bluuebunny/crossref_metadata_2025 huggingface dataset:
The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study
Authors: Feitosa Mateus Paiva Marques , Lima Eduardo Gomes , Abizaid Alexandre Antônio Cunha , Mehran Roxana , Lopes Neuza Helena Moreira , de Assis Fischer Ramos Thiago , Hideo-Kajita Alexandre , Filho Roberto Kalil , Junior Carlos Vicente Serrano
Published: June 2023

Background

Percutaneous coronary intervention (PCI) is one of the most performed well-succeeded therapeutic procedures worldwide, reducing symptoms and improving quality of life. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) produced early after an ischemic renal insult. Osmotic diuresis and the vasoconstriction of the afferent arteriole promoted by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) generate a concern regarding the possibility of dehydration and consequent AKI. There is no consensus on the maintenance or discontinuation of SGTL2i in patients who will undergo PCI. This study aimed to evaluate the safety of empagliflozin in diabetic patients submitted to elective PCI regarding kidney function.

Methods

SAFE-PCI trial is a prospective, open-label, randomized (1:1), single-center pilot study and a follow-up of 30 days. The SGLT2i empagliflozin 25 mg daily was initiated at least 15 days before PCI in the intervention group and maintained until the end of the follow-up period. Serum NGAL was collected 6 h after PCI and creatinine before PCI, 24 h, and 48 h after the procedure. As per protocol, both groups received optimal medical treatment and standard protocol of nephroprotection.

Results

A total of 42 patients were randomized (22 patients in the iSGLT-2 group and 20 patients in the control group). There was no difference between-group baseline data. The primary outcome (NGAL and creatinine values post PCI) did not differ in both groups: the mean NGAL value was 199 ng/dL in the empagliflozin group and 150 ng/dL in the control group (p = 0.249). Although there was an initial increase in creatinine in the SGLT-2i group compared to the control group between baseline creatinine and pre-PCI and 24 h post-PCI creatinine, no difference was detected in creatinine 48 h post-PCI (p = 0.065). The incidence of CI-AKI, determined by KDIGO criteria, in the iSGLT2-group was 13.6% and 10.0% in the control group without statistical difference.

Conclusion

The present study showed that the use of empagliflozin is safe regarding kidney function during elective PCI in patients with T2D when compared with no use of SGLT2i.

Trial registration Our clinical study is registered on ClinicalTrials.gov with the following number: NCT05037695.
Comparison of RNA-Seq analysis data between tracheal mite-infested and uninfested Japanese honey bees (Apis cerana japonica)
Authors: Suzuki Akihiko , Kamakura Masaki , Shiramata Takuya , Nakaoka Shinji , Sakamoto Yoshiko
Published: June 2023

Objective

The purpose of this data set is to investigate differences in RNA-Seq transcriptome profiles between Acarapis woodi-infested and uninfested Japanese honey bees (Apis cerana japonica). The data set is strengthened by data collected from different body parts (head, thorax, and abdomen). The data set will support future studies of molecular biological changes in mite-infested honey bees.

Data description

We collected 5 mite-infested and 5 uninfested A. cerana japonica workers from each of 3 different colonies (designated as A, B, and C). Workers were dissected into 3 body sites (i.e., heads, thoraces, and abdomen), and 5 of each body site were pooled together for RNA extraction, generating a total of 18 RNA-Seq samples (2 infection status × 3 colonies × 3 body sites). FASTQ data files of each sample that were generated by a DNBSEQ-G400 sequencer with the 2 × 100 bp paired-end sequencing protocol are available in the DDBJ Sequence Read Archive under accession number DRA015087 (RUN: DRR415616–DRR415633, BioProject: PRJDB14726, BioSample: SAMD00554139–SAMD00554156, Experiment: DRX401183–DRX401200). The data set is a fine-scale analysis of gene expression in the mite-infested A. cerana japonica workers because 18 RNA-Seq samples are separated by 3 body sites.
GABAergic neurons differentiated from BDNF- and Dlx2-modified neural stem cells restore disrupted neural circuits in brainstem stroke
Authors: Tang Xiangyue , Wu Li , Zhu Juehua , Xu Mindong , Li Shaojun , Zeng Guanfeng , Zhu Shuanggen , Jiang Yongjun
Published: June 2023

Background

Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs.

Methods

We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs.

Results

GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke.

