bluuebunny/crossref_metadata_2025 huggingface dataset:
Encouraging Regular Aortic Valve Opening for EVAHEART 2 LVAD Support Using Virtual Patient Hemodynamic Speed Modulation Analysis
Authors: Martinez Jasmine , Smegner Kelsey , Tomoda Masae , Motomura Tadashi , Chivukula Venkat Keshav
Published: November 2023

This study focuses on investigating the EVAHEART 2 left ventricular assist device (LVAD) toward designing optimal pump speed modulation (PSM) algorithms for encouraging aortic valve (AV) flow. A custom-designed virtual patient hemodynamic model incorporating the EVAHEART 2 pressure-flow curves, cardiac chambers, and the systemic and pulmonary circulations was developed and used in this study. Several PSM waveforms were tested to evaluate their influence on the mean arterial pressure (MAP), cardiac output (CO), and AV flow for representative heart failure patients. Baseline speeds were varied from 1,600 to 2,000 rpm. For each baseline speed, the following parameters were analyzed: 1) PSM ratio (reduced speed/baseline speed), 2) PSM duration (3–7 seconds), 3) native ventricle contractility, and 4) patient MAP of 70 and 80 mm Hg. More than 2,000 rpm virtual patient scenarios were explored. A lower baseline speed (1,600 and 1,700 rpm) produced more opportunities for AV opening and more AV flow. Higher baseline speeds (1,800 and 2,000 rpm) had lower or nonexistent AV flow. When analyzing PSM ratios, a larger reduction in speed (25%) over a longer PSM (5+ seconds) duration produced the most AV flow. Lower patient MAP and increased native ventricle contractility also contributed to improving AV opening frequency and flow. This study of the EVAHEART 2 LVAD is the first to focus on leveraging PSM to enhance pulsatility and encourage AV flow. Increased AV opening frequency can benefit aortic root hemodynamics, thereby improving patient outcomes.
Outcomes of Veno-Arterial Extracorporeal Membrane Oxygenation With Percutaneous Left Ventricular Unloading in Fulminant Myocarditis
Authors: Toda Koichi , Ako Junya , Hirayama Atsushi , Kinugawa Koichiro , Kobayashi Yoshio , Ono Minoru , Nishimura Takashi , Sato Naoki , Shindo Takahiro , Takayama Morimasa , Yasukochi Satoshi , Shiose Akira , Sawa Yoshiki
Published: November 2023

Fulminant myocarditis requiring peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has a high mortality rate. We investigated clinical outcomes of combined use of VA-ECMO and percutaneous left ventricular assist device (VAD) (Impella) for fulminant myocarditis in 104 consecutive patients enrolled in the Japan Registry for Percutaneous VAD (J-pVAD) between October 2017 and January 2020. Patients were followed until hospital discharge and predictors of survival were analyzed with a Cox proportional hazards model. The median support duration of combined use of VA-ECMO and Impella (ECMO/Impella) was 6 days, and the median left ventricular ejection fraction improved from 15% to 52% during support (p < 0.0001). Overall, 66 patients (63%) survived to discharge. Multivariate analysis revealed ECMO/Impella support at a transplant center as an independent predictor of survival (p = 0.0231). Patients treated at transplant centers had better 60 days survival rates when compared to nontransplant centers (83% vs. 55%, p = 0.005). However, baseline characteristics and treatment strategies differed between the two groups. This real-world national registry database suggested the difference in survival after ECMO/Impella support for fulminant myocarditis between transplant and nontransplant centers, which may indicate hospital variations regarding patient management, although further controlled studies are needed.
Informing Clinical Practice Guidelines for Children and Youth With Down Syndrome: A Survey of Key Partners
Authors: Wentz Erin , Conklin Ashley , Martin Kathy , Looper Julia , Shields Nora , Fiss Alyssa
Published: November 2023

Purpose:

The purpose of this work was to describe input from key partners to inform the scope and priorities for a clinical practice guideline (CPG) pertaining to physical therapy services provided to children and youth with Down syndrome (DS).

Methods:

A 68-item survey was completed by interventionists and parents (n = 296) of children and youth with DS.

Results:

The most prevalent physical therapy interventions currently being performed included tummy time, postural control activities, activity-based interventions, and play-based interventions. Key partners agreed on the importance of specific clinical outcomes, needing guidance on frequency and dosage of interventions, common barriers to physical therapy intervention, and needing information for discharge criteria in a future CPG.

