julilili42/papers huggingface dataset:
A 6000-year-long genomic transect from the Bogotá Altiplano reveals multiple genetic shifts in the demographic history of Colombia
2025-05-28

Genetic studies on Native American populations have transformed our understanding of the demographic history of the Americas. However, a region that has not been investigated through ancient genomics so far is Colombia, the entry point into South America. Here, we report genome-wide data of 21 individuals from the Bogotá Altiplano in Colombia between 6000 and 500 years ago. We reveal that preceramic hunter-gatherers represent a previously unknown basal lineage that derives from the initial South American radiation. These hunter-gatherers do not carry differential affinity to ancient North American groups nor contribute genetically to ancient or present-day South American populations. By 2000 years ago, the local genetic ancestry is replaced by populations from Central America associated with the Herrera ceramic complex and survives through the Muisca period despite major cultural changes. These ancient Altiplano individuals show higher affinities to Chibchan speakers from the Isthmus of Panama than to Indigenous Colombians, suggesting a dilution of the Chibchan-related ancestry through subsequent dispersal events.
The alignment model of indirect communication
2025-05-28

Speakers often choose utterances under uncertainty about the potential opinion of the listener. In this case, utterances that do not signal the speaker’s opinion directly may allow the speaker to avoid possible conflict: saying that an election outcome is interesting rather than amazing, even if the speaker is truly excited about it, may give her an option to retreat if it turns out that the listener’s opinion is the opposite. By enhancing the Rational Speech Act framework with a turn-taking pragmatic system, we develop a model of indirect communication that is able to (1) rationalize the choice of indirect utterances when speakers’ opinions do not align; (2) capture complex reasoning about the true interlocutor’s opinion when facing indirect utterances and responses. The model has several novel features: in addition to standard informativeness goals, speaker choices factor in potential divergences of opinions between conversation partners. The listener model further considers multi-turn dialogues rather than isolated utterances: it is able to derive that an utterance like “interesting” can be interpreted positively or negatively depending on preceding discourse. The model, though complex, makes novel, non-trivial qualitative predictions, which are supported by data from three behavioral experiments reported here.
Prediction of survival after de-escalated neoadjuvant therapy in HER2+ early breast cancer: A pooled analysis of three WSG trials.
2025-05-28

502 Background: Current treatment de-escalation strategies in HER2+ early breast cancer (eBC) aim to mitigate acute and late toxicities by reducing or entirely omitting systemic chemotherapy (sCTx). We analyzed the outcomes and investigated predictors of survival in three randomized de-escalation trials investigating short (12-week) neoadjuvant treatments (NAT) with and without sCTx (paclitaxel, pac) in HER2+ eBC. Methods: In total, 713 patients (pts) were analyzed. WSG-ADAPT-HR-/HER2+ (NCT01817452) compared trastuzumab and pertuzumab (T + P, n=92) vs. T +P + pac (n=42); WSG-ADAPT-HR+/HER2+ (NCT01779206) compared trastuzumab emtansine (T-DM1, n=118) vs. T-DM1 + standard endocrine therapy (ET, n=125) vs. T + ET (n=129); WSG-TP-II (NCT03272477) compared neoadjuvant/adjuvant T + P + ET (n=100) vs. T + P + pac (n=107). Omission of further sCTx was allowed in pts with pathological complete response (pCR, ypT0/is ypN0); sCTx was mandatory for non-pCR pts. pCR was the primary endpoint of each trial; survival was a secondary endpoint. Kaplan-Meier method and Cox regression were applied for survival analysis. Results: Median follow-up of 60.7 months was available for 713 pts (sCTx: n=149; sCTx-free NAT: n=564). 395 tumors (55%) were cT2-4, 414 (58%) were grade 3, and 223 pts (31%) were clinically node-positive. Ten (7%) and 74 (13%) pts had iDFS events, 8 (5%) and 51 (9%) had dDFS events, and 6 (4%) and 34 (6%) pts died in the sCTx and sCTx-free NAT groups, respectively. In the sCTx and sCTx-free NAT groups, the respective 5-year survival rates were 98% (95%CI 93, 99) and 97% (95%CI 95, 98) for OS (HR 0.88; 95%CI 0.36, 2.11; p=0.775) and 96% (95%CI 91, 98) and 88% (95%CI 85, 91) for iDFS (HR 0.56; 95%CI 0.29, 1.08; p=0.083). 95 (66%) and 171 (31%) pts had a pCR after sCTx and sCTx-free NAT, respectively. iDFS events occurred in 5 (5%) pts with pCR and 5 (10%) without pCR after sCTx and in 14 (8%) with pCR and 59 (16%) pts without pCR after sCTx-free NAT. 5-year iDFS rates in pts with pCR were 98% (95%CI 91, 99) after sCTx and 94% (95%CI 89, 97) after sCTx-free NAT (HR 0.76; 95%CI 0.27, 2.14; p=0.609). In univariate analysis, iDFS was associated with pCR (HR 0.18; 95%CI 0.04, 0.77) in the sCTx group and with cT (3-4 vs 1: HR 2.54; 95%CI 1.22, 5.28) and cN stage (cN+ vs cN-: HR 2.27; 95%CI 1.44, 3.58), grade (3 vs 1-2: HR 1.79; 95%CI 0.86, 3.74) and pCR (HR 0.47; 95%CI 0.26; 0.84) in the sCTx-free NAT group. Detailed subgroup analyses including the impact of standard chemotherapy on outcome will be presented at the meeting. Conclusions: This pooled analysis demonstrates that de-escalation trials in HER2+ eBC are feasible and safe for patients. 12× weekly paclitaxel + HER2 blockade is an effective and well-tolerated regimen with excellent 5-year survival. The favorable survival after pCR to sCTx-free NAT lays the groundwork for further de-escalation strategies, such as the currently ongoing WSG-ADAPT-HER2-IV evaluating T-DXd as NAT. Clinical trial information: NCT01817452 , NCT01779206 , NCT03272477 .
Associations of road traffic noise with adipose tissue depots and hepatic fat content – Results from the German National Cohort (NAKO)
2025-05-28

