bluuebunny/crossref_metadata_2025 huggingface dataset:
An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety, tolerability, and immune biomarkers from limited case numbers
Authors: Olson Katherine E. , Abdelmoaty Mai M. , Namminga Krista L. , Lu Yaman , Obaro Helen , Santamaria Pamela , Mosley R. Lee , Gendelman Howard E.
Published: May 2023

Background

The clinical utility and safety of sargramostim has previously been reported in cancer, acute radiation syndrome, autoimmune disease, inflammatory conditions, and Alzheimer’s disease. The safety, tolerability, and mechanisms of action in Parkinson’s disease (PD) during extended use has not been evaluated.

Methods

As a primary goal, safety and tolerability was assessed in five PD patients treated with sargramostim (Leukine®, granulocyte–macrophage colony-stimulating factor) for 33 months. Secondary goals included numbers of CD4+T cells and monocytes and motor functions. Hematologic, metabolic, immune, and neurological evaluations were assessed during a 5-day on, 2-day off therapeutic regimen given at 3 μg/kg. After 2 years, drug use was discontinued for 3 months. This was then followed by an additional 6 months of treatment.

Results

Sargramostim-associated adverse events included injection-site reactions, elevated total white cell counts, and bone pain. On drug, blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment. Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased. In the initial 6 months of treatment, transcriptomic and proteomic monocyte tests demonstrated autophagy and sirtuin signaling. This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.

Conclusions

Taken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation.

Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL:https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2.
Overlapped Bayesian spatio-temporal models to detect crime spots and their possible risk factors based on the Opole Province, Poland, in the years 2015–2019
Authors: Drozdowski Rafał , Wielki Rafał , Tukiendorf Andrzej
Published: May 2023

Geostatistical methods currently used in modern epidemiology were adopted in crime science using the example of the Opole province, Poland, in the years 2015–2019. In our research, we applied the Bayesian spatio-temporal random effects models to detect ‘cold-spots’ and ‘hot-spots’ of the recorded crime numbers (all categories), and to ascertain possible risk factors based on the available statistical population (demographic), socio-economic and infrastructure area characteristics. Overlapping two popular geostatistical models in the analysis, ‘cold-spot’ and ‘hot-spot’ administrative units were detected which displayed extreme differences in crime and growth rates over time. Additionally, using Bayesian modeling four categories of possible risk factors were identified in Opole. The established risk factors were the presence of doctors/medical personnel, road infrastructure, numbers of vehicles, and local migration. The analysis is directed toward both academic and police personnel as a proposal for an additional geostatistical control instrument supporting the management and deployment of local police based on easily available police crime records and public statistics.
The gut microbiota as a booster for radiotherapy: novel insights into radio-protection and radiation injury
Authors: Yi Yuxi , Lu Weiqing , Shen Lijun , Wu Yang , Zhang Zhen
Published: May 2023

Approximately 60–80% of cancer patients treated with abdominopelvic radiotherapy suffer post-radiotherapy toxicities including radiation enteropathy and myelosuppression. Effective preventive and therapeutic strategies are lacking for such radiation injury. The gut microbiota holds high investigational value for deepening our understanding of the pathogenesis of radiation injury, especially radiation enteropathy which resembles inflammatory bowel disease pathophysiology and for facilitating personalized medicine by providing safer therapies tailored for cancer patients. Preclinical and clinical data consistently support that gut microbiota components including lactate-producers, SCFA-producers, indole compound-producers and Akkermansia impose intestinal and hematopoietic radio-protection. These features serve as potential predictive biomarkers for radiation injury, together with the microbial diversity which robustly predicts milder post-radiotherapy toxicities in multiple types of cancer. The accordingly developed manipulation strategies including selective microbiota transplantation, probiotics, purified functional metabolites and ligands to microbe-host interactive pathways are promising radio-protectors and radio-mitigators that merit extensive validation in clinical trials. With massive mechanistic investigations and pilot clinical trials reinforcing its translational value the gut microbiota may boost the prediction, prevention and mitigation of radiation injury. In this review, we summarize the state-of-the-art landmark researches related with radio-protection to provide illuminating insights for oncologists, gastroenterologists and laboratory scientists interested in this overlooked complexed disorder.
Performance of the procedure for ultra-rapid extraction and loop-mediated isothermal amplification (PURE-LAMP) method to detect malaria in Haiti
Authors: Vincent Jeanne Perpétue , Existe Alexandre Valcena , Komaki-Yasuda Kanako , Boncy Jacques , Kano Shigeyuki
Published: May 2023

Background

Malaria continues to cause burden in various parts of the world. Haiti, a Caribbean country, is among those aiming to eliminate malaria within a few years. Two surveys were conducted in Haiti during which we aimed to evaluate the performance of the simple and rapid procedure for ultra-rapid extraction–loop-mediated isothermal amplification (PURE-LAMP) method with dried blood spots as an alternative diagnostic method for malaria in the context of low to very low rates of transmission.

