors: Zhang Yuanlong , Zhang Guoxun , Han Xiaofei , Wu Jiamin , Li Ziwei , Li Xinyang , Xiao Guihua , Xie Hao , Fang Lu , Dai Qionghai
Published: April 2023

Widefield microscopy can provide optical access to multi-millimeter fields of view and thousands of neurons in mammalian brains at video rate. However, tissue scattering and background contamination results in signal deterioration, making the extraction of neuronal activity challenging, laborious and time consuming. Here we present our deep-learning-based widefield neuron finder (DeepWonder), which is trained by simulated functional recordings and effectively works on experimental data to achieve high-fidelity neuronal extraction. Equipped with systematic background contribution priors, DeepWonder conducts neuronal inference with an order-of-magnitude-faster speed and improved accuracy compared with alternative approaches. DeepWonder removes background contaminations and is computationally efficient. Specifically, DeepWonder accomplishes 50-fold signal-to-background ratio enhancement when processing terabytes-scale cortex-wide functional recordings, with over 14,000 neurons extracted in 17 h.
A new look at the chalcogen bond: π-hole-based chalcogen (Se, Te) bonding which does not include a σ-hole interaction
Authors: Katlenok Eugene A. , Kuznetsov Maxim L. , Semenov Nikolay A. , Bokach Nadezhda A. , Kukushkin Vadim Yu.
Published: April 2023

Chalcogen bonding which does not include σ-hole interaction.
Visible light mediated regioselective 1,3-oxylallylation of aryl cyclopropanes under redox-neutral conditions
Authors: Wang Ding-Xing , Wang Hui , Xu Yao , Zhang Chi , Feng Chao
Published: April 2023

A photoredox catalysed 1,3-oxylallylation of aryl cyclopropanes was accomplished by reaction with carboxylic acids and allyl sulfones.
Conductive chromotropic fiber filament sensors with ultrahigh stretchability for wearable sensing textiles toward 3D optical motion capture
Authors: Guo Yufei , Guo Yongshi , Wu Jiawei , Wei Liying , Xia Shuhui , Zhu Chuang , Yan Jianhua
Published: April 2023

Conductive and chromotropic Ecoflex fiber filaments with ultrahigh stretchability are fabricated at the meter scaleviaan improved wet-spinning technique for 3D optical motion capture system.
Evaluation of the biological activity of nanoemulsions fabricated by walnut oil (Juglans regia L.)
Authors: Khezri Somayeh , Karimian Sara , Yousefi Ehsan , Es‐haghi Ali
Published: April 2023

Herbal medicines are currently attracting much attention as a potential cancer treatment. Juglans regia’s wide variety of anticancer actions have been demonstrated. The aim of this study is evaluating the cytotoxic and antioxidant effects of walnut oil (J. regia) nanoemulsion (WO‐NE) on CT26 colon cancer cell line. The dimensions and structure of the nanoemulsion were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The 1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) technique was used to determine whether or not the nanoemulsions had any antioxidant properties. The cytotoxic effects of 3‐[4,5‐dimethylthiazol‐2‐yl‐2‐5‐[diphenyltetrazolium bromide] (MTT) on CT26 colon cancer cells and umbilical vein endothelial cells (HUVEC) as normal cells were measured. The DPPH experiment demonstrated that the manufactured nanoemulsion had the ability to scavenge free radicals in a dose‐dependent manner, with an IC50 of approximately 500 µg/mL. The WO‐NE were found to be toxic to both HUVEC and CT26 cancer cells, with an IC50 of 10 ± 2.6 µg/mL for the CT26 and 160 ± 7.1 µg/mL for the HUVEC after 24 h of incubation. For comparison the effects of walnut oil also have been investigated. Due to their antioxidant and anticancer capabilities, the WO‐NE synthesized here have been proposed for future study as potential anti‐tumour agents.
Actin assembly is a physics problem
Authors: Miller Johanna L.
Published: April 2023

Simple mechanical forces may be key to understanding an essential biological process: the formation of cytoskeletal components that give structure to every cell in your body.
Something rotten in the state of Denmark
Authors: Dahn Ryan
Published: April 2023

The Copenhagen Network: The Birth of Quantum Mechanics from a Postdoctoral Perspective, Alexei Kojevnikov, Springer, 2020, $69.99 (paper)
Facial involvement is reflective of patients’ global perception of vitiligo extent
Authors: Merhi Samar , Salameh Pascale , Abboud Mounya , Seneschal Julien , Eleftheriadou Viktoria  , Pane Isabelle , Tran Viet-Thi , Shourick Jason , Ezzedine Khaled 
Published: April 2023

Background

The involvement of visible areas in vitiligo has been found to be correlated with increased psychiatric morbidity. Although multiple tools have been developed to assess vitiligo, no cutoff for improvement or worsening of vitiligo from a patient’s perspective has been established.

