Preliminary Report Research Articles

Abstract 15351: Characteristics of Veterans Enrolled in a Nationwide Home Telemonitoring Blood Pressure (BP) Program

Background: Guidelines recommend home BP monitoring for the diagnosis and management of hypertension. The Veterans Affairs (VA) has a robust nationwide home BP monitoring telehealth (HT) program. Aims: We aimed to determine factors associated with being enrolled in the VA’s HT program using a nationwide cohort. Methods: Veterans with hypertension and a primary care (PC) visit between 4/2013 and 9/2015 were identified and classified as telehealth if they enrolled in the HT program and were issued a home-telehealth BP monitor. Control patients were not enrolled. Patient characteristics including the care assessment needs (CAN) score (validated probability for mortality or hospitalization in the following year) were extracted from the electronic health record (EHR). Results: Over 33 months, 29,927 (2.5%) veterans were enrolled in the HT program and 1,160,506 (97.5%) veterans with hypertension were not enrolled. Compared to controls, HT patients were of similar age (median 66 years), were more likely to be female (5.6% vs 4.6%), be of Black race (28.7% vs 20.1%), have a higher index median systolic BP (158.4 vs 153 mmHg), have a greater number of PC visits in the 2 years prior (11 vs 7 visits), have a higher median probability of a mortality or hospitalization event within 1 year (13% vs 7%) and were on a greater number of antihypertensive medications than those not enrolled (Table). These veterans were seen by 9,301 PC providers, who enrolled the following percentages of their hypertensive patients (% of patients by % of providers): 0% by 22%, <2% by 24.1%, 2-5% by 28.9%, 5-10% by 16.4%, 10-20% by 6.9% and >20% by 1.7%. Conclusion: The VA’s HT program is used by a limited number of Veterans. Those enrolled are sicker and have a greater burden of hypertension than those not enrolled. Most providers have a small percentage of their panel of patients enrolled. This preliminary report comes from a study evaluating the effect of HT on BP control, cardiovascular events, and non-cancer mortality.

416 Urgency to Address Infrastructure in Animal sciences–A Preliminary Report

Abstract The purpose of the ASAS Public Policy Committee (PPC) is to help ASAS shape public policy and public opinion on current issues affecting farms and companion animals. PPC sets goals to make federal agencies aware of the scientific expertise and resources available within ASAS that could be used to develop science-based federal policies affecting poultry and livestock production. Recent reports point to a poor state of agricultural facilities at public colleges of agriculture which puts research priorities related to adaptation to and mitigation of climate change, food safety, zoonotic disease preparedness, animal populations and their care, diet-health, nutrition, biosecurity, new biobased packaging, energy innovations, and advanced market analysis at risk (APLU, 2021). To ascertain input specific to the Animal Sciences (AS), an IRB approved ‘Survey About Infrastructure in Animal Sciences’ (#22-495) was offered by the PPC to department heads and faculty of Animal Science programs across the country. The survey instrument was constructed to allow open-ended responses as well as 5-point Likert scale questions regarding participants views about infrastructure (IF) and thereby learn what members closest to the animal sciences community perceive to be the strengths, weaknesses, and opportunities for improvement in our research infrastructure. Analysis of coded responses in the open-ended questions among varied disciplinary arenas within AS revealed ‘facilities’ as the largest Grand Challenge. About 98% of respondents affirmed sustainable food and animal production is a critical national asset in terms of economic growth and development and 98% indicated an overlooked maintenance of IF in AS undermines national food security. Additionally, 68% indicated the state of core labs, at least for AS programs are only average or below. All respondents (100%) agreed that without comprehensive investment in infrastructure within AS, the USA will continue to fall behind in competing with other countries in areas of research. Study results provided insight into potential consequences of deferred maintenance which should elevate awareness of urgency to address the deficiencies. Since IF needs included future workforce development and working environments, an eroded IF and consequences of deferred maintenance threatens the capacity of AS to pursue Grand Challenges in research and ability to create future workforce readiness of graduates from AS programs.