Methods

Febrile and afebrile people were recruited from three administrative divisions within Haiti: Nippes, Sud and Grand’Anse, during the summers of 2017 (early August to early September) and 2018 (late July to late August). Their blood samples were tested by microscopy, rapid diagnostic tests (RDT), PURE-LAMP and nested PCR to detect Plasmodium infection. Sensitivity, specificity, positive and negative predictive values and kappa statistics were estimated with the nested PCR results as the gold standard.

Results

Among 1074 samples analyzed, a positive rate of 8.3% was calculated based on the nested PCR results. Among febrile participants, the rates in 2017 and 2018 were 14.6% and 1.4%, respectively. Three positives were detected among 172 afebrile participants in 2018 by PURE-LAMP and nested PCR, and all three were from the same locality. There was no afebrile participants recruited in 2017. The PURE-LAMP, RDT and microscopy had respective sensitivities of 100%, 85.4% and 49.4%. All of the testing methods had specificities over 99%.

Conclusions

This study confirmed the high performance of the PURE-LAMP method to detect Plasmodium infection with dried blood spots and recommends its use in targeted mass screening and treatment activities in low endemic areas of malaria.
Investigating the effect of nanolime treatment on the drying kinetics of Clipsham limestone
Authors: Browne Dáire E. , Peverall Robert , Ritchie Grant A. D. , Viles Heather A.
Published: May 2023

Climate change poses an ever-increasing risk to our stone built heritage. Among conservation actions, the use of consolidant products is considered a possible response to this challenge, and the adoption of nanolimes has been widely studied showing promising results. However, while the effectiveness and method of application has been assessed, few studies have probed the changes in drying kinetics following treatment. In fact, a drastic alteration of the water transport might lead to further anomalies. This study investigates the influence of nanolimes dispersed in ethanol on the drying kinetics of Clipsham limestone using cavity ring-down spectroscopy. The degree of treatment was assessed by gravimetry, Raman spectroscopy, optical microscopy, colorimetry, optical profilometry and thin section analysis. Results showed an increase in the dry mass, observable colour changes and decrease in surface roughness. Small but reproducible increases were observed in the evaporation flux for phase I behaviour following treatment, however, no changes were observed in the total mass of water released or the phase II diffusivity. Determination of the activation energy associated with phase II drying was unchanged following treatment . These results indicate that following treatment there has been little-to-no change in the internal surfaces and structure of the stone to affect vapour transport.
Prognostic stratification based on HIF-1α signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma
Authors: Zhuang Hongkai , Zhang Zedan , Chen Bo , Tang Chenwei , Chen Xinming , Tan Wenliang , Yang Lei , Xie Zhiqin , Ma Xiaowu , Wang Qingbin , Wang Bingkun , Shang Changzhen , Chen Yajin
Published: May 2023

Hepatocellular carcinoma (HCC) has a desmoplastic and hypoxic tumor microenvironment (TME), resulting in poor prognosis and treatment resistance. This study aimed to construct a novel prognostic classifier to investigate the degree of hypoxia and immune profiles in HCC. Patients with HCC from public databases were classified into three HIF-1α clusters according to 16 reported HIF-1α-related genes. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α clusters. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α cluster. Besides, oncologic pathways and immune infiltration profiles were also investigated among HCCs with different HIF-1α scores. The reliable predictive abilities of the HIF-1α score system for patients’ survival were impressively suggested by the significant C-indexes and ROC analysis. All enrolled tumors were divided into high-, medium-, and low-HIF-1α score groups. Compared with the other two groups, the high HIF-1α score group exhibited highest enrichment of multiple oncogenic pathways, such as TNF-α signaling via NF-кB, IL6-JAK-STAT3 signaling, mTORC1 signaling, MYC signaling, Hedgehog signaling. Notably, higher HIF-1α scores correlated with advanced immunosuppressive TME. Besides, tumors with high HIF-1α scores represented high non-response rate to transcatheter arterial chemoembolization (TACE) and immune checkpoint blockade (ICB). In conclusion, we developed a novel HIF-1α score system to distinguish HCC with different degree of hypoxia and immune infiltration profiles.
Fundamental concepts and the latest evidence for esophageal pressure monitoring
Authors: Shimatani Tatsutoshi , Kyogoku Miyako , Ito Yukie , Takeuchi Muneyuki , Khemani Robinder G.
Published: May 2023

