bluuebunny/crossref_metadata_2025 huggingface dataset:
phyBWT2: phylogeny reconstruction via eBWT positional clustering
Authors: Guerrini Veronica , Conte Alessio , Grossi Roberto , Liti Gianni , Rosone Giovanna , Tattini Lorenzo
Published: August 2023

Background

Molecular phylogenetics studies the evolutionary relationships among the individuals of a population through their biological sequences. It may provide insights about the origin and the evolution of viral diseases, or highlight complex evolutionary trajectories. A key task is inferring phylogenetic trees from any type of sequencing data, including raw short reads. Yet, several tools require pre-processed input data e.g. from complex computational pipelines based on de novo assembly or from mappings against a reference genome. As sequencing technologies keep becoming cheaper, this puts increasing pressure on designing methods that perform analysis directly on their outputs. From this viewpoint, there is a growing interest in alignment-, assembly-, and reference-free methods that could work on several data including raw reads data.

Results

We present phyBWT2, a newly improved version of phyBWT (Guerrini et al. in 22nd International Workshop on Algorithms in Bioinformatics (WABI) 242:23–12319, 2022). Both of them directly reconstruct phylogenetic trees bypassing both the alignment against a reference genome and de novo assembly. They exploit the combinatorial properties of the extended Burrows-Wheeler Transform (eBWT) and the corresponding eBWT positional clustering framework to detect relevant blocks of the longest shared substrings of varying length (unlike the k-mer-based approaches that need to fix the length k a priori). As a result, they provide novel alignment-, assembly-, and reference-free methods that build partition trees without relying on the pairwise comparison of sequences, thus avoiding to use a distance matrix to infer phylogeny. In addition, phyBWT2 outperforms phyBWT in terms of running time, as the former reconstructs phylogenetic trees step-by-step by considering multiple partitions, instead of just one partition at a time, as previously done by the latter.

Conclusions

Based on the results of the experiments on sequencing data, we conclude that our method can produce trees of quality comparable to the benchmark phylogeny by handling datasets of different types (short reads, contigs, or entire genomes). Overall, the experiments confirm the effectiveness of phyBWT2 that improves the performance of its previous version phyBWT, while preserving the accuracy of the results.
Evaluating the effectiveness of a social and emotional learning program among preschool children in Japan: an experimental cohort study
Authors: Hosokawa Rikuya , Matsumoto Yuki , Nishida Chizuko , Funato Keiko , Mitani Aki
Published: August 2023

Background

Research on school maladjustment has increasingly focused on social skills, such as the ability to control emotions, collaborate with others, and achieve goals. Social and emotional learning (SEL) is one approach to nurturing social skills. However, few preventive interventions to promote SEL have been conducted among young children, particularly in Asian countries, including Japan. Therefore, this study examined the effectiveness of an SEL program—Fun FRIENDS—among children in Japan.

Methods

In mid-2022, the Fun FRIENDS program was administered to 115 children aged 4–5 years, who were enrolled in two kindergartens. The program was administered to the entire class as part of their kindergarten activities. The control group included 93 children in three kindergartens. This study included 94 participants (81.7%) in the intervention group and 66 (71.0%) in the control group, whose parents agreed with the assessment of their skills. Fun FRIENDS is a support program based on a cognitive–behavioral approach. The program aims to teach children how to cope with anxiety and stress and develop resilience and confidence to face difficulties. The program includes 10 sessions, each lasting approximately 1 h and conducted once per week. To examine the program’s effectiveness, teachers evaluated these children’s social skills before and after program implementation using the Social Skill Scale.

Results

Results showed significant post-intervention improvements in self-control and cooperation scores among children in the intervention group, compared with pre-intervention. Further, post-intervention self-control and cooperation scores were significantly higher among children in the intervention group than the control group.

Conclusions

SEL implemented on a class-wide basis could be effective in early childhood. An early approach targeting preschool-aged children is necessary to prevent school maladjustment. A universal approach implemented on a whole-class basis could contribute to improving children’s social skills.
A high-throughput dual system to screen polyphosphate kinase mutants for efficient ATP regeneration in L-theanine biocatalysis
Authors: Gao Hui , Li Mengxuan , Wang Qing , Liu Tingting , Zhang Xian , Yang Taowei , Xu Meijuan , Rao Zhiming
Published: August 2023