Objectives

To determine the minimal clinically important difference (MCID) of the Self-Assessment Vitiligo Extent Score (SA-VES) in patients with vitiligo and to evaluate, from the patient’s perspective, the importance of the change in the involvement of visible areas (face and hands) in patients’ overall perception of disease worsening or improving.

Methods

This was a cross-sectional study in the context of the ComPaRe e-cohort. Adult patients with vitiligo were invited to answer online questionnaires. They completed the SA-VES twice, 1 year apart. In addition, patients answered a 5-point Likert anchor question aimed at assessing their perception of the evolution of the extent of their vitiligo. The MCID was calculated using distribution- and anchor-based approaches. Using ordinal logistic regression, the change of vitiliginous lesions on the face or hands was compared to the overall extent of vitiligo (patches on all body areas).

Results

In total, 244 patients with vitiligo were included in the analyses; 20 (8%) were found to have an improvement in their vitiligo. The MCID in worsened patients was equal to a 1.3% body surface area [95% confidence interval (CI) 1.01–1.43] increase in the SA-VES. For participants with improved vitiligo, the MCID was equal to a decrease in total SA-VES of 1.3% (95% CI 0.867–1.697). Patients’ perceptions of change in their vitiligo was increased sevenfold when it affected the face vs. the rest of the body.

Conclusions

Changes in the facial SA-VES were highly correlated with patients’ impressions of the extent of vitiligo.
A happy accident: a novel turfgrass reference genome
Authors: Phillips Alyssa R , Seetharam Arun S , Albert Patrice S , AuBuchon-Elder Taylor , Birchler James A , Buckler Edward S , Gillespie Lynn J , Hufford Matthew B , Llaca Victor , Romay Maria Cinta , Soreng Robert J , Kellogg Elizabeth A , Ross-Ibarra Jeffrey
Published: April 2023

Poa pratensis, commonly known as Kentucky bluegrass, is a popular cool-season grass species used as turf in lawns and recreation areas globally. Despite its substantial economic value, a reference genome had not previously been assembled due to the genome’s relatively large size and biological complexity that includes apomixis, polyploidy, and interspecific hybridization. We report here a fortuitous de novo assembly and annotation of a P. pratensis genome. Instead of sequencing the genome of a C4 grass, we accidentally sampled and sequenced tissue from a weedy P. pratensis whose stolon was intertwined with that of the C4 grass. The draft assembly consists of 6.09 Gbp with an N50 scaffold length of 65.1 Mbp, and a total of 118 scaffolds, generated using PacBio long reads and Bionano optical map technology. We annotated 256K gene models and found 58% of the genome to be composed of transposable elements. To demonstrate the applicability of the reference genome, we evaluated population structure and estimated genetic diversity in P. pratensis collected from three North American prairies, two in Manitoba, Canada and one in Colorado, USA. Our results support previous studies that found high genetic diversity and population structure within the species. The reference genome and annotation will be an important resource for turfgrass breeding and study of bluegrasses.
A Bayesian two-stage group sequential scheme for ordinal endpoints
Authors: Zhong Chengxue , Miao Hongyu , Pan Haitao
Published: April 2023

Ordinal endpoints are common in clinical studies. For example, many clinical trials for evaluating COVID-19 infection therapies have adopted an ordinal scale as recommended by the World Health Organization. Despite their importance in clinical studies, design methods for ordinal endpoints are limited; in practice, a dichotomized approach is often used for simplicity. Here, we introduce a Bayesian group sequential scheme to assess ordinal endpoints, which considers a proportional-odds (PO) model, a nonproportional-odds (NPO) model, and a PO/NPO-switch model to handle various scenarios. Extensive simulations are conducted to demonstrate desirable performance, and the R package BayesOrdDesign has been made publicly available.
Enslaved Litigants, Emotions, and a Shifting Legal Landscape in Cauca, Colombia (1825–1831)
Authors: Pérez-Villa Ángela
Published: April 2023

