bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic protein phosphorylation inStreptococcus pyogenesduring growth, stationary phase and starvation
Authors: Mikkat Stefan , Kreutzer Michael , Patenge Nadja
Published: November 2023

Background

Phosphorylation of proteins at serine, threonine, and tyrosine residues plays an important role in physiological processes of bacteria such as cell cycle, metabolism, virulence, dormancy, sporulation, and stationary phase functions.Streptococcus pyogenespossesses a single known transmembrane serine/threonine kinase belonging to the class of penicillin-binding protein and serine/threonine-associated (PASTA) kinases. To gain initial insights into the targets and dynamics of protein phosphorylation inS. pyogenesserotype M49 strain 591, we performed a proteomics and phosphoproteomics workflow using cultures from different growth conditions, stationary phase and starvation.

Results

The quantitative analysis of dynamic phosphorylation, which included a subset of 463 out of 815 identified phosphorylation sites, revealed two main types of phosphorylation events, distinguished by the growth phase in which they predominantly occur and their preference for either threonine or serine. A small group of phosphorylation events occurred almost exclusively at threonine residues of proteins related to the cell cycle and was enhanced in growing cells. Many of these phosphorylation sites are highly conserved targets of PASTA kinases in streptococci. The majority of phosphorylation events occurred during stationary phase or starvation, preferentially at serine residues. These phosphorylations may be important for regulatory processes in stationary phase or for persister cell formation, but their function and the kinases responsible for their formation need to be elucidated in further analyses. Moreover, our data indicate that the vast majority of proteins can be phosphorylated, but identification of their phosphopeptides depends on the sensitivity of the proteomic methods used.

Conclusions

PASTA kinase-dependent cell cycle regulation processes found in related bacteria are conserved inS. pyogenes, but account for only a small part of all phosphorylation events. Most phosphorylation events take place during stationary growth phase and starvation. This phenomenon has also been described for some other bacteria and may therefore be a general feature of bacterial protein phosphorylation.
Transcranial electric stimulation modulates firing rate at clinically relevant intensities
Authors: Farahani Forouzan , Khadka Niranjan , Parra Lucas C. , Bikson Marom , Vöröslakos Mihály
Published: November 2023

Notwithstanding advances with low-intensity transcranial electrical stimulation (TES), there remain questions about the efficacy of clinically realistic electric fields on neuronal function. We used Neuropixels 2.0 probe with 384 channels in an in-vivo rat model of TES to detect effects of weak fields on neuronal firing rate. High-density field mapping and computational models verified field intensity (1 V/m in hippocampus per 50 µA of applied skull currents). We demonstrate that electric fields below 0.5 V/m acutely modulate firing rate in 5% of neurons recorded in the hippocampus. At these intensities, average firing rate effects increased monotonically with electric field intensity at a rate of 7 % per V/m. For the majority of excitatory neurons, firing increased for cathodal stimulation and diminished for anodal stimulation. While more diverse, the response of inhibitory neurons followed a similar pattern on average, likely as a result of excitatory drive. Our results indicate that responses to TES at clinically relevant intensities are driven by a fraction of high-responder excitatory neurons, with polarity-specific effects. We conclude that transcranial electric stimulation is an effective neuromodulator at clinically realistic intensities.
An Efficient Computational Method to Create Positive NIPT Samples with Autosomal Trisomy
Authors: Nguyen Tinh H. , Nguyen Huynh V. , Pham Minh D. , Le Vinh S.
Published: November 2023

Noninvasive prenatal test (NIPT) has been widely used for screening trisomy on chromosomes 13 (T13), 18 (T18), and 21 (T21). However, the false negative rate of NIPT algorithms has not been thoroughly evaluated due to the lack of positive samples. In this study, we present an efficient computational approach to create positive samples with autosomal trisomy from negative samples. We applied the approach to establish a low coverage dataset of 1440 positive samples with T13, T18, and T21 aberrations for both mosaic and non-mosaic conditions. We examined the performance of WisecondorX and its improvement, called VINIPT, on both negative and positive datasets. Experiments showed that WisecondorX and VINIPT with a z-score threshold of 3.3 were able to detect all non-mosaic samples with T13, T18, and T21 aberrations (i.e., the sensitivity of 100%). Using a lower z-score threshold of 2.58 when analyzing mosaic samples, both WisecondorX and VINIPT have the overall sensitivity of 99.7% on detecting T13, T18, and T21 aberrations from mosaic samples. WisecondorX has the specificity of 98.5% for the non-mosaic analysis, but a considerably lower specificity of 95% for the mosaic analysis. VINIPT has a much better specificity than WisecondorX, i.e., 99.9% for the non-mosaic analysis, and 98.2% for the mosaic analysis. The results suggest that VINIPT can play as a powerful NIPT tool for the low coverage data.
Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach withPlesiomonas shigelloides
Authors: Hossain Mohammad Uzzal , Rahman A.B.Z Naimur , Hossain Md. Shahadat , Dey Shajib , Chowdhury Zeshan Mahmud , Bhattacharjee Arittra , Ahammad Ishtiaque , Ahmed Md. Imran , Sultana Khandokar Fahmida , Hashem Abu , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md.
Published: November 2023

