julilili42/papers huggingface dataset:
Mid‐term survival and physiological joint angles after double level osteotomy of severe varus osteoarthritis
2025-07-13

Abstract Purpose Double‐level osteotomy (DLO) is a joint‐preserving technique for the treatment of symptomatic varus knee osteoarthritis (OA) in cases of femoral and tibial combined deformity. The study aimed to investigate the mid‐term survival rate (&gt;5 years) and restoration of postoperative joint angles. Methods Sixty‐five knees underwent DLO (medial open wedge high tibial osteotomy (MOWHT) and lateral closing wedge distal femoral osteotomy (LCWDFO) between 2011 and 2015. Minimum follow‐up was 5 years. The survival rate was recorded and, in case of conversion to knee arthroplasty, the time of conversion. Radiographs were obtained preoperatively, 6 weeks postoperatively and at the last follow‐up. On radiographs mechanical tibiofemoral angle (mTFA), mechanical medial proximal tibia angle (mMPTA), mechanical lateral distal femur angle (mLDFA), joint line convergence angle (JLCA) and joint line obliquity (JLO) were measured. The clinical outcome was measured using International Knee Documentation Committee (IKDC), Oxford and Lysholm score. Results Forty‐nine knees (75% follow‐up) were included after 8.0 ± 1.4 years. At the last follow‐up, six knees underwent arthroplasty (7‐year survival rate: 91.8%; 5‐year survival rate: 93.9%) in average after 5.1 ± 2.3 years. Preoperatively, there was a varus deformity of −10.0 ± 2.5° (mTFA). In addition, pathologic knee joint angles with an mMPTA of 84.7 ± 2.2°, an mLDFA of 91.4 ± 2.1°, an JLCA of 3.4 ± 1.8 and a JLO of 3.0 ± 1.9°. Six weeks postoperatively mTFA was 0.7 ± 2.2° with values of mMPTA 91.0 ± 2.3°, mLDFA 86.8 ± 2.0° and JLO of 2.8 ± 2.1°. In the mid‐term, a preserved leg axis (mTFA: −0.9 ± 2.7°) and preserved joint angles (mMPTA: 90.3 ± 2.7°, mLDFA: 87.1 ± 2.3°, JLCA: 4.3 ± 1.9 JLO: 3.2 ± 2.1°) were observed. At the last follow‐up, the IKDC, Oxford Knee Score (OKS) and Lysholm score were: 61.2%, 36.1 points and 78.3 points, respectively. Conclusion The study demonstrates that DLO is an effective surgical technique to restore physiological joint angles in patients with severe preoperative deformity and symptomatic varus OA. Mid‐term results indicate good clinical outcomes and a low conversion rate to TKA. Level of Evidence Level IV.
The Biases in Captive Chimpanzee Cognitive Research: First Insights From the Ape Research Index (ARI) Database
2025-07-13

ABSTRACT Comparative studies provide crucial insights on human behaviour and our evolutionary past, ranging from the roots of human culture and cognition to understanding the mechanisms behind specific phenomena such as addiction. Chimpanzees ( Pan troglodytes ) are the primary model species for comparative cognition research. In particular, captive chimpanzees are important comparative models due to the more controlled settings provided by captivity and the generally easier access than wild populations. This reliance on captive chimpanzees has resulted in the rise of specific research‐intensive facilities that house chimpanzees which, in some cases, are tested regularly throughout their entire lifetimes. These differences in individual research experience history may not only affect performance in tasks, but also overall cognition and motivation to participate in research. The overarching aim of the Ape Research Index (ARI) project is to assess whether research participation over time results in variation in captive chimpanzee cognition and behaviour. To do so, we must first identify whether chimpanzee research participation varies at the group and/or individual level. Accordingly, for this perspectives piece, we carried out a systematic literature review to develop the largest (to our knowledge) database on captive chimpanzee cognitive experiments between 1950 and 2024. Using this (ARI) database, we identified systematic differences in both the extent and type of accumulated research experience in captive chimpanzees within and across facilities. Based on our data, we argue that the current approach in comparative research may be biassing our understanding of ape cognition, and reducing the robustness of insights drawn from these studies. Future work will involve empirically testing these biases in order to validate any behavioural variation potentially emerging from this effect.
Variations in Relevance Judgments and the Shelf Life of Test Collections
2025-07-13

