bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the biotransformation of progesterone to the anticancer compound testololactone by Penicillium chrysogenum Ras3009: kinetic modelling and efficiency maximization
Authors: Abdel-Kareem Marwa M. , Zohri Abdel-Nasser A. , Rasmey Abdel-Hamied M. , Hawary Heba
Published: October 2024

Background

Biotransformation of steroid compounds into therapeutic products using microorganisms offers an eco-friendly and economically sustainable approach to the pharmaceutical industry rather than a chemical synthesis way. The biotransformation efficiency of progesterone into the anticancer compound testololactone using Penicillium chrysogenum Ras3009 has been investigated. Besides, maximization of testololactone formation was achieved by studying the kinetic modelling and impact of some fermentation conditions on the biotransformation process.

Results

The fungal strain Ras3009 was selected among twelve fungal strains as the most runner for the transformation of 81.18% of progesterone into testololactone. Ras3009 was identified phenotypically and genotypically as Penicillium chrysogenum, its 18 S rRNA nucleotide sequence was deposited in the GenBank database by the accession number OR480104. Studying the impact of fermentation conditions on biotransformation efficiency indicated a positive correlation between substrate concentration and testololactone formation until reaching the maximum velocity vmax. Kinetic studies revealed that vmax was $$\:0.0482$$ gL− 1hr− 1 with high accuracy, giving R2 of 0.977. The progesterone transformation efficiency generally increased with time, reaching a maximum of 100% at 42 h with testololactone yield (Ypt/s) 0.8700 mg/mg. Moreover, the study indicated that the enzymatic conversion by P. chrysogenum Ras3009 showed high affinity to the substrate, intracellularly expressed, and released during cell disruption, leading to higher efficiency when using whole microbial cell extract.

Conclusions

Fungi can be promising biocatalysts for steroid transformation into valuable chemicals and pharmaceutical compounds. The study revealed that the new fungal isolate P. chrysogenum Ras3009 possesses a great catalytic ability to convert progesterone into testololactone. Kinetic modelling analysis and optimization of the fermentation conditions lead to higher transformation efficiency and provide a better understanding of the transformation processes.

Graphical abstract
Head-to-head comparison of influenza vaccines in children: a systematic review and meta-analysis
Authors: Garai Réka , Jánosi Ágoston , Krivácsy Péter , Herczeg Vivien , Kói Tamás , Nagy Rita , Imrei Marcell , Párniczky Andrea , Garami Miklós , Hegyi Péter , Szabó Attila József
Published: October 2024

Although vaccination is considered the most effective weapon against influenza, coverage rates, national vaccination policies, and funding vary largely around the globe. Despite their huge potential for achieving herd immunity, child-focused national vaccination strategies that favor pain-free nasal vaccines are uncommon. CENTRAL, Embase, and MEDLINE were last searched on November 13, 2023. Active-controlled randomized controlled trials comparing the live-attenuated intranasal vaccine with the inactivated intramuscular influenza vaccine in children were included. Event rates of laboratory-confirmed influenza virus infection, all-cause mortality, hospitalization, serious adverse events, adverse events, and financial outcomes were extracted based on the PRISMA 2020 Guideline. PROSPERO: CRD42021285412. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random-effects model when at least three comparable outcomes were available. We found no significant difference between quadrivalent live-attenuated intranasal and trivalent inactivated intramuscular (OR = 1.48; 95% CI 0.49–4.45) or between trivalent live-attenuated intranasal and inactivated intramuscular vaccines (OR = 0.77, CI = 0.44–1.34) regarding their efficacy. However, the subgroup analysis of large, multi-center trials indicated that the trivalent live attenuated intranasal influenza vaccine was superior to the trivalent inactivated intramuscular influenza vaccine (12,154 people, OR = 0.50, CI = 0.28–0.88). Only 23 “vaccine-related serious adverse events” were recorded among 17 833 individuals, with no significant difference between methods. The widespread initiation of pediatric national flu vaccination programs prioritizing the live-attenuated intranasal influenza vaccine would be beneficial. Multi-continent, high-quality studies that include children younger than two years old and those living in subtropical and tropical regions are needed to further enhance our understanding.
Targeting CD276 for T cell-based immunotherapy of breast cancer
Authors: Hagelstein Ilona , Wessling Laura , Rochwarger Alexander , Zekri Latifa , Klimovich Boris , Tegeler Christian M. , Jung Gundram , Schürch Christian M. , Salih Helmut R. , Lutz Martina S.
Published: October 2024

Background

Breast cancer (BC) is the most common malignancy in women. Immunotherapy has revolutionized treatment options in many malignancies, and the introduction of immune checkpoint inhibition yielded beneficial results also in BC. However, many BC patients are ineligible for this T cell-based therapy, others do not respond or only briefly. Thus, there remains a high medical need for new therapies, particularly for triple-negative BC. CD276 (B7-H3) is overexpressed in several tumors on both tumor cells and tumor vessels, constituting a promising target for immunotherapy.

