bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of lymphoedema, in particular midline lymphoedema, after treatment for prostate cancer: a retrospective study
Authors: Van Calster Charlotte , Everaerts Wouter , Geraerts Inge , De Groef An , Heroes An-Kathleen , De Vrieze Tessa , Alar Ceyhun , Devoogdt Nele
Published: September 2024

Background

Patients undergoing treatment for prostate cancer may develop lymphoedema of the midline region. This has a substantial impact on a patient’s quality of life and its diagnosis is often delayed or missed. Therefore, the purpose of this study is to compare the characteristics of patients with leg and midline lymphoedema to patients with only leg lymphoedema.

Methods

We retrospectively collected patient-, cancer-, lymphoedema- and lymphoedema treatment-related data of 109 men with lymphoedema after treatment for prostate cancer. First, 42 characteristics were compared between both groups. Second, factors predicting presence of midline lymphoedema were explored by multivariable analyses.

Results

The mean age of the patients with lymphoedema was 68 ( ±7) years and mean BMI is 28 (±4) kg/m2. Median duration of lymphoedema before the first consultation was 27 (9;55) months. Based on univariable analyses, patients with leg and midline lymphoedema had more frequently upper leg lymphoedema (89% (31/35) vs. 69% (51/74), p = 0.026), skin fibrosis (34% (12/35) vs. 16% (12/74), p = 0.034) and lymphatic reconstructive surgery (9% (3/35) vs. 0% (0/71), p = 0.020) than patients with only leg lymphoedema. Additionally, patients with leg and midline lymphoedema reported less frequently lower leg lymphoedema (77% (27/35) vs. 95% (70/74), p = 0.007). Based on the multivariable analysis, not having lower leg lymphoedema, skin fibrosis, performing self-bandaging and self-manual lymphatic drainage appear to be predictors for having midline lymphoedema.

Conclusions

If patients with lymphoedema after prostate cancer do not have lower leg lymphoedema, have skin fibrosis, perform self-bandaging or self-manual lymphatic drainage, they possibly have midline lymphoedema.
Perspectives on a peer-driven intervention to promote pre-exposure prophylaxis (PrEP) uptake among men who have sex with men in southern New England: a qualitative study
Authors: Tao Jun , Parent Hannah , Karki Ishu , Martin Harrison , Marshall Sarah Alexandra , Kapadia Jhanavi , Nunn Amy S. , Marshall Brandon D. L. , Raymond Henry F. , Mena Leandro , Chan Philip A.
Published: September 2024

Background

Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities.

Methods

We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection.

Results

Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects.

Conclusions

Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.
Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages
Authors: Dayarathna Shashika , Senadheera Bhagya , Jeewandara Chandima , Dissanayake Madushika , Bary Farha , Ogg Graham S. , Malavige Gathsaurie Neelika
Published: September 2024

Background

While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.

Methods

Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF.

Results

Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF.

Conclusions

As RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.
A new modular neuroprosthesis suitable for hybrid FES-robot applications and tailored assistance
Authors: Gil-Castillo Javier , Herrera-Valenzuela Diana , Torricelli Diego , Gil-Agudo Ángel , Opisso Eloy , Vidal Joan , Font-Llagunes Josep M. , del-Ama Antonio J. , Moreno Juan C.
Published: September 2024

Background

To overcome the application limitations of functional electrical stimulation (FES), such as fatigue or nonlinear muscle response, the combination of neuroprosthetic systems with robotic devices has been evaluated, resulting in hybrid systems that have promising potential. However, current technology shows a lack of flexibility to adapt to the needs of any application, context or individual. The main objective of this study is the development of a new modular neuroprosthetic system suitable for hybrid FES-robot applications to meet these needs.

Methods

In this study, we conducted an analysis of the requirements for developing hybrid FES-robot systems and reviewed existing literature on similar systems. Building upon these insights, we developed a novel modular neuroprosthetic system tailored for hybrid applications. The system was specifically adapted for gait assistance, and a technological personalization process based on clinical criteria was devised. This process was used to generate different system configurations adjusted to four individuals with spinal cord injury or stroke. The effect of each system configuration on gait kinematic metrics was analyzed by using repeated measures ANOVA or Friedman’s test.

Results

A modular NP system has been developed that is distinguished by its flexibility, scalability and personalization capabilities. With excellent connection characteristics, it can be effectively integrated with robotic devices. Its 3D design facilitates fitting both as a stand-alone system and in combination with other robotic devices. In addition, it meets rigorous requirements for safe use by incorporating appropriate safety protocols, and features appropriate battery autonomy, weight and dimensions. Different technological configurations adapted to the needs of each patient were obtained, which demonstrated an impact on the kinematic gait pattern comparable to that of other devices reported in the literature.

