Related Events Research Articles

The Multifractal Phenomenon of Stock Price Caused by “Tesla Rights Defense Event”

In this paper, we explore the periodicity of the multifractal phenomenon of stock price caused by public relations events using the multifractal detrended fluctuation analysis (MF-DFA) method. The Tesla stock closing price in the context of the Tesla rights defense event is used to obtain the generalized Hurst exponent and multifractal spectrum. We find that the stock price exhibits multifractal characteristics. Afterwards, we conduct a multifractal time-varying analysis using high-frequency data for 12 time periods before and after the Tesla rights defense event, which happened on 19 April 2021. We calculate the [Formula: see text] and [Formula: see text] before and after the rights defense event to measure the degree of multifractal of Tesla stock price. In addition, we also compute the difference between the two [Formula: see text] and two [Formula: see text], which are regarded as [Formula: see text] and [Formula: see text]. The results show that the Tesla stock market efficiency degree raised as the period time increases until the eighth period. And after the eighth period, both [Formula: see text] and [Formula: see text] tend to be stable, and the degree of market efficiency caused by the Tesla rights defense event remains almost unchanged. In addition, we use three broad market indices in the context of the Russia–Ukraine conflict to test the universality. The three broad market indices are Dow Jones Industrial Average (DJIA), Shanghai Stock Exchange Composite Index (SSEC) and Nikkei 225 ETF (N225). The results demonstrate that with the extending of time period, [Formula: see text] and [Formula: see text] gradually stabilize, indicating that public memorability will diminish and the market efficiency almost remains unchanged.

Measuring the evolution of Arab States’ perceptions of the Iranian threat: a quantitative text analysis of Arabic-language state media, 2010–20

ABSTRACT After the Arab Uprisings, inter-state relations in the Middle East became polarized between the two camps of the Saudi-led Gulf Cooperation Council (GCC) and Iran and its allies, which strengthened the threat perception of Iran among Arab states. This study aims to empirically elucidate the changes in the perception of threats against Iran among Arab states through a quantitative text analysis of major state media in 10 Arab states. Through this analysis, we first substantiated that the Arab threat perception of Iran increased, especially in GCC members, after the Arab Uprisings. Second, there were significant differences in threat perception, even among the GCC states, according to their political stance towards key events in international relations. We also propose a new empirical method for studying securitization in critical security theory based on quantitative text analysis.

The Islamic Republic of Iran as a New Member of BRICS

The article analyzes the political, economic and cultural development of Iran throughout the existence of this unique state and its role in regional and world politics. It is claimed that the Islamic Republic of Iran represents one of the oldest civilizations and a serious geopolitical force in the center of Eurasia. The author explores the history of various state entities, that existed on the territory of modern Iran. The article provides an overview of key events in Russian-Iranian relations from the end of the 18th century to the present day, including the wars between the Russian and Persian Empires, the interaction of Moscow and Tehran during the First and Second World Wars, and the era of the Cold War. Special attention is paid to the Iranian Revolution of 1979, which is considered as a symbol of protest against Western domination and an important factor in Reislamization, as well as the Iran-Iraq war of 1980–1988 and its consequences for regional stability. As а part of the study of Iran’s policy in the 21st century, attention is focused on Tehran’s relations with the leading centers of the modern world, including the Russian Federation, the People’s Republic of China, the United States of America. The article describes the impact of Iran’s nuclear program on international relations and the effect of Western sanctions on the socio-economic situation in the Islamic Republic. The author concludes that Iran, which joined the BRICS in 2024, has every chance to become an important player in the global economy and politics. At the same time, the Islamic Republic of Iran is a very valuable asset for the group itself.

