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Ching-Feng Chiu,1–3 Guan-Ying Lai,4 Chung-Hwan Chen,5–7 Chien-Chao Chiu,8 Shao-Wen Hung,8,9 Chi-Fen Chang10 1Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; 2TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan; 3TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan; 4Master Program for Pharmaceutical Manufacture, China Medical University, Taichung 40402, Taiwan; 5Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; 6Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 7Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 8Division of Animal Industry, Animal Technology Laboratories, Agricultural Technology Research Institute, Xiangshan, Hsinchu 300, Taiwan; 9Nursing Department, Yuanpei University, Xiangshan, Hsinchu 300, Taiwan; 10Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan Background: Colorectal cancer is the third leading cause of cancer-related deaths worldwide, and therefore, the development of novel drugs for its prevention and therapy are urgently required. This study aimed to determine the molecular mechanism of 6,7-dihydroxy-2-(4'-hydroxyphenyl)naphthalene (PNAP-6)-induced cytotoxicity in human colorectal cancer (HCT116) cells.Methods: The effects of 2-phenylnaphthalene derivatives on HCT116 cell growth and viability were assessed by MTT assays. The mechanisms involved in the regulation of the extrinsic apoptosis and endoplasmic reticulum (ER) stress pathways by PNAP-6 were analyzed by annexin-V/propidium iodide flow cytometric analysis, Hoechst 33342 fluorescent staining, and Western blotting.Results: PNAP-6 was shown to have an IC50 value 15.20 µM. It induced G2/M phase arrest in HCT116 cells, associated with a marked decrease in cyclin B and CDK1 protein expression and increased caspase activation, PARP cleavage, chromatin condensation, and sub-G1 apoptosis. Moreover, we found that the apoptotic effects of PNAP-6 proceeded through extrinsic apoptosis and ER stress pathways, by increasing the expression of Fas protein and ER stress markers, including PERK, ATF4, CHOP, p-IRE1α, and XBP-1s.Conclusion: These results suggest that 2-phenylnaphthalene derivatives, such as PNAP-6, have potential as new treatments for colorectal cancer. Keywords: colorectal cancer, endoplasmic reticulum stress, extrinsic apoptosis pathway, 2-phenylnaphthalenes

This report provides a summary of the identified evidence gaps and a general discussion of the next steps to advance cancer epidemiology research in Hispanic/Latino (H/L) populations based partly on the workshop, "Cancer Epidemiology in Hispanic Populations," convened by the NCI in September 2021. The cancer burden among H/L populations varies greatly by nativity and country of origin, yet this variation is not often captured due to systemic challenges in how racial/ethnic data have been collected and often reported in aggregate for this heterogeneous population. Developing culturally relevant assessment tools, increasing the representation of H/L participants, and adopting appropriate methodologic approaches are critical to enhancing cancer research. There is a variety of current funding mechanisms that may be used to address these evidence gaps and priorities, including investigator-initiated mechanisms. Cancer epidemiologic research in H/L populations should leverage existing resources where possible. New and ongoing studies should collect information on nativity status, country of origin, and related measures, use culturally specific assessment tools, engage in collaborative science, and maintain strong community engagement to build studies that will meaningfully address the cancer burden experienced by the growing H/L population., (©2024 American Association for Cancer Research.)

Objective: To assess if ventricular size before shunting is correlated with neurodevelopmental outcomes in children with postnatal myelomeningocele closure., Study Design: This retrospective review included children with postnatal surgical closure of myelomeningocele and neuropsychological testing between 2018 and 2023 at the University of California, San Francisco. Frontal-occipital horn ratio (FOHR) was measured immediately before shunt placement or on the first study that reported ventricular stability for nonshunted patients. The primary outcome was full scale IQ (FSIQ) on the Weschler Intelligence Scale. Secondary outcomes included indices of the Weschler scale, the Global Executive Composite from the Behavior Rating Inventory of Executive Function, and the general adaptive composite from the Adaptive Behavior Assessment Scale. Univariable and multivariable regression was used to determine if FOHR was correlated with neuropsychological scores., Results: Forty patients met the inclusion criteria; 26 (65%) had shunted hydrocephalus. Age at neuropsychological testing was 10.9 ± 0.6 years. FOHR was greater in the shunted group (0.64 vs 0.51; P < .001). There were no differences in neuropsychological results between shunted and nonshunted groups. On univariable analysis, greater FOHR was associated with lower FSIQ (P = .025) and lower Visual Spatial Index scores (P = .013), which remained significant on multivariable analysis after adjusting for gestational age at birth, lesion level, shunt status, and shunt revision status (P = .049 and P = .006, respectively). Separate analyses by shunt status revealed that these effects were driven by the shunted group., Conclusions: Greater FOHR before shunting was correlated with lower FSIQ and the Visual Spatial Index scores on the Weschler Intelligence Scales. Larger studies are needed to explore further the relationship between ventricle size, hydrocephalus, and neurodevelopmental outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. Funding: There was no funding for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Regenerative endodontic procedures (REPs) is effective for treating young permanent teeth with pulp necrosis. However, its efficacy on delayed replanted avulsed teeth is unclear., Aim: This retrospective study aimed to assess the efficacy of REPs in treating delayed replanted immature permanent teeth with apical periodontitis., Design: Avulsed teeth receiving REPs were systematically screened based on predetermined criteria. This study assessed the REP outcomes, postoperative periodontal healing, and overall treatment efficacy. Samples were grouped by REP outcomes and root development stage, with Fisher's exact tests used to compare outcomes among different groups., Results: Among the included 17 teeth, 47.1% exhibited successful REPs and periodontal healing. Another 47.1%, due to replacement resorption or REP failure, were categorized as tooth survival. Healing of periapical lesions was observed in 88.2% of the cases, but only 41.2% demonstrated continued root development. Although differences were not significant (p = 0.05), teeth with continued root development had a higher rate of functional healing (85.7%) compared to those without (30%)., Conclusion: Within the limitations of this study, REPs presented reliable outcomes for treating delayed replanted immature permanent teeth with apical periodontitis mainly in periapical lesion healing. Teeth with continued root development after REPs exhibited a higher rate of functional healing. Further investigation is required to explore potential synergies between REP outcomes and periodontal healing., (© 2024 BSPD, IAPD and John Wiley & Sons Ltd.)

Objective: The purpose of this study was to conduct a literature review on transition programs from pediatric to adult care and the role of neurosurgery as individuals with spina bifida (SB) transition, and to provide a framework for neurosurgical providers to assist in the transition to adult-centered care., Methods: A comprehensive literature review was conducted according to the PRISMA statement, with a search in Medline and Embase to identify US clinical programs reporting on their experiences establishing a transition program for adolescents and young adults with SB. Data were collected for authors, year, transition clinic location, model of care for transition clinic, ages served, and specialty clinical team., Results: The literature search yielded 698 articles, 5 of which met the inclusion criteria. These 5 studies included 4 transition programs for which models of care and approach to transition, clinical services involved, establishment of goals, and age of initiation and transition were identified. All programs described setting transition goals, ranging from community services, to self-management, to health care navigation, to patient-driven goals, with 1 program reporting a quality-of-life measurement component to their model., Conclusions: Robust SB transition programs can be established by applying the expanded chronic care model, reviewing lessons learned by other programs, advocating at the institutional level, and seeking support via professional organizations. While the comprehensive role of neurosurgical providers in these programs is still being defined, a shared vision of enhancing the health and quality of life for individuals with SB and their families is needed by all subspecialists involved.