Conclusions:

The results of this survey have given the CPG committee the necessary information to inform the CPG process for children and youth with DS.
Biofoundry-assisted Golden Gate cloning with AssemblyTron
Authors: Bryant John A. , Wright R. Clay
Published: November 2023

Golden Gate assembly is a requisite method in synthetic biology that facilitates critical conventions such as genetic part abstraction and rapid prototyping. However, compared to robotic implementation, manual Golden Gate implementation is cumbersome, error-prone, and inconsistent for complex assembly designs. AssemblyTron is an open-source python package that provides an affordable automation solution using open-source Opentrons OT-2 lab robots. Automating Golden Gate assembly with AssemblyTron can reduce failure-rate, resource consumption, and training requirements for building complex DNA constructs, as well as indexed and combinatorial libraries. Here, we dissect a panel of upgrades to AssemblyTron’s Golden Gate assembly capabilities, which include Golden Gate assembly into modular cloning part vectors, error-prone PCR combinatorial mutant library assembly, and modular cloning indexed plasmid library assembly. These upgrades enable a broad pool of users with varying levels of experience to readily implement advanced Golden Gate applications using low-cost, open-source lab robotics.
Biomineralization and biomechanical trade-offs under heterogeneous environments in the eastern oysterCrassostrea virginica
Authors: Telesca Luca , Linsley Braddock K. , Witek Lukasz , Hönisch Bärbel
Published: November 2023

Accurate biological models are critical to reliably predict vulnerability of marine organisms and ecosystems to rapid environmental changes. Current predictions on the biological impacts of climate change and human-caused disturbances primarily stem from controlled experiments but lack assessments of the mechanisms underlying biotic variations in natural systems. Such information is key to translating experimental models to natural populations, especially for habitat-forming, climate sensitive species with key ecological roles. This study aimed to characterize and quantify spatial patterns of shell biomineralization and biomechanical properties in a key reef-building oyster,Crassostrea virginica, collected from restored reefs along natural estuarine gradients in the Hudson River Estuary (NY, U.S.). We characterized patterns of oyster shell production (i.e., shape and thickness), structure (i.e., abundance of foliated and chalky calcite), mineralogy (i.e., crystal size and density), composition (i.e., organic matrix and Mg/Ca ratios), and mechanical performance (i.e., elastic modulus and hardness) at the macro and micro scale. Our results demonstrate a strong protective capacity ofC. virginicafor compensatory adjustments in shell biomineralization and biomechanics to maintain shell production and protective functions as a response to biotic and abiotic stressors. We reveal salinity as a key predictor of oyster shell structure, mechanical integrity, and resistance to dissolution, and describe the functional role of chalky calcite in shaping shell mechanical performance. Compensatory adjustments along salinity gradients indicate that oysters produce shells withi) high mechanical resistance but increased vulnerability to dissolution under marine conditions, andii) lower structural integrity but higher protection from dissolution under brackish conditions. Our work illustrates that biomineralization and biomechanical adjustments may act as compensatory mechanisms in eastern oysters to maintain overall performance under heterogeneous estuarine environments, and could represent a cornerstone for calcifying organisms to acclimate and maintain their ecological functions in a rapidly changing climate.
Targeting with structural analogs of natural products the purine salvage pathway inLeishmania (Leishmania) infantumby computer-aided drug design approaches
Authors: Barazorda-Ccahuana Haruna Luz , Cárcamo-Rodriguez Eymi Gladys , Centeno-Lopez Angela Emperatriz , Galdino Alexsandro Sobreira , Machado-de-Ávila Ricardo Andrez , Giunchetti Rodolfo Cordeiro , Coelho Eduardo Antonio Ferraz , Chávez-Fumagalli Miguel Angel
Published: November 2023

Visceral Leishmaniasis (VL) has a high death rate with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. To choose structural analogs from natural products that have demonstrated anti-leishmanial and anti-adenine phosphoribosyltransferase (APRT) properties, and that might bind with several targets from the purine salvage pathway, we used computer-aided drug design (CADD) techniques. Computational techniques were used to study the purine salvage pathway fromLeishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to twoL. infantumtargets, no expected toxicity, and potential for oral route administration. This study indicates that the compounds may have anti-leishmanial activity, which grantedin vitroandin vivoexperiments to settle this finding in the future.
Human dynein-dynactin is a fast processive motor in living cells
Authors: Verma Vikash , Wadsworth Patricia , Maresca Thomas J.
Published: November 2023

Minus-end directed transport along microtubules in eukaryotes is primarily mediated by cytoplasmic dynein and its cofactor dynactin. Significant advances have been made in recent years characterizing human dynein-dynactin structure and function using in vitro assays, however, there is limited knowledge about the motile properties and functional organization of dynein-dynactin in living human cells. Total internal reflection fluorescence microscopy (TIRFM) of CRISPR-engineered human cells is employed here to visualize fluorescently tagged dynein heavy chain (DHC) and p50 with high spatio-temporal resolution. We find that p50 and DHC exhibit indistinguishable motility properties in their velocities, run lengths, and run times. The dynein-dynactin complexes are fast (∼1.2 μm/s) and typically run for several microns (∼2.7 μm). Quantification of the fluorescence intensities of motile puncta reveals that dynein-dynactin runs are mediated by at least one DHC dimer while the velocity is consistent with that measured for double dynein (two DHC dimers) complexes in vitro.
Upper Bound on the Mutational Burden Imposed by a CRISPR-Cas9 Gene-Drive Element
Authors: Overton Michael S. , Guy Sean E. , Chen Xingsen , Martsul Alena , Carolino Krypton , Akbari Omar S. , Meyer Justin R. , Kryazhimskiy Sergey
Published: November 2023

CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To estimate how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeastSaccharomyces cerevisiae. Despite its substantial statistical power, our experiment revealed no detectable effect of CCGD or Cas9 alone on the genome-wide rates of mutations or LOH events, suggesting that these rates are affected by less than 30%. Nevertheless, we found that Cas9 caused a slight but significant shift towards more interstitial and fewer terminal LOH events, and the CCGD caused a significant difference in the distribution of LOH events on Chromosome V. Taken together, our results show that these genetic elements impose a weak and likely localized additional mutational burden in the yeast model. Although the mutagenic effects of CCGDs need to be further evaluated in other systems, our results suggest that the effect of CCGDs on off-target mutation rates and genetic diversity may be acceptable.
The applications of circulating cell-free DNA for oral squamous cell carcinoma patients as non-invasive diagnostics of structural variants, fusions and oncoviruses
Authors: Bhattacharya Mahua , Yaniv Dan , Yosefof Eyal , Tzelnick Sharon , Detroja Rajesh , D’Souza Dylan P. , Baum Gidi , Mizrachi Aviram , Bachar Gideon , Morgenstern Milana Frenkel
Published: November 2023

Circulating cell-free DNA (cfDNA) has been widely used as a prognostic marker for different cancers. In this study, we used cfDNA from oral squamous cell carcinoma (OSCC) patients to study various correlation factors that could improve the disease early-stage diagnostics and/or prognosis. We found that OSCC patient cfDNA concentration can serve as an indicator of tumor stage, malignancy, and survival prognosis. Deep genome sequencing of cfDNA revealed genomic alterations, such as copy number variations, fusion gene identification, and viral integrations. Copy number variation analysis suggested correlation with amplification and deletion in chromosome 1 at loci 1q, 2q, 3p, 3q and 8q22. Moreover, at these loci, amplification ofTP53, PIK3CAand other genes related to keratinization in OSCC patients were observed. In addition, we identified the novel fusion gene,TRMO-TRNT1 ‘chimera’,in seven high-grade tumor samples. The parental genes of this chimera,TRMOandTRNT1, are known to play roles in tRNA modification and DNA repair, respectively. Therefore, our study indicates that liquid biopsy may thus serve as a sensitive tool to study OSCC patient genomic alterations by exploring cfDNA circulating in the plasma, by means of an easy-to-use blood test. Finally, we detected integrations of human papilloma virus, simian virus, and enterovirus in the OSCC samples, that may point to the origins of OSCC.
Predictors of symptom trajectory in newly diagnosed ulcerative colitis: a 3-year follow-up cohort study
Authors: Van Den Houte Maaike , Guadagnoli Livia , Ohman Lena , Simren Magnus , Strid Hans , Van Oudenhove Lukas , Svedlund Jan
Published: November 2023

Introduction

Psychological symptoms are associated with poorer ulcerative colitis (UC)-related outcomes. However, the majority of research to date is cross-sectional and longitudinal data is lacking. We aimed to identify patient subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life (HRQoL), and to disentangle the directionality of effects between GI symptom levels and levels of psychological distress.

Methods

Self-reported GI symptom severity, HRQoL, inflammatory biomarkers and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis (LCGA) was used to determine subgroups based on longitudinal trajectories of symptom severity (diarrhea, abdominal pain) and physical and mental HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and GI symptom severity.

Results

Different subgroups were found based on the evolution of diarrhea, abdominal pain, and physical and mental HRQoL over time. Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhea (p = 0.049) and abdominal pain (p = 0.009). Conversely, patients with lower initial levels of diarrhea (p < 0.001) and abdominal pain (p = 0.003) had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment (p = 0.017), suggesting a subgroup of patients for whom initial poor mental health was inflammation-driven. Cross-lagged structural equation models indicated that reductions in diarrhea and abdominal pain preceded reductions in psychological symptoms over time (β=0.75, p <.0001), but not vice versa.

Conclusions

Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Thus, intervening on abdominal pain may help prevent or reduce future psychological distress.
Y and Mitochondrial Chromosomes in the Heterogeneous Stock Rat Population
Authors: Okamoto Faith , Chitre Apurva S , Sanches Thiago Missfeldt , Chen Denghui , Munro Daniel ,   NIDA Center for GWAS in Outbred Rats, Polesskaya Oksana , Palmer Abraham A
Published: November 2023

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial Chromosomes. We genotyped the Y and mitochondrial chromosomes in heterogeneous stock rats (Rattus norvegicus), which were created in 1984 by intercrossing eight inbred strains and have subsequently been maintained as an outbred population for 100 generations. As the Y and mitochondrial Chromosomes do not recombine, we determined which founder had contributed these chromosomes for each rat, and then performed association analysis for all complex traits (n=12,055; intersection of 12,116 phenotyped and 15,042 haplotyped rats).

