bluuebunny/crossref_metadata_2025_split huggingface dataset:
The venom and telopodal defence systems of the centipede Lithobius forficatus are functionally convergent serial homologues
Authors: Schendel Vanessa , Müller Carsten H. G. , Kenning Matthes , Maxwell Michael , Jenner Ronald A. , Undheim Eivind A. B. , Sombke Andy 
Published: June 2024

Abstract
Background
Evolution of novelty is a central theme in evolutionary biology, yet studying the origins of traits with an apparently discontinuous origin remains a major challenge. Venom systems are a well-suited model for the study of this phenomenon because they capture several aspects of novelty across multiple levels of biological complexity. However, while there is some knowledge on the evolution of individual toxins, not much is known about the evolution of venom systems as a whole. One way of shedding light on the evolution of new traits is to investigate less specialised serial homologues, i.e. repeated traits in an organism that share a developmental origin. This approach can be particularly informative in animals with repetitive body segments, such as centipedes.

Results
Here, we investigate morphological and biochemical aspects of the defensive telopodal glandular organs borne on the posterior legs of venomous stone centipedes (Lithobiomorpha), using a multimethod approach, including behavioural observations, comparative morphology, proteomics, comparative transcriptomics and molecular phylogenetics. We show that the anterior venom system and posterior telopodal defence system are functionally convergent serial homologues, where one (telopodal defence) represents a model for the putative early evolutionary state of the other (venom). Venom glands and telopodal glandular organs appear to have evolved from the same type of epidermal gland (four-cell recto-canal type) and while the telopodal defensive secretion shares a great degree of compositional overlap with centipede venoms in general, these similarities arose predominantly through convergent recruitment of distantly related toxin-like components. Both systems are composed of elements predisposed to functional innovation across levels of biological complexity that range from proteins to glands, demonstrating clear parallels between molecular and morphological traits in the properties that facilitate the evolution of novelty.

Conclusions
The evolution of the lithobiomorph telopodal defence system provides indirect empirical support for the plausibility of the hypothesised evolutionary origin of the centipede venom system, which occurred through functional innovation and gradual specialisation of existing epidermal glands. Our results thus exemplify how continuous transformation and functional innovation can drive the apparent discontinuous emergence of novelties on higher levels of biological complexity.
Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial
Authors: Xu Xinghua , Zhang Huaping , Zhang Jiashu , Luo Ming , Wang Qun , Zhao Yining , Gan Zhichao , Xu Bainan , Chen Xiaolei ,   the MISICH study team
Published: June 2024

Abstract
Background
Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy.

Methods
In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0–2 at the 6-month follow-up.

Results
A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000).

Conclusions
Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages.

Trial Registration
ClinicalTrials.gov Identifier: NCT02811614.
Diabetes mellitus and serum organochlorine pesticides mixtures in Mexican women
Authors: Ugalde-Resano Rodrigo , Mérida-Ortega Ángel , Barajas Belén , López-Carrillo Lizbeth , Cebrián Mariano E. 
Published: June 2024

Abstract
Background
Very recently, it has been reported that exposure to different mixtures of organochlorine pesticides (OCP) is associated with the development of diabetes mellitus (DM). In Mexico, DM is a public health problem that might be related to the historical intense use of OCP. We aimed to evaluate, the association between DM and serum concentrations of OCP mixtures, and identify the main contributors within them.

Methods
We conducted a secondary cross-sectional analysis on the control group from a breast cancer population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We identified 214 self-reported diabetic women and 694 non-diabetics. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We determined 24 OCP and metabolites in serum by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of DM and exposure to multiple OCP, and the contribution of each compound within the mixture.

Results
We found a positive adjusted association between DM and an OCP mixture (OR: 2.63, 95%CI: 1.85, 3.74), whose primary contribution arose from p, p’-DDE (mean weight 23.3%), HCB (mean weight 17.3%), trans nonachlor (mean weight 15.4%), o, p’-DDE (mean weight 7.3%), heptachlor epoxide (mean weight 5.9%), oxychlordane (mean weight 4.7%), and heptachlor (mean weight 4.5%). In addition, these OCP along with p, p’-DDT and cis chlordane, were of concern and remained associated when excluding hypertensive women from the analysis (OR 2.55; 95% CI 1.56, 4.18).

