Digital Light Processing to Afford High Resolution and Degradable CO2-Derived Copolymer Elastomers.

Vat photopolymerization 3D printing has proven very successful for the rapid additive manufacturing (AM) of polymeric parts at high resolution. However, the range of materials that can be printed and their resulting properties remains narrow. Herein, we report the successful AM of a series of poly(carbonate-b-ester-b-carbonate) elastomers, derived from carbon dioxide and bio-derived ϵ-decalactone. By employing a highly active and selective Co(II)Mg(II) polymerization catalyst, an ABA triblock copolymer (Mn=6.3 kg mol-1, ÐM=1.26) was synthesized, formulated into resins which were 3D printed using digital light processing (DLP) and a thiol-ene-based crosslinking system. A series of elastomeric and degradable thermosets were produced, with varying thiol cross-linker length and poly(ethylene glycol) content, to produce complex triply periodic geometries at high resolution. Thermomechanical characterization of the materials reveals printing-induced microphase separation and tunable hydrophilicity. These findings highlight how utilizing DLP can produce sustainable materials from low molar mass polyols quickly and at high resolution. The 3D printing of these functional materials may help to expedite the production of sustainable plastics and elastomers with potential to replace conventional petrochemical-based options.

Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics.

BACKGROUND: Intratumour heterogeneity is a hallmark of most solid tumours, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing on patient-derived xenografts (PDXs) to profile spatially resolved cell populations within oestrogen receptor-positive (ER+ ) breast cancer and to elucidate their importance in oestrogen-dependent tumour growth. METHODS: Two PDXs of 'ER-high' breast cancers with opposite oestrogen-mediated growth responses were investigated: oestrogen-suppressed GS3 (80-100% ER) and oestrogen-dependent SC31 (40-90% ER) models. The observation was validated via single-cell analyses on an 'ER-low' PDX, GS1 (5% ER). The results from our spatial and single-cell analyses were further supported by a public ER+ breast cancer single-cell dataset and protein-based dual immunohistochemistry (IHC) of SC31 examining important luminal cancer markers (i.e., ER, progesterone receptor and Ki67). The translational implication of our findings was assessed by clinical outcome analyses on publicly available cohorts. RESULTS: Our space-gene-function study revealed four spatially distinct compartments within ER+ breast cancers. These compartments showed functional diversity (oestrogen-responsive, proliferative, hypoxia-induced and inflammation-related). The 'proliferative' population, rather than the 'oestrogen-responsive' compartment, was crucial for oestrogen-dependent tumour growth, leading to the acquisition of luminal B-like features. The cells expressing typical oestrogen-responsive genes like PGR were not directly linked to oestrogen-dependent proliferation. Dual IHC analyses demonstrated the distinct contribution of the Ki67+ proliferative cells toward oestrogen-mediated growth and their response to a CDK4/6 inhibitor. The gene signatures derived from the proliferative, hypoxia-induced and inflammation-related compartments were significantly correlated with worse clinical outcomes, while patients with the oestrogen-responsive signature showed better prognoses, suggesting that this compartment would not be directly associated with oestrogen-dependent tumour progression. CONCLUSIONS: Our study identified the gene signature in our 'proliferative' compartment as an important determinant of luminal cancer subtypes. This 'proliferative' cell population is a causative feature of luminal B breast cancer, contributing toward its aggressive behaviours.

Examining the validity of the Delis-Kaplan Executive Function System (D-KEFS) in traumatic brain injury.