Diarrhea is the second leading cause of mortality among infants under the age of five. One of the main causes of this disease is multipathogenic infections, which can make the conditions of patients even worse.Plesiomonas shigelloides(P. shigelloides) is one of the pathogenic bacteria that contributes to the pathophysiology of diarrhea and may be implicated in coinfection with other diarrheal pathogens. Therefore, the purpose of this study is to investigate the hypothetical proteins to explore the genetic insights ofP. shigelloidesand its relationships with common diarrheal diseases. For this reason, we used 16S rRNA sequencing together with several biochemical tests to identify the bacteria that we isolated from diarrheal patients (8 years). Afterwards, the whole genome ofP. shigelloideswas sequenced, assembled and annotated in order to obtain the genomic insights ofP. shigelloides. In addition, the common virulence genes of ten (10) common diarrhea-causing bacteria were identified from 100 whole genome sequences. Finally, the system biology approach was applied to predict the coinfection pattern betweenP. shigelloidesand the virulence genes of 10 bacteria. The complete genome sequencing analysis of this bacterium revealed 899 hypothetical proteins from which 33 hypothetical proteins shared the clusters with the 109 virulence genes of 10 distinct diarrheal pathogens, forming a strong interaction based on biological processes, molecular functions, subcellular localization, or pathways. All diarrhea causing bacteria were found to haveP. shigelloidesmicrobial interactions; however,V. choleraeexhibited the strongest relationships, whileC. difficileshowed the weakest. The results of this investigation clearly imply thatP. shigelloidesshares a coinfection pattern with other bacteria that cause diarrhea. Finally, the findings from the complete genome provide new avenues for researchers to pursue their investigation of the pathophysiology of diarrhea.
Developing folate-conjugated miR-34a therapeutic for prostate cancer treatment: Challenges and promises
Authors: Li Wen (Jess) , Wang Yunfei , Liu Xiaozhuo , Wu Shan , Wang Moyi , Turowski Steven G. , Spernyak Joseph A. , Tracz Amanda , Abdelaal Ahmed M. , Sudarshan Kasireddy , Puzanov Igor , Chatta Gurkamal , Kasinski Andrea L. , Tang Dean G.
Published: November 2023

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate-miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate-miR-34a, we found that folate-miR-34a exhibited impressive inhibitory effects on breast, ovarian and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate-miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate’s binding capability to PSMA. These results highlight challenges in specific delivery of folate-miR-34a to PCa due to lack of target (receptor) expression. Our study offers novel insights on the challenges and promises within the field and cast light on the development of ligand-conjugated miR-34a therapeutics for PCa.
Obesity status and its relative factors of captive Asian elephants (Elephas maximus) in China based on body condition assessment
Authors: Tang Yinpu , Jia Ting , Zhou Fangyi , Wang Liang , Zhang Li
Published: November 2023

Obesity is a common health problem in captive wildlife. Since the obesity status of captive Asian elephants (Elephas maximus) in China has not previously been investigated, we recorded seven relevant variables (sex, age, daily feed supply, proportion of high-calorie feed, outdoor enclosure area, outdoor time, and foot disorder) related to obesity in 204 captive Asian elephants through field investigation of 43 elephant-raising facilities. Assessment of obesity was based on visual body condition scoring for each individual. It revealed that obesity was prevalent for captive Asian elephants (especially elephants in zoos) in China. Over 70% of captive Asian elephants in China were overweight or in obesity to various degrees. Statistical analysis showed that for elephants in zoos, insufficient outdoor time might be the primary potential cause of obesity. We suggested facilities to extend the outdoor time and control the supply of high-calorie feed (e.g., fruits, vegetables, pellets, etc.) for captive elephants, thereby alleviating obesity through increased exercise and a suitable energy intake. Moreover, all facilities should implement positive reinforcement training to facilitate regular physical examinations, including foot health checks and blood sampling. This training would improve the ability to collect more precise information relating to elephant health, obesity, and the evaluation of animal welfare.
Assessment of antimicrobial activity of insects’ products and nests used in traditional medicine in Burkina Faso
Authors: Ouango Mamadou , Cissé Hama , Romba Rahim , Drabo Samuel Fogné , Semdé Rasmané , Savadogo Aly , Gnankiné Olivier
Published: November 2023

In Burkina Faso, products and insect nests are used for therapeutic purposes in traditional medicine. However, this use by local populations is marginal and empirical. Our study aimed at evaluating the antimicrobial activity of insect products and their nests. For this purpose, the collected insect products and nests were finely ground. Hydroethanolic extraction of bioactive molecules with potential antibacterial activity was performed according to standard methods. The solid medium diffusion method was used to test the antibacterial activity of hydroethanolic extracts of honey bee, bee wax, propolis, and termite nests against 22 pathogenic strains by inhibition diameter. Imipenem was used as a positive control. The extraction yields varied from 7.33% to 35.38% depending on the content of soluble matter. All products extracts and insect nests tested showed inhibitory activities. The inhibition diameters varied depending on the extract and strain tested. The largest diameter of inhibition (26±0.0 mm) was obtained using the nest extract ofMacrotermes bellicosusagainstSalmonellaTyphimurium ATCC14028. The lowest diameter of inhibition was 07±0.0 mm obtained with honey extract against Pseudomonas aeruginosa ATCC27853. Index multi-resistance of the extracts tested were between 0.2 and 0.6. Interestingly, the inhibition diameters of certain products and nest extracts of insects were sometimes greater than those of imipenem against the strains tested. This study revealed the antimicrobial potential of termite nest extracts and hive products against pathogens.
Evaluation of Phage and Antibiotic Combinations forStaphylococcus aureusBiofilm Eradication: Insights from the Wax Worm Model
Authors: Archana L , Manohar Prasanth , Bozdogan Bulent , Nachimuthu Ramesh
Published: November 2023