Conclusions

The system met the identified technical requirements, showcasing advancements compared to systems reported in the literature. In addition, it demonstrated its versatility and capacity to be combined with robotic devices forming hybrids, adapting well to the gait application. Moreover, the personalization procedure proved to be useful in obtaining various system configurations tailored to the diverse needs of individuals.
Targeting lipid droplets and lipid droplet-associated proteins: a new perspective on natural compounds against metabolic diseases
Authors: Jiang Xinyue , Wang Hongzhan , Nie Kexin , Gao Yang , Chen Shen , Tang Yueheng , Wang Zhi , Su Hao , Dong Hui
Published: September 2024

Background

Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins.

Methods

The keywords “lipid droplets” and “metabolic diseases” were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like “lipid droplets”, “lipid droplet-associated proteins”, “fatty liver disease”, “diabetes”, “diabetic kidney disease”, “obesity”, “atherosclerosis”, “hyperlipidemia”, “natural drug monomers” and “natural compounds”, the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized.

Results

The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases.

Conclusion

Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.

Graphical Abstract
Single-cell transcriptional atlas of tumor-associated macrophages in breast cancer
Authors: Zhang Yupeng , Zhong Fan , Liu Lei
Published: September 2024

Background

The internal heterogeneity of breast cancer, notably the tumor microenvironment (TME) consisting of malignant and non-malignant cells, has been extensively explored in recent years. The cells in this complex cellular ecosystem activate or suppress tumor immunity through phenotypic changes, secretion of metabolites and cell-cell communication networks. Macrophages, as the most abundant immune cells within the TME, are recruited by malignant cells and undergo phenotypic remodeling. Tumor-associated macrophages (TAMs) exhibit a variety of subtypes and functions, playing significant roles in impacting tumor immunity. However, their precise subtype delineation and specific function remain inadequately defined.

Methods

The publicly available single-cell transcriptomes of 49,141 cells from eight breast cancer patients with different molecular subtypes and stages were incorporated into our study. Unsupervised clustering and manual cell annotation were employed to accurately classify TAM subtypes. We then conducted functional analysis and constructed a developmental trajectory for TAM subtypes. Subsequently, the roles of TAM subtypes in cell-cell communication networks within the TME were explored using endothelial cells (ECs) and T cells as key nodes. Finally, analyses were repeated in another independent publish scRNA datasets to validate our findings for TAM characterization.

Results

TAMs are accurately classified into 7 subtypes, displaying anti-tumor or pro-tumor roles. For the first time, we identified a new TAM subtype capable of proliferation and expansion in breast cancer-TUBA1B+ TAMs playing a crucial role in TAMs diversity and tumor progression. The developmental trajectory illustrates how TAMs are remodeled within the TME and undergo phenotypic and functional changes, with TUBA1B+ TAMs at the initial point. Notably, the predominant TAM subtypes varied across different molecular subtypes and stages of breast cancer. Additionally, our research on cell-cell communication networks shows that TAMs exert effects by directly modulating intrinsic immunity, indirectly regulating adaptive immunity through T cells, as well as influencing tumor angiogenesis and lymphangiogenesis through ECs.

Conclusions

Our study establishes a precise single-cell atlas of breast cancer TAMs, shedding light on their multifaceted roles in tumor biology and providing resources for targeting TAMs in breast cancer immunotherapy.
Identification and functional analysis of C-type lectin from mosquito Aedes albopictus in response to dengue virus infection
Authors: Gao Sheng , Xu Haodong , Li Hongbo , Feng Xiao , Zhou Jitao , Guo Renxian , Liang Zihan , Ding Jinying , Li Xin , Huang Yijia , Liu Wenquan , Liang Shaohui
Published: September 2024

Background

C-type lectins (CTLs) are a large family of proteins with sugar-binding activity. CTLs contain an evolutionarily conserved C-type lectin domain (CTLD) that binds microbial carbohydrates in a calcium-dependent manner, thereby playing a key role in both microbial pathogenesis and innate immune responses. Aedes albopictus is an important vector for transmitting dengue virus (DENV) worldwide. Currently, the molecular characteristics and functions of CTLs in Ae. albopictus are largely unknown.

Methods

Transcripts encoding CTL proteins in the Ae. albopictus genome assembly were analyzed via sequence blast. Phylogenetic analysis and molecular characterization were performed to identify the functional domains of the CTLs. Quantitative analysis was performed to determine the gene expression features of CTLs during mosquito development and in different tissues of female adults after blood feeding. In addition, the functional role of CTLs in response to DENV infection was investigated in Ae. albopictus mosquito cells.

Results

We identified 39 transcripts encoding CTL proteins in the Ae. albopictus transcriptome. Aedes albopictus CTLs are classified into three groups based on the number of CTLDs and the domain architecture. These included 29 CTL-Ss (single-CTLDs), 1 immulectins (dual-CTLD) and 9 CTL-Xs (CTLDs with other domains). Phylogenetic analysis and structural modeling indicated that CTLs in Ae. albopictus are highly conserved with the homologous CTLs in Aedes aegypti. The expression profile assay revealed differential expression patterns of CTLs in both developmental stages and in adult female tissues. Knockdown and overexpression of three CTLs (CTL-S12, S17 and S19) confirmed that they can promote dengue virus infection in Ae. albopictus cells.