Transpulmonary pressure is an essential physiologic concept as it reflects the true pressure across the alveoli, and is a more precise marker for lung stress. To calculate transpulmonary pressure, one needs an estimate of both alveolar pressure and pleural pressure. Airway pressure during conditions of no flow is the most widely accepted surrogate for alveolar pressure, while esophageal pressure remains the most widely measured surrogate marker for pleural pressure. This review will cover important concepts and clinical applications for esophageal manometry, with a particular focus on how to use the information from esophageal manometry to adjust or titrate ventilator support. The most widely used method for measuring esophageal pressure uses an esophageal balloon catheter, although these measurements can be affected by the volume of air in the balloon. Therefore, when using balloon catheters, it is important to calibrate the balloon to ensure the most appropriate volume of air, and we discuss several methods which have been proposed for balloon calibration. In addition, esophageal balloon catheters only estimate the pleural pressure over a certain area within the thoracic cavity, which has resulted in a debate regarding how to interpret these measurements. We discuss both direct and elastance-based methods to estimate transpulmonary pressure, and how they may be applied for clinical practice. Finally, we discuss a number of applications for esophageal manometry and review many of the clinical studies published to date which have used esophageal pressure. These include the use of esophageal pressure to assess lung and chest wall compliance individually which can provide individualized information for patients with acute respiratory failure in terms of setting PEEP, or limiting inspiratory pressure. In addition, esophageal pressure has been used to estimate effort of breathing which has application for ventilator weaning, detection of upper airway obstruction after extubation, and detection of patient and mechanical ventilator asynchrony.
Sensor orientation of the TMD seismic network (Thailand) from P-wave particle motions
Authors: Pornsopin Patinya , Pananont Passakorn , Furlong Kevin P. , Sandvol Eric
Published: May 2023

The Thai Meteorological Department (TMD) seismic network began development in 2008. There are a total of 71 seismic stations consisting of 26 borehole stations and 45 surface stations currently installed. The three-component data from the TMD seismic network have been widely used in previous seismological studies. In a recent analysis, we have found that sensor orientation as reported in the site metadata is sometimes significantly incorrect, especially for borehole stations. In this study, we analyze P-wave polarization data from regional and teleseismic earthquakes recorded in the network to estimate the true instrument orientation relative to geographic north and compare that to station metadata. Of the 45 surface stations, we found that at present, ~ 82% are well oriented (i.e., aligned within 0–15° of true north). However, 8 sites have sensors misoriented by more than 15°, and some stations had a temporal change in sensor orientation during an upgrade to the seismic system with replacement of the sensor. We also evaluated sensor orientations for 26 TMD borehole seismic stations, from 2018 to the 2022. For many of the borehole stations, the actual sensor orientation differs significantly from the TMD metadata, especially at short-period stations. Many of those stations have sensor misorientations approaching 180°, due to errors in the ambient noise analysis calibration techniques used during installation. We have also investigated how this sensor misorientation affects previous seismic studies, such as regional moment tensor inversion of earthquakes sources and receiver function stacking. We have found that the large deviations in sensor orientation can result in erroneous results and/or large measurement errors. A cause of the orientation error for borehole sites could be a combination of strong background surface ambient seismic noise coupled with an incorrect reference instrument response.
Perovskite single-crystal thin films: preparation, surface engineering, and application
Authors: Zhang Zemin , Kim Wooyeon , Ko Min Jae , Li Yuelong
Published: May 2023

Perovskite single-crystal thin films (SCTFs) have emerged as a significant research hotspot in the field of optoelectronic devices owing to their low defect state density, long carrier diffusion length, and high environmental stability. However, the large-area and high-throughput preparation of perovskite SCTFs is limited by significant challenges in terms of reducing surface defects and manufacturing high-performance devices. This review focuses on the advances in the development of perovskite SCTFs with a large area, controlled thickness, and high quality. First, we provide an in-depth analysis of the mechanism and key factors that affect the nucleation and crystallization process and then classify the methods of preparing perovskite SCTFs. Second, the research progress on surface engineering for perovskite SCTFs is introduced. Third, we summarize the applications of perovskite SCTFs in photovoltaics, photodetectors, light-emitting devices, artificial synapse and field-effect transistor. Finally, the development opportunities and challenges in commercializing perovskite SCTFs are discussed.
The effect of professional development on in-service STEM teachers’ self-efficacy: a meta-analysis of experimental studies
Authors: Zhou Xuan , Shu Lina , Xu Zhihong , Padrón Yolanda
Published: May 2023