ATP, an important cofactor, is involved in many biocatalytic reactions that require energy. Polyphosphate kinases (PPK) can provide energy for ATP-consuming reactions due to their cheap and readily available substrate polyphosphate. We determined the catalytic properties of PPK from different sources and found that PPK from Cytophaga hutchinsonii (ChPPK) had the best catalytic activity for the substrates ADP and polyP6. An extracellular–intracellular dual system was constructed to high-throughput screen for better catalytic activity of ChPPK mutants. Finally, the specific activity of ChPPKD82N-K103E mutant was increased by 4.3 times. Therefore, we focused on the production of L-theanine catalyzed by GMAS as a model of ATP regeneration. Supplying 150 mM ATP, GMAS enzyme could produce 16.8 ± 1.3 g/L L-theanine from 100 mM glutamate. When 5 mM ATP and 5 U/mL ChPPKD82N-K103E were added, the yield of L-theanine was 16.6 ± 0.79 g/L with the conversion rate of 95.6 ± 4.5% at 4 h. Subsequently, this system was scaled up to 200 mM and 400 mM glutamate, resulting in the yields of L-theanine for 32.3 ± 1.6 g/L and 62.7 ± 1.1 g/L, with the conversion rate of 92.8 ± 4.6% and 90.1 ± 1.6%, respectively. In addition, we also constructed an efficient ATP regeneration system from glutamate to glutamine, and 13.8 ± 0.2 g/L glutamine was obtained with the conversion rate of 94.4 ± 1.4% in 4 h after adding 6 U/ mL GS enzyme and 5 U/ mL ChPPKD82N-K103E, which further laid the foundation from glutamine to L-theanine catalyzed by GGT enzyme. This proved that giving the reaction an efficient ATP supply driven by the mutant enzyme enhanced the conversion rate of substrate to product and maximized the substrate value. This is a positively combination of high yield, high conversion rate and high economic value of enzyme catalysis. The mutant enzyme will further power the ATP-consuming biocatalytic reaction platform sustainably.
Alanine dehydrogenases from four different microorganisms: characterization and their application in L-alanine production
Authors: Gu Pengfei , Ma Qianqian , Zhao Shuo , Li Qiang , Gao Juan
Published: August 2023

Background

Alanine dehydrogenase (AlaDH) belongs to oxidoreductases, and it exists in several different bacteria species and plays a key role in microbial carbon and nitrogen metabolism, spore formation and photosynthesis. In addition, AlaDH can also be applied in biosynthesis of L-alanine from cheap carbon source, such as glucose.

Results

To achieve a better performance of L-alanine accumulation, system evaluation and comparison of different AlaDH with potential application value are essential. In this study, enzymatic properties of AlaDH from Bacillus subtilis 168 (BsAlaDH), Bacillus cereus (BcAlaDH), Mycobacterium smegmatis MC2 155 (MsAlaDH) and Geobacillus stearothermophilus (GsAlaDH) were firstly carefully investigated. Four different AlaDHs have few similarities in optimum temperature and optimum pH, while they also exhibited significant differences in enzyme activity, substrate affinity and enzymatic reaction rate. The wild E. coli BL21 with these four AlaDHs could produce 7.19 g/L, 7.81 g/L, 6.39 g/L and 6.52 g/L of L-alanine from 20 g/L glucose, respectively. To further increase the L-alanine titer, competitive pathways for L-alanine synthesis were completely blocked in E. coli. The final strain M-6 could produce 80.46 g/L of L-alanine with a yield of 1.02 g/g glucose after 63 h fed-batch fermentation, representing the highest yield for microbial L-alanine production.

Conclusions

Enzyme assay, biochemical characterization and structure analysis of BsAlaDH, BcAlaDH, MsAlaDH and GsAlaDH were carried out. In addition, application potential of these four AlaDHs in L-alanine productions were explored. The strategies here can be applied for developing L-alanine producing strains with high titers.
Quercetin inhibits Toxoplasma gondii tachyzoite proliferation and acts synergically with azithromycin
Authors: Abugri Daniel A. , Wijerathne Sandani V. T. , Sharma Homa Nath , Ayariga Joseph A. , Napier Audrey , Robertson Boakai K.
Published: August 2023

Quercetin (QUE) is a natural polyphenol known to have numerous pharmacological properties against infectious and non-infectious diseases. Azithromycin (AZ) is an antibiotic that belongs to the azalide class of antimicrobials and an antiparasitic that is known to be effective in combination with clindamycin against pyrimethamine/sulfadiazine-resistant Toxoplasma gondii tachyzoites in clinical settings. Both compounds are known to target protein synthesis and have anti-inflammatory properties. However, little is known about QUE and AZ synergistic interaction against T. gondii growth. Here, we report for the first time the effects of the combination of QUE and AZ on T. gondii growth. The 50% inhibitory concentration (IC50) for QUE at 72 h of interaction was determined to be 0.50 µM, whereas AZ gave an IC50 value of 0.66 µM at 72 h of interaction with parasites. Combination testing of QUE and AZ in a ratio of 2:1 (QUE:AZ) showed an IC50 value of 0.081 µM. Interestingly, a fractional inhibitory index value of 0.28 was observed, indicating a strong synergy. QUE was also found to upregulate the generation of reactive oxygen species and cause dysfunction of the mitochondria membrane of both intracellular and extracellular T. gondii tachyzoites. Overall, the results indicate that QUE is a novel lead capable of synergizing with AZ for inhibiting T. gondii growth and may merit future investigation in vivo for possible combination drug development.