This study examines the validity of the Delis-Kaplan Executive Function System (D-KEFS) in a traumatic brain injury (TBI) population compared to participants with orthopaedic injuries and normative controls. The utility of the D-KEFS was examined using a between groups design. One hundred patients with mild uncomplicated to severe TBI were recruited from a consecutive cohort of patients admitted as inpatients to a UK Major Trauma Centre and compared to 823 participants from the D-KEFS normative sample and 26 participants with orthopaedic injuries. Data were filtered for performance validity. Sample discrimination was calculated from D-KEFS subtest scores and derived index scores. Sensitivity to TBI severity was established. The TBI participants performed significantly lower on the D-KEFS Trail Making Test, Colour Word Interference, Colour Word Switching, Letter Fluency and Verbal Fluency Category Switching Total Words Correct. The D-KEFS index scores discriminated between TBI, orthopaedic and normative participants with large and moderate effect sizes, respectively. The D-KEFS demonstrated a dose-response relationship with TBI severity. These effects were robust to differences in premorbid intellectual functioning; however, D-KEFS performance was sensitive to performance on tests of mental processing speed. The use of a D-KEFS index score provides a robust and reliable discrimination of TBI patients from healthy control participants. This discrimination is not accounted for by premorbid intellect or the non-specific effects of trauma. The clinical and conceptual implications of these findings are considered.

Eagle jugular syndrome presenting with intracranial hypertension - Diagnosis and illustration of pathophysiology by multi-modality imaging.

Eagle jugular syndrome is an uncommon condition caused by compression of an elongated styloid process onto the internal jugular vein. Its presentation is non-specific but may represent in severe clinical consequences including venous thrombosis and intracranial haemorrhage. Thorough understanding of local anatomy is important in understanding the pathogenesis and establishing the diagnosis. Our case reported here illustrates the use of multimodality imaging, including dynamic Computer tomography manoeuvre, in identifying the site of obstruction and guidance towards successful surgical treatment.

The Effect of Light Pollution on the Sea Finding Behavior of Green Turtle Hatchlings on Lanyu Island, Taiwan.

octurnal animals use their vision and acute hearing to adapt to the nighttime environment. Light pollution has become a serious problem for nocturnal animals in coastal areas, especially nesting sea turtles and sea turtle hatchlings. Hatchlings use visual clues to find the ocean. However, when the artificial light is stronger than the natural light, hatchlings become either misoriented, disoriented or both. Due to rapid tourism development on Lanyu Island, new sources of light pollution, especially streetlights, pose a serious threat to sea turtle hatchlings. In this study, we used a portable lamp constructed by Liteon Inc. on a circular area of a turtle nesting beach to see how artificial light sources could affect green turtle hatchlings' sea finding behavior. In the experiments, we tested hatchling behavior under different lamp settings (strong or weak light intensity; white or yellow light; lamp shield presence or absence) and moon visibilities (moonlit or moonless). The hatchlings' crawling tracks and locations at the end of the trials were recorded. Results showed that the light intensity had no effect on hatchling sea finding behavior. White light had a stronger impact on hatchling sea finding behavior than yellow light. When the lamp shield was installed on moonlit nights, more hatchings were able to find the sea under both white and yellow lights. Thus, it is recommended that light shields be installed on the streetlights of Lanyu Island in order to protect the sea turtle hatchlings effectively.

Functional Objects in Urban Walking Environments and Pedestrian Trajectory Modelling.

Functional objects are large and small physical entities installed in urban environments to offer specific functionalities to visitors, such as shops, escalators, and information kiosks. Instances of the novel notion are focal points of human activities and are significant in pedestrian movement. Pedestrian trajectory modelling in an urban scene is a challenging problem because of the complex patterns resulting from social interactions of the crowds and the diverse relation between pedestrians and functional objects. Many data-driven methods have been proposed to explain the complex movements in urban scenes. However, the methods considering functional objects in their formulation are rare. This study aims to reduce the knowledge gap by demonstrating the importance of pedestrian-object relations in the modelling task. The proposed modelling method, called pedestrian-object relation guided trajectory prediction (PORTP), uses a dual-layer architecture that includes a predictor of pedestrian-object relation and a series of relation-specific specialized pedestrian trajectory prediction models. The experiment findings indicate that the inclusion of pedestrian-object relation results in more accurate predictions. This study provides an empirical foundation for the novel notion and a strong baseline for future work on this topic.

Identification and characterization of a proliferative cell population in estrogen receptor-positive metastatic breast cancer through spatial and single-cell transcriptomics.