Objective: In the global environment in which neurosurgical providers practice, there is a pressing need to identify and highlight online resources to support families shifting from pediatric to adult-centered spina bifida (SB) care in general and neurosurgical care in particular. The purpose of this paper was to identify high-quality resources for clinicians and families of individuals affected by SB to be utilized during the transition years. With knowledge of, and access to, these online resources, neurosurgical providers can aim to make the transition process effective, to improve the quality of care for young adults with SB., Methods: All identified online resources were found on the GOT TRANSITION platform and by searching "spina bifida transition resources" between January and March 2024. Resources were coded for transition focus areas and stratified into predefined categories: 1) education for clinicians, 2) preparation for youth and families, 3) educational/school, and 4) employment and independent living., Results: A total of 160 websites were cataloged; 11% of websites focused on medical provider education, 44% on preparation for youth, 29% on educational/school resources, and 16% on employment and independent living., Conclusions: In the global environment of today's medicine, online transition resources are available to assist clinicians and families in the transition process of individuals living with SB. With improved knowledge and utilization of online transition resources, neurosurgical providers can better serve individuals with SB and their families to improve quality of care with the aim of improving lifelong outcomes.

Objective: Neuronavigation is a useful adjunct for catheter placement during neurosurgical procedures for hydrocephalus or ventricular access. MRI protocols for navigation are lengthy and require sedation for young children. CT involves ionizing radiation. In this study, the authors introduce the clinical application of a 1-minute rapid MRI sequence that does not require sedation in young children and report their preliminary clinical experience using this technique in their pediatric population., Methods: All patients who underwent ventricular catheter placement at a children's hospital using a rapid noncontrast MRI protocol, standard MRI, or head CT from July 2021 to August 2023 were included. Type of procedure, etiology of hydrocephalus, ventricle configuration and size, morphology of ventricles, need for adjunctive intraoperative ultrasound, duration of procedure, accuracy of catheter placement, and need for proximal revision within 90 days were retrospectively recorded and compared across imaging modalities., Results: Sixty-eight patients underwent 83 procedures: 21 underwent CT navigation, 29 standard MRI, and 33 rapid MRI. Patients who received standard MRI more often had tumor etiology, while those who underwent CT and rapid MRI had posthemorrhagic etiology (χ2 = 13.04, p = 0.042). Intraoperative ultrasound was required for 1 patient in the standard MRI group and 1 patient in the CT group. There was no difference in procedure time across groups (p = 0.831). On multivariable analysis, procedure time differed by procedure type, where external ventricular drain placement and proximal revision were faster (p < 0.001 and p < 0.028, respectively). Proximal revision due to obstruction within 90 days occurred in 3 cases (in the same patient with complex loculated hydrocephalus) in the rapid MRI group and 2 cases in the CT group., Conclusions: Although this study was not powered for statistical inference, the authors report on the clinical use of a 1-minute rapid MRI sequence for neuronavigation in hydrocephalus or ventricular access surgery. There were no instances in which intraoperative ultrasound was required as an adjunct for procedures navigated with rapid MRI, and intraoperative time did not differ from that of standard navigation protocols.

Mesoporous tungsten trioxide (WO 3 ) films are prepared by the combination of the template-assisted sol-gel method and ultrasonic spraying deposition (USD) for supercapacitors, and then the surface morphology and electrochemical performance of the films are studied. Compared to WO 3 prepared by the traditional hydrothermal synthesis and spin coating method, the films obtained by USD exhibit advantages such as low cost, minimal material usage, and suitability for large-area in-line manufacturing. Additionally, the mesoporous structure of USD-produced films is also supportive of ion transportation. Due to the high specific surface area of WO 3 films deposited by USD, it is a material capable of use in a high-performance energy storage device. Through the control of spray coats, the film thickness and specific capacitance can be effectively controlled. Electrochemical measurements show that the mesoporous WO 3 films possess excellent electrochemical performance with a maximum specific capacitance of 109.15 F/g at 0.5 A/g. The cycling performance up to 5000 cycles of mesoporous WO 3 films is due to the stable nature of nanocrystalline produced by the combination of USD and sol-gel chemistry., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl 4 )-induced progressive liver fibrosis. Integrative analysis distinguished the sequential responses to injury of hepatocytes, hepatic stellate cells and endothelial cells. Moreover, we reconstructed cell-cell interactions and gene regulatory networks implicated in these processes. These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions, dysfunction for clearance by apoptosis of activated hepatic stellate cells, accumulation of pro-fibrotic signals, and the switch from an anti-angiogenic to a pro-angiogenic program during CCl 4 -induced progressive liver fibrosis. Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

Background: More than 62 million people self-identified as Hispanic/Latino (H/L) in the 2020 United States census. The U.S. H/L population has higher burden of certain cancers compared with their non-Hispanic White counterparts., Methods: Key term search using the NIH Query/View/Report (QVR) system, along with Research, Condition, and Disease Categorization codes identified cancer epidemiology research grants in H/L populations funded by the NCI as a primary or secondary funder from fiscal years 2016 through 2021. Three reviewers identified eligible grants based on specified inclusion/exclusion criteria and a codebook for consistency extracting key characteristics., Results: A total of 450 grants were identified through the QVR system using key words related to H/Ls; 41 cancer epidemiology grants remained after applying exclusion criteria. These grants contained specific aims focused on H/Ls (32%) or included H/Ls as part of a racial/ethnic comparison (68%). NCI was the primary funder of the majority of the grants (85%), and most of the research grants focused on cancer etiology (44%) and/or survivorship (49%). Few grants (10%) investigated environmental exposures., Conclusions: This article provides an overview of NCI-funded cancer epidemiology research in H/L populations from 2016 to 2021. Future cancer epidemiology research should reflect the changing dynamics of the U.S. demography with diverse, representative populations and well-characterized ethnicity., Impact: Research that carefully measures the relevant biological, environmental, behavioral, psychologic, sociocultural, and clinical risk factors will be critical to better understanding the nuanced patterns influencing cancer-related outcomes in the heterogenous H/L population., (©2023 American Association for Cancer Research.)

Background: Benefits from early surgical intervention in preterm infants with intraventricular hemorrhage (IVH) prior to symptomatic ventriculomegaly must be weighed against risks of surgery. We calculated thresholds of common ventriculomegaly indices at a late-intervention institution to predict subsequent symptomatic ventriculomegaly requiring neurosurgery., Methods: We retrospectively reviewed neuroimaging and neurosurgical outcomes in preterm infants with grade III/IV IVH between 2007 and 2020. Frontal-occipital horn ratio (FOHR), frontal-temporal horn ratio (FTHR), anterior horn width (AHW), and ventricular index (VI) were measured. Area under the receiver operating curve (AUC) for predicting intervention (initiated after progressive symptomatic ventriculomegaly) was calculated for diagnostic scan, scans during weeks 1-4, and maximum measurement prior to intervention. Threshold values that optimized sensitivity and specificity were derived., Results: A total of 1254 scans in 132 patients were measured. In all, 37 patients had a neurosurgical intervention. All indices differed between those with and without intervention from the first diagnostic scan (p < 0.001). AUC of maximum measurement was 97.1% (95% CI 94.6-99.7) for FOHR, 97.7% (95% CI 95.6-99.8) for FTHR, 96.6% (95% CI 93.9-99.4) for AHW, and 96.8% (95% CI 94.0-99.5) for VI. Calculated thresholds were FOHR 0.66, FTHR 0.62, AHW 15.5 mm, and VI 8.4 mm > p97 (sensitivities >86.8%, specificities >90.1%)., Conclusion: Ventriculomegaly indices were greater for patients who developed progressive persistent ventriculomegaly from the first diagnostic scan and predicted neurosurgical intervention., Impact: We derived thresholds of common ventriculomegaly indices (ventricular index, anterior frontal horn width, fronto-occipital horn and fronto-temporal horn index) to best predict the development of progressive symptomatic post-hemorrhage hydrocephalus in preterm infants with intraventricular hemorrhage. While current thresholds were established by a priori expert consensus, we report the first data-driven derivation of ventriculomegaly thresholds across all indices for the prediction of symptomatic hydrocephalus. Data-derived thresholds will more precisely weigh the risks and benefits of early intervention., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