Graphical Abstract
A method to recommend cloud manufacturing service based on the spectral clustering and improved Slope one algorithm
Authors: Hu Qiang , Qi Haoquan , Huang Wen , Liu Minghua
Published: August 2023

The booming growth of cloud manufacturing services provides users with more choices. However, cloud manufacturing service recommendation remains a challenging issue due to numerous similar candidate services and diverse user preferences. The purpose of this paper is to provide an efficient and accurate cloud manufacturing service recommendation method. A spectral clustering algorithm is first designed to cluster the cloud manufacturing services. Then the candidate rating service set is constructed based on the service clusters by service function comparison and parameter matching. Finally, an improved Slope one algorithm, which integrates user similarity and service similarity, is proposed to rate the cloud manufacturing services. The top-k services with the highest scores are recommended to the users. Experiments show that the proposed method can provide more accurate service rating with less time consumption. The service recommendation performance of this method is also proved to be superior to other methods in terms of precision, recall, and F-score.
Tackling global health security by building an academic community for One Health action
Authors: Zhang Xiao-Xi , Li Xin-Chen , Zhang Qi-Yu , Liu Jing-Shu , Han Le-Fei , Lederman Zohar , Schurer Janna M. , Poeta Patrícia , Rahman Md. Tanvir , Li Shi-Zhu , Kassegne Kokouvi , Yin Kun , Zhu Yong-Zhang , Xia Shang , He Lu , Hu Qin-Qin , Xiu Le-Shan , Xue Jing-Bo , Zhao Han-Qing , Wang Xi-Han , Wu Logan , Guo Xiao-Kui , Wang Zhao-Jun , Schwartländer Bernhard , Ren Ming-Hui , Zhou Xiao-Nong
Published: August 2023

Background

One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet.

Main text

The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation.

Conclusions

The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

Graphical Abstract
Multi-center evaluation of machine learning-based radiomic model in predicting disease free survival and adjuvant chemotherapy benefit in stage II colorectal cancer patients
Authors: Zhu Hui , Hu Muni , Ma Yanru , Yao Xun , Lin Xiaozhu , Li Menglei , Li Yue , Wu Zhiyuan , Shi Debing , Tong Tong , Chen Haoyan
Published: August 2023

Background

Our study aimed to explore the potential of radiomics features derived from CT images in predicting the prognosis and response to adjuvant chemotherapy (ACT) in patients with Stage II colorectal cancer (CRC).

Methods

A total of 478 patients with confirmed stage II CRC, with 313 from Shanghai (Training set) and 165 from Beijing (Validation set) were enrolled. Optimized features were selected using GridSearchCV and Iterative Feature Elimination (IFE) algorithm. Subsequently, we developed an ensemble random forest classifier to predict the probability of disease relapse.We evaluated the performance of the model using the concordance index (C-index), precision-recall curves, and area under the precision-recall curves (AUCPR).

Results

A radiomic model (namely the RF5 model) consisting of four radiomics features and T stage were developed. The RF5 model performed better than simple radiomics features or T stage alone, with higher C-index and AUCPR, as well as better sensitivity and specificity (C-indexRF5: 0.836; AUCPR = 0.711; Sensitivity = 0.610; Specificity = 0.935). We identified an optimal cutoff value of 0.1215 to split patients into high- or low-score subgroups, with those in the low-score group having better disease-free survival (DFS) (Training Set: P = 1.4e-11; Validation Set: P = 0.015). Furthermore, patients in the high-score group who received ACT had better DFS compared to those who did not receive ACT (P = 0.04). However, no statistical difference was found in low-score patients (P = 0.17).

Conclusion

The radiomic model can serve as a reliable tool for assessing prognosis and identifying the optimal candidates for ACT in Stage II CRC patients.

Trial registration

Retrospectively registered.
The DOTA macrocyclic cavity in metallic radiopharmaceuticals: Mythology or reality?
Authors: Duatti Adriano
Published: August 2023

Background

The hypothetical concept of ‘macrocyclic cavity’ is largely employed as useful model to interpret the affinity of metal ions for the macrocyclic chelating ligand 2,2′,2′′,2′′′-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (H4DOTA). It Is hypothesized that a close matching between the size of the macrocyclic cavity and that of the metallic ion is a key parameter to ensure the high-yield formation of stable coordination metal-DOTA complex. This approach has become popular in the design of radiopharmaceuticals containing radiometals and H4DOTA as chelating group.

Results

Based on X-ray structural data of metallic complexes formed by the ligand H4DOTA upon coordination with a variety of metals, an elementary argument based on Euclidean geometry is presented here that questions the existence of the hypothetical ‘macrocyclic cavity’ within the chelator macrocycle. The geometrical analysis was applied to the complex formed by a Ga3+ ion coordinated to H4DOTA as model compound.

Conclusions

Application of Euclidean geometry to calculate bond angles in the coordination complex of the ligand H4DOTA with the Ga+3 ion, supposed to incorporate a hypothetical ‘macrocyclic cavity’, revealed that this conceptual entity has no physical reality and, therefore, cannot be considered a meaningful description of a stable structural arrangement for metallic radiopharmaceuticals.
Relationship pattern of enteric bacterial load and assessed micronutrients in the gut of Clarias gariepinus fish sampled in the Ibadan municipal zone
Authors: Umma Samuel Bem , Iyiola Adams Ovie , Adeshina Ibrahim
Published: August 2023

Background

Farmed fish are faced with factors like microflora and micronutrients that could impact their prime health. There is no clear understanding of some specific bacterial flora amidst micronutrients in the gut of the African sharp-tooth catfish (Clarias gariepinus); hence, this study investigated the encountered bacterial flora, micronutrients and their interactions with the aid of standard microbiological procedures and atomic absorption spectroscopy.