Conclusions
Our results indicate, for the first time in a Latin-American population, that the concomitant exposure to multiple OCP is associated with DM. Further research is needed since the composition of OCP mixtures may vary according to regional pesticides use patterns.
Upconversion nanoparticles doped optical lens: let’s see the near-infrared light
Authors: Hu Yulin , Xu Baoqi , Li Wei , Liang Lin , Fei Fan , Lin Quankui 
Published: June 2024

AbstractThe human cannot detect light with a wavelength exceeding 700 nm, primarily due to limitations in the physiological structure of the human eye. However, in certain specific scenarios, the ability to detect near-infrared (NIR) light proves to be extremely valuable. To attain this desired capability, NIR up conversion nanoparticles (UCNPs) were prepared and doped in the optical lens materials, aiming to obtain a NIR light “visible” optical lens. It is demonstrated that the doping of UCNPs in the optical lens materials does not significantly impact on their mechanical properties, optical properties, surface properties and it exhibits excellent biocompatibility in cell and animal experiments. More importantly, the UCNPs doping can convert NIR light into visible light within the material effectively and stably. The eyes can “see” the NIR light after wearing such UCNPs doped optical lens. Such NIR light visible optical lens could have great potential in actual applications.
Graphical Abstract
Legal aspects of privacy-enhancing technologies in genome-wide association studies and their impact on performance and feasibility
Authors: Brauneck Alissa , Schmalhorst Louisa , Weiss Stefan , Baumbach Linda , Völker Uwe , Ellinghaus David , Baumbach Jan , Buchholtz Gabriele 
Published: June 2024

AbstractGenomic data holds huge potential for medical progress but requires strict safety measures due to its sensitive nature to comply with data protection laws. This conflict is especially pronounced in genome-wide association studies (GWAS) which rely on vast amounts of genomic data to improve medical diagnoses. To ensure both their benefits and sufficient data security, we propose a federated approach in combination with privacy-enhancing technologies utilising the findings from a systematic review on federated learning and legal regulations in general and applying these to GWAS.
An exploration of the self-similarity of traditional settlements: the case of Xiaoliangjiang Village in Jingxing, Hebei, China
Authors: Peng Peng , Zhou Xiangyun , Wu Shaopu , Zhang Yuechen , Zhao Jiajie , Zhao Limin , Wu Jinyu , Rong Yan 
Published: June 2024

Abstract
In order to retain the characteristics and style of traditional settlements and respect their layout and structure, it is necessary to carry out original planning and expansion of traditional settlements. This model of planning and expansion aims to protect the unique character of the settlement, maintain its original historical and cultural value, and integrate with the surrounding environment. Early research on the space complexity of settlements was dominated by qualitative analysis, and the depth of quantitative research on the spatial form of traditional settlements was insufficient. This article takes Xiaoliangjiang Village in Jingxing County, Shijiazhuang City, Hebei Province, which entered the fifth batch of the list of Chinese traditional villages list, as the research object. The spatial relationship of the settlement was obtained through field surveys and drone oblique photography, and the spatial morphological elements of Xiaoliangjiang Village were analyzed and extracted. Based on three quantitative theories of spatial form, namely topology theory, fractal theory, and space syntax, the self-similarity of settlements is analyzed from the perspectives of buildings, streets, and spaces. The research uses Matlab and DepthMap software to quantitatively analyze the spatial form of Xiaoliangjiang Village and obtains data. Through the analysis of data, it was found that Xiaoliangjiang Village has self-similarity at three levels: buildings, roads and settlement spaces. The buildings iteratively generate various forms of architectural courtyards through the basic “L”-shaped pattern. The spatial structures at all levels of roads and settlement space in Xiaoliangjiang Village are relatively similar, in line with the bottom-up traditional settlement evolutionary law. By studying settlement self-similarity, people can better understand the formation mechanism of traditional settlement space structure and its evolution law. At the same time, it enriches the research perspective of traditional settlements and provides technical support for analyzing the self-similarity of traditional settlements and settlement protection planning.
Noradrenaline infusion prevents anesthesia-induced hypotension in severe aortic stenosis patients undergoing transcatheter aortic valve replacement: a retrospective observational study
Authors: Onishi Kenta , Yoshida Masashi , Ito Hisakatsu , Kawakami Masaaki , Takazawa Tomonori 
Published: June 2024

Abstract
Background
Patients with severe aortic valve stenosis (AS) are particularly prone to developing hypotension during general anesthesia induction, which increases postoperative morbidity and mortality. Although the preventive effect of a single vasopressor dose on anesthesia-induced hypotension has been reported, the effects of continuous vasopressor infusion are unknown. This study aimed to assess the effect of noradrenaline (NAd) infusion on hemodynamic stability during general anesthesia induction in severe AS patients undergoing transcatheter aortic valve replacement (TAVR).

Methods
This single-center, retrospective study included severe AS patients who underwent elective TAVR. Patients in the NAd group received a continuous prophylactic NAd infusion of 0.1 μg/kg/min from the time of anesthesia induction. The control group received inotropes and vasopressors as indicated by the occurrence of hypotension. The primary outcome was the lowest mean blood pressure (MBP) before the start of surgery.

