bluuebunny/crossref_metadata_2025 huggingface dataset:
Food insecurity, income loss, healthcare access, and other exacerbated social inequalities among people experiencing homelessness during the COVID-19 pandemic in Brazil (2021–2023)
Authors: Moura Heriederson Sávio Dias , Canatto Mayla Cristina Dinardi , Berra Thaís Zamboni , Silva Ruan Víctor dos Santos , Rosa Rander Junior , Campos Mônica Chiodi Toscano de , Costa Fernanda Bruzadelli Paulino da , Ribeiro Natacha Martins , Teibo Titilade Kehinde Ayandeyi , Araújo Juliana Soares Tenório de , Tártaro Ariela Fehr , Alves Yan Mathias , Souza Rosa Maria Pinheiro , Uchoa Severina Alice da Costa , Ferezin Letícia Perticarrara , Arcêncio Ricardo Alexandre
Published: July 2024

Background

During COVID-19, the number of people experiencing homelessness increased, further exacerbating the violation of basic rights necessary for human survival. Thus, the study aimed to investigate the inequalities associated with income loss and food insecurity among people experiencing homelessness during the COVID-19 pandemic in Brazil.

Methods

A cross-sectional study was conducted in 24 Brazilian state capitals and the Federal District among the homeless population using a validated instrument. Descriptive analyses and binary logistic regressions were performed.

Results

Among 1512 homeless participants (median age:37, range:18–89), 39.4% had incomplete primary education, 83.7% earned below minimum wage or had no income, 56.5% received government aid, and 87.1% used the Sistema Único de Saúde (Brazilian Public Health System-SUS). During the pandemic, 42.0% faced food difficulties, and 26.3% experienced income loss. Across Brazilian macroregions, lack of employment affected four regions, with high SUS dependency and food scarcity. In the North (72.7%) and Northeast (51.9%), most lacked government aid, while in the Midwest (51.6%), temporary income loss prevailed. In regression analyses, men, black/mixed race, those married or in a stable union, government aid recipients, and SUS users had greater difficulty acquiring food during COVID-19. Men with incomplete high school or higher education and income above minimum wage were less likely to suffer temporary income loss, and black/mixed race individuals and those living on the streets were more likely.

Conclusions

The study showed how socioeconomic factors increased income loss and food acquisition difficulties during COVID-19, exacerbating vulnerability and social inequities for the people experiencing homelessness.
Re-Purposing the Ordering of Routine Laboratory Tests in Hospitalized Medical Patients (RePORT): protocol for a multicenter stepped-wedge cluster randomised trial to evaluate the impact of a multicomponent intervention bundle to reduce laboratory test over-utilization
Authors: Ambasta Anshula , Holroyd-Leduc Jayna M. , Pokharel Surakshya , Mathura Pamela , Shih Andrew Wei-Yeh , Stelfox Henry T. , Ma Irene , Harrison Mark , Manns Braden , Faris Peter , Williamson Tyler , Shukalek Caley , Santana Maria , Omodon Onyebuchi , McCaughey Deirdre , Kassam Narmin , Naugler Chris
Published: July 2024

Background

Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada.

Methods

We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2–3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes.

Discussion

The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work.

Trial Registration

This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic.clinicaltrials.gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1
Transcriptomic response of prostate cancer cells to carbon ion and photon irradiation with focus on androgen receptor and TP53 signaling
Authors: Hänze Jörg , Mengen Lilly M. , Mernberger Marco , Tiwari Dinesh Kumar , Plagge Thomas , Nist Andrea , Subtil Florentine S. B. , Theiss Ulrike , Eberle Fabian , Roth Katrin , Lauth Matthias , Hofmann Rainer , Engenhart-Cabillic Rita , Stiewe Thorsten , Hegele Axel
Published: July 2024

Background

Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling.

Methods

Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis.

Results

Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified.

Conclusion

Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.
Examining the performance of responding to the Khoy earthquake 2022, challenges, strengths, and lessons learned: thematic analysis
Authors: Nazari Saeed , Kolivand Pirhossein , Zamani Elham , Karimi Kivi Hamid , Norouzi Razieh
Published: July 2024

Objective

Disasters in developing countries result in higher human and financial losses compared to global standards, with the death rate being 12 times higher than that of developed countries. Many experts attribute the failures in disaster management to the lack of a system for documenting and analyzing disaster management functions and not leveraging the experiences and lessons learned. This study employed a qualitative data collection approach, utilizing semi-structured interviews with managers, deputies, members of operational teams, and individuals affected by the disaster in the area. This research aims to explore the challenges, strengths, and lessons learned from the response to the Khoy earthquake in Iran.