Background

Galleria mellonella, an advantageous model organism, to investigate the therapeutic potential of bacteriophages. Employing theGalleria mellonella(waxworm) model, this study involved infecting the larvae with pathogenicStaphylococcus aureus, followed by combination treatment with staph phages; vB_Sau_Saa90 and vB_Sau_Saa165 at the concentrations of 107and 109PFU/mL and oxacillin, at 100 mg/kg. The treatment modalities were executed in three distinct orders: pre-phage treatment, simultaneous treatment, and post-phage treatment. Each treatment was administered at 90 min intervals. The health state index of the waxworms was monitored throughout the study.

Results

Among the three treatment orders, both pre-phage treatment and post-antibiotic treatment exhibited the significant outcomes. The survival percentages ranged from 40% to 50%, 30% to 50%, and 50% to 70% across strong, moderate, and weak biofilm conditions. Notably, the phages vB_Sau_Saa90 and vB_Sau_Saa165 displayed remarkable effectiveness in combination with antibiotics. This successful synergy showcased the potential of combinatorial treatment in effectively addressing biofilm-related infections.

Conclusions

This study holds considerable significance as it underscores the suitability ofG. mellonellaas a model organism for exploring bacteriophage-based therapeutic approaches. The study’s findings shed light on the efficacy of combining bacteriophages and antibiotics to targetS. aureusbiofilm cells. The observed results in the waxworm model highlight a promising avenue for managing biofilm infections. However, the need for further validation through larger animal models is emphasized, as this could potentially pave the way for novel treatment strategies with broader clinical implications.
A bibliometric analysis of global research trends on CEO compensation: evidence from the Scopus database
Authors: Alfawareh Faraj Salman , Che Johari Edie Erman , Ooi Chai-Aun
Published: November 2023

Purpose

This study investigates the current trends in CEO compensation by applying a bibliometric technique from the Scopus database.

Design/methodology/approach

The bibliometric analysis examines CEO compensation trends through the Scopus database. Frequency analysis is conducted using Microsoft Excel, while data visualisation is performed using VOSviewer. Finally, citation metrics are carried out using Harzing's Publish or Perish.

Findings

The results reveal that research into CEO compensation has been consistently increasing since 1976. This study identifies the most popular publication trends, the most active institutions, the top funding institutions, annual publication growth, document and source type, publishers, subject area, author co-citations, highly cited articles, top publishing countries, and keyword co-occurrences. Notably, Arizona State University in the United States (US) is the leading institution with the most prominent publications on CEO compensation. The US is the most active country involved in CEO compensation research.

Research limitations/implications

The current research only derived articles from the Scopus database. Nonetheless, the findings provide an in-depth comprehension of the meaning of “CEO compensation” and present the outline of the research trends on the concept, thus significantly facilitating further studies.

Practical implications

The findings can assist researchers in comprehending and classifying the drivers of CEO compensation previously identified and proven in past studies. Additionally, the findings also create opportunities for new researchers to study CEO compensation.

Originality/value

This study is among the pioneering research investigating CEO compensation-related publications and utilising the Scopus database from an international perspective. This study also offers a historical view of CEO remuneration, a summary of the most significant nations, journals, and writers on the topic, and an outline of how CEO remuneration studies have changed over time. These contributions will enable other researchers to focus on this subject.
Reinventing the wheel? Factors influencing relationship: links between sustainability and financial performance. European evidence
Authors: Rahi ABM Fazle , Johansson Jeaneth , Lions Catherine
Published: November 2023

Purpose

This study aims to examine the factors that influence the relationship between sustainability and financial performance (FP) of the European listed companies.

Design/methodology/approach

This study analyzed data from 795 companies in 21 European countries by applying linear mixed-effects multilevel regressions, a two steps system generalized method of moments and quantile regression models to uncover the links between sustainability and FP.

Findings

The past four decades have witnessed abundant research to determine the relationship between corporate sustainability and FP. Thus, conducting further research in 2023 could be seen as “reinventing the wheel.” Yet, earlier research considered firms as isolated entities with sustainability and FP being dependent only on that firm’s actions. By contrast, with the help of network governance theory, this study shows that a firm’s sustainability and FP depend on an interplay among interorganizational actors, such as institutional qualities, macroeconomic factors and an embrace of sustainability. Here, large firms play an essential role. Three significant findings are drawn. First, sustainability performance has a significant impact on FP in the European context. Second, the institutional quality (IQ) of the rule of law and control of corruption plays a crucial role in enhancing sustainability and FP, and finally the interaction of IQ and economic growth helps to increase companies’ market value (Tobin’s Q). The consistent and empirically robust findings offer key lessons to policymakers and practitioners on the interplay among multiple actors in corporate sustainability and FP.

