Viral hepatitis moderates the impact of TGFB1 on neurocognitive impairment.

Recent studies have identified a correlation between chronic viral hepatitis and cognitive impairment, yet the underlying mechanisms remain unclear. This study investigated the influence of TGFB1 genetic polymorphisms on cognitive function in individuals with and without hepatitis infections, hypothesizing that these polymorphisms and the viral hepatitis-induced inflammatory environment interact to affect cognitive abilities. Participants (173 with viral hepatitis and 258 healthy controls) were recruited. Genotyping of TGFB1 SNPs was performed using the C2-58 Axiom Genome-Wide TWB 2.0 Array Plate. Cognitive function was assessed using the MMSE and MoCA tests. Our results showed that healthy individuals carrying the C allele of rs2241715 displayed better performance in sentence writing (p = 0.020) and language tasks (p = 0.022). Notably, viral hepatitis was found to moderate the impact of the rs2241715 genotype on language function (p = 0.002). Similarly, those carrying the T allele of rs10417924 demonstrated superior orientation to time (p = 0.002), with viral hepatitis modifying the influence of the SNP on this particular cognitive function (p = 0.010). Our findings underscore the significant role of TGFß1 in cognitive function and the moderating impact of viral hepatitis on TGFB1 SNP effects. These findings illuminate the potential of TGFB1 as a therapeutic target for cognitive impairment induced by viral hepatitis, thus broadening our understanding of TGFß1 functionality in the pathogenesis of neurodegeneration.

No clear benefit of preventive cranial radiotherapy in childhood Philadelphia-positive acute lymphoblastic leukemia: a retrospective analysis of the EsPhALL2010 study.

Not available.

Understanding Reductions of PM2.5 Concentration and Its Chemical Composition in the United States: Implications for Mitigation Strategies.

Motivated by the recent tightening of the US annual standard of fine particulate matter (PM2.5) concentrations from 12 to 9 µg/m3, there is a need to understand the spatial variation and drivers of historical PM2.5 reductions. We evaluate and interpret the variability of PM2.5 reductions across the contiguous US using high-resolution estimates of PM2.5 and its chemical composition over 1998-2019, inferred from satellite observations, air quality modeling, and ground-based measurements. We separated the 3092 counties into four characteristic regions sorted by PM2.5 trends. Region 1 (primarily Central Atlantic states, 25.9% population) exhibits the strongest population-weighted annual PM2.5 reduction (-3.6 ± 0.4%/yr) versus Region 2 (primarily rest of the eastern US, -3.0 ± 0.3%/yr, 39.7% population), Region 3 (primarily western Midwest, -1.9 ± 0.3%/yr, 25.6% population), and Region 4 (primarily the Mountain West, -0.4 ± 0.5%/yr, 8.9% population). Decomposition of these changes by chemical composition elucidates that sulfate exhibits the fastest reductions among all components in 2720 counties (76% of population), mostly over Regions 1-3, with the 1998-2019 mean sulfate mass fraction in PM2.5 decreasing from Region 1 (29.5%) to Region 4 (11.8%). Complete elimination of the remaining sulfate may be insufficient to meet the new standard for many regions in exceedance. Additional measures are needed to reduce other PM2.5 sources and components for further progress.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

Integrating artificial intelligence modeling and membrane technologies for advanced wastewater treatment: Research progress and future perspectives.

Membrane technologies have become proficient alternatives for advanced wastewater treatment, ensuring high contaminant removal and sustainable resource recovery. Despite significant progress, ongoing research efforts aim to further optimize treatment performance. Among the challenges faced, membrane fouling persists as a relevant obstacle in membrane technologies, necessitating the development of more effective mitigation strategies. Mathematical models, widely employed for predicting treatment performance, generally exhibit low accuracy and suffer from uncertainties due to the complex and variable nature of wastewater. To overcome these limitations, numerous studies have proposed artificial intelligence (AI) modeling to accurately predict membrane technologies' performance and fouling mechanisms. This approach aims to provide advanced simulations and predictions, thereby enhancing process control, optimization, and intensification. This literature review explores recent advancements in modeling membrane-based wastewater treatment processes through AI models. The analysis highlights the enormous potential of this research field in enhancing the efficiency of membrane technologies. The role of AI modeling in defining optimal operating conditions, developing effective strategies for membrane fouling mitigation, enhancing the performance of novel membrane-based technologies, and improving membrane fabrication techniques is discussed. These enhanced process optimization and control strategies driven by AI modeling ensure improved effluent quality, optimized resource consumption, and minimized operating costs. The potential contribution of this cutting-edge approach to a paradigm shift toward sustainable wastewater treatment is examined. Finally, this review outlines future perspectives, emphasizing the research challenges that require attention to overcome the current limitations hindering the integration of AI modeling in wastewater treatment plants.