Results

After conducting 40 interviews and achieving data saturation, we extracted experiences and lessons learned to investigate the performance of responsible organizations in the 2022 Khoy earthquake. The obtained data were categorized into 8 categories and 39 sub-categories. These categories encompassed warning and calling forces, disaster assessment, disaster commanding, emergency housing, supply and distribution of items, organization, and guidance of public participation and charities, psychological support, logistics operations, monitoring, evaluation, documentation, information dissemination, and media management. Planners and operational managers can use the findings to review and revise their action and prevention plans.
APP dyshomeostasis in the pathogenesis of Alzheimer’s disease: implications for current drug targets
Authors: Sirisi Sònia , Sánchez-Aced Érika , Belbin Olivia , Lleó Alberto
Published: July 2024

The Amyloid precursor protein (APP) is a transmembrane glycoprotein from which amyloid-β (Aβ) peptides are generated after proteolytic cleavage. Aβ peptides are the main constituent of amyloid plaques in Alzheimer’s Disease (AD). The physiological functions of APP in the human adult brain are very diverse including intracellular signaling, synaptic and neuronal plasticity, and cell adhesion, among others. There is growing evidence that APP becomes dysfunctional in AD and that this dyshomeostasis may impact several APP functions beyond Aβ generation. The vast majority of current anti-amyloid approaches in AD have focused on reducing the synthesis of Aβ or increasing the clearance of brain Aβ aggregates following a paradigm in which Aβ plays a solo in APP dyshomeostasis. A wider view places APP at the center stage in which Aβ is an important, but not the only, factor involved in APP dyshomeostasis. Under this paradigm, APP dysfunction is universal in AD, but with some differences across different subtypes. Little is known about how to approach APP dysfunction therapeutically beyond anti-Aβ strategies. In this review, we will describe the role of APP dyshomeostasis in AD beyond Aβ and the potential therapeutic strategies targeting APP.
Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway
Authors: An Yue-peng , Yuan Rui , Wang Shan-shan , Yang Su-qing , Zhang Qing
Published: July 2024

Objective

The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU).

Methods

The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues.

Results

Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats.

Conclusion

Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.
Sigmoid and cecum colon volvulus: a case report
Authors: Charo Dilawer Chofan , Mohammad Fares Medhat , Ghmera Mahmoud Issam , Saker Batoul Aksam , Ghosnah Ayman Ali
Published: June 2024

Introduction

Colon volvulus is the twisting of a segment of colon on its mesenteric axis, which can lead to the obstruction of the lumen and the blood supply. Colon volvulus is common in “volvulus belt” countries and can involve the sigmoid (60–70%) and cecum (25–40%).

Case presentation

We report a case of a 47-year-old male, Alawites, who presented with bowel obstruction and dilated abdomen without any specific abdominal pain. Abdominal laparotomy showed both sigmoid and cecum volvulus with no signs of perforation or ischemia.

Discussion and conclusion

One of the possible risk factors of sigmoid colon volvulus is the length of the rectum and sigmoid, while mobile cecum is considered as a possible reason for cecum volvulus. The management remains controversial and is specific for every case, depending mainly on the vitality of the colonic walls and the general condition of the patient.
DUF3055 from Staphylococcus aureus adopts unique strategy for structural distinctiveness
Authors: Kim Hyo Jung , Kim Hyoun Sook
Published: July 2024

Staphylococcus aureus remains a public health threat with the WHO classifying the pathogen as a high priority in the development of new antimicrobial agents. Whole genome sequencing has revealed a number of conserved genes that may be essential for cell viability and infection. Characterising the structure and function of these proteins will inevitably aid development of new antimicrobials. Therefore, this study elucidated the structure of hypothetical protein DUF3055 from S. aureus stain Mu50. The protein possesses an as yet undefined function and a unique fold. The size of DUF3055 made it an ideal candidate for NMR characterisation which in conjunction with circular dichroism revealed the protein to be folded. Crystallisation and structural solution found that the overall dimer fold has a negatively charged surface formed by a β-bulge and tightly crossed α-helices, with a complementary size to a DNA single turn. Our structural observations suggest that hypothetical protein DUF3055 from S. aureus has a role in DNA binding and gene regulation.
Uncovering insights from big data: change point detection of classroom engagement
Authors: Nakamura Kohei , Ishihara Manabu , Horikoshi Izumi , Ogata Hiroaki
Published: July 2024