Practical implications

A synergetic multifaced relationship between governmental institutions and corporations is inevitable for ensuring sustainable development. The degree of intimacy in the relationship, of course, will be determined by the macroeconomic environment.

Originality/value

In this research, this study theoretically and empirically identified that corporate sustainability and FP are not solely dependent on corporate operation. Rather, it is transformed, modified and shaped through an interaction of multiple actors’ trajectories in the macro business environment.
AI Fluid Flow AIFF for Understanding Porous Media Behavior from Micro to Reservoir Scale Aided by Machine Learning
Authors: Alfarisi Omar
Published: November 2023

Developing an optimal water flooding scheme involves considering various petrophysical reservoir properties. These properties, such as permeability, capillary pressure, relative permeability, and wettability, make predicting water flooding outcomes complex. Our research aims to understand oil extraction processes at the laboratory level to design and implement injection schemes at the reservoir scale. We used Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) alongside artificial intelligence semantic segmentation image analyses to observe and analyze fluid behavior in intricate pore throat networks. We explored the in-situ 3D fluid flow profile with NMR-MRI images calibrated with multiple CCA, SCAL, 3D micro-models, and 3D printed reference calibrators. We conclude an Artificial Intelligence (AI) aided flood monitoring process that characterizes and understands complex carbonate sweep efficiency.
Mapping invasive alien plants through citizen science: shortlisting species of concern for the Nilgiris
Authors: Rehel Shiny Mariam , R.S. Reshnu Raj  , Samuel Thomas  , Milind Bunyan  , Anita Varghese  , Ankila J. Hiremath
Published: November 2023

Species introduced from elsewhere are known as alien species. They may be introduced as crop plants or ornamental plants, or for timber. A small proportion of introduced species can become invasive thereby spreading at the cost of native species and habitats, negatively affecting biodiversity, food security, and human wellbeing. Despite the growing recognition of the threat of invasive alien species, we still lack information about the distribution and abundance of species widely accepted to be invasive. To address this information gap regarding invasive alien species distributions, we initiated a pilot citizen science effort to create an atlas of invasive plants in the Moyar-Bhavani landscape of the Nilgiri District. We aimed, through this pilot effort, to develop and test user-friendly mapping protocols and develop an interface for citizen scientists to use. Ultimately, we hope to create a model that can be scaled up to large conservation landscapes, such as the Western Ghats, the central Indian Highlands, and the Himalaya.
Dialectical myth of the Fall
Authors: Trovik Johan
Published: November 2023

This article reinterprets the Dialectic of Enlightenment as a retelling of the Christian myth of the Fall. Through its account of the aporia, which Horkheimer and Adorno maintain stands at its core, the Dialectic of Enlightenment rearticulates the doctrine of original sin. The human condition is presented as tragic, and the source of this tragedy is inscribed into the very structure of human subjectivity. While the Dialectic of Enlightenment refuses to abandon hope, emancipation is reconceptualised on the model of redemption; a kind of fulfilment of human nature, which would at the same time be an escape from it. Horkheimer and Adorno dispense, however, with any transcendent source of grace. Instead, the activity of philosophy itself takes on redemptive quality.
A Case of Fatal Non-Clostridial Gas Gangrene Following Intramuscular Injection: A Diagnostic Challenge and Dilemma at Autopsy
Authors: Das Siddhartha , Ramaswamy N , Sathish K
Published: November 2023

Introduction:

Gas Gangrene following intramuscular injection is a rare but serious condition that can lead to morbidity and mortality. This case conveys a severe and fatal complication following intramuscular injections of diclofenac and vitamin B12 in a diabetic patient.

Case Report:

The patient developed pain and swelling in the left buttock after the injection of vitamin B12 and Diclofenac one on each buttock which worsened over time. He was diagnosed with gas gangrene when he presented to the emergency department. The blood culture identified Klebsiella pneumonia. The patient’s condition rapidly deteriorated, leading to sepsis and acute kidney injury. Despite intensive care management, the patient succumbed five days after admission. At autopsy, gas gangrene of the left lower limb was evident on external examination. Histopathological examination confirmed the acute tubular damage in the kidney and the postmortem blood culture also grew Klebsiella pneumonia and Enterobacter cloacae. The cause of death was determined to be acute tubular necrosis as a result of sepsis due to non-clostridial gas gangrene.