The fundamental property of Cranfield-style evaluations, that system rankings are stable even when assessors disagree on individual relevance decisions, was validated on traditional test collections. However, the paradigm shift towards neural retrieval models affected the characteristics of modern test collections, e.g., documents are short, judged with four grades of relevance, and information needs have no descriptions or narratives. Under these changes, it is unclear whether assessor disagreement remains negligible for system comparisons. We investigate this aspect under the additional condition that the few modern test collections are heavily re-used. Given more possible query interpretations due to less formalized information needs, an ``expiration date'' for test collections might be needed if top-effectiveness requires overfitting to a single interpretation of relevance. We run a reproducibility study and re-annotate the relevance judgments of the 2019~TREC Deep Learning track. We can reproduce prior work in the neural retrieval setting, showing that assessor disagreement does not affect system rankings. However, we observe that some models substantially degrade with our new relevance judgments, and some have already reached the effectiveness of humans as rankers, providing evidence that test collections can expire.
A major trade-off between growth and defense in Arabidopsis thaliana can vanish in field conditions
2025-07-14

When wild plants defend themselves from pathogens, this often comes with a trade-off: the same genes that protect a plant from disease can also reduce its growth and fecundity in the absence of pathogens. One protein implicated in a major growth-defense trade-off is ACCELERATED CELL DEATH 6 (ACD6), an ion channel that modulates salicylic acid (SA) synthesis to potentiate a wide range of defenses. Wild Arabidopsis thaliana populations maintain significant functional variation at the ACD6 locus, with some alleles making the protein hyperactive. In the greenhouse, plants with hyperactive ACD6 alleles are resistant to diverse pathogens, yet they are of smaller stature, their leaves senesce earlier, and they set fewer seeds compared to plants with the standard allele. We hypothesized that ACD6 hyperactivity would not only affect the growth of microbial pathogens but also more generally change leaf microbiome assembly. To test this in an ecologically meaningful context, we compared plants with hyperactive, standard, and defective ACD6 alleles in the same field-collected soil, both outdoors and in naturally lit and climate-controlled indoor conditions, taking advantage of near-isogenic lines as well as a natural accession and a CRISPR-edited derivative. We surveyed visual phenotypes, gene expression, hormone levels, seed production, and the microbiome in each environment. The genetic precision of CRISPR-edited plants allowed us to conclude that ACD6 genotype had no effect on mature field plants in our setting, despite reproducibly dramatic effects on greenhouse plants. We conclude that additional abiotic and/or microbial signals present outdoors—but not in the greenhouse—greatly modulate ACD6 activity. This raises the possibility that the fitness costs of other commonly studied immune system genes may be grossly misjudged without field studies.
Three‐Week Video‐ and Home‐Based Training Program for People with Ataxia: A Pilot Randomized Controlled Trial
2025-07-14