Abstract 2712: Development of GB268, a tri-specific antibody targeting PD-1/CTLA-4/VEGF, with enhanced anti-tumor efficacy and reduced toxicity in pre-clinical studies

Abstract Background: Immunotherapy using immune checkpoint modulators such as anti-PD1/PD-L1 have been widely used in cancer therapy. Combination of checkpoint inhibition using anti-PD1 and anti-CTLA4 has improved therapeutic efficacy but is also accompanied by severe immune related adverse events (irAEs) which limited their clinical use. Bi-specific antibody targeting PD-1/CTLA-4 such as cadonilimab has shown improved clinical benefits with reduced irAEs in cervical cancer. Vascular endothelial growth factor (VEGF) is overexpressed in various solid tumors and anti-VEGF agents inhibit neovascularization and shrink tumor with time. Combined application of bevacizumab and PD-1/PD-L1 blockade displays durable and improved anti-tumor effects. We have recently developed a novel tri-specific antibody GB268, specifically targeting PD-1, CTLA-4 and VEGF with fine-tuned activity & potency for each arm to simultaneously block PD-1/CTLA-4 mediated immune-suppression and VEGF mediated tumor angiogenesis. Methods: GB268 is a hexavalent antibody with symmetrical structure, composed of anti-PD-1 VHH antibody, anti-CTLA-4 VHH antibody, and anti-VEGF conventional antibody. The Fc part is silenced by introducing L234A/L235A mutations. Comprehensive in vitro and in vivo characterization of GB268 have been carried out. Along with in vivo efficacy studies, toxicity has also been evaluated with a murine arthritis model in hPD1/hCTLA4 double-KI mice to assess immune related AEs. Results: GB268 specifically bound to PD-1, VEGF, and CTLA-4 with high affinity and completely blocked PD-1 and VEGF pathways in reporter systems. To reduce the CTLA4 inhibition-induced AEs, the CTLA-4 arm was intentionally designed to only partially block the interaction of CTLA4 to its ligands CD80/CD86, and furthermore, the blockade of CTLA-4 was highly dependent on PD-1 expression. GB268 displayed robust anti-tumor efficacy with attenuated toxicity in murine models. In multiple PBMC-humanized models including A375 melanoma model, HT29 colorectal cancer model, and NCI-H460 NSCLC model, etc., GB268 exhibited significantly better anti-tumor efficacy, compared to PD-1/CTLA-4 bsAb and PD-1/VEGF bsAb, or in the combination of monoclonal antibodies to PD-1, CTLA-4 or VEGF. In arthritis induction model using hPD1/hCTLA4 double KI mice, GB268 had improved tolerance than cadonilimab and at least 20-fold better safety profile than ipilimumab combined with nivolumab. Conclusions: GB268 is a first-in-class anti-PD-1/CTLA-4/VEGF tri-specific antibody with innovative design. Preclinical data demonstrated GB268 is very effective in provoking anti-tumor responses. At the meantime, immune-related AEs is alleviated. Thus, GB268 may emerge as a promising novel therapeutics for cancer treatment. Citation Format: Qinglin Du, Yaxua Lv, Juehua Xu, Fei Peng, Huanhuan Cao, Xueyan Yang, Zhen Qian, Xueqin Li, Yiqi Cao, Qian Ding, Yongcong Tan, Shuhua Han. Development of GB268, a tri-specific antibody targeting PD-1/CTLA-4/VEGF, with enhanced anti-tumor efficacy and reduced toxicity in pre-clinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2712.

A goodness of fit framework for relational event models

Abstract We introduce a novel procedure to assess the goodness of fit in relational event models. Building on existing auxiliary variable approaches developed in network modelling, the procedure involves a comparison between statistics computed on observed relational event sequences and statistics calculated on event sequences simulated from the fitted model. We argue that the internal time structure of the relational mechanisms assumed to generate the observations under the model is an important aspect of the fit of a model to observed relational event sequences. We establish the empirical value of the proposed goodness of fit approach in an analysis of data that we collected on collaborative patient-referral relations among healthcare organizations. The illustrative case study that we develop reveals distinctive features of relational event models that have been ignored or overlooked in received empirical studies.

Safety and Immunogenicity of a Messenger RNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1, Randomized, Clinical Trial.

This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, an mRNA-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults. Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose. A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (SD) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus. This phase 1, first-in-human trial demonstrated mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses. NCT03382405; https://clinicaltrials.gov/ct2/show/NCT03382405.

