bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy
Authors: Wimberger Pauline , Blohmer Jens-Uwe , Krabisch Petra , Link Theresa , Just Marianne , Sinn Bruno Valentin , Simon Eike , Solbach Christine , Fehm Tanja , Denkert Carsten , Kühn Cristin , Rhiem Kerstin , Tesch Hans , Kümmel Sherko , Petzold Andrea , Stötzer Oliver , Meisel Cornelia , Kuhlmann Jan Dominik , Nekljudova Valentina , Loibl Sibylle
Published: March 2023

Background

Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient’s pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow.

Methods

A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab.

Results

At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00).

Conclusion

This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.
HiCAT: a tool for automatic annotation of centromere structure
Authors: Gao Shenghan , Yang Xiaofei , Guo Hongtao , Zhao Xixi , Wang Bo , Ye Kai
Published: March 2023

Significant improvements in long-read sequencing technologies have unlocked complex genomic areas, such as centromeres, in the genome and introduced the centromere annotation problem. Currently, centromeres are annotated in a semi-manual way. Here, we propose HiCAT, a generalizable automatic centromere annotation tool, based on hierarchical tandem repeat mining to facilitate decoding of centromere architecture. We apply HiCAT to simulated datasets, human CHM13-T2T and gapless Arabidopsis thaliana genomes. Our results are generally consistent with previous inferences but also greatly improve annotation continuity and reveal additional fine structures, demonstrating HiCAT’s performance and general applicability.
Metabolic health and adiposity transitions and risks of type 2 diabetes and cardiovascular diseases: a systematic review and meta-analysis
Authors: Zhang Xuhui , Zhu Jinghan , Kim Jean H. , Sumerlin Timothy S. , Feng Qi , Yu Jiazhou
Published: March 2023

Background

Metabolic health status and levels of adiposity are prone to change over time. Mixed results have been reported regarding the extent by which changes in metabolic health and weight affect cardiometabolic risks. This systematic review and meta-analysis aims to examine the association between transitions in metabolic health and adiposity status on risk of incident type 2 diabetes (T2DM) and cardiovascular disease (CVD) events.

Methods

A systematic literature search was conducted on MEDLINE and EMBASE through August 2022 for prospective cohort studies examining transitions in metabolic health and adiposity status and risk of incident T2DM and CVDs without restrictions on language or publication status. Meta-analysis was performed to summarize hazard ratios for T2DM and composite CVD events separately using random-effects model.

Results

A total of 17 studies were included. Compared to stable metabolically healthy status, transition to metabolically unhealthy status significantly increased the risk of incident T2DM and composite CVD events among individuals with normal weight and individuals with overweight/obesity. Compared to stable metabolically unhealthy status, transition to metabolically healthy status significantly lowered the risk among individuals with normal weight and individuals with overweight/obesity. When metabolic health status remained unchanged, progression from normal weight to overweight/obesity significantly increased risk of CVDs but not risk of T2DM.

Conclusion

The impact of change in metabolic health on the risks of T2DM and CVD is more prominent than that of change to body mass index category. Obesity treatment should consider prioritizing improvement in metabolic health parameters over focusing on the extent of weight loss only.
Potential antiviral activities of chrysin against hepatitis B virus
Authors: Bhat Sajad Ahmad , Hasan Syed Kazim , Parray Zahoor Ahmad , Siddiqui Zaheenul Islam , Ansari Shabnam , Anwer Ayesha , Khan Saniya , Amir Fatima , Mehmankhah Mahboubeh , Islam Asimul , Minuchehr Zarrin , Kazim Syed Naqui
Published: March 2023

Background

Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its anti-HBV activity is unexplored.

Methods

In the present study, the anti-hepatitis B activity of chrysin was investigated using the in vitro experimental cell culture model, HepG2 cells. In silico studies were performed where chrysin and lamivudine (used here as a positive control) were docked with high mobility group box 1 protein (HMGB1). For the in vitro studies, wild type HBV genome construct (pHBV 1.3X) was transiently transfected in HepG2. In culture supernatant samples, HBV surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were measured by enzyme-linked immunosorbent assay (ELISA). Secreted HBV DNA and intracellular covalently closed circular DNA (cccDNA) were measured by SYBR green real-time PCR. The 3D crystal structure of HMGB1 (1AAB) protein was developed and docked with the chrysin and lamivudine. In silico drug-likeness, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of finest ligands were performed by using SwissADME and admetSAR web servers.

