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Head and neck cancer (HNC) patients who are unable to return to work after completing treatment might face financial loss and reduced self-esteem. The aim of this study was to identify factors influencing a return to work in HNC cancer patients in the first 6 months after treatment. This cross-sectional study examined HNC patients who completed treatment from the outpatient radiation department of a single cancer center in northern Taiwan. Patients were assessed according to psychological distress, patient-perceived health status, barriers to returning to work, and facilitators of returning to work. Of the 106 HNC patients surveyed, 54.7% successfully returned to work. Barriers to returning to work included poor self-perception of health, greater psychological distress, and age ≥50 years. Patients who had higher psychological distress, returned to work after start of the pandemic, or received reconstruction surgery were less likely to experience a positive environment facilitating a return to work.

We find that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with CFU-E activity (stress CFU-E/sCFU-E) is markedly expanded to restore the erythron. sCFU-E are targets of erythropoietin (Epo) and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2/STAT5-dependent expression of IRS2, thus engaging the pro-growth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R/IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant, JAK2(V617F), in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In myeloproliferative neoplasm patient samples, the number of sCFU-E like cells increases, and inhibition of IGR1R/IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identify a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.Key PointsEpo-induced IRS2 allows engagement of IGF1R signaling to expand a previously unrecognized progenitor population in erythropoietic stress.Truncated EpoR does not support stress CFU-E expansion and protects against JAK2(V617F)-driven erythrocytosis in MPN.

As antibiotics and heavy metals are often mixed in animal feed, their excretion through animal feces would cause bacteria to produce antibiotic resistance genes and heavy metal resistance genes. The pollution of antibiotics resistance gene and heavy metal resistance gene has become a major threat to human health and ecological environment. From the perspective of bacterial evolution, we proposed the importance of bacterial long-term evolution experiments about antibiotics and heavy metals. There is a complex co-selection resistance between antibiotic resistance genes and heavy metal resistance genes, which interact with each other and collectively determine the environmental behavior of bacteria. Horizontal transfer of resistance gene increases its variability in the environment. Mobile genetic elements play an important role in horizontal transfer of resistance gene. As for resistance gene pollution control, advanced oxidation technology has a good resistance gene removal effect. The UV/TiO动物饲料中常混有抗生素和重金属,导致外排的动物粪便中携带有抗生素和重金属,引发细菌产生耐药性和重金属抗性,继而产生抗生素抗性基因和重金属抗性基因。抗生素和重金属抗性基因污染已成为威胁人类身体健康及破坏生态环境的重大问题。本文从细菌进化的角度,明确了细菌的抗生素和重金属长期进化试验对抗性机制研究的重要性;抗生素抗性基因与重金属抗性基因间存在复杂的协同选择抗性,两者间相互影响,共同决定着细菌环境行为;抗性基因的水平转移增加了细菌在环境中的可变性,可移动遗传元件在抗性基因水平转移中发挥着重要作用。在抗性基因污染控制方面,高级氧化技术具有很好的抗性基因去除效果,尤其是UV/TiO

Most fast synaptic inhibitions in the mammalian brain are mediated by GABAA receptors (GABAARs). An appropriate level of GABAAR expression at the cell surface is essential for neurodevelopment and the efficacy of GABAergic synaptic transmission. We previously reported that brefeldin A-inhibited GDP/GTP exchange factor 1 (BIG1), a binding partner of GABAARs, plays an important role in trafficking GABAARs to the cell surface. However, its regulatory mechanisms remain unknown. In the present study, we identified a new cellular protein, 14-3-3ζ, which can interact with the β subunit of GABAARs and BIG1 both in vitro and in vivo and colocalizes in the soma, dendrites and axons of hippocampal neurons. Overexpression of 14-3-3ζ-WT increased the surface expression of BIG1 in dendrites and axons, as well as the binding of BIG1 with GABAAR. Depleted 14-3-3ζ with efficacious siRNA attenuated the interaction between BIG1 and GABAARs and resulted in significant decreases in the surface expression levels of BIG1 and GABAAR. GABAAR agonist treatment increased the expression levels of BIG1 and 14-3-3ζ on the surface, indicating that 14-3-3ζ is involved in regulating BIG1-mediated GABAAR surface expression. Depletion of BIG1 or 14-3-3ζ significantly decreased GABAAR expression at the cell surface and suppressed the GABA-gated influx of chloride ions. These data indicate that the combination of 14-3-3ζ and BIG1 is required for GABAAR membrane expression. Our results provide a potential promising therapeutic target for neurological disorders involving GABAergic synaptic transmission.

