bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumor APOL3 delineates a distinctive immunogenic ferroptosis subset with prognosis prediction in colorectal cancer
Authors: Lv Yang , Zheng Peng , Mao Yihao , Xu Yuqiu , Chang Wenju , Lin Qi , Ji Meiling , Ye Lechi , Tang Wentao , Xu Jianmin
Published: November 2023

With the essential role of lipid transporting signaling in cancer‐related immunity, apolipoprotein L3 (APOL3), a member of the apolipoprotein L gene family, demonstrated significant modulation ability in immunity. However, the expression profile and critical role of APOL3 in colorectal cancer (CRC) remain unclear. This study aimed to investigate the prognostic significance of APOL3 expression and its biological predictive value in CRC. The study enrolled multiple cohorts, consisting of 911 tumor microarray specimens of CRC patients from Zhongshan Hospital, 412 transcriptional data from The Cancer Genome Atlas, and 30 single‐cell RNA sequencing (scRNA‐seq) from internal and external CRC patients. APOL3 mRNA expression was directly acquired from public datasets, and APOL3 protein expression was detected using immunohistochemistry. Finally, the associations of APOL3 expression with clinical outcomes, immune context, and genomic and ferroptotic features were analyzed. Low APOL3 expression predicted poor prognosis and inferior responsiveness to 5‐fluorouracil‐based adjuvant chemotherapy (ACT) and targeted therapy. APOL3 fosters an immune‐active microenvironment characterized by the promotion of ferroptosis, downregulation of macrophages, and upregulation of CD8+ T cell infiltration. Moreover, the expression of APOL3 in CD8+ T cells is intrinsically linked to ferroptosis and immune activation in CRC. In summary, APOL3 serves as an independent prognosticator and predictive biomarker for immunogenic ferroptosis, ACT, and targeted therapy in CRC. Furthermore, the APOL3 signaling activator could be a novel agent alone or in combination with current therapeutic strategies for CRC.
Pressure from insect‐resistant maize on protected butterflies and moths
Authors: Otto Mathias , Papastefanou Phillip , Fahse Lorenz
Published: November 2023

Intensification in agriculture affects many insect species, including butterflies. Insect‐resistant crops, such as Bt (Bacillus thuringiensis) maize, which produces a toxin active against Lepidoptera, are an alternative to insecticide sprays. Genetically modified crops are regulated in most countries and require an environmental risk assessment. In the European Union, such assessments include the use of simulation models to predict the effects on nontarget Lepidoptera (NTL). To support the assessment of protected NTL, we extended an individual‐based, stochastic, spatially explicit mathematical model (LepiX) to include a wider range of exposure scenarios, a species‐sensitivity distribution, and an option for repeated exposure of individuals. We applied the model to transgenic maize DAS‐1507, which expresses a high concentration of Bt toxin in pollen that may be consumed by NTL larvae on their host plants nearby. Even in the most conservative scenario without repeated exposure, mortality estimates for highly sensitive species ranged from 41% to 6% at distances of 10–1000 m from the nearest maize field. Repeated exposure can cause additional mortality and thus is relevant for the overall risk assessment. Uncertainties in both exposure and ecotoxicity estimates strongly influenced the predicted mortalities. Care should be taken to include these uncertainties in the model scenarios used for decision‐making. In accordance with other modeling results, our simulations demonstrated that mean mortality may not be safe for protected species. With its high pollen expression, DAS‐1507 maize may pose risks to sensitive and protected butterfly and moth species that may be difficult to manage. High expression of Bt toxin in pollen is unnecessary for controlling target pests. Consequently, we suggest that Bt maize with high pollen expression not be cultivated in regions where protected butterflies are to be conserved.
Precision endoscopy in colorectal polyps' characterization and planning of endoscopic therapy
Authors: Mandarino Francesco Vito , Danese Silvio , Uraoka Toshio , Parra‐Blanco Adolfo , Maeda Yasuharu , Saito Yutaka , Kudo Shin‐Ei , Bourke Michael J. , Iacucci Marietta
Published: November 2023

Precision endoscopy in the management of colorectal polyps and early colorectal cancer has emerged as the standard of care. It includes optical characterization of polyps and estimation of submucosal invasion depth of large nonpedunculated colorectal polyps to select the appropriate endoscopic resection modality. Over time, several imaging modalities have been implemented in endoscopic practice to improve optical performance. Among these, image‐enhanced endoscopy systems and magnification endoscopy represent now well‐established tools. New advanced technologies, such as endocytoscopy and confocal laser endomicroscopy, have recently shown promising results in predicting the histology of colorectal polyps. In recent years, artificial intelligence has continued to enhance endoscopic performance in the characterization of colorectal polyps, overcoming the limitations of other imaging modes. In this review we retrace the path of precision endoscopy, analyzing the yield of various endoscopic imaging techniques in personalizing management of colorectal polyps and early colorectal cancer.
What Is the Real Value of Design?
Authors: Rae Jeneanne
Published: November 2023

There is growing evidence to suggest that design‐centric companies outperform their peers. Motiv Strategies and DMI explore some of the reasons why.