Results

The bacterial counts in the Ibadan municipal zones were significantly different (P˂0.05) across each sampling week, with prevalence ranging from 0.40 ± 0.1 in Ibadan North to 0.10 ± 0.00 in Ibadan Northwest. The pattern of encountered bacterial flora indicated Ibadan North (Enterobacter species: 3.70 ± 0.07 × 106 CFU/g) as the prevalent. The assessed gut micronutrients were significantly different (P˂0.05) across the farm areas; however, sodium was not significantly different (P˂0.05) in Ibadan Northeast (0.97 ± 0.02) and Ibadan Southwest (0.98 ± 0.01), manganese in Ibadan North (10.50 ± 0.07) and Ibadan Northeast (11.00 ± 0.71), cobalt in Ibadan North (0.00 ± 0.00), Ibadan Northeast (0.00 ± 0.00) and Ibadan Southeast (0.00 ± 0.00). Zinc (92.55 ± 0.01 mg/kg), chromium (13.11 ± 0.22 mg/kg), cadmium (0.82 ± 0.00 mg/kg) and cobalt (6.94 ± 0.22 mg/kg) were predominantly high in Ibadan Northwest, sodium (0.98 ± 0.01 mg/kg) in Ibadan Southwest, lead (4.37 ± 0.01 mg/kg) and copper (34.10 ± 0.07 mg/kg) in Ibadan Southeast. The gut bacterial were positively correlated with manganese, iron, zinc, nickel, potassium and sodium; however, they were negatively correlated with copper, lead, chromium, cadmium and cobalt.

Conclusions

Therefore, the present study identified some fish farm areas in the Ibadan municipal zones with prevalent gut bacterial load; this is possibly due to the state of the culture environment and also the interactions of the gut bacterial flora with micronutrients, which could be a potential health indicator.
MRm-DLDet: a memory-resident malware detection framework based on memory forensics and deep neural network
Authors: Liu Jiaxi , Feng Yun , Liu Xinyu , Zhao Jianjun , Liu Qixu
Published: August 2023

Cyber attackers have constantly updated their attack techniques to evade antivirus software detection in recent years. One popular evasion method is to execute malicious code and perform malicious actions only in memory. Malicious programs that use this attack method are called memory-resident malware, with excellent evasion capability, and have posed huge threats to cyber security. Traditional static and dynamic methods are not effective in detecting memory-resident malware. In addition, existing memory forensics detection solutions perform unsatisfactorily in detection rate and depend on massive expert knowledge in memory analysis. This paper proposes MRm-DLDet, a state-of-the-art memory-resident malware detection framework, to overcome these drawbacks. MRm-DLDet first builds a virtual machine environment and captures memory dumps, then creatively processes the memory dumps into RGB images using a pre-processing technique that combines deduplication and ultra-high resolution image cropping, followed by our neural network MRmNet in MRm-DLDet to fully extract high-dimensional features from memory dump files and detect them. MRmNet receives the labeled sub-images of the cropped high-resolution RGB images as input of ResNet-18, which extracts the features of the sub-images. Then trains a network of gated recurrent units with an attention mechanism. Finally, it determines whether a program is memory-resident malware based on the detection results of each sub-image through a specially designed voting layer. We created a high-quality dataset consisting of 2,060 benign and memory-resident programs. In other words, the dataset contains 1,287,500 labeled sub-images cut from the MRm-DLDet transformed ultra-high resolution RGB images. We implement MRm-DLDet for Windows 10, and it performs better than the latest methods, with a detection accuracy of up to 98.34$$\%$$%. Moreover, we measured the effects of mimicry and adversarial attacks on MRm-DLDet, and the experimental results demonstrated the robustness of MRm-DLDet.
Sleep disorders linked to quality of life in a sample of Egyptian policemen a comparative study between shift workers and non-shift workers
Authors: Naguib Rehab Mohamed , Omar Abdel Nasser Mahmoud , ElKhayat Naglaa Mohamed , Khalil Sherien Ahmed , Kotb Mostafa Ahmed Mohamed , Azzam Lobna
Published: August 2023

Background

Poor sleep is associated with bad health outcomes, worse well-being and decreases in performance, productivity and safety at work. Police officers are exposed to several risk factors including extended work schedules, shift work, occupational stress, dangerous and traumatic events and can, as such, develop sleep problems.

So, this study aimed to compare quality of life, occupational stress level, between shift and non-shift workers’ policemen working at El-Agouza Police Hospital.

This was a cross-sectional comparative study conducted on 64 policemen working in 6 different Police department recruited from sleep clinic neuropsychiatry department at EL-Agouza Police Hospital serving police officers in El-Nile Street, Giza, Egypt. The total included cases were classified to two groups: group I (shift workers) included 32 of shift workers who provide service across, all 24 h of the clock each day of the week (often abbreviated as 24/7), group II (non-shift workers): included 32 of non-shift workers.