Background: Intratumor heterogeneity is a hallmark of most solid tumors, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing technologies to profile spatially resolved cell populations within estrogen receptor-positive (ER + ) metastatic breast cancers and elucidate their importance in estrogen-dependent tumor growth. Methods: Spatial transcriptomics and single-cell RNA-sequencing were performed on two patient-derived xenografts (PDXs) of "ER-high" metastatic breast cancers with opposite estrogen-mediated growth responses: estrogen-suppressed GS3 (80-100% ER) and estrogen-stimulated SC31 (30-75% ER) models. The analyses included samples treated with and without 17ß-estradiol. The findings were validated via scRNA-seq analyses on "ER-low" estrogen-accelerating PDX, GS1 (5% ER). The results from our spatial and single-cell analyses were further supported by the analysis of a publicly available single cell dataset and a protein-based dual immunohistochemical (IHC) evaluation using three important clinical markers [i.e., ER, progesterone receptor (PR), and Ki67]. The translational implication of these results was assessed by clinical outcome analyses on public breast cancer cohorts. Results: Our novel space-gene-function study revealed a "proliferative" cell population in addition to three major spatially distinct compartments within ER + metastatic breast cancers. These compartments showed functional diversity (i.e., estrogen-responsive, proliferative, hypoxia-induced, and inflammation-related). The "proliferative ( MKI67 + )" population, not "estrogen-responsive" compartment, was crucial for estrogen-dependent tumor growth, leading to the acquisition of luminal B features. The cells with induction of typical estrogen-responsive genes such as PGR were not directly linked to estrogen-dependent proliferation. Additionally, the dual IHC analyses demonstrated the distinct contribution of the Ki67 + proliferative cells toward estrogen-mediated growth and their response to palbociclib, a CDK4/6 inhibitor. The gene signatures developed from the proliferative, hypoxia-induced, and inflammation-related compartments were significantly correlated with worse clinical outcomes, while patients with the high estrogen-responsive scores showed better prognosis, confirming that the estrogen-responsive compartment would not be directly associated with estrogen-dependent tumor progression. Conclusions: For the first time, our study elucidated a "proliferative" cell population distinctly distributed in ER + metastatic breast cancers. They contribute differently toward progression of these cancers, and the gene signature in the "proliferative" compartment is an important determinant of luminal cancer subtypes.

An efficient approach to estimate the risk of coronary artery disease for people living with HIV using machine-learning-based retinal image analysis.

BACKGROUND: People living with HIV (PLWH) have increased risks of non-communicable diseases, especially cardiovascular diseases. Current HIV clinical management guidelines recommend regular cardiovascular risk screening, but the risk equation models are not specific for PLWH. Better tools are needed to assess cardiovascular risk among PLWH accurately. METHODS: We performed a prospective study to determine the performance of automatic retinal image analysis in assessing coronary artery disease (CAD) in PLWH. We enrolled PLWH with ≥1 cardiovascular risk factor. All participants had computerized tomography (CT) coronary angiogram and digital fundus photographs. The primary outcome was coronary atherosclerosis; secondary outcomes included obstructive CAD. In addition, we compared the performances of three models (traditional cardiovascular risk factors alone; retinal characteristics alone; and both traditional and retinal characteristics) by comparing the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: Among the 115 participants included in the analyses, with a mean age of 54 years, 89% were male, 95% had undetectable HIV RNA, 45% had hypertension, 40% had diabetes, 45% had dyslipidemia, and 55% had obesity, 71 (61.7%) had coronary atherosclerosis, and 23 (20.0%) had obstructive CAD. The machine-learning models, including retinal characteristics with and without traditional cardiovascular risk factors, had AUC of 0.987 and 0.979, respectively and had significantly better performance than the model including traditional cardiovascular risk factors alone (AUC 0.746) in assessing coronary artery disease atherosclerosis. The sensitivity and specificity for risk of coronary atherosclerosis in the combined model were 93.0% and 93.2%, respectively. For the assessment of obstructive CAD, models using retinal characteristics alone (AUC 0.986) or in combination with traditional risk factors (AUC 0.991) performed significantly better than traditional risk factors alone (AUC 0.777). The sensitivity and specificity for risk of obstructive CAD in the combined model were 95.7% and 97.8%, respectively. CONCLUSION: In this cohort of Asian PLWH at risk of cardiovascular diseases, retinal characteristics, either alone or combined with traditional risk factors, had superior performance in assessing coronary atherosclerosis and obstructive CAD. SUMMARY: People living with HIV in an Asian cohort with risk factors for cardiovascular disease had a high prevalence of coronary artery disease (CAD). A machine-learning-based retinal image analysis could increase the accuracy in assessing the risk of coronary atherosclerosis and obstructive CAD.