Little is known about the relation between traffic noise exposure, an established environmental risk factor for cardiovascular disease, and early obesity-related risk markers such as adipose tissue (AT) and hepatic fat. Therefore, we aimed to assess associations of long-term road traffic noise exposure with AT depots measures from whole-body magnetic resonance imaging (MRI). We analyzed cross-sectional data from 11,343 participants from the population-based German National Cohort (NAKO) who underwent MRI examination between 2014 and 2016, considering visceral (VAT), subcutaneous abdominal (SCAAT), subcutaneous thoracic AT (SCTAT) and hepatic fat content as outcomes. Annual road traffic noise (L<sub>den</sub>) data from the year 2017 (source: central EIONET data repository) was used to calculate weighted mean noise levels on a continuous scale within 10 and 100-meter buffers of participants' residencies. Among 11,101 participants with complete outcome data, 48.7 % were women, and the mean age was 51.9 years. Higher annual L<sub>den</sub> was associated with increased AT depots and hepatic fat content in men (e.g., VAT: 1.72 %-change [95 % confidence interval: [0.14 %; 3.30 %]; SCAAT: 2.18 %-change [0.43 %; 3.93 %], hepatic fat content: 3.57 %-change [1.41 %; 5.78 %] per 10 dB(A) increase in L<sub>den</sub> (10 m)) and women (e.g., VAT: 3.13 %-change [1.09 %; 5.18 %]; SCAAT: 2.38 %-change [0.55 %; 4.20 %], hepatic fat content: 3.08 %-change [1.00 %; 5.21 %] per 10 dB(A) increase in L<sub>den</sub> (10 m)). Associations were robust with all outcomes after adjusting for air pollutants and surrounding greenness, and effect modification by obesity and hypertension was observed for SCAAT, SCTAT and hepatic fat content. Our findings indicate that annual exposure to road traffic noise is associated with increased adipose tissue depots and hepatic fat content, and thus present novel evidence for the cross-sectional association between noise and early MRI-derived metabolic health markers.
Morphological and Molecular Investigation of Non-Simulium damnosum Black Flies in Cameroon Using Nuclear ITS 2 and Mitochondrial Cox 1 Genes
2025-05-28