Conclusion:

This instance of gas gangrene following trivial trauma poses a challenge for the forensic pathologist in establishing the causal association and in determining the causative organism. These are important when medical/surgical intervention is in question to be the cause of a fatal infection like gas gangrene. Ante-mortem/postmortem blood culture can aid in defining the causative organism of gas gangrene but the causal association with the alleged trauma/insult is still a challenge at autopsy. This case report addresses and tries to overcome the diagnostic challenges and dilemmas at autopsy in a case of gas gangrene.
Taxing Times: Coffee in Nineteenth-century Mysore and Coorg
Authors: Shrivastava Sharmila
Published: November 2023

The taxation of coffee in Mysore and Coorg went through three phases during the course of the nineteenth century. Waram tax (1799–1800) of equal sharing of the crop was succeeded by halat (1838) excise duty on the produce exported out of the taluks. Land tax was introduced in Coorg in 1864 and in Mysore in 1881. Coffee was cultivated on high forested hill slopes—in jungles, gardens, backyards, sacred groves and on inam lands. Local tradition, topography of coffee lands, pre-colonial assessment systems and colonialism impacted taxation. The varied sites of coffee cultivation and the long gestation period of the coffee tree influenced imposition of the three taxes. The waram phase was associated with revenue farming (1822–1837) and monopoly over coffee trade. The British administration encouraged the establishment of European plantations. Halat induced expansion of acreage and smuggling of coffee with revenue loss to the state. Increasing demand and competition led to a scarcity of suitable lands. Natives dominated coffee acreage and production in Mysore and preferred halat. Lands were granted with a variable halat and could be resumed if no coffee was planted. European planters wanted a fixed land tax for secure proprietary rights over their estates. A colonial discourse was created on ‘slovenly’ native coffee cultivation, juxtaposed to superior European plantation methods—thereby pressing for acreage assessment of coffee lands. It was introduced in Coorg, which was part of British India. Acreage tax was introduced after almost two decades of European demand in Mysore: a native Indian state. The state, however, did not give full proprietary rights over lands to the planters.
GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers
Authors: Sathe Anuja , Ayala Carlos , Bai Xiangqi , Grimes Susan M. , Lee Byrne , Kin Cindy , Shelton Andrew , Poultsides George , Ji Hanlee P.
Published: November 2023

Background

Understanding the mechanistic effects of novel immunotherapy agents is critical to improving their successful clinical translation. These effects need to be studied in preclinical models that maintain the heterogenous tumor microenvironment (TME) and dysfunctional cell states found in a patient’s tumor. We investigated immunotherapy perturbations targeting co-stimulatory molecule GITR and co-inhibitory immune checkpoint TIGIT in a patient-derived ex vivo system that maintains the TME in its near-native state. Leveraging single-cell genomics, we identified cell type-specific transcriptional reprogramming in response to immunotherapy perturbations.

Methods

We generated ex vivo tumor slice cultures from fresh surgical resections of gastric and colon cancer and treated them with GITR agonist or TIGIT antagonist antibodies. We applied paired single-cell RNA and TCR sequencing to the original surgical resections, control, and treated ex vivo tumor slice cultures. We additionally confirmed target expression using multiplex immunofluorescence and validated our findings with RNA in situ hybridization.

Results

We confirmed that tumor slice cultures maintained the cell types, transcriptional cell states and proportions of the original surgical resection. The GITR agonist was limited to increasing effector gene expression only in cytotoxic CD8 T cells. Dysfunctional exhausted CD8 T cells did not respond to GITR agonist. In contrast, the TIGIT antagonist increased TCR signaling and activated both cytotoxic and dysfunctional CD8 T cells. This included cells corresponding to TCR clonotypes with features indicative of potential tumor antigen reactivity. The TIGIT antagonist also activated T follicular helper-like cells and dendritic cells, and reduced markers of immunosuppression in regulatory T cells.

Conclusions

We identified novel cellular mechanisms of action of GITR and TIGIT immunotherapy in the patients’ TME. Unlike the GITR agonist that generated a limited transcriptional response, TIGIT antagonist orchestrated a multicellular response involving CD8 T cells, T follicular helper-like cells, dendritic cells, and regulatory T cells. Our experimental strategy combining single-cell genomics with preclinical models can successfully identify mechanisms of action of novel immunotherapy agents. Understanding the cellular and transcriptional mechanisms of response or resistance will aid in prioritization of targets and their clinical translation.
Bridging language barriers in developing valid health policy research tools: insights from the translation and validation process of the SHEMESH questionnaire
Authors: Shalev Ligat , Helfrich Christian D. , Ellen Moriah , Avirame Keren , Eitan Renana , Rose Adam J.
Published: November 2023

Background

The use of research tools developed and validated in one cultural and linguistic context to another often faces challenges. One major challenge is poor performance of the tool in the new context. This potentially impact the legitimacy of health policy research conducted with informal adaptations of existing tools which have not been subjected to formal validation. Best practices exist to guide researchers in adapting and validating research tools effectively. We present here, as an extended example, our validation of the SHEMESH questionnaire ('Organizational Readiness to Change Assessment'; In Hebrew: 'SHE'elon Muchanut Ergunit le'SHinuy'), a Hebrew-language version of the Organizational Readiness to Change Assessment (ORCA). SHEMESH is tailored to support implementation science projects, whose aim is to promote a more rapid and complete adoption of evidence-based health policies and practices.

Methods

The SHEMESH included originally eleven questions from the Evidence (item 1–4) and Context (items 5–11) domains. We validated SHEMESH through the following steps: 1. Professional translation to Hebrew and discussion of the translation by multidisciplinary committee; 2. Back-translation into English by a different translator to detect discrepancies; 3. Eleven cognitive interviews with psychiatric emergency department physicians and nurses; and 4. Pilot testing and psychometric analyses, including Cronbach’s alpha for subscales and factor analyses.