Conclusions

The CTL genes in Ae. albopictus mosquito and other mosquito species are evolutionarily conserved and exhibit different developmental and tissue expression features. The functional assay indicated that three CTLs in Ae. albopictus mosquitoes are involved in promoting dengue virus infection. Our study revealed that CTLs play important roles in both the physiological processes and viral infection in mosquito vectors.

Graphical Abstract
Inhibitory effect of human indoleamine 2,3-dioxygenase 1 (hIDO1) by kazinols of 1,3-diphenylpropane derivatives
Authors: Oh Taehoon , Jung Sunin , Oh Seon Min , Park Mi Hyeon , Kim Hyoung-Geun , Lee Su-Yeon , Ko Sung-Kyun , Ryu Hyung Won
Published: September 2024

This study focused on identifying and characterizing 1,3-diphenylpropane derivatives from flavonoids that inhibit human indoleamine 2,3-dioxygenase 1 (hIDO1) enzymes, which play a role in immune regulation and are associated with various diseases. A series of isolated metabolites (1–7) demonstrated modest to high inhibition of hIDO1, with binding degree values ranging from 26.31 to 72.17%. In particular, during a target-based screening of natural products using hIDO1, kazinol J (6, a 1,3-diphenylpropane derivative) was found to potently inhibit hIDO1, with a binding degree of 72.17% at 1 ppm. Kazinol J (6) showed concentration-dependent and mixed inhibition kinetics and achieved slow and time-dependent inhibition of hIDO1. Additionally, docking simulations were performed to evaluate the inhibitory potential and binding interactions of the compounds with hIDO1. These findings suggest that these 1,3-diphenylpropane derivatives can serve as therapeutic agents for conditions involving hIDO1 dysregulation, such as cancer, autoimmune disorders, and infectious diseases.
Smallholder access to purchased seeds in the presence of pervasive market imperfections and rainfall shocks: panel data evidence from Malawi and Ethiopia
Authors: Makate Clifton , Angelsen Arild , Holden Stein Terje , Westengen Ola Tveitereid
Published: September 2024

Seed purchasing enables farmers to respond to adverse events that may cause chronic and temporary seed insecurity by allowing them to exploit opportunities associated with accessing new seeds. However, as with other inputs, seed purchasing is complicated by pervasive market imperfections and climate risk common in Sub-Sahara Africa. This study uses balanced household panel data for Malawi (2010–2018) and Ethiopia (2012–2016) and applies dynamic random effects Probit and Tobit models to assess how seed purchase decisions are affected by earlier participation in the market, lagged rainfall shocks, and historical climate variables. Our findings show that there are nonlinear effects of lagged seed purchase decisions on subsequent decisions with strong initial effects (weakening over time). For instance, initial maize seed purchase decisions are associated with about 11 and 22% higher probability of purchase and 1 and 2% higher shares of seed volumes purchased in later rounds in Malawi and Ethiopia, respectively. Seed purchase decisions also respond to climate variability and shocks. For instance, lagged drought shocks enhance subsequent maize purchase decisions in both countries. Historical average rainfall and temperature enhance maize seed purchase decisions in both countries. Overall, results point to state dependency on the demand side of the seed market, leading to selective access to purchased seeds. Also, seed purchase in smallholder farming is a liquidity and risk-dependent input choice. Policy efforts need to continue targeting reducing transaction costs and other barriers to entry into seed markets to enhance access to off-farm seed and support adaptation to rainfall shocks.
Modelling user notification scenarios in privacy policies
Authors: Kuznetsov Mikhail , Novikova Evgenia , Kotenko Igor
Published: September 2024

The processing of personal data gives a rise to many privacy concerns, and one of them is to ensure the transparency of data processing to end users. Usually this information is communicated to them using privacy policies. In this paper, the problem of user notification in case of data breaches and policy changes is addressed, besides an ontology-based approach to model them is proposed. To specify the ontology concepts and properties, the requirements and recommendations for the legislative regulations as well as existing privacy policies are evaluated. A set of SPARQL queries to validate the correctness and completeness of the proposed ontology are developed. The proposed approach is applied to evaluate the privacy policies designed by cloud computing providers and IoT device manufacturers. The results of the analysis show that the transparency of user notification scenarios presented in the privacy policies is still very low, and the companies should reconsider the notification mechanisms and provide more detailed information in privacy policies.
Radiological and spirometric changes in relation to drugs used in post COVID pulmonary fibrosis in a cohort of COVID-19 survivors
Authors: Hamoda Mohamed , El-Maksoud Amina Abd , Yousef Aida M. , Fahmy Dalia Monir , Tohlob Mohamed
Published: September 2024

Background

It has been proposed that prolonged use of anti-inflammatory and anti-fibrotic drugs diminish the probability of development of lung fibrosis. Prolonged low-dose corticosteroid may prevent remodeling of the lung in survivors. Pirfenidone and colchicine may exhibit anti-fibrotic and anti-inflammatory properties as well.