In April 2021, a coalition of employee resource groups called the Federation of Asian American, Native Hawaiian, and Pacific Islander Network, or FAN, was established at the National Institutes of Health (NIH). The coalition aims to be a unifying voice that represents and serves these diverse communities. Discussion within the group centered around the persistent inequities and the lack of inclusion that the Asian American communities have long endured. Two common themes emerged from these discussions: (1) a leadership gap for Asian Americans in senior leadership and managerial positions, and (2) the everyday experience of exclusion. Asian Americans represent nearly 20% of the NIH permanent workforce yet make up only 6% of the senior leadership positions. These two issues reflect the sentiment that Asian Americans often feel invisible or forgotten in the discourse of structural racism and organizational inequities, especially in organizations in which they are numerically overrepresented. The purpose of this manuscript is to raise awareness of Asian American concerns in the federal workforce and how current employment and workforce analytic practices in this domain might contribute to the invisibility. To accomplish this goal, we will (1) describe relevant historical and contemporary contexts of Asian American experience undergirding their inclusion and visibility concerns; (2) present data analyses from available data sources to provide a deeper understanding of the Asian American leadership gap and lack of inclusion concerns; (3) highlight data availability and analytic challenges that hinder the ability to address the inequity and invisibility issues; and (4) recommend practices in data collection, measurement, and analysis to increase the visibility of this community in the federal workforce., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Goon, Bruce, Lun, Lai, Chu and Le.)

Objective: To investigate differences and calculate pooled incidence of any intraventricular haemorrhage (IVH), severe IVH (Grade III/IV, sIVH) and ventriculoperitoneal shunt (VPS) placement in preterm infants across geographical, health and economic regions stratified by gestational age (GA)., Design: MEDLINE, Embase, CINAHL and Web of Science were searched between 2010 and 2020. Studies reporting rates of preterm infants with any IVH, sIVH and VPS by GA subgroup were included. Meta-regression was performed to determine subgroup differences between study designs and across United Nations geographical regions, WHO mortality strata and World Bank lending regions. Incidence of any IVH, sIVH and VPS by GA subgroups<25, <28, 28-31, 32-33 and 34-36 weeks were calculated using random-effects meta-analysis., Results: Of 6273 publications, 97 met inclusion criteria. Incidence of any IVH (37 studies 87 993 patients) was: 44.7% (95% CI 40.9% to 48.5%) for GA <25 weeks, 34.3% (95% CI 31.2% to 37.6%) for GA <28 weeks, 17.4% (95% CI 13.8% to 21.6%) for GA 28-31 weeks, 11.3% (95% CI 7.3% to 17.0%) for GA32-33 weeks and 4.9% (95% CI 1.4% to 15.2%) for GA 34-36 weeks. Incidence of sIVH (49 studies 328 562 patients) was 23.7% (95% CI 20.9% to 26.7%) for GA <25 weeks, 15.0% (95% CI 13.1% to 17.2%) for GA <28 weeks, 4.6% (95% CI 3.5% to 6.1%) for GA 28-31 weeks, 3.3% (95% CI 2.1% to 5.1%) for GA 32-33 weeks and 1.8% (95% CI 1.2% to 2.8%) for GA 34-36 weeks. Europe had lower reported incidence of any IVH and sIVH relative to North America (p<0.05). Proportion of VPS across all GA groups was 8.4% (95% CI 4.7% to 14.7%) for any IVH and 17.2% (95% CI 12.2% to 26.2%) for sIVH. Heterogeneity was high (I 2 >90%) but 64%-85% of the variance was explained by GA and study inclusion criteria., Conclusions: We report the first pooled estimates of IVH of prematurity by GA subgroup. There was high heterogeneity across studies suggesting a need for standardised incidence reporting guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Air pollution exposure has been associated with a multitude of diseases and poses a significant concern to public health. For targeted environmental risk communication and interventions to be effective, it is important to correctly identify characteristics associated with worry of harm from air pollution., Methods: Using responses from 3,630 participants of the Health Information National Trends Survey 4 Cycle 2, we assessed worry of harm from exposure to indoor (IAP) and outdoor (OAP) air pollution separately. Multinomial logistic regression models were used to calculate odds ratios and 95% confidence intervals., Results: Hispanics were more likely to worry about harm from IAP and OAP compared to non-Hispanic whites. Participants who lived in metropolitan counties were more likely to worry about harm from IAP and OAP compared to those who lived in rural counties. Finally, those who believed their chance of getting cancer was high were more likely to worry about harm from IAP and OAP compared to those who thought their likelihood of getting cancer was low., Conclusions: Worry of harm from IAP and OAP varied across sociodemographic and cancer-related characteristics. Public health professionals should consider these characteristics when developing targeted environmental risk communication and interventions., (© 2022. The Author(s).)

