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Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

Abstract Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Introduction: SARS-CoV-2 infection frequently causes neurological symptoms. Cognitive alterations are among the most frequent symptoms, and may persist beyond the acute phase of infection. Methods: We conducted a narrative review of the literature. Results: Hospitalised patients, and especially critically ill patients, are at greater risk of developing cognitive symptoms. Post–COVID-19 cognitive symptoms, unlike those associated with other viral illnesses, have been observed in patients with mild infection, and present some atypical features. Cognitive symptoms may last longer in COVID-19 than in other infectious processes, and more frequently affect young people. Post–COVID-19 cognitive symptoms share common features with those described in chronic fatigue syndrome, including a similar profile with affective symptoms. Brief screening tests for cognitive impairment present suboptimal diagnostic performance, and standardised criteria are needed to ensure correct diagnosis.Post–COVID-19 cognitive impairment can have a significant impact on the patient's quality of life and functional independence, regardless of other post–COVID-19 symptoms. Currently, no specific treatments have been approved for post–COVID-19 cognitive impairment, although cognitive stimulation may be useful in some patients. Conclusions: Post–COVID-19 cognitive symptoms are common and are often associated with other systemic symptoms. Neuropsychological evaluation may be useful for diagnosis and to quantify their severity and long-term prognosis. Detailed, and individualised assessment of cognitive impairment may enable the design of treatment plans. Resumen: Introducción: La infección por SARS-Cov2 con frecuencia causa síntomas neurológicos. Los síntomas cognitivos se encuentran entre los síntomas más frecuentes y pueden persistir más allá de la fase aguda de la infección. Metodología: Revisión narrativa de la literatura. Resultados: El riesgo de padecer síntomas cognitivos es mayor en pacientes hospitalizados, especialmente en pacientes críticos. Los síntomas cognitivos post-COVID, a diferencia de los que aparecen en otros cuadros virales, se han observado en pacientes con infección leve y presentan algunos rasgos atípicos. La duración de la sintomatología cognitiva puede ser superior a otros procesos infecciosos y afectar con mayor frecuencia a personas jóvenes. Los síntomas cognitivos post-COVID comparten rasgos comunes con los descritos en el síndrome de la fatiga crónica, incluyendo un perfil similar de síntomas afectivos asociados. Los tests rápidos de cribado de deterioro cognitivo tienen un rendimiento diagnóstico subóptimo y son necesarios criterios estandarizados para un correcto diagnóstico.El deterioro cognitivo post-COVID puede ocasionar un impacto significativo en la calidad de vida y en la autonomía funcional del paciente, de forma independiente al resto de síntomas post-COVID. En la actualidad no existen tratamientos específicos aprobados para el deterioro cognitivo post-COVID, aunque la estimulación cognitiva puede ser útil en algunos pacientes. Conclusiones: Los síntomas cognitivos post-COVID son frecuentes, y con asiduidad se asocian a otros síntomas sistémicos. Una evaluación neuropsicológica puede ser de utilidad para el diagnóstico y para cuantificar su severidad y pronóstico a largo plazo. Una caracterización detallada e individualizada del deterioro cognitivo permite establecer medidas de tratamiento.

As atmospheric carbon dioxide concentrations continue to rise and global temperatures increase, there is growing concern about the sustainability, health, and carbon sequestration potential of forest ecosystems. Variable retention harvesting (VRH) has been suggested to be a potential method to increase forest biodiversity, growth, and carbon (C) sequestration. A field trial was established in an 88-year-old red pine (Pinus resinosa Ait.) plantation in southern Ontario, Canada, using a completely randomized design to examine the response of tree productivity and other forest values to five harvesting treatments: 33% aggregate retention (33A), 55% aggregate retention (55A), 33% dispersed retention (33D), and 55% dispersed retention (55D) in comparison to an unharvested control (CN). In this study, we explored the impacts of VRH on aboveground stem radial growth and annual C increment. Standard dendrochronological methods and allometric equations were used to quantify tree- and stand-level treatment effects during a five-year pre-harvest (2009–2013) and post-harvest (2014–2018) period. Tree-level growth and C increment were increased by the dispersed retention pattern regardless of retention level. At the stand level, the total C increment was highest at greater retention levels and did not vary with retention pattern. These results suggest that the choice of retention level and pattern can have a large influence on management objectives as they relate to timber production, climate change adaptation, and/or climate change mitigation.

