bluuebunny/crossref_metadata_2025_split huggingface dataset:
MARVELD3 inhibits the epithelial‐mesenchymal transition and cell migration by suppressing the Wnt/β‐catenin signaling pathway in non–small cell lung cancer cells
Authors: Li Shirong , Qi Saiping , Li Yanmeng , Zhang Chunpan , Sun Lan , Liu Chunquan , Wang Haoyan 
Published: April 2023

AbstractBackgroundThe epithelial‐mesenchymal transition (EMT), featured by abatement of cell–cell contact, is related to exacerbating non–small cell lung cancer (NSCLC) by inducing metastasis. MAL and relevant proteins for vesicle trafficking and membrane link domain 3 (MARVELD3) is a novel tight junction protein participated in the EMT. There is limited information available about the mechanism of MARVELD3 in NSCLC. In this trial, the inhibition effect of MARVELD3 on human NSCLC cells will be discussed.MethodsMARVELD3 expression was measured in NSCLC tissues and para‐carcinoma tissues. The expression of MARVELD3 and EMT‐related genes were examined in transforming growth factor (TGF)‐β1‐induced NSCLC cells. NSCLC cells with MARVELD3‐knockdown and overexpressed were established to analyze the relationship between MARVELD3 and EMT and cell migration. The Wnt/β‐catenin pathway expression was also analyzed in NSCLC cell models and clinic species.ResultsLower protein levels of MARVELD3 were observed in NSCLC samples than para‐carcinoma specimens, and the decreased expression of MARVELD3 in NSCLC specimens was associated with tumor metastasis. E‐Cadherin and MARVELD3 expression was reduced in TGF‐β1 treated NSCLC cells, whereas increased Vimentin expression was detected. MARVELD3 changed the EMT‐related genes and induced cell migration. In addition, Wnt/β‐catenin pathway and target genes, MYC and CCND1, expressions were inhibited in MARVELD3 overexpressed NSCLC cells.ConclusionsTGF‐β1 induced EMT in human NSCLC cells can be suppressed by MARVELD3 through Wnt/β‐catenin signaling pathway. These results indicate that MARVELD3 might be a potential therapeutic modality useful in the treatment of NSCLC.
Effective alcohol policies are associated with reduced consumption among demographic groups who drink heavily
Authors: Casswell Sally , Huckle Taisia , Parker Karl , Graydon‐Guy Thomas , Leung June , Parry Charles , Torun Perihan , Sengee Gantuya , Pham Cuong , Gray‐Phillip Gaile , Callinan Sarah , Chaiyasong Surasak , MacKintosh Anne Marie , Meier Petra , Randerson Steve 
Published: April 2023

AbstractBackgroundAlcohol policies stand out among other noncommunicable disease‐relevant policies for the lack of uptake. Composite indicators have been developed to measure the effects of alcohol control policy. We investigated whether drinking patterns among demographic groups from general population samples of drinkers from diverse countries are associated with alcohol control policy as measured by the International Alcohol Control (IAC) Policy Index.MethodsRepresentative samples of adult drinkers from 10 countries (five high‐income and five middle‐income) were surveyed about alcohol consumption, using beverage and location‐specific questions.MeasurementsThe IAC Policy Index was analyzed with frequency, typical occasion quantity, and volume consumed. Analyses used mixed models that included interactions between country IAC Policy Index score and age group, gender, and education level.FindingsEach increase in IAC policy index score (reflecting more effective alcohol policy) was associated with a 13.9% decrease in drinking frequency (p = 0.006) and a 16.5% decrease in volume (p = 0.001). With each increase in IAC Policy Index score, both genders decreased for all three measures, but men less so than women. Women decreased their typical occasion quantity by 1.2% (p = 0.006), frequency by 3.1% (p < 0.001), and total volume by 4.2% (p < 0.001) compared to men. Low and mid‐education groups decreased their typical occasion quantity by 2.6% (p < 0.001) and 1.6% (p = 0.001), respectively, compared to high education, while for drinking frequency the low education group increased by 7.0% (p < 0.001). There was an overall effect of age (F = 19.27, p < 0.0001), with 18–19 and 20–24‐year‐olds showing the largest decreases in typical occasion quantity with increasing IAC policy index score.ConclusionsThe IAC Policy Index, reflecting four effective policies, was associated with volume and frequency of drinking across 10 diverse countries. Each increase in the IAC Policy Index was associated with lower typical quantities consumed among groups reporting heavy drinking: young adults and less well‐educated. There is value in implementing such alcohol policies and a need to accelerate their uptake globally.
Trends in alcohol‐impaired crashes in California, 2016 to 2021: A time series analysis for alcohol involvement and crash distribution among demographic subgroups
Authors: Mehranbod Christina A. , Gobaud Ariana N. , Branas Charles C. , Chen Qixuan , Giovenco Daniel P. , Humphreys David K. , Rundle Andrew G. , Bushover Brady R. , Morrison Christopher N. 
Published: April 2023