This article reconstructs judicial practice in Cauca, Republic of Colombia, through the close reading of two criminal court cases involving enslaved litigants during the early transition from colony to independent state. In 1825, the enactment of laws that created new courts, judgeships, and procedures aimed to restructure and strengthen judicial practice in a nascent republic convulsed by internal division, which would disintegrate politically in 1831. Enslaved people—who had a long engagement with the law since colonial times—litigated in this context of political and judicial transformation in cases about adultery, theft, murder, vagrancy, cruelty, and freedom. This article sheds light on how these litigants were caught in the tensions that emerged between low- and high-ranking legal authorities over conflicting understandings of the role of religious thinking and the use of emotions in the adjudication of criminal cases and their appeals. In addition to drawing from the rich scholarship on slavery and the law in Latin America, this article broadly addresses recent calls from Latin America-based scholars to nourish national historiographies by inserting “the emotional” into the analytical framework. Through this approach, enslaved litigants appear moving through an uneven judicial apparatus in which authorities tried balancing their desire to uphold new procedural rules to create a secular legal sphere on the one hand and their personal religious convictions and status as enslavers on the other.
Pharmacological Interventions for the Prevention of Antipsychotic-Induced Weight Gain in People With Schizophrenia: A Cochrane Systematic Review and Meta-Analysis
Authors: Agarwal Sri Mahavir , Stogios Nicolette , Faulkner Guy E J , Hahn Margaret
Published: April 2023

Patients with schizophrenia are burdened by higher rates of obesity, cardiovascular disease and reduced life expectancy than the general population. In addition to illness, genetic and lifestyle factors, the associated weight gain and metabolic adverse effects of antipsychotic (AP) medications are known to exacerbate and accelerate these cardiometabolic problems significantly. Given the detrimental consequences of weight gain and other metabolic disturbances, there is an urgent need for safe and effective strategies to manage these issues as early on as possible. This review summarizes the literature of adjunctive pharmacological interventions aimed at preventing AP-induced weight gain.
Immature and activated phenotype of blood NK cells is associated with acute rejection in adult liver transplant
Authors: Song Shifei , Zhi Yao , Tian Guangyao , Sun Xiaodong , Chen Yuguo , Qiu Wei , Jiao Wenyu , Huang Heyu , Yu Ying , Li Mingqian , Lv Guoyue
Published: April 2023

Natural killer (NK) cells contribute to liver transplant (LTx) rejection. However, the blood-circulating NK-cell dynamics of patients who experience acute rejection (AR) are unclear. Herein, we longitudinally profiled the total NK cells and their subsets, along with the expression of activating and inhibitory receptors in sequential peripheral blood mononuclear cell samples, spanning from before LTx to the first year after LTx of 32 patients with AR and 30 patients under a steady immune status. Before transplantation, patients with AR (rejectors) contained a significantly higher proportion of the immature CD56brightCD16– subset and a lower cytolytic CD56dimCD16+ in the total blood-circulating NK cells than patients with steady immunity. Both subsets contained a high NKp30-positive population, and CD56dimCD16+ additionally exhibited a high NKp46-positive ratio. The NKp30-positive ratio in CD56dimCD16+ subset showed the most prominent AR predictive ability before LTx and was an independent risk factor of LTx AR. After transplantation, the blood-circulating NK cells in rejectors maintained a higher CD56brightCD16− and lower CD56dimCD16+ composition than the controls throughout the first year after LTx. Moreover, both subsets maintained a high NKp30-positive ratio, and CD56dimCD16+ retained a high NKp46-positive ratio. The blood-circulating NK cell subset composition was consistent during AR, while the expressions of NKp30 and NKp46 were augmented. Collectively, a more immature CD56brightCD16− subset composition and an activated phenotype of high NKp30 expression were the general properties of blood-circulating NK cells in rejected LTx recipients, and the NKp30-positive ratio in CD56dimCD16+ NK subset before LTx possessed AR predictive potential.
The challenge of medication adherence to reduce cardiovascular risk in primary care: a mixed design multi-center study in underserved populations
Authors: Puschel K , Gonzalez K , Varas J , Sateler J , Aravena H , Greig D , Escalona G , Palominos M , Rioseco A , Cea A , Thompson B
Published: April 2023

Background

Cardiovascular disease is a leading cause of death in Latin America. Internationally, low medication adherence is associated with 15% to 40% of excess cardiovascular deaths. In Latin America, the magnitude of low medication adherence and the factors associated with it, are not well known, especially among socially vulnerable populations. The aim of this study is to estimate the magnitude and associated factors of low medication adherence in a socially vulnerable population with high cardiovascular risk in Chile.

