The information on the projected climate changes over China is of great importance for preparing the nation’s societal adaptiveness to the future natural ecosystem. This study reports the surface ...mean temperature changes during 2014–2100 over China and its four sub-regions (Northern China, Northwestern China, Southern China, and the Tibetan Plateau) by analyzing 20 models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) under three Shared Socio-economic Pathway (SSP) scenarios: SSP126, SSP245 and SSP585. The multi-model ensemble mean (MMEM) of 20 CMIP6 models has cold biases over China during 1979–2014, with improved performance compared with the CMIP5 models. In contrast, the CMIP6 models simulate well in the spatial climatology with lower warming rates over China. Relative to 1986–2005, the regionally averaged surface mean temperatures from the MMEM over China under SSP126, SSP245, SSP585 scenarios are projected to increase by 1.31 °C, 1.32 °C, 1.45 °C in the near-term (2021–2040), 1.75 °C, 2.06 °C, 2.66 °C in the mid-term (2041–2060), and 1.08 °C, 2.97 °C, 5.62 °C in the long-term (2081–2100), respectively. The CMIP6 models simulate accelerated warming occurs over the Northwestern China and the Tibetan Plateau, suggesting that the arid and semi-arid regions are particularly sensitive to future climate warming. We quantify uncertainty for future projections of temperature changes over China, and the main sources of uncertainty are model and scenario uncertainty particularly for the regions with the largest cold bias. This suggests that the observational constraints on these regions will lead to significant improvements for climatic projections over China.
When multiple influential covariates need to be balanced during a clinical trial, stratified blocked randomization and covariate-adaptive randomization procedures are frequently used in trials to ...prevent bias and enhance the validity of data analysis results. The latter approach is increasingly used in practice for a study with multiple covariates and limited sample sizes. Among a group of these approaches, the covariate-adaptive procedures proposed by Pocock and Simon are straightforward to be utilized in practice. We aim to investigate the optimal design parameters for the patient treatment assignment probability of their developed three methods. In addition, we seek to answer the question related to the randomization performance when additional covariates are added to the existing randomization procedure. We conducted extensive simulation studies to address these practically important questions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types
. Intratumoral host-microbiota studies have so far largely relied on bulk tissue ...analysis
, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies
and single-cell RNA sequencing
to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling
, we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion-adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.
Species that propagate by sexual reproduction actively guard against the fertilization of an egg by multiple sperm (polyspermy). Flowering plants rely on pollen tubes to transport their immotile ...sperm to fertilize the female gametophytes inside ovules. In Arabidopsis, pollen tubes are guided by cysteine-rich chemoattractants to target the female gametophyte
. The FERONIA receptor kinase has a dual role in ensuring sperm delivery and blocking polyspermy
. It has previously been reported that FERONIA generates a female gametophyte environment that is required for sperm release
. Here we show that FERONIA controls several functionally linked conditions to prevent the penetration of female gametophytes by multiple pollen tubes in Arabidopsis. We demonstrate that FERONIA is crucial for maintaining de-esterified pectin at the filiform apparatus, a region of the cell wall at the entrance to the female gametophyte. Pollen tube arrival at the ovule triggers the accumulation of nitric oxide at the filiform apparatus in a process that is dependent on FERONIA and mediated by de-esterified pectin. Nitric oxide nitrosates both precursor and mature forms of the chemoattractant LURE1
, respectively blocking its secretion and interaction with its receptor, to suppress pollen tube attraction. Our results elucidate a mechanism controlled by FERONIA in which the arrival of the first pollen tube alters ovular conditions to disengage pollen tube attraction and prevent the approach and penetration of the female gametophyte by late-arriving pollen tubes, thus averting polyspermy.
Conducting secure computations to protect against malicious adversaries is an emerging field of research. Current models designed for malicious security typically necessitate the involvement of two ...or more servers in an honest-majority setting. Among privacy-preserving data mining techniques, significant attention has been focused on the classification problem. Logistic regression emerges as a well-established classification model, renowned for its impressive performance. We introduce a novel matrix encryption method to build a maliciously secure logistic model. Our scheme involves only a single semi-honest server and is resilient to malicious data providers that may deviate arbitrarily from the scheme. The d-transformation ensures that our scheme achieves indistinguishability (i.e., no adversary can determine, in polynomial time, which of the plaintexts corresponds to a given ciphertext in a chosen-plaintext attack). Malicious activities of data providers can be detected in the verification stage. A lossy compression method is implemented to minimize communication costs while preserving negligible degradation in accuracy. Experiments illustrate that our scheme is highly efficient to analyze large-scale datasets and achieves accuracy similar to non-private models. The proposed scheme outperforms other maliciously secure frameworks in terms of computation and communication costs.
Lithium (Li) metal has been extensively investigated as an anode for rechargeable battery applications due to its ultrahigh theoretical specific capacity and the lowest redox potential. However, ...significant challenges including dendrite growth and low Coulombic efficiency are still hindering the practical applications of rechargeable Li metal batteries. It is demonstrated that long‐term cycling of Li metal batteries can be realized by the formation of a transient high‐concentration electrolyte layer near the surface of Li metal anode during high rate discharge process. The highly concentrated Li+ ions in this transient layer will immediately be solvated by the available solvent molecules and facilitate the formation of a stable and flexible solid electrolyte interphase (SEI) layer composed of a poly(ethylene carbonate) framework integrated with other organic/inorganic lithium salts. This SEI layer largely suppresses the corrosion of Li metal anode attacked by free organic solvents and enables the long‐term operation of Li metal batteries. The fundamental findings in this work provide a new direction for the development of Li metal batteries that could be operated at high current densities for a wide range of applications.