We found the eight founders had 8 distinct Y and 4 distinct mitochondrial Chromosomes, however only two of each were observed in our modern heterogeneous stock rat population (Generations 81-97). Despite the unusually large sample size, the p-value distribution did not deviate from expectations; there were no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and mitochondrial Chromosomes were strongly associated with expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern heterogeneous stock rats there are no Y and mitochondrial Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and mitochondrial Chromosomes that do not appear in modern heterogeneous stock rats, nor do they address effects that may exist in other rat populations, or in other species.

Article Summary

Heterogeneous stock rats were created in 1984 by intercrossing eight inbred strains. This genetically and phenotypically diverse population has been used for numerous genetic studies. We developed a method (leveraging existing data) to identify the founder strain origin of Y and mitochondrial Chromosomes in modern heterogeneous stock rats. We examined effects of these chromosomes’ genotype on behavioral, physiological, and gene expression traits among 12,055 rats. We found no significant associations, except for expression of genes located on these chromosomes.
DDX3X and DDX3Y constitutively form nano-sized RNA-protein clusters that foster enzymatic activity
Authors: Yanas Amber , Shweta Him , Owens Michael C. , Liu Kathy Fange , Goldman Yale E.
Published: November 2023

DEAD-box helicases, which are crucial for many aspects of RNA metabolism, often contain intrinsically disordered regions (IDRs), whose functions remain unclear. Using multiparameter confocal microscopy, we reveal that sex chromosome-encoded homologous RNA helicases, DDX3X and DDX3Y, form nano-sized RNA-protein clusters (RPCs) that foster their catalytic activitiesin vitroand in cells. The IDRs are critical for the formation of these RPCs. A thorough analysis of the catalytic cycle of DDX3X and DDX3Y by ensemble biochemistry and single molecule photon bursts in the confocal microscope showed that RNA release is a major step that differentiates the unwinding activities of DDX3X and DDX3Y. Our findings provide new insights that the nano-sized helicase RPCs may be the normal state of these helicases under non-stressed conditions that promote their RNA unwinding and act as nucleation points for liquid-liquid phase separation under stress. This mechanism may apply broadly among other members of the DEAD-box helicase family.
PrimPol variant V102A with altered primase and polymerase activities
Authors: Boldinova Elizaveta O. , Filina Yulia V. , Miftakhova Regina R. , Shamsutdinova Yana F. , Makarova A.V.
Published: November 2023

PrimPol is a human DNA primase-polymerase which restarts DNA synthesis beyond DNA lesions and non-B DNA structures blocking replication. Disfunction of PrimPol in cells leads to slowing of DNA replication rates in mitochondria and nucleus, accumulation of chromosome aberrations, cell cycle delay, elevated sensitivity to DNA-damaging agents. PrimPol has been suggested to be associated with the development of ophthalmic diseases, elevated mitochondrial toxicity of antiviral drugs and increased cell resistance to chemotherapy. Here, we describe a rare missense PrimPol variant V102A with altered biochemical properties identified in patients suffering from ovarian and cervical cancer. The Val102Ala substitution dramatically reduced both the primase and DNA polymerase activities of PrimPol as well as specifically decreased its ability to incorporate ribonucleotides. We suggest that substitutions in this region would likely distort the active site and affect the catalytic activity of PrimPol.
Predicting future hospital antimicrobial resistance prevalence using machine learning
Authors: Vihta Karina-Doris , Pritchard Emma , Pouwels Koen B. , Hopkins Susan , Guy Rebecca L , Henderson Katherine , Chudasama Dimple , Hope Russell , Muller-Pebody Berit , Walker Ann Sarah , Clifton David , Eyre David W.
Published: November 2023

Objectives

Predicting antimicrobial resistance (AMR), a top global health threat, nationwide at a hospital level could help target interventions. Using machine learning, we exploit historical AMR and antimicrobial usage to predict future AMR.

Methods

Antimicrobial use and AMR prevalence in bloodstream infections in hospitals in England were obtained per hospital group (Trust) and financial year (FY, April-March) for 22 pathogen-antibiotic combinations (FY2016-2017-FY2021-2022). XGBoost model predictions were compared to previous value taken forwards, difference between the previous two years taken forwards and linear trend forecasting (LTF). XGBoost feature importances were calculated to aid interpretability.

Results

Relatively limited year-to-year variability in AMR prevalence within Trust-pathogen-antibiotic combinations meant previous value taken forwards achieved a low mean absolute error (MAE). XGBoost models performed similarly, while difference between the previous two years taken forwards and LTF were consistently worse. XGBoost considerably outperformed all other methods in Trusts with a larger change in AMR prevalence from FY2020-2021 (last training year) to FY2021-2022 (held-out test set). Feature importance values indicated that complex relationships were exploited for predictions.