Phenotypic similarity-based approach for variant prioritization for unsolved rare disease: a preliminary methodological report

Rare diseases (RD) have a prevalence of not more than 1/2000 persons in the European population, and are characterised by the difficulty experienced in obtaining a correct and timely diagnosis. According to Orphanet, 72.5% of RD have a genetic origin although 35% of them do not yet have an identified causative gene. A significant proportion of patients suspected to have a genetic RD receive an inconclusive exome/genome sequencing. Working towards the International Rare Diseases Research Consortium (IRDiRC)’s goal for 2027 to ensure that all people living with a RD receive a diagnosis within one year of coming to medical attention, the Solve-RD project aims to identify the molecular causes underlying undiagnosed RD. As part of this strategy, we developed a phenotypic similarity-based variant prioritization methodology comparing submitted cases with other submitted cases and with known RD in Orphanet. Three complementary approaches based on phenotypic similarity calculations using the Human Phenotype Ontology (HPO), the Orphanet Rare Diseases Ontology (ORDO) and the HPO-ORDO Ontological Module (HOOM) were developed; genomic data reanalysis was performed by the RD-Connect Genome-Phenome Analysis Platform (GPAP). The methodology was tested in 4 exemplary cases discussed with experts from European Reference Networks. Variants of interest (pathogenic or likely pathogenic) were detected in 8.8% of the 725 cases clustered by similarity calculations. Diagnostic hypotheses were validated in 42.1% of them and needed further exploration in another 10.9%. Based on the promising results, we are devising an automated standardized phenotypic-based re-analysis pipeline to be applied to the entire unsolved cases cohort.

New records of the white-cheeked macaque provide range extension for the endangered primate in Gaoligong Mountains.

White-cheeked macaque Macaca leucogenys is a recently described primate species discovered by camera-trap surveys in the Medog region in 2015. The species was thought to be narrowly distributed in southeastern Tibet. However, knowledge on the distribution and conservation of the species is quite limited. Based on a systematic camera-trapping survey, we report the occurrence of the species in the Gaoligong Mountains, over 350km southeast of the nearest known population. We recorded 3025 photographs of white-cheeked macaques representing 481 independent records from 59 camera-trap stations with total trapping efforts of 18,437 camera days. Notably, part of the newly discovered locations of the white-cheeked macaque are outside of nature reserves without any formal protection and management. Our survey also confirms the occurrence of ten primate species in the Gaoligong Mountains, accounting for 35.7% of China's primates, including the Skywalker hoolock gibbon Hoolock tianxing and the Myanmar snub-nosed monkey Rhinopithecus strykeri etc. These findings reveal a new distribution record for the white-cheeked macaque and further highlight the conservation values of Gaoligong Mountains for globally threatened primate species. We also provide a preliminary report on the daily activity patterns of this endangered species, which enriches the bio-ecological data of the poorly studied species. We believe the report has significant implications for understanding the ecology of the species and improving conservation planning.

Examining the neurodevelopmental and motor phenotypes of Bohring-Opitz syndrome (ASXL1) and Bainbridge-Ropers syndrome (ASXL3).

Chromatin Modifying Disorders (CMD) have emerged as one of the most rapidly expanding genetic disorders associated with autism spectrum disorders (ASD). Motor impairments are also prevalent in CMD and may play a role in the neurodevelopmental phenotype. Evidence indicates that neurodevelopmental outcomes in CMD may be treatable postnatally; thus deep phenotyping of these conditions can improve clinical screening while improving the development of treatment targets for pharmacology and for clinical trials. Here, we present developmental phenotyping data on individuals with Bohring-Optiz Syndrome (BOS - ASXL1) and Bainbridge-Ropers Syndrome (BRS - ASXL3) related disorders, two CMDs highly penetrant for motor and developmental delays. To phenotype the motor and neurodevelopmental profile of individuals with ASXL1 and ASXL3 related disorders (BOS and BRS). To provide a preliminary report on the association of motor impairments and ASD. Neurodevelopmental and motor phenotyping was conducted on eight individuals with pathogenic ASXL1 variants and seven individuals with pathogenic ASXL3 variants, including medical and developmental background intake, movement and development questionnaires, neurological examination, and quantitative gait analysis. Average age of first developmental concerns was 4 months for individuals with BOS and 9 months in BRS. 100% of individuals who underwent the development questionnaire met a diagnosis of developmental coordination disorder. 71% of children with BOS and 0% of children with BRS noted movement difficulty greatly affected classroom learning. Participants with BRS and presumed diagnoses of ASD were reported to have more severe motor impairments in recreational activities compared to those without ASD. This was not the case for the individuals with BOS. Motor impairments are prevalent and pervasive across the ASXL disorders with and without ASD, and these impairments negatively impact engagement in school-based activities. Unique neurodevelopmental and motor findings in our data include a mixed presentation of hypo and hypertonia in individuals with BOS across a lifespan. Individuals with BRS exhibited hypotonia and greater variability in motor skills. This deep phenotyping can aid in appropriate clinical diagnosis, referral to interventions, and serve as meaningful treatment targets in clinical trials.