Background: Greater ventriculomegaly in preterm infants with intraventricular hemorrhage (IVH) has been associated with worse neurodevelopmental outcomes in infancy. We aim to explore the relationship between ventriculomegaly and school-age functional outcome., Methods: Retrospective review of preterm infants with Grade III/IV IVH from 2006 to 2020. Frontal-occipital horn ratio (FOHR) was measured on imaging throughout hospitalization and last available follow-up scan. Pediatric Cerebral Performance Category (PCPC) scale was used to assess functional outcome at ≥4 years. Ordinal logistic regression was used to determine the relationship between functional outcome and FOHR at the time of Neurosurgery consult, neurosurgical intervention, and last follow-up scan while adjusting for confounders., Results: One hundred and thirty-four infants had Grade III/IV IVH. FOHR at consult was 0.62 ± 0.12 and 0.75 ± 0.13 at first intervention (p < 0.001). On univariable analysis, maximum FOHR, FOHR at the last follow-up scan, and at Neurosurgery consult predicted worse functional outcome (p < 0.01). PVL, longer hospital admission, and gastrotomy/tracheostomy tube also predicted worse outcome (p < 0.05). PVL, maximum FOHR, and FOHR at consult remained significant on multivariable analysis (p < 0.05). Maximum FOHR of 0.61 is a fair predictor for moderate-severe impairment (AUC 75%, 95% CI: 62-87%)., Conclusions: Greater ventricular dilatation and PVL were independently associated with worse functional outcome in Grade III/IV IVH regardless of neurosurgical intervention., Impact: Ventriculomegaly measured by frontal-occipital horn ratio (FOHR) and periventricular leukomalacia are independent correlates of school-age functional outcomes in preterm infants with intraventricular hemorrhage regardless of need for neurosurgical intervention. These findings extend the known association between ventriculomegaly and neurodevelopmental outcomes in infancy to functional outcomes at school age. FOHR is a fair predictor of school-age functional outcome, but there are likely other factors that influence functional status, which highlights the need for prospective studies to incorporate other clinical and demographic variables in predictive models., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: Premature neonates have a high risk of intraventricular hemorrhage (IVH) at birth, the blood products of which activate inflammatory cascades that can cause hydrocephalus and long-term neurological morbidities and sequelae. However, there is no consensus for one treatment strategy. While the mainstay of treatment involves CSF diversion to reduce intracranial pressure, a number of interventions focus on blood product removal at various stages including extraventricular drains (EVD), intra-ventricular thrombolytics, drainage-irrigation-fibrinolytic therapy (DRIFT), and neuroendoscopic lavage (NEL)., Methods: We performed a systematic review and meta-analysis to compare the risks and benefits commonly associated with active blood product removal treatment strategies. We searched MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases through Dec 2020 for articles reporting on outcomes of EVDs, thrombolytics, DRIFT, and NEL. Outcomes of interest were rate of conversion to ventriculoperitoneal shunt (VPS), infection, mortality, secondary hemorrhage, and cognitive disability., Results: Of the 10,398 articles identified in the search, 23 full-text articles representing 22 cohorts and 530 patients were included for meta-analysis. These articles included retrospective, prospective, and randomized controlled studies on the use of EVDs (n = 7), thrombolytics (n = 8), DRIFT therapy (n = 3), and NEL (n = 5). Pooled rates of reported outcomes for EVD, thrombolytics, DRIFT, and NEL for ventriculoperitoneal shunt (VPS) placement were 51.1%, 43.3%, 34.3%, and 54.8%; for infection, 15.4%, 12.5%, 4.7%, and 11.0%; for mortality, 20.0%, 11.6%, 6.0%, and 4.9%; for secondary hemorrhage, 5.8%, 7.8%, 20.0%, and 6.9%; for cognitive impairment, 52.6%, 50.0%, 53.7%, and 50.9%. Meta-regression using type of treatment as a categorical covariate showed no effect of treatment modality on rate of VPS conversion or cognitive disability., Conclusion: There was a significant effect of treatment modality on secondary hemorrhage and mortality; however, mortality was no longer significant after adjusting for year of publication. Re-hemorrhage rate was significantly higher for DRIFT (p < 0.001) but did not differ among the other modalities. NEL also had lower mortality relative to EVD (p < 0.001) and thrombolytics (p = 0.013), which was no longer significant after adjusting for year of publication. Thus, NEL appears to be safer than DRIFT in terms of risk of hemorrhage, and not different than other blood-product removal strategies in terms of mortality. Outcomes-in terms of shunting and cognitive impairment-did not differ. Later year of publication was predictive of lower rates of mortality, but not the other outcome variables. Further prospective and randomized studies will be necessary to directly compare NEL with other temporizing procedures., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Ventriculosubgaleal shunts (VSGSs) require fewer cerebrospinal (CSF) aspirations than ventricular access devices (VADs) for temporization of posthemorrhagic ventricular dilatation (PHVD) in preterm infants. Cost of postoperative CSF aspiration has not been quantified., Methods: We reviewed CSF aspiration and laboratory studies obtained in preterm infants with PHVD and VAD at our institution between 2009 and 2020. Cost per aspiration was calculated for materials, labs, and Medicare fee schedule for ventricular puncture through implanted reservoir. We searched PubMed, Cochrane Library, Embase, CINAHL, and Web of Science for meta-analysis of pooled mean number of CSF aspirations and proportion of patients requiring aspiration., Results: Thirty-five preterm infants with PHVD had VAD placed with 22.2 ± 18.4 aspirations per patient. Labs were obtained after every aspiration per local protocol. Cost per aspiration at our institution was USD 935.51. Of 269 published studies, 77 reported on VAD, 29 VSGS, and 13 both. Five studies on VAD (including the current study) had a pooled mean of 25.8 aspirations per patient (95% CI: 16.7-34.8). One study on VSGS reported a mean of 1.6 ± 1.7 aspirations. Three studies on VAD (including the current study) had a pooled proportion of 97.4% of patients requiring aspirations (95% CI: 87.9-99.5). Four studies on VSGS had a pooled proportion of 36.5% requiring aspirations (95% CI: 26.9-47.2). Frequency of lab draws ranged from weekly to daily. Based on costs at our institution, mean number of aspirations, and proportion of patients requiring aspirations, cost difference ranged between USD 4,243 and 23,235 per patient and USD 500,903 and 2.36 million per 100 patients depending on frequency of taps and Medicare locality., Discussion/conclusion: Lower number of CSF aspirations using VSGS can be associated with considerably lower cost compared to VAD., (© 2022 S. Karger AG, Basel.)

Objective: While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood., Methods: Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time., Results: The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014)., Conclusions: Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Background: Intracranial hemorrhage (ICH) is a devastating complication for patients with ventricular assist devices (VADs). The safety of emergent anticoagulation reversal with four-factor prothrombin complex concentrate (PCC) and optimal timing of anticoagulation resumption are not clear. In addition, lactate dehydrogenase (LDH) is used as a biomarker for thromboembolic risk, but its utility in guiding anticoagulation management after reversal with PCC has not be described., Methods: We retrospectively reviewed a consecutive series of patients with VADs presenting with ICH between 2014 and 2020 who received four-factor PCC for rapid anticoagulation reversal. We collected the timing of PCC administration, timing of resumption of anticoagulation, survival, occurrence of thromboembolic events, and LDH levels throughout hospitalization., Results: We identified 16 ICH events in 14 patients with VADs treated with rapid anticoagulation reversal using four-factor PCC (11 intraparenchymal, 4 subdural, 1 subarachnoid hemorrhage). PCC was administered at a mean of 3.3 ± 0.3 h after imaging diagnosis of ICH. Overall mortality was 63%. Survivors had higher presenting Glasgow Coma Scale (median 15, interquartile range [IQR] 15-15 versus 14, IQR 8-14.7, P = 0.041). In all six instances where the patient survived, anticoagulation was resumed on average 9.16 ± 1.62 days after reversal. There were no thromboembolic events prior to resumption of anticoagulation. Three events occurred after anticoagulation resumption and within 3 months of reversal: VAD thrombosis in a patient with thrombosis at the time of reversal, ischemic stroke, and readmission for elevated LDH in the setting of subtherapeutic international normalized ratio., Conclusions: Our limited series found no thromboembolic complications immediately following anticoagulation reversal with PCC prior to resumption of anticoagulation. LDH trends may be useful to monitor thromboembolic risk after reversal., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: To investigate the difference of parent's cognition of children's orofacial myofunctional therapy (OMT) and its influencing factors, to provide reference for children's OMT., Methods: Self-designed questionnaire was used to investigate the basic information and related problems of 98 parents whose children received OMT. SPSS 22.0 software package was used for statistical analysis., Results: The parents' total cognition of OMT was relatively low (23.47%). The cognition of malocclusion (68.4%) was significantly different from that of orofacial dysfunction (26.5%), the therapeutic significance of OMT (28.6%) and the attitude of specific treatment of orofacial myofunctional therapy (23.5%) (P<0.001). Parents with different backgrounds had different recognition of OMT: the cognitive degree of parents over 50 years old was low(13.33%), while the cognitive degree of the parents with high educational background was high (48.08%). There was no significant difference in cognition among different gender, occupation and family monthly income. High recognition had good compliance and cooperation. Comparing with low recognition, the difference from high recognition on compliance and cooperation was significant(P<0.01)., Conclusions: OMT is a long-term treatment process, which needs children's perseverance and active cooperation. The curative effect mainly depends on the children's compliance and cooperation. Higher awareness is the premise of good compliance and cooperation. To improve the recognition of OMT and avoid occurrence of malocclusion, it is necessary to strengthen education of OMT, especially for parents with special backgrounds.