The high-energy tail of energetic electron precipitation: solar wind drivers and geomagnetic responses

Compositional NOx changes caused by energetic electron precipitation (EEP) at a specific altitude and those co-dependent on vertical transport are referred to as the EEP direct and indirect effect, respectively. The direct effect of EEP at lower mesospheric and upper stratospheric altitudes is linked to the high-energy tail of EEP (≳ 300 keV). The relative importance of this direct effect on NOx, ozone, and atmospheric dynamics remains unresolved due to inadequate particle measurements and scarcity of polar mesospheric NOx observations. An accurate parameterization of the high-energy tail of EEP is, therefore, crucial. This study utilizes EEP flux data from MEPED aboard the POES/Metop satellites from 2004–2014. Data from both hemispheres (55–70° N/S) are combined in daily flux estimates. 164 peaks above the 90th percentile of the ≳ 30 keV flux are identified. These peaks are categorized into absolute E1 and E3 events representing weak and strong ≳ 300 keV responses, respectively. A subset of absolute E1 and E3 events with similar ≳ 30 keV responses is termed overlapping events. Additionally, relative E1 and E3 events are determined by the relative strength of the ≳ 300 keV response, scaled by the initial ≳ 30 keV flux. A comparison between E1 and E3 events aims to identify solar wind and geomagnetic conditions leading to high-energy EEP responses and to gain insight into the conditions that generate a high-energy tail, independent of the initial ≳ 30 keV flux level. Superposed epoch analysis of mesospheric NO density from SOFIE confirms an observable direct impact on lower mesospheric chemistry associated with the absolute E3 events. A probability assessment based on absolute events identifies specific thresholds in the solar wind-magnetosphere coupling function (epsilon) and the geomagnetic indices Kp*10 and Dst, capable of determining the occurrence or exclusion of absolute E1 and E3 events. Elevated solar wind speeds persisting in the recovery phase of a deep Dst trough appear characteristic of overlapping and relative E3 events. This study provides insight into which parameters are important for accurately modeling the high-energy tail of EEP.

Safety, Tolerability, and Pharmacokinetics of the Monoamine Oxidase B Inhibitor, HEC122505, and its Major Metabolite After Single- andMultiple- Ascending Dose, and Food Effect Study in Healthy Chinese Subjects.

HEC122505 is a potent and selectively monoamine oxidase B inhibitor that is safe and well-tolerated in preclinical models of Parkinson's disease. The objectives of single ascending dose and multiple dose pharmacokinetic trials of HEC122505 oral tablets were to determine the safety and tolerability of HEC122505, and to examine the food effect on thepharmacokinetic parameters of HEC122505 and its major metabolite HEC129870. The phase I study (NCT04625361) consisted of three arms: single ascending dose study (5, 20, 50, 100, 200, 300 or 400 mg HEC122505 tablets or placebo), multiple ascending dose study (20, 50 or 100 mg HEC122505 tablets or placebo once daily), and food effect (100 mg HEC122505 tablets single dose after a high-fat, high-calorie meal). All subjects completed all trial arms and were analyzed as planned. Pharmacokinetic analysis showed that HEC122505 rapidly absorbed with the time to peak plasma concentration (Tmax) ranged from 0.5 to 1.75h. In addition, maximum plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose proportional manner. Food effect study showed that a high-fat, high-calorie meal had no significant effect on the pharmacokinetics ofHEC122505 and its major metabolite HEC129870, suggesting that HEC122505 could be administered in both fasted and fed state in clinical trials. The subsequent multiple-dose study evaluated doses from 20 to 100mg dose once daily for up to 8days. HEC122505 reached steady state after approximately 5days with a once daily dose. In these studies, all dose of HEC122505 was generally safe and well tolerated. No grade ≥ 3 drug related adverse events (AEs) occurred. HEC122505 was generally safe and well tolerated in the single ascending dose (ranging from 5 to 400 mg) and multiple ascending dose (50 to 200 mg once daily doses) studies. All the drug related adverse events (AEs) were Grade ≤ 2. There were no deaths, no subjects discontinued the trial due to AEs, and there were no other serious AEs. The safety and pharmacokinetic profile support once daily administration of HEC122505.