Methods

We analyzed tumor samples of 25 patients using immunohistochemistry to assess CD276 levels. The potential of CC-3, a novel bispecific CD276xCD3 antibody, for BC treatment was evaluated using various functional in vitro assays.

Results

Pronounced expression of CD276 was observed in all analyzed tumor samples including triple negative BC. In analyses with BC cells, CC-3 induced profound T cell activation, proliferation, and T cell memory subset formation. Moreover, treatment with CC-3 induced cytokine secretion and potent tumor cell lysis.

Conclusion

Our findings characterize CD276 as promising target and preclinically document the therapeutic potential of CC-3 for BC treatment, providing a strong rationale for evaluation of CC-3 in BC patients in a clinical trial for which the recruitment has recently started.
Acupuncture may play a key role in anti-depression through various mechanisms in depression
Authors: Li Peng , Zhao Jiangna , Wei Xiuxiang , Luo Longfei , Chu Yuzhou , Zhang Tao , Zhu Anning , Yan Juntao
Published: October 2024

Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.
Dihydroartemisinin suppresses the susceptibility of Anopheles stephensi to Plasmodium yoelii by activating the Toll signaling pathway
Authors: Liu Tingting , Zheng Dan , Wang Jing , Li Xin , Yu Shasha , Liu Zhilong , Zheng Feifei , Zhao Caizhi , Yang Xuesen , Wang Ying
Published: October 2024

Background

Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi.

Methods

Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes.

Results

DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection.

Conclusions

DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium.

Graphical Abstract
Curcumin attenuates ochratoxin A and hypoxia co-induced liver injury in grass carp (Ctenopharyngodon idella) by dual targeting endoplasmic reticulum stress and apoptosis via reducing ROS content
Authors: Wu Liangqin , Zhao Piao , Wu Pei , Jiang Weidan , Liu Yang , Ren Hongmei , Jin Xiaowan , Zhou Xiaoqiu , Feng Lin
Published: October 2024

Background

Ochratoxin A (OTA) is a toxin widely found in aquafeed ingredients, and hypoxia is a common problem in fish farming. In practice, aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA, but no studies exist in this area. This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin (CUR).

Methods

A total of 720 healthy juvenile grass carp (11.06 ± 0.05 g) were selected and assigned randomly to 4 experimental groups: control group (without OTA and CUR), 1.2 mg/kg OTA group, 400 mg/kg CUR group, and 1.2 mg/kg OTA + 400 mg/kg CUR group with three replicates each for 60 d. Subsequently, 32 fish were selected, divided into normoxia (18 fish) and hypoxia (18 fish) groups, and subjected to hypoxia stress for 96 h.

Results

CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacuolation and nuclear excursion. The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3, 8, 9, Bax, and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2, and attenuation of endoplasmic reticulum stress (ERS) by reducing Grp78 expression and chop levels. This may be attributed to the fact that the addition of CUR increased the levels of catalase (CAT) and glutathione reductase (GSH), increased antioxidant capacity, and ensured the proper functioning of respiratory chain complexes I and II, which in turn reduced the high production of reactive oxygen species (ROS), thus alleviating apoptosis and ERS.

