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Binyi Xiao,* Jianhong Peng,* Jinghua Tang,* Rongxin Zhang, Cong Li, Junzhong Lin, Peirong Ding, Desen Wan, Zhizhong Pan, Xiaojun Wu Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China *These authors contributed equally to this work Objectives: Gastrointestinal stromal tumor (GIST) liver metastasis (GLM) is a special subset of advanced GIST, because its lesions are easier to define and assess. We aim to determine the role of liver metastasectomy for patients with GLM in the era of tyrosine kinase inhibitor (TKI) therapy. Methods: We reviewed patients with metastatic GIST who received surgery or other treatments in Sun Yat-sen University Cancer Center between January 1991 and December 2017. Patients with metastases confined to the liver and with no previous metastasis to other locations were included into the study and were classified into surgical and non-surgical groups. All patients received 400 mg/d imatinib after the operation. We compared progression-free survival (PFS) and overall survival (OS) between the two groups. Results: A total of 102 patients were included into the study. Of them, 21 (20.1%) underwent surgery for liver metastases and 81 (79.9%) received TKI therapy alone. During the operation, six patients received radiofrequency ablation for suspicious or unresectable lesions. Three-year PFS rate was 77.5% in the surgical group and 65.5% in the non-surgical group (P=0.027); 5-year OS rate was 85.7% and 59.6%, respectively (P=0.008). About 22.1% of patients had metastases of less than three in the surgical group, while the rate was 42.9% in the non-surgical group (P=0.011). Patients with metastases of less than three had longer PFS than those with three or more, with a 3-year PFS rate of 72.8% and 65.8%, respectively (P=0.019). But their difference in 5-year OS rate was not significant (91.7% vs 55.3%, P=0.08). Conclusion: Followed by continuous TKI therapy, R0 surgery significantly prolongs the survival of patients with GLM, regardless of the extent of disease or the phase of metastasis. Keywords: gastrointestinal stromal tumor, liver metastasis, surgery, metastasectomy

Objective: We evaluated residual incontinence, depression, and quality of life among Malawian women who had undergone vesicovaginal fistula (VVF) repair 12 or more months previously.Design: Prospective cohort study.Setting: Fistula Care Centre in Lilongwe, Malawi.Population: Women who had undergone VVF repair in Lilongwe, Malawi at least 12 months prior to enrolment.Methods: Self-report of urinary leakage was used to evaluate for residual urinary incontinence; depression was evaluated with the Patient Health Questionnaire-9; quality of life was evaluated with the King's Health Questionnaire.Main Outcome Measures: Prevalence and predictors of residual incontinence, quality of life scores, and prevalence of depression and suicidal ideation.Results: Fifty-six women (19.3%) reported residual urinary incontinence. In multivariable analyses, predictors of residual urinary incontinence included: pre-operative Goh type 3 [adjusted risk ratio (aRR) 2.82; 95% confidence interval (CI) 1.61-5.27) or Goh type 4 1.08-2.78), positive postoperative cough stress test (aRR = 2.42; 95% CI 1.24-4.71) and the positive 1-hour postoperative pad test (aRR = 2.20; 95% CI 1.08-4.48). Women with Goh types 3 and 4 VVF reported lower quality of life scores. Depressive symptoms were reported in 3.5% of women; all reported residual urinary incontinence.Conclusions: While the majority of women reported improved outcomes in the years following surgical VVF repair, those with residual urinary incontinence had a poorer quality of life. Services are needed to identify and treat this at-risk group.Tweetable Abstract: Nearly one in five women reported residual urinary incontinence at follow up, 12 or months after vesicovaginal fistula repair. [ABSTRACT FROM AUTHOR]

Objective: Determine whether a 1-hour pad test at discharge can identify continence status within 120 days of obstetric vesicovaginal fistula (VVF) repair.Design: Prospective cohort study.Setting: Fistula Care Centre in Lilongwe, Malawi.Population: Women with VVF who underwent repair between January 2012 and December 2014.Methods: Data on demographics, obstetric history, physical exam findings, operative management, postoperative findings, and follow up evaluations were collected on women with VVF repair.Main Outcome Measures: Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and a receiver operating curve (ROC) were calculated to assess the utility of using a discharge pad test at three thresholds to identify women likely to be continent at follow up.Results: After VVF repair, 346 women had a 1-hour pad test performed at the time of hospital discharge and completed follow up within 120 days of repair. Of these, 79.8% (n = 276) were completely continent, whereas 20.2% (n = 70) had some degree of incontinence. The sensitivity and specificity of a negative 1-hour pad test at predicting continence is 68.1% and 82.9%, respectively. With this prevalence, a negative pad test at a 1.5-g threshold demonstrates a high predictive value (PPV = 94.0%, 95% CI 90.0-96.9) in detecting women with continence after repair.Conclusions: At the 1.5-g threshold, a negative pad test at discharge identifies 94% of women who will remain continent after VVF repair. Adding the pad test to fistula care can identify women who are likely to remain continent and may not need further therapies in settings where resources are limited and follow up after repair is difficult.Tweetable Abstract: A negative pad test after repair is associated with continued continence at follow up. [ABSTRACT FROM AUTHOR]