Results

Following translation and cognitive interviews, SHEMESH was administered to 222 psychiatrists and nurses. Pearson correlation showed significant and strong correlations of items 1–4 to the Evidence construct and items 6–11 to the Context construct. Item 5 did not correlate with the other items, and therefore was removed from the other psychometric procedures and eventually from the SHEMESH. Factor analysis with the remaining 10 items yielded two factors, which together explained a total of 69.7% of variance. Cronbach's Alpha scores for the two subscales were high (Evidence, 0.887, and Context, 0.852).

Conclusions

This multi-step validation process of the SHEMESH questionnaire may serve as a comprehensive guideline for others who are willing to adapt research tools that were developed in other languages. Practically, SHEMESH has been validated for use in implementation science research projects in Israel.
The UK Crop Microbiome Cryobank: a utility and model for supporting Phytobiomes research
Authors: Ryan Matthew J. , Mauchline Tim H. , Malone Jacob G. , Jones Susan , Thompson Catriona M. A. , Bonnin J. Miguel , Stewart Helen , Yau Payton T. O. , Taketani Rodrigo G. , Clark Ian M. , Holden Nicola
Published: November 2023

Plant microbiomes are the microbial communities essential to the functioning of the phytobiome—the system that consist of plants, their environment, and their associated communities of organisms. A healthy, functional phytobiome is critical to crop health, improved yields and quality food. However, crop microbiomes are relatively under-researched, and this is associated with a fundamental need to underpin phytobiome research through the provision of a supporting infrastructure. The UK Crop Microbiome Cryobank (UKCMC) project is developing a unique, integrated and open-access resource to enable the development of solutions to improve soil and crop health. Six economically important crops (Barley, Fava Bean, Oats, Oil Seed Rape, Sugar Beet and Wheat) are targeted, and the methods as well as data outputs will underpin research activity both in the UK and internationally. This manuscript describes the approaches being taken, from characterisation, cryopreservation and analysis of the crop microbiome through to potential applications. We believe that the model research framework proposed is transferable to different crop and soil systems, acting not only as a mechanism to conserve biodiversity, but as a potential facilitator of sustainable agriculture systems.
Using DMAIC for in-plant logistic activities improvement
Authors: Bonetti Sérgio de Andrade , Bueno Adauto , Silva Rodolfo Benedito Zattar da , Paredes Fernando José Gómez , Bianco Débora
Published: November 2023

Goal: In-plant logistics activities are important for increasing the performance of the supply chains, so our research aims to study the application of Six Sigma tools for in-plant logistics activities in the cement industry. Our research contributes to the literature by developing a real case study that provides insights into the practical implementation of continuous improvement programs.
Design / Methodology / Approach: This study uses the Industrial Case Study in a large cement plant, a branch of a multinational business group, in Brazil’s Middle-west region. This research applies Define, Measure, Analyze, Improve, Control (DMAIC) guidelines with Statistical Process Control tools for solving a real problem for out-control processes. From this, we propose an improvement plan to correct flaws in the in-plant cement loading and unloading process (in-plant logistics).
Results: The results suggest that based on the control chart, the studied in-plant logistics activities were out of control. These processes exhibit a high variability, between 3σ and 5σ, presenting 26 problems with causes related to machine, measure, and human resources. An out-control action plan was proposed aiming for improvements to solve these problems.
Limitations of the investigation: On the out-control action plan, this study presents an improvement proposal. The action plan does not fully develop the control step for DMAIC.
Practical implications: Managers in the cement industry can use our case for insights and learning about improvement programs, especially for the in-plant logistics activities addressing processing-based manufacturing environments.
Originality / Value: Our research contributes a real case study that applies the DMAIC methodology, with a specific focus on in-plant logistics activities. By developing the application of improvement programs within the cement industry, our study offers practical insights into how processing industries can effectively implement such programs.
Oxidation of Tris(2-Methoxy-5-Bromophenyl)Antimony by tert-Butylhydroperoxide in the Presence of Compounds Containing a Mobile Hydrogen Atom
Authors:   South Ural State University, Chelyabinsk, Russian Federation, Efremov A. , Sharutin V.
Published: November 2023