Results

Occurrence of sleep disorders was significantly higher in the shift workers compared to the non-shift worker group (p < 0.01).

Conclusions

In the current population-based study of police officers, poor sleep quality was more prevalent among officers who were engaged in shift work. The findings are consistent with prior evidence that night shift carried the greatest risk of poor sleep quality because night-shift officers have to make some adaptations that compensate for their natural circadian patterns.
A retrospective observational study over surgical management of giant thoracic tumours: horrendous but manageable
Authors: Darbari Anshuman , Dutt Bhaskar , Kumar Ajay , Goswami Aakansha Giri , Starlet Abisho R.
Published: August 2023

Background

Giant thoracic tumour (GTT) does not have a clear definition, but, as per usual terminology, they are thoracic masses whose long axis is > 10 cm or covering more than 50% of the hemithorax. The mediastinum is a unique space in the thoracic cavity that can have a wide range of masses of different cellular origins imposing both diagnostic and therapeutic challenges. This retrospective observational study aims to evaluate the surgical treatment outcomes of giant intrathoracic tumours and final histopathological diagnosis with evidence for manageability. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines has been followed for reporting this observational study.

Results

Between January 2018 and December 2022, the medical data of a total of 11 patients (06 males, 05 females; age range, 05 to 52 years) who underwent radical surgery for GTT in our centre were retrospectively reviewed in this observational study. We evaluated presenting symptoms, radiological findings, presumptive pathological diagnosis, and surgically excised mass gross and histopathological examination. Six (54.5%) of our patients were male, and five (45.5%) were female. The age range was between 05 and 52 years. The tumour localisations of our patients were five (45.5%) hemithorax and six (54.5%) mediastinal. The largest excised mass was 26 × 24 × 12 cm, and the heaviest mass was 3600 g. All patients underwent conventional open surgery. The overall survival was 100%, with no immediate postoperative mortality, indicating an excellent prognosis despite a dreadful appearance.

Conclusion

Due to neighbouring vascular structures, the surgical resection of manoeuvres in this crucial cavity with the excision of giant masses may be difficult and tricky. Preoperative diagnostic investigations and planning play a significant role in accurately localising the mass and the invasion possibility of adjacent vital structures. The results of this study may provide scientific evidence to guide the treatment of giant thoracic tumours in clinical practice.
A resected case of malignant peripheral nerve sheath tumor arising in the cervical esophagus
Authors: Nakagawa Eito , Miura Akinori , Suzuki Kunihito , Saito Katsumasa , Shinohara Hajime , Ueno Koudai , Naito Yu , Motoi Toru
Published: August 2023

We report herein a case of malignant peripheral nerve sheath tumor (MPNST), an extremely rare, esophageal malignancy. A 67-year-old, female patient presented with a nodular lesion in the cervical esophagus which was detected on follow-up computed tomography (CT) after surgery for bilateral breast cancer and gastric cancer. Upper gastrointestinal endoscopy revealed a hemispheric, submucosal lesion in the cervicothoracic esophagus. Endoscopic ultrasound-guided fine needle aspiration cytology revealed spindle-shaped cells with nuclear atypia and positive staining for the S100 protein, a neurogenic marker. Based on clear CT findings of lesion growth over two years, MPNST was diagnosed, and treatment for sarcoma was begun. After one course of preoperative chemotherapy, open resection of the esophagus was performed, revealing a solid, white tumor with a maximum diameter of 1.8 cm. The tumor was histopathologically found to be located within the intrinsic muscularis propria. Based on this finding, low-grade MPNST with a schwannoma-like component at its margins was diagnosed. Approximately 50% of MPNST cases occur against a background of neurofibromatosis type 1 (NF1) while about 40% occur sporadically, and 10% occur after irradiation. The patient’s history of radiotherapy for left breast cancer may have contributed to the development of the MPNST.
Resource availability and capacity to implement multi-stranded cholera interventions in the north-east region of Nigeria
Authors: Elimian Kelly , Musah Anwar , Dewa Ozius , King Carina , Crawford Katerina , Pembi Emmanuel , Ike Ifeanyi , Myles Puja , Pritchard Catherine , Forsberg Birger Carl , Alfven Tobias
Published: August 2023

Background

Limited healthcare facility (HCF) resources and capacity to implement multi-stranded cholera interventions (water, sanitation, and hygiene (WASH), surveillance, case management, and community engagement) can hinder the actualisation of the global strategic roadmap goals for cholera control, especially in settings made fragile by armed conflicts, such as the north-east region of Nigeria. Therefore, we aimed to assess HCF resource availability and capacity to implement these cholera interventions in Adamawa and Bauchi States in Nigeria as well as assess their coordination in both states and Abuja where national coordination of cholera is based.

Methods

We conducted a cross-sectional survey using a face-to-face structured questionnaire to collect data on multi-stranded cholera interventions and their respective indicators in HCFs. We generated scores to describe the resource availability of each cholera intervention and categorised them as follows: 0–50 (low), 51–70 (moderate), 71–90 (high), and over 90 (excellent). Further, we defined an HCF with a high capacity to implement a cholera intervention as one with a score equal to or above the average intervention score.

