bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Different Seed Sources and Planting Tube Sizes on Germination and Early Growth of Baobab Seedlings in Malawi
Authors: Ndong Ngagne , Mhango Jarret , Ngulube Elisha
Published: November 2024

Baobab is an important multipurpose fruit tree which provides food and economic values along the sub‐Saharan African countries. Although there has been remarkable research on domestication of Adansonia digitata, understanding the variation on seed germination and early growth of baobab among different seed sources and planting tube sizes is essential for silvicultural practices at the nursery stages, massive domestication and conservation strategies. The study assessed the effect of different planting tube sizes on seed germination and early growth of baobab seedlings of 10 Malawi subpopulations. Two‐way ANOVA revealed significant interaction (p < 0.001) between subpopulations and planting tube sizes on germination percentage and early growth in the number of leaves, root collar diameter, plant height, tuber length and tuber weight. Both seed source and different planting tube sizes significantly affected the germination and early growth of baobab. In conclusion, germination and growth of baobab is influenced by subpopulations and planting tube sizes. The results signify that different genotypes responded differently to the microclimate of tube sizes on germination and growth of baobab.
Combining Counterfactual Regret Minimization With Information Gain to Solve Extensive Games With Unknown Environments
Authors: Qiu Chen , Wang Xuan , Ma Tianzi , Wen Yaojun , Zhang Jiajia
Published: November 2024

Counterfactual regret minimization (CFR) is an effective algorithm for solving extensive‐form games with imperfect information (IIEGs). However, CFR is only allowed to be applied in known environments, where the transition function of the chance player and the reward function of the terminal node in IIEGs are known. In uncertain situations, such as reinforcement learning (RL) problems, CFR is not applicable. Thus, applying CFR in unknown environments is a significant challenge that can also address some difficulties in the real world. Currently, advanced solutions require more interactions with the environment and are limited by large single‐sampling variances to narrow the gap with the real environment. In this paper, we propose a method that combines CFR with information gain to compute the Nash equilibrium (NE) of IIEGs with unknown environments. We use a curiosity‐driven approach to explore unknown environments and minimize the discrepancy between uncertain and real environments. In addition, by incorporating information into the reward, the average strategy calculated by CFR can be directly implemented as the interaction policy with the environment, thereby improving the exploration efficiency of our method in uncertain environments. Through experiments on standard testbeds such as Kuhn poker and Leduc poker, our method significantly reduces the number of interactions with the environment compared to the different baselines and computes a more accurate approximate NE within the same number of interaction rounds.
Determinants of Visceral Leishmaniasis in Addis Zemen Health Center, Northwest Ethiopia
Authors: Gedamu Atsedemariam Nigus , Andargie Asrat Atsedeweyn , Aguade Aragaw Eshetie , Tezera Samuel Derso
Published: November 2024

Background: Visceral leishmaniasis (VL) is one of the public health issues in some areas of Ethiopia, and over 3.2 million people are at risk with an estimated 4000 new cases occurring each year in the country. This study was conducted to determine the prevalence of VL and its associated risk factors in Addis Zemen Health Center, Northwest Ethiopia.

Methods: Data were collected from Addis Zemen Health Center and meteorological office in Addis Ababa from 2012 to 2016. Univariate and multivariate analyses were conducted to identify the determinants of VL. According to the result obtained from the retrospective data analysis, a total of 4100 suspected VL patients diagnosed by rk39 in Addis Zemen Health Center from Libokemkem and nearby districts.

Results: The overall prevalence of VL among study participants were 30% (1230/4100). Of this, the prevalence of VL among male and female study participants was 86.8% and 13.2%, respectively. The proportion of sex infected by VL was 3.26 times higher in male than female (AOR = 3.26, 95% CI: 2.42–4.40). The risk of acquiring VL in those people living in rural area was 62% more likely than those residing in urban (AOR = 1.62, 95% CI: 1.29–2.04). People that were traveled to the endemic area of VL were 18.44 times more likely to be affected than the people who have not traveled once (AOR = : 18.44, 95% CI: 14.49–23.47). Age, sex, residence, season, travel history to endemic areas, and mean monthly precipitation were found to be statistically significant for VL at 5% significance level.

Conclusion and Recommendation: The prevalence of VL in the present study was high with the highest prevalence in the rural areas. Therefore, there is a need of the immediate establishment of sound control and prevention program in rural areas.
Breast Cancer Subtype–Specific Organotropism Is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery
Authors: Jiang Wen-Jing , Zhou Tian-Hao , Huang Huan-Jing , Li Lin-Sen , Tan Hao , Zhang Rui , Wang Qing-Shan , Feng Yu-Mei
Published: November 2024

Breast cancer subtypes display different metastatic organotropism. Identification of the mechanisms underlying subtype-specific organotropism could help uncover potential approaches to prevent and treat metastasis. In this study, we found that forkhead box F2 (FOXF2) promoted the seeding and proliferative recovery from dormancy of luminal breast cancer (LumBC) and basal-like breast cancer (BLBC) cells in the bone by activating the NF-κB and BMP signaling pathways. FOXF2 promoted LumBC cell seeding but not proliferative recovery in the lung by activating the BMP signaling pathway. Conversely, FOXF2 suppressed the seeding and proliferative recovery of BLBC cells in the lung by repressing the TGFβ signaling pathway. FOXF2 directly upregulated RelA/p65 transcription and expression in LumBC and BLBC cells by binding to the RELA proximal promoter region and RelA/p65 bound to the FOXF2 proximal promoter region to upregulate expression, forming a positive feedback loop. Targeting the NF-κB pathway efficiently prevented the metastasis of FOXF2-overexpressing breast cancer cells to the bone, whereas inhibiting TGFβ signaling blocked the metastasis of BLBC with low FOXF2 expression to the lung. These findings uncover critical mechanisms of breast cancer subtype–specific organotropism and provide insights into precision assessment and treatment strategies.