Nodal Heterogeneity can Induce Ghost Triadic Effects in Relational Event Models.

Temporal network data is often encoded as time-stamped interaction events between senders and receivers, such as co-authoring scientific articles or communication via email. A number of relational event frameworks have been proposed to address specific issues raised by complex temporal dependencies. These models attempt to quantify how individual behaviour, endogenous and exogenous factors, as well as interactions with other individuals modify the network dynamics over time. It is often of interest to determine whether changes in the network can be attributed to endogenous mechanisms reflecting natural relational tendencies, such as reciprocity or triadic effects. The propensity to form or receive ties can also, at least partially, be related to actor attributes. Nodal heterogeneity in the network is often modelled by including actor-specific or dyadic covariates. However, comprehensively capturing all personality traits is difficult in practice, if not impossible. A failure to account for heterogeneity may confound the substantive effect of key variables of interest. This work shows that failing to account for node level sender and receiver effects can induce ghost triadic effects. We propose a random-effect extension of the relational event model to deal with these problems. We show that it is often effective over more traditional approaches, such as in-degree and out-degree statistics. These results that the violation of the hierarchy principle due to insufficient information about nodal heterogeneity can be resolved by including random effects in the relational event model as a standard.

Impacts of El Niño diversity on East Asian summertime precipitation extremes

AbstractThis study examines the impacts of Eastern Pacific (EP) and Central Pacific (CP) El Niño on summertime extreme precipitation over East Asia during the El Niño decay phase. The findings reveal distinct patterns of extreme precipitation for the two El Niño types. During EP El Niño, more intense extreme precipitation occurs over south of the Yangtze River (SYR), while suppressed extremes are observed over Mei-Yu rainband in China, Baiu in Japan, and Changma in South Korea (MBC). Conversely, CP El Niño leads to weaker (stronger) extreme precipitation over SYR (MBC). This study also differentiates between tropical cyclone (TC) and non-TC related precipitation, showing that TCs have minimal influence on the overall extreme precipitation compared to non-TC related events. Further investigation reveals that EP and CP El Niño distinctly influence atmospheric circulation patterns, thereby causing different distributions of non-TC extreme precipitation. Specifically, during EP El Niño, sea surface temperature (SST) warming signals in the tropical Indian Ocean induce the southward displacement of the South Asia High (SAH), westerly jet (WJ), and Western Pacific subtropical high (WPSH). This amplifies moisture flux convergence, elevating the likelihood of intense extreme precipitation over SYR. Conversely, MBC experiences moisture flux divergence, resulting in fewer precipitation extremes. During CP El Niño, SST warming signals in the Maritime Continent prompt the northward shift of SAH, WJ, and WPSH by modulating local Hadley circulations. These anomalies lead to strengthened moisture convergence (divergence) over MBC (SYR), consequently resulting in a higher (lower) likelihood of intense extreme precipitation over MBC (SYR).

Topical Diclofenac Versus Oral Ibuprofen Versus Diclofenac + Ibuprofen for Emergency Department Patients With Acute Low Back Pain: A Randomized Study