Results
The study included 68 patients in the NAd group and 113 in the control group. The lowest MBP before the start of surgery was significantly higher in the NAd group than in the control group (63 ± 15 vs 47 ± 13 mmHg, P < 0.01). MBP immediately before intubation was also significantly higher in the NAd group (75 ± 17 vs 57 ± 16 mmHg, P < 0.01). Differences in postoperative complications between the groups were negligible.

Conclusion
Continuous administration of NAd at 0.1 μg/kg/min in patients with severe AS might prevent hypotension during general anesthesia induction for TAVR.
Impact of ATRX loss on survival and immune microenvironment in multiple sarcoma subtypes.
Authors: Denu Ryan Austin , Lazcano Segura Rossana , Farooqi Ahsan Saleem , Ingram Davis , Wani Khalida M. , Cai Yiming , Torres Keila E , Keung Emily Zhi-Yun , Roland Christina Lynn , Somaiah Neeta , Ying Haoqiang , Huse Jason T. , Rai Kunal , Conley Anthony Paul , Patel Shreyaskumar , Wang Wei-Lien , Lazar Alexander J. , Nassif Haddad Elise F 
Published: June 2024

11511 Background: Sarcomas are heterogeneous mesenchymal malignancies often with few treatment options and poor outcomes. ATRX is commonly altered in sarcoma, with loss-of-function (LOF) mutations observed in up to 35% of cases. ATRX plays roles in DNA damage response, telomere maintenance, and epigenetic regulation. However, the impact of ATRX loss on sarcoma biology and the potential of ATRX mutation to serve as a prognostic biomarker in sarcoma are under investigation. Methods: The predominant alteration seen in ATRX in sarcoma is LOF mutation, thus tumor specimens were scored for presence or absence of ATRX staining by immunohistochemistry (IHC) in clinically-annotated tissue microarrays (TMAs) including 95 patients with uterine leiomyosarcoma (ULMS), 127 with soft tissue leiomyosarcoma (STLMS), 82 with undifferentiated pleomorphic sarcoma (UPS), and 84 with well-differentiated/dedifferentiated liposarcoma (WD/DDLPS). We also performed IHC staining using a panel of immune cell markers and checkpoints on the ULMS TMA, including CD8, CD20, CD68, PDL1, CTLA4, CD47, and CD163, among others. Kaplan-Meier analysis with log rank tests were used to assess the impact of ATRX loss on overall survival (OS), disease-specific survival (DSS), and progression free survival (PFS). Cox proportional hazards modeling was used to determine whether ATRX loss is an independent predictor of survival. T tests, ANOVA, and Chi squared tests were used to test for association between ATRX loss and immune markers in the ULMS TMA. Results: ATRX loss was seen in 14.1% of STLMS (n = 18), 52.6% of ULMS (n = 50), 36.6% of UPS (n = 30), and 8.3% of WD/DDLPS (n = 7). In univariate analysis, ATRX loss was associated with significantly worse OS (HR 0.50, 95% CI 0.31-0.80, p = 0.004) and PFS (HR 0.51, 95% CI 0.33-0.81, p = 0.004) in ULMS, worse DSS in UPS (HR 0.46, 95% CI 0.23-0.95, p = 0.03), and worse PFS in WD/DDLPS (HR 0.13, 95% CI 0.02-0.73, p = 0.02). In multivariate analyses, ATRX loss was also associated with worse OS and PFS in ULMS and worse DSS in UPS. In ULMS, ATRX loss was associated with increased density of CD8+ T cells (p = 0.01), PDL1 expression (p = 0.03), CTLA4 expression (p = 0.049), IDO-positive tumor cells (p = 0.01), and CD163-positive cells (p = 0.003). Conclusions: ATRX loss is associated with worse outcomes in ULMS, UPS, and WD/DDLPS. ATRX loss is also associated with a distinct immune microenvironment in ULMS characterized by T cell exhaustion and immunosuppressive M2 macrophages. Future work will focus on understanding the molecular underpinnings of these associations and potential ways to exploit these findings therapeutically.
Anti-angiogenic TKIs in patients with advanced Ewing sarcoma: A systematic review and single-arm meta-analysis.
Authors: Castro Caio , Belluco Ana Paula , Michelon Isabella , Dacoregio Maria Inez , N. Priantti Jonathan , Vilbert Maysa , Koch Hein Erica C. , Cavalcante Ludimila 
Published: June 2024