Expectations of big data across various fields, including education, are increasing. However, uncovering valuable insights from big data is like locating a needle in a haystack, and it is difficult for teachers to use educational big data on their own. This study aimed to understand changes in student participation rates during classes and teachers’ teaching styles by analyzing educational big data. In the analysis, data from 120 students and two mathematics class teachers at a public junior high school in Japan were used. We applied the pruned exact linear time (PELT) algorithm to automatically identify significant changes in student participation during class. Based on the information obtained, we analyzed the interaction logs of teachers’ e-book readers and clarified the relationship between student participation rates and teacher behavior patterns. Change point detection using the PELT algorithm showed a high F1-score of 0.7929, indicating good overall performance. We also investigated whether there was a relationship between class differences and teachers’ actions and found a statistically significant difference. The results provide clues for improving student learning engagement and teachers’ teaching styles, and they are expected to improve the quality of education by automatically identifying notable cases from educational big data. However, further research is required to improve data analysis methods, such as adjusting the parameters of algorithms based on the situation.
Does ‘sub-threshold’ ventilatory stress promote healing after lung injury?
Authors: Marini John J. , Kummer Rebecca L. , Rocco Patricia R. M.
Published: July 2024

Excessive tidal stretching may initiate damage or retard healing after lung injury. However, it is seldom considered whether intracycle power and ventilatory forces of lesser magnitude than those required to cross an injury threshold might stimulate or accelerate beneficial adaptive responses. Acute lung injury is a dynamic process that may exhibit phase-dependent reparative responses to mechanical stress broadly similar to physical training, body trauma or sepsis. We propose that lower stress may not always be better through all phases of ARDS; moderately high tidal airway pressures that stay below the threshold of global injury may have potential to speed healing of the injured lung.
Investigation of fingolimod-induced lymphocyte sequestration on inflammatory response and neurological damages after cardiac arrest
Authors: Abi Zeid Daou Yara , Lidouren Fanny , Bois Antoine , Watanabe Naoto , Jendoubi Ali , Faucher Estelle , Surenaud Mathieu , Chateau-Joubert Sophie , Hue Sophie , Ghaleh Bijan , Kohlhauer Matthias , Tissier Renaud
Published: July 2024

Background

A sepsis-like syndrome is known to occur after cardiac arrest, leading to cerebral infiltration by white blood cells (WBC). We hypothesized that pharmacological sequestration of WBC, and more specifically lymphocytes within lymphoid tissues, could reduce the cerebral infiltration by these inflammatory cells and subsequent acute brain injury in a porcine model of cardiac arrest. Lymphocyte sequestration was induced by the sphingosine-1 phosphate receptors agonist fingolimod.

Methods

In a first set of experiments, anesthetized pigs underwent a sham instrumentation with no cardiac arrest (n = 4). They received an administration of fingolimod (1 mg/kg, i.v.) in order to confirm its effect on WBC. In a second set of experiments, animals randomly received fingolimod or saline two hours prior to an episode of ventricular fibrillation (14 min) with subsequent resuscitation (n = 6 in each group). Neurological injury was assessed 24 h after resuscitation.

Results

In the first set of experiments, WBC and blood lymphocyte counts were significantly reduced by − 61 ± 10% and − 75 ± 6% two hours after fingolimod administration. In the second set of experiments, blood lymphocyte counts, but not WBC, were also significantly reduced after cardiac arrest in Fingolimod vs Control group. However, most cytokine blood levels were not different among groups, including Interleukin (IL)-1ra, IL-8 or IL-18 blood levels. A difference was only observed for IL-6, which decreased in Fingolimod vs Control (e.g., 5.6 ± 4.8 vs 59.4 ± 20.6 pg/ml at 2 h after cardiac arrest, respectively; p = 0.126). Neurofilament light chain (NFL) blood levels were not different among groups (57 ± 25 vs 84 ± 41 pg/ml in Fingolimod vs Control at 6 h after resuscitation, respectively). After awakening, 3 and 2 animals were prematurely euthanized for ethical reasons due to recurrent seizures in Fingolimod and Control groups, respectively. At Day 1, neurological dysfunction score was not different between groups (87 ± 7 vs 87 ± 5% in Fingolimod vs Control, respectively). Conversely, a decrease in the number of CD3 + cells was observed in the brain of surviving animals in Fingolimod vs Control group (3.10 ± 0.50 vs 7.53 ± 0.57 CD3 + cells/field, respectively; p = 0.0286).