Results

Data showed that chrysin significantly decreases HBeAg, HBsAg secretion, supernatant HBV DNA and cccDNA, in a dose dependent manner. The docking studies demonstrated HMGB1 as an important target for chrysin as compared to lamivudine. Chrysin revealed high binding affinity and formed a firm kissing complex with HMGB1 (∆G = − 5.7 kcal/mol), as compared to lamivudine (∆G = − 4.3 kcal/mol), which might be responsible for its antiviral activity.

Conclusions

The outcome of our study establishes chrysin as a new antiviral against HBV infection. However, using chrysin to treat chronic HBV disease needs further endorsement and optimization by in vivo studies in animal models.

Graphical Abstract
Association between 2D:4D ratios and sprinting, change of direction ability, aerobic fitness, and cumulative workloads in elite youth soccer players
Authors: Nobari Hadi , Eken Özgür , Prieto-González Pablo , Oliveira Rafael , Brito João Paulo
Published: March 2023

Background

The aim of this study was two-fold: (i) to determine the correlation between 2D:4D, maximal oxygen uptake (VO2max), body fat percentage (BF%), maximum heart rate (HRmax), change of direction (COD), and accumulated acute and chronic workload variables; (ii) to verify if the length of the second digit divided by fourth digit (2D:4D) can explain fitness variables and accumulated training load.

Methods

Twenty elite young football players (age: 13.26 ± 0.19 years; height: 165.8 ± 11.67 cm; body mass: 50.70 ± 7.56 kg; VO2max, 48.22 ± 2.29 ml.kg− 1.min− 1) participated in the present study. Anthropometric and body composition variables (e.g., height, body mass, sitting height, age, BF%, body mass index, right and left finger 2D:4D ratios) were measured. The following fitness tests were also conducted: 30 − 15 Intermittent Fitness Test (VO2max and HRmax), COD (5-0-5 agility test), and speed (10-30msprint test. HRmax and the training load were also measured and monitored using the Rate of Perceived Exertion during the 26 weeks.

Results

There were associations between HRmax and VO2max, between 2D and 4D lengths and Left and Right hand ratios. Also, in AW with Right and Left 4D. The CW and de ACWR with the Right 4D. There were other associations between physical test variables and workload variables.

Conclusions

Under-14 soccer players with low right and left-hand 2D:4D ratios did not perform better in the selected fitness tests to assess VO2max, COD, or sprint ability. However, it cannot be ruled out that the absence of statistically significant results may be related to the small sample size and the maturational heterogeneity of the participants.
Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts
Authors: Lantero-Rodriguez Juan , Vrillon Agathe , Fernández-Lebrero Aida , Ortiz-Romero Paula , Snellman Anniina , Montoliu-Gaya Laia , Brum Wagner S. , Cognat Emmanuel , Dumurgier Julien , Puig-Pijoan Albert , Navalpotro-Gómez Irene , García-Escobar Greta , Karikari Thomas K. , Vanmechelen Eugeen , Ashton Nicholas J. , Zetterberg Henrik , Suárez-Calvet Marc , Paquet Claire , Blennow Kaj
Published: March 2023

Background

Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer’s disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231.

Methods

CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n=212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n=175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ $$-$$
-
). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ1–42/40 ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231).

Results

High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ− groups (Paris cohort: P ˂0.0001 for all; BIODEGMAR cohort: P ˂0.05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A−T− and A+T− groups (P ˂0.0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0.86 to 0.96) and discriminating AT groups (AUCs=0.79 to 0.98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts.

Conclusions

CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings.
ETV2/ER71, the key factor leading the paths to vascular regeneration and angiogenic reprogramming
Authors: Kim Tae Min , Lee Ra Ham , Kim Min Seong , Lewis Chloe A. , Park Changwon
Published: March 2023

Extensive efforts have been made to achieve vascular regeneration accompanying tissue repair for treating vascular dysfunction-associated diseases. Recent advancements in stem cell biology and cell reprogramming have opened unforeseen opportunities to promote angiogenesis in vivo and generate autologous endothelial cells (ECs) for clinical use. We have, for the first time, identified a unique endothelial-specific transcription factor, ETV2/ER71, and revealed its essential role in regulating endothelial cell generation and function, along with vascular regeneration and tissue repair. Furthermore, we and other groups have demonstrated its ability to directly reprogram terminally differentiated non-ECs into functional ECs, proposing ETV2/ER71 as an effective therapeutic target for vascular diseases. In this review, we discuss the up-to-date status of studies on ETV2/ER71, spanning from its molecular mechanism to vasculo-angiogenic role and direct cell reprogramming toward ECs. Furthermore, we discuss future directions to deploy the clinical potential of ETV2/ER71 as a novel and potent target for vascular disorders such as cardiovascular disease, neurovascular impairment and cancer.
DFFNDDS: prediction of synergistic drug combinations with dual feature fusion networks
Authors: Xu Mengdie , Zhao Xinwei , Wang Jingyu , Feng Wei , Wen Naifeng , Wang Chunyu , Wang Junjie , Liu Yun , Zhao Lingling
Published: March 2023

