bluuebunny/crossref_metadata_2025 huggingface dataset:
DREAM3R: Durvalumab with chemotherapy as first-line treatment in advanced pleural mesothelioma—A phase 3 randomized trial.
Authors: Forde Patrick M. , Nowak Anna K. , Kok Peey-Sei , Brown Chris , Sun Zhuoxin , Anagnostou Valsamo , O'Byrne Kenneth John , Yip Sonia , Cook Alistair , Lesterhuis Willem Joost , Hughes Brett Gordon Maxwell , Pavlakis Nick , Brahmer Julie R. , Kindler Hedy L. , Tsao Anne S. , Zauderer Marjorie Glass , Ramalingam Suresh S. , Stockler Martin R.
Published: June 2022

TPS8599

Background: Combination PD1/CTLA4 immune checkpoint blockade and platinum-pemetrexed (CP) chemotherapy are standard first-line options for the treatment of unresectable malignant pleural mesothelioma (MPM). Two recent, single-arm, phase 2 trials (DREAM and PrE0505) combining the PD-L1 inhibitor durvalumab and standard first line CP both exceeded pre-specified efficacy criteria. The Phase 3 DREAM3R trial aims to determine the effectiveness of including durvalumab with first line CP chemotherapy in advanced MPM. Methods: Treatment-naïve patients with advanced MPM will be randomized (2:1) to either durvalumab 1500 mg every 3 weeks plus chemotherapy (cisplatin 75 mg/m2 or carboplatin AUC 5 and pemetrexed 500 mg/m2) every 3 weeks for 4-6 cycles (Arm A), followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal, versus doublet chemotherapy alone for 4-6 cycles with all patients monitored for progression. The target sample size is 480 patients recruited over 27 months, with follow up for an additional 24 months. This provides over 85% power if the true hazard ratio for overall survival (OS) is 0.70, with 2-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Key eligibility criteria include: MPM of any histological subtype; measurable disease per RECIST 1.1 modified for mesothelioma (mRECIST 1.1); ECOG PS 0-1; and adequate hematologic, renal, and liver function. Exclusions: Prior systemic anticancer treatment for MPM, diagnosis based solely on cytology or fine needle aspiration biopsy, contraindication to immunotherapy or conditions requiring immunosuppressive agents or corticosteroids. Patients will be further stratified at randomization by: Age (18-70 years vs. > 70), sex, histology (epithelioid vs. non-epithelioid), planned platinum (cisplatin vs. carboplatin) and geographic region (USA vs. ANZ). The primary endpoint is OS. Secondary endpoints include progression-free survival; objective tumor response; adverse events; health-related quality of life; and healthcare resource use in ANZ. Tertiary correlative objectives aim to further explore and validate potential prognostic and/or predictive biomarkers (including those identified in the DREAM and PrE0505 studies, PD-L1 expression, tumor mutation burden, genomic characteristics, and HLA subtypes) via tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. The study is active and enrolling in both ANZ and in the US. Clinical trial information: NCT04334759 and ACTRN 12620001199909.
A phase I/II multisite study of rucaparib and pembrolizumab maintenance therapy in stage IV non-squamous non–small cell lung cancer after initial therapy with carboplatin, pemetrexed, and pembrolizumab.
Authors: Qin Angel , Morgensztern Daniel , Waqar Saiama Naheed , Owen Dwight Hall , Gadgeel Shirish M. , Kalemkerian Gregory Peter , Zhao Lili , Ramnath Nithya
Published: June 2022

TPS9138

Background: Carboplatin, pemetrexed, and pembrolizumab (CPP) followed by pemetrexed and pembrolizumab maintenance is a standard of care (SOC) for non-squamous metastatic non-small cell lung cancer (NSCLC), based on results of the KEYNOTE-189 study. The progression free survival (PFS) on this study was 8.8 months. There is increasing data to support that certain sporadic tumors harbor somatic mutations in genes of the homologous recombinant repair (HRR) pathway resulting in a “BRCAness” phenotype rendering sensitivity to PARP inhibitors (PARPi). TCGA data suggest up to 38% of NSCLC have mutations in HRR pathway genes. Furthermore, treatment with PARPi is shown to upregulate PD-L1 expression, which is associated with pembrolizumab response in NSCLC. We therefore hypothesized that maintenance therapy with a PARPi and pembrolizumab will improve PFS compared to SOC pemetrexed and pembrolizumab. Methods: This is a single arm, multi-site, investigator-initiated phase I/II study that is enrolling treatment-naïve patients with stage IV nonsquamous metastatic NSCLC without any targetable driver mutations eligible for CPP. Patients without progression after 4 cycles of CPP then proceed to maintenance with rucaparib 600mg PO BID and pembrolizumab 200mg IV every 21 days. The primary objective is efficacy assessed by PFS and second objectives include overall survival, safety, tolerability, and objective response rate (ORR). Correlatives in this study include PD-L1 expression, tumor mutational burden (TMB), and measurements of HRR deficiency as assessed by homologous repair deficiency (HRD) and loss of heterozygosity (LOH) using established methods. Key exclusion criteria include untreated brain metastases and prior exposure to a PARPi or PD-1/PD-L1 inhibitor. The phase I cohort which consisted of 6 patients treated with the approved full doses of rucaparib and pembrolizumab was completed without dose limiting toxicity (DLT). Using a Bayesian decision-theoretic two-stage design, the first stage will enroll 38 patients. If predefined PFS parameters are met, an additional 17 patients, for a total of 55 patients, will be enrolled. To date, 21 patients have been enrolled. Clinical trial information: NCT03559049.
FoRT 05-BEAT: A phase II randomized trial comparing atezolizumab versus atezolizumab + bevacizumab as first-line treatment in patients with PD-L1 high advanced/metastatic NSCLC.
Authors: Migliorino Rita , Landi Lorenza , Galetta Domenico , Soregaroli Daniela , Ricciardi Serena , Minuti Gabriele , Montrone Michele , Marech Ilaria , Morabito Alessandro , Berardi Rossana , Novello Silvia , Rocco Danilo , Pilotto Sara , Zanelli Francesca , Bengala Carmelo , Delmonte Angelo , Aieta Michele , Cortinovis Diego Luigi , Cappuzzo Federico
Published: June 2022