A look at why design‐centric companies have outperformed the S&P 500 by 164 percent over the past 10 years.
Assessing the causal association between human blood metabolites and the risk of gout
Authors: Xie Yufeng , Li Yanfang , Zhang Jianmei , Chen Yun , Ren Rong , Xiao Lu , Chen Min
Published: November 2023

Background

The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout.

Methods

We applied a two‐sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome‐wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR‐Egger, weighted median, Cochran's Q test, Egger intercept test, and leave‐one‐out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways.

Results

After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38–0.67; P = 1.65 × 10−6). Metabolic pathway analysis identified one pathway that may be associated with the disease.

Conclusion

This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout.
Meta‐analytical evidence that males prefer virgin females
Authors: Richardson Jon , Zuk Marlene
Published: November 2023

Males are often predicted to prefer virgin over non‐virgin females because of the reduced risk of sperm competition. Does this prediction hold across studies? Our systematic meta‐analysis of 138 studies, mainly conducted in invertebrates, confirms that males generally prefer virgin females. However, males preferred virgin females even in species with last male sperm precedence, suggesting that sperm competition alone does not drive male preferences. Furthermore, our results suggest that males may reject mated females even when no alternative exists. Preference for virgins is unlikely to influence female reproductive success since virginity cannot be selected for, but strong preference for virgin females could swamp or reinforce selection on other traits. Our results add to growing evidence that males are not indiscriminate in mating. However, given the unexplained heterogeneity in effect sizes, we urge caution in assuming that males will prefer virgins and recommend considering the natural context of mating decisions.
Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new‐onset sleepiness in some post‐COVID patients
Authors: Menzler Katja , Mayr Petra , Knake Susanne , Cassel Werner , Viniol Christian , Reitz Lena , Tsalouchidou Panagiota‐Eleni , Janzen Annette , Anschuetz Katja , Mross Peter , Koehler Ulrich
Published: November 2023

Background and purpose

Infection with COVID‐19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post‐COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post‐COVID syndrome using polysomnography.

Methods

Thirty‐four patients with post‐COVID syndrome and new‐onset fatigue and sleepiness after a SARS‐CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020).

Results

Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long‐term treatment of their OSAS and all reported discontinuation of daytime symptoms.

Conclusions

Post‐COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post‐COVID syndrome.
Spatial and temporal trends in the relative abundance of Caspian sturgeon during 2006–2022
Authors: Fazli Hasan , Abdolmaleki Shahram , Kaymaram Farhad , Khoshghalb Mohammad Reza Behrouz
Published: November 2023

We used the bycatch of Caspian sturgeon to quantify the species composition, length structure, spatial and temporal distribution, temporal dynamics of relative abundance (indexed as catch‐per‐unit‐effort, CPUE), effects of fingerlings released, and to forecast future sturgeon stock status. Dynamic factor analysis of temporal changes in species CPUE was used to quantify relationships to environmental variables (sea surface temperature, chlorophyll‐a, sea surface level, and river discharge) during 2006–2022. We found that the Guilan subarea had the lowest relative abundance and differed from all other subareas. Fish abundance was highest in October and November, particularly in Mazandaran and Golestan coastal waters. Relative fish abundance declined significantly over time. Acipenser persicus was the most abundant species, followed by Aciperser gueldenstaedtii, Aciperser stellatus, Aciperser nudiventris, and Huso huso. The annual number of fingerlings released decreased during 2000–2021. Over the years, environmental variables such as sea surface level, sea surface temperature, and chlorophyll‐a showed different trends, with sea surface temperature generally increasing, chlorophyll‐a generally decreasing, sea surface level decreasing nearly linearly, and river discharge varying erratically without a trend in the southern Caspian Sea during 2006–2022. The relative abundance of all species decreased and was significantly related to sea surface level. Fish abundance was forecasted to decline by 2025, as sea surface temperature increases and sea surface level decreases. Illegal, unreported, and unregulated (IUU) harvest of sturgeon must be effectively regulated to ensure the survival and recovery of sturgeon populations in the Caspian Sea.
Enhanced growth resistance but no decline in growth resilience under long‐term extreme droughts
Authors: Wang Xiaona , Xu Taoran , Xu Chenxi , Liu Hongyan , Chen Zhenju , Li Zongshan , Li Ximeng , Wu Xiuchen
Published: November 2023

