Miracle-dz/UniFAR-FTUs huggingface dataset:
Tracking antigen‐specific TCR clonotypes in SARS‐CoV‐2 infection reveals distinct severity trajectories

Despite the importance of antigen‐specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in‐depth single‐cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS‐CoV‐2 infection. Our in‐depth analysis revealed that hyperactive or improper T‐cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen‐specific T‐cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin‐6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B‐cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single‐cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.
Nomogram based on multiparametric analysis of early‐stage breast cancer: Prediction of high burden metastatic axillary lymph nodes

The Z0011 and AMAROS trials found that axillary lymph node dissection (ALND) was no longer mandatory for early‐stage breast cancer patients who had one or two metastatic axillary lymph nodes (mALNs). The aim of our study was to establish a nomogram which could be used to quantitatively predict the individual likelihood of high burden mALN (≥3 mALN).
Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease

Background and Objectives Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. Methods Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society–Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. Results A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV—off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy—until requiring a modification—was DBS. Discussion Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. Classification of Evidence This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.
Efficacy of electroacupuncture in improving postoperative ileus in patients receiving colorectal surgery: a systematic review and meta-analysis

Background: This meta-analysis aimed to evaluate the efficacy and safety of electroacupuncture (EA) in improving postoperative ileus after colorectal surgery. Methods: Electronic databases (e.g. Medline) were screened to identify randomized controlled trials that focused on the association between EA and postoperative ileus. Time to first flatus served as the primary outcome, while the secondary outcomes included time required for the recovery of other gastrointestinal functions (e.g. bowel sound recovery), time to tolerability of liquid/solid food, postoperative pain scores, risk of overall complications, and hospital length of stay. Results: Our meta-analysis focusing on 16 studies with a total of 1562 patients demonstrated positive associations of EA with shorter times to the first flatus [mean difference (MD): −10.1 h, P<0.00001, n=1562], first defecation (MD: −11.77 h, P<0.00001, n=1231), bowel sound recovery (MD: −10.76 h, P<0.00001, n=670), tolerability of liquid (MD: −16.44 h, P=0.0002, n=243), and solid food (MD: −17.21 h, P=0.005, n=582) than those who received standard care. The use of EA was also correlated with a lower risk of overall complications (risk ratio:0.71, P=0.04, n=1011), shorter hospital length of stay (MD: −1.22 days, P=0.0001, n=988), and a lower pain score on postoperative days two (standardized MD: −0.87, P=0.009, n=665) and three (standardized MD: −0.45, P<0.00001, n=795), without a difference in time to first ambulation. Conclusion: Our findings showed an association between EA and enhanced gastrointestinal functional recovery and reduced pain severity following colorectal surgery, highlighting the potential benefits of incorporating EA into perioperative care to enhance recovery outcomes in this setting.
Neural correlates of negative life events and their relationships with alcohol and cannabis use initiation

Abstract Objective Negative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one’s life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms. Methods This study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories. Results Dose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation. Conclusions Controllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.
Parental age effect on the longevity and healthspan in Drosophila melanogaster and Caenorhabditis elegans

Several studies have investigated the effect of parental age on biological parameters such as reproduction, lifespan, and health; however, the results have been inconclusive, largely due to inter-species variation and/or modest effect sizes. Here, we examined the effect of parental age on the lifespan, reproductive capacity, and locomotor activity of genetic isogenic lines of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. We found that the progeny of successive generations of old parents had significantly shorter lifespans than the progeny of young parents in both species. Moreover, we investigated the fertility, fecundity, and locomotor activity of C. elegans. Interestingly, both the shorter lifespan and deteriorated healthspan of the progeny were significantly improved by switching to only one generation of younger parents. Collectively, these data demonstrate that the detrimental effect of older parental age on the longevity of the progeny can be reversed, suggesting the existence of a beneficial non–genetic mechanism.
Modelling hydrological consequences of climate change in the permafrost region and assessment of their uncertainty

A physically-based, distributed model of runoff generation in the permafrost regions is presented. The model describes processes of snow cover formation, taking into account blowing snow sublimation, snowmelt, freezing and thawing of the ground, water detention by a basin storage, infiltration, evaporation, overland, subsurface and channel flow. An important feature of the model is the detailed description of water and heat transfer within the active layer of soil during its seasonal thawing and freezing. A case study has been carried out for the Pravaya Hetta River basin (the catchment area is 1200 km2) of Western Siberia within the Lower Ob River basin. The basin is located in tundra and forest-tundra vegetation zones. It has been shown that after precipitation, melt of ground ice is the second largest input to the basin water balance and accounts for about 70 percent of annual precipitation. Seasonal snow losses due to sublimation during blowing snow transport can reach almost 30 percent of the maximum snow accumulation. The model has been applied to assess the impact of climate change on hydrological processes in the permafrost basin. Uncertainty of the simulated hydrological consequences of climate change has been assessed by the multi-scenario approach. Simulated runoff response to the projected climate change varies significantly as a result of the uncertainty of the climate change scenario.
Tumor necrosis factor-α (TNF-α) -308G >a promoter polymorphism (rs1800629) promotes Asians in susceptibility to Plasmodium falciparum severe malaria: A meta-analysis