TPS9145

Background: Several ongoing phase III studies are evaluating the efficacy of first-line atezolizumab in combination with chemotherapy in patients with non small-cell lung cancer (NSCLC). Among angiogenesis inhibitors, bevacizumab is approved as first-line therapy in combination with chemotherapy or in combination with erlotinib in patients with NSCLC harboring activating EGFR mutations. Recent evidence (Wallin 2016) suggests that the combination of atezolizumab and bevacizumab increases intra-tumoral CD8+T cells, suggesting that dual VEGF and PD-L1 inhibition improves antigen-specific T-cell migration. In addition, preliminary clinical data suggested a strong synergistic effects of bevacizumab with immune checkpoint inhibitors. There is therefore a strong rationale for investigating the combination of atezolizumab and bevacizumab in patients with advanced/metastatic NSCLC. The FoRT 05-BEAT is a multicenter, Italian, phase II, randomized study comparing atezolizumab monotherapy versus the combination of atezolizumab and bevacizumab in patients with chemo-naive metastatic NSCLC and high levels of PD-L1 expression. Methods: The trial was conducted in 35 Italian centers: chemotherapy naive metastatic NSCLC patients, with high levels of PD-L1 expression (PD-L1 TPS ≥50% or TC/IC 3 scoring) were randomly assigned to atezolizumab monotherapy (1200 mg every 3 weeks) or to the combination of atezolizumab (1200 mg every 3 weeks) and bevacizumab (15 mg/kg every 3 weeks).The primary endpoint is overall survival (OS) rate at 18 months. Secondary endpoints include response rate (RR), PFS, OS according to presence of bone and/or hepatic metastases. Safety considerations will be considered. Exploratory analysis of predictive biomarker on tumor tissue and blood samples has been planned. Sample size has been calculated assuming a 18 months OS of 50% in the atezolizumab arm. Therefore, a total of 186 patients is needed to detect an absolute improvement of 20%, thus obtaining a 18mOS of 70% in the combination arm, with a power of 80% at a significance level of 5%. Taking into account the percentage of patients lost-to-follow-up, the sample size has been increased by 10% (N = 206 patients, 103 per arm). At the drafting of this abstract, 57 patients have already been enrolled (47 randomized). Clinical trial information: NCT03896074.
Phase 1/2 study of BLU-451, a central nervous system (CNS) penetrant, small molecule inhibitor of EGFR, in incurable advanced cancers with EGFR exon 20 insertion (ex20ins) mutations.
Authors: Spira Alexander I. , Yu Helena Alexandra , Sun Lova , Nguyen Danny , Pearson Paul , Shim-Lopez Jennifer , Hausman Diana Felice , Le Xiuning
Published: June 2022

TPS9155

Background: Oncogenic EGFR ex20ins mutations, found in ̃2% of non-small cell lung cancers (NSCLC) and a small percentage of other cancers, are generally not responsive to EGFR-targeted agents that have been approved for treatment of NSCLC with a common EGFR mutation, including L858R and exon 19 deletion. Similar to these more common types of EGFR-mutated NSCLC, CNS metastases are a challenge with EGFR ex20ins NSCLC and are associated with poor outcomes. While two EGFR ex20ins-targeting drugs were recently approved by the FDA (amivantamab and mobocertinib), neither have established CNS activity. BLU-451 is a CNS penetrant, wild type-sparing, covalent small molecule inhibitor of EGFR ex20ins as well as atypical (G719C, G719S, L861Q) and common EGFR mutants. Preclinical data have shown BLU-451 to have potent antitumor activity, including in an intracranial xenograft model, which has led to its clinical development in EGFR-mutant NSCLC. Methods: BLU-451-1101 (NCT05241873) is a phase 1/2, global, open-label study designed to evaluate single-agent BLU-451 in patients with NSCLC harboring EGFR ex20ins that has progressed following prior treatment for incurable recurrent or metastatic disease. Patients with Eastern Cooperative Oncology Group performance status 0–1 and EGFR ex20ins, exon 18 G719X or exon 21 L861Q mutant NSCLC (phases 1 and 2) or other cancers except primary CNS tumors (phase 1 only) are eligible. Patients with known ROS, RAF, ALK, or EGFR C797S mutations will be excluded. Stable, asymptomatic brain metastases are permitted, and active asymptomatic brain metastases are permitted in specific cohorts. Primary endpoints are determination of maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and tolerability (phase 1), in addition to evaluation of antitumor activity at the RP2D by RECIST v1.1 (phase 2). Secondary endpoints are evaluation of pharmacokinetics (PK) and antitumor activity by RECIST v1.1.(phase 1) and PK, safety, tolerability, and CNS antitumor activity (phase 2). Dose escalation will utilize a 3+3 design with up to 6 patients per cohort in phase 1 dose escalation and up to 12 per cohort in phase 1 dose expansion. Phase 2 will enroll patients in 3 cohorts (n = 18 each): patients with prior platinum-based chemotherapy and an EGFR ex20ins-targeted agent; patients with prior platinum but no EGFR ex20ins-targeted agent; and patients with active asymptomatic brain metastases with prior platinum with or without an EGFR ex20ins-targeted agent. The study is planned for approximately 40 centers in North America, the Asia-Pacific region, and/or Europe. Clinical trial information: NCT05241873.
Clinical Usefulness of the Growth Hormone–Releasing Peptide-2 Test for Hypothalamic-Pituitary Disorder
Authors: Suzuki Sawako , Ruike Yutarou , Ishiwata Kazuki , Naito Kumiko , Igarashi Katsushi , Ishida Akiko , Fujimoto Masanori , Koide Hisashi , Horiguchi Kentaro , Tatsuno Ichiro , Yokote Koutaro
Published: June 2022

Context

Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies, including secondary adrenal insufficiency (AI). A growth hormone–releasing peptide-2 (GHRP2) test, which is widely used for the diagnosis of patients with GHD, is thought to induce release of not only growth hormone (GH) but also ACTH. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear.