Background: This study enhances knowledge of black fly biodiversity in Cameroon by integrating morphological and molecular analyses. A total of 19 Simulium species were identified from 1184 pupae collected across 13 sites, using morphological examination of gills and DNA sequencing of Cox1 and ITS2 markers. Key findings include the first report of 2 not yet described (based on identification keys used) species in Cameroon and confirmation of S. vorax and S. dentulosum as known vectors of onchocerciasis. DNA sequences have been deposited in GenBank for reference. Methods: Combining morphological and molecular approaches revealed more species diversity than previously described, showing the potential of molecular techniques in black fly study. Notably, the presence of species not typically associated with human-biting behavior (e.g., S. cervicornutum) raises the possibility that such flies could act as vectors under favorable conditions. Conclusion: This study underscores the importance of identifying Simulium species for understanding their role in pathogen transmission. The results provide a foundation for further research on undescribed Simulium species and their potential vectorial capacities. Future studies should explore the ecological and behavioral factors influencing vector status, especially in the context of environmental changes. By bridging morphology and DNA analysis, this research advances the study of black flies and sets the stage for improved vector monitoring and disease control in Cameroon and beyond.
Temporal Resonance as a Scalar Field: A Testable Framework for Local Time Deviations
2025-05-28

<title>Abstract</title> We propose a testable theoretical framework in which proper-time deviations are modeled by a real scalar field τ (x) defined on spacetime. This field obeys a Klein–Gordon-type equation sourced by the trace of the energy-momentum tensor. The framework predicts localized and resonantly amplified time-shifts induced by energetic systems, suggesting measurable deviations in high-precision atomic clocks or interferometric setups. We discuss analytical solutions, quantization, nonlinear effects, and experimental implications of the theory.
Patient outcomes in WSG-ADAPT according to NATALEE and MonarchE risk criteria.
2025-05-28

601 Background: In HR+/HER2- high-risk early breast cancer (eBC), abemaciclib and ribociclib improve the efficacy of standard endocrine treatment (ET), as shown in MonarchE (abemaciclib) and NATALEE (ribociclib). However, the absolute benefit varies according to prognostic factors. We analyzed the outcome of prognostic groups based on MonarchE and/or NATALEE inclusion criteria in the WSG-ADAPT trial considering Recurrence Score (RS, OncotypeDx) and Ki-67 response after preoperative ET. Methods: In WSG-ADAPT (NCT01779206), patients (pts) with clinically high-risk HR+/HER2- eBC (cT2-4 or cN+ or G3 or Ki67 ≥ 15%) initially received a 3-week standard ET before surgery or sequential biopsy. Pts with c/pN2-3 or G3 with Ki67 &gt; 40% were randomized directly to chemotherapy (CT trial) evaluating (neo)adjuvant 4 × paclitaxel q2w vs. 8 × nab-paclitaxel q1w, followed by epirubicin + cyclophosphamide q2w, followed by ET. pN0-1 pts with RS 0-11 or RS 12-25 with ET-response (central Ki67 postET ≤ 10%) received ET alone (ET trial); RS 12-25 pts without ET-response entered CT trial. Pts with N1-3 or T3 or T2, N0 with either Ki-67 ≥ 20% or G3 or RS &gt; 25 were classified as NATALEE high-risk, pts with N2-3 or N1 with either T3-4 or G3 or Ki-67 ≥ 20% were classified as MonarchE high-risk. Results: In the WSG-ADAPT ET trial, 303 (14.2%) and 784 (36.7%) of 2135 pts were classified as MonarchE and NATALEE high-risk, respectively. In the CT trial, 963 (43.2%) and 1572 (70.5%) of 2230 pts were classified as MonarchE and NATALEE high-risk. After 60 months of median follow-up, both high-risk vs. low-risk classifications were highly prognostic for iDFS and dDFS in ET and CT trials. However, low-risk pts (by both classifications) in the ET trial had 5-y iDFS and dDFS of 94.7% and 96.4%, respectively, vs. 90.1% and 93.6% for high-risk by just NATALEE but not by MonarchE criteria (p = n.s.) and vs. 88.3% and 88.9% in both NATALEE and MonarchE high-risk pts (p &lt; 0.001). In the ET-only cohort, survival outcomes were similar between pN0 and pN1 pts at high-risk by NATALEE but not by MonarchE criteria (5-y iDFS of 87.7% vs. 90.2%; p = n.s. and 5-y dDFS of 91.7% vs. 91.9%; p = n.s.). In the CT trial, 5-y iDFS and dDFS rates were 93.9% and 94.9%, respectively, for NATALEE low-risk pts vs. 84.7% and 87.0% for high-risk by NATALEE but not by MonarchE criteria and vs. 77.7% and 79.6% for MonarchE high-risk pts. Conclusions: Among 4365 pts in the WSG-ADAPT trial, subgroups classified as high-risk by NATALEE and MonarchE criteria had poor outcomes. However, N0-1 pts who were high-risk by NATALEE but not MonarchE criteria and pts with RS ≤ 25 and/or ET response had only slightly inferior outcomes compared to low-risk pts with ET therapy alone. Assuming a hazard ratio of 0.7 for a ribociclib effect, as shown in NATALEE, an absolute benefit of approx. 2% fewer dDFS events after 5 years can be assumed in this group based on the WSG-ADAPT experience. Shared decision-making will be key in this intermediate-risk group. Clinical trial information: NCT01779206 .
Differences in the relationships between interoceptive sensibility and self-objectification in women with high and low body dissatisfaction: A network analysis
2025-05-28