Abstract Background Gait and balance impairment is a disabling clinical feature in people with degenerative cerebellar ataxia. Objectives We performed a rater‐blinded, parallel 3‐arm randomized controlled trial with delayed‐start‐design (exploratory proof‐of‐concept study) to assess whether, compared to control, people with mild/moderate hereditary ataxia benefit from additional video‐based training with different frequencies, and how clinical characteristics interact with training success. Methods Digital gait/balance measures were assessed before and after a three‐week video‐based training program at home (Train20: 4 × 20min/week, n = 11; Train40: 2 × 40min/week, n = 11; control: standard medical care, n = 10). Group differences at baseline and changes over time were assessed using ANOVA. Linear mixed models were conducted to examine the influence of clinical variables on outcomes over time. Further exploratory analyses were performed using intraclass correlation coefficients (ICC), and paired t‐tests within each group. Results All variables showed good to excellent test–retest reliability (ICC ≥0.69). No significant interactions between group and measurement time were found for clinical or gait/balance variables ( p ≥ 0.338). However, participants with higher initial disease severity, greater impairment in activities of daily living, and better well‐being showed significant improvements in feet‐together stance ( p = 0.04), normal ( p = 0.01), and backward gait ( p = 0.03). Exploratory analyses showed improvement only in Train40. Conclusions Although the protocol did not lead to general improvements in people with mild/moderate ataxia, irrespective of training frequency, those with higher initial disease severity, higher functional impairment, and better mental well‐being showed significant benefits. Greater attention should be given to the impact of well‐being to enhance motor training outcomes. Longer, less frequent sessions may offer greater potential for improvement.
Self-other generalisation shapes social interaction and is disrupted in borderline personality disorder
2025-07-14

Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task – the Intentions Game. We involved humans with ( n =50) and without ( n =53) a diagnosis of borderline personality disorder and assessed whether infractions to self-other generalisation may explain prior findings of disrupted social learning and instability. Healthy controls initially used their preferences to predict others and were influenced by their partners, leading to self-other convergence. In contrast, individuals with borderline personality disorder maintained distinct self-other representations when learning about others. This allowed for equal predictive performance compared to controls despite reduced updating sensitivity. Furthermore, we explored theory-driven individual differences underpinning contagion. Overall, the findings provide a clear explanation of how self-other generalisation constrains and assists learning, and how childhood adversity is associated with separation of internalised beliefs. Our model makes clear predictions about the mechanisms of social information generalisation concerning both joint and individual reward.
Sequence variability of BamA and FadL candidate vaccinogens suggests divergent evolutionary paths of Treponema pallidum outer membrane proteins
2025-07-14

ABSTRACT Knowledge of Treponema pallidum subspecies pallidum ( TPA ) outer membrane protein (OMP) sequence variability is essential for understanding spirochete proliferation within endemic populations as well as the design of a globally effective syphilis vaccine. Our group has identified extracellular loops (ECLs) of TPA BamA (TP0326) and members of the FadL family (TP0548, TP0856, TP0858, TP0859, and TP0865) as potential components of a multivalent vaccine cocktail. As part of a consortium to explore TPA strain diversity, we mapped the variability of BamA and FadL orthologs in 186 TPA strains from Malawi, China, and Colombia onto predicted 3D structures. The 186 genomes fell into eight subclades (five Nichols- and three SS14-lineage) with substantial geographic restriction. Single nucleotide variants accounted for the large majority of proteoforms, with variability notably higher within the Nichols-lineage strains. Most mutations were in regions of the proteins predicted to be extracellular and harboring B cell epitopes. We observed a striking difference in the degree of variability between the six OMPs, suggesting that these proteins are following divergent evolutionary paths. Concatenation of OMP sequences recapitulated the phylogenetic structure of the TPA strains, effectively segregating within clades and largely clustering by subclades. Finally, we noted that BamA and FadL candidate ECL vaccinogens, previously shown to elicit antibodies that kill treponemes during in vitro cultivation, are well conserved. Taken as a whole, our study establishes a structural-phylogenetic approach for analyzing the forces shaping the host-pathogen interface in syphilis within endemic populations while informing the selection of vaccine targets. IMPORTANCE Syphilis remains a major global health concern, reinforcing the need for a safe and effective vaccine. Understanding the variability of TPA OMPs is essential for tracking pathogen evolution and informing vaccine design. Here, we analyzed the variability of six TPA OMPs in 186 strains from Malawi, China, and Colombia, identifying protein-specific evolutionary patterns. Most mutations were localized in extracellular regions and, notably, appeared to correlate with the phylogenetic structure of TPA . Despite OMP heterogeneity, several candidate vaccinogens remained highly conserved, reinforcing their potential as globally effective vaccine targets. Our study establishes a structural-phylogenetic framework for dissecting the forces shaping the host-spirochete interface within endemic populations and provides a foundation for designing a globally effective syphilis vaccine.
Stack Management for MPLS Network Actions: Integration of Nodes with Limited Hardware Capabilities
2025-07-14