Objective: To determine the relationship between timing of initiation of temporizing neurosurgical treatment and rates of ventriculoperitoneal shunt (VPS) and neurodevelopmental impairment in premature infants with post-hemorrhagic ventricular dilatation (PHVD)., Study Design: We searched MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane Center Register of Controlled Trials for studies that reported on premature infants with PHVD who underwent a temporizing neurosurgical procedure. The timing of the temporizing neurosurgical procedure, gestational age, birth weight, outcomes of conversion to VPS, moderate-to-severe neurodevelopmental impairment, infection, temporizing neurosurgical procedure revision, and death at discharge were extracted., Results: Sixty-two full-length articles and 6 conference abstracts (n = 2533 patients) published through November 2020 were included. Pooled rate for conversion to VPS was 60.5% (95% CI, 54.9-65.8), moderate-severe neurodevelopmental impairment 34.8% (95% CI, 27.4-42.9), infection 8.2% (95% CI, 6.7-10.1), revision 14.6% (95% CI, 10.4-20.1), and death 12.9% (95% CI, 10.2-16.4). The average age at temporizing neurosurgical procedure was 24.2 ± 11.3 days. On meta-regression, older age at temporizing neurosurgical procedure was a predictor of conversion to VPS (P < .001) and neurodevelopmental impairment (P < .01). Later year of publication predicted increased survival (P < .01) and external ventricular drains were associated with more revisions (P = .001). Tests for heterogeneity reached significance for all outcomes and a qualitative review showed heterogeneity in the study inclusion and diagnosis criteria for PHVD and initiation of temporizing neurosurgical procedure., Conclusions: Later timing of temporizing neurosurgical procedure predicted higher rates of conversion to VPS and moderate-severe neurodevelopmental impairment. Outcomes were often reported relative to the number of patients who underwent a temporizing neurosurgical procedure and the criteria for study inclusion and the initiation of temporizing neurosurgical procedure varied across institutions. There is need for more comprehensive outcome reporting that includes all infants with PHVD regardless of treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The study of gene-environment (GxE) interactions is a research priority for the NCI. Previously, our group analyzed NCI's extramural grant portfolio from fiscal years (FY) 2007 to 2009 to determine the state of the science in GxE research. This study builds upon our previous effort and examines changes in the landscape of GxE cancer research funded by NCI., Methods: The NCI grant portfolio was examined from FY 2010 to 2018 using the iSearch application. A time-trend analysis was conducted to explore changes over the study interval., Results: A total of 107 grants met the search criteria and were abstracted. The most common cancer types studied were breast (19.6%) and colorectal (18.7%). Most grants focused on GxE using specific candidate genes (69.2%) compared with agnostic approaches using genome-wide (26.2%) or whole-exome/whole-genome next-generation sequencing (NGS) approaches (19.6%); some grants used more than one approach to assess genetic variation. More funded grants incorporated NGS technologies in FY 2016-2018 compared with prior FYs. Environmental exposures most commonly examined were energy balance (46.7%) and drugs/treatment (40.2%). Over the time interval, we observed a decrease in energy balance applications with a concurrent increase in drug/treatment applications., Conclusions: Research in GxE interactions has continued to concentrate on common cancers, while there have been some shifts in focus of genetic and environmental exposures. Opportunities exist to study less common cancers, apply new technologies, and increase racial/ethnic diversity., Impact: This analysis of NCI's extramural grant portfolio updates previous efforts and provides a review of NCI grant support for GxE research., (©2020 American Association for Cancer Research.)

Purpose: To study the clinical prognosis of laterally luxated primary teeth after 6-month follow-up without treatment., Methods: Patients with laterally luxated primary teeth, visiting Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from March 2018 to March 2019, were selected for the study. Based on the inclusion and exclusion criteria, totally 45 patients with 57 primary teeth were included. The reposition outcomes and pulp prognosis were reviewed at the end of follow-up. The data were analyzed using SPSS 23.0 software package., Results: During a 6-month follow-up, 92.98% of the luxated teeth showed spontaneous reposition while only 31.58% of the traumatic teeth were back to the original position. Regarding the pulp healing complications, 54.39% of the luxated teeth exhibited no clinical symptoms, and 14.04% of the evaluated teeth displayed pulp canal obliteration, and pulp necrosis happened in 31.58% of the injured teeth. There was significant difference in the reposition outcome between labial-palatal luxation and mesial-distal luxation(P<0.05), but no significant difference was found in pulp prognosis between the two luxation types(P>0.05). Spontaneous reposition and crown discoloration observed in most of the evaluated cases, were the earliest signs after one-month follow-up. Periapical translucent image and root resorption due to periapical inflammation showed within the first three months after injury, pulp canal obliteration appeared after 6 months., Conclusions: In general, most of the laterally luxated teeth left without treatment can reposition spontaneously and show lower incidence of pulp necrosis compared with mature permanent teeth in half a year after injury. The direction of luxation does not affect pulp prognosis but has an influence on teeth reposition procedure.

Background: Given the morbidity and cost associated with cerebrospinal fluid shunt infections, many neurosurgical protocols implement "no-touch" technique to minimize infection. However, current surgical tools are not designed specifically for this task and surgeons often resort to using their hands to connect the shunt catheter to the valve., Objective: To develop an efficient and effective shunt assembly tool., Methods: Prototypes were designed using computer assisted software and machined in stainless steel. The amount of time and number of attempts it took volunteers to connect a Bacticel shunt catheter to a Delta valve were recorded using the new tool and standard shodded mosquitos. Scanning electron microscopy (SEM) was done on manipulated catheters to assess potential damage. Practicing neurosurgeons provided feedback., Results: Nonsurgeon (n = 13) volunteers and neurosurgeons (n = 6) both completed the task faster and with fewer attempts with the new tool (mean 7.18 vs 15.72 s and 2.00 vs 6.36 attempts, P < .0001; mean 2.93 vs 5.96 s and 1.06 vs 2.94 attempts, P < .001, respectively). SEM of 24 manipulated catheters showed no microscopic damage. 100% of neurosurgeons surveyed (n = 10) would adapt the tool in their practice, 90% preferred use of the new tool compared to their existing method, and 100% rated it easier to use compared to existing instruments., Conclusion: The new tool shortened the time and number of attempts to connect a shunt catheter to a valve. Neurosurgeons preferred the new tool to existing instruments. There was no evidence of catheter damage with the use of this tool., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Amine-terminated self-assembled monolayers are molecular nanolayers, typically formed via wet-chemical solution on specific substrates for precision surface engineering or interface modification. However, homogeneous assembling of a highly ordered monolayer by the facile, wet method is rather tricky because it involves process parameters, such as solvent type, molecular concentration, soaking time and temperature, and humidity level. Here, we select 3-aminopropyltrimethoxysilane (APTMS) as a model molecule of aminosilane for the silanization of nanoporous carbon-doped organosilicate (p-SiOCH) under tightly controlled process environments. Surface mean roughness ( R a ) and the water contact angle (θ) of the p-SiOCH layers upon silanization at a 10% humidity-controlled environment behave similarly and follow a three-stage evolution: a leap to a maximum at 15 min for R a (from 0.227 to 0.411 nm) and θ (from 25 to 86°), followed by a gradual decrease to 0.225 nm and 69 o , finally leveling off at the above values (>60 min). The -NH 3 + fraction indicating monolayer disorientation evolves in a similar fashion. The fully grown monolayer is highly oriented yielding an unprecedented low -NH 3 + fraction of 0.08 (and 0.92 of upright -NH 2 groups). However, while having a similar thickness of approximately 1.4 ± 0.1 nm, the molecular layers grown at 30% relative humidity exhibit a significantly elevated -NH 3 + fraction of 0.42, indicating that controlling the humidity is vital to the fabrication of highly oriented APTMS molecular layers. A bonding-structure evolution model, as distinct from those offered previously, is proposed and discussed.