Conclusion

Year-to-year resistance has generally changed little within Trust-pathogen-antibiotic combinations. In those with larger changes, XGBoost models could improve predictions, enabling informed decisions, efficient resource allocation, and targeted interventions.
The International Tables Symmetry Database
Authors: de la Flor Gemma , Kroumova Eli , Hanson Robert M. , Aroyo Mois I.
Published: November 2023

The International Tables Symmetry Database (https://symmdb.iucr.org/), which is part of International Tables for Crystallography, is a collection of individual databases of crystallographic space-group and point-group information with associated programs. The programs let the user access and in some cases interactively visualize the data, and some also allow new data to be calculated `on the fly'. Together these databases and programs expand upon and complement the symmetry information provided in International Tables for Crystallography Volume A, Space-Group Symmetry, and Volume A1, Symmetry Relations between Space Groups. The Symmetry Database allows users to learn about and explore the space and point groups, and facilitates the study of group–subgroup relations between space groups, with applications in determining crystal-structure relationships, in studying phase transitions and in domain-structure analysis. The use of the International Tables Symmetry Database in all these areas is demonstrated using several examples.
Identification of Kikuchi lines in electron diffraction patterns collected in small-angle geometry
Authors: Mitura Zbigniew , Szwachta Grzegorz , Kokosza Łukasz , Przybylski Marek
Published: November 2023

It is demonstrated that Kikuchi features become clearly visible if reflection high-energy electron diffraction (RHEED) patterns are filtered using digital image processing software. The results of such pattern transformations are shown for SrTiO3 with mixed surface termination for data collected at different azimuths of the incident electron beam. A simplified analytical approach for the theoretical description of filtered Kikuchi patterns is proposed and discussed. Some examples of raw and filtered patterns for thin films are shown. RHEED patterns may be treated as a result of coherent and incoherent scattering of electron waves. The effects of coherent scattering may be considered as those occurring due to wave diffraction by an idealized crystal and, usually, only effects of this type are analysed to obtain structural information on samples investigated with the use of RHEED. However, some incoherent scattering effects mostly caused by thermal vibrations of atoms, known as Kikuchi effects, may also be a source of valuable information on the arrangements of atoms near the surface. Typically, for the case of RHEED, Kikuchi features are hidden in the intensity background and researchers cannot easily recognize them. In this paper, it is shown that the visibility of features of this type can be substantially enhanced using computer graphics methods.
Synthesis, crystal structure and computational analysis of 2,7-bis(4-chlorophenyl)-3,3-dimethyl-1,4-diazepan-5-one
Authors: Akila Shanmugasundaram , Vidhyasagar Thankakan , Winfred Jebaraj John Peter , Thiruvalluvar Aravazhi Amalan , Rajeswari Krishnan
Published: November 2023

In the title compound, C19H20Cl2N2O, the seven-membered 1,4-diazepane ring adopts a chair conformation while the 4-chlorophenyl substituents adopt equatorial orientations. The chlorophenyl ring at position 7 is disordered over two positions [site occupancies 0.480 (16):0.520 (16)]. The dihedral angle between the two benzene rings is 63.0 (4)°. The methyl groups at position 3 have an axial and an equatorial orientation. The compound exists as a dimer exhibiting intermolecular N—H...O hydrogen bonding with R
2
2(8) graph-set motifs. The crystal structure is further stabilized by C—H...O hydrogen bonds together with two C—Cl...π (ring) interactions. The geometry was optimized by DFT using the B3LYP/6–31 G(d,p) level basis set. In addition, the HOMO and LUMO energies, chemical reactivity parameters and molecular electrostatic potential were calculated at the same level of theory. Hirshfeld surface analysis indicated that the most important contributions to the crystal packing are from H...H (45.6%), Cl...H/H...Cl (23.8%), H...C/C...H (12.6%), H...O/O...H (8.7%) and C...Cl/Cl...C (7.1%) interactions. Analysis of the interaction energies showed that the dispersion energy is greater than the electrostatic energy. A crystal void volume of 237.16 Å3 is observed. A molecular docking study with the human oestrogen receptor 3ERT protein revealed good docking with a score of −8.9 kcal mol−1.
2-{1-[(6R,S)-3,5,5,6,8,8-Hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl]ethylidene}-N-methylhydrazinecarbothioamide
Authors: Melo Ana Paula Lopes de , Flores Alex Fabiani Claro , Bresolin Leandro , Tirloni Bárbara , Oliveira Adriano Bof de
Published: November 2023