IntroductionTopical non-steroidal anti-inflammatory drugs (NSAIDs) are useful for a variety of musculoskeletal injuries. It is not known whether topical NSAIDs should be used for patients presenting with acute non-radicular musculoskeletal low back pain (LBP). MethodsWe conducted a randomized, placebo-controlled double-blind study in which ED patients 18-69 years with acute, non-traumatic, non-radicular, musculoskeletal LBP were randomized at the time of discharge to treatment with oral ibuprofen 400mg orally + placebo topical gel, 1% diclofenac topical gel + oral placebo, or ibuprofen 400mg + 1% diclofenac topical gel. We measured outcomes using the Roland Morris Disability Questionnaire (RMDQ), a 24-item yes/no instrument about the impact of back pain on a respondent’s daily activities. The primary outcome was change in RMDQ between ED discharge and two days later. Medication related adverse events were elicited by asking whether the study medications caused any new symptoms. Results3281 patients were screened for participation and 198 were randomized. Overall, 36% of the population were women, the mean age was 40 years (SD 13), and the median RMDQ score at baseline was 18 (25th, 75th percentile: 13, 22) indicating substantial low back related functional impairment. 183 (92%) participants provided primary outcome data. By two days after the ED visit, the ibuprofen + placebo group had improved by 10.1(95%CI 7.5 to 12.7), the diclofenac gel + placebo group by 6.4(95%CI 4.0 to 8.8), and the ibuprofen + diclofenac gel by 8.7(95%CI 6.3 to 11.1). The 95%CI for between group differences were as follows-- ibuprofen versus diclofenac: 3.7 (0.2, 7.2); ibuprofen versus both medications 1.4 (-2.1, 4.9); diclofenac versus both medications -2.3 (-5.7, 1.0). Medication related adverse events were reported by 3/60 (5%) ibuprofen patients, 1/63 (2%) diclofenac patients, and 4/64 (6%) patients who got both. ConclusionsAmong patients with non-traumatic, non-radicular acute musculoskeletal low back pain discharged from an ED, topical diclofenac was probably less efficacious than oral ibuprofen. It demonstrated no additive benefit when co-administered with oral ibuprofen.

Abstract A021: Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer

Abstract Introduction: The purpose of this study is to evaluate exemestane, an aromatase inhibitor, as a potential agent for the chemoprevention of endometrial cancer. Experimental procedures: This is a multi-center, phase IIA, single arm ‘window of opportunity’ pilot study of 25 mg per day of exemestane for 21-42 days in postmenopausal patients undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer. The primary objective is to determine if there is a decrease in proliferation index, measured by percent Ki-67 expression in endometrial tissue, from pre-treatment to post-exposure. Results of Ki-67 are compared with a historic control cohort of tumors from patients matched by preoperative histologic diagnosis, age, BMI category. Specimens from the historic control cohort included a preoperative endometrial biopsy as well as a surgical specimen, separated in time by less than 42 days. Secondary outcomes include comparison of Ki67 to historic controls, circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety and adverse effects. Summary of Data: Forty patients accrued to the study between January of 2018 and March of 2021. The mean age was 63 (range 52-75). Thirty-nine patients (97.5%) self identifiedself-identified as white; 1 patient (2.5%) identified as Asian. The mean BMI was 40.3 (SD 9.75, range 22.8-60.5). Preoperative diagnoses included EIN, grade 1 endometrial adenocarcinoma, and grade 2 endometrial adenocarcinoma in 11 (27.5%), 26 (65%), and 3 (7.5%) patients respectively. Thirty-nine patients (97.5%) were compliant with exemestane dosing. All patients completed the study and no patients discontinued or interrupted therapy due to treatment related adverse events. Thirty-eight patients had evaluable specimens for both pre and post-treatment Ki-67 analysis. Median Ki-67 score decreased from 40.7% [IQR (33.9%, 50.3] at baseline to 18.1% [IQR (8.8%, 31.8%)]. This represents a median absolute change from baseline of -20.4% [IQR (-29.9, -6.7), p<0.001]. In total, percentage of Ki-67 in tumor cells declined in 31 patients and increased in 7 patients. In the historic control cohort, patients also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7%, -1.3%), p<0.001]. However, the decrease in Ki-67 was greater in the study patients than the matched historic controls, with a median difference between the groups of -13.4% [IQR= (-23.3%, 6.9%), p=0.0095]. Serum estradiol levels did not change significantly between baseline and post-treatment (p=0.16). There was a small but significant increase from baseline to post-treatment in serum progesterone (0.14 ng/mL vs 0.37 ng/mL, p<0.001). Conclusion: In this pilot window of opportunity study, exemestane demonstrates anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the chemoprevention of endometrial cancer. Citation Format: Britt K. Erickson, Lisa Barrioullet, Rebecca C. Arend, Dina El-Rayes, Mahmoud Khalifa, Amy Skubitz, Kristin Boylan, Andrew Nelson, Bharat Thyagarajan, Thomas Havighurst, Richard Chappell, Eileen Dimond, Katina Deshong, Goli Samimi, Eva Szabo, Howard Bailey. Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A021.