This meta-analysis examined the effectiveness of teacher professional development (PD) training on improving in-service STEM teachers’ self-efficacy in the K-12 teaching context. Twenty-one articles yielded 48 effect size estimates, incorporating 1412 teachers in the final analyses. Results indicated that the overall effect size of PD training on K-12 STEM teachers’ self-efficacy was strong at g = 0.64 (p < 0.01). This review contributes to the STEM teacher self-efficacy literature and confirms the significant impact of PD on improving STEM teachers’ self-efficacy. Results regarding the impact of substantive PD characteristics provide policymakers and practitioners seeking to improve STEM teacher self-efficacy with information for improving PD. Recommendations for researchers are also discussed in the paper.
Knowledge mapping and visualization of current sarcopenia and cancer research: a bibliometric analysis
Authors: Mohammed Marwa , Li Jianan
Published: May 2023

Background

Cancer survivors face broad challenges in weight loss due to multiple factors. Sarcopenia prevalence among cancer survivors has a wide range and is associated with worse outcomes. Sarcopenia and cancer attract global attention. The use of bibliometrics analysis in this area of interest still needs to be identified. This study was performed to assess the global trends and patterns of sarcopenia and cancer-related scientific publications.

Methods

Web of Science (WOS) and articles indexed in Science Citation Index Expanded. VOS viewer (Leiden University, Leiden, Netherlands) and R-studio using bibliometrics and R package were used for quantitative analysis of the dataset (year of publications, number of publications, institutes, journals, total citations, H-index status, authors, hotspots of institutes, Keywords, research area, and funding sponsor.

Results

Our analysis extracted 384 publications from 172 journals written by 2525 authors from the Institute for Web of Science Core Collection database. Overall, 384 articles from the WOS database met the inclusion criteria. The number of published papers has risen since 2014. The results showed that Japan, China and the USA contributed the most to this field. Moreover, our results recognized future research trends and the current condition of sarcopenia and cancer research based on the top 10 most cited articles and the keyword analysis. Finally, the leading author's analysis demonstrated that Shen Xian from Wenzhou Medical University, China, Baracos and Vickie E from the University of Alberta, Switzerland, were the most productive, active, and influential authors.

Conclusion

Our study demonstrates a comprehensive and objective overview of the up-to-date status of sarcopenia and cancer research. These data would benefit scholars who need information on sarcopenia and cancer research. It would be a reference guide for researchers wanting to conduct additional studies related to the topic.
Nasal mucocutaneous leishmaniasis (MCL) with necrotizing granulomatous inflammation inducing cytotoxic T-cell lymphoma in a male Yemeni patient
Authors: Ibrahim Hamdi , Hamid Khairy Abd El , Aziz Tarek Abd El , Samir El bahwashy Ahmed , Khattab Hamed , Aaref Basma , Elsayed Essam
Published: May 2023

Leishmaniasis is a protozoal infection transmitted by sandfly vector; there are three main types of leishmaniasis: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). Herein, we present a case of endonasal mucocutaneous leishmaniasis in a 34-year-old Yemeni patient who presented with disfiguring nasal swelling associated with fever, a swab from the lesion and direct microscopic examination proved to have mucocutaneous leishmaniasis; he was successfully treated with intravenous antimonial stibogluconate, 1 month after treatment biopsy from the lesion revealed cytotoxic T-cell lymphoma, the purpose is to alert the physicians and otolaryngologists to consider leishmaniasis in the differential diagnosis of nasal granulomas and also to highlight the importance of early diagnosis of cancer in survivors of cutaneous leishmaniasis, especially in areas where cutaneous leishmaniasis is still highly prevalent, as the chronic local inflammation may disfigure the face if not recognized early and adequately treated; also, early cancer diagnosis can prevent mortality
Clinicopathological Characteristics and Outcomes of Anal Squamous Cell Carcinoma Patients With and Without HIV Infection in Sub-Saharan Africa
Authors: Mduma Emmanuel , Dharsee Nazima , Samwel Kandali , Mwita Chacha J. , Lidenge Salum J.
Published: May 2023

PURPOSE

In the past 20 years, the burden of anal cancer (AC) increased by 60% in the United States and over three-fold in Africa. Rates of AC have increased by 20× in people living with HIV and the highest (50×) in men with HIV who have sex with men. However, in sub-Saharan Africa (SSA) where HIV is endemic, data on clinicopathological characteristics and outcomes of patients with AC are lacking. To address this, we have investigated AC disease presentation, treatment outcomes, and its predictors in a cohort of patients who were either HIV-infected or HIV-uninfected in SSA.

METHODS

We conducted a retrospective cohort study of patients with anal squamous cell carcinoma (SCC) treated at Ocean Road Cancer Institute in Dar es Salaam, Tanzania from January 2014 to December 2019. Associations between the study outcomes and their predictors were analyzed using univariate and multivariate analysis models.