A 35-gene mutation profile predicts the therapeutic outcome of patients with esophageal squamous cell carcinoma receiving neo-adjuvant chemoradiation.

Esophageal cancer is a common malignancy worldwide with a poor prognosis without radical resection. Neoadjuvant concurrent chemoradiotherapy (NACRT) followed by esophagectomy is widely used for treating locally advanced esophageal cancer in the thorax. The study aimed to assess mutation profiles and their correlation with therapeutic outcomes in patients diagnosed with locally advanced thoracic esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted on 62 patients with ESCC who underwent NACRT. All patients received concurrent chemoradiotherapy (CCRT) utilizing intensity-modulated radiation therapy alongside concurrent chemotherapy with a cisplatin-based regimen. A 35-gene next-generation sequencing (NGS) panel detecting 402 genetic variants was used, which has been proven predictive in ESCC patients who received definitive chemoradiation. The 35-gene mutation profiles were analyzed in pre-treatment biopsies. The results reveled there were variants correlated with pathological complete remission or partial response, overall survival, and progression-free survival. A combination of p.Pro1319Ser and p.Arg2159Gly mutations in the MUC17 gene demonstrated an adverse impact on pathological response (OR [95% CI] = 7.00 (3.07-15.94), P < 0.001). Additionally, the variants located in the MUC17, MUC4, and MYH4 genes exhibited notably effects on tumor recurrence or mortality. Patients harboring either the MUC17 p.Thr2702Val or MUC4 p.Thr3355Ser mutation displayed a more than four-fold increased risk for disease recurrence or mortality. We concluded that specific mutations correlated to the pathological complete response in ESCC receiving neoadjuvant chemoradiation can be identified through the utilization of 35-gene expression profiles. Further investigation into the pathophysiological roles of MUC17 and MUC4 mutations in ESCC is warranted.

Lighting Up Nucleolus To Report Mitochondria Damage Using a Mitochondria-to-Nucleolus Migration Probe.

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

Call to Action: The Rise of Pediatric Gun Violence During the COVID-19 Pandemic.

This study examines and describes circumstances involving non-fatal firearm injuries in a pediatric population from a Level I Pediatric Trauma Center in the southeastern U.S. Researchers analyzed Firearm Injury Questionnaire (FIQ) data collected from 144 children and adolescents, aged 2-17 years, who were treated in the emergency department and/or admitted to the hospital for non-fatal firearm injuries. Descriptive statistics are presented regarding participant demographics and FIQ responses, such as caregiver information, mental health history, adverse childhood experience (ACE) exposure, firearm access, injury intent, relationship to shooter, type of firearm used, and context of injury. Most patients identified as Black (82%) and male (75%), with most injuries categorized as intentional (72%) versus unintentional (24%) assaults. The average ACEs score was .60, with only 37% of patients' reporting any ACE experience; however, nearly half (47%) of patients reported experiencing a traumatic event beyond an identified ACE. Community violence was the most common context that attributed to patients' assaults (56%). As U.S. pediatric gun injury and fatality trends are increasing, this study provides timely data regarding pediatric firearm injuries and exposure to community violence. These findings highlight the need to provide integrated health services to pediatric patients experiencing non-fatal firearm injuries. Researchers discuss public health implications for integrated mental health care services, hospital- and school-based violence intervention programs, policy recommendations, and directions for future research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00568-4.

Augmented Reality in Spine Surgery: A Case Study of Atlantoaxial Instrumentation in Os Odontoideum.

Despite advancement in surgical innovation, C1-C2 fixation remains challenging due to risks of screw malposition and vertebral artery (VA) injuries. Traditional image-based navigation, while useful, often demands that surgeons frequently shift their attention to external monitors, potentially causing distractions. In this article, we introduce a microscope-based augmented reality (AR) navigation system that projects both anatomical information and real-time navigation images directly onto the surgical field. In the present case report, we discuss a 37-year-old female who suffered from os odontoideum with C1-C2 subluxation. Employing AR-assisted navigation, the patient underwent the successful posterior instrumentation of C1-C2. The integrated AR system offers direct visualization, potentially minimizing surgical distractions. In our opinion, as AR technology advances, its adoption in surgical practices and education is anticipated to expand.

Physical activity patterns, sleep quality, and stress levels among rotating-shift nurses during the COVID-19 pandemic.