AbstractBackgroundIn 2020, the COVID‐19 pandemic and control measures changed alcohol consumption in the United States (US) and globally. Before the pandemic, alcohol‐impaired crashes contributed to approximately one‐third of all road traffic crash injuries and fatalities nationally. We examined the impact of the COVID‐19 pandemic on crashes and examined differences in alcohol‐involved crashes across various subgroups.MethodsThe University of California Berkeley Transportation Injury Mapping Systems provided information on all crashes reported to the California Highway Patrol from January 1, 2016 through December 31, 2021. Using autoregressive integrated moving average (ARIMA) models applied to weekly time series data, we estimated the effect of California's first mandatory statewide shelter‐in‐place order (March 19, 2020) on crashes per 100,000 population. We also examined crash subgroups according to crash severity, sex, race/ethnicity, age, and alcohol involvement.ResultsIn California, the mean crash rate per week before the pandemic (January 1, 2016–March 18, 2020) was 9.5 crashes per 100,000 population, and 10.3% of those were alcohol‐involved. After the initiation of the COVID‐19 stay‐at‐home order, the percentage of crashes that were alcohol‐involved rose to 12.7%. Overall, the crash rate across California decreased significantly (−4.6 crashes per 100,000; 95% CI: −5.3, −3.9), including across all examined subgroups, with the greatest decrease among the least severe crashes. However, there was a 2.3% absolute increase in the proportion of crashes that were alcohol‐involved (0.02 crashes per 100,000; 95% CI: 0.02, 0.03).ConclusionsThe initiation of a COVID‐19 stay‐at‐home ordinance in California was associated with a substantial decrease in overall crash rates. While crashes have returned to pre‐pandemic levels, alcohol‐involved crashes remain elevated. The initiation of the stay‐at‐home order significantly increased alcohol‐impaired driving, which has remained elevated.
Irritability in bipolar disorder and unipolar disorder measured daily using smartphone‐based data: An exploratory post hoc study
Authors: Faurholt‐Jepsen Maria , Busk Jonas , Tønning Morten Lindberg , Bardram Jakob Eyvind , Frost Mads , Vinberg Maj , Kessing Lars Vedel 
Published: April 2023