Objective

We aimed to determine the clinical utility of the GHRP2 test in patients with hypothalamic-pituitary disorders, particularly for AI concomitant with GHD.

Methods

The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests, and/or insulin tolerance tests (ITTs) were performed on 36 patients with hypothalamic-pituitary disorder.

Results

Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD, and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cutoff value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cutoff value (1.55-fold and 10 µg/dL, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI.

Conclusion

We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking or delaying diagnosis of secondary AI that frequently accompanies GHD.
Clinical Appropriateness of Telehealth: A Qualitative Study of Endocrinologists’ Perspectives
Authors: Sitter Kailyn E , Wong Denise H , Bolton Rendelle E , Vimalananda Varsha G
Published: June 2022

Background

Outpatient endocrinology care delivered by telehealth is likely to remain common after the pandemic. There are few data to guide endocrinologists’ judgments of clinical appropriateness (safety and effectiveness) for telehealth by synchronous video. We examined how, in the absence of guidelines, endocrinologists determine clinical appropriateness for telehealth, and we identified their strategies to navigate barriers to safe and effective use.

Methods

We conducted qualitative, semi-structuredinterviews with 26 purposively selected US endocrinologists. We used a directed content analysis to characterize participant perceptions of which patients and situations were clinically appropriate for telehealth and to identify adaptations they made to accommodate telehealth visits.

Results

Endocrinologists’ perspectives about appropriateness for telehealth were influenced by clinical considerations, nonclinical patient factors, and the type and timing of the visit. These factors were weighed differently across individual participants according to their risk tolerance, values related to the physical examination and patient relationships, and impressions of patient capabilities and preferences. Some participants made practice adaptations that increased their comfort offering telehealth to a wider swath of patients.

Conclusions

Endocrinologists’ judgments about clinical appropriateness of telehealth for different patient situations varied widely across participants. The risk of such divergent approaches to determining appropriateness is unintended and clinically unwarranted variation in use of telehealth, compromising quality of care. Expert consensus is needed to guide endocrinologists now, along with studies to anchor future evidence-based guidelines for determining clinical appropriateness of telehealth in endocrinology.
Near-infrared Autofluorescence Features of Parathyroid Carcinoma
Authors: Merrill Andrea L , Sims Sarah S , Dedhia Priya H , Rossfeld Kara , Lott Limbach Abberly , Duh Quan-Yang , Phay John E
Published: June 2022

Introduction

Parathyroid carcinoma is very rare, and intraoperative definitive diagnosis can be elusive with currently available diagnostics. Near-infrared (NIR) autofluorescence is an emerging tool that identifies parathyroid glands in real time. It is not known whether NIR autofluorescence can detect parathyroid carcinoma intraoperatively.

Methods

Patients with preoperative suspicion for parathyroid carcinoma were identified from ongoing studies examining parathyroid autofluorescence with a NIR camera and probe. Specimens from these patients were examined intraoperatively to determine their autofluorescence patterns.

Results

Three patients with suspected parathyroid carcinoma were identified preoperatively. Intraoperative NIR autofluorescence imaging showed a relative lack of autofluorescence for all cases, in contrast to parathyroid adenomas and normal parathyroid glands, which typically exhibit significant autofluorescence. Final pathology confirmed parathyroid carcinoma in all cases.

Conclusion

Parathyroid carcinoma can be difficult to confirm prior to final pathology review. Our 3 cases suggest that absence of NIR autofluorescence may suggest the likelihood of parathyroid carcinoma, but more studies are needed to investigate this experience.
TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection
Authors: Nguyen Lam Ngoc Thao , Nguyen Lam Nhat , Zhao Juan , Schank Madison , Dang Xindi , Cao Dechao , Khanal Sushant , Wu Xiao Y. , Zhang Yi , Zhang Jinyu , Ning Shunbin , Wang Ling , El Gazzar Mohamed , Moorman Jonathan P. , Yao Zhi Q.
Published: June 2022

We investigated the role of telomerase and telomere repeat-binding factor 2 (TRF2 or TERF2) in T-cell dysfunction in chronic viral infection. We found that the expression and activity of telomerase in CD4+ T (CD4T) cells from patients with hepatitis C virus (HCV) infections or people living with HIV (PLWH) were intact, but TRF2 expression was significantly inhibited at the post-transcriptional level, suggesting that TRF2 inhibition is responsible for the CD4T cell dysfunction observed during chronic viral infection. Silencing TRF2 expression in CD4T cells derived from healthy subjects induced telomeric DNA damage and CD4T cell dysfunction without affecting telomerase activity or translocation – similar to what we observed in CD4T cells from HCV patients and PLWH. These findings indicate that premature T-cell aging and dysfunction during chronic HCV or HIV infection are primarily caused by chronic immune stimulation and T-cell overactivation and/or proliferation that induce telomeric DNA damage due to TRF2 inhibition, rather than telomerase disruption. This study suggests that restoring TRF2 presents a novel approach to prevent telomeric DNA damage and premature T-cell aging, thus rejuvenating T-cell functions during chronic viral infection.
Nuclear F-actin and Lamin A antagonistically modulate nuclear shape
Authors: Mishra Sampada , Levy Daniel L.
Published: June 2022