Significance: FOXF2 regulates signaling pathways in a subtype-specific manner to coordinate the fate of disseminated breast cancer cells in distant organs, suggesting that FOXF2 functions could be harnessed to prevent organ-specific metastasis.

See related commentary by Bado, p. 639
Stayin' Alive: Targeting Chromatin Regulators of Clonal Hematopoiesis Promotes CD8 T-cell Stemness
Authors: Qiu Xingjian , Yang Aaron , Poholek Amanda C.
Published: November 2024

T-cell exhaustion remains a significant barrier to immunotherapeutic success for many patients with solid tumors. Growing evidence suggests that enhanced survival and self-renewal properties of a stem-like precursor T-cell population are correlated with a survival advantage in immunotherapy. In a recent study published in Science, Kang and colleagues found that three epigenetic regulators commonly mutated in clonal hematopoiesis also control precursor T-cell progression to exhaustion. By leveraging the finding that patients with enhanced survival in myelodysplastic syndrome had T-cell mutations in the ASXL1 gene, this study demonstrates that loss of ASXL1 in T cells preserves their stem cell–like properties of self-renewal and survival, leading to increased antitumor responses when combined with immunotherapy in both mouse models and human cancers. These findings have significant implications for new therapeutic options that target epigenetic modifiers promoting exhaustion together with immune checkpoint blockade to improve response rates in patients.
Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies
Authors: Haffner Michael C. , Morris Michael J. , Ding Chien-Kuang C. , Sayar Erolcan , Mehra Rohit , Robinson Brian , True Lawrence D. , Gleave Martin , Lotan Tamara L. , Aggarwal Rahul , Huang Jiaoti , Loda Massimo , Nelson Peter S. , Rubin Mark A. , Beltran Himisha
Published: November 2024

Lineage plasticity and histologic transformation from prostate adenocarcinoma to neuroendocrine (NE) prostate cancer (NEPC) occur in up to 15% to 20% of patients with castration-resistant prostate cancer (CRPC) as a mechanism of treatment resistance and are associated with aggressive disease and poor prognosis. NEPC tumors typically display small cell carcinoma morphology with loss of androgen receptor (AR) expression and gain of NE lineage markers. However, there is a spectrum of phenotypes that are observed during the lineage plasticity process, and the clinical significance of mixed histologies or those that co-express AR and NE markers or lack all markers is not well defined. Translational research studies investigating NEPC have used variable definitions, making clinical trial design challenging. In this manuscript, we discuss the diagnostic workup of metastatic biopsies to help guide the reproducible classification of phenotypic CRPC subtypes. We recommend classifying CRPC tumors based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, other morphologic variant, or mixed morphology) and IHC markers with a priority for AR, NK3 homeobox 1, insulinoma-associated protein 1, synaptophysin, and cell proliferation based on Ki-67 positivity, with additional markers to be considered based on the clinical context. Ultimately, a unified workup of metastatic CRPC biopsies can improve clinical trial design and eventually practice.
Figure S2 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Patients were divided into three groups based on the percentages of CD8+ T cells
Bleeding Complications between Bivalirudin and Heparin for Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia
Authors: Credille Caroline , Eason Caitlin R. , Evans Lauren L. , Bothwell Samantha , Gien Jason , Vaughn Alyssa E. , Kinsella John P. , Varma Pavika , Liechty Kenneth W. , Derderian S. Christopher
Published: November 2024

Introduction: Neonates with congenital diaphragmatic hernia (CDH) who undergo repair while on extracorporeal membrane oxygenation (ECMO) are at risk of developing post-operative bleeding complications. Balanced anticoagulation is critical to maintain ECMO flow and avoid bleeding. Heparin has historically been our first-line anticoagulant; however, recently, we transitioned to bivalirudin, a direct thrombin inhibitor. The objective of this pilot study was to compare post-operative surgical bleeding complications between the two groups. Methods: We performed a single center retrospective cohort study of patients who underwent CDH repair while on ECMO between 2008 and 2023. Neonates were stratified based on the type of anticoagulant initiated after CDH repair. Outcomes included bleeding requiring surgical re-operation, intracranial hemorrhage, volume of blood products transfused, number of circuit changes, days on ECMO, and overall survival. Results: Among 62 neonates with CDH who underwent repair on ECMO, 44 (71%) were managed post-CDH repair with heparin and 18 (29%) with bivalirudin. One (5.6%) neonate managed with bivalirudin underwent re-operation following CDH repair for a bleeding complication compared to 17 (38.6%) managed with heparin (p = 0.022). In addition, the bivalirudin cohort utilized half of the total blood product volume compared to the heparin cohort (p = 0.020). Despite these benefits, there were no significant differences between groups for incidence of intracranial hemorrhage, number of circuit changes, days on ECMO, and overall survival. Conclusion: Anticoagulation with bivalirudin in neonates who underwent CDH repair while on ECMO was associated with decreased surgical bleeding complications and less total blood product transfused. This pilot analysis is the first to compare heparin to bivalirudin and stresses the importance of a multicenter study.
Unregulated wild orchid trade in Manipur: an analysis of the Imphal Valley markets from the Indo-Burma hotspot
Authors: Kamei Kambuikhonlu Kabuini  , Maibam Dhanaraj Meitei
Published: November 2024