The frequency, intensity, and duration of extreme droughts, with devastating impacts on tree growth and survival, have increased with climate change over the past decades. Assessing growth resistance and resilience to drought is a crucial prerequisite for understanding the responses of forest functioning to drought events. However, the responses of growth resistance and resilience to extreme droughts with different durations across different climatic zones remain unclear. Here, we investigated the spatiotemporal patterns in growth resistance and resilience in response to extreme droughts with different durations during 1901–2015, relying on tree‐ring chronologies from 2389 forest stands over the mid‐ and high‐latitudinal Northern Hemisphere, species‐specific plant functional traits, and diverse climatic factors. The findings revealed that growth resistance and resilience under 1‐year droughts were higher in humid regions than in arid regions. Significant higher growth resistance was observed under 2‐year droughts than under 1‐year droughts in both arid and humid regions, while growth resilience did not show a significant difference. Temporally, tree growth became less resistant and resilient to 1‐year droughts in 1980–2015 than in 1901–1979 in both arid and humid regions. As drought duration lengthened, the predominant impacts of climatic factors on growth resistance and resilience weakened and instead foliar economic traits, plant hydraulic traits, and soil properties became much more important in both climatic regions; in addition, such trends were also observed temporally. Finally, we found that most of the Earth system models (ESMs) used in this study overestimated growth resistance and underestimated growth resilience under both 1‐year and 2‐year droughts. A comprehensive ecophysiological understanding of tree growth responses to longer and intensified drought events is urgently needed, and a specific emphasis should be placed on improving the performance of ESMs.
China's conservation and restoration of coastal wetlands offset much of the reclamation‐induced blue carbon losses
Authors: Fan Bingxiong , Li Yangfan
Published: November 2023

China's coastal wetlands have experienced large losses and gains with rapid coastal reclamation and restoration since the end of the 20th century. However, owing to the difficulties in mapping soil organic carbon (SOC) in blue carbon stocks of coastal wetlands on a national scale, little is known about the spatial pattern of SOC stock in China's coastal wetlands and the loss and gain of SOC stock following coastal reclamation, conservation, and restoration over the past decades. Here, we developed a SOC stock map in China's coastal wetlands at 30 m spatial resolution, analyzed the spatial variability and driving factors of SOC stocks, and finally estimated SOC losses and gains due to coastal reclamation and wetland management from 1990 to 2020. We found that the total SOC stocks in China's coastal wetlands were 77.8 Tg C by 2020 with 3.6 Tg C in mangroves, 8.8 Tg C in salt marshes, and 65.4 Tg C in mudflats. Temperature, rainfall, and seawater salinity exerted the highest relative contributions to SOC spatial variability. The spatial trend of SOC density gradually decreased from south to north except for Liaoning province, with the lowest density in Shandong province. About 24.9% (19.4 Tg C) of SOC stocks in China's coastal wetlands were lost due to high‐intensity reclamation, but SOC stock gained from conservation and restoration offset the reclamation‐induced losses by 58.2% (11.3 Tg C) over the past three decades. These findings demonstrated the great potential of conservation and restoration of coastal wetlands in reversing the loss trend of blue carbon and contributing to the mitigation of climate change toward carbon neutrality. Our study provides significant spatial insights into the stocks, sequestration, and recovery capacity of blue carbon following rapid urbanization and management actions, which benefit the progress of global blue carbon management.
Climate change and cooling equity: Spatial dynamics of vulnerable populations
Authors: Kim Sungyop , Kim Dohyung
Published: November 2023

Climate change disproportionately affects low‐income and minority populations. This study identified vulnerable populations to extreme heat, focusing on home air conditioning. State and municipal laws and regulations usually consider home air conditioning an amenity rather than a requirement for habitability such as heat, water, and electricity. Using the historical census data and the American Housing Survey data, this study identified the vulnerable populations to extreme heat and their spatial dynamic in Los Angeles County, CA. This study found that low‐income minority populations are more likely to live without home air conditioning, and they are more likely to be exposed to extreme heat in the coming years if their residential location patterns continue. Changing spatial patterns of low‐income and minority populations need to be incorporated into urban and regional planning for climate change. State regulations and municipal codes should require air conditioning as a habitability requirement for cooling equity. Also, cooling stations that provide immediate relief for those without home air conditioning need strategic placements based on the locational concentration of the vulnerable populations.
Blockchain technology for enhancing sustainable food systems: A consumer perspective
Authors: Panghal Anupama , Pan Sharmistha , Vern Priyanka , Mor Rahul S. , Jagtap Sandeep
Published: November 2023