A transient layer of highly concentrated electrolyte can be formed in the vicinity of a Li metal anode by fast lithium stripping or high C‐rate discharge. The highly concentrated Li+ ions in this transient layer immediately coordinate with the available solvents and facilitate the formation of a highly flexible and stable solid electrolyte interphase (SEI) layer on the Li surface, effectively mitigating the Li corrosion by free organic solvents and enabling the sustainable operation of Li metal batteries.
Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly ...understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.
•SF3B1 mutation causes alternative splicing in cell lines and primary CLL cells•SF3B1 mutation-associated splice variants are enriched for 3′ splice sites•SF3B1 mutation induces RNA changes affecting multiple CLL-associated pathways•SF3B1 mutation modulates Notch signaling through an RNA splice variant of DVL2
Wang et al. perform transcriptomic characterization of bulk or single primary human chronic lymphocytic leukemia cells harboring SF3B1 mutations, identifying several dysregulated cancer-related pathways resulting from altered expression of KLF8, TERC, or TERT or altered splicing of DVL2 mRNA.
Background/Objectives
Dementia‐related behavioral symptoms and functional dependence result in poor quality of life for persons with dementia and their caregivers. The goal was to determine whether a ...home‐based activity program (Tailored Activity Program; TAP‐VA) would reduce behavioral symptoms and functional dependence of veterans with dementia and caregiver burden.
Design
Single‐blind (interviewer), parallel, randomized, controlled trial (Clinicaltrials.gov: NCT01357564).
Setting
Veteran's homes.
Participants
Veterans with dementia and their family caregivers (N = 160 dyads).
Intervention
Dyads in TAP‐VA underwent 8 sessions with occupational therapists to customize activities to the interests and abilities of the veterans and educate their caregivers about dementia and use of customized activity. Caregivers assigned to attention control received up to 8 telephone‐based dementia education sessions with a research team member.
Measurements
Primary outcomes included number of behaviors and frequency of their occurrence multiplied by severity of occurrence; secondary outcomes were functional dependence, pain, emotional well‐being, caregiver burden (time spent caregiving, upset with behaviors) and affect at 4 (primary endpoint) and 8 months.
Results
Of 160 dyads (n = 76 TAP‐VA; n = 84 control), 111 completed 4‐month interviews (n = 51 TAP‐VA; n = 60 control), and 103 completed 8‐month interviews (n = 50 TAP‐VA; n = 53 control). At 4 months, compared to controls, the TAP‐VA group showed reductions in number (difference in mean change from baseline = −0.68, 95% CI = −1.23 to −0.13) and frequency by severity (−24.3, 95% CI = −45.6 to −3.1) of behavioral symptoms, number of activities needing assistance with (−0.80, 95% CI = −1.41 to −0.20), functional dependence level (4.09, 95% CI = 1.06, 7.13), and pain (−1.18, 95% CI = −2.10 to −0.26). Caregivers of veterans in TAP‐VA reported less behavior‐related distress. Benefits did not extend to 8 months.
Conclusion
TAP‐VA had positive immediate effects and no adverse events. Because TAP‐VA reduces behavioral symptoms, slows functional dependence, and alleviates pain and caregiver distress, it is a viable treatment option for families.
In this randomized trial of two physical therapy interventions for patients with walking impairment after stroke, locomotor training on a treadmill including body-weight support was not superior to a ...home-exercise program supervised by a physical therapist.
More than 790,000 Americans have a new or recurrent stroke yearly,
1
and two thirds of the 6.4 million survivors may have significant limitations in walking
2
and are at high risk for falls,
3
fractures,
4
and further decline in mobility.
5
Walking speed predicts the level of disability. At a walking speed of more than 0.8 m per second, full mobility in the community is likely; at a walking speed of less than 0.4 m per second, mobility is limited to the home; and at speeds of 0.4 to 0.8 m per second, mobility is limited to short walks in the community.
6
Improving . . .
Gait velocity is a powerful indicator of function and prognosis after stroke. Gait velocity can be stratified into clinically meaningful functional ambulation classes, such as household ambulation ...(<0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (>0.8 m/s). The purpose of the current study was to determine whether changes in velocity-based community ambulation classification were related to clinically meaningful changes in stroke-related function and quality of life.
In subacute stroke survivors with mild to moderate deficits who participated in a randomized clinical trial of stroke rehabilitation and had a baseline gait velocity of 0.8 m/s or less, we assessed the effect of success versus failure to achieve a transition to the next class on function and quality of life according to domains of the Stroke Impact Scale (SIS).
Of 64 eligible participants, 19 were initially household ambulators, and 12 of them (68%) transitioned to limited community ambulation, whereas of 45 initially limited community ambulators, 17 (38%) became full community ambulators. Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not. Among household ambulators, those who transitioned to limited or full community ambulation had significantly better SIS scores in mobility (P=0.0299) and participation (P=0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (P=0.0085).
A gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators. Household ambulators possibly had more severe stroke deficits, reducing the risk of "ceiling" effects in SIS-measured activities of daily living and instrumental activities of daily living. Outcome assessment based on transitions within a mobility classification scheme that is rooted in gait velocity yields potentially meaningful indicators of clinical benefit. Outcomes should be selected that are clinically meaningful for all levels of severity.
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