Unsustainable and illegal trade of wild orchids at local and international markets is a well-known conservation issue throughout the world. Local as well as international trade of wild orchids is under-reported and under-researched. The study assessed wild orchids traded in markets of the Imphal Valley, the northeastern Indian state of Manipur in 2022–23. Eighty-two wild orchid species from 33 genera were observed to be traded including the wild orchid species, viz., Paphiopedilum hirsutissimum, Renanthera imschootiana, and Vanda coerulea, protected under the Wildlife (Protection) Act, 1972 of India. The local wild orchid trade in Imphal is unregulated, unchecked and unmonitored, which is a serious concern for the conservation of wild orchid species in Manipur and within the Indo-Burma hotspot.
Purity of Faith, Madhhab Partisanship, and Legitimising Ideology in the Great Seljuq Sultanate
Authors: Tor D.G.
Published: November 2024

The madhhab is usually investigated from the standpoint of fiqh. But there was also a social aspect to the importance of the madhhab, which at no time played a more crucial social role than during the Seljuq period (1040–1194). In particular, Ḥanafī madhhab affiliation became both the post-conquest ideological justification for Seljuq rule, and the glue holding together the two elements of the Seljuq ruling class: The Turkish magnates and the Khurasani bureaucrats. This article proves three points: First, that the original Seljuq conquest neither looked like nor purported to be the religious mission the Seljuqs later claimed it was; second, it traces the post-facto madhhab-based justification of their rule which the Seljuqs adopted, and its success in obtaining Khurasani support for the Seljuq regime; and, finally, it shows also the negative consequences this ideology of partisan Ḥanafism had on the internal peace of their realm and its urban flourishing.
All the Dead Boys Look Like Me
Authors: Lalude Olalekan Moyosore
Published: November 2024

Nigeria criminalised same sex marriages in 2014 which put a state approval to homophobic violence and discrimination. Just in 2021, Ghana made a similar and even more dangerous move towards homophobia when its parliament had a bill proposed towards the criminalisation of the advocacy for gay people and would legitimise prosecution of the members of the lgbt+. These developments have left sexual minorities vulnerable by making them open to attacks from homophobic people and creating institutionalised discrimination. Through a phenomenological research approach, this study would examine how legal frameworks influence the recognition and protection of rights for sexual minorities in Ghana and Nigeria. Unstructured interviews with members of the lgbt and human rights advocates would be conducted both in Nigeria and Ghana. Content analysis, especially conceptual analysis, would be done on the Constitution of the Republic of Ghana 1992 and the Constitution of the Federal Republic of Nigeria, human rights norms, journal articles and other secondary materials. This study would conclude that homophobia cedes state agency to non-state actors and undermines the right to life as protected in the Ghanaian and Nigerian constitutions. Strategies for advocacy against homophobia and for the protection of the rights of sexual minorities would be recommended.
Baptist and Catholic? Tradition and Authority in the Baptist Theology of Stephen R. Holmes
Authors: Fellows Philip
Published: November 2024

This article begins by analysing the principles at the heart of Stephen R. Holmes’ vision of Baptist theology and ecclesiology. It then examines Holmes’ work on the authority of theological Tradition. It is demonstrated that Holmes argues for a pneumatologically rooted and consensual understanding of Tradition that locates its authority in the testimony of the whole church to the voice and will of the Spirit interpreting the texts he inspired. In the final third of the argument, these two areas of Holmes’ work are brought into dialogue to generate an authentically Baptist conception of the authority of Tradition to bind the local church. It is suggested that this can help Baptists and others holding to some form of congregational church government resolve issues in their commitment to the catholicity and unity of the Church, provide a more secure ground for theological discernment, and enable more fruitful ecumenical dialogue.
Constructions of Religion in Swedish Newspaper Articles on Funerals during the covid-19 Pandemic
Authors: Jarnkvist Karin
Published: November 2024

This study examines the discursive construction of religion in Swedish newspaper articles on funerals during the covid-19 pandemic. Thirty articles from the six most prominent newspapers were analyzed using Multimodal cda and intersectionality. Most articles deal with religion as an institution, followed by religion as a group and individual religiosity. Religion is constructed in intersection with ethnicity and gender. The CoS is privileged, portraying Lutheran Christians as professionals. Minority religions are positioned as ‘the other’, something ‘problematic’ or ‘different’ from ‘Swedish (secular) values’ and ways of living. Migrant men and women are portrayed stereotypically. However, alternative narratives are told by well-educated and influential representatives of different minority religions, giving these religions a ‘voice’. I argue that increased religious literacy is needed among media workers if the reporting should be based on equality within and between the power categories of gender, ethnicity, and religion.
Dispute Resolution in the AfCFTA Investment Protocol: a Preliminary Assessment and Proposal for Business and Human Rights Arbitration
Authors: Ogunranti Akinwumi
Published: November 2024