Epiphytic bryophytes (EB) are some of the most commonly found plant species in tropical montane cloud forests, and they play a disproportionate role in influencing the terrestrial hydrological and nutrient cycles. However, it is difficult to estimate the abundance of EB due to the nature of their "epiphytic" habitat. This study proposes an allometric scaling approach implemented in twenty-one 30 × 30 m plots across an elevation range in 16,773 ha tropical montane cloud forests of northeastern Taiwan to measure EB biomass, a primary metric for indicating plant abundance and productivity. A general allometry was developed to estimate EB biomass of 100 cm 2 circular-shaped mats ( n = 131) with their central depths. We developed a new point-intercept instrument to rapidly measure the depths of EB along tree trunks below 300 cm from the ground level (sampled stem surface area (SSA)) ( n = 210). Biomass of EB of each point measure was derived using the general allometry and was aggregated across each SSA, and its performance was evaluated. Total EB biomass of a tree was estimated by referring to an in-situ conversion model and was interpolated for all trees in the plots ( n = 1451). Finally, we assessed EB biomass density at the plot scale of the study region. The general EB biomass-depth allometry showed that the depth of an EB mat was a salient variable for biomass estimation ( R 2 = 0.72, p < 0.001). The performance of upscaling from mats to SSA was satisfactory, which allowed us to further estimate mean (±standard deviation) EB biomass of the 21 plots (272 ± 104 kg ha -1 ). Since a significant relationship between tree size and EB abundance is commonly found, regional EB biomass may be mapped by integrating our method and three-dimensional remotely sensed airborne data., Competing Interests: Cho-ying Huang is an Academic Editor for PeerJ., (© 2020 Lai et al.)

Purpose: To determine the age medians for crown and root length completion stages of permanent teeth (except for the third molars) and to study gender differences in crown and root length completion stages by radiographic examinations., Methods: The development of permanent teeth (except for the third molars) was evaluated from 3304 panoramic radiographs of children aged between 3 and 18 years by Haavikko's method. Statistical analysis was performed using SPSS 25.0 software package. Age medians for crown and root length completion stages of permanent teeth were calculated. Gender differences were analyzed by Mann-Whitney U test., Results: There were no significant gender differences in crown completion stages of central incisor and first molar, of which P values were 0.143 (for maxillary central incisor), 0.122 (for maxillary first molar), 0.191 (for mandibular central incisor) and 0.558 (for mandibular first molar), while girls were found to be ahead of boys for crown completion stages of other teeth. In maxilla, girls were found to be ahead of boys for root length completion stages except for lateral incisor, second premolar and second molar, of which P values were 0.057, 0.130 and 0.294; in mandible, except for second premolar and second molar, girls were observed to be ahead of boys for root length completion stages, of which P values were 0.428 and 0.057., Conclusions: It is concluded that girls are advanced than boys for crown and root length completion stages in most teeth. There is a similarity in gender differences for crown and root length completion stages between maxilla and mandible.

Purpose: To study changes of children caries activity after treatment under general anesthesia, and to analyze effect of caries treatment under general anesthesia on oral health behavior and growth index of children., Methods: Patients who met criteria and were treated under general anesthesia were included in this study. Informed consent for this study was obtained from parents. Before and after treatment, children's oral health conditions were examined; height, weight were recorded; the caries activity was evaluated. In addition, questionnaires related to oral health behavior and early childhood oral health impact scales were fulfilled by parents. The patients were followed for 6 months after treatment. The data were analyzed using SPSS 25.0 software package., Results: The average dmft of children before treatment was 14.02. Patients with supplemental feeding during sleep and additional bottle feeding in the first 6 months had higher dmft. The incidence of caries relapse was 25.67% after 3 months and 50% after 6 months. Caries activity decreased dramatically after treatment. Among three follow-up results, Cariostat scores at the 3rd month were the lowest. After general anesthesia, the eating frequency and sweets intake decreased obviously, and the time for tooth-brushing was longer, while the children's mealtime was significantly shorter. The number of children in normal BMI range significantly increased after dental general anesthesia., Conclusions: Dental general anesthesia can reduce caries activity and improve oral health behavior, nutritional status, physical and mental health of children in a short term. However, a large number of patients were still at a high risk of caries relapse after treatment.

Objective: As the use of left ventricular assist devices (LVADs) has expanded, cerebrovascular complications have become an increasing source of morbidity and mortality in this population. Intracranial hemorrhage (ICH) in particular remains a devastating complication in patients who undergo LVAD placement with no defined management guidelines. The authors therefore reviewed surgical and anticoagulation management and outcomes of patients with LVADs who presented to their institution with ICH., Methods: This retrospective cohort study assessed outcomes of patients who underwent LVAD placement at a single institution between 2007 and 2016 and in whom imaging demonstrated ICH., Results: During the study period, 281 patients had a HeartMate II or HeartWare LVAD placed. There were 37 episodes of ICH (recurrent in 3 cases). ICHs were categorized as intraparenchymal hemorrhage (IPH; n = 22, 59%), subdural hemorrhage (SDH; n = 6, 16%), and subarachnoid hemorrhage (SAH; n = 9, 24%). Neurosurgical intervention was deemed necessary in 27.3%, 66.7%, and 0% of patients with IPH, SDH, and SAH, respectively; overall survival > 30 days for each type of hemorrhage was 41%, 83%, and 89%, respectively. No patients had LVAD thrombus as a result of reversal of anticoagulation. Combined with prior reports, good outcomes are seen more often following surgery for SDH than for IPH (57% vs 7%, p = 0.004) in patients who underwent VAD placement., Conclusions: Patients with IPH who undergo LVAD placement have poor outcomes regardless of anticoagulation reversal or neurosurgical intervention, whereas those with SDH may have good outcomes with medical and surgical intervention, and those with SAH appear to do well without anticoagulation reversal or surgery. When needed, anticoagulation reversal was not associated with an increase in LVAD thrombosis in this series.

Purpose: The aim of this study was to evaluate the cushion property of mouthguards when the impact object came from different directions., Methods: A 3D finite element model of upper central incisor, periodontal ligament and alveolar bone was developed based on cone-beam CT (CBCT) images of a plastic teeth model. The mouthguards were modeled in 5 different thickness (T: 0, 1.5, 3, 4.5 and 6 mm) and a nonlinear dynamic impact analysis, in which the finite element models were collided by a steel ball from different directions (D: angles between the impact direction and the long axis of tooth were 30°, 60°, 90°, 120°, respectively), was performed. The stress cushion efficiency was calculated., Results: The stress cushion efficiency of the mouthguards varied with different thicknesses and impact directions. When T=1.5 mm and 3 mm, the stress cushion efficiency was minimal as D=60° and maximal as D=120°. However, when T=4.5 mm and 6 mm, the stress cushion efficiency was minimal as D=90° and maximal as D=30°. Moreover, the stress cushion efficiency of mouthguards improved with the increasing thickness in each impact direction., Conclusions: The impact direction affects the stress cushion efficiency of mouthguards, which however is influenced by the thickness of mouthguards.