Drug combination therapies are promising clinical treatments for curing patients. However, efficiently identifying valid drug combinations remains challenging because the number of available drugs has increased rapidly. In this study, we proposed a deep learning model called the Dual Feature Fusion Network for Drug–Drug Synergy prediction (DFFNDDS) that utilizes a fine-tuned pretrained language model and dual feature fusion mechanism to predict synergistic drug combinations. The dual feature fusion mechanism fuses the drug features and cell line features at the bit-wise level and the vector-wise level. We demonstrated that DFFNDDS outperforms competitive methods and can serve as a reliable tool for identifying synergistic drug combinations.
An optimal control problem for single-spot pulsed laser welding
Authors: Herzog Roland , Strelnikov Dmytro
Published: March 2023

We consider an optimal control problem for a single-spot pulsed laser welding problem. The distribution of thermal energy is described by a quasilinear heat equation. Our emphasis is on materials which tend to suffer from hot cracking when welded, such as aluminum alloys. A simple precursor for the occurrence of hot cracks is the velocity of the solidification front. We therefore formulate an optimal control problem whose objective contains a term which penalizes excessive solidification velocities. The control function to be optimized is the laser power over time, subject to pointwise lower and upper bounds. We describe the finite element discretization of the problem and a projected gradient scheme for its solution. Numerical experiments for material data representing the EN AW 6082-T6 aluminum alloy exhibit interesting laser pulse patterns which perform significantly better than standard ramp-down patterns.
Phylogeny-guided genome mining of roseocin family lantibiotics to generate improved variants of roseocin
Authors: Chaudhary Sandeep , Kishen Shweta , Singh Mangal , Jassal Sunanda , Pathania Reeva , Bisht Kalpana , Sareen Dipti
Published: March 2023

Roseocin, the two-peptide lantibiotic from Streptomyces roseosporus, carries extensive intramolecular (methyl)lanthionine bridging in the peptides and exhibits synergistic antibacterial activity against clinically relevant Gram-positive pathogens. Both peptides have a conserved leader but a diverse core region. The biosynthesis of roseocin involves post-translational modification of the two precursor peptides by a single promiscuous lanthipeptide synthetase, RosM, to install an indispensable disulfide bond in the Rosα core along with four and six thioether rings in Rosα and Rosβ cores, respectively. RosM homologs in the phylum actinobacteria were identified here to reveal twelve other members of the roseocin family which diverged into three types of biosynthetic gene clusters (BGCs). Further, the evolutionary rate among the BGC variants and analysis of variability within the core peptide versus leader peptide revealed a phylum-dependent lanthipeptide evolution. Analysis of horizontal gene transfer revealed its role in the generation of core peptide diversity. The naturally occurring diverse congeners of roseocin peptides identified from the mined novel BGCs were carefully aligned to identify the conserved sites and the substitutions in the core peptide region. These selected sites in the Rosα peptide were mutated for permitted substitutions, expressed heterologously in E. coli, and post-translationally modified by RosM in vivo. Despite a limited number of generated variants, two variants, RosαL8F and RosαL8W exhibited significantly improved inhibitory activity in a species-dependent manner compared to the wild-type roseocin. Our study proves that a natural repository of evolved variants of roseocin is present in nature and the key variations can be used to generate improved variants.
Effectiveness of telemedicine diabetic retinopathy screening in the USA: a protocol for systematic review and meta-analysis
Authors: Padilla Conde Tania , Robinson Lauren , Vora Paras , Ware S. Lee , Stromberg Arnold , Bastos de Carvalho Ana
Published: March 2023

Background

Diabetic retinopathy (DR) is the leading cause of vision loss among adults in the USA. Vision loss associated with diabetic retinopathy can be prevented with timely ophthalmologic care, and therefore, it is recommended that individuals with diabetes have annual retinal examinations. There is limited evidence on whether using telemedicine to screen for DR in primary care clinics in the USA effectively leads to increased DR screening rates. The objective of this systematic review is to collate evidence from existing studies to investigate the effectiveness of telemedicine DR screening (TDRS) in primary care clinics on DR screening rates.