This paper examines whether the Investment Protocol to the African Continental Free Trade Area (AfCFTA) Agreement aligns with international human rights law’s (IHRL) standards on the right to equality, non-discrimination, and access to an effective remedy. It argues that the Protocol’s dispute resolution model, which tilts towards ISDS, is incompatible with IHRL. This paper recommends incorporating the Hague Rules on Business and Human Rights Arbitration (Hague Rules) into the Protocol to create an IHRL-compatible dispute system, especially regarding enforcing human rights, environment, and climate obligations against investors and states. As African countries finalize the annex to the Protocol, they must replace ISDS with a BHR Arbitration framework as the dispute settlement regime within which investment players must enforce their rights.
A review of the genus Kalanchoe (Crassulaceae subfam. Cotyledonoideae) in the Euro-Mediterranean area, with an annotated catalogue and identification key
Authors: GALLO LORENZO , SMITH GIDEON F.
Published: November 2024

The genus Kalanchoe (with Bryophyllum included in its synonymy) (Crassulaceae subfam. Cotyledonoideae) has a wide natural geographical distribution range that stretches from Madagascar to some islands in the Indian Ocean off the east coast of Africa, to most of sub-Saharan and northern North Africa, and to the Near, Middle, and Far East. However, several representatives of the genus have been spread across mild-climate and even temperate parts of the world well beyond their natural distribution ranges because of their medicinal uses and because they are cultivated for ornamental (both indoor and outdoor) horticultural purposes. In addition, a number of taxa have become notorious in invasions biology as a result of casual introductions that probably resulted from surplus horticultural material being irresponsibly discarded. In the Euro-Mediterranean region 13 Kalanchoe taxa have spread widely into the natural and built environment. In the present paper the nomenclature of the 13 variously naturalised taxa is updated and corrected, and their country-level presence and spread in the Euro-Mediterranean are recorded. An analytical key is provided to facilitate the identification of the taxa that have escaped from cultivation in the Euro-Mediterranean region. A list of taxa that are cultivated but that have not become weedy, nor naturalised or invasive in the study area is provided. Most of the kalanchoes recorded here is illustrated.
Dianthus malyeri (Caryophyllaceae), a new species from Türkiye
Authors: BAĞÇIVAN GÜLŞAH , DAŞKIN RUZİYE
Published: November 2024

Dianthus malyeri (sect. Dentati) is described and illustrated as a new species from Bursa Province, in northwestern Anatolia, Türkiye. The new species morphologically resembles D. elegans, but distinctly differs in its longer, with more nodes stems, shorter leaves, shorter calyx, as well as shorter petals with 6–11-toothed at apex. A detailed description, photographs, a morphological comparision with D. elegans vars. elegans and cous, IUCN conservation status assessment, distribution map, notes on ecology of the new species are presented.
Wnt5a promotes Kupffer cell activation in trichloroethylene-induced immune liver injury
Authors: Gao Lei , Ding Ya-Ni , Zhou Peng-Cheng , Dong Luo-Lun , Peng Xin-Yu , Tang Yi-Ru , Zhu Qi-Xing , Zhang Jia-Xiang
Published: November 2024

Trichloroethylene (TCE) is a volatile, colorless liquid that is widely used as a chlorinated organic vehicle in industrial production and processing industries. Many workers exposed to trichloroethylene may develop trichloroethylene hypersensitivity syndrome (THS). However, the underlying mechanism of THS is still unclear, especially liver injury. The present study aimed to investigate whether Wnt5a/c-Jun N-terminal kinase (JNK) is involved in and regulates liver injury caused by TCE exposure and to provide new directions for the prevention and treatment in clinical settings of liver injury caused by TCE exposure. We used 6- to 8-week-old SPF-grade BALB/c female mice to establish a TCE sensitization model and explored the mechanism through inhibitor intervention. We found that the expression of Wnt5a/JNK was significantly elevated in the liver of TCE sensitization-positive mice. Inhibitors of Wnt Production 2 (IWP-2) are known antagonists of the Wnt pathway. TCE-sensitization mice treated with IWP-2 showed downregulated Wnt5a/JNK expression, reduced Kupffer cell activation, and decreased liver injury. At the same time, we found that phosphorylated JNK in TCE-sensitization mouse livers and extracted Kupffer cells showed a significant downward trend after inhibition of Wnt5a function. We also found that a specific JNK inhibitor, SP600125, decreased the secretion of cytokines and chemokines and decreased Kupffer cell activation. We demonstrated that Wnt5a/JNK was involved in the regulation of liver injury in TCE-sensitization mice and that it exacerbated liver injury by activating Kupffer cells and releasing chemokines. We therefore hypothesized that Kupffer cell activation was affected by JNK, which reduced chemokine and cytokine secretion and attenuated liver injury in TCE-sensitization mice.
Exploring Personality Traits, Coping Strategies, and 5-Year Change in Blood Pressure in Young Adults: The African-PREDICT Study
Authors: Papenfus Anchenique , Botha Karel , Mels Carina , Cockeran Marike
Published: November 2024