Conclusions

These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.
VTGAN: hybrid generative adversarial networks for cloud workload prediction
Authors: Maiyza Aya I. , Korany Noha O. , Banawan Karim , Hassan Hanan A. , Sheta Walaa M.
Published: June 2023

Efficient resource management approaches have become a fundamental challenge for distributed systems, especially dynamic environment systems such as cloud computing data centers. These approaches aim at load-balancing or minimizing power consumption. Due to the highly dynamic nature of cloud workloads, traditional time series and machine learning models fail to achieve accurate predictions. In this paper, we propose novel hybrid VTGAN models. Our proposed models not only aim at predicting future workloads but also predicting the workload trend (i.e., the upward or downward direction of the workload). Trend classification could be less complex during the decision-making process in resource management approaches. Also, we study the effect of changing the sliding window size and the number of prediction steps. In addition, we investigate the impact of enhancing the features used for training using the technical indicators, Fourier transforms, and wavelet transforms. We validate our models using a real cloud workload dataset. Our results show that VTGAN models outperform traditional deep learning and hybrid models, such as LSTM/GRU and CNN-LSTM/GRU, concerning cloud workload prediction and trend classification. Our proposed model records an upward prediction accuracy ranging from $$95.4\%$$

95.4
%

to $$96.6\%$$

96.6
%

.
Measuring the impact of the state of emergency on crime trends in Japan: a panel data analysis
Authors: Shimada Takahito , Suzuki Ai , Amemiya Mamoru
Published: June 2023

Purpose/Background

City-specific temporal analysis has been commonly used to investigate the impact of COVID-19-related behavioural regulation policies on crime. However, these previous studies fail to consider differences in the intensity of intervention among cities and the impact of these behavioural regulation policies on crime trends nationwide. This study performs panel data analyses to examine how the declaration of a state of emergency (SoE) affected ambient population and crime in Japan, taking advantage of the fact that the SoE was implemented at different times in different prefectures.

Methods

The current study uses two sets of panel data of 47 prefectures for 22 weeks from February to July 2020: (1) the data on ambient population in five types of locations provided by the Google Mobility Reports, and (2) official crime data of six types of crime: residential burglary, commercial burglary, theft of/from vehicle, bicycle theft, sexual assault, and violence and injury. Firstly, an ordinary least squares regression analysis was performed to examine the impact of the SoE on the ambient population. Then a negative binomial model with fixed effects was adopted to examine the effect of the ambient population on the crime trends.

Findings

The SoE declaration was found to increase the ambient population in ‘residential’, and decrease that in other settings including ‘workplaces’, ‘transit stations’, and ‘retail and recreation’ in targeted prefectures. Spill-over effects of the SoE were observed on the ambient population of non-SoE prefectures. The ambient population have impacted five out of the six types of crime examined, except for sexual assault. After controlling for the ambient population, we observed an increase in commercial burglary and theft of/from the vehicle in all prefectures during the SoE weeks, compared to the weeks when the SoE was not declared.

Conclusions

The declaration of the SoE during the COVID-19 pandemic changed the ambient population in the SoE-prefectures, resulting the changes in crime levels as well. In addition, the implementation of the SoE in specific prefectures was found to have a contextual impact on national-level crime trends. Furthermore, the implementation of the SoE caused changes in some crime types that could not be explained by the changes in the ambient population, suggesting that the implementation of the SoE affected offenders’ decision-making. It is also worth noting that the changes in ambient population and crime trends during the pandemic were observed in Japan where the behavioural regulation policy without law enforcement was introduced.
Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report
Authors: Matsumoto Tasuku , Noma Kazuhiro , Maeda Naoaki , Kato Takuya , Moriwake Kazuya , Kawasaki Kento , Hashimoto Masashi , Tanabe Shunsuke , Shirakawa Yasuhiro , Fujiwara Toshiyoshi
Published: June 2023

Background

The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT.

Case presentation

A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment.

Conclusion

A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.
Connecting dryland fine-fuel assessments to wildfire exposure and natural resource values at risk
Authors: Wells Adam G. , Munson Seth M. , Villarreal Miguel L. , Sesnie Steven E. , Laushman Katherine M.
Published: June 2023

Background

Wildland fire in arid and semi-arid (dryland) regions can intensify when climatic, biophysical, and land-use factors increase fuel load and continuity. To inform wildland fire management under these conditions, we developed high-resolution (10-m) estimates of fine fuel across the Altar Valley in southern Arizona, USA, which spans dryland, grass-dominated ecosystems that are administered by multiple land managers and owners. We coupled field measurements at the end of the 2021 growing season with Sentinel-2 satellite imagery and vegetation indices acquired during and after the growing season to develop predictions of fine fuel across the entire valley. We then assessed how climate, soil, vegetation, and land-use factors influenced the amount and distribution of fine fuels. We connected fine fuels to fire management points, past ignition history, and socio-economic vulnerability to evaluate wildfire exposure and assessed how fuel related to habitat of the endangered masked bobwhite quail (Colinus virginianus ridgwayi).