The Palamas Archaeological Project. A preliminary report of the 2022 fieldwork conducted by the ongoing Greek–Swedish archaeological field programme in Palamas, region of Karditsa, Thessaly

This paper presents the preliminary results from the 2022 fieldwork of the Palamas Archaeological Project, an ongoing Greek–Swedish collaboration in the region of Karditsa, Thessaly. Working over the course of two separate field seasons, the project team conducted aerial, architectural, fieldwalking, and geophysical surveys at a number of sites within the survey area, including at the important multi-phase fortified settlements at Metamorfosi and Vlochos. Limited excavations were also conducted at the latter site, producing new evidence for the Hellenistic and Early Byzantine phases of the ancient city, including a probable cemetery. The work continues to add to the knowledge of the archaeology of the region, highlighting the long and dynamic history of human habitation in western Thessaly.

Combination Treatment with Sonrotoclax (BGB-11417), a Second-Generation BCL2 Inhibitor, and Zanubrutinib, a Bruton Tyrosine Kinase (BTK) Inhibitor, Is Well Tolerated and Achieves Deep Responses in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (TN-CLL/SLL): Data from an Ongoing Phase 1/2 Study

Background: The combination of BCL2 and BTK inhibitors has shown synergistic activity. The combination of venetoclax, a BCL2 inhibitor, and ibrutinib, a BTK inhibitor, is an effective treatment for CLL/SLL. Sonrotoclax (BGB-11417) is a BH3 mimetic that binds and inhibits BCL2 with potency >10x that of venetoclax in biochemical assays. Zanubrutinib, a next-generation BTK inhibitor, has shown improved PFS with fewer cardiac adverse events (AEs) vs ibrutinib in a randomized study of patients with CLL/SLL (Brown et al. N Engl J Med. 2023). BGB-11417-101 (NCT04277637) is an ongoing, first-in-human, phase 1/1b dose-escalation/expansion study of patients with various B-cell malignancies. In a preliminary report, sonrotoclax, alone or in combination with zanubrutinib, was well tolerated at all doses tested up to 640 mg. This abstract describes the safety and efficacy data from patients with treatment-naïve (TN) CLL/SLL who received the combination of sonrotoclax and zanubrutinib. Methods:Patients received zanubrutinib (320 mg QD or 160 mg BID) 8-12 weeks before starting sonrotoclax using a ramp-up schedule starting from 1 mg to the intended target dosage of 160 mg or 320 mg QD (doubling weekly [W] or 30% increase every day 5 d/week [D]) to mitigate risk of tumor lysis syndrome (TLS). Patients were treated until progression, unacceptable toxicity, or could elect to stop. TLS was assessed per Howard (2011) criteria; mitigation included mandatory oral hydration and antihyperuricemics. Primary endpoint was safety (reported per CTCAEs v5.0); a secondary endpoint was ORR (per iwCLL 2008 criteria) and minimal residual disease assessed in blood by ERIC flow every 24 weeks (uMRD4; <1 CLL cell per 10,000 leukocytes, or <0.01%) was an exploratory endpoint. Results: As of May 21, 2023, 94 patients with TN-CLL/SLL were enrolled (sonrotoclax 160 mg QD, n=41 [26 W, 15 D] and 320 mg QD, n=53 [25 W, 28 D]); 15 patients were still receiving zanubrutinib monotherapy and 79 started sonrotoclax (160 mg, n=32 [25 W, 7 D] and 320 mg, n=47 [24 W, 23 D]). Median follow-up was 8.5 mo (range: 0.6-18.2) for all patients; 160 mg, 12.1 mo (range: 0.6-18.2); 320 mg, 7.0 mo (range: 1.1-14.6). No deaths have occurred, and all patients remain on study. Treatment-emergent AEs (TEAEs) occurring in ≥20% patients who received sonrotoclax plus zanubrutinib (n=79) are listed in theTable; TEAE frequencies were similar between the two sonrotoclax cohorts. Contusion, neutropenia, and low-grade gastrointestinal toxicity were the most common TEAEs; neutropenia was the most common grade ≥3 TEAE (n=13 [17%]). No cases of clinical or laboratory TLS occurred in either ramp-up schedule; no patient experienced atrial fibrillation. One TEAE (cryptococcal meningitis at 11 weeks treated with azoles) led to treatment discontinuation. Sonrotoclax dose holds occurred in 17 patients (22%) for a median duration of 11 days (range: 3-37) and three patients (4%) had dose reduction. The most common TEAEs resulting in dose holds were COVID-19 (n=9 [11%]) and diarrhea (n=3 [4%]). A total of 56 patients had a response assessment. The ORR was 100% (CR: 160 mg, n=9 [36%]; 320 mg, n=6 [19%]). Across all doses, rate of CR increased with time; overall median time to CR was 10.1 mo (range: 5.4, 17.1). No progression was reported in either cohort (Figure). Week 24 blood uMRD4 rates were 50% (n=12/24) in 160 mg and 65% (n=13/20) in 320 mg patients. Week 48 blood uMRD4 rates were 73% in 160 mg (n=11/15) and 100% (n=1/1) in 320 mg; no patient has lost uMRD4. Conclusion: Sonrotoclax (160 mg and 320 mg) in combination with zanubrutinib was well tolerated in patients with TN CLL/SLL. Only one patient discontinued treatment and three patients had dosage reductions. No TLS was seen with either ramp-up schedule. Acknowledging the short follow up, efficacy is encouraging with 100% ORR in assessed patients and no PFS events. High rates of blood uMRD4 occurred early. Based on these data, a phase 3 study assessing this combination is planned.