Background: Although circulating 25-hydroxyvitamin D [25(OH)D] concentrations were linked to liver cancer and chronic liver disease (CLD) in laboratory studies, few epidemiologic studies have addressed the associations. Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we measured 25(OH)D in baseline serum of 202 incident liver cancer cases and 225 CLD deaths that occurred during nearly 25 years of follow-up, and 427 controls. ORs and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. We examined predetermined clinically defined cut-points, and season-specific and season-standardized quartiles. Results: Low serum 25(OH)D concentrations were associated with higher risk of liver cancer (<25 nmol/L vs. ≥50 nmol/L: 1.98; 95% CI, 1.22-3.20; P trend across categories = 0.003) and CLD mortality (1.93; 95% CI, 1.23-3.03; P trend = 0.006) in models adjusted for age and date of blood draw. After additional adjustment for body mass index, diabetes, smoking, and other potential confounders, the association remained statistically significant for liver cancer (1.91; 95% CI, 1.16-3.15; P trend = 0.008), but was somewhat attenuated for CLD mortality (1.67; 95% CI, 1.02-2.75; P trend = 0.05). Associations were similar for analyses using season-specific and season-standardized quartiles, and after excluding participants with diabetes, or hepatitis B or C. Conclusions: Our results suggest a possible preventive role for vitamin D against liver cancer and CLD, although the importance of the liver for vitamin D metabolism and the lack of information about underlying liver disease makes reverse causality a concern. Impact: Future studies are needed to evaluate associations of vitamin D with liver cancer and liver disease in other populations, particularly those with a different constellation of risk factors. Cancer Epidemiol Biomarkers Prev; 27(9); 1075-82. ©2018 AACR ., (©2018 American Association for Cancer Research.)

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues., (Published by Elsevier Inc.)

Background: All Singaporean males undergo medical screening prior to compulsory military service. A history of possible food allergy may require referral to a specialist Allergy clinic to ensure that special dietary needs can be taken into account during field training and deployment., Objective: To study the pattern of food allergy among pre-enlistees who were referred to a specialist allergy clinic to work up suspected food allergy., Methods: Retrospective study of all pre-enlistees registered in the Clinical Immunology/Allergy New Case Registry referred to the Allergy Clinic from 1 August 2015 to 31 May 2016 for suspected food allergy., Results: One hundred twenty pre-enlistees reporting food allergy symptoms other than rash alone were referred to the Allergy Clinic during the study period. Of these, 77 (64.2%) had food allergy. Among those with food allergy, mean age was 19.1 ± 1.5 years. They comprised predominantly Chinese (66.2%) and Malays (20.8%). The most commonly reported foods were shellfish/crustaceans (78%), peanut (15.6%), and egg (6.5%). Self-limiting oral allergy syndrome, OAS (itchy lips and throat with/without lip angioedema) was the most common manifestation (n = 33, 42.9%) followed by anaphylaxis (n = 23, 29.9%). Majority of OAS was from shellfish/crustacean (90.6%); of which shrimp (30.3%), crab (15.2%), and lobster (3.0%) were the most common. Mild childhood asthma (69.7%), allergic rhinitis (6.3%), and eczema (6.1%) were the most common atopic conditions among individuals with shellfish/crustacean OAS. This pattern was similar for shellfish/crustacean anaphylaxis. Skin prick tests were most commonly positive for shrimp (OAS 87.1% vs. anaphylaxis 100%), crab (OAS 95.8% vs. 90.9%), and lobster (OAS 91.7% vs. 63.6%)., Conclusion: OAS to shellfish/crustaceans was more common than anaphylaxis among this study population of young males referred for food allergy symptoms other than rash alone.

Very large international and ethnic differences in cancer rates exist, are minimally explained by genetic factors, and show the huge potential for cancer prevention. A substantial portion of the differences in cancer rates can be explained by modifiable factors, and many important relationships have been documented between diet, physical activity, and obesity, and incidence of important cancers. Other related factors, such as the microbiome and the metabolome, are emerging as important intermediary components in cancer prevention. It is possible with the incorporation of newer technologies and studies including long follow-up and evaluation of effects across the life cycle, additional convincing results will be produced. However, several challenges exist for cancer researchers; for example, measurement of diet and physical activity, and lack of standardization of samples for microbiome collection, and validation of metabolomic studies. The United States National Cancer Institute convened the Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention Workshop on June 28-29, 2016, in Rockville, Maryland, during which the experts addressed the state of the science and areas of emphasis. This current paper reflects the state of the science and priorities for future research. Cancer Epidemiol Biomarkers Prev; 27(3); 233-44. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Epidemiologic evidence on the association between nut consumption and lung cancer risk is limited. Methods: We investigated this relationship in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, a population-based case-control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2,098 lung cases for EAGLE and 18,533 incident cases in AARP. Diet was assessed by food frequency questionnaire for both studies. Multivariable ORs and HRs and respective 95% confidence intervals (CI) were calculated using unconditional logistic regression and Cox proportional hazards regression for EAGLE and AARP, respectively. Results: Higher frequency of intake of nut consumption was inversely associated with overall lung cancer risk (highest vs. lowest quintile, OR EAGLE = 0.74; 95% CI, 0.57-0.95; HR AARP = 0.86; 95% CI, 0.81-0.91), regardless of smoking status. Results from the prospective cohort showed similar associations across histologic subtypes and a more pronounced benefits from nut consumption for those who smoked 1 to 20 cigarettes/day (OR EAGLE = 0.61; 95% CI, 0.39-0.95; HR AARP = 0.83; 95% CI, 0.74-0.94). Conclusions: Nut consumption was inversely associated with lung cancer in two large population-based studies, and associations were independent of cigarette smoking and other known risk factors. Impact: To our knowledge, this is the first study that examined the association between nut consumption and lung cancer risk by histologic subtypes and smoking intensity. Cancer Epidemiol Biomarkers Prev; 26(6); 826-36. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Insulin resistance likely increases the risk of chronic liver disease (CLD) and liver cancer, but long-term prospective studies with measured fasting glucose and insulin are lacking. We evaluated the associations of prediagnostic fasting glucose, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) with liver cancer and CLD mortality in a prospective study of Finnish male smokers with extended follow-up time (≤22 years) and information on known risk factors using data from 138 incident primary liver cancer cases, 216 CLD deaths, and 681 matched controls. Fasting glucose and insulin were measured in baseline serum. We used unconditional logistic regression to estimate ORs and 95% confidence intervals adjusted for age, alcohol, education, smoking, body mass index, and hepatitis B and C viral status. Among those without self-reported diabetes, glucose was positively associated with liver cancer [quartile 3 vs. quartile 1 (Q3/Q1): OR = 1.88; 1.03-3.49; Q4/Q1: OR = 2.40; 1.33-4.35; P trend = 0.002], and undiagnosed, biochemically defined, diabetes was associated with higher risk of liver cancer (OR = 2.95; 1.46-5.96) and CLD mortality (OR = 1.88; 1.00-3.56). Serum insulin and HOMA-IR were also positively associated with liver cancer (Q4/Q1: OR = 3.41; 1.74-6.66; P trend < 0.0001; OR = 3.72; 1.89-7.32, P trend < 0.0001, respectively) and CLD (OR = 2.51; 1.44-4.37; P trend = 0.0002; OR = 2.31; 1.34-3.97; P trend = 0.001, respectively), with stronger associations observed for liver cancer diagnosed >10 years after baseline. In conclusion, elevated fasting glucose and insulin and insulin resistance were independently associated with risk of liver cancer and CLD mortality, suggesting a potentially important etiologic role for insulin and glucose dysregulation even in the absence of diagnosed diabetes. Cancer Prev Res; 9(11); 866-74. ©2016 AACR., Competing Interests: None to disclose., (©2016 American Association for Cancer Research.)