RESULTS

A total of 59 patients with anal SCC were retrieved and had at least 2-year follow-up. The mean age was 53.9 (standard deviation ±10.5) years. While none of the patients presented with stage I disease, 64.4% had locally advanced disease. HIV infection was the major comorbidity (64.4%). The rate of complete remission at the end of treatment was at 49% while the 2-year overall survival (OS) and local recurrence-free survival were 86.4% and 91.3%, respectively. Despite high HIV coinfection in the cohort, AC treatment outcomes were not significantly associated with HIV status. Disease stage ( P = .012) and grade ( P = .030) were significantly associated with 2-year OS.

CONCLUSION

Patients with anal SCC in Tanzania present mainly with locally advanced disease associated with high HIV prevalence. In this cohort, the SCC grade was independently associated with treatment outcomes unlike other factors such as HIV coinfection.
Striking universalities in stochastic resetting processes
Authors: Smith Naftali R. , Majumdar Satya N. , Schehr Grégory
Published: May 2023

Given a random process

which undergoes stochastic resetting at a constant rate r to a position drawn from a distribution

, we consider a sequence of dynamical observables

associated to the intervals between resetting events. We calculate exactly the probabilities of various events related to this sequence: that the last element is larger than all previous ones, that the sequence is monotonically increasing, etc. Remarkably, we find that these probabilities are “super-universal”, i.e., that they are independent of the particular process

, the observables A

k
's in question and also the resetting distribution

. For some of the events in question, the universality is valid provided certain mild assumptions on the process and observables hold (e.g., mirror symmetry).
CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation
Authors: Zheng Huiwen , Zhang Xiaobo , Fu Jing , Xue Yifan , Chen Zhi , Yang Guobin , Chen YiPing , Chen Di , Yuan Guohua
Published: May 2023

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip (Stub1) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.
Transcriptome-wide probing reveals RNA thermometers that regulate translation of glycerol permease genes inBacillus subtilis
Authors: Jolley Elizabeth A. , Yakhnin Helen , Tack David C. , Babitzke Paul , Bevilacqua Philip C.
Published: May 2023

RNA structure regulates bacterial gene expression by several distinct mechanisms via environmental and cellular stimuli, one of which is temperature. While some genome-wide studies have focused on heat shock treatments and the subsequent transcriptomic changes, soil bacteria are less likely to experience such rapid and extreme temperature changes. Though RNA thermometers (RNATs) have been found in 5′ untranslated leader regions (5′ UTRs) of heat shock and virulence-associated genes, this RNA-controlled mechanism could regulate other genes as well. Using Structure-seq2 and the chemical probe dimethyl sulfate (DMS) at four growth temperatures ranging from 23°C to 42°C, we captured a dynamic response of theBacillus subtilistranscriptome to temperature. Our transcriptome-wide results show RNA structural changes across all four temperatures and reveal nonmonotonic reactivity trends with increasing temperature. Then, focusing on subregions likely to contain regulatory RNAs, we examined 5′ UTRs to identify large, local reactivity changes. This approach led to the discovery of RNATs that control the expression ofglpF(glycerol permease) andglpT(glycerol-3-phosphate permease); expression of both genes increased with increased temperature. Results with mutant RNATs indicate that both genes are controlled at the translational level. Increased import of glycerols at high temperatures could provide thermoprotection to proteins.
Harmonisation of welfare indicators for macaques and marmosets used or bred for research
Authors: Prescott Mark J. , Leach Matthew C. , Truelove Melissa A.
Published: May 2023

Background: Accurate assessment of the welfare of non-human primates (NHPs) used and bred for scientific purposes is essential for effective implementation of obligations to optimise their well-being, for validation of refinement techniques and novel welfare indicators, and for ensuring the highest quality data is obtained from these animals. Despite the importance of welfare assessment in NHP research, there is little consensus on what should be measured. Greater harmonisation of welfare indicators between facilities would enable greater collaboration and data sharing to address welfare-related questions in the management and use of NHPs.

Methods: A Delphi consultation was used to survey attendees of the 2019 NC3Rs Primate Welfare Meeting (73 respondents) to build consensus on which welfare indicators for macaques and marmosets are reliable, valid, and practicable, and how these can be measured.

Results: Self-harm behaviour, social enrichment, cage dimensions, body weight, a health monitoring programme, appetite, staff training, and positive reinforcement training were considered valid, reliable, and practicable indicators for macaques (≥70% consensus) within a hypothetical scenario context involving 500 animals. Indicators ranked important for assessing marmoset welfare were body weight, NHP induced and environmentally induced injuries, cage furniture, huddled posture, mortality, blood in excreta, and physical enrichment. Participants working with macaques in infectious disease and breeding identified a greater range of indicators as valid and reliable than did those working in neuroscience and toxicology, where animal-based indicators were considered the most important. The findings for macaques were compared with a previous Delphi consultation, and the expert-defined consensus from the two surveys used to develop a prototype protocol for assessing macaque welfare in research settings.