Results

One hundred and twenty HCFs (55 in Adamawa and 65 in Bauchi) were surveyed in March 2021, most of which were primary healthcare centres (83%; 99/120). In both states, resource availability for WASH indicators had high to excellent median scores; surveillance and community engagement indicators had low median scores. Median resource availability scores for case management indicators ranged from low to moderate. Coordination of cholera interventions in Adamawa State and Abuja was high but low in Bauchi State. Overall, HCF capacity to implement multi-stranded cholera interventions was high, though higher in Adamawa State than in Bauchi State.

Conclusions

The study found a marked variation in HCF resource availability and capacity within locations and by cholera interventions and identified cholera interventions that should be prioritised for strengthening as surveillance and laboratory, case management, and community engagement. The findings support adopting a differential approach to strengthening cholera interventions for better preparedness and response to cholera outbreaks.
Bfra-loaded nanoparticles confer protection against paratuberculosis infection
Authors: Liu Yiduo , Chen Yulan , Liang Zhengmin , Luo Lijia , Wang Yuanzhi , Wang Haoran , Ge Xin , Sreevatsan Srinand , Zhou Xiangmei
Published: August 2023

Paratuberculosis is a chronic wasting disease of granulomatous enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis, MAP) resulting in heavy economic losses to dairy industries worldwide. Currently, commercial vaccines were not effective in preventing pathogen shedding and were reported with serious side effects. To develop a novel and smarter paratuberculosis vaccine, we utilized PLGA nanoparticles encapsulating the Bfra antigen (Bfra-PLGA NPs). We observed that mice vaccinated with Bfra-PLGA NPs exhibited an enhanced secretory IFN-γ, CD4+ T cells response and antibody IgG against MAP infection. In addition, secretions of the inflammatory cytokine TNF-α and IL-10 were increased following treatment with Bfra-PLGA NPs. A significant reduction in bacterial load was observed in the livers and spleens of animals vaccinated with Bfra-PLGA NPs. Furthermore, Bfra-PLGA NPs were effective to alleviate the pathological lesions of livers in mice. Overall, our approach provides a rational basis for employing PLGA nanoparticles to develop improved vaccines that induced protective immunity against paratuberculosis.

Graphical Abstract
Improving mental health care in depression: A call for action
Authors: Eder Julia , Dom Geert , Gorwood Philip , Kärkkäinen Hikka , Decraene Andre , Kumpf Ulrike , Beezhold Julian , Samochowiec Jerzy , Kurimay Tamas , Gaebel Wolfgang , De Picker Livia , Falkai Peter
Published: August 2023

Depressive disorders have one of the highest disability-adjusted life years (DALYs) of all medical conditions, which led the European Psychiatric Association to propose a policy paper, pinpointing their unmet health care and research needs. The first part focuses on what can be currently done to improve the care of patients with depression, and then discuss future trends for research and healthcare. Through the narration of clinical cases, the different points are illustrated. The necessary political framework is formulated, to implement such changes to fundamentally improve psychiatric care. The group of European Psychiatrist Association (EPA) experts insist on the need for (1) increased awareness of mental illness in primary care settings, (2) the development of novel (biological) markers, (3) the rapid implementation of machine learning (supporting diagnostics, prognostics, and therapeutics), (4) the generalized use of electronic devices and apps into everyday treatment, (5) the development of the new generation of treatment options, such as plasticity-promoting agents, and (6) the importance of comprehensive recovery approach. At a political level, the group also proposed four priorities, the need to (1) increase the use of open science, (2) implement reasonable data protection laws, (3) establish ethical electronic health records, and (4) enable better healthcare research and saving resources.
Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase Ib/II study.
Authors: Wang Xiaojia , Lee Keun Seok , Zeng Xiaohua , Sun Tao , Im Young-Hyuck , Li Huiping , Wang Kun , Li Huiyan , Zhou Ping , Bao Yuanyuan , Jiang Zefei
Published: August 2023

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Background: Despite HER2-targeted agents improving outcomes in HER2-positive (+) BC, some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. Preliminary results from this Phase Ib/II trial (NCT04276493) showed that zani plus docetaxel had a manageable safety profile and demonstrated promising antitumor activity in pts with advanced HER2+ BC; here we present the updated data following enrollment completion. Methods: Cohort 1 of this open-label study is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ BC who may have received prior neoadjuvant/adjuvant therapy. Cohort 1a pts received zani 30 mg/kg intravenously (IV), Cohort 1b pts received zani 1800 mg IV, both with docetaxel 75 mg/m2 IV every 3 weeks. The primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR) and disease control rate (DCR). Results: As of Nov 22, 2022, 37 pts(median age 55.0 years [range: 33-80]) were assigned to Cohort 1a (n=10) or 1b (n=27). Median study follow-up was 15.5 months (range: 1.1-29.3); patients received a median of 13 treatment cycles (range 1-37) and 18 (48.6%) pts remained on treatment. Of the 33-efficacy evaluable (EE) pts, confirmed ORR was 90.9% (95% confidence interval [CI]: 75.7, 98.1). Efficacy data are summarized in the table. In total, 36 (97.3%) pts experienced ≥1 treatment-related adverse event (TRAE); 25 (67.6%) pts experienced ≥grade 3 TRAEs. The most common ≥grade 3 TRAEs were decreased neutrophil count, experienced by 18 (48.6%) pts, and decreased white blood cell count, experienced by 7 (18.9%) pts. Serious TRAEs occurred in 6 (16.2%) pts; no TRAEs led to death. Conclusions: Zani combined with docetaxel demonstrated promising antitumor activity as 1L therapy for advanced HER2+ BC, with a manageable safety profile. Clinical trial information: NCT04276493 . [Table: see text]
Disparities in delayed diagnosis and pain management among African American women with breast cancer.
Authors: Leach Virginia
Published: August 2023