The MPLS Network Actions (MNA) framework enhances MPLS forwarding with a generalized encoding for manifold extensions such as network slicing and in-situ OAM (IOAM). Network actions in MNA are encoded in Label Stack Entries (LSEs) and are added to the MPLS stack. Routers have a physical limit on the number of LSEs they can read, called the readable label depth (RLD). With MNA, routers must be able to process a minimum number of LSEs which requires a relatively large RLD. In this paper, we perform a hardware analysis of an MNA implementation and identify the reason for a large RLD requirement in the MNA protocol design. Based on this, we present a mechanism that reduces the required RLD for MNA nodes by restructuring the MPLS stack during forwarding. We then introduce the novel stack management network action that enables the proposed mechanism as well as its integration in networks with MNA-incapable nodes. The feasibility of the mechanism on programmable hardware is verified by providing a P4-based implementation. Further, the effects on the required RLD, ECMP, and packet overhead are discussed.
Hydrogen Activation by a σσ*-Carbene Through Quantum Tunneling
2025-07-15

The electronic structure of carbenes arises from the occupation of a σ and a π frontier orbital. While parent methylene possesses a triplet ground state (σ<sup>1</sup>π<sup>1</sup>), substituents are capable of stabilizing the singlet as the ground state (σ<sup>2</sup>π<sup>0</sup> or σ<sup>0</sup>π<sup>2</sup>) by altering the frontier orbital energies. Here, we reveal that the 1,2[I]-shift isomer of 2-iodopyridine, the <i>N</i>-iodo Hammick intermediate, features a resonance between its carbene σ and N-I bond σ* orbitals, rendering them frontier orbitals. This singlet carbene is efficiently generated via UV photolysis of 2-iodopyridine in solid neon at 4.4 K and reacts with molecular hydrogen - but not deuterium - via N-I bond cleavage enabled by quantum tunneling. Instanton theory computations demonstrate the preference for a concerted hydrogen addition mechanism at elevated temperatures, while hydrogen atom abstraction dominates below 100 K despite a higher kinetic barrier for this process. Our findings introduce an unprecedented carbene class, unlocking new opportunities for reactivity and electronic structure explorations.
Influence of wastewater type on the distribution of microbial community compositions including pathogenic bacteria within wastewater treatment processes
2025-07-15

Abstract Many wastewater treatment plants (WWTPs) utilize biological processes to remove organic matter using microbial communities. The present study elucidates the distributions of microbial communities and potential pathogenic bacterial compositions from influent, activated sludge, and effluent of secondary clarifier samples from 10 WWTPs treating municipal ( n = 5), hospital ( n = 2), and livestock ( n = 3) wastewater using 16S rRNA high-throughput amplicon sequencing. Despite the regional differences in location, similar microbial community compositions and pathogenic bacteria distributions were observed from WWTPs treating the same wastewater type. The highest operational taxonomic unit richness, phylogenetic diversity, and evenness were found in municipal WWTPs. Redundancy analysis showed that the concentration of phosphate significantly influences the abundance of pathogenic bacteria in WWTPs. The phylum Proteobacteria (37–68%) was the most dominant bacteria across all samples. Corynebacterium and Pseudomonas were the dominant potential pathogenic bacteria in livestock and municipal WWTPs; the two hospital WWTPs had Klebsiella and Pseudomonas as the dominant genera. The presence of pathogenic bacteria across multiple WWTP locations and wastewater types indicates the need for in-depth monitoring in various stages of wastewater treatment processes as well as in discharged wastewater.
Proteome profiling of plant Cajal bodies uncovers kingdom-specific components
2025-07-15