AbstractObjectiveTo investigate (i) the proportions of time with irritability and (ii) the association between irritability and affective symptoms and functioning, stress, and quality of life in patients with bipolar disorder (BD) and unipolar depressive disorder (UD).MethodsA total of 316 patients with BD and 58 patients with UD provided self‐reported once‐a‐day data on irritability and other affective symptoms using smartphones for a total of 64,129 days with observations. Questionnaires on perceived stress and quality of life and clinical evaluations of functioning were collected multiple times during the study.ResultsDuring a depressive state, patients with UD spent a significantly higher proportion of time with presence of irritability (83.10%) as compared with patients with BD (70.27%) (p = 0.045). Irritability was associated with lower mood, activity level and sleep duration and with increased stress and anxiety level, in both patient groups (p‐values<0.008). Increased irritability was associated with impaired functioning and increased perceived stress (p‐values<0.024). In addition, in patients with UD, increased irritability was associated with decreased quality of life (p = 0.002). The results were not altered when adjusting for psychopharmacological treatments.ConclusionsIrritability is an important part of the symptomatology in affective disorders. Clinicians could have focus on symptoms of irritability in both patients with BD and UD during their course of illness. Future studies investigating treatment effects on irritability would be interesting.
The step‐down approach in children with cow's milk allergy: Results of a randomized controlled trial
Authors: Nocerino Rita , Coppola Serena , Carucci Laura , de Giovanni di Santa Severina Anna Fiorenza , Oglio Franca , de Michele Roberta , di Sessa Ilaria , Masino Antonio , Bedogni Giorgio , Berni Canani Roberto 
Published: April 2023

AbstractBackgroundThe Step‐Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid‐based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus  rhamnosus GG (EHCF + LGG).MethodsRandomized controlled trial involving IgE‐mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double‐blind placebo‐controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored.ResultsSixty IgE‐mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91–0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29–0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001–0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23–0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2–4, Bender's method). A normal body growth pattern was observed in the two study groups.ConclusionIn IgE‐mediated CMA children the step‐down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition.
Management of vagus nerve stimulation therapy in the peri‐operative period
Authors: Broderick L. , Tuohy G. , Solymos O. , Lakhani S. , Staunton B. , Ennis P. , Clark N. , Moppett I. K. , Chalissery A. , Kilbride R. D. , Sweeney K. J. , O'Brien D. , O'Hare A. , Harvey A. , Larkin C. M. 
Published: April 2023

SummaryVagus nerve stimulation is a well‐established treatment option for patients with drug‐resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri‐operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.
False prosperity: Rethinking government support for farmers’ cooperatives in China
Authors: Chen Feifei , Xu Zhigang , Luo Yufeng 
Published: April 2023

AbstractThe rapid development of farmers’ cooperatives in rural China cannot be separated from government support. To ensure the growth of farmers’ cooperatives, the Chinese government uses it as a key performance indicator for its local institutions. Superficially, rural China's cooperative population and membership size witnessed rapid growth during the first decade after the Farmers’ Specialized Cooperatives Law was enacted in 2007; however, such government intervention also leads to non‐standard phenomena due to market distortion. Using nationally representative survey data from 504 cooperatives in Jiangsu, Jilin, and Sichuan provinces, this paper provides a reliable estimate of the “shell cooperative” rate around 2014. The empirical study sheds further light on the role of government during the period of rapid but chaotic growth by a subset containing 241 marketing cooperatives. Results show that direct administrative intervention leads to the emergence of many shell cooperatives (approximately 37%). Further study also confirms that task‐oriented policy support is only positively associated with the nominal coverage ratio but has no significant relationship with cooperatives’ function. This study provides new insights into the formation of shell cooperatives and suggests that direct administrative intervention may not be a good strategy for promoting the sustainable development of farmers’ cooperatives.
Internal hernia caused by exposed structures after laparoscopic lateral lymph node dissection for rectal cancer: A case report
Authors: Sakamoto Shinya , Inada Ryo , Kuroda Eri , Kumon Kento , Toshima Toshiaki , Okabayashi Takehiro 
Published: April 2023