Mechanism-Driven and Clinically Focused Development of Botanical Foods as Multitarget Anticancer Medicine: Collective Perspectives and Insights from Preclinical Studies, IND Applications and Early-Phase Clinical Trials.

Cancer progression and mortality remain challenging because of current obstacles and limitations in cancer treatment. Continuous efforts are being made to explore complementary and alternative approaches to alleviate the suffering of cancer patients. Epidemiological and nutritional studies have indicated that consuming botanical foods is linked to a lower risk of cancer incidence and/or improved cancer prognosis after diagnosis. From these observations, a variety of preclinical and clinical studies have been carried out to evaluate the potential of botanical food products as anticancer medicines. Unfortunately, many investigations have been poorly designed, and encouraging preclinical results have not been translated into clinical success. Botanical products contain a wide variety of chemicals, making them more difficult to study than traditional drugs. In this review, with the consideration of the regulatory framework of the USFDA, we share our collective experiences and lessons learned from 20 years of defining anticancer foods, focusing on the critical aspects of preclinical studies that are required for an IND application, as well as the checkpoints needed for early-phase clinical trials. We recommend a developmental pipeline that is based on mechanisms and clinical considerations.

Plant-mediated synthesis of silver-doped ZnO nanoparticles with high sonocatalytic activity: Sonocatalytic behavior, kinetic and thermodynamic study.

Together with the rapid growth of technology, the discharge of wastewater from industry into environment had become a hot topic among society nowadays. More attention had been given to the development of water treatment techniques. In this study, sonocatalysis was proposed to degrade the organic pollutants using silver-doped zinc oxide (Ag-ZnO) nanoparticles which were synthesized via green synthesis process using Clitoria ternatea Linn (Asian Pigeonwings flower). The characterization results revealed that the incorporation of Ag into the ZnO lattice decreased the crystallite size and increased the specific surface area of ZnO nanoparticles. It is noteworthy that about 98% of sonocatalytic degradation efficiency of malachite green (MG) was successfully achieved within 30 min in the presence of 5 wt.% Ag-ZnO with 1.0 g/L of catalyst loading under 500 mg/L of initial dye concentration, 80 W of ultrasonic power, 45 kHz of ultrasound frequency, and 2.0 mM of oxidant concentration. The kinetic study showed that the sonocatalytic degradation of organic dye was fitted well into second-order kinetic model with high R2 value (0.9531). In the thermodynamic study, negative value of standard Gibbs free energy and low value of activation energy (+ 24.43 kJ/mol) were obtained in the sonocatalytic degradation of MG using the green-synthesized Ag-ZnO sample. HIGHLIGHTS: • Facile synthesis of silver-doped zinc oxide nanoparticles using plant extract which act as reducing and stabilizing agents • Optical, physical, and chemical characterization of green-synthesized nanomaterials were performed • Evaluation of sonocatalytic degradation of organic dye using green-synthesized nanomaterials • Sonocatalytic behavior, kinetic and thermodynamic studies of sonocatalytic reaction.

Sarcopenia in people living with HIV in Hong Kong: which definition correlates with health outcomes?