Objective: To compare primiparous and multiparous women who develop obstetric fistula (OF) and to assess predictors of fistula location.Design: Cross-sectional study.Setting: Fistula Care Centre at Bwaila Hospital, Lilongwe, Malawi.Population: Women with OF who presented between September 2011 and July 2014 with a complete obstetric history were eligible for the study.Methods: Women with OF were surveyed for their obstetric history. Women were classified as multiparous if prior vaginal or caesarean delivery was reported. The location of the fistula was determined at operation: OF involving the urethra, bladder neck, and midvagina were classified as low; OF involving the vaginal apex, cervix, uterus, and ureters were classified as high.Main Outcome Measures: Demographic information was compared between primiparous and multiparous women using chi-squared and Mann-Whitney U-tests. Multivariate logistic regression models were implemented to assess the relationship between variables of interest and fistula location.Results: During the study period, 533 women presented for repair, of which 452 (84.8%) were included in the analysis. The majority (56.6%) were multiparous when the fistula formed. Multiparous women were more likely to have laboured <1 day (62.4 versus 44.5%, P < 0.001), delivered a live-born infant (26.8 versus 17.9%, P = 0.026), and have a high fistula location (37.5 versus 11.2%, P < 0.001). Multiparity [adjusted odds ratio (aOR) = 4.55, 95% confidence interval (CI) 2.27-9.12)] and history of caesarean delivery (aOR = 4.11, 95% CI 2.45-6.89) were associated with development of a high fistula.Conclusions: Multiparity was common in our cohort, and these women were more likely to have a high fistula. Additional research is needed to understand the aetiology of high fistula including potential iatrogenic causes.Tweetable Abstract: Multiparity and caesarean delivery were associated with a high tract fistula in our Malawian cohort. [ABSTRACT FROM AUTHOR]

Research shows a connection between periodontal disease and cardiovascular conditions. However, oral health problems can be prevented. This evidence-based protocol provides nurses with effective hygiene care methods to improve oral health among functionally dependent and cognitively impaired older adults. [ABSTRACT FROM AUTHOR]

Front-line caregivers in nursing homes frequently provide bereavement support to family members before and after the death of a nursing home resident. Use of the evidence-based guideline 'Family Bereavement Support Before and After the Death of a Nursing Home Resident' (Davidson, 2002) can reduce uncertainty and increase the confidence of staff providing before and after death care to families, and can ensure all families receive consistent bereavement support. [ABSTRACT FROM AUTHOR]

Background: The ingestion of caustic substances induces an extensive spectrum of injuries to the aerodigestive tract which include extensive necrosis and perforation of the esophagus and stomach. The gold standard of safely assessing depth, extent of injury, and appropriate therapeutic regimen is esophagogastroduodenoscopy (EGD). The objective of this study was to report our clinical experience and to evaluate the role of a 6-point EGD classification system of injury in predicting outcomes in adult patients diagnosed with caustic agent ingestion.Methods: The study was a retrospective medical chart review from 273 patients admitted to the Chang Gung Memorial Hospital in Tao-Yuan, Taiwan between June 1999 and July 2006 for treatment of caustic ingestion. The patients underwent EGD within 24 hours of admission and mucosal damage was graded using Zagar's modified endoscopic classification scheme. After treatment, patients were followed in the outpatient clinic for a minimum of 6 months.Results: A total of 273 patients were included for analysis. Grade 3b injury was the most common caustic injury (n = 82, 30.03%), followed by grade 2b injuries (n = 62, 22.71%). Stricture was the most common complication (n = 66, 24.18%), followed by aspiration pneumonia (n = 31, 11.36%), and respiratory failure (n = 21, 7.69%). Compared to grade 3a mucosal injury, grade 3b mucosal injuries were at greater risk of prolonged hospital stay (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.25-4.80), ICU admission (OR: 10.82; 95% CI: 2.05-200.39), and gastrointestinal (OR: 4.15; 95% CI: 1.55-13.29) and systemic complications (OR: 4.07; 95% CI: 1.81-14.07).Conclusion: In patients with caustic ingestion, EGD should be performed within 12 to 24 hours and categorized according to a 6-point scale. Patients with grade 3b burns identified on endoscopy have high rates of morbidity. The 6-point scale is useful for predicting immediate and long-term complications, and guiding appropriate therapy. [ABSTRACT FROM AUTHOR]