Conclusions

In conclusion, our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia. This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.
Introducing object-oriented modelling to cybercrime scripting: visualisation for improved analysis
Authors: Madarie Renushka , Weulen Kranenbarg Marleen , de Poot Christianne
Published: October 2024

Crime script analysis as a methodology to analyse criminal processes is underdeveloped. This is apparent from the various approaches in which scholars apply crime scripting and present their cybercrime scripts. The plethora of scripting methods raise significant concerns about the reliability and validity of these scripting studies. In this methodological paper, we demonstrate how object-oriented modelling (OOM) could address some of the currently identified methodological issues, thereby refining crime script analysis. More specifically, we suggest to visualise crime scripts using static and dynamic modelling with the Unified Modelling Language (UML) to harmonise cybercrime scripts without compromising their depth. Static models visualise objects in a system or process, their attributes and their relationships. Dynamic models visualise actions and interactions during a process. Creating these models in addition to the typical textual narrative could aid analysts to more systematically consider, organise and relate key aspects of crime scripts. In turn, this approach might, amongst others, facilitate alternative ways of identifying intervention measures, theorising about offender decision-making, and an improved shared understanding of the crime phenomenon analysed. We illustrate the application of these models with a phishing script.
Visceral adiposity in postmenopausal women is associated with a pro-inflammatory gut microbiome and immunogenic metabolic endotoxemia
Authors: Gaber Mohamed , Wilson Adam S. , Millen Amy E. , Hovey Kathleen M. , LaMonte Michael J. , Wactawski-Wende Jean , Ochs-Balcom Heather M. , Cook Katherine L.
Published: October 2024

Background

Obesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed “metabolic endotoxemia.” We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women.

Methods

Fifty postmenopausal women (mean age 78.8 ± 5.3 years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4 mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6 weeks.

Results

Women in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet.

Conclusions

Increased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms.
Estimation of transpulmonary driving pressure using a lower assist maneuver (LAM) during synchronized ventilation in patients with acute respiratory failure: a physiological study
Authors: Liu Ling , He Hao , Liang Meihao , Beck Jennifer , Sinderby Christer
Published: October 2024

Background

We previously showed in animals that transpulmonary driving pressure (PL) can be estimated during Neurally Adjusted Ventilatory Assist (NAVA) and Neural Pressure Support (NPS) using a single lower assist maneuver (LAM). The aim of this study was to test the LAM-based estimate of PL (PL_LAM) in patients with acute respiratory failure.

Methods

This was a prospective, physiological, and interventional study in intubated patients with acute respiratory failure. During both NAVA and simulated NPS (high and low levels of assist), a LAM was performed every 3 min by manually reducing the assist to zero for one single breath (by default, ventilator still provides 2 cmH2O). Following NAVA and NPSSIM periods, patients were sedated and passively ventilated in volume control and pressure control ventilation, to obtain PL during controlled mechanical ventilation (PL_CMV). PL using an esophageal balloon (PL_Pes) was also compared to PL_LAM and PL_CMV. We measured diaphragm electrical activity (Edi), ventilator pressure (PVent), esophageal pressure (Pes) and tidal volume. PL_LAM and PL_Pes were compared to themselves, and to PL_CMV for matching flows and volumes.

Results

Ten patients were included in the study. For the group, PL_LAM was closely similar to PL_CMV, with a high correlation (R2 = 0.88). Bland–Altman analysis revealed a low Bias of 0.28 cmH2O, and 1.96SD of 5.26 cmH2O. PL_LAM vs PL_Pes were also tightly related (R2 = 0.77).

Conclusion

This physiological study in patients confirms our previous pre-clinical data that PL_LAM is as good an estimate as PL_Pes to determine PL, in spontaneously breathing patients on assisted mechanical ventilation.

Trial registration The study was registered at clinicaltrials.gov (ID NCT05378802) on November 6, 2021
Novel intravascular tantalum oxide-based contrast agent achieves improved vascular contrast enhancement and conspicuity compared to Iopamidol in an animal multiphase CT protocol
Authors: Heimer Maurice M. , Sun Yuxin , Grosu Sergio , Cyran Clemens C. , Bonitatibus Peter J. , Okwelogu Nikki , Bales Brian C. , Meyer Dan E. , Yeh Benjamin M.
Published: October 2024

Background

To assess thoracic vascular computed tomography (CT) contrast enhancement of a novel intravenous tantalum oxide nanoparticle contrast agent (carboxybetaine zwitterionic tantalum oxide, TaCZ) compared to a conventional iodinated contrast agent (Iopamidol) in a rabbit multiphase protocol.

Methods

Five rabbits were scanned inside a human-torso-sized encasement on a clinical CT system at various scan delays after intravenous injection of 540 mg element (Ta or I) per kg of bodyweight of TaCZ or Iopamidol. Net contrast enhancement of various arteries and veins, as well as image noise, were measured. Randomized scan series were reviewed by three independent readers on a clinical workstation and assessed for vascular conspicuity and image artifacts on 5-point Likert scales.

