bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in research on the efficacy of traditional Chinese herbal medicine in combating African swine fever
Authors: Yang Yuwei , Zhao Ya , Zhang Qiang , Jin Meilin
Published: June 2024

African swine fever (ASF) is a highly contagious disease of domestic and wild pigs caused by African swine fever virus (ASFV). The mortality rate associated with ASF is remarkably high, almost approaching 100%. Since the introduction of ASF into China in 2018, its rapid spread has caused marked economic losses in the country’s swine industry. To date, there are no safe and effective commercial vaccines or antiviral drugs against ASF; thus, there is an urgent need to develop novel prevention and control strategies. Traditional Chinese medicine (TCM), which comprises various herbs that are abundant in various potential functional components, holds great promise for the prevention and control of ASF. Here, we provide a comprehensive review of the advancements in TCM and the effects of its compound formulas against ASF, including the antiviral abilities, immunoregulatory activities, and practical application of these formulas for the prevention and control of ASF. We specifically examined the potential and constraints of natural product-derived extracts and TCM formulas in combating ASFV. This review aims to offer insights and ideas for the holistic management and containment of ASF.
Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.
Authors: Lockney Natalie A , Smith Derek , Mundy Lindsay , Kilpatrick Phyllis , Butler Taylor , Kohutek Zachary , Cmelak Anthony , All Sean , Whitaker Ryan , Murphy Barbara A.
Published: June 2024

12123

Background: Pain is ubiquitous in head and neck cancer (HNC) patients undergoing radiotherapy (RT) with up to 40% developing chronic pain. Gabapentin initiated concurrently with RT reduces pain intensity, opioid use, and dysphagia; however, gabapentin may not fully control pain, and dose escalation may be limited by toxicity. Novel non-opioid analgesic combinations administered concurrent with RT may address these limitations. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor modulates mood and pain and is involved in central sensitization. Blocking the NMDA receptor may decrease the development and severity of neuropathic pain and decrease/prevent central sensitization. In combination with other analgesics, ketamine may enhance acute and chronic pain control at lower doses thus avoiding dose-limited toxicities. We report results from the dose-finding phase I study of gabapentin plus intranasal (NAS) ketamine in HNC patients undergoing RT; phase II is ongoing. Methods: Eligibility: locally advanced non-metastatic HNC planned for primary or adjuvant RT with or without concurrent chemotherapy. Primary objective of phase I was to determine the maximum tolerated dose (MTD) or maximum planned dose (MPD) for NAS ketamine combined with gabapentin (300mg TID). Planned dose levels (DL) were DL1: 10 mg TID, DL2: 20 mg TID, DL3: 30 mg TID and DL 4: 40 mg TID. A phase II expansion was planned at the MTD/MPD to confirm safety and feasibility. Results: Eleven patients were enrolled during phase I, which has been completed. No dose limiting toxicities (DLTs) were noted at DL1, DL2 or DL3. Two DLTs were reported at DL4: grade 2 dizziness and grade 2 sedation. The MTD was ketamine 30 mg NAS TID. Six patients are enrolled on the phase II trial at the MTD which is ongoing. Conclusions: The MTD of NAS ketamine was 30mg TID combined with gabapentin 300mg. The Phase II expansion is ongoing. Clinical trial information: NCT05156060 .
Identification of pharmaceutics with selective activity against melanoma-associated leptomeningeal disease using patient-derived circulating tumor cells.
Authors: Law Vincent , Bayle Simon , Duckett Derek R. , Forsyth Peter A. J.
Published: June 2024