Background: Innovative strategies are essential to meet the World Health Organization's 90/70/90 cervical cancer elimination targets, aiming for 90% access to precancer treatment globally by 2030. In low-and middle-income countries (LMICs) where most cervical cancer cases occur, access to precancer treatment is severely limited. Scalable solutions like self-administered topical therapies can help close this gap. In a recent Phase I trial ( ClinicalTrials.gov NCT05362955 ), we demonstrated safety and adherence to self-administered intravaginal 5% 5-Fluorouracil (5FU) cream as an adjuvant therapy for cervical precancer among women living with HIV (WLWH) in rural Kenya. To understand women's experiences with self-administered 5FU, we evaluated the acceptability of this intervention among trial participants., Methods: All 12 participants from the Phase I trial completed a structured questionnaire and in-depth semi-structured interviews in their preferred language, focusing on their experiences with 5FU self-administration, challenges faced, and overall acceptability of the intervention, including whether they would use it again or recommend it to someone who needed it. Quantitative data were analyzed using descriptive statistics. In the qualitative study, acceptability was defined as "the perception that a given treatment is agreeable, palatable, or satisfactory." A thematic analysis was conducted using five dimensions of acceptability: content, complexity, comfort, delivery, and credibility., Results: The mean age was 43.9 years (SD 4.4), and 7 (58%) had primary education or less. While some participants reported feelings of uncertainty when they started using 5FU, at the end of the study, all twelve participants strongly agreed that the cream was safe and were confident they used it correctly. Most participants (91.7%) experienced no discomfort with the vaginal applicator, and most reported using tampons overnight after 5FU use, as recommended. Qualitative findings revealed that favorable perceptions of self-administered 5FU were driven by its ease of use, the discrete nature of the treatment, and the comfort of home application. The main challenges included correctly measuring the study drug, finding a private place at home to self-administer, and the need to use condoms during treatment. Compared to their previous ablation or excision treatments, participants found 5FU to be less painful, and all would prefer a self-administered treatment instead of a procedure if it were an option., Conclusion: Self-administered intravaginal 5FU as an adjuvant treatment for cervical precancer among women living with HIV in Kenya was highly acceptable. Randomized studies of 5FU and other topical therapies in LMICs are needed to evaluate their use in closing the current precancer treatment gaps in these settings.

Singlet oxygen is a crucial reactive oxygen species (ROS) in photodynamic therapy (PDT). However, the hypoxic tumor microenvironment limits the production of cytotoxic singlet oxygen through the light irradiation of PDT photosensitizers (PSs). This restriction poses a major challenge in improving the effectiveness of PDT. To overcome this challenge, researchers have explored the development of singlet oxygen carriers that can capture and release singlet oxygen in physiological conditions. Among these developments, anthracene-based endoperoxides, initially discovered almost 100 years ago, have shown the ability to generate singlet oxygen controllably under thermal or photo stimuli. Recent advancements have led to the development of a new class of self-sensitized anthracene-endoperoxides, with potential applications in enhancing PDT effects for hypoxic tumors. This review discusses the current research progress in utilizing self-sensitized anthracene-endoperoxides as singlet oxygen carriers for improved PDT. It covers anthracene-conjugated small organic molecules, metal-organic complexes, polymeric structures, and other self-sensitized nano-structures. The molecular structural designs, mechanisms, and characteristics of these systems will be discussed. This review aims to provide valuable insights for developing high-performance singlet oxygen carriers for hypoxic-tumor PDT., (© 2024 Wiley‐VCH GmbH.)

Introduction: Postcolonoscopy colorectal cancers primarily occur in the right-sided colon because of missed adenomas and serrated polyps (SPs). Water exchange (WE) improves cleanliness and visibility of the right-sided colon. We hypothesized that WE could reduce the right-sided colon adenoma (rAMR) and SP miss rate (rSPMR) compared to standard colonoscopy., Methods: We randomly assigned 386 colonoscopy patients to insertion with either WE or CO2 insufflation. During the first withdrawal, polypectomies were performed up to the hepatic flexure. A second endoscopist, blinded to the insertion technique, reexamined the right-sided colon. The miss rate was determined by dividing the number of additional adenomas or SPs by the total number detected in both examinations. The primary outcome was the combined rAMR and rSPMR., Results: WE significantly decreased the combined rAMR and rSPMR (22.2% vs 32.2%, P < 0.001) and rSPMR alone (22.5% vs 37.1%, P = 0.002) compared to CO2 insufflation, but not rAMR (21.8% vs 29.8%, P = 0.079). Additionally, WE significantly increased the detection of SP per colonoscopy (SPPC) in the right-sided colon (0.95 ± 1.56 vs 0.50 ± 0.79, P < 0.001). Multivariate logistic regression analysis showed that ≥2 SPs in the right-sided colon was an independent predictor of rSPMR (odds ratio [OR], 3.47; 95% confidence interval [CI], 1.89─6.38), along with a higher right-sided colon Boston Bowel Preparation Scale score (OR, 0.55; 95% CI, 0.32─0.94)., Conclusions: The significant reduction in rSPMR and increase in right-sided colon SPPC suggest that colonoscopy insertion using WE is a valid alternative to CO2 insufflation (Clinical trial registration number: NCT04124393)., (Copyright © 2024 by The American College of Gastroenterology.)

Selective separation of 137 Cs is significant for the sustainable development of nuclear energy and environmental protection, due to its strong radioactivity and long half-life. However, selective capture of 137 Cs + from radioactive liquid waste is challenging due to strong coulomb interactions between the adsorbents and high-valency metal ions. Herein, we propose a strategy to resolve this issue and achieve specific Cs + ion recognition and separation by modulating the stacking modes of layered perovskites. We demonstrate that among niobate-based perovskites, ALaNb 2 O 7 (A = Cs, H, K, and Li), HLaNb 2 O 7 shows an outstanding selectivity for Cs + even in the presence of a large amount of competing M n+ ions (M n+  = K + , Ca 2+ , Mg 2+ , Sr 2+ , Eu 3+ , and Zr 4+ ) owing to its suitable void fraction and space shape, brought by the stacking mode of layers. The Cs + capture mechanism is directly elucidated at molecular level by single-crystal structural analyses and density functional theory calculations. This work not only provides key insights in the design and property optimization of perovskite-type materials for radiocesium separation, but also paves the way for the development of efficient inorganic materials for radionuclides remediation., (© 2024. The Author(s).)

