Single Event Research Articles

Can agronomic options alleviate the risk of compound drought-heat events during the wheat flowering period in southeastern Australia?

The impacts of compound drought-heat (DH) events on crops are more devastating than a single extreme event of drought or heat. Previous studies mainly assessed the change of individual extreme climate events. However, studies quantifying the characteristics of DH events during crop growth periods are still lacking. To the best of our knowledge, there is no study that has quantified the potential of adjusting sowing time and changing cultivars to reduce the risk of DH events for wheat in Australia. We aimed to (1) develop a combined index to capture the DH events occurring during the wheat flowering period at six study sites in southeastern Australia’s wheat belt; (2) quantify the changes in the frequency (DHF), duration (DHD), and intensity (DHI) of DH events under future climate; and (3) identify feasible agronomic options to reduce the risk of DH events. We used the APSIM model driven by climate projections from 27 GCMs for the period of 1981–2100 to simulate the wheat flowering time and daily plant available water (PAW) at 0–100 cm soil layer. The wheat sensitive period (WSP) was defined as the period from 2 weeks before flowering to 2 weeks after flowering time. A DH event occurs when the daily maximum temperature is higher than 28 ℃ and daily PAW is less than 40% of plant available water capacity for three consecutive days or more. Then, we assessed the DHF, DHD, and DHI under projected climate change. Finally, we investigated the potential of changing sowing time and cultivars to alleviate DHF, DHD, and DHI under different climate scenarios. According to the average values across six sites, the DHF, DHD, and DHI during the WSP increased by 15%, 12%, and 0.9% in 2040 s, and 49%, 44%, and 5% in 2080 s, respectively, compared to 2000 s. Such increases in DH events were mainly due to enhanced heat events. Early sowing and planting better-performing wheat cultivars with early flowering had great potential to lower the risk of future DH events. They could reduce the DHF, DHD, and DHI by 15%− 100%, 18%− 100%, and 16%− 100%, respectively, compared to without adaptation options. However, the strategy may introduce an increased frost risk across six sites, especially in regions with climates that are less dry and hot, such as Mudgee and Wagga Wagga. We expect our modelling work can provide useful information for developing effective agronomic management practices to help Australian wheat growers better prepare for DH events under climate change. The newly proposed DH framework can be applied to other dryland wheat growing regions globally.

Pilot study on evaluation indices for aircraft noise considering sound quality

In Japan, Lden is currently used as an evaluation index for aircraft noise. It is based on the A-weighted sound pressure. It evaluates differences in noise loudness, but it does not necessarily take into account differences due to changes in sound quality. Over the past several decades, single event of aircraft noise has been significantly reduced. As a result, we have experienced a change from the "noisy" sound quality of the old generation jets to the "soft" sound quality of the recent aircrafts. Has the sound quality really improved, and has its improvement been evaluated? On the other hand, since the 2000's, we have sometimes experienced hearing the extraordinary tonal sounds from landing aircraft. It has the characteristics of pure tonal tone with 250-500 Hz and has a short duration and a prominent level fluctuation. Doessuch a sudden tonality change, which is also negatively perceived, not affect the evaluation? This paper describes the results of trial calculation in order to examine the possibility of evaluating aircraft noise considering its sound quality, based on several indices such as EPNL, loudness, sharpness, and Tonal Audibility (TA), in addition to the A-weighted noise (LAmax, LEA), and its comparative verification including differences in aircraft generations.

구술 증언에 재현된 대전 ‘골령골’과 한국전쟁 지도의 필요성

This study attempts to examine the reality of the Korean War Appearing in the Daejeon region based on the oral experiences of the generation that experienced the Korean War. In particular, by paying attention to 'Golryeonggol-valley' in the Daejeon region, through the meaning and imaginative geographies contained in a specific place that is narrated and reproduced through memory, this study explores the necessity and possibilities of Korean War topographic maps.
 Common elements of war experience stories that appear in oral narratives are as follows: 1) While you were studying, eating, or working at school, you suddenly heard that there was a war and that you had to evacuate, and you had to evacuate. 2) The North Korean People's Army that came first was not bad, and actually did well for the civilians. 3) Later, the North Korean People's Army ordered people to cook in private homes and plundered all household items and food, including all kinds of food and livestock. 4) That the North Korean People's Army brutally massacred soldiers' families, police families, village heads, district heads, etc. 5) Like farmhand laborers, people who suffered sadness in the neighborhood, walked around wearing red armbands, tyrannized the people in the neighborhood by telling them who in the neighborhood were family members of soldiers or police officers, or who served as village heads or district heads. 6) In Daejeon, they heard that the military and police killed many civilians. In particular, the well massacre of Daejeon Prison and the civilian massacre of Golryeonggol-valley (Sannae) related to the Bodo League are mentioned most heavily.
 The Korean War is not the same in all regions. Not describing the war situation uniformly can be said to be an effective approach in that it does not 'only' attribute the war to a single event. That is the reason the works of 'recording' the stories of people who directly experienced the Korean War through oral records, and reproducing and talking about the 'truth' of it through literary imagination are more necessary.