This paper explores the potential of blockchain technology (BCT) in promoting sustainable food production and consumption (SFPC) from a consumer perspective. India, a significant global food producer, faces challenges related to affordability and food logistics due to transport and labour constraints. Food safety concerns, that is, foodborne illnesses and quality issues, alongside unexpected events like COVID‐19 and geopolitical conflicts, threaten SFPC. In recent times, consumer focus has shifted a lot towards food safety and security. The study adopted exploratory factor analysis (EFA) to identify the factors strengthening consumer trust through BCT. The EFA helped classify the items into five factors, that is, reliability, sustainability, impact on health, trust and switching intentions. The results reveal that these factors are the most significant reasons consumers are willing to accept a blockchain‐enabled food system over a traditional system. The study findings will benefit organisations willing to introduce blockchain within their operations to improve the consumer base. It will also prove to be helpful for researchers and academicians to understand consumer perspectives towards BCT for SFPC.
Machine learning and single‐cell transcriptome profiling reveal regulation of fibroblast activation through THBS2/TGFβ1/P‐Smad2/3 signalling pathway in hypertrophic scar
Authors: Song Binyu , Zhu Yuhan , Zhao Ying , Wang Kai , Peng Yixuan , Chen Lin , Yu Zhou , Song Baoqiang
Published: November 2023

Hypertrophic scar (HS) is a chronic inflammatory skin disorder characterized by excessive deposition of extracellular matrix, and the mechanisms underlying their formation remain poorly understood. We analysed scRNA‐seq data from samples of normal skin and HS. Using the hdWGCNA method, key gene modules of fibroblasts in HS were identified. Non‐negative matrix factorization was employed to perform subtype analysis of HS patients using these gene modules. Multiple machine learning algorithms were applied to screen and validate accurate gene signatures for identifying and predicting HS, and a convolutional neural network (CNN) based on deep learning was established and validated. Quantitative reverse transcription‐polymerase chain reaction and western blotting were performed to measure mRNA and protein expression. Immunofluorescence was used for gene localization analysis, and biological features were assessed through CCK8 and wound healing assay. Single‐cell sequencing revealed distinct subpopulations of fibroblasts in HS. HdWGCNA identified key gene characteristics of this population, and pseudotime analysis was conducted to investigate gene variation during fibroblast differentiation. By employing various machine learning algorithms, the gene range was narrowed down to three key genes. A CNN was trained using the expression of these key genes and immune cell infiltration, enabling diagnosis and prediction of HS. Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFβ1/P‐Smad2/3 pathway. Our study identifies unique fibroblast subpopulations closely associated with HS and provides biomarkers for the diagnosis and treatment of HS.
Responsible Investors: Who They Are, What They Want
Authors: Lydenberg Steve
Published: November 2023

This article by a long‐time partner in Domini Social Investments, a well‐known socially responsible investment firm, begins by describing four different approaches that institutional investors have currently adopted as they account for environmental, social, and governance (ESG) considerations in their investment decisions: (1) the incorporation of internationally accepted ESG norms and standards (as set forth in, for example, the FTSE4Good Indexes); (2) the use of industry‐specific ESG ratings and rankings (such as those used for the Dow Jones Sustainability Indexes); (3) the integration of ESG considerations into stock valuation (as advocated, for example, in the Principles of Responsible Investment); and (4) the identification of companies whose business models successfully address the most pressing societal needs (often referred to as “impact investing”).

The article then seeks to answer the question: what corporate ESG programs and policies can be most effectively used by managers seeking to attract institutional investors using these different approaches?

The author describes three kinds of corporate ESG programs. In one approach, corporate managers focus on strengthening relations with non‐investor stakeholders, including employees, the environment, and local communities. In the second approach, corporations seek to create “shared value” by emphasizing products and services that help address society's most pressing needs. The third approach focuses on identifying and addressing the firm's industry‐specific ESG performance indicators (KPIs) that are most material to stockholders and other stakeholders.

Given institutional investors' growing commitment to the incorporation of ESG concerns, corporate managers should understand the range of investors' approaches to ESG and how to account for them in their strategic planning. At the same time, they are encouraged to develop comprehensive ESG policies and goals, devote adequate resources to their implementation, and communicate efforts effectively to these investors and to the public.
Access to Non‐reimbursed Expensive Cancer Treatments: A Justice Perspective
Authors: Smids Jilles , Bunnik Eline M.
Published: November 2023