Background: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation., Results: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia., Conclusion: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Senescent cells play a vital role in the pathogenesis of musculoskeletal (MSK) diseases, such as chronic inflammatory joint disorders, rheumatoid arthritis (RA), and osteoarthritis (OA). Cellular senescence in articular joints represents a response of local cells to persistent stress that leads to cell-cycle arrest and enhanced production of inflammatory cytokines, which in turn perpetuates joint damage and leads to significant morbidities in afflicted patients. It has been recently discovered that clearance of senescent cells by novel "senolytic" therapies can attenuate the chronic inflammatory microenvironment of RA and OA, preventing further disease progression and supporting healing processes. To identify patients who might benefit from these new senolytic therapies and monitor therapy response, there is an unmet need to identify and map senescent cells in articular joints and related musculoskeletal tissues. To fill this gap, new imaging biomarkers are being developed to detect and characterize senescent cells in human joints and musculoskeletal tissues. This review article will provide an overview of these efforts. New imaging biomarkers for senescence cells are expected to significantly improve the specificity of state-of-the-art imaging technologies for diagnosing musculoskeletal disorders., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.

Background: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated., Methods: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays., Results: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade., Conclusions: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.

Precise and reliable monitoring of DNA adenine methyltransferase (Dam) activity is essential for disease diagnosis and biological analysis. However, existing techniques for detecting Dam activity often rely on specific DNA recognition probes that are susceptible to DNA degradation and exhibit limited target sensitivity and specificity. In this study, we designed and engineered a stable and dynamic DNA nanodevice called the d ouble-l o op interl o cked DNA ci r cuit (DOOR) that enables the sensitive and selective monitoring of Dam activity in complex biological environments. The DOOR incorporates two interlocked specialized sequences: a palindromic sequence for Dam identification and an initiator sequence for signal amplification. In the presence of Dam, the DOOR is cleaved by double-stranded DNA phosphodiesterase I endonuclease, generating massive double-stranded DNA (dsDNA) units. These units can self-assemble into a long dsDNA scaffold, thereby enhancing the subsequent reaction kinetics. The dsDNA scaffold further triggers a hyperbranched hybrid chain reaction to produce a fluorescent 3D DNA nanonet, enabling more precise monitoring of the Dam activity. The DOOR device exhibits excellent sensitivity, specificity, and stability, rendering it a powerful tool for studying DNA methylation in various biological processes and diseases.

Background: The COVID-19 pandemic affected global access to health services, including contraception We sought to explore effects of the pandemic on family planning (FP) service provision and use in South Africa and Zambia, including on implant and intrauterine device (IUD) users' desire and ability to obtain removal., Methods: Between August 2020 and April 2021, we conducted surveys with 537 women participating in an ongoing longitudinal contraceptive continuation study. We also carried out in-depth interviews with 39 of the survey participants and 36 key informants involved in FP provision. We conducted descriptive analysis of survey responses and thematic analysis of interviews., Results: Contraceptive use changed minimally in this sample with the emergence of COVID-19. Fewer than half of women (n=220) reported that they tried to access FP since the start of the pandemic. The vast majority of those seeking services were using short-acting methods and 95% were able to obtain their preferred method. The proportion of women not using a method before and after the start of the pandemic did not change in Zambia (31%), and increased from 8% to 10% in South Africa. Less than 7% of implant or IUD users in either country reported wanting removal. Among the 22 who sought removal, 10 in Zambia and 6 in South Africa successfully obtained removal. In qualitative interviews, those reporting challenges to service access specifically mentioned long queues, deprioritization of contraceptive services, lack of transportation, stock-outs, and fear of contracting COVID-19 at a facility. Key informants reported stock-outs, especially of injectables, and staff shortages as barriers., Conclusions: We did not find a substantial impact of COVID-19 on contraceptive access and use among this sample; however, providers and others involved in service provision identified risks to continuity of care. As the COVID-19 pandemic wanes, it continues to be important to monitor people's ability to access their preferred contraceptive methods., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Callahan RL et al.)

In sub-Saharan Africa, adolescent girls and young women aged 15-24 (AGYW) experience high risk of early and unintended pregnancy. We assessed the impact of youth-friendly health services (YFHS) on pregnancy risk among AGYW who participated in the Girl Power study. In 2016, Girl Power randomly assigned four government-run health centers in Lilongwe, Malawi, to provide a standard (n=1) or youth-friendly (n=3) model of service delivery. At six and 12 months, study participants (n=250 at each health center) self-reported their current pregnancy status and received a urine pregnancy test. Because of missing pregnancy test results, we used multiple imputation to correct for outcome misclassification in self-reported pregnancy status, and applied the parametric g-formula on the corrected data to estimate the effect of YFHS on the 12-month risk of pregnancy. After correcting for outcome misclassification, the risk of pregnancy under the scenario where all health centers offered YFHS was 15.8% compared to 23.2% under the scenario where all health centers offered standard of care (risk difference: -7.3%, 95% CI: -15.5%, 0.8%). Access to a model of YFHS that integrates provider training with youth-friendly clinic modifications and community outreach activities may decrease risk of pregnancy among AGYW relative to standard of care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer., Methods: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing., Findings: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis., Interpretation: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach., Funding: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China., Methods: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed., Results: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits., Conclusions: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China., (© 2024. The Author(s).)