Results

Overall, net vascular contrast enhancement achieved with TaCZ was superior to Iopamidol (p ≤ 0.036 with the exception of the inferior vena cava at 6 s (p = 0.131). Vascular contrast enhancement achieved with TaCZ at delays of 6 s, 40 s, and 75 s was superior to optimum achieved Iopamidol contrast enhancement at 6 s (p ≤ 0.036. Vascular conspicuity was higher for TaCZ in 269 of 300 (89.7%) arterial and 269 of 300 (89.7%) venous vessel assessments, respectively (p ≤ 0.005), with substantial inter-reader reliability (κ = 0.61; p < 0.001) and strong positive monotonic correlation between conspicuity scores and contrast enhancement measurements (ρ = 0.828; p < 0.001).

Conclusion

TaCZ provides absolute and relative contrast advantages compared to Iopamidol for improved visualization of thoracic arteries and veins in a multiphase CT protocol.

Relevance statement

The tantalum-oxide nanoparticle is an experimental intravenous CT contrast agent with superior cardiovascular and venous contrast capacity per injected elemental mass in an animal model, providing improved maximum contrast enhancement and prolonged contrast conspicuity. Further translational research on promising high-Z and nanoparticle contrast agents is warranted.

Key Points

There have been no major advancements in intravenous CT contrast agents over decades.

Iodinated CT contrast agents require optimal timing for angiography and phlebography.

Tantalum-oxide demonstrated increased CT attenuation per elemental mass compared to Iopamidol.

Nanoparticle contrast agent design facilitates prolonged vascular conspicuity.

Graphical Abstract
Prescription of quadruple therapy in heart failure with reduced ejection fraction during hospitalization
Authors: Hatoum Ibrahim
Published: October 2024

Background

Hospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition.

Methods

We conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors.

Results

From September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function.

Conclusions

The low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients.
Trends in case detection rate for leprosy and factors associated with disability among registered patients in Zanzibar, 2018–2021
Authors: Said Ali Habib , Mwanga Hussein , Hussein Ally Kassim
Published: October 2024

Background

Leprosy is still a disease of public health concern. Globally, 2–3 million people are thought to be affected by leprosy’s disease-related disabilities. Regarding leprosy status in Zanzibar, limited information is available. Determining changes in detection rates and factors associated with disability is crucial for treatment and preventative strategies for this debilitating disease. This study aimed to determine trends in case detection rate for leprosy and risk factors for disability among registered patients in Zanzibar, from 2018 to 2021. The study included all leprosy patients who received treatment in Zanzibar's 11 districts between 2018 and 2021. The study design used was an analytical cross-sectional. Prevalence and new case detection rate (NCDR) were calculated. Multivariable Poisson regression analyses were used to identify factors associated with leprosy disability. Crude and adjusted prevalence ratios (APR) and their respective 95% confidence intervals (CI) were reported. P-values ≤ 0.05 were considered significant.

Results

Of the 490 leprosy cases reported between 2018 and 2021, 469 (95.7%) were new patients, and 349 (71.2%) were multi-bacillary. The disease was found to be more common in males 296 (60.4%). The average prevalence was 7/100,000 population, while the average NCDR was 7/100,000 from 2018 to 2021. There was a significant decrease in disability grades from diagnosis to the end of treatment over 4 years (P < 0.001). Male sex (APR 1.55; 95% CI 1.18–2.04), advanced age (APR 5.01; 95% CI 1.91–13.17), multi-bacillary (APR 6.99; 95% CI 3.16–15.44) and HIV negative patients (APR 1.51; 95% CI 1.11–2.06) were more likely to develop physical disability.

Conclusion

This study found that leprosy disability grades at diagnosis compared to the end of treatment declined during 4 years. There was no significant change in point prevalence and NCDR during the 4-year study period. Disability was associated with male sex, advanced age, multi-bacillary, and HIV-negative patients. To prevent leprosy-related disability and transmission, health education, early case detection, and adequate multidrug therapy should be prioritized.
Honey password vaults tolerating leakage of both personally identifiable information and passwords
Authors: An Chao , Xiao YuTing , Liu HaiHang , Wu Han , Zhang Rui
Published: October 2024