The reaction between a racemic mixture of (R,S)-fixolide and 4-methylthiosemicarbazide in ethanol with a 1:1 stoichiometric ratio and catalysed with HCl, yielded the title compound, C20H31N3S [common name: (R,S)-fixolide 4-methylthiosemicarbazone]. There is one crystallographically independent molecule in the asymmetric unit, which is disordered over the aliphatic ring [site-occupancy ratio = 0.667 (13):0.333 (13)]. The disorder includes the chiral C atom, the neighbouring methylene group and the methyl H atoms of the methyl group bonded to the chiral C atom. The maximum deviations from the mean plane through the disordered aliphatic ring amount to 0.328 (6) and −0.334 (6) Å [r.m.s.d. = 0.2061 Å], and −0.3677 (12) and 0.3380 (12) Å [r.m.s.d. = 0.2198 Å] for the two different sites. Both fragments show a half-chair conformation. Additionally, the N—N—C(=S)—N entity is approximately planar, with the maximum deviation from the mean plane through the selected atoms being 0.0135 (18) Å [r.m.s.d. = 0.0100 Å]. The molecule is not planar due to the dihedral angle between the thiosemicarbazone entity and the aromatic ring, which amounts to 51.8 (1)°, and due to the sp
3-hybridized carbon atoms of the fixolide fragment. In the crystal, the molecules are connected by H...S interactions with graph-set motif C(4), forming a mono-periodic hydrogen-bonded ribbon along [100]. The Hirshfeld surface analysis suggests that the major contributions for the crystal cohesion are [(R,S)-isomers considered separately] H...H (75.7%), H...S/S...H (11.6%), H...C/C...H (8.3% and H...N/N...H (4.4% for both of them).
Will commodity futures reduce systemic risk in the spot market? Evidence from Chinese commodity market
Authors: Liu Qing , Feng Yun , Xu Mengxia
Published: November 2023

Purpose

This paper aims to investigate whether the establishment of commodity futures can effectively hedge systemic risk in the spot network, given the context of financialization in the commodity futures market.

Design/methodology/approach

Utilizing industry association data from the Chinese commodity market, the authors identify systemically important commodities based on their importance in the production process using multiple graph analysis methods. Then the authors analyze the effect of listing futures on the systemic risk in the spot market with the staggered difference-in-differences (DID) method.

Findings

The findings suggest that futures contracts help reduce systemic risks in the underlying spot network. Systemic risk for a commodity will decrease by approximately 5.7% with the introduction of each corresponding futures contract, since the hedging function of futures reduces the timing behavior of firms in the spot market. Establishing futures contracts for upstream commodities lowers systemic risks for downstream commodities. Energy commodities, such as crude oil and coal, have higher systemic importance, with the energy sector dominating systemic importance, while some chemical commodities also have considerable systemic importance. Meanwhile, the shortest transmission path for risk propagation is composed of the energy industry, chemical industry, agriculture/metal industry and final products.

Originality/value

The paper provides the following policy insights: (1) The role of futures contracts is still positive, and future contracts should be established upstream and at more systemically important nodes in the spot production chain. (2) More attention should be paid to the chemical industry chain, as some chemical commodities are systemically important but do not have corresponding futures contracts. (3) The risk source of the commodity spot market network is the energy industry, and therefore, energy-related commodities should continue to be closely monitored.
Being innovative is not enough: a semi-parametric assessment of the efficiency of post-incubation innovative firms
Authors: Longo Maria Cristina , Guccio Calogero , Martorana Marco Ferdinando
Published: November 2023

Purpose

This paper aims to assess whether incubation affects the technical efficiency of innovative firms after entering the market. The study of efficiency allows firms to understand how well resources have been used in production processes. The research intends to contribute to the literature on the performance of incubated firms.

Design/methodology/approach

This study estimates the relative efficiency of innovative firms adopting a DEA-based two-stage semi-parametric method. Incubation, firm age and initial capital are used for explaining the relative performance of previously incubated firms compared to non-incubated ones over a six-year period of activity. This research focuses on Italian innovative firms using a large sample of companies.

Findings

Results show that incubators have a positive and significant effect on efficiency for firms that have been in the market for more than two years. Efficiency also improves with age and with the level of initial capital of the firm.

Research limitations/implications

This analysis is limited to the quantitative dimension of inputs as reported in the balance sheets, without qualitative considerations.

Practical implications

Findings enhance firms' understanding of the role of incubators as neutral places to develop a business culture of efficiency. From an empirical standpoint, this study provides useful insights to start-uppers who intend to attend incubation programs. Overall, incubators matter to the extent that they enable new firms, net of those that fail to survive in the first two years of activity, to improve their efficiency in the use of inputs. This research also suggests incubators consider the start-ups’ potential of being efficient.

Social implications

Findings provide tips to policymakers when they are called upon to propose funding programs to support prominent firms entering the business scalability.

Originality/value

This study contributes to the literature on the relative performance of post-incubated firms, highlighting the efficiency frontier analysis. This methodological approach is relatively new in this field. It allows researchers to study the innovative firms' performance in relative terms, that is with respect to the input level. It integrates the performance-based with efficiency frontier analysis. Also, this study reinforces the idea that incubators prepare start-ups to develop capacities and managerial skills, which will be useful in post-incubation life to improve their cost competitiveness.
“Tracing the Everyday Sensory Heritage of Kolkata Streets”—“Sohorer Songbedon”: A museological review
Authors: Banerjee Soumita , Roy Kunaljeet
Published: November 2023