AbstractInternal hernias secondary to exposed structures after lateral lymph node dissection (LLND) for rectal cancer are rare. A 53‐year‐old man who underwent laparoscopic ultra‐low anterior resection and bilateral LND presented to our emergency department with sudden‐onset severe abdominal pain and vomiting. Computed tomography demonstrated a closed loop obstruction of the intestine in the right lateral pelvic cavity and a significantly dilated small bowel in the abdominal cavity. Laparoscopic surgery revealed small bowel migration into the space between the right ureter and umbilical artery. The herniated bowel was laparoscopically reduced, and the small bowel exhibited no ischemic changes. Meanwhile, the hernial orifice was left unrepaired. The patient was discharged on the seventh postoperative day without complications. An internal hernia caused by exposed structures after lymphadenectomy should be a differential diagnosis in patients who have undergone LLND for rectal cancer and then present with severe abdominal pain and vomiting.
Laparoscopic treatment for multiple huge diospyrobezoars in the stomach
Authors: Namikawa Tsutomu , Utsunomiya Masato , Yokota Keiichiro , Maeda Hiromichi , Kitagawa Hiroyuki , Martins Rogério Nascimento , Suganuma Narufumi , Kobayashi Michiya , Hanazaki Kazuhiro , Seo Satoru 
Published: April 2023

AbstractWe report a case of a patient with multiple diospyrobezoars, a phytobezoar attributed to persimmons (Diospyros kaki) consumption, in the stomach, who was treated with laparoscopic complete surgical excision. A 76‐year‐old man with gastric phytobezoars presented to our hospital. Abdominal contrast‐enhanced computed tomography revealed three well‐defined, oval, nonhomogeneous masses with a mottled appearance in the stomach. Esophagogastroduodenoscopy revealed three large brown solid phytobezoars and gastric ulcers at the gastric angle. The clinical diagnosis was diospyrobezoar, and, due to the huge masses, the patient eventually underwent laparoscopic treatment when the medical and endoscopic approaches were unsuccessful. After gastrotomy in the anterior wall of the stomach, the phytobezoar was mobile inside the stomach, which was opened beside the gastric incision. The three phytobezoars were removed through the wound protector using sponge‐holding forceps; the hole in the gastrotomy was closed in the mucosal and seromuscular layers with an intracorporeal suture technique. The weight and size of the phytobezoars were 140 g and 115 × 55 × 50 mm, 70 g and 55 × 45 × 35 mm, and 60 g and 50 × 40 × 35 mm, respectively. The patient was discharged on the 8th postoperative day without any complications. Laparoscopic surgery to extract bezoar is the treatment of choice for this rare entity, because it is a safe and effective approach.
A critical role for altered red cell cation permeability in pathogenesis of sickle cell disease and other haemolytic anaemias
Authors: Gibson John S. , Stewart Gordon W. 
Published: April 2023

The aetiology of sickle cell disease is well known, but pathogenesis is complicated and details remain uncertain. A thorough understanding may suggest novel ways for designing more effective therapies. One area of importance, covered here in Nader et al., is the altered cation permeability of sickle cells and how the co‐ordinated operation of a number of membrane transport proteins contributes to disease progression, all driven by the initial event of HbS polymerisation. There are echoes here of the cation leaks of hereditary stomatocytosis. Nader et al. propose a central role for PIEZO1, a novel mechanosensitive channel found in red cells, which may be aberrantly activated in sickle cells following HbS polymerisation and which may have potential as a novel target for future chemotherapies.Commentary on: Nader et al. Piezo1 activation augments sickling propensity and the adhesive properties of sickle red blood cells in a calcium‐dependent manner. Br J Haematol 2023;202:657–668.
Contribution of whole slide imaging‐based deep learning in the assessment of intraoperative and postoperative sections in neuropathology
Authors: Shi Liting , Shen Lin , Jian Junming , Xia Wei , Yang Ke‐Da , Tian Yifu , Huang Jianghai , Yuan Bowen , Shen Liangfang , Liu Zhengzheng , Zhang Jiayi , Zhang Rui , Wu Keqing , Jing Di , Gao Xin 
Published: April 2023