Nuclear shape influences cell migration, gene expression and cell cycle progression, and is altered in disease states like laminopathies and cancer. What factors and forces determine nuclear shape? We find that nuclei assembled in Xenopus egg extracts in the presence of dynamic F-actin exhibit a striking bilobed nuclear morphology with distinct membrane compositions in the two lobes and accumulation of F-actin at the inner nuclear envelope. The addition of Lamin A (encoded by lmna), which is absent from Xenopus eggs, results in rounder nuclei, suggesting that opposing nuclear F-actin and Lamin A forces contribute to the regulation of nuclear shape. Nuclear F-actin also promotes altered nuclear shape in Lamin A-knockdown HeLa cells and, in both systems, abnormal nuclear shape is driven by formins and not Arp2/3 or myosin. Although the underlying mechanisms might differ in Xenopus and HeLa cells, we propose that nuclear F-actin filaments nucleated by formins impart outward forces that lead to altered nuclear morphology unless Lamin A is present. Targeting nuclear actin dynamics might represent a novel approach to rescuing disease-associated defects in nuclear shape.
A Note οn the Impacts of the 1810 Seismic Sequence on Crete
Authors: Stiros Stathis , Horsch Georgios
Published: June 2022

An intermediate depth earthquake sequence with an unusually strong aftershock hit Crete in 1810 and was felt in a very broad area.  This seismic sequence was believed to have caused a death toll of about 2000-3000 and destroyed a major part of houses in the wider Heraklion area.  In this article we present an unpublished note for this earthquake sequence from the memoirs of Frangiskos Limbritis, military and political personality in Crete, and analyze certain other notes from Crete and conclude that the death toll in Heraklion which was mainly affected was of the order of 300 and that structural damage was smaller than what believed in the past and was mostly rapidly repaired, especially in the meizoseismal area which roughly covers the present-day Heraklion prefecture (max intensities VIII-IX).
A posteriori error analysis and optimal control for phase field equations
Authors: Πλάκα Δήμητρα
Published: June 2022

Αρχικά, αποδεικνύονται εκ των υστέρων εκτιμήσεις σφάλματος για την εξίσωση Allen-Cahn, για σχήματα χαμηλής τάξης (implicit Euler) στον χρόνο σε συνδυασμό με σύμμορφα γραμμικά πεπερασμένα στοιχεία (conforming FEM) στο χώρο. Συγκεκριμένα, αποδεικνύονται εκ των υστέρων εκτιμήσεις στην φυσική ενεργειακή νόρμα που επάγει το συναρτησιακό Ginzburg-Landau, χρησιμοποιώντας κατάλληλη συνάρτηση δομικής. Εφαρμόζοντας τεχνικές ελλειπτικής ανακατασκευής σε συνδυασμό με επειχερήματα συνέχειας και ενεργειακά και την φασματική εκτίμηση του γραμικκοποιημένου τελεστή Allen-Cahn γύρω από την διακριτή λύση. Το κυρίως αποτέλεσμα οδηγεί επίσης σε εκτίμηση στην φυσική ενεργειακή νόρμα, ενώ η εκτίμηση σφάλματος απαιτεί να ικανοποιέιται μια συνθήκη εξάρτησης των παραμέτρων διακριτοποίησης ως προς την παράμετρο ‘ε’ , του πλάτους της διεπιφάνειας. Στη συνέχεια, αποδεικνύονται εκ των υστέρων εκτιμήσεις σφάλματος για τo αριθμητικό σχήμα που αποτελείται από την ασυνεχή μέθοδο Galerkin στον χρόνο και την ασυνεχή μέθοδο Galerkin εσωτερικής ποινικοποίησης στον χώρο. Η συνθήκη, που πρέπει να ικανοποιείται, παρουσιάζει εξίσου “καλή” ‘ε’-εξάρτηση σε σύγκριση την αντίστοιχη συνθήκη του απλούστερου πλήρως διακριτού σχήματος. Κεντρικό ρόλο στην απόδειξη των παραπάνω εκτίμησεων έχει η χρήση τεχνικών χωροχρονικής ανακατασκευής για προβλήματα ανώτερης τάξης. Το βασικό κίνητρο για τη μελέτη αυτής της μεθόδου είναι οι δυνατότητες που προσφέρει για ουσιαστική μείωση της υπολογιστικής πολυπλοκότητας κάνοντας χρήση λίγων αλλά "μεγάλων" στοιχείων γενικού σχήματος σε περιοχές-συγκέντρωσεις της λύσης (περιοχές διαφορετικής φάσης), ενώ χρησιμοποιούνται έντονα εκλεπτυσμένα στοιχεία στις περιοχές γύρω από την διεπιφάνεια για την επίλυση των στρωμάτων.Τέλος, μελέτηθηκε ένα σχετιζόμενο πρόβλημα βέλτιστου ελέγχου. Συγκεκριμένα, εξετάστηκε το πρόβλημα ελαχιστοποίησης κατάλληλου συναρτησιακού έλξης μέσω της χρήσης συνάρτησης ελέγχου τύπου κατανομής που ικανοποιεί χωρο-χρονικά σημειακά φράγματα. Μέρος της εργασίας είναι η μελέτη ύπαρξης ελαχίστου καθώς και των αναγκαίων και ικανών συνθηκών πρώτης και δεύτερης τάξης. Η κύρια συνεισφορά είναι η απόδειξη κατάλληλων εκτιμήσεων σφαλμάτων για τις μεταβλητές κατάστασης, δυϊκής, και ελέγχου, υπό τις περιορισμένες συνθήκες ομαλότητας.
Staphylococci and zoonotic potential : oral carriage and antibiotic susceptibility in stray dogs and cats in Algeria
Authors: Ait-Oudhia Khatima
Published: June 2022