Generation of de novo miRNAs from template switching during DNA replication.

The mechanisms generating novel genes and genetic information are poorly known, even for microRNA (miRNA) genes with an extremely constrained design. All miRNA primary transcripts need to fold into a stem-loop structure to yield short gene products ([Formula: see text]22 nt) that bind and repress their mRNA targets. While a substantial number of miRNA genes are ancient and highly conserved, short secondary structures coding for entirely novel miRNA genes have been shown to emerge in a lineage-specific manner. Template switching is a DNA-replication-related mutation mechanism that can introduce complex changes and generate perfect base pairing for entire hairpin structures in a single event. Here, we show that the template-switching mutations (TSMs) have participated in the emergence of over 6,000 suitable hairpin structures in the primate lineage to yield at least 18 new human miRNA genes, that is 26% of the miRNAs inferred to have arisen since the origin of primates. While the mechanism appears random, the TSM-generated miRNAs are enriched in introns where they can be expressed with their host genes. The high frequency of TSM events provides raw material for evolution. Being orders of magnitude faster than other mechanisms proposed for de novo creation of genes, TSM-generated miRNAs enable near-instant rewiring of genetic information and rapid adaptation to changing environments.

Occupational injuries in workers of a Spanish bank.

In 2017, 69 108 work-related traffic injuries with medical leave were documented, constituting 12% of all occupational injuries (OI) in Spain. The aim of this study was to describe OI within a Spanish bank company during 2017. A cross-sectional analysis was conducted using the company's mandatory OI records, presenting data in both absolute (n) and relative (%) frequencies. The chi-square test was employed for comparisons. Among the company's 10 399 employees, 176 OI cases were recorded. Most were minor musculoskeletal incidents, with one severe myocardial infarction and one mild anxiety episode. Lower limb injuries were the most prevalent. Injuries of the trunk (P < 0.001), neck (P < 0.05), and upper limbs (P < 0.001) were linked to workplace factors. Approximately 62% of OI occurred outside the workplace and resulted in more extended medical leave (P < 0.01). Traffic-related injuries accounted for 39% of OI cases and caused 49% of days lost due to OI (P < 0.001).Female gender (P < 0.001) and age over 40 years (P < 0.05) were significantly associated with OI. In our study, musculoskeletal injuries were the most common, with a single cardiovascular event being the most severe. OI occurring outside the workplace was more frequent and led to longer medical leaves. Notably, traffic-related injuries were especially significant, exceeding official statistics 4-fold.

Health Care Resource Utilization (HCRU) and Cost of Management of Cytokine Release Syndrome (CRS) and Neurological Events (NEs) in Patients with R/R Follicular Lymphoma (FL) Receiving Lisocabtagene Maraleucel (liso-cel) in the TRANSCEND FL Study

Background: Adverse events (AEs) such as CRS and NEs of varying severity have been associated with CAR T cell therapies, including liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. Liso-cel has previously demonstrated clinically meaningful responses in patients with R/R FL in the phase 2 TRANSCEND FL study (NCT04245839). In addition, previous research among patients with large B-cell lymphoma has suggested an acceptable safety profile with few grade ≥ 3 CRS/NEs, and safety data from TRANSCEND FL are in line with this larger dataset. However, there is limited to no research published on estimates of HCRU and costs related to the management of CRS/NEs among liso-cel-treated patients with FL. This analysis evaluated HCRU and estimated costs of managing CRS/NEs by grade and concurrency for patients with R/R FL who received liso-cel treatment in the TRANSCEND FL study. Methods: Retrospective analyses were conducted for liso-cel-treated patients with R/R FL (second line or later) who experienced CRS/NEs within 90 days after infusion using patient-level HCRU data from the TRANSCEND FL study databases. HCRU captured included facility (standard inpatient [IP] and ICU hospitalizations), length of stay (LOS), diagnostics (eg, laboratory and imaging), procedures (eg, dialysis and mechanical ventilation), and medications (eg, oncology supportive care, prophylactics, and other AE management). Costs of managing CRS/NEs were estimated using a microcosting methodology in which 1) HCRU from the time of AE onset through resolution was identified and 2) the most recently available unit costs sourced from public databases or literature (US Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, and IBM ® Micromedex ® RED BOOK ®) were applied to each HCRU and adjusted to 2023 US dollars using the Consumer Price Index. Analyses were stratified by AE grade and concurrency of events (CRS or NEs only, nonconcurrent CRS and NEs, and concurrent CRS and NEs). Patients with nonconcurrent and concurrent CRS/NEs were categorized by the highest-grade event experienced. Results: CRS only occurred in 59/130 (45%) patients, NEs only occurred in 4/130 (3%), and CRS and/or NEs occurred in 79/130 (61%). Of the 79 patients who experienced CRS and/or NEs, 75 (95%) were grade ≤ 2 and 4 (5%) were grade 3; no grade 4 or 5 CRS/NEs were observed. Most CRS/NEs were experienced as a single event (63/79 [80%]). Patients who experienced CRS and/or NEs had a median (range) age of 60 (23‒78) years and were predominantly male (51/79 [65%]). Estimated median management costs ranged from $20,306 (grade 1 CRS only) to $50,400 (grade 3 CRS or NEs; Figure). The largest contributor to median management costs across CRS/NE categories was facility HCRU. Key HCRU and total LOS (standard IP hospitalization and ICU stay days among hospitalized patients) are shown in the Table. Almost all patients (78/79 [99%]) had a standard IP hospitalization, and only 1 patient (1%) with a grade 3 CRS only event was admitted to the ICU. Median (range) total LOS for IP/ICU admission was 1.5 days longer among patients with grade 3 versus grade ≤ 2 CRS and/or NEs (5.5 [3‒8] days vs 4 [1‒14] days). Although there were very few grade 3 events (n = 4) to assess, patients with grade 3 versus grade ≤ 2 CRS and/or NEs also had higher rates of utilization for some medications (eg, tocilizumab: 3/4 [75%] vs 28/75 [37%]; corticosteroids: 4/4 [100%] vs 19/75 [25%]). Conclusions: While most patients with R/R FL treated with liso-cel in the TRANSCEND FL study experienced treatment-emergent CRS and/or NEs, they were almost all of low severity (grade ≤ 2) and experienced as single events. Management costs for CRS/NEs, primarily related to facility HCRU, increased with greater AE severity and concurrency. The additional median cost for a patient with grade 3 versus grade ≤ 2 CRS or NEs was $22,586, representing an 88% increase in cost; however, this finding must be considered in the context of the small number of overall grade 3 events (n = 4) and ICU admissions (n = 1). CAR T cell therapies with few associated higher severity AEs provide a potential option to optimize resource use and costs for the management of CRS/NEs in patients with FL.