Hydrometeorological events have been the predominant type of natural hazards to affect communities across Canada. While climate change is a concern to all Canadians, Indigenous communities in Canada have been disproportionately more affected by these extreme climate events than non-Indigenous communities. As the impacts of climate change intensify, it becomes increasingly important that high-resolution climate services are made available to Indigenous decision makers for the development of climate change adaptation plans. This paper examined extreme climate trends in the Six Nations of the Grand River reserve, the most populated Indigenous community in Canada. A set of 12 indices were used to evaluate changes in extreme climate events from 1951 to 2013, and 2006 to 2099 under Representative Concentration Pathways (RCP) 4.5 and 8.5. Results indicated that from 1951 to 2013, Six Nations became warmer and wetter with an average temperature increase of 0.7 °C and precipitation increase of 42 mm. Over this period, the frequency and duration of extreme heat and extreme precipitation events also increased, while extreme cold events decreased. In the future (2006 to 2099), temperature is expected to increase by 3 to 6 °C, while seasonal precipitation is expected to increase in winter, early spring, and fall. Projected rate of increase of heatwaves is 0.4 to 1.5 days per year and extreme annual rainfall events is 0.2 to 0.5 mm per year under both RCP scenarios. The climate information and data provide by this study will help Six Nations’ decision makers in planning for climate change impacts.

Abstract Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p

Understanding the feedback of ecosystem carbon uptake on climate change at temporal and spatial scales is crucial for developing ecosystem models. Previous studies have focused on the role of spring and autumn phenology in regulating carbon sequestration in forest stands, but few on the impact of physiological status in summer. However, plant accumulated the most carbon in summer compared with spring and autumn, therefore, it is of great significance to explore the role of summer phenological metrics on the variability of carbon sequestration. Using 514 site-years of flux data obtained at 40 FLUXNET sites including three forest ecosystems (i.e. evergreen needleleaf forest (ENF), deciduous broadleaf forest (DBF) and mixed forest (MF)) in Europe and North America, we compared the potential of physiological and phenological metrics of Gross Primary Production (GPP) and Ecosystem Respiration (RECO) in explaining the interannual and spatial variability (IAV and SV) of forest net ecosystem production (NEP). In view of the better performance of physiological metrics, we developed the maximum carbon uptake index (MCUI), which integrated the physiology metrics of photosynthesis and respiration in summer, and further explored its ability in explaining the IAV and SV of NEP. The results suggest that the MCUI had a better ability than respiration-growth length ratio (RGR) in predicting NEP for all three forest types. The interpretation of MCUI based on meteorological variables illustrated that the controlling meteorological factors of MCUI differed substantially among ecosystems. The summer shortwave radiation had the greatest influence on MCUI at DBF sites, while the soil water content played an important but opposite role at ENF and DBF sites, and no significant meteorological driver was found at MF sites. The higher potential of MCUI in explaining IAV and SV of NEP highlights the importance of summer physiology in controlling the forest carbon sequestration, and further confirms the significant role of peak plant growth in regulating carbon cycle of forest ecosystems. Understanding the drivers of peak plant growth is therefore of a great significance for further improving the precious of ecosystem model in the future.

Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.

Solar activity modulates cosmic ray (CR) particles with different magnitudes on different time scales. CR modulations have been studied using ground-based detectors, primarily neutron monitors, distributed around the world. In 2002, CR research began in Saudi Arabia with the installation of the first CR detector at the King Abdulaziz City for Science and Technology (KACST) in Riyadh (lat. 24 43; long. 46 40; Rc ~ 14.4 Gv), the capital of Saudi Arabia. The facility is located in the central Arabian Peninsula. Because of its high cutoff rigidity, the site is ideal for monitoring CR variations and is of great significance to the research community.Different CR detectors employing various measuring techniques have been developed and installed, at this site, to record the intensity of cosmic rays on different time scales and assess their correlation with atmospheric and climatic parameters. They include scintillator detectors, single-channel and rotatable telescopes, multi-wire detectors, CARPET detectors, small mobile detector, and mini-neutron monitors. In this paper, we briefly describe these detectors and offer observations on their use in CR research.