This study aimed at identifying species of staphylococci isolated from the oral cavity of dogs and cats, in Algeria, and to determine their antibiotic susceptibility.Oral swabs were collected from 70 healthy animals (35dogs and 35cats) and were grown in Mannitol Salt Agar medium.Isolates were identified using API staph commercial kits and then confirmed with MALDI-TOF MS associated with SARAMIS software.Coagulase-positive staphylococci (CoPS) were tested for antibiotic susceptibility by disk diffusion method.On the 70 sampled animals, 59 were carriers of staphylococci in the oral cavity and more than one species was detected in 11 of them. Seventy (70) staphyloccoccal isolates were obtained belonging to 10 defferent species. Coagulase-negative staphylococci (CoNS) were most prevalent (81.42% ),of which the dominant species was S. xylosus (40%).Other coagulase-negative species,such as S, simulans (14.28%), S ,sciuri (11.42%) , S. saprophyticus (10%),S. capitis (2.85%),S, cohnii subsp cohnii (1.42%), and S, epidermidis (1.42%) were also isolated.The remaining n.13 CoPS included : S. intermedius (2.85%),S .pseudintermedius (8.57%) and S. intermedius group (SIG) (4.28%). No strain of S. aureus was found.Results of antimicrobial resistance showed that 61.53% of CoPS isolates were resistant to at least two drugs.The highest rate of resistance was observed against penicillin,ampicillin and tetracycline (53.84% for each drug),while amoxicillin-clavulanate was active on most isolates.In Algeria,Stray dogs and cats are carriers of many staphylococci species in the oral cavity, including multidrug resistant CoPS, which could be transmitted to humans through bites.
Effect of some medicinal herbs on natural humoral immunity in turkeys Running title: Effect of herbs on natural in turkeys
Authors: Sotirov Lilyan
Published: June 2022

Infectious diseases cause devastating economic losses in the poultry industry. It is important to boost factors of natural immunity to improve defense against infectious diseases in birds. The experimental groups (105 turkey poults allocated to 7 treatment groups) received basal diet plus 1% dry herbs or 0.01% essential oils supplements obtained from the herbs (Chamomilla; Rosemary; Lavender; Oregano; Thyme; St. John's Wort). Blood serum lysozyme concentrations, the alternative pathway of complement activation (APCA), and betalysin activities were determined. The highest blood lysozyme concentrations were determined among the control group and groups supplemented with dry herbs - rosemary, oregano, and thyme. АPCA activity was the highest in the thyme-supplemented group followed by the non-supplemented one. Betalysin activities were the highest in groups receiving lavender, thyme, and oregano, while the lowest levels were found out in chamomile-supplemented birds. In groups treated with essential oils (EO), blood serum lysozyme concentration was the highest in the group treated with rosemary EO, followed by the control group, while the lowest activity was established in birds that received EO from Saint John’s wort. The highest APCA activity was found in the lavender-treated group, and the lowest – in rosemary-treated turkeys. The highest betalysin activity was found among the groups treated with thyme, oregano, and Saint John’s wort, and the lowest activity was determined in the control group. It could be concluded that studied herbs possess an important immunomodulating potential in turkeys, which could improve their health and consequently, their productive performance.
Relationships between glucose-6-phosphate dehydrogenase, glutathione peroxidase, reduced nicotinamide adenine dinucleotide phosphate, total protein, malondialdehyde, total glutathione and vitamin C parameters in goat milk cells
Authors: Kazak Filiz , Karafakıoglu Yasemin , Başpınar Nuri , Peker Akalın Pınar
Published: June 2022

In this study, to reveal the antioxidant potential of goat milk cells, the activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GPx) and the levels of reduced nicotinamide adenine dinucleotide phosphate (NADPH), total glutathione (tGSH),malondialdehyde (MDA), vitamin C (Vit C) and total protein (TP) in goat milk cells were determined and correlations between these parameters were evaluated. Milk samples were collected from 19 clinically healthy goats from a private goat farm. Briefly, milk cells were collected from milk by centrifugation and than they were sonicated. Supernatant G6PD, GPx activities and NADPH, tGSH, MDA, Vit C and total protein levels were determined by spectrophotometric methods. As regards correlations: milk cell MDA levels were positively correlated with milk cell Vit C (r=0.488, P<0.05) and milk cell NADPH (r=0.589, P<0.05) levels. Milk cell TP levels were positively correlated with milk cell GPx activity (r=0.689,P<0.01). There was positive correlation between milk cell GPx activity and milk cell NADPH levels (r=0.497, P<0.05). Milk cell tGSH levels were positively correlated with milk cell Vit C (r=0.574, P<0.05) and milk cell NADPH (r=0.848, P<0.01) levels. Milk cell NADPH was positively correlated with milk cell G6PD activity (r=0.474, P<0.05). As a conclusion, antioxidant potential of goat milk cells were evaluated and discusses. Key Words: Goat milk cell, GPx, G6PD, NADPH, tGSH
Antibacterial activity of cinnamon oil against multidrug-resistant Salmonellaserotypes and anti-quorum sensing potential
Authors: Kiymaci Merve Eylul , Kaskatepe Banu , Soyer Yesim
Published: June 2022