Total ionizing dose and single event effect response of 22 nm ultra-thin body and buried oxide fully depleted silicon-on-insulator technology

The test chip including transistors and Static Random Access Memory (SRAM) is proposed and fabricated by an advanced 22 nm Ultra-Thin Body and Buried Oxide Fully Depleted Silicon-on-Insulator (UTBB FD-SOI) technology. Experimental results of Co-60 irradiation and heavy ion experiments are presented. Total Ionizing Dose (TID) experiment results show that the threshold voltage shift of the transistor is about 100 mV when the dose is 500 krad(Si) and the SRAM irradiated to a dose of at least 300 krad(Si) can maintain its functionality, which means that 22 nm UTBB FD-SOI devices exhibit significantly improved total dose tolerance performance compared to the previous generation process. TID-induced threshold voltage shift in conventional-well nMOSFET can be mitigated by applying biasing to back-gate, while back-gate biasing is invalid for TID mitigation of the conventional-well pMOSFET. Heavy ion experimental results make known that 22 nm UTBB FD-SOI technology has contributions to Single Event Effect (SEE) hardness and the hardened SRAM has higher single event upset (SEU) tolerance and even SEU immunity. The research indicates that the circuits manufactured by 22 nm UTBB FD-SOI technology have great potential space applications in harsh radiation environments.

Chromoanagenesis in Haematological Malignancy: Review of Samples from Patients with Acute Leukemia and MDS