Methods

Relevant studies will be identified through searching MEDLINE/PubMed interface, Scopus, and Web of Science from their inception until November 2021, as well as searching reference lists of included studies and previous related review articles or systematic reviews. There will be no restrictions on study design. Eligible studies will include subjects with either type 1 or type 2 diabetes, will evaluate telemedicine technology for screening of DR, will have been conducted in the USA, and will report DR screening rates or data necessary for calculating such rates. Two reviewers will screen search results independently. Risk-of-bias assessment and data extraction will be carried out by two reviewers. The version 2 of the Cochrane risk-of-bias tool (RoB 2) and the Newcastle-Ottawa scale (NOS) tool will be used to assess the quality and validity of individual studies. If feasible, we will conduct random-effects meta-analysis where appropriate. If possible, we will conduct subgroup analyses to explore potential heterogeneity sources (setting, socio-economic status, age, ethnicity, study design, outcomes). We will disseminate the findings through publications and relevant networks.

Discussion

This protocol outlines the methods for systematic review and synthesis of evidence of TDRS and its effect on DR screening rates. The results will be of interest to policy makers and program managers tasked with designing and implementing evidence-based services to prevent and manage diabetes and its complications in similar settings.

Systematic review registration

PROSPERO CRD42021231067.
Predictive models in extracorporeal membrane oxygenation (ECMO): a systematic review
Authors: Giordano Luca , Francavilla Andrea , Bottio Tomaso , Dell’Amore Andrea , Gregori Dario , Navalesi Paolo , Lorenzoni Giulia , Baldi Ileana
Published: March 2023

Purpose

Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the last years to provide hemodynamic and respiratory support in critically ill patients. In this scenario, prognostic scores remain essential to choose which patients should initiate ECMO.

This systematic review aims to assess the current landscape and inform subsequent efforts in the development of risk prediction tools for ECMO.

Methods

PubMed, CINAHL, Embase, MEDLINE and Scopus were consulted. Articles between Jan 2011 and Feb 2022, including adults undergoing ECMO reporting a newly developed and validated predictive model for mortality, were included. Studies based on animal models, systematic reviews, case reports and conference abstracts were excluded. Data extraction aimed to capture study characteristics, risk model characteristics and model performance. The risk of bias was evaluated through the prediction model risk-of-bias assessment tool (PROBAST). The protocol has been registered in Open Science Framework (https://osf.io/fevw5).

Results

Twenty-six prognostic scores for in-hospital mortality were identified, with a study size ranging from 60 to 4557 patients. The most common candidate variables were age, lactate concentration, creatinine concentration, bilirubin concentration and days in mechanical ventilation prior to ECMO. Five out of 16 venous-arterial (VA)-ECMO scores and 3 out of 9 veno-venous (VV)-ECMO scores had been validated externally. Additionally, one score was developed for both VA and VV populations. No score was judged at low risk of bias.

Conclusion

Most models have not been validated externally and apply after ECMO initiation; thus, some uncertainty whether ECMO should be initiated still remains. It has yet to be determined whether and to what extent a new methodological perspective may enhance the performance of predictive models for ECMO, with the ultimate goal to implement a model that positively influences patient outcomes.
Delphi survey on the most promising areas and methods to improve systematic reviews’ production and updating
Authors: Mahmić-Kaknjo Mersiha , Tomić Vicko , Ellen Moriah E. , Nussbaumer-Streit Barbara , Sfetcu Raluca , Baladia Eduard , Riva Nicoletta , Kassianos Angelos P. , Marušić Ana
Published: March 2023

Background

Systematic reviews (SRs) are invaluable evidence syntheses, widely used in biomedicine and other scientific areas. Tremendous resources are being spent on the production and updating of SRs. There is a continuous need to automatize the process and use the workforce and resources to make it faster and more efficient.

Methods

Information gathered by previous EVBRES research was used to construct a questionnaire for round 1 which was partly quantitative, partly qualitative. Fifty five experienced SR authors were invited to participate in a Delphi study (DS) designed to identify the most promising areas and methods to improve the efficient production and updating of SRs. Topic questions focused on which areas of SRs are most time/effort/resource intensive and should be prioritized in further research. Data were analysed using NVivo 12 plus, Microsoft Excel 2013 and SPSS. Thematic analysis findings were used on the topics on which agreement was not reached in round 1 in order to prepare the questionnaire for round 2.