Methods

This retrospective observational study was conducted at post COVID-19 clinic, Mansoura University Hospitals, during the period between October 2020 and March 2022. This study included 104 patients who had COVID-19 pneumonia confirmed either by RT-PCR or radiologically by CT scan and divided into 3 groups; group A (corticosteroids only) included 33 (31.7%) patients, group B (corticosteroids and colchicine) included 56 (53.8%) patients, and group C (corticosteroids, colchicine, and pirfenidone) included 15 (14.4%) patients. All patients were assessed during follow-up visits in post COVID-19 clinic 1 and 3 months after discharge by evaluation of resting SpO2, spirometry, and radiological assessment. Patients’ data during hospitalization was collected from hospital electronic systems.

Results

There was non-statistically significant improvement in FEV1 in group A while there was statistically significant improvement in FEV1 in groups B and C (P value = 0.002 and 0.041, respectively) 1 month and 3 months after discharge. Group B exhibited more statistically significant improvement in FVC as well compared to group C (P value = 0.003 and 0.025, respectively) while group A showed non-statistically significant improvement in FVC. There was a statistically significant decrease in CT severity score in all the groups during follow-up with P value < 0.001 in groups A and B and to less extent less statistically significant decrease in group C comparing the 3 groups to each other.

Conclusion

The use of colchicine added to corticosteroids after acute phase of COVID-19 pneumonia resulted in statistically significant improvement regarding functional and radiological changes during follow-up when compared to corticosteroids alone. The addition of pirfenidone (which is a relatively expensive drug) to corticosteroids and colchicine did not add more statistically significant improvement in functional or radiological changes.
Results From First-in-Human Phase I Dose-Escalation Study of a Novel Bicycle Toxin Conjugate Targeting EphA2 (BT5528) in Patients With Advanced Solid Tumors
Authors: Bashir Babar , Wang Judy S. , Falchook Gerald , Fontana Elisa , Arkenau Hendrik-Tobias , Carter Louise , Galot Rachel , Basu Bristi , Greystoke Alastair , Subbiah Vivek , Richardson Debra L. , Orr Hanna , Bennett Gavin , Sharma Rajiv , Xu Hongmei , Paganoni Paola , Xu Cong , Campbell Carly , McKean Meredith
Published: September 2024

PURPOSE

BT5528 is a Bicycle Toxin Conjugate, a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting EphA2 tumor antigen, linked to a cytotoxin (monomethyl auristatin E [MMAE]). EphA2 is overexpressed in many solid tumors and contributes to oncogenesis, tumor-associated angiogenesis, and metastasis.

MATERIALS AND METHODS

The primary objectives were to investigate the safety and tolerability of BT5528 and to define the maximum-tolerated dose, if observed, and recommended phase II dose (RP2D)/expansion dose. Dose escalation exploring once every week or once every 2 weeks administration of BT5528 employed a 3 + 3 dose-escalation design for the first two dose levels, followed by a Bayesian logistic regression model. Secondary and exploratory end points included preliminary efficacy and the pharmacokinetics of BT5528 and MMAE.

RESULTS

Forty-five patients were enrolled and received BT5528 doses between 2.2 mg/m
2
once every week to 10.0 mg/m
2
once every 2 weeks within the dose-escalation stage of the study. The most frequent BT5528-related adverse events (AEs) were nausea (44.4%), diarrhea (35.6%), and fatigue (33.3%), and the most common grade ≥3 BT5528-related AE was neutropenia/neutrophil count decrease (22.2%). Dose level 6.5 mg/m
2
once every 2 weeks was selected as a RP2D. At 6.5 mg/m
2
once every 2 weeks, the overall response rate was 6.7%, and the disease control rate was 20.0%. BT5528 and MMAE pharmacokinetics are generally dose proportional. BT5528 has a short half-life (0.4-0.7 hours), and the half-life of MMAE is longer (35-47 hours).

CONCLUSION

BT5528 was well tolerated and demonstrated favorable and preliminary antitumor activity. We believe these data provide preliminary validation of a Bicycle Toxin Conjugate approach to EphA2 tumor antigen. The study is ongoing and is evaluating BT5528 as monotherapy at a RP2D of 6.5 mg/m
2
once every 2 weeks.
Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis
Authors: Chibaudel Benoist , Raeisi Morteza , Cohen Romain , Yothers Greg , Goldberg Richard M. , Bachet Jean-Baptiste , Wolmark Norman , Yoshino Takayuki , Schmoll Hans-Joachim , Kerr Rachel , Lonardi Sara , George Thomas J. , Shacham-Shmueli Einat , Shi Qian , André Thierry , de Gramont Aimery
Published: September 2024

PURPOSE

The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined.