Background: Complex chromosome rearrangements (CCRs) include a variety of structural aberrations grouped as chromothripsis, chromoanasynthesis and chromoplexy. Although the underlying mechanisms for these phenomena are unknown and likely to be different, they appear to originate from a single event. While chromothripsis and chromoanasynthesis affect limited genome sites their role and genome associations in haematological malignancy remain to be elucidated. Aims: This study aimed to provide clarity on the location, incidence and association with TP53 gene profile of chromothripsis (cth) and chromoanasynthesis (cha) events in MDS/AML. Methods: We analysed data from routine investigations carried out by haematological malignancy diagnostic service (HMDS) at University College London Hospital (UCLH) on 2,506 samples of acute myeloid leukaemia (AML) and myelodysplasia (MDS), including G-banding, FISH (Cytocell), chromosome microarray analysis (CMA, Agilent) and target NGS(Illumina). Analysis of 87 samples with complex bone marrow karyotypes were reported following the ISCN 2020 as: (i) cth(alternating disomy and heterozygous loss along a chromosome or chromosomal segment) or (ii) cha (deletions and one or two copy number gains in a single chromosome or chromosome region including copy number variants without the clustered breakpoints of chromothripsis). Statistical analysis used RStudio (v 1.4.1106) to carry Pearson's chi-squared (χ²) and Fisher's exact (2-sided) tests. Results: Complex karyotypes harbouring cth and cha type aberrations were detected in 65 out of 727 AML and 22 out of 1779 MDS samples. The cth events were seen alongside cha in 67% of cases, rarely presenting as a sole abnormality (2%), while cha alone was found in 31% of samples. Most frequently cth was mapped at chromosome 21 (17%), chromosome 7 (15%), chromosome 17 and 19 (13%) and chromosome 5 (11%) (Fig.1a). In this cohort of 87cases, chromothripsis was found to be associated with TP53 deletions ( TP53Del/WT) in 7 (7%) and with TP53 mutations ( TP53Dpl/mut) in 22 (25%), while concurrent TP53 deletions and mutations ( TP53Del/mut) were detected in 29 (33%) ( p = 0.0005). Samples with TP53Del/mut harboured cth in chromosomes 7 (7%), 17 (6%), 8, 9, 19 and 21 (5%) whilst cases with TP53Dpl/mut had cth in chromosomes 21 (9%), 19 (8%), 5 (7%) and 7 (5%). (Fig 1 b). The cha aberrations generally followed the genome location of cth events with some exception. Firstly, chromosomes X,13 and 21 appear to have only cth and is seen at slightly higher level on chromosome 19 (cth 13% vs cha 9%). Secondly, cha was most frequently seen on 5q (61 %), chromosome 17 (40%) and 7q (34%). However, the same chromosomes also had the greatest number of cases presenting with concurrent cth and cha, seen in 63/87 (72%) for chromosome 5, 46/87 (53%) for chromosome 17 and 43/87 (49%) for chromosome 7. Importantly, only cases harbouring 5q deletions showed a statistically significant association with TP53 status ( p = 0.0011) in this cohort irrespective of cth and cha presence. Notably, 24/29 cases (83%) with TP53Del/mut were cth positive and had 5q31 deletion. This finding is an important observation but not in keeping with reports of exclusive association of TP53 mutations with concurrent 5q and 7q loss (1, 2 and 3). The concurrent recording of cth and cha performed by this study could explain the discrepancy, most likely due to high frequency of cha events in 5q. Summary This study highlights issues pertinent to risk stratification in routine diagnostic settings: (i) MDS/AML cases with complex genome harbouring either or both cth and cha share common TP53 aberrations (del/mut) and (ii) deletion of 5q31 is positively associated with TP53 aberrations and presence of cth events. (iii) CMA offers a comprehensive, sensitive, fast and financially superior way to detect cth, cha events along with genome complexity compared to G banding complemented by FISH. Overall, combining CMA and TP53 mutation screening offers a fast, reliable way to detect high risk disease in MDS/AML. Keywords: Complex genome, CMA, chromothripsis, TP53 mutations

Complement Activation Is Increased in Antiphospholipid Syndrome-Related Ischemic Stroke with Higher Risk Features

Introduction: Antiphospholipid syndrome (APS) patients with arterial thrombosis, mostly ischemic stroke, have concerningly high rates of recurrent thrombosis despite antithrombotic treatment, with over 20% thrombosis recurrence within two years. Complement activation is increased in thrombotic APS patients, although its role has not been fully investigated in APS-related stroke. This study aimed to evaluate the degree of complement activation in APS-related ischemic stroke, transient ischemic attack (TIA) or other ischemic brain injury patients and whether complement activation correlated with APS severity and platelet hyperreactivity as a potential mechanism for increased thrombotic risk. Method: Patients with confirmed APS by Sydney Criteria and imaging-proven ischemic stroke, TIA or other ischemic brain injury were recruited, subcategorized as high-risk APS (HR-APS, n=30) and lower-risk APS (LR-APS, n=41). HR-APS included triple antiphospholipid antibody (aPL) positive, anticoagulant refractory or both arterial and venous thromboembolism patients. LR-APS included patients with a single thrombotic event who were single or double aPL positive. Ischemic stroke patients without aPL (n=40) and healthy donors (n=40) were utilized as controls. Patients with active cancer, inflammation, infection or use of hydroxychloroquine, immunosuppression and heparins were excluded. Complement activation markers were measured as Bb fragment (Bb), C3a-desArg (C3a), C5a-des-Arg (C5a), and SC5b-9 using ELISA (MicroVue kits, Quidel Corp, Pathway Diagnostics Ltd). Complement-mediated cell killing was measured by the modified Ham (mHam) test, which determines the degree of cell lysis after adding patient serum to a paroxysmal nocturnal hemoglobinuria cell line (PIGA-null TF-1 cells) lacking cell surface complement regulators. A positive result was considered 20% or greater cell killing. Flow cytometry was used to evaluate whether complement activation correlated with platelet hyperreactivity. For this, plasma from mHam positive patients was added to healthy donor whole blood and procoagulant platelet response was measured as the absolute change in proportion of platelet events that were positive for annexin V and P-selectin following stimulation with thrombin 2U/mL. Results: There was no significant difference in median age between the patient cohorts, ranging from 49 to 56 years, although the healthy controls were younger, with median age 36 (range 25-73, p&amp;lt;0.001). Circulating complement activation markers were all significantly increased in the APS cohorts compared to healthy controls (p&amp;lt;0.01). The most prominent increase was observed in C3a levels: HR-APS median (interquartile range - IQR) 215 ng/mL (137.1-297.4), LR-APS 290.8 ng/mL (120.3-450.3) and healthy controls 62 ng/mL (27.9-121.1)(p=0.004 and p&amp;lt;0.0001 compared to healthy controls, respectively); and Bb fragment levels: HR-APS 1.2 µg/mL (IQR 1.0-1.4), LR-APS 1.3 µg/mL (IQR 1.0-1.5) and healthy controls 0.8 µg/mL (IQR 0.7-0.9)(both p&amp;lt;0.0001 compared to healthy controls). However, only C3a, SC5b-9 and Bb fragment levels in LR-APS remained significantly elevated when compared to stroke controls (p=0.0009, p=0.01 and p=0.03, respectively). There were no differences between HR-APS and LR-APS, nor between stroke controls and healthy controls. Complement-mediated cell killing was also significantly higher in APS patients overall, median (IQR) proportion of non-viable cells 18% (IQR 12-33), compared to stroke controls: 10% (IQR 8-15, p&amp;lt;0.0001) and healthy controls: 12.5% (IQR 6.3-17, p=0.0009). Notably, HR-APS had significantly higher proportion of positive mHam tests (60%), compared to LR-APS: 36.6%, stroke controls: 12.5%, and healthy controls: 17.5% (p&amp;lt;0.0001, Figure 1A). Importantly, HR-APS patients with positive mHam results (n=5) induced a substantially higher increase in procoagulant platelets, median 17.2% (IQR 11.2-28.6), whereas healthy controls (n=4) only resulted in median change of -0.7% (IQR -7.0-1.4, p=0.02) (Figure 1B). Conclusion: Preliminary data suggest that APS-related ischemic stroke, TIA or ischemic brain injury are associated with increased, functionally important, complement activation, more prominent in higher risk disease. Complement-mediated platelet hyperreactivity may have a contributory role that remains to be established.