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Background: Breast Cancer (BC) mortality rates disproportionately affect African American (AA) women over other racial or ethnic group in the United States. Research demonstrates AA women also have disparate rates of an accurate diagnosis and pain management care. Methods: This study addressed barriers to care in diagnosis and pain management care experienced by members of a non-profit organization called the Tigerlily Foundation (TLF), a breast cancer advocacy organization, who design culturally relevant educational materials to support medically underserved populations. This qualitative study interviewed AA women in an IRB-approved study (University of Illinois at Urbana-Champaign). The total duration of each interview lasted a maximum of 1 hour and 45 minutes with participants answering one pre-interview questionnaire for demographic purposes and completing one interview. Results: Among 20 AA women breast cancer survivors, it was discovered participants 90% were delayed, dismissed, and denied screening options to detect their breast cancer diagnosis as early as possible. After several months of displaying anomalies within their breasts (i.e., lump, swelling, pain, nipple discharge), participants had to negotiate with their PCPs to finally get a mammogram, ultrasound, and biopsy. 70% of participants described radiation as excruciating pain. Pain management varied as 10% of participants were offered access to a wound care specialist and received adequate medication to cope with the pain, while 90% of participants received nothing. Those who did not receive assistance tried homeopathic solutions for pain management. Conclusions: Notable differences among AA women breast cancer survivors demonstrated the need for healthcare institutions to review potentially racially bias policies harming this demographic of patients. Future studies among AA populations with disparate breast cancer diagnosis and pain management are needed to improve health outcomes.
Automated classification of disease response in radiology reports using natural language processing.
Authors: Ong Hai Xiang , Cai Yiyu , Yi Zi Meng , Tee Wen Hui , Tan Ying Cong Ryan Shea , Tan Wei Chong , Bakr Azam Abu
Published: August 2023

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Background: Classification of disease response is an essential task in cancer research and needs to be done at scale. Automating this process can improve efficiency in the generation of real-world evidence, potentially leading to better patient outcomes. We aim to develop and evaluate Natural Language Processing (NLP) models for this task. Methods: Using 6203 computed tomography (CT) and 1358 magnetic resonance imaging (MRI) reports from 587 patients with lung cancer of all stages seen at the National Cancer Centre Singapore (NCCS), we trained four NLP models (BioBERT, RadBERT-RoBERTA, BioClinicalBERT, GatorTron) to classify the reports into one of four categories: no evidence of disease, stable disease, partial response or disease progression. Model output was compared against human-curated ground truth and performance was evaluated by accuracy. Results: Of the 4 models, GatorTron performed the best (accuracy = 97.1%), followed by RadBERT-RoBERTA (accuracy = 96.2%), BioBERT (accuracy = 94.2%), with BioClinicalBERT being last (accuracy = 90.4%). NLP Model runtimes for the dataset were relatively short, with BioBERT and BioClinicalBERT taking 3 minutes per epoch, RadBERT-RoBERTA taking 6 minutes per epoch, and GatorTron taking 10 minutes per epoch on a single central processing unit (CPU). Conclusions: We have demonstrated the effectiveness of NLP models for classifying disease responses in radiology reports of lung cancer patients. This has the potential to help derive progression-free survival for real-world evidence generation.
Comparisons between HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 ER+ HER2- breast cancer.
Authors: Ahn Sung Gwe , Kook Yoonwon , Bae Soong June , Lee Sae Byul , Jeong Joon
Published: August 2023

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Background: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among ER+HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. Methods: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 IHC and SISH test. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS)>25. Multivariable binary logistic-regression analysis was performed. Results: Of these, 944 (41.1%) were assigned in the HER2-zero, and 1351 (58.9%) were in the HER2-low. The averages of RS were 17.082 in the HER2-zero breast cancer and 18.503 in the HER2-low, respectively (P-value<0.005). HER2 score identified by qRT-PCR was 8.912 in the HER2 zero group and was 9.337 in the HER2 low group (P<0.005). When we compared a proportion of high RS between two groups, the high RS rate was 12.4% (117 of 944) in the HER2-zero, while it was 17.0% (230 of 1351) in the HER2-low (p=0.002). In multivariable analysis, HER2-low was demonstrated as an independent factor for high RS with an odds ratio 1.517 (1.172-1.964) independent of ER, PR, and Ki67. Within the subgroup with invasive ductal carcinoma, the high RS rates of HER2-low and HER2-zero were 19% and 14%, respectively. In the all patients, recurrence-free survival and overall survival did not differ between HER2-low and HER2-zero groups. Conclusions: Within ER+HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among ER+HER2- breast cancer remains as an area that requires further study.
Phase 3 randomized controlled trial comparing the effectiveness of dexamethasone in reducing cancer-associated fatigue in patients on palliative chemotherapy.
Authors: Radhakrishnan Venkatraman , Vihari Vamsi , Gopalakrishnan Vidhya , Dasapathi Venkata Siva Kiran Kumar , Jayachandran Perumal Kalaiyarasi , Rajaraman Swaminathan , Veeraiah Surendran
Published: August 2023