Conclusion

Fingolimod-induced WBC sequestration, and more specifically lymphocytes sequestration, did not improve clinical neurological dysfunction following cardiac arrest although it reduced cerebral infiltration by lymphocytes.
Pre and perinatal predictors on autism spectrum disorders: a case-control study in the west of Iran
Authors: Jenabi Ensiyeh , Salehi Amir Mohammad , Ayubi Erfan , Seyedi Mahdieh , Khazaei Salman , Jourmand Hanieh
Published: July 2024

Introduction

The constellation of pre and perinatal predictors are introduced as predictor for autism spectrum disorders (ASD), however, the information about the direction and strength of these predictors are lacking in Western, Iran. The current study aimed to determine the pre and perinatal predictors of ASD among children in this region.

Methods

This case-control study was conducted in Hamadan, Western Iran during January to March 2022. The study included 100 children with ASD who referred to the autism center as case group. Hundred children without ASD from registration system of health service centers were selected as control group and were matched (1:1) to cases by age and place of residency. A structured questionnaire about pre and perinatal predictors of ASD was developed by an expert panel. The questionnaire was administered by interviewing the mothers of children.

Results

Boy gender (OR: 3.51, 95% CI: 1.74–7.10, p-value < 0.001), small for gestational age (SGA) (3.92, 1.64–9.39, 0.002), maternal diabetes (3.51, 1.03–24.95, 0.04) and family history of mental disorders (3.64, 1.18–11.27, 0.04) were identified as significant predictors in a multivariable analysis.

Conclusion

Our study emphasizes on the importance of screening and monitoring for ASD in the boys, those with history of SGA, from mothers with history of diabetes and with family history of mental disorders. Proposing the replication of findings emphasizes the necessity of conducting studies with larger sample sizes.
“Everyone has their own problems and realities so the religious community cannot judge someone.” Contraception motivations and perceived consequences among young contraceptive users who practice a religion in Burkina Faso
Authors: Bazié Fiacre , Speizer Ilene S. , Maytan-Joneydi Amelia , Boukary Kindo , Troaré Moh Fatimata , Agali Balki Ibrahim , Onadja Yentema , Guiella Georges
Published: July 2024

Background

Numerous factors at the individual, interpersonal, and societal levels are related to contraceptive use (or non-use) among adolescents and youth. Little is known about the role of religion as an individual and community-level influencer of contraceptive use among young women.

Methods

Using in-depth interviews with 24 young contraceptive users ages 18–24 who practice their Catholic, Protestant or Muslim religion in two cities in Burkina Faso, this study examines motivations and perceived consequences of contraceptive use. By including users of modern contraception who were both single and married, a range of perspectives are provided.

Results

Generally, the young women interviewed who practice their religion and use contraception perceived that their religion was not supportive of contraceptive use. A few exceptions were provided, including perceived acceptance of use of some methods for married women for spacing purposes; this was specifically identified as acceptable among Muslim respondents. Sexual activity and contraceptive use were not acceptable by any of the religions for unmarried young women. That said, young women, both married and unmarried, reported their motivations for use that often related to their and their children’s health and the realities of life. Contraceptive use was considered a private matter which meant that the religious community would not find out about women’s use.

Conclusions

Recognizing that some women are willing and able to use contraception even without the perceived support of their religious communities might help to push social norms to change and be more accepting of contraceptive use that meets young women’s and families’ circumstances.
METTL14 contributes to the progression of nasopharyngeal carcinoma through regulating the stability of AOC1 mRNA
Authors: Hu Changan , Song Shengguan , Zhao Shanglong , Xue Zhen , Zhu Xiwen
Published: July 2024

Background

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa with a high incidence rate all over the world. Methyltransferase-like 14 (METTL14) is a major RNA N6-adenosine methyltransferase implicated in tumor progression by regulating RNA function. This study is designed to explore the biological function and mechanism of METTL14 in NPC.

Methods

METTL14 and Amine oxidase copper containing 1 (AOC1) expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of METTL14, AOC1, Cyclin D1, B-cell lymphoma-2 (Bcl-2), and N-cadherin were measured using western blot. Cell proliferation, cycle progression, apoptosis, migration, and invasion were assessed using 5-ethynyl-2’-deoxyuridine (EdU), Colony formation, flow cytometry, wound scratch, and transwell assays. The interaction between METTL14 and AOC1 was verified using RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), and dual-luciferase reporter assays. The biological role of METTL14 on NPC tumor growth was examined by the xenograft tumor model in vivo.

Results

METTL14 and AOC1 were highly expressed in NPC tissues and cells. Moreover, METTL14 knockdown might block NPC cell proliferation, migration, invasion, and induce cell apoptosis in vitro. In mechanism, METTL14 might enhance the stability of AOC1 mRNA via m6A methylation. METTL14 silencing might repress NPC tumor growth in vivo.