Impact of Brentuximab Vedotin in Patients with Breast Implant-Associated Anaplastic Large Cell Lymphoma with Capsule Infiltration Requiring Chemotherapy

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T-cell lymphoma most frequently arising around a textured surface breast implant. It has been shown that capsule infiltration (T2, T3 and T4 of the TNM staging system) was an adverse prognostic factor. In this context, chemotherapy (with or without brentuximab vedotin [BV]) may be proposed, considering other factors such as metastatic disease or incomplete resection. Furthermore, the need for adjuvant chemotherapy in patients with stage IIA (T4N0M0) and complete en-bloc excision without residual disease is debated. Aim: To assess the management of BIA-ALCL with capsule infiltration, in particular: 1) To assess the impact of BV in those patients; 2) To evaluate the need for adjuvant chemotherapy in patients with stage IIA and complete en-bloc excision without residual disease. Methods: Since 2016, a national multidisciplinary meeting has been implemented by the French National Cancer Institute (NCI) to optimize management of patients with BIA-ALCL, particularly those with advanced disease. Meanwhile, a national registry has been set up by the LYSA, in collaboration with health authorities. Central pathological review has been carried out within the French NCI-labeled Lymphopath network. Results: From 2009 to 2023, 125 patients with BIA-ALCL were recorded, of which 111 (94 from France and 17 from Belgium) had complete data and were included in the present analysis. Overall, median age at diagnosis of BIA-ALCL was 58 years (24-82 years). Reasons for initial implantation were breast cancer reconstruction (n=54; 49%), cosmetic (n=45; 41%) or other (n=12; 10%). The median interval from first implantation to diagnosis of BIA-ALCL was 12.3 years (4-40 years). The median number of implants in the breast involved by BIA-ALCL was 2 (1-8), including at least one silicone implant in 95 (86%) patients, and at least one textured implant in all informative cases (n=102; Most often Allergan Biocell implants). At diagnosis of BIA-ALCL, 78/110 (71%) patients presented with periprosthetic effusion only, 20 (18%) had effusion and a breast mass, 6 (5.5%) had a breast mass only, and 6 (5.5%) had neither. At pathological examination of the capsule, T-stage was T1 (confined to effusion or a layer on luminal side of capsule) in 73/111 (66%) cases, T2-T3 (capsule infiltration) in 5 (4.5%) cases, T4 (lymphoma infiltrates beyond the capsule) in 32 (29%) cases, and unclassifiable in 1 case. Moreover, 18/111 (16%) patients had at least one non-breast extranodal involvement. Among the 36 patients with capsule infiltration (5 T2-T3 and 31 T4), 13 (including 11 T4) were treated with BV-CH(E)P regimen, 12 (all T4) with a CHOP/CHOP-like regimen, and 11 (including 8 T4) did not receive any chemotherapy. The main reasons for receiving chemotherapy were metastatic disease, incomplete resection, or no surgery. Patients who did not receive chemotherapy had a localized disease (3 stage IB/IC and 8 stage IIA) with complete en-bloc excision and no residual disease. Patients treated with BV-CH(E)P regimen and CHOP/CHOP-like regimen had similar characteristics without significant differences regarding age, clinical presentation, stage and surgery. After a median follow-up of 47 months from BIA-ALCL diagnosis, for BV-CH(E)P and CHOP/CHOP-like groups, the respective 4-year PFS rates were 100% and 57% (p=0.01), and the respective 4-year OS rates were 100% and 73% (p=0.07). Regarding the 11 patients who did not receive chemotherapy, 4-year PFS and OS were both 75%, which corresponds to a single event being a death without progression occurring more than 3 years after the diagnosis of lymphoma (4-year lymphoma-specific survival was 100%). Conclusions: 1) In patients with capsule infiltration requiring chemotherapy, BV-CH(E)P regimen was associated with improved PFS and OS compared with CHOP/CHOP-like regimen; 2) Patients with stage IIA and complete en-bloc excision without residual disease had favorable outcome without the need for adjuvant chemotherapy. These results should be confirmed prospectively.