Venetoclax in Combination with Pediatric-Inspired Chemotherapy in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia: Results of a Phase I Trial

Introduction: Young adults with acute lymphoblastic leukemia (ALL) have favorable outcomes compared with historical standards when treated with an asparaginase-containing pediatric regimen (Stock et al., Blood 2019). We have demonstrated the safety and efficacy of pediatric inspired chemotherapy (PIC) for adults up to age 60 (MSK protocol 12-266, Geyer et al., Haematologica 2021). However, cure rates for adults with ALL remain below 60%, prompting the need for novel agents. Venetoclax (ven) is a BCL2 inhibitor being tested in several clinical trials for ALL. Here, we present the first report of ven used in combination with a multiagent, asparaginase-containing chemotherapy regimen for the upfront treatment of ALL. Methods: We conducted a Phase I, single-center, single-arm clinical trial (NCT05386576) to evaluate the safety and efficacy of ven in combination with PIC in adults with newly diagnosed ALL. Adults aged ≤60 years diagnosed with Philadelphia chromosome negative ALL were eligible for the study. The primary objective was to evaluate the safety of ven in combination with asparaginase-based PIC and identify the maximum tolerated dose and recommended phase II dose. The secondary objectives were to assess the rate of complete remission (CR) and measurable residual disease (MRD) negative CR at day 15 and 28 of Induction I, and end of Induction II. The regimen consisted of 6 treatment phases as previously published (12-266). Ven was administered at a final dose of 400mg (with a rapid dose escalation from 100mg over 3 days) during Induction I (days 5-7 dose escalation, days 7-28 full dose), Induction II (days 1-14 and 29-42), Intensification I & II (days 1-22), and Re-Induction I & II (days 1-14 and 29-42). Measurable residual disease (MRD) was assessed by multiparameter flow cytometry with 10 -4 sensitivity. We used historical data from 22 patients (pts) treated on our previous study, who received the same chemotherapy backbone without ven, as a comparator. Median follow up was calculated using the reverse Kaplan Meier indicator. Duration of treatment was compared using the Wilcoxon rank-sum test. Proportions of pts who achieved MRD-CR were compared with the chi squared test. Results: At the time of analysis, 8 pts had enrolled in the study; all 8 pts completed induction I and 6 (75%) pts had completed induction II (Table 1). Median follow up was 171 days. The median age was 38.5 years (min 25, max 60). 50% of pts had B-cell ALL, and 50% T-cell (including 1 patient with early T-cell progenitor). One patient (12.5%) had CNS disease (CNS 3) at diagnosis. Four (50%) pts had intermediate risk cytogenetics by CALGB 19802 classification (Stock et al., Cancer 2013), 2 (25%) had unfavorable, and 1 (12.5%) favorable. Two (40% of B-ALL) had a Philadelphia-like phenotype. During Induction I & II, 4 (50%) pts experienced febrile neutropenia, 6 (75%) grade 4 thrombocytopenia, and all 8 (100%) grade 4 neutropenia. No dose limiting toxicities, as defined per protocol, were observed. The average duration of Induction I on study was 46.6 days compared to 43.6 on 12-266 (p = 0.11). The average duration of Induction II on study for pts who had completed it at the time of analysis was 102 days compared to 74 days on 12-266 (p = 0.02), primarily due to cytopenias. Three (37.5%) of pts achieved an MRD negative CR by the end of Induction I. Of the 6 pts who had completed Induction II by time of analysis, 5 (83%) had achieved an MRD- CR, compared to 81% on 12-266 (p = 0.90) and 1 patient had refractory extramedullary disease. We assessed kinetics and depth of response by plotting the average blast percentage in the bone marrow by flow cytometry across three different timepoints. Pts on the study had numerically lower blast percentages at day 15, end of Induction I and end of Induction II compared to 12-266 (Figure 1). At the time of this analysis, no patient who entered CR had experienced disease relapse. Conclusions: Ven addition to a PIC backbone was overall safe with high MRD negative remission rates in this preliminary report. Compared to historical controls, pts treated with ven had a longer duration of Induction II primarily due to cytopenias, and we are amending the study to shorten ven duration during induction II. Pts treated with ven had a numerically faster reduction in bone marrow blasts compared to historical controls. Longer follow up in a larger patient population in this ongoing study will be required to assess long term toxicity and efficacy of this regimen.