Conclusion

METTL14 might boosted the development of NPC cells partly by regulating the stability of AOC1 mRNA, which provided a promising therapeutic target for NPC treatment.
Unveiling the dynamics and impact of emotional presence in collaborative learning
Authors: Tan Siaw Eng , Jung Insung
Published: July 2024

This study aims to understand the dynamics and impact of emotional presence in a collaborative learning environment and its effects on the learning process and outcomes. Emotional presence, defined as the experience of emotion arising from cognitive appraisals in learner-environment interactions, encompasses four dimensions: interest-curiosity, emotional regulation, expression management, and emotional awareness. Using a mixed-methods approach, we surveyed 33 Japanese college students engaged in collaborative learning activities and conducted in-depth interviews with 10 participants to gather qualitative insights. The study revealed that emotional presence evolves throughout the collaborative process, with increased emotional regulation in response to complex tasks, reflecting learners’ adaptations to varying task demands. It highlighted the importance of emotional regulation in shaping the learning process and improving outcomes in collaborative learning. Our findings suggest that heightened emotional presence, with increased emotional awareness and regulation, fosters cognitive development and learner well-being, supporting more effective and fulfilling collaborative learning experiences. The study also emphasizes the crucial role of cognitive appraisal in shaping emotional experiences, significantly influencing outcomes in technology-enhanced environments. The study concludes by proposing future research directions, such as examining the longitudinal impacts of emotional presence and exploring interventions to enhance emotional regulation skills in diverse learning contexts.
Improved homomorphic evaluation for hash function based on TFHE
Authors: Wei Benqiang , Lu Xianhui
Published: July 2024

Homomorphic evaluation of hash functions offers a solution to the challenge of data integrity authentication in the context of homomorphic encryption. The earliest attempt to achieve homomorphic evaluation of SHA-256 hash function was proposed by Mella and Susella (in: Cryptography and coding—14th IMA international conference, IMACC 2013. Lecture notes in computer science, vol 8308. Springer, Heidelberg, pp 28–44, 2013. https://doi.org/10.1007/978-3-642-45239-0_3.) based on the BGV scheme. Unfortunately, their implementation faced significant limitations due to the exceedingly high multiplicative depth, rendering it impractical. Recently, a homomorphic implementation of SHA-256 based on the TFHE scheme (Homomorphic evaluation of SHA-256. https://github.com/zama-ai/tfhe-rs/tree/main/tfhe/examples/sha256_bool) brings it from theory to reality, however, its current efficiency remains insufficient. In this paper, we revisit the homomorphic evaluation of the SHA-256 hash function in the context of TFHE, further reducing the reliance on gate bootstrapping and enhancing evaluation latency. Specifically, we primarily utilize ternary gates to reduce the number of gate bootstrappings required for logic functions in message expansion and addition of modulo $$2^{32}$$

2
32

in iterative compression. Furthermore, we demonstrate that our optimization techniques are applicable to the Chinese commercial cryptographic hash SM3. Finally, we give specific comparative implementations based on the TFHE-rs library. Experiments demonstrate that our optimization techniques lead to an improvement of approximately 35–50% compared with the state-of-the-art result under different cores.
Promising short-term outcomes of free-hand burring technique to implant second-generation metaphyseal cone in Asian knees – a case series
Authors: Leung Thomas Ka Chun , Chan Ping Keung , Fu Henry , Cheung Amy , Luk Michelle Hilda , Lau Lawrence Chun Man , Chiu Kwong Yuen
Published: July 2024

Background

The second-generation metaphyseal cone was useful in managing bone defects in revision knee arthroplasty. However, due to the anatomical constraints in Asian osteometry, the authors utilized a novel free-hand burring technique instead of cannulated reaming for bone preparation. We reported the short-term outcomes of our surgical techniques specific to Asian osteometry.

Methods

We conducted a case series by consecutively recruiting 13 female and 12 male patients (involving 25 knees), with a mean age of 71 years (range, 54–88 years). The patients underwent revision total knee arthroplasty during the period from April 2017 to June 2022. Twenty-three tibial cones and 4 femoral cones using free-hand burring technique were implanted. The mean follow-up duration was 51 months (range 18–80 months). Due to the relatively small bone size and meta-diaphyseal center mismatch in the Asian knees, the free-hand burring technique instead of the cannulated reaming technique was adopted in preparing for cone implantation. The clinical outcomes were knee ranges of motion, the Knee Society Knee scores (KSS), end-of-stem pain, infection, and the need for revision surgery. The radiological outcomes included osteointegration, fracture, and loosening.