When the cost‐effectiveness of newly approved cancer treatments is insufficient or unclear, they may not (immediately) be eligible for reimbursement through basic health insurance in publicly funded healthcare systems. Patients may seek access to non‐reimbursed treatment through other channels, including individual funding requests made to hospitals, health insurers, or pharmaceutical companies. Alternatively, they may try to pay out of pocket for non‐reimbursed treatments. While currently little is known of these practices, they run counter to a deeply held egalitarian ethos that is prevalent in many publicly funded healthcare systems. In this article, we investigate to what extent this ethos can be grounded in theories of justice, notably egalitarianism and prioritarianism. We argue that allowing out‐of‐pocket payments by patients themselves, in principle, is not unjust from the perspective of either of these theories, provided that it does not raise in‐practice justice‐based concerns, for instance by displacing more cost‐effective care, to the detriment of other patients, or by failing to treat patients equally. In contrast, we conclude that the practice of making exceptions for individual patients by health insurers or healthcare providers does run counter to the justice‐based requirements of equal treatment.
FKBP3 aggravates the malignant phenotype of diffuse large B‐cell lymphoma by PARK7‐mediated activation of Wnt/β‐catenin signalling
Authors: Xing Xiaojing , Liu Meichen , Wang Xuguang , Guo Qianxue , Wang Hongyue , Wang Wenxue
Published: November 2023

Diffuse large B‐cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506‐binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co‐immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/β‐catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/β‐catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.
The rostral micro‐tooth morphology of blue marlin, Makaira nigricans
Authors: Pacher Korbinian , Breuker Michael , Hansen Matthew J. , Kurvers Ralf H. J. M. , Häge Jan , Dhellemmes Felicie , Domenici Paolo , Steffensen John F. , Krause Stefan , Hildebrandt Thomas , Fritsch Guido , Bach Pascal , Sabarros Philippe S. , Zaslansky Paul , Mahlow Kristin , Müller Johannes , Armas Rogelio González , Ortiz Hector Villalobos , Galván‐Magaña Felipe , Krause Jens
Published: November 2023

Billfish rostra potentially have several functions; however, their role in feeding is unequivocal in some species. Recent work linked morphological variation in rostral micro‐teeth to differences in feeding behavior in two billfish species, the striped marlin (Kajikia audax) and the sailfish (Istiophorus platypterus). Here, we present the rostral micro‐tooth morphology for a third billfish species, the blue marlin (Makaira nigricans), for which the use of the rostrum in feeding behavior is still undocumented from systematic observations in the wild. We measured the micro‐teeth on rostrum tips of blue marlin, striped marlin, and sailfish using a micro–computed tomography approach and compared the tooth morphology among the three species. This was done after an analysis of video‐recorded hunting behavior of striped marlin and sailfish revealed that both species strike prey predominantly with the first third of the rostrum, which provided the justification to focus our analysis on the rostrum tips. In blue marlin, intact micro‐teeth were longer compared to striped marlin but not to sailfish. Blue marlin had a higher fraction of broken teeth than both striped marlin and sailfish, and broken teeth were distributed more evenly on the rostrum. Micro‐tooth regrowth was equally low in both marlin species but higher in sailfish. Based on the differences and similarities in the micro‐tooth morphology between the billfish species, we discuss potential feeding‐related rostrum use in blue marlin. We put forward the hypothesis that blue marlin might use their rostra in high‐speed dashes as observed in striped marlin, rather than in the high‐precision rostral strikes described for sailfish, possibly focusing on larger prey organisms.
Peptide receptor chemoradionuclide therapy for neuroendocrine neoplasms: A systematic review
Authors: Chan Dennis S. , Kanagaratnam Aran L. , Pavlakis Nick , Chan David L.
Published: November 2023

Peptide receptor chemoradionuclide therapy (PRCRT), the addition of radiosensitising chemotherapy to peptide receptor radionuclide therapy (PRRT), has been used in individual centres for neuroendocrine neoplasms (NENs), but there are few data to date regarding its efficacy and safety. We conducted a systematic review to document the efficacy and side effect profile of this combination. We searched for studies including ≥5 patients with advanced NENs who received PRCRT. Major databases were searched and supplemented by handsearching of major conferences from 2019 to 2023. Data extracted included clinicopathological characteristics, trial setting and doses of chemotherapy and PRRT administered. Endpoints included overall survival (OS), progression‐free survival (PFS) and adverse events (AEs); summarised qualitatively because of the marked heterogeneity in patient populations, trial designs and treatments administered. Eligible studies (24) included: 14 retrospective studies (643 patients) and 10 prospective studies (521 patients). For PRRT, most studies used 177Lu (n = 21), with combination 177Lu + 90Y (n = 2), 111In (n = 1) and 225Ac (n = 1). Chemotherapy regimens included capecitabine (n = 8), capecitabine and temozolomide (n = 5), 5‐fluorouracil (n = 4) or a mixture of regimens (n = 6). Most studies included Grade 1–2 NENs. In prospective studies, median OS exceeded 2 years in most studies (range not reached by end of follow‐up—86 months). In retrospective studies, median OS ranged from 7 months to 55 months and was not reached in many studies. PFS data ranged from 31 months—not reached in prospective cohorts and from 4 months—not reached in retrospective cohorts. Grade 3/4 AEs were commonly haematological, with majority being reversible or having no ongoing clinical impact. For advanced NENs, PRCRT treatment has demonstrated promising clinical outcomes and was well tolerated, although identified studies were heterogeneous. Further randomised trial data are required to clarify the place of this combination modality in the NEN treatment paradigm.
Cryolipolysis in the United States—Review of the clinical data
Authors: Hetzel John , Awad Nardin , Bhupalam Vishnu , Nestor Mark
Published: November 2023