We do carry an impression of the places where we grow up or the places we touch in our daily life—somehow it gets mapped in our minds. That is how we create a sensory bonding with the place via our perception; how it smells, how it tastes, or what kind of a phonic place it is. But somehow, with the rapid pace of urbanization and mechanization of age‐old occupations, these senses are being lost to the citizens in an urban area which we get to hear from our fore generations. “Tracing the everyday Sensory Heritage of Kolkata Streets”—“Sohorer Songbedon” is an attempt in a form of an exhibition from a group of enthusiastic geographers for the city of Kolkata (Calcutta) to bring back some iconic hereditary sounds and smells of the city to the mass. While visiting the exhibition, we interacted with the organizers and a group of visitors through some semi‐structured interviews, and simultaneously some observations were also made. The purpose of the visit lied in experiencing how our city and its various pockets can emerge through its sensory scape without one being physically present there and also let the people know about such an initiative which was staged for the first time in the city. The aim was also to witness if these sensory components from the city perceptible could evoke any repercussions among the visitors or not. In museology, with the gaining importance of intangible expressions of heritage objects and interpretation of the visitors of the flowing information in the event, this one could have been used as a profound example of such kind in the future.
Effect of the dual sodium‐glucose co‐transporter‐1 and ‐2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta‐analysis of randomized controlled trials
Authors: Bantounou Maria Anna , Sardellis Panagiotis , Thuemmler Rosa , Black Boada Daniel , Kaczmarek Justyna , Mahmood Ribeya , Plascevic Josip , Philip Sam
Published: November 2023

Aim

To investigate the renal safety profile of sotagliflozin, a novel sodium‐glucose co‐transporter‐1 and ‐2 inhibitor, in patients with type 1 diabetes and type 2 diabetes, with or without renal impairment, as well as its efficacy in decreasing the risk of further renal events, with an emphasis on those with previous renal impairment.

Methods

Embase, Medline, CENTRAL and Scopus were searched from their inception until 24 April 2023 for randomized controlled trials that reported estimated glomerular filtration rate (eGFR), urinary albumin excretion or composite renal events (CRE). The Cochrane risk of bias 2 tool was used. Mean difference, relative risk (RR) and 95% confidence intervals were estimated (PROSPERO: CRD42023425583).

Results

Fourteen studies were included in this review (n = 17 574 participants; intervention n = 9312, control n = 8262). The median follow‐up was 24.5 (Q1 = 15.25, Q3 = 28) months. Four studies recruited participants with renal impairment; baseline eGFR ranged from 23.8 to 50.5 mL/min/1.73m2. The change in eGFR for studies (n = 6) with a follow‐up of 52 weeks or longer was −1.23 (−1.45, −1.01) mL/min/1.73m2. Sotagliflozin did not significantly alter urinary albumin excretion. No change was observed in the risk of CRE (n = 6 studies; RR = 0.82 [0.61, 1.12]), including in participants with renal impairment. High risk of bias was a limitation of this review.

Conclusions

Sotagliflozin did not adversely affect renal function or change the risk of key renal outcomes, including for participants with pre‐existing renal impairment. Therefore, sotagliflozin was safe; however, further research is needed to determine its efficacy in reducing the risk of diabetic kidney disease.
Effectiveness of a fourth SARS‐CoV‐2 vaccine dose in previously infected individuals from Austria
Authors: Chalupka Alena , Richter Lukas , Chakeri Ali , El‐Khatib Ziad , Theiler‐Schwetz Verena , Trummer Christian , Krause Robert , Willeit Peter , Benka Bernhard , Ioannidis John P. A. , Pilz Stefan
Published: November 2023

Introduction

Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID‐19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections. We estimated the risk of COVID‐19 deaths and SARS‐CoV‐2 infections according to vaccination status in previously infected individuals in Austria.

Methods

This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID‐19 deaths (primary outcome) and SARS‐CoV‐2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1‐HR) X 100.

Results

Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID‐19 deaths and 89,056 SARS‐CoV‐2 infections. rVE for four versus three vaccine doses was −24% (95% CI: −120 to 30) against COVID‐19 deaths, and 17% (95% CI: 14–19) against SARS‐CoV‐2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow‐up until June 2023. Adjusted HR (95% CI) for all‐cause mortality for four versus three vaccinations was 0.79 (0.74–0.85).

Discussion

In previously infected individuals, a fourth vaccination was not associated with COVID‐19 death risk, but with transiently reduced risk of SARS‐CoV‐2 infections and reversal of this effect in longer follow‐up. All‐cause mortality data suggest healthy vaccinee bias.
Systematic distributions of interaction strengths across tree interaction networks yield positive diversity–productivity relationships
Authors: Yu Wentao , Albert Georg , Rosenbaum Benjamin , Schnabel Florian , Bruelheide Helge , Connolly John , Härdtle Werner , von Oheimb Goddert , Trogisch Stefan , Rüger Nadja , Brose Ulrich
Published: November 2023