11531 Background: The treatment of patients with localized Ewing Sarcoma (ES) is well established; however, strategies for relapsed disease remain uncertain. Encouraging outcomes have surfaced from early-phase trials assessing tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties in this population. Hence, we conducted a systematic review and meta-analysis to synthesize current data on efficacy and safety of TKIs in patients with ES. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials and cohort studies assessing anti-angiogenic TKIs in the treatment of advanced ES patients who had received at least one previous line of therapy. Main outcomes were objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), and safety. Heterogeneity was assessed using I2 statistics. All analyses were conducted using R software (v.4.2.2), employing random effects models. Results: We included 10 studies: four phase II clinical trials and six retrospective cohort studies, comprising 191 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib and sorafenib. Median age in each study varied from 15 to 33 years, and 48.6% of patients had received ≥2 previous lines of therapy. In a pooled analysis of all ES patients treated with TKIs, the ORR was 30.1% (95%IC 16.3-43.8; I2=83.14%) and DCR was 66.8% (95%IC 59.4-73.5; I2=3.97%). In a comparative analysis stratified by drug, anlotinib was associated with an increased ORR (p<0.01) and no difference was seen in DCR among TKIs assessed (p=0.26). Seven studies evaluated TKIs in monotherapy, while the others included patients treated with TKIs + chemotherapy (CT); TKI+CT displayed higher ORR (p=0.04) and DCR (p=0.05), in a subgroup analysis by treatment strategies. The median PFS varied from 3.5 to 16.0 between drugs, and the overall median PFS was 4.4 months (95%CI 3.4-10). Dose reduction and interruption of treatment due to toxicity were reported in 39.6% and 6% of patients, respectively. Most common grade 3 or 4 adverse events were leukopenia (24.5%), anemia (8.8%), hypertension (5.6%), and diarrhea (4.3%). Conclusions: Anti-angiogenic TKIs are well tolerated and have shown anti-tumoral activity and clinical benefit in the treatment of patients with advanced Ewing sarcoma. Prospective randomized trials with adequate control groups are warranted to further evaluate the benefits of these agents. [Table: see text]
Novel models for the functional characterization of SDHA germline variants to predict cancer risk.
Authors: Kent Jason , Heinrich Michael C. 
Published: June 2024

11532 Background: SDHA mutations are the most common cause of SDH-deficient GIST. More than 80% of SDHA-mutant GIST are associated with heterozygous germline mutations. Enhanced cancer surveillance of individuals carrying a known pathogenic germline SDHA mutation has the potential to detect early-stage tumors, allowing for curative surgery. However, of the > 1000 SDHA missense variants listed in ClinVar, > 95% are VUS. We must improve our ability to interpret the significance of SDHA variants before genetic sequencing can be utilized to its fullest potential for assessing cancer risk. Methods: We generated a novel clonal SDHA knock out (SDHAKO) human cell line with complete loss of SDHA expression and enzymatic activity. We next generated a clonal cell line harboring one copy of a landing pad cassette, allowing for site-specific integration of transfected expression cassettes mediated by Bxb1 recombinase. We validated that wild-type SDHA cDNA restored SDHA expression and enzymatic activity to levels equivalent to the parental HAP1 cells. We then selected 17 known benign variants (B,LB) and 21 known cancer missense variants (P, LP). In addition, we selected six missense variants associated with primary mitochondrial disease rather than cancer. Lastly, we selected 22 missense VUS. We created a mutant cell line in our KO landing pad cell line for each SDHA variant, as well as a control nonsense variant (SDHAR31X). Cell lines were analyzed for normalized SDH activity measurements (SDHAWT activity score = 1) Results: As expected, benign variants were collectively WT-like, with a mean Activity Score of 0.917. However, there was substantial variability amongst individual variants, with SDHAY55H having the lowest score at 0.215. Although known PMD variants (mean Activity Score = 0.358) were associated with lower functionality than that of benign variants, the extent of SDH dysfunction corresponding to cancer variants (mean Activity Score = 0.007) was substantially lower. Notably, all but one cancer variant could be described as functionally amorphic, as their Activity Scores were not significantly different from that of a control null variant, SDHAR31X, whose mean Activity Score was 0.004. We used the Activity Scores of these clinical control variants to establish thresholds to classify "cancer-like" or "benign-like" variants, which meet ACMG/AMP criteria for PS3_strong and BS_3 strong evidence according to an OddsPath calculation. We biochemically profiled 22 cell lines expressing a SDHA VUS. Using functional data and ACMG criteria, 3 variants could be reclassified as "Likely Benign", 14 could be reclassified as "Likely Pathogenic", and 5 remained a VUS (77% successfully reclassified). Conclusions: Functional characterization of SDHA germline missense variants has the potential to identify individuals who will benefit from genetic counseling and enhanced cancer screening procedures.