Honey vaults are useful tools for password management. A vault usually contains usernames for each domain, and the corresponding passwords, encrypted with a master password chosen by the owner. By generating decoy vaults for incorrect master password attempts, honey vaults force attackers with the vault’s storage file to engage in online verification to distinguish the real vaults, thus thwarting offline guessing attacks. However, sophisticated attackers can acquire additional information, such as personally identifiable information (PII) and partial passwords contained within the vault from various data breaches. Since many users tend to incorporate PII in their passwords, attackers may utilize PII to distinguish the real vault. Furthermore, if attackers may learn partial passwords included in the real vault, it can exclude numerous decoy vaults without the need for online verification. Indeed, both leakages pose serious threats to the security of the existing honey vault schemes. In this paper, we explore two attack variants of the inspired attack scenario, where the attacker gains access to the vault’s storage file along with acquiring PII and partial passwords contained within the real vault, and design a new honey vault scheme. For security assurance, we prove that our scheme is secure against one of the aforementioned attack variants. Moreover, our experimental findings suggest enhancements in security against the other attack. In particular, to evaluate the security in multiple leakage cases where both the vault’s storage file and PII are leaked, we propose several new practical attacks (called PII-based attacks), building upon the existing practical attacks in the traditional single leakage case where only the vault’s storage file is compromised. Our experimental results demonstrate that certain PII-based attacks achieve a 63–70% accuracy in distinguishing the real vault from decoys in the best-performing honey vault scheme (Cheng et al. in Incrementally updateable honey password vaults, pp 857–874, 2021). Our scheme reduces these metrics to 41–50%, closely approaching the ideal value of 50%.
Discogenic chronic low back pain management: intradiscal radiofrequency biacuplasty versus conservative treatment
Authors: Elawady Mostafa Mohamed , Nassar Hassan Gamal Eldeen , Elgammal Tarek Mohamed , Abdel Hafez Ahmed Ali , Bessar Ahmed Awad
Published: October 2024

Background

This prospective bicentric study aims to evaluate and compare the efficacy of intradiscal radiofrequency biacuplasty (IDB) versus conservative management (CM) in treating chronic discogenic low back pain (CDLBP).

Methods

Forty-four patients with CDLBP were randomly assigned to either the biacuplasty group or the conservative management group. The biacuplasty group received treatment with two radiofrequency (RF) needles, positioned bilaterally on the annulus fibrosus under fluoroscopic guidance and local anaesthesia, to administer bipolar RF. Patients were monitored for 6 months, with the allowance of pain medication as needed. In the conservative management group, patients who continued to experience low back pain after three months were permitted to switch to the biacuplasty group. The study was conducted over two years, starting on July 1, 2020.

Results

The studied groups had comparable age and gender distributions, with no significant difference in BMI. The Oswestry Disability Index (ODI) was assessed at baseline, 1 month, 3 months, and 6 months. At baseline, no significant difference was observed between the groups (p = 0.263). However, at the 1-month, 3-month, and 6-month follow-up, the biacuplasty group exhibited significantly lower ODI scores compared to the conservative management group (all p < 0.001), indicating that biacuplasty was more effective in reducing disability caused by chronic low back pain.

Conclusions

Intradiscal radiofrequency biacuplasty is a minimally invasive interventional technique that has proven effective for patients with CDLBP who do not respond to conservative management.
A preliminary study on decomposition and seasonality of insect succession of decomposing rabbit carcasses at El-Sharkia Governorate, Egypt
Authors: Shaurub El-Sayed H. , Salem Abeer M. , Zaher Eman E.
Published: October 2024

Background

Studying insect succession on carcasses is important in estimating the postmortem interval. This study aims to identify the decomposition stages of decomposing rabbit carcasses and to find out the relationship between seasonal variations and abundance of insects colonizing rabbit carcasses at El-Sharkia Governorate, Egypt.

Methods

Three domestic rabbits (weighing 1300 g each) were killed by a sharp knife. The carcasses were exposed to the sun, left to decompose and inspected twice daily at 6-h intervals to collect insects. Maggots were collected and reared.