Body dissatisfaction is a normative experience with the potential to impact women’s mental and physical health. It is closely related to self-objectification, where the body is viewed as an object for aesthetic evaluation rather than for its functional attributes. Self-objectification not only affects women’s body image but is associated with diminished subjective awareness of, and attention towards, internal bodily states (i.e., interoceptive sensibility). This study uses network analysis and network comparison to investigate the relationships between features of interoceptive sensibility and self-objectification in women with high (N = 348) and low (N = 354) body dissatisfaction. The results firstly revealed significant differences in the connections between interoceptive sensibility and self-objectification in women with high and low body dissatisfaction (p = 0.026). High body dissatisfaction in women was characterised by lower levels of body listening, self-regulation, and body trusting. Alternatively, high emotional awareness was most central to women with low body dissatisfaction. This study highlights the central role of interoceptive sensibility in body dissatisfaction and identifies key features of interoceptive sensibility to target for improving body dissatisfaction.
Sulfonohydrazide as a potential inhibitor of SARS-CoV-2 infection
2025-05-28

The COVID-19 pandemic caused immense mortality and morbidity reporting 704,753,890 cases worldwide. The repercussions of this pandemic are still being felt in the form of newly evolving variants and infections. The pandemic has pointed towards the need for the development of new and effective agents against SARS-CoV-2 infection. Sulfonohydrazides are a class of compounds with a wide range of therapeutic potential. The present study aims to identify the anti-SARS-CoV-2 potential of Sulfonohydrazide compounds. Twenty-five Sulfonohydrazides derivatives were evaluated for anti-viral potential via plaque reduction assay (PRA) and cytopathic effect (CPE) analysis in-vitro. Treatment point assay was employed for the strategic evaluation of antiviral compound at the particular stages of the SARS-CoV-2 life cycle. Gene expression analysis was also carried out, which was supported by immunofluorescence assays targeting the N and S proteins of SARS-CoV-2, alongside fold-change analysis, to identify a robust and multifaceted approach for the understanding of viral dynamics. Moreover, ligand-inhibitor interactions were assessed by in- silico studies. Compound 24 (4(E)-4-methyl-N'-(2,3,4-trihydroxybenzylidene)benzenesulfonohydrazide) was identified as the most potent molecule that inhibited SARS-CoV-2 infection (92.85 ± 3.57%) via PRA. The time point assay revealed that the effect of the compound might be at the entry point, which might be due to the down-regulation of the Spike (S) and Angiotensin-converting enzyme 2 (ACE-2) genes by the compound. The gene expression analysis of ORF1a/b by qRT-PCR indicated reduction in viral load after compound treatment, as indicated by a higher cycle threshold (Ct) value. Moreover, the compound 24 also downregulated the expression of S, RdRp, and ACE-2. Furthermore, the interaction of compound 24 with S, RdRp, and ACE-2 was predicted via molecular docking, which validated the interaction and possible anti-SARS-CoV-2 effect. Additionally, immunofluorescence staining analysis of spike and nucleocapsid proteins also showed downregulation in SARS-CoV-2 infected cells. Overall, the acquired data suggested that Sulfonohydrazide derivative 24 inhibits SARS-CoV-2 entry and replication.
Low-dose anti-PD-(L)1 inhibitor strategies: A systematic review.
2025-05-28