The antimicrobial resistance due to Salmonella and other foodborne pathogenic microorganisms, witnessed in recent years, has become a significant health concern. Bacteria use chemical signals to communicate each other and regulate their behavior including virulence. Depending increased antibiotic resistance, new drug development strategies being investigating and the usability of active ingredients of various medicinal and aromatic plants is especially tested as an alternative. The aim of this study was to determine the anti-quorum sensing (QS) activity of cinnamon oil (CO) on pigment production of Chromobacterium violaceum and to evaluate antibacterial activity against multidrug resistant (MDR) S. enterica serotypes. Anti QS activity was tested using biosensor strain and antibacterial activity was determined by microdilution method according to EUCAST standards. CO was found effective on QS mechanisms of Chromobacterium violaceum with pigment inhibition. Nineteen foodborne pathogens isolated from different poultry/cow sourced foods and serotyped as S. enterica serovar Infantis (15), Kentucky (1), Newport (1), Telaviv (1), and Typhimurium (1). S. enterica Infantis strains were found resistant to three or more antibiotics and categorized as MDR. The results concluded that CO has strong antibacterial activity against all S. enterica serotypes with MIC between 0.125 µg ml-1 and 1.0 µg ml-1. This research demonstrates CO is a potential candidate for developing new antimicrobial agents, antiseptic solutions or natural food preservatives against MDR Salmonella isolates also a potential as an anti-QS agent.
The seroepidemiology of pestivirus infection in sheep in Afyonkarahisar province of Turkey and the analysis of associated risk factors
Authors: INCE Omer Baris
Published: June 2022

Border disease virus (BDV) is a pestivirus that causes considerable economic losses in the sheep industry due to its effect on breeding and health. This study's goal was to determine the seroprevalence of pestivirus infection, the ratio of persistently infected (PI) animals, and risk factors associated with the disease in sheep flocks between 2019-2020. To this end, 460 blood serum samples collected from eight sheep flocks were examined using commercial Enzyme-Linked Immuno-Sorbent Assay (ELISA) test kits to determine the presence of antibodies (Ab) and antigens (Ag) against pestiviruses (bovine viral diarrhea virus, border disease virus). Risk factors associated with pestivirus infection were statistically evaluated in terms of significance in the logistic regression model according to epidemiological data and information obtained from flock owners. Individual seropositivity was analyzed by Generalized Estimating Equations (GEEs) for associated responses. The overall apparent animal level seroprevalence was estimated to be 24.57% (95% CI: 20.85-28.7). The overall true seroprevalence was calculated to be 25.51% (95% CI: 21.65-29.60). The rate of positive sheep in each flock varied between 8.33-57.14%. The ratio of PI sheep among the 460 animals tested was found to be 0.43%. The relationship between the age groups was statistically significant (p-value:0.0002<0.05; χ2:13.15). Management type, age, the presence of cattle in the farm, landscape and the status of other clinical diseases were identified as important risk factors associated with individual pestivirus seropositivity. The results of this study indicate that it will contribute to the creation of national control eradication and monitoring plans and the development of strategies and that the potential risk of sheep as a pestivirus reservoir, especially for cattle that use common pastures, should be considered in future studies.
Comparing protein content of pollen and his impact on the lenght of life of honeybees
Authors: Radev Zheko
Published: June 2022

The objective of the research work was to compare the protein content of pollen from some plants visited frequently by honey bees in Bulgarian and Australian flora, and study the length of life of worker honey bees fed by pollen with different protein content. In this study the number of the same floral species, were described nine. Most number of favorite plants for honey bees are from Asteraceae – 5. The percentage of the total protein content in the compared bee-collected pollen grains ranged from: 11.5% for Chondrilla juncea to 25.1% for that of Brassica napus, and the average value was 18.5% for Bulgarian species, and 13.8% for Helianthus annuus to 25.9% for that of Trifolium repens, and the average value was 19.3% for Australian species. It is made a systematic comparison between Bulgarian and Australian protein content in pollen, but significant differences of the two groups were not found. Proteins are one of the the main components of honey bee-collected pollen, and can vary among different pollen plant species source. The very similar results in Bulgarian study compared to the published ones note the conservatism of pollen, despite the very long distance between Bulgaria and Australia, but having in mind if the Australian results come from inside country. It could be said that the honey bees in Bulgaria and Australia consume pollen with the same amount protein content from the same floral species. The length of live of worker bees ranged from 25 days when they consumed pollen from Brassica napus (25.1% protein content) to 14.3 days when they consumed pollen from Zea mays (17%). The present study was performed to make also a systematic comparison between length of life worker bees fed by pollen with different protein content and significant differences were found. The worker honey bees lived longer when they consumed pollen with higher protein content.
Clinical, Radiographic And Bronchoscopic Findings of Tracheal Collapse in A Calf
Authors: TÜMER Kenan Çağrı , POLAT Eren
Published: June 2022

A six-day-old calf was presented to the XXX University Veterinary Teaching Hospital with a history of wheezing (noisy respiration), dyspnea that worsens with exercise and drinking. The calf shown upper respiratory tract symptoms including extended head and neck, dilated nostrils, severe inspiratory stridor with characteristic “honking” sound, and exophthalmos. Upon these findings, we suspected upper airway obstruction and decided to perform cervical-thoracal radiography and bronchoscopy to obtain detailed visualization of the upper respiratory tract.  On the thorax radiograph, significant tracheal narrowing was visible at the thoracic inlet, and it was beginning at the caudal cervical region (C5) and extending to the cranial thorax (T1). Also, severe dorsoventrally narrowing was displayed approximately 15 cm after entering the trachea using bronchoscopy. The tracheal collapse was diagnosed in this case based on clinical, radiographical, and bronchoscopy findings. It is important to remember that tracheal collapse should be considered in the differential diagnosis in calves that show upper respiratory tract symptoms such as extended head and neck, dilated nostrils, severe inspiratory stridor with characteristic “honking” sound.
Microbiological characterization of fresh bee pollens from the Aegean region of Turkey
Authors: Altintas Levent , Sevin Sedat , Kahraman Hatice Ahu , Tutun Hidayet , Sababoglu Ezgi , Keyvan Erhan
Published: June 2022