Results

Mean knee range of motion improved from 83 degrees (range 0°–120°) preoperatively to 106 degrees (range 60°–125°) postoperatively (P < 0.001). Mean KSS improved significantly from 29 (range 0–70) to 69 (range 5–100) (P < 0.001). All cones were osteointegrated. One case had transient end-of-stem pain, two developed intraoperative minor femoral fractures and one suffered from recurrent infection that did not require cone revision. Cone revision-free survivorship was 100%. There was no aseptic loosening.

Conclusions

The second-generation cone implanted with free-hand burring bone preparation yielded promising short-term outcomes in Asian knees.
Early effect of different bifurcation techniques on left ventricular mechanics in elective percutaneous coronary intervention
Authors: Elsheikh Amr Nasser , Elsaeid Ayman , Sharafeldin Samia , Elshedoudy Sahar , ElGendy Ehab
Published: July 2024

Background

Bifurcation lesions are prevalent amongst patients with symptomatic coronary artery disease subjected to percutaneous coronary intervention (PCI). Recent consensus commends a conservative (provisional) approach when managing the side branch. Here, the aim was to explore the immediate impact of different bifurcation techniques (one stent and two stent strategies) on left ventricular LV) myocardial functions using speckle tracking echocardiography in patients subjected to elective PCI. Sixty two consecutive patients diagnosed with coronary bifurcation lesion (CBL) were enrolled. Patients were categorized into: one-stent strategy (Provisional group, n = 44) and a two-stent strategy (TAP, DK crush, or Culotte technique, n = 18), based on the coronary bifurcation site, angle, side branch diameter and Medina classification. LVEF%, regional and global longitudinal strain (GLS), and E/E' were measured before and within 24 h post PCI.

Results

In both provisional and 2- stent technique, the mitral inflow velocities and mitral annular velocities showed improvement with significant reduction in E/e' (P < 0.03 and P < 0.001) respectively while LVEF% did not change. There were no significant changes in any other echo parameters post PCI. In provisional group, there were significant improvements in LAD (P < 0.001), RCA (P < 0.01) territories and GLS (P < 0.01). Δ LAD was expressively higher (34.5%) compared with Δ LCX (9.6%) and ΔRCA (25.4%), P < 0.001, P < 0.01 respectively. In the 2-stent technique group, there were significant improvements in peak longitudinal strain of LAD territory (P < 0.01), RCA territory (P < 0.01) and GLS (P < 0.01) respectively. Δ LAD territory was significantly higher in provisional group in comparison with the 2- stent technique group. Δ GLS was correlated inversely to Gensini score in provisional group and to the number of vessel diseased in 2-stent technique group.

Conclusion

PCI of the bifurcation lesion positively impact myocardial function. Both bifurcation techniques improve LV mechanical properties using 2D strain imaging while LV EF% remains unchanged.
Contraceptive use, unmet need, and demand satisfied for family planning across Cameroon: a subnational study including indirect effects of COVID-19 and armed conflict on projections
Authors: Nsashiyi Raïssa Shiyghan , Rahman Md Mizanur , Ndam Lawrence Monah , Hashizume Masahiro
Published: July 2024

Background

Cameroon is among countries that have made notable investments nationwide in line with the Family Planning 2030 initiative. This study examines the progress made across the 10 regions and 58 divisions of the country, including potential impairments following COVID-19 and armed conflict.

Methods

In this time-series analysis, parameters were sourced from 5 Demographic and Health Surveys and 3 Multiple Indicator Cluster Surveys conducted between 1991 and 2018. The Family Planning Estimation Tool (FPET) was used to estimate key family planning indicators among married women of reproductive age. Data from official country reports and FPET results were incorporated into Bayesian models to assess how projections (from 2020 to 2030) would vary given varying contractions (i.e., 0%, 5%, 10%, and 25% annually) to services coverage.

Results

Nationally, modern contraceptive prevalence rate (mCPR) and demand satisfied with modern (contraceptive) methods reached 16.8% (95% credible interval 12.0 to 23.0) and 37.6% (28.7 to 47.0), respectively; and unmet need for modern methods decreased to 27.9% (22.9 to 33.7) in 2022. Notable improvements were observed in the East region and Boumba et Ngoko division, with annual mCPR trends of 2.1 percentage points (%p) (− 0.2 to 4.2) and 7.0%p (4.5 to 9.3) from 2015–2020; and 2030 projections of 58.7% (41.3 to 74.0) and 79.1% (65.0 to 89.0), respectively. The least performing in terms of demand satisfied with modern methods include Adamawa at the regional and Boyo at the divisional level, with 2030 projections of 45.5% (26.5 to 65.1) and 0.4% (0.2 to 0.8), respectively. The northern regions (Adamawa, Far North, and North) recorded the lowest levels of unmet need for modern methods. To achieve ≥ 75% demand satisfied with modern methods in 2030, an additional 1.4 (0.6 to 2.2) million modern contraceptive users are required. Given large reductions (− 25% annually) in services coverage post-COVID-19/armed conflict (2020 to 2030), the South region could experience the most significant contraction in projected mCPR, with a decrease of − 9.2%.