2032

Background: Patients with advanced stage of melanoma may develop leptomeningeal disease (LMD), a rare form metastasis in the meninges. Unfortunately, there are currently no rationally designed treatments for melanoma-associated LMD (M-LMD) and the prognosis is dismal; with survival measured in weeks. A major barrier to developing effective therapies for this disease is the absence of model systems, such as patient-derived cerebral spinal fluid-circulating tumor cell (PD-CSF-CTC) models to identify and assess novel therapeutics. Added to this challenge is the difficulty of collecting and analyzing M-LMD specimens in the clinic and at autopsy. To address these hurdles, we have made considerable progress recently in overcoming these barriers via CSF and tissue collection (in clinic and rapid autopsy) and successfully propagating CSF-CTCs from M-LMD patients in vitro and in xenograft mouse models. These valuable resources have allowed us to perform proteomic and transcriptomic analyses of CSF and PD-CSF-CTCs, respectively. By comparing M-LMD -omics data against those from normal brain and extracranial disease, we have found unique LMD-specific biological pathways. In this study, we identified clinical compounds that could target these biological pathways and have efficacy against PD-CSF-CTCs in vitro and in vivo. Methods: PD-CSF-CTCs were propagated from individual M-LMD patients. Next, we have developed a 384-well high throughput cell-based assay and performed a pilot screening of more than 1,400 FDA-approved small molecule compound library using Echo to identify pharmaceutics that inhibit cell proliferation. Clinical compounds with the highest sensitivity were selected for validation of efficacy in vivo via intrathecal (IT) delivery of patient-derived cell lines to establish M-LMD xenografts. Results: Of the 1,436 FDA-approved small molecule compounds, 57 (~3.9%) exerted 95% proliferation inhibition and 20 (~1.4%) had 100% killing effect in PD-CSF-CTCs and murine melanoma cell lines. The compounds with the highest sensitivity include ponatinib (EC50: 1.85 – 4.06e-06), sorafenib (EC50: 9.57 – 9.77e-06), ceritinib (EC50: 1.84 – 2.05e-06) and homoharringtonine (HHT) (3.63 – 4.11e-08). In a randomized murine M-LMD preclinical trial, we selected HHT, since it is a cephalotaxine ester compound that can penetrate the brain. Our results show that HHT was well-tolerated in vivogiven systemically or IT via a murine Ommaya. We found M-LMD mice that received 14.5ng HHT (g.d. IT) showed significant prolonged median survival (control vs. HHT, P value: 0.0006; Mantel Cox test). Conclusions: This is the first demonstration of an approach that allows for the rational development of therapeutics in M-LMD. Results will provide crucial new insights into biology and will identify drug candidates that may be suitable for future clinical trials.
Detection of immune-related adverse events among hospitalized patients using large language models.
Authors: Sun Virginia H. , Heemelaar Julius C. , Hadzic Ibrahim , Raghu Vineet K. , Wu Chia-Yun , Zubiri Leyre , Suero-Abreu Giselle Alexandra , Ghamari Azin , Wu Jessica , Villani Alexandra-Chloé , Ho Jor Sam , Mooradian Megan J. , Sise Meghan E. , Zlotoff Daniel A. , Blum Steven Michael , Dougan Michael L. , Sullivan Ryan J. , Neilan Tomas G. , Reynolds Kerry Lynn , Thomas Molly Fisher ,   MGH Severe Immunotherapy Complications Service
Published: June 2024

2638

Background: Immune checkpoint inhibitor (ICI)-induced colitis, hepatitis, and pneumonitis are common immune-related adverse events (irAEs); however, the true incidence for these irAEs remains incompletely understood. Chart review is the gold standard for their detection but is time-consuming and cannot be implemented in large cohorts. The use of ICD codes is limited in sensitivity and specificity. Large language models (LLMs) are a scalable method of answering queries from human-generated text, though there is no data on the use of LLM for the identification of irAEs. Therefore, we investigated the application of a LLM to identify ICI-colitis, hepatitis, and pneumonitis among hospitalized patients, comparing its performance to manual chart review and ICD codes. Methods: Hospital admissions of patients on ICI therapy from February 5th, 2011, to November 3rd, 2021, were manually reviewed by a multidisciplinary immunotoxicity team using established published definitions for the presence of ICI colitis, hepatitis, and pneumonitis. Standard ICD codes and a LLM pipeline with retrieval-augmented generation (RAG) were used to detect irAEs. Performance was measured via sensitivity, specificity, and model runtime. The LLM was validated with a second dataset of inpatients with ICI colitis, hepatitis, and pneumonitis admitted from November 4th, 2021, to September 5th, 2023. Results: Among 5,677 hospitalized patients on ICI therapy in the initial cohort, there were 132 cases adjudicated with ICI colitis, 57 with ICI hepatitis, and 47 with ICI pneumonitis. The LLM was more sensitive in detecting all three irAEs compared to ICD codes (94.2% vs. 71.8%), achieving significance for ICI hepatitis (p<0.001) and pneumonitis (p=0.006), while having similar specificities (92.5% vs 91.1%, Table 1). The LLM approach was also efficient, spending an average of 9.42s per chart, compared to an estimated 15 minutes per chart for individual chart review. The mean sensitivity and specificity of the LLM on the validation dataset for adjudicated ICI colitis (n=20), hepatitis (n=24), and pneumonitis (n=6) were 96.9% and 93.2%, respectively. Conclusions: LLMs serve as a useful tool for the detection of ICI colitis, hepatitis, and pneumonitis, significantly outperforming ICD-codes in accuracy and manual chart review in efficiency.[Table: see text]
Phase II dose optimization with EZH2/EZH1 inhibitor tulmimetostat in patients (pts) with advanced solid tumors or hematologic malignancies.
Authors: Oaknin Ana , Banda Kalyan , Drescher Charles , Ribrag Vincent , Kindler Hedy L. , Walter Harriet S. , Tewari Alok , Pons-Tostivint Elvire , Lakhani Nehal J. , Harvey R. Donald , Sullivan Ryan J. , Zinzani Pier Luigi , Gonzalez Martin Antonio , Eberst Lauriane , Manso Sánchez Luis , Thakur Anjali , Kann Lennart , Reddy Archana , Faulhaber Nicola , Duska Linda
Published: June 2024