ABSTRACT. The aim of this study is to characterize the microbiological safety of Turkish fresh bee pollen for the first time. Twenty-one fresh bee pollen samples were purchased from local beekeepers between September 2020 and October 2020 in Muğla, İzmir, Kütahya and Afyon provinces in the Aegean region of Turkey. The samples were analyzed for total aerobic bacteria, total coliform bacteria, total psychotropic microorganism, total lactic acid bacteria, Staphyloccus aureus, sulfite-reducing clostridia spores, yeast and mold. Total ochratoxin and aflatoxin levels were measured using lateral flow kit in samples contaminated with mycotoxigenic molds. The counts of the microorganisms ranged from 3.70 to 5.42 log CFU g-1 for the aerobic mesophilic, 3.0 to 5.40 log CFU g -1 for psychrotrophs, 3.85 to 5.78 log CFU g -1 for lactic acid bacteria (LAB), 3.0 to 5.45 log CFU g-1 for yeasts-molds, and <10 to 5.0 log CFU g-1 for total coliforms in the samples. Besides, S. aureus and sulfite reducing clostridia were not detected among the samples. The predominant mold genera in samples were Aspergillus sp. Penicillium sp. and Alternaria sp. Five samples contaminated with mycotoxicogenic molds had aflatoxins in the range of 2.96-9.71 µg/kg. According to the study results, comprehensive prevention, control and surveillance strategies need to be established to reduce bacteria and mycotoxin contaminations in fresh bee pollen. Legal regulation of bee pollen as food supplement and legal limit of mycotoxins in bee pollen should be defined.
Hemato-biochemical Profile of Ostriches (Struthio Camelus) based on Gender and Age of Birds
Authors: Umar Dr zaima , Qureshi Anas sarwar , Shahid Rehmatullah , Deeba Farah
Published: June 2022

The present study was conducted to determine the hematobiochemical analysis of ostrich (Struthio camelus) with respect to gender and progressive age. A total of 40 apparently healthy ostriches of both genders and two progressive age groups; young one (1 year to 2.4 years: group A); and adult (2.5 years to 5 years: group B) in equal number were used in this study. Blood samples were collected from the wing vein of the ostriches maintained in one of the ostrich farms near the Gogra in Pakistan. For hematobiochemistry analysis, the serum samples were obtained by centrifugation @ 500g for ten minutes) of collected blood samples and kept in 1ml aliquots. The hematobiochemical parameters included total protein, glucose, urea, uric acid, creatinine, aspartate amino transferase, alanine aminotransferase, gamma Glutamyl transferase, lactic dehydrogenase, alkaline phosphatase, cholesterol, triglycerides, sodium, potassium, calcium, phosphorus and magnesium. The results showed a significant age-related difference (P<0.05) in all serum biochemical values, however, the non-significant difference (P<0.05) were observed in males and females within the same age group. The mean values of cholesterol, HDL-C, uric acid and creatinine were non-significant (P>0.05) between two age groups from immature to adult age and between the genders of the same age group. The statistical analysis explained that sodium (Na) and potassium (K) values were significantly (P<0.05) increased in immature than the adult ostriches. Keeping in view these findings, we may conclude that this preliminary study embarked on establishing a set of reference values in serum biochemistry of ostrich in Pakistan.
Case Report: Acute myocardial infarction with acute left ventricular failure and acute renal damage following mRNA-1273 vaccination: Possible adverse effect of COVID-19 vaccination?
Authors: Hossain Mohammad Ali , Rashid Md. Utba , Barsha Sabrina Yesmin , Khan Md. Abdullah Saeed , Haque Miah Md. Akiful , Rahman Mohammad Lutfor , Hossian Mosharop , Bhuiyan AKM Mohiuddin , Nabi Mohammad Hayatun , Hawlader Mohammad Delwer Hossain
Published: June 2022

Background: Evaluating potential vaccine side effects is often a prerequisite to combat the coronavirus disease 2019 (COVID-19) pandemic more effectively in a low-resource setting where herd immunity could be the most feasible option.

Case report: Here, we present, an 80-year-old man with multiple comorbidities was admitted into the coronary care unit at Ibn Sina Medical College Hospital (Dhaka, Bangladesh) with severe central chest pain and respiratory distress after receiving the first dose of Moderna vaccine on July 26, 2021. On admission, his blood pressure was 110/70 mmHg, pulse 90 beats/min, respiratory rate 22 breaths/min, temperature 36.7°C. He had a vesicular breath sound with bilateral basal crepitations and normal heart sounds. On the ECG, significant changes were observed. Other lab findings were significant troponin-I: 1.72 ng/ml, trace protein and glucose in the urine, total white blood cell count: 12820/cm3; HbA1c, 7.5%; serum creatinine, 1.56 mg/dl; serum electrolytes: sodium 133 mmol/L, chloride 92 mmol/L. The patient had a medical history of prior myocardial infarction, diabetes mellitus, and hypertension but no chronic kidney disease, cerebrovascular disease, or bronchial asthma. After admission, he was treated conservatively with necessary medications and monitored periodically. The patient was diagnosed with acute myocardial infarction with left ventricular failure with acute kidney injury on chronic kidney disease with diabetes mellitus and hypertension. He was discharged from the hospital on day six with proper medicinal support with full recovery.