Conclusions: Together the Delphi results and proto-protocol enable those working with research NHPs to more effectively assess the welfare of the animals in their care and to collaborate to advance refinement of NHP management and use.
4’-fluorouridine as a potential COVID-19 oral drug?: a review
Authors: Abas Abdul Hawil , Tallei Trina Ekawati , Fatimawali Fatimawali , Celik Ismail , Alhumaydhi Fahad A. , Emran Talha Bin , Dhama Kuldeep , Rabaan Ali A. , Garout Mohammed A. , Halwani Muhammad A. , Al Mutair Abbas , Alhumaid Saad , Harapan Harapan
Published: May 2023

The available antiviral drugs against coronavirus disease 2019 (COVID-19) are limited. Oral drugs that can be prescribed to non-hospitalized patients are required. The 4′-fluoruridine, a nucleoside analog similar to remdesivir, is one of the promising candidates for COVID-19 oral therapy due to its ability to stall viral RdRp. Available data suggested that 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Although  4'-fluorouridine is considered as strong candidates, further studies are required to determine its efficacy in the patients and  it’s genetic effects on humans. In this review, we the antiviral activity of 4′-fluorouridine is reviewed and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is compiled and discussed.
The altered lung microbiome dynamics in patients with moderate and severe COPD compared to the healthy group in the Indian population
Authors: Hazra Druti , SM Fayaz , Chawla Kiran , Sintchenko Vitali , Martinez Elena , Magazine Rahul , Siddalingaiah Nayana
Published: May 2023

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls.

Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. 

Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson’s index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonas and Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group.

Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.
Economic effects of the war in Ukraine and recession
Authors: korriku belisa , TARTARAJ AZETA
Published: May 2023

Background: The economic effects of wars and recessions can have significant impacts on consumer attitudes and behaviors. Understanding how these attitudes and behaviors change impacts during challenging economic times is crucial for financial education and management. 

Methods: A survey was conducted to investigate the financial attitudes and behaviors of individuals during a recessionary period. The survey was distributed from January 15th  to February 28th, 2023 and included questions about age, financial education level, savings behavior, attitudes towards debt, gender and financial management behavior, age and financial education, and income and savings behavior. Data were analyzed using t-tests and ANOVA. 

Results: Participants with higher income levels had higher levels of savings and investing behaviors than those with lower income levels. Participants with a higher level of formal education in finance had higher levels of budgeting and investing behaviors than those with a lower level of formal education in finance. Additionally, participants who reported higher levels of self-rated financial knowledge had higher levels of all financial management behaviors (budgeting, saving, investing, and debt management) compared to those with lower self-rated financial knowledge. 

Conclusions: The findings suggest that financial education and management programs should target individuals with lower income levels and less formal education in finance. Additionally, promoting self-rated financial knowledge may be a useful strategy for improving financial management behaviors. Future research could explore the effectiveness of different financial education and management programs on improving financial attitudes and behaviors during recessionary periods.
Case Report: Callosal disconnection syndrome manifesting as mixed frontal-callosal-posterior alien hand syndrome following extensive corpus callosum infarct
Authors: Zainudin Muhamad Faizal , Soo Kar Chuan , Nyein Yin Khin
Published: May 2023

Alien hand syndrome (AHS) is a rare neurological phenomenon first described by Goldstein over a century ago. The most widely recognized variants in literature are frontal, callosal, and posterior AHS. AHS due to the corpus callosum lesion can occur alone or as part of callosal disconnection syndrome (CDS). This report presents a unique CDS case manifesting clinical features from all three AHS variants, resulting from an extensive corpus callosum infarct.

Our patient exhibited various clinical features from the three AHS variants, which include grasping, groping, and difficulty releasing objects from the hand (anterior); intermanual conflict (callosal); arm levitation, mild hemiparesis, and hemisensory loss (posterior). Additionally, the extensive disruption of the corpus callosal fibers produced neurological manifestations of CDS, such as cognitive impairment, ideomotor and constructional apraxia, behavioral disorder, and transcortical motor aphasia. We employed a range of rehabilitation interventions, such as mirror box therapy, limb restraint strategy, verbal cue training, cognitive behavioral therapy, bimanual hand training, speech and language therapy, and pharmacological treatment with clonazepam. The patient showed almost complete resolution of CDS and AHS features by nine months post-stroke