This sub-study of the African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT) explored possible early psychological predictors of change in blood pressure. In a sample of normotensive at baseline black and white South Africans ( n = 105; mean age at baseline 24.93), this study investigated the relationship between personality traits, coping strategies, and 24-hour ambulatory blood pressure measured at baseline and 5-year follow-up. Another aim was to investigate a possible mediating effect of coping strategies on the relationship between personality traits and change in blood pressure. Extraversion, agreeableness, openness, and problem-solving skills were identified as possible protective factors against cardiovascular risk, confirming previous research in this regard. However, the effect of these was different for gender and ethnic subgroups. Preconditions for a possible mediation role for coping in the relationship between personality and change in blood pressure were not met. Future research should further explore gender and ethnic differences in the relationship between personality, coping, and cardiovascular health.
Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics
Authors: Hu Lingyu , Wang Xiaoguang , Song Zhengwei , Chen Fei , Wu Bin
Published: November 2024

Background

Pancreatic cancer is known for its poor prognosis and resistance to conventional therapies, largely due to the presence of cancer stem cells (CSCs) and aggressive angiogenesis. Effectively targeting these CSCs and associated angiogenic pathways is crucial for effective treatment. This study leverages single-cell multi-omics to explore a novel therapeutic approach involving Chimeric Antigen Receptor (CAR) macrophages engineered to target the c-Met protein on pancreatic CSCs.

Methods

We employed single-cell RNA sequencing to analyze pancreatic cancer tissue, identifying c-Met as a key marker of CSCs. CAR macrophages were engineered using a lentiviral system to express a c-Met-specific receptor. The phagocytic efficiency of these CAR macrophages against pancreatic CSCs was assessed in vitro, along with their ability to inhibit angiogenesis. The in vivo efficacy of CAR macrophages was evaluated in a mouse model of pancreatic cancer.

Results

CAR macrophages demonstrated high specificity for c-Met + CSCs, significantly enhancing phagocytosis and reducing the secretion of angiogenic factors such as VEGFA, FGF2, and ANGPT. In vivo, these macrophages significantly suppressed tumor growth and angiogenesis, prolonging survival in pancreatic cancer-bearing mice.

Conclusion

CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies.
The miR-1269a/PCDHGA9/CXCR4/β-catenin pathway promotes colorectal cancer invasion and metastasis
Authors: Mei Haitao , Luo Qingshan , Weng Junyong , Hao Jialing , Cai Jinfeng , Zhou Runkai , Bian Ce , Ye Yingzi , Luo Shengzheng , Wen Yugang
Published: November 2024

Background

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This research focuses on investigating the impact and underlying molecular mechanisms of protocadherin gamma subfamily A, 9 (PCDHGA9) on the invasion and metastasis of CRC, aiming to identify more precise molecular markers for the diagnosis and prognosis of CRC.

Methods

PCDHGA9 expression was detected using quantitative real-time quantitative polymerase chain reaction (RT-qPCR) in 63 pairs of colorectal cancer tissues. Differential gene expression from high-throughput sequencing was analyzed using ingenuity pathway analysis (IPA) to explore the biological functions of PCDHGA9 and its potential regulated genes. Bioinformatics tools were employed to explore potential upstream regulatory microRNAs of PCDHGA9. Dual-luciferase assays were performed to demonstrate the regulation between PCDHGA9 and miR-1269a. Protein mass spectrometry suggested an interaction between PCDHGA9 and HOXA1. JASPAR predicted that HOXA1 may act as a transcription factor of CXCR4. Coimmunoprecipitation, dual-luciferase assays, and nuclear–cytoplasmic fractionation experiments confirmed the molecular mechanism involving PCDHGA9, CXCR4, HOXA1, and β-catenin. Transwell, wound healing, and western blot assays were conducted to confirm the impact of PCDHGA9, miR-1269a, and CXCR4 on the invasion, metastasis, and epithelial–mesenchymal transition (EMT) functions of CRC cells in in vitro experiments. A whole-body fluorescence imaging system was used to evaluate the combined impact of miR-1269a and PCDHGA9 on the invasion and metastasis of CRC in in vivo experiments.

Results

The expression of PCDHGA9 was found to be lower in CRC tissues compared with their corresponding adjacent tissues. Low expression of PCDHGA9 potentially correlated with worse prognosis and increased chances of invasion and metastasis in CRC. miR-1269a was highly expressed in CRC tissues and acted as a negative regulator for PCDHGA9, promoting invasion, migration, and EMT of CRC cells. PCDHGA9’s interaction with HOXA1 downregulated CXCR4, a transcription factor, leading to accumulation of β-catenin and further promoting invasion, migration, and EMT of CRC cells.

Conclusions

PCDHGA9, acting as a tumor suppressor, is downregulated by miR-1269a. The low level of PCDHGA9 activates the Wnt/β-catenin pathway by releasing its interaction with HOXA1, promoting the expression of CXCR4, and causing invasion, migration, and EMT in CRC.