PATIENTS AND METHODS

One thousand five hundred and ninety-five patients with stage II CC receiving FP or FPOX were pooled. The overall survival (OS) benefit of OX was analyzed using Kaplan-Meier curves and unadjusted Cox models stratified by study. Three thousand and fifty-nine patients with stage III CC were used only for interaction tests between the allocated chemotherapy and stage.

RESULTS

In the pooled analysis of stage II patients, independent prognostic factors in multivariable analysis were sex, age, perforation/obstruction, and tumor sidedness. There was a significant interaction in OS between stage and allocated chemotherapy with hazard ratios (HRs) of 1.03 for stage II (95% CI, 0.82 to 1.29;
P
= .813) and 0.82 for stage III (95% CI, 0.73 to 0.92;
P
= .001;
P
int
= .073). There was no benefit from the addition of OX to FP for any of the prognostic factors. The number of high-risk factors tested was not predictive of OX benefit. According to the currently agreed clinicopathologic risk classification, no OS benefit of OX was observed, as HR was 0.86 (95% CI, 0.63 to 1.18;
P
= .349).

CONCLUSION

No OS benefit of adjuvant OX was found in high-risk stage II CC, regardless of the definition used to characterize tumors as having a high risk for recurrence. Hence, our analysis suggests that OX should not be the standard of care for adjuvant chemotherapy for stage II CC, even in high-risk patients.
Thyroid Hormone Receptors as Tumor Suppressors in Cancer
Authors: Zhu Xuguang , Cheng Sheue-yann
Published: September 2024

Accumulated research has revealed the multifaceted roles of thyroid hormone receptors (TRs) as potent tumor suppressors across various cancer types. This review explores the intricate mechanisms underlying TR-mediated tumor suppression, drawing insights from preclinical mouse models and cancer biology. This review examines the tumor-suppressive functions of TRs, particularly TRβ, in various cancers using preclinical models, revealing their ability to inhibit tumor initiation, progression, and metastasis. Molecular mechanisms underlying TR-mediated tumor suppression are discussed, including interactions with oncogenic signaling pathways like PI3K-AKT, JAK-STAT, and transforming growth factor β. Additionally, this paper examines TRs’ effect on cancer stem cell activity and differentiation, showcasing their modulation of key cellular processes associated with tumor progression and therapeutic resistance. Insights from preclinical studies underscore the therapeutic potential of targeting TRs to impede cancer stemness and promote cancer cell differentiation, paving the way for precision medicine in cancer treatment and emphasizing the potential of TR-targeted therapies as promising approaches for treating cancers and improving patient outcomes.
Robotic Recto-Sigmoid Resection with Total Intracorporeal Colorectal Anastomosis (TICA) in Recurrent Ovarian Cancer
Authors: Palmieri Luca , Santullo Francesco , Lodoli Claudio , Certelli Camilla , Abatini Carlo , Rosati Andrea , Oliva Riccardo , Fagotti Anna , Scambia Giovanni , Gallotta Valerio
Published: September 2024

Background

About 70% of women affected by ovarian cancer experience relapse within 2 years of diagnosis. Traditionally, the standard treatment for recurrent ovarian cancer (ROC) has been represented by systemic chemotherapy.1 Recently, several retrospective studies have suggested that secondary cytoreductive surgery could provide better clinical outcomes than chemotherapy alone, in the case of complete tumor cytoreduction.2,3 About 50% of patients with ROC have a pelvic component of the disease and 22% of patients present isolated pelvic recurrence, often involving the rectum.4,5 Minimally invasive secondary cytoreductive surgery is a feasible option and is associated with favorable perioperative outcomes.6–8 It is crucial to fully explore the peritoneal cavity before starting cytoreductive procedures in order to confirm the absence of carcinomatosis.9 The robotic system facilitates the identification of anatomical structures and makes it easier to perform complex surgical steps in narrow spaces. It also allows the integrated use of surgical tools such as intraoperative ultrasound and indocyanine green application.

Methods

In this video, we present the case of a 64-year-old woman who experienced a rectal recurrence of ovarian cancer after a platinum-free interval of 12 months. We describe, in a step-by-step manner, the surgical procedure of a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis (TICA).10–12

Results

Robotic secondary cytoreduction with complete gross resection was achieved. The patient did not report any intraoperative or postoperative complications. Final histology confirmed ROC.