INTRODUCTION: Sarcopenia is an important clinical syndrome in older people living with HIV (PLWH). With a change to the Asia sarcopenia definition in 2019, we aimed to determine whether health outcomes were associated with different definitions of sarcopenia among Asian PLWH. METHODS: We performed a prospective cross-sectional study enrolling PLWH aged ≥35 years from January 2018 to November 2021. We defined sarcopenia by the Asia Working Group of Sarcopenia (AWGS) criteria in 2014 and 2019. AWGS-2014 included low muscle mass plus weak handgrip strength and/or slow gait speed. AWGS-2019 included low muscle mass plus low muscle strength or physical performance, while the presence of all defines severe sarcopenia. We measured appendicular skeletal muscle mass using dual-energy X-ray absorptiometry, handgrip strength, usual gait speed, five-time chair stand test and Short Physical Performance Battery. Correlations between each sarcopenia definition and health-related quality of life (using EQ-5D-5L and SF-36) and functional disability were determined. RESULTS: One hundred and fifty Asian PLWH were enrolled, 132 (88%) were male, mean age was 60±10 years, duration of HIV diagnosis was 13 (IQR 8-18) years and current CD4 count was 574 (IQR 362-762) cells/mm3 , 67 (45%) had multimorbidity, 64 (43%) had polypharmacy. Prevalence of sarcopenia by AWGS-2014, AWGS-2019 and severe sarcopenia was 17.3%, 27.3% and 18.0%, respectively. Age, education and polypharmacy were associated with sarcopenia. Sarcopenia (AWGS-2014) and severe sarcopenia were associated with mobility, physical functioning and physical component score (SF-36). All three criteria were associated with impaired instrumental activities of daily living (IADL). After age and sex adjustment, sarcopenia (AWGS-2014) (adjusted odds ratio/aOR 5.4, 95% confidence interval/CI 2.0-15.1) and severe sarcopenia (aOR 5.1, 95% CI 1.9-14.0) were associated with mobility and physical component score (SF-36) (ß coefficients -5.3342, p = 0.022 and -5.412, p = 0.019). Sarcopenia (AWGS 2014) (aOR 5.2, 95% CI 1.7-16.2), sarcopenia (AWGS-2019) (aOR 4.5, 95% CI 1.5-13.1) and severe sarcopenia (aOR 3.5, 95% CI 1.1-10.9) were associated with impaired IADL in fully adjusted models. CONCLUSIONS: In a sample of Asian PLWH, 17.3%, 27.3% and 18.0% had sarcopenia as defined by AWGS-2014, AWGS-2019 and severe sarcopenia, respectively. Sarcopenia by AWGS-2014 and severe sarcopenia correlated with parameters of poor health outcomes, while sarcopenia by AWGS-2019 correlated with functional disability.

It Takes Two to Tango: Synergistic Expandable Graphite-Phosphorus Flame Retardant Combinations in Polyurethane Foams.

Due to the high flammability and smoke toxicity of polyurethane foams (PUFs) during burning, distinct efficient combinations of flame retardants are demanded to improve the fire safety of PUFs in practical applications. This feature article focuses on one of the most impressive halogen-free combinations in PUFs: expandable graphite (EG) and phosphorus-based flame retardants (P-FRs). The synergistic effect of EG and P-FRs mainly superimposes the two modes of action, charring and maintaining a thermally insulating residue morphology, to bring effective flame retardancy to PUFs. Specific interactions between EG and P-FRs, including the agglutination of the fire residue consisting of expanded-graphite worms, yields an outstanding synergistic effect, making this approach the latest champion to fulfill the demanding requirements for flame-retarded PUFs. Current and future topics such as the increasing use of renewable feedstock are also discussed in this article.

Modeling the Impact of Vaccination on COVID-19 and Its Delta and Omicron Variants.

