bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal associations between subjective cognitive impairment, pain and depressive symptoms in home‐dwelling older adults: Modelling within‐person effects
Authors: Nakanishi Miharu , Perry Marieke , Bejjani Rachele , Yamaguchi Satoshi , Usami Satoshi , van der Steen Jenny T. 
Published: May 2024

AbstractObjectivesCognitive impairment, pain and depressive symptoms are common and interrelated factors in older adults. However, the directionality and specificity of their association remains unclarified. This study explored whether these factors prospectively increase reciprocal risk and examined the longitudinal association between these factors and quality of life (QoL).MethodsThis study used longitudinal data from The Older Persons and Informal Caregivers Survey Minimal Data Set (TOPICS‐MDS; the Netherlands). Older adults self‐reported cognitive impairment, pain, depressive symptoms and QoL at baseline and after 6 and 12 months of follow‐up. The Random Intercept Cross‐Lagged Panel Model was used to assess the prospective association between the three factors, while a multilevel linear regression analysis in a two‐level random intercept model was used to examine the longitudinal associations between the three factors and QoL at the within‐person level.ResultsThe data of 11,582 home‐dwelling older adults with or without subjective cognitive impairment were analysed. At the within‐person level, pain at 6 months was associated with subsequent depressive symptoms (β = 0.04, p = 0.024). The reverse association from depression to pain, and longitudinal associations between pain and subjective cognitive impairment and between depressive symptoms and subjective cognitive impairment were non‐significant. Pain, depressive symptoms and subjective cognitive impairment showed a significant association with poor QoL 6 months later.ConclusionsA directional relationship was observed from pain to depressive symptoms. Pain reduction holds a potential benefit in the prevention of depressive symptoms, ultimately optimising the QoL of older adults.
The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand
Authors: Pupacdi Benjarath , Loffredo Christopher A. , Budhu Anuradha , Rabibhadana Siritida , Bhudhisawasdi Vajarabhongsa , Pairojkul Chawalit , Sukeepaisarnjaroen Wattana , Pugkhem Ake , Luvira Vor , Lertprasertsuke Nirush , Chotirosniramit Anon , Auewarakul Chirayu U. , Ungtrakul Teerapat , Sricharunrat Thaniya , Sangrajrang Suleeporn , Phornphutkul Kannika , Albert Paul S. , Kim Sungduk , Harris Curtis C. , Mahidol Chulabhorn , Wang Xin Wei , Ruchirawat Mathuros ,   the TIGER‐LC Consortium
Published: May 2024

AbstractThailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER‐LC consortium‐based population study covering all high‐incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011–2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06–2.11 to 2.91; 95% CI: 1.82–4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64–0.96) and iCCA (HR 0.84; 95% CI: 0.70–0.99). Risk factor co‐exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer‐term survivors, including behavioral changes to reduce exposures.
Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database
Authors: Muramatsu Keiji , Aoyama Yoko , Shigemi Daisuke , Yasunaga Hideo , Fushimi Kiyohide , Matsuda Shinya 
Published: May 2024

AbstractObjectiveTo clarify the relationship between the prognosis of patients with placental abruption (PA) and the healthcare delivery system using data from a large national inpatient database in Japan.MethodsUsing the Diagnosis Procedure Combination database, we conducted a retrospective cohort study with the data of patients in almost 1000 hospitals with the primary diagnosis of PA who were hospitalized from April 2014 to March 2021. We divided the hospitals into four groups based on the number of deliveries per month. We performed multilevel logistic regression analysis to analyze the relationship between hospital case volume and maternal end‐organ injury (MEOI).ResultsAltogether, 8222 patients were included for analysis; among whom, 3575 (44%) were transferred by ambulance. MEOI was noted in 977 patients (12%) with no obvious difference by hospital case volume. Ambulance transfer, age, gestational weeks at admission, delivery on the first day of hospitalization, and history of eclampsia were significantly associated with a higher incidence of MEOI, but the hospital case volume was not.ConclusionUsing a Japanese administrative database, our study shows that hospital case volume was not significantly associated with the severity of maternal illness among patients with PA.
Imaging of pain using positron emission tomography
Authors: Zhou Yu‐Peng , Zhang Lauren L. , Sun Yang , Brugarolas Pedro 
Published: May 2024