Results

The high amount of fine fuel (400–3600 kg/ha; mean = 1392 kg/ha) predicted by our remote sensing model (R2 = 0.63) for 2021 compared to previous years in the valley was stimulated by near-record high growing season precipitation that was 177% of the 1990–2020 mean. Fine fuel increased across the valley if it was contained within the wildlife refuge boundary and had lower temperature and vapor pressure deficit, higher soil organic content, and abundant annual plants and an invasive perennial grass (R2 = 0.24). The index of potential exposure to wildfire showed a clustering of high exposure centered around roads and low-density housing development distant from fire management points and extending into the upper elevations flanking the valley. Within the Buenos Aires National Wildlife Refuge, fine fuel increased with habitat suitability for the masked bobwhite quail within and adjacent to core habitat areas, representing a natural resource value at risk, accompanied with higher overall mean fine fuel (1672 kg/ha) in relation to 2015 (1347 kg/ha) and 2020 (1363 kg/ha) means.

Conclusions

By connecting high-resolution estimates of fine fuel to climatic, biophysical and land-use factors, wildfire exposure, and a natural resource value at risk, we provide a pro-active and adaptive framework for fire risk management within highly variable and rapidly changing dryland landscapes.
Value of TI-RADS and elastography strain ratio in predicting malignant thyroid nodules: experience from a single center in Egypt
Authors: Okasha Hussein Hassan , Mansor Mona , Sheriba Nermine , Abdelfattah Yasmine , Abdelfatah Dalia , Orabi Hussein El , Elebrashy Ibrahim N. , Saif Aasem , Meligi Amr A. El , Elshazli Mostafa , Elhadidy Khaled Elsayed , Abushady Manal M. , Islam Elham E. , Yosef Tarek M. , Salama Ahmed Saad El Din , Ouf Tarek I. , Said Sami Mufeed , Eid Yara M. , Mohsen Ahmed Amr , Rizk Mary N. , Yousief Elham , Elrawi Hoda , Ahmed Thoraya M. , Roshdy Eman , Sedrak Heba Kamal , Din Hala Gamal El , Aboulsoud Samar , El-Sawy Shereen Sadik , El-Feki Mohamed A. , Alzamzamy Ahmed , Elenin Sameh Abou , Tag-Adeen Mohammed , Abdelhameed Huda , Awad Abeer
Published: June 2023

Introduction

Thyroid nodules are highly prevalent in the general population; therefore, it is crucial to discriminate benign from malignant nodules. A practical thyroid imaging reporting and data system (TI-RADS) for thyroid nodules and ultrasound elastography are valuable tools not only for characterization of nodules but also for the selection of tumors for fine-needle aspiration cytology (FNAC).

Objective

This study aimed to evaluate the diagnostic accuracy of US evaluation in the prediction of malignant thyroid nodules and evaluate the role of the elastography score, strain ratio (SR), and the TI-RADS scoring system as non-invasive tools in differentiation between malignant and benign thyroid nodules.

Material and methods

A total of 1269 patients were evaluated between February 2017 and April 2020 by a single expert thyroid ultrasound operator. The final diagnosis was achieved from cytological and/or histological evaluation and follow-up for at least 1 year.

Results

There were 1088 females and 181 males with a mean age of 44 ± 10 SD. The final diagnosis was 1197 benign nodules and 72 malignant nodules. Most malignant nodules were scored elastography score 4 (83.3%) and TI-RADS category 5 (86.11%). We found that nodules with antero-posterior to transverse (A-P/T) diameter > 1, have 21 times more risk to be malignant than those with A-P/T diameter < 1, patients with solitary thyroid nodules have 4.5 times to develop malignancy compared to those with multinodular goiter (MNG), nodules with absent halo have 4 times more risk of malignancy. Furthermore, microcalcifications in thyroid nodules increase the risk of malignancy 9 times compared to those without calcifications. SR was found to be an excellent discriminator to differentiate between benign and malignant nodules with P < 0.001. Also, we found that for every unit increase in SR, the risk of malignancy increased by 20%. We reported that the accuracy of ultrasonography in the detection of malignant thyroid nodules had a sensitivity of 89%, specificity of 98%, 70% PPV, and 99.3% NPV, with an overall accuracy of 97.2%.

Conclusion

The application of ultrasonographic non-invasive criteria for thyroid nodules in clinical practice might significantly reduce the number of unnecessary FNAC. Elastography, SR, and TI-RADS classification could be good predictors for malignant thyroid nodules.
Genomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab
Authors: Lipsyc-Sharf Marla , Jain Esha , Collins Laura C. , Rosenberg Shoshana M. , Ruddy Kathryn J. , Tamimi Rulla M. , Schapira Lidia , Come Steven E. , Peppercorn Jeffrey M. , Borges Virginia F. , Warner Ellen , Snow Craig , Krop Ian E. , Kim Dewey , Weiss Jakob , Zanudo Jorge Gomez Tejeda , Partridge Ann H. , Wagle Nikhil , Waks Adrienne G.
Published: June 2023

PURPOSE

Erb-B2 receptor tyrosine kinase 2 ( ERBB2)–positive breast cancer (BC) is particularly common in young women. Genomic features of ERBB2-positive tumors before and after chemotherapy and trastuzumab (chemo + H) have not been described in young women and are important for guiding study of therapeutic resistance in this population.