Results

The rabbit carcasses underwent four decomposition stages: fresh, bloat, decay and dry stages. The identified families and their respective collected species included three dipteran families: Calliphoridae (Lucilia sericata, Chrysomya megacephala, and Chrysomya albiceps), Sarcophagidae (Sarcophaga argyrostoma) and Muscidae (Musca domestica and Synthesiomyia nudiseta), three coleopteran families. Histeridae (Saprinus semistriatus), Cleridae (Necrobia rufipes) and Dermestidae (Dermestes frischii and Attagenus gloriosus) and three hymenopteran families: Chalcididae (Brachymeria femorata), Vespidae (Vespa orientalis) and Formicidae (Monomorium sp.). Carrion fauna was dominated by dipteran and coleopteran species, with calliphorid and sarcophagid flies found to play a significant role in carrion consumption process.

Conclusion

The succession pattern and decomposition rate were season dependent. The information collected may help establish the basic database for entomological forensic investigations in the future.

Graphical abstract
Role of blood urea nitrogen to creatinine ratio in the assessment of hypovolemia who have undergone major surgeries- a cross-sectional study
Authors: Malugari Anish Reddy , K Mahesh Kumar , Silambanan Santhi
Published: October 2024

Background

Major surgeries are being carried for certain ailments. Surgeries can be major or minor depending on the extent of intervention. Major surgeries are prone to cause lots of complications such as shock, haemorrhage, wound infection, deep vein thrombosis, pulmonary complications, organ rejection, reactions to anaesthetics etc. Early identification of complications could reduce morbidity and mortality. Laboratory variables used in the assessment of hypovolemia include blood urea nitrogen, sodium, osmolality, hematocrit, and arterial blood gas. This study was undertaken to assess the utility of blood urea nitrogen: creatinine ratio (BCR) in the utility of assessment of hypovolemia in the first post-operative day in individuals who had major surgeries.

Methods and materials

The retrospective cross-sectional study included participants from the Departments of Orthopedic Surgery, Obstetrics and Gynecology, General Surgery and Cardiothoracic Surgery. Patients who underwent major surgeries between January 2019 and January 2020 were included. Study participants of 30 to 60 years of both genders were recruited into the study. Data were collected from the Medical Records of a tertiary care hospital in Chennai, India. Ethics approval was obtained, the institutional ethics committee (Ref: CSP/21/SEP/99/479 dated 30–12-2021). Waiver of consent was obtained since the patients were treated and discharged from the hospital. The data were analyzed by SPSS version 16. P value ≤ 0.05 was taken to be significant.

Results

BCR showed statistically significant difference across the groups with P = 0.02. BCR showed statistically significant difference between cardiac patients with total knee replacement and total abdominal hysterectomy surgeries. BCR showed positive correlation with age, fluids intake and negative correlation with pulse rate and respiratory rate.

Conclusion

BCR is a simple diagnostic tool for identifying hypovolemia in individuals who undergo major surgeries especially in the first postoperative day. It is significantly altered across the groups with highest value in individuals who have undergone knee replacement surgeries. BCR has high specificity and positive predictive value.
Wideband tympanometry in otitis Media
Authors: Elbattat Shymaa M. , Elgharib Amany M. , Gabr Takwa A.
Published: October 2024

Background

Otitis media with effusion (OME) is one of the most frequent infectious diseases in children and is the most common cause of acquired hearing loss in childhood. Diagnosis of OME is mainly dependent on the single-frequency tympanometry. Wideband tympanometry (WBT) is an emerging technology that has been utilized to overcome the limitations of conventional tympanometric procedures. This study aimed to evaluate the diagnostic value of wideband acoustic absorbance in children suffering from otitis media.

Methods

This study included a control group of 50 children with 100 ears with bilateral normal peripheral hearing and bilateral normal middle ear function and a study group which included 100 children with 176 ears complaining of otitis media. Measures included subjects history, basic audiological evaluation and wideband tympanometry. Resonant frequency, tympanometric peak pressure and middle ear absorbance were measured from wideband tympanometry and compared in both groups.

Results

There was a statistically significant reduction of resonsnce frequency in the study group in comparison to the control group. Also, there was a statistically significant reduction of tympanometric peak pressure in the study group in comparison to the control group. As regards the absorbance, there was a statistically significant reduction of absorbance in the study group in comparison to the control group at all tested frequencies (250Hz- 8000Hz). The best area under the receiver operating characteristic curve values for diagnosing OM were obtained at all tested frequencies. Data of this work showed that higher values were mainly at 250Hz, 500Hz and 1kHz (0.84, 0.88 and 0.93 respectively).