ABSTRACT Insight into the molecular composition of cellular microenvironments is essential for understanding their function. Membraneless organelles (MLO), such as the nuclear Cajal body (CB), play fundamental roles in eukaryotic cells, but their very nature poses a challenge to biochemical isolation. Despite the relevance of the CB for cell function in plants and animals, its proteome remains to be profiled. Here, we purify plant CBs using a combination of biochemical isolation and fluorescence-activated particle sorting (FAPS) and define their proteome by mass spectrometry. Our work identifies 15 and 95 proteins uniquely localized and enriched in CBs, respectively, of which 22 are also labelled by CB markers in proximity labelling assays. CB proteins are preferentially involved in RNA processing, chromatin organization, and gene expression. While a partial overlap with known animal CB proteins exists, our data reveal a distinct, kingdom-specific CB proteome. These results provide the first comprehensive proteome of CBs and establishes a foundation for dissecting the molecular functions of this organelle across multicellular lineages.
The Clock and the Brain: Circadian Rhythm and Alzheimer’s Disease
2025-07-15

Alzheimer’s Disease (AD) is the most common type of dementia. The circadian system, which is controlled by the master clock in the Suprachiasmatic Nucleus (SCN) of the hypothalamus, is crucial for various physiological processes. Studies have shown that changes in the circadian rhythms can deteriorate neurodegenerative diseases. Changes in the SCN are associated with cognitive decline in AD. The cognitive impairments in AD, especially memory dysfunctions, may be related to Circadian Rhythm Disturbances (CRDs). Moreover, rhythmic expression of clock genes is disrupted in AD patients. There is a circadian pattern of inflammatory processes in AD, and dysregulation of core clock genes promotes neuroinflammation. The present narrative review addresses the intricate link between CRDs and AD, revisiting the relevant cellular and molecular mechanisms. The association between CRDs and AD highlights the need for further investigation of the underlying mechanisms.
Accelerated vs. conventionally fractionated postoperative radiotherapy of non-small cell lung cancer—final results of the prematurely terminated PORTAF trial
2025-07-15

Abstract Purpose A prolonged overall treatment time (OTT) has been demonstrated to adversely affect the primary radiation therapy (RT) outcome in various solid tumors, including non-small cell lung cancer (NSCLC). Retrospective data from our group suggested an advantage of shorter OTT also for postoperative RT (PORT) in patients with NSCLC. The PORTAF trial (ClinicalTrials.gov: NCT02189967) was initiated to prospectively test this hypothesis. Methods The multicenter prospective randomized phase II trial in patients with NSCLC investigated whether an accelerated schedule of PORT (7 fractions per week, 2 Gy per fraction, OTT 3.5–4 weeks) improved outcome compared to conventional fractionation (5 fractions per week, 2 Gy per fraction, OTT 5–6 weeks). Target volumes and total radiation doses were stratified in both treatment arms based on individual risk factors. Primary endpoint of the study was locoregional tumor control (LRTC) 36 months after PORT, with 154 patients to be included in each arm. Results Due to slow accrual and changed indications for PORT, we prematurely closed the trial in 2019. Between 2014 and 2019, eight recruiting centers included 27 evaluable patients. An interim safety analysis performed for the first 21 patients showed nonsignificant differences regarding grade 3 toxicities between the treatment arms, thus not meeting the termination criteria. LRTC was not significantly different between accelerated (73%) and conventionally fractionated RT (92%; p = 0.535). Noteworthily, in 21 FDG-PET/CT restagings before RT, an unexpectedly high number of locoregional recurrences ( n = 4) and distant metastases ( n = 2) were seen, resulting in changed treatment intentions for these patients. Conclusion The prematurely closed PORTAF trial did not find significant differences in 3‐year LRTC when comparing accelerated versus conventionally fractionated irradiation. The observed additional benefit of FDG-PET/CT restaging prior to PORT should be further investigated in a larger cohort to optimize patient selection and avoid unnecessary side-effects.