3097

Background: Phase I dose-finding recommended a Phase II dose of 350 mg for the investigational oral, next-generation, dual EZH2/EZH1 inhibitor tulmimetostat (1), with preliminary Phase II results previously reported (2). To find an optimal dose, design of the ongoing Phase II part was later updated under the FDA’s dose-optimization paradigm (NCT04104776). Here we report updated preliminary findings including dose expansions. Methods: Phase II is evaluating tulmimetostat ≤350 mg once daily (QD) in 28-day cycles in 6 disease-based cohorts. The dose-optimization design randomizes further pts with ovarian clear cell carcinoma (OCCC; M2)/endometrial carcinoma (EC; M3) to 200/300 mg tulmimetostat QD. Primary endpoint is objective response rate (complete response [CR]/partial response [PR]); secondary objectives include pharmacokinetics/pharmacodynamics and safety. Results: As of Oct 15, 2023, 117 pts received ≥1 dose (safety set); 111 had ≥1 post-baseline tumor assessment or discontinued prior to it (efficacy set). Median time since diagnosis was 2.8 years (0–19.6); 86.3% of pts had ≥2 prior lines of therapy. At cut-off, best responses of ≥1 CR/PR were seen in 5 cohorts (Table). 74.4% had dose modifications due to treatment-emergent adverse events (TEAEs), 41.9% had ≥1 serious TEAE, and 9.4% discontinued therapy due to TEAEs. Most frequent TEAEs (≥35% of pts; any grade/Grade ≥3) considered possibly related to treatment were diarrhea (49.6%/10.3%), thrombocytopenia (48.7%/24.8%), anemia (39.3%/16.2%), and nausea (35.9%/2.6%). Phase I/II data showed a direct correlation between increasing doses (50–375 mg) or exposure (area under the curve 0–24 hours or maximum concentration) and larger changes in gene expression, which plateau at higher doses (≥225–≤375 mg). Conclusions: The evolving Phase II data, including early data from lower doses, continue to show signs of antitumor activity/disease stabilization. The safety profile is consistent with EZH2 inhibition. These preliminary findings in heavily pretreated pts with multiple tumor types and evolving dose-optimization data support ongoing investigation of tulmimetostat. 1. Lakhani et al. ASCO 2021. 2. Drescher et al. ASCO 2023. Clinical trial information: NCT04104776 . [Table: see text]
The microtubule-destabilizing agent AUS_001 as a candidate for glioblastoma therapy.
Authors: Koutsioumpa Marina , Carlson Aaron L. , DesRochers Tessa , Chan Peter Y.W. , Risinger April L. , Adams Robert , Bardy Cedric , Thomas Daniel , Lelie Herman
Published: June 2024

3114

Background: The development of novel drugs targeting glioblastoma (GBM) is crucial due to the aggressive nature of this brain cancer, which often resists current treatments. Microtubules are a well-established target for cancer treatment, however there is a need to identify microtubule targeting agents (MTAs) with decreased toxicity and the ability to also retain efficacy in drug-resistant tumors. The novel MTA, AUS_001 has been shown to impede the growth of 15 established glioma cell lines with a half-maximal inhibitory concentration in the range of 0.04-0.246uM. The goal of the current study was to explore its potential in GBM treatment. Methods: Co-cultures of primary Human brain endothelial cells, pericytes and astrocytes layered in an insert were applied for the assessment of Blood Brain Barrier (BBB) permeability. AUS_001 efficacy against GBM was studied in vitro and in an ex vivo platform of advanced 3D cell culture systems. Differences in drug response were investigated between a Temozolomide (TMZ)-resistant human GBM cell line and parental cells. The ability of AUS_001 to overcome taxane-associated drug resistance was explored in P-glycoprotein (P-gp) and βIII-tubulin over-expression models of drug resistance. A microelectrode array system was used to assess the electrical activity and functionality of human Pluripotent Stem Cell (hPSC)-derived midbrain and cortical neurons, upon dose escalation drug treatments followed by a full media change to allow the recovery period. Results: By employing a 3D Human BBB Model, we demonstrated that AUS_001 is a good BBB permeability substrate. AUS_001 prevents the growth of Parental Primary Patient-Derived GBM and Patient-Derived Glioma Lines enriched in Cancer Stem cells under 2D culturing conditions with high potency. To this end, we evaluated the effect of AUS_001 in 3D spheroids originating from primary GBM patient-derived tumors that include all cells present in each patient’s primary tumor. AUS_001 efficiently prevented the growth of these tumors, including cases where the standard of care, TMZ was not effective. Notably, 2D GBM cultures with acquired TMZ resistance retained sensitivity to the cytotoxic effects of AUS_001. We also found that AUS_001 is less prone to mechanisms of resistance to currently approved MTAs, including increased expression of the βIII-isotype of tubulin or the P-gp drug efflux pump. An in vitro neurotoxicity model revealed that functional damage caused by AUS_001 was reversible, while paclitaxel-treated neurons suffered sustained neurotoxicity. Conclusions: Collectively, we show that AUS_001 has the potential to circumvent significant limitations of clinically approved MTAs, including brain penetration, drug resistance and peripheral neuropathy, making it a promising approach for the treatment of GBM.
An innovative supply chain & logistics model for tackling humanitarian crises with the support of internet of things (IoT) technologies and unmanned aerial vehicles (drones)
Authors: Αρετουλάκη Ελένη
Published: June 2024