The multifactorial pathogenesis of severe malaria is partly attributed to host genes, such as those encoding cytokines involved in complex inflammatory reactions, namely tumor necrosis factor-alpha (TNF-α). However, the relationship between TNF-α -308G >A gene polymorphism (rs1800629) and the severity of Plasmodium falciparum (P. falciparum) malaria remains unclear, which prompts a meta-analysis to obtain more precise estimates. The present meta-analysis aimed to better understand this correlation and provide insight into its association in populations with different ethnicities. Literature search outcomes included eight eligible articles in which TNF-α -308G >A polymorphism was determined in uncomplicated malaria (UM) and severe malaria (SM) of P. falciparum as represented in the case and control groups. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated in standard homozygous, recessive, dominant, and codominant genetic models. Subgroup analysis was based on ethnicity, i.e., Africans and Asians. The analyses included overall and the modified outcomes; the latter was obtained without the studies that deviated from the Hardy-Weinberg Equilibrium. The significant data also underwent sensitivity treatment but not publication bias tests because the number of studies was less than ten. Interaction tests were applied to differential outcomes between the subgroups. Overall and HWE-compliant analyses showed no significant association between the TNF-α -308G >A polymorphism and susceptibility to P. falciparum SM (ORs = 1.10–1.52, 95%CIs = 0.68–2.79; Pa = 0.24–0.68). Stratification by ethnicity revealed that two significant associations were found only in the Asians favoring SM for dominant (OR = 1.95, 95% CI = 1.06–3.61, Pa = 0.03) and codominant (OR = 1.83, 95% CI = 1.15–2.92, Pa = 0.01) under the random-effects model, but not among the African populations. The two significant Asian associations were improved with a test of interaction with P-value of0.02–0.03. The significant core outcomes were robust. Results of the meta-analysis suggest that TNF-α -308G >A polymorphism might affect the risk of P. falciparum SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the TNF-α -308G >A association with the clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion.
Plate rigidity inversion in southern California using interseismic GPS velocity field

SUMMARY This paper presents an inversion method using the interseismic velocity field to determine effective rigidity of the lithosphere. The method is based on the minimization of a cost function defined as the quadratic measure of the difference between measured and modelled velocity fields on a discrete set of points. The continuous mapping of the rigidity is fulfilled with a limited set of parameters and the forward solution is achieved using a plane stress finite element code. The computation of the cost function gradient in the parameters’ space allows one to iteratively find the best parameters set through a suitable optimization algorithm. We first design a benchmark including an abrupt rigidity variation that cannot be described by a continuous function. For such a case, we show that increasing the number of parameters is a way to accurately describe sharp variations of the rigidity map. Then, we use a dense GPS velocity field over the southwestern United States to estimate the corresponding rigidity variations for different spatial resolutions of the parameters’ grid. We analyse the conceptual and practical difficulties associated with our methodology. Finally, rigidity maps obtained by our inversion method in southwestern United States and particularly across the San Andreas Fault System are reviewed and compared to current plate rigidity estimates and geophysical data over this area.
Successive Granitic Magma Batches During Pluton Emplacement: the Case of Cabeza de Araya (Spain)