Methods

The study is based on a mixed-methods design. It included a multicenter cross-sectional design of a randomly selected clinical population of 900 participants, and a qualitative design based on the analytical framework model, that included patients and health team members, from three primary care clinics in Chile.

Results

Only 24.6% from the 886 (out of 900) patients who completed the study had “high” medication adherence, 24.9% had “regular,” and 50.4% had “low” adherence. Depression was the main factor associated with regular and low adherence combined (OR: 2.12; 95%CI:1.55-2.89). Confusion and tiredness were identified as barriers for adherence. Main facilitators reported by patients included better understanding of the medications, and availability of reminders. Clearer information and family support were identified by team members as initiators for improving adherence.

Conclusion

Low medication adherence is highly prevalent among patients with high cardiovascular risk in a low-income population in Chile. Quantitatively, depression was a significant risk factor for regular and low adherence; qualitatively, confusion and tiredness were identified as barriers. Clearer information and family support are identified as potential facilitators.

What is new?

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Cardiovascular disease is a growing epidemic in Latin America

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Low medication adherence is a significant risk factor for cardiovascular disease

What are de clinical implications?

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Low medication adherence is highly prevalent in socially vulnerable populations of high cardiovascular risk in Chile.

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Depression increased the risk of low medication adherence by more than two times in high-risk populations and is associated with the perception of confusion and tiredness in this group of patients.

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Primary care teams recognize the relevance of providing clearer information, reminder systems and developing family support strategies for improving medication adherence.
Disrupted maturation of white matter microstructure after concussion contributes to internalizing behavior problems in female children
Authors: Nishat Eman , Scratch Shannon E , Ameis Stephanie H , Wheeler Anne L
Published: April 2023

1.

Some children that experience a concussion exhibit long-lasting emotional and behavioral problems post-injury, with greater rates of persistent problems in females. Establishing the contribution of (1) pre-existing behavioral problems and (2) disrupted maturation of the brain’s vulnerable white matter, to long-lasting behavioral problems has been a challenge due to a lack of pre-injury behavioral and imaging data. From the Adolescent Brain Cognitive Development Cohort, this study examined 204 11-12-year-old children who experienced a concussion after baseline data collection at age 9-10-years-old. Internalizing and externalizing behavioral problems were assessed with the Child Behavior Checklist. In 99 of these children with MRI data available, white matter microstructure was characterized in deep and superficial white matter by neurite density from restriction spectrum image modeling of diffusion MRI. Linear regressions modeled 1) post-concussion behavior symptoms controlling for pre-injury behavior, 2) the impact of concussion on white matter maturation, and 3) the contribution of deviations in white matter maturation to post-concussion behavior symptoms. When controlling for preinjury scores, post-injury internalizing and externalizing scores were higher in female but not male children with concussion compared to children with no concussion. Group comparisons of change in neurite density over two years reflecting white matter maturation demonstrated an age-dependent effect whereby younger female children had less change in neurite density over time than younger children with no concussion. In female children with concussion, less change in superficial white matter neurite density over time was associated with more internalizing behavior problems. These results suggest that in female children, concussions are associated with behavior problems beyond those that exist pre-injury, and injury to the brain’s vulnerable white matter may be a biological substrate underlying persistent internalizing behaviors.
Multimodal anatomical mapping of subcortical regions in Marmoset monkeys using high-resolution MRI and matched histology with multiple stains
Authors: Saleem Kadharbatcha S , Avram Alexandru V , Yen Cecil Chern-Chyi , Magdoom Kulam Najmudeen , Schram Vincent , Basser Peter J
Published: April 2023

Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys inex vivousing a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla. Additionally, we registered these multimodal MRI volumes to the high-resolution images of matched whole-brain histology sections with seven different stains obtained from the same brain specimens. At high spatial resolution, the microstructural parameters and fiber orientation distribution functions derived with MAP-MRI can distinguish the subregions of many subcortical and deep brain structures, including fiber tracts of different sizes and orientations. The good correlation with multiple but distinct histological stains from the same brain serves as a thorough validation of the structures identified with MAP-MRI and other MRI parameters. Moreover, the anatomical details of deep brain structures found in the volumes of MAP-MRI parameters are not visible in conventional T1W or T2W images. The high-resolution mapping using novel MRI contrasts, combined and correlated with histology, can elucidate structures that were previously invisible radiologically. Thus, this multimodal approach offers a roadmap toward identifying salient brain areasin vivoin future neuroradiological studies. It also provides a useful anatomical standard reference for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research (Saleem et al., 2023). Additionally, we conducted a cross-species comparison between marmoset and macaque monkeys using results from our previous studies (Saleem et al., 2021). We found that the two species had distinct patterns of iron distribution in subregions of the basal ganglia, red nucleus, and deep cerebellar nuclei, confirmed with T2W MRI and histology.
Nucleolar structure connects with global nuclear organization
Authors: Wang Chen , Ma Hanhui , Baserga Susan J. , Pederson Thoru , Huang Sui
Published: April 2023

The nucleolus is a multi-functional nuclear body. To tease out the roles of nucleolar structure without resorting to multi-action drugs, we knocked down RNA polymerase I subunit RPA194 in HeLa cells by siRNA. Loss of RPA194 resulted in nucleolar structural segregation and effects on both nucleolus-proximal and distal nuclear components. The perinucleolar compartment was disrupted, centromere-nucleolus interactions were significantly reduced, and the intranuclear locations of specific genomic loci were altered. Moreover, Cajal bodies, distal from nucleoli, underwent morphological and compositional changes. To distinguish whether these global reorganizations are the results of nucleolar structural disruption or inhibition of ribosome synthesis, the pre-ribosomal RNA processing factor, UTP4, was also knocked down, which did not lead to nucleolar segregation, nor the intranuclear effects seen with RPA195A knockdown, demonstrating that they do not arise from a cessation of ribosome synthesis. These findings point to a commutative system that links nucleolar structure to the maintenance and spatial organization of certain nuclear bodies and genomic loci.
RNA multiscale simulations as an interplay of electrostatic, mechanical properties, and structures inside viruses
Authors: Cruz-León Sergio , Assenza Salvatore , Poblete Simón , Guzman Horacio V.
Published: April 2023

Multiscale simulations have broadened our understanding of RNA structure and function. Various methodologies have enabled the quantification of electrostatic and mechanical interactions of RNA at the nanometer scale. Atom-by-atom simulations, coarse-grained strategies, and continuum models of RNA and its environment provide physical insight and allow to interpret diverse experiments in a systematic way. In this chapter, we present and discuss recent advances in a set of methods to study nucleic acids at different scales. In particular, we introduce details of their parameterization, recent applications, and current limitations. We discuss the interaction of the proteinacous virus capsid, RNA with substrates, compare the properties of RNA and DNA and their interaction with the environment, and analyze the application of these methods to reconstruct the structure of the virus genome structure. Finally, the last lines are dedicated to future developments and challenges ahead.
Non-canonical RNA substrates of Drosha lack many of the conserved features found in primary microRNA stem-loops
Authors: Gu Karen , Mok Lawrence , Wakefield Matthew J. , Chong Mark M.W.
Published: April 2023

The RNase III enzyme Drosha has a central role in microRNA (miRNA) biogenesis, where it is required to release the stem-loop intermediate from primary (pri)-miRNA transcripts. However, it can also cleave stem-loops embedded within messenger (m)RNAs. This destabilizes the mRNA causing target gene repression and appears to occur primarily in stem cells. While pri-miRNA stem-loops have been extensively studied, such non-canonical substrates of Drosha have yet to characterized in detail. In this study, we employed high-throughput sequencing to capture all polyA-tailed RNAs that are cleaved by Drosha in mouse embryonic stem cells (ESCs) and compared the features of non-canonical versus miRNA stem-loop substrates. First, mRNA substrates are less efficiently processed than miRNA stem-loops. Sequence and structural analyses revealed that these mRNA substrates are also less stable and more likely to fold into alternative structures than miRNA stem-loops. Moreover, they lack the sequence and structural motifs found in miRNAs stem-loops that are required for precise cleavage. Notably, we discovered a non-canonical Drosha substrate that is cleaved in an inverse manner, which is a process that is normally inhibited by features in miRNA stem-loops. Our study thus provides valuable insights into the recognition of non-canonical targets by Drosha.