Results

Sixty percent (33/55) of the invited participants completed round 1; 44% (24/55) completed round 2. Participants reported average of 13.3 years of experience in conducting SRs (SD 6.8). More than two thirds of the respondents agreed/strongly agreed the following topics should be prioritized: extracting data, literature searching, screening abstracts, obtaining and screening full texts, updating SRs, finding previous SRs, translating non-English studies, synthesizing data, project management, writing the protocol, constructing the search strategy and critically appraising. Participants have not considered following areas as priority: snowballing, GRADE-ing, writing SR, deduplication, formulating SR question, performing meta-analysis.

Conclusions

Data extraction was prioritized by the majority of participants as an area that needs more research/methods development. Quality of available language translating tools has dramatically increased over the years (Google translate, DeepL). The promising new tool for snowballing emerged (Citation Chaser). Automation cannot substitute human judgement where complex decisions are needed (GRADE-ing).

Trial registration

Study protocol was registered athttps://osf.io/bp2hu/.
Existence and stability analysis for Caputo generalized hybrid Langevin differential systems involving three-point boundary conditions
Authors: Boutiara A. , Matar Mohammed M. , Abdeljawad Thabet , Jarad Fahd
Published: March 2023

This research inscription gets to grips with two novel varieties of boundary value problems. One of them is a hybrid Langevin fractional differential equation, whilst the other is a coupled system of hybrid Langevin differential equation encapsuling a collective fractional derivative known as the ψ-Caputo fractional operator. Such operators are generated by iterating a local integral of a function with respect to another increasing positive function Ψ. The existence of the solutions of the aforehand equations is tackled by using the Dhage fixed point theorem, whereas their uniqueness is handled using the Banach fixed point theorem. On the top of this, the stability within the scope of Ulam–Hyers of solutions to these systems are also considered. Two pertinent examples are presented to corroborate the reported results.
Efficient lattice-based revocable attribute-based encryption against decryption key exposure for cloud file sharing
Authors: Huang Boxue , Gao Juntao , Li Xuelian
Published: March 2023

Cloud file sharing (CFS) has become one of the important tools for enterprises to reduce technology operating costs and improve their competitiveness. Due to the untrustworthy cloud service provider, access control and security issues for sensitive data have been key problems to be addressed. Current solutions to these issues are largely related to the traditional public key cryptography, access control encryption or attribute-based encryption based on the bilinear mapping. The rapid technological advances in quantum algorithms and quantum computers make us consider the transition from the tradtional cryptographic primitives to the post-quantum counterparts. In response to these problems, we propose a lattice-based Ciphertext-Policy Attribute-Based Encryption(CP-ABE) scheme, which is designed based on the ring learing with error problem, so it is more efficient than that designed based on the learing with error problem. In our scheme, the indirect revocation and binary tree-based data structure are introduced to achieve efficient user revocation and dynamic management of user groups. At the same time, in order to further improve the efficiency of the scheme and realize file sharing across enterprises, the scheme also allows multiple authorities to jointly set up system parameters and manage distribute keys. Furthermore, by re-randomizing the user’s private key and update key, we achieve decryption key exposure resistance(DKER) in the scheme. We provide a formal security model and a series of security experiments, which show that our scheme is secure under chosen-plaintext attacks. Experimental simulations and evaluation analyses demonstrate the high efficiency and practicality of our scheme.
Securing medical image privacy in cloud using deep learning network
Authors: S Gayathri , S Gowri
Published: March 2023