METHODS

From a large prospective cohort of women age 40 years or younger with BC, we identified patients with ERBB2-positive BC and tumor tissue available before and after chemo + H. Whole-exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes.

RESULTS

Twenty-two women had successful WES on samples from at least one time point; 12 of these had paired sequencing results from before and after chemo + H and 10 had successful sequencing from either time point. TP53 was the only significantly recurrently mutated gene in both pre- and post-treatment samples. MYC gene amplification was observed in four post-treatment tumors. Seven of 12 patients with paired samples showed acquired and/or clonally enriched alterations in cancer-related genes. One patient had an increased clonality putative activating mutation in ERBB2. Another patient acquired a clonal hotspot mutation in TP53. Other genomic changes acquired in post-treatment specimens included alterations in NOTCH2, STIL, PIK3CA, and GATA3. There was no significant change in median ERBB2 CN (20.3 v 22.6; Wilcoxon P = .79) between paired samples.

CONCLUSION

ERBB2-positive BCs in young women displayed substantial genomic evolution after treatment with chemo + H. Approximately half of patients with paired samples demonstrated acquired and/or clonally enriched genomic changes in cancer genes. ERBB2 CN changes were uncommon. We identified several genes warranting exploration as potential mechanisms of resistance to therapy in this population.
Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess
Authors: Ng Jennifer L , Lim Ee Mun , Zhang Rui , Beilby John P , Watts Gerald F , Brown Suzanne J , Stuckey Bronwyn G A
Published: June 2023

Context

Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies.

Objective

We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP).

Methods

A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis.

Results

Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively.

Conclusion

LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.
Bare
Authors: Faflak Joel
Published: June 2023

This essay examines Intimacies, structured as an asymmetrical dialogue between two of the most astringent commentators of Freud and psychoanalysis: Leo Bersani and Adam Phillips. This dialogue takes place at both the intimate and extimate limits of what Bersani calls impersonal narcissism. By this Bersani asks us to move past the psychic dynamics of ego formation and their implicit violence to make way for a mode of relationality in which subjects coexist absent of any demands on one another. This approach draws from Bersani’s own eviscerating critique of the heteronormative deformation of identity to communicate what, after the Romantic poet William Wordsworth, could be called the “bare truth” of subject formation past even the need for subjects.
Before
Authors: Tuhkanen Mikko
Published: June 2023

Can we appear in the world otherwise than seduced by the promise of its suffering? Persistently returning to this question, Leo Bersani seeks the potential for the human subject’s nonsadistic reinitiation. He does this by visiting the “ontological laboratories” of Baudelaire, Freud, and Caravaggio, among others. This essay threads the work of this experimentation across his texts, assessing the appeal and anguish of the summons to the undoing—a before—of life’s actualized forms.
Ghosts
Authors: Hollywood Amy
Published: June 2023

This essay describes Bersani’s exploration of oneness and difference in Emily Brontë’s Wuthering Heights, and relates it to a larger discussion of trauma, love, and afterlife.
Sadism
Authors: Kaufman Eleanor
Published: June 2023

While Leo Bersani makes repeated stringent critiques of relationality and other-oriented sexuality, drawing on an array of literary examples including Gide, Proust, and Robbe-Grillet, he evinces a somewhat ambiguous relation to the question of sadism and to sadism’s inherent relation to masochism. Very similar notions of self-shattering not structured by the other, the world, or the couple are formulated by Gilles Deleuze in the late 1960s, but in this case as characteristics of Sadean demonstrative reason fully distinct from a psychoanalytic position that would insist on the relation between sadism and masochism. This missed connection between Deleuze and Bersani is broached through Deleuze’s reading of Michel Tournier’s rewriting of Robinson Crusoe.
Mitochondrial transfer from cancer-associated fibroblasts increases migration in aggressive breast cancer
Authors: Goliwas Kayla F. , Libring Sarah , Berestesky Emily , Gholizadeh Shayan , Schwager Samantha C. , Frost Andra R. , Gaborski Thomas R. , Zhang Jian , Reinhart-King Cynthia A.
Published: June 2023

Cancer-associated fibroblasts (CAFs) have distinct roles within the tumor microenvironment, which can impact the mode and efficacy of tumor cell migration. CAFs are known to increase invasion of less-aggressive breast cancer cells through matrix remodeling and leader–follower dynamics. Here, we demonstrate that CAFs communicate with breast cancer cells through the formation of contact-dependent tunneling nanotubes (TNTs), which allow for the exchange of cargo between cell types. CAF mitochondria are an integral cargo component and are sufficient to increase the 3D migration of cancer cells. This cargo transfer results in an increase in mitochondrial ATP production in cancer cells, whereas it has a negligible impact on glycolytic ATP production. Manually increasing mitochondrial oxidative phosphorylation (OXPHOS) by providing extra substrates for OXPHOS fails to enhance cancer cell migration unless glycolysis is maintained at a constant level. Together, these data indicate that tumor–stromal cell crosstalk via TNTs and the associated metabolic symbiosis is a finely controlled mechanism by which tumor cells co-opt their microenvironment to promote cancer progression and may become a potential therapeutic target.
Src- and Abl-family kinases activate spleen tyrosine kinase to maximize phagocytosis and Leishmania infection
Authors: Ullah Imran , Barrie Umaru , Kernen Rebecca M. , Mamula Emily T. , Khuong Francis Tho Huu , Booshehri Laela M. , Rhodes Emma L. , Bradford James M. , Datta Arani , Wetzel Dawn M.
Published: June 2023