Study region: Hudson Bay Lowlands watersheds, Ontario, Canada. Study Focus: The rivers in the Hudson Bay Lowlands are a major source of freshwater entering the Arctic Ocean and they also cause major floods. In recent decades, this region has been affected by major changes in hydroclimatic processes attributed to climate change and natural climate variability. In this study, we used ERA5 reanalysis data, hydrometric observations, and the hydrological model MESH, to investigate the impact of atmospheric circulation on the inter-decadal variability of streamflow between 1979 and 2018 in the Hudson Bay Lowlands. The natural climate variability was assessed using a weather regimes approach based on the discretization of daily geopotential height anomalies (Z500) from ERA5 reanalysis, as well as large scale oceanic and atmospheric variability modes. New hydrological insights: The results showed an anomalous convergence of atmospheric moisture flux between 1995–2008 that enhanced precipitation and increased streamflow in the western part of the region. This moisture convergence was likely driven by the combination of (i) low pressure anomalies in the East Coast of North America and (ii) low pressure anomalies in western regions of Canada, associated with the cold phase of the pacific decadal oscillation (PDO). Since 2009, streamflow remains high, likely due to more groundwater discharge associated with the degradation of permafrost.

Photosynthetic light use efficiency (LUE) determines the ability of a plant to assimilate atmospheric carbon dioxide to biomass and is known to be controlled by environmental conditions, light regimes and forest age. The photochemical reflectance index (PRI), derived from leaf or canopy remotely sensed spectra, has been shown to be an effective and accurate estimator of LUE. In this study, we propose a new LUE estimation method that separates the PRI into daily maximal PRI (PRI0) for indicating daily maximal light use efficiency (LUEmax) and ΔPRI, defined as the difference between PRI0 and instantaneous PRI, for estimating the diurnal physiological stress (fstress). We develop and apply the method across three temperate pine stands and a deciduous stand of different ages, in Southern Ontario, Canada. Half hourly canopy level spectra were acquired from a tower-based spectro-radiometer system (AMSPEC-III) over the growing season at the four stands. Results show that the PRI0 predicted well LUEmax (R2 > 0.6, p

Abstract Pakistan is the country with mega freshwater fish diversity of native and alien species. In the presence of enormous native fishes varies species of exotic fishes have been introduced into the freshwater bodies of Pakistan which are competing with native freshwater fish fauna and making them deprive of food and habitat as well. Intentional or accidental introductions of animals, plants and pathogens away from their native niche is considered as major leading problem for biodiversity of invaded habitat. Three years study (from January 2017 to December 2019) was conducted in freshwater bodies of Province Punjab, Pakistan. Study was designed to know exotic species impacts on the distribution of native species of fishes. During current survey a total of 68 (indigenous and exotic) fish species belonging to 14 families were recorded from head Qadirabad, head Baloki, Islam headworks and Rasul barrage. Statistical analysis showed that Shannon-Wiener diversity index was the highest (1.41) at both Rasul barrage and Islam headworks but, invasive species were present in very less number in these study sites i.e. Oreochromis mozambicus, O. niloticus, Hypophthalmichthys nobilis, Carassius auratus, Ctenophryngdon idella, Cyprinus carpio and H. molitrix. The diversity index showed that comparatively low diversity was present in both area head Qadirabad (1.30) and head Baloki (1.4) due to high pressure of invasive species. Direct observation of species and statistical analysis showed that aliens’ species produced negative impact on the local fish fauna diversity, evenness, and numbers. It is concluded that many factors are impacts on the diversity of native fishes, but alien (invasive) species also play a major role to reduction of native species, because aliens’ species produce competition for native species. So it is urgent need to analysis the aliens and native food web and roosting sites in Pakistan, in future.

Abstract: γδT cells are key players in cancer immune surveillance because of their ability to recognize malignant transformed cells, which makes them promising therapeutic tools in the treatment of cancer. However, the biological mechanisms of how γδT-cell receptors (TCRs) interact with their ligands are poorly understood. Within this context, we describe the novel allo-HLA–restricted and CD8α-dependent Vγ5Vδ1TCR. In contrast to the previous assumption of the general allo-HLA reactivity of a minor fraction of γδTCRs, we show that classic anti-HLA–directed, γδTCR-mediated reactivity can selectively act on hematological and solid tumor cells, while not harming healthy tissues in vitro and in vivo. We identified the molecular interface with proximity to the peptide-binding groove of HLA-A*24:02 as the essential determinant for recognition and describe the critical role of CD8 as a coreceptor. We conclude that alloreactive γδT-cell repertoires provide therapeutic opportunities, either within the context of haplotransplantation or as individual γδTCRs for genetic engineering of tumor-reactive T cells.