The worldwide usage of Internet of Things (IoT) applications enhanced the utilization of consumer devices, such as smartphones, computers, screening equipment used in hospitals that merely rely on imaging techniques. Numerous images got generated over the cloud platform in a daily basis ad create storage complexity. On the other hand, securing the data stored in the cloud is important. Instead of storing large amount of data into the cloud, lightweight dynamic processing of data suppresses the complex issues in cloud security. Here secure cloud-based image processing architecture is discussed. Privacy preserving medical data communication is considered as the specific research scope. Cryptographic technique used to encode the original data and decode the data at the other end is currently in usage as conventional design. Providing privacy to the medical records through adding noise and denoising the same records is the proposed idea. The proposed work is keenly focused on creating a light weight cloud architecture that communicates the medical data effectively with privacy perseverance using deep learning technique. In the proposed system, the design of an efficient image denoising scheme with a hybrid classification model is created to ensure reliable and secure communication. Deep learning algorithms merged to form a Pseudo-Predictive Deep Denoising Network (PPDD). The proposed system's benefit is ensuring added security in Dark Cloud using a newly structured algorithm. The original data is packed in the Deep cloud using the Gaussian noise act as a key. The complete packing and unpacking of medical data is encapsulated by the transformed images. Over the cloud premise, the data is highly secured and invisible to the malicious users. To reduce the storage complexity, the dynamic data is unpacked and denoise process is applied at the edge devices. During the authorized access period alone, the data is decrypted and accessible at the edge nodes. The maximum process is dynamically happen in the cloud without depending on the storage boundary. The performance of proposed PPDD network model is evaluated through Signal to noise ratio (SNR), Similarity index (SI),Error Rate(ER) and Contrast to noise ratio(CNR). The proposed architecture is comparatively validated with existing state-of-art approach.
Data transmission reduction formalization for cloud offloading-based IoT systems
Authors: Elouali Aya , Mora Mora Higinio , Mora-Gimeno Francisco José
Published: March 2023

Computation offloading is the solution for IoT devices of limited resources and high-cost processing requirements. However, the network related issues such as latency and bandwidth consumption need to be considered. Data transmission reduction is one of the solutions aiming to solve network related problems by reducing the amount of data transmitted. In this paper, we propose a generalized formal data transmission reduction model independent of the system and the data type. This formalization is based on two main ideas: 1) Not sending data until a significant change occurs, 2) Sending a lighter size entity permitting the cloud to deduct the data captured by the IoT device without actually receiving it. This paper includes the mathematical representation of the model, general evaluation metrics formulas as well as detailed projections on real world use cases.
Feasibility, safety, and acceptability of intranasal heroin-assisted treatment in Switzerland: protocol for a prospective multicentre observational cohort study
Authors: Westenberg Jean N. , Meyer Maximilian , Strasser Johannes , Krausz Michael , Dürsteler Kenneth M. , Falcato Luis , Vogel Marc
Published: March 2023

Background

Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT.

Methods

This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health.

Conclusions

The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.
A systematic review of substance use screening in outpatient behavioral health settings
Authors: Woodward Diana , Wilens Timothy E. , Glantz Meyer , Rao Vinod , Burke Colin , Yule Amy M.
Published: March 2023

Objective

Despite the frequent comorbidity of substance use disorders (SUDs) and psychiatric disorders, it remains unclear if screening for substance use in behavioral health clinics is a common practice. The aim of this review is to examine what is known about systematic screening for substance use in outpatient behavioral health clinics.

Methods

We conducted a PRISMA-based systematic literature search assessing substance use screening in outpatient adult and pediatric behavioral health settings in PubMed, Embase, and PsycINFO. Quantitative studies published in English before May 22, 2020 that reported the percentage of patients who completed screening were included.

Results

Only eight articles met our inclusion and exclusion criteria. Reported prevalence of screening ranged from 48 to 100%, with half of the studies successfully screening more than 75% of their patient population. There were limited data on patient demographics for individuals who were and were not screened (e.g., gender, race) and screening practices (e.g., electronic versus paper/pencil administration).

Conclusions

The results of this systematic review suggest that successful screening for substance use in behavioral health settings is possible, yet it remains unclear how frequently screening occurs. Given the high rates of comorbid SUD and psychopathology, future research is necessary regarding patient and clinic-level variables that may impact the successful implementation of substance use screening.

Trial registry A methodological protocol was registered with the PROSPERO systematic review protocol registry (ID: CRD42020188645).
“Just fighting for my life to stay alive”: a qualitative investigation of barriers and facilitators to community re-entry among people with opioid use disorder and incarceration histories
Authors: Hoffman Kim A. , Thompson Emma , Gaeta Gazzola Marina , Oberleitner Lindsay M. S. , Eller Anthony , Madden Lynn M. , Marcus Ruthanne , Oberleitner David E. , Beitel Mark , Barry Declan T.
Published: March 2023

Background

During the period of community re-entry immediately following release from jail or prison, individuals with opioid use disorder (OUD) face structural barriers to successful re-entry and high risk of overdose. Few published studies investigate experiences in the immediate period (i.e., first 24 h) of re-entry among people with OUD.

Aim

To understand the barriers and facilitators to treatment and reintegration of people with OUD during the initial transition from carceral settings back into the community.