Oxidation of tris(2-methoxy-5-bromophenyl)antimony with tertiary butylhydroperoxide in the presence of water, benzoic acid, 2,6-dihydroxybenzoic acid and 2-chloro-4-fluorophenol in diethyl ether leads to formation of tris(2-methoxy-5-bromophenyl)antimony oxide (1), tris(2-methoxy-5-bromophenyl)antimony dibenzoate (2), -oxo[hexakis(2-methoxy-5-bromophenyl)-bis(2,6-dihydroxybenzoato)diantimony] (3), -oxo[hexakis(2-methoxy-5-bromophenyl)-bis(2-chloro-4-fluorophenoxo)diantimony] (4), respectively. The compounds have been identified by X-ray diffraction analysis. According to the X-ray diffraction data, the crystal of solvate 1 with chloroform consists of centrosymmetric binuclear molecules containing the Sb2O2 cycle with tetragonal coordination of the antimony atoms (the Sb–O bond lengths are 1.961(4) and 2.041(5) Å, the Sb–C distances are 2.114(6)–2.153(6) Å). In solvate 2 with benzene the antimony atoms have a distorted trigonal-bipyramidal coordination with the oxygen atoms of carboxylate ligands in axial positions (Sb–O 2.075(4), 2.105(4) Å), the carbonyl oxygen atoms are coordinated with the central metal atom (Sb∙∙∙O=C 3.023(6), 3.077(8) Å), the Sb–C bond lengths (2.104(5)–2.112(5) Å) are significantly less than in 1. The ranges of variation in the Sb–C bond lengths in the practically linear binuclear molecule of solvate 3 with acetonitrile are 2.101(5)–2.106(5) and 2.100(5)–2.104(5) Å (the SbOSb angle equals 178.05(18)). The bond lengths of antimony atoms with the bridging oxygen atom (1.925(4), 1.936(4) Å) are less than the sum of the covalent radii of antimony and oxygen, as well as the distances between the antimony atom and the terminal carboxyl ligand (Sb–O 2.263(4), 2.214(4) Å). The carbonyl oxygen atoms are coordinated with the central metal atom (Sb∙∙∙O=C 3.484(8), 3.512(9) Å) to a lesser extent than in 2. The crystal of solvate 4 with benzene contains two types of crystallographically independent corner molecules (the SbOSb angles are 163.75(18), 164.27(19)), the difference in lengths of the Sb–Obridge (1.939(11)–1.981(13) Å) and Sb–Oterm (2.096(11)–2.208(11) Å) is not as sharp as in the case of complex 3. Complete tables of atom coordinates, bond lengths and valence angles are deposited at the Cambridge Crystallographic Data Center (No. 2070383 (1); No. 2074511 (2); No. 1970910 (3); No. 2064392 (4); deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk/data_request/cif).
Synthesis and Structure of Tetraphenyl¬antimony 1-Naphtalenesulfonate
Authors:   South Ural State University, Chelyabinsk, Russian Federation, Sharutina O.
Published: November 2023

Interaction of equimolar amounts of pentaphenylantimony and 1-naphtalenesulfonic acid in benzene led to tetraphenylantimony 1-naphtalene monohydrate Ph4SbOSO2Naft-1∙H2O (1), the structure of which was then characterized. According to the X-ray diffraction data, obtained on an automatic four-circle D8 Quest Bruker diffractometer (two-axis CCD detector, МоКα radiation, λ = 0.71073 Å, graphite monochromator) at 293 K for crystal 1: [C34H29O4SSb, M 655.38; triclinic syngony, symmetry group Р-1; cell parameters: a = 9.456(3), b = 12.541(4), c = 13.980(6) Å; α = 74.151(15) deg., β = 79.979(19) deg., γ = 68.178(12) deg.; V = 1475.7(9) Å3; crystal size 0.5×0.5×0.23 mm; reflection index intervals –12 ≤ h ≤ 12, –16 ≤ k ≤ 16, –18 ≤ l ≤ 18; total reflections 20654; independent reflections 5934; Rint 0.0385; GOOF 1.202; R1 = 0.1215, wR2 = 0.3556; residual electron density 1.98/2.53 e/Å3], the antimony atoms have a distorted trigonal-bipyramidal coordination with the carbon and oxygen atoms in the axial positions (the CSbO angle is 172.3(6)°, the Sb∙∙∙O distance equals 2.84(1) Å). The SbC and SO bond lengths in 1 change within a narrow range (2.000(13)2.132(13) Å and 1.441(4)1.456(4) Å). The structural organization in crystal 1 is caused by weak intermolecular contacts of the S=О···Н–C type, 2.50–2.71 Å. Complete tables of atom coordinates, bond lengths and valence angles for structure 1 are deposited at the Cambridge Crystallographic Data Center (No. 2115624; deposit@ccdc.cam.ac.uk; http://www.ccdc.cam.ac.uk).
A New Method for the Synthesis of Tetraphenylbismuth 1-Naphthalenesulfonate
Authors:   South Ural State University, Chelyabinsk, Russian Federation, Rybakova A.
Published: November 2023