Η παρούσα διατριβή εξετάζει τη συνέργεια και τη διαλειτουργικότητα των μη επανδρωμένων εναέριων οχημάτων, τα οποία συνήθως αναφέρονται ως drones, με άλλες Τεχνολογίες Πληροφορικής και Επικοινωνιών (ΤΠΕ) στη Διαχείριση της Εφοδιαστικής Αλυσίδας Ανακούφισης Καταστροφών (ΔΑΚ). Ρίχνει φως στην κατακερματισμένη εφαρμογή αυτών των τεχνολογιών σε περιβάλλοντα καταστροφών και παρουσιάζει την AIRDROP, μια καινοτόμα ολιστική πλατφόρμα που σχεδιάστηκε, με σκοπό να αξιοποιήσει τα συλλογικά πλεονεκτήματα των drones και των διαφόρων ΤΠΕ για την ενίσχυση της ΔΑΚ. Ξεκινώντας με μια συστηματική βιβλιογραφική ανασκόπηση, η μελέτη αυτή εντοπίζει τα υπάρχοντα ερευνητικά κενά στη χρήση των drones και των ΤΠΕ στον υπό εξέταση τομέα, και παράλληλα θέτει τα θεμέλια για τη σύλληψη της ιδέας ανάπτυξης της πλατφόρμας AIRDROP. Μεταβαίνοντας από τη θεωρητική διερεύνηση σε εφαρμόσιμα αποτελέσματα, η έρευνα αναλύει συστηματικά τις απαιτήσεις της πλατφόρμας (requirements engineering) μέσω μιας μεθοδικής διαδικασίας που περιλαμβάνει την εκμαίευση απαιτήσεων (requirements elicitation), τον προσδιορισμό απαιτήσεων (requirements specification) και την επακόλουθη τεκμηρίωσή τους (requirements validation). Η διαδικασία αυτή όχι μόνο μεταφράζει τη μέχρι στιγμής θεωρητική προσέγγιση σε μια βιώσιμη σχεδιαστική λύση, αλλά και αξιολογεί εμπειρικά τη σκοπιμότητα και τον αντίκτυπό της, θέτοντας έτσι σε λειτουργία τις προβλεπόμενες συνέργειες μεταξύ drones και ΤΠΕ. Επιπλέον, η παρούσα διατριβή παρουσιάζει έναν ολοκληρωμένο οδικό χάρτη για τα μεταγενέστερα προτεινόμενα βήματα της πλατφόρμας AIRDROP, ο οποίος περιλαμβάνει την λεπτομερή ανάλυση των παρεχόμενων υπηρεσιών της, τις λειτουργικές της δυνατότητες, την τεχνολογική ολοκλήρωση τους, τα αρχιτεκτονικά σχέδια, καθώς και τα πρωτότυπα διεπαφής χρήστη. Μέσω αυτής της προσπάθειας, η διατριβή στοχεύει να συμβάλει σημαντικά τόσο στον ακαδημαϊκό διάλογο όσο και στις πρακτικές στρατηγικές ΔΑΚ, επιδιώκοντας να ανοίξει νέους δρόμους για βελτιωμένες παρεμβάσεις ανθρωπιστικής βοήθειας, ωφελώντας σημαντικά τις ευάλωτες κοινότητες που πλήττονται από καταστροφές.
Sex difference in body image, exercise motivation and social comparison among Instagram users: a cross sectional study
Authors: Nimiya Aysha , K.G Vasudha , Shetty Sharanya B , Pai Keshava , N S Reshma , K Radhika , D'Souza Mariella , D'Souza Priyanka
Published: June 2024

In the 21st century, impact of social media, particularly Social Networking Sites (SNSs) has been linked to a wide range of human beliefs and expectations. Growing body of research has indicated that body image concerns along with exercise motivation and social comparison are on the rise among young adults. The present study aimed to examine the sex difference in body image, exercise motivation and social comparison among people who use Instagram in the age group 20-30. A total of 212 participants (men=106, women=106) aged 20-30 years, who are users of Instagram completed Body Self Image Questionnaire Short Form as a measure of Body image, Exercise Motivation Inventory – 2 as a measure of Exercise Motivation and Instagram as a Tool for Social Comparison as a measure of Social Comparison. Results showed that a significant difference in body image exist across gender with body image issues higher among females and significant difference in exercise motivation across gender with exercise motivation higher among males. No sex differences were seen in social comparison. It was concluded that body image concerns are higher among females and the drive for exercise is higher among males who used Instagram. It was found that body image concerns were higher among people who exercised regularly as well as among those who followed fitness related pages on Instagram as compared to those who did not. These results provide an insight into the sex differences between the variables and future directions can be aimed at conducting an in-depth analysis using body image, exercise motivation and social comparison.
Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential candidacy for adjuvant immune checkpoint inhibition
Authors: Vlachostergios Panagiotis J. , Papathanassiou Maria , Anagnostou Maria , Thodou Eleni , Tamposis Ioannis , Mitrakas Lampros , Zachos Ioannis , Koukoulis George K. , Samara Maria , Tzortzis Vassilios
Published: June 2024