Leishmania spp. are obligate intracellular parasites that must be internalized by phagocytic cells to evade immune responses and cause disease. The uptake of both Leishmania promastigotes (insect-stage parasites) and amastigotes (proliferative-stage parasites in humans and mice) by phagocytes is thought to be mainly host cell driven, not parasite driven. Our previous work indicates that host Src- and Abl-family kinases facilitate Leishmania entry into macrophages and pathogenesis in murine cutaneous leishmaniasis. Here, we demonstrate that host spleen tyrosine kinase (SYK) is required for efficient uptake of Leishmania promastigotes and amastigotes. A Src-family kinase–Abl-family kinase–SYK signaling cascade induces Leishmania amastigote internalization. Finally, lesion size and parasite burden during Leishmania infection is significantly decreased in mice lacking SYK in monocytes or by treatment with the SYK inhibitor entospletinib. In summary, SYK is required for maximal Leishmania uptake by macrophages and disease in mice. Our results suggest potential for treating leishmaniasis using host cell-directed agents.
Short-term surgical complications following fast-track medial unicompartmental knee arthroplasty
Authors: Bredgaard Jensen Christian , Gromov Kirill , Petersen Pelle B. , Jørgensen Christoffer C. , Kehlet Henrik , Troelsen Anders
Published: June 2023

Aims

Medial unicompartmental knee arthroplasty (mUKA) is an advised treatment for anteromedial knee osteoarthritis. While long-term survival after mUKA is well described, reported incidences of short-term surgical complications vary and the effect of surgical usage on complications is less established. We aimed to describe the overall occurrence and treatment of surgical complications within 90 days of mUKA, as well as occurrence in high-usage centres compared to low-usage centres.

Methods

mUKAs performed in eight fast-track centres from February 2010 to June 2018 were included from the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Database. All readmissions within 90 days of surgery underwent chart review and readmissions related to the surgical wound or the prosthesis were recorded. Centres were categorized as high-usage centres when using mUKA in ≥ 20% of annual knee arthroplasties. The occurrence of complications between high- and low-usage centres were compared using Fisher’s exact test.

Results

We included 3,757 mUKAs: 2,377 mUKAs from high-usage centres and 1,380 mUKAs from low-usage centres. Surgical complications within 90 days occurred in 69 cases (1.8%), 45 (1.9%) in high-usage centres and 24 (1.7%) in low-usage centres (odds ratio (OR) 1.1 (95% confidence interval (CI) 0.65 to 1.8)). The most frequent complications were periprosthetic joint infections (PJIs) (n = 18; 0.48%), wound-related issues (n = 14; 0.37%), and periprosthetic fractures (n = 13; 0.35%). Bearing dislocations (n = 7; 0.19%) occurred primarily in procedures from high-usage centres. In high-usage centres, seven periprosthetic fractures (0.29%) occurred compared to six (0.43%) in low-usage centres (OR 0.68 (95% CI 0.20 to 2.0)). In high-usage centres, nine PJIs (0.38%) occurred compared to nine (0.65%) in low-usage centres (OR 0.58 (95% CI 0.22 to 1.6)).

Conclusion

Surgical complications are rare after fast-track mUKA surgery and with no difference in overall occurrence of surgical complications between high- and low-usage centres, although the risk of some specific surgical complications may favour high-usage centres.

Cite this article: Bone Jt Open 2023;4(6):457–462.
The General Hopelessness Scale: Development of a measure of hopelessness for non-clinical samples
Authors: Drinkwater Ken , Denovan Andrew , Dagnall Neil , Williams Chris
Published: June 2023