Phase I Trial of Allogeneic Donor Gamma Delta T Cell Infusion Post-Hematopoietic Cell Transplantation, an Interim Safety Report

Background Patients with 2017 European LeukemiaNet (ELN) adverse risk acute myeloid leukemia (AML) are at 40% risk of relapse leading to poor survival after allogeneic hematopoietic cell transplantation (allo-HCT) (Hansen TCT 2021, Jimenez BMT 2021). Ex vivo donor-derived gamma delta T cells (GDT) expanded with artificial antigen presented calls (aAPC) are a novel therapy with potent MHC-independent antineoplastic cytotoxicity. An ongoing phase 1/1b study is evaluating the safety and potential efficacy of ex vivo expanded donor GDT after reduced-intensity conditioning (RIC) allo-HCT in patients with ELN adverse risk AML ( NCT05015426). We report on manufacturing, safety, and correlative biology of expanded donor GDT after allo-HCT in the first 5 treated patients (Table 1). Methods The primary endpoint is the maximum-tolerated dose (MTD) of allogeneic donor GDT as a single infusion at day 60 after RIC allo-HCT. Next generation sequencing was used for measurable residual disease (MRD) assessment pre-HCT and post-GDT infusion. Donor GDT collected from the same donor of the allo-HCT were enriched from non-mobilized leukapheresis product by stimulation with zoledronic acid and IL-2 for 7 days followed by alpha beta T cell depletion using the Miltenyi CliniMACS. Enriched GDT (>90% TCRVδ2) were then co-cultured with irradiated aAPCs in Wilson Wolf G-Rex 100MCS over 10 days (Boucher J. Immunother 2023). This single center, investigator-initiated phase 1 trial is testing 3 distinct dose cohorts of infused GDT (5 x 10 6 cells/kg, 2.5 x 10 7 cells/kg, and 1 x 10 8 cells/kg) with acceptable range of 25% margin. A Bayesian optimal interval design is used to guide dose escalation/de-escalation decisions. Results First 3 patients enrolled in dose level 1 (DL1) cohort received GDT dose of 6.25 x 10 6 cells/kg, while last 2 patients enrolled in DL2 cohort received 3.13 x 10 7 cells/kg dose. Dose-limiting toxicities (DLT) were evaluated for 42 days following GDT infusion and no DLT were observed. None of the treated patients experienced cytokine release syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or graft-versus-host disease (GVHD) during DLT period. Among patients treated on DL1, patient #01 had ASXL1 AML with MRD pos (VAF 43.9%) prior to RIC haploidentical (Haplo) HCT. He is in ongoing complete remission (CR) 9 months post-HCT and has had no GVHD. Patient #02 had MRD pos (VAF 61.7%) AML with TP53 mutation/complex karyotype prior to RIC matched sibling donor allo-HCT. He is in CR and has mild chronic GVHD at 7 months post-HCT. Patient #03 with pre-HCT MRD negRUNX1 AML is in ongoing CR 7 months post-RIC Haplo HCT with no GVHD. At day 28 and day 120 post-GDT, all 3 patients were MRD neg in bone marrow and had 100% bone marrow and peripheral blood leukocyte and granulocyte chimerism. In DL2 cohort, patient #04 with RUNX1 AML and patient #05 with t(9;22) AML both were MRD neg prior to RIC Haplo HCT and remain in CR with no GVHD at 5 and 4 months post-HCT, respectively. At day 28 post-GDT, both patients were MRD neg and had 100% chimerism. Patient #05 had a fall during DLT period in a setting of orthostatic hypotension requiring hospitalization for 24 hours for hydration. This was the only grade 3 adverse event observed in this trial. Serum cytokines analyzed included IL2, IL6, IL15, IFNγ, TNFα, Angiopoietin 1&2, and GM-CSF (Figure 1). We compared results prior and up to 90 days post-GDT infusion and found no significant differences, which can explain no CRS or ICANS events yet observed on this trial. Immunophenotype (TCRVδ2, TCRVδ1, PD1, CTLA4, TIGIT and CD28) of GDT was analyzed in samples of donor apheresis, pre- and post-enrichment, infused GDT product and at days 28 and 90 post-infusion. GDT (TCRVδ2) persisted at day 28 and day 90 post-infusion and expressed low levels of cell surface inhibitory receptors. Conclusion This preliminary interim report demonstrates favorable safety and tolerability of donor GDT therapy with no CRS, ICANS or GVHD in first 5 patients treated in this trial. All these patients with adverse risk AML are in ongoing MRD neg CR following RIC allo-HCT, including 2 pre-HCT MRD pos cases with TP53 AML and AXSL1 AML. Early results of this trial are promising, which provides validation for continued testing of adoptive transfer of ex vivo expanded donor GDT. Updated results of this trial will be presented at the annual conference.