Conclusions

Family planning outcomes vary significantly across subnational territories of Cameroon. While the East region shows notable success, greater attention is needed in the northern regions. Strategies must be adaptive to address unprecedented emergencies that may disrupt access to services.
First-in-human phase I clinical trial of RSO-021, a first-in class covalent inhibitor of mitochondrial peroxiredoxin 3 (PRX3), in patients with malignant pleural effusion due to mesothelioma and other advanced solid tumors (MITOPE).
Authors: Fennell Dean Anthony , Dulloo Sean , Lord Simon , Thistlethwaite Fiona , Blyth Kevin G , Szlosarek Peter Wojciech , Maskell Nick , Popat Sanjay , Aujayeb Avinash , Aktas Burak Y , Javed Sohail Rooman , Herrero Colomina Julio , Cunniff Brian , Duncan Jarrett , Graham Philippa , Bexon Alice Susannah , Naumov George N , Spicer James F.
Published: July 2024

3019

Background: Malignant cells rely on buffering oxidative stress through mitochondrial PRX3. Oxidative stress is selectively lethal to cancer cells and may be leveraged therapeutically. RSO-021 is a naturally-occurring, sulfur-rich, cyclic oligopeptide of the thiopeptide class, which covalently inactivates PRX3, leading to catastrophic oxidative stress and cell death. We conducted a phase 1 study to explore safety and identify the maximum tolerated dose (MTD) of intra-pleural RSO-021 in patients with mesothelioma, or other predominantly pleural cancer, with pleural effusion. Methods: MITOPE was a multicenter trial of weekly intrapleural RSO-021 (90, 120, and 180 mg) with a 3 + 3 dose-escalation design. The primary objective was to assess RSO-021 safety/tolerability. Secondary objectives included establishing local and systemic pharmacokinetic profiles and early anti-tumor activity. We defined dose-limiting toxicity (DLT) as grade (G) ≥3 non-hematological AEs with exceptions for some manageable G3 AEs that resolved within 72 h and complicated G4 hematological AEs or those lasting >7 days. We also studied inflammatory and pharmacodynamic markers in local/systemic samples. Efficacy was assessed using mRECIST 1.1 (mesothelioma) and RECIST 1.1 (other tumors). Results: Of 15 patients treated (90 mg/wk, n=7; 120 mg/wk, n=6; 180 mg/wk, n=2), 12 (80%) had ≥3 prior anti-cancer regimens; 12 (80%) had mesothelioma. See table for AE and efficacy data. The commonest all-grade treatment-related AEs (TRAE) were fatigue (33%), pyrexia (20%), and elevated creatinine (20%). Three patients (20%) had DLTs: G3 dyspnea and G3 acute inflammatory response at 120 mg/wk; G3 dyspnea at 180 mg/wk. MTD was 90 mg/wk. Pro-inflammatory cytokines in pleural fluid/serum correlated with AEs suggestive of local inflammation. Prophylaxis mitigated local inflammatory TRAEs. PRX3 target binding in cell pellets from pleural fluid confirmed on-target activity. Systemic exposure was minimal. Disease control was 70% in 10 evaluable patients. The partial response at 90 mg/wk was a 59% reduction in mesothelioma target lesions. Median PFS at MTD was 5.7 months (95% CI, 1.4-NR). Two patients had disease control (DC) >30 wks. Conclusions: Weekly intrapleural RSO-021 was safe with signs of anti-tumor activity in patients with pleural mesothelioma. Phase 2 exploration of this novel agent is ongoing at 2 doses, as a single agent and in combination. Clinical trial information: NCT05278975 . [Table: see text]
Efficacy and safety of eribulin-based chemotherapy in patients with advanced breast cancer: A single-centre retrospective study.
Authors: Li Yuting , Han Dan , Hu Ting , Xiong Jie , Zhao Yanxia
Published: July 2024