Our case report highlights distinctive clinical variations of AHS and the challenging correlation between clinical manifestations and neuroanatomical substrates. Future studies are necessary to explore the intricate neural connections and the precise function of the corpus callosum. This can be achieved by combining comprehensive neuropsychological testing with diffusion tensor tractography studies. It is also essential to develop a validated tool to standardize AHS assessment. Finally, the scarcity of evidence in rehabilitation interventions necessitates further studies to address the wide knowledge gap in AHS and CDS management.
MEANING-GENERATING FUNCTION OF THE EMOTIVE CONTEXT
Authors: Minibaeva Svetlana V. , Zheltikova Tatiana V.
Published: May 2023

In this article, by means of lexico-semantic and lexico-stylistic analysis, it is proved that the emotive context performs a special meaning-generating function in a literary text, influencing the meaning of the text as a whole and the reader’s understanding of it.

Purpose. The purpose of the article is to identify the role of emotive context in the semantic structure of a literary text.

Methods. Methodologically, the article is an interdisciplinary one, based on the use of both general scientific methods (observation, comparison, interpretation) and linguistic ones (lexico-semantic analysis of words and expressions, semantic analysis of the text). The key research method was content analysis used to analyze V. Pelevin’s story News from Nepal in the emotive aspect, taking into account the psycho-emotional content of the context.

Results. The special role of the emotive context in the semantic structure of a literary text is proved, the latter being the meaning-generating function of the emotive context, represented by emotive vocabulary, emotive markers, derivational means, fixing the nonverbal expression of emotive content, etc. The analysis of emotive contexts allowing to deepen understanding of the content of the text as a whole is presented.
STYLISTIC AND GRAMMATICAL POTENTIAL OF ENGLISH TOURISM DISCOURSE
Authors: Evseev Andrey B.
Published: May 2023

Purpose. The paper aims at discovering stylistic and grammatical peculiarities in tourism discourse based on VisitBritain.com text corpus; analyzing its application scope and mission; specifying “tourism discourse” as a notion.

Methodology. Used in the paper are general scientific methods (synthesis, generalization), analysis of the text corpus, method of linguistic analysis.

Results. The issue of tourism discourse as a separate unit, not a subtype of advertising discourse, remains highly disputable nowadays. The present paper analyses the theoretical basis of notions of “discourse” and “tourism discourse”; determines the levels and communication means in tourism; substantiates the hypothesis on multi-component and multi-modal structure of tourism discourse as a linguistic phenomenon. In the practical part of the research, the author draws special attention to the specifics of the English tourism discourse in terms of typology, lexicology and morphology. The paper concludes by saying that tourism discourse is different from advertising one as well as requires further investigation into the issue.

Practical implications. The results presented in the article can be used both in theory and applications, i.e., further inquiry into the pragmatic constituent of tourism discourse and its interdisciplinarity; compilation of corpora of tourist texts in the English language; adaptation of the English tourism discourse for present-day realities and addressees’ demands.
THE FAMILY SAGA BY E. KOLINA (FROM THE NOVEL SAGA OF THE POOR GOLDMANS)
Authors: Rui Li
Published: May 2023

Rationale. The study of genre specificity of fiction works of modern literature is important in connection with the actualization of domestic genres of mass literature. The name of saga genre is actively used by creators of women’s novels, in particular by E. Kolina. It seems necessary to examine the transformation of the attributes of the saga genre in the context of such novels.

Purpose. The article reveals the specificity of the family saga genre in E. Kolina’s novel The Saga of the Poor Goldmans.

Materials and methods. The material is a novel by E. Kolina The Saga of the Poor Goldmans (2007). In the framework of the family saga genre the analysis of the novel by E. Kolina was based on the method of narrative and theoretical analysis which was completed with the methods of psychoanalytic approach to the understanding of the main character’s specificity.

Results. The analysis of E. Kolina’s work showed the specifics of the saga genre in the novel The Saga of the Poor Goldmans. It was pointed out that E. Kolina’s saga does not always realize the traditional features of the genre, namely, historicism and equality of moral values in choosing characters’ life guidelines. It is shown that the image of home and family in the novel does not correspond to the principles of the genre, as home and family in the novel of E. Kolina’s novel no longer symbolizes the ancestral nest and strong family ties. The representation of the actual and retrospective image of the family in the novel is described. The motif of growing up in the novel is presented as the main one in highlighting the theme of childhood, realized in the motif of getting rid of teenage complexes based on envy of one sister to another.