Background: We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD's goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes., Methods: Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource., Results: As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented., Conclusions: The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database., Impact: Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. Cancer Epidemiol Biomarkers Prev; 25(10); 1392-401. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer., Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression., Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC., Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC., Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed., (©2015 American Association for Cancer Research.)

Background: Recent data suggest the possible benefits of α-tocopherol and β-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited., Methods: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) β-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes., Results: Supplemental α-tocopherol, β-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period., Conclusions: Long-term supplemental α-tocopherol or β-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

In this study, we applied a metal catalyst etching method to fabricate a nano/microhole array on a Si substrate for application in solar cells. In addition, the surface of an undesigned area was etched because of the attachment of metal nanoparticles that is dissociated in a solution. The nano/microhole array exhibited low specular reflectance (<1%) without antireflection coating because of its rough surface. The solar spectrum related total reflection was approximately 9%. A fabricated solar cell with a 40-μm hole spacing exhibited an efficiency of 9.02%. Comparing to the solar cell made by polished Si, the external quantum efficiency for solar cell with 30 s etching time was increased by 16.7%.

Unlabelled: Helicobacter have been detected in human bile and hepatobiliary tissue. Despite evidence that Helicobacter species promote gallstone formation and hepatobiliary tumors in laboratory studies, it remains unclear whether Helicobacter species contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to 15 Helicobacter pylori proteins was associated with subsequent incidence of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We included 64 biliary cancers, 122 liver cancers, and 224 age-matched controls which occurred over the course of 22 years. Helicobacter pylori seropositivity was defined as those positive to ≥ 4 antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major hepatobiliary cancer risk factors. Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of ampula of Vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (95% confidence interval [CI]: 0.79-62.33), 2.21 (0.19-25.52), 10.67 (0.76-150.08), and 1.20 (0.42-3.45), respectively, with an OR of 5.47 (95% CI: 1.17-25.65) observed for the biliary tract cancers combined. ORs above 1 were observed for many of the investigated antigens, although most of these associations were not statistically significant., Conclusion: Seropositivity to H. pylori proteins was associated with an increased risk of biliary tract cancers in ATBC. Further studies are needed to confirm our findings and to determine how H. pylori might influence the risk of biliary tract cancer., (© 2014 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers., Methods: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models., Results: Higher β-carotene and retinol levels were associated with less liver cancer (β-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (β-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of β-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels., Conclusions: Our findings suggest that higher concentrations of β-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

Background: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist., Objective: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy., Methods: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug., Results: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB., Conclusion: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.

Purpose: Hyperinsulinemia is hypothesized to influence prostate cancer risk. Thus, we evaluated the association of circulating C-peptide, which is a marker of insulin secretion, and leptin, which is secreted in response to insulin and influences insulin sensitivity, with prostate cancer risk., Methods: We identified prostate cancer cases (n = 1,314) diagnosed a mean of 5.4 years after blood draw and matched controls (n = 1,314) in the Health Professionals Follow-up Study. Plasma C-peptide and leptin concentrations were measured by ELISA. Odds ratios (ORs) and 95 % confidence intervals (CI) were estimated taking into account the matching factors age and history of a PSA test before blood draw and further adjusting for body mass index, diabetes, and other factors., Results: Neither C-peptide (quartile [Q]4 vs. Q1: OR 1.05, 95 % CI 0.82-1.34, p-trend = 0.95) nor leptin (Q4 vs. Q1: OR 0.85, 95 % CI 0.65-1.12, p-trend = 0.14) was associated with prostate cancer risk. Further, neither was associated with risk of advanced or lethal disease (n = 156 cases; C-peptide: Q4 vs. Q1, OR 1.18, 95 % CI 0.69-2.03, p-trend = 0.78; leptin: Q4 vs. Q1, OR 0.74, 95 % CI 0.41-1.36, p-trend = 0.34)., Conclusions: In this large prospective study, circulating C-peptide and leptin concentrations were not clearly associated with risk of prostate cancer overall or aggressive disease. Well into the PSA era, our findings do not appear to be supportive of the hypothesis that hyperinsulinemia influences risk of total or aggressive prostate cancer.

Mental illness stigma has adverse effects on both the caregivers' psychological well-being and the effectiveness of care that consumers receive. While anti-stigma interventions for family caregivers from Western settings have recently shown efficacy, these interventions may not be equally applicable across culturally diverse groups. Specifically, Chinese immigrant caregivers experience heightened internalized stigma, which predisposes the adoption of harmful coping strategies and reduced quality of social networks. We present an anti-stigma intervention based on a peer-family group format, co-led by a clinician and a trained family caregiver, to counter stigma among Chinese immigrants. Data are presented from a brief intervention administered to a pilot sample of 11 Chinese immigrant caregivers that provides: psychoeducation, strategies to counter experienced discrimination, and techniques to resist internalized stigma. Case vignettes illustrate implementation of this intervention, and how the peer-family format via interactive contact counteracts internalized stereotypes, encourages adaptive coping strategies, and reinvigorates social networks. Quantitative results further suggest preliminary efficacy in reducing internalized stigma for caregivers who evidenced at least some prior internalized stigma. This study constitutes an initial but important step towards reducing mental illness stigma among Asian Americans, for whom stigma has played a powerful role in the delay and underuse of treatment.

Background: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore., Methods: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis., Results: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512)., Conclusion: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Statement of Problem: Secondary caries is considered to be the most important and common reason for the replacement of all types of restorations., Purpose: The purpose of the study was to evaluate in vitro both the anticaries efficacy and marginal integrity of amalgam, glass ionomer cement, and composite resin restorations in a cariogenic condition., Material and Methods: Class II cavities were prepared on 60 extracted teeth, which were assigned to 3 groups and restored either with amalgam, glass ionomer, or composite resin. After thermal cycling and sterilization, the teeth were set in an artificial carious environment for 10 days. The bacteria from the margin of the restorations were then collected, and microleakage was evaluated by means of dyeing. According to the locations, the demineralization of tooth tissue around the restoration was divided into 3 parts: artificial outer lesion, artificial enamel wall lesion, and artificial dentin wall lesion. The depths of the artificial outer lesion and the areas of the artificial enamel and dentin wall lesions were investigated with a confocal laser scanning microscope after all the specimens had been stained with 0.1 mM Rhodamine B. Statistical analyses consisted of 1-way ANOVA and Kruskal-Wallis tests (α=.05)., Results: No significant difference was noted in terms of the number of bacteria around the restorations for the 3 materials; the microleakage of amalgam was the least among the 3 types of restorations; the outer enamel lesion depth around the glass ionomer cement was the lowest, and the wall lesion area around the amalgam was the smallest., Conclusions: No definite inhibitory effect of fluoride releasing restorative materials (glass ionomer) was apparent on Lactobacillus acidophilus in this study. The amalgam restorations showed the best marginal integrity and the smallest artificial wall lesion among the 3 types of restorations., (Copyright © 2013 Editorial Council for the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.)

Background: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations., Methods: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models., Results: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee., Conclusion: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.