The mechanical parameters of materials in a dam body and dam foundation tend to change when dams are reinforced in aging processes. It is important to use an early-warning index to reflect the safety status of dams, particularly of heightened projects in the impoundment period. Herein, a new method for monitoring the safety status of heightened dams is proposed based on the deformation monitoring data of a dam structure, a statistical model, and finite-element numerical simulation. First, a fast optimization inversion method for estimation of dam mechanical parameters was developed, which used the water pressure component extracted from a statistical model, an improved inversion objective function, and a genetic optimization iterative algorithm. Then, a finite element model of a heightened concrete gravity dam was established, and the deformation behavior of the dam with rising water levels in the impoundment period was simulated. Subsequently, mechanical parameters of aged dam parts were calculated using the fast optimization inversion method with simulated deformation and the water pressure deformation component obtained by the statistical model under the same conditions of water pressure change. Finally, a new early-warning index of dam deformation was constructed by means of the forward-simulated deformation and other components of the statistical model. The early-warning index is useful for forecasting dam deformation under different water levels, especially high water levels.

In this work, the time-dependent behaviors of dual-channel amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) under negative bias illumination stress (NBIS) are systematically discussed. The dual-channel comprised two different IGZO layers fabricated by tuning the oxygen flow during deposition. The presence of heterojunctions enhanced field-effect mobility by 1.5× owing to the confinement of carriers in buried channels because of an energy barrier. However, after long periods of NBIS stress, the degradation of a-IGZO TFTs resulted in the entrapment of photo-generated electron–hole pairs at interface defects. The conduction path migrated to the surface channel. Results from extracting the hysteresis window and utilizing capacitance–voltage measurements have indicated a channel migration phenomenon due to the entrapment of electrons and holes at the surface and buried channel interfaces.

Script identification is an essential step in the text extraction pipeline for multi-lingual application. This paper presents an effective approach to identify scripts in scene text images. Due to the complicated background, various text styles, character similarity of different languages, script identification has not been solved yet. Under the general classification framework of script identification, we investigate two important components: feature extraction and classification layer. In the feature extraction, we utilize a hierarchical feature fusion block to extract the multi-scale features. Furthermore, we adopt an attention mechanism to obtain the local discriminative parts of feature maps. In the classification layer, we utilize a fully convolutional classifier to generate channel-level classifications which are then processed by a global pooling layer to improve classification efficiency. We evaluated the proposed approach on benchmark datasets of RRC-MLT2017, SIW-13, CVSI-2015 and MLe2e, and the experimental results show the effectiveness of each elaborate designed component. Finally, we achieve better performances than those competitive models, where the correct rates are 89.66%, 96.11%, 98.78% and 97.20% on PRC-MLT2017, SIW-13, CVSI-2015 and MLe2e, respectively.

Objectives To investigate the prognostic value of the preoperative systemic immune‐inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC‐SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). Materials and Methods We retrospectively reviewed the clinical records of patients with OC‐SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden’s index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). Results The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p, The SII is defined as platelet × neutrophil/lymphocyte counts. Increased SII values predict poor distant control and overall survival in patients with oral cancer treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a tight follow‐up surveillance schedule or adjuvant systemic treatment may be advisable pending independent confirmation of our data.

Meaning in life (MIL) is an important individual difference characteristic related to well-being, and has been receiving increasing research attention. We investigated the role of MIL in the link between proactive personality and well-being, with a focus on life satisfaction and mental health. Participants were 364 undergraduate students who completed a survey measuring proactive personality, MIL, stress, depression, and anxiety. Results reveal that proactive personality and MIL were positively correlated with life satisfaction and negatively correlated with stress, anxiety, and depression. In addition, MIL fully mediated the relationship between proactive personality and life satisfaction, and fully and independently mediated the association between proactive personality and mental health (stress, anxiety, and depression). Our results confirm the mediating role of MIL in the relationship between proactive personality and well-being. Practical implications of the study include potential methods for interventions that could improve individuals' well-being by targeting and enhancing MIL.