Conclusion

Totally robotic rectosigmoid resection is a feasible option in isolated bowel recurrences. Thanks to continuous technical evolution, robot-assisted surgery has the potential to have a central role in the fight against solid tumors. Integration of multiple pre- and intraoperative technologies allows personalized surgery to be performed for each different patient.13,14
Tradycja inkaska i jej rola w kreowaniu tożsamości narodowej Peruwiańczyków
Authors: Wójcik Karolina
Published: September 2024

The following work aims to assess the extent to which the heritage of Inca culture can act as a unifying element of contemporary Peruvian society. The article analyses the difficulties that contemporary Peruvian society encounters in trying to shape a common national identity in the context of multiethnicity and multiculturalism. The division between pre-Columbian, colonial and Spanish perspectives is one such problem. The text elucidates these social divisions resulting from the legacy of colonialism after the era of great geographical discoveries in the 16th century and seeks to understand the inherited legacy of the pre-Columbian Inca civilisation and its contribution to shaping the unified national identity. The introduction specifies the research goal of the work, which is to determine whether the Inca culture is a unifying factor in today’s Peruvian society. Then, a brief mention of the history of Spanish colonialism in Peru is made to move on to the contemporary challenges facing the people of this country. These include primarily dealing with decolonisation and objectification of indigenous peoples, protection and management of the Inca cultural heritage, mass tourism and the feeling of subordination to European civilisation. The article concludes with a view that the aforementioned issues cannot be resolved in the near future due to the political crisis in Peru. The article is based on Polish, English and Spanish literature on the subject. The Polish authors include the works of M. Kania, whose research includes the history, sociology and politics of Peru. An essential help in formulating conclusions was Defensa de la Hispanidad, a work by R. de Maeztu recently translated into Polish by A. Styczyńska and M. Wójtowicz-Wcisło.
Code and Data Repository for Decision Making Under Cumulative Prospect Theory: An Alternating Direction Method of Multipliers
Authors: Cui Xiangyu , Jiang Rujun , Shi Yun , Xiao Rufeng , Yan Yifan
Published: September 2024

The goal of this software is to demonstrate the effectiveness of the ADMM method proposed in this paper in the problem of decision making under cumulative prospect theory, as compared to other methods, as well as the effectiveness of the model when applied to empirical study.
Case Report: A Rare Case Of Bilateral Tibial Plafond Fracture In A Young Soldier
Authors:   Department of Orthopedics, Armed Forces Medical College, Pune, Maharashtra, India,, Pande Hrishikesh , Meisheri Hardik ,   Department of Orthopedics, Military Hospital Chennai, Chennai, Tamil Nadu, India.
Published: September 2024

Introduction: Tibial pilon fractures, involving the weight-bearing surface of the distal tibia, present a formidable challenge for orthopedic surgeons due to their complex nature and the delicate soft tissue envelope surrounding the ankle joint.Early approaches to pilon fractures often resulted in poor outcomes, but modern principles of internal fixation and anatomical reconstruction have significantly improved patient prognosis. Despite advancements in surgical techniques and implants, achieving anatomical reduction of the articular surface remains a significant hurdle. Case Report: This article presents a case report of a 27-year-old male soldier who sustained bilateral tibial pilon fractures following a fall from height. The patient underwent surgical intervention with differing approaches due to the complexity of the fractures. A combination of minimally invasive plate osteosynthesis (MIPPO) and external fixation was employed to address the fractures. The patient was followed up for 06 months post-op. Conclusion: The importance of respecting the soft tissue envelope in surgical planning and timing, as well as the role of advanced imaging techniques such as CT scanning in preoperative assessment is crucial to achieving a successful outcome.While tibial pilon fractures remain complex injuries, advancements in surgical management have led to improved outcomes. However, ongoing research and innovation are necessary to address the multifaceted challenges associated with these fractures and optimize patient care. Keywords: Pilon, MIPPO, ex-FIX
Research and Industry News
Authors: Curtis Susan , Daukantas Patricia , Kim Meeri , Kirkland Alessia , Lanford Hannah , Sender Rachel , Wills Stewart
Published: September 2024

Giant-clam light conversion / Multichannel X-rays / Fine eye details /
Ti:sapphire laser on chip / Holotomography / Climate change impacts /
Industry news
Integrated photonic modular arithmetic processor
Authors: Wu Yuepeng , Guo Hongxiang , Zhang Bowen , Qiu Jifang , Yang Zhisheng , Wu Jian
Published: September 2024

Integrated photonic computing has emerged as a promising approach to overcome the limitations of electronic processors in the post-Moore era. However, present integrated photonic computing systems face challenges in achieving high-precision calculations, consequently limiting their potential applications, and their heavy reliance on analog-to-digital (AD) and digital-to-analog (DA) conversion interfaces undermines their performance. Here we propose an innovative photonic computing architecture featuring scalable calculation precision and, to our knowledge, a novel photonic conversion interface. By leveraging the residue number system (RNS) theory, the high-precision calculation is decomposed into multiple low-precision modular arithmetic operations executed through optical phase manipulation. Those operations directly interact with the digital system via our proposed optical digital-to-phase converter (ODPC) and phase-to-digital converter (OPDC). Through experimental demonstrations, we showcase a calculation precision of 9 bits and verify the feasibility of the ODPC/OPDC photonic interface. This approach paves the path towards liberating photonic computing from the constraints imposed by limited precision and AD/DA converters.
Formation of quasi-bound states in the continuum in a single deformed microcavity
Authors: Liu Shuai , Wu Bo-Han , Huang Jeffrey , Zhang Zheshen
Published: September 2024