Highly selective capture of radiocesium is an urgent need for environmental radioactive contamination remediation and spent fuel disposal. Herein, a strategy is proposed for construction of "inorganic ion-imprinted adsorbents" with ion recognition-separation capabilities, and a metal sulfide Cs 2.33 Ga 2.33 Sn 1.67 S 8 ·H 2 O (FJSM-CGTS) with "imprinting effect" on Cs + is prepared. We show that the K + activation product of FJSM-CGTS, Cs 0.51 K 1.82 Ga 2.33 Sn 1.67 S 8 ·H 2 O (FJMS-KCGTS), can reach adsorption equilibrium for Cs + within 5 min, with a maximum adsorption capacity of 246.65 mg·g -1 . FJMS-KCGTS overcomes the hindrance of Cs + adsorption by competing ions and realizes highly selective capture of Cs + in complex environments. It shows successful cleanup for actual 137 Cs-liquid-wastes generated during industrial production with removal rates of over 99%. Ion-exchange column filled with FJMS-KCGTS can efficiently treat 540 mL Cs + -containing solutions (31.995 mg·L -1 ) and generates only 0.12 mL of solid waste, which enables waste solution volume reduction. Single-crystal structural analysis and density functional theory calculations are used to visualize the "ion-imprinting" process and confirm that the "imprinting effect" originates from the spatially confined effect of the framework. This work clearly reveals radiocesium capture mechanism and structure-function relationships that could inspire the development of efficient inorganic adsorbents for selective recognition and separation of key radionuclides., (© 2024. The Author(s).)

Background: The World Health Organization recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi., Methods: We utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis-cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to

Urban heat islands will occur if city neighborhoods contain insufficient green spaces to create a comfortable environment, and residents' health will be adversely affected. Current satellite imagery can only effectively identify large-scale green spaces and cannot capture street trees or potted plants within three-dimensional building spaces. In this study, we used a deep convolutional neural network semantic segmentation model on Google Street View to extract environmental features at the neighborhood level in Taipei City, Taiwan, including the green vegetation index (GVI), building view factor, and sky view factor. Monthly temperature data from 2018 to 2021 with a 0.01° spatial resolution were used. We applied a linear mixed-effects model and geographically weighted regression to explore the association between pedestrian-level green spaces and ambient temperature, controlling for seasons, land use information, and traffic volume. Their results indicated that a higher GVI was significantly associated with lower ambient temperatures and temperature differences. Locations with higher traffic flows or specific land uses, such as religious or governmental, are associated with higher ambient temperatures. In conclusion, the GVI from street-view imagery at the community level can improve the understanding of urban green spaces and evaluate their effects in association with other social and environmental indicators., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT). Venn analysis revealed 119 DE mRNAs that were down-regulated in the LPS + YT vs LPS comparison but up-regulated in the CN vs LPS comparison, primarily enriched in Gene Ontology terms related to immune and inflammatory responses. Furthermore, through Venn analysis of YT vs CN and LPS + YT vs LPS comparisons, we identified 178 DE mRNAs and 432 DE lncRNAs. Among these transcripts, we validated the expression of Tent5c at the protein and mRNA levels. Additionally, siRNA-knockdown of Tent5c attenuated the expression of pro-inflammatory genes (TNF-α, IL-1β, Agrn, and Fpr2), cellular morphological changes, NLRP3 and p-P65 protein levels, immunofluorescence staining of p-P65 and number of cells with ASC-speck induced by LPS. Furthermore, Tent5c overexpression further potentiated the aforementioned indicators in the context of mild hypothermia with LPS treatment. Collectively, our findings highlight the significant role of Tent5c down-regulation in mediating the anti-inflammatory effects of mild hypothermia., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous studies have found associations between the incidence of metabolic syndrome (MetS) and exposure to air pollution or road traffic noise. However, investigations on environmental co-exposures are limited. This study aimed to investigate the association between co-exposure to air pollution and road traffic noise and MetS and its subcomponents. Participants living in Taipei City who underwent at least two health checkups between 2010 and 2016 were included in the study. Data were sourced from the MJ Health database, a longitudinal, large-scale cohort in Taiwan. The monthly traffic noise exposure (L den and L night ) was computed using a dynamic noise map. Monthly fine particulate data at one kilometer resolution were computed from satellite imagery data. Cox proportional hazards regression models with month as the underlying time scale were used to estimate hazard ratios (HRs) for the impact of PM 2.5 and road traffic noise exposure on the risk of developing MetS or its subcomponents. Data from 10,773 participants were included. We found significant positive associations between incident MetS and PM 2.5 (HR: 1.88; 95% CI 1.67, 2.12), L den (HR: 1.10; 95% CI 1.06, 1.15), and L night (HR: 1.07; 95% CI 1.02, 1.13) in single exposure models. Results further showed significant associations with an elevated risk of incident MetS in co-exposure models, with HRs of 1.91 (95% CI 1.69, 2.16) and 1.11 (95% CI 1.06, 1.16) for co-exposure to PM 2.5 and L den , and 1.90 (95% CI 1.68, 2.14) and 1.08 (95% CI 1.02, 1.13) for co-exposure to PM 2.5 and L night . The HRs for the co-exposure models were higher than those for models with only a single exposure. This study provides evidence that PM 2.5 and noise exposure may elevate the risk of incident MetS and its components in both single and co-exposure models. Therefore, preventive approaches to mitigate the risk of MetS and its subcomponents should consider reducing exposure to PM 2.5 and noise pollution., (© 2024. The Author(s).)