Noting concerns about the non-clinical efficacy of the Beck Hopelessness Scale (BHS), specifically the instrument’s ability to discriminate between lower levels of hopelessness, this paper describes the development of the General Hopelessness Scale (GHS) for use with general samples. Following a literature review an item pool assessing the breadth of the hopelessness construct domain was created. This was then placed in survey form and assessed within two independent studies. Study 1 (N= 305, 172 women, 133 men,Mage = 28.68) explored factorial structure, item performance, and convergent validity of the GHS in relation to standardised measures of self-esteem and trait hopelessness. In Study 2 (N= 326, 224 women, 102 men,Mage = 26.52), scrutiny of the GHS occurred using confirmatory factor analysis and invariance tests, alongside item performance and convergent validity analyses relative to measures of affect, optimism, and hope. Factor analysis (using minimum average partial correlations and exploratory factor analysis) within Study 1 revealed the existence of four dimensions (Negative Expectations, Hope, Social Comparison, and Futility), which met Rasch model assumptions (i.e., good item/person fit and item/person reliability). Further psychometric assessment within Study 2 found satisfactory model fit and gender invariance. Convergent validity testing revealed moderate to large associations between the GHS and theoretically relevant variables (self-esteem, trait hopelessness, affect, optimism, and hope) across Study 1 and 2. Further examination of performance (reliability and ceiling and floor effects) within Study 1 and 2 demonstrated that the GHS was a satisfactory measure in non-clinical settings. Additionally, unlike the BHS, the GHS does not assume that administrators are trained professionals capable of advising on appropriate interventions.
Comparing different models to forecast the number of mass shootings in the United States: An application of forecasting rare event time series data
Authors: Lei Xue , MacKenzie Cameron A.
Published: June 2023

The number of mass shootings in the United States has increased in the recent decades. Understanding the future risk of the mass shootings is critical for designing strategies to mitigate the risk of mass shootings, and part of understanding the future risk is to forecast the frequency or number of mass shootings in the future. Despite the increasing trend in mass shootings, they thankfully remain rare events with fewer than 10 mass shootings occurring in a single year. Limited historical data with substantial annual variability poses challenges to accurately forecasting rare events such as the number of mass shootings in the United States. Different forecasting models can be deployed to tackle this challenge. This article compares three forecasting models, a change-point model, a time series model, and a hybrid of a time series model with an artificial neural network model. Each model is applied to forecast the frequency of mass shootings. Comparing among results from these models reveals advantages and disadvantages of each model when forecasting rare events such as mass shootings. The hybrid ARIMA-ANN model can be tuned to follow variation in the data, but the pattern of the variation may not continue into the future. The mean of the change-point model and the ARIMA model exhibit much more less annual variation and are not influenced as much by the inclusion of a single data point. The insights generated from the comparison are beneficial for selecting the best model and accurately estimating the risk of mass shootings in the United States.
The role of manganese in morphogenesis and pathogenesis of the opportunistic fungal pathogen Candida albicans
Authors: Wildeman Asia S. , Patel Naisargi K. , Cormack Brendan P. , Culotta Valeria C.
Published: June 2023

Metals such as Fe, Cu, Zn, and Mn are essential trace nutrients for all kingdoms of life, including microbial pathogens and their hosts. During infection, the mammalian host attempts to starve invading microbes of these micronutrients through responses collectively known as nutritional immunity. Nutritional immunity for Zn, Fe and Cu has been well documented for fungal infections; however Mn handling at the host-fungal pathogen interface remains largely unexplored. This work establishes the foundation of fungal resistance against Mn associated nutritional immunity through the characterization of NRAMP divalent metal transporters in the opportunistic fungal pathogen, Candida albicans. Here, we identify C. albicans Smf12 and Smf13 as two NRAMP transporters required for cellular Mn accumulation. Single or combined smf12Δ/Δ and smf13Δ/Δ mutations result in a 10–80 fold reduction in cellular Mn with an additive effect of double mutations and no losses in cellular Cu, Fe or Zn. As a result of low cellular Mn, the mutants exhibit impaired activity of mitochondrial Mn-superoxide dismutase 2 (Sod2) and cytosolic Mn-Sod3 but no defects in cytosolic Cu/Zn-Sod1 activity. Mn is also required for activity of Golgi mannosyltransferases, and smf12Δ/Δ and smf13Δ/Δ mutants show a dramatic loss in cell surface phosphomannan and in glycosylation of proteins, including an intracellular acid phosphatase and a cell wall Cu-only Sod5 that is key for oxidative stress resistance. Importantly, smf12Δ/Δ and smf13Δ/Δ mutants are defective in formation of hyphal filaments, a deficiency rescuable by supplemental Mn. In a disseminated mouse model for candidiasis where kidney is the primary target tissue, we find a marked loss in total kidney Mn during fungal invasion, implying host restriction of Mn. In this model, smf12Δ/Δ and smf13Δ/Δ C. albicans mutants displayed a significant loss in virulence. These studies establish a role for Mn in Candida pathogenesis.
How to achieve the net-zero target? Lessons learned from past transformations
Authors: Guthauser Annina , Pütz Marco , Seidl Irmi , Olschewski Roland
Published: June 2023