Background The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non-VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions Preliminary findings from this ongoing study support the prognostic value of non-VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
Association of intradialytic hypertension and antihypertensive medication use in patients undergoing maintenance hemodialysis: a prospective observational study
Authors: Sherif Mariam , Zachariah Seeba , Jagdale Rajaram
Published: June 2024

Background In patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis, intradialytic hypertension and intradialytic hypotension are the common complications. The study aimed to collect and assess intradialytic Blood Pressure (BP) complications and their association with different factors, including BP medication. Methods This was a prospective observational study, conducted at the hemodialysis center in a teaching hospital in the UAE, that provide a specialist’s care for the patients receiving ongoing hemodialysis. Patient demographics, medications used, lab data and the peridialytic BP (pre-, intra-, and post-) dialytic BP were collected for a period of 6 months. SPSS Version 29, Armonk, NY was used for statistical analysis. Pearson Chi-square test and Fischer’s Exact test were used to compare the association between categorical variables to intradialytic hypertension and hypotension. Results Blood pressure data was collected from 47 hemodialysis patients for a total of 2616 hemodialysis sessions during the 6 months study period. Beta-blockers (68%) and calcium channel blockers (66%) were the commonly used antihypertensive medications in the study population. Intradialytic hypertension events were diagnosed in 49 hemodialysis sessions and intradialytic hypotension was diagnosed in 23 hemodialysis sessions. On comparing the effect of antihypertensive medication to the occurrence of intradialytic BP complications, ARBs and alpha-1 blockers showed no association to intradialytic hypertension, but beta-blockers and calcium channel blockers use were associated with increased number of intradialytic hypertension events (p-value <0.05). On the other hand, antihypertensive medication use showed no association with intradialytic hypotension. Conclusions Patients using ARBs or alpha-1 blockers had higher intradialytic hypertension events. Beta-blocker and calcium channel users had lower intradialytic hypertension events. Antihypertensive use showed no association with intradialytic hypotension events.
A cross sectional study on endemicity of VIM, NDM, KPC, IPM & OXA-48 genes in Carbapenemase producing Klebsiella pneumoniae and Escherichia coli from a tertiary hospital using mCIM, eCIM, and PCR in Central India
Authors: Kunjalwar Radha , Mudey Gargi
Published: June 2024

Background Carbapenem-resistant Enterobacteriaceae (CRE) represent a growing global health concern, necessitating comprehensive investigations into their prevalence and resistance mechanisms. This study protocol focuses on detecting carbapenemase genes, including blaVIM, blaNDM, blaKPC, blaIPM, and blaOXA-48, in clinical isolates of Klebsiella pneumoniae and Escherichia coli from a tertiary hospital in Eastern India. The rise of carbapenem resistance poses challenges to effective antimicrobial therapy and infection control strategies. Methods Conducted at the Department of Microbiology, Jawaharlal Nehru Medical College, the study employs a cross-sectional design from July 2022 to December 2023. The sample size calculation follows Daniel’s formula, considering a non-response rate of 10%. Modified Carbapenem Inactivation Method (mCIM) and EDTA-Modified Carbapenem Inactivation Method (eCIM) will be used for phenotypic detection, along with polymerase chain reaction (PCR) for genotypic confirmation. Antibiotic susceptibility testing using the Kirby-Bauer Disk Diffusion method will complement resistance profiling. Expected Outcome Anticipated outcomes include insights into the efficacy of mCIM and eCIM in detecting carbapenem resistance, the prevalence of carbapenemase genes in Klebsiella pneumoniae and Escherichia coli, and the antibiotic resistance pattern of carbapenemase-producing CRE. This study aims to provide valuable data for guiding empirical treatment strategies and reinforcing infection control measures in the region.
VIRGINIA WOOLF, FEMININO, ESCRITA E ESCUTA: ALGUMAS REVERBERAÇÕES
Authors: Da Rocha Barros Vinicius , De Souza Mériti , Albrecht Fernanda , Valentim Eccher Pedro
Published: June 2024

O artigo se refere às dimensões da escrita e da escuta clínica no que concerne ao feminino. Percorremos aspectos dessas dimensões nos seus entrelaces com o feminino: da escrita de autoras como Virginia Woolf, até a escuta de um caso clínico. Recorremos a pressupostos conceituais e metodológicos das teorizações freudianas e pós-freudianas, mantendo o diálogo com referências pós-estruturalistas, para discutir textos que abordam a escrita e o feminino, bem como, para analisar recortes de um caso clínico. Entendemos que concepções e experiências do feminino se articulam a escrita e a prática clínica, apresentando possibilidades para a escuta do feminino e para ampliar o trabalho crítico em relação à hegemonia falocêntrica.
Ensuring that cyber security is fit for the future of manufacturing
Authors: Carroll Dominic
Published: June 2024

A cyber attack can have particularly devastating results on manufacturing organisations. More than half have turned to external providers to fully manage their security, while many more outsource at least some operations. But are the security service providers up to the task? And how can a manufacturer better align security with the organisation and its specific requirements?
All in One
Authors: Evans Benedict , Wordsworth Saul
Published: June 2024