Background

Noninvasive body contouring is becoming more popular in the United States as an alternative to liposuction. The most popular of these methods, cryolipolysis, uses precisely controlled cooling to reduce focal adiposities. The number of cryolipolysis procedures performed annually has experienced rampant growth in United States markets, and the indications have likewise diversified. In light of this change, it is imperative to perform an updated review of available US safety and efficacy data on cryolipolysis.

Aims

To examine the safety and efficacy of cryolipolysis treatments in the United States using data extracted from research performed exclusively at US‐based sites.

Methods

In order to identify relevant studies, a literature search was conducted on PubMed using the terms “CoolSculpting” OR “cryolipolysis” OR “lipocryolysis.” Articles were manually reviewed to exclude literature reviews, research not performed on humans, studies on experimental combinations of techniques, and any studies not performed in the United States.

Results

The initial literature search returned 246 results. Following manual review, a total of 18 studies were selected for data extraction. Mean reduction in fat thickness by ultrasound was 2.0–5.1 mm or 19.6%–32.3%; mean reduction by body caliper was 2.3–7 mm or 14.9%–21.5%. Side effects were mild and transient. Four instances of PAH were documented in 3453 treatment cycles.

Conclusions

Cryolipolysis is a safe, modestly effective method for reducing focal adiposity. Complications are rare and treatable. However, US‐based studies are few in number and often of low power and/or quality. More high‐quality research is needed for all aspects of cryolipolysis.
Placement of peripherally inserted central catheter through upper versus lower limb vein in neonates: A meta‐analysis of randomized controlled trials
Authors: Zhao Xuetang , Liu Yingfei , Li Xiaoyan , Wei Li , Bian Lanzheng , Peng Mingqi
Published: November 2023

Aim

Peripherally inserted central catheter (PICC) is an important treatment for the drug and nutrition administration in neonates. We aimed to evaluate the effects and safety of PICC placement through upper versus lower limb vein in neonates, to provide insights into the clinical PICC nursing care.

Design

A meta‐analysis.

Methods

We searched the Cochrane Library, Web of Science, PubMed, Science Direct, China national knowledge infrastructure, Wanfang Data Knowledge Service Platform, China Weipu Database, China Biomedical Literature Database for published randomized controlled trials (RCTs) on the placement of PICC via upper limb and lower limb venipuncture. Two reviewers independently evaluated and cross‐checked the quality of the included studies in accordance with the quality standards of the Cochrane Manual. We used RevMan 5.3 software for statistical processing.

Results

A total of 12 RCTs were included in this meta‐analysis. Meta‐analysis indicated that compared with upper limb veins, PICC insertion through lower limb veins is beneficial to increase the one‐time puncture success rate (relative risk [RR]  =  0.73, 95% confidence interval [CI]: 0.68–0.79) and the indwelling time (mean difference [MD] =  −3.60, 95% CI: −5.35 to −1.86), reduce the operation time (MD =  10.37, 95% CI: 7.48–13.26), estimated bleeding volume (MD =  0.55, 95% CI: 0.34–0.75), incidence of catheter ectopia (RR  =  2.46, 95% CI: 1.81–3.35), PICC‐associated infection (RR  =  2.82, 95% CI: 1.65–4.83), exosmosis (RR  =  2.45, 95% CI: 1.49–4.04, p < .001) and phlebitis (RR  =  1.40, 95% CI: 1.03–1.90). No significant difference in the Incidence of catheter obstruction between the upper and lower limb veins (RR  =  1.20, 95% CI: 0.73–1.97, p = .48) was found.

Public Contribution

There are certain advantages in neonatal PICC puncture through the lower limb vein. The lower limb vein may be the preferred choice for neonatal PICC puncture.
Do Realists Predict?
Authors: Porpora Douglas
Published: November 2023

As Petter Naess observes, some specifically prominent voices within CR have expressly denied our ability to predict much in the social domain while others express great caution about endorsing any such ability. In print, Naess has been the most prominent CR voice defending predictability, but there are others of us critical realists who share Naess's view. The purpose of this paper is to further defend the view that critical realists have no special problem with predicting events. We just do not grant prediction the same status that positivists do. The argument here is parallel to Porpora's that critical realists can and do run regressions but without granting them the same explanatory status as positivism.
‘Delicate ironies quite imperceptible on its surface’: Henry S. Whitehead's weird tales and American empire in the Caribbean
Authors: Goodrum Michael
Published: November 2023