MO72-6 Health-related quality of life in different states of Thai patients with breast cancer – preliminary report

MO72-6 Health-related quality of life in different states of Thai patients with breast cancer – preliminary report

Defense style and psychopathology in oncological patients: a preliminary report.

Previous studies shows that 30-40% of oncological and hematological patients report symptoms of distress compatible with a psychiatric disorder. The use of various and mostly unconscious defense mechanisms is implemented to cope with increased suffering after a cancer diagnosis. In this preliminary report, we explored the presence of defense mechanisms and their associations with psychopathological dimensions in a sample of late-stage cancer patients without history of psychiatric disorders. We recruited 50 patients (28 females, 18-64 years old) with cancer diagnosis without prior history of any substance use disorder or psychiatric disorders. All participants were given the following self-report questionnaires: the Symptom Checklist 90 (SCL-90) and the 40-item version of the Defense Style Questionnaire (DSQ-40). In our study we demonstrated significant psychiatric distress in a third of our patients (defined as SCL-90 ≥2 points). A Pearson correlation analysis on all patients shows that psychotic defense styles were correlated with hostility, obsessive-compulsive, anxiety, somatization, interpersonal sensitivity, and psychoticism, while neurotic defense styles correlated with somatization. Our results are in line with previous findings showing that one third of cancer patients suffers from a psychiatric disorder. Moreover, we found that somatization correlates with both psychotic and neurotic defense mechanism styles. This demonstrates the importance of assessing oncological patients coping mechanisms to achieve best possible treatment.

Preliminary report on Permian radiolarians from the Numakuma peninsula in Japan: Paleontological evidence for the presence of the Ultra-Tamba Belt

Preliminary report on Permian radiolarians from the Numakuma peninsula in Japan: Paleontological evidence for the presence of the Ultra-Tamba Belt

Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report.

Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (-57.7% vs -42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.

Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.

Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.