1526 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-(L)1 pathway have revolutionized cancer therapy, but their high costs significantly limit accessibility, particularly in low- and middle-income countries (LMICs). Low-dose regimens may offer a viable solution to this challenge. This systematic review analysed study designs, dosing strategies, clinical outcomes, and potential cost savings of low-dose ICIs. Methods: A PRISMA/EQUATOR compliant systematic search of WebOfScience, Cochrane Central Register of Clinical Trials, ASCO and ESMO conference databases was conducted until October 10 th , 2024. Studies investigating reduced-dose anti-PD(L)1 from those FDA/EMA-approved regimens were included. Data were categorized by dose and country income level. Results: From 1,751 records, 25 studies (4 clinical trials, 21 observational studies) involving 1,793 participants met inclusion criteria, with 1,202 receiving low-dose ICIs. Two studies used non-inferiority designs, and 21 evaluated participants across multiple treatment lines. The population had a median age of 53.1 years (range 19–84), 26% female, 88% with advanced disease, and 9% ECOG ≥2. Most studies were conducted in Asia (81.4%, n = 1,459), with head and neck (22.8%, n = 409) and non-small cell lung cancers (17.3%, n = 311) being most studied. 48% studies were from LMICs, 44% from high-income countries (HIC), and 8% from upper middle-income countries (UMIC). India contributed the most (studies, k = 12, 839 participants). Nivo ( k = 21), pembro ( k = 6) and atezo ( k = 1) were assessed. The most common regimens were Nivo40mg Q2W ( k = 7), Nivo20mg Q3W ( k = 6) and Nivo20mg Q2W ( k = 5) [Table 1]. A radiological response rate between 5-75% was noted when low-dose ICI was used as monotherapy ( k = 10). High variability in participant selection and interventions restricts further conclusions about efficacy and safety. The median projected savings were 83.3% (25–99.40%), with ≥70% savings in half of the studies. Conclusions: This review described the use of low-dose anti-PD(L)1 drugs, especially in healthcare settings with limited resources, highlighting radiological responses observed with monotherapy. Non-inferiority or near-equivalence randomized clinical trials will be helpful in establishing their clinical validity. Tumor type(origin from participants assessed) HNSCCn=409 NSCLC n=311 HCCn=93 RCC n=73 HL n=70 Multiple n=57 Melanoma n=56 Gastric/GEJ n=42 Gyne n=35 CCR n=30 Cervical n=20 Thymic n=6 LMIC 409 57 57 42 30 20 UMIC 23 6 HIC 311 93 16 47 56 35 Number of studies (k) assessing each dose per tumor k: 6 k: 4 k: 2 k: 2 k: 3 k: 2 k: 1 k: 1 n: 1 n: 1 n: 1 n: 1 Nivo 0.3 mg/Kg Q2W <jats:td colspan="1"
A Validation Workflow for Novel Oligonucleotide Sequences to Expand the Multiplexing Capacity of the CO-Detection by indEXing (CODEX) Platform
2025-05-28

Antibody-based multiplexed tissue imaging has the potential to provide critical advances in biological discoveries and their translation for clinical applications. With the increasing introduction of markers and modalities for spatial analysis, there is an according demand for the expansion of multiplexing capacities of such imaging platforms. CO-Detection by indEXing (CODEX) is a widely used multiplexed tissue imaging platform that utilizes DNA-conjugated antibodies for imaging. The multiplexing capacity of CODEX is limited by the availability of unique DNA-oligonucleotide sequences for antibody barcoding. In this study, we demonstrate a workflow for the validation and the introduction of novel sets of candidate DNA-oligonucleotide sequences for CODEX. Through cross-validation multicycle experiments with the already published library of DNA barcodes, we here present a set of 27 novel oligonucleotide sequences for CODEX, increasing the potential multiplexing capacity to 85+ markers. We confirmed the utility of the new barcodes using a 74-plex antibody panel on a multitumor tissue microarray of paraffin-embedded tissues. The workflow presented here provides a reproducible method for extending the plexity of the CODEX platform, facilitating a deeper understanding of tissue microenvironments.