AbstractThe pathological diagnosis of intracranial germinoma (IG), oligodendroglioma, and low‐grade astrocytoma on intraoperative frozen section (IFS) and hematoxylin–eosin (HE)‐staining section directly determines patients' treatment options, but it is a difficult task for pathologists. We aimed to investigate whether whole‐slide imaging (WSI)‐based deep learning can contribute new precision to the diagnosis of IG, oligodendroglioma, and low‐grade astrocytoma. Two types of WSIs (500 IFSs and 832 HE‐staining sections) were collected from 379 patients at multiple medical centers. Patients at Center 1 were split into the training, testing, and internal validation sets (3:1:1), while the other centers were the external validation sets. First, we subdivided WSIs into small tiles and selected tissue tiles using a tissue tile selection model. Then a tile‐level classification model was established, and the majority voting method was used to determine the final diagnoses. Color jitter was applied to the tiles so that the deep learning (DL) models could adapt to the variations in the staining. Last, we investigated the effectiveness of model assistance. The internal validation accuracies of the IFS and HE models were 93.9% and 95.3%, respectively. The external validation accuracies of the IFS and HE models were 82.0% and 76.9%, respectively. Furthermore, the IFS and HE models can predict Ki‐67 positive cell areas with R2 of 0.81 and 0.86, respectively. With model assistance, the IFS and HE diagnosis accuracy of pathologists improved from 54.6%–69.7% and 53.5%–83.7% to 87.9%–93.9% and 86.0%–90.7%, respectively. Both the IFS model and the HE model can differentiate the three tumors, predict the expression of Ki‐67, and improve the diagnostic accuracy of pathologists. The use of our model can assist clinicians in providing patients with optimal and timely treatment options.
Design, synthesis, and molecular docking studies of novel quinoxaline derivatives as anticancer agents
Authors: Ali Sazan Haji , Osmaniye Derya , Sağlık Begüm Nurpelin , Levent Serkan , Özkay Yusuf , Kaplancıklı Zafer Asım 
Published: April 2023

AbstractAs lung cancer was placed foremost part among other types of cancer in terms of mortality. Recent researches are widely focused on developing multi‐targeted and site‐specific targeted drug designs. In the present study, we designed and developed a series of quinoxaline pharmacophore derivatives as active EGFR inhibitors for the treatment of non‐small cell lung cancer. The compounds were synthesized through a condensation reaction between hexane‐3,4‐dione and methyl 3,4‐diaminobenzoate as a first step. Their structures were confirmed by 1H‐NMR, 13C‐NMR, and HRMS spectroscopic methods. Cytotoxicity (MTT) were applied to determine anticancer activity of the compounds against breast (MCF7), fibroblast (NIH3 T3), and lung (A549) cell lines as EGFR inhibitors. Doxorubicin was used as a reference agent, compound 4i exhibited a significant effect among other derivatives with IC50 = 3.902 ± 0.098 μM value against A549 cell line. The docking study showed that the best position on EGFR receptor could be observed with 4i. From the obtained evaluations of the designed series, compound 4i was a promising agent as EGFR inhibitor for further investigation and evaluation studies in the future.
Unaccompanied migrant children and indebted relations: Weaponizing safeguarding
Authors: Leon Lucy , Rosen Rachel 
Published: April 2023

AbstractUK statutory guidance for practitioners suggests that indebtedness is an area where safeguarding red flags should be raised and action taken to minimize the risk of exploitation. Yet, our research shows that unaccompanied migrant children have complex indebted relationships, which can range from extractive to connective. Drawing on interviews with unaccompanied children, we show that these indebted relationships can include financial debt to smugglers, responsibilities to support transnational families, as well as social obligations to peers and others. Their accounts present a nuanced understanding of the taboo nature of indebted relationships, not to be shared with the practitioners in their lives. This is due, in part, to the potential threat of reporting to the Home Office, which might jeopardize their immigration status. In response to this weaponization of social care, we demonstrate how children turn to peer networks of support, creating their own alternative forms of social protection. In so doing, we complicate critiques of adultification, which traditionally highlight the ways that racially minoritized children may be treated as adults—to their detriment. In so doing, we show that because indebtedness is normatively linked to adulthood, unaccompanied children's hopes and fears may be rendered unsayable and therefore unsupportable in social care, all in the name of safeguarding.