Graphical Abstract
Epidemiology of healthcare-associated bloodstream infection in South African neonatal units
Authors: Dramowski Angela , Bolton Larisse , Bekker Adrie , Engelbrecht Arnoldus , Erasmus Louisa , Fataar Aaqilah , Geldenhuys Chandre , Kunneke Marlize , Roux Dave Le , Connell Natasha O’ , Reddy Kessendri , Rhoda Natasha , Tooke Lloyd , Wates Mark , Wessels Thandi , van Schalkwyk Cari , Whitelaw Andrew
Published: November 2024

Background

Reports of healthcare-associated bloodstream infection (HA-BSI) epidemiology in African neonatal units are limited.

Methods

We conducted a cross-sectional study (2017–2018) in nine neonatal units in the Western Cape Province, South Africa, including central, regional and district hospitals (416 beds) using laboratory and clinical records. Patient demographics, HA-BSI rates, pathogen spectrum, and hospital outcomes and empiric antibiotic coverage rates were determined.

Results

Over two years, 23,748 neonates were admitted with unit occupancy rates ranging from 79 to 93%. 485 HA-BSI episodes occurred, with median onset at 11 (IQR 7–24) days of life. Most HA-BSI episodes (348; 72%) affected very low birth weight neonates (< 1500 g). The overall HA-BSI rate was 2.0/1000 patient days. The highest HA-BSI rate was observed at the central unit with onsite surgery (3.8/1000 patient days). Crude HA-BSI mortality was 31.8% (154/485) with two-thirds of deaths occurring within three days of BSI onset. Higher mortality was observed for Gram-negative/fungal BSI compared to Gram-positive BSI (RR 1.5; 95%CI 1.1-2.0; p = 0.01) and very preterm neonates (gestation < 32 weeks) versus ≥ 32 weeks (RR 1.5; 95%CI 1.1–2.1; p = 0.01). Mean estimated empiric antibiotic coverage rates varied by unit type: 66–79% for piperacillin-tazobactam plus amikacin, 60–76% for meropenem and 84–92% for meropenem plus vancomycin.

Conclusion

Most HA-BSI events affected preterm neonates at the central hospital with onsite surgery. One-third of patients with HA-BSI died, with highest mortality in preterm infants and Gram-negative/fungal BSI. Empiric antibiotic regimens provide moderate coverage of circulating pathogens but require annual review given increasing carbapenem resistance rates.
Nephrology providers’ perspective and use of mortality prognostic tools in dialysis patients
Authors: Bergeron Jennifer , Marchese Christina , Jensen Colton , Meagher Sean , Kennedy Amanda G. , Tompkins Bradley , Cheung Katharine L.
Published: November 2024

Background

Mortality prognostic tools exist to aid in shared decision making with kidney failure patients but are underutilized. This study aimed to elucidate nephrology providers’ practice patterns and understand barriers to prognostic tool use.

Methods

Nephrology providers (8 physicians and 2 nurse practitioners) at an academic medical center underwent semi-structured interviews regarding their experience and perspective on the utility of mortality prognostic tools. Common themes were identified independently by 2 reviewers using grounded theory. Three six-month mortality prognostic tools were applied to the 279 prevalent dialysis patients that the interviewed providers care for. The C statistic was calculated for each tool via logistic regression and subsequent ROC analysis. Nephrology providers reviewed the performance of the prognostication tools in their own patient population. A post interview reassessed perspectives and any change in attitudes regarding the tools.

Results

Nephrology providers did not use these mortality prognostic tools in their practice. Key barriers identified were provider concern that the tools were not generalizable to their patients, providers’ trust in their own clinical judgement over that of a prognostic tool, time constraints, and lack of knowledge about the data behind these tools. When re-interviewed with the results of the three prognostic tools in their patients, providers thought the tools performed as expected, but still did not intend to use the tools in their practice. They reported that these tools are good for populations, but not individual patients. The providers preferred to use clinical gestalt for prognostication.

Conclusion

Although several well validated prognostic tools are available for predicting mortality, the nephrology providers studied do not use them in routine practice, even after an educational intervention. Other approaches should be explored to help incorporate prognostication in shared-decision-making for patients receiving dialysis.
Detecting sleep and physical activity changes across the perinatal period using wearable technology
Authors: Claydon Elizabeth A. , Lilly Christa L. , Caswell Erin D. , Quinn Dawna C. , Rowan Shon P.
Published: November 2024

Background

Pregnant women may not experience disruptions in sleep duration throughout the course of pregnancy, however, their sleep quality is dramatically impaired. Sleep quality deteriorates throughout pregnancy, reaching its lowest in the third trimester. The purpose of this study was to understand the change in sleep patterns across the perinatal period, as well as the impact of physical activity on sleep.

Methods

A total of 18 physically active women trying to conceive wore a WHOOP strap (a fitness monitor) across the perinatal period. Daily behavior changes were tracked including time awake, hours in deep sleep, physical activity, and time in moderate to vigorous physical activity.

Results

Women maintained overall physical activity levels during and after pregnancy and averaged 20.70 min of physical activity and 6.97 h of sleep per day. Total time in awake hours increased postpartum. Moderate-vigorous physical activity minutes improved deep sleep hours overall (Est. = 0.003 h, p < 0.0001) and during pregnancy (Est. = 0.00001 h, p = 0.0004). Similar effects were found for all activity minutes, although in post pregnancy the moderating impact of activity minutes no longer maintained significance (p = 0.09).\.