Transformations–defined as deep, radical, non-linear, multi-dimensional, systemic processes of change–are required to avert serious threats to humanity and the environment. In this study, we have analysed past transformations in Switzerland in four environmental domains, with the aim to draw conclusions for current challenges, such as the net-zero transformation. Firstly, we have conceptualised and defined transformations. Secondly, we have applied and further developed two theoretical frameworks to (i) identify actual transformations in the four domains, and (ii) analyse crucial characteristics of these profound changes. Furthermore, we have examined relevant enabling and hindering factors for transformations. Our study is based on literature review and expert interviews, as well as triangulation workshops to align the collected information. We conclude that providing general blueprints for transformations is not possible due to the complexity and context-specific nature of these processes. However, for the net-zero transformation to be successful, we found that unprecedent efforts are needed with respect to pace, sectors involved, levels of initiative, mindset change in the broader population, and involvement of technology and research. Specifically, we recommend fast action to (i) implement a steering committee combined with citizens’ assemblies and cross-sectoral discussion platforms, (ii) encourage different actors to take initiatives at multiple levels, and (iii) enable a broad mindset change across different societal groups.
Putting the Artificial Intelligence in Alternative Dispute Resolution
Authors: Abbott Ryan , Elliott Brinson S.
Published: June 2023

This article argues that the evolving regulatory and governance environment for artificial intelligence (AI) will significantly impact alternative dispute resolution (ADR). Very recently, AI regulation has emerged as a pressing international policy issue, with jurisdictions engaging in a sort of regulatory arms race. In the same way that existing ADR regulations impact the use of AI in ADR, so too will new AI regulations impact ADR, among other reasons, because ADR is already utilizing AI and will increasingly utilize AI in the future. Appropriate AI regulations should thus benefit ADR, as the regulatory approaches in both fields share many of the same goals and values, such as promoting trustworthiness.

Keywords: artificial intelligence; online dispute resolution; alternative dispute resolution; regulation; governance; trustworthiness; transparency; fairness; diversity; explainability.
Preliminary Investigative Study on the Blood Pressure-Lowering Potential of Aqueous Leaf Extract of Simarouba glauca (AESG) on Normotensive Adult Wistar Rats
Authors: Osagie-Eweka Sammy Davies E. , Orhue Noghayin E. J. , Amaechina Fabian C. , Omogbai Eric K. I. , Moke Emuesiri Goodies
Published: June 2023

Studies have shown that plants possess medicinal properties and compounds are beneficial in managing and treating diseases, including high blood pressure and related cardiovascular conditions. Simarouba glauca (SG) has been widely reported to possess antibacterial activity, anti-oxidant, anti-proliferative and hemolytic activity; amongst others. However, there is paucity of data on its effect on blood pressure. Hence, the study research aimed at assessing the hypotensive prospect inherent in the aqueous leaf extract of Simarouba glauca (AESG) on normotensive male Wistar rats. The study was conducted using adult male Wistar rats (n = 3), a urethane/thiopental (1205/20 mg/kg) anesthesia and a chart paper attached to Ugo Basile Uni-recorder Model 400700 data capsule. Under full anesthesia, the ratâ€™s trachea and the carotid artery were cannulated for assisted respiration and blood pressure measurement. At stable variables; following the administration of 0.2 mL normal saline, the AESG was administered intravenously via the caudal vein at 2.5 and 5.0 mg/kg body weight dose respectively. The data was recorded on a chart; indicated the characteristic dose-dependent hypotensive effect of AESG on normotensive rats; at doses of 2.5 mg/kg and 5.0 mg/kg, with marked decreases in the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) from basal levels of 127.83 Â± 1.01 mmHg, 91.00 Â± 1.00 mm Hg and 103.27 Â± 0.99 mm Hg respectively. The outcome of the preliminary investigation indicates that the AESG demonstrated a hypotensive effect on the BP of normotensive male Wistar rats dependent on varying doses administered; indicative of further evaluation.
Ethnobotanical Survey of Aromatic and Medicinal Plants Used in Traditional Medicine and Agri-Food in The Fez-Meknes Region
Authors: El Finou Hamza , Salhi Nadia , Halmoune Asma , El Rhaffari Lhoussaine
Published: June 2023

In order to identify the medicinal plants used in agri-food and traditional medicine by the population of Fez-Meknes region (Morocco), a floristic and ethnobotanical study was carried out in 4 provinces of this region (Fez, Meknes, Azrou, Taza). Questionnaire forms were used to survey the usual users of the plants and herbalists and to collect as much information as possible on the therapeutic and dietary use of aromatic and medicinal plants in the region. For plants used for food, our survey identified 29 species divided into 26 genera and 16 families, including herbaceous plants (70%), trees (16.60%), shrubs (10%) and bushes (3.30%). The study of the medicinal flora used in traditional medicine also allowed the inventory 81 species belonging to 47 families. Leaves are the most commonly used part and the majority of remedies were prepared in the form of infusion (47%) and decoction (26%). Among all the diseases treated, digestive diseases are the most cited (25%), followed by dermatological diseases (21%). The present study allowed us to evaluate some traditional practices used by the Fez-Meknes region population. In this context, it is essential to carry out similar investigations in other regions of the kingdom, in order to safeguard this precious natural heritage by means of a monograph that is as complete as possible and to validate the remedies and preparations identified using rigorous scientific protocols.
Immunoprotective Effect of Cocos nucifera Oil on Sheep Red Blood Cell-Induced Immunocompromised Rats
Authors: Idu MacDonald , Debby Igori , Gabriel Benjamin Ogunma
Published: June 2023