THE NEXAT INITIALLY TURNS HEADS DUE TO ITS UNUSUAL DIMENSIONS – IT TRAVERSES FIELDS LONGITUDINALLY. BUT WHAT’S REALLY GAME-CHANGING ABOUT THIS VEHICLE IS ITS MODULAR FUNCTIONALITY, WHICH MAKES IT ADAPTABLE TO ALL ASPECTS OF CROP PRODUCTION, DISPENSING WITH THE NEED FOR TRACTORS IN THE FIELD
Pectoralis Major Transfer For Anterior Recurrent Dislocation of Reverse Total Shoulder Arthroplasty: A Case Report
Authors:   Department of Orthopaedic Surgery, Yeosu Baek Hospital, Jeollanam-do, 59709, Republic of Korea., Baek Chang Hee , Kim Bo Taek ,   Department of Orthopaedic Surgery, Yeosu Baek Hospital, Jeollanam-do, 59709, Republic of Korea., Kim Jung Gon ,   Department of Orthopaedic Surgery, Yeosu Baek Hospital, Jeollanam-do, 59709, Republic of Korea.
Published: June 2024

Introduction: Reverse total shoulder arthroplasty (RTSA) has revolutionized the treatment landscape for a spectrum of shoulder pathologies, extending its indications from rotator cuff arthropathy to encompass irreparable rotator cuff lesions, fractures, inflammatory arthritis, and tumors. However, the exponential increase in RTSA usage has brought a proportional rise in associated complications, with dislocation being one of the most common early post-operative complications. Case Report: This case report details a 65-year-old right-hand dominant male patient presenting with chronic pain and weakness in the right shoulder, diagnosed with advanced glenohumeral arthritis and massive irreparable rotator cuff tears. The patient underwent a Bony Increased-Offset RTSA (BIO-RTSA) procedure, coupled with subscapularis repair. Postoperatively, the patient experienced pain and instability, culminating in an atraumatic anterior dislocation at 4 months. Despite conservative management, recurrent dislocations persisted. Revision surgery was performed with an increase in the linear component size for containment. About 1 year postoperative of the revision surgery, recurrent dislocation reoccurred. Re-revision surgery was performed with secondary pectoralis major (PM) transfer for subscapularis deficiency due to re-tear from recurrent dislocation, and with an increased humeral tray size for better containment. About 1-year and 6-month post-operative to the re-revision surgery, the patient achieved restored stability, improved range of motion, and reported satisfaction with the outcome. Conclusion: This case report underscores the challenges of managing recurrent anterior dislocation after RTSA. The successful use of secondary PM transfer highlights its efficacy as a salvage procedure in restoring stability for persistent anterior dislocation after RTSA. Yet, further clinical studies are warranted to establish the role of such interventions in the management for RTSA-associated complications. Level of Evidence IV; Case report Keywords: Reverse total shoulder arthroplasty, pectoralis major transfer, irreparable rotator cuff tear, rotator cuff arthroplasty, tendon transfer.
Orthopedic Manifestations of Disseminated Cryptococcal neoformans Infection in an Immunocompromised Patient: a Case Report
Authors:   Department of Orthopaedic Surgery, The University of Toledo Medical Center, Toledo, OH,, Yatsonsky David , Gunn Jenna ,   The University of Toledo College of Medicine and Life Sciences, Toledo, OH,, Zajac Kelsee ,   The University of Toledo College of Medicine and Life Sciences, Toledo, OH,, Burke Connor ,   The University of Toledo College of Medicine and Life Sciences, Toledo, OH,, Bair Jeffrey ,   Department of Orthopaedic Surgery, Section of Orthopaedic Trauma and Adult Reconstruction, ProMedica Toledo Hospital, Toledo, OH.
Published: June 2024

Introduction: Cryptococccus neoformans is a fungus which typically presents in immunocompromised hosts, commonly presenting as meningoencephalitis. There have been very few documented incidents of intramuscular manifestations of this pathogen. Case Report: We report on a case of a 45-year-old caucasian male with disseminated Cryptococcus neoformans who developed cryptococcal intramuscular abscesses of all extremities and osteomyelitis of the left upper limb. Clinical treatment and surgical debridement of the forearm was performed. Persistent infection resulted in a left humeral amputation and ultimately the patient’s death. This is one of the few documented intramuscular abscesses of Cryptococcus neoformans. Conclusion: Orthopedic manifestations of cryptococcal infections are rare; however, awareness and prompt diagnosis may improve outcomes. Keywords: Immunocompromised, Cryptococcus neoformans, intramuscular abscesses, Osteomyelitis.
Post-Traumatic Radio-ulnar Synostosis Managed by the Excision of the Bone Bridge and Palmaris Longus Encircling Loop over the Ulna: A Case Report
Authors:   Department of Orthopaedics Surgery, Government Medical College Haldwani, Uttarakhand, India., Dharmshaktu Ganesh Singh , Dharmshaktu Ishwar Singh ,   Department of Orthopaedics Surgery, Government Medical College Haldwani, Uttarakhand, India., Yadav Krishna Dev Singh ,   Department of Orthopaedics Surgery, Government Medical College Haldwani, Uttarakhand, India.
Published: June 2024