Conclusions

Wearable technology, including fitness monitors such as WHOOP straps offer a convenient and less invasive way to track sleep and physical activity during the perinatal period. The findings of this study indicate a positive connection between sleep and engaging in moderate to vigorous activity and any activity throughout the perinatal period. These results may help inform clinical and practical recommendations for physical activity to improve sleep outcomes for pregnant women.
Puberty and NeuroDevelopment in adolescents (PANDA): a study protocol
Authors: Bray Katherine O. , Durbin Olivia , Hartanto Stephanie , Khetan Muskan , Liontos Daniel , Manuele Sarah J. , Zwaan Isabel , Ganella Despina , Herting Megan M. , Kim Jee Hyun , O’Connell Michele , Pozzi Elena , Schwartz Orli , Seal Marc , Simmons Julian , Vijayakumar Nandita , Whittle Sarah
Published: November 2024

Background

Biopsychosocial changes during adolescence are thought to confer risk for emotion dysregulation, and in particular, anxiety disorders. However, there are substantial gaps in our knowledge about the biological mechanisms underlying anxiety during adolescence, and whether this contributes to the higher prevalence in females. The Puberty and NeuroDevelopment in Adolescents (PANDA) study aims to examine links between biological (sex hormones, cortisol) and social environmental factors and brain function during adolescence, with a focus on key processes (emotion regulation, fear learning) identified as relevant for the development of anxiety disorders.

Methods

PANDA is a cross-sectional study with an observational design that aims to recruit a total of 175 adolescents aged 11-16 (majority female) and their parents/guardians, from the community. Brain function will be examined using magnetic resonance imaging (MRI), including functional MRI tasks of emotion regulation and fear learning. Hormones will be measured from hair (i.e., cortisol) and weekly saliva samples (i.e., oestradiol, progesterone, five across a month in females). Questionnaires and semi-structured interviews will be used to assess mental health and social environmental factors such as parenting and adverse childhood experiences. An online study of 113 adolescents was also incorporated during the COVID-19 pandemic as a questionnaire-only sub-study.

Discussion

Strengths of this study include the collection of multiple saliva samples to assess variability in hormone levels, examination of the timing of adverse childhood experiences, inclusion of both maternal and paternal parental factors, exploration of mechanisms through the examination of brain structure and function, and multi-method, multi-informant collection of mental health symptoms. This study addresses important gaps in the literature and will enhance knowledge of the biological and environmental contributors to emotion dysregulation and anxiety in adolescents.
Breastfeeding support during the Covid-19 pandemic in England: analysis of a national survey
Authors: Quigley Maria A. , Harrison Sian , Levene Ilana , Buchanan Phyllis , McLeish Jenny , Alderdice Fiona
Published: November 2024

Background

Breastfeeding support interventions are associated with longer breastfeeding duration. Contemporary nationally representative data on breastfeeding support as reported by women in England is lacking. Using English national maternity survey data, we describe sources and modes of breastfeeding support as reported by women who gave birth in 2020; sources of support are compared with earlier maternity surveys (2014, 2016, 2018). We also explore the characteristics associated with source/mode of support in 2020 (n = 4,611).

Methods

Women who breastfed were asked about sources of breastfeeding support (midwife; other health professional; other formal breastfeeding support such as breastfeeding specialist, breastfeeding support group, peer supporter; and partner/friend/relative), how this help was given and whether they would have liked more help from a health professional with breastfeeding. Adjusted risk ratios (aRR) for the association between sociodemographic and pregnancy-related variables and each source/mode of support were estimated using modified Poisson regression.

Results

From 2014 to 2020 support from midwives and other health professionals declined (from 84.0% to 64.7%, and 61.6% to 15.5% respectively) whereas other formal breastfeeding support and informal support from partners/friends/relatives remained constant at 27–31% and 34–38% respectively. The proportion of women who wanted more help with breastfeeding increased from 30% in 2014–2018 to 46% in 2020. In 2020, women most likely to want more help with breastfeeding were nulliparous (aRR = 1.64, 95%CI:1.50–1.79), younger (aRR = 1.21, 95%CI:1.03–1.42) and of Pakistani ethnicity (aRR = 1.30, 95%CI:1.06–1.60). Receiving breastfeeding support over the phone (35%) was more common than via video call (13%) or text message (5%); these percentages varied according to socio-demographic and pregnancy-related factors.

Conclusions

Breastfeeding support has declined in recent years, and did not meet the needs of many women during the pandemic. Planning for a future emergency should include adequate provision of breastfeeding support particularly if staff are redeployed into other roles. The characteristics associated with support can inform service planning and delivery. Future research should use these factors to develop novel ideas for intervention, such as directly targeting partners or other informal networks with educational or psychosocial interventions.
Willingness of population health survey participants to provide personal health information and biological samples
Authors: Jaswal Harpreet , Ialomiteanu Anca , Hamilton Hayley , Rehm Jürgen , Wells Samantha , Shield Kevin D.
Published: November 2024

Background

Biological sample collection and data linkage can expand the utility of population health surveys. The present study investigates factors associated with population health survey respondents’ willingness to provide biological samples and personal health information.

Methods

Using data from the 2019 Centre for Addiction and Mental Health (CAMH) Monitor survey (n = 2,827), we examined participants’ willingness to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information. Associations of willingness to provide such information with socio-demographic, substance use, and mental health details were also examined. Question order effects were tested using a randomized trial.