Theory and practice of basin-wide floodwater utilization: typical implementing measures in China

Floodwater utilization (FU) helps alleviate water shortages in regions with uneven rainfall. This study focuses on basin-wide FU, considering diverse water infrastructure and the delicate balance between flood risks and water scarcity. FU measures including optimizing reservoir flood limited water level (FLWL), extending the use of flood detention areas, and compensatory use of channel capacities, were reviewed and exemplified by real-world applications in China. The proposed procedure for implementing FU involves assessing FU potential, selecting appropriate utilization methods, and conducting a comprehensive evaluation of the associated risks and benefits. Using the Nansi Lake basin in China, as a synthesis example, the current-level FU potential and FU rate are estimated to be 1.47 km3/yr and 65%. This FU value exceeds the theoretical potential, indicating the severe crowding out of ecological water uses. Multi-stage FLWL through raising the post-flood FLWL from 34.20 m to 34.35 m could increase the reservoir (the upper Nansi Lake) ability to refill by 19.1%. Appropriate control of the sluices of interconnected rivers could conserve up to 0.135 km3 of floodwater from a single flood event without increasing flood risk.

Fractal Dimension as a discriminative feature for high accuracy classification in motor imagery EEG-based brain-computer interface

Background and ObjectiveThe brain-computer interface (BCI) technology acquires human brain electrical signals, which can be effectively and successfully used to control external devices, potentially supporting subjects suffering from motor impairments in the interaction with the environment. To this aim, BCI systems must correctly decode and interpret neurophysiological signals reflecting the intention of the subjects to move. Therefore, the accurate classification of single events in motor tasks represents a fundamental challenge in ensuring efficient communication and control between users and BCIs. Movement-associated changes in electroencephalographic (EEG) sensorimotor rhythms, such as event-related desynchronization (ERD), are well-known features of discriminating motor tasks. Fractal dimension (FD) can be used to evaluate the complexity and self-similarity in brain signals, potentially providing complementary information to frequency-based signal features. MethodsIn the present work, we introduce FD as a novel feature for subject-independent event classification, and we test several machine learning (ML) models in behavioural tasks of motor imagery (MI) and motor execution (ME). ResultsOur results show that FD improves the classification accuracy of ML compared to ERD. Furthermore, unilateral hand movements have higher classification accuracy than bilateral movements in both MI and ME tasks. ConclusionsThese results provide further insights into subject-independent event classification in BCI systems and demonstrate the potential of FD as a discriminative feature for EEG signals.

Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development.

The synchronization of canonical fast sleep spindle activity (12.5-16 Hz, adult-like) precisely during the slow oscillation (0.5-1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5-6, 8-11, and 14-18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups-but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.

Direct Quantification of Nanoplastics Neurotoxicity by Single‐Vesicle Electrochemistry

AbstractNanoplastics are recently recognized as neurotoxic factors for the nervous systems. However, whether and how they affect vesicle chemistry (i.e., vesicular catecholamine content and exocytosis) remains unclear. This study offers the first direct evidence for the nanoplastics‐induced neurotoxicity by single‐vesicle electrochemistry. We observe the cellular uptake of polystyrene (PS) nanoplastics into model neuronal cells and mouse primary neurons, leading to cell viability loss depending on nanoplastics exposure time and concentration. By using single‐vesicle electrochemistry, we find the reductions in the vesicular catecholamine content, the frequency of stimulated exocytotic spikes, the neurotransmitter release amount of single exocytotic event, and the membrane‐vesicle fusion pore opening‐closing speed. Mechanistic investigations suggest that PS nanoplastics can cause disruption of filamentous actin (F‐actin) assemblies at cytomembrane zones and change the kinetic patterns of vesicle exocytosis. Our finding shapes the first quantitative picture of neurotoxicity induced by high‐concentration nanoplastics exposure at a single‐cell level.