Conclusion

Findings of this study suggested that wide band tympanometry can be used efficiently in various degrees of OM.
Pre-emptive augmentative biological control of
Spodoptera frugiperda
in Europe using
Trichogramma
spp.
Authors: Kenis Marc , Zhong Yongzhi , Fontes João , Kenis Julien , Herz Annette , Babendreier Dirk
Published: October 2024

Background

Fall armyworm,
Spodoptera frugiperda
, is a highly invasive pest of maize and other crops worldwide. It has recently been detected in Europe, and it is urgent to test and develop new sustainable control methods adapted to the European context and market.
Trichogramma
spp. are egg parasitoids that are sometimes used as biological control agent against
S. frugiperda
in other continents. However, a major issue using
Trichogramma
spp. against this pest is that females cannot reach all eggs in an egg mass, which is usually composed of one to three layers of eggs, often covered with scales and hair. Three European
Trichogramma
species were tested for their ability to parasitize egg masses with one to three layers and with or without hair and scale cover.

Methods

Trichogramma brassicae
,
T. dendrolimi
and
T. cacoeciae
were offered five types of
S. frugiperda
egg masses: one-layer without hair; one-layer with hair; two-layers without hair; two-layers with hair; three-layers with hair. For each treatment, an egg mass laid on paper was placed in a small vial saturated with females, to be sure that all reachable eggs would be parasitized. For each egg mass, the number of eggs in each layer was counted. Fifteen replicates were made per treatment, as well as 10 control vials without
Trichogramma
sp. Parasitism rates were calculated for each egg mass.

Results

There were significant differences in the ability of parasitoid species to oviposit through hair and scales and to reach the lower egg layers.
Trichogramma dendrolimi
was the most efficient species and
T. cacoeciae
the least. Depending on the number of egg layers and hair and scales, parasitism rates by
T. brassicae
,
T. dendrolimi
and
T. cacoeciae
varied between 99 and 41%, 100 and 43% and 100 and 28%, respectively.

Conclusions

The assays confirmed that
Trichogramma
females cannot easily oviposit through thick layers of hair and scales but overall parasitism rates were higher than found previously. Important variations between species were found, and more
Trichogramma
sp. and other local natural enemies should be tested pre-emptively before
S. frugiperda
has invaded Europe.
Trajectory mapping through channel state information by triangulation method and fine-tuning
Authors: Abuhoureyah Fahd , Wong Yan Chiew , Mohd Isira Ahmad Sadhiqin
Published: October 2024

Trajectory mapping techniques have widespread applications in diverse fields, including robotics, localization, smart environments, gaming, and tracking systems. However, existing free devices encounter challenges in representing trajectories, thereby limiting the effectiveness of applications such as robotics, localization, and tracking systems. The imprecise mappings generated by these methods lead to suboptimal performance and unreliable results. The proposed approach leverages WiFi sensing through channel state information (CSI), triangulation techniques, and a fine-tuning mechanism to enhance trajectory precision within indoor environment trajectory mapping. The proposed solution employs a domain adapter fine-tuning technique to enable location-independent tracking via CSI, minimizing errors. The use of CSI MIMO signals for trajectory mapping offers enhanced spatial resolution, robust multipath handling, and improved accuracy in tracking movement by leveraging multiple antenna channels and exploiting the rich information embedded in signal reflections and scattering, while triangulation aids in accurately determining the location of objects or targets. Furthermore, incorporating a fine-tuning mechanism refines the generated trajectories. The findings demonstrate substantial enhancements in mapping precision, with an accuracy of 95.5% in tracking 13 paths within the new domain. These results underscore the effectiveness of the proposed approach in overcoming the limitations of existing methods and achieving highly accurate trajectory mapping.
Can We Offset Local Recurrence in Locally Advanced Non–Small Cell Lung Cancer? The Merry-Go-Round of Radiation Dose Escalation and Stubborn Outcomes
Authors: Owen Dawn , Chapman Christina Hunter
Published: October 2024

The Oncology Grand Rounds series is designed to place original reports published in the
Journal
into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in
Journal of Clinical Oncology
, to patients seen in their own clinical practice.
Combined high-resolution H3K27ac epigenomic and single-cell transcriptional profiling as a signature predictive of response to neoadjuvant immune checkpoint inhibitors (ICI) in urothelial cancer (UC).
Authors: Bellmunt Joaquim , Hully Margot , Epstein Ilana B. , Liria Sonsoles , Xie Yingtian , Muñoz Miguel , Garoz Paula , Fernandez Nuria , Buisán Oscar , CHOUEIRI Toni K. , Cabrera Cecilia , Long Henry , Cejas Paloma
Published: October 2024