Bound states in the continuum (BICs) hold significant promise in manipulating electromagnetic fields and reducing losses in optical structures, leading to advancements in fundamental research and practical applications. Despite their observation in various optical systems, the behavior of BIC in whispering-gallery-modes (WGMs) optical microcavities, essential components of photonic integrated chips, has yet to be thoroughly explored. In this study, we propose and experimentally identify a robust mechanism for generating quasi-BIC in a single deformed microcavity. By introducing boundary deformations, we construct stable unidirectional radiation channels as leaking continuum shared by different resonant modes and experimentally verify their external strong mode coupling. This results in drastically suppressed leaking loss of one originally long-lived resonance, manifested as more than a threefold enhancement of its quality (Q) factor, while the other short-lived resonance becomes more lossy, demonstrating the formation of Friedrich–Wintgen quasi-BICs as corroborated by the theoretical model and experimental data. This research will provide a practical approach to enhance the Q-factor of optical microcavities, opening up potential applications in the area of deformed microcavities, nonlinear optics, quantum optics, and integrated photonics.
Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications
Authors: Pozhydaieva Nadiia , Billau Franziska Anna , Wolfram-Schauerte Maik , Ramírez Rojas Adán Andrés , Paczia Nicole , Schindler Daniel , Höfer Katharina
Published: September 2024

Lytic bacteriophages hold substantial promise in medical and biotechnological applications. Therefore a comprehensive understanding of phage infection mechanisms is crucial. CRISPR-Cas systems offer a way to explore these mechanisms via site-specific phage mutagenesis. However, phages can resist Cas-mediated cleavage through extensive DNA modifications like cytosine glycosylation, hindering mutagenesis efficiency. Our study utilizes the eukaryotic enzyme NgTET to temporarily reduce phage DNA modifications, facilitating Cas nuclease cleavage and enhancing mutagenesis efficiency. This approach enables precise DNA targeting and seamless point mutation integration, exemplified by deactivating specific ADP-ribosyltransferases crucial for phage infection. Furthermore, by temporally removing DNA modifications, we elucidated the effects of these modifications on T4 phage infections without necessitating gene deletions. Our results present a strategy enabling the investigation of phage epigenome functions and streamlining the engineering of phages with cytosine DNA modifications. The described temporal modulation of the phage epigenome is valuable for synthetic biology and fundamental research to comprehend phage infection mechanisms through the generation of mutants.
Prevalence and covariates of depression among older adults in Nepal: A systematic review and meta-analysis
Authors: Khanal Gayatri , Selvamani Y. , Thapa Suman , Chinnaiyan Saravanan
Published: September 2024

Globally, depression is the most common mental health condition in older individuals which is a significant emerging public health problem in developing countries like Nepal. Older adults with depression are overlooked in Nepal due to the paucity of updated evidences on geriatric depression. The current study is aimed to determine the prevalence of depression and its covariates among older adults. PRISMA-compliant searches of the PubMed, Scopus, NepMed/Nepjol, and Google Scholar databases were conducted from 2013 to 2023. The included papers’ quality was assessed using a JBI quality appraisal technique. The data were analysed using R statistical program. Heterogenicity was assessed by I2test. Random-effects model was used to calculate the pooled prevalence of depression. Twenty studies from three regions of Nepal including 5728 older adults were assessed. In Nepal, geriatric depression affected 52% of the overall population (95% CI = 44%, 59%). The pooled prevalence in the subgroup analysis was higher in the central region and among older adults living in old age homes. The presence of chronic diseases, ≥ 70 years of age, female, illiterate, limitation of Instrumental activities of daily living (IADL), and feeling of loneliness were the independent predictors of geriatric depression. Egger (p < 0.0002) and Harbord (p< 0.0001) indicated the presence of publication bias. Even though the estimation of depression differs with geographic region and study settings, one out of two older adults in Nepal had depression, suggesting the need for public health interventions to support and reduce geriatric depression in Nepal.
High-dose radiation-induced immunogenic cell death of bladder cancer cells leads to dendritic cell activation
Authors: Zeng Xianlin , Luo Daiqin , Zhang Shuai , Cui Zhonghui , Wang Yun , Chen Jin , Zhang Shichao , Teng Lijing , Hu Zuquan , Liu Lina , Zhou Shi , Zeng Zhu , Long Jinhua
Published: September 2024