Vaccination is an important means to fight against the spread of the SARS-CoV-2 virus and its variants. In this work, we propose a general susceptible-vaccinated-exposed-infected-hospitalized-removed (SVEIHR) model and derive its basic and effective reproduction numbers. We set Hong Kong as an example and calculate conditions of herd immunity for multiple vaccines and disease variants. The model shows how the number of confirmed COVID-19 cases in Hong Kong during the second and third waves of the COVID-19 pandemic would have been reduced if vaccination were available then. We then investigate the relationships between various model parameters and the cumulative number of hospitalized COVID-19 cases in Hong Kong for the ancestral, Delta, and Omicron strains. Numerical results demonstrate that the static herd immunity threshold corresponds to one percent of the population requiring hospitalization or isolation at some point in time. We also demonstrate that when the vaccination rate is high, the initial proportion of vaccinated individuals can be lowered while still maintaining the same proportion of cumulative hospitalized/isolated individuals.

Lower-Limb Muscle Activity During Aquatic Treadmill Running in Individuals With Anterior Cruciate Ligament Reconstruction.

INTRODUCTION: While anterior cruciate ligament (ACL) tears are commonly managed with ACL reconstruction (ACL-R), 35% of ACL-R individuals fail to return to the preinjury elite sport level. Persistent neuromuscular deficits in the hamstrings and quadriceps have been observed. It has been proposed that aquatic therapy can be used to optimize neuromuscular control after ACL-R. OBJECTIVES: (1) To compare muscle activity in ACL-R individuals during aquatic treadmill (ATM) running at different water depths and (2) to compare muscle activity during ATM running between ACL-R and healthy individuals. METHODS: A total of 38 participants, including 18 ACL-R individuals (mean postoperative time [SD] = 25.8 [25.0] mo) and 20 healthy individuals were recruited. Muscle activity of biceps femoris (BF), rectus femoris (RF), tibialis anterior, and medial gastrocnemius during land treadmill and ATM running at mid-shin, mid-thigh, and waist levels were recorded using surface electromyography (sEMG).  The sEMG signals of the selected muscles were normalized and expressed in % Maximal Voluntary Contraction (%MVC). Muscle activity of the ACL-R, ACL-contralateral, and healthy control limbs at different water depths was compared. RESULTS: Among the 3 groups, the ACL-R group demonstrated the most prominent percentage increase of 101.97% (P = .001) at mid-shin level, 139.66% (P = .001) at mid-thigh level, and 141.97% (P < .001) at waist level, respectively, in %MVC when compared to land. In the ACL-R group, muscle activity of BF in the stance phase (BFSt) was significantly higher than the control group on land at all water depths. Muscle activity of RF in the swing phase (RFSw) in the ACL-R group significantly increased in all water depths immersion when compared to land, respectively. CONCLUSION: This study showed an increasing trend in muscle activity of BFSt and RFSw in ACL-R individuals during ATM running at increased water depths. ATM running could be implemented as neuromuscular training in rehabilitation after ACL-R.

The effect of drying methods on the physicochemical and antioxidant properties of Bintangor orange (Citrus nobilis) powders.

BACKGROUND: Bintangor oranges are a mandarin species that is abundant in vitamin C and beta-carotene. However, due to its short shelf life, the fresh fruit can be converted into powder form, which is comparatively more stable. METHODS: This study compares the effects of spray drying, freeze drying, drum drying, vacuum oven drying, and convection oven drying on the physicochemical properties of Bintangor orange powder, including vitamin C and total carotenoid content. The physicochemical properties analyzed for the powders were color analysis, moisture content, water activity, hygroscopicity, degree of caking, wettability, flowability, water solubility index, and bulk density. RESULTS: Our results showed that freeze dried and convection oven dried powders retained their color so that the powder was the same as the original puree. All powders used in this showed an acceptable moisture content level, with a range of 2.11–2.31%. Spray dried and drum dried powders had the lowest value of moisture content and water activity. Moreover, spray dried powders showed the lowest value in hygroscopicity and bulk density and took the shortest time to wet the powder. The highest solubility and flowability properties were 12.99%, 0.39 g/mL, 18.39 s, 96.08%, and 19.17°, respectively. However, the freeze drying method retained the highest value for both nutritional pigments of vitamin C and total carotenoid content, 18.31 mg/g and 91.32 μg/g, respectively. CONCLUSIONS: Freeze drying is the most suitable drying method with favorable powder properties compared to spray drying, drum drying, vacuum oven drying and convection oven drying.