AbstractPositron emission tomography (PET) is a noninvasive molecular imaging technique that utilizes biologically active radiolabeled compounds to image biochemical processes. As such, PET can provide important pathophysiological information associated with pain of different etiologies. Consequently, the information obtained using PET often combined with magnetic resonance imaging or computed tomography can provide useful information for diagnosing and monitoring changes associated with pain. This review covers the most important PET tracers that have been used to image pain including tracers for fundamental biological processes such as glucose metabolism and cerebral blood flow, to receptor‐specific tracers such as ion channels and neurotransmitters. For each tracer, we describe the structure and radiochemical synthesis of the tracer followed by a brief summary of the available preclinical and clinical studies. By providing a summary of the PET tracers that have been employed for PET imaging of pain, this review aims to serve as a reference for preclinical, translational, and clinical investigators interested in molecular imaging of pain. Finally, the review ends with an outlook of the needs and opportunities in this area.
Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb–drug interaction and drug‐induced kidney injury
Authors: Duan Xiaoyan , Bai Wanting , Hu Jiahuan , Wu Jinjin , Tan Huixin , Wang Fenghe , Lang Xuli , Wang Baolian , Hu Jinping 
Published: May 2024

AbstractMultidrug and toxin extrusion protein 1 (MATE1), an efflux transporter mainly expressed in renal proximal tubules, mediates the renal secretion of organic cationic drugs. The inhibition of MATE1 will impair the excretion of drugs into the tubular lumen, leading to the accumulation of nephrotoxic drugs in the kidney and consequently potentiating nephrotoxicity. Screening and identifying potent MATE1 inhibitors can predict or minimize the risk of drug‐induced kidney injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter‐mediated food/herb–drug interactions. Our objective was to investigate the inhibitory effects of flavonoids on MATE1 in vitro and in vivo and to assess the effects of flavonoids on cisplatin‐induced kidney injury. Thirteen flavonoids exhibited significant transport activity inhibition (>50%) on MATE1 in MATE1‐MDCK cells. Among them, the six strongest flavonoid inhibitors, including irisflorentin, silymarin, isosilybin, sinensetin, tangeretin, and nobiletin, markedly increased cisplatin cytotoxicity in these cells. In cisplatin‐induced in vivo renal injury models, irisflorentin, isosilybin, and sinensetin also increased serum creatinine and blood urea nitrogen levels to different degrees, especially irisflorentin, which exhibited the most potent nephrotoxicity with cisplatin. The pharmacophore model indicated that the hydrogen bond acceptors at the 3, 5, and 7 positions may play a critical role in the inhibitory effect of flavonoids on MATE1. Our findings provide helpful information for predicting the potential risks of flavonoid‐containing food/herb–drug interactions and avoiding the exacerbation of drug‐induced kidney injury via MATE1 mediation.
Mechanistic insights into the role of cyclodextrin in the regioselective radical CH trifluoromethylation of aromatic compounds
Authors: Kawashima Kyohei , Lu Xu , Kuninobu Yoichiro , Mori Toshifumi 
Published: May 2024

AbstractThe regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD‐substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.
Modifiable protective factors for mental health resilience in the offspring of depressed parents: A high‐risk longitudinal cohort spanning adolescence and adulthood
Authors: Padaigaitė‐Gulbinienė Eglė , Hammerton Gemma , Powell Victoria , Rice Frances , Collishaw Stephan 
Published: May 2024

AbstractBackgroundSeveral protective factors have been identified for mental health (MH) resilience in adolescent offspring of depressed parents. However, it is unclear if these effects persist into adulthood.MethodsDepressed parents and their offspring (N = 188) from the Early Prediction of Adolescent Depression study were assessed four times (mean offspring ages 12.39, 13.77, 14.82, and 23.41). Mental health resilience was examined using residual scores (better‐than‐expected mood‐, behaviour‐, or anxiety‐related MH at mean age 23 given risk exposure), and categorically as sustained good MH across adolescence and young adulthood.ResultsOnly 9.2% of young adults demonstrated sustained good MH. Parents of resilient individuals showed lower comorbidity (anxiety, antisocial behaviour and harmful drinking) and higher depression remission. Considering adolescent protective factors, weak evidence was observed of associations of mood‐resilience with adolescent peer‐relationship quality (β = −0.20, 95%CI:−0.36, −0.04); friendship quality (β = −0.14, 95%CI:−0.31, 0.02); risk adjustment (β = −0.16, 95%CI:‐0.34, 0.03) and dysfunctional attitudes (β = 0.18, 95%CI:0.01, 0.35). There was weak evidence of behavioural‐resilience association with parent positive expressed emotion (β = −0.15, 95%CI:−0.31, 0.02) and offspring exercise (β = −0.37, 95%CI:−0.77, 0.03). No adolescent protective factors showed an association with anxiety‐resilience. For sustained good MH, there was weak evidence of an association with inhibitory control (OR = 0.39, 95%CI:0.14, 1.07). Strong evidence was observed for associations between young adult‐reported peer relationship quality and mood‐resilience (β = −0.35, 95%CI:−0.53, −0.17), behavioural‐resilience (β = −0.33, 95%CI:−0.51, −0.14) and anxiety‐resilience (β = −0.34, 95%CI:−0.53, −0.14), while weak evidence was observed of an association of social activities with anxiety‐resilience (β = −0.51, 95%CI:−0.97, −0.06).ConclusionsWe found limited evidence for the long‐lasting effects of adolescent protective factors on adult MH resilience. Social factors remained protective into young adulthood, while family factors did not. Early preventative intervention might not be sufficient to maintain good long‐term MH, and young people will likely require more prolonged support.
Convenient synthesis and antibacterial evaluation of new bipyrazolyl and pyrazolopyridazine derivatives utilizing 4‐acetyl‐5‐methyl‐N‐phenyl‐1‐(p‐tolyl)‐1H‐pyrazole‐3‐carboxamide as a versatile precursor
Authors: Kamel Monica G. , Helmy Mirna T. , Saleh Fatma M. , Hassaneen Hamdi M. , Shehata Omar A. , Laboud Yara N. 
Published: May 2024