Merging socioecological variables to predict risk of Chagas disease

How far are we from predicting the occurrence of zoonotic diseases? In this paper we have made use of both socioecological and ecological variables to predict Chagas disease occurrence. Chagas disease involves, Trypanosoma cruzi, a complex life-cycle parasite which requires two hosts: blood-feeding triatomine insects and vertebrate hosts including humans. We have used a common risk assessment method combined with datasets that imply critical environmental and socioeconomic drivers of Chagas dynamics to predict the occurrence of this disease. We also carried out a network analysis to assess the interactions among triatomines and mammal host species given their human contact via whether hunted, domesticated or associated with anthropogenic landscapes in Mexico. We found that social backwardness variation, lack of health services and altitude had the largest relative influence Chagas events. Triatoma pallidipennis made use of the largest host diversity. Host species shared by the highest number of different triatomines were a woodrat, the highly appreciated bushmeat, and racoon. These results indicate both the predominance of socio-economic factors over ecological ones, and how close we are from predicting zoonotic diseases.

Thoracoscopic Intercostal Nerve Block with Cocktail Analgesics for Pain Control After Video-Assisted Thoracoscopic Surgery: A Prospective Cohort Study.

To evaluate whether using a cocktail of intercostal nerve blocks (TINB) during thoracoscopic surgery results in better clinical outcomes than patient-controlled analgesia (PCIA). Patients in two medical groups undergoing video-assisted thoracoscopic surgery (VATS) for pulmonary nodules in West China Hospital of Sichuan University were collected consecutively between March 2022 and December 2022. The groups were divided into two subgroups based on their analgesic program, which were TINB group and PCIA group. The primary outcome was the visual analogue scale (VAS) of the two groups at different stage after surgery and after discharge. Any analgesic related adverse events (ARAEs) were also recorded. A total of 230 patients who underwent VATS were enrolled, in which 113 patients (49.1%) received a cocktail TINB after surgery, and 117 patients (50.9%) received a PCIA. After PSM, 62 patients in each group were selected. The difference of resting VAS (RVAS) and active VAS (AVAS) at different stage during hospitalization was only related to the change of period (p < 0.05, p < 0.05), and the two groups showed no significant differences in RVAS or AVAS during hospitalization (p = 0.271, p = 0.915). However, the rates of dizziness (4.84% vs 25.81%, p = 0.002), nausea and vomiting (0 vs 22.58%, p < 0.05), fatigue (14.52% vs 34.87%, p = 0.012), and insomnia (0 vs 58.06%, p < 0.05) in TINB group were lower than that in PCIA group. Besides, AVAS and RVAS at 7, 14, and 30 days after discharge in TINB group were both significantly lower than that in PCIA group (p < 0.05, p < 0.05). Cocktail TINB provided better analgesia after discharge and reduced the incidence of ARAEs in patients undergoing VATS.

The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

Research Progression in the Mechanism of Bone Metastasis and Bone-Targeted Drugs in Prostate Cancer