Introduction and preliminary application report for a novel 3D printed perforator navigator for fibular flap surgery

The aim of this study was to introduce and report on a 3D-printed perforator navigator and its clinical application.Integrated imaging and 3D printing techniques were employed for the design and manufacture of a perforator navigator. Key techniques included establishing a digital image coordinate system, localizing perforator fascia piercing points, creating a reference plane for the perforator course, and projecting the perforator course onto the body surface.All cases of maxillofacial defect repaired with free fibular myocutaneous flaps, from January 2019 to January 2022, were reinvestigated. Patients treated using traditional perforator localization methods were assigned into group Ⅰ, while those who had a navigator used during treatment were allocated to group Ⅱ. Outcome measurements included perforator positioning accuracy, perforator preparation time (PT), and flap growth score. Capillary refilling time and degree of flap swelling were recorded on the 1st, 3rd, and 7th days after surgery. On the 10th day after surgery, the flap survival situation was graded.In total, 25 patients were included in the study. Perforator preparation time for group Ⅱ was significantly less (p ＝ 0.04) than for group Ⅰ (1038.6 ± 195.4 s versus 1271.4 ± 295.1 s. In group Ⅱ, the mean positioning deviation for the perforator navigator was 2.12 cm less than that for the high-frequency color Doppler (p ＝ 0.001). Group Ⅱ also had a higher score than group Ⅰ for overall flap growth evaluation (nonparametric rank sum test, p ＝ 0.04).Within the scale of the study, it seems that perforator localization and navigation using a 3D-printed navigator is technically feasible, and helps to improve the clinical outcome of free fibular flaps. The perforator navigator will play a useful role in displaying the perforator course, improving the accuracy of perforator localization, reducing surgical injury, and ultimately enhancing flap success rate.

Preparing the Romanian National Archaeological Datasets for ARIADNE

The contribution of the Romanian National Institute of Heritage (NIH) to the ARIADNE catalogue consists of 22,298 cultural resources, 18,277 of which are archaeological sites and 4021 are fieldwork reports. The two types of data were extracted from the two repositories that INP manages: the National Archaeological Repertory and the Chronicle of Archaeological Research. In Romania, the legislation regarding the protection of archaeological heritage establishes the National Archaeological Repertory as the means of managing the scientific data relating to the archaeological heritage, and of mapping archaeological sites as well as the threats to them. In addition, the same legislation stipulates that preliminary excavation reports should be published in a volume edited by the National Archaeology Commission, if the research was financed by public funds. As a result, for better dissemination, the reports are uploaded to a database. Both the Repertory and the Chronicle are accessible online through the INP management web portal. In order to fulfil the NIH's obligations within the ARIADNEplus project, several corrections and changes were made to the structures of both repositories (RAN and Chronicle) and data had to be updated. First of all, a photo upload module that illustrates both an archaeological site, perceived as a landscape, and its various components was developed. At the same time, the NIH team carried out a campaign to map the archaeological sites using coordinates in the WGS84 system, using various cartographic resources, such as topographic maps, aerial photographs and satellite images. The third activity consisted of creating a hierarchical list of archaeological site types and their components to support a more accurate description and retrieval of database records. Conversion of the RAN archaeological records to AO-Cat compliant RDF data was the fourth activity conducted by NIIH in order to include the RAN records in the ARIADNE Knowledge Base. Subsequently, a hierarchical list of the archaeological periods used in Romanian archaeology was developed, where every period is described by three main components: name, time interval and geographical area. This list has been converted to the PeriodO format and will be imported into the gazetteer.

76 Follow-up of the Therapeutic Effects of Integrative Neuropsychological Training Model for Executive Functions Deficits in School-age Children Born Very Low Birth Weight with Normal Early Development-A Preliminary Report