Direct Quantification of Nanoplastics Neurotoxicity by Single-Vesicle Electrochemistry.

Nanoplastics are recently recognized as neurotoxic factors for the nervous systems. However, whether and how they affect vesicle chemistry (i.e., vesicular catecholamine content and exocytosis) remains unclear. This study offers the first direct evidence for the nanoplastics-induced neurotoxicity by single-vesicle electrochemistry. We observe the cellular uptake of polystyrene (PS) nanoplastics into model neuronal cells and mouse primary neurons, leading to cell viability loss depending on nanoplastics exposure time and concentration. By using single-vesicle electrochemistry, we find the reductions in the vesicular catecholamine content, the frequency of stimulated exocytotic spikes, the neurotransmitter release amount of single exocytotic event, and the membrane-vesicle fusion pore opening-closing speed. Mechanistic investigations suggest that PS nanoplastics can cause disruption of filamentous actin (F-actin) assemblies at cytomembrane zones and change the kinetic patterns of vesicle exocytosis. Our finding shapes the first quantitative picture of neurotoxicity induced by high-concentration nanoplastics exposure at a single-cell level.

Mediterranean meteotsunamis of May 2021 and June 2022

Meteorological tsunamis (i.e., tsunami-like waves of atmospheric origin) are regularly observed in the Mediterranean Sea. During a single event, destructive flooding usually occurs in one location or limited area. However, in May 2021 and June 2022, strong meteotsunamis hit several Mediterranean locations up to 500 km apart. In the morning hours of the 24th of May 2021, a meteotsunami hit Bonifacio on the island of Corsica (western Mediterranean, France) and in the afternoon hours of the same day, another meteotsunami hit Široka Bay on the island of Ist (Adriatic Sea, Croatia), 500 km away. About 13 months later, on the 26th of June 2022, a meteotsunami hit Ciutadella on the island of Menorca (Spain) and two days later Bonifacio, 400 km away. Sea-level and atmospheric pressure data and satellite imagery, as well as synoptic conditions, associated with both events were analysed in detail. It has been confirmed that in the Mediterranean, meteotsunamis occur when meteotsunamigenic synoptic conditions prevail over the area, with a strong southwesterly jet stream embedded in dynamically or convectively unstable atmospheric layers standing out as the most important condition. The meteotsunamigenic potential of each of the three bays (Ciutadella, Bonifacio, Široka Bay) was investigated by considering: (1) the potential for Proudman resonance on the shelves offshore of the bays, (2) the orientation of the mouth of the bay and (3) the frequency of meteotsunamigenic synoptic conditions over the area. The strongest and most frequent meteotsunamis occur at locations where the shelf characteristics (width, depth, orientation), bay mouth orientation and distribution of general synoptic conditions, have characteristics that support the amplification of long-ocean waves and their propagation toward the bay mouth.

Probable human origin of the SARS-CoV-2 polybasic furin cleavage motif

BackgroundThe key evolutionary step leading to the pandemic virus was the acquisition of the PRRA furin cleavage motif at the spike glycoprotein S1/S2 junction by a progenitor of SARS-CoV-2. Two of its features draw attention: (i) it is absent in other known lineage B beta-coronaviruses, including the newly discovered coronaviruses in bats from Laos and Vietnam, which are the closest known relatives of the covid virus; and, (ii) it introduced the pair of arginine codons (CGG-CGG), whose usage is extremely rare in coronaviruses. With an occurrence rate of only 3%, the arginine CGG codon is considered a minority in SARS CoV-2. On the other hand, Laos and Vietnam bat coronaviruses contain receptor-binding domains that are almost identical to that of SARS-CoV-2 and can therefore infect human cells despite the absence of the furin cleavage motif.ResultsBased on these data, the aim of this work is to provide a detailed sequence analysis between the SARS-CoV-2 S gene insert encoding PRRA and the human mRNA transcripts. The result showed a 100% match to several mRNA transcripts. The set of human genes whose mRNAs match this S gene insert are ubiquitous and highly expressed, e.g., the ATPase F1 (ATP5F1) and the ubiquitin specific peptidase 21 (USP21) genes; or specific genes of target organs or tissues of the SARS-CoV-2 infection (e.g., MEMO1, SALL3, TRIM17, CWC15, CCDC187, FAM71E2, GAB4, PRDM13). Results suggest that a recombination between the genome of a SARS-CoV-2 progenitor and human mRNA transcripts could be the origin of the S gene 12-nucleotide insert encoding the S protein PRRA motif.ConclusionsThe hypothesis of probable human origin of the SARS-CoV-2 polybasic furin cleavage motif is supported by: (i) the nature of human genes whose mRNA sequence 100% match the S gene insert; (ii) the synonymous base substitution in the arginine codons (CGG-CGG); and (iii) further spike glycoprotein PRRA-like insertions suggesting that the acquisition of PRRA may not have been a single recombination event.