Abstract4‐(3‐(Dimethylamino)acryloyl)‐5‐methyl‐N‐phenyl‐1‐(p‐tolyl)‐1H‐pyrazole‐3‐carboxamide was prepared via refluxing of 4‐acetyl‐5‐methyl‐N‐phenyl‐1‐(p‐tolyl)‐1H‐pyrazole‐3‐carboxamide with dimethylformamide dimethyl acetal. The target bipyrazoles were obtained from regioselective reaction of the latter enaminone with different hydrazonoyl halides at reflux in chloroform in the presence of trimethylamine. The regioselectivity was confirmed chemically upon refluxing with hydrazine hydrate in ethanol. The structures of the newly synthesized compounds were established on the basis of their elemental analyses and spectral data. The specified compounds were tested for antibacterial activity against gram‐negative bacteria (Escherichia coli) and (Pseudomonas aeruginosa) and a gram‐positive bacteria (Bacillus subtilis) and (Staphylococcus aureus) using disk diffusion method. Antibacterial studies revealed that compounds 8a, 10b, 10c, 11d, and 14b showed weak to moderate activity against the tested bacteria compared to ampicillin.
New oxadiazol‐5‐ones derivatives and their performance as angiotensin‐converting enzyme (ACE) inhibitors
Authors: Ferreira Larissa Fernanda Lima , Lins Ilária Martina Silva , Feitosa Sidney Gustavo Diniz , Ferreira Jivaldo Gonçalves , Maciel Larissa Gonçalves , Araújo Alice Valença , dos Anjos Janaína Versiani 
Published: May 2024

AbstractAngiotensin‐converting enzyme inhibitors are widely used in treating arterial hypertension, acting on the renin‐angiotensin‐aldosterone system and controlling blood pressure. We present a novel, greener, and faster methodology to assess the 1,2,4‐oxadiazol‐5‐one ring and perform molecular modifications to obtain angiotensin‐converting enzyme (ACE) inhibitors using this heterocyclic core. Molecular docking simulations indicate that the tested compounds exhibited an affinity for the ACE binding site, with scores comparable to the commercial inhibitor lisinopril. However, in vitro assays revealed that the compounds were ineffective in inhibiting ACE activity. The lack of inhibition may be related to the compounds' more apolar nature. These results emphasize the importance of integrating computational and experimental approaches in developing new drugs, providing valuable insights for planning future studies to optimize the activity of synthesized compounds.
Paleoneurology of stem palaeognaths clarifies the plesiomorphic condition of the crown bird central nervous system
Authors: Widrig Klara E. , Navalón Guillermo , Field Daniel J. 
Published: May 2024

AbstractLithornithidae, an assemblage of volant Palaeogene fossil birds, provide our clearest insights into the early evolutionary history of Palaeognathae, the clade that today includes the flightless ratites and volant tinamous. The neotype specimen of Lithornis vulturinus, from the early Eocene (approximately 53 million years ago) of Europe, includes a partial neurocranium that has never been thoroughly investigated. Here, we describe these cranial remains including the nearly complete digital endocasts of the brain and bony labyrinth. The telencephalon of Lithornis is expanded and its optic lobes are ventrally shifted, as is typical for crown birds. The foramen magnum is positioned caudally, rather than flexed ventrally as in some crown birds, with the optic lobes, cerebellum, and foramen magnum shifted further ventrally. The overall brain shape is similar to that of tinamous, the only extant clade of flying palaeognaths, suggesting that several aspects of tinamou neuroanatomy may have been evolutionarily conserved since at least the early Cenozoic. The estimated ratio of the optic lobe's surface area relative to the total brain suggests a diurnal ecology. Lithornis may provide the clearest insights to date into the neuroanatomy of the ancestral crown bird, combining an ancestrally unflexed brain with a caudally oriented connection with the spinal cord, a moderately enlarged telencephalon, and ventrally shifted, enlarged optic lobes.
Five‐Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub‐Concussive Overpressures
Authors: Glikstein Rafael , Melkus Gerd , Portela de Oliveira Eduardo , Brun‐Vergara Maria Lucia , Schwarz Betty Anne , Ramsay Tim , Zhang Tinghua , Skinner Christopher 
Published: May 2024