A global warming hiatus occurred during 1998 and 2012 but its effects on phenology are unclear. Here the authors examine the trends in spring and autumn phenology in the northern hemisphere and the effects of the warming hiatus and show that phenology change rate in the northern hemisphere slowed down during the warming hiatus.

Abstract We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics.

The present systematic research on cultural, morphological, and pathogenic variability was carried out on eighty isolates of Sclerotinia sclerotiorum collected from major common bean production belts of North Kashmir. The isolates were found to vary in both cultural and morphological characteristics such as colony color and type, colony diameter, number of days for sclerotia initiation, sclerotia number per plate, sclerotial weight, and size. The colony color ranged between white and off-white with the majority. The colony was of three types, in majority smooth, some fluffy, and a few fluffy-at-center-only. Colony diameter ranged between 15.33 mm and 29 mm after 24 h of incubation. The isolates took 4 to 7 days for initiation of sclerotia and varied in size, weight, and number per plate ranging between 14 and 51.3. The sclerotial arrangement pattern on plates was peripheral, sub peripheral, peripheral, and subperipheral, arranged at the rim and scattered. A total of 22 Mycelial compatibility groups (MCGs) were formed with seven groups constituted by a single isolate. The isolates within MCGs were mostly at par with each other. The six isolates representing six MCGs showed variability in pathogenicity with isolate G04 as the most and B01 as the least virulent. The colony diameter and disease scores were positively correlated. Sclerotia were observed to germinate both myceliogenically and carpogenically under natural temperate conditions of Kashmir. Germplasm screening revealed a single resistant line and eleven partially resistant lines against most virulent isolates.

Introduction Despite innovative treatments, the impairment in real-life functioning in subjects with schizophrenia (SCZ) remains an unmet need in the care of these patients. Recently, real-life functioning in SCZ was associated with abnormalities in different electrophysiological indices. It is still not clear whether this relationship is mediated by other variables, and how the combination of different EEG abnormalities influences the complex outcome of schizophrenia. Objectives The purpose of the study was to find EEG patterns which can predict the outcome of schizophrenia and identify recovered patients. Methods Illness-related and functioning-related variables were measured in 61 SCZ at baseline and after four-years follow-up. EEGs were recorded at the baseline in resting-state condition and during two auditory tasks. We performed Sparse Partial Least Square (SPLS) Regression, using EEG features, age and illness duration to predict clinical and functional features at baseline and follow up. Through a Linear Support Vector Machine (Linear SVM) we used electrophysiological and clinical scores derived from SPLS regression, in order to classify recovered patients at follow-up. Results We found one significant latent variable (p

Introduction Different electrophysiological indices have been investigated to identify diagnostic and prognostic markers of schizophrenia (SCZ). However, these indices have limited use in clinical practice, since both specificity and association with illness outcome remain unclear. In recent years, machine learning techniques, through the combination of multidimensional data, have been used to better characterize SCZ and to predict illness course. Objectives The aim of the present study is to identify multimodal electrophysiological biomarkers that could be used in clinical practice in order to improve precision in diagnosis and prognosis of SCZ. Methods Illness-related and functioning-related variables were measured at baseline in 113 subjects with SCZ and 57 healthy controls (HC), and after four-year follow-up in 61 SCZ. EEGs were recorded at baseline in resting-state condition and during two auditory tasks (MMN-P3a and N100-P3b). Through a Linear Support Vector Machine, using EEG data as predictors, four models were generated in order to classify SCZ and HC. Then, we combined unimodal classifiers’ scores through a stacking procedure. Pearson’s correlations between classifiers score with illness-related and functioning-related variables, at baseline and follow-up, were performed. Results Each EEG model produced significant classification (p < 0.05). Global classifier discriminated SCZ from HC with accuracy of 75.4% (p < 0.01). A significant correlation (r=0.40, p=0.002) between the global classifier scores with negative symptoms at follow-up was found. Within negative symptoms, blunted affect showed the strongest correlation. Conclusions Abnormalities in electrophysiological indices might be considered trait markers of schizophrenia. Our results suggest that multimodal electrophysiological markers might have prognostic value for negative symptoms.