Urban greenery can help to improve air quality, reduce health risks and create healthy livable urban communities. This study aimed to explore the role of urban greenery in reducing air pollution at the community level in Tainan City, Taiwan, using air quality sensors and street-view imagery. We also collected the number of road trees around each air quality sensor site and identified the species that were best at absorbing PM 2.5 . Three greenness metrics were used to assess community greenery in this study: two Normalized Difference Vegetation Indices (NDVI) from different satellites and the Green View Index (GVI) from Google Street View (GSV) images. Land-use Regression (LUR) was used for statistical analysis. The results showed that a higher GVI within a 500 m buffer was significantly associated with decreased PM 2.5 . Neither NDVI metrics within a 500 m circular buffer were significantly associated with decreased PM 2.5 . Evergreen trees were significantly associated with lower ambient PM 2.5 , compared with deciduous and semi-deciduous trees. Because localized changes in air quality profoundly affect public health and environmental equity, our findings provide evidence for future urban community greenspace planning and its beneficial impacts on reducing air pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy., Methods: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method., Results: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%., Conclusions: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Background: The perioperative outcomes of a partial hepatectomy for hepatocellular carcinoma (HCC) have improved. However, high recurrence rates after a curative hepatectomy for HCC is still an issue. This study aimed to analyze the difference between various recurrence patterns., Methods: We retrospectively reviewed 754 patients with HCC who underwent a curative hepatectomy between January 2012 and March 2021. Patients with recurrent events were categorized into three types: regional recurrence (type I), multiple intrahepatic recurrence (type II), or presence of any distant metastasis (type III)., Results: The median follow-up period was 51.2 months. Regarding recurrence, 375 (49.7%) patients developed recurrence, with 244 (32.4%), 51 (6.8%), and 80 (10.6%) patients having type I, II, and III recurrence, respectively. Type III recurrence appeared to be more common in male patients and those with major liver resection, vascular invasion, a large tumor size (>5 cm), a higher tumor grade, and higher levels of AST and AFP ( p < 0.05). Patients who had distant metastasis at recurrence had the shortest recurrence time and the worst overall survival ( p < 0.001 and p < 0.001)., Conclusions: our study demonstrated that recurrence with distant metastasis occurred earliest and had the worst outcome compared to regional or multiple intrahepatic recurrences.

Objective: To explore the experiences of Malawian women who underwent a human papillomavirus (HPV)-based screen-triage-treat algorithm for cervical cancer (CxCa) prevention. This algorithm included GeneXpert® HPV testing of self-collected vaginal samples, visual inspection with acetic acid (VIA) and colposcopy for HPV-positive women, and thermal ablation of ablation-eligible women., Method: In-depth interviews were conducted with participants of a trial that evaluated the feasibility of a HPV-based screen-triage-treat algorithm among women living with HIV and HIV negative women in Lilongwe, Malawi. Participants were recruited from 3 groups: 1) HPV-negative; 2) HPV-positive/VIA-negative; 3) HPV-positive/VIA-positive and received thermal ablation. Interviews explored baseline knowledge of CxCa and screening, attitudes towards self-collection, and understanding of test results. Content analysis was conducted using NVIVO v12., Results: Thematic saturation was reached at 25 interviews. Advantages of HPV self-collection to participants were convenience of sampling, same-day HPV results and availability of same-day treatment. There was confusion surrounding HPV-positive/VIA-negative results, as some participants still felt treatment was needed. Counseling, and in particular anticipatory guidance, was key in helping participants understand complex screening procedures and results. Overall, participants expressed confidence in the HPV screen-triage-treat strategy., Discussion: HPV testing through self-collected samples is a promising tool to increase CxCa screening coverage. A multi-step screening algorithm utilizing HPV self-testing, VIA triage and thermal ablation treatment requires proper counseling and anticipatory guidance to improve patient understanding. Incorporating thorough counseling in CxCa screening programs can change women's perspectives about screening, build trust in healthcare systems, and influence healthcare seeking behavior towards routine screening and prevention., 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 © 2024 Lee, McGue, Chapola, Dunda, Tang, Ndovie, Msowoya, Mwapasa, Smith and Chinula.)