The reaction of pentaphenylbismuth with triphenylantimony bis(1-naphthalenesulfonate) in benzene led to tetraphenylbismuth 1-naphthalenesulfonate, yielding 38%, which after recrystallization from water was identified as Ph4BiOSO2C10H7  H2O hydrate (1). Structure 1 (colorless crystals with mp 178 °C) was determined by X-ray diffraction analysis (XRD) on an automatic four-circle D8 Quest Bruker diffractometer (МоКα radiation, λ = 0.71073 Å, graphite monochromator) at 293 K. Crystal size 0.27 × 0.25 × 0.09 mm, P–1, a = 9.542 (5), b = 12.595 (5), c = 13.998 (5) Å,  = 74.228 (15), β = 80.06 (2), = 68.758 (15) deg., V = 1503.7 (12) Å3, Z = 2. Data collection area for 2 equaled 5.72–77.8, reflection index intervals were –16 ≤ h ≤ 16, –22 ≤ k ≤ 22, –24 ≤ l ≤ 24; a total of 102981 reflections were measured, 17181 independent reflections, refinement variables 364, μ = 5.968 mm–1; GOOF 0.987, the final values of the divergence factors R1 = 0.0534 and wR2 = 0.0941 (for reflexes F2> 2 (F2), R1 = 0.1619 and wR2 = 0.1163 (for all reflections), residual electron density 2.65 /–1.05 e/Å3. The bismuth atom in molecule 1 has a strongly distorted trigonal-bipyramidal coordination with the arenesulfonate substituent in the axial position. The СBiС bond angles are 100.52 (8) -119.28 (7), the Bi–C and Bi–O distances are 2.179 (2) -2.212 (2) and 2.915 (1) Å, respectively. Two molecules 1 are combined into dimers through hydrogen bonds between the hydrogen atoms of two water molecules and the oxygen atoms of two naphthalenesulfonate groups.
Synthesis and Structure of 6-Amino-5-nitro-2-propargylsulfanyl-4(3H)-pyrimidinone
Authors:   South Ural State University, Chelyabinsk, Russian Federation, Artem’eva E. , Petrova K.
Published: November 2023

6-Amino-5-nitro-2-propargylsulfanyl-4(3H)-pyrimidinone (1) has been synthesized for the first time by the reaction of 6-amino-5-nitroso-2-propargylsulfanyl-4(3H)-pyrimidinone with tert-butyl hydroperoxide at equimolar ratio of the reactants leading to selective oxidation of ni-troso group to a nitro one. The product is a crystalline substance, soluble in aromatic hydrocar-bons, resistant to air oxygen and moisture. The compound has been characterized by IR and 1H NMR spectroscopy and X-ray diffraction analysis. The IR spectrum of 1 contains absorption bands at 3290 (NH2, st), 2855 (S–CH2, st), 1684 (C=O, st) and 1595 (NO2, st) cm–1. In the 1H NMR spectrum of 1 there are singlets of SCH2 protons at 3.87 ppm and С≡CH at 3.12 ppm. Downfield, there are singlets of NH2 group protons at 7.77 ppm and pyrimidine ring NH protons at 10.89 ppm. According to X-ray diffraction analysis data, in the crystal there are two types of crystallographically independent molecules, geometrical parameters of which are slightly different. X-ray diffraction data show that the crystal cell contains molecules of the used solvent, dimethylformamide. The planes of the nitro and thio groups are parallel to the plane of the heterocyclic fragment. C–NO2 and C–NH2 bond lengths are 1.452(2) and 1.317(2) Å, which is usual for compounds of these classes. The CAr–S distance is 1.748(2) Å. The structural arrangement of molecules in a crystal is due to O•••H hydrogen bonding (1.91(2)–2.70(1) Å) and intermolecular N•••O interactions (2.767(3)–2.984(3) Å). Also, there are face-to-face stacking interactions, the distances between centroids of aromatic rings are 4.13–4.46 Å.
Temperature Dependences of the Saturated Vapor Pressure of Tin (IV) Complexes with Polydentate Ligands
Authors:   G.A. Razuvaev Institute of Organometallic Chemistry of the RAS,  Nizhny Novgorod, Russian Federation, Lazarev N. , Petrov B. , Piskunov A. , Pochekutova P. , Semenov V.
Published: November 2023

The present paper is a continuation of the previously pursued studies of thermal properties of the Sn(IV) complexes with tridentate iminopyridine ligands. The study of thermal properties including temperature dependences of the saturated vapor pressure for Sn(IV) complexes with the tridentate iminopyridine ligands by differential scanning calorimetry (DSC) and the Knudsen effusion method leads to the use of the studied compounds as luminescent materials, as well as components for nonlinear optics. Coordination compounds of tin (IV) containing tridentate Schiff bases were chosen as objects of research: 2,4-di-tert-butyl-6-((phenyl (pyridin-2-yl)methylene)amino)phenolatotrichlorotin(IV) (1), 4-methyl-2-((phenyl (pyridin-2-yl)methylene)amino)phenolatotrichlorotin(IV) (2), 4-chloro-2-((phenyl (pyridin-2-yl)methylene)amino) phenolatotrichlorotin(IV) (3). These compounds were obtained by tem-plate synthesis from tin tetrachloride, various o-aminophenols, and α-carbonyl substituted pyri-dines; they contain an iminopyridine function and are capable of covalently binding to a metal by a phenolic group. Phase transitions of compounds 1–3 were studied by DSC in the temperature range 25–500 °C. For all studied complexes an endothermic transition correlated to melting was revealed. The melting points of the studied compounds were taken to be the temperature values corresponding to the onset of the transition, according to the standard Netzsch Software Proteus method: 300, 320 and 330 °C for 1–3, respectively. The temperature dependences of the saturated vapor pressure were obtained for the studied complexes, using the Knudsen effusion method with the weight recording of the amounts of sublimated substances. As a result of the experiments it was found that compounds 1–3 sublimated in the temperature ranges of 239–244, 228–260 and 226–256 °C, respectively. Thermodynamic parameters of sublimation processes were calculated.