The aim of this study is to investigate the immunoprotective effects of cold-pressed coconut oil in immunocompromised rat. Standard procedure was used to perform this research work with a modified method. The effect of immunomodulatory properties of coconut oil was evaluated after challenging the animals with 0.3 ml sheep red blood cells (SRBCs) intraperitoneally and further treated with graded doses (0.25, 0.5 and 1.0 ml/kg i.p) of the oil extract for 21 days. The hematological, CD4, CD8 biochemical and histopathological analysis were evaluated. Result obtained from this study showed a significant increase in hematological indexes (WBC: 11.70; LYM: 9.9 GRAN: 8.0 and HGB: 15.57) across the treated groups, but majorly at lowest dose (0.25 ml/kg). More so a significant increase in CD4 and CD8 Count specifically at 0.25 ml/kg (7.763 and 7.830). Anti-oxidant property of the oil extract at 0.25 ml/kg had a significant reduction in malondialdehyde with an increased in antioxidant enzymes (SOD, CAT and GPx) when compared with untreated control. The body weight of the animals in the treated groups showed a significant increase at 0.25 ml/kg of the oil extract when compared with the untreated control. Liver function test (ALT, AST and ALP) showed no significant increase in the treatment groups when compared with the controls. The histopathological result reveals a normal physiological structure of the heart, lungs, spleen, liver and kidney in lowest dose of the oil extract.  In conclusion, this study validated the ethnomedicinal property of the plant.
Antihypertensive Drugs Therapy in Hypertension and Covid-19 Comorbidity
Authors: Moke Emuesiri Goodies , Ahama Endurance Efe , Toloyai Pere-Ebi Yabrade , Enaohwo Mamerhi Taniyohwo , Basil Ekuerhare , Umukoro Emuesiri Kohworho , Eduviere Anthony Taghogho , Udumebraye Ikuesirioghene , Udufowe Choice
Published: June 2023

The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak began at the end of 2019 in Wuhan, China, and has spread to over 200 countries. Many comorbidities have shown to be associated with the severity of the viral infection with hypertension being one of the highest rated comorbidities since loss of the ACE2 receptor due to SARS-Cov-2 infection can lead to increased blood pressure. The effects and clinical characteristics associated with the use of beta-blockers, angiotensin receptor blockers (ARB), and calcium-channel blockers (CCB) shows not to affect the outcome of covid-19, except in angiotensin converting enzyme inhibitor (ACEI) which may have negative outcomes on covid-19 infected patients. Many comorbidities have shown to be associated with the severity of the viral infection.
Synthesis and Characterization of Cinnamon Loaded BSA Microparticles with Antidiabetic Properties
Authors: Wanniarachchi Binuki , Sathsarani H.M.W.K. , Jayawardena Bimali M. , Dewangani H.G.N.
Published: June 2023

Conventional medicine that is being used to treat diabetes exert adverse side effects and therefore scientists have focused on natural hypoglycemic agents. “Sri Wijaya” (CCSW) is an accession of Cinnamomum zeylanicum, which shows higher hypoglycemic activity. Pressured water extract of its dried quills can be used as an antidiabetic nutraceutical. Higher stability, ease of storage and transportation, make powder form nutraceuticals more preferred. The objective of this study was to develop cinnamon encapsulated microparticles as a powder form nutraceutical with higher hypoglycemic activity. Four different products were synthesized. Two of them were synthesized using bovine serum albumin (BSA) (8.8 % (w/v), pH=5) in the presence of citric acid and ascorbic acid as cross-linking agents separately. The other products were synthesized using BSA (20 mg/ mL, pH=9) in the presence of same cross-linking agents. Antidiabetic activity of the products was determined using alpha-amylase and alpha glucosidase inhibition assays and compared with that of crude cinnamon extract and positive control acarbose. Since the product synthesized using BSA (20 mg/ mL, pH=9) and citric acid showed the highest alpha amylase inhibition activity, solubility, cinnamon loading percentage and cinnamon entrapment efficiency those conditions were concluded as the optimum conditions required to synthesize microparticles with higher hypoglycemic activity. Particle size, polydispersity index, and zeta potential of that product were 1.281 ± (0.004) µm, 0.460 ± (0.018) and -1.09 ± (0.03) mV respectively. According to the SEM image, microparticles have a spherical morphology. The UV-visible spectrum and the FT-IR spectrum confirm the entrapment of cinnamon compounds.