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

This study aimed to assess the utility of serum YKL-40 and serum dipeptidyl peptidase IV (DPP4) as biomarkers for distinguishing between type 2 (T2)-high and T2-low asthma in the Chinese population. Additionally, we sought to explore the associations of serum YKL-40 and DPP4 levels with asthma characteristics and conventional markers. A real-world observational cross-sectional study was conducted, involving a total of 75 adult asthma patients. We collected general information, including demographics and medical history. Measurements included complete blood count, fractional exhaled nitric oxide (FeNO), post-bronchodilator spirometry, serum YKL-40 and serum DPP4 levels. Asthma endotypes, T2-high and T2-low, were defined through a comprehensive review of existing literature and expert group discussions. Logistic and linear regression models were employed. Our findings indicated no significant association between serum YKL-40 or serum DPP4 levels and T2-high asthma across all models. In the fully adjusted model, their odds ratios (OR) were 0.967 (95% CI: 0.920-1.017) and 0.997 (95% CI: 0.993-1.001), respectively. Notably, serum YKL-40 exhibited a positive correlation with FeNO (β = 0.382, 95% CI: 0.230-0.533) after adjusting for confounding factors. This association, however, diminished in patients under 40 years old (P = .24), males (P = .25), and those with FEV1%pred of 80% or higher (P = .25). Serum DPP4 demonstrated a negative correlation with FEV1/FVC in the fully adjusted model (β: -0.005, 95% CI: -0.009, -0.000). Among Chinese adult asthma patients, a positive correlation was observed between serum YKL-40 levels and FeNO in females aged over 40 with FEV1%pred less than 80%. Additionally, a weak negative correlation was found between serum DPP4 levels and FEV1/FVC. However, neither serum YKL-40 nor serum DPP4 levels exhibited the capability to differentiate between T2-high and T2-low asthma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To estimate demand for medication abortion (MAB) among North Carolina (NC) college students and describe access to nearest clinics offering MAB to each campus., Methods: We calculated demand using 2019-2020 campus demographics and NC abortion statistics. We used a mystery client technique to gather MAB cost and appointment wait times at the closest clinics and calculated travel distances and times., Results: We estimated that 2,517 NC students seek MAB annually. Twenty-one clinics were closest to NC's 111 colleges and universities, including five in neighboring states. Mean cost was $450, with an average wait time of six days to appointment. The average round-trip travel distance was 58 miles and time to the nearest clinic was 84 min by car., Conclusions: Many NC college students likely obtain MAB every year and face high costs, long wait times and distances to care, which has likely worsened after the overturning of Roe v. Wade .

Objective: The aim of this study was to understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation., Methods: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations., Results: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with nonoptimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations [tenofovir relative risk (RR): 0.098, P = 0.75; lamivudine RR: 0.142, P = 0.54]. Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition and lamivudine/tenofovir CVF concentrations (RR: 1.33, P = 0.531)., Conclusion: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate current abortion access in the United States based on geographic location and to forecast access according to the landscape of abortion care in the year after the Dobbs v Jackson Women's Health Organization decision., Methods: Addresses of abortion-providing clinics were identified using web-based directories from Planned Parenthood, the National Abortion Foundation, Abortion Finder, and Power to Decide. Using geographic coordinates and the OpenStreetMap road network, Valhalla's Isochrone application programming interface was used to calculate the areas within a 30-, 60-, and 90-minute driving distance from these clinics. The population of reproductive-aged women (15-49 years) in the tracts inside or outside the accessible areas was determined using the U.S. Census American Community Survey for 2020. Review of legislative and judicial actions for 2023 determined at-risk states. Clinic locations and laws are accurate as of June 2, 2023., Results: The addresses of 750 abortion facilities were geocoded. Currently, 41.4% (30.8 million) of women do not have access to an abortion clinic within a 30-minute drive, and 29.3% and 23.6% do not have access within a 60-minute and 90-minute drive, respectively. When accounting for the combined population with no access, severely limited access, and at-risk of losing access, 53.5% of women do not have access within a 30-minute drive, and 45.6% and 43.0% do not have access within a 60-minute and 90-minute drive, respectively., Discussion: Two of every five American women do not have access to an abortion facility within a 30-minute drive, and one in four lack access within a 90-minute drive. These proportions could significantly increase if access is restricted further with state bans proposed in 2023., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated., Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. IHC staining was used to assess the expression of APM-related genes in clinical samples., Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were mined in the APMrs-high group. APM-related genes were further validated in our in-house samples., Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Global precipitation is becoming increasingly intense due to the extreme climate. Therefore, creating new technology to manage water resources is crucial. To create a sustainable urban and ecological environment, a water level and water quality control system implementing artificial intelligence is presented in this research. The proposed smart monitoring system consists of four sensors (two different liquid level sensors, a turbidity and pH sensor, and a water oxygen sensor), a control module (an MCU, a motor, a pump, and a drain), and a power and communication system (a solar panel, a battery, and a wireless communication module). The system focuses on low-cost Internet of Things (IoT) devices along with low power consumption and high precision. This proposal collects rainfall from the preceding 10 years in the application region as well as the region's meteorological bureau's weekly weather report and uses artificial intelligence to compute the appropriate water level. More importantly, the adoption of dynamic adjustment systems can reserve and modify water resources in the application region more efficiently. Compared to existing technologies, the measurement approach utilized in this study not only achieves cost savings exceeding 60% but also enhances water level measurement accuracy by over 15% through the successful implementation of water level calibration decisions utilizing multiple distinct sensors. Of greater significance, the dynamic adjustment systems proposed in this research offer the potential for conserving water resources by more than 15% in an effective manner. As a result, the adoption of this technology may efficiently reserve and distribute water resources for smart cities as well as reduce substantial losses caused by anomalous water resources, such as floods, droughts, and ecological concerns.