This article mounts an initial exploratory engagement with the weird fiction of Henry S. Whitehead, framed by American imperial expansion into the Caribbean in the interwar years. It situates Whitehead and his work within the wider historical context and shows how Whitehead himself used and played with history as part of his fiction. The article considers the role of light in Whitehead's fiction and imperial projects, as well as the way that Whitehead's work, as horror fiction, both shapes and seeks to dispel notions of the Caribbean as a space of horror. As well as offering some initial conclusions, the article seeks to open further lines for future investigation.
Exploring Pseudomonas syringae pv. tomato biofilm‐like aggregate formation in susceptible and PTI‐responding Arabidopsis thaliana
Authors: Xiao Wantao N. , Nunn Garrett M. , Fufeng Angela B. , Belu Natalie , Brookman Rowan K. , Halim Abdul , Krysmanski Evan C. , Cameron Robin K.
Published: November 2023

Bacterial biofilm‐like aggregates have been observed in plants, but their role in pathogenicity is underinvestigated. In the present study, we observed that extracellular DNA and polysaccharides colocalized with green fluorescent protein (GFP)‐expressing Pseudomonas syringae pv. tomato (Pst) aggregates in Arabidopsis leaves, suggesting that Pst aggregates are biofilms. GFP‐expressing Pst, Pst ΔalgU ΔmucAB (Pst algU mutant), and Pst ΔalgD ΔalgU ΔmucAB (Pst algU algD mutant) were examined to explore the roles of (1) alginate, a potential biofilm component; (2) Pst AlgU, thought to regulate alginate biosynthesis and some type III secretion system effector genes; and (3) intercellular salicylic acid (SA) accumulation during pathogen‐associated molecular pattern‐triggered immunity (PTI). Pst formed extensive aggregates in susceptible plants, whereas aggregate numbers and size were reduced in Pst algU and Pst algD algU mutants, and both multiplied poorly in planta, suggesting that aggregate formation contributes to Pst success in planta. However, in SA‐deficient sid2‐2 plants, Pst algD algU mutant multiplication and aggregate formation were partially restored, suggesting plant‐produced SA contributes to suppression of Pst aggregate formation. Pst algD algU mutants formed fewer and smaller aggregates than Pst algU mutants, suggesting both AlgU and AlgD contribute to Pst aggregate formation. Col‐0 plants accumulated low levels of SA in response to Pst and both mutants (Pst algU and Pst algD algU), suggesting the regulatory functions of AlgU are not involved in suppressing SA‐mediated plant defence. Plant PTI was associated with highly reduced Pst aggregate formation and accumulation of intercellular SA in flg22‐induced PTI‐responding wild‐type Col‐0, but not in PTI‐incompetent fls2, suggesting intercellular SA accumulation by Arabidopsis contributes to suppression of Pst biofilm‐like aggregate formation during PTI.
A train reaction: the infrastructural politics and mobility injustices accompanying Hanoi's new urban railway Line 2A
Authors: Turner Sarah , Nguyen Binh N. , Hykes Madeleine
Published: November 2023

In 2008, Vietnam's Prime Minister approved the construction of the ‘Hanoi Urban Railway System’, a major infrastructure project for the country's capital city. The construction of Line 2A, the first line of this 8‐line railway, took ten years to complete, and was finally inaugurated in November 2021. Spanning 13 km across the city centre, Line 2A encountered more than just construction setbacks, with its reputation tarnished by contractor choice, accidents, and public scepticism over safety and accessibility. Sowing further seeds of doubt in the minds of many Hanoi residents is the fact that two‐thirds of the original financing came from preferential loans from Vietnam's large northern neighbour, conditional on the contractor and key materials being sourced from Vietnam's large, northern neighbour. Moreover, the project is informally categorized as part of Vietnam's large northern neighbour's Belt and Road Initiative. Drawing from conceptual literature regarding infrastructural politics and mobility (in)justice, we analyse how Hanoi residents have experienced and negotiated the construction of this Chinese‐Vietnamese infrastructure project. In particular, we consider how the livelihoods of those directly affected by the railway's operations, namely motorbike taxi‐drivers, have been impacted to date.
Evaluation of the outcomes of the Quebec provincial suicide prevention gatekeeper training on knowledge, recognition of attitudes, perceived self‐efficacy, intention to help, and helping behaviors
Authors: Montiel Corentin , Mishara Brian L.
Published: November 2023

Introduction

Gatekeeper (GK) training is a suicide prevention strategy in which community members learn to identify individuals at risk of suicide and refer them for appropriate help. Despite its widespread use, few studies have investigated its effects, including changes in helping behaviors.

Aims

To assess the impact of GK training on participants' knowledge, recognition of the influence of attitudes, perceived self‐efficacy, intention to help and helping behaviors, and to identify variables associated with GK behaviors.