Practical implications. The results of the analysis can be used to describe the genres of mass literature, as well as in pedagogical activities, in particular in the teaching of literary theory.
Consecuencias jurídicas internacionales de la intervención de terceros Estados en procesos secesionistas. El caso del Procés/International legal consequences of the intervention of third States in secessionist processes. The case of the Procés
Authors: Torroja Mateu Helena
Published: May 2023

Este trabajo analiza algunas de las consecuencias jurídicas internacionales de la implicación de Estados extranjeros en el proceso de secesión catalán, presentando los datos de los que se dispone hasta ahora. Se seleccionan los comportamientos de la Federación de Rusia y del Reino de Bélgica y se analiza la posible subsunción de estos hechos en la norma internacional relativa a la prohibición de intervención en los asuntos de otros Estados. Se demuestra la difícil, si no imposible, imputación de responsabilidad internacional en ambos casos. Pero, a la vez, los hechos muestran el interés ruso por ejercer su influencia en la zona y la irresponsabilidad política de algunos líderes secesionistas que consideraron que la República catalana bien valía la sumisión a un Estado autoritario como Rusia. Por su parte, el silencio de los dos Gobiernos de España ante los hechos de Waterloo, muestran, hacia el exterior, un posicionamiento de Estado débil ante los socios europeos y euroatlánticos; hacia el interior muestran a unos gobernantes con poco aprecio por la defensa de la Democracia y el Estado de Derecho, así como con un total desprecio por el derecho a la libre determinación interna de toda la población estatal.
Forward to the Past: Short-Term Effects of the Rent Freeze in Berlin
Authors: Hahn Anja M. , Kholodilin Konstantin A. , Waltl Sofie R. , Fongoni Marco
Published: May 2023

In 2020, Berlin introduced a rigorous rent-control policy responding to soaring prices by capping rents: the Mietendeckel (rent freeze). The German Constitutional Court revoked the policy only one year later. Although successful in lowering rents during its duration, the consequences for Berlin’s rental market and close-by markets are per se not clear. This article evaluates the short-term causal supply-side effects in terms of prices, quantities, and landlords’ strategic behavior. We develop a theoretical framework capturing the key features of first-generation rent control policies and Berlin-specific aspects. Using a rich pool of detailed rent advertisements, predictions are tested, and further empirical causal inference techniques are applied for comparing price trajectories of dwellings inside and outside the policy’s scope. Mechanically, advertised rents drop significantly upon the policy’s enactment. A substantial rent gap along Berlin’s administrative border emerges, and rapidly growing rents in Berlin’s (unregulated) adjacent municipalities are observed. Landlords started adopting a hedging strategy insuring themselves against the risk of contractually long-term fixed low rents following a potentially unconstitutional law. Whereas this hedge was beneficial for landlords, the risk was completely borne by tenants. Moreover, the number of available properties for rent dropped significantly, a share of which appears to be permanently lost for the rental sector. This hampers a successful housing search for first-time renters and people moving within the city. Overall, negative consequences for renters appear to outweigh positive ones.

This paper was accepted by Victoria Ivashina, finance.

Funding: This research benefits from funding by the FNR Luxembourg National Research Fund [CORE Grant 3886] (ASSESS) and the OeNB Anniversary Fund [Grant 18767] (LocHouse). M. Fongoni further thanks the Department of Economics at the University of Strathclyde for support and acknowledges funding from the French government under the “France 2030” investment plan managed by the French National Research Agency [Reference ANR-17-EURE-0020] and from the Excellence Initiative of Aix-Marseille University - A*MIDEX.

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4775 .
Matrix e Esquizoanálise: elementos para pensar a produção e a reprodução da realidade
Authors: Rossi André , Trindade Tarso Ferrari
Published: May 2023

Este artigo tem por objetivo evidenciar e debater a noção de socius, conceito chave dentro da Esquizoanálise para pensar sua teoria da produção e reprodução social, utilizando-se do filme Matrix como um intercessor, incluindo suas diversas produções multimídias. Tomando como fio condutor, dentro do universo do longa-metragem, a estória da construção e desenvolvimento do software denominado matrix e sua relação com a humanidade, problematizamos o modo de funcionamento do sistema capitalista no contemporâneo, utilizando-nos do conceito das três sínteses, presente n’O Anti-Édipo. Mostramos de que modo a produção e reprodução dos vários socius não se encontram aprioristicamente determinados, como se fossem estruturas imutáveis e universais, mas, sim, estão em constante construção e reconstrução. Faz-se mister também destacar que a crítica pós-estruturalista da noção de estrutura não pode ser tomada erroneamente como se esta última tivesse desaparecido completamente e o sujeito fosse lançado em um campo puramente empírico.  Cabe a nós, sujeitos históricos e também em incessante constituição e reconstituição, pensar os embates sociais de nosso tempo, problematizando as estratégias de enfrentamento ao capitalismo assumindo o aspecto trágico do processo de produção maquínico da realidade.