e13121

Background: Eribulin, a nontaxane microtubule dynamics inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. This retrospective study aimed to assess efficacy and safety of Eribulin-based chemotherapy in ABC patients, especially for patients exhibiting HER2-0 and HER2-low status (immunohistochemistry [IHC] 1+ or IHC 2+with a negative in situ hybridization assay). Methods: This single-center retrospective study planned to include 126 ABC patients from January 2020 to December 2023. Enrolled participants received Eribulin either as monotherapy or in combination with other regiments such as anti-angiogenic therapy, PD-1 inhibitor, or alternative chemotherapy in clinical practice. The primary outcomes included progression-free survival (PFS) and safety assessments. Results: A total of 84 patients with ABC received Eribulin were enrolled. Patients' baselines were summarized as follows: The median age was 53.3 years (range 30.0–86.0 years). 53 (63.1%) patients were HER2-low while 40 (47.6%) patients were hormone receptor (HR) positive. 63.1% patients have received at least one line chemotherapy before the use of Eribulin. According to the K-M survival analysis, the median PFS was 6.0 (range 3.2-11.3) months for all patients. The median PFS was longer for patients received aromatase inhibitors (AI) for over 6 months than patients with AI naive (median 10.1 vs 6.6 months; p=0.192) in HR positive patients. Patients who received CDK4/6 therapy had longer PFS than patients (median 10.7 vs 6.6 months; p=0.38). There was a trend toward prolonged PFS in the HER2-0 group compared with HER2-low group (median 10.13 vs 6.03 months; p=0.154), although there was no significant difference. A nonsignificant improvement of PFS was observed in HR-/HER2-0 patients, compare with HR-/HER2-low patients (median 16.4 vs 4.7mo; p=0.21). Meanwhile the median PFS of HER2-0 and HER2-Low was similar in HR positive patients. The objective response rate was 35.5% in HER2-0 group and 30.2% in HER2-low group. In multivariate cox regression, Eribulin as first line treatment (HR, 4.028; 95% CI, 1.131-14.337) and HER2-0 (HR, 2.903; 95% CI, 1.257-6.702) showed prognostic values regarding PFS. Common grade 3 or 4 adverse events that were reported in more than 10% were neutropenia (41.6%) and leukopenia (26.2%). No treatment-related deaths were reported. Conclusions: This single-center study demonstrated encouraging efficacy and safety in the ABC patients treated with Eribulin. Significant PFS benefit was associated with Eribulin treatment in patients with HER2-0 compared with HER2-low. This study still needs longer follow-up to evaluate its efficacy more comprehensively.
Immunotherapy plus chemotherapy versus chemotherapy alone in perioperative treatment for locally advanced gastric cancer: A systematic review and meta-analysis.
Authors: Silva Isadora Mamede Mendes da , Oliveira João Pedro , Maia Melissa , de Liz Caio Dabbous , Oliveira Audrey Cabral Ferreira de , Alves Ana Caroline Fonseca
Published: July 2024

e16083

Background: The standard care for locally advanced gastric (LAGC) or gastroesophageal junction (GEJ) cancer is perioperative chemotherapy (CTX) with surgery. The therapeutic landscape has evolved with PD-1 and PD-L1 inhibitors, showing promise in advanced or metastatic disease. Investigating their role in locally advanced disease is an active research area. In response, we conducted a meta-analysis to evaluate the effectiveness of perioperative immunotherapy with CTX in LAGC/GEJ patients. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing perioperative PD-1 and PD-L1 inhibitors in combination with CTX versus CTX alone for LAGC/GEJ. Evaluated outcomes included pathological complete response (pCR), R0 resection rate, downstaging rate, and treatment-related adverse events (TRAE) with a grade ≥ 3. Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,452 patients from six RCTs, 1,228 (50.08%) received immunotherapy. Combining immunotherapy with CTX showed substantial improvements in pCR (RR 2.83; 95% CI 1.78-4.50; p < 0.001). This effect persisted in the FLOT CTX subgroup (RR 2.15; 95% CI 1.37-3.38; p < 0.001). Additionally, downstaging outcomes were superior in the immunotherapy group, with ypT0 (RR 1.96; 95% CI 1.50-2.55; p < 0.001) and ypN0 (RR 1.36; 95% CI 1.19-1.54; p < 0.001). However, no significant differences were observed in the R0 resection rate (RR 1.01; 95% CI 0.98-1.04; p = 0.603) and TRAE grade 3 or higher (RR 1.05; 95% CI 0.98-1.13; p = 0.177). Conclusions: These findings emphasize the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, indicating an improved pathological response compared to CTX alone. As expected, these positive outcomes persisted in the FLOT regimen. Our results provide evidence supporting the combination of immunotherapy and CTX as a perioperative treatment option for LAGC/GEJ patients.