We present a dynamic scenario of granite emplacement in the upper INTRODUCTION crust for the pluton of Cabeza de Araya (Extramadura, Spain), Various mechanisms have been suggested to account for based on interpretations of gravity data, internal structures and the emplacement of granitic bodies. They range from geochemical variations. The three-dimensional shape of the pluton forceful intrusion, via diapirism (Cruden, 1988) or dyking is derived from the inversion of gravity data, and the magma flow (Clemens & Mawer, 1992), to permitted intrusion assisted structures are obtained by mapping the rock anisotropy of magnetic by deformation (Hutton, 1982; Castro, 1985; Guinesusceptibility. The deepest zones of the pluton, which also correspond berteau et al., 1987; Hutton et al., 1990). Between these to vertical lineations, are interpreted as feeder zones from which modes, ballooning (Brun et al., 1990), nested diapirs magma upwelled. These feeders form small, distinct areas connected (Bouchez & Diot, 1990; Paterson & Vernon, 1995), to the pluton’s floor 6 km below the present surface level. We propose stoping (Paterson & Fowler, 1993) and also recognition that the two main feeders of the pluton represent tension gashes that of the ubiquity of syntectonic magmatism (Hutton, 1997) formed at the base of the brittle crust and served as conduits for call for a competition, depending on the crustal level the magma that was ready to be tapped. In the southern half of of observation, between mechanisms driven by magma the pluton, granite type A is cross-cut by type B in the magmatic pressure and those involving tectonic accommodation. state. These magmas show a continuum in their chemistries attributed Evidence for the original segregation and ascent of to progressive differentiation. A fine-grained leucocratic granite, more felsic magmas (now frozen as plutons) is difficult to evolved chemically, cross-cuts the surrounding facies and crops out observe in the field. As a consequence, these processes above the southern feeder zone. It is interpreted as a late magma have to be inferred from petrological and rheological batch, coming from a different source, that intruded into the models of both the magma and country rock (e.g. Cruden, incompletely crystallized surrounding facies. The normal petrographic 1988; Weinberg & Podladchikov, 1994). Stages of magma zoning of the massif of Cabeza de Araya is therefore viewed as a generation and transport have, however, little influence succession of continuous and discontinuous infillings, sequentially on the mode of the final ponding of the magma, which, permissive and forceful, of increasingly evolved magma batches into in turn, is not directly observable in the field. In addition a reservoir that opened at varying rates within the brittle crust. to considerations from regional geology, information from
The Italian present-day stress map

SUMMARY In this paper, we present a significant update of the Italian present-day stress data compilation not only to improve the knowledge on the tectonic setting of the region or to constrain future geodynamic models, but also to understand the mechanics of processes linked to faulting and earthquakes. In this paper, we have analysed, revised and collected new contemporary stress data from borehole breakouts and we have assembled earthquake and fault data. In total, 206 new quality-ranked entries complete the definition of the horizontal stress orientation and tectonic regime in some areas, and bring new information mainly in Sicily and along the Apenninic belt. Now the global Italian data set consists of 715 data points, including 499 of A–Cquality,representinganincreaseof37percentcomparedtothepreviouscompilation.The alignment of horizontal stresses measured in some regions, closely matches the ∼N–S firstorder stress field orientation of ongoing relative crustal motions between Eurasia and Africa plates. The Apenninic belt shows a diffuse extensional stress regime indicating a ∼NE–SW direction of extension, that we interpret as related to a second-order stress field. The horizontal stress rotations observed in peculiar areas reflect a complex interaction between first-order stress field and local effects revealing the importance of the tectonic structure orientations. In particular, in Sicily the new data delineate a more complete tectonic picture evidencing adjacent areas characterized by distinct stress regime: northern offshore of Sicily and in the Hyblean plateau the alignment of horizontal stresses is consistent with the crustal motions, whereas different directions have been observed along the belt and foredeep.
Risk identification for the development of large-artery vasospasm after aneurysmatic subarachnoid hemorrhage – a multivariate, risk-, and location-adjusted prediction model

Background Vasospasm of the large cerebral arteries (CVS) after aneurysmatic subarachnoid hemorrhage (aSAH) reduces cerebral perfusion and causes delayed cerebral ischemia. Although endovascular spasmolysis shows convincing angiographic results, patients often do not improve in outcome. Delayed recognition of CVS contributes substantially to this effect. Therefore, this study aimed to confirm established and to identify unknown risk factors for CVS, which can be used for risk stratification. Methods In this monocentric, retrospective cohort study of 853 patients with aSAH, we compared demographics, clinical, and radiographic parameters at the time of aneurysm occlusion between patients who developed CVS and those who did not. Significant cohort differences were included as predictors in a multivariate analysis to address confounding. Logistic regression models were used to determine odds ratios (ORs) for the presence of CVS for each predictor. Results Of the 853 patients treated with aSAH, 304 (32%) developed CVS. In the univariable analysis, CVS was significantly associated with young age, female sex, aneurysm location, modified Fisher score, Barrow Neurological Institute (BNI) score, and surgical interventions. In the multivariable regression analysis, we identified BNI score (OR 1.33, 95% CI 1.11 to 1.58, p=0.002), decompressive craniectomy (OR 1.93, 95% CI 1.22 to 3.04, p=0.005), and aneurysm clipping (OR 2.22, 95% CI 1.50 to 3.29, p<0.001), as independent risk factors. Conclusions Young female patients with high BNI scores who undergo surgical interventions are more likely to develop CVS and should therefore be monitored most intensively after aneurysm occlusion.
Transcranial Doppler ultrasonography in bacterial meningitis: A systematic review

Bacterial meningitis remains a global threat due to its high mortality. It is estimated that >1.2 million cases of bacterial meningitis are reported annually. Intracranial vasculopathy is an important, under‐documented complication, easily detected by transcranial Doppler (TCD) ultrasonography. Following the PRISMA Guidelines, we reviewed the utility of TCD in bacterial meningitis.