Methods

From January–December 2017, we conducted 42 semi-structured qualitative interviews with patients with a history of incarceration who were receiving methadone at a not-for-profit, low-barrier opioid treatment program. Interviews probed participants’ community re-entry experiences immediately following incarceration. Interviews were transcribed and analyzed using a Thematic Analysis approach.

Results

The main themes described the experiences during the 24 h following release, reacclimating and navigating re-entry barriers, and re-entry preparedness and planning. Participants noted the initial 24 h to be a period of risk for returning to substance use or an opportunity to engage with OUD treatment as well as a tenuous period where many lacked basic resources such as shelter or money. When discussing the subsequent re-entry period, participants noted social challenges and persistent barriers to stable housing and employment. Participants overall described feeling unprepared for release and suggested improvements including formal transition programs, improved education, and support to combat the risk of overdose and return to substance use after incarceration.

Conclusions

In this study that qualitatively examines the experiences of people with incarceration histories and OUD enrolled in methadone treatment, we found that participants faced many barriers to community re-entry, particularly surrounding basic resources and treatment engagement. Participants reported feeling unprepared for release but made concrete suggestions for interventions that might improve the barriers they encountered. Future work should examine the incorporation of these perspectives of people with lived experience into the development of transition programs or re-entry classes.
Targeted treatment of T-cell acute lymphoblastic leukemia: latest updates from the 2022 ASH Annual Meeting
Authors: Xu Jieyu , Zhu Hong-Hu
Published: March 2023

T-cell acute lymphoblastic leukemia (T-ALL) occurs in approximately 25–30% of adult ALL. Currently, treatment approaches for adult patients with T-ALL remain quite limited, with intensive multiagent chemotherapy serving as the backbone; however, the cure rate remains unsatisfactory. Thus, the discovery of novel therapeutic strategies, especially targeted therapies, is crucial. Clinical research efforts are now focused on adding targeted therapy that has selective activity for T-ALL to the backbone chemotherapy regimen. To date, nelarabine remains the only targeted agent specifically approved for relapsed T-ALL, and the use of nelarabine in the first-line regimen is still being studied. Meanwhile, a number of novel targeted therapies with low toxicity, such as immunotherapies, are being actively investigated. Chimeric antigen receptor (CAR) T-cell therapy for the treatment of T-cell malignancies has not been as successful as in treating B-ALL due to fratricide. Numerous approaches are now being designed to address this challenge. Novel therapies targeting molecular aberrations in T-ALL are also actively investigated. T-ALL lymphoblasts overexpress BCL2 protein, which makes it an intriguing therapeutic target. This review summarizes the latest updates on targeted treatment of T-ALL from the 2022 ASH annual meeting.
In-depth study of tomato and weed viromes reveals undiscovered plant virus diversity in an agroecosystem
Authors: Rivarez Mark Paul Selda , Pecman Anja , Bačnik Katarina , Maksimović Olivera , Vučurović Ana , Seljak Gabrijel , Mehle Nataša , Gutiérrez-Aguirre Ion , Ravnikar Maja , Kutnjak Denis
Published: March 2023

Background

In agroecosystems, viruses are well known to influence crop health and some cause phytosanitary and economic problems, but their diversity in non-crop plants and role outside the disease perspective is less known. Extensive virome explorations that include both crop and diverse weed plants are therefore needed to better understand roles of viruses in agroecosystems. Such unbiased exploration is available through viromics, which could generate biological and ecological insights from immense high-throughput sequencing (HTS) data.

Results

Here, we implemented HTS-based viromics to explore viral diversity in tomatoes and weeds in farming areas at a nation-wide scale. We detected 125 viruses, including 79 novel species, wherein 65 were found exclusively in weeds. This spanned 21 higher-level plant virus taxa dominated by Potyviridae, Rhabdoviridae, and Tombusviridae, and four non-plant virus families. We detected viruses of non-plant hosts and viroid-like sequences and demonstrated infectivity of a novel tobamovirus in plants of Solanaceae family. Diversities of predominant tomato viruses were variable, in some cases, comparable to that of global isolates of the same species. We phylogenetically classified novel viruses and showed links between a subgroup of phylogenetically related rhabdoviruses to their taxonomically related host plants. Ten classified viruses detected in tomatoes were also detected in weeds, which might indicate possible role of weeds as their reservoirs and that these viruses could be exchanged between the two compartments.