Background: Colorectal cancer with mismatch repair deficiency is usually less aggressive and associated with a lower risk of distant metastasis. Immune checkpoint inhibition, rather than traditional chemoradiotherapy, has shown great advantages in treating such patients., Objective: This study aimed to verify the hypothesis that locally very advanced (T4b) colorectal cancer without distant metastases might present with higher probability of mismatch repair deficiency and be more sensitive to neoadjuvant immune checkpoint inhibition., Design: This study was designed as a single-center retrospective observational study., Settings: The study was conducted in a tertiary referral center in China., Patients: The study included patients who were clinically diagnosed with T4bM0 colorectal cancer from 2008 to 2019., Main Outcome Measures: Clinicopathological characteristics, mismatch repair status, and survival outcomes of patients with mismatch repair deficiency were analyzed., Results: A total of 268 patients were included. The incidence of patients with mismatch repair deficiency in the T4bM0 population was 27.6% (75/268), with 84.0% (63/75) in the colon and 16.0% (12/75) in the rectum. For tumors located in the proximal colon, 45.0% (50/111) exhibited mismatch repair deficiency, whereas the incidence of mismatch repair deficiency in sigmoid colon cancer and rectal cancer was only 15.9% (25/157). Neoadjuvant immune checkpoint inhibition significantly reduced the open surgery rate ( p = 0.000) and multivisceral resection rate ( p = 0.025). The pathological complete remission rate in the neoadjuvant immune checkpoint inhibition group was significantly higher than that in neoadjuvant chemoradiotherapy/chemotherapy group (70.0% vs 0%; p = 0.004). No tumor downstaging was observed after neoadjuvant chemotherapy. Neoadjuvant immune checkpoint inhibition provided significantly better disease-free survival ( p = 0.0078) and relatively longer overall survival ( p = 0.15) than other groups., Limitations: This study is limited by the possible selection bias and small sample size., Conclusions: Our data depicted the high incidence of mismatch repair deficiency in T4bM0 mismatch repair deficiency and the effectiveness of the neoadjuvant immune checkpoint inhibition group in organ preservation. Precision oncology requires identification of the protein status of mismatch repair at initial diagnosis to make a rational treatment decision for these patients. See Video Abstract at http://links.lww.com/DCR/B952 ., La Inhibicin Del Punto De Control Inmunitario Neoadyuvante Mejora La Preservacin De Rganos En El Cncer Colorrectal Tbm Con Deficiencia De Reparacin De Errores De Coincidencia Un Estudio Observacional Retrospectivo: ANTECEDENTES:Los pacientes con cáncer colorrectal con deficiencia en la reparación de desajustes suelen (dMMR) ser menos agresivos y se asocian con un menor riesgo de metástasis a distancia. La inhibición del punto de control inmunitario, en lugar de la quimiorradioterapia tradicional, ha mostrado grandes ventajas en el tratamiento de estos pacientes.OBJETIVO:Este estudio tuvo como objetivo verificar nuestra hipótesis de que el CCR localmente muy avanzado (T4b) sin metástasis a distancia podría presentarse con una mayor probabilidad de dMMR y ser más sensible a la inhibición del punto de control inmunitario neoadyuvante.DISEÑO:Este estudio fue diseñado como un estudio observacional retrospectivo de un solo centro.CONFIGURACIÓN:El estudio se realizó en un centro de referencia terciario en China.PACIENTES:Se incluyeron pacientes con diagnóstico clínico de CCR T4bM0 desde 2008 hasta 2019.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron las características clinicopatológicas, el estado de MMR y los resultados de supervivencia de los pacientes con dMMR.RESULTADOS:Se incluyeron un total de 268 pacientes. La incidencia de dMMR en la población T4bM0 fue del 27,6% (75/268), con un 84,0% (63/75) en colon y un 16,0% (12/75) en recto. Para los tumores ubicados en el colon proximal, el 45,0% (50/111) exhibió dMMR, mientras que la incidencia de dMMR en el cáncer de colon sigmoideo y el cáncer de recto fue solo del 15,9% (25/157). La inhibición del punto de control inmunitario neoadyuvante redujo significativamente la cirugía abierta y la tasa de resección multivisceral ( p = 0,000 y p = 0,025, respectivamente). La tasa de PCR en el grupo de inhibición del punto de control inmunitario neoadyuvante fue significativamente mayor que en el grupo de quimiorradioterapia/quimioterapia neoadyuvante (70,0% frente a 0%, p = 0,004). No se observó reducción del estadio del tumor después de la quimioterapia neoadyuvante. La inhibición del punto de control inmunitario neoadyuvante proporcionó una supervivencia sin enfermedad significativamente mejor ( p = 0,0078) y una supervivencia general relativamente más larga ( p = 0,15) que otros grupos.LIMITACIONES:Este estudio está limitado por el posible sesgo de selección y el pequeño tamaño de la muestra.CONCLUSIONES:Nuestros datos representan la alta incidencia de dMMR en T4bM0 CRC y la eficacia del grupo de inhibición del punto de control inmunitario neoadyuvante en la preservación de órganos. La oncología de precisión requiere la identificación del estado de la proteína MMR en el diagnóstico inicial para tomar una decisión de tratamiento racional para estos pacientes especiales. Consulte el Video Resumen en http://links.lww.com/DCR/B952 . (Traducción-Dr. Yesenia Rojas-Khalil )., (Copyright © The ASCRS 2022.)