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Background: Short-term steroids (< 2 weeks) have been used to alleviate fatigue in patients with advanced cancer. However, the efficacy and safety of long-term steroids (12 weeks) in patients with advanced cancer receiving palliative chemotherapy have not been studied. Methods: The study was an open-label, placebo-controlled, phase 3 RCT to evaluate the efficacy and safety of low dose dexamethasone (DEX) in reducing chemotherapy and cancer associated fatigue. Patients aged 18-60 years with performance status ≤2, undergoing palliative chemotherapy for advanced solid malignancies were randomized 1:1 to receive either DEX (4mg/day) or a placebo for 12 weeks. Fatigue was measured using the Symbolic Assessment of Fatigue Extent (SAFE) scale and EORTC FA12 scale, and QOL was assessed using the EORTC QLQ c30 at baseline, 6 weeks, and 12 weeks.The primary endpoint was to compare fatigue between the study arms at 6 weeks. Secondary endpoints were to compare fatigue at 12 weeks, QOL and toxicities. With a power of 80%, α of 5%, 126 patients (including 25% drop-outs) were required to show the superiority of DEX in reducing SAFE fatigue extent score by 50% at 6 weeks. Results: A total of 126 patients were randomized (64 in the placebo arm and 62 in the DEX arm) between Oct 2018-Sep 2022. The median age was 46.5 years and 67% were females. Metastatic breast (28%) and lung (16%) cancer were the common diagnosis. Twelve and 23 patients in the placebo arm and 13 and 22 patients in the DEX arm did not undergo week 6 and 12 assessment respectively due to disease progression. The results showed no significant differences in mean SAFE scores, FA12 scores, or QOL between the study arms at 6 and 12 weeks, except for higher FA12 social sequelae in the DEX arm at 12 weeks (P = 0.048) (Table). There were no significant differences in toxicities between the arms. Conclusions: The results of this study suggest that low-dose DEX is not effective in reducing chemotherapy associated fatigue or improving QOL in patients with advanced cancer. Clinical trial information: CTRI/2018/08/015222 .[Table: see text]
Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175.
Authors: Vu Nam , Manh Dao Tien , Cuong Nguyen Viet , Son Nguyen Hong , Viet Tran Quoc , Onishi Hiroshi
Published: August 2023

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Background: Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most prevalent form of this disease. While surgery remains the cornerstone of treatment for early-stage NSCLC, patients with locally advanced or inoperable NSCLC require alternative therapeutic strategies. Purpose: to assess the long-term survival data and determine the associated factors impacting survival outcomes for patients with locally advanced unresectable non-small cell lung cancer (NSCLC) treated with radiotherapy. Methods: We retrospectively analyzed patients diagnosed with inoperable stage III of NSCLC who received radiation therapy at Hospital 175 from January 2019 to June 2022. The patients had a performance status score (PS) of 0-2 and only one primary lung tumor. We collected patients' background information, including age, gender, pathology, TNM, combination chemotherapy, PET/CT characteristics, and radiotherapy plan parameters. All patients received radiotherapy, at a dose equivalent to 60Gy or more. During radiation therapy, patients were monitored for radiation toxicity. We used the Kaplan-Meier method to estimate overall survival (OS) rate and the Cox regression model to identify the risk factors affecting the treatment outcomes. Results: A total of 240 cases, male: 75%, PS 0, 1, 2 respectively: 24%, 72%, 4%. Histopathological types: squamous cell (9%), glandular cell (83.5%), others (7.5%). Which, subgroups of stages IIIA, IIIB, and IIIC: are 32%, 48%, and 20%. The rate of patients having chemotherapy before radiation was 80.3%, and having PET/CT scans was 43.5%. Patients with radiation alone: 73.4% and concurrent chemoradiotherapy: 26.6%. Median follow-up time: 16.3 months, median OS: 19.5 months. OS rates after 1, 2, and 3 years are 76.2%, 38.8%, and 27.4%, respectively. The most common toxicity was grade 2 esophagitis. Patients who received concurrent chemoradiotherapy had a better prognosis than those who received radiation therapy alone. Regimen of radiation therapy, age, histopathological type, and lymph node metastasis were significant factors affecting overall survival outcomes. Conclusions: Radiotherapy is an essential part of treatment for inoperable NSCLC. The best survival benefit is achieved with concurrent chemoradiotherapy. Besides, age, lymph node metastasis, and histopathological type are also potential factors that can influence patient outcomes.