Methods

Mixed linear effects and forward stepwise logistic regressions were used to analyze data from 159 participants receiving the Quebec Provincial GK Training program offered by five different suicide prevention centers using pretest, posttest and 6‐month follow‐up questionnaires.

Results

Participants' knowledge of the GK role and suicide prevention, intention to help, self‐efficacy, knowledge of services, and recognition of the influence of attitudes significantly increased following training. Most changes decreased at follow‐up but remained higher than at pretest. Lower levels of education and higher intention to help were significant predictors of engaging in helping behaviors in the first 6 months after receiving training.

Conclusions

The Quebec GK training appears to be effective in preparing participants for their role but does not appear to significantly increase helping behaviors.
Addressing medial student knowledge deficits in ‘hospital‐to‐home’ transitions of care using a constructivism theory‐based workshop intervention
Authors: Browne Anne C. , Murphy Ella , Finn Yvonne , Cantillon Peter
Published: November 2023

Introduction

Effective teaching and learning initiatives on transitions of patient care, especially from hospital to home, are frequently lacking within medical school curricula. We trialled an integrated test‐enhanced active learning strategy to prepare students for the safe management of these patient transitions.

Methods

This randomised, prospective, single blinded, interventional study assessed medical students' knowledge, regarding patients' hospital‐to‐home transition. The intervention was a purpose‐designed transitions of care workshop, the assessment tool was a multiple‐choice assessment based on prior studies. Students were randomly allocated to the application of the assessment both pre‐ and post‐workshop or to assessment solely post‐workshop to determine the potential for the assessment to prime student learning.

Results

Sixteen students enrolled for the workshops. Significant knowledge gaps were identified. No student identified that medication errors were the most common source of post‐discharge adverse events. Only 42% of participants knew that age >65 contributes to medication non‐adherence, with 50% knowing that the medical reconciliation process should include discontinued medications.

The workshop increased student knowledge, addressing identified knowledge gaps (74% pre‐workshop versus 87% post‐workshop, p < 0.005). Students self‐perceived level of competency after completing the workshop intervention was increased (5.5 pre‐workshop versus 15 post‐workshop, p < 0.001). All aspects of student self‐assessed competency increased significantly from the pre‐workshop scores. There was no priming effect of the pre‐workshop assessment on student knowledge scores or perceived competency.

Discussion

Important gaps in student knowledge skills and attitudes exist regarding the hospital to home transition. Our active learning strategy addressed these gaps, enhancing student understanding and confidence around transitions of patient care.
On the social nature of artefacts
Authors: Juvshik Tim
Published: November 2023

Recent work in metaphysics has focused on the nature of artefacts, most accounts of which assume that artefacts depend on the intentions of their individual makers. Artefacts are thus importantly different from institutional kinds, which involve collective intentions. However, recent work in social ontology has yielded renewed focus on the social dimensions of various kinds, including artefacts. As a result, some philosophers have suggested that artefacts have a distinctly social dimension that goes beyond their makers' individual intentions but which stops short of the collective intentionality of institutional kinds. I aim to combine these insights into an account of artefacts that involves disjunctive conditions of mind‐dependence: Artefacts can either depend on the singular intentions of their makers or they can depend on the collective acceptance of particular social groups. Whether the first or second disjunct is satisfied depends on the artefact's context of creation. I'll argue that this applies not to artefact kinds but to individual artefacts. I then consider two objections to my view based on Robinson Crusoe cases and show how my account allows us to fit artefacts into a taxonomy of social kinds.
Meet in the middle: Could cell mediated‐immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis
Authors: Campos Sílvia Vidal , Teixeira Lisete Ribeiro , Freire Maristela Pinheiro , Mamana Ana Carolina , Machado Clarisse Martins
Published: November 2023

Background

Cytomegalovirus (CMV) can cause tissue‐invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV‐specific cell immune recovery (CMV‐CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV‐CIR, using QuantiFERON‐CMV assay (Qiagen Group), in the first year after LTx.

Methods

Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV‐seropositive recipients (R+) and only CMV‐seropositive donor and negative recipient (D+/R−) received a 6‐month‐prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON‐CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils.

Results

Thirty‐eight patients were included. On days 45, 90, and 365 days post‐LTx, 60%, 72%, and 81% QuantiFERON‐CMV were reactive, respectively. Eleven patients (28.9%) presented CMV‐disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p = .027) but failed on DNAemia/CMV infection (p = .148). Daily prophylaxis, for D+/R− patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON‐CMV (adjusted OR .27, 95%CI .12–.60, p = .02).

Conclusion

QuantiFERON‐CMV may be another diagnostic tool to help stratify CMV‐disease risk and individualized antiviral prophylaxis after LTx.

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