BackgroundThe Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5‐year longitudinal trial was conducted in follow‐up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure.PurposeTo examine brain MRI findings in military personnel exposed to multiple repeated blast exposures.Study TypeFive‐year longitudinal prospective trial.PopulationNinety‐two males aged 23–42 with an average of 9.4 years of blast exposure.Field Strength/Sequence3 T brain MRI/T1‐weighted 3D with reconstruction in three planes, T2‐weighted, T2‐weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2‐weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging.AssessmentAll MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form.Statistical TestsMatching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers.ResultsA significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678–1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442–1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513–1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively.Data ConclusionThere were significant changes in brain volume, white matter lesions, and enlargement of VR spaces.Evidence Level2Technical EfficacyStage 2
Wuliangye strong aroma baijiu promotes intestinal homeostasis by improving gut microbiota and regulating intestinal stem cell proliferation and differentiation
Authors: Zhu Hui , Gu Baoxiang , Zhao Dong , Ma Yi , Mehmood Muhammad Aamer , Li Yuzhu , Yang Kangzhuo , Wang Yumeng , He Manli , Zheng Jia , Wang Ning 
Published: May 2024

AbstractBACKGROUNDWuliangye strong aroma baijiu (hereafter, Wuliangye baijiu) is a traditional Chinese grain liquor containing short‐chain fatty acids, ethyl caproate, ethyl lactate, other trace components, and a large proportion of ethanol. The effects of Wuliangye baijiu on intestinal stem cells and intestinal epithelial development have not been elucidated. Here, the role of Wuliangye baijiu in intestinal epithelial regeneration and gut microbiota modulation was investigated by administering a Lieber–DeCarli chronic ethanol liquid diet in a mouse model to mimic long‐term (8 weeks’) light/moderate alcohol consumption (1.6 g kg−1 day−1) in healthy human adults.RESULTSWuliangye baijiu promoted colonic crypt proliferation in mice. According to immunofluorescence and reverse transcription‐quantitative polymerase chain reaction analyses, compared with the ethanol‐only treatment, Wuliangye baijiu increased the number of intestinal stem cells and goblet cells and the expression of enteroendocrine cell differentiation markers in the mouse colon. Furthermore, gut microbiota analysis showed an increase in the relative abundance of microbiota related to intestinal homeostasis following Wuliangye baijiu administration. Notably, increased abundance of Bacteroidota, Faecalibaculum, Lachnospiraceae, and Blautia may play an essential role in promoting stem‐cell‐mediated intestinal epithelial development and maintaining intestinal homeostasis.CONCLUSIONSIn summary, these findings suggest that Wuliangye baijiu can be used to regulate intestinal stem cell proliferation and differentiation in mice and to alter gut microbiota distributions, thereby promoting intestinal homeostasis. This research elucidates the mechanism by which Wuliangye baijiu promotes intestinal health. © 2024 Society of Chemical Industry.
Risk Factors Are Not Very Risky Once a Normal Embryonic Heart Rate is Seen in Early Pregnancy
Authors: Doubilet Peter M. , Guo Yang 
Published: May 2024

ObjectivesTo assess first‐trimester prognosis when an early pregnancy sonogram demonstrates a normal embryonic heart rate and to determine how a number of risk factors affect prognosis.MethodsOur study population consisted of 6597 first‐trimester scans with gestational age (GA) ≤ 7.0 weeks (all with crown‐rump length [CRL] <10 mm), normal embryonic heart, and known first‐trimester outcome. We recorded GA; CRL; heart rate; first‐trimester outcome; maternal age; presence, absence, and size of subchorionic hematoma; presence or absence of vaginal bleeding; and presence, absence, and size of uterine fibroids. We assessed first‐trimester outcome in the study population and subsets based on the above data.ResultsFirst‐trimester outcome was successful in 6030 of the 6597 cases (91.4%). The prognosis was somewhat worse with each of the following risk factors: maternal age ≥35 years, large subchorionic hematoma, and large or multiple uterine fibroids (P < .02, chi‐squared or Cochran's test for trend, for all of these items). The rate of successful outcome was in the range of 83–88% with each of these risk factors and 93.8% in the absence of any of these factors.ConclusionsThe presence of a normal embryonic heart rate on an early first‐trimester sonogram is a reassuring finding, indicating a likelihood of good first‐trimester outcome of at least 83% even in the presence of risk factors, and of over 90% in the absence of such factors.