Objective:The preschool children born very low birth weight(VLBW) still have executive functions(EFs) deficits even with normal early development(Ni, Huang, & Guo, 2011). Consequently, early intervention might be more important than expected. This study aims to investigate the follow-up outcome of the therapeutic effects of integrative neuropsychological training model(INTM) focused on EFs for school-age VLBW children with EFs deficits.Participants and Methods:The VLBW children, recruited from the Regional Cohort Network for premature infants who were admitted to neonatal intensive care units, had normal scores in Bayley and Wechsler Intelligence systems before 6 years old. They also received follow-up neuropsychological assessment for EFs at 6 or 8-year-old. The deficits of EFs were defined from the result of Digit Span Subtest of WISC-IV, Knox's Cube Test(KCT), Tower of London(ToL), Wisconsin Card Sorting Test(WCST), and Comprehensive Nonverbal Attention Test Battery(CNAT). A total of 8 VLBW children with EFs deficits were recruited and received EFs training at 6 or 8-year-old. The INTM combined with Comprehensive Memory Training System(CMTS), Executive FUNction Training(EFT), and multi-ecological materials focused on enhancing the four aspects of EFs, including working memory, planning, cognitive flexibility, and inhibition ability. Then, they received follow-up neuropsychological assessment for EFs at 8 or 10-year-old.Results:The results showed that all children got benefits from 20 hours of INTM and most of the EF aspects remained improved at follow-up. A total of 8 VLBW children with an average of 3.4 aspects EFs deficits had an average of 1.4 aspects of EFs deficits left at the follow-up. More precisely, 5 of them had 1 aspects of EFs deficits and 3 of them had 2 aspects of EFs deficits.Conclusions:This study revealed that such a short-term INTM had long-term effects in enhancing the EFs of those VLBW children who had normal early development but later grew into EFs deficits at school-age. Besides, their EFs are still improving even after two years of intervention. Further study on more subjects with longer follow-up might help VLBW children to achieve better neuropsychological function.

3 Newsround

‘Newsround’ offers a platform for new discoveries that do not appear within the specialist contributions of this year’s Archaeological Reports, but which nevertheless warrant emphasis, either as a result of their particular characteristics or for the contribution they make to broader archaeological narratives. This section is not intended to be exhaustive, but rather an overview of archaeological research in Greece. It comprises largely preliminary reports (results of excavations that took place up to and including August 2023, where possible) that complement the digital content made available through Archaeology in Greece Online (https://chronique.efa.gr). Due to the diachronic nature of a number of the sites, and for ease of reference, the material is organized geographically in the first instance and then chronologically (earliest to latest) within each section as far as possible.

Assessment of knowledge and beliefs concerning mental disorders among medical students - preliminary report.

The aim of the study was to assess attitudes towards people with mental disorders. The survey was carried out in a group of 93 students of the fifth year of medical studies (medical faculty) including 59 women and 34 men, aged 24.34 ± 1.28 years. In the conducted research, personal contact with a psychiatrist due to problems with their own mental health was declared by 23% of respondents. The choice of psychiatry as a field of specialization was declared by 19% of students. In the analysis of the questionnaire on beliefs, as many as 83% of respondents considered that mental illness is a cause for shame. Analyzing the attitude of the respondents to treatment, it was shown that as many as 80% of people believed that compulsory hospitalization is a right procedure. It should be emphasized that only 31% of the surveyed students believed that people with mental disorders should decide to have offspring, and 36% of people thought that mentally disturbed people would not be good as parents. As many as 30% of respondents believed that people with mental disorders more often commit crimes than healthy people, and 42% of students showed a lack of determination in this aspect. The results of the research suggest the necessity of expanding knowledge and shaping appropriate attitudes towards people with mental disorders among future doctors.

Preliminary report of the Japanese version of the International Olympic Committee Sport Mental Health Assessment Tool 1

Abstract: Objective: The International Olympic Committee (IOC) Sport Mental Health Assessment Tool 1 (SMHAT-1) is an athlete-specific screening tool developed to identify mental health symptoms in elite athletes and potential need for referral to care. We aimed to report the prevalence using the Japanese version of the SMHAT-1 in a Japanese sport context. Methods: Web-based anonymous self-report data of 220 competing Japan Rugby Top League rugby players were analyzed. The players answered all screening questionnaires of the SMHAT-1 containing the assessment for multiple mental health symptoms for sport-related psychological distress (step 1), and the following specific symptoms (step2): anxiety, depression, sleep disturbance, alcohol misuse, substance misuse, and disordered eating. The prevalence of each symptom was calculated. The false-negative rate (FNR) for step 1 identifying athletes that were positively screened on the subsequent step 2, was computed. Results: 65% players experienced the sport-related psychological distress while the prevalence of mental health symptoms ranged from 4.5% for substance misuse to 72.3% for alcohol misuse. Step 1 correctly detected all positive screened cases for anxiety, depression and suicidal ideation. In addition, a small proportion of cases were FNR for sleep disturbance (9.1%) and substance misuse (2.6%). 64.9% and 35.1% of cases were FNR for alcohol misuse and disordered eating, respectively. Conclusion: The SMHAT-1 might have acceptable performance in detect anxiety, depression, and suicidal ideation, however, it should be noted that false negatives also exist for other common mental health symptoms like disordered eating and sleep problems.