To improve the sensory quality of aged flue-cured tobacco (FCT), Bacillus subtilis subsp, H11 was inoculated on aged FCT leaves named Pingdingshan DCFB. The metagenome and thecharacteristic aroma substances of aged FCT with different fermentation times (0 h, 12 h, 24 h, and 36 h) were systematically analyzed. The results showed that the content of aroma components and sensory quality of aged FCT were significantly improved when the strain was treated at 35 °C with 25% moisture for 24 h. The inoculation of H11 had a strong influence on the microbial composition and metabolism of the aged FCT leaf surface. Five microorganisms Pantoea (35.04%, 20.12-56.95%), Enterobacter (22.16, 13.60-39.82%), Pseudomonas (12.12, 3.13-26.17%), Terribacillus (8.00%, 4.65-13.01%) and Bacillus (6.54%, 0.67-16.96%) accounted for the largest proportion during the process of fermentation. The content of most neutral flavor components such as ketones and aldehydes in FCT after fermentation was higher than that priorto fermentation. After 24 h fermentation, 3-furfural, 5-methylfurfural, dihydrokiwi lactone and megalotrienone increased by 71.42%, 49.19%, 21.09%, and 10.56%, respectively. Correlation analysis between groups showed that Pseudomonas was significantly correlated with (E, E)-2, 4-heptadienal (P 0.05), Franconibacter was correlated with damascus ketone (P 0.05), and Terribacillus was related to the production of β-citral (P 0.05). GH9 may be involved in the formation of damasone (P 0.05), and 4-cyclopentene-1, 3-dione was significantly correlated with glycoside hydrolase family 5 (GH5) (P 0.05). The correlation between 4-oxyisophorone and GH31, GH103, GH73, and GH3 was significant (P 0.05). Microorganisms and GHs may play important roles in FCT fermentation.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Postirradiation sarcoma (PIS) is a rare radiation-induced malignancy after nasopharyngeal carcinoma (NPC) treatment.We retrospectively screened 9,185 NPC patients between 2000 and 2020 and identified 41 patients with PIS according to the modified Cahan's criteria: (1) the PIS must have arisen within a previous radiation field; (2) a latent period must have existed; (3) histologically proved sarcoma; (4) the tissue in which the PIS arose must have been healthy prior to the radiation. The initial radiation therapy techniques used were 2D (25; 61.0%), 3D (7; 17.1%), and IMRT (9; 22%).The time (year) from radiotherapy (RT) to PIS was longer when using 2D or 3D irradiation techniques (median, 14.2; range, 3.4-28.1; Q1-Q3, 8.6-19.7) than when using IMRT (median, 6.6; range, 3.8-15.7; Q1-Q3, 4.5-11.7; P =.026). The time (year) from RT to PIS diagnosis was significantly longer when using lower radiation energy from cobalt-60 (median, 15.8; range, 10.4-28.4; Q1-Q3, 12.5-23.8) than when using a higher radiation energy of 6 or 10 MV (median, 10.2; range, 3.4-23.3; Q1-Q3, 6.5-16.1; P =.006). The 2-year overall survival rates for patients who underwent surgery, radical radiotherapy, systemic therapy alone and no treatment were 60.7 %, 42.9 %, 0 % and 0 %, respectively (P =.000). Of the 3 retrievable initial RT dosimetry plans for NPC, the D95 values (dose that covers 95 % of the PIS volume) for PIS were 6267, 6344 and 5820 cGy, respectively.High radiation energy and modern techniques may shorten NPC PIS latency. Surgery may be associated with improved survival if feasible.