AIM: To examine the associations between physical activity patterns, sleep quality, and stress levels among rotating-shift nurses during the COVID-19 pandemic. BACKGROUND: Stress adversely impacts hospital nurses, particularly those on rotating shifts. The effects of physical activity patterns and sleep quality on the stress levels of these nurses during the COVID-19 pandemic warrant investigation. METHODS: A multicenter cross-sectional study was conducted with 550 eligible registered hospital nurses, randomly selected from four hospitals during the COVID-19 pandemic in Taiwan. The work schedule type of these nurses was categorized into rotating shifts (working at least two shifts in a month, involving day, evening, and night shifts) or fixed-day shifts (working only the day shift). Data were collected on sociodemographic characteristics, physical activity patterns (sedentary or active), sleep quality (poor or adequate), and stress levels for analysis. RESULTS: Rotating-shift nurses with active physical activity patterns exhibited lower stress levels compared with those with sedentary patterns. Nurses who experienced adequate sleep quality had lower stress levels compared with those with poor sleep quality among rotating and fixed-day shift nurses. CONCLUSIONS: Active physical activity patterns and adequate sleep quality were associated with lower stress levels among rotating-shift nurses during the pandemic. Promoting active physical activity and enhancing sleep quality are essential strategies for reducing stress in these nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Strategies aimed at promoting physical activity and improving sleep quality should be integral components of health promotion programs and policymaking efforts directed at nursing leaders, to foster a healthy and supportive work environment and enhance the welfare of rotating-shift hospital nurses. REPORTING METHOD: The study is reported using the statement of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).

Multicolour and lineage-specific interphase chromosome Flow-FISH: method development and clinical validation.

Flow cytometry can be applied in the detection of fluorescence in situ hybridisation (FISH) signals to efficiently analyse chromosomal aberrations. However, such interphase chromosome (IC) Flow-FISH protocols are currently limited to detecting a single colour. Furthermore, combining IC Flow-FISH with conventional multicolour flow cytometry is difficult because the DNA-denaturation step in FISH assay also disrupts cellular integrity and protein structures, precluding subsequent antigen-antibody binding and hindering concurrent labeling of surface antigens and FISH signals. We developed a working protocol for concurrent multicolour flow cytometry detection of nuclear IC FISH signals and cell surface markers. The protocol was validated by assaying sex chromosome content of blood cells, which was indicative of chimerism status in patients who had received sex-mismatched allogeneic haematopoietic stem cell transplants (allo-HSCT). The method was also adapted to detect trisomy 12 in chronic lymphocytic leukaemia (CLL) subjects. We first demonstrated the feasibility of this protocol in detecting multiple colours and concurrent nuclear and surface signals with high agreement. In clinical validation experiments, chimerism status was identified in clinical samples (n=56) using the optimised IC Flow-FISH method; the results tightly corresponded to those of conventional slide-based FISH (R2=0.9649 for XX cells and 0.9786 for XY cells). In samples from patients who received sex-mismatched allo-HSCT, individual chimeric statuses in different lineages could be clearly distinguished with high flexibility in gating strategies. Furthermore, in CLL samples with trisomy 12, this method could demonstrate that enriched trisomy 12 FISH signal was present in B cells rather than in T cells. Finally, by performing combined labelling of chromosome 12, X chromosome, and surface markers, we could detect rare residual recipient CLL cells with trisomy 12 after allo-HSCT. This adaptable protocol for multicolour and lineage-specific IC Flow-FISH advances the technique to allow for its potential application in various clinical contexts where conventional FISH assays are currently being utilised.

Controlled NiOx Defect Engineering to Harnessing Redox Reactions in Perovskite Photovoltaic Cells via Atomic Layer Deposition.

Albeit the undesirable attributes of NiOx, such as low conductivity, unmanageable defects, and redox reactions occurring at the perovskite/NiOx interface, which impede the progress in inverted perovskite solar cells (i-PSCs), it is the most favorable choice of technology for industrialization of PSCs. In this study, we propose a novel Ni vacancy defect modulate approach to leverage the conformal growth and surface self-limiting reaction characteristics of the atomic layer deposition (ALD)-fabricated NiOx by varying the O2 plasma injection time (tOE) to induce self-doping. Consequently, NiOx thin films with enhanced conductivity, an appropriate Ni3+/Ni2+ ratio, stable surface states, and ultrathinness are realized as hole-transporting layers (HTLs) in p-i-n PSCs. As a result of these improvements, ALD-NiOx-based devices exhibit the highest power conversion efficiency (PCE) of 19.86% and a fill factor (FF) of 81.86%. Notably, the optimal interfacial defects effectively suppressed the severe reaction between the perovskite and NiOx. This suppression is evidenced by the lowest decay rate observed in a harsh environment, lasting for 500 consecutive hours. The proposed approach introduces the possibility of a hierarchical distribution of defects and offers feasibility for the fabrication of large-area, uniform, and high-quality films.

Biologic and clinical analysis of childhood gamma delta T-ALL identifies LMO2/STAG2 rearrangements as extremely high-risk.

Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (yo T-ALL) is a poorly understood disease. We studied 200 children with yo T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. yo T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by Poly(ADP-ribose) polymerase (PARP) inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric yo T-ALL.