Prostate cancer is a particularly slow growing cancer, the early stage of the disease is not easy to detect, the some major clinical manifestations include low back pain, urgent and frequent urination, urinary pain, and other urethral symptoms. These symptoms are often experienced after surgical resection or drug castration treatment. Early-stage, prostate cancer is curable, and with disease progression many clinical symptoms become worse with high probability of metastasis. Bone is the most common site of advanced metastasis of prostate cancer. Bone metastasis is a continuous and complex pathological process regulated by tumor cells and bone microenvironment, in which epithelial-mesenchymal transformation, homing and dormancy, reactivation, and proliferation of tumor cells are closely related to its occurrence and development. Several cytokines such as Receptor activator of NF-κB ligand (RANK-L) is overexpressed in bone microenvironment and prostate cancer. RANKL, chemokine family, and integrins are involved in bone metastasis of prostate cancer through complex interaction mechanisms. A variety of bone-targeting drugs such as bisphosphonates, RANKL inhibitors (denosumab) and radiotherapy drugs (radium-223, strontium-89, samarium-153), tyrosine kinase inhibitors, integrin-targeted drugs, etc. are approved for the prevention and treatment of skeletal related events caused by bone metastasis in prostate cancer patients. In this review, the biological mechanism of bone metastasis in prostate cancer and the research progress of bone-targeting drugs are reviewed.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Interaksi Tektonik Konvergen Dan Pola Struktur Di Pulau Atauro, Timor-Leste

This study examines convergent tectonic interactions and structural patterns on Atauro Island, Timor-Leste. Atauro Island is located near the convergence zone of the Australian and Eurasian plates within the tectonic framework of the Sunda Arc. The interaction between these plates has shaped a variety of geological features, including folded mountains, rising faults, and plateaus. In addition, these tectonic interactions are also significant in their influence on mineralization patterns on Atauro Island, involving various forms of mineralization such as precious and base metal deposits, hydrothermal systems, and related volcanic events. The research provides important insights into the tectonic history and evolution of the area. The methods used in this study involve a number of steps and approaches to collect data, analyze geological phenomena, and understand the geological processes that occur. The results, important about the types of rocks present on Atauro Island, include andesite igneous rocks and volcanic intermediate igneous rocks. Overall, this study provides a deeper understanding of the geological processes that occur on Atauro Island due to convergent tectonic interactions, as well as the potential mineral resources contained on the island.  

Quality assessment of gene repertoire annotations with OMArk.

In the era of biodiversity genomics, it is crucial to ensure that annotations of protein-coding gene repertoires are accurate. State-of-the-art tools to assess genome annotations measure the completeness of a gene repertoire but are blind to other errors, such as gene overprediction or contamination. We introduce OMArk, a software package that relies on fast, alignment-free sequence comparisons between a query proteome and precomputed gene families across the tree of life. OMArk assesses not only the completeness but also the consistency of the gene repertoire as a whole relative to closely related species and reports likely contamination events. Analysis of 1,805 UniProt Eukaryotic Reference Proteomes with OMArk demonstrated strong evidence of contamination in 73 proteomes and identified error propagation in avian gene annotation resulting from the use of a fragmented zebra finch proteome as a reference. This study illustrates the importance of comparing and prioritizing proteomes based on their quality measures.

Use of Abzolem ® in Pressure Injuries: Experience of an Exploratory Study

Introduction: Pressure injuries represent a significant and prevalent public health problem in bedridden and institutionalized patients. The correct management of pressure injuries is essential for preventing complications, enhancing patient well-being, and reducing the overall burden on healthcare systems. It underscores the importance of a holistic and patient-centered approach to wound care. Preventive measures and the action of a multidisciplinary team are essential to the correct treatment of pressure injuries. There are multiple active dressings and topical solutions to treat and protect the wounds, among them the hyperoxygenated fatty acids, such as Abzolem®. Objective: Evaluate and verify the effectiveness and safety of the use of Abzolem® in the treatment of patients with pressure injuries grade I and II. Materials and methods: an exploratory study was carried out on 6 patients residing in a long-term establishment in Santiago of Chile with grade I and II pressure injuries in which Abzolem® was used for twice-daily dressings. Results: The use of Abzolem® led to a significant improvement in grade I pressure injuries in 10 ± 3 days and grade II pressure injuries in 15 ± 3 days, without related adverse events and with good tolerance by patients. Conclusion: The use of hyperoxygenated fatty acids, such as Abzolem® corresponds to a safe therapeutic alternative, easy to apply, and effective in the treatment of grade I and II pressure injuries.