Introduction: Radioulnar synostosis is an uncommon complication of forearm fractures and presents with varying degrees of restricted forearm movement. The diaphysial distal third synostosis is less common and excision of the synostosis is fraught with risk of re-ossification. Use of inert or biological interposing material has thus been accompanied with the synostosis excision and various methods have been described. There is still no consensus on the ideal treatment method. Case Report: We, hereby, report a case of a long-standing radioulnar synostosis with rotational restriction of movement. Despite the movement restriction, the patient could perform basic activities of daily living and wanted to improve the movements. The presence of diaphyseal radioulnar synostosis was conformed on the radiographs and computerized tomography scan. A volar forearm approach was used and the bony bridge was excised. The ipsilateral native palmaris longus (PL) tendon was extracted from distal wrist crease and with its proximal attachment intact, circumferentially wrapped around the ulnar raw surface as an interposing material. Apart from this, free fat was also placed at the synostosis site. In the long-term follow-up of 10 years, there was no radiological evidence of re-ossification noted. The clinical improvement was not much but the patient was performing activities of daily living with no discomfort. Conclusion: The use of an encircling loop of the native PL tendon, over the raw surface of one of the forearm bones, may be another useful method to decrease the chances of recurrence following the excision of the synostosis. Keywords: Post-traumatic synostosis, radioulnar synostosis, excision, forearm bone synostosis, heterotopic ossification, management.
Desmoplastic Fibroblastoma of the Ankle: A Case Report of a Rare Localization and a Literature Review
Authors:   Department of Orthopedic Surgery, Centre Chirurgical Emile Gallé, University Hospital of Nancy, Nancy, France., Cuinet Thomas , Couraudon Alexandre ,   Department of Orthopedic Surgery, Centre Chirurgical Emile Gallé, University Hospital of Nancy, Nancy, France., Lefevre Maxime ,   Department of Orthopedic Surgery, Centre Chirurgical Emile Gallé, University Hospital of Nancy, Nancy, France., Fernandez Andrea ,   Department of Orthopedic Surgery, Centre Chirurgical Emile Gallé, University Hospital of Nancy, Nancy, France., Galois Laurent ,   Department of Orthopedic Surgery, Centre Chirurgical Emile Gallé, University Hospital of Nancy, Nancy, France.
Published: June 2024

Introduction: Desmoplastic fibroblastoma is a rare, slow-growing benign soft tissue tumor. It has a wide anatomical distribution and mainly affects adult males. Fourteen percent of cases occur in the ankle or foot. Case Report: In this study, we report a rare location of desmoplastic fibroblastoma on the ankle of a 76-year-old female, discovered as a slowly growing mass. Discussion: Desmoplastic fibroblastoma is an anatomical and clinical entity. It appears macroscopically as a pseudocartilaginous structure and histologically as a stellate or spindle-shaped fibroblastic proliferation in a collagenous stroma. Conclusion: Desmoplastic fibroblastoma has anatomical specificities and should still be clearly distinguished from certain malignant tumors. Keywords: Ankle, benign tumor, fibroblastoma.
Editionen - Opuscula Johannis de Ragusio de fide Saracenorum / Schriften des Johannes von Ragusa zum Glauben der Sarazenen
Authors: Langeloh Jacob
Published: June 2024

Johannes von Ragusa u. a. Schriften zum Islam und zur Mission
Una propuesta de categorización en la elaboración participativa de mapas: / A Proposal for the Categorization of Participatory Map-Making: Cuatro estudios de caso en Colombia / Four Case Studies from Colombia
Authors: Barrera Lobatón Myriam Susana
Published: June 2024