Results

The proportion of respondents willing to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information were 19.9%, 36.2%, 82.1%, and 17%, respectively. Willingness significantly varied by age, race, employment, non-medical prescription opioid use (past year), cocaine use (lifetime), and psychological distress. Significant question order effects were observed. Respondents were more likely to be willing to provide a saliva sample when this question was asked first compared to first being asked for direct data linkage. Similarly, respondents were more likely to be willing to allow for probabilistic data linkage when this question was asked first compared to first being asked for a saliva sample.

Conclusion

A lack of willingness to provide biological samples or permit data linkage may lead to representivity issues in studies which rely on such information. The presence of question order effects suggests that the willingness of respondents can be increased through strategic ordering of survey structures.
Examining the changes in the prevalence of Hepatitis a in Türkiye: systematic review and metaanalysis
Authors: Karakaya Suzan Özge , Bektaş Murat , Altındiş Mustafa , Kaya Özge , Eroğlu Ayşe , Çetinkaya Özdemir Serap , Tecik Seda , Emecen Ahmet Naci , Çınar Nursan
Published: November 2024

Background

The incidence of Hepatitis A is increasing worldwide. Yearly classification of Hepatitis A Seroprevalence for different times in different regions of Türkiye allows indirect measurement of year-specific incidence rates of HAV infection and can be considered the best way to define Hepatitis A status. This study aimed to examine the change in the incidence of hepatitis A by systematically evaluating the available data on the seroprevalence of anti-HAV antibodies in the Turkish population.

Methods

Studies published between First January, 2000- 31 December 2023 that meet the inclusion criteria searched between 16.09.2023 and 31.01.2024 in nine databases (MEDLINE, Web of Science, PubMed, ScienceDirect, Scopus, Eric, CINAHL Complate, TR DİZİN, TÜBİTAK Ulakbim). Independently by two reviewers evaluated all titles and abstracts with consensus-based decision making. The Joanna Briggs Institution (JBI) Analytical Cross Sectional Studies and Prevelance Studies list were used in this study. Pooled prevalence was calculated using 95% confidence intervals. Heterogeneity between studies was assessed by Cochrane’s Q and I2. The random effect model was selected by Cochrane’s Q and I2. Funnel plots were used for publication bias. The data were analyzed via Jamovi 1.2.22.

Results

Data were extracted from 63 studies. Pooled prevalence was calculated using 95% confidence intervals. Funnel plots were used for publication bias. In this meta-analysis, data were obtained from all geographical regions of Türkiye, and the general prevalence of Hepatitis A in the population was found to be 53% [95% CI 0.47, 0.59; I2 = 99.94%]. In subgroup analysis conducted by year, the prevalence of hepatitis A was 45% [95% CI 0.22, 0.67; I2 = 99.8%] between 2002 and 2006, 52% [95% CI 0.39, 0.65; I2 = 99.54%] between 2007 and 2011, 60% [95% CI 0.49, 0.70; I2 = 99.9%] between 2012 and 2016, and 51% [95% CI 0.41, 0.61; I2 = 99.97%] as of 2017. Additionally, a systematic review revealed that vaccination, socioeconomic status, and sex may also affect HAV seroprevalence.

Conclusions

HAV seroprevalence in Türkiye; It was observed that it increased between 2002 and 2016 and decreased until today as of 2017. This systematic review provide a comprehensive overview of HAV virus epidemiology and identify key knowledge gaps, contributing crucial information for influencing factors.

Trial registration

PROSPERO ID = CRD42023464384.
What really makes residents tick or burn out? Insights from a National survey
Authors: Zloto Ofira , Henenfeld Maxim , Weinstein Orly
Published: November 2024

Background

To examine the satisfaction rates and burnout feelings amongst residents physicians in different specialties and to examine associated affecting factors.

Method

Clalit Health Services (CHS) is the largest health maintenance provider in Israel. A survey was designed by an interdisciplinary team with questions addressing residency and the balance between residency and personal life, as well as the balance between residency and personal life, and was sent to all residents of CHS via personal email from March to May 2022.

Results

Four hundred sixty seven residents completed the survey. The mean satisfaction rate from the residency was 7.4 (± 1.93, 2–10). The highest satisfaction rate from residency was amongst anesthetics, psychiatrists and ophthalmologists ( 8.6, 8.1 and 8.0, respectively) while the lowest was among general surgeons, oncologists, plastic surgeons and orthopedic surgeons (6.8, 6.8, 6.7, 6.1, respectively). There was no correlation between satisfaction rates and monthly working hours or number of overnight shifts. Seventy four percent feel frequent burnout due to high workload and 68% feel frequent burnout due to high number of administrative tasks. Seventy three percent chose the work environment in their department as most influential of their residency experience, 61% chose relations between attending physicians and residents as most significant, and 60% chose the education during the residency as most influential during their residency training.

Conclusions

Satisfaction rates from the residency training require improvement, with differences between the residencies. Number of working hours and number of overnight shifts did not correlate with the satisfaction rates. The factor that influences the most between satisfactory rate and less burnout is the relationship with colleagues and good training programs. Major efforts should be done to improve these factors.