Restoring eastern hellbender (Cryptobranchus a. alleganiensis) populations through translocation of headstarted individuals

AbstractFreshwater biodiversity is declining at a fast pace despite significant efforts directed toward the management and conservation of aquatic systems. Eastern hellbenders are one of North America's most iconic stream amphibian species, a sentinel of stream health, and are experiencing rapid population declines throughout most of their range. Common conservation strategies include headstarting; however, the success of this strategy for rebuilding hellbender populations and the most optimal release scenarios have largely been unassessed. We use a cohort of 205 animals released in several Ohio watersheds to evaluate the success of headstarting and reintroduction efforts over 3 years. Using PIT‐tag surveys over 25 occasions between July 2018 and November 2021 and capture–recapture models, we found that 3‐year apparent survival post‐release was 0.162 ± 0.061, with lower survival in year 1 (0.383 ± 0.058) and greater in years 2 (0.696 ± 0.086) and 3 (0.609 ± 0.154). Using demographic simulations, we found that releasing cohorts of N = 100 individuals at fewer suitable sites several times (e.g., 3 releases, 2 or 3 years apart) would be a better strategy compared to single release events across multiple sites. Additional simulations showed that eastern hellbender headstarting programs using wild eggs can be highly beneficial in producing more animals reaching adulthood (up to 7 times, if survival in captivity is assumed to be 100%) compared to development in the wild. This study emphasizes the need to monitor the success of reintroduction programs and provides evidence that headstarting can be a viable strategy for rebuilding eastern hellbender populations.

Global information enhancement and subgraph-level weakly contrastive learning for lightweight weakly supervised document-level event extraction

Document-level event extraction (DEE) is a branch of information extraction task that is valuable but difficult at present. To effectively implement DEE, previous works with better performance are often accompanied by larger parameters and computation. In this paper, we propose a novel framework based on global information enhancement and subgraph-level weakly contrastive learning, which bring better performance at lower extra computing costs. We verify the effectiveness of our method in a lightweight DEE model. The experimental results indicate that our proposed method outperforms other approaches in terms of the F1 score for both overall event extraction evaluation and single event extraction. In the inference phase, our model uses only 25% of the GPU memory required by the optimal model and maintains the advantage of 6.4 times faster inference speed.

Anticoagulation prophylaxis patterns following retroperitoneal lymph node dissection for testis cancer

IntroductionRetroperitoneal lymph node dissection (RPLND) is the standard of care for testicular cancer in various disease settings. Deep vein thrombosis (DVT) complications have been reported to occur in <1% of primary RPLND cases and up to 3% of postchemotherapy (PC-RPLND) cases. While prophylactic anticoagulation (AC) has been well-documented to reduce DVT rates in patients undergoing surgery in general, the benefit of prophylactic AC in RPLND has not been assessed. In this retrospective cohort study, we seek to address this unmet need by evaluating the rates and associated risk factors of DVT and pulmonary embolism (PE) with a national and institutional database, assess the changing patterns in DVT prophylaxis with postoperative AC following RPLND, and quantify the potential benefit of prophylactic AC in patients who have undergone RPLND using a risk-stratified approach. MethodsThe National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent RPLND during the 10-year period from 2011 to 2021. An institutional database was queried for all patients undergoing RPLND from 2013 to 2022. Patient characteristics and operative outcomes were compared between the NSQIP and the institutional database. The institutional database was stratified by prior oncologic treatment (i.e., primary RPLND vs. PC-RPLND) and outcomes were compared. Postoperative AC rate was determined and trended by year. The use of postoperative AC and PE events were stratified by clinical stage. The absolute risk reduction (ARR) of AC prophylaxis on PE events and the number needed to treat (NNT) with AC prophylaxis to prevent a single PE event was determined. ResultsIn total, the NSQIP database query resulted in 779 patients and our institutional database query resulted in 188 patients. The rate of DVT and PE was 1.2% and 0.5% vs. 2.1% and 1.6% in the NSQIP and institutional cohort, respectively. The rate of postoperative AC following RPLND in patients from the institutional database increased from 5% in 2013 to 43% in 2022 (P = 0.01). There were no statistically significant differences in complication rates, including bleeding events, chyle leaks, or hospital readmissions amongst patients who were prescribed AC at discharge and those who were not. No stage I patients developed PEs and no stage I patients were prescribed AC. The ARR for AC prophylaxis for development of PE was found to be 0.023 for the clinical stage II and stage III cohorts. The NNT to prevent a single PE with AC was 44 and 43 for the stage II and stage III cohorts, respectively. ConclusionsAC appears beneficial with minimal risk of harm after RPLND, especially in patients with higher risk of developing DVT/PE, highlighting the safety and efficacy of this regimen. There was a significant increase in the rate of AC prophylaxis at discharge amongst patients undergoing RPLND in the institutional database from 2013 to 2022. A risk-stratified protocol of postoperative AC following RPLND appears reasonable, and further prospective trials are warranted to formally confirm this recommendation.