Historical records truthfully document human life and environment associated with climate changes. We quantify official historical records of China dating back last 2000 years to examine the disasters due to anomalous temperatures of cold or hot, irregular precipitations of wet or dry, and floods in inland/coastal or Northern/Southern areas in four seasons that possibly linked to solar activities during 1-1825 CE (Common Era). It is found that the proportion of disaster years is positively associated with the time periods, and therefore, both the cases with high and low solar activity (HSA and LSA) leading are under study. Statistical results show that extreme cold weather occurs particularly in the Winter and Spring during LSA periods. Irregularities precipitations, including heavy rain/hail/snow and severe drought are significantly frequent during LSA periods, while floods on inland and coastal river basins tend to occur more frequently in LSA and HSA periods, respectively. The disasters owing to irregularities precipitations and floods frequently happen in Summer and Autumn, which suggests that the irregular precipitations could cause the floods. All the disasters occur significantly in the Northern China, which suggests the climate boundary of the Qinling–Huaihe Line along at about 33°N being essential. In total, all the disasters due to the anomalously cold temperatures, irregular precipitations, and floods tend to occur during the LSA periods.

Oral dysfunction is a common adverse event of treatment and may affect oral health–related quality of life (OHRQoL). This study aimed to identify factors associated with OHRQoL in patients with oral squamous cell carcinoma (OSCC) within the first three months posttreatment. This cross-sectional study examined OSCC patients who received treatment from the outpatient radiation department of a single cancer center in northern Taiwan. Demographic and clinical characteristics were recorded, and patients were assessed using the Self-Care Behaviors Scale (SCB), Oral Health Impact Profile (OHIP), and Karnofsky Performance Status (KPS) questionnaires. Among 148 OSCC patients, 11.5% reported being underweight and 70.3% reported normal weight. The most common self-care factors associated with adverse effects were decreased appetite and fatigue. Psychological disability, functional limitation, and physical pain were the most negative OHRQoL factors. Poor OHRQoL was associated with more severe adverse effects after self-care behaviors, using feeding tubes during treatment, and having BMI less than 25, which together explained 33.5% of the variance in OHRQoL. The severity of adverse effects after self-care behaviors and using feeding tubes during treatment strongly influenced overall OHRQoL and seven specific dimensions of OHRQoL.

BackgroundWe sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC).MethodsThe study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled.ResultsThe 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122–1.966;p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047–2.583;p = 0.031).ConclusionEarly missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.

Purpose To identify factors associated with resilience in primary caregivers of patients with advanced oral cavity cancer within the first 6 months post-treatment. Design A cross-sectional study. Methods We recruited patient-primary caregiver dyads from the outpatient radiation department of a medical center in Northern Taiwan. Patients were assessed using a set of structured questionnaires to measure performance status and demographic and clinical characteristics. Primary caregivers were measured in their social support, resilience, and care characteristics. Results Of the 148 dyads surveyed, 33.8% of primary caregivers reported moderately low to moderate resilience, and 61.5% reported low resilience. Greater resilience of primary caregivers was associated with the primary caregiver factors of younger age, lower educational level, and more affectionate social support; and greater resilience was associated with the patient factors of better performance status and older age. These factors explained 40.4% of the variance in resilience. Conclusions Patients' performance status and primary caregivers' affectionate social support strongly influence overall resilience and each domain of resilience. Clinical relevance Providing primary caregivers with sufficient social resources and a support group can help them cope with the demands of caregiving for loved ones with oral cavity cancer.

The patient was an 88-year-old woman with a 10-year history of hypertension. She was suspected to have been hit by a car. At the time of the event, she was conscious and able to stand on her own and had no obvious injuries. She was sent home, but she lapsed into unconsciousness and was nonresponsive after 2 hours. She was sent to the hospital, and her heartbeat and breathing stopped. After half an hour of rescue attempts, her heartbeat did not recover, and she was declared dead. During the autopsy, a small subcutaneous hemorrhage was observed below the right knee joint. No obvious internal organ injuries or bone fractures were observed. The deceased also had mild atherosclerosis in the coronary arteries and an old cerebral infarction in the right cerebellum. The tissue histopathological tests showed distinct fat embolism in multiple organs, including the brain, lungs, kidneys, liver, and pancreas. A postmortem blood biochemistry test of the heart blood showed that the levels of low-density lipoprotein, cholesterol, triglycerides, and free fatty acids in the blood were increased, and the level of C-reactive protein was elevated. According to the autopsy results, the direct cause of death was multiorgan fat embolism. This case suggests that aging, hypertension, and hyperlipidemia may be risk factors for nontraumatic fat embolism under stressful conditions.