resumen: Este artículo propone una categorización de cartografías en espacios de participación, con base en las experiencias del Grupo de Investigación de Espacio, Tecnología y Participación (ESTEPA) de la Universidad Nacional de Colombia. Toma, a manera de ilustración, cuatro ejemplos realizados en diferentes contextos de Colombia, resultando en distintas formas cartográficas, las cuales, aunque se superponen, no tienen las mismas posibilidades de transformar los territorios. El análisis se fundamenta en el proceso de comunicación en el que un mensaje es emitido por una persona o un grupo de personas y, a su vez, recibido por otro. Este ejercicio tiene un propósito e involucra una forma de ver el mundo (ontología) y relaciones de poder (política). Los ejemplos seleccionados consideran sus emisores, los métodos y herramientas que se utilizan, el mensaje o intención de la acción de cartografiar, el receptor y quienes participan en su elaboración. Las categorías cartográficas propuestas, sin ser exhaustivas y reconociendo que tienen aspectos que se superponen, son: participativa, social, alternativa, colaborativa y convencional. La categorización busca ofrecer un marco teórico-metodológico de referencia que permita, a quienes utilizan la cartografía y la participación, considerar el verdadero impacto del ejercicio de cartografiar en los territorios, así como validar académicamente otras formas de hacer investigación. abstract: This article proposes a categorization of cartographies in participatory spaces, based on the experiences of the Space, Technology and Participation Research Group (ESTEPA) at the Universidad Nacional de Colombia. Four case studies carried out in different contexts in Colombia are given as examples of the different mechanisms to show distinct forms of mapping, which, although overlapping, do not have the same possibilities of transforming territories. The analysis is based on the communication process in which a message is issued by one person or a group of people and in turn received by another. This exercise is purposedriven and involves a way of seeing the world (ontology) and power relations (politics). The selected examples consider their creators, the methods and tools used, the message or intention of the mapping action, the recipient, and those who participate in its preparation. The proposed cartographic categories, without being exhaustive and recognizing that they have overlapping aspects, are: participatory, social, alternative, collaborative and conventional. The categorization seeks to offer a theoretical-methodological framework of reference that allows those who use cartography and participation to consider the true impact of the exercise of mapping in territories, as well as academically validate different ways of doing research.
Can deep neural networks work with amplitude and phase input of defocused images?
Authors: Yin Siyuan , Cao Ruizhi , Liang Mingshu , Shen Cheng , Zhou Haowen , Zhang Oumeng , Yang Changhuei
Published: June 2024

Deep neural network (DNN) models, particularly convolutional neural networks (CNNs), have demonstrated remarkable performance in biomedical image classification due to their ability to automatically learn features from large datasets. One common challenge in the preparation of large, microscopic datasets for DNN tasks is sample defocusing, potentially impairing the model performance. To handle defocusing, computational imaging, or specifically quantitative phase imaging (QPI), performs digital refocusing by using both the phase and the amplitude of the complex optical field. This leads us to investigate whether feeding the complex field into DNN would potentially address the defocusing problem as in-focus information is implicitly encoded in the complex field. In this paper, we assess the feasibility of employing neural networks to directly process full amplitude and phase data from a defocus plane without digital refocusing. Our specific focus lies in understanding the tolerance for defocus in image classification neural networks when amplitude and phase are taken as inputs. To accomplish this, we used Fourier ptychography microscopy (FPM) to acquire in-focus phase and amplitude images of two distinct object types – normal red blood cells and echinocytes. We then digitally propagate the complex field to generate progressively defocused images of the samples to serve as training and testing datasets for image classification neural networks. While the digitally defocused images contain sufficient information to recover the original in-focus images, we observed that current standard implementations of deep learning models are unable to effectively utilize the defocused field to distinguish between the two cell types. We conclude that the physical-model-based digital refocusing capability of QPI remains indispensable for overcoming defocusing issues in current standard DNN models.
Four-wave mixing in a laser diode gain medium induced by the feedback from a high-Q microring resonator
Authors: Sokol Daria , Dmitriev Nikita , Chermoshentsev Dmitry , Koptyaev Sergey , Masalov Anatoly , Lobanov Valery , Bilenko Igor , Shitikov Artem
Published: June 2024

Laser diodes are widely used and play a crucial role in myriad modern applications including nonlinear optics and photonics. Here, we explore the four-wave mixing effect in a laser diode gain medium induced by the feedback from the high-Q microring resonator. This phenomenon can be observed at laser frequency scan close to the microresonator eigenfrequency, prior to the transition of the laser diode from a free-running to a self-injection locking regime. The effect opens up the possibility for generation of remarkably low-noise, stable, and adjustable microwave signals. We provide detailed numerical study of this phenomena proven with experimental results and demonstrate the generation of the signals in the GHz-range. The obtained results reveal the stability of such regime and disclose the parameters' ranges enabling to achieve it. Cumulatively, our findings uncover novel laser diode operation regime and pave the way for the creation of a new type chip-scale, low-noise microwave sources, which are highly demand for diverse applications, including telecommunication, metrology and sensing.
A bioelectronic device for electric field treatment of wounds reduces inflammation in an in vivo mouse model
Authors: Hernandez Cristian O. , Hsieh Hao-Chieh , Zhu Kan , Li Houpu , Yang Hsin-ya , Recendez Cynthia , Asefifeyzabadi Narges , Nguyen Tiffany , Tebyani Maryam , Baniya Prabhat , Lopez Andrea Medina , Alhamo Moyasar A. , Gallegos Anthony , Hsieh Cathleen , Barbee Alexie , Orozco Jonathan , Soulika Athena M. , Sun Yao-Hui , Aslankoohi Elham , Teodorescu Mircea , Gomez Marcella , Norouzi Narges , Isseroff Roslyn Rivkah , Zhao Min , Rolandi Marco
Published: June 2024

Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.
Association of renal function with mortality among hospitalized patients treated with remdesivir for COVID-19
Authors: Gonzalez Suarez Maria Lourdes , Mara Kristin C. , Rivera Christina G. , Chesdachai Supavit , Draper Evan , Razonable Raymund R.
Published: June 2024

Background and aim

Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function.

Methods

We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups.

Results

The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30–59; OR 1.46 for eGFR 15–29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2.

Conclusions

Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.