Understanding the mechanisms underlying diversity–productivity relationships (DPRs) is crucial to mitigating the effects of forest biodiversity loss. Tree–tree interactions in diverse communities are fundamental in driving growth rates, potentially shaping the emergent DPRs, yet remain poorly explored. Here, using data from a large‐scale forest biodiversity experiment in subtropical China, we demonstrated that changes in individual tree productivity were driven by species‐specific pairwise interactions, with higher positive net pairwise interaction effects on trees in more diverse neighbourhoods. By perturbing the interactions strength from empirical data in simulations, we revealed that the positive differences between inter‐ and intra‐specific interactions were the critical determinant for the emergence of positive DPRs. Surprisingly, the condition for positive DPRs corresponded to the condition for coexistence. Our results thus provide a novel insight into how pairwise tree interactions regulate DPRs, with implications for identifying the tree mixtures with maximized productivity to guide forest restoration and reforestation efforts.
An ethnic group specific deprivation index for measuring neighbourhood inequalities in England and Wales
Authors: Lloyd Christopher D. , Catney Gemma , Wright Richard , Ellis Mark , Finney Nissa , Jivraj Stephen , Manley David , Wood Sarah
Published: November 2023

The measurement of deprivation for small areas in the UK has provided the basis for the development of policies and targeting of resources aimed at reducing spatial inequalities. Most measures summarise the aggregate level of deprivation across all people in a given area, and no account is taken of differences between people with differing characteristics, such as age, sex or ethnic group. In recognition of the marked inequalities between ethnic groups in the UK, and the distinctive geographies of these inequalities, this paper presents a new ethnic group‐specific neighbourhood deprivation measure—the Ethnic Group Deprivation Index (EGDI). This index, using a custom cross‐tabulated 2021 Census dataset on employment, housing tenure, education and health by ethnic group, reveals the small area geographies of ethnic inequalities that have to date received scant attention, and yet have profound impacts on life chances and well‐being. Drawing on the methodological framework of the widely used English Index of Multiple Deprivation (IMD) and for the same geographies (Lower Layer Super Output Areas), the EGDI measures deprivation for each ethnic group using data from the 2021 Census of England and Wales. The EGDI reveals the complex geographies of ethnic inequality and demonstrates that while one ethnic group in a neighbourhood may have high relative levels of deprivation, another ethnic group in that same neighbourhood may experience very low relative levels. The EGDI explores ethnic inequalities within and between neighbourhoods, complementing and augmenting existing measures by offering an important means of better understanding ethnic inequalities. The EGDI can be used to help shape locally and culturally sensitive policy development and resource allocation.
Cross‐validity of the end‐of‐life care management scale via a cross‐sectional study
Authors: Kaneda Akiko , Kanoya Yuka
Published: November 2023

Aim

To examine the cross‐validity of the end‐of‐life care management scale (EOLCM scale).

Method

This cross‐sectional study used a self‐report questionnaire. Participants were care managers who had not participated in a previous study that developed the EOLCM scale. The survey items included participants' demographic information, the EOLCM scale, the number of end‐of‐life (EOL) cases managed in the last three years, and two concurrent scales, namely the Multidisciplinary Cooperation Behavior Scale for Medical and Nursing Professionals in Home Care and the “MITORI” Care Scale to Evaluate Nursing Care for Patients with End‐Stage Cancer and Their Families. "MITORI" means providing care near the dying person. Internal consistency of the EOLCM scale was assessed via Cronbach's alpha. The model's goodness‐of‐fit was assessed via a confirmatory factor analysis (CFA). Construct validity was determined using the correlation coefficients between the scores of the EOLCM scale and concurrent scales, and the number of EOL cases managed in the last three years.

Results

Valid responses were received from 501 care managers. Cronbach's αs were 0.824 and >0.709 for the entire scale and each factor, respectively. The model fit indices for the CFA were goodness‐of‐fit index = 0.916, adjusted goodness‐of‐fit index = 0.892, comparative fit index = 0.947, and root mean square error of approximation = 0.053. Correlation coefficients between the concurrent scales and the EOLCM scale, and between the number of EOL cases and the EOLCM scale ranged from 0.623 to 0.817 (P < 0.001) and from 0.103 to 0.244 (P < 0.001), respectively.

Conclusion

The EOLCM scale showed acceptable cross‐validity. Further studies are required to examine its cross‐cultural and predictive validities. Geriatr Gerontol Int 2024; 24: 48–52.
Gene therapy for adenosine deaminase severe combined immune deficiency—An unexpected journey of four decades
Authors: Kohn Donald B.
Published: November 2023

Severe combined immune deficiency due to adenosine deaminase deficiency (ADA SCID) is an inborn error of immunity with pan‐lymphopenia, due to accumulated cytotoxic adenine metabolites. ADA SCID has been treated using gene therapy with a normal human ADA gene added to autologous hematopoietic stem cells (HSC) for over 30 years. Iterative improvements in vector design, HSC processing methods, and clinical HSC transplant procedures have led nearly all ADA SCID gene therapy patients to achieve consistently beneficial immune restoration with stable engraftment of ADA gene‐corrected HSC over the duration of observation (as long as 20 years). One gene therapy for ADA SCID is approved by the European Medicines Agency (EMA) in the European Union (EU) and another is being advanced to licensure in the U.S. and U.K. Despite the clear‐cut benefits and safety of this curative gene and cell therapy, it remains challenging to achieve sustained availability and access, especially for rare disorders like ADA SCID.