Clinical Course and Treatment Implications of Combination Immune Checkpoint Inhibitor-Mediated Hepatitis: A Multicentre Cohort.

BACKGROUND: Immune-related adverse events can occur after treatment with immune checkpoint inhibitors (ICI), limiting treatment persistence. We aimed to evaluate the clinical course of ICI-mediated hepatitis (IMH) associated with combination ipilimumab and nivolumab treatment. METHODS: A retrospective cohort study including consecutive patients with metastatic melanoma treated with ipilimumab and nivolumab between 2013 and 2018 was conducted at two tertiary care centres. IMH was defined by the Common Terminology Criteria for Adverse Events (CTCAE). We determined the proportion of patients developing IMH, and compared the duration, treatment patterns and outcomes, stratified by hepatitis severity. Kaplan-Meier survival analysis was used to evaluate time to hepatitis resolution, and a linear mixed-effects model was used to compare longitudinal outcomes by treatment. RESULTS: A total of 63 patients were included. Thirty-two patients (51%) developed IMH (34% Grade 1-2, 66% Grade 3-4), at a median of 34 days (IQR 20 to 43.5 days) after the first dose. Baseline FIB4 index ≥1.45 was associated with IMH (OR 3.71 [95% CI: 1.03 to 13.38], P = 0.04). Ninety-four per cent (30/32) of patients had liver enzyme normalization after a median duration of 43 days (IQR 26 to 70 days). Corticosteroid use was not associated with faster IMH resolution or less ICI discontinuation. A total of 24 patients died during the study; no deaths were attributable to hepatitis-related complications. Fifty-three per cent (17/32) of patients resumed anti-PD-1 monotherapy and three patients developed IMH recurrence. CONCLUSIONS: Approximately half of the patients treated with combination ipilimumab and nivolumab developed IMH in this cohort. However, most patients experienced uncomplicated IMH resolution.

Reassessing Undergraduate Polymer Chemistry Laboratory Experiments for Virtual Learning Environments.

Chemistry laboratory experiments are invaluable to students' acquisition of necessary synthetic, analytical, and instrumental skills during their undergraduate studies. However, the COVID-19 pandemic rendered face-to-face (f2f), in-person teaching laboratory experiences impossible from late 2019-2020 and forced educators to rapidly develop new solutions to deliver chemistry laboratory education remotely. Unfortunately, achieving learning and teaching objectives to the same caliber of in-person experiments is very difficult through distance learning. To overcome these hurdles, educators have generated many virtual and remote learning options for not only foundational chemistry courses but also laboratory experiments. Although the pandemic challenged high-level chemistry education, it has also created an opportunity for both students and educators to be more cognizant of virtual learning opportunities and their potential benefits within chemistry curriculum. Irrespective of COVID-19, virtual learning techniques, especially virtual lab experiments, can complement f2f laboratories and offer a cost-efficient, safe, and environmentally sustainable alternative to their in-person counterparts. Implementation of virtual and distance learning techniques-including kitchen chemistry and at-home laboratories, prerecorded videos, live-stream video conferencing, digital lab environment, virtual and augmented reality, and others-can provide a wide-ranging venue to teach chemistry laboratories effectively and encourage diversity and inclusivity in the field. Despite their relevance to real-world applications and potential to expand upon fundamental chemical principles, polymer lab experiments are underrepresented in the virtual platform. Polymer chemistry education can help prepare students for industrial and academic positions. The impacts of polymers in our daily life can also promote students' interests in science and scientific research. Hence, the translation of polymer lab experiments into virtual settings improves the accessibility of polymer chemistry education. Herein, we assess polymer experiments in the emergence of virtual learning environments and provide suggestions for further incorporation of effective polymer teaching and learning techniques into virtual settings.

Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts.

Xenoestrogens and phytoestrogens are referred to as "foreign estrogens" that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.