The transient photocurrent (TPC) technique was performed to explore the dynamics of excitons and carriers at organic active layer/buffer layer interfaces. A special device with ITO/PEIE/NPB/C60/Al structure was designed to study the interfacial processes at the NPB/C60 interface. An external electrical field was provided to neutralize the built-in electrical field of the device. Interestingly, a new phenomenon was observed, wherein the polarity of the TPC changed from negative to positive under an external electrical field. The initial negative signal was ascribed to exciton separation by the built-in field in C60, and the subsequent positive signal can be attributed to the diffusion of electrons that accumulate at the NPB/C60 interface. TPC measurements shown that further increasing the external electrical field causes polarity to change twice. Analyzing the two changes in polarity revealed that the NPB did not only extract holes from C60 but also provided an effective interface for exciton dissociation.

Situated between the North China Craton to the east and the Tarim Craton to the west, the northern Alxa area in westernmost Inner Mongolia in China occupies a key location for interpreting the late-stage tectonic evolution of the southern Central Asian Orogenic Belt. New LA-ICP-MS zircon U–Pb dating results reveal 282.2 ± 3.9 Ma gabbros and 216.3 ± 3.2 Ma granites from the Yagan metamorphic core complex in northern Alxa, NW China. The gabbros are characterized by low contents of Si, Na, K, Ti and P and high contents of Mg, Ca, Al and Fe. These gabbros have arc geochemical signatures with relative enrichments in large ion lithophile elements and depletions in high field strength elements, as well as negative εNd(t) (−0.91 to −0.54) and positive εHf(t) (2.59 to 6.37) values. These features indicate that a depleted mantle magma source metasomatized by subduction fluids/melts and contaminated by crustal materials was involved in the processes of magma migration and emplacement. The granites show high-K calc-alkaline and metaluminous to weakly peraluminous affinities, similar to A-type granites. They have positive εNd(t) (1.55 to 1.99) and εHf(t) (5.03 to 7.64) values. These features suggest that the granites were derived from the mixing of mantle and crustal sources and formed in a postcollisional tectonic setting. Considering previous studies, we infer that the final closure of the Palaeo-Asian Ocean in the central part of the southern Central Asian Orogenic Belt occurred in late Permian to Early–Middle Triassic times.

We applied environmentally friendly ferric complexes (i.e., FeCl3/PPh3) to one of the most widely-used controlled/living polymerizations (CRP), atom transfer radical polymerisation (ATRP), for the preparation of well-defined poly(methyl methacrylate) (PMMA) homo- and block (co)polymers. Iron-catalysed supplemental activator and reducing agent (SARA) and activators regenerated by electron transfer (ARGET) ATRPs were investigated using cost-effective Cu(0), Fe(0), and the natural antioxidant proanthocyanidins (PC) as reducing agents. With different ratios of Fe(III)/Cu(0) and Fe(III)/Fe(0) for ATRPs of MMA, the former exhibited fast apparent reaction rates (kapps >3 × 10−5 s−1), but showed large PDI values (>1.6); the latter exhibited moderate kapps ( = ca. 7 × 10−6–3 × 10−5 s−1) with low PDI values (

In this study, a new Multivariable Grey Model (1,m) aimed at interval grey number sequences with known possibility functions is built using the kernel and degree of greyness under new definitions. Based on the new model, formulae are deduced to calculate and predict the upper and lower bounds of interval grey numbers. Since the grey system model and fog- and haze-prone weather have the same characteristics of uncertainty, this model was applied to simulate and predict the measurable indicators of fog and haze in Nanjing, China. We selected visibility data and particulate matter data with a diameter of 2.5 µm to build a new Multivariable Grey Model (1,2) with a new kernel and degree of greyness sequence. In addition, we established the traditional Multivariable Grey Model (1,2) with the original kernel and degree of greyness and the Auto-Regressive Integrated Moving Average Model (1,1,0). The results show that the new Multivariable Grey Model (1,2) has the best simulation and prediction effects among the three models, with average relative errors of simulation and prediction at 1.32% and 0.32%, respectively. To further verify the validity and feasibility of the proposed model, we added another real-world example to establish the three models mentioned above. The results prove that the proposed model has evidently superior performance to another two models.

Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.

Simple Summary Chronic rhinosinusitis (CRS) is a common treatment complication in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. In this study, we aimed to investigate the incidence and severity of CRS in NPC patients who underwent intensity-modulated proton therapy (IMPT) by evaluating the sinus mucosa change in imaging studies, and we compared these patients with those who underwent volume-modulated arc therapy (VMAT). This was a retrospective case–control study in which 53 and 54 patients were treated with IMPT and VMAT, respectively. We noted that patients in the IMPT group had a significantly lower incidence and decreased severity of sinus mucosa abnormality than those with VMAT. Better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed. IMPT techniques deposit the bulk of their radiation doses in highly confined areas, allowing lower exposure of non-target organs during irradiation, which results in more sinonasal mucosa being retained. Abstract In the past decade, patients with nasopharyngeal cancer (NPC) have been deemed candidates for proton radiotherapy, due to the large and comprehensive target volumes and the necessity for the retention of the surrounding healthy tissues. In this study, we aimed to compare the incidence and severity of post-irradiation sinusitis by detecting sinus mucosa diseases (SMDs) via the magnetic resonance imaging (MRI) of patients with NPC after intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT). A total of 53 patients in the IMPT group and 54 patients in the VMAT group were enrolled in this study. There were significantly lower endoscopic scores and Lund–Mackay staging scores determined from MRI scans in the IMPT group during different follow-up periods. For the most vulnerable sinuses, the incidence and severity of SMD were the highest during the third post-radiotherapy month in both groups. These decreased steadily, and there was no significant increase in the incidence and severity of SMD during the second post-radiotherapy year in the IMPT group. Our data show that NPC patients with IMPT have a significantly lower incidence and decreased severity of SMD than those with VMAT. A better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed.

Objective To identify the factors associated with barriers to and facilitators of return to work (RTW) in head and neck cancer (HNC) patients in the first six months post-treatment. Methods This cross-sectional study examined HNC patients who completed treatment from the outpatient radiation department of a single cancer center in northern Taiwan from October 2018 to July 2020. Demographic and clinical characteristics were recorded, and patients were assessed using the Return to Work Barrier Scale, Return to Work Facilitator Scale, Distress Thermometer, Numeric Rating Scale, and Karnofsky Performance Status Scale questionnaires. Results Of the 106 HNC patients surveyed, 54.7% successfully RTW. Barriers to RTW included patient-perceived worst health status, greater symptom burden, and age ≥55 years. These factors explained 34.6% of the variance in overall barriers to RTW. Facilitators of RTW were lower psychological distress and who did not receive reconstruction surgery. These factors explained 17.9% of the variance in facilitators to RTW. Conclusion Patient-perceived health status and age most strongly influence RTW in HNC patients. HNC patients who can RTW should be encouraged to do so, and clinician awareness of potential barriers can aid patients in their RTW.

Whether women with a history of miscarriage or stillbirth have an increased risk of diabetes is inconclusive. We aimed to systematically assess the association between them.We searched PubMed, Web of Science and Scopus through November 2022. Random-effect model for meta-analysis was applied to calculate pooled odds ratios and corresponding 95 % confidence intervals (CIs) when heterogeneity was 40 %.Thirteen cohort studies and eight case-control studies with a total of 529,990 participants were included. Women ever experiencing a miscarriage had a 1.15-fold risk of non-gestational diabetes (95% CI: 1.02-1.28) and a 1.62-fold risk of gestational diabetes (95% CI: 1.32-1.98) compared to those never experiencing a miscarriage. Of them, women with three or more miscarriages had a 1.99-fold risk of non-gestational diabetes (95% CI: 1.36-2.91). The risk of non-gestational diabetes among women ever experiencing a stillbirth was 1.21 times compared with those never experiencing a stillbirth (95% CI: 1.03-1.41). Pooled results did not support a stable association between stillbirth and gestational diabetes risk (odds ratio:1.91, 95% CI: 1.00-3.64).A history of miscarriage or stillbirth was associated with an increased risk of diabetes in women. Future studies are needed to explore whether prediabetic metabolic conditions contribute to this association.

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.