Radiotherapy is a commonly used method in the treatment of bladder cancers (BC). Radiation-induced immunogenic cell death (ICD) is related to the immune response against cancers and their prognoses. Even though dendritic cells (DC) act as powerful antigen-presenting cells in the body, their precise role in this ICD process remains unclear. Accordingly, an in vitro study was undertaken to ascertain whether high-dose radiation-induced ICD of BC cells could regulate the immune response of DC. The results indicated that high-dose radiation treatments of BC cells significantly increased their levels of apoptosis, blocked their cell cycle in the G2/M phase, increased their expression of ICD-related proteins, and upregulated their secretion of CCL5 and CCL21 which control the directed migration of DC. It was also noted that expression of CD80, CD86, CCR5, and CCR7 on DC was upregulated in the medium containing the irradiated cells. In conclusion, the present findings illustrate that high-dose radiation can induce the occurrence of ICD within BC cells, concomitantly resulting in the activation of DC. Such findings could be of great significance in increasing the understanding how radiotherapy of BC may work to bring about reductions in cell activity and how these processes in turn lead to immunoregulation of the function of DC.
Evaluation of genetic diversity and population structure of Annamocarya sinensis using SCoT markers
Authors: Pan Hong , Deng Libao , Zhu Kaixian , Shi Deju , Wang Feiyong , Cui Guofa
Published: September 2024

Annamocarya sinensis (Dode) Leroy, a relict plant from the Tertiary period, is a member of Annamocarya genus in the Juglandaceae family. Despite its wide distribution in Guangxi Province, the habitats of this species had become fragmented and isolated, causing it facing deterioration. For protecting this endangered species, it is crucial to understand its status in the wild and genetic diversity. In this study, 216 A. sinensis accessions from 18 populations in Guangxi were examined using Start Codon Target Polymorphism (SCoT) markers for PCR amplification, genetic diversity, and population structure analysis. Out of the 20 SCoT primers used, 222 sites were amplified, with 185 being polymorphic (PPB of 83.33%). Polymorphic information content values ranged from 0.4380 to 0.4999, Nei’s genetic diversity index ranging from 0.1573 to 0.2503, and Shannon diversity index ranged from 0.1583 to 0.3812. Through AMOVA analysis, the total genetic diversity and genetic diversity within populations was calculated out as 0.3271 and 0.1542 respectively, the genetic differentiation coefficient between populations was 0.5286, with a gene flow 0.4458. Cluster analysis categorized A. sinensis germplasm into three groups, while population structure analysis divided all accessions into three ancestral sources with 19.91% showing mixed ancestral origins. No significant correlation was observed between genetic and geographical distance on the Mentel test (r = 0.07348, p = 0.7468). Overall, A. sinensis displays a relatively rich genetic diversity at the species level, albeit with a fairly uniform genetic background and high genetic differentiation. This study provides a crucial basis for the conservation and innovative use of A. sinensis germplasm resources.
Persistent hypertension among postpartum women with comorbid HIV and preeclampsia in Zambia
Authors: Mukosha Moses , Hatcher Abigail , Lubeya Mwansa Ketty , Maposa Innocent , Chi Benjamin H. , Mutale Wilbroad
Published: September 2024

Background

Persistent hypertension is common after preeclampsia and is causally tied to later cardiovascular risks. This study examined whether being HIV-infected and on antiretroviral therapy (ART) is associated with persistent postpartum hypertension among women diagnosed with preeclampsia.

Methods

We conducted a six-month prospective cohort study at Kanyama and Women and Newborn hospitals from January 01, 2022, to June 30, 2023, among 190 women diagnosed with preeclampsia (59 HIV-positive, 131 HIV-negative). Sociodemographic and clinical characteristics were collected at delivery, six weeks, three months and six months after giving birth. Persistent hypertension was diagnosed if a participant presented with elevated blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg and/or taking medication for hypertension at the study visit. We used a generalized estimating equation to describe the relationship between treated HIV and persistent hypertension six months following delivery.

Results

We retained 136 participants (71.6%) to six months postpartum, at a median age of 30 years. Overall, persistent hypertension at six weeks, three months, and six months postpartum was common (37.4%, 17.1% and 16.9%, respectively). Six-week postpartum prevalence was higher in the HIV group than HIV-negative group (54.6% vs 28.8%, p<0.001), with no measurable difference at three months (24.3% vs 13.2%, p = 0.145) or six months (18.2% vs 16.3%, p = 0.787). Multivariable analysis demonstrates higher odds (adjusted odds ratio [aOR] = 1.68, 95% CI: 1.09–2.60) of persistent hypertension among the HIV+treatment group than HIV-negative counterparts after accounting for age, body mass index and time since delivery.

Conclusion

We demonstrate an elevated risk of persistent hypertension among postpartum women with comorbid preeclampsia and treated HIV. Peripartum patients in HIV-endemic settings may benefit from timely detection of hypertension and treatment interventions to improve health outcomes.