4595

Background:
Multiple molecular predictors have been associated with response to ICI in metastatic UC (mUC), including clonal TMB, APOBEC mutagenesis and multiple RNA signatures. Tumor-intrinsic and tumor-extrinsic (microenvironmental) properties can drive resistance to PD-1/PD-L1 inhibitors, although the factors that determine resistance specifically in MIBC remains incompletely characterized. Epigenomic analysis combined with single cell (sc) technology can reveal mechanisms of response involving both cancer cells and the microenvironment.
Methods:
We identified two MIBC patients’ cohorts from Dana-Farber Cancer Institute (DFCI) and from Hospital Trias i Pujol in Spain treated with neoadjuvant therapy with ICI with tissue available pre- and post- treatment. Molecular profiling was performed with H3K27ac in Formalin-Fixed Paraffin-Embedded (FFPE) blocks and scRNAseq from Fresh Frozen (FF) and FFPE tissues. For the analysis, we performed peak calling, unsupervised analysis (using our internal pipeline), comparison of enhancers with a published datasets (using Cistrome toolkit) and sc analysis using Seurat.
Results:
35 patients with pre and post available samples were included in the analysis. The H3K27ac enhancer analysis revealed a signature predictive of treatment response to immunotherapy. Comparison with publicly available ChIP-seq datasets showed that enhancers more active in pre-treatment samples in responders were highly represented in lymphoid lineages. In contrast, the enhancers less active in responders were associated with squamous differentiation. When translated to a gene expression signature, we found enhancers at novel and known genes described in UC that included
CYTOR, TGFBR2
and
IKZF1(
involved in immunotherapy response) and
FYN, PDE4B
and
GPR174
involved in cell migration, microenvironment and EMT among the top ten genes. We projected the gene signature over a scRNAseq atlas resulting from 20 patients that includes all inflammatory lineages, and found an increase within specific T cell populations and a reduction of B and plasma cells in responders as compared to non-responders in the pre-treatment samples.
Conclusions:
Our combined epigenetic and scRNAseq strategy revealed the existence of specific microenvironment and tumor states in pre-treatment samples from MIBC. We also provided a novel gene signature predictive of response. Prospective validation is ongoing.
Real-world efficacy and safety of inetetamab-based therapy in patients with HER2-positive metastatic breast cancer with prior trastuzumab exposure: A multi-center retrospective study.
Authors: Duan Yangyang , Sun Tao , Chen Zhanhong , Ouyang Quchang , Li Kai , Yan Min , Lv Zheng , Li Zhaohui , Man Li , Luo Xu , Dong Yuyang , Jing Mingxi , Wang Yan , Guo Xiangyu , Xu Junnan , Li Xiaorui
Published: October 2024

e13007

Background:
Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody (mAb). There was still no direct data with large sample sizes to evaluate the efficacy of inetetamab-based therapy in HER2-positive metastatic breast cancer patients who had previously received trastuzumab treatment. This study aimed to observe the larger-scale real-world efficacy and safety of inetetamab, analyze the characteristics of the benefit population and explore more excellent treatment choices.
Methods:
A multicenter retrospective real-world study which collected the clinicopathological data of HER2-positive metastatic breast cancer patients treated with inetetamab in multicenters in China. The progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of patients who received inetetamab therapy were estimated. Adverse events (AEs) were classified based on the Common Toxicity Criteria established by the National Cancer Institute.
Results:
A total of 500 patients were included in the final analysis according to the established inclusion criteria. The median PFS was 7 months in the overall cohort. The median number of treatment lines administered was three. The ORR was 28.6%, and the DCR was 89.2%. Meanwhile, patients who received a combination treatment of inetetamab, tyrosine kinase inhibitors (TKIs) and chemotherapy achieved the most prolonged PFS of 9.0 months and the higher ORR of 29.3%. The most common treatment-related AEs were neutropenia (36.4%) and leukopenia (31.4%), which were generally well-tolerated.
Conclusions:
Inetetamab demonstrated promising efficacy and safety in HER2-positive metastatic breast cancer patients who had prior exposure to trastuzumab, particularly in combination with TKIs and chemotherapy. Further research and comparative analysis should be necessary for therapeutic benefits.