Conclusions: Though acute cardiac complications following COVID-19 vaccines are unusual, this case report can contribute to further molecular research to identify the possible role of vaccine compounds in triggering such complications among the general population.
Uzupełniające źródła finansowania instytucji kultury – działalność gospodarcza (usługi, handel, gospodarowanie mieniem), lokowanie wolnych środków oraz sponsoring
Authors: Kołaczkowski Bartosz , Ratajczak Małgorzata
Published: June 2022

Przedmiotem opracowania jest problematyka uzupełniających wobec dotacji źródeł finansowania instytucji kultury, za które autorzy uznali działalność gospodarczą (usługi, handel, gospodarowanie mieniem), lokowanie wolnych środków oraz sponsoring. Rozważania zawarte w poszczególnych jego częściach mają na celu udzielenie odpowiedzi na pytania: czy środki te stanowić mogą istotne źródło finansowania instytucji kultury? Czy regulacja prawna ich dotycząca jest na tyle przejrzysta, by efektywne korzystanie z nich było niekłopotliwe dla osób zarządzających tymi instytucjami? Czy mogą one zrównoważyć skutki finansowe pandemii, a może nawet zastąpić podstawowe źródła finansowania kultury, jakim są dotacje? Autorzy wykazują, że wspomniane wyżej uzupełniające źródła finansowania instytucji kultury mogą wprawdzie stanowić istotne źródła finansowania działalności kulturalnej, jednak absolutnie nie zwalnia to państwa i samorządów terytorialnych z obowiązku dbałości o rozwój polskiej kultury, ponadto środki te w większości przypadków nie zrównoważą negatywnych skutków finansowych pandemii. W dodatku regulacja prawna ich dotycząca jest rozproszona i nadmiernie nieraz skomplikowana.
Efektywność ekonomiczna i jakość przedmiotu zamówienia publicznego
Authors: Taraszkiewicz Magdalena
Published: June 2022

Efektywność ekonomiczna oraz jakość przedmiotu zamówienia to dwie nowe zasady wprowadzone przez ustawodawcę do ustawy z dnia 11 września 2019 r. Prawo zamówień publicznych. W ich myśl obowiązkiem zamawiającego jest nie tylko dbanie o oszczędne wydatkowanie środków publicznych, lecz także poszukiwanie takiej oferty, która przedstawia najlepszy stosunek jakości przedmiotu zamówienia do posiadanych przez zamawiającego środków finansowych. Nie oznacza to jednak najwyżej jakości, lecz jakości proporcjonalnej do posiadanych środków finansowych. Efektywność i jakość muszą współgrać ze sobą, aby zapewnić prawidłową realizację przedmiotu zamówienia. Toteż ważne jest zdefiniowane tych pojęć.
Samuel Bogumił Linde Toruniowi
Authors: Ptaszyk Marian
Published: June 2022

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Organizacja urzędu rejonowego na przykładzie urzędów rejonowych w Toruniu i Grudziądzu
Authors: Ciechanowski Hadrian
Published: June 2022

W artykule przedstawiona została organizacja wewnętrzna urzędów rejonowych działających w latach 1990-1998. Problem przedstawiony został na przykładzie urzędów rejonowych w Toruniu i Grudziądzu. Na podstawie przeprowadzonej analizy wyróżnione zostały dwa okresy w organizacji tych urzędów: lata 1990-1992 oraz 1993-1998. W pierwszym okresie ich struktura była pionowa, a urzędy posiadały liczną kadrę. W drugim okresie nastąpiły natomiast spłaszczenie struktur organizacyjnych oraz wyraźny spadek liczby zatrudnionych. Badania oparte zostały na aktach prawnych oraz materiałach archiwalnych.
Face pattern recognition using Expectation-Maximization (EM) algorithm
Authors: Purwadi Joko , Hernadi Julan , Suryantoro M. Danang
Published: June 2022

This paper discuss about the use face patteren recognition which is now days become popular especialy on smartphone lock screen system. The method used in this research are the Expectation – Maximization (EM) Algorithm. EM Algorithm is an iterative optimization method for the estimation of Maximum Likelihood (ML) which is used in incomplete data problems.  there are 2 stages, namely the Expectation stage E (E-step) and the Maximization stage M (M-step).  These two stages will continue to be carried out until they reach a convergent value. The result of the research shows that EM Algorthm produce high accuracy, it’s about 95% on the data training and 83% accuracy on the data testing.
Effectiveness of Microsoft Kaizala and Google Classroom towards students’ mathematical communication skill and self-efficacy in learning statistics
Authors: Andriyani Andriyani , Santosa Achadi Budi , Saryadi Wahyu
Published: June 2022

This study aims to describe the effectiveness and differences in the effectiveness of the learning platform with Google Classroom and Microsoft Kaizala in terms of self-efficacy and students' mathematical communication skills. The population of this research is the XII grade students of SMK Negeri 1 Giritronto Wonogiri which consists of sevent classes. From the existing population, two classes were taken randomly, namely twelfth grade of TKJ-I and twelfth grade of TKJ-II as research samples. Twelfth grade of TKJ-I was given treatment by learning using the Microsoft Kaizala platform, while twelfth grade of TKJ-II was given treatment using the Google Classroom platform. The research data were analyzed by statistical one sample t-test, MANOVA test with Hotelling's T2 at a significant level of 0.05 and univariate test to determine which platform is more effective. The results showed that: (1) statistical learning using the Microsoft Kaizala platform was effective in terms of mathematical communication and self-efficacy, while the Google Classroom platform was effective in terms of mathematical communication but not effective in terms of self-efficacy; (2) there is a difference in effectiveness between the Microsoft Kaizala platform and Google Classroom. The Microsot Kaizala platform is more effective than Google Classroom in terms of the mathematical communication skills of class twelfth grade students of SMK Negeri 1 Giritronto Wonogiri.