Conclusions

We showed that even in relatively well studied agroecosystems, such as tomato farms, a large part of very diverse plant viromes can still be unknown and is mostly present in understudied non-crop plants. The overlapping presence of viruses in tomatoes and weeds implicate possible presence of virus reservoir and possible exchange between the weed and crop compartments, which may influence weed management decisions. The observed variability and widespread presence of predominant tomato viruses and the infectivity of a novel tobamovirus in solanaceous plants, provided foundation for further investigation of virus disease dynamics and their effect on tomato health. The extensive insights we generated from such in-depth agroecosystem virome exploration will be valuable in anticipating possible emergences of plant virus diseases and would serve as baseline for further post-discovery characterization studies.
Induced secondary metabolites of the beneficial fungus Trichoderma harzianum M10 through OSMAC approach
Authors: Staropoli Alessia , Iacomino Giuseppina , De Cicco Paola , Woo Sheridan L. , Di Costanzo Luigi , Vinale Francesco
Published: March 2023

Background

Fungi biosynthesize a wide range of chemically diverse secondary metabolites during processes of competition with other micro- and macro-organisms, symbiosis, parasitism, or pathogenesis. Some of these natural compounds have antibiotic properties, which allow the microbe to inhibit and/or kill their microbial competitors.

Results

In the course of an ongoing search for novel bioactive metabolites from Trichoderma harzianum M10 using OSMAC (One Strain MAny Compounds) strategy, a bioactive chromone derivative has been isolated. The 5-hydroxy-2,3-dimethyl-7-methoxychromone (1), purified for the first time from T. harzianum M10 and induced in specific medium (potato dextrose broth, PDB) and condition (light and shaking), has been obtained as pure crystals and its structure has been fully characterized using X-ray and spectroscopic methods. This metabolite revealed a significant antibiotic activity against Rhizoctonia solani (45% of growth inhibition after 24 h of incubation at a concentration of 100 ng plug−1) and significantly reduced the viability of colorectal human cancer cells in a concentration-dependent manner. Moreover, metabolomic analysis allowed the identification of compounds modulated by the cultivating conditions. Among the statistically different molecules detected it was possible to identify siderophores, such as ferricrocin and coprogen B, harzianic acid (and its derivatives), and butenolides.

Conclusion

OSMAC strategy represents a valuable approach to overcome the limitations of experiments performed under laboratory conditions. Indeed, it is possible to modulate metabolites production by changing medium and conditions applied to the cultures. A specific set of conditions induced the production of a secondary metabolite never isolated from T. harzianum M10. The compound, a methoxychromone derivative, characterized by X-ray diffraction, mass spectrometry, IR, and NMR, displayed antimicrobial and antitumor activities.

Graphical Abstract
Inflight calibration of the optical navigation camera for the extended mission phase of Hayabusa2
Authors: Yamada Manabu , Kouyama Toru , Yumoto Koki , Tatsumi Eri , Takaki Naofumi , Yokota Yasuhiro , Morota Tomokatsu , Sakatani Naoya , Hayakawa Masahiko , Matsuoka Moe , Honda Rie , Honda Chikatoshi , Kameda Shingo , Suzuki Hidehiko , Cho Yuichiro , Yoshioka Kazuo , Ogawa Kazunori , Shirai Kei , Sawada Hirotaka , Sugita Seiji
Published: March 2023

After delivering its sample capsule to Earth, the Hayabusa2 spacecraft started its extended mission to perform a flyby of asteroid 2001 CC21 in 2026 and rendezvous with asteroid 1998 KY26 in 2031. During the extended mission, the optical navigation camera (ONC) of Hayabusa2 will play an important role in navigation and science observations, but it has suffered from optical deterioration after the spacecraft’s surface contact with and sampling of asteroid Ryugu. Furthermore, the sensitivity of the telescopic camera (ONC-T) has continued to decrease for more than a year, posing a serious problem for the extended mission. These are problems that could potentially be encountered by other sample-return missions involving surface contact. In this study, we evaluated the long-term variation of ONC performance over the 6.5 years following the launch in 2014 to predict how it will perform during observations of the two target asteroids in its extended mission (6 and 11 years from the Earth return, respectively). Our results showed several important long-term trends in ONC performance, such as transmission, dark noise level, and hot pixels. During the long cruising period of the extended mission, we plan to observe both zodiacal light and exoplanet transits as additional science targets. The accuracy of these observations is sensitive to background noise level and stray-light contamination, so we conducted new test observations to search for the lowest stray light, which has been found to depend on spacecraft attitude. The results of these analyses and new test observations suggest that the Hayabusa2 ONC will be able to conduct cruising, flyby, and rendezvous observations of asteroids with sufficient accuracy.

Graphical Abstract